sovuna

Important safety information

Cardiomyopathy and Ventricular Arrhythmias : Fatal or life-threatening cardiomyopathy and ventricular arrhythmias were reported. (5.1) Retinal Toxicity : Irreversible retinal damage is related to cumulative dosage and treatment duration. Baseline retinal exam and exams during treatment are recommended. (5.2) Serious Skin Reactions: Stevens Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis have been reported. (5.3) Worsening of Psoriasis: Avoid in patients with psoriasis. (5.4) Risks Associated with Use in Porphyria: Avoid in patients with porphyria. Hepatotoxicity was reported in patients with porphyria cutanea tarda (5.5) Hematologic Toxicity : Discontinue if myelosuppression occurs. (5.6) Renal Toxicity: Consider phospholipidosis as a possible cause of renal injury in patients with underlying connective tissue disorders. Discontinue SOVUNA if renal toxicity is suspected or demonstrated by tissue biopsy in any organ system. (5.1, 5.8, 5.11) 5.1 Cardiomyopathy and Ventricular Arrhythmias Fatal and life-threatening cases of cardiotoxicity, including cardiomyopathy, have been reported in patients treated with SOVUNA. Signs and symptoms of cardiac compromise have occurred during acute and chronic SOVUNA treatment. In multiple cases, endomyocardial biopsy showed association of the cardiomyopathy with phospholipidosis in the absence of inflammation, infiltration, or necrosis. Drug-induced phospholipidosis may occur in other organ systems [see Warnings and Precautions (5.8, 5.11)]. Patients may present with ventricular hypertrophy, pulmonary hypertension and conduction disorders including sick sinus syndrome. ECG findings include atrioventricular, right or left bundle branch block. SOVUNA has a potential to prolong the QT interval. Ventricular arrhythmias (including torsades de pointes) have been reported in SOVUNA-treated patients. The magnitude of QT prolongation may increase with increasing concentrations of the drug. Therefore, the recommended dose should not be exceeded [see Adverse Reactions (6) , Overdosage (10)]. Avoid SOVUNA administration in patients with congenital or documented acquired QT prolongation and/or known risk factors for prolongation of the QT interval such as: Cardiac disease, e.g., heart failure, myocardial infarction. Proarrhythmic conditions, e.g., bradycardia (< 50 bpm). History of ventricular dysrhythmias. Uncorrected hypokalemia and/or hypomagnesemia. Concomitant administration with QT interval prolonging agents as this may lead to an increased risk for ventricular arrhythmias [see Drug Interactions (7.1)]. Therefore, SOVUNA is not recommended in patients taking other drugs that have the potential to prolong the QT interval. Correct electrolyte imbalances prior to use. Monitor cardiac function as clinically indicated during SOVUNA therapy. Discontinue SOVUNA if cardiotoxicity is suspected or demonstrated by tissue biopsy. 5.2 Retinal Toxicity Irreversible retinal damage was observed in some patients treated with hydroxychloroquine sulfate and it is related to cumulative dosage and treatment duration. In patients of Asian descent, retinal toxicity may first be noticed outside the macula. Risk factors for retinal damage include daily hydroxychloroquine sulfate dosages ≥5 mg/kg of actual body weight, durations of use greater than five years, renal impairment, use of concomitant drug products such as tamoxifen citrate, and concurrent macular disease. Within the first year of starting SOVUNA, a baseline ocular examination is recommended including best corrected distance visual acuity (BCVA), an automated threshold visual field (VF) of the central 10 degrees (with retesting if an abnormality is noted), and spectral domain ocular coherence tomography (SD-OCT). For patients at higher risk of retinal damage, monitoring should include annual examinations which include BCVA, VF and SD-OCT. For patients without significant risk factors, annual retinal exams can usually be deferred until five years of treatment. In patients of Asian descent, it is recommended that visual field testing be performed in the central 24 degrees instead of the central 10 degrees. If ocular toxicity is suspected, discontinue SOVUNA and monitor the patient closely given that retinal changes and visual disturbances may progress even after cessation of therapy. 5.3 Serious Skin Reactions Serious adverse reactions have been reported with the use of SOVUNA including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP). Monitor for serious skin reactions, especially in patients receiving a drug that may also induce dermatitis. Advise patients to seek medical attention promptly if they experience signs and symptoms of serious skin reactions such as blisters on the skin, eyes, lips or in the mouth, itching or burning, with or without fever [see Warnings and Precautions (5.4,5.5), Adverse Reactions (6)]. Discontinue SOVUNA if these severe reactions occur. 5.4 Worsening of Psoriasis Administration of SOVUNA to patients with psoriasis may precipitate a severe flare-up of psoriasis. Avoid SOVUNA in patients with psoriasis, unless the benefit to the patient outweighs the possible risk. 5.5 Risks Associated with Use in Porphyria Administration of SOVUNA to patients with porphyria may exacerbate porphyria. Avoid SOVUNA in patients with porphyria. Hepatotoxicity Associated with Porphyria Cutanea Tarda Cases of hepatotoxicity have been reported when hydroxychloroquine was used in patients with porphyria cutanea tarda (PCT). Patients received dosages ranging from 200 mg twice weekly to 400 mg daily. Most of the PCT-related cases presented with marked elevations in transaminases (>20 times upper limit of the reference range) within days to a month of hydroxychloroquine initiation. In some cases, PCT was diagnosed only after the occurrence of treatment-induced liver injury, when hydroxychloroquine was prescribed for an approved indication. Some of the cases were associated with other risk factors for hepatic injury (e.g., alcohol use, concomitant hepatotoxic medications). Measure liver tests promptly in patients who report symptoms that may indicate liver injury, such as fatigue, rash, nausea, dark urine, or jaundice. In this clinical context, if the patient is found to have abnormal serum liver tests (e.g., ALT level greater than three times the upper limit of the reference range, total bilirubin greater than two times the upper limit of the reference range), interrupt treatment with SOVUNA, and investigate further to establish the probable cause. The safety and effectiveness of SOVUNA for the treatment of PCT have not been established and SOVUNA is not approved for this use. 5.6 Hematologic Toxicity SOVUNA may cause myelosuppression including aplastic anemia, agranulocytosis, leukopenia, or thrombocytopenia. Monitor blood cell counts periodically in patients on prolonged SOVUNA therapy. If the patient develops myelosuppression which cannot be attributable to the disease, discontinue the drug. 5.7 Hemolytic Anemia Associated with G6PD Deficiency Hemolysis has been reported in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Monitor for hemolytic anemia as this can occur, particularly in association with other drugs that cause hemolysis. 5.8 Skeletal Muscle Myopathy or Neuropathy Skeletal muscle myopathy or neuropathy leading to progressive weakness and atrophy of proximal muscle groups, depressed tendon reflexes, and abnormal nerve conduction, have been reported. Muscle and nerve biopsies have shown associated phospholipidosis. Drug-induced phospholipidosis may occur in other organ systems [see Warnings and Precautions (5.1, 5.11)]. Assess muscle strength and deep tendon reflexes periodically in patients on long-term therapy with…