Summary of the new FDA drug approvals for October and November 2017.

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

2. FDA Approval
• Abilify Mycite® (aripiprazole tablets with sensor) – approved
11/13/2017 (New dosage form)
• Drug-device combination product comprised of aripiprazole tablets
embedded with an Ingestible Event Marker (IEM) sensor intended to
track drug ingestion
• Indicated for:
• Treatment of adults with schizophrenia
• Treatment of bipolar I disorder:
• Acute treatment of adults with manic and mixed episodes as monotherapy and as
adjunct to lithium or valproate
• Maintenance treatment of adults as monotherapy and as adjunct to lithium or
valproate
• Adjunctive treatment of adults with major depressive disorder (MDD)
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207202lbl.pdf

3. Abilify Mycite®
• Formulation / Administration:
• Tablets with sensor: 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 30 mg
• Administer once daily without regard to meals
• Swallow whole; do not divide, crush, or chew
• Warnings/Precautions:
• The ability of Abilify Mycite® to improve patient compliance or modify
aripiprazole dosage has not been established.
• Use to track drug ingestion in “real-time” or during an emergency is not
recommended because detection may be delayed or not occur
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207202lbl.pdf

4. Abilify Mycite®
• Drug Interactions:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207202lbl.pdf

5. Abilify Mycite®
• Adverse Reactions:
• All previous ADRs remain unchanged (some specific info noted below)
• Includes Black box warning for elderly patients with dementia-related
psychosis and suicidal thoughts and behaviors
• Commonly observed (incidence ≥5% and at least twice that for placebo)
in adult patients:
• Schizophrenia: akathisia
• Bipolar mania (monotherapy): akathisia, sedation, restlessness, tremor, and
extrapyramidal disorder
• Bipolar mania (adjunctive therapy with lithium or valproate): akathisia,
insomnia, and extrapyramidal disorder
• MDD (adjunctive treatment to antidepressant therapy): akathisia, restlessness,
insomnia, constipation, fatigue, and blurred vision
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207202lbl.pdf

6. FDA Approval
• Fasenra® (benralizumab) – approved 11/8/17
• An interleukin-5 receptor alpha-directed cytolytic monoclonal antibody
(IgG1, kappa)
• Indicated for the add-on maintenance treatment of patients with severe
asthma aged 12 years and older, and with an eosinophilic phenotype
• Adverse Reactions:
• Most common (incidence greater than or equal to 5%) include headache
and pharyngitis
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761070s000lbl.pdf

7. Fasenra® (benralizumab)
• Formulation / Administration:
• Injection: 30mg/mL solution in a single-dose prefilled syringe (see below)
• Administer by subcutaneous injection
• Recommended dose is 30mg every 4 weeks for the first 3 doses, followed
by once every 8 weeks thereafter
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761070s000lbl.pdf

8. Fasenra® (benralizumab)
• Warnings/Precautions:
• Not for treatment of other eosinophilic conditions
• Not for relief of acute bronchospasm or status asthmaticus
• Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, rash)
have occurred after. Discontinue in the event of a hypersensitivity
reaction.
• Do not discontinue systemic or inhaled corticosteroids abruptly upon
initiation of therapy with. Decrease corticosteroids gradually, if
appropriate.
• Parasitic (Helminth) Infection: Treat patients with pre-existing helminth
infections before therapy. If patients become infected while receiving
Fasenra® and do not respond to anti-helminth treatment, discontinue
until the parasitic infection resolves.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761070s000lbl.pdf

9. FDA Approval
• Prevymis® (letermovir) – approved 11/14/17
• A CMV DNA terminase complex inhibitor
• Indicated for prophylaxis of cytomegalovirus (CMV) infection and disease
in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic
stem cell transplant (HSCT)
• Formulation / Administration:
• Tablet: 240mg; 480mg
• Injection: 240mg/12mL (20mg/mL) or 480mg/24mL (20mg/mL) in a
single-dose vial
• Usual Dosing: 480mg administered once daily orally or as an intravenous
(IV) infusion over 1 hour through 100 days post-transplant
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209939Orig1s000,209940Orig1s000lbl.pdf

10. Prevymis® (letermovir)
• Dose adjustments:
• If co-administered with cyclosporine, the dosage should be decreased to
240mg once daily
• Closely monitor serum creatinine levels in patients with CLcr less than
50mL/min
• Not recommended for patients with severe (Child-Pugh C) hepatic
impairment
• Contraindicated with:
• Pimozide
• Ergot Akaloids
• Pitavastatin and simvastatin when co-administered with cyclosporine
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209939Orig1s000,209940Orig1s000lbl.pdf

