Nifuroxazide

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

Composition:

Active substance: nifuroxazide;

One tablet contains nifuroxazide calculated as 100% substance – 200 mg;

Excipients: microcrystalline cellulose; povidone; lactose monohydrate; calcium stearate; coating mixture "Opadry II Yellow" 33G22623 containing: hypromellose; lactose monohydrate; titanium dioxide (E 171); polyethylene glycol 3000 (macrogol); triacetin; quinoline yellow (E 104); yellow FCF (E 110); iron oxide yellow (E 172); indigocarmine (E 132).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: yellow, oval-shaped, film-coated tablets with a biconvex surface, with a break line on one side and the inscription "KMP" on the other side. The core is visible upon breaking, bright yellow in color.

Pharmacotherapeutic group. Antimicrobial agents used in intestinal infections. Nifuroxazide. ATC code A07AX03.

Pharmacological Properties

Pharmacodynamics

Nitrofurazone is an antimicrobial agent derived from nitrofuran. Its mechanism of action is not fully understood. It is believed that nitrofurazone inhibits dehydrogenase activity and disrupts protein synthesis in pathogenic bacteria. The antimicrobial and antiparasitic properties of nitrofurazone may be attributed to the presence of an amino group. The local activity and lack of penetration into organs and body tissues determine the uniqueness of nitrofurazone compared to other nitrofuran derivatives, as this antidiarrheal agent lacks systemic effects.

Nitrofurazone 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: Yersinia spр., Escherichia spр., Citobacter spр., Enterobacter spр., Klebsiella spр., Salmonella spр.

At medium therapeutic doses, it exhibits bacteriostatic activity, while at higher doses, it acts bactericidally. At therapeutic doses, it practically does not disturb the balance of normal bacterial flora of the large intestine, does not induce the development of resistant strains of pathogenic microorganisms, and does not lead to cross-resistance of bacteria to other antimicrobial agents. This allows nitrofurazone to be used 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 within the intestinal lumen. The therapeutic effect is achieved within the first hours of treatment.

Pharmacokinetics

After oral administration, nitrofurazone is partially absorbed (10–20%) from the gastrointestinal tract and extensively metabolized, with metabolites predominantly circulating in the blood. Biotransformation of nitrofurazone occurs in the intestine, and more than 20% is excreted unchanged. Nitrofurazone and its metabolites are excreted in feces. The rate of elimination depends on the amount of drug administered and on gastrointestinal motility. Overall, elimination of nitrofurazone is slow, allowing it to remain in the gastrointestinal tract for a prolonged period.

In preclinical safety studies, nitrofurazone demonstrated mutagenic potential. The carcinogenic potential of nitrofurazone was evaluated in mice (50/sex/group) and rats (52/sex/group) that received nitrofurazone in their diet for 2 years at doses of 0, 200, 600, or 1800 mg/kg/day. Despite its mutagenic properties, carcinogenicity of nitrofurazone was not demonstrated in either mice or rats.

Based on 2-year studies in mice and rats (5400 mg/m² and 10800 mg/m², respectively), using surface area comparisons with 11- and 22-fold safety factors, the maximum human dose is determined to be 1800 mg (493 mg/m² assuming a patient weight of 60 kg).

Clinical Characteristics.

Indications.

Acute infectious diarrhea.

Contraindications.

Hypersensitivity to nifuroxazide and to other nitrofuran derivatives or to any of the excipients.

Interaction with other medicinal products and other forms of interaction.

Concomitant administration (at the same time) of other oral medicinal products should be avoided due to the strong adsorptive properties of nifuroxazide.

Nifuroxazide is not recommended for simultaneous use with adsorbents, alcohol-containing preparations, drugs that may cause disulfiram-like reactions, and drugs that depress the central nervous system (CNS).

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

Special precautions for use

During treatment with nitroxoline, alcohol consumption is strictly prohibited (see section "Interaction with other medicinal products and other forms of interaction").

Treatment with nitroxoline does not exclude dietary management and rehydration. If diarrhea does not stop after 3 days from the beginning of treatment, further diagnostic evaluation is required to determine the cause of symptoms. Antibiotic therapy may become necessary. If needed, concomitant rehydration therapy should be administered according to the patient's age, clinical condition, and severity of diarrhea.

If oral or intravenous rehydration is indicated, 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 an 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-based foods are recommended. The decision on consumption of dairy products should be made individually.

If diarrhea is accompanied by clinical signs indicating severe disease (worsening general condition, fever, signs of intoxication), nitroxoline should be administered together with antibacterial agents used for treatment of intestinal infections, as the drug is not absorbed from the gastrointestinal tract and does not enter systemic circulation. The drug should not be used as monotherapy for intestinal infections complicated by sepsis.

If hypersensitivity reactions occur (dyspnea, facial swelling, swelling of lips, tongue, skin rash, itching), administration of nitroxoline must be stopped immediately.

The medicinal product contains lactose. Patients with rare hereditary disorders of carbohydrate metabolism, such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption syndrome, should not take this medicinal product.

The product contains the colorant tartrazine (E 110), which may cause allergic reactions.

Use during pregnancy or breastfeeding

Pregnancy

There is limited data on the use of nitroxoline in pregnant women. Data from animal studies on reproductive toxicity are insufficient. Nitroxoline has a potential mutagenic effect. Therefore, nitroxoline is not recommended during pregnancy and should not be administered to women of reproductive age 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 (gastrointestinal absorption of approximately 10–20% of the dose), its concentration in milk is likely to be low. However, effects on the gastrointestinal 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

Based on animal studies, there is insufficient information on the effect of nitroxoline on fertility.

Ability to influence reaction rate while driving or operating machinery

Nitroxoline does not affect reaction speed while driving or operating machinery.

Dosage and Administration

Nifuroxazide is administered orally, independent of food intake.

Adults and children aged 7 years and older: 1 tablet (200 mg) 3–4 times daily (daily dose: 600–800 mg).

Duration of treatment: no longer than 7 days.

Children.

Nifuroxazide 200 mg tablets are indicated for children aged 7 years and older. For children under 7 years of age, nifuroxazide should be administered in another pharmaceutical form.

Overdose.

One case of overdose has been reported, accompanied by transient symptoms of diarrhea and drowsiness. 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, usually of skin type (rash, pruritus, urticaria, pustular eruption). In isolated cases, dyspnea and severe hypersensitivity reactions, including angioneurotic edema and anaphylactic shock, may occur.

Gastrointestinal disorders: Individual cases of hypersensitivity to nitrofurazone manifest as abdominal pain, nausea, vomiting, and exacerbation of diarrhea. If the intensity of these symptoms is mild, no specific treatment or discontinuation of nitrofurazone is required, as symptoms subside rapidly. If the exacerbation is pronounced, nitrofurazone administration should be discontinued. The patient should subsequently avoid taking nitrofurazone and other nitrofuran derivatives.

Skin and subcutaneous tissue disorders: Skin reactions such as skin rash occur rarely.

One case of pustular eruption in an elderly patient and one case of nodular pruritus associated with contact allergy to nitrofurazone have been reported.

Reporting of adverse reactions following marketing authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and pharmacists, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Pharmacovigilance Information System at the following link: https://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 of children.

Packaging. 10 tablets per blister, 1 or 2 blisters per carton.

Prescription status. Prescription only.

Manufacturer.

JSC "Kyivmedpreparat".

Manufacturer's location and address of business operations.

139 Saksaganskogo Street, Kyiv, 01032, Ukraine.