Version May 2024
Chagas disease (T. cruzi infection; American trypanosomiasis) (alternative agent) (off-label use): Oral: 8 to 10 mg/kg/day in 3 to 4 divided doses for 90 days (Bern 2007; CDC 2019a; HHS [OI adult 2020]; Kappagoda 2011).
West African trypanosomiasis (T. brucei gambiense infection; sleeping sickness), with confirmed or suspected CNS involvement (off-label use): Oral: 15 mg/kg/day in 3 divided doses for 10 days, in combination with eflornithine (CDC 2019b; Kappagoda 2011; Priotto 2009; WHO 2019).
Missed dose: If a dose is missed, take the next dose as soon as possible; if it is ≤3 hours until the next scheduled dose, skip the missed dose and continue treatment as scheduled. Do not take a double dose to make up for a missed dose.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). Nifurtimox concentrations may be increased in patients with end-stage renal disease on hemodialysis; use with caution.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Refer to adult dosing.
(For additional information see "Nifurtimox: Pediatric drug information")
American trypanosomiasis (Chagas disease; Trypanosoma cruzi infection): Note: Dose should be adjusted if body weight changes during treatment.
Weight-directed dosing (CDC 2021a; Red Book [AAP 2021]; manufacturer's labeling):
Infants, Children, and Adolescents <18 years:
Weight 2.5 to <41 kg: Oral: 10 to 20 mg/kg/day in 3 divided doses for 60 days.
Weight ≥41 kg: Oral: 8 to 10 mg/kg/day in 3 divided doses for 60 days.
Weight-band (fixed) dosing (manufacturer's labeling):
Infants, Children, and Adolescents <18 years: Note: Treat for 60 days.
2.5 to 4.5 kg: Oral: 15 mg 3 times daily.
>4.5 to <9 kg: Oral: 30 mg 3 times daily.
9 to <13 kg: Oral: 45 mg 3 times daily.
13 to <18 kg: Oral: 60 mg 3 times daily.
18 to <22 kg: Oral: 75 mg 3 times daily.
22 to <27 kg: Oral: 90 mg 3 times daily.
27 to <35 kg: Oral: 120 mg 3 times daily.
35 to <41 kg: Oral: 180 mg 3 times daily.
41 to <51 kg: Oral: 120 mg 3 times daily.
51 to <71 kg: Oral: 180 mg 3 times daily.
71 to <91 kg: Oral: 240 mg 3 times daily.
≥91 kg: Oral: 300 mg 3 times daily.
African trypanosomiasis (sleeping sickness), second-stage disease (with CNS involvement), caused by Trypanosoma brucei gambiense: Limited data available:
Infants, Children, and Adolescents: Oral: 15 mg/kg/day in 3 divided doses for 10 days in combination with IV eflornithine for 7 days (NECT regimen) (CDC 2021b; Red Book [AAP 2021]; WHO 2019).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Nifurtimox concentrations may be increased in patients with end-stage renal disease on hemodialysis; use with caution and monitor closely. Some experts would avoid use in patients with severe renal dysfunction (Bern 2007; Kappagoda 2011).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); some experts would avoid use in patients with severe hepatic dysfunction (Bern 2007; Kappagoda 2011).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Abdominal pain (13%), decreased appetite (11%), vomiting (15%)
Nervous system: Headache (13%)
1% to 10%:
Dermatologic: Skin rash (6%), urticaria (2%)
Endocrine & metabolic: Weight loss (3%)
Gastrointestinal: Diarrhea (5%), nausea (8%)
Hematologic & oncologic: Anemia (3%), eosinophilia (2%)
Nervous system: Dizziness (3%)
Miscellaneous: Fever (7%)
<1%:
Cardiovascular: Syncope
Dermatologic: Pruritus
Hematologic & oncologic: Leukopenia, neutropenia
Nervous system: Anxiety, drowsiness, fatigue, irritability, paresthesia, seizure, vertigo
Neuromuscular & skeletal: Arthralgia, asthenia, myalgia, tremor
Postmarketing:
Hematologic & oncologic: Thrombocytopenia
Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction
Immunologic: Drug reaction with eosinophilia and systemic symptoms
Nervous system: Agitation, amnesia, apathy, myasthenia, polyneuropathy, psychotic symptoms, sleep disorder
Hypersensitivity to nifurtimox or any component of the formulation; alcohol consumption during treatment.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• CNS effects: May cause muscle weakness or tremors, which may impair physical abilities; patients must be cautioned about performing tasks such as operating machinery or driving if weakness or tremors occur.