11. Prevymis® (letermovir)
• Other Drug Interactions:
• Prevymis® is a moderate inhibitor of CYP3A and of OATP1B1/3
transporters
• Can increase concentrations of the following medications:
• Amiodarone
• HMG Co-A Reductase Inhibitors
• CYP3A substrates
• Can decrease concentrations of the following medications:
• Warfarin
• Phenytoin
• Omeprazole / Pantoprazole
• Administration with rifampin is NOT recommended
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209939Orig1s000,209940Orig1s000lbl.pdf

12. Prevymis® (letermovir)
• Adverse Reactions:
• Most common are nausea, diarrhea, vomiting, peripheral edema, cough,
headache, fatigue, and abdominal pain
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209939Orig1s000,209940Orig1s000lbl.pdf

13. FDA Approval
• Vyzulta® (latanoprostene bunod ophthalmic solution) –
approved 11/2/17
• A prostaglandin analog
• Indicated for the reduction of intraocular pressure in patients with open-
angle glaucoma or ocular hypertension
• Formulation / Administration:
• Topical ophthalmic solution: 0.24 mg/mL latanoprostene bunod (0.024%)
• One drop in the affected eye(s) once daily in the evening
• Contact lenses should be removed prior to the administration because
this product contains benzalkonium chloride. Lenses may be reinserted
15 minutes after administration
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207795Orig1s000lbl.pdf

14. Vyzulta® (latanoprostene bunod ophthalmic
solution)
• Storage
• Unopened bottle should be stored refrigerated at 2 - 8℃ (36 - 46℉). Once
a bottle is opened it may be stored at 2 - 25℃ (36 - 77℉) for 8 weeks
• Warnings/Precautions:
• Increased pigmentation of the iris and periorbital tissue (eyelid) can
occur. Iris pigmentation is likely to be permanent
• Gradual changes to eyelashes including increased length, increased
thickness and number of eyelashes. Usually reversible upon
discontinuation of treatment
• Adverse Reactions:
• Most common ocular adverse reactions with incidence ≥ 2% are
conjunctival hyperemia (6%), eye irritation (4%), eye pain (3%), and
instillation site pain (2%)
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207795Orig1s000lbl.pdf

15. Another Me Too Drug?
• Vyzulta® is nearly identical to that of latanoprost
• Distinguished, however, by the integration of an NO-donating moiety (a
terminal butyl nitrate ester functional group) in lieu of an isopropyl ester
• Hydrolyzed by endogenous corneal esterases into latanoprost acid – the
active component of latanoprost – and butanediol mononitrate, which is
further metabolized to NO and the inactive 1,4-butanediol
Clin Ophthalmol. 2016; 10: 2035–2050.

16. FDA Approval
• Juluca® (dolutegravir; rilpivirine) – approved 11/21/17
• A two-drug combination of dolutegravir, a human immunodeficiency
virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI), and
rilpivirine, a HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI)
• Indicated as a complete regimen for the treatment of HIV-1 infection in
adults to replace the current antiretroviral regimen in those who are
virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a
stable antiretroviral regimen for at least 6 months with no history of
treatment failure and no known substitutions associated with resistance
to the individual components
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/210192s000lbl.pdf

17. Juluca® (dolutegravir; rilpivirine)
• Formulation / Administration:
• Each tablet contains: 50mg of dolutegravir (equivalent to 52.6mg
dolutegravir sodium) and 25mg of rilpivirine (equivalent to 27.5mg
rilpivirine hydrochloride)
• One tablet taken orally once daily with a meal
• Rifabutin co-administration: Take an additional 25-mg tablet of rilpivirine
with Juluca® once daily with a meal for the duration of the rifabutin co-
administration
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/210192s000lbl.pdf

18. Juluca® (dolutegravir; rilpivirine)
• Warnings/Precautions:
• Severe skin and hypersensitivity reactions characterized by rash,
constitutional findings, and sometimes organ dysfunction, including liver
injury, have been reported with the individual components. Discontinue
immediately if signs or symptoms of severe skin or hypersensitivity
reactions develop, as a delay in stopping treatment may result in a life-
threatening reaction
• Hepatotoxicity has been reported in patients receiving a dolutegravir-or
rilpivirine-containing regimen. Monitoring for hepatotoxicity is
recommended
• Depressive disorders have been reported with the use of rilpivirine-or
dolutegravir-containing regimens. Immediate medical evaluation is
recommended for severe depressive symptoms
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/210192s000lbl.pdf

