Phentolamine is an alpha-adrenergic receptor antagonist administered parentally and ophthalmically. Phentolamine is similar in action to phenoxybenzamine and has a shorter duration of action. Approved uses of parenteral phentolamine include diagnosis of pheochromocytoma and treatment of hypertension in pheochromocytoma, prevention of tissue necrosis after norepinephrine extravasation, and reversal of soft tissue anesthesia. Ophthalmic phentolamine is approved for reversal of mydriasis produced by adrenergic agonists (e.g., phenylephrine) or parasympatholytic (e.g., tropicamide) agents in adults and pediatric patients 3 years and older. Parenteral phentolamine has also been used to treat hypertensive crisis associated with monoamine oxidase inhibitor (MAOI) therapy and in combination with papaverine to treat erectile dysfunction (ED). According to ED treatment guidelines, oral phosphodiesterase type 5 (PDE5) inhibitors are considered first-line therapy. Second-line treatment options include intracavernous injection and intra-urethral therapy. Intracavernous injection therapy is the most effective nonsurgical treatment for ED, with predictable and sustained response. However, it is invasive and carries notable side effects including priapism and penile fibrosis. Phentolamine injection is contraindicated for use in patients with any coronary artery disease due to cardiac stimulating effects and corresponding increase in myocardial oxygen demand.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Reconstitution
-Dissolve 5 mg of phentolamine in 1 mL of Sterile Water for Injection.
-Storage: Do not store reconstituted solution; use upon preparation.
IV Push
-Inject the reconstituted solution rapidly.
Continuous IV infusion
-For prevention of necrosis/sloughing after extravasation from continuous IV norepinephrine, 10 mg of phentolamine may be added to each 1,000 mL of norepinephrine infusion. The pressor effect of norepinephrine is not altered.
Intramuscular Administration
Reconstitution
-Dissolve 5 mg of phentolamine in 1 mL of Sterile Water for Injection.
-Storage: Do not store reconstituted solution; use upon preparation.
Intramuscular injection
-Inject deeply into a large muscle.
Subcutaneous Administration
-For extravasation treatment, make a solution by diluting phentolamine in 0.9% Sodium Chloride Injection according to desired dosage.
--Adults and Pediatric patients: Dilute to a concentration of 0.5 to 1 mg/mL.
-Neonates: Dilute to a concentration of 0.25 to 0.5 mg/mL.
-Use a 27- to 30-gauge needle and make multiple small injections around the extravasation site.
Other Injectable Administration
Submucosal Administration
-Administer following the dental procedure using the same location(s) and technique(s) (infiltration or nerve block injection) used for the administration of the local anesthetic.
Intracavernous Administration
NOTE: Phentolamine is not approved by the FDA for intracavernous administration.
-This administration method should only be prescribed by specially trained physicians. Patients should be trained and observed for appropriate self-administration technique prior to prescribing.
-After the appropriate dose has been drawn into the syringe, the head of the penis is held between the thumb and forefinger. The penis is stretched lengthwise along the thigh while sitting upright or slightly reclined. Position the needle of the syringe so that the drug will be injected as described by your prescriber. Follow the directions given to you by your prescriber. After injection, the syringe should be withdrawn. Apply pressure to the injection site with an alcohol swab for 5 minutes (or until bleeding stops). The injection site and side of the penis should be rotated to minimize local adverse effects related to repeated local injections.
Ophthalmic Administration
-One single-patient-use vial can be used to dose both dilated eyes.
-Discard the single-patient-use vial immediately after use.
-Do not touch vial tip to the eye or to any other surface to prevent eye injury or contamination.
Acute and prolonged hypotensive episodes, sinus tachycardia, cardiac arrhythmias, and/or angina have all occurred with parenteral administration of phentolamine. These effects may be due to the drug's cardiac-stimulating and vasodilatory effects. Other adverse effects seen with phentolamine therapy include weakness, dizziness, flushing, and orthostatic hypotension. Flushing may be due to dilation of the facial blood vessels. During reversal of soft tissue anesthesia in studies of pediatric and adult patients (n = 418), phentolamine (OraVerse) was associated with tachycardia, bradycardia, and elevations in blood pressure (hypertension) in 5%, 2%, and < 3% of patients, respectively.
Nasal congestion can occur with the parenteral use of phentolamine and is probably caused by phentolamine's vasodilatory effect on blood vessels in the nasal mucosa. Nasal congestion has also been reported post-marketing with OraVerse.
Nausea and vomiting can occur with the parenteral use of phentolamine. Diarrhea secondary to phentolamine may result from stimulation of GI smooth muscle. During reversal of soft tissue anesthesia in studies of pediatric and adult patients (n = 418), phentolamine (OraVerse) was associated with diarrhea, vomiting, and upper abdominal pain in less than 3% of patients. Dysgeusia was reported in 6% of patients treated with phentolamine ophthalmic solution in clinical trials.
