Nifuroxazide richter

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

Composition:

Active substance: nifuroxazide;

5 mL of suspension contains 220 mg of nifuroxazide (220 mg/5 mL);

Excipients: carbomer, sucrose, sodium hydroxide (E 524), citric acid monohydrate (E 330), simethicone, methylparaben (E 218), banana flavor, purified water.

Pharmaceutical form. Oral suspension.

Main physicochemical characteristics: light yellow suspension with banana odor; may slightly sediment during 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 for the treatment of intestinal infections.

ATC code A07AX03.

Pharmacological properties.

Pharmacodynamics.

Nitrofurazone is an antimicrobial agent, a derivative of nitrofuran. Its mechanism of action is not fully understood. The antimicrobial and antiparasitic properties of nifuroxazide may be 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 nifuroxazide compared to other nitrofuran derivatives, since this antidiarrheal agent has no systemic effect. It is effective against Gram-positive and Gram-negative bacteria: Streptococcus pyogenes, Staphylococcus aureus, E. coli, Salmonellae, Shigellae.

Pharmacokinetics.

After oral administration, the drug is partially absorbed (10–20%) from the gastrointestinal tract and extensively metabolized, with circulating components in the blood being mainly metabolites.

At therapeutic doses, nifuroxazide does not significantly suppress normal intestinal microflora, does not induce the emergence of resistant microbial forms, and does not promote 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 mutagenic potential.

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 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) 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 nitroxoline, 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.

Nitroxoline should not be used concomitantly with adsorbents, alcohol-containing products, drugs that may cause disulfiram-like reactions, and drugs that depress the central nervous system.

Special precautions for use.

• Nitrofurazone 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, a systemically acting antibiotic should be considered, since nitrofurazone is not absorbed from the gastrointestinal tract.
• If hypersensitivity reactions occur (dyspnea, facial swelling, swelling of lips, tongue, skin rash, pruritus), nitrofurazone should be discontinued immediately.
• Normal eating should be maintained, but during diarrhea, dietary recommendations should be followed: avoid raw vegetables and fruits, spicy foods, frozen products, and cold beverages. Consumption of dairy products should be decided on a case-by-case basis. Baked meat and rice are recommended.
• During treatment of diarrhea, continuous additional oral rehydration is necessary to compensate for fluid loss caused by diarrhea: it is recommended to 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 required depending on the patient's age and condition. When administering oral or intravenous rehydration, instructions for dilution and use of the designated solutions must be strictly followed.

• Patients should avoid alcoholic beverages during treatment with nitrofurazone due to the risk of a disulfiram-like reaction, which may manifest as worsening diarrhea, vomiting, abdominal pain, sensation of warmth in the face and upper body, hyperemia, tinnitus, dyspnea, and tachycardia.
• Nitrofurazone Richter, oral suspension, 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 sucrose intolerance or fructose malabsorption.
• The medicinal product contains methylparahydroxybenzoate (E 218), which may cause an allergic reaction (delayed type).

Use during pregnancy or breastfeeding.

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

Breastfeeding. It is unknown whether nitrofurazone or its metabolites are excreted in breast milk. Since nitrofurazone 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 gut microbiome of breastfed infants cannot be excluded. Due to the lack of clinical experience with nitrofurazone-containing medicinal products during breastfeeding, their use is not recommended.

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

Ability to affect reaction speed when driving or operating machinery.

No effect.

Method of Administration and Dosage

Method of Administration

Take orally, independent of food intake.

Dosage

The maximum daily dose of nifuroxazide is 800 mg. The duration of treatment should not exceed 7 days.

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

Adults: 5 mL of suspension four times daily.

Before use, the suspension should be shaken thoroughly to obtain a homogeneous mixture. The measured dose of suspension may be taken with water.

Children

Do not administer to children under 2 years of age.

Overdose

Specific information regarding symptoms of nifuroxazide overdose is not available.

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

Adverse reactions.

• Blood and lymphatic system disorders: one case of granulocytopenia has been reported.
• Immune system disorders: allergic reactions including angioneurotic edema (Quincke's edema), anaphylactic shock, urticaria, and skin 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 worsening of diarrhea. If such mild symptoms occur, no specific treatment or discontinuation of nitroxoline is required, as symptoms resolve quickly. However, if symptoms are severe, nitroxoline should be discontinued. 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 pustular eruption in an elderly patient and one case of nodular prurigo associated with contact allergy to nitroxoline have been reported.

Shelf life. 3 years.

Shelf life after first opening – 3 months.

Storage conditions.

Store at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging.

90 ml in a bottle; 1 bottle with a dosing spoon in a cardboard package.

Prescription status.

Prescription only.

Manufacturer.

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

Manufacturer's address and place of business.

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

Marketing Authorization Holder.

JSC "Gedeon Richter", Hungary.

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

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