New drugs
DASIGLUCAGON INJECTION
(Zegalogue—Zealand Pharma)
Drug class: Antihypoglycemic.
Indication: Autoinjector and prefilled syringe for S.C. injection to treat severe hypoglycemia in pediatric and adult patients ages 6 years and older who have diabetes.
Recommended dosage and administration: 0.6 mg for adults and pediatric patients ages 6 years and older, administered via injection into the lower abdomen, buttocks, thigh, or outer upper arm. Call for emergency assistance immediately after administering the dose. If there has been no response after 15 minutes, an additional dose from a new device may be administered while waiting for emergency assistance. When the patient has responded to treatment, give oral carbohydrates. Each device contains a single dose of dasiglucagon and cannot be reused.
Common adverse effects: Nausea, vomiting, headache, diarrhea, and injection site pain in adults; nausea, vomiting, headache, and injection site pain in children.
Warnings and precautions: Contraindicated in patients with pheochromocytoma (a rare tumor that usually starts in the cells of one of the adrenal glands) because the drug may stimulate the release of catecholamines from the tumor and result in substantial increase in blood pressure; risk of hypoglycemia in patients with insulinoma; hypersensitivity and allergic reactions; lack of efficacy in patients with decreased hepatic glycogen.
LONCASTUXIMAB
TESIRINE-LPYL
(Zynlonta—ADC Therapeutics SA)
Drug class: CD19-directed antibody and alkylating agent conjugate.
Indication: Treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma.
Recommended dosage and administration: 0.15 mg/kg every 3 weeks for two cycles, then 0.075 mg/kg every 3 weeks for subsequent cycles, via I.V. infusion over 30 minutes on day 1 of each cycle (every 3 weeks). Patients should be premedicated with dexamethasone 4 mg orally or intravenously twice daily for 3 days beginning the day before administration of loncastuximab tesirine-lpyl.
Common adverse effects: Laboratory abnormalities, thrombocytopenia, increased gamma-glutamyltransferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea, musculoskeletal pain.
Warnings and precautions: Risk of edema and effusions, myelosuppression, fatal and serious infections, cutaneous reactions, and embryo–fetal toxicity.
PEGCETACOPLAN
(Empaveli—Apellis Pharmaceuticals)
Drug class: Targeted C3 inhibitor.
Indication: To treat adults with paroxysmal nocturnal hemoglobinuria (PNH), a rare, life-threatening blood disease.
Recommended dosage and administration: 1,080 mg by S.C. infusion twice weekly via a commercially available pump.
Common adverse effects: Injection site reactions, infections, diarrhea, abdominal pain, respiratory tract infection, viral infection, fatigue.
Boxed warning: Meningococcal infections may occur and may become rapidly life-threatening or fatal if not recognized and treated early. Use of the drug may predispose individuals to serious infections, especially those caused by encapsulated bacteria. Pegcetacoplan is available only through a restricted program under a REMs.
New indications
DAPAGLIFLOZIN
(Farxiga—AstraZeneca)
Drug class: Sodium–glucose cotransporter 2 inhibitor.
Indication: To reduce the risk of kidney function decline, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease who are at risk of disease progression. Originally approved in 2014 to improve glycemic control in adults with type 2 diabetes in addition to diet and exercise.
Recommended dosage and administration: 5 to 10 mg once daily depending on eGFR; see prescribing information for complete instructions.
Common adverse effects: Dehydration, serious urinary tract infections, genital yeast infections, metabolic acidosis, or ketoacidosis.
Warnings and precautions: Risk of serious hypersensitivity reactions and life-threatening cases of Fournier’s Gangrene. Patients should consider a lower dose of insulin or insulin secretagogue to reduce the risk of hypoglycemia if they are also taking dapagliflozin. Patients should also be assessed for their volume status and kidney function before starting dapagliflozin.
DOSTARLIMAB
(Jemperli—GlaxoSmithKline)
Drug class: Programmed death receptor-1 (PD-1)–blocking antibody.
Indication: Treatment of patients with recurrent or advanced mismatch repair deficient (dMMR) endometrial cancer, as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing chemotherapy.
Recommended dosage and administration: Doses 1–4: 500 mg every 3 weeks; subsequent dosing beginning 3 weeks after dose 4 (dose 5 onward): 1,000 mg every 6 weeks, administered as an I.V. infusion over 30 minutes.
Common adverse effects: Fatigue, nausea, diarrhea, anemia, constipation.
Warnings and precautions: Risk of serious immune-mediated adverse effects, including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Women who are pregnant or breastfeeding should not take dostarlimab because it may cause harm to a developing fetus or newborn baby. Dostarlimab’s safety and effectiveness in pediatric patients are not known.
NIVOLUMAB
(Opdivo—Bristol-Myers Squibb)
Drug class: PD-1 blocking monoclonal antibody.
Indication: In combination with certain types of chemotherapy, nivolumab is the first FDA-approved immunotherapy for initial treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.
Recommended dosage and administration: See prescribing information for complete instructions.
Common adverse effects: Peripheral neuropathy, nausea, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain, constipation, musculoskeletal pain.
Warnings and precautions: Risk of serious immune-mediated adverse effects, including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.
New formulation
NALOXONE HYDROCHLORIDE
NASAL SPRAY
(Kloxxado—Hikma Pharmaceuticals)
Drug class: Opioid antagonist.
Indication: Higher 8-mg dose for emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression, in adult and pediatric patients. FDA had previously approved 2-mg and 4-mg naloxone nasal spray products.
Recommended dosage and administration: The nasal spray delivers 8-mg of naloxone into the nasal cavity and can be administered by individuals with or without medical training. If naloxone is administered quickly, it can counter the opioid overdose effects, usually within minutes.
Common adverse effects: Use of naloxone in patients who are opioid dependent may result in opioid withdrawal characterized by body aches, diarrhea, increased heart rate, fever, runny nose, sneezing, goose bumps, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure.
FDA revokes EUA for bamlanivamb
On April 16, FDA revoked the emergency use authorization (EUA) for the investigational monoclonal antibody therapy bamlanivimab when administered alone for treatment of mild to moderate COVID-19 in adults and pediatric patients ages 12 years and older who weigh at least 40 kg.
In a news release, the agency said it made the decision because of the sustained increase of SARS-CoV-2 viral variants that are resistant to bamlanivimab alone. Resistance may result in an increased risk for treatment failure.
Alternative monoclonal antibody therapies remain available under EUA for the same uses as previously authorized for bamlanivimab alone, including REGEN-COV (casirivimab and imdevimab, administered together) and bamlanivimab and etesevimab administered together, stated FDA.
According to the news release, recent data from CDC’s national genomic surveillance program showed an increased frequency of SARS-CoV-2 variants that are expected to be resistant to bamlanivimab administered alone. As of mid-March 2021, approximately 20% of viruses sequenced in the United States were reported as variants expected to be resistant to bamlanivimab alone—an increase from approximately 5% in mid-January 2021.
Currently, there are no testing technologies that enable health care providers to test individual patients for SARS-CoV-2 viral variants before starting treatment with monoclonal antibodies. To reduce the likelihood of treatment failure, providers should use empiric treatment with monoclonal antibody therapies that are expected to work broadly against variants across the nation.
FDA said it will continue working closely with other federal governmental agencies, including CDC and NIH, on surveillance of variants that may affect the monoclonal antibody therapies authorized for emergency use.