Priapism has occasionally been reported after intracavernosal injection of phentolamine into the penis. Penile ecchymosis is a common adverse effect of this treatment, as is transient pain. Ejaculation dysfunction has also been reported.
During reversal of soft tissue anesthesia in 2 studies of pediatric and adult patients (n = 418) who underwent mandibular or maxillary procedures, phentolamine (OraVerse) was associated with moderate dental pain in < 10% of patients. Pain specific to the injection site occurred in 5% of patients, and post-procedural pain was reported in 6% of patients. Injection site reaction was reported in < 3% of patients; symptoms included facial swelling, jaw pain, oral pain, pruritus, and tenderness. No severe pain was reported.
Cerebrovascular spasm and cerebrovascular occlusion have been reported following phentolamine administration. During reversal of soft tissue anesthesia in studies of pediatric and adult patients (n = 418), phentolamine (OraVerse) was associated with headache in 3% of patients. The incidence of headache increased with increasing dosage. Paresthesias occurred in < 3% of patients. Paraesthesias were transient and resolved within 48 hours.
The most common ocular adverse reactions reported in patients receiving phentolamine ophthalmic solution in clinical trials were ocular pain, stinging, and burning (16%) and conjunctival hyperemia (12%).
Phentolamine injection is contraindicated for use in patients with acute myocardial infarction, a history of myocardial infarction, coronary insufficiency, angina, or any evidence of coronary artery disease due to the drug's cardiac stimulating effects and corresponding increase in myocardial oxygen demand. Reflex tachycardia can exacerbate angina. Use of the OraVerse phentolamine product is not contraindicated in these conditions, as tachycardia and cardiac arrhythmias are uncommon with administration; however, use precaution in patients with a history of cardiovascular disease.
Phentolamine should be used with caution in patients with gastric and duodenal ulcers because the drug has a histamine-like effect. Phentolamine can stimulate secretion of gastric acid and pepsin in the stomach, which can aggravate peptic ulcer disease.
There are no adequate and well-controlled studies of systemic phentolamine use in human pregnancy. In animal studies, administration of phentolamine at oral doses 24 to 30 times the usual daily human dose (based on a 60 kg human) resulted in slightly decreased growth and slight skeletal immaturity of the fetuses. Immaturity was manifested by increased incidence of incomplete or unossified calcanei and phalangeal nuclei of the hind limb and of incompletely ossified sternebrae. Phentolamine did not affect embryonic or fetal development in the rabbit at oral doses 20 times the usual daily human dose (based on a 60 kg human). No teratogenic or embryotoxic effects were observed in animal studies. Use phentolamine during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no available data with phentolamine ophthalmic solution administration in pregnant women to inform of a drug-associated risk. Ophthalmic phentolamine is absorbed systemically with a median peak concentration of 0.45 ng/mL. When use is necessary during pregnancy, proper lacrimal occlusion after dosage will help limit the risk of maternal systemic absorption.
There are no data regarding the presence of phentolamine in human milk, the effects on the breastfed infant, or the effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for phentolamine and any potential adverse effects on the breastfed infant from phentolamine, or from the underlying maternal condition. When use of phentolamine ophthalmic solution is necessary during breast-feeding, proper lacrimal occlusion after dosage will help limit the risk of maternal systemic absorption.
Phentolamine ophthalmic solution is not recommended when active ocular inflammation (e.g., iritis or uveitis) is present because adhesions (synechiae) may form between the iris and the lens.
Advise contact lens wearers to remove their contact lenses prior to the instillation of phentolamine ophthalmic solution and wait 10 minutes after dosing before reinserting their contact lenses.
General Dosing Information
-For the diagnosis of pheochromocytoma, urinary assay of catecholamines and other biochemical assays have generally replaced the phentolamine blocking test for reasons of accuracy and safety. The phentolamine blocking test should be only be used when additional confirmatory evidence is needed and the risks involved in conducting the test have been considered.
-The phentolamine blocking test is most reliable in detecting pheochromocytoma in patients with sustained hypertension and is somewhat reliable in those with paroxysmal hypertension. Patients with hypertension without pheochromocytoma may get false-positive test results.
For pheochromocytoma diagnosis:
Intravenous dosage:
Adults: 5 mg IV. For at least 24 hours before the test (preferably 48 to 72 hours), all non-essential medication should be withheld. Prior to administration, the patient should be resting in a supine position until blood pressure is stabilized and a base pressure is established by blood pressure readings taken every 10 minutes for at least 30 minutes. Following needle insertion, delay drug administration until a pressor response to venipuncture has subsided. Inject phentolamine rapidly and record pressure immediately following injection, at 30 second intervals for the first 3 minutes, and at 60 second intervals for the next 7 minutes. A blood pressure reduction greater than 35 mm Hg systolic and 25 mm Hg diastolic is considered a positive test. Return to pre-injection pressures should occur within 15 to 30 minutes following administration. Confirm any positive response with diagnostic procedures, preferably by measurement of urinary catecholamines and their metabolites.
