Nifuroxazide

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NIFUROXAZIDE

Composition:

Active substance: nifuroxazide;

5 ml of suspension contains 220 mg of nifuroxazide (220 mg/5 ml);

Excipients: carbomer, sucrose, sodium hydroxide, citric acid monohydrate, simethicone emulsion, methylparahydroxybenzoate (E 218), banana flavoring, purified water.

Pharmaceutical form. Oral suspension.

Main physicochemical properties: a suspension from light-yellow to bright-yellow in color with a characteristic banana odor. Stratification of the suspension may occur during storage, which becomes homogeneous again after shaking.

Pharmacotherapeutic group. Antimicrobial agents used for the treatment of intestinal infections. ATC code A07AX03.

Pharmacological properties.

Pharmacodynamics.

Nifuroxazide is an antimicrobial agent, a derivative of 5-nitrofuran. 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. Local activity and lack of penetration into organs and body tissues confer uniqueness to nifuroxazide compared to other nitrofuran derivatives, as this antidiarrheal agent lacks systemic effects. It is effective against Gram-positive and Gram-negative bacteria: Streptococcus pyogenes, Staphylococcus aureus, E. coli, Salmonellae, Shigellae.

Nifuroxazide demonstrates mutagenic potential.

The carcinogenic potential of nifuroxazide was evaluated in mice (50/sex/group) and rats (52/sex/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.

Based on 2-year studies in mice and rats (5400 mg/m² and 10800 mg/m², respectively), using surface area comparison with 11- and 22-fold coefficients, the maximum human dose is 1800 mg (493 mg/m² assuming a patient weight of 60 kg).

Pharmacokinetics.

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

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

Clinical characteristics.

Indications.

Acute infectious diarrhea.

Contraindications.

Hypersensitivity to nifuroxazide, to other 5-nitrofuran derivatives, or to any of the excipients of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

Nifuroxazide is not recommended to be used concomitantly with adsorbents, alcohol-containing preparations, agents that may cause disulfiram-like reactions, and agents that depress the central nervous system.

Special precautions for use

Nifuroxazide should not be used for more than 7 days. There are no indications for prolonged therapy. If diarrhea persists for more than 3 days after initiation of treatment, further diagnostic evaluation is required to determine the underlying cause of symptoms. Antibiotic therapy may become necessary.

In cases of severe invasive diarrhea with clinical signs of general weakness, fever, and symptoms of intoxication, systemic-acting antibiotics should be considered, since nifuroxazide is not absorbed from the gastrointestinal tract.

If hypersensitivity reactions occur (dyspnea, facial swelling, swelling of lips, tongue, skin rashes, pruritus), administration of nifuroxazide must be discontinued immediately.

Dietary recommendations during diarrhea should be observed: avoid fresh vegetables and fruits, spicy foods, frozen foods and beverages. Consumption of dairy products should be decided individually, depending on the specific case. Baked meat and rice are recommended.

If intensive rehydration is not required, fluid losses should be compensated by drinking large amounts of fluids containing salt and sugar (based on an average daily requirement of 2 liters of water for an adult).

In cases of severe and prolonged diarrhea, intense vomiting, or refusal to eat, intravenous rehydration is necessary, depending on the patient's age and condition. When administering oral or intravenous rehydration, instructions for dilution and use of the designated solutions must be strictly followed.

Alcohol consumption is strictly prohibited during treatment due to the risk of a disulfiram-like reaction, which may manifest as worsening diarrhea, vomiting, abdominal pain, sensation of warmth in the face and upper body, skin hyperemia, tinnitus, dyspnea, and tachycardia.

The medicinal product Nifuroxazide, oral suspension, contains sucrose; specifically, 5 mL of the preparation contains 1.35 g of sucrose, equivalent to 0.1125 carbohydrate exchange units (1 CEU = 12 g of carbohydrates). This should be taken into account when prescribing the drug to patients with diabetes mellitus. The drug is not recommended for patients with hereditary sucrose intolerance or fructose malabsorption.

The medicinal product contains methyl parahydroxybenzoate (E 218), which may cause allergic reactions (delayed-type).

Use during pregnancy or breastfeeding.

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

Breastfeeding. 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, effects on the gut 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. Based on animal studies, there is insufficient data on the effect of nifuroxazide on fertility.

Ability to affect reaction speed when driving or operating machinery.

Nifuroxazide does not affect the speed of reaction when driving or operating machinery.

Dosage and Administration.

Take orally, independent of food intake. The suspension should be shaken well before use. Do not exceed the recommended dose.

Children from 2 years of age: 5 ml of suspension three times daily.

Adults: 5 ml of suspension four times daily.

Treatment duration – no more than 7 days.

Children.

Do not administer to children under 2 years of age.

Overdose.

Specific information regarding symptoms of nifuroxazide overdose is not available.

One case of nifuroxazide overdose has been reported in a 2-year-old child who ingested an unknown quantity of the oral suspension. The child experienced somnolence and diarrhea, which subsequently resolved spontaneously. If nifuroxazide overdose is suspected, careful observation of the patient is recommended, along with symptomatic and supportive treatment.

Side effects.

Blood and lymphatic system disorders: one case of granulocytopenia has been reported.

Immune system disorders: allergic reactions are possible, including angioneurotic edema (Quincke's edema), anaphylactic shock, urticaria, and pruritus. If an allergic reaction occurs, the drug must be discontinued. The patient should subsequently avoid taking nitroxoline and other nitrofuran derivatives.

Gastrointestinal disorders: individual cases of hypersensitivity to nitroxoline may manifest as abdominal pain, nausea, vomiting, and exacerbation of diarrhea. If such symptoms of mild intensity occur, there is no need for specific treatment or discontinuation of nitroxoline, as symptoms resolve quickly. However, if the exacerbation is pronounced, the drug should be discontinued and the patient should subsequently avoid taking nitroxoline and other nitrofuran derivatives.

Skin and subcutaneous tissue disorders: skin reactions such as rash and pruritus occur rarely. In isolated cases, pustulosis (in elderly patients) and nodular pruritus (in patients with contact allergy to nitroxoline) have been observed.

Shelf life. 3 years.

Shelf life after first opening – 14 days.

Storage conditions.

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

Keep out of reach of children.

Packaging.

100 mL of the drug in a bottle/vial with a tamper-evident closure.

Bottle/vial with a dosing spoon in a carton.

Prescription status.

Prescription only.

Manufacturer.

Public Joint-Stock Company "Scientific and Production Center "Boryspil Chemical and Pharmaceutical Plant".

Manufacturer's address and place of business.

17 Myru Street, Kyiv, 03134, Ukraine.