Updates from FDA
APhA Staff
New Drugs
ATRASENTAN
(Vanrafia—Novartis)
Drug class: Vanrafia is an endothelin receptor antagonist.
Indication: Vanrafia is indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy at risk of rapid disease progression, generally a urine protein to creatinine ratio greater than or equal to 1.6 g/g. This indication is approved under accelerated approval based on a reduction of proteinuria. It has not been established whether Vanrafia slows kidney function decline in patients with primary immunoglobulin A nephropathy. Continued approval for the indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial.
Recommended dosage and administration: The recommended dosage is 0.75 mg orally once daily with or without food.
Common adverse effects: The most common adverse reactions are peripheral edema and anemia.
Boxed warning: Vanrafia may cause major birth defects if used during pregnancy. Exclude pregnancy before start of treatment. Use effective contraception before start of treatment, during treatment, and 2 weeks after treatment. Discontinue Vanrafia if pregnancy occurs.
Other warnings and precautions: Vanrafia is contraindicated in pregnancy and hypersensitivity. Hepatotoxicity, fluid retention, and decreased sperm counts may occur. Advise patients not to breastfeed during treatment. Avoid concomitant use with strong or moderate CYP3A inducers and OATP1B1/B3 inhibitors.
GEPOTIDACIN
(Blujepa—GSK)
Drug class: Blujepa is a triazaacenaphthylene bacterial type II topoisomerase inhibitor.
Indication: Blujepa is indicated for the treatment of female adult and pediatric patients 12 years and older weighing at least 40 kg with uncomplicated UTIs caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus, and Enterococcus faecalis. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Blujepa and other antibacterial drugs, Blujepa should be used only to treat infections that are proven or strongly suspected
Recommended dosage and administration: The recommended dosage is 1,500 mg (two 750 mg tablets) taken orally, twice daily, approximately 12 hours apart, for 5 days. Administer Blujepa after a meal to reduce the possibility of GI intolerance.
Common adverse effects: The most common adverse reactions are diarrhea, nausea, abdominal pain, flatulence, headache, soft feces, dizziness, vomiting, and vulvovaginal candidiasis.
Warnings and precautions: Use is contraindicated in history of hypersensitivity to Blujepa. Avoid use of Blujepa in patients with a history of QTc prolongation or with relevant preexisting cardiac disease and in patients receiving drugs that prolong the QTc interval. Due to an increase in Blujepa exposure, avoid concomitant administration of Blujepa with strong CYP3A4 inhibitors and in patients with severe renal impairment. Dysarthria and other adverse reactions have been reported in patients receiving Blujepa. Monitor patients with underlying medical conditions that may be exacerbated by acetylcholinesterase inhibition and patients receiving succinylcholine-type neuromuscular blocking agents, systemic anticholinergic medications, or non-depolarizing neuromuscular blocking agents. Hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving Blujepa. If an allergic reaction to Blujepa occurs, discontinue the drug and institute appropriate supportive measures. Clostridioides difficile Clostridioides difficile infection has been reported with nearly all systemic antibacterial agents, including Blujepa. Evaluate patients who develop diarrhea. Avoid coadministration of Blujepa with strong CYP3A4 inhibitors and inducers, as well as with drugs that are extensively metabolized by CYP3A4 and have a narrow therapeutic window. Due to an increase in digoxin exposures, consider monitoring digoxin serum concentration, as appropriate, with concomitant administration of Blujepa. Avoid use of Blujepa is patients with severe renal or hepatic impairment.
FITUSIRAN
(Qfitlia—Genzyme)
Drug class: Qfitlia is an antithrombin-directed small interfering ribonucleic acid.
Indication: Qfitlia is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients aged 12 years and older with hemophilia A or B with or without factor VIII or IX inhibitors.
Recommended dosage and administration: The recommended starting dose is 50 mg once every 2 months. Qfitlia should be administered subcutaneously. Monitor antithrombin activity using an FDA cleared test. Maintain antithrombin activity between 15% and 35% by adjusting the dose and/or frequency of administration.
Common adverse effects: The most common adverse reactions are viral infection, nasopharyngitis, and bacterial infection.
