Version January 2024
Acute ischemic stroke, BP management with reperfusion therapy (off-label use):
Note: Prior to reperfusion therapy (thrombolytic and/or mechanical thrombectomy), maintain a target BP of ≤185/110 mm Hg. If BP remains >185/110 mm Hg, do not administer thrombolytic. During and 24 hours after start of thrombolytic therapy, maintain a target BP of ≤180/105 mm Hg; if hypertension is refractory or diastolic BP >140 mm Hg, consider alternative therapy (Ref).
Continuous IV infusion: Initial: 1 to 2 mg/hour; titrate by doubling the dose at 90 second intervals (maximum dose: 21 mg/hour; 1 L/day due to lipid load restriction) (Ref). As BP approaches goal, may titrate more slowly (eg, increase dose by less than doubling 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 BP may occur. Data are limited beyond 72 hours.
Hypertension:
Note: When used for hypertensive emergency, in general, reduce mean arterial blood pressure gradually by ~10% to 20% over the first hour, then by an additional 5% to 15% over the next 23 hours. Invasive blood pressure monitoring is recommended for appropriate dose titration (Ref).
Continuous IV infusion: Initial: 1 to 2 mg/hour; titrate by doubling the dose at 90-second intervals; as blood pressure approaches goal, increase dose by smaller increments every 5 to 10 minutes to achieve the target blood pressure. Each 1 to 2 mg/hour increase in dose produces an additional reduction of ~2 to 4 mm Hg in systolic blood pressure; usual dosage range: 4 to 6 mg/hour; maximum dose (not well established): average 21 mg/hour over 24 hours (ie, equivalent to a maximum volume of 1 L/day due to lipid load restriction). Data are limited for use beyond 72 hours.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No adjustment required with initial infusion rate.
No adjustment required with initial infusion rate.
Refer to adult dosing. Initiate at the low end of the dosage range.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Atrial fibrillation (21%)
Gastrointestinal: Nausea (5% to 21%)
1% to 10%:
Gastrointestinal: Vomiting (3%)
Nervous system: Headache (6%)
Renal: Acute kidney injury (9%)
<1%:
Cardiovascular: Acute myocardial infarction, syncope
Respiratory: Dyspnea
Postmarketing:
Cardiovascular: Hypotension, tachycardia (reflex)
Dermatologic: Psoriasis (Song 2021)
Endocrine & metabolic: Increased serum triglycerides
Gastrointestinal: Intestinal obstruction
Hypersensitivity: Hypersensitivity reaction
Respiratory: Hypoxemia (Short 2020), oxygen saturation decreased
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
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 (AHA/ACC/HFSA [Heidenreich 2022]).
• Pheochromocytoma: Use in hypertension associated with pheochromocytoma has not been studied.
Other warnings/precautions:
• Infection risk: To limit the potential for contamination, maintain aseptic technique while handling; use within 12 hours of puncturing vial.
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 (edta) disodium, egg yolk phospholipids, soybean oil]
No
Emulsion (Cleviprex Intravenous)
25 mg/50 mL (per mL): $1.99
50 mg/100 mL (per mL): $1.99
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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.
Hypertension: Management of hypertension when oral therapy is not feasible or not desirable.
Acute ischemic stroke, BP management with reperfusion therapy
Clevidipine may be confused with cladribine, clofarabine, clomiPRAMINE
Cleviprex may be confused with Claravis
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: 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. Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy
Dantrolene: May enhance the hyperkalemic effect of Calcium Channel Blockers. Dantrolene may enhance the negative inotropic effect of Calcium Channel Blockers. Risk X: Avoid combination
Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Indoramin: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Inhalational Anesthetics: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Loop Diuretics: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the adverse/toxic effect of Calcium Channel Blockers (Dihydropyridine). Specifically, the risk of hypotension or muscle weakness may be increased. Risk C: Monitor therapy
Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: 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. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Prazosin: Antihypertensive Agents may enhance the hypotensive effect of Prazosin. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: 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. Risk D: Consider therapy modification
Terazosin: Antihypertensive Agents may enhance the hypotensive effect of Terazosin. Risk C: Monitor therapy
Urapidil: Antihypertensive Agents may enhance the hypotensive effect of Urapidil. Risk C: Monitor therapy
Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be used in patients trying to conceive. Clevidipine is not considered a preferred agent for use in pregnant patients; consider transitioning to a preferred agent in patients planning to become pregnant (ACC/AHA [Whelton 2018]; ACOG 2019; NICE 2019).
Adverse events have been observed in animal reproduction studies.
Chronic maternal hypertension is associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to the duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 2019).
Patients with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]). Calcium channel blockers may be used to treat hypertension in pregnant patients; however, clevidipine is only available as an IV infusion. If a patient needs IV therapy for hypertension during pregnancy, other agents may be preferred (ACOG 2019; ESC [Cífková 2020]; ESC [Regitz-Zagrosek 2018]).
It is not known if clevidipine is present in breast milk.
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.
BP; heart rate; 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. Monitor triglycerides with concurrent administration with propofol (or other sources of lipids) (Kaur 2018).
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.
Onset of action: 2 to 4 minutes after start of infusion
Duration: IV: 5 to 15 minutes
Distribution: Vdss: 0.17 L/kg
Protein binding: >99.5%
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.
Half-life elimination: Biphasic: Initial: 1 minute (predominant); Terminal: ~15 minutes
Excretion: Urine (63% to 74%); feces (7% to 22%)
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