Pegvisomant is a growth hormone receptor antagonist, designed to block the effects of excessive growth hormone production by pituitary gland tumors. The drug is given subcutaneously and is used specifically for the treatment of acromegaly. Pegvisomant is an analog of human growth hormone that has been structurally altered to act as a growth hormone receptor antagonist. Pegvisomant is a protein of recombinant DNA origin, synthesized using Escherichia coli bacteria, containing 191 amino acid residues to which several polyethylene glycol polymers are covalently bound. Rather than inhibiting growth hormone secretion from the tumor, as do current medical treatments for acromegaly (e.g., dopamine-agonists and somatostatin analogues) pegvisomant blocks the action of growth hormone at the tissue level. Pegvisomant has an established efficacy and tolerability profile for the treatment of acromegaly.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Extemporaneous Compounding-Oral
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Injectable Administration
Subcutaneous Administration
-Administer pegvisomant by subcutaneous injection only; avoid intravenous administration.
-The loading dose of pegvisomant should be given under physician supervision.
-Provide proper training in subcutaneous injection technique to patients or their caregivers so they can receive once daily subcutaneous injections.
Loading dose preparation:
-Reconstitute 2 vials of pegvisomant each containing 20 mg with supplied diluent [2 vials of lyophilized powder and 2 of the 2.25 mL syringes (each syringe contains 1 mL of diluent - Sterile Water for Injection)].
-Remove the first package (1 vial of lyophilized powder containing 20 mg of pegvisomant and one 2.25 mL syringe containing the diluent) from the refrigerator about 10 minutes prior to the planned injection time.
-Reconstitute the first 20 mg vial with diluent. When using the diluent in the 2.25 mL syringe, inject the contents of the syringe slowly onto the sides of the vial. Do not inject the diluent directly on the powder.
-Slowly swirl the solution to ensure that all of the lyophilized powder has gone into solution. If foaming is seen, the solution is likely damaged and therefore inappropriate to inject. Do not invert the vial or shake the solution.
-Visually inspect the reconstituted solution for particulate matter and discoloration prior to administration. The reconstituted solution should be clear. If the solution is cloudy, do not use it.
-Once reconstituted, the solution will contain 20 mg/mL of pegvisomant. Withdraw 1 mL reconstituted pegvisomant solution and administer within 6 hours of reconstitution.
-Repeat steps to reconstitute the second 20 mg dose.
Subcutaneous administration of loading dose:
-Inject the first reconstituted pegvisomant solution (20 mg/mL) subcutaneously into the patient's upper arm, upper thigh, abdomen, or buttocks using a 90-degree angle.
-Inject the second dose of 20 mg into a different site.
Reconstitution/Dilution of daily maintenance doses:
-Remove the vial dose (containing 10, 15, 20, 25 or 30 mg of pegvisomant), as well as the 2.25 mL syringe (each syringe contains 1 mL of diluent - Sterile Water for Injection) from the refrigerator about 10 minutes prior to administration time.
-Reconstitute by injecting 1 mL of the diluent provided (Sterile Water for Injection) into the vial, aiming the stream of diluent against the glass wall of the vial. Do not directly inject the diluent onto the vial powder.
-Do not invert or shake the vial as denaturation of the pegvisomant may occur.
-Slowly swirl the solution to ensure that all of the lyophilized powder has gone into solution. If foaming is seen, the solution is likely damaged and therefore inappropriate to inject.
-The reconstituted solution should be clear and colorless.
-Withdraw the dose (1 mL reconstituted solution) from the vial. The solution must be administered within 6 hours of reconstitution.
Subcutaneous administration of daily maintenance doses:
-Inject the reconstituted pegvisomant solution subcutaneously into the patient's upper arm, upper thigh, abdomen, or buttocks using a 90-degree angle.
A state of functional growth hormone (GH) deficiency may result from the administration of pegvisomant, despite the presence of elevated serum GH levels. Therefore, during treatment with pegvisomant, patients should be carefully observed for the clinical signs and symptoms of a GH-deficient state, and serum IGF-I concentrations should be monitored and maintained within the age-adjusted normal range through appropriate pegvisomant dose adjustments.
