Nifurtimox
Nifurtimox Uses, Dosage, Side Effects, Food Interaction and all others data.
Chagas disease, caused by a parasite known as Trypanosoma cruzi (T.cruzi), is a vector-transmitted disease affecting animals and humans in the Americas. It is commonly known as American Trypanosomiasis.
The CDC estimates that approximately 8 million people in Central America, South America, and Mexico are infected with T. cruzi, without symptoms. If Chagas disease is left untreated, life-threatening sequelae may result.
Nifurtimox, developed by Bayer, is a nitrofuran antiprotozoal drug used in the treatment of Chagas disease. On August 6 2020, accelerated FDA approval was granted for its use in pediatric patients in response to promising results from phase III clinical trials. Continued approval will be contingent upon confirmatory data. A convenient feature of Bayer's formulation is the ability to divide the scored tablets manually without the need for pill-cutting devices.
| Trade Name | Nifurtimox |
| Availability | Prescription only |
| Generic | Nifurtimox |
| Nifurtimox Other Names | Nifurtimox, Nifurtimoxum |
| Related Drugs | pentamidine, benznidazole, fexinidazole, Lampit, Nebupent |
| Weight | 120mg, 30mg |
| Type | Oral tablet |
| Formula | C10H13N3O5S |
| Weight | Average: 287.29 Monoisotopic: 287.057591705 |
| Protein binding | The plasma protein binding of nifurtimox is approximately 42%. It is primarily bound to albumin. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Nifurtimox is an antiparasitic drug used for the treatment of Chagas disease (Trypanosoma cruzi infection).
Nifurtimox is indicated in pediatric patients under 18 weighing at least 2.5 kg. Continued approval of this drug for this indication is dependent upon confirmatory clinical trial results.
Nifurtimox is also used to associated treatment for these conditions: Chagas Disease
How Nifurtimox works
The mechanism of action of nifurtimox has not been fully elucidated, however, is believed to occur by the activation of nitroreductase enzymes that produce reactive metabolites with a series of deleterious effects on Trypanosoma cruzi, the parasite causing Chagas disease. The antiprotozoal actions of nifurtimox occur both intracellularly and extracellularly. Inhibition of parasite dehydrogenase activity is another purported mode of action of nifurtimox that warrants further research.
Toxicity
There is limited information in the literature regarding overdose with nifurtimox. Some symptoms of nifurtimox toxicity may include weight loss, anorexia, nausea, vomiting, vertigo, headache, nervous excitation, insomnia, convulsions, drowsiness, arthralgias, myalgias, disorientation, abdominal pain, mucosal edema, and skin manifestations. These symptoms are adverse effects of nifurtimox and are likely to be exaggerated with increased exposure.
Food Interaction
- Avoid alcohol. Alcohol use during nifurtimox treatment may increase undesirable adverse effects.
- Take with food.
[Major] CONTRAINDICATED: Use of alcohol or products containing alcohol during therapy with nitrofurans may result in a disulfiram-like reaction in some patients.
The presumed mechanism is inhibition of aldehyde dehydrogenase (ALDH) by nitrofurans in a manner similar to disulfiram.
Following ingestion of alcohol, inhibition of ALDH results in increased concentrations of acetaldehyde, the accumulation of which can produce an unpleasant physiologic response referred to as the 'disulfiram reaction'.
Symptoms include flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion.
Severe reactions may result in respiratory depression, cardiovascular collapse, arrhythmia, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death.
ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of nifurtimox.
When a single 120 mg oral dose of nifurtimox was administered with a high-fat meal (800 to 1000 calories; approximately 60% fat) in adult Chagas patients, nifurtimox peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 68% and 71%, respectively, compared to administration under fasted conditions.
Nifurtimox was administered with food in clinical trials.
MANAGEMENT: Consumption of alcohol is considered contraindicated during nifurtimox therapy.
To ensure maximal oral absorption, nifurtimox should be administered with food.
Volume of Distribution
Nifurtimox crosses the blood-brain barrier and the placenta.
Elimination Route
The average AUC of nifurtimox is estimated between 1676-2670 μg∙h/L. One pharmacokinetic study of healthy volunteers revealed an AUC of 5430 ng∙ml-1 Cmax ranges between 425-568 μg/L (26–50%) after a single dose of 20 mg with food in adults. Tmax is 4 hours, ranging from 2 to 8 hours post-dose in the fed state. In a pharmacokinetic study of healthy volunteers, serum concentration was low, likely due to the first-pass effect.
Half Life
The elimination half-life of nifurtimox ranges from 2.4–3.6 hours. A pharmacokinetic study of healthy volunteers and patients with renal failure revealed respective mean half-lives of 2.95 h and 3.95 h.
Clearance
One pharmacokinetic study of nifurtimox revealed a clearance of 193.4 l∙h-1. In patients without renal failure; clearance was 99.7 l∙h-1.
Elimination Route
In the fed state, 44% of the dose was mainly recovered in the urine as metabolites. Fecal and biliary excretion of nifurtimox have not been studied.
Innovators Monograph
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