Adolescents and Children: 0.05 to 0.1 mg/kg/dose IV with a maximum single dose of 5 mg has been suggested. The manufacturer recommends a dose of 1 mg IV for children and 5 mg IV for adults (adolescents not specified). For at least 24 hours before the test (preferably 48 to 72 hours), all non-essential medication should be withheld. Prior to administration, the patient should be resting in a supine position until blood pressure is stabilized and a base pressure is established by blood pressure readings taken every 10 minutes for at least 30 minutes. Following needle insertion, delay drug administration until a pressor response to venipuncture has subsided. Inject phentolamine rapidly and record pressure immediately following injection, at 30-second intervals for the first 3 minutes, and at 60-second intervals for the next 7 minutes. A blood pressure reduction greater than 35 mm Hg systolic and 25 mm Hg diastolic is considered a positive test. Return to pre-injection pressures should occur within 15 to 30 minutes following administration. Confirm any positive response with diagnostic procedures, preferably by measurement of urinary catecholamines and their metabolites.
Intramuscular dosage:
Adults: 5 mg IM. For at least 24 hours before the test (preferably 48 to 72 hours), all non-essential medication should be withheld. Prior to administration, the patient should be resting in a supine position until blood pressure is stabilized and a base pressure is established by blood pressure readings taken every 10 minutes for at least 30 minutes. Record pressure every 5 minutes for 30 to 45 minutes following injection. A blood pressure reduction greater than 35 mm Hg systolic and 25 mm Hg diastolic within 20 minutes following injection is considered a positive test. Confirm any positive response with diagnostic procedures, preferably by measurement of urinary catecholamines and their metabolites.
Adolescents and Children: 0.05 to 0.1 mg/kg/dose IM with a maximum single dose of 5 mg has been suggested. The manufacturer recommends a dose of 3 mg IM for children and 5 mg IM for adults (adolescents not specified). For at least 24 hours before the test (preferably 48 to 72 hours), all non-essential medication should be withheld. Prior to administration, the patient should be resting in a supine position until blood pressure is stabilized and a base pressure is established by blood pressure readings taken every 10 minutes for at least 30 minutes. Record pressure every 5 minutes for 30 to 45 minutes following injection. A blood pressure reduction greater than 35 mm Hg systolic and 25 mm Hg diastolic within 20 minutes following injection is considered a positive test. Confirm any positive response with diagnostic procedures, preferably by measurement of urinary catecholamines and their metabolites.
For the treatment of hypertension before or during pheochromocytomectomy:
Intramuscular dosage or Intravenous dosage:
Adults: 5 mg IM or IV 1 to 2 hours before surgery, repeat if needed. May give 5 mg IV during surgery if needed.
Adolescents and Children: 0.05 to 0.1 mg/kg/dose IV or IM up to a maximum dose of 5 mg given 1 to 2 hours prior to surgery has been suggested. The manufacturer recommends a dose of 1 mg IV or IM for children and 5 mg IV of IM for adults (adolescents are not specified). Repeat every 2 to 4 hours as needed to control blood pressure. During surgery, repeat IV as needed to control symptoms of epinephrine intoxication.
For the prevention or treatment of dermal necrosis or sloughing following extravasation of IV norepinephrine or other drugs* associated with alpha-adrenergic effects (e.g., dopamine, dobutamine, epinephrine, phenylephrine):
Subcutaneous dosage:
Adults: 5 to 10 mg phentolamine in 10 mL 0.9% Sodium Chloride injected into affected area within 12 hours of catecholamine extravasation (10 mg maximum total dose). Infiltrate the area as soon as possible to prevent tissue necrosis. Visible hyperemia and increased tissue warmth at the site of extravasation are signs of effective treatment.
Infants, Children, and Adolescents: Infiltrate area with 1 to 5 mL (in 5 divided doses) of a 0.5 to 1 mg/mL solution (made by diluting 5 to 10 mg in 10 mL 0.9% Sodium Chloride injection). Inject into affected area within 12 hours of extravasation. Do not exceed 0.1 to 0.2 mg/kg or 5 mg total. Visible hyperemia and increased tissue warmth at the site of extravasation are signs of effective treatment.
Neonates: Infiltrate area with 1 mL of solution made by diluting 2.5 to 5 mg in 10 mL of 0.9% Sodium Chloride injection. Give 5 divided doses subcutaneously around the site. Inject into affected area within 12 hours of extravasation. Do not exceed 0.1 mg/kg or 2.5 mg total. Visible hyperemia and increased tissue warmth at the site of extravasation are signs of effective treatment.
Intravenous dosage:
Adults, Adolescents, Children, Infants, and Neonates: The manufacturer suggests that to prevent extravasation, 10 mg of phentolamine can be added to each 1,000 mL of norepinephrine IV infusion solution without affecting the pressor effects of norepinephrine.