Boxed warning: Serious thrombotic events have occurred in patients treated with Qfitlia with risk factors including persistent antithrombin activity less than 15%, Qfitlia 80 mg once monthly dosing, an indwelling venous catheter, and the post-operative setting when bleed management guidelines were not followed. Interrupt Qfitlia in patients with a thrombotic event and manage as clinically indicated. Gallbladder disease has occurred in patients treated with Qfitlia, some requiring cholecystectomy or developing complications. Monitor for signs and symptoms of gallbladder disease. Consider interruption or discontinuation of Qfitlia if gallbladder disease occurs. Consider alternative treatment for hemophilia if there is history of symptomatic gallbladder disease.
Other warnings and precautions: Obtain liver tests at baseline and then monthly for at least 6 months after initiating Qfitlia and after dose increases, and periodically thereafter. Liver test elevations may require Qfitlia interruption or discontinuation.
New Dosage Forms
LOSARTAN POTASSIUM
ORAL SOLUTION
(Arbli—Scienture)
Drug class: Arbli is an angiotensin II receptor blocker.
Indication: Arbli is indicated for the treatment of hypertension, to lower BP in adults and children older than 6 years, reduction of the risk of stroke in patients with hypertension and left ventricular hypertrophy, and treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria in patients with T2D and a history of hypertension.
Recommended dosage and administration: For treatment of hypertension, the usual adult starting dose is 50 mg orally once daily and the usual pediatric starting dose is 0.7 mg/kg orally once daily (up to 50 kg). For hypertensive patients with left ventricular hypertrophy, the usual starting dose is 50 mg orally once daily, and if further BP response is needed, the dose can be increased to 100 mg orally once daily and/or hydrochlorothiazide 12.5 mg can be added, increasing up to 25 mg daily. For nephropathy in patients with T2D, the usual dose is 50 mg once daily, and the dose can be increased to 100 mg orally once daily if further BP response is needed.
Common adverse effects: The most common adverse reactions are dizziness, upper respiratory infection, nasal congestion, and back pain.
Boxed warning: When pregnancy is detected, discontinue Arbli as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
Other warnings and precautions: Arbli is contraindicated in patients with a history of hypersensitivity to any component of the medication and in patients with diabetes concomitantly taking aliskiren. Correct volume or salt depletion prior to administration of Arbli to prevent hypotension. Monitor renal function and potassium in susceptible patients. If Arbli is taken concomitantly with agents that increase serum potassium, there is a risk for hyperkalemia. If taken concomitantly with lithium, there is a risk for lithium toxicity. Taking Arbli with NSAIDs may increase the risk of renal impairment and reduce diuretic, natriuretic, and antihypertensive effects. If there is dual inhibition of the renin-angiotensin system, there is an increased risk of renal impairment, hypotension, syncope, and hyperkalemia. Advise patients not to breastfeed during treatment and for 2 days after the last dose. Arbli is not recommended in pediatric patients less than 2 years old or pediatric patients with a glomerular filtration rate less than 30 mL/min/m2. In patients with hepatic impairment, the recommended starting dose is 25 mg once daily.
CHLORTHALIDONE
(Hemiclor—PRM Pharma)
Drug class: Hemiclor is a thiazide- like diuretic.
Indication: Hemiclor is indicated for the treatment of hypertension in adults.
Recommended dosage and administration: The recommended starting dose is 12.5 mg or 25 mg once daily. The dose may be doubled after 2 to 4 weeks as needed based on individual response, up to a maximal dose of 100 mg once daily.
Common adverse effects: The most common adverse reactions are electrolyte abnormalities and metabolic disturbances.
Warnings and precautions: Hemiclor is contraindicated in anuria and hypersensitivity to chlorthalidone or other sulfonamide-derived drugs. Acute kidney injury may occur while taking Hemiclor, and patients with preexisting kidney disease may be at a higher risk. Monitor serum electrolytes periodically. Systemic lupus erythematosus may occur. Insulin requirements and oral hypoglycemic agent dosages may require adjustments while taking Hemiclor. Patients may also experience increased responsiveness to tubocurarine or decreased arterial responsiveness to norepinephrine. Lithium renal clearance is reduced by chlortalidone, increasing the risk of lithium toxicity. Hemiclor may cause fetal harm and breastfeeding during treatment is not recommended. In older patients, there is no overall difference in response compared with younger patients, but care should be taken in dose selection in patients with impaired renal function. Alterations of fluid and electrolyte balance should be monitored in patients with hepatic impairment. ■