Inotersen Disease Interactions

Inotersen can cause glomerulonephritis that may result in dialysis-dependent renal failure. The use of inotersen is contraindicated in patients with history of acute glomerulonephritis. Caution is advised if used in patients with renal impairment. Close monitoring of renal parameters is recommended. If glomerulonephritis is suspected, pursue prompt diagnosis and initiate immunosuppressive treatment as soon as possible. Inotersen- treated patients who develop glomerulonephritis will require monitoring and treatment for nephrotic syndrome and its manifestations. If acute glomerulonephritis is confirmed, inotersen should be permanently discontinued. Use caution with nephrotoxic drugs and other drugs that may impair renal function.

Inotersen causes reductions in platelet count that may result in sudden and unpredictable thrombocytopenia that can be life-threatening. The use of inotersen is contraindicated in patients with a platelet count below 100 x 10^9/L. Close monitoring is recommended and caution is advised in patients with history of thrombocytopenia or at risk. If a patient develops signs or symptoms of thrombocytopenia, obtain a platelet count as soon as possible, and hold inotersen dosing unless the platelet count is confirmed to be acceptable. Recheck the platelet count as soon as possible if a platelet measurement is uninterpretable (e.g., clumped sample). Patients and caregivers should be instructed to be vigilant for symptoms of thrombocytopenia and seek immediate medical help if they have concerns. Glucocorticoid therapy is strongly recommended in patients with a platelet count below 50 x 10^9/L, and in patients with suspected immune-mediated thrombocytopenia.

Inotersen has not been studied in patients with moderate or severe hepatic impairment. Additionally, patients taking inotersen have shown elevation of hepatic enzymes. Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin at baseline and every four months during treatment. If a patient develops clinical signs or symptoms suggestive of hepatic dysfunction (e.g., unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine), promptly measure serum transaminases and total bilirubin and interrupt or discontinue treatment with inotersen.

Inotersen has not been studied in patients with severe renal impairment or end-stage renal disease. Caution is advised if used in these patients. No dose adjustment is necessary in patients with mild to moderate renal impairment (estimated glomerular filtration rate [eGFR] =30 to <90 mL/min/1.73m2).

Treatment with inotersen leads to a decrease in serum vitamin A levels. Caution is advised in patients with history of vitamin A deficiency. Supplementation at the recommended daily allowance of vitamin A is advised for patients taking inotersen. Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness).