Cleviprex

Dihydropyridine Calcium Channel Blockers

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Clevidipine is a sterile, milky-white injectable emulsion.[34680]

Intravenous Administration

Do not dilute.
Invert the vial gently several times to ensure emulsion uniformity before administration.
Administer via a central or peripheral line using an infusion device that allows calibrated infusion rates.
Commercially available standard plastic cannulae may be used.
Do not administer clevidipine in the same line as other medications. Clevidipine may be administered with Sterile Water for Injection, 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and Lactated Ringer's Injection, Lactated Ringer's Injection, and 10% Amino Acid Injection.
Monitor blood pressure and heart rate continuously during infusion, and then until vital signs are stable. Monitor patients who receive prolonged clevidipine infusions and are not transitioned to other antihypertensive therapies for at least 8 hours after the infusion is stopped. These patients may need follow-up adjustments in blood pressure control.
When an oral antihypertensive agent is being started, consider the lag time of onset of the oral agent's effect. Continue blood pressure monitoring until desired effect is achieved.
Storage: Once the stopper is punctured, use within 12 hours and discard any unused portion.[34680]

Severe

atrial fibrillation / Early / 21.0-21.0
renal failure (unspecified) / Delayed / 9.0-9.0
cardiac arrest / Early / 0-1.0
myocardial infarction / Delayed / 0-1.0
ileus / Delayed / Incidence not known
heart failure / Delayed / Incidence not known

Moderate

hypotension / Rapid / Incidence not known
sinus tachycardia / Rapid / Incidence not known
hypertriglyceridemia / Delayed / Incidence not known
dyspnea / Early / Incidence not known

Mild

nausea / Early / 4.8-21.0
headache / Early / 6.3-6.3
vomiting / Early / 3.2-3.2
syncope / Early / 0-1.0

Cleviprex

Rx

Intravenous dihydropyridine calcium channel blocker
Used for hypertension when oral therapy is not feasible or desirable
Delivered in a lipid emulsion vehicle

For the treatment of hypertension when oral therapy is not feasible or desirable. Intravenous dosage Adults

1 to 2 mg/hour continuous IV infusion, initially. Double the dose every 90 seconds until the blood pressure approaches goal, then increase by less than double every 5 to 10 minutes as needed. A 1 to 2 mg/hour increase will generally result in an additional 2 to 4 mmHg decrease in systolic blood pressure. Usual dose: 4 to 6 mg/hour. Usual Max: 21 mg/hour; severe hypertension may require doses up to 32 mg/hour. Max: 1,000 mL/24 hours due to lipid load restrictions. Max duration: 72 hours. Discontinue or titrate downward while appropriate oral therapy is established.[34680] [64716] [65597] [65598]

Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Acebutolol: (Moderate) Use clevidipine and acebutolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Isometheptene has sympathomimetic properties. Patients taking antihypertensive agents may need to have their therapy modified. Careful blood pressure monitoring is recommended.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
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: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Acrivastine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Adenosine: (Moderate) Use adenosine with caution in the presence of calcium-channel blockers due to the potential for additive or synergistic depressant effects on the sinoatrial and atrioventricular nodes.
Aldesleukin, IL-2: (Moderate) Calcium channel blockers may potentiate the hypotension seen with aldesleukin, IL 2.
Alemtuzumab: (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents.
Alfentanil: (Moderate) Monitor patients for bradycardia and hypotension when alfentanil is coadministered with clevidipine. Alfentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with alfentanil is increased in patients receiving clevidipine.
Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, like calcium channel blockers, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
Amifostine: (Major) Patients receiving calcium-channel 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 for 24 hours before chemotherapy doses of amifostine, patients should not receive amifostine.
Aminolevulinic Acid: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
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; Dextroamphetamine Salts: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
Apomorphine: (Moderate) Use of calcium-channel blockers and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Apraclonidine: (Minor) Apraclonidine had minimal effects on heart rate and blood pressure during clinical studies in patients with glaucoma. However, it is theoretically possible that additive blood pressure reductions could occur when apraclonidine is combined with the use of antihypertensive agents. Use caution during concurrent use, especially in patients with severe, uncontrolled cardiovascular disease, including hypertension.
Articaine; Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
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) Use clevidipine and atenolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
Atenolol; Chlorthalidone: (Moderate) Use clevidipine and atenolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
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: (Minor) Benzphetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
Betaxolol: (Moderate) Use clevidipine and betaxolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
Bisoprolol: (Moderate) Use clevidipine and bisoprolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Use clevidipine and bisoprolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
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.
Brimonidine; Timolol: (Moderate) Use clevidipine and timolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Brompheniramine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Brompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Bupivacaine; Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
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.
Calcium: (Minor) Monitor blood pressure during concurrent use of calcium and calcium-channel blockers. Concomitant use may reduce the response to calcium-channel blockers.
Carbidopa; Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Carbidopa; Levodopa; Entacapone: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
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.
Carvedilol: (Moderate) Use clevidipine and carvedilol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility. Monitor ECG and blood pressure if diltiazem is coadministered with carvedilol.
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 calcium-channel blockers. Monitor blood pressure and heart rate.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
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 calcium-channel blockers. Monitor blood pressure and heart rate.
Chlorpheniramine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Cocaine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Codeine; Phenylephrine; Promethazine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
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.
Danazol: (Minor) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates like calcium-channel blockers.
Dantrolene: (Moderate) Concurrent use with skeletal muscle relaxants and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
Desloratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Desogestrel; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Dexbrompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Dexmedetomidine: (Moderate) Concomitant administration of dexmedetomidine and calcium-channel blockers could lead to additive hypotension and bradycardia; use together with caution. Dexmedetomidine can produce bradycardia or AV block and should be used cautiously in patients who are receiving antihypertensive drugs that may lower the heart rate such as calcium-channel blockers.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
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 calcium-channel 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: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Dorzolamide; Timolol: (Moderate) Use clevidipine and timolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
Drospirenone; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
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: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Empagliflozin: (Moderate) Administer antidiabetic agents with caution in patients receiving calcium-channel blockers. These drugs may cause hyperglycemia leading to a temporary loss of glycemic control in patients receiving antidiabetic agents. Close observation and monitoring of blood glucose is necessary to maintain adequate glycemic control.
