PCSK9 INHIBITORS, ARNIS, FUNNY CHANNEL INHIBITORS: ARE YOU SURE THESE ARE REALLY CARDIAC DRUGS? ALLORIE SMITH, PHARM.D. CARDIOVASCULAR UPDATE CONFERENCE FEBRUARY 9, 2012
OBJECTIVES Explain the pharmacology of Repatha, Praluent, Entresto, and Corlanor. Learn the indications and doses for each of the medications listed above. Discuss the literature behind the approval of the drugs above
EVOLOCUMAB (REPATHA ) ALIROCUMAB (PRALUENT ) PCSK9 INHIBITORS
PCSK9 INHIBITORS: CLASSIFICATION AND MOA Class: Proprotien convertase subtilisin kexin type 9 inhibitor (PCSK-9) antibody MOA: Binds to the PCSK-9 and prevents it from binding and degradation the the LDL receptors. This allows for the LDL receptors to return to the liver cell surface and clear LDL from the blood, lowering LDL-C levels
Normal Activity With Repatha
PCSK9 INHIBITORS: INDICATIONS AND DOSING REPATHA Adjunct to diet and maximum statin dose in primary hyperlipidemia 140 mg subq every 2 weeks 420 mg subq monthly Adjunct to diet and other LDL lowering therapies for homozygous familial hypercholesterolemia 420 mg subq monthly PRALUENT Adjunct to diet and maximum statin dose in primary hyperlipidemia 75 mg subq every 2 weeks May increase to 150 mg subq every 2 weeks if needed to achieve LDL lowering goals
PCSK9 INHIBITORS : SIDE EFFECTS REPATHA Nasopharyngitis (11%) URI (9%) Flu (9%) Gastreoenteritis (6%) Injection side reaction (6%) UTI (5%) Less than 5% Dizziness (4%), Myalgia (4%), Hypertension (3%), Fatigue (2%), Nausea (2%), Bruise (1%) PRALUENT Injection site reactions (7%) Influenza (6%) Diarrhea (5%) Less than 5% Increased liver enzymes (3%), Myalgia (4%), Spasms (3%), cough(3%) Post marketing data/case reports: confusion, memory impairment
PCSK9 INHIBITORS : DRUG INTERACTIONS / CONTRAINDICATIONS REPATHA Interactions Belimumab PRALUENT Interactions Belimumab Contraindications Hypersensitivity Contraindications Hypersensitivity
PCSK9 INHIBITORS : PRICING REPATHA ~$650 per 140 mg injection $5 copay coupon for commercial insurance PRALUENT ~$670 per 75mg or 150mg injection $0 copay for 6 months then $10 thereafter coupon for commercial insurance
REPATHA : PHASE III STUDY RESULTS MENDEL 2: J Am Coll Cardiol. 2014 Jun 17;63(23):2531-40 LAPLACE-2: JAMA. 2014 May 14;311(18):1870-82. DESCARTES : N Engl J Med. 2014 May 8;370(19):1809-19. GAUSS-2 : J Am Coll Cardiol. 2014 Jun 17;63(23):2541-8. RUTEHRFORD-2: Lancet. 2015 Jan 24;385(9965):331-40. TESLA PART B: Lancet. 2015 Jan 24;385(9965):341-50. OSLER 1: Circulation. 2014 Jan 14;129(2):234-43.
PRALUENT : PHASE III STUDY RESULTS ODYSSEY MONO : Future Cardiol. 2015;11(1):27-37. ODYSSEY COMBO 1: Am Heart J. 2015 Jun;169(6):906-915 ODYSSEY COMBO 2 : Eur Heart J. 2015 May 14;36(19):1186-94. ODYSSEY ALTERNATIVE : J Clin Lipidol. 2014 Nov-Dec;8(6):554-61. ODYSSEY FH 1 AND 2 : Eur Heart J. 2015 Nov 14;36(43):2996-3003 ODYSEEY LONG TERM : N Engl J Med. 2015 Apr 16;372(16):1489-99.
