Nifuroxazide baum pharm

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT Nifuroxazide Baoum Pharm

Composition:

Active substance: nifuroxazide;

1 capsule contains 200 mg of nifuroxazide;

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

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

Pharmaceutical form. Capsules.

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

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

Pharmacological Properties.

Pharmacodynamics.

Nifuroxazide is an antimicrobial agent, a derivative of 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 tissues determine the uniqueness of nifuroxazide compared to other nitrofuran derivatives, as 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, 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 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 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 animals of each sex per group) and rats (52 animals of each sex per group), which received nifuroxazide in the diet for 2 years at doses of 0, 200, 600, or 1800 mg/kg/day. Despite 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) were 11 and 22 times higher than the maximum human dose of 1800 mg (493 mg/m² for a 60 kg patient), when adjusted to 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 may be used in combination with drugs commonly used in 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 should not be used simultaneously with adsorbents, alcohol-containing preparations, drugs that may cause disulfiram-like reactions, or drugs that depress the central nervous system.

Alcohol consumption is strictly prohibited during nifuroxazide 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 trunk, hyperemia, tinnitus, dyspnea, 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. If necessary, concomitant rehydration therapy should be administered depending on patient's age, condition, and severity of diarrhea.

In case of prescription of oral or intravenous rehydration, instructions for dilution and use of designated 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 requirement of 2 liters of water).

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

If diarrhea is accompanied by such clinical manifestations as deterioration of general condition, fever, or signs of intoxication, nitroxoline should be prescribed together with antibacterial agents used for treatment of intestinal infections, since nitroxoline is partially absorbed (10–20%) from the gastrointestinal tract and extensively metabolized, with metabolites predominantly circulating in blood. The drug should not be prescribed as monotherapy for intestinal infections complicated by septicemia.

Nitroxoline 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 drug 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 risk of disulfiram-like reaction, which manifests as worsening of diarrhea, vomiting, abdominal pain, sensation of warmth in the face and upper body, hyperemia, tinnitus, dyspnea, and tachycardia.

Use during pregnancy or breastfeeding.

Pregnancy. Data on use of nitroxoline for treatment of pregnant women are limited. Animal studies on reproductive toxicity are insufficient. Nitroxoline has a potential mutagenic effect. Therefore, nitroxoline is not recommended during pregnancy and should not be prescribed to women of childbearing potential who do not use 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, an effect on the gastrointestinal microbiome of breastfed infants cannot be excluded. Due to lack of clinical experience with nitroxoline-containing drugs during breastfeeding, their use is not recommended.

Fertility. Based on animal studies, there is insufficient information on 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.

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, the duration of treatment may be extended depending on the patient's clinical condition.

Children. For the treatment of children under 6 years of age, prescribe nifuroxazide 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. The occurrence of an allergic reaction requires discontinuation of the medicinal product. Afterwards, the patient must avoid taking nifuroxazide and other nitrofuran derivatives.

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

In cases of mild symptoms, no specific treatment or discontinuation of nifuroxazide is required, as symptoms subside quickly. If the exacerbation is pronounced, administration of the medicinal product should be discontinued, and further intake of nifuroxazide and other nitrofuran derivatives should be avoided.

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 nifuroxazide 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 ongoing 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 through the Automated Pharmacovigilance Information System at the following link: http://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions.

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

Packaging. 10 capsules per blister, 2 blisters per carton.

Prescription status. Prescription only.

Manufacturer. LLC "DKP "Pharmaceutical Factory".

Manufacturer's address and location of business activity. Stanishivka village, Zhytomyr district, Zhytomyr region, 12430, Korolova Street, b. 4, Ukraine.

Marketing Authorization Holder. Limited Liability Company "Representation of Baum Pharma GmbH".

Address of the Marketing Authorization Holder. 66 Shyroka Street, Lviv, 79052, Ukraine.