Updates from FDA
New drugs
EPTINEZUMAB-JJMR
(Vyepti—Lundbeck)
Drug class: Calcitonin gene–
related peptide antagonist
Indication: First I.V.-only preventive treatment of migraine in adult patients
Recommended dosage: 100 mg as an I.V. infusion over approximately 30 minutes every 3 months; some patients may benefit from a 300-mg dosage.
Adverse effects: Nasopharyngitis, hypersensitivity
Contraindications, warnings, and precautions: Contraindicated in patients with serious hypersensitivity to eptinezumab-jjmr or to any of the excipients; reactions have included angioedema, urticaria, facial flushing, and rash.
OSILODROSTAT
(Isturisa—Novartis)
Drug class: Steroidogenesis inhibitor
Indication: First FDA-approved drug to directly address cortisol overproduction by blocking the 11-beta-hydroxylase enzyme and preventing cortisol synthesis in adults with Cushing’s disease who either cannot undergo pituitary gland surgery or have undergone the surgery but still have the disease
Recommended dosage: Initial dose, 2 mg by mouth twice daily in the morning and evening; provider may reevaluate dosage later, depending on patient’s response. Available in 1-, 5-, and 10-mg tablets.
Adverse effects: Adrenal insufficiency, headache, vomiting, nausea, fatigue, edema
Warnings and precautions: Hypocortisolism, QTc prolongation, elevations in adrenal hormone precursors and androgens
ISATUXIMAB-IRFC
(Sarclisa—Sanofi-Aventis)
Drug class: CD38-directed cytolytic antibody
Indication: In combination with pomalidomide and dexamethasone, treatment of multiple myeloma in adult patients who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor
Recommended dosage: 10 mg/kg via I.V. infusion every week for 4 weeks, followed by every 2 weeks in combination with pomalidomide and dexamethasone until disease progression or unacceptable toxicity
Adverse effects: Neutropenia, infusion-related reactions, pneumonia, upper respiratory tract infection, diarrhea, anemia, lymphopenia, thrombocytopenia
Warnings and precautions: I.V. infusion-related reactions; neutropenia; higher incidences of second primary malignancies; potential laboratory test interference; potential harm to a developing fetus (women who are pregnant should not use the drug, and women planning to become pregnant should use effective contraceptives during and for at least 5 months after treatment)
New indications
NINTEDANIB
(Ofev—Boehringer Ingelheim)
Drug class: Kinase inhibitor
Indication: Treatment of patients with chronic fibrosing interstitial lung disease with a progressive phenotype
Recommended dosage: 150 mg twice daily approximately 12 hours apart, taken with food. Recommended dosage in patients with mild hepatic impairment (Child-Pugh A): 100 mg twice daily approximately 12 hours apart, taken with food.
Adverse effects: Diarrhea, nausea, stomach pain, vomiting, liver problems, decreased appetite, headache, weight loss
Warnings and precautions: Hepatic impairment, elevated liver enzymes and drug-induced liver injury, GI disorders, potential embryo-fetal toxicity, arterial thromboembolic events, bleeding, and GI perforation. P-glycoprotein and CYP3A4 inhibitor drugs, including ketoconazole and erythromycin, may increase nintedanib exposure, and patients taking these inhibitors with nintedanib should be closely monitored.
NERATINIB
(Nerlynx—Puma Biotechnology)
Drug class: Kinase inhibitor
Indication: In combination with capecitabine, treatment of advanced or metastatic HER2-positive breast cancer in adult patients who have received two or more prior anti-HER2-based regimens
Recommended dosage: 240 mg (6 tablets) orally once daily with food on days 1 to 21 of a 21-day cycle plus capecitabine (750 mg/m2 orally twice daily) on days 1 to 14 of a 21-day cycle until disease progression or unacceptable toxicities
Adverse effects: Diarrhea, nausea, vomiting, decreased appetite, constipation, fatigue/asthenia, decreased weight, dizziness, back pain, arthralgia, urinary tract infection, upper respiratory tract infection, abdominal distention, renal impairment, muscle spasms
Warnings and precautions: Diarrhea, hepatotoxicity, embryo-fetal toxicity
FIDAXOMICIN
(Dificid—Merck)
Drug class: Macrolide antibacterial
Indication: Treatment of Clostridioides (formerly Clostridium) difficile–
associated diarrhea in children ages 6 months and older; new oral suspension also approved
Recommended dosage: For pediatric patients ages 6 months to younger than 18 years weighing at least 12.5 kg and able to swallow: one 200-mg tablet orally twice daily for 10 days. Oral suspension: For pediatric patients weighing at least 4 kg, twice daily for 10 days using an oral dosing syringe, according to weight-based dosing as specified in the full prescribing information.
