Furazolidone

Furazolidone is an antibacterial agent, anti-protozoal agent belonging to the pharmacological class of Furazolidone derivatives.

Furazolidone has been approved to relieve symptoms and also for the treatment and maintenance of Targeted and symptomatic therapy of diarrhea and enteritis caused by bacteria or protozoa that are susceptible to the drug.

Absorption studies utilizing radiolabeled furazolidone have demonstrated its effective absorption after oral administration. However, information regarding the volume of distribution and protein binding of furazolidone is not currently available. Furazolidone undergoes rapid and extensive metabolism, primarily through nitro-reduction, resulting in the formation of two major metabolites: 3-amino-2-oxazolidone (AOZ) and beta-hydroxyethylhydrazine (HEH). AOZ is responsible for inhibiting monoamine oxidase. The detoxification and elimination of furazolidone primarily occur through conjugation with glutathione. The exact route of elimination for furazolidone has not been specified.

The common side effects involved in using Furazolidone are IHypotension (reduced blood pressure), Urticaria (hives), Fever, Arthralgia (joint pain), Rash, Gastrointestinal discomfort (stomach upset), Nausea, Vomiting, Headache, Dizziness, Weakness, Malaise.

Furazolidone is available in the form of Tablets, Oral suspension.

Furazolidone belongs to the pharmacological class of Furazolidone derivatives.

Furazolidone, along with its associated free radical products, is thought to interact with DNA and initiate cross-linking. This drug exhibits a high affinity for bacterial DNA, which makes it especially effective at inducing mutations (both transitions and transversions) within the bacterial chromosome.

Furazolidone has been approved to relieve symptoms and also for the treatment and maintenance of Targeted and symptomatic therapy of diarrhea and enteritis caused by bacteria or protozoa that are susceptible to the drug.

Furazolidone is found to be available in the form of Tablets, Oral suspension.

Furazolidone can be used in the following treatment:

• Targeted and symptomatic therapy of diarrhea and enteritis caused by bacteria or protozoa that are susceptible to the drug.

Furazolidone can help to relieve symptoms and also for the treatment and maintenance of Targeted and symptomatic therapy of diarrhea and enteritis caused by bacteria or protozoa that are susceptible to the drug.

Furazolidone is approved for use in the following clinical indications:

• Targeted and symptomatic therapy of diarrhea and enteritis caused by bacteria or protozoa that are susceptible to the drug.

Targeted and symptomatic therapy of diarrhea and enteritis caused by bacteria or protozoa that are susceptible to the drug.

Average Dosage for Adults: The recommended dosage for adults is one 100 mg tablet taken four times daily.

Furazolidone (furazolidone) LIQUID is composed of furazolidone 50 mg per 15 ml (3.33 mg per ml) in a light-yellow aqueous vehicle. It also contains suitable flavoring, suspending agents, and preservatives. The stability of the liquid formulation is ensured during storage. Prior to administering Furazolidone Liquid, shake the bottle vigorously. It should be dispensed in amber bottles.

Average Dosage for Adults: The recommended dosage for adults is two tablespoonfuls taken four times daily.

The above dosage is based on an average dose of 5 mg of furazolidone per kg (2.3 mg per lb) of body weight, given in four equally divided doses within 24 hours. The maximum recommended dose is 8.8 mg of furazolidone per kg (4 mg per lb) of body weight per 24 hours, as exceeding this dose may lead to nausea or vomiting. If these side effects are severe, the dosage should be reduced.

In most cases, diarrhea treated with Furazolidone will show improvement within 2 to 5 days of therapy. Some patients may require a longer duration of treatment. If there is no satisfactory clinical response within 7 days, it suggests that the pathogen is resistant to Furazolidone, and the drug should be discontinued. It is not contraindicated to use adjunctive therapy with other antibacterial agents or bismuth salts. However, when administering furazolidone in higher doses or for more than five days, the indications should be carefully considered in relation to the potential risks of hypertensive crisis associated with monoamine oxidase inhibition. Patients should be informed about drugs and foods that can predispose them to hypertensive crises.

Tablets: Furazolidone tablets are typically available in strengths of 100 mg or 200 mg per tablet.

Suspension/Liquid: Furazolidone suspension or liquid formulations are often available in a concentration of 50 mg/5 ml or 50 mg/15 ml. This means that each 5 ml or 15 ml of the suspension contains 50 mg of furazolidone.

• Dosage Adjustments in Kidney Patients:

No dosage adjustments have been found.

• Dosage Adjustments in Hepatic Impairment Patients:

No dosage adjustments have been found.

• Dosage Adjustments in Pediatric Patients:
• Furox one tablets :

Average Dosage for Children:

For children aged 5 years or older, the recommended dosage of furazolidone is 25 to 50 mg (¼ to ½ tablet) to be taken four times daily. If necessary, the tablet may be crushed and administered along with a spoonful of corn syrup.

