Saxagliptin is an oral dipeptidyl peptidase-4 (DPP-4) inhibitor. Saxagliptin is used in the treatment of type 2 diabetes mellitus (T2DM) in adults. Among treatment-naive adults receiving saxagliptin with a baseline mean hemoglobin A1C of 7.7% to 8%, the mean reduction in A1C was 0.7% to 0.9%; clinical trials pre-market reported mean A1C reductions of 0.4 to 0.5%. First-line T2DM therapy depends on comorbidities, patient-centered treatment factors, and management needs. Therapy with a sodium-glucose co-transporter 2 (SGLT2) inhibitor or GLP-1 receptor agonist (GLP-1 RA), with or without metformin based on glycemic needs, is appropriate initial therapy for patients with T2DM with or at high risk for atherosclerotic cardiovascular disease (ASCVD)/indicators of high-risk, heart failure (HF), or chronic kidney disease (CKD). In patients without indicators of high-risk or established cardiovascular disease (CVD), HF, or CKD, the DPP-4 inhibitors are a therapeutic option which are generally well tolerated, have a neutral effect on weight, and have an intermediate efficacy for glucose lowering with minimal risk of hypoglycemia when used as monotherapy. Saxagliptin was initially FDA approved in 2009.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Saxagliptin may be taken with or without food.
-Do not split or cut tablets.
Serious hypersensitivity reactions have been reported in patients during the first 3 months of therapy with saxagliptin; some reports occurred after the first dose. These reactions included anaphylaxis or anaphylactoid reactions, angioedema, and exfoliative skin conditions (e.g., exfoliative dermatitis). Among clinical trial recipients who received saxagliptin 2.5 mg or 5 mg daily alone or in combination with metformin, a thiazolidinedione, or glyburide, 1.5% had a hypersensitivity-related event such as urticaria and facial edema. In contrast, 0.4% of placebo recipients had these events. Of note, most patients in the add-on placebo or saxagliptin trials had been taking the other antidiabetic agent before trial initiation. Rash (unspecified) was also reported and led to drug discontinuation in 0.2%, 0.3%, and 0% of patients receiving saxagliptin 2.5 mg, saxagliptin 5 mg, and placebo, respectively. Cases of bullous rash, specifically bullous pemphigoid or pemphigus, requiring hospitalization have been reported with DPP-4 inhibitor use. Treatment with topical or systemic immunosuppressives and discontinuation of the DPP-4 inhibitor has typically resulted in resolution of the rash. Inform patients of the risk of serious rash and tell them to report development of blisters or erosions while receiving saxagliptin. If a serious reaction is suspected, discontinue saxagliptin and refer the patient to a dermatologist for diagnosis and appropriate treatment.
Saxagliptin may cause lymphopenia. As compared with data from placebo recipients, the mean decrease in the absolute lymphocyte count ranged from 84 to 100 cells/microliter among patients treated with saxagliptin. In the SAVOR trial, a lymphocyte count of 750 cells/microliter or less was reported in 1.6% (136/8,280) of saxagliptin receipts and 1% (78/8,212) of placebo receipts. In another trial, a lymphocyte count of 750 cells/microliter or less occurred in 0.5% of saxagliptin 2.5 mg recipients, in 1.5% of saxagliptin 5 mg recipients, 1.4% of saxagliptin 10 mg recipients, and in 0.4% of placebo recipients. Some patients had recurrent decreases upon saxagliptin rechallenge that led to saxagliptin discontinuation; lymphopenia led to drug discontinuation in 0.1% and 0.5% versus 0% in patients receiving 2.5 mg and 5 mg saxagliptin and placebo, respectively. Measure the lymphocyte count if clinically indicated. The effect of saxagliptin on lymphocyte counts among patients with lymphocyte abnormalities such as HIV is unknown. Other lab abnormalities associated with drug discontinuation include blood creatinine increased (0% to 0.3%) and blood creatinine phosphokinase increased (0.1% to 0.2%). An event of thrombocytopenia, consistent with a diagnosis of idiopathic thrombocytopenic purpura, has been reported with saxagliptin use. The relationship of this event to saxagliptin is not known.
Abdominal pain and vomiting may be associated with saxagliptin. In a pooled analysis of clinical trial data, abdominal pain occurred in 2.4% of saxagliptin 2.5 mg recipients, in 1.7% of saxagliptin 5 mg recipients, and in 0.5% of placebo recipients. Vomiting occurred in 2.2% of saxagliptin 2.5 mg recipients, in 2.3% of saxagliptin 5 mg recipients, and in 1.3% of placebo recipients. Gastroenteritis occurred in 1.9% of saxagliptin 2.5 mg recipients, in 2.3% of saxagliptin 5 mg recipients, and in 0.9% of placebo recipients.
During clinical trials, headache was reported in 6.5% of saxagliptin patients compared to 5.9% of placebo patients. Among treatment-naive patients who took both saxagliptin 5 mg and metformin, 7.5% reported headache compared to 5.2% who only took metformin.
Hypoglycemia has been reported with saxagliptin use. When used as monotherapy, hypoglycemia was reported in 4% of patients receiving a 2.5 mg dose and 5.6% receiving a 5 mg dose; comparatively 4.1% receiving placebo reported hypoglycemia. Hypoglycemia occurred in a similar percentage of patients who received saxagliptin or placebo plus either metformin or a thiazolidinedione. In contrast, more patients who received saxagliptin plus glyburide had reported hypoglycemia; 13.3% of 248 saxagliptin 2.5 mg plus glyburide recipients, 14.6% of 253 saxagliptin 5 mg plus glyburide recipients, and 10.1% of 267 placebo plus glyburide recipients; hypoglycemia was reported in 1.6% of patients receiving saxagliptin monotherapy and in none of the placebo-treated patients. When comparing saxagliptin to glipizide in patients with inadequate control on metformin, the incidence of hypoglycemia was lower in patients treated with saxagliptin/metformin (3% for saxagliptin/metformin vs. 36.3% for glipizide/metformin). Saxagliptin has been studied as add-on therapy in patients already receiving insulin; the overall incidence of reported hypoglycemia was 18.4% for saxagliptin 5 mg and 19.9% for placebo. Alternatively, the incidence of confirmed symptomatic hypoglycemia (fingerstick blood glucose 50 mg/dL or less) was higher with saxagliptin 5 mg (5.3%) when compared to placebo (3.3%). In a 12-week trial in patients with moderate or severe renal impairment or end-stage renal disease, hypoglycemia was reported in 20% of those receiving saxagliptin 2.5mg and in 22% receiving placebo; confirmed symptomatic hypoglycemia was found in 4 saxagliptin patients (4.7%) and 3 placebo patients (3.5%).
As monotherapy, a similar percentage of patients who got either saxagliptin or placebo had peripheral edema: 3.6% of saxagliptin 2.5 mg recipients, 2% of saxagliptin 5 mg recipients, and 3% of placebo recipients. However, peripheral edema was reported more commonly in patients treated with the combination of saxagliptin and a thiazolidinedione as compared with patients treated with the combination of placebo and a thiazolidinedione. Among patients who received saxagliptin plus either rosiglitazone or pioglitazone, 3.1% of 192 patients who got saxagliptin 2.5 mg daily and 8.1% of 186 patients who got saxagliptin 5 mg daily had peripheral edema. In contrast, 4.3% of 184 patients who got placebo added on to either thiazolidinedione had the event. None of the peripheral edema reports resulted in saxagliptin discontinuation. Among patients who received either saxagliptin or placebo as add-on to metformin, 2.1% of saxagliptin 2.5 mg recipients, and 2.1% of saxagliptin 5 mg recipients, and 2.2% of placebo recipients had peripheral edema. Among patients who received either saxagliptin or placebo as add-on to glyburide, 2.4% of saxagliptin 2.5 mg recipients, and 1.2% of saxagliptin 5 mg recipients, and 2.2% of placebo recipients had peripheral edema.
More cases of tuberculosis infection were reported among saxagliptin-treated patients than in comparator-treated patients, although causality cannot be associated with saxagliptin use due to limited data. There were 6 (0.12%) reports of tuberculosis infection among 4959 saxagliptin-treated patients in an unblinded, controlled, clinical trial database. In the 2868 comparator-treated patients, no cases of tuberculosis were reported. Two of the 6 cases were confirmed by laboratory testing. None of these cases occurred in the United States or Western Europe. There have been no spontaneous reports of tuberculosis associated with saxagliptin. There has also been 1 report of a potential opportunistic infection of foodborne fatal salmonella sepsis after a patient took saxagliptin for 600 days. Other infectious-related adverse effects reported with saxagliptin use include sinusitis (2.6% to 2.9%), naso-pharyngitis (6.9%), upper respiratory tract infection (7.7%) and urinary tract infection (6.8%).