Most adverse events with pegvisomant were of mild to moderate intensity and of limited duration. Adverse event data are from 80 pegvisomant and 32 placebo recipients. Chest pain (unspecified) occurred in 4% to 8% of pegvisomant recipients vs. 0% of placebo recipients; peripheral edema occurred in 4% to 8% of pegvisomant recipients vs. 0% of placebo recipients; hypertension occurred in 8% of pegvisomant recipients vs. 0% of placebo recipients; infection occurred in 23% of pegvisomant recipients vs. 6% of placebo recipients; flu syndrome occurred in 4% to 12% of pegvisomant recipients vs. 0% of placebo recipients; sinusitis occurred in 4% to 8% of pegvisomant recipients vs. 3% of placebo recipients; nausea occurred in 8% to 14% of pegvisomant recipients vs. 3% of placebo recipients; diarrhea occurred in 4% to 14% of pegvisomant recipients vs. 3% of placebo recipients; pain occurred in 4% to 14% of pegvisomant recipients vs. 6% of placebo recipients; back pain occurred in 4% to 8% of pegvisomant recipients vs. 3% of placebo recipients; dizziness occurred in 4% to 8% of pegvisomant recipients vs. 6% of placebo recipients; and paresthesias occurred in 7% of pegvisomant recipients vs. 6% of placebo recipients.
An injection site reaction occurs with pegvisomant injection in 4% to 11% of patients. Cases of lipohypertrophy (lipodystrophy) have been reported in patients receiving pegvisomant. In a double-blind, 12-week, placebo-controlled study (n = 80), there was one case (1.3%) of injection site lipohypertrophy reported in a patient receiving 10 mg/day. The patient recovered while on treatment. During open-label trials of pegvisomant 10 mg/kg (n = 147), 2 patients developed lipohypertrophy. One patient recovered while on treatment and the other patient discontinued treatment. In an observational registry in patients with acromegaly treated with pegvisomant (n = 1,288), lipohypertrophy was reported in 6 (0.5%) of patients. Injection sites should be rotated daily to minimize the risk of lipohypertrophy.
During clinical trials, elevated hepatic enzymes (1.2% to 12%), some requiring discontinuation of therapy, were reported. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations more than 10 times the upper limit of normal (ULN) were reported in 2 patients (0.8%) who received pegvisomant. One patient experienced elevated transaminase concentrations upon rechallenge with pegvisomant, suggesting a probable causal relationship to pegvisomant administration. The second patient had a liver biopsy that showed chronic hepatitis of unknown etiology. Serum hepatic enzyme concentrations returned to normal in both patients within a few months of discontinuing the drug. Postmarketing reports have identified elevated hepatic enzymes up to 20 times ULN with elevation in total bilirubin more than 2 times ULN. In many of the cases, the hepatic enzyme elevations improved or normalized with time after discontinuing treatment. AST and ALT elevations did not appear to be associated with pegvisomant dose but generally occurred within 4 to 12 weeks of therapy initiation. Obtain liver function tests (LFTs, e.g., ALT, AST, total bilirubin, and alkaline phosphate concentrations) before pegvisomant initiation. If a patient develops signs or symptoms (e.g., jaundice) suggestive of hepatitis or other liver injury, perform a comprehensive hepatic workup immediately and discontinue pegvisomant if liver injury is confirmed. If a patient develops LFTs of at least 3 times the ULN but less than 5 times the ULN without an increase in total bilirubin and without signs or symptoms of hepatitis or other liver injury, continue pegvisomant and continue to monitor LFTs weekly to determine if further increases occur; perform a comprehensive hepatic workup to discern if an alternative cause of liver dysfunction is present. Immediately discontinue pegvisomant if a patient develops any transaminase elevation of at least 5 times the ULN or at least 3 times the ULN with any increase in total bilirubin with or without signs or symptoms of hepatitis or other liver injury. Cautious reinitiation of pegvisomant with frequent LFT monitoring may be considered if LFTs normalize, regardless of whether an alternative cause of the hepatic dysfunction is discovered. Inform patients about the need for serial monitoring of LFTs and for immediate pegvisomant discontinuation and physician consultation for jaundice.
In clinical trials, approximately 17% of patients experienced low titer, non-neutralizing anti-growth hormone antibody formation. Although the presence of these antibodies did not appear to impact the efficacy of pegvisoment, the long-term clinical significance of these antibodies is unknown. No assay for anti-pegvisomant antibodies is commercially available for patients receiving pegvisomant.
