Updates from FDA
New drugs
IBREXAFUNGERP
(Brexafemme—Scynexis)
Drug class: Triterpenoid antifungal.
Indication: First nonazole once-daily oral treatment for vulvovaginal candidiasis (vaginal yeast infection).
Recommended dosage and administration: 300 mg (two 150-mg tablets) twice a day for one day for women and postmenarchal girls, for a total treatment dosage of 600 mg. May be taken with or without food. Before initiating treatment, verify pregnancy status in females of reproductive potential.
Common adverse effects: Diarrhea, nausea, abdominal pain, dizziness, vomiting.
Warnings and precautions: Risk of fetal toxicity; advise females of reproductive potential to use effective contraception during treatment.
INFIGRATINIB
(Truseltiq—BridgeBio Pharma)
Drug class: Tyrosine kinase inhibitor.
Indication: Treatment of patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring a fibroblast growth factor receptor 2 fusion or other rearrangement as detected by an FDA-approved test.
Recommended dosage and administration: 125 mg orally once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles. Patients take medication on an empty stomach at least 1 hour before or 2 hours after food, at approximately the same time each day. The capsules must be swallowed whole with a glass of water and should not be crushed, chewed, or dissolved.
For patients with mild and moderate renal impairment and for those with mild hepatic impairment, dosage is 100 mg orally once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles. For patients with moderate hepatic impairment, dosage is 75 mg orally once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles.
Common adverse effects: Nail toxicity, stomatitis, dry eye, fatigue, alopecia, palmar-plantar erythrodysesthesia syndrome, arthralgia, dysgeusia, constipation, abdominal pain, dry mouth, eyelash changes, diarrhea, dry skin, decreased appetite, blurred vision, vomiting.
Warnings and precautions: Ocular toxicity; hyperphosphatemia and soft tissue mineralization; embryo-fetal toxicity.
OLANZAPINE/SAMIDORPHAN
(Lybalvi—Alkermes)
Drug class: Atypical antipsychotic (olanzapine) and opioid antagonist (samidorphan).
Indication: Once-daily oral treatment for adults with schizophrenia, and for adults with bipolar I disorder (as a maintenance monotherapy or for acute treatment of manic or mixed episodes, and as monotherapy or an adjunct to lithium or valproate).
Recommended dosage and administration: See prescribing information for detailed instructions.
Common adverse effects: Schizophrenia, weight gain, somnolence, dry mouth, headache; bipolar I disorder, manic or mixed episodes, asthenia, dry mouth, constipation, increased appetite, somnolence, dizziness, tremor; bipolar I disorder, manic or mixed episodes, adjunct to lithium or valproate: dry mouth, dyspepsia, weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia, paresthesia.
Boxed warning: Older adult patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. The medication is not approved for treatment of patients with dementia-related psychosis.
Other warnings and precautions: Cerebrovascular adverse reactions in older adult patients with dementia-related psychosis; precipitation of opioid withdrawal in patients who are dependent on opioids; vulnerability to life-threatening opioid overdose; neuroleptic malignant syndrome; drug reaction with eosinophilia and systemic symptoms; metabolic changes; tardive dyskinesia; orthostatic hypotension and syncope; leukopenia, neutropenia, and agranulocytosis; seizures; potential for cognitive and motor impairment; anticholinergic (antimuscarinic) effects; hyperprolactinemia.
Contraindications: Patients who are using opioids or who are undergoing acute opioid withdrawal. If administered with lithium or valproate, refer to the lithium or valproate prescribing information for the contraindications for those products.
SOTORASIB
(Lumakras—Amgen)
Drug class: Inhibitor of the RAS GTPase family.
Indication: Treatment of adult patients with KRAS G12C–mutated locally advanced or metastatic non–small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.
Recommended dosage and administration: 960-mg tablets taken orally once daily, swallowed whole with or without foods.
Common adverse effects: Diarrhea, musculoskeletal pain, nausea, fatigue, liver damage, cough.