In patients receiving saxagliptin (pooled analysis for 2.5 mg, 5 mg, and 10 mg) and placebo, the incidence rate of bone fractures was 1 and 0.6 per 100 patient-years, respectively. For patients receiving saxagliptin, the incidence rates of these fractures did not increase over time. The relationship of this event to saxagliptin is not known.
Acute pancreatitis has been reported in a randomized clinical trial and in postmarketing reports in patients taking saxagliptin or other members of the dipeptidyl peptidase-4 (DPP4) inhibitors class. Acute pancreatitis was confirmed in 17 of 8,240 (0.2%) patients treated with saxagliptin compared to 9 of 8,173 (0.1%) patients receiving placebo during a cardiovascular outcomes trial enrolling participants with established arthrosclerotic cardiovascular disease (ASCVD) or multiple risk factors for ASCVD (SAVOR trial). Pre-existing risk factors for pancreatitis were identified in 88% (15/17) of patients receiving saxagliptin and in 100% (9/9) of those receiving placebo. The FDA continues to evaluate the potential for risk for pancreatitis with saxagliptin and related drugs. Patients should be carefully monitored for signs and symptoms of pancreatitis. If pancreatitis is suspected, immediately discontinue saxagliptin and initiate appropriate management. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using saxagliptin.
An increased risk of hospitalization for heart failure has been reported in patients receiving saxagliptin in a randomized, placebo-controlled postmarketing trial (SAVOR). The study included 16,492 patients with type 2 diabetes who had either a history of cardiovascular events or a risk for cardiovascular events. Patients were randomized to receive either saxagliptin therapy (n = 613) or placebo (n = 609) over a median of 2.1 years. Saxagliptin did not reduce or increase the risk of the primary composite end point of cardiovascular death, myocardial infarction, or ischemic stroke. However, 3.5% of patients in the saxagliptin group were hospitalized for heart failure compared to 2.8% of patients in the placebo group (HR 1.27, 95% CI 1.07 to 1.51; p = 0.007). The SAVOR trial was not specifically designed to assess heart failure risk. Observe patients receiving saxagliptin for signs and symptoms of heart failure. If heart failure develops, consider discontinuing the drug and monitoring for diabetic control.
Cases of severe, sometimes disabling, arthralgia (joint pain) have been reported with the use of dipeptidyl peptidase-4 (DPP-4) inhibitors, including saxagliptin. Advise patients not to discontinue therapy but to contact their health care professional immediately if they experience severe and persistent joint pain while taking saxagliptin. Consider saxagliptin as a possible cause of joint pain and discontinue if appropriate. The FDA has identified 33 cases of severe arthralgia with the use of DPP-4 inhibitors, all of which resulted in substantial reduction of the patient's prior level of activity and, in 10 cases, required hospitalization. In the reported cases, the onset of symptoms occurred from 1 day to several years after the start of therapy with a DPP-4 inhibitor. Symptoms resolved with discontinuation of therapy, usually in less than a month; however, some patients experienced a recurrence of joint pain when restarting the same drug or switching to another DPP-4 inhibitor.
Renal-related adverse reactions have been reported with saxagliptin and include increased serum creatinine, worsening of renal impairment, and acute renal failure (unspecified). Rhabdomyolysis has been reported during postmarketing experience with saxagliptin. Adverse reactions related to renal impairment were reported in patients during the SAVOR trial (a multicenter, multinational, randomized, double-blind study evaluating the cardiovascular risk in patients saxagliptin vs. placebo). Laboratory changes (i.e., doubling of serum creatinine compared with baseline and serum creatinine above 6 mg/dL) were reported in 5.8% (483/8,280) of saxagliptin-treated patients and 5.1% (422/8,212) of placebo-treated subjects. The most frequently reported adverse reactions included renal impairment (2.1% vs. 1.9%), acute renal failure (1.4% vs. 1.2%), and renal failure (0.8% vs. 0.9%) in the saxagliptin vs. placebo groups, respectively. From baseline to the end of treatment, there was a mean decrease in estimated glomerular filtration rate (eGFR) of 2.5 mL/minute/1.73 m2 for saxagliptin-treated patients and a mean decrease of 2.4 mL/minute/1.73 m2 for placebo-treated patients. More subjects randomized to saxagliptin (421/5,227; 8.1%) vs. placebo (344/5,073; 6.8%) had downward shifts in eGFR from greater than 50 mL/minute (i.e. normal or mild renal impairment) to 50 mL/minute or less (i.e. moderate or severe renal impairment). The proportions of subjects with renal adverse reactions increased with worsening baseline renal function and increased age, regardless of treatment assignments. Increased serum creatinine led to drug discontinuation in 0.3%, 0%, and 0% of patients receiving saxagliptin 2.5 mg, saxagliptin 5 mg, and placebo, respectively. Increased creatine phosphokinase led to drug discontinuation in 0.1%, 0.2%, and 0% of patients receiving saxagliptin 2.5 mg, saxagliptin 5 mg, and placebo, respectively.
Saxagliptin is contraindicated in patients with a history of a serious hypersensitivity reaction to saxagliptin, such as anaphylaxis, urticaria, angioedema, or exfoliative dermatitis or other serious skin conditions (serious rash), including Stevens-Johnson Syndrome. A risk of serious hypersensitivity reactions or anaphylaxis has been reported in patients during the first 3 months of therapy with saxagliptin; some reports occurred after the first dose. Use caution in patients with a history of angioedema to another dipeptidyl peptidase-4 (DPP-4) inhibitor because it is unknown whether such patients will be predisposed to angioedema with saxagliptin. Postmarketing cases of serious rash, specifically bullous pemphigoid, requiring hospitalization have been reported with DPP-4 inhibitor use. Treatment with topical or systemic immunosuppressives and discontinuation of the DPP-4 inhibitor has typically resulted in resolution of the rash. Inform patients of the risk of serious rash and tell them to report development of blisters or erosions while receiving saxagliptin. If a serious reaction is suspected, discontinue saxagliptin and refer the patient to a dermatologist for diagnosis and appropriate treatment.
Do not use saxagliptin for the treatment of type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis (DKA). Both conditions require insulin receipt.
Temporary use of insulin in place of oral antidiabetic agents may be necessary during periods of physiologic stress (e.g., burns, systemic infection, trauma, surgery, or fever).
Changes in gastric emptying may alter blood glucose control; monitor patients with diarrhea, gastroparesis, GI obstruction, ileus, or vomiting taking saxagliptin carefully.
Acute pancreatitis has been reported in a randomized clinical trial and in postmarketing reports in patients taking saxagliptin or other members of the dipeptidyl peptidase-4 (DPP4) inhibitors class. Acute pancreatitis was confirmed in 17 of 8,240 (0.2%) patients treated with saxagliptin compared to 9 of 8,173 (0.1%) patients receiving placebo during a cardiovascular outcomes trial enrolling participants with established arthrosclerotic cardiovascular disease (ASCVD) or multiple risk factors for ASCVD (SAVOR trial). Preexisting risk factors for pancreatitis were identified in 88% (15/17) of patients receiving saxagliptin and in 100% (9/9) of those receiving placebo. The FDA continues to evaluate the risk for pancreatitis from saxagliptin and related agents. Prior to initiating therapy with saxagliptin, consider other risk factors for pancreatitis, such as a previous history of pancreatitis. Saxagliptin has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at an increased risk for the development of pancreatitis while using saxagliptin. Carefully monitor all patients for signs and symptoms of pancreatitis. Inform patients that persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting, is the hallmark symptom of acute pancreatitis. If pancreatitis is suspected, immediately discontinue saxagliptin and initiate appropriate management.
Conditions that predispose patients to developing hyperglycemia may alter saxagliptin efficacy. Hyperglycemia related conditions include drug interactions, female hormonal changes, high fever, severe psychological stress, and uncontrolled hypercortisolism, or hyperthyroidism. More frequent blood glucose monitoring may be necessary in patients with these conditions.
Conditions that predispose patients to developing hypoglycemia may alter antidiabetic agent efficacy. Conditions associated with hypoglycemia include debilitated physical condition, drug interactions, malnutrition, uncontrolled adrenal insufficiency, pituitary insufficiency, or hypothyroidism. More frequent blood glucose monitoring may be necessary in patients with these conditions. The incidence of confirmed hypoglycemia was increased over that of placebo when saxagliptin was used in combination with a sulfonylurea or with insulin. In order to minimize the risk of hypoglycemia when saxagliptin is used in combination with sulfonylurea or insulin, a lower dose of the sulfonylurea or insulin may be required.
