Clevidipine Butyrate (Monograph)

Brand name: Cleviprex
Drug class: Dihydropyridines

Medically reviewed by Drugs.com on Sep 10, 2024. Written by ASHP.

Introduction

Calcium-channel blocking agent; dihydropyridine derivative.

Uses for Clevidipine Butyrate

Hypertension

Used to reduce BP when oral antihypertensive therapy not feasible or desirable.

Calcium-channel blockers considered one of several preferred antihypertensive drug classes for initial management of hypertension; other preferred options include ACE inhibitors, angiotensin II receptor antagonists, and thiazide diuretics.

Clevidipine used for management of perioperative hypertension (e.g., in cardiac surgery), essential hypertension, and severe hypertension (e.g., hypertensive emergencies).

Some experts state that clevidipine is one of the preferred agents for the management of hypertensive emergencies in patients with certain comorbidities such as acute pulmonary edema, acute renal failure, and acute sympathetic discharge or catecholamine excess states (e.g., pheochromocytoma^{† [off-label]}, post-carotid endarterectomy status). (See Pheochromocytoma under Cautions.)

Clevidipine Butyrate Dosage and Administration

General

• Individualize dosage according to the patient’s response to achieve the desired BP reduction.

• Monitor BP and heart rate continuously during IV infusion and until vital signs are stable. In patients being transferred to an oral antihypertensive agent, continue BP monitoring until the desired effect is achieved.

• Patients who receive prolonged infusions and are not transferred to other antihypertensives should be monitored for rebound hypertension for ≥8 hours following discontinuance of infusion. (See Rebound Hypertension under Cautions.)

• Hypertensive emergency in adults with a compelling indication (i.e., severe preeclampsia or eclampsia, pheochromocytoma crisis^{† [off-label]}): Reduce SBP to <140 mm Hg during the first hour.

• Hypertensive emergency in adults with a compelling indication (acute aortic dissection): Reduce SBP to <120 mm Hg within first 20 minutes.

• Hypertensive emergency in adults without a compelling indication: Initially, reduce SBP by ≤25% within the first hour, followed by further BP reduction if stable to 160/110 or 160/100 mm Hg within the next 2–6 hours; avoid excessive declines in BP that could precipitate renal, cerebral, or coronary ischemia. If this BP is well tolerated and the patient is clinically stable, may implement further gradual reductions toward normal BP in the next 24–48 hours.

Administration

IV Administration

Administer by IV infusion into a central or peripheral vein using an infusion device allowing calibrated infusion rates.

Commercially available standard plastic cannulae may be used to administer the infusion.

Vials are for single use only.

Use strict aseptic technique since emulsion can support microbial growth.

Invert vials gently several times before use to ensure uniformity of the emulsion prior to administration.

Administration must be completed within 12 hours after initial puncture of the vial stopper; discard any unused portions after 12 hours.

Do not administer in the same IV line as other drugs.

Clevidipine emulsion should not be diluted; however, it may be administered with sterile water for injection, 0.9% sodium chloride injection, 5% dextrose injection, 5% dextrose and 0.9% sodium chloride injection, lactated Ringer’s and 5% dextrose injection, lactated Ringer’s injection, or 10% amino acid injection.

Standardize 4 Safety

Standardized concentrations for clevidipine have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. Because recommendations from the S4S panels may differ from the manufacturer’s prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. For additional information on S4S (including updates that may be available), see [Web].

Dosing units differ from concentration units

Dosage

Available as clevidipine butyrate; dosage expressed in terms of the salt.

Adults

Hypertension

IV

Initially, 1–2 mg/hour. Initially, dosage may be doubled at short (90-second) intervals; as BP approaches the desired value, increase dosage in smaller increments (less than doubling) at 5- to 10-minute intervals.

An increase in dosage of approximately 1–2 mg/hour generally produces an additional 2- to 4-mm Hg decrease in SBP. Desired therapeutic responses usually occur at dosages of 4–6 mg/hour.

Patients with severe hypertension: Most patients have received maximum dosages of ≤16 mg/hour; however, dosages up to 32 mg/hour may be required.

Patients being transferred to an oral antihypertensive agent: Discontinue clevidipine or decrease dosage while appropriate oral therapy is established; consider lag time to onset of the oral antihypertensive agent’s effects.

Prescribing Limits

Adults

Hypertension

IV

Usually, maximum 16 mg/hour; limited, short-term experience with dosages up to 32 mg/hour and limited experience with infusion durations >72 hours at any dosage.

Do not administer >1 L of clevidipine emulsion in a 24-hour period (average clevidipine butyrate dosage of 21 mg/hour) because each mL of emulsion contains 200 mg of lipids. (See Lipid Intake under Cautions.)

