NIFURTIMOX Drug Interactions: What You Need to Know

INTERACTIONS Concomitant use of LAMPIT with alcohol may increase the incidence and severity of undesirable effects similar to other nitrofurans and nitroheterocyclic compounds. LAMPIT is contraindicated in patients who consume alcohol during treatment [see Dosage and Administration ( 2.2 ) Contraindications ( 4 )].

LAMPIT tablets are contraindicated in:

• Patients with known hypersensitivity to nifurtimox or any of the excipients in LAMPIT [see Warnings and Precautions ( 5.4 )].
• Patients who consume alcohol during treatment [see Drug Interactions ( 7 )]
• Known hypersensitivity to nifurtimox or to any of the excipients in LAMPIT. ( 4 )
• Alcohol consumption during treatment. (4)

AND PRECAUTIONS

• Potential for Genotoxicity and Carcinogenicity. ( 5.1 )
• Embryo-Fetal Toxicity: May cause fetal harm. Pregnancy testing is recommended for females of reproductive potential. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. Advise males to use condoms with female partners of reproductive potential. ( 2.3 , 5.2 , 8.1 , 8.3 )
• Worsening Neurological and Psychiatric Conditions: Patients with a history of brain injury, seizures, psychiatric disease, serious behavioral alterations may experience worsening of their conditions when receiving LAMPIT. Administer LAMPIT under close medical supervision in these patients or if neurological disturbances or psychiatric drug reactions occur. ( 5.3 )
• Hypersensitivity: Hypersensitivity reactions including hypotension, angioedema, dyspnea, pruritus, rash or other severe skin reactions have been reported with the use of nifurtimox, discontinuation of treatment is recommended. ( 5.4 )
• Decreased Appetite and Weight Loss: Check body weight every 14 days as dosage may need to be adjusted. ( 5.5 )
• Porphyria: Treatment with nitrofuran derivatives, such as LAMPIT, may precipitate acute attacks of porphyria. Administer LAMPIT under close medical supervision in patients with porphyria. ( 5.6 )

5.1 Potential for Genotoxicity and Carcinogenicity Genotoxicity Genotoxicity of LAMPIT has been demonstrated in humans, in vitro in several bacterial species and mammalian cell systems, and in vivo in rodents <span class="opacity-50 text-xs">[see Nonclinical Toxicology ( 13.1 )]</span> . A study evaluating the cytogenetic effect of nifurtimox in pediatric patients ranging from 7 months to 14 years of age with Chagas disease demonstrated a 13-fold increase in chromosomal aberrations.

Carcinogenicity

Carcinogenicity has been observed in mice and rats treated chronically with nitrofuran agents which are structurally similar to nifurtimox. Similar data have not been reported for LAMPIT [see Nonclinical Toxicology ( 13.1 )] . It is not known whether LAMPIT is associated with carcinogenicity in humans.

5.2 Embryo-Fetal Toxicity Based on findings from animal studies, LAMPIT can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, nifurtimox administered orally to pregnant rats, and rabbits during organogenesis was associated with reduced maternal body weights in rats, and abortions, fetal death, and smaller litter sizes in rabbits at doses approximately equivalent to and 2-times, respectively, the maximum recommended human dose (MRHD) of 10 mg/kg/day. Fetal malformations were observed in pregnant rabbits administered nifurtimox doses less than the MRHD <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.1 )]</span>. Advise pregnant women of the potential risk to a fetus. Pregnancy testing is recommended for females of reproductive potential prior to initiating treatment with LAMPIT <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.3 )]</span> . Advise females of reproductive potential to use effective contraception during treatment with LAMPIT and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use condoms during treatment and for 3 months after the last dose of LAMPIT <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.1 , 8.3 ) and Clinical Pharmacology ( 12.3 )]</span>.

5.3 Worsening of Neurological and Psychiatric Conditions Patients with a history of brain injury, seizures, psychiatric disease, or serious behavioral alterations may experience worsening of their conditions when receiving LAMPIT. Administer LAMPIT under close medical supervision in these patients and in patients who develop neurological disturbances or psychiatric drug reactions.

5.4 Hypersensitivity Cases of hypersensitivity have been reported in patients receiving therapy with nifurtimox. The hypersensitivity could be a reaction induced by nifurtimox or an immune response triggered by Chagas disease during treatment. Hypersensitivity reactions could be accompanied by hypotension, angioedema (including laryngeal or facial edema), dyspnea, pruritus, rash or other severe skin reactions. At the first sign of serious hypersensitivity, discontinue treatment with LAMPIT <span class="opacity-50 text-xs">[see Contraindications ( 4 )]</span>.

5.5 Decreased Appetite and Weight Loss Decreased appetite and weight loss were reported in patients treated with LAMPIT in the clinical trials. During treatment with LAMPIT, patients can lose their appetite or experience nausea/vomiting which can result in weight loss. Check body weight every 14 days, as the dosage may have to be adjusted <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.2 )]</span>.

5.6 Porphyria Treatment with nitrofuran derivatives, such as LAMPIT, may precipitate acute attacks of porphyria. Administer LAMPIT tablets under close medical supervision in patients with porphyria.