Empagliflozin; Linagliptin: (Moderate) Administer antidiabetic agents with caution in patients receiving calcium-channel blockers. These drugs may cause hyperglycemia leading to a temporary loss of glycemic control in patients receiving antidiabetic agents. Close observation and monitoring of blood glucose is necessary to maintain adequate glycemic control.
Empagliflozin; Linagliptin; Metformin: (Moderate) Administer antidiabetic agents with caution in patients receiving calcium-channel blockers. These drugs may cause hyperglycemia leading to a temporary loss of glycemic control in patients receiving antidiabetic agents. Close observation and monitoring of blood glucose is necessary to maintain adequate glycemic control.
Empagliflozin; Metformin: (Moderate) Administer antidiabetic agents with caution in patients receiving calcium-channel blockers. These drugs may cause hyperglycemia leading to a temporary loss of glycemic control in patients receiving antidiabetic agents. Close observation and monitoring of blood glucose is necessary to maintain adequate glycemic control.
Ephedrine: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by calcium-channel blockers. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Ephedrine; Guaifenesin: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by calcium-channel blockers. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Epirubicin: (Moderate) Close cardiac monitoring is recommended throughout therapy in patients receiving concomitant therapy with epirubicin and calcium-channel blockers. Individuals receiving these medications together are at increased risk of developing heart failure.
Epoprostenol: (Moderate) Calcium-channel blockers can have additive hypotensive effects with other antihypertensive agents. This additive effect can be desirable, but the patient should be monitored carefully and the dosage should be adjusted based on clinical response.
Esmolol: (Contraindicated) Esmolol is contraindicated with clevidipine use in close proximity (within a few hours). Fatal cardiac arrests have occurred in patients receiving esmolol and another cardiodepressant calcium channel blocker.
Ethanol: (Moderate) Alcohol interacts with antihypertensive agents, such as clevidipine, by potentiating their hypotensive effect.
Ethinyl Estradiol; Norelgestromin: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Ethinyl Estradiol; Norethindrone Acetate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Ethinyl Estradiol; Norgestrel: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
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.
Etomidate: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
Etonogestrel; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
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.
Fentanyl: (Moderate) Monitor patients for bradycardia and hypotension when fentanyl is coadministered with clevidipne. Fentanyl may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with fentanyl is increased in patients receiving clevidipine.
Fexofenadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
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.
General anesthetics: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
Ginkgo, Ginkgo biloba: (Moderate) Ginkgo biloba appears to inhibit the metabolism of calcium-channel blockers, perhaps by inhibiting the CYP3A4 isoenzyme. A non-controlled pharmacokinetic study in healthy volunteers found that the concurrent administration of ginkgo with nifedipine resulted in a 53% increase in nifedipine peak concentrations. More study is needed regarding ginkgo's effects on CYP3A4 and whether clinically significant drug interactions result.
Ginseng, Panax ginseng: (Moderate) Ginseng appears to inhibit the metabolism of calcium-channel blockers, perhaps by inhibiting the CYP3A4 isoenzyme. A non-controlled pharmacokinetic study in healthy volunteers found that the concurrent administration of ginseng with nifedipine resulted in a 30% increase in nifedipine peak concentrations. More study is needed regarding ginseng's effects on CYP3A4 and whether clinically significant drug interactions result.
Guaifenesin; Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
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.
Hydrocodone; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
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 calcium-channel 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.
Iloprost: (Moderate) Calcium-channel blockers can have additive hypotensive effects with other antihypertensive agents. This additive effect can be desirable, but the patient should be monitored carefully and the dosage should be adjusted based on clinical response.
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.
Intravenous Lipid Emulsions: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
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 of MAOIs with calcium-channel 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.
Isoflurane: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
Isoproterenol: (Moderate) The pharmacologic effects of isoproterenol may cause an increase in blood pressure. If isoproterenol is used concomitantly with antihypertensives, the blood pressure should be monitored as the administration of isoproterenol can compromise the effectiveness of antihypertensive agents.
Isosorbide Dinitrate, ISDN: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Isosorbide Mononitrate: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Ketamine: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
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) Use clevidipine and labetalol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as calcium-channel blockers, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Lanreotide: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.
Lasmiditan: (Moderate) Monitor heart rate if lasmiditan is coadministered with calcium-channel blockers as concurrent use may increase the risk for bradycardia. Lasmiditan has been associated with lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
Levonorgestrel; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Lidocaine; Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
Lisdexamfetamine: (Minor) Lisdexamfetamine might increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
Lithium: (

