Updates from FDA
APhA Staff
New Approval
MIRDAMETINIB
(Gomelki—SpringWorks Therapeutics)
Drug class: Gomelki is a kinase inhibitor.
Indication: Gomelki is indicated for the treatment of adult and pediatric patients 2 years and older with neurofibromatosis type 1 who have symptomatic plexiform neurofibromas not amenable to complete resection.
Recommended dosage and administration: The recommended dosage of Gomelki is 2 mg/m2 orally twice daily, with or without food, for the first 21 days of each 28-day cycle. Continue treatment with Gomelki until disease progression or unacceptable toxicity occurs. Gomelki is available as a capsule and as a tablet for oral suspension.
Common adverse effects: The most common adverse reactions are rash, diarrhea, nausea, musculoskeletal pain, vomiting, fatigue, increased creatine phosphokinase, abdominal pain, headache, paronychia, left ventricular dysfunction, and decreased neutrophil count.
Warnings and precautions: Ocular toxicity may occur. Conduct comprehensive ophthalmic assessments prior to initiating Gomelki, at regular intervals during treatment, and for new or worsening visual changes or blurred vision. Continue, withhold, reduce the dose, or permanently discontinue Gomelki based on severity. Assess ejection fraction by echocardiogram prior to initiating Gomelki, every 3 months during the first year, then as clinically indicated thereafter. Withhold, reduce the dose, or permanently discontinue Gomelki based on severity of left ventricular dysfunction. Dermatologic adverse reactions may occur. Initiate supportive care at first signs of dermatologic adverse reactions, including rash. Withhold, reduce the dose, or permanently discontinue Gomelki based on severity of dose. Gomelki can cause fetal harm. Advise patients of reproductive potential of the possible risk to a fetus and to use effective contraception. Advise patients not to breastfeed during treatment. Gomelki may impair fertility in females.
VIMSELTINIB
(Romvimza—Deciphera Pharmaceuticals)
Drug class: Romvimza is a kinase inhibitor.
Indication: Romvimza is indicated for the treatment of adult patients with symptomatic tenosynovial giant cell tumor for which surgical resection will potentially cause worsening functional limitation or severe morbidity.
Recommended dosage and administration: The recommended dosage of Romvimza is 30 mg orally twice weekly, with a minimum of 72 hours between doses as described in the blister package. Dosage modifications for hepatotoxicity and drug interactions may be necessary. Romvimza is available as capsules.
Common adverse effects: The most common adverse reactions are increased AST, periorbital edema, fatigue, rash, increased cholesterol, peripheral edema, face edema, decreased neutrophils, decreased leukocytes, pruritus, and increased ALT.
Warnings and precautions: Elevated AST and ALT can occur. Evaluate liver tests prior to initiation of treatment and during treatment. Romvimza can cause fetal harm. Advise patients of reproductive potential of the possible risk to a fetus and to use effective contraception. Some strengths of Romvimza contain FD&C Yellow No. 5 and No. 6 as color additives, which may cause allergic reactions in certain susceptible patients. Increases in serum creatinine can occur without affecting renal function. Use alternative measures that are not based on serum creatinine to assess renal function. Avoid concomitant use of Romvimza with P-gp substrates, BCRP substrates, and OCT2 substrates. Concomitant use may increase exposure of these substrates. Advise patients not to breastfeed during treatment.
New dosage forms
RISDIPLAM
(Evrysdi—Genentech)
Drug class: Evrysdi is a survival of motor neuron 2 (SMN2) splicing modifier.
Indication: Evrysdi is indicated for the treatment of spinal muscular atrophy in pediatric and adult patients.
Recommended dosage and administration: Administer once daily with or without food based on age and body weight. In patients younger than 2 years old, the recommended daily dose is 0.15 mg/kg of Evrysdi oral solution. In patients 2 months to less than 2 years, the recommended daily dose is 0.2 mg/kg of Evrysdi oral solution. For patients 2 years and older weighing less than 20 kg, the recommended daily dose is 0.25 mg/kg of Evrysdi oral solution. For patients 2 years and older weighing 20 kg or more, the recommended daily dosage is 5 mg of Evrysdi oral solution or tablets. Swallow Evrysdi tablets whole with water or dispersed in nonchlorinated drinking water. Administer Evrysdi for oral solution with the provided oral syringe. Evrysdi for oral solution must be constituted by a health care provider prior to dispensing.