Use saxagliptin with caution in patients who have a history of or who have increased risk factors for heart failure, including patients with existing cardiac disease or kidney disease. Observe patients receiving saxagliptin for signs and symptoms of heart failure. If heart failure develops, consider discontinuing the drug. An increased risk of hospitalization for heart failure has been reported in patients receiving saxagliptin in a randomized, placebo-controlled postmarketing trial (SAVOR). The study included 16,492 patients with type 2 diabetes who had either a history of cardiovascular events or a risk for cardiovascular events. Patients were randomized to receive either saxagliptin therapy (n = 613) or placebo (n = 609) over a median of 2.1 years. Saxagliptin did not reduce or increase the risk of the primary composite end point of cardiovascular death, myocardial infarction, or ischemic stroke. However, 3.5% of patients in the saxagliptin group were hospitalized for heart failure compared to 2.8% of patients in the placebo group (HR 1.27, 95% CI 1.07 to 1.51; p = 0.007). The SAVOR trial was not specifically designed to assess heart failure risk.
A saxagliptin dosage adjustment is required in patients with moderate or severe renal impairment including renal failure and those patients on dialysis. Renal function assessment is recommended for all patients before saxagliptin initiation. Periodic renal function assessment is recommended during saxagliptin receipt. Saxagliptin may increase the risk of heart failure, particularly in patients who already have heart or renal disease. Observe patients with renal disease receiving saxagliptin for signs and symptoms of heart failure. If heart failure develops, consider discontinuing the drug.
Cases of severe, sometimes disabling, arthralgia (joint pain) have been reported with the use of dipeptidyl peptidase-4 (DPP-4) inhibitors, including saxagliptin. Advise patients not to discontinue therapy but to contact their health care professional immediately if they experience severe and persistent joint pain while taking saxagliptin. Consider saxagliptin as a possible cause of joint pain and discontinue if appropriate. The FDA has identified 33 cases of severe arthralgia with the use of DPP-4 inhibitors, all of which resulted in substantial reduction of the patient's prior level of activity and, in 10 cases, required hospitalization. In the reported cases, the onset of symptoms occurred from 1 day to several years after the start of therapy with a DPP-4 inhibitor. Symptoms resolved with discontinuation of therapy, usually in less than a month; however, some patients experienced a recurrence of joint pain when restarting the same drug or switching to another DPP-4 inhibitor.
During saxagliptin clinical trials, 42% (n = 11,301) of patients were 65 years and older and 10.7% (n = 1,210) of patients in clinical trials were 75 years of age and older; no overall differences in safety or efficacy were observed between older and younger adult patients receiving saxagliptin alone. Greater sensitivity of some geriatric individuals to saxagliptin cannot be ruled out, particularly if the geriatric patient has co-existing cardiac or kidney disease, which may increase the risk for heart failure or renal impairment in some geriatric patients. Observe patients receiving saxagliptin for signs and symptoms of heart failure, and if heart failure develops, consider discontinuing the drug and monitoring for diabetic control. Dosage adjustment based on renal function may be needed. Periodic renal function assessment is recommended during use.
No adequate and well-controlled studies of saxagliptin use during human pregnancy exist; only use during pregnancy if clearly needed. Saxagliptin does cross the placenta in pregnant rats. Saxagliptin was not teratogenic at any dose tested when administered to pregnant rats and rabbits during periods of organogenesis. Incomplete ossification of the pelvis, a form of developmental delay, occurred in rats at a dose of 240 mg/kg, or approximately 1,503 and 66-times the human exposure to saxagliptin and the active metabolite, respectively, at the maximum recommended human dose (MRHD) of 5 mg. Maternal toxicity and reduced fetal body weights were observed at 7,986 and 328-times the human exposure at the MRHD for saxagliptin and the active metabolite, respectively. Minor skeletal variations in rabbits occurred at a maternally toxic dose of 200 mg/kg, or approximately 1,432 and 992 times the MRHD. The American College of Obstetricians and Gynecologists (ACOG) and the American Diabetes Association (ADA) continue to recommend human insulin as the standard of care in women with diabetes mellitus or gestational diabetes mellitus (GDM) requiring medical therapy; insulin does not cross the placenta.
Saxagliptin should be used with caution during breast-feeding. There is no information regarding the presence of saxagliptin in human milk, the effects on the breastfed infant, or the effects on milk production. However, saxagliptin is present in rat milk (1:1 ratio). Consider the developmental and health benefits of breast-feeding should be considered along with the clinical need for saxagliptin and any potential adverse effects on the breastfed child from the drugs or from the underlying maternal condition. If saxagliptin is discontinued and blood glucose is not controlled on diet and exercise alone, insulin therapy may be considered. Other oral hypoglycemics may also be considered. Metformin monotherapy may be appropriate for some patients as available studies indicate low excretion in milk and that maternal use during breast-feeding is not expected to result in side effects to a healthy nursing infant. Some experts recommend using metformin with caution if the patient is breast-feeding a newborn or a premature neonate with reduced renal function. Because acarbose has limited systemic absorption, which results in minimal maternal plasma concentrations, clinically significant exposure via breast milk is not expected; therefore, this agent may be an alternative if postprandial glucose control is needed. Glyburide may be a suitable alternative since it was not detected in the breast milk of lactating women who received single and multiple doses of glyburide. If any oral hypoglycemics are used during breast-feeding, the nursing infant should be monitored for signs of hypoglycemia, such as increased fussiness or somnolence.
Safety and efficacy of saxagliptin have not been established in children. One clinical trial suggested that saxagliptin was not effective for reducing hemoglobin A1C compared to placebo or dapagliflozin in children and adolescents 10 to 17 years of age with type 2 diabetes mellitus.
For the treatment of type 2 diabetes mellitus as an adjunct to diet and exercise:
Oral dosage:
Adults: 2.5 or 5 mg PO once daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Therapeutic Drug Monitoring:
-Individualize glycemic goals based on a risk-benefit assessment.
-Use higher goals in patients with persistent hypoglycemia.
-Monitor post-prandial glucose concentrations if there is an inconsistency between pre-prandial glucose and A1C concentrations and to help assess basal-bolus regimens.
Blood glucose goals for adults with type 1 or type 2 diabetes :
-Pre-prandial = 80 to 130 mg/dL
-Peak post-prandial = less than 180 mg/dL
A1C goals for adults with type 1 or type 2 diabetes :
-Assess A1C at least 2 times a year in patients who are meeting treatment goals (and who have stable glycemic control). Perform A1C test quarterly in patients whose therapy has changed or who are not meeting glycemic goals.
-In general, an A1C target is less than 7% in nonpregnant adults. -A more stringent goal of less than 6.5% may be appropriate for selected individual patients if this can be achieved without significant hypoglycemia or other adverse effects.
-Less stringent goals (e.g., A1C less than 8%) may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular/macrovascular complications, or extensive comorbid conditions.
Maximum Dosage Limits:
-Adults
5 mg/day PO.
-Geriatric
5 mg/day PO.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Not indicated.
Patients with Hepatic Impairment Dosing
No dosage adjustments are needed.
Patients with Renal Impairment Dosing
eGFR 45 mL/minute/1.73 m2 or more: No dosage adjustment needed.
eGFR less than 45 mL/minute/1.73 m2: Limit dose to 2.5 mg PO once daily.
Intermittent hemodialysis
Limit dose to 2.5 mg PO once daily. Administer the dose after hemodialysis.
*non-FDA-approved indication
Acebutolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Acetaminophen; Aspirin: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Acetaminophen; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Acetaminophen; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Acetazolamide: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Acrivastine; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Adagrasib: (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with adagrasib due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A substrate; adagrasib is a strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased the saxagliptin AUC up to 3.7-fold.
Albuterol; Budesonide: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Amoxicillin; Clarithromycin; Omeprazole: (Major) The saxagliptin dose is limited to 2.5 mg once daily when coadministered with a strong CYP3A4/5 inhibitor such as clarithromycin. The concomitant use of clarithromycin and antidiabetic agents can result in significant hypoglycemia, especially with antidiabetic drugs metabolized via CYP3A4/5. Careful monitoring of blood glucose is recommended.
Amphetamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Amphetamine; Dextroamphetamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Androgens: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Apalutamide: (Moderate) Monitor for increased blood sugars if coadministration of saxagliptin with apalutamide is necessary. Saxagliptin is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased saxagliptin exposure by 76%.
