Label Changes for:
Changes have been made to the CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS sections of the safety label.
Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
PLR Conversion; refer to label.
- LAMPRENE is contraindicated in patients with known hypersensitivity to clofazimine or any of the excipients of LAMPRENE.
WARNINGS AND PRECAUTIONS
Abdominal Obstruction and Other Gastrointestinal Adverse Reactions (new heading)
- 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.
- Cases of Torsades 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 Torsades de Pointes cases, the patient must remain under medical surveillance. In all these patients, monitor trocardiograms (ECGs) for QT prolongation and cardiac rhythm disturbances.
- QT prolongation has also been reported in patients who were receiving LAMPRENE with bedaquiline at the recommended dosage regimen for each drug. Monitor ECGs if LAMPRENE is coadministered to patients receiving bedaquiline, 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.
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.
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.
The following serious adverse reactions are discussed in greater detail in other sections of the labeling:
- Abdominal Obstruction and Gastrointestinal Adverse Reactions
- QT Prolongation
- Skin and Body Fluid Discoloration and Other Skin Reactions
- Psychological Effects of Skin Discoloration
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 Less Than 1% of Patients
- Ocular: addition of maculopathy (bull’s eye retinopathy).
USE IN SPECIFIC POPULATIONS
- There are no data with LAMPRENE use in pregnant women to inform associated risk. Retardation of fetal skull ossification, increased incidences of abortions and stillbirths, and impaired neonatal survival were observed in mice following prenatal exposure to LAMPRENE at 25 mg/kg, equivalent to the 0.6 times maximum recommended human daily dose (200 mg), based on body surface area comparisons. Advise pregnant women of the potential risk to the fetus.
- The background risk of major birth defects and miscarriage for the indicated population is unknown; however, in the U.S. general population, the estimated background risk of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies.
Fetal/neonatal adverse reactions
- The skin of infants born to pregnant mothers who had received LAMPRENE during pregnancy is pigmented at birth. Limited data is available regarding the reversibility of discoloration. Based on previous observations, discoloration gradually faded over the first year.
- There are no studies of LAMPRENE use in pregnant women. Few cases of clofazimine use during pregnancy have been reported in the literature. These reports indicate that the skin of infants born to women who had received LAMPRENE during pregnancy was deeply pigmented at birth. LAMPRENE should be used during pregnancy only if the potential benefit justifies the risk to the fetus.
- Embryofetal toxicity studies were conducted in rats, rabbits and mice. In mice LAMPRENE-induced embryotoxicity and fetotoxicity was evident. Retardation of fetal skull ossification, increased incidences of abortions and stillbirths, and impaired neonatal survival were observed following prenatal exposure to LAMPRENE at 25 mg/kg, equivalent to the 0.6 times maximum recommended human daily dose [MRHD] (200 mg), based on body surface area comparisons. The skin and fatty tissue of offspring became discolored approximately 3 days after birth, which was attributed to the presence of clofazimine in the maternal milk. No developmental effects were observed in rat or rabbits orally administered clofazimine during organogenesis at doses up to 50 mg/kg and 15 mg/kg,(equivalent to about 2.4 and 1.5 times the MRHD of 200 mg based on body surface area) respectively. These animal studies were conducted according to the standards at the time of initial drug approval (1986) and not under current regulatory standards.
- LAMPRENE is excreted in human milk. Skin discoloration has been observed in breast fed neonates of mothers receiving clofazimine.
- The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LAMPRENE and any potential adverse effects on the breastfed infant from LAMPRENE or from the underlying maternal condition.
Females and Males of Reproductive Potential
- Sexually-active females of reproductive potential should have a pregnancy test prior to starting treatment with LAMPRENE.
- Animal studies have shown LAMPRENE to be harmful to the developing fetus. Advise sexually active females of reproductive potential to use effective contraception (methods that result in less than 1 % pregnancy rates) when using LAMPRENE during treatment and for at least 4 months after stopping treatment with LAMPRENE.
- Advise males taking LAMPRENE to use a condom during intercourse while on treatment and for at least 4 months after stopping treatment with LAMPRENE.
- Impaired female fertility (reduced number of offspring and lower proportion of implantations) was observed in one study in rats receiving LAMPRENE. There are no non-clinical data on male fertility.
Patients with HIV Co-infection (addition)
- Response to treatment, including treatment of erythema nodosum leprosum reactions, is not altered in HIV-positive and immunocompromised leprosy patients. Dose adjustments of LAMPRENE are not required in these patients.
PATIENT COUNSELING INFORMATION
Information for Patients
- Inform patients to take LAMPRENE with meals.
- Inform patients to report abdominal pain or other gastrointestinal symptoms, such as nausea or vomiting, to their healthcare provider.
- Inform patients that LAMPRENE frequently causes a red to brownish-black discoloration of the skin as well as discoloration of the conjunctivae, tears, sweat, sputum, urine, and feces. Advise patients that skin discoloration may take several months or years to resolve after the conclusion of therapy with LAMPRENE.
- Inform patients that skin discoloration may result in psychological effects and advise them to report any symptoms of depression or suicidal ideation.
- Advise females of reproductive potential to use effective contraception while taking LAMPRENE and for at least 4 months after stopping treatment with LAMPRENE. It is also recommended that they have a pregnancy test prior to starting treatment with LAMPRENE.
- Advise males taking LAMRENE to use a condom during intercourse while taking LAMPRENE and for at least 4 months after stopping treatment.
- Inform patients of the importance of compliance with the prescribed drug regimen in order to prevent drug resistance. Irregularity in administration of medication and poor compliance can lead to delayed and incomplete cure, and could result in infecting other people. Poor compliance can result in disease progression and ultimately result in the development of disabilities and deformities. Whenever possible, ensure that non-compliant patients receive adequate assessment, health education and supervised treatment.
- Instruct patients on the recognition of signs and symptoms of inflammatory reactions and relapses during and following completion of treatment, and instruct them regarding the importance of immediately reporting the earliest manifestations of these signs to their healthcare provider.