PCSK9 INHIBITORS, ARNIS, FUNNY CHANNEL INHIBITORS: ARE YOU SURE THESE ARE REALLY CARDIAC DRUGS?

Transcription

1 PCSK9 INHIBITORS, ARNIS, FUNNY CHANNEL INHIBITORS: ARE YOU SURE THESE ARE REALLY CARDIAC DRUGS? ALLORIE SMITH, PHARM.D. CARDIOVASCULAR UPDATE CONFERENCE FEBRUARY 9, 2012

2 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

3 EVOLOCUMAB (REPATHA ) ALIROCUMAB (PRALUENT ) PCSK9 INHIBITORS

4 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

5 Normal Activity With Repatha

6 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

7 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

8 PCSK9 INHIBITORS : DRUG INTERACTIONS / CONTRAINDICATIONS REPATHA Interactions Belimumab PRALUENT Interactions Belimumab Contraindications Hypersensitivity Contraindications Hypersensitivity

9 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

10 REPATHA : PHASE III STUDY RESULTS MENDEL 2: J Am Coll Cardiol Jun 17;63(23): LAPLACE-2: JAMA May 14;311(18): DESCARTES : N Engl J Med May 8;370(19): GAUSS-2 : J Am Coll Cardiol Jun 17;63(23): RUTEHRFORD-2: Lancet Jan 24;385(9965): TESLA PART B: Lancet Jan 24;385(9965): OSLER 1: Circulation Jan 14;129(2):

11 PRALUENT : PHASE III STUDY RESULTS ODYSSEY MONO : Future Cardiol. 2015;11(1): ODYSSEY COMBO 1: Am Heart J Jun;169(6): ODYSSEY COMBO 2 : Eur Heart J May 14;36(19): ODYSSEY ALTERNATIVE : J Clin Lipidol Nov-Dec;8(6): ODYSSEY FH 1 AND 2 : Eur Heart J Nov 14;36(43): ODYSEEY LONG TERM : N Engl J Med Apr 16;372(16):

12 SACUBITRIL / VALSARTAN (ENTRESTO )

13 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

14 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

15

16 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

17 ENTRESTO : DRUG INTERACTIONS / CONTRAINDICATION DRUG INTERACTIONS ACEI Aliskiren Lithium Trimethoprim Simeprevir CONTRAINDICATIONS History of angioedema Plavix [package insert] Lexi-comp Micromedex

18 ENTRESTO : PHASE III STUDY PARADIGM-HF N Engl J Med Sep 11; 371(11): Pharmacotherapy. 2012;32(12):e348-e386

19 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

20 IVABRADINE (CORLANOR )

21 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 maintain dose Resting heart rate <60 or Symptoms of bradycardia reduce to 2.5 mg BID

22 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

23 Corlanor Website

24 CORLANOR : SIDE EFFECTS Bradycardia (10%) Hypertension (8.9%) A Fib (8.3%) Phosphene (2.8%)

25 CORLANOR : DRUG INTERACTIONS / CONTRAINDICATION DRUG INTERACTIONS QT prolongating agents CYP 3A4 drugs CONTRAINDICATIONS Decompensated CHF Pacemaker dependent Baseline bradycardia Hepatic impairment Hypotension Heart block

26 CORLANOR : STUDY BEAUTIFUL: Lancet Sep 6;372(9641): SHIFT: Lancet Sep 11;376(9744): SIGNIFY: N Engl J Med Sep 18; 371: Pharmacotherapy. 2012;32(12):e348-e386

27 CORLANOR : PRICING $375 for 60 tablets $20 copay coupon for commercial insurance

28 REFERENCE Corlanor [package insert]. Thousand Oaks, CA: Amgen; Entresto [package insert]. East Hanover, NJ: Novartis; Lexi-Comp Online. Lexi-Drugs Online. Hudson, OH: Lexi-Comp, Inc.; Accessed January 25, Micromedex Healthcare Series. DRUGDEX System. Greenwood Village, CO: Thomson Healthcare; Accessed January 25, Praluent [package insert]. Bridgewater, NJ: Sanofi-Aventis; Repatha [package insert]. Thousand Oaks, CA: Amgen; 2015.

29 PCSK9 INHIBITORS, ARNIS, FUNNY CHANNEL INHIBITORS: ARE YOU SURE THESE ARE REALLY CARDIAC DRUGS? ALLORIE SMITH, PHARMD CARDIOVASCULAR UPDATE CONFERENCE FEBRUARY 9, 2012