Nifuroxazide richter

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

Composition:

Active substance: nifuroxazide;

1 tablet contains 100 mg of nifuroxazide;

Excipients: colloidal anhydrous silicon dioxide, potato starch, gelatin, talc, magnesium stearate; coating: hypromellose (E 464), polyethylene glycol, quinoline yellow (E 104), titanium dioxide (E 171), talc.

Pharmaceutical form. Coated tablets.

Main physicochemical properties: yellow, coated, round, biconvex tablets. Diameter approximately 9 mm.

Pharmacotherapeutic group.

Antimicrobial agents used for the treatment of intestinal infections.

ATC code A07AX03.

Pharmacological Properties

Pharmacodynamics

Nitrofurantoin is an antimicrobial agent belonging to the nitrofuran class. Its mechanism of action is not fully understood. It is believed that nitrofurantoin inhibits dehydrogenase activity and disrupts protein synthesis in pathogenic bacteria. The antimicrobial and antiparasitic properties of nitrofurantoin are possibly due to the presence of an amino group. Local activity and lack of penetration into organs and tissues determine the uniqueness of nitrofurantoin compared to other nitrofuran derivatives, as this antidiarrheal agent does not exert systemic effects.

Nitrofurantoin is effective against most causative agents of intestinal infections (including mutant strains resistant to other antimicrobial agents). It exerts local antibacterial action within the intestinal lumen against certain gram-positive bacteria of the genus Staphylococcus and certain gram-negative bacteria of the family Enterobacteriaceae, including: Yersinia sp., Escherichia sp., Citrobacter sp., Enterobacter sp., Klebsiella sp., Salmonella sp.

At medium therapeutic doses, it exhibits bacteriostatic activity, while at higher doses it acts bactericidally. At therapeutic doses, it hardly disturbs the balance of saprophytic bacterial flora of the large intestine, does not induce the development of resistant strains of pathogenic microorganisms or cross-resistance of bacteria to other antimicrobial agents, allowing, if necessary, its use in combination therapy with systemic antibacterial drugs for generalized infections. In viral-origin intestinal infections, it prevents the development of bacterial superinfection. The efficacy of the drug is independent of the pH in the intestinal lumen. Therapeutic effect is achieved within the first hours of treatment.

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.

Preclinical Safety Data

Nitrofurantoin demonstrates mutagenic potential.

The carcinogenic potential of nitrofurantoin was evaluated in mice (50 animals of each sex per group) and rats (52 animals of each sex per group) that received nitrofurantoin in their diet for 2 years at doses of 0, 200, 600, or 1800 mg/kg/day. Despite its mutagenic properties, carcinogenicity of nitrofurantoin 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 and to other nitrofuran derivatives or to any of the excipients of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

• Concomitant administration of other oral medicinal products should be avoided due to the strong adsorptive properties of nifuroxazide.
• Simultaneous use of nifuroxazide with adsorbents, alcohol-containing products, medicinal products that may cause disulfiram-like reactions, and CNS depressants is not recommended.
• Consumption of alcoholic beverages during treatment with nifuroxazide is strictly prohibited due to the risk of developing a disulfiram-like reaction, manifested by exacerbation of diarrhea, vomiting, abdominal pain, feeling of warmth in the face and upper part of the body, hyperemia, tinnitus, dyspnea, and tachycardia.

Special precautions for use.

• Nitroxolin 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, it is advisable to use a systemic-acting antibiotic, since nitroxolin is not absorbed from the gastrointestinal tract.
• If hypersensitivity reactions occur (dyspnea, facial swelling, swelling of lips, tongue, skin rash, pruritus), nitroxolin administration must be discontinued immediately.
• During diarrhea treatment, continuous additional oral rehydration is required to compensate for fluid loss caused by diarrhea: patients should consume large amounts of fluids containing salt and sugar (based on an average daily requirement of 2 liters of water for an adult). In cases of severe and prolonged diarrhea, intense vomiting, or anorexia, intravenous rehydration is necessary, depending on the patient's age and condition. When performing oral or intravenous rehydration, instructions for dilution and use of the prescribed solutions must be strictly followed.
• Patients should avoid alcoholic beverages during nitroxolin treatment due to the risk of developing a disulfiram-like reaction, which may manifest as worsening diarrhea, vomiting, abdominal pain, facial flushing, hyperemia, sensation of heat in the face and upper body, tinnitus, respiratory distress, and tachycardia.
• It is recommended to continue eating; however, during diarrhea, dietary recommendations should be observed: avoid fresh vegetables and fruits, spicy foods, frozen products, and cold beverages. Baked meat and rice are recommended.

Use during pregnancy or breastfeeding.

Pregnancy. Data on the use of nitroxolin in pregnant women are limited. Animal studies on reproductive toxicity are insufficient. Nitroxolin exhibits mutagenic potential. Therefore, nitroxolin is not recommended during pregnancy and should not be administered to women of reproductive potential who are not using effective contraception.

Breastfeeding. It is unknown whether nitroxolin or its metabolites are excreted in breast milk. Since nitroxolin has low bioavailability (gastrointestinal absorption of approximately 10–20% of the dose), its concentration in milk is likely to be low. However, effects on the gut microbiome of breastfed infants cannot be ruled out. Due to the lack of clinical experience with nitroxolin-containing medicinal products during breastfeeding, their use is not recommended.

Fertility. Based on animal studies, there is insufficient information regarding the effect of nitroxolin on fertility.

Ability to affect reaction speed when driving or operating machinery.

Nitroxolin does not affect the ability to drive or operate machinery.

Method of Administration and Dosage

The tablets should be taken orally, whole, with a sufficient amount of water, independently of food intake. The maximum daily dose is 800 mg.

Adults and children aged 15 years and older: 200 mg (2 tablets of 100 mg) 4 times daily.

Children aged 6 years and older: 200 mg (2 tablets of 100 mg) 3–4 times daily.

Duration of treatment should not exceed 7 days. If symptoms persist, consult a physician.

Children.

Nifuroxazide Richter 100 mg tablets can be used in children aged 6 years and older. For children under 6 years of age, Nifuroxazide Richter in the form of suspension is recommended.

Overdose.

Specific information regarding symptoms of nifuroxazide overdose is not available.

One case of nifuroxazide overdose has been reported with the oral suspension in a 2-year-old child who ingested an unknown quantity of the drug. The child experienced somnolence and diarrhea, which subsequently resolved. In case of suspected nifuroxazide overdose, careful observation of the patient is recommended, along with symptomatic and supportive treatment.

Adverse Reactions.

• Of the blood and lymphatic system: one case of granulocytopenia has been reported.
• Of the immune system: allergic reactions, including anaphylactic shock, angioneurotic edema, urticaria, and pruritus.
• Of the gastrointestinal tract: individual cases of hypersensitivity to nifuroxazide may manifest as abdominal pain, nausea, vomiting, and worsening of diarrhea. If such symptoms of mild intensity occur, no specific treatment or discontinuation of nifuroxazide is required, as symptoms subside rapidly. However, if exacerbation is pronounced, administration of nifuroxazide should be discontinued. In the future, the patient should avoid taking nifuroxazide and other nitrofuran derivatives.
• Of the skin and subcutaneous tissue: skin reactions such as skin rash occur rarely.

One case of pustulosis in an elderly patient and one case of nodular prurigo associated with contact allergy to nifuroxazide have been reported.

Shelf life.

4 years.

Storage conditions.

Store at a temperature not exceeding 25°C.

Keep out of reach and sight of children.

Packaging.

24 (24×1) tablets in a blister, 1 blister per cardboard pack.

Prescription category.

Prescription only.

Manufacturer.

Sp. z o.o. "Gedeon Richter Poland".

Address of manufacturer and location of its operations.

5 J. Poniatowski Street, Grodzisk Mazowiecki, 05–825, Poland.

Marketing Authorization Holder.

JSC "Gedeon Richter".

Address of the Marketing Authorization Holder and/or its representative.

H-1103 Budapest, 19–21 Demrédi Street, Hungary.