Common adverse effects: The most common adverse reactions are fever, diarrhea, rash, upper respiratory tract infection, lower respiratory tract infection, constipation, vomiting, and cough.
Warnings and precautions: Avoid coadministration with drugs that are substrates of multidrug and toxin extrusion transporters. Based on animal data, Evrysdi may cause fetal harm.
HYDROCHLOROTHIAZIDE
(Inzirqo—Novitium Pharma)
Drug class: Inzirqo is a thiazide diuretic.
Indication: Inzirqo is indicated for the treatment of hypertension in adult and pediatric patients alone or in combination with other antihypertensive agents, to lower BP and for the treatment of edema associated with congestive heart failure, hepatic cirrhosis, and renal disease including the nephrotic syndrome in adult and pediatric patients.
Recommended dosage and administration: Inzirqo is available as a powder for oral suspension. For the treatment of hypertension in adults, the recommended initial dose is 25 mg orally daily given as a single dose. As needed, increase the dose to 50 mg orally daily, given as a single or two divided doses. For the treatment of edema in adults, the recommended dose is 25 mg to 100 mg orally daily as a single or divided dose. Consider intermittent therapy to reduce the risk of electrolyte imbalances. For the treatment of hypertension and edema in pediatric patients, the recommended dosage is 1 mg/kg to 2 mg/kg orally per day in one or two divided doses. Do not exceed 37.5 mg per day in patients less than 2 years old or 100 mg per day in children 2 to less than 13 years old. Patients less than 6 months old may require doses up to 3 mg/kg orally per day in two divided doses.
Common adverse effects: Inzirqo is contraindicated in anuria, hypersensitivity to hydrochlorothiazide or any ingredient in Inzirqo, and hypersensitivity to sulfonamide-derived drugs. Monitor kidney function periodically. Monitor and correct serum electrolytes prior to use and monitor periodically. Monitor blood glucose, lipid levels, uric acid, and calcium levels periodically. Exacerbation or activation of systemic lupus erythematosus may occur. Monitor for acute angle-closure glaucoma and acute myopia. Concomitant use with NSAIDs may lead to increased risk of renal impairment and loss of diuretic and antihypertensive effect. Concomitant use with cholestyramine and colestipol may reduce the absorption of thiazides and concomitant use with lithium may increase lithium concentrations, causing toxicity. Dosage adjustments of antidiabetic medications may be required if taken concomitantly.
NILOTINIB CAPSULES
(Nilotinib—Cipla)
Drug class: Nilotinib is a kinase inhibitor.
Indication: Nilotinib is indicated for the treatment of adult patients with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia in chronic phase and adult patients with chronic phase and accelerated phase chronic myeloid leukemia resistant or intolerant to prior therapy that included imatinib.
Recommended dosage and administration: The recommended dosage for individuals with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase is 300 mg orally twice daily. For individuals with resistant or intolerant Philadelphia positive chronic myeloid leukeumia in chronic or accelerated phase, the recommended dosage is 400 mg orally twice daily. Reduce the starting dose in patients with baseline hepatic impairment. Dose adjustments and reductions may be necessary based on toxicity.
Common adverse effects: The most common adverse reactions are nausea, rash, headache, fatigue, pruritus, vomiting, diarrhea, cough, constipation, arthralgia, nasopharyngitis, pyrexia, night sweats, myelosuppression, thrombocytopenia, neutropenia, and anemia.
Boxed warning: Nilotinib prolongs the QT interval. Prior to administration and periodically, monitor for hypokalemia or hypomagnesemia and correct deficiencies. Obtain ECGs to monitor the QTc at baseline, 7 days after initiation, and periodically thereafter, and following any dose adjustments. Sudden deaths have been reported. Do not administer Nilotinib to patients with hypokalemia, hypomagnesemia, or long QT syndrome. Avoid use of concomitant drugs known to prolong the QT interval and strong CYP3A4 inhibitors. Avoid food 2 hours before and 1 hour after taking the dose.
Other warnings and precautions: Nilotinib is contraindicated in patients with hypokalemia, hypomagnesemia, and long QT syndrome. Monitor complete blood count during therapy and manage by treatment interruption or dose reduction. Evaluate cardiovascular status and monitor and manage cardiovascular risk factors during Nilotinib therapy. Monitor serum lipase and if elevations are accompanied by abdominal symptoms, interrupt doses and consider appropriate diagnostics to exclude pancreatitis. Monitor hepatic function tests monthly or as clinically indicated. Nilotinib capsules can cause hypophosphatemia, hypokalemia, hypocalcemia, and hyponatremia. Correct electrolyte abnormalities prior to initiating Nilotinib and monitor periodically during therapy. Tumor lysis syndrome may occur so maintain adequate hydration and correct uric acid levels prior to initiating therapy. Hemorrhage from any site may occur. Advise patients to report signs and symptoms of bleeding and medically manage as needed. Monitor patients for rapid weight gain, swelling, and shortness of breath. Manage medically. Growth retardation has been reported in pediatric patients treated with Nilotinib. Monitor growth and development in pediatric patients. Nilotinib can cause fetal harm. Advise patients of reproductive potential of the possible risk to a fetus and to use effective contraception. Patients must have typical BCR–ABL transcripts. An FDA-authorized test with a detection limit below MR4.5 must be used to determine eligibility for discontinuation. Patients must be frequently monitored by the FDA-authorized test to detect possible loss of remission. Avoid concomitant administration with strong CYP3A inhibitors or reduce Nilotinib dose if concomitant use cannot be avoided. Avoid concomitant use with strong CYP3A inducers. Use short-acting antacids or H2 blockers as an alternative to PPIs. Advise patients not to breastfeed during therapy.
New combinations
AZTREONAM AND AVIBACTAM
(Emblaveo—Abbvie)
Drug class: Emblaveo is a combination of aztreonam, a monobactam antibacterial, and avibactam, a β-lactamase inhibitor.
Indication: Emblaveo is indicated in combination with metronidazole in patients 18 years and older who have limited or no alternative options for the treatment of complicated intra-abdominal infections, including those caused by the following gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae complex, Citrobacter freundii complex, and Serratia marcescens. Approval for this indication is based on limited clinical safety and efficacy data for Emblaveo. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Emblaveo and other antibacterial drugs, Emblaveo should only be used to treat infections that are proven or strongly suspected to be caused by bacteria.
Recommended dosage and administration: The recommended dosage in adults is based on estimated creatine clearance. Emblaveo should be administered over an infusion time of 3 hours. In patients with a CrCl greater than 50 mL/min, the loading dose is 2.67 g and the maintenance dose is 2 g with a dosing interval of every 6 hours. In patients with a CrCl greater than 30 to less than or equal to 50 mL/min, the recommended loading dose is 2.67 g with a maintenance dose of 1 g every 6 hours. In patients with a CrCl greater than 15 mL/min to less than or equal to 30 mL/min, the loading dose is 1.8 g and the maintenance dose is 0.9 g every 8 hours. In patients with a CrCl less than or equal to 15 mL/min and those on hemodialysis, the recommended loading dose is 1.33 g with a maintenance dose of 0.9 g every 12 hours. Dosing interval is calculated from the start of one infusion to the start of the subsequent one. Administer metronidazole concurrently. The recommended duration of treatment is 5 to 14 days.
Common adverse effects: The most common adverse reactions are hepatic adverse reactions, anemia, diarrhea, hypokalemia, and pyrexia.
Warnings and precautions: Emblaveo is contraindicated in individuals with a known hypersensitivity to the components of the medication. Hypersensitivity reactions were noted in patients treated with Emblaveo, including rash, flushing, and bronchospasm. In case of hypersensitivity reactions, immediately discontinue Emblaveo and initiate appropriate medications and supportive care. Cases of toxic epidermal necrolysis have been reported. If transaminase elevations are noted, consider discontinuation, if clinically indicated, and monitor patients for resolution of any pertinent clinical and laboratory findings. Clostridioides Dificile–associated diarrhea has been reported. Evaluate if diarrhea occurs. ■