Skip to Content

Clevidipine

Pronunciation

(klev ID i peen)

Index Terms

  • Clevidipine Butyrate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Emulsion, Intravenous:

Cleviprex: 0.5 mg/mL (50 mL, 100 mL) [contains edetate disodium, egg yolk phospholipids, soybean oil]

Brand Names: U.S.

  • Cleviprex

Pharmacologic Category

  • Antihypertensive
  • Calcium Channel Blocker
  • Calcium Channel Blocker, Dihydropyridine

Pharmacology

Dihydropyridine calcium channel blocker with potent arterial vasodilating activity. Inhibits calcium ion influx through the L-type calcium channels during depolarization in arterial smooth muscle, producing a decrease in mean arterial pressure (MAP) by reducing systemic vascular resistance.

Distribution

Vdss: 0.17 L/kg

Metabolism

Rapid hydrolysis primarily by esterases in blood and extravascular tissues to an inactive carboxylic acid metabolite and formaldehyde; carboxylic acid metabolite is further metabolized by glucuronidation or oxidation to the pyridine derivative.

Excretion

Urine (63% to 74%); feces (7% to 22%)

Onset of Action

2 to 4 minutes after start of infusion

Duration of Action

IV: 5 to 15 minutes

Half-Life Elimination

Biphasic: Initial: 1 minute (predominant); Terminal: ~15 minutes

Protein Binding

>99.5%

Use: Labeled Indications

Hypertension: Management of hypertension when oral therapy is not feasible or not desirable.

Contraindications

Hypersensitivity to clevidipine or any component of the formulation; allergy to soybeans, soy products, eggs, or egg products; patients with defective lipid metabolism (eg, pathologic hyperlipidemia, lipoid nephrosis or acute pancreatitis if accompanied by hyperlipidemia); severe aortic stenosis

Dosing: Adult

Hypertension: IV: Initial: 1 to 2 mg/hour

Titration: Initial: Dose may be doubled at 90-second intervals toward blood pressure goal. As blood pressure approaches goal, dose may be increased by less than double every 5 to 10 minutes. Note: For every 1 to 2 mg/hour increase in dose, an approximate reduction of 2 to 4 mm Hg in systolic blood pressure may occur.

Usual maintenance: 4 to 6 mg/hour; maximum: 21 mg/hour (1,000 mL/24 hours due to lipid load restriction). Most patients in clinical trials were treated with doses ≤16 mg/hour. In patients with severe hypertension, there is limited short-term experience with doses up to 32 mg/hour. Data is limited beyond 72 hours

Dosing: Geriatric

Refer to adult dosing. Initiate at the low end of the dosage range.

Dosing: Renal Impairment

No adjustment required with initial infusion rate.

Dosing: Hepatic Impairment

No adjustment required with initial infusion rate.

Administration

IV: Maintain aseptic technique. Do not use if contamination is suspected. Do not dilute. Invert vial gently several times to ensure uniformity of emulsion prior to administration. Administer as a slow continuous infusion via central or peripheral line, using infusion device allowing for calibrated infusion rates.

Dietary Considerations

Clevidipine is formulated in an oil-in-water emulsion containing 200 mg/mL of lipid (2 kcal/mL). If on parenteral nutrition, may need to adjust the amount of lipid infused. Emulsion contains soybean oil, egg yolk phospholipids, and glycerin.

Compatibility

Do not mix with or administer in same line with other medications.

Storage

Store in refrigerator at 2°C to 8°C (36°F to 46°F). Unopened vials are stable for 2 months at room temperature. Use within 12 hours of puncturing vial; discard any tubing and unused portion, including that currently being infused. Protect from light during storage. Do not freeze.

Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Atosiban: Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Calcium Channel Blockers (Nondihydropyridine): Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Monitor therapy

Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Efavirenz: May decrease the serum concentration of Calcium Channel Blockers. Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy

Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

QuiNIDine: Calcium Channel Blockers (Dihydropyridine) may decrease the serum concentration of QuiNIDine. Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of QuiNIDine. QuiNIDine may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Adverse Reactions

>10%:

Cardiovascular: Atrial fibrillation (21%)

Central nervous system: Insomnia (12%)

Gastrointestinal: Nausea (5% to 21%)

Miscellaneous: Fever (19%)

1% to 10%:

Central nervous system: Headache (6%)

Gastrointestinal: Vomiting (3%)

Hematologic & oncologic: Postprocedural hemorrhage (3%)

Renal: Acute renal failure (9%)

Respiratory: Pneumonia (3%), respiratory failure (3%)

<1% (Limited to important or life-threatening): Dyspnea, hypersensitivity reaction, hypotension, intestinal obstruction, myocardial infarction, oxygen saturation decreased, reflex tachycardia, syncope, thrombophlebitis

Warnings/Precautions

Concerns related to adverse effects:

• Hypertriglyceridemia: Clevidipine is formulated within a 20% fat emulsion (0.2 g/mL); hypertriglyceridemia is an expected side effect with high-dose or extended treatment periods; median infusion duration in clinical trials was approximately 6 hours (Aronson 2008). Patients who develop hypertriglyceridemia (eg, >500 mg/dL) are at risk of developing pancreatitis. A reduction in the quantity of concurrently administered lipids may be necessary to compensate for the amount of lipid in the infusion. Use is contraindicated in patients with defective lipid metabolism (eg, pathologic hyperlipidemia, lipoid nephrosis or acute pancreatitis if accompanied by hyperlipidemia).

• Cardiovascular effects: Systemic hypotension may occur; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. Reflex tachycardia may occur and may result in angina or myocardial infarction in patients with obstructive coronary disease. In both situations, reduce clevidipine dose or discontinue if profound; do not treat clevidipine-induced tachycardia with beta-blockers. Rebound hypertension may occur with prolonged use in patients not transitioned to other antihypertensive therapy; monitor these patients carefully for at least 8 hours after discontinuation of infusion.

Disease-related concerns:

• Heart failure (HF): Dihydropyridine calcium channel blockers may cause negative inotropic effects and exacerbate HF. Avoid use in patients with HF due to lack of benefit and/or worse outcomes with calcium channel blockers in general (ACCF/AHA [Yancy 2013]).

• Pheochromocytoma: Use in hypertension associated with pheochromocytoma has not been studied.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Infection risk: To limit the potential for contamination, maintain aseptic technique while handling; use within 12 hours of puncturing vial.

Monitoring Parameters

Blood pressure and heart rate continually during infusion and until vital signs are stable after discontinuation (Keating 2014); patients who receive prolonged infusions of clevidipine and are not transitioned to other antihypertensive therapy should be monitored for at least 8 hours after discontinuation.

Consult individual institutional policies and procedures.

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Untreated chronic maternal hypertension is associated with adverse events in the fetus, infant, and mother. If treatment for hypertension during pregnancy is needed, other agents are preferred (ACOG 2012).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, vomiting, or nausea. Have patient report immediately to prescriber tachycardia, abnormal heartbeat, severe dizziness, passing out, urinary retention, change in amount of urine passed, vision changes, shortness of breath, excessive weight gain, or swelling of arms or legs (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Hide