Cleviprex – Why have I never heard of this stuff?

You are called to transport a 62 year-old female that has been admitted to a critical access hospital with a history of hypertension and acute neurological decompensation (onset of left sided weakness 4 hours prior to initial patient contact). Her initial NIH Stroke Scale is 24.  She is being transported to a neuro-interventional stroke center 50 miles away.

This patient was admitted to the local intensive care unit with a sustained blood pressure of 240/165 in both upper extremities. She was electively intubated prior to transport for airway protection secondary to continued neurologic decompensation.

Initial Assessment/Report:

Upon transport team arrival, the patient is intubated, sedated and supported by mechanical ventilation. Her heart rate is 62 bpm, blood pressure 165/88 (114), an oxygen saturation of 98% and an end-tidal CO₂ (EtCO₂) of 36 mmHg. Her spontaneous respiratory rate is 20 bpm, with a set rate (SIMV) of 14 bpm. Additional ventilator settings include an FiO₂ of 0.21 and a PEEP of 5 cmH₂O.  She has equal pupils, left sided paralysis and facial droop. She would cough, gag and track caregivers with her eyes when stimulated.

During the assessment, it is noted that the patient has two fluid infusions that are both milky white in color running in 2 separate peripheral lines. As any astute provider would ask, you query the bedside nurse as to the reason Diprivan is infusing in 2 separate lines.

This equally astute nurse answers with a well-deserved eye roll, “One line is Diprivan at 30mcg/kg/min and the second line is Cleviprex at 8 mg/hr.”

And again, as an astute provider of aeromedical care, you consult Dr. Google…“What is Cleviprex?”

Ok…I looked at Wikipedia First…Don’t Judge!

• Dihydropyridine Calcium Channel Blocker
  • AKA an L-Type Calcium Channel Blocker
  • Decreases the SVR but does not reduce pre-load (these drugs have no effect on venous capacity).
  • Decreased mean arterial pressures without affecting cardiac filling pressures.

the following information directly from Cleviprex package insert:

https://resources.chiesiusa.com/Cleviprex/CLEVIPREX_US_PI.pdf

• It is a lipid based infusion
• Pre-mixed infusion of 0.5 mg/1cc (available in 50cc, 100cc and 250cc bottles)
• Must infuse by itself or with Sterile Water, 0.9 NS, D5W, D5NS, D5LR or 10% amino acids
• It is recommended that the tubing and drug be changed every 12 hours
• The drug is light sensitive (keep drug in its original packaging until ready to use.  Once spiked, the drug can be exposed to light)
• Drug must be refrigerated (at 36-46 degrees F=Do not freeze).
  • Once exposed to room temperature (77 degrees F) it must be used within 2 months. 
  • Once the drug is removed from the refrigerator it must remain in room temperature storage
• It is safe for peripheral and central administration
• Avoid in patients with-
  • Severe Aortic Stenosis
  • Defective Lipid Metabolism
  • Allergies to Soy Beans, Soy Products, Eggs and Egg Products
  • Can exacerbate heart failure through the drug’s negative inotropic effects (this drug does not slow the heart rate)
  • This drug crosses the placenta and is secreted in the breast milk

Pharmacodynamics and Cleviprex Dosing:

• Start the drip at 1-2 mg/hr
• Double the dose about every 90 seconds (Once the blood pressure nears goal slow the titration speed or amount of drug titration)
• Drug effect may plateau at ~25% reduction in initial blood pressure
• Most patients achieve goal blood pressure with 4-6 mg/hr of Cleviprex
• Maximum Dose in most patients is 16 mg/hr.  However, 32 mg/hr of Cleviprex has been used with severe hypertension (consult pharmacy services regarding the “lipid load” of increased doses of this drug)
• Very short half-life (approximately 1 minute). Terminal half-life is 15 minutes
• Drug elimination primarily by esterases in the blood and extravascular tissues (does not have organ dependent elimination)
• Secreted in the stool and urine
• Watch for reflex tachycardia as the blood pressure is lowered with this drug

A summary video of drug effects:

ESCAPE-1 Trial : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724192/

If you would like to read a very in-depth description of the pharmacokinetics of Cleviprex…

https://www.ncbi.nlm.nih.gov/pubmed/15492770

Pharmacodynamic, pharmacokinetic and clinical effects of clevidipine, an ultrashort-acting calcium antagonist for rapid blood pressure control. Cardiovasc Drug Rev. 2004 Fall;22(3):227-50.

…And Let’s Not Forget YouTube…

Cost:

Summary:

Although Cleviprex (clevidpine) has been released since August of 2008 (and has been studied and proven to be beneficial in cardiac, neurovascular, operative and vascular patients) this may be a “new” drug to transport providers.  The very short half-life, low infusion volume and safety profile of this Calcium Channel Blocking infusion make it a viable option for the rapid blood pressure correction in patients experiencing hypertensive crisis and vascular pathologies that may have precarious hemodynamic states. 

References:

Awad, A. S., & Goldberg, M. E. (2010). Role of clevidipine butyrate in the treatment of acute hypertension in the critical care setting: a review. Vascular health and risk management, 6, 457.

Clevidipine. (2019, October 9). Retrieved November 11, 2019, from https://en.wikipedia.org/wiki/Clevidipine.

Clevidipine Package Insert. (2017, July). Retrieved October 2019, from https://resources.chiesiusa.com/Cleviprex/CLEVIPREX_US_PI.pdf.

CLEVIPREX® (clevidipine): Official HCP Website. (n.d.). Retrieved November 12, 2019, from https://cleviprex.com/?gclid=EAIaIQobChMI64-MhruG5gIVrx6tBh1HMQyUEAAYASAAEgJKuPD_BwE.

Espina, I. M., & Varon, J. (2012). Clevidipine: a state-of-the-art antihypertensive drug under the scope. Expert opinion on pharmacotherapy, 13(3), 387-393.

Finger, J. R., Kurczewski, L. M., & Brophy, G. M. (2017). Clevidipine versus nicardipine for acute blood pressure reduction in a neuroscience intensive care population. Neurocritical care, 26(2), 167-173.

Nordlander, M., Sjöquist, P. O., Ericsson, H., & Rydén, L. (2004). Pharmacodynamic, pharmacokinetic and clinical effects of clevidipine, an ultrashort‐acting calcium antagonist for rapid blood pressure control. Cardiovascular drug reviews, 22(3), 227-250.

Peacock IV, W. F., Angeles, J. E., Soto, K. M., Lumb, P. D., & Varon, J. (2009). Parenteral clevidipine for the acute control of blood pressure in the critically ill patient: a review. Therapeutics and clinical risk management, 5, 627.