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]
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
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
Dosage and Administration
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.
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.
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
Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination
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
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. 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-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. 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
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. 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
Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Consider therapy modification
Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Test Interactions
May lead to false-negative aldosterone/renin ratio (ARR) (Funder 2016).
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%, postmarketing, and/or case reports: Dyspnea, hypersensitivity reaction, hypotension, increased serum triglycerides, intestinal obstruction, myocardial infarction, oxygen saturation decreased, syncope, tachycardia (reflex), 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
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events have been observed in animal reproduction studies.
Chronic maternal hypertension may increase the risk of birth defects, low birth weight, preterm delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to duration and severity of maternal hypertension. Untreated hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, myocardial infarction, preeclampsia, stroke, and delivery complications (ACOG 203 2019).
Calcium channel blockers may be used to treat hypertension in pregnant women; however, clevidipine is only available as an IV infusion. If a patient needs IV therapy for hypertension during pregnancy, other agents are more commonly utilized (ACOG 203 2019; ESC [Regitz-Zagrosek 2018]). Females with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]).
Patient Education
What is this drug used for?
- It is used to lower blood pressure.
Frequently reported side effects of this drug
- Headache
- Vomiting
- Nausea
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.
- Fast heartbeat
- Abnormal heartbeat
- Severe dizziness
- Passing out
- Vision changes
- Shortness of breath
- Excessive weight gain
- Swelling of arms or legs
- Signs of a significant reaction like 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. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