During post-marketing use with pegvisomant, systemic hypersensitivity reactions including anaphylactic/anaphylactoid reactions, laryngospasm, and angioedema have been reported. In addition, patients reported generalized skin reactions consisting of rash (unspecified), erythema, pruritus, and urticaria. Some patients required hospitalization. Symptoms did not re-occur in all patients after re-challenge.
One patient withdrew from pre-marketing clinical studies of pegvisomant because of substantial weight gain.
Pegvisomant is contraindicated in patients with known hypersensitivity to pegvisomant or any of its ingredients. The vials in the package of the injection have stoppers that are not made with natural rubber latex.
In an observational registry in patients with acromegaly treated with pegvisomant, MRIs were compared to previous ones and a change in tumor volume was reported as significant locally only if the diameter increased by more than 3 mm for microadenomas or by more than 20% for macroadenomas. All MRI changes considered significant at the local reading were reanalyzed centrally. Of the 747 patients who had a MRI reported at baseline and at least once during follow up in the study, 51 (7%) were reported to have an increase by local MRI. Of these, 16 patients (2%) had confirmation of the increase, 6 had a decrease, 12 had no change, 1 had insufficient data, and 16 patients did not have a central MRI reading. All patients with neoplastic disease with such tumors, including those who are being treated with pegvisomant, should be carefully monitored for signs of tumor enlargement.
Elevated hepatic enzymes and bilirubin have occurred with pegvisomant therapy. Obtain hepatic transaminase concentrations (ALT and AST), total bilirubin (TBIL), and alkaline phosphatase (ALP) concentrations before drug initiation. In patients with normal baseline liver function tests (LFTs), monitor LFTs at monthly intervals during the first 6 months of treatment, quarterly for the next 6 months, and then bi-annually for the next year. In patients with LFTs that are elevated, but less than or equal to 3 times ULN, monitor LFTs monthly for at least 1 year after initiation of therapy and then bi-annually for the next year. Some patients with hepatic disease (i.e., transaminases more than 3 times the upper limit of normal or ULN) should not receive pegvisomant unless the cause for the transaminase elevations is known. Determine if cholelithiasis or choledocholithiasis is present, especially in patients with a history of prior therapy with somatostatin analogs. If the decision to treat is made, transaminases and clinical symptoms should be monitored very closely. Pegvisomant may cause hepatotoxicity; drug cessation may be required. In patients who develop LFT elevations of 3 but less than 5 times ULN (without signs or symptoms of hepatitis or other liver injury or increase in serum TBIL) therapy may be continued, however, liver tests should be monitored weekly to determine if further increases occur. A comprehensive hepatic workup is also needed to discern if an alternative cause of liver dysfunction is present. If liver tests are at least 5 times ULN, or transaminase elevations with any increase in serum TBIL are present, pegvisomant should be discontinued immediately. A comprehensive hepatic workup should be performed. Additionally, if signs or symptoms suggestive of hepatitis or other liver injury observed, immediately perform a comprehensive hepatic workup. If liver injury is confirmed, the drug should be discontinued.
Glucose tolerance may increase in some patients being treated with pegvisomant; growth hormone decreases insulin sensitivity by opposing the effects of insulin on carbohydrate metabolism, and pegvisomant antagonizes the effect of growth hormone. Although none of the acromegalic patients with diabetes mellitus who were treated with pegvisomant during the clinical studies developed clinically relevant hypoglycemia, such patients should have their blood glucose monitored regularly, with doses of anti-diabetic medications reduced as necessary.
There are no adequate, well controlled studies of pegvisomant use in pregnant women. Animal reproduction studies showed no evidence of teratogenic effects associated with pegvisomant treatment during organogenesis. There was a slight increase in post-implantation loss observed when pegvisomant was administered to rabbits at a dose equivalent to 6-times the maximum human dose. As animal reproduction studies are not always predictive of human response, pegvisomant should only be used during pregnancy if clearly needed.
It is not known if pegvisomant is excreted into human breast milk. Because many drugs are excreted in human milk, breast-feeding mothers should receive pegvisomant therapy cautiously.
Safety and efficacy of pegvisomant has not been established in neonates, infants, children and adolescents < 18 years of age.
A laboratory test interference may occur with pegvisomant. Pegvisomant has significant structural similarity to growth hormone (GH) which causes it to cross-react in commercially available GH assays. Since serum concentrations of therapeutically effective doses of pegvisomant are generally 100 to 1,000 times higher than the actual serum GH concentrations seen in patients with acromegaly, measurements of serum GH concentrations will appear falsely elevated. The pegvisomant dosage should not be based on growth hormone (GH) concentrations or signs and symptoms of acromegaly. Titrate the dosage to normalize serum IGF-I concentrations (serum IGF-I concentrations should be measured every 4 to 6 weeks). It is unknown whether patients who remain symptomatic while achieving normalized IGF-I concentrations would benefit from increased pregvisomant dosage.
For the treatment of acromegaly in patients who have had an inadequate response to surgery and/or radiation therapy and/or other medical therapies, or for whom these therapies are not appropriate:
Subcutaneous dosage:
Adults: 40 mg subcutaneously loading dose, followed by 10 mg subcutaneously once daily. Adjust dose in 5-mg increments, up to 30 mg per day, based on serum IGF-I concentrations.
Therapeutic Drug Monitoring:
Titrate the dosage to normalize serum IGF-I concentrations (serum IGF-I concentrations should be measured every 4 to 6 weeks). The dosage should not be based on growth hormone (GH) concentrations or signs and symptoms of acromegaly. It is not known if patients who remain symptomatic while achieving normalized IGF-I concentrations would benefit from increased pegvisomant dosage.
-Increase the dosage by 5 mg increments every 4 to 6 weeks if IGF-I concentrations are elevated.
-Decrease the dosage by 5 mg decrements every 4 to 6 weeks if IGF-I concentrations are below the normal range.
-Due to differences in pharmacokinetics, IGF-I levels should also be monitored when a pegvisomant dose given in multiple injections (e.g., 2 x 15 mg injections once daily) is converted to a single daily injection (e.g., 30 mg injection once daily).
Maximum Dosage Limits:
-Adults
40 mg loading dose; 30 mg/day during maintenance therapy.
-Elderly
40 mg loading dose; 30 mg/day during maintenance therapy.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Patients with transaminases more than 3 times the upper limit of normal (ULN), should not receive pegvisomant until a comprehensive workup establishes the cause of the patient's liver dysfunction. Monitor closely if treatment is initiated. If hepatotoxicity occurs during treatment in any patient, drug cessation may be required. Monitor liver function tests (LFTs) concentrations before pegvisomant initiation and periodically during drug receipt.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Acarbose: (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.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Acetaminophen; Codeine: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Acetaminophen; Hydrocodone: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Acetaminophen; Oxycodone: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Alfentanil: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Alogliptin: (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.
Alogliptin; Metformin: (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.
Alogliptin; Pioglitazone: (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.
Antidiabetic Agents: (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.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Aspirin, ASA; Oxycodone: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Atropine; Difenoxin: (Moderate) Diphenoxylate/difenoxin is a synthetic opiate agonist with a chemical structure similar to that of meperidine. In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Belladonna; Opium: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Benzhydrocodone; Acetaminophen: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Bexagliflozin: (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.
Bromocriptine: (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.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Canagliflozin: (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.
Canagliflozin; Metformin: (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.
Celecoxib; Tramadol: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Chlorpheniramine; Codeine: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Chlorpheniramine; Hydrocodone: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Codeine: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Codeine; Guaifenesin: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Codeine; Phenylephrine; Promethazine: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Codeine; Promethazine: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Dapagliflozin: (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.
Dapagliflozin; Metformin: (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.
Dapagliflozin; Saxagliptin: (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.
Diphenoxylate; Atropine: (Moderate) Diphenoxylate/difenoxin is a synthetic opiate agonist with a chemical structure similar to that of meperidine. In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Dulaglutide: (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.
Empagliflozin: (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.
Empagliflozin; Linagliptin: (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.
Empagliflozin; Linagliptin; Metformin: (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.
Empagliflozin; Metformin: (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.
Ertugliflozin: (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.
Ertugliflozin; Metformin: (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.
Ertugliflozin; Sitagliptin: (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.
Exenatide: (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.
Fentanyl: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Glimepiride: (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.
Glipizide: (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.
Glipizide; Metformin: (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.
Glyburide: (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.
Glyburide; Metformin: (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.
Homatropine; Hydrocodone: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Hydrocodone: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Hydrocodone; Ibuprofen: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Hydromorphone: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Ibuprofen; Oxycodone: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Insulin Aspart: (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.
Insulin Aspart; Insulin Aspart Protamine: (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.
Insulin Degludec; Liraglutide: (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.
Insulin Detemir: (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.
Insulin Glargine: (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.
