Updates from FDA
New drugs
CENOBAMATE
(Xcopri—SK Life Science)
Drug class: Antiepileptic
Indication: Treatment of partial-onset seizures in adults
Recommended dosage: Following a titration period of 12.5 mg once daily, maintenance dose is 200 mg once daily; some patients may need an additional titration to 400 mg daily, the maximum recommended dose, based on their clinical response and tolerabil-ity. For patients with mild or moderate hepatic impairment, the maximum recommended dosage is 200 mg once daily.
Adverse effects: Sleepiness, dizziness, fatigue, double vision, headaches
Warnings and precautions: Risk of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multior-gan hypersensitivity; QT shortening (which can be associated with ventricular fibrillation). Do not use in patients with hypersensi-tivity to cenobamate or any of the inactive ingredients or Familial Short QT syndrome.
Risk of suicidal thoughts or behavior; monitor for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
May cause neurological adverse reactions, including sleepiness and fatigue, dizziness, trouble with walking and coordination, trouble with thinking, and visual changes. Advise patients not to drive or operate machinery until the effect of the drug is known.
CEFIDEROCOL
(Fetroja—Shionogi & Co.)
Drug class: Cephalosporin antibacterial
Indication: Treatment of patients ages 18 years or older with complicated urinary tract infections, including kidney infections caused by susceptible Gram-negative microorganisms, who have limited or no alternative treatment options
Recommended dosage: 2 g administered by injection every 8 hours by I.V. infusion over 3 hours in patients with creatinine clearance (CrCL) 60 to 119 mL/min. Dose adjustments are required for patients with CrCL less than 60 mL/min and for patients with CrCL 120 mL/min or greater.
Adverse effects: Diarrhea, constipation, nausea, vomiting, elevations in liver tests, rash, infusion site reactions, candidiasis, cough, headache, hypokalemia. Should not be used in individuals with a known history of severe hypersensitivity to beta-lactam antibacterial drugs.
Boxed warning: Higher all-cause mortality rate was observed in patients receiving cefiderocol compared with patients treated with other antibiotics in a trial with critically ill patients who had multidrug-resistant, Gram-negative bacterial infections. Some of the deaths were a result of worsening or complications of infection or of underlying comorbidities. The drug’s efficacy has not been established for treatment of these types of infections.
VOXELOTOR
(Oxbryta—Global Blood Therapeutics)
Drug class: Hemoglobin S polymerization inhibitor
Indication: Treatment for adults and children ages 12 years and older with sickle cell disease
Recommended dosage: 1,500 mg orally once daily with or without food; for patients with severe hepatic impairment (Child Pugh C), 1,000 mg orally once daily
Adverse effects: Headache, diarrhea, abdominal pain, nausea, rash, fatigue, pyrexia
Warnings and precautions: Hypersensitivity and potential laboratory interference (may interfere with measurement of Hb sub-types HbA, HbS, and HbF by high-performance liquid chromatography)
IVOSIRAN
(Givlaari—Alnylam Pharmaceuticals)
Drug class: Aminolevulinate synthase 1-directed small interfering RNA
Indication: Treatment of adults with acute hepatic porphyria
Recommended dosage: 2.5 mg/kg once monthly by S.C. injection
Adverse effects: Nausea, injection site reactions
Warnings and precautions: Anaphylactic reactions, hepatic and renal toxicities, and injection site reactions. Hepatic toxicity was mostly transaminase elevation. Renal toxicity was mostly serum creatinine elevation and decreases in estimated glomerular filtra-tion rate.
CRIZANLIZUMAB-TMCA
(Adakveo—Novartis)
Drug class: Selectin blocker
Indication: Treatment for patients ages 16 years and older to reduce the frequency of vaso-occlusive crisis, a common and painful complication of sickle cell disease
Recommended dosage: 5 mg/kg administered by I.V. infusion over 30 minutes on week 0, week 2, and every 4 weeks thereafter
Adverse effects: Nausea, arthralgia, back pain, pyrexia
Warnings and precautions: Monitor patients for infusion-related reactions and discontinue crizanlizumab-tmca for severe reactions. Also monitor for interference with automated platelet counts or platelet clumping (run tests as soon as possible or use citrate tubes).
LUSPATERCEPT–AAMT
(Reblozyl—Celgene)
Drug class: Erythroid maturation agent
Indication: Treatment of anemia in adult patients with beta thalassemia (also known as “Cooley’s anemia,” an inherited rare blood disorder) who require regular red blood cell transfu-sions
Recommended dosage: 1 mg/kg once every 3 weeks by S.C. injection; review hemoglobin (Hgb) results prior to each administration.
