Nifuroxazide - vishfa

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NIFUROXAZIDE-VISHPHA (NIFUROXAZIDE-VISHPHA)

Composition:

Active ingredient: nifuroxazide;

1 capsule contains nifuroxazide 200 mg;

Excipients: microcrystalline cellulose, corn starch, sucrose, povidone K-25, magnesium stearate;

Gelatin capsule: gelatin, titanium dioxide (E171), iron oxide red (E172), tartrazine (E102).

Dosage form. Capsules.

Main physicochemical properties: hard gelatin capsules with a yellow body and a red-brown cap. The contents of the capsules are a bright yellow powder.

Pharmacotherapeutic group. Antidiarrheals, intestinal anti-inflammatory/antiseptics. Other intestinal antiseptics. Nifuroxazide. ATC code A07AX03.

Pharmacological properties.

Pharmacodynamics.

Nifuroxazide is an antimicrobial agent, a derivative of nitrofuran. Its mechanism of action has not been fully elucidated. 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 determine the uniqueness of nifuroxazide compared to other nitrofuran derivatives, since this antidiarrheal agent does not exert systemic effects. It is effective against Gram-positive and Gram-negative bacteria: Streptococcus pyogenes, Staphylococcus aureus, Escherichia coli, Salmonellae, Shigellae.

Pharmacokinetics.

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

Nifuroxazide and its metabolites are excreted in feces. The rate of metabolite elimination depends on the amount of administered drug and gastrointestinal motility. Overall, elimination of nifuroxazide is slow — 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 demonstrates a potential mutagenic effect.

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 nifuroxazide, other 5-nitrofuran derivatives, or any component of the medicinal product.
• Age under 6 years. For treatment of children under 6 years of age, nifuroxazide should be administered in the form of a suspension.
• Pregnancy.

Interaction with other medicinal products and other forms of interaction.

Nifuroxazide-Vishfa may be used in combination with drugs commonly used for the treatment of diarrhea: rehydration solutions, antibiotics, chemotherapeutic agents, spasmolytics, and analgesics.

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

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

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

Special precautions for use.

Treatment with nitroxoline does not exclude dietary regimen and rehydration. If diarrhea does not stop after 3 days of treatment, dosage should be reviewed and a decision on rehydration therapy should be made. When necessary, concomitant rehydration therapy should be administered according to patient's age, clinical condition, and severity of diarrhea.

In cases requiring oral or intravenous rehydration, instructions for dilution and administration of designated rehydration solutions must be strictly followed. If such rehydration is not required, fluid losses should be compensated by drinking large amounts of fluids containing salt and sugar (based on average daily fluid requirement of 2 liters).

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

If diarrhea is accompanied by such clinical symptoms as worsening general condition, fever, or signs of intoxication, nitroxoline should be administered together with antibacterial agents used for treatment of intestinal infections, since nitroxoline is partially absorbed (10–20%) from the gastrointestinal tract and undergoes extensive metabolism, with its metabolites being predominantly present in the bloodstream. The drug should not be used as monotherapy in intestinal infections complicated by sepsis.

Nitroxoline-Vishfam contains sucrose (0.031 g per capsule), which should be taken into account by patients with diabetes mellitus when calculating total daily intake of carbohydrates and sugars. The medicinal product is not recommended for patients with hereditary sucrose intolerance or fructose malabsorption.

The gelatin capsule contains the colorant tartrazine (E 102), which may cause 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, facial flushing and warmth in the upper body, hyperemia, tinnitus, dyspnea, and tachycardia.

Use during pregnancy or breastfeeding.

Pregnancy. Data on the use of nitroxoline in pregnant women are limited. Animal studies on reproductive toxicity are insufficient. Nitroxoline has shown potential mutagenic activity. Therefore, nitroxoline 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 nitroxoline or its metabolites are excreted in breast milk. Since nitroxoline has low bioavailability (approximately 10–20% of the dose is absorbed from the gastrointestinal tract), 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 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, independent of food intake.

Adults and children aged 15 years and older: 200 mg (1 capsule of 200 mg) 4 times daily. Maximum daily dose of nifuroxazide — 800 mg.

Children aged 6 years and older: 1 capsule of 200 mg 3–4 times daily. Daily dose of nifuroxazide — 600–800 mg.

Duration of treatment — no more than 7 days. If necessary, administration of the drug may be prolonged depending on the patient's clinical condition.

Children. For treatment of children under 6 years of age, nifuroxazide should be administered in the form of a suspension.

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 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 intake of nitroxoline and other nitrofuran derivatives.

Gastrointestinal disorders: isolated cases of hypersensitivity to nitroxoline may manifest as abdominal pain, nausea, vomiting, and exacerbation of diarrhea.

If such symptoms are mild, no specific therapy or discontinuation of nitroxoline is required, as symptoms subside quickly. However, if the exacerbation is pronounced, administration of the drug should be discontinued and subsequent avoidance of nitroxoline and other nitrofuran derivatives is necessary.

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 prurigo associated with contact allergy to nitroxoline have been reported.

If any adverse reactions occur, administration of the medicinal product should be discontinued and medical advice must be sought immediately.

Reporting of adverse reactions following marketing authorization of the medicinal product is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and 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: http://aisf.dec.gov.ua.

Shelf life: 3 years.

Storage conditions

Keep out of reach of children. Store in the original packaging at a temperature not exceeding 25 °C.

Packaging: 10 capsules in a blister, 2 blisters per carton.

Prescription status: Prescription only.

Manufacturer: LLC "DKP "Pharmaceutical Factory".

Manufacturer's address and location of operations: 4, Korolova St., Stanishivka, Zhytomyr district, Zhytomyr region, 12430, Ukraine.