Insulin Glargine; Lixisenatide: (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.
Insulin Glulisine: (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.
Insulin Lispro: (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.
Insulin Lispro; Insulin Lispro Protamine: (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.
Insulin, Inhaled: (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.
Isophane Insulin (NPH): (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.
Levorphanol: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Linagliptin: (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.
Linagliptin; Metformin: (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.
Liraglutide: (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.
Lixisenatide: (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.
Mecasermin, Recombinant, rh-IGF-1: (Major) Pegvisomant is a growth hormone receptor antagonist used in the treatment of acromegaly; administration results in a significant decrease of endogenous serum IGF-1 levels. Use caution if coadministering mecasermin and pegvisomant.
Meperidine: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Metformin: (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.
Metformin; Repaglinide: (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.
Metformin; Saxagliptin: (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.
Metformin; Sitagliptin: (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.
Methadone: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Miglitol: (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.
Morphine: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Morphine; Naltrexone: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Nateglinide: (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.
Oliceridine: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Opiate Agonists: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Oxycodone: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Oxymorphone: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Pioglitazone: (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.
Pioglitazone; Glimepiride: (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.
Pioglitazone; Metformin: (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.
Pramlintide: (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.
Regular Insulin: (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.
Regular Insulin; Isophane Insulin (NPH): (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.
Remifentanil: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Repaglinide: (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.
Rosiglitazone: (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.
Saxagliptin: (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.
Semaglutide: (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.
Sitagliptin: (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.
Sufentanil: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Tapentadol: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Tramadol: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Tramadol; Acetaminophen: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
Pegvisomant is an analogue of human growth hormone that functions as a growth hormone receptor antagonist. In order for growth hormone (GH) to function properly, the GH molecule binds to two adjacent GH receptors, resulting in dimerization of the two receptors and then receptor activation. The most important result of this activation is the stimulation of the production of insulin-like growth factor-I (IGF-I), which mediates most of the actions of GH. As an analogue of GH, pegvisomant has nine mutations that increase its affinity for one of the binding sites on the GH receptor and abolishes the second binding site, thereby preventing functionally correct dimerization of the receptor. Pegvisomant is a highly selective ligand for the GH receptor, and it is not known to cross react with other receptors. After pegvisomant binds to the GH receptor a decreased production of IGF-I by the liver and other tissues is seen. As serum IGF-I levels return to normal patients should experience a decrease in the physical signs and symptoms of acromegaly, including soft-tissue swelling, arthralgia, excessive perspiration, and fatigue.
Pegvisomant is administered as a subcutaneous injection. Pegvisomant's route of elimination has not been studied in humans; less than 1% of administered drug is recovered in the urine over 96 hours. The rate of clearance is reduced by covalently bound polyethylene glycol (PEG) polymers in the pegvisomant molecule. Following multiple doses, the clearance of pegvisomant is lower than seen following a single dose. The mean total body systemic clearance following multiple doses is estimated to range between 28 to 36 mL/hour for subcutaneous doses ranging from 10 to 20 mg/day, respectively. Pegvisomant is eliminated from serum with a mean half-life of approximately 6 days following both single and multiple doses. Clearance of pegvisomant increases with body weight.
Seventy-five percent of patients reach the maximal reduction in serum IGF-I within 2 weeks after initiation of therapy that is sustained throughout treatment. Other patients, however, may not reach maximal reductions in IGF-I levels until 12 to 14 weeks of therapy.
-Route-Specific Pharmacokinetics
Subcutaneous Route
Peak serum concentrations of pegvisomant are generally not attained until 33 to 77 hours after subcutaneous administration. Relative to a 10 mg intravenous dose, the mean extent of absorption of a 20 mg subcutaneous dose is 57%. The relative bioavailability of 1 injection of 30 mg pegvisomant was compared to 2 injections of 15 mg pegvisomant in a single dose study. The AUC and Cmax of pegvisomant when administered as a single-daily injection of 30 mg was approximately 6% and 4% greater, respectively, as compared to when administered as 2 injections of 15 mg. Pegvisomant does not distribute extensively into tissues, suggested by the mean apparent volume of distribution of 7 liters. Following a single subcutaneous administration, the Cmax and AUC increase disproportionately as the dose increases; mean serum pegvisomant concentrations after 12 weeks of therapy with daily doses of 10, 15, and 20 mg were 6,600, 16,000, and 27,000 ng/mL, respectively.