Warnings and precautions: Sotorasib should be withheld if patients develop symptoms of interstitial lung disease and permanently discontinued if interstitial lung disease is confirmed.
Health care professionals should monitor a patient’s liver function tests before they begin taking the medication and during treatment. If a patient develops liver damage, sotorasib should be withheld, the dose reduced, or the medication permanently discontinued. Patients should avoid taking acid-reducing agents, drugs that induce or are substrates for certain enzymes in the liver, and drugs that are substrates of the P-glycoprotein while taking sotorasib.
AMIVANTAMAB-VMJM
(Rybrevant—Janssen)
Drug class: Bispecific epidermal growth factor receptor (EGFR)–directed and MET receptor–directed antibody.
Indication: First treatment for adult patients with NSCLC whose tumors have EGFR exon 20 insertion mutations, as detected by an FDA-approved companion diagnostic, the Guardant360 CDx (Guardant Health).
Recommended dosage and administration: 1,050 mg (three vials) in patients weighing less than 80 kg; 1,400 mg (four vials) in patients weighing 80 kg or more. Administer weekly for 4 weeks, with the initial dose as a split infusion in week 1 on day 1 and day 2, then every 2 weeks thereafter.
Common adverse effects: Rash; infusion-related reactions; skin infections around the fingernails or toenails; muscle and joint pain; shortness of breath; nausea; fatigue; swelling in the lower legs, hands, or face; mouth sores; cough; constipation; vomiting; changes in certain blood tests.
Warnings and precautions: Amivantamab-vmjw should be withheld if patients develop symptoms of interstitial lung disease and permanently discontinued if interstitial lung disease is confirmed. Patients taking amivantamab-vmjw should limit sun exposure during and for 2 months after treatment. The medication may cause problems with vision. It can also cause fetal harm when administered to a pregnant woman. Confirm pregnancy status of females of reproductive potential before initiating treatment.
Sotrovimab gains EUA for treatment of mild to moderate COVID-19
On May 26, FDA issued an emergency use authorization (EUA) for the investigational monoclonal antibody therapy sotrovimab (GlaxoSmithKline) to treat mild to moderate COVID-19 in adults and pediatric patients ages 12 years and older who weigh at least 40 kg (about 88 lb). The patients must have positive results of direct SARS-CoV-2 viral testing and be at high risk for progression to severe COVID-19, including hospitalization or death. This includes, for example, individuals who are age 65 years and older or individuals who have certain medical conditions.
Sotrovimab is administered intravenously by health care providers as a 500-mg single dose. The EUA requires that fact sheets be made available to health care providers and to patients, parents, and caregivers. The fact sheets include dosing instructions, potential adverse effects, and drug interactions. Potential adverse effects of sotrovimab include anaphylaxis and infusion-related reactions, rash, and diarrhea.
The data supporting this EUA for sotrovimab are based on an interim analysis from a randomized, double-blind, placebo-controlled clinical trial in 583 nonhospitalized adults with mild to moderate COVID-19 symptoms and a positive SARS-CoV-2 test result. Of these patients, 291 received sotrovimab, and 292 received a placebo within 5 days of onset of COVID-19 symptoms. The primary endpoint was progression of COVID-19 (defined as hospitalization for more than 24 hours for acute management of any illness or death from any cause) through day 29. Hospitalization or death occurred in 21 (7%) patients who received placebo compared with 3 (1%) patients treated with sotrovimab, an 85% reduction.
Sotrovimab is not authorized for patients who are hospitalized or require oxygen therapy due to COVID-19. The treatment has not shown benefit in patients hospitalized for COVID-19, and monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients who require high-flow oxygen or mechanical ventilation.
FDA is continuing to evaluate sotrovimab’s safety and effectiveness for treatment of COVID-19 and is carefully monitoring circulating viral variants and their sensitivity to monoclonal antibodies authorized to treat COVID-19, including sotrovimab. Lab testing showed that sotrovimab retains activity against the current circulating variants first reported in the United Kingdom, South Africa, Brazil, California, New York, and India.