Nifuroxazide alkaloid

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NIFUROXAZIDE ALKALOID®

Composition:

Active ingredient: nifuroxazide;

5 ml of oral suspension contains 200 mg of nifuroxazide;

Excipients: sorbitol non-crystallizing solution, glycerin, carbomer 940, polysorbate 80, disodium edetate, sodium benzoate, sodium citrate dihydrate, sodium saccharin, banana flavoring, taste correctant, simethicone emulsion, purified water.

Pharmaceutical form. Oral suspension.

Main physicochemical properties: a homogeneous yellow suspension with a characteristic banana odor.

Pharmacotherapeutic group. Antidiarrheal agents, drugs used in the treatment of infectious and inflammatory intestinal diseases. Antimicrobial agents for the treatment of intestinal infections. Nifuroxazide. ATC code A07AX03.

Pharmacological Properties.

Pharmacodynamics.

Nifuroxazide is a derivative of 5-nitrofuran, acting exclusively within the intestinal lumen. The mechanism of action of nifuroxazide is not fully understood. The antimicrobial and antiparasitic properties of nifuroxazide and other nitrofuran derivatives are attributed to the NO2 group, which is particularly effective in the treatment of intestinal infections. The drug is especially effective against gram-positive bacteria: Streptococcus pyogenes, Staphylococcus pyogenes, and gram-negative bacteria: Escherichia coli, Salmonella, and Shigella.

Pharmacokinetics.

After oral administration, the drug is partially absorbed (10–20%) from the gastrointestinal tract and is extensively metabolized. The majority of the active substance circulates in the blood in the form of metabolites. It is primarily excreted from the body in feces.

Preclinical Safety Data.

Nifuroxazide demonstrates mutagenic potential.

The carcinogenic effect 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 normalized to body surface area.

Clinical characteristics.

Indications.

Acute infectious diarrhea.

Contraindications.

Hypersensitivity to nifuroxazide, other 5-nitrofuran derivatives, or to any of the excipients of the medicinal product.

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 use of nifuroxazide with central nervous system (CNS) depressants and drugs that may cause dependence is not recommended.

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, or drugs that may cause disulfiram-like reactions.

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, sensation of warmth in the face and upper part of the body, hyperemia, tinnitus, dyspnea, and tachycardia.

Special precautions for use.

If diarrhoea symptoms persist for more than 48 hours during treatment with the drug, the treatment should be re-evaluated and the appropriateness of continuing the drug administration should be assessed.

Alcohol consumption is prohibited during nifuroxazide therapy due to the risk of developing a disulfiram-like reaction.

Treatment with nifuroxazide does not exclude the need for dietary management and rehydration. If necessary, concomitant rehydration therapy should be administered according to the patient's age, clinical condition, and severity of diarrhoea.

Rehydration should be the main component in the treatment of acute diarrhoea in children. Children should be provided with frequent fluid intake (every 15 minutes).

Prevention or treatment of dehydration should be performed using oral or intravenous rehydration solutions. If rehydration is indicated, it is recommended to use solutions specifically designed for this purpose, prepared according to the instructions for dilution and administration. The required volume of oral rehydration solutions depends on the degree of body weight loss. Intravenous rehydration is required in cases of severe diarrhoea, intense vomiting, or refusal to eat.

If such rehydration is not necessary, fluid losses should be compensated by drinking large amounts of fluids containing salt and sugar (approximately 2 litres per day on average).

Dietary recommendations during diarrhoea should be followed: avoid certain foods such as raw vegetables and fruits, leafy greens, spicy foods, and frozen foods and beverages. Rice and grilled meat are recommended. The decision on consuming dairy products should be made on a case-by-case basis.

If diarrhoea is accompanied by clinical signs indicating severe disease (worsening general condition, fever, signs of intoxication), nifuroxazide should be administered together with systemic-acting antibacterial agents used for the treatment of intestinal infections, as the drug is not absorbed in the intestine and does not enter systemic circulation.

The medicinal product should not be prescribed as monotherapy for the treatment of intestinal infections complicated by sepsis.

The product contains sorbitol. If the patient has known intolerance to certain sugars, consultation with a physician is recommended before taking this medicinal product. If hypersensitivity reactions occur (dyspnoea, facial swelling, swelling of lips or tongue, skin rash, pruritus), nifuroxazide administration should be discontinued immediately.

Use during pregnancy or breastfeeding.

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

Breastfeeding. It is unknown whether nifuroxazide or its metabolites are excreted in breast milk. Since nifuroxazide 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 nifuroxazide-containing medicinal products during breastfeeding, their use is not recommended.

Fertility. There is insufficient information from animal studies regarding the effect of nifuroxazide on fertility.

Ability to influence reaction speed when driving or operating machinery.

No effect.

Method of administration and dosage.

For oral use.

Measure the dose using a measuring cup.

Shake the suspension well before use!

Adults:

200 mg — 5 ml of suspension 4 times daily.

Children:

12 years of age and older: 5 ml 3–4 times daily (600–800 mg of nifuroxazide daily);

from 2 to 12 years of age: 5 ml 3 times daily (600–800 mg of nifuroxazide daily).

Duration of treatment — no more than 7 days.

Children.

Do not administer to children under 2 years of age.

Overdose.

Symptoms of overdose have not been described. In case of suspected nifuroxazide overdose, the patient should be closely monitored and supportive and symptomatic treatment should be administered.

Adverse reactions.

Immune system: allergic reactions are possible, including angioneurotic edema, urticaria, pruritus, skin rash, Quincke's edema, and anaphylactic shock. If an allergic reaction occurs, the drug must be discontinued.

Blood and lymphatic system: one case of granulocytopenia has been reported.

Gastrointestinal tract: in cases of individual hypersensitivity to rifamycin, abdominal pain, nausea, vomiting, and exacerbation of diarrhea may occur. If these symptoms are mild, no specific therapy or discontinuation of nifuroxazide is required, as symptoms resolve quickly. However, if exacerbation is pronounced, nifuroxazide should be discontinued. In such cases, further use of nitrofuran derivatives should be avoided.

Skin and subcutaneous tissues: rare (from > 1/10,000 to < 1/1,000) skin reactions in the form of skin rash. One case of pustular eruption in an elderly patient has been reported. One case of nodular dermatitis, developed due to contact allergic reaction to nifuroxazide, has been described.

Reporting of adverse reactions after drug registration is highly important. It enables continuous monitoring of the benefit-risk balance of this medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of drug efficacy via the Automated Pharmacovigilance Information System at the following link: http://aisf.dec.gov.ua/.

Shelf life.

Unopened vial: 3 years.

An opened vial should be stored for no more than 6 months under the recommended storage conditions.

Do not use after the expiry date stated on the packaging.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging.

90 mL of suspension in a dark glass bottle with a screw plastic cap with tamper-evident seal; one bottle with a measuring cup in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

ALKALOID AD Skopje.

ALKALOID AD Skopje.

Manufacturer's name and address of manufacturing site.

Boulevard Aleksandar Makedonski 12, Skopje, 1000, Republic of North Macedonia.

Boulevard Aleksandar Makedonski 12, Skopje, 1000, Republic of North Macedonia.