This is a selection of recently approved FDA medications from August 2017

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

2. FDA Approval
• Mavyret® (glecaprevir and pibrentasvir) – approved 8/3/2017
• A fixed-dose combination of glecaprevir, a hepatitis C virus (HCV) NS3/4A
protease inhibitor, and pibrentasvir, an HCV NS5A inhibitor
• Indicated for the treatment of patients with chronic HCV genotype (GT)
1, 2, 3, 4, 5 or 6 infection without cirrhosis and with compensated
cirrhosis (Child-Pugh A).
• Also indicated for the treatment of adult patients with HCV genotype 1
infection, who previously have been treated with a regimen containing
an HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf

3. Mavyret® (glecaprevir and pibrentasvir)
• Formulation / Administration
• Prior to the initiation of therapy, test all patients for HBV infection by
measuring HBsAg and anti-HBc
• Available as a tablet: 100mg of glecaprevir and 40 mg pibrentasvir
• Recommended dosage: Three tablets (total daily dose: glecaprevir 300
mg and pibrentasvir 120 mg) taken orally once daily with food
• Dose adjustments in Renal/Hepatic Impairment:
• Not recommended in patients with moderate hepatic impairment (Child-
Pugh B); and is contraindicated in patients with severe hepatic
impairment (Child-Pugh C)
• No dosage adjustment is required in patients with mild, moderate or
severe renal impairment, including those on dialysis
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf

4. Mavyret® (glecaprevir and pibrentasvir)
• Duration as listed below: • 1. In clinical trials, subjects were
treated with prior regimens containing
ledipasvir and sofosbuvir or daclatasvir
with pegylated interferon and ribavirin.
• 2. In clinical trials, subjects were
treated with prior regimens containing
simeprevir and sofosbuvir, or
simeprevir, boceprevir, or telaprevir
with pegylated interferon and ribavirin
• 3. PRS=Prior treatment experience with
regimens containing interferon,
pegylated interferon, ribavirin, and/or
sofosbuvir, but no prior treatment
experience with an HCV NS3/4A PI or
NS5A inhibitor.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf

5. Mavyret® (glecaprevir and pibrentasvir)
• Drug Interactions:
• Contraindicated for coadministration with atazanavir and rifampin
• Carbamazepine, efavirenz, and St. John’s wort may decrease
concentrations of glecaprevir and pibrentasvir
• Coadministration of carbamazepine, efavirenz containing regimens, and
St. John’s wort with glecaprevir and pibrentasvir is not recommended
• Digoxin: Measure serum digoxin concentrations before initiating. Reduce
digoxin concentrations by decreasing the dose by approximately 50% or
by modifying the dosing frequency and continue monitoring
• Atazanavir: Coadministration is contraindicated
• Darunavir, Lopinavir, Ritonavir: Coadministration is not recommended
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf

6. Mavyret® (glecaprevir and pibrentasvir)
• Drug Interactions (continued):
• Statins: Coadministration may increase the concentration of atorvastatin,
lovastatin, and simvastatin. Increased statin concentrations may increase
the risk of myopathy, including rhabdomyolysis. Coadministration with
these statins is not recommended.
• Reduce pravastatin dose by 50%
• Rosuvastatin may be administered at a dose that does not exceed 10 mg
• Use the lowest approved dose of fluvastatin or pitavastatin. If higher doses are
needed, use the lowest necessary statin dose based on a risk/benefit
assessment
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf

7. FDA Approval
• Carospir® (spirinolactone) oral suspension –Approved 8/4/2017
• Is an antagonist of aldosterone indicated for:
• Treatment of NYHA Class III-IV heart failure and reduced ejection fraction
to increase survival, manage edema, and to reduce the need for
hospitalization for heart failure
• Add-on therapy for the treatment of hypertension, to lower blood
pressure. Lowering blood pressure reduces the risk of fatal and nonfatal
cardiovascular events, primarily strokes and myocardial infarctions
• The management of edema in adult cirrhotic patients when edema is not
responsive to fluid and sodium restrictions
• Initial approval in US – 1960!
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209478s000lbl.pdf

8. Carospir® (spirinolactone)
• Formulations / Administration:
• Oral suspension: 25mg/5ml
• Can be taken with or without food, but should be taken consistently with
respect to food
• Not therapeutically equivalent to Aldactone
• In patients requiring a dose greater than 100 mg, use another formulation.
Doses of the suspension greater than 100 mg may result in spironolactone
concentrations higher than expected
• Heart Failure: Initiate treatment at 20 mg once daily
• Hypertension: Initiate treatment at 20 to 75 mg daily in either single or
divided doses
• Edema associated with Hepatic Cirrhosis: Initiate therapy in a hospital
setting and titrate slowly. The initial recommended daily dose is 75 mg in
either single or divided doses
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209478s000lbl.pdf

