The document summarizes recent FDA drug approvals and new formulations in June 2018. Key approvals included Moxidectin for onchocerciasis, Epidiolex for seizures associated with Lennox-Gastaut or Dravet syndrome, Zemdri for complicated urinary tract infections, Mektovi in combination with Braftovi for melanoma with BRAF mutations, and Aristada Initio, a new extended-release injectable formulation for initiating Aristada treatment of schizophrenia. Each drug is briefly described including indications, dosing regimens, warnings and common adverse reactions.

1. A MONTHLY
DOSE OF EDUCATION
Brian Pelletier, PharmD, BCGP, FASCP
CEO, A Dose of Education, LLC
June 2018

2. FDA Approval
• Moxidectin® – approved 6/13/18
• An anthelmintic indicated for the treatment of onchocerciasis due to
Onchocerca volvulus in patients aged 12 years and older
• Formulation and Administration:
• Tablets: 2mg
• Patients aged 12 years and older: Take 8 mg (four 2 mg tablets) as a single
oral dose, with or without food.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210867lbl.pdf

3. Moxidectin®
• Warning/Precautions:
• Cutaneous, Ophthalmological and/or Systemic Adverse Reactions of
Varying Severity (Mazzotti Reaction)
• Symptomatic Orthostatic Hypotension
• Encephalopathy in Loa loa co-infected patients
• Edema and Worsening of Onchodermatitis
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210867lbl.pdf

4. Moxidectin® - Adverse Reactions
• eosinophilia
• pruritus
• musculoskeletal pain
• headache
• lymphopenia
• tachycardia
• rash
• abdominal pain
• hypotension
• pyrexia
• leukocytosis
• influenza-like illness
• neutropenia
• cough
• lymph node pain
• dizziness
• diarrhea
• hyponatremia, and
• peripheral swelling
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210867lbl.pdf

5. FDA Approval
• Epidiolex® (cannabidiol) – approved 6/25/2018
• Indicated for the treatment of seizures associated with Lennox-Gastaut
syndrome or Dravet syndrome in patients 2 years of age and older
• Warnings and Precautions:
• Hepatocellular Injury: Can cause transaminase elevations
• Somnolence and Sedation:
• Suicidal Behavior and Ideation
• Hypersensitivity Reactions
• Withdrawal of Antiepileptic Drugs: Should be gradually withdrawn to
minimize the risk of increased seizure frequency and status epilepticus
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf

6. Epidiolex® (cannabidiol)
• Formulation and Administration:
• Oral solution: 100mg/ml
• Obtain serum transaminases (ALT and AST) and total bilirubin levels in all
patients prior to starting treatment
• Recommended starting dosage is 2.5 mg/kg taken orally twice daily (5
mg/kg/day)
• After one week, for patients tolerating Epidiolex® the dosage can be
increased to a maintenance dosage of 5 mg/kg twice daily
• Can be increased up to a maximum recommended maintenance dosage
of 10 mg/kg twice daily (20 mg/kg/day)
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf

7. Epidiolex® (cannabidiol)
• Administration continued:
• Discard any unused medication remaining 12 weeks after first opening
the bottle
• Dose Adjustments:
• Dose adjustment is recommended in patients with moderate (Child-Pugh
B) hepatic impairment or severe (Child-Pugh C) hepatic impairment
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf

8. Epidiolex® (cannabidiol)
• Adverse Reactions:
• Most common adverse reactions (incidence ≥ 10% and notably more
frequent than placebo) are:
• Somnolence;
• Decreased appetite;
• Diarrhea;
• Transaminase elevations;
• Fatigue, malaise, and asthenia;
• Rash;
• Insomnia, sleep disorder, and poor quality sleep; and
• Infections
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf

9. Epidiolex® (cannabidiol)
• Drug Interactions:
• Moderate or strong inhibitors of CYP3A4 or CYP2C19: Consider dose
reduction of EPIDIOLEX®
• Strong inducer of CYP3A4 or CYP2C19: Consider dose increase
EPIDIOLEX®
• Consider a dose reduction of substrates of UGT1A9, UGT2B7, CYP2C8,
CYP2C9, and CYP2C19 (e.g., clobazam)
• Substrates of CYP1A2 and CYP2B6 may also require dose adjustment
• Concomitant use with valproate increases the incidence of liver enzyme
elevations. Discontinuation or reduction of EPIDIOLEX® and/or
concomitant valproate should be considered
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf

10. FDA Approval
• Zemdri® (plazomicin) – approved 6/25/2018
• An aminoglycoside antibacterial indicated for the treatment of patients
18 years of age or older with Complicated Urinary Tract Infections (cUTI)
including Pyelonephritis.
• See Black Box Warning on next slide
• Formulation and Administration:
• Injection 500 mg/10 mL (50 mg/mL) is a single-dose vial containing
plazomicin sulfate equivalent to 500 mg plazomicin free base.
• Administer 15 mg/kg every 24 hours by intravenous (IV) infusion over 30
minutes to patients 18 years of age or older with creatinine clearance
greater than or equal to 90 mL/min.
• Recommended duration of treatment is 4 to 7 days for cUTI, including
pyelonephritis.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210303Orig1s000lbl.pdf

11. Zemdri® (plazomicin)

12. Zemdri® (plazomicin)
• Dose Adjustments:
• Renal Impairment
• Warnings and Precautions:
• Hypersensitivity Reactions, including anaphylaxis
• Clostridium difficile-Associated Diarrhea
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210303Orig1s000lbl.pdf
Estimated CLcr a (mL/min) Recommended Dosage for ZEMDRI® Dosing Interval
Greater than or equal to 60 to less than 90 15 mg/kg Every 24 hours
Greater than or equal to 30 to less than 60 10 mg/kg Every 24 hours
Greater than or equal to 15 to less than 30 10 mg/kg Every 48 hours

13. Zemdri® (plazomicin)
• Most common adverse reactions (> 1% of patients) are
• Decreased renal function;
• Diarrhea;
• Hypertension;
• Headache;
• Nausea and vomiting; and
• Hypotension
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210303Orig1s000lbl.pdf

14. Zemdri® (plazomicin)
• Storage:
• Vials - 500 mg/10 mL (50 mg/mL) refrigerated at 2°C to 8°C (36°F to 46°F)
• Dilution and Preparation:
• The appropriate volume for the required dose should be diluted in 0.9%
Sodium Chloride Injection or Lactated Ringer’s Injection to achieve a final
volume of 50 mL for intravenous infusion
• After dilution, solution for administration is stable for 24 hours at room
temperature at concentrations of 2.5 mg/mL to 45 mg/mL in the
following solutions:
• 0.9% Sodium Chloride Injection
• Lactated Ringer’s Injection
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210303Orig1s000lbl.pdf

15. Mektovi® (binimetinib)
• Most common (≥25%) adverse reactions in patients receiving
the combination were:
• fatigue,
• nausea,
• diarrhea,
• vomiting,
• abdominal pain, and
• arthralgia
• Discontinuation of therapy due to adverse reactions occurred
in 5% of patients receiving the combination; the most common
reasons were hemorrhage and headache.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210498lbl.pdf

16. FDA Approval
• Mektovi® (binimetinib) – approved 6/27/2018
• A Kinase inhibitor, approved in combination with encorafenib for patients
with unresectable or metastatic melanoma with a BRAF V600E or V600K
mutation
• Formulation and Administration:
• Tablets: 15mg
• The recommended doses are binimetinib 45 mg orally twice daily (and
encorafenib 450 mg orally once daily)
• For patients with moderate or severe hepatic impairment the
recommended dose is 30 mg orally twice daily.
• If encorafenib is permanently discontinued, discontinue binimetinib
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210498lbl.pdf

17. Mektovi® (binimetinib)
• Warnings/Precautions:
• Cardiomyopathy: Assess left ventricular ejection fraction (LVEF) before
initiating treatment, after one month of treatment, then every 2 to 3
months thereafter. The safety has not been established in patients with
LVEF below 50%.
• Venous Thromboembolism
• Ocular Toxicities
• Interstitial Lung Disease (ILD)
• Hepatotoxicity
• Rhabdomyolysis
• Hemorrhage: Major hemorrhagic events can occur
• Embryo-Fetal Toxicity
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210498lbl.pdf