For the treatment of hypertensive emergency* related to any catecholamine excess, such as interactions between MAO-inhibitors and sympathomimetic amines or tyramine-containing foods; or resulting from clonidine withdrawal syndrome:
Intravenous dosage:
Adults: 5 mg IV every 10 minutes as needed to lower blood pressure to target range. Dose range: 5 to 15 mg.
For the treatment of erectile dysfunction (ED)*:
-for the treatment of erectile dysfunction (ED)* in combination with papaverine and alprostadil:
Intracavernous dosage:
Adults males: 0.2 to 0.4 mg of phentolamine with 8 to 16 mg of papaverine and 10 to 20 mcg of alprostadil (prostaglandin E1 or PGE1) per intracavernous injection. Individualized dosages are determined by series of trial injections under physician supervision. The injections should be given no more than 3 times per week, with a minimum of 24 hours between doses. Triple drug therapy with papaverine, phentolamine, and alprostadil is most effective, with response rates of up to 92%. Per guidelines, second-line treatment options for ED include intracavernous injection and intra-urethral therapy. Intracavernous injection therapy is the most effective nonsurgical treatment for ED, with predictable and sustained response. However, it is invasive and caries notable side-effects including priapism and penile fibrosis. Careful dose selection, proper patient education, and continued monitoring by a prescribing physician is warranted for successful non-oral treatment of ED. Follow-up visits for ED patients, regardless of therapy, are necessary to determine whether therapy continues to be effective and whether cardiovascular health has significantly changed.
-for the treatment of erectile dysfunction (ED)* in combination with papaverine:
Intracavernous dosage:
Adults males: 0.25 to 1.5 mg of phentolamine with 7.5 to 45 mg of papaverine per intracavernous injection. Individualized dosages are determined by series of trial injections under physician supervision. The injections should be given no more than 3 times per week, with a minimum of 24 hours between doses. Per guidelines, second-line treatment options for ED include intracavernous injection and intra-urethral therapy. Intracavernous injection therapy is the most effective nonsurgical treatment for ED, with predictable and sustained response. However, it is invasive and caries notable side-effects including priapism and penile fibrosis. Careful dose selection, proper patient education, and continued monitoring by a prescribing physician is warranted for successful non-oral treatment of ED. Follow-up visits for ED patients, regardless of therapy, are necessary to determine whether therapy continues to be effective and whether cardiovascular health has significantly changed.
For soft-tissue anesthesia reversal including the associated functional deficits resulting from an intraoral submucosal injection of a local anesthetic containing a vasoconstrictor:
Submucosal dosage:
Adults, Adolescents, and Children weighing 30 kg or more: 0.1 to 0.8 mg/dose (0.25 to 2 cartridges) administered by infiltration or nerve block injection; the same location and technique used for local anesthetic administration should be used. Recommended dose is based on the number of cartridges of local anesthetic with vasoconstrictor used. For one-fourth cartridge of local anesthetic, give 0.1 mg (0.25 cartridge of phentolamine); for one-half cartridge of local anesthetic, give 0.2 mg (0.5 cartridge of phentolamine); for 1 cartridge of local anesthetic, give 0.4 mg (1 cartridge of phentolamine); for 2 cartridges of local anesthetic, give 0.8 mg (2 cartridges of phentolamine).
Children 3 years and older weighing 15 to 29 kg: 0.1 to 0.2 mg/dose (0.25 to 0.5 cartridge) administered by infiltration or nerve block injection; the same location and technique used for local anesthetic administration should be used. Recommended dose is based on the number of cartridges of local anesthetic with vasoconstrictor used. For one-fourth cartridge of local anesthetic, give 0.1 mg (0.25 cartridge of phentolamine); for one-half cartridge of local anesthetic, give 0.2 mg (0.5 cartridge of phentolamine). The maximum recommended dose is 0.2 mg (0.5 cartridge).
For mydriasis reversal following pharmacologically-induced mydriasis produced by adrenergic agonists or parasympatholytic agents:
Ophthalmic dosage:
Adults: Instill 1 or 2 drops in each dilated eye following the completion of the ophthalmic examination or procedure. If 2 drops are instilled, the second drop should be administered 5 minutes after the first drop.
Children and Adolescents 12 to 17 years: Instill 1 or 2 drops in each dilated eye following the completion of the ophthalmic examination or procedure. If 2 drops are instilled, the second drop should be administered 5 minutes after the first drop.
Children 3 to 11 years: Instill 1 drop in each dilated eye following the completion of the ophthalmic examination or procedure.
Maximum Dosage Limits:
-Adults
10 mg subcutaneously; 5 mg IV/IM; however, a higher dose of 15 mg IV has been used off-label for hypertensive emergency; 0.8 mg submucosal injection; 2 drops/eye/day for ophthalmic solution.
-Geriatric
10 mg subcutaneously; 5 mg IV/IM; however, a higher dose of 15 mg IV has been used off-label for hypertensive emergency; 0.8 mg submucosal injection; 2 drops/eye/day for ophthalmic solution.
