Updates from FDA
New drugs
BREXUCABTAGENE AUTOLEUCEL
(Tecartus—Kite Pharma)
Drug class: CD19-directed genetically modified autologous T cell immunotherapy.
Indication: Treatment of adult patients diagnosed with mantle cell lymphoma who have not responded to or who have relapsed following other kinds of treatment.
Recommended dosage: For autologous and I.V. use only. Dosage is patient specific. See prescribing info for details.
Common adverse effects: Pyrexia, cytokine release syndrome, hypotension, encephalopathy, fatigue, tachycardia, arrhythmia, infection, chills, hypoxia, cough, tremor, musculoskeletal pain, headache, nausea, edema, motor dysfunction, constipation, diarrhea, decreased appetite, dyspnea, rash, insomnia, pleural effusion, and aphasia.
Boxed warning: Cytokine release syndrome and neurologic toxicities. Tecartus is available through a restricted program under a Risk Evaluation and Mitigation Strategy program.
Other warnings and precautions: Hypersensitivity reactions, severe infections, prolonged cytopenias, hypogammaglobulinemia, secondary malignancies, effects on ability to drive and use machines.
BUDESONIDE, GLYCOPYRROLATE, FORMOTEROL FUMARATE
(Breztri Aerosphere—AstraZeneca)
Drug class: Combination of an inhaled corticosteroid (budesonide), an anticholinergic (glycopyrrolate), and a long-acting beta2-adrenergic agonist (formoterol fumarate).
Indication: Maintenance treatment of patients with COPD.
Recommended dosage: Two inhalations twice daily administered by oral inhalation.
Common adverse effects: Upper respiratory tract infection, pneumonia, back pain, oral candidiasis, influenza, muscle spasm, UTI, cough, sinusitis, and diarrhea.
Warnings and precautions: Do not use in combination with additional therapy containing LABA because of risk of overdose. Increased risk of pneumonia; potential worsening of infections; risk of impaired adrenal function when transferring from systemic corticosteroids; hypercorticism and adrenal suppression; paradoxical bronchospasm; decrease in bone mineral density; glaucoma and cataracts with long-term use of inhaled corticosteroids; worsening of urinary retention; hypokalemia and hyperglycemia. Use with caution in patients with cardiovascular disorders, convulsive disorders, thyrotoxicosis, diabetes, and ketoacidosis. Budesonide and formoterol fumarate systemic exposure may increase in patients with severe hepatic impairment. Use should only be considered in patients with severe renal impairment if benefit outweighs the risk.
Drug interactions: Strong cytochrome P450 3A4 inhibitors; other adrenergic drugs; diuretics, xanthine derivatives, or steroids; monoamine oxidase inhibitors and tricyclic antidepressants; beta-blockers; anticholinergics.
CALCIPOTRIENE AND BETAMETHASONE DIPROPIONATE
(Wynzora—MC2 Therapeutics)
Drug class: Combination of a vitamin D analog (calcipotriene) and a corticosteroid (betamethasone dipropionate).
Indication: Topical treatment of plaque psoriasis in patients aged 18 years and older.
Recommended dosage and administration: Apply to affected areas once daily for up to 8 weeks. Discontinue therapy when control is achieved. Do not use more than 100 g per week. Do not use with occlusive dressings unless directed by a physician. Avoid use on the face, groin, or axillae, or if skin atrophy is present at the treatment site. Not for oral, ophthalmic, or intravaginal use.
Common adverse effects: Upper respiratory infection, headache, and application site irritation.
Warnings and precautions: Hypercalcemia and hypercalciuria, effects on endocrine system, and ophthalmic adverse reactions.
DECITABINE AND CEDAZURIDINE
(Inqovi—Astex Pharmaceuticals)
Drug class: Combination of a nucleoside metabolic inhibitor (decitabine) and a cytidine deaminase inhibitor (cedazuridine).
Indication: Treatment of adult patients with myelodysplastic syndromes and chronic myelomonocytic leukemia.