Aprepitant, Fosaprepitant: (Moderate) Use caution if saxagliptin and aprepitant, fosaprepitant are used concurrently and monitor for an increase in saxagliptin-related adverse effects, for several days after administration of a multi-day aprepitant regimen. Saxagliptin is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of saxagliptin. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Aripiprazole: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Articaine; Epinephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Asenapine: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Aspirin, ASA: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Aspirin, ASA; Caffeine: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Aspirin, ASA; Dipyridamole: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Aspirin, ASA; Omeprazole: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Aspirin, ASA; Oxycodone: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Atazanavir: (Major) The metabolism of saxagliptin is primarily mediated by CYP3A4/5. The saxagliptin dose is limited to 2.5 mg once daily when coadministered with a strong CYP3A4/5 inhibitor such as atazanavir. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have also been reported with use of anti-retroviral protease inhibitors. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Atazanavir; Cobicistat: (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with cobicistat due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor with a single 100 mg dose of saxagliptin and a single 20 mg dose of saxagliptin increased the saxagliptin AUC by 2.45-fold and 3.67-fold, respectively. (Major) The metabolism of saxagliptin is primarily mediated by CYP3A4/5. The saxagliptin dose is limited to 2.5 mg once daily when coadministered with a strong CYP3A4/5 inhibitor such as atazanavir. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have also been reported with use of anti-retroviral protease inhibitors. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Atenolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Atenolol; Chlorthalidone: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
atypical antipsychotic: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Azelastine; Fluticasone: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Azilsartan; Chlorthalidone: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Beclomethasone: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Benzphetamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Beta-blockers: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Betamethasone: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Betaxolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Bismuth Subsalicylate: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Bisoprolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Bortezomib: (Moderate) During clinical trials of bortezomib, hypoglycemia and hyperglycemia were reported in diabetic patients receiving antidiabetic agents. Patients taking antidiabetic agents and receiving bortezomib treatment may require close monitoring of their blood glucose levels and dosage adjustment of their medication.
Brexpiprazole: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Brimonidine; Timolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Brompheniramine; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Brompheniramine; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Budesonide: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Budesonide; Formoterol: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Bumetanide: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
Bupivacaine; Epinephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Carbonic anhydrase inhibitors: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Cariprazine: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Carteolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Carvedilol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Ceritinib: (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with ceritinib due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor with a single 100 mg dose of saxagliptin and a single 20 mg dose of saxagliptin increased the saxagliptin AUC by 2.45-fold and 3.67-fold, respectively.
Cetirizine; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Chloramphenicol: (Minor) Monitor patients for hypoglycemia if saxagliptin and chloramphenicol are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as chloramphenicol.
Chloroquine: (Major) Careful monitoring of blood glucose is recommended when chloroquine and antidiabetic agents, including the dipeptidyl peptidase-4 inhibitors, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with chloroquine and an antidiabetic agent.
Chlorothiazide: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Chlorpheniramine; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Chlorpheniramine; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Chlorpromazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Chlorthalidone: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Choline Salicylate; Magnesium Salicylate: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Chromium: (Moderate) Chromium dietary supplements may lower blood glucose. As part of the glucose tolerance factor molecule, chromium appears to facilitate the binding of insulin to insulin receptors in tissues and to aid in glucose metabolism. Because blood glucose may be lowered by the use of chromium, patients who are on antidiabetic agents may need dose adjustments. Close monitoring of blood glucose is recommended.
Ciclesonide: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Ciprofloxacin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Clarithromycin: (Major) The saxagliptin dose is limited to 2.5 mg once daily when coadministered with a strong CYP3A4/5 inhibitor such as clarithromycin. The concomitant use of clarithromycin and antidiabetic agents can result in significant hypoglycemia, especially with antidiabetic drugs metabolized via CYP3A4/5. Careful monitoring of blood glucose is recommended.
Clonidine: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Clozapine: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Cobicistat: (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with cobicistat due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor with a single 100 mg dose of saxagliptin and a single 20 mg dose of saxagliptin increased the saxagliptin AUC by 2.45-fold and 3.67-fold, respectively.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Codeine; Phenylephrine; Promethazine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Codeine; Promethazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Conjugated Estrogens: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis.
Conjugated Estrogens; Bazedoxifene: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis.
Conjugated Estrogens; Medroxyprogesterone: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Corticosteroids: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Cortisone: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Daclatasvir: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Dalfopristin; Quinupristin: (Major) The manufacturer recommends limiting the saxagliptin dose to 2.5 mg/day if used with strong CYP3A4/5 inhibitors such as dalfopristin; quinupristin. The metabolism of saxagliptin is primarily mediated by CYP3A4/5, and maximum serum concentrations and exposure of saxagliptin are increased when administered with strong inhibitors. Monitor patients for hypoglycemia if these drugs are used together.
Danazol: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Darunavir: (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with darunavir due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A substrate; darunavir is a strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased the saxagliptin AUC up to 3.7-fold.
Darunavir; Cobicistat: (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with cobicistat due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor with a single 100 mg dose of saxagliptin and a single 20 mg dose of saxagliptin increased the saxagliptin AUC by 2.45-fold and 3.67-fold, respectively. (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with darunavir due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A substrate; darunavir is a strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased the saxagliptin AUC up to 3.7-fold.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with cobicistat due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor with a single 100 mg dose of saxagliptin and a single 20 mg dose of saxagliptin increased the saxagliptin AUC by 2.45-fold and 3.67-fold, respectively. (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with darunavir due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A substrate; darunavir is a strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased the saxagliptin AUC up to 3.7-fold.
Deflazacort: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Delafloxacin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Delavirdine: (Major) The manufacturer recommends limiting the saxagliptin dose to 2.5 mg/day if used with strong CYP3A4/5 inhibitors such as delavirdine. The metabolism of saxagliptin is primarily mediated by CYP3A4/5, and maximum serum concentrations and exposure of saxagliptin are increased when administered with strong inhibitors. Monitor patients for hypoglycemia if these drugs are used together.
Desloratadine; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Desogestrel; Ethinyl Estradiol: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Dexamethasone: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Dexmethylphenidate: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Dextroamphetamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Diazoxide: (Minor) Diazoxide, when administered intravenously or orally, produces a prompt dose-related increase in blood glucose level, due primarily to an inhibition of insulin release from the pancreas, and also to an extrapancreatic effect. The hyperglycemic effect begins within an hour and generally lasts no more than 8 hours in the presence of normal renal function. The hyperglycemic effect of diazoxide is expected to be antagonized by certain antidiabetic agents (e.g., insulin or a sulfonylurea). Blood glucose should be closely monitored.
Dienogest; Estradiol valerate: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Diethylpropion: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Digoxin: (Moderate) The AUC and Cmax of digoxin may be increased in the presence of saxagliptin. Dosage adjustment of digoxin is not recommended, but patients receiving these 2 drugs at the same time should be monitored closely.
Diltiazem: (Minor) Saxagliptin did not meaningfully alter the pharmacokinetics of diltiazem. However, coadministration increased the maximum serum saxagliptin concentration by 63% and the systemic exposure by 2.1-fold. As expected, the maximum serum concentration of the saxagliptin active metabolite was decreased by 44% and the systemic exposure was decreased by 36%. Saxagliptin dose adjustment is not advised when coadministered with diltiazem.
Diphenhydramine; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Disopyramide: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving disopyramide concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
Dobutamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Dopamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Dorzolamide; Timolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Doxapram: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Dronedarone: (Minor) Monitor patients for hypoglycemia if saxagliptin and dronedarone are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as dronedarone.
Drospirenone: (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Drospirenone; Estetrol: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Drospirenone; Estradiol: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Drospirenone; Ethinyl Estradiol: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Elagolix; Estradiol; Norethindrone acetate: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Elbasvir; Grazoprevir: (Moderate) Administering metformin; saxagliptin with elbasvir; grazoprevir may result in elevated saxagliptin plasma concentrations. Saxagliptin is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events. (Moderate) Closely monitor blood glucose levels if elbasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as elbasvir.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with cobicistat due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor with a single 100 mg dose of saxagliptin and a single 20 mg dose of saxagliptin increased the saxagliptin AUC by 2.45-fold and 3.67-fold, respectively.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with cobicistat due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor with a single 100 mg dose of saxagliptin and a single 20 mg dose of saxagliptin increased the saxagliptin AUC by 2.45-fold and 3.67-fold, respectively.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Ephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Ephedrine; Guaifenesin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Epinephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Erythromycin: (Minor) Saxagliptin plasma concentrations are expected to increase in the presence of moderate CYP 3A4/5 inhibitors such as erythromycin, but saxagliptin dose adjustment is not advised.
Esmolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Esterified Estrogens: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis.
Esterified Estrogens; Methyltestosterone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together. (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis.
Estradiol: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis.
Estradiol; Levonorgestrel: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Estradiol; Norethindrone: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Estradiol; Norgestimate: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Estradiol; Progesterone: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Estrogens: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis.