• GI effects: Loss of appetite and nausea/vomiting leading to weight loss have been reported. Monitor body weight every 2 weeks during treatment and adjust dosage based on weight as needed.
• Hypersensitivity reaction: Hypersensitivity reactions, sometimes accompanied by angioedema (including laryngeal or facial edema), dyspnea, hypotension, pruritus, rash, or other severe skin reactions, have been reported. The hypersensitivity may be due to nifurtimox or an immune response caused by Chagas disease during treatment. Discontinue use at the first sign of serious hypersensitivity.
• Peripheral neuropathy: Use has been associated with peripheral neuropathy; monitor for signs and symptoms during therapy (Crespillo-Andujar 2018; Forsyth 2016; Kappagoda 2011).
Disease-related concerns:
• Hepatic impairment: Use with caution and close monitoring in patients with hepatic impairment.
• Neurological conditions: Use with caution and close monitoring in patients with a history of brain injury or seizures; worsening of the condition may occur.
• Porphyria: Use with caution in patients with porphyria; nitrofuran derivatives may precipitate acute attacks of porphyria.
• Psychiatric disease: Use with caution and close monitoring in patients with a history of psychiatric disease or serious behavioral alterations; worsening of the condition may occur.
• Renal impairment: Use with caution and close monitoring in patients with end-stage renal disease requiring hemodialysis (serum concentrations are increased).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Lampit: 30 mg, 120 mg [contains corn starch]
No
Tablets (Lampit Oral)
30 mg (per each): $3.00
120 mg (per each): $3.60
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Nifurtimox is only available for the treatment of African trypanosomiasis (in combination with eflornithine) with an individual IND from the FDA. Additional IND information is available at https://www.fda.gov/drugs/types-applications/investigational-new-drug-ind-application.
Oral: Administer with food. Tablets are functionally scored and may be split at the scored lines by hand; do not break mechanically with a tablet splitting device. In patients unable to swallow whole or half tablets, tablet may be dispersed in water. Place ~2.5 mL of water in a spoon and place the prescribed dose into the water. Allow the tablet(s) to disintegrate (usually <30 seconds) until a slurry is formed. Administer the slurry immediately with food.
West African trypanosomiasis: If vomiting occurs within 30 minutes of dose, repeat the same dose. If vomiting occurs within 30 to 60 minutes of dose, a half dose should be given. If vomiting occurs >1 hour after dose, no additional dose is necessary. If nausea or vomiting persists, consider administering domperidone or metoclopramide before subsequent doses. If treatment is interrupted, the missing doses should be added at the end of treatment for a total of 30 doses of nifurtimox (WHO 2019).
Oral: Administer with food. Tablets are functionally scored and may be split at the scored lines by hand; do not break mechanically with a tablet splitting device. In patients unable to swallow whole or half tablets, tablet may be dispersed in water. Place ~2.5 mL of water in a spoon and place the prescribed dose into the water. Allow the tablet(s) to disintegrate (usually <30 seconds) until a slurry is formed. Administer the slurry immediately with food.
African trypanosomiasis (sleeping sickness; T. brucei gambiense infection): If vomiting occurs within 30 minutes of dose, repeat the same dose. If vomiting occurs within 30 to 60 minutes of dose, a half dose should be given. If vomiting occurs >1 hour after dose, no additional dose is necessary. If nausea or vomiting persists, consider administering domperidone (not available in the United States) or metoclopramide before subsequent doses (WHO 2019).
Missed doses:
American trypanosomiasis (Chagas disease; T. cruzi infection): If a dose is missed, administer as soon as possible; if it is ≤3 hours until the next scheduled dose, skip the missed dose and continue treatment as scheduled. Do not take a double dose to make up for a missed dose.
African trypanosomiasis (sleeping sickness; T. brucei gambiense infection): If treatment is interrupted, the missing doses should be added at the end of treatment for a total of 30 doses of nifurtimox (WHO 2019).
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Nifurtimox may cause teratogenicity, reproductive toxicity, and genotoxicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Chagas disease (Trypanosoma cruzi infection; American trypanosomiasis): Treatment of Chagas disease in pediatric patients <18 years of age and weighing ≥2.5 kg.