• Furazolidone (furazolidone) LIQUID composition:

Each 15 ml tablespoonful of Furazolidone Liquid contains 50 mg of Furazolidone, equivalent to 3.33 mg per ml, in a light-yellow aqueous vehicle. The formulation is supplemented with suitable flavoring, suspending, and preservative agents. (Refer to Inactive Ingredients for details.) The product demonstrates stability during storage. Before administering Furazolidone Liquid, it is important to vigorously shake the bottle. Dispensing the liquid in amber bottles is recommended.

• Average Dosage for Children:
• For children aged 5 years or older: The recommended dosage is ½ to 1 tablespoonful (7.5-15.0 ml) to be taken four times daily.
• For children aged 1 to 4 years: The recommended dosage is 1 to 1½ teaspoonfuls (5.0-7.5 ml) to be taken four times daily.
• For children aged 1 month to 1 year: The recommended dosage is ½ to 1 teaspoonful (2.5-5.0 ml) to be taken four times daily.

Due to furazolidone's MAO inhibitory properties, dietary restrictions should be continued for at least 2 weeks after discontinuing the medication. This includes avoiding tyramine- or high pressor amine-containing foods such as aged cheese, beer, reduced-alcohol and alcohol-free beer and wine, red and white wine, sherry, liqueurs, yeast or protein extracts, fava or broad bean pods, smoked or pickled meat, poultry, or fish, fermented sausage (bologna, pepperoni, salami, summer sausage), and any overripe fruit. Other foods such as yogurt, sour cream, cream cheese, cottage cheese, chocolate, and soy sauce, when consumed fresh and in moderation, are considered unlikely to cause serious problems.

Furazolidone may be contraindicated under the following conditions:

• To prevent the occurrence of an Antabuse-like reaction, which can happen in certain patients, it is advised to avoid consuming alcohol during furazolidone therapy and for four days after its completion.
• Generally, monoamine oxidase (M.O.) drugs, tyramine-containing foods, and indirectly acting sympathomimetic amines should be avoided or used cautiously in patients receiving furazolidone.
• Furazolidone should not be administered to infants under 1 month of age. The presence of furazolidone in breast milk of lactating women has not been determined, and therefore, its safety in this circumstance has not been established.
• Prior hypersensitivity or allergic reactions to furazolidone are considered contraindications to its use.

• Monoamine Oxidase Inhibition:Furazolidone effectively inhibits monoamine oxidase, as demonstrated experimentally by increased sensitivity to tyramine and amphetamines, as well as direct measurement of monoamine oxidase inhibition in humans.
• Tyramine and Amphetamine Sensitivity: To achieve a two to threefold enhancement of tyramine and amphetamine sensitivities, a five-day administration of furazolidone in recommended doses is necessary. Adults receiving the recommended dose of 400 mg/day for five days are not at significant risk of hypertensive crisis due to monoamine oxidase inhibition. No clinical reports of hypertensive crises have been reported, even with larger doses or prolonged treatment periods. Controlled studies conducted for over 48 consecutive months with daily doses of 400 mg of Furazolidone (furazolidone) did not show signs or symptoms of hypertensive crisis.
• Accumulation of Monoamine Oxidase Inhibition: However, if furazolidone is administered in doses higher than recommended or for a duration exceeding five days, the potential hazards of hypertensive crisis related to the accumulation of monoamine oxidase inhibition must be considered. In such cases, patients should be informed about drugs and foods that may predispose them to hypertensive crises. This includes other monoamine oxidase inhibitors, tyramine-containing foods (such as broad beans, yeast extracts, strong unpasteurized cheeses, beer, wine, pickled herring, chicken livers, and fermented products), and indirectly-acting sympathomimetic amines (found in nasal decongestants and anorectics). Sedatives, antihistamines, tranquilizers, and narcotics should also be used with caution and at reduced dosages.

Other Considerations:

• Orthostatic hypotension and hypoglycemia may occur.
• Furazolidone has shown tumorigenic activity in chronic, high-dose oral administration studies in rodents. It has promoted the development of mammary neoplasia in rats and has caused significant increases in malignant lung tumors in mice. The relevance of these findings to short-term therapy in humans is not established.

Concurrent use of alcohol with furazolidone may rarely lead to a disulfiram-like reaction. This reaction is characterized by facial flushing, difficulty breathing, slight fever, and tightness in the chest. These effects typically resolve on their own within 24 hours without lasting consequences. Patients should be advised to abstain from consuming alcoholic beverages while taking furazolidone and for 4 days after discontinuing the medication

The distribution of furazolidone in breast milk is currently unknown. However, it is advised to avoid breastfeeding in infants up to 1 month of age due to the potential risk of hemolytic anemia caused by glutathione instability during the early neonatal period.

Pregnancy:

Teratogenic Effects - Category C

Clinical studies involving humans have not been conducted to investigate the potential effects of furazolidone. Nevertheless, there have been no reported instances of teratogenic effects on the human fetus or newborn infants.

Animal studies in which furazolidone was administered at doses significantly higher than the recommended human dosage over extended periods have not demonstrated any adverse effects on the developing fetus.

