Nifuroxazide

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

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).

Pharmaceutical form. Capsules.

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

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

Pharmacological Properties

Pharmacodynamics

Nitrofurazone is an antimicrobial agent derived from nitrofuran. Its mechanism of action has not been fully elucidated. 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 body tissues make nifuroxazide unique 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— it remains in the gastrointestinal tract for a prolonged period.

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 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 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 derivatives of 5-nitrofuran, or any other component of the medicinal product.
• Children under 6 years of age. For treatment of children under 6 years of age, nifuroxazide should be administered as 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, and drugs that suppress the central nervous system.

Alcohol consumption is strictly prohibited during treatment with nifuroxazide 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 body, hyperemia, tinnitus, difficulty breathing, and tachycardia.

Special precautions for use.

Treatment with rifaximin 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 made. When necessary, concomitant rehydration therapy should be administered depending on patient's age, clinical condition, and severity of diarrhea.

In case of oral or intravenous rehydration, instructions for dilution and administration of the prescribed 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 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 manifestations as deterioration of general condition, fever, or signs of intoxication, rifaximin should be prescribed together with antibacterial agents used for treatment of intestinal infections, since rifaximin is partially absorbed (10–20%) from the gastrointestinal tract and extensively metabolized, with its metabolites being predominantly present in the bloodstream. The drug should not be used as monotherapy in intestinal infections complicated by sepsis.

Rifaximin contains sucrose (0.031 g per capsule), which should be taken into account in diabetic patients when calculating total daily carbohydrate and sugar intake. The drug is not recommended for patients with hereditary fructose or sucrose intolerance.

The gelatin capsule contains the coloring agent 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, manifested by worsening of diarrhea, vomiting, abdominal pain, sensation of warmth in the face and upper body, hyperemia, tinnitus, breathing difficulty, and tachycardia.

Use during pregnancy or breastfeeding.

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

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

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

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

Dosage and Administration

Take orally, independently 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 nitroxoline — 800 mg.

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

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

Children. For treatment of children under 6 years of age, prescribe nitroxoline 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.

Side effects.

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 taking 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 these 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 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 associated with contact allergy to nitroxoline have been reported.

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

Reporting of adverse reactions following drug registration 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: 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 per blister, 1 blister per carton.

Prescription status. Prescription only.

Manufacturer: LLC "DKP "Pharmaceutical Factory".

Manufacturer's location and address of business activity: 4, Korolova St., Stanyshivka Village, Zhytomyr District, Zhytomyr Oblast, 12430, Ukraine.