Recommended dosage: One tablet (35 mg decitabine and 100 mg cedazuridine) taken orally once daily on days 1 through 5 of each 28-day cycle. Take on an empty stomach.
Common adverse effects: Fatigue, constipation, hemorrhage, myalgia, mucositis, arthralgia, nausea, dyspnea, diarrhea, rash, dizziness, febrile neutropenia, edema, headache, cough, decreased appetite, upper respiratory tract infection, pneumonia, increased transaminase, decreased leukocytes, decreased platelet count, decreased neutrophil count, and decreased hemoglobin.
Warnings and precautions: The drug may cause myelosuppression and embryo-fetal toxicity. Advise patients not to breastfeed during therapy. Inform patients the drug can impair fertility.
Drug interactions: Avoid coadministration with drugs metabolized by cytidine deaminase.
FOSTEMSAVIR
(Rukobia—ViiV Healthcare)
Drug class: HIV-1 gp120-directed attachment inhibitor
Indication: Treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations.
Recommended dosage: One tablet taken twice daily with or without food.
Common adverse effects: Nausea.
Warnings and precautions: Immune reconstitution syndrome; QTc prolongation; elevations in hepatic transaminases in patients with hepatitis B or C virus co-infection.
Contraindications: Hypersensitivity to fostemsavir or any of the formulation’s components; coadministration with strong cytochrome P450 CYP3A inducers.
TAFASITAMAB-CXIX
(Monjuvi—Morphosys)
Drug class: CD19-directed cytolytic antibody.
Indication: Use in combination with lenalidomide for treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low-grade lymphoma, and who are not eligible for autologous stem cell transplant.
Recommended dosage: 12 mg/kg as an I.V. infusion according to dosing schedule in prescribing information. Administer in combination with lenalidomide for a maximum of 12 cycles and then continue tafasitamab-cxix as monotherapy until disease progression or unacceptable toxicity.
Common adverse effects: Neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, and decreased appetite.
Warnings and precautions: Infusion-related reactions, myelosuppression, infections, embryo-fetal toxicity. Advise patients not to breastfeed.
New Indications
CALCIUM, MAGNESIUM, POTASSIUM, AND SODIUM OXYBATES
(Xywav—Jazz Pharmaceuticals)
Drug class: Central nervous system depressant.
Indication: Treatment of cataplexy or excessive daytime sleepiness in patients aged 7 years and older with narcolepsy.
Recommended dosage: For pediatric patients 7 years and older, the recommended starting dosage, titration regimen, and maximum total nightly dosage are based on body weight. Taken orally.
Common adverse effects: In children, enuresis, nausea, headache, vomiting, weight decreased, decreased appetite, and dizziness. In adults, headache, nausea, dizziness, decreased appetite, parasomnia, diarrhea, hyperhidrosis, anxiety, and vomiting.
Boxed warning: Central nervous system depression and abuse and misuse.
Warnings and precautions: Central nervous system depression; depression and suicidality; confusion or anxiety; and parasomnias. Caution patients against hazardous activities requiring complete mental alertness or motor coordination within first 6 hours of dosing or after first initiating treatment until certain that the drug does not affect them adversely.
Contraindications: In combination with sedative hypnotics or alcohol; succinic semialdehyde dehydrogenase deficiency.
CANNABIDIOL
(Epidiolex—Greenwich Biosciences)
Drug class: Cannabidiol.
Indication: Treatment of seizures associated with tuberculosis sclerosis complex in patients aged one year and older.
Recommended dosage: 2.5 mg/kg by mouth twice daily. Increase the dose weekly by 2.5 mg/kg twice daily, as tolerated, to a recommended maintenance dosage of 12.5 mg/kg twice daily. Epidiolex is available as an oral solution of 100 mg/mL.
Common adverse effects: Diarrhea, transaminase elevations, decreased appetite, somnolence, pyrexia, and vomiting.
