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Cleviprex (clevidipine) Review | #MEDSHED

Updated: Jul 24, 2023

My favorite lipid emulsion for hypertensive emergencies — keep the propofol for sedation

 

I have no relationships to report with the drug manufacturer. It is extremely effective, working like butter in the right hands. IMAGE


The content of this article is an educational reference intended to supplement your current practice, and encouraged to prompt the reader to come to their own conclusion about the drug. I welcome all discussions about medications!

Cleviprex (clevidipine) is a novel L-type intravenous dihydropyridine calcium channel blocker with potent blood pressure lowering effects. The medication is similar to Cardene (nicardipine), but with more favorable pharmacokinetics.


 

What is the mechanism of action for clevidipine?

  • Inhibits L-type calcium channels during depolarization, resulting in vasodilation by reducing systemic vascular resistance

Dosing parameters can be a bit tricky and requires hands-on titration

  • Initial: 1–2 mg/hr (max 21 mg/hr)

  • Titration: double rate every 90 seconds until approaching blood pressure goal, then extend titration interval to 5 to 15 minutes

  • Maintenance: 4–6 mg/hr is usually the sweet spot for most patients, but can go up to maximum of 21 mg/hr

  • Limited efficacy and safety data with infusions > 72 hours

  • If the medication is new to you, give your friendly neighrborhood emergency medicine or critical care pharmacist a call 😀.

Favorable pharmacokinetics makes clevidipine an ideal agent

Cleviprex (clevidipine) package insert, Cardene (nicardipine) package insert, Cleviprex (clevidipine). Dosage Forms. Hudson, OH: Lexicomp, Feb 24 2023. http://online.lexi.com/.Jan 30 2023., Nicardipine. Dosage Forms. Hudson, OH: Lexicomp, Feb 24 2023. http://online.lexi.com/.Jan 30 2023. My masterpiece


General clinical indications for clevidipine (literature analysis intended for GREYZONE series)

  • Indicated for hypertensive emergencies when oral options are inappropriate

  • Reduces SVR, resulting in AFTERLOAD reduction

  • Minimal effect on preload in comparison to nitroglycerin



  • Ideal agent for intracranial hemorrhages given lipophilicity and readily crosses the blood brain barrier. In the right patient cases, it’s great to use when transitioning to oral calcium channel blockers.



  • Keep in your toolbox as an alternative to Nipride (sodium nitroprusside) in the setting of acute aortic syndromes. Esmolol and clevidipine run together well for aortic dissections.


  • Comparable to nitroglycerin, sodium nitroprusside, and nicardipine for lowering blood pressure, and had a similar incidence of adverse drugs reactions in cardiac surgery patients.

Considerations in the practical application and usage of clevidipine

  • Dosing recommendations derived from The Eclipse Trials, linked above. Patients were in a controlled environment (medications titrated pre-surgery cuff every 15 minutes prior to procedure, then every 5 during procedure).

  • This is where mistakes happen. Unfamiliar drug. Follow package insert/electronic resource. Titrate every 90 seconds? Say no more. You may have an obtunded patient around 10 minutes.

  • I reserve utilizing clevidipine when acute blood pressure lowering is required greater than 20% reduction within 1–2 hours and/or working with tight blood pressure parameters.

  • Really the only indications that make sense to me (so far) for patients coming through the door are non-ruptured aortic dissections and BP reduction < 185/110 mmHg for alteplase administration.

  • Hypertensive emergencies in the setting of pregnancy wouldn’t apply here given clevidipine hasn’t had enough evidence to make a recommendation for this patient population.

  • For a majority of hypertensive emergencies, you’ll start with IV pushes (labetolol, hydralazine, etc). Additionally, you’ll likely need to get a CT scan to determine etiology of symptoms.

  • IV pushes are more feasible with limited access (contrast administration) compared to getting clevidipine procured, primed into pump, and playing catch-up (just to overshoot), especially if you’re in CT. Don’t delay care for a fancy, “newer” drug.

  • Reserving clevidipine for cases like dissections and ischemic strokes (for alteplase administration) allows you to stay on top of tight parameters with the short half-life

  • Always take into account lingering antihypertensive effects of meds given prior. Hydralazine is garbage given its unpredictable pharmacokinetics.

  • Priorities over clevidipine with 1 point of IV access (in most cases): contrast and alteplase.

  • Clevidipine should only be considered with at least 2 points of access to ensure timely diagnostics and therapies.

Clevidipine readily crosses the blood barrier given lipophilicity

  • In the setting of ischemic strokes, an IV bolus of labetolol should buy you time to determine response to labetolol dose in relation to target BP, prompting another bolus vs clevidipine running at 2–6 mg/hr to SAFELY give alteplase. There’s a risk of overshooting with repeat doses of labetolol. Oh sugar, the duration of four hours isn’t doing our patient good.