Estropipate: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis.
Ethinyl Estradiol; Norelgestromin: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Ethinyl Estradiol; Norethindrone Acetate: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Ethinyl Estradiol; Norgestrel: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Ethotoin: (Minor) Phenytoin and other hydantoins have the potential to increase blood glucose and thus interact with antidiabetic agents pharmacodynamically. Monitor blood glucose for changes in glycemic control. Dosage adjustments may be necessary in some patients.
Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Etonogestrel: (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Etonogestrel; Ethinyl Estradiol: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Fenofibrate: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and fibric acid derivative use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Fenofibric Acid: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and fibric acid derivative use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Fexofenadine; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Fibric acid derivatives: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and fibric acid derivative use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Fludrocortisone: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Flunisolide: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Fluoxetine: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 (DPP-4) inhibitor and fluoxetine use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Fluphenazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Fluticasone: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Fluticasone; Salmeterol: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Fluticasone; Vilanterol: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Fluvoxamine: (Minor) Monitor patients for hypoglycemia if saxagliptin and fluvoxamine are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as fluvoxamine.
Formoterol; Mometasone: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Fosamprenavir: (Moderate) Closely monitor for changes in glycemic control and hyperglycemia if saxagliptin is coadministered with fosamprenavir. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Fosphenytoin: (Minor) Phenytoin and other hydantoins have the potential to increase blood glucose and thus interact with antidiabetic agents pharmacodynamically. Monitor blood glucose for changes in glycemic control. Dosage adjustments may be necessary in some patients.
Furosemide: (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Garlic, Allium sativum: (Moderate) Patients receiving antidiabetic agents should use dietary supplements of Garlic, Allium sativum with caution. Constituents in garlic might have some antidiabetic activity, and may increase serum insulin levels and increase glycogen storage in the liver. Monitor blood glucose and glycemic control. Patients with diabetes should inform their health care professionals of their intent to ingest garlic dietary supplements. Some patients may require adjustment to their hypoglycemic medications over time. One study stated that additional garlic supplementation (0.05 to 1.5 grams PO per day) contributed to improved blood glucose control in patients with type 2 diabetes mellitus within 1 to 2 weeks, and had positive effects on total cholesterol and high/low density lipoprotein regulation over time. It is unclear if hemoglobin A1C is improved or if improvements are sustained with continued treatment beyond 24 weeks. Other reviews suggest that garlic may provide modest improvements in blood lipids, but few studies demonstrate decreases in blood glucose in diabetic and non-diabetic patients. More controlled trials are needed to discern if garlic has an effect on blood glucose in patients with diabetes. When garlic is used in foods or as a seasoning, or at doses of 50 mg/day or less, it is unlikely that blood glucose levels are affected to any clinically significant degree.
Gemfibrozil: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and fibric acid derivative use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Gemifloxacin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glecaprevir; Pibrentasvir: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
Glimepiride: (Moderate) A lower sulfonylurea dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with a sulfonylurea, the incidence of hypoglycemia was increased compared to a placebo used in combination with a sulfonylurea.
Glipizide: (Moderate) A lower sulfonylurea dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with a sulfonylurea, the incidence of hypoglycemia was increased compared to a placebo used in combination with a sulfonylurea.
Glipizide; Metformin: (Moderate) A lower sulfonylurea dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with a sulfonylurea, the incidence of hypoglycemia was increased compared to a placebo used in combination with a sulfonylurea.
Glyburide: (Moderate) A lower sulfonylurea dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with a sulfonylurea, the incidence of hypoglycemia was increased compared to a placebo used in combination with a sulfonylurea.
Glyburide; Metformin: (Moderate) A lower sulfonylurea dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with a sulfonylurea, the incidence of hypoglycemia was increased compared to a placebo used in combination with a sulfonylurea.
Grapefruit juice: (Minor) Saxagliptin plasma concentrations are expected to increase in the presence of moderate CYP 3A4/5 inhibitors such as grapefruit juice, but saxagliptin dose adjustment is not advised.
Green Tea: (Moderate) Green tea catechins have been shown to decrease serum glucose concentrations in vitro. Patients with diabetes mellitus taking antidiabetic agents should be monitored closely for hypoglycemia if consuming green tea products.
Guaifenesin; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Guaifenesin; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Hydantoins: (Minor) Phenytoin and other hydantoins have the potential to increase blood glucose and thus interact with antidiabetic agents pharmacodynamically. Monitor blood glucose for changes in glycemic control. Dosage adjustments may be necessary in some patients.
Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Hydrocortisone: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Hydroxychloroquine: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor (DPP-4) and hydroxychloroquine use; a DPP-4 dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Hydroxyprogesterone: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ibuprofen; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Iloperidone: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Imatinib: (Minor) Monitor patients for hypoglycemia if saxagliptin and imatinib, STI-571 are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as imatinib, STI-571.
Indapamide: (Moderate) A potential pharmacodynamic interaction exists between indapamide and antidiabetic agents, like saxagliptin. Indapamide can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia.
Indinavir: (Major) The metabolism of saxagliptin is primarily mediated by CYP3A4/5. Limit the saxagliptin dose to 2.5 mg once daily when coadministered with a strong CYP3A4/5 inhibitor such as indinavir. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have also been reported with use of anti-retroviral protease inhibitors. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Insulin Aspart: (Moderate) A lower insulin dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with insulin, the incidence of hypoglycemia was increased compared to a placebo used in combination with insulin.
Insulin Aspart; Insulin Aspart Protamine: (Moderate) A lower insulin dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with insulin, the incidence of hypoglycemia was increased compared to a placebo used in combination with insulin.
Insulin Degludec: (Moderate) A lower insulin dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with insulin, the incidence of hypoglycemia was increased compared to a placebo used in combination with insulin.
Insulin Degludec; Liraglutide: (Moderate) A lower insulin dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with insulin, the incidence of hypoglycemia was increased compared to a placebo used in combination with insulin.
Insulin Detemir: (Moderate) A lower insulin dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with insulin, the incidence of hypoglycemia was increased compared to a placebo used in combination with insulin.
Insulin Glargine: (Moderate) A lower insulin dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with insulin, the incidence of hypoglycemia was increased compared to a placebo used in combination with insulin.
Insulin Glargine; Lixisenatide: (Moderate) A lower insulin dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with insulin, the incidence of hypoglycemia was increased compared to a placebo used in combination with insulin.
Insulin Glulisine: (Moderate) A lower insulin dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with insulin, the incidence of hypoglycemia was increased compared to a placebo used in combination with insulin.
Insulin Lispro: (Moderate) A lower insulin dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with insulin, the incidence of hypoglycemia was increased compared to a placebo used in combination with insulin.
Insulin Lispro; Insulin Lispro Protamine: (Moderate) A lower insulin dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with insulin, the incidence of hypoglycemia was increased compared to a placebo used in combination with insulin.
Insulin, Inhaled: (Moderate) A lower insulin dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with insulin, the incidence of hypoglycemia was increased compared to a placebo used in combination with insulin.
Insulins: (Moderate) A lower insulin dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with insulin, the incidence of hypoglycemia was increased compared to a placebo used in combination with insulin.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with saxagliptin may result in increased serum concentrations of saxagliptin. Saxagliptin is a substrate of the hepatic isoenzyme CYP3A4); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4. Caution and close monitoring for adverse effects, such as hypoglycemia, are advised if these drugs are used together.
Isocarboxazid: (Moderate) Monitor blood glucose during concomitant saxagliptin and monoamine oxidase inhibitor (MAOI) use; a saxagliptin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Minor) Coadministration of saxagliptin and rifampin decreased the maximum serum saxagliptin concentration by 53% and the systemic exposure by 76%. As expected, the maximum serum concentration of the saxagliptin active metabolite was increased by 39%; no significant change in the systemic exposure was noted. Saxagliptin dose adjustment is not advised when coadministered with rifampin, as the plasma dipeptidyl peptidase-4 activity over a 24-hour period was unaffected.
Isoniazid, INH; Rifampin: (Minor) Coadministration of saxagliptin and rifampin decreased the maximum serum saxagliptin concentration by 53% and the systemic exposure by 76%. As expected, the maximum serum concentration of the saxagliptin active metabolite was increased by 39%; no significant change in the systemic exposure was noted. Saxagliptin dose adjustment is not advised when coadministered with rifampin, as the plasma dipeptidyl peptidase-4 activity over a 24-hour period was unaffected.
Isophane Insulin (NPH): (Moderate) A lower insulin dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with insulin, the incidence of hypoglycemia was increased compared to a placebo used in combination with insulin.
