Nifuroxazide

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NIFUROXAZIDE

Composition:

Active substance: nifuroxazide;

1 tablet contains 0.1 g of nifuroxazide;

Excipients: potato starch, povidone, colloidal anhydrous silicon dioxide, talc, magnesium stearate;

coating: hypromellose (hydroxypropylmethylcellulose), titanium dioxide (E 171), polyethylene glycol (macrogol), quinoline yellow (E 104).

Pharmaceutical form. Coated tablets.

Main physico-chemical properties: yellow, round, biconvex coated tablets.

Pharmacotherapeutic group.

Antidiarrheal agents; drugs used for the treatment of infectious and inflammatory intestinal diseases. Antimicrobial agents used in intestinal infections. Nifuroxazide. ATC code A07AX03.

Pharmacological Properties

Pharmacodynamics

Nifuroxazide is an antimicrobial agent belonging to the nitrofuran derivative class. Its mechanism of action is not fully understood. The antimicrobial and antiparasitic properties of nifuroxazide are possibly due to the presence of an amino group. The local activity and lack of penetration into organs and tissues distinguish nifuroxazide from other nitrofuran derivatives, as this antidiarrheal agent lacks systemic effects. It is effective against both gram-positive and gram-negative bacteria: Streptococcus pyogenes, Staphylococcus aureus, E. coli, Salmonellae, Shigellae.

Pharmacokinetics

After oral administration, the drug is partially absorbed (10–20%) from the gastrointestinal tract and extensively metabolized, with the main circulating components in the blood being metabolites. Biotransformation of nifuroxazide occurs in the intestine, and approximately 20% of the administered dose is excreted unchanged. Nifuroxazide and its metabolites are eliminated in feces. The rate of elimination depends on the administered dose and gastrointestinal motility. Overall, elimination of nifuroxazide is slow, allowing it to remain in the gastrointestinal tract for an extended period.

At therapeutic doses, nifuroxazide does not significantly suppress normal intestinal microflora, does not induce the emergence of resistant microbial forms, and does not lead to the development of cross-resistance to other antibacterial agents. The therapeutic effect is achieved within the first hours of treatment.

Preclinical Safety Data

Nifuroxazide demonstrates mutagenic potential.

The carcinogenic potential of nifuroxazide was evaluated in mice (50 animals of each sex per group) and rats (52 animals of each sex per group) that received nifuroxazide in the diet for 2 years at doses of 0, 200, 600, or 1800 mg/kg/day. Despite its mutagenic properties, carcinogenicity of nifuroxazide was not demonstrated in either mice or rats.

The doses administered to mice and rats (5400 mg/m² and 10,800 mg/m², respectively) exceeded the maximum human dose of 1800 mg (493 mg/m² for a 60 kg patient) by 11 and 22 times, respectively, when adjusted for body surface area.

Clinical characteristics.

Indications.

Acute infectious diarrhea.

Contraindications.

Hypersensitivity to nitroxoline and to other 5-nitrofuran derivatives or to any of the excipients.

Interaction with other medicinal products and other forms of interaction.

Concomitant administration of other oral medicinal products should be avoided due to the strong adsorptive properties of nitroxoline.

Nitroxoline is not recommended to be used concomitantly with adsorbents, drugs that may cause disulfiram-like reactions, and drugs that depress the central nervous system (CNS).

Special precautions for use.

Treatment with nifuroxazide does not exclude dietary management and rehydration. If diarrhea persists after 3 days of treatment, dosage should be reassessed and a decision on rehydration made; if necessary, concomitant rehydration therapy should be administered according to the patient's age, clinical condition, and severity of diarrhea.

When oral or intravenous rehydration is indicated, the instructions for dilution and use of the prescribed solutions must be strictly followed. If such rehydration is not required, fluid losses should be compensated by increased intake of fluids containing salt and sugar (based on an average daily requirement of 2 liters of water).