Adverse effects: Pyrexia, abdominal pain, vomiting, diarrhea, constipation, increased aminotransferases, rash
Warnings and precautions: Acute hypersensitivity reactions; development of drug-resistant bacteria (should only be used to treat C. difficile–associated diarrhea)
New formulation
DIAZEPAM NASAL SPRAY
(Valtoco—Neurelis)
Drug class: Benzodiazepine/antiepileptic
Indication: Short-term treatment of seizure clusters (also known as “acute repetitive seizures”) in patients ages 6 years and older
Recommended dosage: Dosage is dependent on the patient’s age and weight; 5- and 10-mg doses are administered as a single spray into one nostril. Administration of 15- and 20-mg doses requires two nasal spray devices, one spray into each nostril. A second dose, when required, may be administered at least 4 hours after the initial dose (use a new blister pack).
Adverse effects: Somnolence, headache, nasal discomfort
Warnings and precautions: Increased central nervous system (CNS)–depressant effect when used with alcohol or other CNS depressants; suicidal behavior and ideation
Boxed warning: Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death
New vaccines
INFLUENZA A (H5N1) MONOVALENT
VACCINE, ADJUVANTED
(Audenz—Seqirus)
Drug class: Inactivated cell-based vaccine
Indication: Protects individuals ages 6 months and older against influenza A (H5N1) virus, also known as “bird flu” because of its prevalence in avians. The vaccine can be stockpiled for first responders and rapidly deployed during a pandemic.
Recommended dosage: Two doses (0.5 mL each) 21 days apart intramuscularly
Adverse effects: In adults, injection site pain, fatigue, headache, malaise, myalgia, arthralgia, and nausea; in infants and children, tenderness, irritability, sleepiness, change in eating habits, fever, injection site pain, myalgia, fatigue, malaise, headache, loss of appetite, nausea, arthralgia
Warnings and precautions: Hypersensitivity reactions. If Guillain-Barré syndrome has occurred within 6 weeks of receipt of a prior influenza vaccine, the decision to give Audenz should be based on careful consideration of the potential benefits and risks.
New generics
PYRIMETHAMINE
(Daraprim generic—Cerovene)
Drug class: Antiparasitic
Indication: Treatment of toxoplasmosis, an infection caused by the parasite Toxoplasma gondii, when used with a sulfonamide
Recommended dosage: Adult starting dose: 50 mg to 75 mg daily, with 1 g to 4 g daily of a sulfonamide of the sulfapyrimidine type (e.g., sulfadoxine) for 1 to 3 weeks, depending on patient’s response and tolerance to therapy. Pediatric dosage is 1 mg/kg/day divided into two equal daily doses, with the usual pediatric sulfonamide dosage; after 2 to 4 days, this dose may be reduced to one-half and continued for approximately 1 month.
Adverse effects: Hypersensitivity reactions that can occasionally be severe, such as Stevens–Johnson syndrome and toxic epidermal necrolysis; erythema multiforme; anaphylaxis; and elevated blood concentration of phenylalanine, particularly when pyrimethamine is administered at the same time as a sulfonamide
Warnings and precautions: Anorexia and vomiting, megaloblastic anemia, pancytopenia, neutropenia, atrophic glossitis, hematuria, cardiac rhythm disorders; hematologic effects at low doses in certain individuals; pulmonary eosinophilia (rare). Should not be used in patients with known hypersensitivity to pyrimethamine or with documented megaloblastic anemia due to folate deficiency. Use with caution in patients with impaired kidney or liver function, possible folate deficiency, or receiving therapy affecting folate levels, such as phenytoin.
Women who are taking the drug should not become pregnant. Keep out of the reach of children.
ALBUTEROL SULFATE
INHALATION AEROSOL
(ProAir HFA generic—
Perrigo Pharmaceutical)
Drug class: Beta2-adrenergic agonist
Indication: First generic to treat or prevent bronchospasm in patients ages 4 years and older with reversible obstructive airway disease and to prevent exercise-induced bronchospasm in patients ages 4 years and older
Recommended dosage: To prevent bronchospasm, two inhalations every 4 to 6 hours; to prevent exercise-induced bronchospasm, two inhalations 15 to 30 minutes before exercise. Prime the inhaler before using for the first time and when it has not been used for more than 2 weeks by releasing four test sprays into the air, away from the face.