Isoproterenol: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Itraconazole: (Major) Do not exceed 2.5 mg PO daily of saxagliptin when combined with itraconazole; monitor for evidence of hypoglycemia. Itraconazole is a strong CYP3A4 inhibitor; saxagliptin is a CYP3A4 substrate. Coadministration of another strong CYP3A4 inhibitor increased the saxagliptin AUC up to 3.7-fold.
Ketoconazole: (Major) Saxagliptin is a p-glycoprotein substrate, and the metabolism of saxagliptin is primarily mediated by CYP3A4/5. Ketoconazole is a strong inhibitor of both p-glycoprotein and CYP3A4/5. Saxagliptin did not meaningfully alter the pharmacokinetics of ketoconazole, but coadministration increased the maximum serum saxagliptin concentration by 62% and the systemic exposure by 2.5-fold. As expected, the maximum serum concentration of the saxagliptin active metabolite was decreased by 95% and the systemic exposure was decreased by 91%. In another study, the maximum serum saxagliptin concentration increased by 2.4-fold and the systemic exposure increased by 3.4-fold. The saxagliptin dose is limited to 2.5 mg once daily when coadministered with a strong CYP 3A4/5 inhibitor such as ketoconazole.
Labetalol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Lanreotide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) The saxagliptin dose is limited to 2.5 mg once daily when coadministered with a strong CYP3A4/5 inhibitor such as clarithromycin. The concomitant use of clarithromycin and antidiabetic agents can result in significant hypoglycemia, especially with antidiabetic drugs metabolized via CYP3A4/5. Careful monitoring of blood glucose is recommended.
Ledipasvir; Sofosbuvir: (Moderate) Closely monitor blood glucose levels if ledipasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agent(s) may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as ledipasvir. (Moderate) Closely monitor blood glucose levels if sofosbuvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as sofosbuvir.
Letermovir: (Moderate) An increase in the plasma concentration of saxagliptin may occur if given with letermovir. Limit the saxagliptin dose to 2.5 mg once per day if the patient is also receiving cyclosporine because the magnitude of this interaction may be increased. Saxagliptin is primarily metabolized by CYP3A4. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Concurrent administration with another strong CYP3A4 inhibitor increased the maximum plasma concentration and exposure of saxagliptin by 1.62- and 2.45-fold, respectively.
Leuprolide; Norethindrone: (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Levobunolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Levofloxacin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Levoketoconazole: (Major) Saxagliptin is a p-glycoprotein substrate, and the metabolism of saxagliptin is primarily mediated by CYP3A4/5. Ketoconazole is a strong inhibitor of both p-glycoprotein and CYP3A4/5. Saxagliptin did not meaningfully alter the pharmacokinetics of ketoconazole, but coadministration increased the maximum serum saxagliptin concentration by 62% and the systemic exposure by 2.5-fold. As expected, the maximum serum concentration of the saxagliptin active metabolite was decreased by 95% and the systemic exposure was decreased by 91%. In another study, the maximum serum saxagliptin concentration increased by 2.4-fold and the systemic exposure increased by 3.4-fold. The saxagliptin dose is limited to 2.5 mg once daily when coadministered with a strong CYP 3A4/5 inhibitor such as ketoconazole.
Levonorgestrel: (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Levonorgestrel; Ethinyl Estradiol: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Levothyroxine: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
Levothyroxine; Liothyronine (Porcine): (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
Levothyroxine; Liothyronine (Synthetic): (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
Lidocaine; Epinephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Linezolid: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
Liothyronine: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
Lisdexamfetamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Lithium: (Moderate) Lithium may cause variable effects on glycemic control when used in patients receiving antidiabetic therapy. Blood glucose concentrations should be closely monitored if lithium is taken by the patient. Dosage adjustments may be necessary.
Lonafarnib: (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with lonafarnib due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A4 substrate; lonafarnib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the saxagliptin AUC up to 3.7-fold.
Lonapegsomatropin: (Moderate) Patients with diabetes mellitus should be monitored closely during somatropin (recombinant rhGH) therapy. Antidiabetic drugs (e.g., insulin or oral agents) may require adjustment when somatropin therapy is instituted in these patients. Growth hormones, such as somatropin, may decrease insulin sensitivity, leading to glucose intolerance and loss of blood glucose control. Therefore, glucose levels should be monitored periodically in all patients treated with somatropin, especially in those with risk factors for diabetes mellitus.
Lopinavir; Ritonavir: (Major) The metabolism of saxagliptin is primarily mediated by CYP3A4/5. The saxagliptin dose is limited to 2.5 mg once daily when coadministered with a strong CYP3A4/5 inhibitor such as ritonavir. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have also been reported with use of anti-retroviral protease inhibitors, such as ritonavir. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated. (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients, including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Loratadine; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Lorcaserin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may decrease the systemic exposure of saxagliptin; if used together, monitor blood glucose concentrations closely. Saxagliptin is a substrate of CYP3A (primary). Lumacaftor is a strong CYP3A inducer. Induction of saxagliptin metabolism through the CYP3A pathway may lead to decreased drug efficacy.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may decrease the systemic exposure of saxagliptin; if used together, monitor blood glucose concentrations closely. Saxagliptin is a substrate of CYP3A (primary). Lumacaftor is a strong CYP3A inducer. Induction of saxagliptin metabolism through the CYP3A pathway may lead to decreased drug efficacy.
Lumateperone: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Lurasidone: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Mafenide: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Magnesium Salicylate: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Mecasermin, Recombinant, rh-IGF-1: (Moderate) Use caution in combining mecasermin, recombinant, rh-IGF-1 or mecasermin rinfabate (rh-IGF-1/rh-IGFBP-3) with antidiabetic agents. Patients should be advised to eat within 20 minutes of mecasermin administration. Glucose monitoring is important when initializing or adjusting mecasermin therapies, when adjusting concomitant antidiabetic therapy, and in the event of hypoglycemic symptoms. An increased risk for hypoglycemia is possible. The hypoglycemic effect induced by IGF-1 activity may be exacerbated. The amino acid sequence of mecasermin (rh-IGF-1) is approximately 50 percent homologous to insulin and cross binding with either receptor is possible. Treatment with mecasermin has been shown to improve insulin sensitivity and to improve glycemic control in patients with either Type 1 or Type 2 diabetes mellitus when used alone or in conjunction with insulins.
Medroxyprogesterone: (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Methamphetamine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Methazolamide: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
Methenamine; Sodium Salicylate: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Methylphenidate: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Methylprednisolone: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Methyltestosterone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Metolazone: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Metoprolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present. (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Metyrapone: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
Midodrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Mifepristone: (Moderate) Monitor patients for hypoglycemia if saxagliptin and mifepristone are used together; dosage reduction of saxagliptin may be needed in some patients. In patients taking CYP3A substrates, the manufacturer of mifepristone recommends that the lowest dose of the CYP3A substrate that achieves the proper clinical response and tolerability be used. When potent CYP3A inhibitors are used, the initial dose of saxagliptin should be limited to 2.5 mg/day; mifepristone is a CYP3A inhibitor and has been noted to increase concentrations of CYP3A substrates. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Mometasone: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Monoamine oxidase inhibitors: (Moderate) Monitor blood glucose during concomitant saxagliptin and monoamine oxidase inhibitor (MAOI) use; a saxagliptin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Moxifloxacin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Nadolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Naproxen; Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Nebivolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Nebivolol; Valsartan: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Nefazodone: (Major) The metabolism of saxagliptin is primarily mediated by CYP3A4/5. The saxagliptin dose is limited to 2.5 mg once daily when coadministered with a strong CYP 3A4/5 inhibitor such as nefazodone.
Nelfinavir: (Major) The metabolism of saxagliptin is primarily mediated by CYP3A4/5. Limit the saxagliptin dose to 2.5 mg once daily when coadministered with a strong CYP3A4/5 inhibitor such as nelfinavir. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Niacin, Niacinamide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Nicotine: (Minor) Monitor blood glucose concentrations for needed antidiabetic agent dosage adjustments in diabetic patients whenever a change in either nicotine intake or smoking status occurs. Nicotine activates neuroendocrine pathways (e.g., increases in circulating cortisol and catecholamine levels) and may increase plasma glucose. The cessation of nicotine therapy or tobacco smoking may result in a decrease in blood glucose.
