May 2018 FDA New Drug Approvals

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

FDA Approval
• Lokelma® (sodium zirconium cyclosilicate) – approved 5/18/18
• A potassium binder indicated for the treatment of hyperkalemia in adults
• Formulation and Administration:
• For oral suspension: 5 g per packet or 10 g per packet
• Recommended starting dose is 10 g administered three times a day for
up to 48 hours
• For maintenance treatment, recommended dose is 10 g once daily (can
range from 5 g every other day to 15 g daily)
• Adjust dose at one-week intervals as needed (by 5 g daily) to obtain
desired serum potassium target range
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/207078s000lbl.pdf

Lokelma® (sodium zirconium cyclosilicate)
• Warning/Precautions:
• Gastrointestinal Adverse Events in Patients with Motility Disorders.
• Edema
• Adverse Reactions:
• Most common is mild to moderate edema
• Drug Interactions:
• In general, other oral medications should be administered at least 2
hours before or 2 hours after

Lokelma® (sodium zirconium cyclosilicate)
• Reconstitution:
• Instruct patients to empty the entire contents of the packet(s) into a
drinking glass containing approximately 3 tablespoons of water or more if
desired. Stir well and drink immediately. If powder remains in the
drinking glass, add water, stir and drink immediately. Repeat until no
powder remains to ensure the entire dose is taken.
• Mechanism of Action:
• Preferentially captures potassium in exchange for hydrogen and sodium.
In vitro, has a high affinity for potassium ions, even in the presence of
other cations such as calcium and magnesium.
• Increases fecal potassium excretion through binding of potassium in the
lumen of the gastrointestinal tract. Binding of potassium reduces the
concentration of free potassium in the gastrointestinal lumen, thereby
lowering serum potassium levels.

FDA Approval
• Lucemyra® (lofexidine) – approved 5/18/2018
• A central alpha-2 adrenergic agonist indicated for mitigation of opioid
withdrawal symptoms to facilitate abrupt opioid discontinuation in adults
• The usual dosage is three 0.18 mg tablets taken orally 4 times daily at 5-
to 6-hour intervals, treatment may be continued for up to 14 days with
dosing guided by symptoms
• Discontinue with a gradual dose reduction over 2 to 4 days.
• Tablets: 0.18 mg

Lucemyra® (lofexidine)
• Most common adverse reactions (incidence ≥ 10% and notably more
frequent than placebo) are:
• Orthostatic hypotension
• Bradycardia
• Hypotension
• Dizziness,
• Somnolence,
• Sedation, and
• Dry mouth

• Warnings/Precautions:
• Risk of Hypotension, Bradycardia, and Syncope
• Risk of QT Prolongation
• Increased risk of CNS Depression with Concomitant use of CNS
Depressant Drugs
• Increased risk of Opioid Overdose after Opioid Discontinuation
• Risk of Discontinuation Symptoms

• Methadone: Methadone and LUCEMYRA both prolong the QT interval.
ECG monitoring is recommended when used concomitantly.
• Oral Naltrexone: Concomitant use may reduce efficacy of oral naltrexone.
• CYP2D6 Inhibitors: Concomitant use of paroxetine resulted in increased
plasma levels. Monitor for symptoms of orthostasis and bradycardia with
concomitant use of a CYP2D6 inhibitor.
• https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209229s000lbl.pdf

• Dose Adjustments:
• Renal Impairment
• CLcr 30-89.9 ml/min: 2 tablets 4 times a day
• CLcr <30 ml/min: 1 tablet 4 times a day
• Hepatic Impairment
• Mild: 3 tablets 4 times a day
• Moderate: 2 tablets 4 times a day
• Severe: 1 tablet 4 times a day
• https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209229s000lbl.pdf

FDA Approval
• Aimovig® (erenumab-aooe) – approved 5/17/2018
• A calcitonin gene-related peptide receptor antagonist indicated for the
preventive treatment of migraine in adults
• A human immunoglobulin G2 (IgG2) monoclonal antibody that has high
affinity binding to the calcitonin gene-related peptide receptor.
Erenumab-aooe is produced using recombinant DNA technology in
Chinese hamster ovary (CHO) cells.

Aimovig® (erenumab-aooe)
• Injection: 70 mg/mL solution in a single-dose prefilled SureClick®
autoinjector
• Injection: 70 mg/mL solution in a single-dose prefilled syringe
• Recommended dosage is 70 mg once monthly; some patients may
benefit from a dosage of 140 mg once monthly
• The 140 mg dose is administered once monthly as two consecutive
injections of 70 mg each
• Administer in the abdomen, thigh, or upper arm subcutaneously only
• Adverse Reactions
• Injection site reactions
• Constipation

FDA Approval
• Doptelet® (avatrombopag) – approved 5/21/2018
• A thrombopoietin receptor agonist indicated for the treatment of
thrombocytopenia in adult patients with chronic liver disease who are
scheduled to undergo a procedure
• Tablet: 20mg
• Begin dosing 10 to 13 days prior to a scheduled procedure.
• Patients should undergo their procedure within 5 to 8 days after the last
dose.
• Should be taken orally with food once daily for 5 consecutive days.
• The recommended dose is based on a patient’s platelet count prior to a
scheduled procedure (see next slide)

Doptelet® (avatrombopag)
• Recommended Dose/Duration:
• Most common are pyrexia, abdominal pain, nausea, headache, fatigue,
and edema peripheral
Platelet Count (x109/L) Once Daily Dose Duration
Less than 40 60 mg (3 tablets) 5 days
40 to less than 50 40 mg (2 tablets) 5 days

Doptelet® (avatrombopag)
• Thrombotic/Thromboembolic Complications: Thrombopoietin (TPO)
receptor agonists have been associated with thrombotic and
thromboembolic complications in patients with chronic liver disease.
Monitor platelet counts and for thromboembolic events and institute
treatment promptly.

FDA Approval
• Palynziq® (pegvaliase-pqpz) – approved 5/24/2018
• A phenylalanine-metabolizing enzyme indicated to reduce blood
phenylalanine concentrations in adult patients with phenylketonuria who
have uncontrolled blood phenylalanine concentrations greater than 600
micromol/L on existing management.
• Formulation:
• Injection: 2.5 mg/0.5 mL, 10 mg/0.5 mL, and 20 mg/mL in a single-dose
prefilled syringe

Palynziq® (pegvaliase-pqpz)
• Black Boxed Warning: Risk of Anaphylaxis
• Anaphylaxis has been reported after administration and may occur at
any time during treatment.
• Administer the initial dose under the supervision of a healthcare
provider equipped to manage anaphylaxis, and closely observe patients
for at least 60 minutes following injection. Prior to self-injection,
confirm patient competency with self-administration, and patient’s and
observer’s (if applicable) ability to recognize signs and symptoms of
anaphylaxis and to administer auto-injectable epinephrine, if needed.
• Prescribe auto-injectable epinephrine. Prior to first dose, instruct the
patient and observer (if applicable) on its appropriate use. Instruct the
patient to seek immediate medical care upon its use. Instruct patients
to carry auto-injectable epinephrine with them at all times during
Palynziq treatment.
• Available only through a restricted program called the Palynziq REMS.

• Administration 1/3:
• Obtain baseline blood phenylalanine concentration before initiating
treatment.
• The recommended initial dosage is 2.5 mg subcutaneously once weekly
for 4 weeks.
• Titrate the dosage in a step-wise manner over at least 5 weeks based on
tolerability to achieve a dosage of 20 mg subcutaneously once daily. See
full prescribing information for titration regimen.
• Assess patient tolerability, blood phenylalanine concentration, and
dietary protein and phenylalanine intake throughout treatment.

• Consider increasing the dosage to a maximum of 40 mg subcutaneously
once daily in patients who have been on 20 mg once daily continuously
for at least 24 weeks and who have not achieved either a 20% reduction
in blood phenylalanine concentration from pre-treatment baseline or a
blood phenylalanine concentration less than or equal to 600 micromol/L.
• Discontinue in patients who have not achieved at least a 20% reduction
in blood phenylalanine concentration from pre-treatment baseline or a
blood phenylalanine concentration less than or equal to 600 micromol/L
after 16 weeks of continuous treatment with the maximum dosage of 40
mg once daily.
• Reduce the dosage and/or modify dietary protein and phenylalanine
intake, as needed, to maintain blood phenylalanine concentrations within
a clinically acceptable range and above 30 micromol/L