Due to furazolidone's MAO inhibitory properties, dietary restrictions should be continued for at least 2 weeks after discontinuing the medication. This includes avoiding tyramine- or high pressor amine-containing foods such as aged cheese, beer, reduced-alcohol and alcohol-free beer and wine, red and white wine, sherry, liqueurs, yeast or protein extracts, fava or broad bean pods, smoked or pickled meat, poultry, or fish, fermented sausage (bologna, pepperoni, salami, summer sausage), and any overripe fruit. Other foods such as yogurt, sour cream, cream cheese, cottage cheese, chocolate, and soy sauce, when consumed fresh and in moderation, are considered unlikely to cause serious problems.

The adverse reactions related to Furazolidone can be categorized as follows:

Common:

• Hypotension (reduced blood pressure)
• Urticaria (hives)
• Fever
• Arthralgia (joint pain)
• Rash
• Gastrointestinal discomfort (stomach upset)
• Nausea
• Vomiting
• Headache
• Dizziness
• Weakness
• Malaise

• Antidepressants (tricyclic)
• Monoamine oxidase (MAO) inhibitors
• Sympathomimetics (direct- or indirect-acting), such as amphetamines, ephedrine, or phenylephrine
• Tyramine- or other high pressor amine-containing foods and beverages

Concurrent use of these medications, foods, and beverages with furazolidone may theoretically trigger sudden and severe hypertensive reactions due to furazolidone's MAO inhibitory properties. Experimental studies have shown that a dose of 400 mg daily for 5 days can increase sensitivity to tyramine and amphetamines by 2- to 3-fold. However, in typical therapeutic doses, furazolidone does not usually pose a significant risk of hypertensive crises due to MAO inhibition, and there have been no reported clinical cases of this interaction. Nevertheless, if furazolidone is administered in higher-than-recommended doses or for an extended duration, there may be an increased risk of hypertensive crises due to the accumulation of monoamine oxidase.

The following are the side effects involving Furazolidone:

• Hypotension (reduced blood pressure)
• Urticaria (hives)
• Fever
• Arthralgia (joint pain)
• Rash
• Gastrointestinal discomfort (stomach upset)
• Nausea
• Vomiting
• Headache
• Dizziness
• Weakness
• Malaise

Pregnancy:

Teratogenic Effects - Category C

Clinical studies involving humans have not been conducted to investigate the potential effects of furazolidone. Nevertheless, there have been no reported instances of teratogenic effects on the human fetus or newborn infants.

Animal studies, in which furazolidone was administered at doses significantly higher than the recommended human dosage over extended periods, have not demonstrated any adverse effects on the developing fetus.

Lactation:

The distribution of furazolidone in breast milk is currently unknown. However, it is advised to avoid breastfeeding in infants up to 1 month of age due to the potential risk of hemolytic anemia caused by glutathione instability during the early neonatal period.

Pediatric:

Due to the potential risk of hemolytic anemia caused by immature enzyme systems (specifically glutathione instability) during the early neonatal period, the use of furazolidone is not advised in infants up to 1 month of age.

Geriatric Use:

There is a lack of available information regarding the impact of age on the effects of furazolidone in geriatric patients.

Physicians should be knowledgeable as well as vigilant about the treatment and identification of overdosage of Furazolidone.

No information has been provided .

Pharmacodynamics

Furazolidone exhibits a wide-ranging antibacterial effect that effectively targets a variety of pathogens found in the gastrointestinal tract. This includes pathogens such as E. coli, staphylococci, Salmonella, Shigella, Proteus, Aerobacter aerogenes, Vibrio cholerae, and Giardia lamblia. The mechanism of its bactericidal activity is attributed to its ability to disrupt DNA replication and protein synthesis. By interfering with these essential processes, Furazolidone helps minimize the emergence of resistant microorganisms, enhancing its overall antimicrobial efficacy.

Pharmacokinetics

Absorption:

Studies using radiolabeled drugs have demonstrated that furazolidone is effectively absorbed after oral administration.

Distribution:

Limited pharmacokinetic data are available for humans. However, recent findings indicate that variable plasma concentrations were observed in individuals receiving therapeutic doses. In a study involving 8 meningitis patients, cerebrospinal fluid (CSF) concentrations were found to be comparable to serum concentrations. Additionally, significant concentrations of furazolidone have been detected in rat bile.

Biotransformation:

Furazolidone undergoes rapid and extensive metabolism, with the primary identified metabolic pathway involving nitro-reduction to form the aminofuran derivative.

Elimination:

Radiolabeled drug studies have shown that more than 65% of an orally administered dose of furazolidone is excreted in the urine of both humans and animals. Additionally, the drug has been found in feces.

1. https://go.drugbank.com/drugs/DB00614
2. https://www.rxlist.com/Furazolidone-drug.htm#warnings
3. https://www.sciencedirect.com/topics/medicine-and-dentistry/furazolidone
4. https://www.drugs.com/cons/furazolidone.html
5. https://www.e-lactancia.org/media/papers/Furazolidone-DS-Drugs1995.pdf