A monthly Dose of Education summarizing the most recent FDA approvals

1. A MONTHLY
DOSE OF EDUCATION
Brian Pelletier, PharmD, BCGP, FASCP
CEO, A Dose of Education, LLC
July 2017

2. FDA Approval
• Zypitamag® (pitavastatin) – approved 7/14/2017
• HMG-CoA reductase inhibitor indicated for patients with primary
hyperlipidemia or mixed dyslipidemia as an adjunctive therapy to diet to
reduce elevated total cholesterol (TC), low- density lipoprotein
cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and to
increase high-density lipoprotein cholesterol (HDL-C)
• Type 2 approval – new active ingredient
• Formulation / Administration
• Administered orally (tablet):
• 1mg, 2mg, and 4mg dosage sizes available
• Can be taken with or without food, any time of day
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208379s000lbl.pdf

3. Zypitamag® (pitavastatin)
• Dose adjustment in renal impairment:
• Moderate to severe (less than 30ml/min) AND ESRD on hemodialysis;
• Starting dose of 1mg once daily; can titrate to a maximum of 2mg once
daily
• Drug Interactions:
• Erythromycin: Combination increases pitavastatin exposure. Limit to 1 mg
once daily
• Rifampin: Combination increases pitavastatin exposure. Limit to 2 mg
once daily
• Concomitant lipid-lowering therapies: Use with fibrates or lipid-modifying
doses (≥ 1 g/day) of niacin increases the risk of adverse skeletal muscle
effects. Caution should be used.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208379s000lbl.pdf

4. FDA Approval
• Vosevi® (sofosbuvir, velpatasvir, and voxilaprevir) - approved 7/19/2017
• Fixed-dose combination of sofosbuvir, a hepatitis C virus (HCV) nucleotide
analog NS5B polymerase inhibitor, velpatasvir, an HCV NS5A inhibitor, and
voxilaprevir, an HCV NS3/4A protease inhibitor
• Indicated for the treatment of adult patients with chronic HCV infection
without cirrhosis or with compensated cirrhosis (Child-Pugh A) who have:
• genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an
HCV regimen containing an NS5A inhibitor.
• genotype 1a or 3 infection and have previously been treated with an HCV
regimen containing sofosbuvir without an NS5A inhibitor.
• Additional benefit over sofosbuvir/velpatasvir was not shown in adults with genotype
1b, 2, 4, 5, or 6 infection previously treated with sofosbuvir without an NS5A
inhibitor.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209195s000lbl.pdf

5. Vosevi®
• Formulation/Administration:
• One tablet taken by mouth daily with food
• One tablet = 400 mg of sofosbuvir, 100 mg of velpatasvir, and 100 mg of
voxilaprevir
• Recommended Treatment Regimen and Duration:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209195s000lbl.pdf

6. Vosevi®
• Dosage Recommendations:
• No dosage recommendations for severe renal impairment or in ESRD
• Higher exposures (up to 20-fold) of the predominant sofosbuvir metabolite
• Not recommended in patients with moderate or severe hepatic
impairment (Child-Pugh B or C) due to higher exposures of voxilaprevir
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209195s000lbl.pdf

7. Vosevi®
• Drug Interactions:
• Antacids – separate administration by 4 hours
• Drugs that are inducers of P-gp and/or moderate to potent inducers of
CYP2B6, CYP2C8, or CYP3A4 (e.g., St. John’s wort, carbamazepine) may
significantly decrease plasma concentrations leading to reduced
therapeutic effect
• Not to be co-administered with rifampin
• Co-administration with amiodarone is not recommended due to serious
symptomatic bradycardia
• Co-administration with Vosevi® may increase the concentrations of all
statins, including atorvastatin, fluvastatin, lovastatin, and simvastatin; use
with rosuvastatin not recommended
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209195s000lbl.pdf

8. FDA Approval
• Nerlynx® (neratinib) – Approved 7/17/2017
• Kinase inhibitor indicated for the extended adjuvant treatment of adult
patients with early stage HER2-overexpressed/amplified breast cancer, to
follow adjuvant trastuzumab-based therapy
• Formulations/Dosing
• Available in 40mg tablets
• 240 mg (6 tablets) given orally once daily with food, continuously for one
year (should be swallowed whole)
• Dose reductions are appropriate based on individual safety and
tolerability
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208051s000lbl.pdf

9. Nerlynx® (neratinib)
• Hepatic Impairment:
• Reduce starting dose to 80 mg
• Note well: Monitor liver function tests monthly for the first 3 months of
treatment, then every 3 months while on treatment and as clinically
indicated – dose reductions or discontinuation indicated based on
severity of hepatotoxicity
• Antidiarrheal prophylaxis:
• Initiate loperamide (4mg) with the first dose and continue during first 2
cycles (56 days) of treatment
• Weeks 1-2: 4mg TID
• Weeks 3-8: 4mg BID
• Weeks 9-52: as needed (not to exceed 16mg per day)
• Maintain 1-2 bowel movements per day
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208051s000lbl.pdf

10. Nerlynx® (neratinib)
• Drug Interactions:
• Gastric acid reducing agents:
• Avoid concomitant use with proton pump inhibitors (PPI)
• Avoid concomitant use with H2-receptor antagonists
• Separate by 3 hours after antacid dosing
• Strong or moderate CYP3A4 inhibitors: Avoid concomitant use
• Strong or moderate CYP3A4 inducers: Avoid concomitant use
• P-glycoprotein (P-gp) substrates: Monitor for adverse reactions of narrow
therapeutic agents (e.g. digoxin) that are P-gp substrates when used
concomitantly
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208051s000lbl.pdf

11. Thank you!