  • It works well if you are near alteplase blood pressure administration goals. You can run clevidipine at a lower rate and park it to remain within blood pressure goal to ensure perfusion of the brain.

Clevidipine and esmolol combined are a reasonable alternative for aortic dissections

  • For impending SHTF aortic dissections (non-ruptured), beta blockade must be achieved (and sustained) prior to starting vasodilators, such as clevidipine, to prevent reflex tachycardia. More stress on the aorta, and that’s bad. Again, labetolol can be a great transitional drug to esmolol/clevidipine as both are compatible.

Titration considerations because a lot is probably going on

  • Remember, you’ll be working with a blood pressure cuff initially. Cycle it at 5 minutes; anything less will give you a false reading and/or misrepresent clevidipine response.

  • If you need immediate blood pressure reduction, start 2 mg/hr and then increase to 4 mg/hr at the 90 second mark. The five-minute interval BP reading should give you the best sense of 4 mg/hr since it’ll be closest to steady state since its been infusing for more than 270 seconds, giving you more information to work with.

  • Getting to 8mg/hr within 5 minutes risks overshooting, by a lot actually since technically it’d be running at 8 mg/hr for 2 minutes and the BP cuff reading is likely playing catch up. And that’s if you’re on the dot with uptitrating.

  • Starting 1 mg/hr, increasing to 2 mg/hr at 90 seconds, 4 mg/hr at 180 seconds will leave you with less accurate information for the next titration. You could be undertreating and waiting until another cuff cycle, or you risk overshooting and worsen hypoperfusion.

  • The maintenance range is 4 — 6mg/hr, so I’d like to get to 4 mg/hr closest to steady state to either increase to 6 mg/hr vs double to 8mg/hr to achieve goal safely, for most cases.

  • Notice how I’ve only been working within a timeframe of 5–10 minutes. With a half-life of around one minute, this makes sense if we’re maximizing the pharmacokinetics.

  • May be a small difference, but time is brain/heart/life tbh. It’s important to review these things because it’s fairly newer to some hospitals, there’s a lot of fresh, new team members given the high COVID turnover, and a lack of consistency within health care systems.

  • If clevidipine is available at your facility, loop in your friendly emergency medicine or critical care pharmacist to get you familiar with the medication.

Several other reasons why clevidipine stays in my drug bank

  • Clevidipine is metabolized via red blood cell and tissue esterases compared to renal or hepatic clearance. There is less concern for accumulation/efficacy secondary to organ dysfunction and drug-to-drug interactions.

  • Compatible with more medications used in acute hypertensive emergencies amongst my tools compared to nicardipine.

  • You’ll often find yourself in a pickle when iodine is needed with one point of access. Hence, I only consider it with two lines.

  • If you overshoot your target BP goal, pause the infusion. Hypotension is usually responsive to fluids. Additionally, blood pressures should improve given clevidipine’s short half life (~1 minute).

  • There are guidelines on blood pressure goals. I tend to shoot for 10 mmHg above that to goal minimize the risk of overshooting.

  • This shouldn’t be your first-line antihypertensive in a majority of acute hypertensive emergencies since it’ll take time to procure medication, prime tubing, set up pump, etc.

  • Utilize intravenous push (labetalol, hydralazine) to buy you time as you’re setting up the pump, when appropriate. Keep it simple.

  • Even though clevidipine is newer than nicardipine, the cost per vial is actually less than nicardipine (see above table per Lexicomp). This doesn’t include drug acquisition costs, contract agreements, etc. Although, it’s definitely a conversation starter if this isn’t a part of your formulary.

I am not saying go crazy with clevidipine, but it has a good use for that specific patient in experienced hands

Clevidipine is an excellent tool to keep as a part of your toolbox. Being able to actively titrate a rapid-acting, fast-off antihypertensive with an experienced caregiver in the emergency department minimizes potentially overshooting/undertreating. The high potency and rapid onset does increase the risk of harm in those unfamiliar with the medication. There will be some cases when nicardipine is preferred (hypertriglycerdemia, soy/egg product allergy, familarity, etc). Just like every other pharmacologic agent in your drug bank, clevidipine has a great use for the right patient.


If you would like for me to cover specific topics, have questions on any material discussed, or simply reach out, drop a comment below.


 

I do not have any relationships to report. This is for educational purposes only. This is not medical advice. As always, patient-centered care relies on your clinical judgement. Refer to institutional policies, guidelines, and standard operating manuals to abide by employer requirements. Emergency medicine pharmacist responsibilities referenced are within the context of writer’s practicing state; practice according to your state law. The content of this article are based on my views and personal experiences, and are not representative of any affiliation I am associated with.

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