Clevidipine for Acute Management in the Neurological Intensive Care Unit Dorota K. Szarlej, PharmD 1, Jessica L. McKeon, PharmD 1, Akta S. Patel, PharmD 1, Amber E. King, PharmD 2 1Department of Pharmacy, Thomas Jefferson University Hospital; 2Jefferson School of Pharmacy, Department of Pharmacy Practice, Thomas Jefferson University

INTRODUCTION RESULTS Clevidipine Use DISCUSSION

Clevidipine is a third generation intravenous dihydropyridine calcium Demographics & Baseline Characteristics Parameter Results • Clevidipine use was deemed appropriate in 7 of 20 patients (35%) channel antagonist approved for treatment of acute when based on contraindications and adequate trials of other agents. Mean  me o n clevidipine infusion 50.6 hours (range 6-140 hours) oral therapy is not feasible or desirable. It is an arterial vasodilator that is Parameter Results Mean dose 7.5 mg/hr • A cost analysis showed a projected cost savings of $3940 if the other metabolized by plasma esterases; therefore, it is eliminated independently Male, n (%) 9 (45) 65% of patients had received another recommended agent instead of 1 Mean  me to bloo d pressure goal* 62.6 minu tes of the liver and kidney. Clevidipine has been studied for the control of Fem ale, n (%) 11 (55) clevidipine. This estimation was determined by comparing the actual perioperative hypertension 2-5 as well as for the management of hyper- Mean age in years (range) 45.7 (24 -77) *in patients who were not already at goal (n =11) cost of clevidipine based on patients’ doses and duration to the cost 6 tensive crises when immediate blood pressure control is clinically Past me dical histo ry, n (%) of another first-line agent assuming it was given at the maximum rate necessary. Benefits include its tolerability, rapid onset and offset, and easy • Hypertension 17 (85) for the same duration that clevidipine was used. titration with predictable response. Other continuously infused intravenous 3 (15) Clevidipine Safety antihypertensives used in the neurocritical care patient population include • Heart fail ure/c ardiomyopat hy • Although elevated were seen in 5 patients, there were , labetalol, and esmolol; however these medications are • 2 (10) no cases of . Parameter Results, n (%) Comm en ts limited by contraindications, adverse reactions, titration ability, and • Diabetes 5 (25) • Limitations to this medication use evaluation include the retrospective Hypot ension requ iri ng fluid bolus 1 pa ent o n bot h cl evidipine 7 • Intracerebral hem orrhage 1 (5) 3 (15) duration of action. In addition, the formulation of clevidipine is beneficial or use o f vasopressors (21 mg/hr) a nd labeta lol data collection using electronic nursing charting, small sample size, in fluid-restricted patients when compared to other agents which deliver • Ac ute ischem ic 5 (25) and cost analysis assumptions. Several a ri bu ted to ot her causes Decreased o xygen sat ura on* 7 (78 )** significantly more volume. • Atri al fibrill aon 2 (10) (i. e. a spir a on, sepsis) • The findings were presented to the Neuroscience Subcommittee of • Asthma 4 (20) All o n concurr ent propofol; TG the P&T Committee as well as the P&T Committee, resulting in the Incr eased t rigl yceri des (TG) 5 (25) Guideline Recommendations for use of Antihypertensives in • Ac ute kidn ey injury 4 (20) incr eases ranged from 50-215% creation of institutional guidelines in August 2013. These were approved by the Medical Executive Committee in September 2013. Neurological Hypertensive Emergencies • Chronic kidn ey disease 5 (25) *defined as increasing oxygen requirements after clevidipine started in non-intubated patients Adming diagnosis, n (%) **among non-intubated patients (n=9) The guidelines allow clevidipine to be used as the first-line agent only for patients with intracerebral hemorrhage and unsecured intracranial Cond ion Recomm end aons/Commen ts Sugg ested Agen ts • Intracerebral hem orrhage 5 (25 ) (1 with dissecon) aneurysm. Clevidipine may be used for 24 hours, after which time its • Ac ute ischem ic stroke 4 (20) Redu ce bloo d pressure by no more t han 10 -15% in If SB P >220 o r DB P 121 -140 mmHg: labetalol use must be reevaluated and the feasibility of switching to another the first 24 hours; treat only for t he foll owing or nic ardipine • Sub arachn oid hem orr hage/aneurysm 4 (20) ind ic a ons: (TG) Increases Associated with Clevidipine Initiation agent be addressed. • Plann ed t hrombolysis a nd BP >185 /110 mm Hg. 2 (10) Ac ute ischem ic stroke7-8 If DB P >140 mmHg: nitropruss ide • Anoxic brain injury Targ et BP < 18 0/105 mm Hg • Evidence o f concomitant noncerebral a cute Other agents (hydralaz ine, enalapril at , etc) • Crypto cocc al me ningis 2 (10) TG (mg/dL) a er end o rg an damage may be considered when a pp ropri ate • Brain t umor 1 (5) Paen t Inial TG (mg/dL) • BP >22 0/120 mm Hg clevi dipine iniaon • Ar teri ovenous malforma on 1 (5) 1 643 1294 CONCLUSION Treat only when SB P >200 a nd DB P >110 o r MAP >130 • Seizure 1 (5) 2 103 325 • SB P >200 o r MA P >150 : • Clevidipine is the most expensive continuous intravenous Ce ntral li ne a ccess, n (%) 12 (60) 3 85 166 o aggr essive t reat me nt with IV infusion anti-hypertensive. • SB P >180 o r MA P >130 with possibility o f 4 131 256 elevated ICP: Nic ardipine • Clevidipine remains an appropriate choice for acute blood intermient o r connu ous IV Intracerebral