Nifuroxazide

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT NIFUROXAZIDE (NIFUROXAZIDE)

Composition:

Active substance: nifuroxazide;

5 ml of suspension contains 220 mg of nifuroxazide;

Excipients: carbomer; sucrose; sodium hydroxide (E 524); citric acid monohydrate (E 330); simethicone; methylparahydroxybenzoate (E 218); banana flavoring; purified water.

Pharmaceutical form. Oral suspension.

Main physicochemical properties: light yellow suspension with a banana odor, which may slightly sediment upon storage, but after shaking returns to a homogeneous suspension without leaving a dense sediment at the bottom of the vial.

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

Pharmacological Properties

Pharmacodynamics

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

Pharmacokinetics

After oral administration, nitrofurazone is partially absorbed (10–20%) from the gastrointestinal tract and extensively metabolized, with metabolites being primarily present in the bloodstream. Biotransformation of nitrofurazone also occurs in the intestine, and approximately 20% of the administered dose is excreted unchanged. Nitrofurazone and its metabolites are excreted in feces. The rate of elimination depends on the administered dose and gastrointestinal motility. Overall, elimination of nitrofurazone is slow, allowing it to remain in the gastrointestinal tract for a prolonged period.

At therapeutic doses, nitrofurazone 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. Therapeutic effect is achieved within the first hours of administration.

In preclinical safety studies, nitrofurazone demonstrated mutagenic potential. The carcinogenic potential of nitrofurazone was evaluated in mice (50 animals of each sex per group) and rats (52 animals of each sex per group) that received nitrofurazone in their diet for 2 years at doses of 0, 200, 600, or 1800 mg/kg/day. Despite its mutagenic properties, no evidence of carcinogenicity was demonstrated in either mice or rats.

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

Clinical characteristics.

Indications. Acute diarrhea of infectious etiology.

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 should not 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

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

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

Prevention or treatment of dehydration should be carried out using oral or intravenous rehydration solutions. If oral rehydration is indicated, it is recommended to use appropriate rehydration solutions according to the manufacturer's instructions for dilution and administration. The required volume of oral rehydration solution depends on the degree of body weight loss. Intravenous rehydration is required in cases of severe or prolonged diarrhea, intense vomiting, or refusal to take fluids, depending on the patient’s age and condition.

If intravenous 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).

Dietary recommendations during diarrhea should be observed: avoid fresh vegetables and fruits, spicy foods, and frozen foods and drinks. Rice is recommended as a preferred food. The decision regarding consumption of dairy products should be made on a case-by-case basis.

If diarrhea is accompanied by clinical signs indicating severe disease (worsening general condition, fever, signs of intoxication), the medicinal product Nitroxoline should be administered together with systemic-acting antibacterial agents used for the treatment of intestinal infections. Nitroxoline should not be used as monotherapy for intestinal infections complicated by sepsis.

If you have known intolerance to certain sugars, consult your doctor before taking this medicinal product. The medicinal product contains methylparahydroxybenzoate (E 218), which may cause delayed-type allergic reactions.

Alcohol consumption is strictly prohibited during treatment due to the risk of developing a disulfiram-like reaction, which may manifest as worsening diarrhea, vomiting, abdominal pain, flushing of the face and upper body, hyperemia, tinnitus, breathing difficulties, and tachycardia.

Use during pregnancy or breastfeeding

Pregnancy. Clinical data on the use of nitroxoline in pregnant women are limited. Reproductive toxicity studies in animals are insufficient. Nitroxoline has mutagenic potential. Therefore, nitroxoline 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 nitroxoline or its metabolites are excreted in breast milk. Since nitroxoline has low bioavailability (gastrointestinal absorption of approximately 10–20% of the dose), the amount excreted in milk is likely to be low. However, an effect on the gut microbiome of breastfed infants cannot be excluded. Due to the lack of clinical experience with nitroxoline-containing medicinal products during breastfeeding, their use is not recommended.

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

Ability to affect reaction speed when driving or operating machinery. No effect.

Dosage and Administration.

Take orally, regardless of food intake. Before administration, the medicinal product should be shaken to obtain a homogeneous suspension. If necessary, the suspension can be taken with water.

Do not exceed the recommended dose.

Children aged 2 years and older: 5 ml of suspension three times daily.

Adults: 5 ml of suspension four times daily.

Treatment duration should not exceed 7 days.

The dose should be measured using the spoon provided in the drug package.

Children. Not recommended for children under 2 years of age.

Overdose.

One case of overdose has been reported, accompanied by transient symptoms of diarrhea and drowsiness. In case of overdose, careful observation, gastric lavage, and symptomatic and supportive treatment are recommended.

Adverse Reactions

• Haematopoietic 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. In cases of mild symptoms, no specific therapy or discontinuation of nitroxoline is required, as symptoms resolve quickly. However, if the exacerbation is pronounced, administration of 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.

One case of pustulosis in an elderly patient and one case of nodular pruritus in the presence of contact allergy to nitroxoline have been reported.

Reporting of suspected adverse reactions

Reporting of adverse reactions following drug registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua .

Shelf life. 3 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. After opening the bottle, store for no more than 14 days. Keep out of reach of children.

Packaging. 100 ml in a bottle; 1 bottle with a measuring spoon in a carton.

Prescription status. Prescription only.

Manufacturer. JSC "Halychpharm".

Manufacturer's address and location of its business activities.

6/8 Opryshkivska Street, Lviv, 79024, Ukraine.