Dietary recommendations during diarrhea should be observed: avoid fresh vegetables and fruits, spicy foods, frozen products and beverages. Rice-based foods are recommended. Consumption of dairy products should be evaluated on a case-by-case basis.

If diarrhea is accompanied by clinical signs indicating severe disease (worsening general condition, fever, signs of intoxication), nifuroxazide should be administered together with systemic antibacterial agents used for the treatment of intestinal infections, as the drug is not absorbed in the gastrointestinal tract and does not enter systemic circulation. Nifuroxazide must not be used as monotherapy for intestinal infections complicated by sepsis.

Alcoholic beverages and medicinal products containing alcohol must not be consumed during treatment with nifuroxazide due to the risk of a disulfiram-like reaction, which may manifest as worsening diarrhea, vomiting, abdominal pain, sensation of heat, skin hyperemia, tinnitus, dyspnea, tachycardia, and anxiety.

Use during pregnancy or breastfeeding.

Pregnancy

Clinical data on the use of nifuroxazide in pregnant women are limited. Reproductive toxicity data from animal studies are insufficient. Nifuroxazide has shown mutagenic potential. Therefore, nifuroxazide is not recommended during pregnancy and should not be administered to women of childbearing potential who are not using effective contraception.

Lactation

It is unknown whether nifuroxazide or its metabolites are excreted in breast milk. Since nifuroxazide has low bioavailability (gastrointestinal absorption of approximately 10–20% of the dose), its concentration in milk is likely to be low. However, an effect on the gastrointestinal microbiome of breastfed infants cannot be excluded. Due to the lack of clinical experience with nifuroxazide-containing medicinal products during breastfeeding, their use is not recommended.

Fertility

There is insufficient data from animal studies regarding the effect of nifuroxazide on fertility.

Ability to affect reaction speed when driving or operating machinery.

Nifuroxazide does not affect the ability to drive vehicles or operate machinery.

Method of Administration and Dosage

For adults and children aged 7 years and older, the recommended dose is 2 tablets taken 4 times daily (every 6 hours). The drug should be administered orally, swallowed with a small amount of water, regardless of food intake. The duration of treatment should not exceed 7 days. During treatment of acute diarrhea, continuous oral or intravenous fluid replacement must be ensured, depending on the patient's overall condition.

Children.

Nifuroxazide, 0.1 g coated tablets, should be administered to children aged 7 years and older. For children under 7 years of age, nifuroxazide in the form of a suspension is recommended.

Overdose.

Symptoms of overdose are unknown. In case of overdose, gastric lavage and symptomatic treatment are recommended.

Side effects.

Adverse reactions may rarely occur.

Blood and lymphatic system disorders: granulocytopenia.

Gastrointestinal disorders: individual hypersensitivity reactions to nitroxoline may manifest as abdominal pain, nausea, vomiting, and exacerbation of diarrhea. If such symptoms of mild intensity occur, no specific therapy or discontinuation of nitroxoline is required, as symptoms resolve quickly. If exacerbation is pronounced, nitroxoline administration should be discontinued. The patient should subsequently avoid taking nitroxoline and other nitrofuran derivatives.

Skin disorders: allergic reactions are possible, including pruritus, skin rashes, and urticaria. One case of pustular eruption in an elderly patient and one case of nodular prurigo associated with contact allergy to nitroxoline have been reported.

In isolated cases, dyspnea and severe hypersensitivity reactions, including angioneurotic edema and anaphylactic shock, may occur.

If an allergic reaction occurs, the drug must be discontinued. The patient should subsequently avoid taking nitroxoline and other nitrofuran derivatives.

Shelf life.

3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

No. 10, No. 30 (10×3) in blister packs.

Prescription status.

Prescription only.

Manufacturer/Marketing Authorization Holder.

LLC "Ternopharm".

Manufacturer's address / Address of the marketing authorization holder.

4 Fabrychna St., Ternopil, 46010, Ukraine.

Tel./fax: (0352) 521-444, www.ternopharm.com.ua