Clevidipine

CLASS

  • A dihydropyridine calcium channel blocker

INDICATIONS

  1. Acute hypertensive crisis
  2. Perioperative BP control

ADMINISTRATION / DOSING

  • Intravenous (IV)
  • Infusion: Comes neat, 50 mg in 100 mL (0.5 mg/mL)
    • Start infusion at 1-2 mg/h, doubling every 90 seconds until BP target achieved
      • The most common maintenance dose is 4-6 mg/h
      • Peak BP effect of 2-10 min after initiation
      • As BP target approaches, slow adjustment rate down to every 5-10 min
      • MAX infusion rate of 32 mg/h
    • Infusion duration/rate may be limited by lipid emulsion
  • There is no experience in using clevidipine in the paediatric population
  • There is no experience with the use of clevidipine for greater than 72 hours

MECHANISM OF ACTION

  • Vasoselective (arterioles), short-acting, dihydropyridine, L-type calcium channel antagonist
  • Studies suggest action on arterial blood pressure and sparing of venous capacitance vessels (unlike GTN and SNiP)
  • Also acts on coronary artery smooth muscle to reduce vascular resistance and myocardial oxygen requirements
  • Minimal effect on myocardial cells
  • Ultra-short onset of action

PHARMACEUTICS

  • Excipients: soya oil, glycerol, egg lecithin, oleic acid, disodium acetate, water for injection and sodium hydroxide for pH
  • Store at 2-8oC, protect from light
  • Supplied in glass vials with a grey silicone butyl-elastomer stopper
  • Clevidipine is a white to off-white powder, and it is practically insoluble in water
  • pH of 6.0-8.0
  • 0.2 g of lipid per 1 mL

PHARMACOKINETICS

  • Absorption
    • Bioavailability is close to 100%
    • Peak plasma levels are achieved at ~1.3 hours post PO dose
  • Distribution
    • >99.5% protein bound
    • Steady-state Vd of 0.17 L/kg
  • Metabolism
    • Rapid metabolism by hydrolysis primarily by esterases in the blood and extravascular tissues (unlikely to be affected by hepatic and/or renal disease)
    • Primary metabolite is the carboxylic acid (inactive) and formaldehyde (the production of which at the max infusion of 32 mg/h is at least several hundred times less than endogenous formation)
    • Carboxylic acid is then further metabolised by glucuronidation or oxidation to a pyridine derivative
    • No effect on the P450 enzyme system
  • Elimination
    • Clearance of the primary metabolite is 0.03 L/h/kg with metabolite terminal T1/2 of ~9 hours
    • T1/2: 1 min / Terminal T1/2 of 15 min
    • 83% of drug excreted in urine and faeces, with major fraction of ~63-74% in the urine

PHARMACODYNAMICS

  • CVS
    • Dose-dependent reduction in systemic vascular resistance
    • No effect on venous capacitance vessels, thus no change in cardiac preload
    • Reflex tachycardia
    • Coronary artery vasodilator
    • Increased rates of atrial fibrillation in post-operative patients
  • RESP
    • Unknown effects on pulmonary vascular resistance
  • CNS:
    • May cause a headache, nausea
  • GIT
    • Calcium channel blockers are known to decrease gut motility and cause constipation
  • GUT
    • Calcium channel blockers are known to decrease renovascular resistance
  • OTHER
    • May cause flushing

CONTRAINDICATIONS

  • Patients with defective lipid metabolism such as pathologic hyperlipaemia, lipoid nephrosis, or acute pancreatitis from hyperlipidaemia
  • Allergies to soybeans, soy products, egg or egg products
  • Caution with severe aortic stenosis (as with any anti-hypertensive infusions) may reduce myocardial oxygen delivery

INTERACTIONS

  • Clopidogrel – may result in a reduction of the antiplatelet effect
  • Lacosamide – in combination with any calcium channel blocker may prolong PR interval
  • Digoxin – in combination with any calcium channel blocker may result in complete heart block
  • Dantrolene – in combination with any calcium channel blocker may result in severe hyperkalaemia
  • Epirubicin – in combination with any calcium channel blocker may increase the risk of heart failure

EVIDENCE

  • ACCELERATE Trial (2013): Intracerebral haemorrhage (ICH) (surgical and non-surgical patients) pilot study looking at the effectiveness of monotherapy with clevidipine in maintaining blood pressure targets. It was an effective monotherapy agent, BP targets were met within 5 minutes.
  • ECLIPSE Trial (2008): Perioperative cardiac surgery blood pressure management comparing clevidipine, nitroglycerin, sodium nitroprusside, and nicardipine. Data analysed from three prospective, randomised, open-label, parallel comparison studies. 61 medical centres, 1512 patients included. No difference in myocardial infarction, stroke, or renal dysfunction; no difference in mortality for clevidipine, nitroglycerin or nicardipine. Mortality was significantly increased for sodium nitroprusside patients compared with clevidipine.

LITFL

References

  • Aronson S, Dyke CM, Stierer KA, Levy JH, Cheung AT, Lumb PD, Kereiakes DJ, Newman MF. The ECLIPSE trials: comparative studies of clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine for acute hypertension treatment in cardiac surgery patients. Anesth Analg. 2008 Oct;107(4):1110-21. doi: 10.1213/ane.0b013e31818240db. PMID: 18806012.
  • Australian Injectable Drugs Handbook, 8th Edition. (2022). Retrieved 01 September 2022, from https://aidh.hcn.com.au/
  • Australian Medicines Handbook. (2022). Retrieved 01 September 2022, from https://amhonline.amh.net.au/
  • Graffagnino C, Bergese S, Love J, Schneider D, Lazaridis C, LaPointe M, Lee K, Lynch G, Hu MY, Williams GC. Clevidipine rapidly and safely reduces blood pressure in acute intracerebral hemorrhage: the ACCELERATE trial. Cerebrovasc Dis. 2013;36(3):173-80. doi: 10.1159/000351149. Epub 2013 Oct 12. PMID: 24135526.
  • IBM Micromedex. (2022). Retrieved 01 September 2022, from https://www.micromedexsolutions.com

Cite this article as: James Pearlman, "Clevidipine," In: LITFL - Life in the FastLane, Accessed on November 29, 2022, https://litfl.com/clevidipine/.

Critical Care

Compendium

ICU Advanced Trainee BMedSci [UoN], BMed [UoN], MMed(CritCare) [USyd] from a broadacre farm who found himself in a quaternary metropolitan ICU. Always trying to make medical education more interesting and appropriately targeted; pre-hospital and retrieval curious; passionate about equitable access to healthcare; looking forward to a future life in regional Australia. Student of LITFL.

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.