Dosing & Uses
Dosage Forms & Strengths
tablet
- 30mg
- 120mg
Chagas Disease (Orphan)
Investigational in the United States for adults (approved by FDA for children aged <18 yr)
Investigational in the United States
Orphan designation for Chagas Disease (American Trypanosomiasis)
Dosage Forms & Strengths
tablet
- 30mg
- 120mg
Chagas Disease
Indicated in children and adolescents (<18 years of age and weighing ≥2.5 kg) for the treatment of Chagas disease (American Trypanosomiasis), caused by Trypanosoma cruzi
<2.5 kg: Not established
≥2.5 to <40 kg: 10-20 mg/kg/day PO divided q8hr
≥40 kg: 8-10 mg/kg/day PO divided q8hr
Recommended duration of treatment is 60 days
Adjust dosage accordingly if body weight decreases during treatment
Refer to the prescribing information for individual dosages based on body weight
Dosage Modifications
Renal impairment
- Pharmacokinetics are unknown
- Published literature suggests increased blood concentrations in patients with end-stage renal disease requiring hemodialysis
Hepatic impairment
- Pharmacokinetics are unknown
Dosing Considerations
Females of reproductive potential: Obtain pregnancy test before initiating treatment
Discontinue consumption of alcohol during treatment
Adverse Effects
>10%
Vomiting (14.6%)
Abdominal pain (13.2%)
Headache (12.8%)
Decreased appetite (10.5%)
1-10%
Nausea (8.2%)
Pyrexia (7.3%)
Rash (5.5%)
Diarrhea (4.6%)
Decreased weight (2.7%)
Dizziness (2.7%)
Anemia (2.7%)
Urticaria (2.3%)
Eosinophilia (2.3%)
<1%
Vertigo
Arthralgia
Myalgia
Paresthesia
Tremor
Irritability
Anxiety
Pruritus
Fatigue
Somnolence
Seizure
Syncope
Neutropenia
Leukopenia
Postmarketing Reports
Hypersensitivity reactions, including anaphylaxis
Vertigo
Angioedema
Drug reaction with eosinophilia and systemic symptoms (DRESS)
Muscle weakness
Amnesia
Polyneuropathy
Apathy
Agitation
Psychotic behavior
Sleep disorder
Thrombocytopenia
Warnings
Contraindications
Hypersensitivity to nifurtimox or any of the excipients
Alcohol consumption during treatment
Cautions
Genotoxicity has been demonstrated in humans, in vitro in several bacterial species and mammalian cell systems, and in vivo in rodents; a study in treated children with Chagas disease aged 7 months to 14 years demonstrated a 13-fold increase in chromosomal aberrations
Carcinogenicity has been observed in mice and rats treated chronically with nitrofuran agents which are structurally similar to nifurtimoximilar data have not been reported; association with carcinogenicity is unknown
May cause fetal harm when administered to pregnant females
May worsen conditions in patients with history of brain injury, seizures, psychiatric disease, or serious behavioral alterations; closely monitor these patients and in patients who develop neurological disturbances or psychiatric drug reactions during treatment
Cases of hypersensitivity reported; reaction may be induced by nifurtimox or an immune response triggered by Chagas disease during treatment; at first sign of serious hypersensitivity, discontinue treatment
Decreased appetite and weight loss were reported; patients can lose their appetite or experience nausea/vomiting which can result in weight loss; check body weight every 14 days and adjust dose accordingly
Nitrofuran derivatives may precipitate acute attacks of porphyria; administer tablets under close medical supervision in patients with porphyria
Drug interaction overview
-
Alcohol
- Alcohol consumption during treatment is contraindicated
- Alcohol may increase the incidence and severity of undesirable effects similar to other nitrofurans and nitroheterocyclic compounds
Pregnancy & Lactation
Pregnancy
Based on animal studies, may cause fetal harm when administered to pregnant females
Published postmarketing reports on use during pregnancy are insufficient to inform a drug-associated risk of birth defects and miscarriage
Pregnancy test recommended before initiating treatment
Report drug exposure
- If administered during pregnancy
- If patient becomes pregnant during treatment or within 6 months following last dose
- Report exposure by calling 1-888-842-2937
Animal data