Warnings and precautions: Hepatocellular injury, somnolence and sedation, suicidal behavior and ideation, hypersensitivity reactions, withdrawal of antiepileptic drugs. Must be dispensed with a patient Medication Guide.
Drug interactions: Moderate or strong inhibitors of CYP3A4 or CYP2C19 and strong inducers of CYP3A4 or CYP2C19. Dose adjustments may be required for substrates of UGT1A9, UGT2B7, CYP2C8, CYP2C9, CYP2C19, CYP1A2, and CYP2B6.
FDA approves new I.V. opioid for acute pain
On August 7, FDA approved the opioid agonist oliceridine (Olinvyk—Trevena) to manage acute pain in adult patients whose pain is severe enough to require an I.V. opioid analgesic and for whom alternative treatments are inadequate. The drug is indicated for short-term I.V. use in hospitals or other controlled clinical settings.
“Addressing the opioid crisis remains a top priority for the FDA,” said Douglas Throckmorton, MD, deputy director for regulatory programs in FDA’s Center for Drug Evaluation and Research, in a statement. “We will continue to do everything we can to reduce the number of Americans who are addicted to opioids and cut the rate of new addiction through a number of cross-agency initiatives.”
Oliceridine’s safety profile is similar to other opioids. Its most common adverse reactions are nausea, vomiting, dizziness, headache, constipation, pruritus, and hypoxia. The drug may increase the risk for QT interval prolongation with daily doses exceeding 27 mg; life-threatening respiratory depression in patients who are older, have cachexia, or have chronic pulmonary disease; adrenal insufficiency; and severe hypotension. It may also increase risks of sedation and respiratory depression in patients with increased intracranial pressure, brain tumors, head injury, or impaired consciousness.
Oliceridine carries a boxed warning for addiction, abuse, and misuse; life-threatening respiratory depression; neonatal opioid withdrawal syndrome; and risks from concomitant use with benzodiazepines or other central nervous system depressants.
When treating patients, providers should use the lowest effective dosage for the shortest duration based on individual treatment goals, severity of pain, patient response, prior analgesic experience, and risk factors for substance use disorder. The initial dose should be 1.5 mg. Supplemental doses of 0.75 mg can be administered hourly as needed starting 1 hour after the initial dose. Oliceridine’s total daily dose should not exceed 27 mg.
Patients with significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; known or suspected GI obstruction; or hypersensitivity to oliceridine should not take the drug. If patients experience adverse reactions, contact Trevena at 1-844-465-4686 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
FDA approves first oral drug for spinal muscular atrophy
On August 7, FDA approved risdiplam (Evrysdi—Genentech, Inc.) for treatment of spinal muscular atrophy (SMA) in patients aged 2 months and older. Risdiplam, a survival of motor neuron 2 (SMN2) splicing modifier, is only the second drug and the first oral drug approved to treat the disease, which causes weakness and muscle wasting due to loss of lower motor neurons.
“Evrysdi is the first drug for this disease that can be taken orally, providing an important treatment option for patients with SMA, following the approval of the first treatment for this devastating disease less than four years ago,” said Billy Dunn, MD, director of the Office of Neuroscience in FDA’s Center for Drug Evaluation and Research, in a statement.
Risdiplam must be constituted by a pharmacist before dispensing. It is administered orally once daily after a meal using the provided oral syringe. The recommended daily dosage is 0.2 mg/kg for patients aged 2 months to younger than 2 years; 0.25 mg/kg for those aged 2 years and older weighing less than 20 kg; and 5 mg for those aged 2 years and older weighing 20 kg or more.
The most common adverse effects for patients with later-onset SMA are fever, diarrhea, and rash. Patients with infantile-onset SMA had similar adverse reactions, along with upper respiratory tract infection, pneumonia, constipation, and vomiting.
Risdiplam should not be taken with drugs that are substrates of multidrug and toxin extrusion transporters. Patients with hepatic impairment should not use the drug.