Adverse effects: Headache, bone pain, arthralgia, fatigue, cough, abdominal pain, diarrhea, dizziness
Warnings and precautions: Increased risk of thrombosis/throm-boembolism (monitor patients for signs and symptoms of thromboem-bolic events and institute treatment promptly); hypertension (monitor blood pressure during treatment and initiate antihypertensive treatment if neces-sary); embryo-fetal toxicity (advise females of reproductive potential of the potential risk to a fetus
New indication
ACALABRUTINIB
(Calquence—AstraZeneca)
Drug class:
Drug class:Drug class: Kinase inhibitor
Indication: Treatment of adults with chronic lymphocytic leukemia or small lymphocytic lymphoma as an initial or subsequent therapy
Recommended dosage: 100 mg orally approximately every 12 hours; swallow whole with water, with or without food. Patients should not break, open, or chew capsules.
Adverse effects: Anemia, neutropenia, upper respiratory tract infection, thrombocytopenia, headache, diarrhea, musculoskeletal pain
Warnings and precautions: Risk of atrial fibrillation and flutter (monitor for symptoms of arrhythmias); serious infections; bleeding; low blood counts (monitor blood work regularly); other malignancies, such as skin cancers and other solid tumors (ad-vise patients to use sun protection). Females of reproductive age should use effective contraception during treatment. Women who are pregnant or breastfeeding should not take acalabrutinib because it may harm a developing fetus or newborn baby or cause delivery complications.
New formulation
RILUZOLE ORAL FILM
(Exservan—Aquestive Therapeutics))
Drug class: Benzothiazole
Indication: Treatment of patients with amyotrophic lateral sclerosis (ALS) who have trouble swallowing. The dissolving oral film form of riluzole can be taken without water and slows down worsening ALS and prolongs survival. Studies have demonstrated the product’s bioequivalence to Rilutek.
Recommended dosage: 50 mg twice daily, at least 1 hour before or 2 hours after a meal
Adverse reactions: Oral hypoesthesia, asthenia, nausea, decreased lung function, hypertension, abdominal pain
Warnings and precautions: Risk of hepatic injury, neutropenia, and interstitial lung disease. Use is not recommended in patients with baseline elevations of serum aminotransferases greater than five times the upper limit of normal. The drug should be discontinued if there is evidence of liver dysfunction or if interstitial lung disease develops. Advise patients to report any febrile illness.
Adalimumab-afzb, biosimilar to Humira, approved for multiple inflammatory conditions
FDA approved adalimumab-afzb (Abrilada—Pfizer), a tumor necrosis factor blocker and biosimilar to adalimumab (Humira), to treat certain patients with rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.
FDA approval was based on the review of a comprehensive data package, including results from the REFLECTIONS B538-02 clinical comparative study, which evaluated the efficacy, safety, and immunogenicity of adalimumab-afzb and found no clinically meaningful differences compared to adalimumab, each taken in combination with methotrexate, in patients with moderate to severe rheumatoid arthritis.
The recommended dosage depends on the indication; see the prescribing information for complete details.
The labeling carries a boxed warning that patients treated with adalimumab are at increased risk for developing serious infections that may lead to hospitalization or death, including tuberculosis, bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections due to other opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. The drug should be discontinued if a patient develops a serious infection or sepsis. Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers including adalimumab products. Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have occurred in adolescent and young adults with inflammatory bowel disease treated with TNF blockers including adalimumab products
The most common adverse reactions in clinical trials were infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash.
FDA approves first generics of Gilenya
FDA granted approvals of generic fingolimod (Gilenya) to HEC Pharm, Biocon, and Sun Pharmaceutical Industries for treatment of relapsing forms of multiple sclerosis (MS) in adult patients. The drug reduces the frequency of clinical exacerbations and delays the accumulation of physical disability. The recommended dosage is 0.5 mg orally once daily, with or without food.
Common adverse effects include headache, elevation of liver enzymes, diarrhea, cough, influenza, sinusitis, back pain, abdominal pain, and pain in the extremities.
Fingolimod must be dispensed with a Medication Guide that contains important information about its uses and risks. Serious risks include slowing of the heart rate, especially after the first dose; serious infections; progressive multifocal leukoencephalopathy, a rare brain infection that can occur in patients with weakened immune systems and usually leads to death or severe disability; vision problems; swelling and narrowing of the blood vessels in the brain (posterior reversible encephalopathy syndrome); respiratory problems, liver injury, increased blood pressure, and skin cancer.
Fingolimod may cause harm to a developing fetus; health professionals should advise women of child-bearing age of the potential risk to the fetus and to use effective contraception.