FDA label 6cd78b1f-dd04-43d8-8cee-dcd1113c2abb

5 WARNINGS AND PRECAUTIONS Abdominal obstruction and other gastrointestinal adverse reactions: LAMPRENE may deposit in intestinal mucosa causing intestinal disturbances, including abdominal obstruction, bleeding, splenic infarction and death. Reduce dose or discontinue LAMPRENE if patient complains of pain in abdomen or other gastrointestinal symptoms. ( 5.1 ) QT prolongation: QT prolongation and Torsade de Pointes may occur with LAMPRENE. Concomitant use with other QT prolonging drugs or bedaquiline may cause additive QT prolongation. Monitor ECGs and discontinue LAMPRENE if significant ventricular arrhythmia or QTcF interval greater than or equal to 500 ms develop. ( 5.2 ) Skin and body fluid discoloration and other skin reactions: Advise patients that skin and body fluid discoloration frequently occur with use of LAMPRENE. ( 5.3 ) Depression and suicide due to skin discoloration. Monitor patients for psychological effects of skin discoloration. ( 5.4 ) 5.1 Abdominal Obstruction and Other Gastrointestinal Adverse Reactions Clofazimine may accumulate in various organs as crystals, including the mesenteric lymph nodes and histiocytes at the lamina propria of the intestinal mucosa, spleen and liver. Deposition in the intestinal mucosa may lead to intestinal obstruction that may necessitate exploratory laparotomy. Splenic infarction, gastrointestinal bleeding, and death have been reported. If a patient complains of pain in the abdomen, nausea, vomiting, or diarrhea, initiate appropriate medical investigations and reduce the daily dose of LAMPRENE, or increase the dosing interval or discontinue the drug. Doses of LAMPRENE of more than 100 mg daily should be given for as short a period as possible (less than 3 months) and only under close medical supervision. 5.2 QT Prolongation Cases of Torsade de Pointes with QT prolongation have been reported in patients receiving dosage regimens containing higher than 100 mg daily dose of LAMPRENE or in combination with QT prolonging medications. For QT prolongation and Torsade de Pointes cases, the patient must remain under medical surveillance. In all these patients, monitor electrocardiograms (ECGs) for QT prolongation and cardiac rhythm disturbances [see Dosage and Administration (2.1), Drug Interactions (7.1)] . QT prolongation has also been reported in patients who were receiving concomitant LAMPRENE and bedaquiline at the recommended dosages. Monitor ECGs in patients taking LAMPRENE and bedaquiline concomitantly, and discontinue LAMPRENE if clinically significant ventricular arrhythmia is noted or if the QTcF interval is 500 ms or greater. If syncope occurs, obtain an ECG to detect QT prolongation. 5. 3 Skin and Body Fluid Discoloration and Other Skin Reactions LAMPRENE causes orange-pink to brownish-black discoloration of the skin, as well as discoloration of the conjunctivae, tears, sweat, sputum, urine and feces in 75%-100% of patients. Advise patients that skin discoloration is likely to occur and that it may take several months or years to reverse after the conclusion of therapy. Other skin reactions associated with LAMPRENE therapy include ichthyosis, dry skin, and pruritus. 5. 4 Psychological Effects of Skin Discoloration Skin discoloration due to LAMPRENE therapy has been reported to result in depression and suicide. Advise patients regarding skin discoloration and monitor for depression or suicidal ideation during LAMPRENE therapy.

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Abdominal Obstruction and Gastrointestinal Adverse Reactions [ s ee Warnings and Precautions (5.1)] QT Prolongation [ s ee Warnings and Precautions (5.2) ] Skin and Body Fluid Discoloration and Other Skin Reactions [ s ee Warnings and Precautions (5.3)] Psychological Effects of Skin Discoloration [ s ee Warnings and Precautions (5.4)] The following adverse reactions associated with the use of LAMPRENE were identified. Because these adverse reactions are reported from different studies, these adverse reactions cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions Occurring In More Than 1% of Patients Skin : Pigmentation from pink to brownish-black in 75% to 100% of the patients within a few weeks of treatment; ichthyosis and dryness (8% to 28%); rash and pruritus (1% to 5%). Gastrointestinal : Abdominal and epigastric pain, diarrhea, nausea, vomiting, gastrointestinal intolerance (40% to 50%). Ocular : Diminished vision, conjunctival and corneal pigmentation due to clofazimine crystal deposits; dryness; burning; itching; irritation. Other : Discoloration of urine, feces, sputum, sweat; elevated blood sugar; elevated erythrocyte sedimentation rate (ESR). Adverse Reactions Occurring In Less Than 1% of Patients Skin : Phototoxicity, erythroderma, acneiform eruptions, monilial cheilosis. Gastrointestinal : Bowel obstruction, gastrointestinal bleeding, anorexia, constipation, weight loss, hepatitis, jaundice, eosinophilic enteritis, enlarged liver. Ocular : Maculopathy (bull’s eye retinopathy). Nervous : Dizziness, drowsiness, fatigue, headache, giddiness, neuralgia, taste disorder. Psychiatric : Depression and suicide secondary to skin discoloration. Laboratory : Elevated levels of albumin, serum bilirubin, and aspartate aminotransferase (AST); eosinophilia; hypokalemia. Other : Splenic infarction, thromboembolism, anemia, cystitis, bone pain, edema, fever, lymphadenopathy, vascular pain. Most common adverse reactions reported in 40% to 50% of patients are skin and body fluid discoloration, abdominal and epigastric pain, diarrhea, nausea, vomiting, gastrointestinal intolerance. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.