Adverse effects: Headache, rapid heart rate, pain, dizziness, sore throat, rhinitis, chest pain, palpitations, tremor, nervousness
Warnings and precautions: Life-threatening paradoxical bronchospasm, cardiovascular effects, immediate hypersensitivity reactions, hypokalemia, changes in blood glucose. A need for more doses than usual may be a sign of deterioration of asthma that requires treatment reevaluation. Not a substitute for corticosteroids. Excessive use may be fatal (do not exceed recommended dose).
FDA approves two unique nonstatin drugs that lower LDL-C
For the first time in nearly 2 decades, FDA has approved two new oral nonstatin drugs that lower LDL-C: bempedoic acid (Nexletol) and bempedoic acid and ezetimibe (Nexlizet), both manufactured by Esperion.
Indicated for adjunct use with diet and maximally tolerated statin therapy, the once-daily medications provide additional lowering of LDL-C in adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease.
Bempedoic acid, the first in a new class of drugs, lowers LDL-C by inhibiting cholesterol synthesis in the liver. Approval was based on the results of the global Phase III LDL-C lowering study of more than 3,000 patients. Administered with moderate- or high-intensity statins, the drug led to an average of 18% placebo-corrected decrease in LDL-C. Bempedoic acid’s effect on cardiovascular morbidity and mortality has not been determined.
Bempedoic acid and ezetimibe—the first nonstatin, LDL-C lowering combination medication ever approved—lowers elevated LDL-C by inhibiting cholesterol synthesis in the liver and absorption in the intestine.
Approval was supported by the Phase III fixed combination drug product LDL-C lowering program, as well as safety data from the Phase III bempedoic acid trial and the existing ezetimibe safety profile. When added on to maximally tolerated statins, the combo drug lowered LDL-C by 38% percent compared with placebo.
Label warnings and precautions include hyperuricemia, with the development of gout in a small percentage of patients, as well as increased risk of tendon rupture or injury. In the clinical trials, adverse events reported most frequently were upper respiratory tract infections, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia, and elevated liver enzymes. The majority were mild to moderate in severity.
Additional adverse events reported for bempedoic acid and ezetimibe were diarrhea, arthralgia, sinusitis, fatigue, and influenza.
Bempedoic acid will be available by prescription on March 30, 2020, and bempedoic acid and ezetimibe will be available in July 2020. Both drugs are expected to cost about $10 per fill for up to a 3-month supply, according to Esperion.
Sofosbuvir/velpatasvir has new indication for children 6 years and older
FDA approved sofosbuvir/velpatasvir (Epclusa—Gilead Sciences) in combination with ribavirin to treat hepatitis C virus (HCV) in children ages 6 years and older or weighing at least 37 pounds (17 kg) with any of the six HCV genotypes—or strains—without cirrhosis or with mild cirrhosis. It was previously approved to treat HCV in adults.
Approval was based on an open-label, multicenter clinical trial that included 173 treatment-naive and treatment-experienced pediatric patients ages 6 years and older without cirrhosis or with mild cirrhosis. No meaningful differences in pharmacokinetics or safety and efficacy results were seen in pediatric patients compared with adults.
The most common adverse reactions, fatigue and headache, were consistent with those observed in clinical trials with adults.
A boxed warning cautions that hepatitis B virus (HBV) reactivation has been reported in patients infected with both HCV and HBV who were taking or had completed treatment with HCV antivirals and were not taking HBV antivirals. HBV reactivation has resulted in hepatitis that occurs suddenly and escalates quickly, kidney failure, and death.
Health care providers should test all patients for evidence of current or prior HBV infection before initiating sofosbuvir and velpatasvir and continue to monitor patients throughout treatment.
Recommended dosage is based on weight; see the prescribing information.
First adjuvanted quadrivalent flu vaccine approved for older adults
FDA has approved the first adjuvanted quadrivalent influenza vaccine (Fluad Quadrivalent—Seqirus) to help protect adults ages 65 years and older against seasonal influenza caused by influenza virus subtypes A and types B.
The inactivated flu vaccine was designed with the same MF59 adjuvant technology as Fluad but includes an additional strain.
Individuals should not receive the vaccine if they have a severe allergic reaction to any component of the vaccine, including egg protein, or have had a severe reaction after a previous dose of any influenza vaccine.
If Guillain-Barré syndrome has occurred within 6 weeks of previous influenza vaccination, the decision to administer should be based on careful consideration of the potential benefits and risks.
Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine. The immune response in immunocompromised persons, including those receiving immunosuppressive therapy, may be lower than in immunocompetent persons.
In addition, fainting may occur, and procedures should be in place to avoid injury from falling.
In clinical trials, the most common adverse events reported in adults aged 65 years and older were injection site pain, headache, and fatigue.