New FDA Drug Approvals

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

2. FDA Approval
• Akynzeo® (fosnetupitant/palonosetron) – approved 4/19/2018
• For injection, indicated in combination with dexamethasone in adults for
the prevention of acute and delayed nausea and vomiting associated
with initial and repeat courses of highly emetogenic cancer
chemotherapy
• A combination of palonosetron, a serotonin-3 (5-HT3) receptor
antagonist, and netupitant or fosnetupitant, substance P/neurokinin-1
(NK-1) receptor antagonists: palonosetron prevents nausea and vomiting
during the acute phase and netupitant/fosnetupitant prevents nausea
and vomiting during both the acute and delayed phase after cancer
chemotherapy
• Capsules are available (approved 2014) as 300 mg netupitant/0.5 mg
palonosetron
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210493s000lbl.pdf

3. Akynzeo® (fosnetupitant/palonosetron)
• Formulation and Administration:
• 235 mg fosnetupitant/0.25 mg palonosetron lyophilized powder in a
single-dose vial for reconstitution
• Reconstituted in 50 ml of 5% Dextrose Injection, USP or 0.9% Sodium
Chloride Injection, USP and administered as 30-minute infusion starting
approximately 30 minutes prior to the start of chemotherapy
• Warning/Precautions:
• Hypersensitivity reactions, including anaphylaxis, have been reported in
patients receiving palonosetron, with or without known hypersensitivity
to other 5-HT3 receptor antagonists.
• Serotonin syndrome has been reported with 5-HT3 receptor antagonists
alone but particularly with concomitant use of serotonergic drugs.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210493s000lbl.pdf

4. Akynzeo® (fosnetupitant/palonosetron)
• Adverse Reactions:
• Most common adverse reactions (≥3%) for capsules are headache,
asthenia, dyspepsia, fatigue, constipation and erythema. The safety
profile for injection was generally similar to that seen with capsules.
• Drug Interactions
• CYP3A4 Substrates: inhibition of CYP3A4 by netupitant can result in
increased plasma concentrations of the concomitant drug for 6 days after
single dosage administration; avoid concomitant CYP3A4 substrates for
one week, if feasible. If not avoidable, consider dose reduction of the
CYP3A4 substrate
• CYP3A4 Inducers (e.g., rifampin): decreased plasma concentrations of
netupitant; avoid use
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210493s000lbl.pdf

5. FDA Approval
• Crysvita® (burosumab-twza) – approved 4/17/2018
• Fibroblast growth factor 23 (FGF23) blocking antibody indicated for the
treatment of X-linked hypophosphatemia (XLH) in adult and pediatric
patients 1 year of age and older
• Formulation:
• For subcutaneous use only
• 10 mg/mL, 20 mg/mL, or 30 mg/mL in a single-dose vial
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761068s000lbl.pdf

6. Crysvita® (burosumab-twza)
• Administration:
• Pediatric XLH: Starting dose regimen is 0.8 mg/kg of body weight
rounded to the nearest 10 mg, administered every two weeks. The
minimum starting dose is 10 mg up to a maximum dose of 90 mg
• Dose may be increased up to approximately 2 mg/kg (maximum 90 mg),
administered every two weeks to achieve normal serum phosphorus
• Adult XLH: Dose regimen is 1 mg/kg body weight rounded to the nearest
10 mg up to a maximum dose of 90 mg administered every four weeks
• Adverse Reactions:
• In pediatric XLH patients: headache, injection site reaction, vomiting,
pyrexia, pain in extremity, vitamin D decreased
• In adult XLH patients: back pain, headache, tooth infection, restless leg
syndrome, vitamin D decreased, dizziness, constipation, blood
phosphorus increased
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761068s000lbl.pdf

7. Crysvita® (burosumab-twza)
• Warnings/Precautions:
• Hypersensitivity: Discontinue if serious hypersensitivity reactions occur
and initiate appropriate medical treatment.
• Hyperphosphatemia and Risk of Nephrocalcinosis: For patients already
taking Crysvita®, dose interruption and/or dose reduction may be
required based on a patient’s serum phosphorus levels.
• Injection Site Reactions: Administration may result in local injection site
reactions. Discontinue if severe injection site reactions occur and
administer appropriate medical treatment.
• Do not use with oral phosphate and active vitamin D analogs.
• Do not initiate if serum phosphorus is within or above the normal range
for age.
• Contraindicated in patients with severe renal impairment or end stage
renal disease
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761068s000lbl.pdf

8. FDA Approval
• Tavalisse® (fostamatinib disodium hexahydrate)
• A kinase inhibitor indicated for the treatment of thrombocytopenia in
adult patients with chronic immune thrombocytopenia (ITP) who have
had an insufficient response to a previous treatment
• The major metabolite of fostamatinib, R406, inhibits signal transduction of Fc-
activating receptors and B-cell receptor. R406 reduces antibody-mediated
destruction of platelets
• Formulation and Administration:
• Tablets: 100 mg, 150 mg
• Initiate at 100 mg orally twice daily with or without food. After 4 weeks,
increase to 150 mg twice daily, if needed, to achieve platelet count at
least 50 x 109/L as necessary to reduce the risk of bleeding.
• Manage adverse reactions using dose reduction, interruption of treatment, or
discontinuation.
• Discontinue after 12 weeks of treatment if the platelet count does not
increase to a level sufficient to avoid clinically important bleeding.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209299lbl.pdf

9. Tavalisse® (fostamatinib)
• Warnings/Precautions:
• Hypertension: Monitor blood pressure every 2 weeks until stable, then
monthly. Manage hypertension using standard antihypertensive
treatment and, if needed, interrupt, reduce or discontinue.
• Hepatotoxicity: Monitor LFTs monthly. If LFT levels are elevated,
interrupt, reduce or discontinue.
• Diarrhea: Manage diarrhea with supportive measures. If diarrhea
becomes severe, interrupt, reduce or discontinue.
• Neutropenia: Monitor ANC monthly, and for infection. If neutrophil count
decreases below 1.0 x 109/L, interrupt, reduce or discontinue.
• Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of potential
risk to a fetus and to use effective contraception.
• Pregnancy: Advise women of the risk to a fetus.
• Lactation: Advise women not to breastfeed.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209299lbl.pdf

10. Tavalisse® (fostamatinib)
• Adverse Reactions:
• Most common adverse reactions are diarrhea, hypertension, nausea,
respiratory infection, dizziness, ALT/AST increased, rash, abdominal pain,
fatigue, chest pain and neutropenia
• Drug Interactions:
• Strong CYP3A4 Inhibitors: Concomitant use with a strong CYP3A4
inhibitor increases exposure to R406 (the major active metabolite)
• Strong CYP3A4 Inducers: Concomitant use is not recommended
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209299lbl.pdf

11. New Approved Indication
• Jynarque® (tolvaptan)
• New indication: To slow kidney function decline in adults at risk of
rapidly progressing autosomal dominant polycystic kidney disease
(ADPKD).
https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2018/204441Orig1s000ltr.pdf

12. New Combination and New Dosage Form
• Hydrocodone bitartrate and guaifenesin (4/25/2018)
• Approval provides for the use of Hydrocodone Bitartrate and
Guaifenesin, 5mg/400mg Tablets for the symptomatic relief of cough and
to loosen mucus associated with the common cold in patients 18 years of
age and older
• Initial approval in 2014
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208085s000lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2018/208085Orig1s000ltr.pdf

13. Thank you!