Moderate) Monitor for neurologic adverse reactions during concomitant use of lithium and calcium channel blockers. Concomitant use may increase the risk of neurologic adverse reactions, such as ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.
Lopinavir; Ritonavir: (Moderate) Ritonavir is expected to decrease the hepatic CYP metabolism of calcium-channel blockers (mainly through CYP3A4 inhibition) resulting in increased calcium-channel blocker concentrations. Ritonavir also prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
Loratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel 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 clevidipine 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.
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.
Melatonin: (Moderate) Monitor blood pressure during concomitant calcium-channel blocker and melatonin use. Melatonin may impair the efficacy of calcium-channel blockers. In a placebo-controlled study, melatonin evening ingestion led to significant increases in blood pressure (6.5 mmHg systolic and 4.9 mmHg diastolic) and heart rate (3.9 bpm) throughout the day in patients taking a calcium channel blocker Melatonin appeared to antagonize the antihypertensive effects of the calcium channel blocker.
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: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like calcium-channel blockers. Close monitoring of blood pressure is advised.
Methoxsalen: (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
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 derivatives. Methylphenidate derivatives can reduce the hypotensive effect of antihypertensive agents, including calcium-channel blockers.
Metoprolol: (Moderate) Use clevidipine and metoprolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Use clevidipine and metoprolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
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) Use clevidipine and nadolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
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 calcium-channel blockers. Monitor blood pressure and heart rate.
Nebivolol: (Moderate) Use clevidipine and nebivolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
Nebivolol; Valsartan: (Moderate) Use clevidipine and nebivolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and calcium-channel blockers may prolong neuromuscular blockade.
Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially calcium-channel blockers. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Niacin; Simvastatin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents, especially calcium-channel blockers. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Nirmatrelvir; Ritonavir: (Moderate) Ritonavir is expected to decrease the hepatic CYP metabolism of calcium-channel blockers (mainly through CYP3A4 inhibition) resulting in increased calcium-channel blocker concentrations. Ritonavir also prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
Nitrates: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
Nitroglycerin: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as calcium-channel blockers. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with a calcium-channel blocker.
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.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Norethindrone; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Norgestimate; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Fluoxetine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Samidorphan: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
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) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by calcium-channel blockers. If these drugs are used together, closely monitor for changes in blood pressure.
Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and calcium-channel blockers who are susceptible to hypotension.
Pasireotide: (Major) Pasireotide may cause a decrease in heart rate. Closely monitor patients who are also taking drugs associated with bradycardia such as calcium-channel blockers. Dose adjustments of calcium-channel blockers may be necessary.
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.
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 of MAOIs with calcium-channel 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.
Phenylephrine: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Photosensitizing agents (topical): (Minor) Preclinical data suggest that calcium-channel blockers could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Pindolol: (Moderate) Use clevidipine and pindolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
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.
Prazosin: (Moderate) Prazosin is well-known to produce a 'first-dose' phenomenon. Some patients develop significant hypotension shortly after administration of the first dose. The first dose response (acute postural hypotension) of prazosin may be exaggerated in patients who are receiving beta-adrenergic blockers, diuretics, or other antihypertensive agents. Concomitant administration of prazosin with other antihypertensive agents is not prohibited, however. This can be therapeutically advantageous, but lower dosages of each agent should be used. The use of alpha-blockers with verapamil can lead to excessive hypotension; In addition, verapamil has been reported to increase the AUC and Cmax of prazosin.
Prilocaine; Epinephrine: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
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: (Moderate) Phenylephrine's cardiovascular effects may reduce the antihypertensive effects of calcium-channel blockers. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear to be at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Propofol: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
Propranolol: (Moderate) Use clevidipine and propranolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Use clevidipine and propranolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
Pseudoephedrine; Triprolidine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by calcium-channel blockers. Monitor blood pressure and heart rate.
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 of MAOIs with calcium-channel 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 during concurrent use of an MAOI and a calcium-channel blocker.
Remifentanil: (Moderate) The risk of significant hypotension and/or bradycardia during therapy with remifentanil may be increased in patients receiving calcium-channel blockers due to additive hypotensive effects.
Risperidone: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Ritonavir: (Moderate) Ritonavir is expected to decrease the hepatic CYP metabolism of calcium-channel blockers (mainly through CYP3A4 inhibition) resulting in increased calcium-channel blocker concentrations. Ritonavir also prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including calcium channel blockers) has not been evaluated. If coadministration of these drugs is warranted, do so with caution and careful monitoring. Decreased calcium-channel blocker doses may be warranted.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients.
Sevoflurane: (Major) The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with general anesthetics may be potentiated by calcium-channel blockers. Alternatively, general anesthetics can potentiate the hypotensive effects of calcium-channel blockers. When used concomitantly, anesthetics and calcium-channel blockers should be titrated carefully to avoid excessive cardiovascular depression.
Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by calcium-channel blockers. False study results are possible in patients with drug-induced hyper- or hypo-responsiveness; thorough patient history is important in the interpretation of results.
Sufentanil: (Moderate) Monitor patients for bradycardia and hypotension when sufentanil is coadministered with clevidipine. Sufentanil may cause bradycardia. The risk of significant hypotension and/or bradycardia during therapy with sufentanil is increased in patients receiving clevidipine.
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.
Tamsulosin: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
Temsirolimus: (Moderate) Monitor for signs and symptoms of angioedema if temsirolimus is administered concomitantly with clevidipine Angioedema has been reported in patients taking mammalian target of rapamycin (mTOR) inhibitors in combination with another calcium channel blocker.
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 calcium-channel 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) Use clevidipine and timolol with caution due to risk for additive negative effects on heart rate, AV conduction, and/or cardiac contractility.
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.
Tranylcypromine: (Major) Avoid concomitant use of calcium-channel blockers and tranylcypromine due to the risk of additive hypotension. Potential for this interaction persists for up to 10 days after discontinuation of tranylcypromine (or 4 to 5 half-lives after discontinuation of the calcium-channel blocker). If a medication-free interval is not feasible, initiate therapy at the lowest appropriate dose and monitor blood pressure closely.
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.
Valdecoxib: (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.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with calcium channel blockers is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use with calcium channel blockers could enhance the rate of verteporfin uptake by the vascular endothelium, resulting in enhanced photosensitivity.

