Nifuroxazide

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NIFUROXAZIDE (NIFUROXAZID)

Composition:

Active substance: nifuroxazide;

5 ml of suspension contains 220 mg of nifuroxazide;

Excipients: confectioner's sugar, carbomer 934, simethicone, methylparahydroxybenzoate (E 218), sodium hydroxide, citric acid monohydrate, flavor "Peach" (containing propylene glycol), purified water.

Pharmaceutical form. Oral suspension.

Main physicochemical properties: light yellow colored suspension, with a characteristic aromatic odor, sweet to taste. Stratification may occur upon storage, which is eliminated by shaking.

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

Pharmacological Properties.

Pharmacodynamics.

Nitrofurazone is an antimicrobial agent derived from nitrofuran. Its mechanism of action is not fully understood. The antimicrobial and antiparasitic properties of nifuroxazide may be due to the presence of an amino group. Local activity and lack of penetration into organs and tissues of the body determine the uniqueness of nifuroxazide compared to other nitrofuran derivatives, since this antidiarrheal agent lacks systemic effects. It is effective against Gram-positive and Gram-negative bacteria: Streptococcus pyogenes, Staphylococcus aureus, E. coli, Salmonellae, Shigellae.

Pharmacokinetics.

After oral administration, nifuroxazide is partially absorbed (10–20%) from the gastrointestinal tract and is extensively metabolized, with the main circulating components in the blood being metabolites.

Nifuroxazide and its metabolites are excreted in feces. The rate of metabolite elimination depends on the amount of 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 cause 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.

Preclinical safety data

Nifuroxazide shows a potential mutagenic effect.

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.

Studies with nifuroxazide were conducted over two years in mice and rats at doses of 5400 mg/m² and 10800 mg/m², respectively, based on body surface area normalization, which exceeded the maximum recommended human dose of 1800 mg (493 mg/m² for a 60 kg patient) by 11 and 22 times, respectively.

Clinical characteristics.

Indications.

Acute infectious diarrhea.

Contraindications.

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

Interaction with medicinal products and other types of interactions.

Nitroxoline should not be used concomitantly with sorbents, alcohol-containing products, drugs that may cause disulfiram-like reactions, and drugs 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 does not resolve within 3 days of starting 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 antibiotics effective against intestinal infections should be administered, as nifuroxazide is not absorbed from the gastrointestinal tract and does not enter systemic circulation.

The drug should not be used as monotherapy for intestinal infections complicated by sepsis.

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

Normal food intake should be maintained; however, during diarrhea, dietary recommendations should be followed: avoid raw vegetables and fruits, spicy foods, frozen products, and cold beverages. Consumption of dairy products should be decided on a case-by-case basis. Baked meat and rice are recommended.

During treatment of diarrhea, continuous oral rehydration is essential to compensate for fluid loss caused by diarrhea: patients should drink large amounts of fluids containing salt and sugar (with an average daily requirement of 2 liters of water for an adult).

In cases of severe or prolonged diarrhea, intense vomiting, or anorexia, intravenous rehydration should be administered according to the patient's age and clinical condition. When administering oral or intravenous rehydration, instructions for dilution and use of the designated solutions must be strictly followed.

Rehydration should be the cornerstone in the management of acute diarrhea in children. Children should be given frequent small amounts of fluids (every 15 minutes).

Patients should avoid alcohol during treatment with nifuroxazide due to the risk of developing a disulfiram-like reaction, which may manifest as worsening diarrhea, vomiting, abdominal pain, facial flushing, warmth in the face and upper body, hyperemia, tinnitus, dyspnea, and tachycardia.

Nifuroxazide contains confectionery sugar, which should be taken into account when prescribing the drug to patients with diabetes mellitus. The drug is not recommended for patients with hereditary fructose or sucrose intolerance.

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

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 potential mutagenic activity. Therefore, nifuroxazide is not recommended during pregnancy and should not be prescribed 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 (approximately 10–20% of the dose is absorbed from the gastrointestinal tract), the amount excreted 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, its use is not recommended.

Fertility

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

Ability to affect reaction rate while driving or operating machinery

No effect.

Administration and Dosage.

Take orally, independent of food intake. Shake the suspension well before use. The maximum daily dose of nifuroxazide is 800 mg.

Children aged 2 years and older: 5 ml of suspension 3 times a day.

Adults: 5 ml of suspension 4 times a day.

Duration of treatment should not exceed 7 days.

Children. Do not administer to children under 2 years of age.

Overdose.

Cases of overdose have not been reported. In case of overdose, gastric lavage and symptomatic treatment are recommended.

Adverse reactions.

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

Immune system disorders: allergic reactions, including angioneurotic edema (Quincke's edema), anaphylactic shock, dyspnea, 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. In cases of mild symptoms, no specific treatment or discontinuation of nitroxoline is required, as symptoms resolve quickly. If the exacerbation is severe, nitroxoline administration should be discontinued. 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. One case of pustulosis in an elderly patient and one case of nodular pruritus associated with contact allergy to nitroxoline have been reported.

Shelf life. 3 years.

Storage conditions. Store at a temperature not exceeding 25 °C in the original packaging, in a place inaccessible to children.

Packaging. 90 ml in a bottle or jar; 1 bottle or jar with a measuring cup in a carton.

Prescription status. Prescription only.

Manufacturer. LLC "DKP "Pharmaceutical Factory".

Manufacturer's address and place of business.
4 Korolyova St., village Stanishevska, Zhytomyr district, Zhytomyr region, 12430, Ukraine.