Nirmatrelvir; Ritonavir: (Major) The metabolism of saxagliptin is primarily mediated by CYP3A4/5. The saxagliptin dose is limited to 2.5 mg once daily when coadministered with a strong CYP3A4/5 inhibitor such as ritonavir. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have also been reported with use of anti-retroviral protease inhibitors, such as ritonavir. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Norepinephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Norethindrone: (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Norethindrone; Ethinyl Estradiol: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Norgestimate; Ethinyl Estradiol: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Norgestrel: (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Octreotide: (Moderate) Monitor patients receiving octreotide concomitantly with insulin or other antidiabetic agents for changes in glycemic control and adjust doses of these medications accordingly. Octreotide alters the balance between the counter-regulatory hormones of insulin, glucagon, and growth hormone, which may result in hypoglycemia or hyperglycemia. The hypoglycemia or hyperglycemia which occurs during octreotide acetate therapy is usually mild but may result in overt diabetes mellitus or necessitate dose changes in insulin or other hypoglycemic agents. In patients with concomitant type1 diabetes mellitus, octreotide is likely to affect glucose regulation, and insulin requirements may be reduced. Symptomatic hypoglycemia, which may be severe, has been reported in type 1 diabetic patients. In Type 2 diabetes patients with partially intact insulin reserves, octreotide administration may result in decreases in plasma insulin levels and hyperglycemia.
Ofloxacin: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Olanzapine: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Olanzapine; Fluoxetine: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 (DPP-4) inhibitor and fluoxetine use; a DPP-4 inhibitor dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Olanzapine; Samidorphan: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Olopatadine; Mometasone: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Orlistat: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
Oxandrolone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Oxymetholone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Paliperidone: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Pasireotide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Pegvisomant: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pegvisomant treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pegvisomant increases sensitivity to insulin by lowering the activity of growth hormone, and in some patients glucose tolerance improves with treatment. Patients with diabetes treated with pegvisomant and antidiabetic agents may be more likely to experience hypoglycemia.
Pentamidine: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
Pentoxifylline: (Moderate) Pentoxiphylline has been used concurrently with antidiabetic agents without observed problems, but it may enhance the hypoglycemic action of antidiabetic agents. Patients should be monitored for changes in glycemic control while receiving pentoxifylline in combination with antidiabetic agents.
Perphenazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Perphenazine; Amitriptyline: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Phendimetrazine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Phenelzine: (Moderate) Monitor blood glucose during concomitant saxagliptin and monoamine oxidase inhibitor (MAOI) use; a saxagliptin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Phenothiazines: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Phentermine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Phentermine; Topiramate: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Phenytoin: (Minor) Phenytoin and other hydantoins have the potential to increase blood glucose and thus interact with antidiabetic agents pharmacodynamically. Monitor blood glucose for changes in glycemic control. Dosage adjustments may be necessary in some patients.
Pindolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Pioglitazone; Glimepiride: (Moderate) A lower sulfonylurea dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with a sulfonylurea, the incidence of hypoglycemia was increased compared to a placebo used in combination with a sulfonylurea.
Posaconazole: (Minor) Monitor patients for hypoglycemia if saxagliptin and posaconazole are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as posaconazole.
Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Prednisolone: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Prednisone: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Prilocaine; Epinephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Prochlorperazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Progesterone: (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Progestins: (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Promethazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Promethazine; Dextromethorphan: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Promethazine; Phenylephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Propranolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Pseudoephedrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Pseudoephedrine; Triprolidine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Quetiapine: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Quinine: (Moderate) Monitor patients for hypoglycemia if saxagliptin and quinine are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as quinine.
Quinolones: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitors and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Racepinephrine: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Regular Insulin: (Moderate) A lower insulin dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with insulin, the incidence of hypoglycemia was increased compared to a placebo used in combination with insulin.
Regular Insulin; Isophane Insulin (NPH): (Moderate) A lower insulin dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with insulin, the incidence of hypoglycemia was increased compared to a placebo used in combination with insulin.
Relugolix; Estradiol; Norethindrone acetate: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Ribociclib: (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with ribociclib due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor with a single 100 mg dose of saxagliptin and a single 20 mg dose of saxagliptin increased the saxagliptin AUC by 2.45-fold and 3.67-fold, respectively.
Ribociclib; Letrozole: (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with ribociclib due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor with a single 100 mg dose of saxagliptin and a single 20 mg dose of saxagliptin increased the saxagliptin AUC by 2.45-fold and 3.67-fold, respectively.
Rifampin: (Minor) Coadministration of saxagliptin and rifampin decreased the maximum serum saxagliptin concentration by 53% and the systemic exposure by 76%. As expected, the maximum serum concentration of the saxagliptin active metabolite was increased by 39%; no significant change in the systemic exposure was noted. Saxagliptin dose adjustment is not advised when coadministered with rifampin, as the plasma dipeptidyl peptidase-4 activity over a 24-hour period was unaffected.
Risperidone: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Ritonavir: (Major) The metabolism of saxagliptin is primarily mediated by CYP3A4/5. The saxagliptin dose is limited to 2.5 mg once daily when coadministered with a strong CYP3A4/5 inhibitor such as ritonavir. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have also been reported with use of anti-retroviral protease inhibitors, such as ritonavir. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Salicylates: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Salsalate: (Moderate) Monitor blood glucose during concomitant saxagliptin and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Saquinavir: (Major) The metabolism of saxagliptin is primarily mediated by CYP3A4/5. Limit the saxagliptin dose to 2.5 mg once daily when coadministered with a strong CYP 3A4/5 inhibitor such as saquinavir. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of anti-retroviral protease inhibitors. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Patients receiving antidiabetic agents should be periodically monitored for changes in glycemic control when hormone therapy is instituted or discontinued. Estrogens can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving 50 mcg or more of ethinyl estradiol (or equivalent) per day in combined oral contraceptives (COCs), which are not commonly used in practice since the marketing of lower dose COCs, patches, injections and rings. The presence or absence of a concomitant progestin may influence the significance of any hormonal effect on glucose homeostasis. (Minor) Progestins can decrease the hypoglycemic effects of antidiabetic agents by impairing glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for changes in diabetic control when hormone therapy is instituted or discontinued.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Sofosbuvir: (Moderate) Closely monitor blood glucose levels if sofosbuvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as sofosbuvir.
Sofosbuvir; Velpatasvir: (Moderate) Closely monitor blood glucose levels if sofosbuvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as velpatasvir.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Closely monitor blood glucose levels if sofosbuvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as velpatasvir. (Moderate) Closely monitor blood glucose levels if voxilaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as voxilaprevir.
Somapacitan: (Moderate) Patients with diabetes mellitus should be monitored closely during somapacitan therapy. Antidiabetic drugs (e.g., insulin or oral agents) may require adjustment when somapacitan therapy is instituted in these patients. Growth hormones, such as somapacitan, may decrease insulin sensitivity, leading to glucose intolerance and loss of blood glucose control. Therefore, glucose levels should be monitored periodically in all patients treated with somapacitan, especially in those with risk factors for diabetes mellitus.
Somatrogon: (Moderate) Monitor for loss of glycemic control if concomitant use of somatrogon and antidiabetic drugs is necessary; a dose adjustment of the antidiabetic drug may be needed. Growth hormones, such as somatrogon, may decrease insulin sensitivity, leading to glucose intolerance and loss of blood glucose control.
Somatropin, rh-GH: (Moderate) Patients with diabetes mellitus should be monitored closely during somatropin (recombinant rhGH) therapy. Antidiabetic drugs (e.g., insulin or oral agents) may require adjustment when somatropin therapy is instituted in these patients. Growth hormones, such as somatropin, may decrease insulin sensitivity, leading to glucose intolerance and loss of blood glucose control. Therefore, glucose levels should be monitored periodically in all patients treated with somatropin, especially in those with risk factors for diabetes mellitus.
Sotalol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Streptogramins: (Major) The manufacturer recommends limiting the saxagliptin dose to 2.5 mg/day if used with strong CYP3A4/5 inhibitors such as dalfopristin; quinupristin. The metabolism of saxagliptin is primarily mediated by CYP3A4/5, and maximum serum concentrations and exposure of saxagliptin are increased when administered with strong inhibitors. Monitor patients for hypoglycemia if these drugs are used together.
Sulfacetamide; Sulfur: (Moderate) Niacinamide interferes with glucose metabolism and can result in hyperglycemia. Monitor patients taking antidiabetic agents for changes in glycemic control if niacinamide is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Sulfadiazine: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sulfasalazine: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sulfonamides: (Moderate) Monitor blood glucose during concomitant dipeptidyl peptidase-4 inhibitor and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sulfonylureas: (Moderate) A lower sulfonylurea dose may be required when used in combination with saxagliptin to minimize the risk of hypoglycemia. When saxagliptin was used in combination with a sulfonylurea, the incidence of hypoglycemia was increased compared to a placebo used in combination with a sulfonylurea.
Sympathomimetics: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Tacrolimus: (Moderate) Tacrolimus has been reported to cause hyperglycemia. Monitor for worsening of glycemic control if therapy with tacrolimus is initiated in patients receiving antidiabetic agents.