SACUBITRIL / VALSARTAN (ENTRESTO )
ENTRESTO : INDICATION AND DOSAGE Heart failure Patients previously taking the equivalent of >10 mg/day of enalapril or >160 mg of Valsartan Start 49mg/51 mg BID, double the dose every 2-4 weeks to the target dose of 97 mg/ 103 mg BID Patients previously taking the equivalent of <10 mg/day of enalapril or <160 mg of Valsartan Start 24mg/26 mg BID, double the dose every 2-4 weeks to the target dose of 97 mg/ 103 mg BID
ENTRESTO CLASSIFICATION AND MOA Class: Angiotensin Receptor Blocker (ARB) and Neprilysin Inhibitor MOA: ARB: Blocks angiotensin receptors Neprilysin inhibitor: prodrug that inhibits neprilysin and increase levels of naturetic peptides
ENTRESTO : SIDE EFFECTS Hypotension (~18%) Hyperkalemia (up to 16%) Increase in SCR (up to 16%) Cough (9%) Less than 5%: Hypotension, Dizziness, Decreased H/H, Angioedema, Renal failure
ENTRESTO : DRUG INTERACTIONS / CONTRAINDICATION DRUG INTERACTIONS ACEI Aliskiren Lithium Trimethoprim Simeprevir CONTRAINDICATIONS History of angioedema Plavix [package insert] Lexi-comp Micromedex
ENTRESTO : PHASE III STUDY PARADIGM-HF N Engl J Med. 2014 Sep 11; 371(11): 993-1004 Pharmacotherapy. 2012;32(12):e348-e386
ENTRESTO : PRICING All strengths: ~$450 for 60 tablets 30 days free coupon valid for all insurances (commercial and government) $10 copay card for commercial insurance
IVABRADINE (CORLANOR )
CORLANOR : INDICATIONS AND DOSAGE Heart failure Initial dose: 5 mg BID Adjustments after two weeks Resting HR > 60 increase to 7.5 mg BID (max dose) Resting HR between 50-60 maintain dose Resting heart rate <60 or Symptoms of bradycardia reduce to 2.5 mg BID
CORLANOR : CLASSIFICATION AND MOA Class: MISC Cardiovascular agent NO FUN!!! I think we should call them funny channel inhibitors MOA: Selective and specific inhibition of the hyperpolarizationactivated cyclin nucleotide-gated channels (I f channels or funny channels) within the SA node of the cardiac tissue Slows diastolic depolarization and firing of the SA node which reduces heart rate
Corlanor Website https://www.corlanorhcp.com/~/media/amgen/full/www-corlanorhcp-com/diagrammoa3.ashx?la=en&hash=89dd72f9a1ac0e2f6a32d9ab4e30f6a77073ab05
CORLANOR : SIDE EFFECTS Bradycardia (10%) Hypertension (8.9%) A Fib (8.3%) Phosphene (2.8%)
CORLANOR : DRUG INTERACTIONS / CONTRAINDICATION DRUG INTERACTIONS QT prolongating agents CYP 3A4 drugs CONTRAINDICATIONS Decompensated CHF Pacemaker dependent Baseline bradycardia Hepatic impairment Hypotension Heart block
CORLANOR : STUDY BEAUTIFUL: Lancet. 2008 Sep 6;372(9641):807-16. SHIFT: Lancet. 2010 Sep 11;376(9744):875-85. SIGNIFY: N Engl J Med. 2014 Sep 18; 371:1091-1099 Pharmacotherapy. 2012;32(12):e348-e386
CORLANOR : PRICING $375 for 60 tablets $20 copay coupon for commercial insurance
REFERENCE Corlanor [package insert]. Thousand Oaks, CA: Amgen; 2015. Entresto [package insert]. East Hanover, NJ: Novartis; 2015. Lexi-Comp Online. Lexi-Drugs Online. Hudson, OH: Lexi-Comp, Inc.; 2016. http://online.lexi.com. Accessed January 25, 2016. Micromedex Healthcare Series. DRUGDEX System. Greenwood Village, CO: Thomson Healthcare; 2016. http://www.thomsonhc.com/. Accessed January 25, 2016. Praluent [package insert]. Bridgewater, NJ: Sanofi-Aventis; 2015. Repatha [package insert]. Thousand Oaks, CA: Amgen; 2015.
PCSK9 INHIBITORS, ARNIS, FUNNY CHANNEL INHIBITORS: ARE YOU SURE THESE ARE REALLY CARDIAC DRUGS? ALLORIE SMITH, PHARMD CARDIOVASCULAR UPDATE CONFERENCE FEBRUARY 9, 2012