hem orrhage 7,9 o 5 153 230 me dic aons whil e maintaining CPP ≥60 Labeta lol Antihypertensive Continuous Infusions Tried Before Clevidipine pressure management. mm Hg • SB P >180 o r MA P >130 without evidence o f • However, due to its high cost, the duration of therapy can be elevated ICP: targeted as a cost-reduction initiative. o consider modest BP redu con (e.g. MA P 110 o r BP 16 0/90 ) using intermient o r connu ous IV me dic a ons Cost and Volume Comparison of IV Antihypertensives for • Triglyceride monitoring is essential, particularly in patients who Nicardipine are receiving concomitant propofol. Aneurysmal sub arachn oid Nic ardipine o r cl evidipine may be beer t han Continuous Infusion in the Neurological ICU 10 SB P >160 incr eases t he ri sk of re -bleeding Esmolol hem orr hage labetalol and nitroprusside No paents had Maximum • Comparative studies are needed to help determine clevidipine’s contrai nd icaons Labet alol dose of 15 Ag ent Price Range per Day Vo lume pe r Day place in therapy. to other first-li ne mg/hr reached ag ents in 5/10 cases 1-21 mg/ hr Clevidipine was added to the formulary at our institution in December 2010 None Clevidipine 48 mL – 1 L $61 -$1311 with restriction to cardiac and neurological intensive care units. Because of n=8 n=10 1.2 L – 3.6 L (0.1 mg/mL) Nic ardipine 5-15 mg/ hr its cost, it was recommended by the Pharmacy and Therapeutics (P&T) 600 mL – 1.8 L (0.2 mg/mL) (ph armacy prepared) $54 -$162 Committee to evaluate its appropriateness of use as well as safety and 120 mL – 360 mL (1 mg/mL) REFERENCES efficacy. Nic ardipine* 1. The Medicines Company. Cleviprex ® (Clevidipine) Injectable Emulsion, for intravenous use Prescribing Information. Parsippany, NJ; 2011. n=1 n=1 $493 -$14 78 1.2 L – 3.6 L (0.1 mg/mL) (0.1 mg/mL premixed bags) 2. Powrozynk AVV, Vuylsteke A, Naughton C, et al. Comparison of clevidipine with in the control of blood pressure after coronary artery surgery. Eur J Anesth 2003;20:697-703. 1-2 mg/min Labeta lol 288 mL – 576 mL $21 -$41 3. Levy JH, Mancao MY, Gitter R, et al. Clevidipine effectively and rapidly controls elevated blood pressure preoperatively in patients: the results of the randomized, placebo-controlled efficacy study of clevidipine assessing its preoperative METHODS 0.3 -3 mcg /kg/min • Of the patients who did not receive continuous antihypertensive Esmolol** 252 mL – 1 L hypertensive effect in cardiac surgery-1. Anesth Analg 2007;105:918-25. infusions prior to clevidipine: $26 -$265 4. Singla N, Warltier DC, Gandhi SD, et al. Treatment of acute postoperative hypertension in cardiac surgery patients: an efficacy study Twenty patients receiving clevidipine in the Jefferson neurological of clevidipine assessing its postoperative antihypertensive effect in cardiac surgery-2 (ESCAPE-2), a randomized, double-blind, intensive care units (NICUs) between September 2011 and December 2012 – Two patients received intermittent parenteral antihypertensives prior to clevidipine * Prior to the nicardipine shortage, premixed bags were typically used only when rates were less placebo-controlled trial. Anesth Analg 2008;107:59-67. were retrospectively identified. Patient information including age, gender, – One patient had an acute during admission. Cardiology than 5 mg/hr 5. Aronson S, Dyke CM, Stierer KA, et al. The ECLIPSE trials: comparative studies of clevidipine to , sodium nitroprusside, and nicardipine for acute hypertension treatment in cardiac surgery patients. Anesth Analg 2008;107:1110-21. recommended intermittent IV metoprolol, which was not ordered allergies, height, weight, admitting diagnosis, and past medical history **Esmolol dose and volume based on 70-kg patient 6. Pollack CV, Varon J, Garrison NA, et al. Clevidipine, an intravenous dihydropyridine blocker, is safe and effective for was collected. Indication for use, dose, duration of therapy, concomitant – Two patients had nicardipine ordered first but it was not administered the treatment of patients with acute severe hypertension. Ann Emerg Med 2009;53:329-38. antihypertensive administration, blood pressure measurements, time to 7. Marik PE and Varon PE. Hypertensive crises: challenges and management. Chest 2007;131:1949-62. • The patient who received esmolol reached the maximum dose; achieve blood pressure goal, and adverse events were also assessed. Clevidipine Cost 8. Jauch EC, Saver JL, Adams HP, et al. Early management of acute ischemic stroke. Stroke 2013. then nicardipine was added and titrated to the maximum dose. 9. Morgenstern LB, Hemphill JC, Anderson C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: Published guidelines were reviewed to determine whether clevidipine was • The mean cost per patient was $831.53 a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2010;41:2108-29. an appropriate choice for the indication. Cost of therapy was calculated • Eight patients received intermittent parenteral antihypertensives prior • This does not account for drug waste attributed to discarding the drug 10. Connolly ES, Rabinstein AA, Carhuapoma JR, et al. Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage. Stroke 2012;43:1711-37 for each patient. to clevidipine initiation: every 12 hours – Labetalol: 5 patients Disclosures: Dorota K. Szarlej, Jessica L. McKeon, Akta S. Patel and Amber E. King – Hydralazine: 2 patients have no disclosures to report – Metoprolol: 1 patient