18. FDA Approval
• Braftovi® (encorafenib) – approved 6/27/2018
• A kinase inhibitor indicated, in combination with binimetinib, for the
treatment of patients with unresectable or metastatic melanoma with a
BRAF V600E or V600K mutation
• Not indicated for treatment of patients with wild-type BRAF melanoma
• Formulation:
• Capsules: 50mg and 75mg
• Recommended dose is 450 mg orally once daily in combination with
binimetinib
• If binimetinib is withheld, reduce BRAFTOVI® to a maximum dose of 300
mg once daily until binimetinib is resumed
• Further dose reduction to 200mg may be appropriate due to ADRs
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210496lbl.pdf

19. Braftovi® (encorafenib)
• Warnings and Precautions:
• New Primary Malignancies, cutaneous and non-cutaneous
• Tumor Promotion in BRAF Wild-Type Tumors
• Hemorrhage
• Uveitis
• QT Prolongation: Withhold for QTc of 500 ms or greater
• Embryo-Fetal Toxicity
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210496lbl.pdf

20. Braftovi® (encorafenib)
• Most common (≥25%) adverse reactions in patients receiving
the combination were:
• fatigue,
• nausea,
• diarrhea,
• vomiting,
• abdominal pain, and
• arthralgia
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210496lbl.pdf

21. Braftovi® (encorafenib)
• Drug Interactions:
• Strong or moderate CYP3A4 inhibitors: Concomitant use may increase
encorafenib plasma concentration. If concomitant use cannot be avoided,
modify dose.
• Strong or moderate CYP3A4 inducers: Concomitant use may decrease
encorafenib plasma concentrations. Avoid concomitant use.
• Sensitive CYP3A4 substrates: Concomitant use may increase toxicity or
decrease efficacy of these agents. Avoid hormonal contraceptives.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210496lbl.pdf

22. New Formulations
• Aristada Initio® (aripiprazole lauroxil)
• ER injectable suspension, for IM use
• In combination with oral aripiprazole, is indicated for the initiation of
ARISTADA® when used for the treatment of schizophrenia in adults
• Administer one 675 mg injection and one 30 mg dose of oral aripiprazole
in conjunction with the first ARISTADA injection
• Only to be used as a single dose and is not for repeated dosing
• Administer by intramuscular injection in either the deltoid or gluteal
muscle by a healthcare professional
• Not interchangeable with Aristada®
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209830lbl.pdf

23. New Formulations
• Lympak® (doxycycline)
• A tetracycline class drug indicated for the treatment of early Lyme
disease (as evidenced by erythema migrans) due to Borrelia burgdorferi
in adults and pediatric patients 8 years of age and older weighing 45 kg
and above
• Tablets: 100mg
• Recommended dose of 100 mg every 12 hours, for 21 days
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209844s000lbl.pdf
• Ablysinol® (alcohol)
• An ablative agent indicated to induce controlled cardiac septal infarction
to improve exercise capacity in adults with symptomatic hypertrophic
obstructive cardiomyopathy who are not candidates for surgical
myectomy
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/207987lbl.pdf

24. New Formulations
• Nocdurna® (desmopressin acetate)
• A vasopressin analog indicated for the treatment of nocturia due to
nocturnal polyuria in adults who awaken at least 2 times per night to void
• Sublingual Tablets: 27.7 mcg of desmopressin acetate (equivalent to
25 mcg of desmopressin) and 55.3 mcg of desmopressin acetate
(equivalent to 50 mcg of desmopressin)
• Women: 27.7 mcg daily, one hour before bedtime, administered
sublingually without water
• Men: 55.3 mcg daily, one hour before bedtime, administered sublingually
without water
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022517s000lbl.pdf

25. New Dosage Forms
• Nuplazid® (pimavanserin):
• Introduction of a 34 mg capsule strength.
• Introduction of a 10 mg tablet strength for patients administered
concomitant CYP3A4 inhibitors.
• Approved for a combined capsule and tablet label as well as the removal
of the 17 mg tablet strength.
https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2018/210793Orig1s000,207318Orig1s003ltr.pdf
• Qbrexza (glyopyrronium tosylate):
• An anticholinergic indicated for topical treatment of primary axillary
hyperhidrosis in adults and pediatric patients 9 years of age and older
• A single-use cloth pre-moistened with 2.4% glycopyrronium solution
• For topical use only. Apply once daily to both axillae using a single cloth
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210361lbl.pdf

26. Thank you!