West African trypanosomiasis (Trypanosoma brucei gambiense infection; sleeping sickness), with confirmed or suspected CNS involvement
Nifurtimox may be confused with nifuroxazide, nitrofurantoin, nitazoxanide.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): May enhance the adverse/toxic effect of Nifurtimox. Risk X: Avoid combination
Food increases Cmax, AUC, and Tmax. Management: Administer with food.
Evaluate pregnancy status prior to use; pregnancy testing is required prior to use in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for 6 months after the last nifurtimox dose. Patients with partners who could become pregnant should use condoms during therapy and for 3 months after the last nifurtimox dose.
Based on data from animal reproduction studies, in utero exposure to nifurtimox may cause fetal harm.
Outcome data related to the use of nifurtimox in pregnancy are limited (Kuemmerle 2022; Schmid 2012).
Other agents may be preferred for the treatment of West African trypanosomiasis in pregnant patients when therapy cannot be postponed until after delivery. Nifurtimox should not be used during pregnancy unless treatment is considered life-saving for the mother (WHO 2019). Treatment of Chagas disease in pregnancy does not prevent transmission to the newborn; maternal treatment with nifurtimox is considered contraindicated by some guidelines and use should be postponed until after delivery (Carlier 2019; Meymandi 2018).
Data collection to monitor pregnancy and infant outcomes following exposure to nifurtimox is ongoing. Health care providers are encouraged to enroll patients who become pregnant within 6 months of the last dose or who are exposed to nifurtimox during pregnancy in the pregnancy safety study (1-888-842-2937).
Nifurtimox is present in breast milk (Moroni 2019).
Data related to the presence of nifurtimox in breast milk are available from a study of 10 lactating patients, 1 to 11 months postpartum, treated for Chagas disease. Patients were administered nifurtimox 8 to 12 mg/kg/day for 30 days and breast milk was sampled after ~3 and ~10 days of treatment. The highest breast milk concentration was 9.5 mg/L. Using the highest breast milk concentration from one patient, the authors of the study calculated the relative infant dose (RID) of nifurtimox to be 14.54%, based on the weight-adjusted maternal dose of 9.8 mg/kg/day, providing an estimated dose to the breastfed infant of 1.42 mg/kg/day. Using data from all 10 patients, the median concentration of nifurtimox in breast milk was 2.15 mg/L, providing a RID of 6.7%. Adverse events were not observed in the breastfed infants. Two infants required treatment for congenital Chagas disease (Moroni 2019). In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).
Data related to the use of nifurtimox for the treatment of West African trypanosomiasis in breastfeeding patients are limited (Kuemmerle 2022; Schmid 2012).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. However, breastfeeding may continue when nifurtimox is used for the treatment of West African trypanosomiasis in lactating patients (WHO 2019). Infants exposed to nifurtimox via breast milk should be monitored for adverse events, including decreased appetite, irritability, pyrexia, rash, or vomiting.
Take with food. Avoid alcohol.
Pregnancy test prior to use in patients who could become pregnant.
Additional monitoring is dependent on the anticipated length of treatment:
Treatment course ≤10 days: Renal function, hepatic function, and CBC at baseline and during treatment if clinically indicated.
Treatment course >10 days: Renal function, hepatic function, and CBC at baseline, at least once during treatment (some experts recommend every 4 to 6 weeks [Bern 2020]), and at therapy completion; periodically screen for peripheral neuropathy during treatment (Kappagoda 2011; Olivera 2017). Monitor body weight every 2 weeks during therapy.
Not well described. It has been suggested that nifurtimox is metabolized/activated by type I (oxygen insensitive) and type II (oxygen sensitive) nitroreductases, leading to production of toxic intermediate metabolites and/or reactive oxygen species that induce DNA damage and cell death of both intracellular and extracellular forms of T. cruzi.
Absorption: Rapidly absorbed (WHO 1995). Administration with a high-fat meal (800 to 1,000 calories; ~60% fat) increased Cmax and AUC by 68% and 71%, respectively.
Protein binding: 42%.
Metabolism: Extensively metabolized in the liver, where nitroreduction occurs through CYP450 reductase (Bern 2007; WHO 1995).
Half-life elimination: 2.4 to 3.6 hours.
Time to peak: Median: 4 hours (range: 2 to 8 hours).
Excretion: Urine: ~27% (fasted conditions) to 44% (fed conditions), primarily as metabolites.
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