Special Populations

Hepatic Impairment

Hypertension

IV

Initially, 1–2 mg/hour.

Renal Impairment

Hypertension

IV

Patients with moderate to severe renal impairment: Initially, 1–2 mg/hour.

Geriatric Patients

Careful dosage selection, usually starting at the low end of the dosing range, recommended due to possible age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Cautions for Clevidipine Butyrate

Contraindications

• Defective lipid metabolism (e.g., pathologic hyperlipemia, lipoid nephrosis, acute pancreatitis associated with hyperlipemia).

• Severe aortic stenosis (because afterload reduction may reduce myocardial oxygen delivery).

• Known hypersensitivity to soybeans, soy products, eggs, or egg product.

Warnings/Precautions

Hypotension and Reflex Tachycardia

Possible hypotension and reflex tachycardia.

Reduce dosage if either systemic hypotension or reflex tachycardia occurs. Use of β-adrenergic blocking agents for treatment for clevidipine-induced tachycardia is not recommended.

Lipid Intake

Lipid intake restrictions may be necessary for patients with substantial disorders of lipid metabolism since commercially available clevidipine is an oil-in-water emulsion.

May need to restrict concurrently administered lipids to compensate for the lipid content of the clevidipine formulation (1 mL of clevidipine emulsion contains 0.2 g of fat [2 kcal]). Clevidipine is contraindicated in patients with defective lipid metabolism. (See Contraindications.)

Negative Inotropic Effects

Potential negative inotropic effects; may precipitate or worsen heart failure. Carefully monitor patients with heart failure.

β-Adrenergic Blocker Withdrawal

Clevidipine is not a β-adrenergic blocking agent and offers no protection against abrupt withdrawal of concomitant β-adrenergic blocking agent therapy; withdraw therapy with β-adrenergic blocking agents gradually.

Rebound Hypertension

Rebound hypertension reported following discontinuance of prolonged clevidipine infusions (up to 72 hours) in patients who were not transferred to other antihypertensive therapy. Monitor for rebound hypertension for at least 8 hours following discontinuance of infusion.

Pheochromocytoma

Manufacturer states that use of clevidipine in the treatment of hypertension associated with pheochromocytoma not established. However, some experts state that the drug may be used in patients with a hypertensive emergency associated with acute sympathetic discharge or catecholamine excess states (e.g., pheochromocytoma, post-carotid endarterectomy status).

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether clevidipine is distributed into milk. Consider possible infant exposure when clevidipine is used in nursing women.

Pediatric Use

Safety and efficacy not established in children <18 years of age.

Geriatric Use

Safety and efficacy in those ≥65 years of age similar to that in younger adults.

Common Adverse Effects

Nausea, vomiting, chest discomfort, headache, atrial fibrillation, fever, insomnia, acute renal failure, edema.

Drug Interactions

No clinical drug interaction studies performed to date.

Does not appear to inhibit or induce CYP isoenzymes at clinically relevant concentrations in vitro.

Clevidipine Butyrate Pharmacokinetics

Absorption

Onset

Reduces SBP by 4–5% within 2–4 minutes after initiation of an IV infusion of 0.4 mcg/kg per minute.

Duration

Full recovery of BP generally occurs within 5–15 minutes following discontinuance of infusion.

Distribution

Extent

Rapidly distributed.

Plasma Protein Binding

>99.5%.

Elimination

Metabolism

Rapidly metabolized via hydrolysis, principally by esterases in the blood and extravascular tissues, to form an inactive carboxylic acid metabolite and formaldehyde.

Elimination Route

Excreted in urine (63–74%) and in feces (7–22%).

Half-life

Multiphasic; initial half-life is about 1 minute (accounts for 85–90% of elimination) and terminal half-life is about 15 minutes.

Special Populations

Elimination unlikely to be affected by hepatic or renal dysfunction.

Stability

Storage

Parenteral

Injectable Emulsion

2–8°C; protect form light by storing in carton. Do not freeze.

Vials may be removed from refrigerator and stored at 25°C for ≤2 months; however, may not be returned to refrigerator.

Compatibility

Parenteral

Solution Compatibility

Actions

• Inhibits transmembrane influx of calcium ions during depolarization in arterial smooth muscle.

• Reduces mean arterial BP by decreasing systemic vascular resistance, but does not appear to reduce cardiac filling pressure (i.e., preload), confirming lack of effects on venous capacitance vessels.

Advice to Patients

• Importance of advising patients with underlying hypertension that they require continued monitoring of their condition and importance of taking oral antihypertensive drugs as directed.

• Importance of contacting a clinician immediately if symptoms of a new hypertensive emergency occur (e.g., neurologic symptoms, visual changes, evidence of CHF).

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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