Nifuroxazide

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NIFUROXAZIDE

Composition:

Active ingredient: nifuroxazid;

5 ml of suspension contains 200 mg of nifuroxazid;

Excipients: sucrose, carbomer, citric acid monohydrate, sodium hydroxide, methylparaben (E 218), banana flavoring (contains propylene glycol), ethanol 96%, purified water.

Pharmaceutical form. Oral suspension.

Main physicochemical properties: yellow-colored liquid with a banana odor.

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

Pharmacological Properties.

Pharmacodynamics.

Nitroxoline is an antimicrobial agent, a derivative of nitrofuran. The antimicrobial and antiparasitic properties of nitroxoline are 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 nitroxoline compared to other nitrofuran derivatives, since, in addition to its antidiarrheal effect, it lacks systemic effects. It is effective against Gram-positive and Gram-negative bacteria: Streptococcus pyogenes, Staphylococcus aureus, E. coli, Salmonella, Shigella.

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 nitroxoline occurs in the intestine. Nitroxoline and its metabolites are excreted in feces. The rate of elimination of the drug depends on the amount of the administered drug and gastrointestinal motility.

At therapeutic doses, nitroxoline hardly suppresses 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.

Preclinical Safety Data.

Nitroxoline demonstrates mutagenic potential.

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

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

Clinical characteristics.

Indications.

Acute infectious diarrhea.

Contraindications.

Hypersensitivity to nifuroxazide, other 5-nitrofuran derivatives, or any component of the drug.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of nifuroxazide with sorbents, as well as with medicinal products containing ethanol, is not recommended.

Nifuroxazide should not be used concomitantly with drugs that may cause disulfiram-like reactions or with central nervous system (CNS) depressants.

Special precautions for use.

Treatment with nifuroxazide does not exclude dietary management and rehydration. If necessary, concomitant rehydration therapy should be applied according to the patient's age, condition, and severity of diarrhea.

Rehydration should be the main component in the treatment of acute diarrhea in children. Children should be given fluids frequently (every ¼ hour).

Prevention or treatment of dehydration should be performed using oral or intravenous rehydration solutions. If oral rehydration is indicated, it is recommended to use solutions specifically designed for this purpose, following the instructions for dilution and administration. The required volume of oral rehydration solutions depends on the degree of body weight loss. In cases of severe diarrhea, intense vomiting, or refusal to eat, intravenous rehydration is required.

If such rehydration is not necessary, fluid loss should be compensated by drinking large amounts of fluids containing salt and sugar (based on an average daily requirement of 2 liters of water).

Dietary recommendations during diarrhea should be followed: avoid consumption of fresh vegetables and fruits, spicy foods, frozen foods, and beverages. Rice is recommended. The decision regarding consumption of dairy products should be made on an individual basis.

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

Nifuroxazide contains sucrose, 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 intolerance or hereditary sucrose intolerance.

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

Alcohol consumption is strictly prohibited during treatment due to the risk of developing a disulfiram-like reaction, manifested by worsening diarrhea, vomiting, abdominal pain, sensation of warmth in the face and upper body, hyperemia, tinnitus, difficulty breathing, and tachycardia.

This medicinal product contains a small amount of ethanol (alcohol), less than 100 mg per dose.

This medicinal product contains 0.75 mmol (or 30 mg) of sodium per dose. Caution is advised when administering to patients on a sodium-restricted diet.

Shelf life of the drug after opening the bottle – 28 days.

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, 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 information from animal studies regarding the effect of nifuroxazide on fertility.

Ability to affect reaction speed when driving or operating machinery.

No effect.

Dosage and Administration.

Nifuroxazide should be administered orally, regardless of food intake, at regular intervals. The suspension should be shaken before use. The maximum daily dose is 800 mg (20 ml).

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.

Rarely – abdominal pain, nausea, exacerbation of diarrhea. These symptoms do not require discontinuation of treatment with the drug. In individual cases, hypersensitivity reactions are possible, including rash, pruritus, dyspnea, Quincke's edema, anaphylactic shock, which require discontinuation of the drug and administration of symptomatic therapy.

The medicinal product contains methylparahydroxybenzoate (E 218), which may cause an allergic reaction.

Shelf life.

3 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

90 ml in a bottle or flask; 1 bottle or flask in a carton together with a measuring spoon.

Prescription status.

Prescription only.

Manufacturer/Marketing Authorization Holder.

LLC "Ternopharm".

Address of manufacturer and location of its business activity / address of the marketing authorization holder.

46010, 4 Fabrychna St., Ternopil, Ukraine.

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