- Administered orally during organogenesis was associated with reduced fetal body weights in mice, reduced maternal and fetal body weights in rats
- Treatment with nifurtimox did not produce fetal toxicity and no nifurtimox-related fetal malformations were observed
- Abortions, reduced maternal weight gain, and reduced numbers of live fetuses in rabbits when orally administered during organogenesis at doses approximately equal to the MRHD in rodents and 2-times the MRHD in rabbits
- An increased incidence of a fetal skeletal malformation (fusion of caudal vertebral bodies) occurred in rabbits at nifurtimox doses ~0.2x the MRHD
- Advise pregnant women of the potential risk to a fetus
Disease-associated maternal and/or embryo/fetal risk
- Published data from studies on chronic Chagas disease during pregnancy are inconsistent
- Treatment of chronic Chagas disease during pregnancy is not recommended
- Acute symptomatic Chagas disease is rare in pregnant females; however, symptoms may be serious or life-threatening
- If a pregnant female presents with acute symptomatic Chagas disease, evaluate the risks versus benefits of treatment to the mother and the fetus
Contraception
- Females of reproductive potential: Use effective contraception during treatment and for 6 months after final dose
- Males with female partners of reproductive potential: Use condoms during treatment and for 3 months after final dose
Infertility
- May impair fertility in males of reproductive potential
- Effects were not reversible in 75% of animals at 11 weeks after dosing
Lactation
Published literature demonstrates that nifurtimox is present in human breast milk with an estimated infant daily dose of less than 15% of the recommended daily dose for pediatric patients with Chagas disease
No adverse effects reported on the small number of infants who were breastfed by treated mothers
There is no information on the effects of nifurtimox on milk production
Monitor infants for vomiting, rash, decreased appetite, pyrexia and irritability if exposed to drug
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Antiprotozoal agent
Mechanism of action is not fully understood
May react with the nucleic acids of the parasite and inhibits trypanothione reductase, a parasite-specific antioxidant defense enzyme
Absorption
Peak plasma time: 4 hr
Peak plasma concentration: 425-568 mcg/L (single 120-mg dose)
AUC: 1676-2670 mcg⋅hr/L (single 120-mg dose)
Effects of food
- Following a single 120-mg dose in adults, peak plasma concentration increased 68%, AUC increased 71%, and peak plasma time increased by 1 hr with a high-fat meal (800–1000 calorie, ~60% fat) compared to fasted conditions
Distribution
Passes blood brain barrier and placental barrier
Protein bound: 42%
Metabolism
Primarily mediated via nitroreductases
2 major pharmacologically inactive metabolites (M-4, M-6) and several other minor metabolites in pooled human plasma
M-4 is a rearranged cysteine conjugate of nifurtimox
Elimination
Half-life: 2.4-3.6 hr
Excretion H4
Urine: ~44% (fed state); ~27% (fasted state); recovered mainly as metabolites
Administration
Oral Administration
Administer with food
Tablets are functionally scored; may be split into one-half (eg, 15 mg and 60 mg respectively) at scored lines by hand; do not break tablets mechanically with a tablet splitting device
Unable to swallow whole or half tablets
- Prepare a slurry as an alternate method of administration
- Disperse prescribed dose in ~2.5 mL of water into a spoon
- Allow tablet(s) to disintegrate (typically less than 30 seconds; forms a slurry (liquid suspension)
- Administer slurry immediately with food
Missed dose
- >3 hr of next scheduled dose: Take as soon possible
- ≤3 hr of next scheduled dose: Skip missed dose and continue treatment as prescribed; do not take a double dose to make up for a missed dose
Storage
Store at controlled room temperature 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
Store tablets in the original bottle with child-resistant closures and do not remove the desiccant
Keep bottle with tightly closed and protect from moisture
Images
Formulary
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