• Blood Phenylalanine Monitoring and Diet:
• Obtain blood phenylalanine concentrations every 4 weeks until a
maintenance dosage is established.
• After a maintenance dosage is established, periodically monitor blood
phenylalanine concentrations.
• Counsel patients to monitor dietary protein and phenylalanine intake,
and adjust as directed by their healthcare provider.
• Premedication:
• Consider premedication for hypersensitivity reactions.
• Administration Instructions:
• Rotate injection sites. If more than one injection is needed for a single
dose, the injection sites should be at least 2 inches away from each other

• Hypersensitivity Reactions, Other than Anaphylaxis
• Most common ADR are Injection site reactions, arthralgia,
hypersensitivity reactions, headache, generalized skin reactions lasting at
least 14 days, pruritus, nausea, abdominal pain, oropharyngeal pain,
vomiting, cough, diarrhea, and fatigue.
• Monitor patients treated with Palynziq® and concomitantly with other
PEGylated products for hypersensitivity reactions including anaphylaxis.

FDA Approval
• Olumiant® (baricitinib) – approved 5/31/2018
• A Janus kinase (JAK) inhibitor indicated for the treatment of adult
patients with moderately to severely active rheumatoid arthritis who
have had an inadequate response to one or more TNF antagonist
therapies
• Use of in combination with other JAK inhibitors, biologic DMARDs, or
with potent immunosuppressants such as azathioprine and cyclosporine
is not recommended.

Olumiant® (baricitinib)
• Black Boxed Warning: Serious Infections, Malignancy, and Thrombosis
• Serious infections leading to hospitalization or death, including
tuberculosis and bacterial, invasive fungal, viral, and other
opportunistic infections, have occurred in patients.
• If a serious infection develops, interrupt treatment until the infection is
controlled.
• Prior to starting, perform a test for latent tuberculosis; if it is positive,
start treatment for tuberculosis prior to starting.
• Monitor all patients for active tuberculosis during treatment, even if
the initial latent tuberculosis test is negative.
• Lymphoma and other malignancies have been observed in patients.
• Thrombosis, including deep venous thrombosis, pulmonary embolism,
and arterial thrombosis, some fatal, have occurred in patients treated.
Patients with symptoms of thrombosis should be evaluated promptly.

• Tablets (not scored): 2 mg
• The recommended dose is 2 mg once daily.
• May be used as monotherapy or in combination with methotrexate or
other DMARDs.
• Anemia: Avoid initiation or interrupt treatment in patients with
hemoglobin less than 8 g/dL.
• Lymphopenia: Avoid initiation or interrupt treatment in patients with an
Absolute Lymphocyte Count less than 500 cells/mm3.
• Neutropenia: Avoid initiation of interrupt treatment in patients with an
Absolute Neutrophil Count less than 1000 cells/mm3.

• Dose Adjustments:
• Hepatic Impairment: Use not recommended in patients with severe
hepatic impairment
• Renal Impairment: Use not recommended in patients with moderate to
severe renal impairment
• Not recommended in patients taking strong Organic Anion Transporter 3
(OAT3) inhibitors (e.g., probenecid).
• Include upper respiratory tract infections, nausea, herpes simplex, and
herpes zoster.

• Serious Infections: Avoid use in patients with active, serious infection,
including localized infections. If a serious infection develops, interrupt
therapy until the infection is controlled. Do not give to patients with
active tuberculosis.
• Thrombosis: Use with caution in patients who may be at increased risk.
• Gastrointestinal Perforations: Use with caution in patients who may be at
increased risk.
• Laboratory Assessment: Recommended due to potential changes in
lymphocytes, neutrophils, hemoglobin, liver enzymes, and lipids.
• Vaccinations: Avoid use with live vaccines.

New Formulation
• Lamivudine and Tenofovir Disoproxil Fumarate
• 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
• 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.

New Combination
• Consensi® (amlodipine/celecoxib) – 5/31/2018
• A combination of amlodipine besylate, a calcium channel blocker, and
celecoxib, a nonsteroidal anti-inflammatory drug (NSAID), indicated for
patients for whom treatment with amlodipine for hypertension and
celecoxib for osteoarthritis are appropriate.
• Administration and Formulation:
• Tablets (amlodipine/celecoxib): 2.5 mg/200 mg, 5 mg/200 mg, or 10
mg/200 mg
• Start at (amlodipine/celecoxib) 5 mg/200 mg (2.5 mg/200 mg for small,
elderly, or frail patients or hepatic impairment) orally once daily. Titrate
as needed for blood pressure control.

May 2018 FDA New Drug Approvals

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