Tegaserod: (Moderate) Because tegaserod can enhance gastric emptying in patients with diabetes, blood glucose can be affected, which, in turn, may affect the clinical response to antidiabetic agents. The dosing of antidiabetic agents may require adjustment in patients who receive tegaserod concomitantly.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Testosterone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Thiazide diuretics: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Thioridazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Thyroid hormones: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
Timolol: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Tipranavir: (Major) The manufacturer recommends limiting the saxagliptin dose to 2.5 mg/day if used with strong CYP3A4/5 inhibitors such as tipranavir boosted with ritonavir. The metabolism of saxagliptin is primarily mediated by CYP3A4/5, and maximum serum concentrations and exposure of saxagliptin are increased when administered with strong inhibitors. Monitor patients for hypoglycemia if these drugs are used together. New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have also been reported with use of anti-retroviral protease inhibitors. A possible mechanism is impairment of beta-cell function. Onset averaged approximately 63 days after initiating protease inhibitor therapy but has occurred as early as 4 days after beginning therapy. Diabetic ketoacidosis has occurred in some patients including patients who were not diabetic prior to protease inhibitor treatment. Patients on antidiabetic therapy should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
Torsemide: (Minor) Torsemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Trandolapril; Verapamil: (Minor) Saxagliptin plasma concentrations are expected to increase in the presence of moderate CYP 3A4/5 inhibitors such as verapamil, but saxagliptin dose adjustment is not advised.
Tranylcypromine: (Moderate) Monitor blood glucose during concomitant saxagliptin and monoamine oxidase inhibitor (MAOI) use; a saxagliptin dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Triamcinolone: (Moderate) Monitor blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Triamterene: (Minor) Triamterene can interfere with the hypoglycemic effects of antidiabetic agents. This can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity. (Minor) Triamterene can interfere with the hypoglycemic effects of antidiabetic agents. This can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
Trifluoperazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Tucatinib: (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with tucatinib due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A4 substrate; tucatinib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor with a single 100 mg dose of saxagliptin and a single 20 mg dose of saxagliptin increased the saxagliptin AUC by 2.45-fold and 3.67-fold, respectively.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
Verapamil: (Minor) Saxagliptin plasma concentrations are expected to increase in the presence of moderate CYP 3A4/5 inhibitors such as verapamil, but saxagliptin dose adjustment is not advised.
Vitamin B Complex Supplements: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) The saxagliptin dose is limited to 2.5 mg once daily when coadministered with a strong CYP3A4/5 inhibitor such as clarithromycin. The concomitant use of clarithromycin and antidiabetic agents can result in significant hypoglycemia, especially with antidiabetic drugs metabolized via CYP3A4/5. Careful monitoring of blood glucose is recommended.
Voriconazole: (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with voriconazole due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A4 substrate; voriconazole is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor with a single 100 mg dose of saxagliptin and a single 20 mg dose of saxagliptin increased the saxagliptin AUC by 2.45-fold and 3.67-fold, respectively.
Zafirlukast: (Minor) Monitor patients for hypoglycemia if saxagliptin and zafirlukast are used together. The metabolism of saxagliptin is primarily mediated by CYP3A4/5; saxagliptin plasma concentrations may increase in the presence of moderate CYP 3A4/5 inhibitors such as zafirlukast.
Ziprasidone: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Saxagliptin is a competitive dipeptidyl peptidase-4 (DPP-4) inhibitor, which exerts its actions in patients with type 2 diabetes by slowing the inactivation of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic polypeptide (GIP). Both GLP-1 and GIP are released by the intestine throughout the day, and their concentrations are increased in response to a meal. Normally, both GLP-1 and GIP are inactivated by DPP-4 within minutes. The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. GLP-1 also lowers glucagon secretion from pancreatic alpha cells leading to reduced hepatic glucose production, and GLP-1 slows gastric emptying time, which decreases postprandial glucose excursions. Saxagliptin increases insulin release and decreases glucagon concentrations in the circulation in a glucose-dependent manner; GLP-1 does not increase insulin secretion when the glucose concentration is less than 90 mg/dL. Saxagliptin is of benefit in patients with type 2 diabetes mellitus as their GLP-1 concentrations are decreased in response to a meal. Although GLP-1 concentrations are reduced, the insulin response to GLP-1 is preserved. Among patients with type 2 diabetes mellitus who receive saxagliptin, both fasting and postprandial serum glucose concentrations are reduced in a glucose-dependent manner. The long-term safety of DPP-4 inhibitors is currently under investigation as DPP-4 is not an enzyme specific for the breakdown of incretin hormones. In fact, DPP-4 is responsible for the metabolism of many peptides including pancreatic peptide YY, neuropeptide Y, and growth hormone-releasing hormone. DPP-4 is involved with T-cell activation and is expressed on lymphocytes as CD26. Long-term neurological or immunological consequences of inhibiting DPP-4 are unknown.
Saxagliptin is administered orally. In vitro, protein binding of saxagliptin and its active metabolite was negligible. Metabolism is primarily mediated hepatically by CYP3A4/5 to produce 5-hydroxy saxagliptin, which is one-half as potent as saxagliptin as a DPP-4 inhibitor. Saxagliptin and its active metabolite are renally eliminated; some active renal excretion appears to occur. After a 50 mg oral, radiolabeled dose, 24% of the dose was excreted renally as saxagliptin, and 36% was excreted renally as 5-hydroxy saxagliptin. In addition to renal excretion, some fecal elimination also occurs. Of the administered radioactivity, 22% was recovered in the feces; some was excreted in the bile, and some was unabsorbed drug from the gastrointestinal tract. Among healthy patients who took a single 5 mg oral dose, the mean plasma terminal half-life was 2.5 hours for saxagliptin and 3.1 hours for 5-hydroxy saxagliptin.
Inhibition of dipeptidyl peptidase-4 (DPP-4) enzyme by saxagliptin lasts for 24 hours. After an oral glucose load or meal, the circulating concentrations of active glucagon-like peptide-1 and glucose-dependent insulinotrophic polypeptide increased 2- to 3-fold. Also, glucagon concentrations decreased and glucose-dependent insulin secretion from pancreatic beta cells increased.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4/5, P-glycoprotein (P-gp)
Saxagliptin is a CYP3A4/5 substrate. Thus, strong CYP 3A4/5 inhibitors or inducers will alter pharmacokinetic parameters. Neither saxagliptin nor its active metabolite are inhibitors of CYP isozymes 3A4, 2C9, 2D6, 1A2, 2C19, 2A6, 2E1, or 2B6 or inducers of CYP 3A4, 2B6, 2C9, or 1A2. Saxagliptin is also is a P-glycoprotein (P-gp) substrate but is not a significant inhibitor or inducer of P-gp.
-Route-Specific Pharmacokinetics
Oral Route
After a 5 mg oral dose, the mean time to the maximum saxagliptin concentration was 2 hours, and the mean time to the maximum concentration of the active metabolite, 5-hydroxy saxagliptin, was 4 hours. Administration of saxagliptin with a high-fat meal increased the time to the maximum saxagliptin concentration by about 20 minutes, and the systemic exposure increased by 27%.
-Special Populations
Hepatic Impairment
In patients with any degree of hepatic impairment, the mean AUC of saxagliptin increased by approximately 77% and the mean AUC of 5-hydroxy saxagliptin decreased by 33% as compared with data from healthy patients. A saxagliptin dosage adjustment in patients with hepatic insufficiency is not recommended, as these differences in systemic exposure are not expected to be clinically significant.
Renal Impairment
In a pharmacokinetic study of patients with varying degrees of chronic renal impairment, the degree of renal impairment did not affect the Cmax of saxagliptin or its metabolite. However, in subjects with moderate renal impairment (eGFR 30 to less than 45 mL/minute/1.73 m2), severe renal impairment (eGFR 15 to less than 30 mL/minute/1.73 m2), and ESRD patients on hemodialysis, the AUC values of saxagliptin or its active metabolite were more than 2-fold higher than the AUC values in subjects with normal renal function. Therefore, saxagliptin dosage adjustment is recommended for patients with moderate or severe renal impairment (eGFR less than 45 mL/minute/1.73 m2). After a 4-hour hemodialysis session, roughly 23% of a saxagliptin dose is removed; both saxagliptin and its active metabolite, 5-hydroxy saxagliptin, are removed by hemodialysis.
Geriatric
Among patients 65 to 80 years of age, the geometric mean maximum saxagliptin concentration was 23% higher, and the geometric mean AUC was 59% higher as compared with data from adult patients 18 to 40 years of age. Saxagliptin dose adjustment based on age alone is not needed; however, consider the effects of age on renal function.