Drug reference

Nifurtimox

Antiprotozoal · Antiparasitic for Chagas Disease and African Trypanosomiasis

AntiprotozoalAntiparasitic for Chagas Disease and African Trypanosomiasis

CDSCO approvedSchedule H

EXCRETION

—

not curated

INTERACTIONS

1 major

SEVERE in our sources

PREGNANCY

—

not curated

Top interactionssee all 2 →

EthanolSevereDatabaseDDInter

Mechanism

Nifurtimox is a nitroheterocyclic compound (nitrofuran) that undergoes intracellular nitroreduction to generate reactive oxygen species (superoxide anion, hydrogen peroxide, hydroxyl radicals) and electrophilic nitroreduction intermediates that damage DNA, lipids, and proteins. Trypanosoma cruzi is particularly susceptible because it lacks efficient antioxidant defense mechanisms (deficient in catalase and glutathione peroxidase) compared to mammalian cells. It is one of only two drugs (with benznidazole) active against Chagas disease.

Indications

Chagas diseaseTrypanosoma cruzi infectionLate-stage Gambian trypanosomiasis (in combination with eflornithine)American trypanosomiasis (Chagas disease) caused by T. cruziLate-stage African sleeping sickness (in combination with eflornithine)Acute T. cruzi infection (including congenital)Early chronic T. cruzi infection (patients <18 years of age)T. cruzi reactivationSecond-stage T. b. gambiense HAT (in combination with eflornithine)

Dosing

Adult: Chagas disease: 8-10 mg/kg/day in 3 divided doses with meals for 60-90 days.
Pediatric: Dosed per kg body weight with meals; 60-90 day course
Renal adjustment: Contraindicated in advanced renal failure.
Max dose: 10 mg/kg/day

Pharmacokinetics

Onset

Peak plasma levels observed after about 3.5 h

Half-life

About 3 h

Bioavailability

well absorbed

Metabolism

Undergoes rapid biotransformation, probably via a presystemic first-pass effect; high concentrations of several unidentified metabolites are found.

Excretion

<0.5% of the original drug is excreted in urine

Side effects

Common

NauseaVomitingAbdominal painAnorexiaHeadacheRestlessnessInsomniaparesthesiasweaknesstremorsAnorexia and weight loss (50–81%)Nausea and vomiting (15–50%)Abdominal discomfort (12–40%)Headaches (13–70%)Dizziness and vertigo (12–33%)Anxiety and depression (10–49%)Insomnia (10–54%)Myalgia (13–30%)Memory loss (6–14%)

Serious

Peripheral neuropathy
Seizures
Psychosis
Hypersensitivity reactions (dermatitis, fever, icterus, pulmonary infiltrates, anaphylaxis)
Nausea
Vomiting
Myalgia
Weakness
Peripheral neuropathy (after prolonged treatment)
GI symptoms (after prolonged treatment, leading to weight loss)
Peripheral neuropathy (2–5%)
Leukopenia (<1%)
Convulsions (<5%, when used in combination with eflornithine for HAT)
Psychosis (<5%, when used in combination with eflornithine for HAT)

Pregnancy & lactation

Lactation

A negative pregnancy test is mandatory before initiating treatment, as the recommended drugs have not been proven to be safe in pregnancy.

Drug interactions

Ethanol

Severe

Database

Drug interaction classified as: metabolism

Source: DDInter

Fexinidazole

Moderate

Textbook

Resistance generated to one drug in the field (e.g., through changes in NTR1 expression levels) could lead to clinical resistance to both compounds.

Monitor for signs of treatment failure. This underscores a vulnerability in current treatment strategy. The text implies shared resistance is a concern for treatment strategy, not a direct drug-drug adverse effect in a patient. So, this should be noted for physicians when choosing treatment options, but it is not a traditional drug-drug interaction in the sense of one modifying the effects of the other in the body of the patient.

Source: G&G 14e · p1309-1324

4 additional low-confidence interactions hidden — those rows lack a documented mechanism or management plan in our sources.