Clevidipine/Cleviprex Intravenous Inj Emulsion: 0.5mg, 1mL

Adults

32 mg/hour IV (Max: 1,000 mL/24 hours due to lipid load restrictions).

Geriatric

32 mg/hour IV (Max: 1,000 mL/24 hours due to lipid load restrictions).

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Clevidipine is an arterial selective dihydropyridine L-type calcium channel blocker. L-type calcium channels mediate the influx of calcium during depolarization in arterial smooth muscle cells. Clevidipine is associated with greater inotropic versus chronotropic selectivity and is associated with systemic, coronary, and pulmonary vasodilation without effects on venous capacitance vessels. In normal, healthy patients, clevidipine has been shown to cause reductions in systemic and pulmonary vascular resistance and mean arterial pressure, and an increase in stroke volume, with no change in venous return or cardiac filling pressure.

Clevidipine is administered intravenously. It is highly bound to plasma proteins (more than 99.5%) with a steady-state Vd of 0.17 L/kg in arterial blood. Metabolism occurs primarily via esterases in the blood and extravascular tissues. The majority (83%) of the drug is excreted in the urine (63% to 74%) and feces (7% to 22%). Arterial blood concentrations decrease in a multi-phase pattern after termination of infusion. The initial phase half-life is approximately 1 minute, accounting for 85% to 90% of the elimination of clevidipine. Terminal half-life is approximately 15 minutes.[34680]
 
Affected cytochrome P450 isoenzymes and drug transporters: none
At concentrations achieved in clinical practice, clevidipine and its major metabolite are unlikely to inhibit or induce any CYP enzymes.[34680] At high concentrations (i.e., concentrations not likely to be seen in clinical practice), in vitro data suggest it may induce CYP3A4 and inhibit CYP2C9, CYP2C19, and CYP3A4.[34334]

Intravenous Route

Clevidipine produces a 4% to 5% reduction in systolic blood pressure within 2 to 4 minutes of starting an infusion. In most patients, full recovery of blood pressure is achieved in 5 to 15 minutes after discontinuation.[34680]

Pregnancy

Available data from postmarketing reports of clevidipine use during pregnancy are not sufficient to determine a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Use clevidipine during pregnancy only if the potential benefit justifies the potential risk to the fetus. Clevidipine has been shown to cross the placenta in rats. Clevidipine was associated with increased incidences of intrauterine deaths, slightly reduced fetal weight, delayed skeletal development, abortion, and embryo lethality in animals that received doses higher than the expected human dose. In pregnant rats, a dose-related increase in mortality, length of gestation, and prolonged parturition occurred with clevidipine doses of 13, 35, and 55 mg/kg/day. No evidence of embryo-fetal malformation was observed with continuous intravenous clevidipine infusions in pregnant rats and rabbits at 2.8 and 7.6 times the maximum recommended human dose (MRHD) of 16 mg/hour, respectively. In pregnant rats and rabbits, embryo-fetal toxicity was observed with continuous intravenous infusion doses of 7.6 to 12 times the expected MRHD when administered during the period of major embryonic organogenesis.[34680]

It is not known whether clevidipine is excreted in human milk; consider possible infant exposure when clevidipine is administered to a breast-feeding woman.[34680] Previous American Academy of Pediatrics (AAP) recommendations considered the use of other calcium-channel blockers such as diltiazem and verapamil to be usually compatible with breast-feeding.[27500]