9. FDA Approval
• Duzallo® (lesinurad and allopurinol) – Approved 8/18/2017
• A combination of lesinurad, a URAT1 inhibitor, and allopurinol, a xanthine
oxidase inhibitor
• Indicated for the treatment of hyperuricemia associated with gout in
patients who have not achieved target serum uric acid levels with a
medically appropriate daily dose of allopurinol alone.
• Formulation / Administration:
• Available in two strengths – 200mg lesinurad/300mg allopurinol and
200mg lesinurad/200mg allopurinol (both tablets)
• Should be taken in the morning with food and water
• Patients should be instructed to stay well hydrated
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209203s000lbl.pdf

10. Duzallo® (lesinurad and allopurinol)
• Dose adjustments in Renal/Hepatic impairment:
• Do not use in patients with eCLcr less than 45 ml/min; recommend
discontinuing if eCLcr persistently falls below 45 ml/min
• Lower dose of 200mg/200mg recommended for eCLcr 45 – 60 ml/min
• Not recommended in patients with severe hepatic impairment
• Other Precautions:
• Do not take more than one tablet of Duzallo® per day
• Do not combine Duzallo® with Zurampic® (lesinurad)
• Use one tablet in place of equivalent portion of the total daily allopurinol
dose. TDD of allopurinol should be maintained at the time of initiating
Duzallo®
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209203s000lbl.pdf

11. Duzallo® (lesinurad and allopurinol)
• Contraindications:
• Severe renal impairment, end stage renal disease, kidney transplant
recipients, or patients on dialysis
• Tumor lysis syndrome or Lesch-Nyhan syndrome
• Known hypersensitivity to allopurinol, including previous occurrence of
skin rash
• Drug Interactions:
• Mercaptopurine or Azathioprine: Reduce mercaptopurine or azathioprine
dose to approximately one-third to one-fourth of the usual dose and
closely monitor for therapeutic response and the appearance of toxicity.
• Warfarin: Carefully monitor prothrombin time.
• Moderate Cytochrome P450 2C9 (CYP2C9) Inhibitors: Use with caution.
• CYP3A Substrates: Monitor for efficacy of the CYP3A substrate.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209203s000lbl.pdf

12. FDA Approval
• Vabomere® (meropenem/vaborbactam) – Approved 8/29/2017
• Combination of meropenem, a penem antibacterial, and vaborbactam, a
beta-lactamase inhibitor
• Indicated for the treatment of patients 18 years and older with
complicated urinary tract infections (cUTI) including pyelonephritis
caused by designated susceptible bacteria
• Formulation / Administration:
• Administer 4 grams (meropenem 2 grams and vaborbactam 2 grams)
every 8 hours by intravenous infusion over 3 hours for up to 14 days, in
patients 18 years of age and older with an estimated glomerular filtration
rate (eGFR) ≥50 mL/min/1.73m2
• Each vial is 2 grams (meropenem 1 gram and vaborbactam 1 gram)
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209776lbl.pdf

13. Vabomere® (meropenem/vaborbactam)
• Dose adjustments in Renal Impairment:
• Dosage adjustment is recommended in patients with renal impairment
who have an eGFR less than 50 mL/min
• Doses adjusted for renal impairment should be administered after a
hemodialysis session
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209776lbl.pdf

14. Vabomere® (meropenem/vaborbactam)
• Drug Interactions:
• Valproic Acid:
• The valproic acid concentrations may drop below the therapeutic
range as a result of this interaction, therefore increasing the risk of
breakthrough seizures
• Co-administration of probenecid is not recommended
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209776lbl.pdf

15. Other August FDA Approvals
• Idhifa® (enasidenib) - 8/1/17
• An isocitrate dehydrogenase-2 inhibitor indicated for the treatment of
adult patients with relapsed or refractory acute myeloid leukemia (AML)
with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an
FDA- approved test.
• https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s00
0lbl.pdf
• Besponsa® (inotuzumab ozogamicin) – 8/17/2017
• A CD22-directed antibody-drug conjugate (ADC) indicated for the
treatment of adults with relapsed or refractory B-cell precursor acute
lymphoblastic leukemia (ALL).
• https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761040s00
0lbl.pdf

16. Other August FDA Approvals
• Benznidazole
• A nitroimidazole antimicrobial, is indicated in pediatric patients 2 to 12
years of age for the treatment of Chagas disease (American
trypanosomiasis), caused by Trypanosoma cruzi .
• This indication is approved under accelerated approval based on the
number of treated patients who became Immunoglobulin G (IgG)
antibody negative against the recombinant antigens of T. cruzi. Continued
approval for this indication may be contingent upon verification and
description of clinical benefit in confirmatory trial.
• https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209570lbl.
pdf

17. Thank you!