-Adolescents
0.2 mg/kg (Max: 5 mg/dose) subcutaneously; 5 mg/dose IV/IM; 0.8 mg/dose submucosal injection; 2 drops/eye/day for ophthalmic solution.
-Children
12 years weighing 30 kg or more: 0.2 mg/kg (Max: 5 mg/dose) subcutaneously; 5 mg/dose IV/IM; 0.8 mg/dose submucosal injection; 2 drops/eye/day for ophthalmic solution.
12 years weighing 15 to 29 kg: 0.2 mg/kg (Max: 5 mg/dose) subcutaneously; 5 mg/dose IV/IM; 0.2 mg/dose submucosal injection; 2 drops/eye/day for ophthalmic solution.
3 to 11 years weighing 30 kg or more: 0.2 mg/kg (Max: 5 mg/dose) subcutaneously; 5 mg/dose IV/IM; 0.8 mg/dose submucosal injection; 1 drop/eye/day for ophthalmic solution.
3 to 11 years weighing 15 to 29 kg: 0.2 mg/kg (Max: 5 mg/dose) subcutaneously; 5 mg/dose IV/IM; 0.2 mg/dose submucosal injection; 1 drop/eye/day for ophthalmic solution.
3 to 11 years weighing less than 15 kg: 0.2 mg/kg subcutaneously; 5 mg/dose IV/IM; 1 drop/eye/day for ophthalmic solution; safety and efficacy of other formulations have not been established.
1 to 2 years: 0.2 mg/kg subcutaneously; 5 mg/dose IV/IM; safety and efficacy of other formulations have not been established.
-Infants
0.2 mg/kg subcutaneously; safety and efficacy of other formulations have not been established.
-Neonates
0.1 mg/kg subcutaneously; safety and efficacy of other formulations have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
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
Acebutolol: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Acetaminophen; Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Acetaminophen; Ibuprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Acetaminophen; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Acetaminophen; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Acrivastine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Alfuzosin: (Major) Alfuzosin should not be administered in combination with other alpha-blockers. The pharmacokinetic and pharmacodynamic interactions between alfuzosin and other alpha-blockers (used for high blood pressure or for benign prostatic hyperplasia) have not been determined. However, interactions or side effects (dizziness, hypotension, syncope, etc.) may be expected from the duplication of pharmacologic effects.
Ambrisentan: (Moderate) Although the duration of action of phentolamine is short, its onset is very rapid. The hypotensive effects of phentolamine can be additive with that of other antihypertensive agents.
Amifostine: (Major) Patients receiving alpha-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
Amlodipine; Celecoxib: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Amphetamine: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Phentolamine may decrease, but not completely reverse, the pressor response of amphetamine overdose. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
Amphetamine; Dextroamphetamine: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Phentolamine may decrease, but not completely reverse, the pressor response of amphetamine overdose. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
Amphetamines: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Phentolamine may decrease, but not completely reverse, the pressor response of amphetamine overdose. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
Apomorphine: (Moderate) Use of phentolamine and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Aripiprazole: (Moderate) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Articaine; Epinephrine: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Asenapine: (Moderate) Secondary to alpha-blockade, asenapine can produce vasodilation that may result in additive effects during concurrent use of antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of asenapine and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Atenolol: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Atenolol; Chlorthalidone: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Avanafil: (Moderate) Concomitant use of avanafil and an alpha-blocker may increase the risk for symptomatic hypotension. To minimize the risk for harm if concomitant use is necessary, optimize the dose of one medication before starting the other, initiate therapy at the lowest recommended dose, and monitor blood pressure. Both medications are vasodilators and may have an additive blood pressure lowering effect when used together.
Baclofen: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
Benzphetamine: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Phentolamine may decrease, but not completely reverse, the pressor response of amphetamine overdose. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
Beta-blockers: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Betaxolol: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Bisoprolol: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Bortezomib: (Moderate) Patients on antihypertensive agents receiving bortezomib treatment may require close monitoring of their blood pressure and dosage adjustment of their medication. During clinical trials of bortezomib, hypotension was reported in roughly 12 percent of patients.
Brexpiprazole: (Moderate) Due to brexpiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
Brimonidine; Timolol: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Bromocriptine: (Minor) Bromocriptine has only minimal affinity for adrenergic receptors; however, hypotension can occur during bromocriptine administration. Orthostatic hypotension occurs in 6% of acromegaly patients receiving the drug. Hypotension occurred frequently (approximately 30%) in postpartum studies, which in rare cases approached a decline in supine pressure of almost 60 mmHg. It is unknown if bromocriptine is the exact cause of this effect. However, the drug should be used cautiously with other medications known to lower blood pressure such as antihypertensive agents. Monitoring of blood pressure should be considered, especially during the initial weeks of concomitant therapy.
Brompheniramine; Dextromethorphan; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Brompheniramine; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Brompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Bupivacaine; Epinephrine: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Bupivacaine; Meloxicam: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Cabergoline: (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including alpha-blockers. Cabergoline has been associated with hypotension. Initial doses higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure.
Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
Carteolol: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Carvedilol: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Celecoxib: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Celecoxib; Tramadol: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Cetirizine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Chlorpheniramine; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Chlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Codeine; Phenylephrine; Promethazine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Co-Enzyme Q10, Ubiquinone: (Moderate) Co-enzyme Q10, ubiquinone (CoQ10) may lower blood pressure. CoQ10 use in combination with antihypertensive agents may lead to additional reductions in blood pressure in some individuals. Patients who choose to take CoQ10 concurrently with antihypertensive medications should receive periodic blood pressure monitoring. Patients should be advised to inform their prescriber of their use of CoQ10.
Desloratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Dexbrompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Dexmethylphenidate: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidates can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Dextroamphetamine: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Phentolamine may decrease, but not completely reverse, the pressor response of amphetamine overdose. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Dextromethorphan; Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agents. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving other antihypertensive agents.
Diclofenac: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Diclofenac; Misoprostol: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Diethylpropion: (Major) Diethylpropion has vasopressor effects and may limit the benefit of alpha-blockers. Although leading drug interaction texts differ in the potential for an interaction between diethylpropion and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications.
Diflunisal: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Diphenhydramine; Ibuprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Diphenhydramine; Naproxen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Diphenhydramine; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Dobutamine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Dopamine: (Major) In general, alpha-blockers should not be used during dopamine infusion. The undesired peripheral vasoconstriction observed with high-dose dopamine is opposed by alpha-adrenergic blockers. The renal, mesenteric, or cerebral vasodilatory properties resulting from dopaminergic-receptor stimulation are not affected by alpha-blockers .
Dorzolamide; Timolol: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Duloxetine: (Moderate) Orthostatic hypotension and syncope have been reported during duloxetine administration. The concurrent administration of antihypertensive agents and duloxetine may increase the risk of hypotension. Monitor blood pressure if the combination is necessary.
Dutasteride; Tamsulosin: (Major) Tamsulosin should not be administered in combination with other alpha-blockers. The pharmacokinetic and pharmacodynamic interactions between tamsulosin and other alpha-blockers (used for high blood pressure or for benign prostatic hyperplasia) have not been determined. However, interactions or side effects (dizziness, hypotension, syncope, etc.) may be expected from the duplication of pharmacologic effects.
Ephedrine: (Moderate) Carefully monitor blood pressure in patients who have received both ephedrine and alpha-blockers; alpha-blockers antagonize the pressor effect of ephedrine.
Ephedrine; Guaifenesin: (Moderate) Carefully monitor blood pressure in patients who have received both ephedrine and alpha-blockers; alpha-blockers antagonize the pressor effect of ephedrine.
Epinephrine: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Epoprostenol: (Minor) Epoprostenol can have additive effects when administered with other antihypertensive agents, including alpha-blockers. These effects can be used to therapeutic advantage, but dosage adjustments may be necessary.
Esmolol: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Estradiol: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormonal contraceptives should be monitored to confirm that the desired antihypertensive effect is being obtained.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking alpha-blockers. Concomitant use may increase the risk for hypotension.
Etodolac: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Fenoprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Fexofenadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Finasteride; Tadalafil: (Moderate) Concomitant use of tadalafil and an alpha-blocker may increase the risk for symptomatic hypotension. To minimize the risk for harm if concomitant use is necessary, optimize the dose of one medication before starting the other, initiate therapy at the lowest recommended dose, and monitor blood pressure. Both medications are vasodilators and may have an additive blood pressure lowering effect when used together. In healthy volunteer studies, maximal placebo-subtracted decreases in systolic blood pressure with combination therapy ranged from 1 mmHg to 9.8 mmHg.
Flurbiprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Hydrocodone; Ibuprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Ibuprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Ibuprofen; Famotidine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Ibuprofen; Oxycodone: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Ibuprofen; Pseudoephedrine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Iloperidone: (Moderate) Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Indomethacin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Isocarboxazid: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy with antihypertensives such as alpha-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
Isoproterenol: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Isosorbide Mononitrate: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Ketoprofen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Ketorolac: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Labetalol: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Levobunolol: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Lidocaine; Epinephrine: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Lisdexamfetamine: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Phentolamine may decrease, but not completely reverse, the pressor response of amphetamine overdose. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
Lofexidine: (Major) Because the central alpha-2 agonist effects of lofexidine can cause hypotension and orthostasis, the drug should be avoided, if possible, in combination with other medications that can significantly decrease blood pressure such as the antihypertensive alpha-blockers. If coadministration is required, blood pressure should be monitored, particularly after dose changes of either agent. Adjustments should be made as clinically indicated. Patients being given lofexidine in an outpatient setting should be capable of and instructed on self-monitoring for hypotension, orthostasis, bradycardia, and associated symptoms. If clinically significant or symptomatic hypotension and/or bradycardia occur, the next dose of lofexidine should be reduced in amount, delayed, or skipped.
Loratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Macitentan; Tadalafil: (Moderate) Concomitant use of tadalafil and an alpha-blocker may increase the risk for symptomatic hypotension. To minimize the risk for harm if concomitant use is necessary, optimize the dose of one medication before starting the other, initiate therapy at the lowest recommended dose, and monitor blood pressure. Both medications are vasodilators and may have an additive blood pressure lowering effect when used together. In healthy volunteer studies, maximal placebo-subtracted decreases in systolic blood pressure with combination therapy ranged from 1 mmHg to 9.8 mmHg.
Meclofenamate Sodium: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Mefenamic Acid: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Meloxicam: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Methamphetamine: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. Phentolamine may decrease, but not completely reverse, the pressor response of amphetamine overdose. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
Methohexital: (Moderate) Concurrent use of methohexital and alpha-blockers increases the risk of developing hypotension and hypothermia.
Methylphenidate Derivatives: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidates can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Methylphenidate: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidates can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Metoprolol: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Midodrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Nabumetone: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Nadolol: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Naproxen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Naproxen; Esomeprazole: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Naproxen; Pseudoephedrine: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease. (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Nebivolol: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Nebivolol; Valsartan: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Nicotine: (Moderate) Nicotine use may reduce the clinical effects of the alpha-blockers. If significant changes in nicotine intake occur, the dosages of these drugs may need adjustment.
Nitrates: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Nitroglycerin: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
Nitroprusside: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
Nonsteroidal antiinflammatory drugs: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Norepinephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly. Also, because norepinephrine is an alpha-adrenergic agonist, drugs with alpha-blocking activity such as alpha-blockers directly counteract the vasopressor effects of norepinephrine.
Oxaprozin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Oxymetazoline: (Major) Caution is advised when administering phentolamine with oxymetazoline. Phentolamine, an alpha adrenergic blocker, would likely antagonize the sympathomimetic effects of oxymetazoline, alpha adrenergic agonists; thereby reducing the effectiveness of oxymetazoline.
Pentoxifylline: (Moderate) Pentoxifylline has been used concurrently with antihypertensive drugs (beta blockers, diuretics) without observed problems. Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced.
Phendimetrazine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Phenelzine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy with antihypertensives such as alpha-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
Phentermine: (Moderate) Monitor for desired antihypertensive effect of alpha-blockers when administered with phentermine, Sympathomimetics like phentermine can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Phentermine; Topiramate: (Moderate) Monitor for desired antihypertensive effect of alpha-blockers when administered with phentermine, Sympathomimetics like phentermine can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Pindolol: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Piroxicam: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Prilocaine; Epinephrine: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
Procainamide: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
Promethazine; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
Propranolol: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Pseudoephedrine; Triprolidine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Rasagiline: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy with antihypertensives such as alpha-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
Risperidone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidates can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
Sildenafil: (Moderate) Concomitant use of sildenafil and an alpha-blocker may increase the risk for symptomatic hypotension. To minimize the risk for harm if concomitant use is necessary, optimize the dose of one medication before starting the other, initiate therapy at the lowest recommended dose, and monitor blood pressure. Both medications are vasodilators and may have an additive blood pressure lowering effect when used together.
Silodosin: (Major) Silodosin should not be administered in combination with other alpha-blockers. The pharmacokinetic and pharmacodynamic interactions between silodosin and other alpha-blockers (used for high blood pressure or for benign prostatic hyperplasia) have not been determined. However, interactions or side effects (dizziness, hypotension, syncope, etc.) may be expected from the duplication of pharmacologic effects.
Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by concurrent phentolamine. False study results are possible in patients with drug-induced hyper- or hypo-responsiveness; thorough patient history is important in the interpretation of procedure results.
Sotalol: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Sulfacetamide; Sulfur: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents.
Sulindac: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Sumatriptan; Naproxen: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Tadalafil: (Moderate) Concomitant use of tadalafil and an alpha-blocker may increase the risk for symptomatic hypotension. To minimize the risk for harm if concomitant use is necessary, optimize the dose of one medication before starting the other, initiate therapy at the lowest recommended dose, and monitor blood pressure. Both medications are vasodilators and may have an additive blood pressure lowering effect when used together. In healthy volunteer studies, maximal placebo-subtracted decreases in systolic blood pressure with combination therapy ranged from 1 mmHg to 9.8 mmHg.
Tamsulosin: (Major) Tamsulosin should not be administered in combination with other alpha-blockers. The pharmacokinetic and pharmacodynamic interactions between tamsulosin and other alpha-blockers (used for high blood pressure or for benign prostatic hyperplasia) have not been determined. However, interactions or side effects (dizziness, hypotension, syncope, etc.) may be expected from the duplication of pharmacologic effects.
Tetrabenazine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents.
Thalidomide: (Moderate) Thalidomide and other agents that slow cardiac conduction such as alpha-blockers should be used cautiously due to the potential for additive bradycardia.
Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Timolol: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
Tizanidine: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
Tolmetin: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
Trandolapril; Verapamil: (Moderate) Additive pharmacodynamic effects are especially prominent when verapamil is co-administered with alpha-blockers. The use of alpha-blockers with verapamil can lead to excessive hypotension.
Tranylcypromine: (Contraindicated) The use of hypotensive agents and tranylcypromine is contraindicated by the manufacturer of tranylcypromine because the effects of hypotensive agents may be markedly potentiated.
Trazodone: (Minor) Due to additive hypotensive effects, patients receiving antihypertensive agents concurrently with trazodone may have excessive hypotension. Decreased dosage of the antihypertensive agent may be required when given with trazodone.
Vardenafil: (Moderate) Concomitant use of vardenafil and an alpha-blocker may increase the risk for symptomatic hypotension. To minimize the risk for harm if concomitant use is necessary, optimize the dose of one medication before starting the other, initiate therapy at the lowest recommended dose, and monitor blood pressure. Both medications are vasodilators and may have an additive blood pressure lowering effect when used together.
Verapamil: (Moderate) Additive pharmacodynamic effects are especially prominent when verapamil is co-administered with alpha-blockers. The use of alpha-blockers with verapamil can lead to excessive hypotension.
Vitamin B Complex Supplements: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Ziprasidone: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.
Cardiovascular effects
Phentolamine is a potent short-acting, competitive antagonist of alpha-adrenergic receptors. Like phenoxybenzamine, phentolamine antagonizes both alpha1- and alpha2-receptors. Prazosin, another alpha-receptor antagonist, differs from both of these agents in that it is selective for the alpha1-receptor. Phentolamine reduces peripheral resistance via antagonism of the alpha1-receptors and possibly alpha2-receptors on vascular smooth muscle. Antagonism at alpha2-receptors cause cardiac stimulation due to an enhanced release of norepinephrine from sympathetic nerves. Phentolamine has positive inotropic and chronotropic effects on cardiac muscle and vasodilator effects on vascular smooth muscle. The clinical effects of phentolamine include cardiac stimulation caused by a decrease in peripheral resistance and an increase in cardiac output. Postural hypotension is often observed accompanied by reflex tachycardia that can precipitate cardiac arrhythmias and myocardial ischemia. These actions make phentolamine useful in treating hypertension caused by increased circulating levels of epinephrine and norepinephrine, as occurs in pheochromocytoma.
Erectile dysfunction
The effects of phentolamine in treating erectile dysfunction are mediated by alpha-adrenergic blockade in penile blood vessels. The drug's actions cause relaxation of the trabecular cavernous smooth muscles and dilation of the penile arteries, which increases arterial blood flow into the corpus cavernosa and subsequently causes an erection. The glans and corpus spongiosum swell minimally, if at all.
Mydriasis reversal
Phentolamine is a relatively non-selective alpha-1 and alpha-2 adrenergic antagonist. Phentolamine reversibly binds to alpha-1 adrenergic receptors on the iris dilator muscle, thereby reducing pupil diameter. Phentolamine directly antagonizes the mydriatic effect of an alpha-1 adrenergic agonist, and indirectly reverses mydriasis induced by muscarinic antagonist effects on the iris sphincter muscle.
Reversal of soft tissue anesthesia
The mechanism by which OraVerse (phentolamine injection for dental use) produces reversal of soft tissue anesthesia and associated functional deficits is not fully understood.
Phentolamine is primarily administered intravenously and intramuscularly as an injection solution or ophthalmically as an ocular solution. The injection can also be given subcutaneously to prevent local tissue necrosis when vasoconstrictor drugs extravasate, or it can be given by infiltration or nerve block for reversal of soft tissue anesthesia. The pharmacokinetics of phentolamine are largely unknown. Following IV administration of a single dose, approximately 13% of the dose is excreted in urine unchanged. The half-life of the drug in blood is 19 minutes following intravenous administration.
-Route-Specific Pharmacokinetics
Other Route(s)
Submucosal Route
After phentolamine (OraVerse) administration, 100% of the drug is available. Peak concentrations occur in 10 to 20 minutes, and systemic exposure increases linearly with increasing dosages. The half-life of phentolamine after submucosal administration is 2 to 3 hours.
Ophthalmic Route
The onset of action after administration of phentolamine ophthalmic solution generally occurs in 30 minutes, with the maximal effect seen in 60 to 90 minutes, and the effect lasting at least 24 hours. The peak concentrations are achieved between 15 minutes and 1 hour after dosing with the median value of 0.45 ng/mL.
-Special Populations
Pediatrics
The Cmax of phentolamine (OraVerse) was approximately 3.5-fold higher in children who weighed 15 to 30 kg compared to children who weighed more than 30 kg. The AUC was similar between the two groups. The pharmacokinetics in children weighing 30 kg or more are similar to the pharmacokinetics observed in adults.