19. Juluca® (dolutegravir; rilpivirine)
• Drug Interactions:
• Because Juluca® is a complete regimen, co-administration with other
antiretroviral medications for the treatment of HIV-1 infection is not
recommended
• Drugs that induce or inhibit CYP3A4 or UGT1A1 may affect the plasma
concentrations
• Drugs that increase gastric pH or containing polyvalent cations may
decrease plasma concentrations
• Consider alternatives with drugs with a known risk of Torsade de Pointes
• Contraindicated with:
• Anticonvulsants, PPIs, St. John’s wort (see table 1 and 4 for additional
medications and explanation)
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/210192s000lbl.pdf

20. Juluca® (dolutegravir; rilpivirine)
• Dose adjustments:
• Renal impairment:
• In patients with severe renal impairment (creatinine clearance less than 30
mL/min) or end-stage renal disease, increased monitoring for adverse effect s
is recommended
• Hepatic impairment:
• The effect of severe hepatic impairment (Child-P ugh Score C) on the
pharmacokinetics of dolutegravir or rilpivirine is unknown
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/210192s000lbl.pdf

21. Other October FDA Approvals
• Lyrica CR® (pregabalin)
1
– 10/11/2017:
• New Formulation: Extended release tablets (82.5mg, 165mg, and 330mg)
• Byurdeon® Bcise™ (exanatide)
2
– 10/20/2017:
• New Dose Form: Extended-release injectable suspension
• Varubi® (rolapitant)3 – 10/25/2017:
• New Dosage Form: Injectable emulsion, for intravenous use
1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209501s000lbl.pdf
2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209210s000lbl.pdf
3. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208399s000lbl.pdf

22. Other October FDA Approvals
• Daptomycin
1
– 10/20/2017
• New Formulation: 350 mg/vial for the treatment of adult patients with
Complicated Skin and Skin Structure Infections (cSSSI) and
Staphylococcus aureus Bloodstream Infections (Bacteremia), including
those with Right-Sided Infective Endocarditis, caused by Methicillin-
Susceptible and Methicillin-Resistant Isolates
• Calquence® (acalabrutinib)
2
– 10/31/2017
• New Molecular Entity: To treat adults with mantle cell lymphoma
1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209949s000lbl.pdf
2. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=210259

23. Other October FDA “Tentative” Approvals
• Fosaprepitant
1
- 10/12/2017
• New Formulation: 150mg/ml vial
• Pemfexy® (pemetrexed)
2
– 10/26/2017
• New Formulation: 25mg/ml vial
• Prexxartan® (valsartan)
3
– 10/30/2017
• New Dosage Form: Oral solution – 4mg/ml
1. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=210064
2. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=209472
3. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=209139

24. Other November FDA Approvals
• Civanti® (aprepitant)1 – 11/9/2017:
• New Dosage Form: injectable emulsion; a substance P/neurokinin-1
(NK1) receptor antagonist, indicated in adults, in combination with other
antiemetic agents, for the prevention of:
• Acute and delayed nausea and vomiting associated with initial and repeat
courses of highly emetogenic cancer chemotherapy (HEC) including high- dose
cisplatin
• Nausea and vomiting associated with initial and repeat courses of moderately
emetogenic cancer chemotherapy (MEC)
• Tekturna® (aliskiren)2 – 11/14/2017:
• New Dosage Form: oral pellets; renin inhibitor (RI) indicated for
the treatment of hypertension in adults and children 6 years of age and
older, to lower blood pressure
1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209296s000lbl.pdf
2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/210709s000lbl.pdf

25. Other November FDA Approvals
• Hemlibra® (emicizumab)
1
– 11/16/2017
• To prevent or reduce the frequency of bleeding episodes in adult and
pediatric patients with hemophilia A who have developed antibodies
called Factor VIII (FVIII) inhibitors
• Mepsevii® (vestronidase alfa-vjbk)
2
– 11/15/2017
• To treat pediatric and adult patients with an inherited metabolic
condition called mucopolysaccharidosis type VII (MPS VII), also known as
Sly syndrome.
1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761083s000lbl.pdf
2. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=761047

26. Thank you!