Furadantin

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

Composition:

Active substance: nitrofurantoin;

1 tablet contains 100 mg of nitrofurantoin;

Excipients: potato starch, colloidal anhydrous silicon dioxide, calcium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: round, flat tablets of yellow or greenish-yellow color with a score line.

Pharmacotherapeutic group. Antibacterial agents. Nitrofuran derivatives.

ATC code J01X E01.

Pharmacological Properties

Pharmacodynamics

Nitrofurantoin is an antimicrobial agent of the nitrofuran group, a urinary antiseptic.

Antimicrobial properties are due to nitrofurantoin's ability to affect various microbial enzyme systems. Nitrofurantoin, by achieving high concentrations in urine, is particularly effective in treating urinary tract infections.

Nitrofurantoin has bacteriostatic activity (the drug is bactericidal at high concentrations).

The spectrum of antibacterial activity includes most microorganisms causing urinary tract infections. Bacterial resistance to nitrofurantoin is rare.

Microorganisms sensitive to nitrofurantoin: Enterococci, Escherichia coli, Citrobacter spp., Streptococci group B, Staphylococcus aureus, Staphylococcus epidermidis, as well as those less commonly causing urinary tract infections: Salmonella spp., Bacteroides spp., Streptococcus pneumoniae; moderately sensitive: Klebsiella pneumoniae, Enterobacter spp., Proteus spp., Providencia spp.; resistant to the drug: Pseudomonas aeruginosa, Serratia spp., Proteus mirabilis, Pseudomonas cepacia, Acinetobacter spp.

Pharmacokinetics

Nitrofurantoin is well absorbed from the gastrointestinal tract. Bioavailability is approximately 50% (food increases bioavailability). Plasma protein binding ranges from 60–95%. It is partially metabolized in the liver. 30–50% of the dose is rapidly excreted unchanged in urine, which explains the bacteriostatic and bactericidal effects of the drug in urinary tract infections. Effective therapeutic concentrations of nitrofurantoin in blood and tissues are not achieved. Elimination half-life is 0.5–1 hour. High urinary concentrations of the drug persist for up to 12 hours. Maximum serum concentration after administration of 100 mg is reached within 30 minutes. In anuria or renal insufficiency with creatinine clearance below 45 ml/min, antibacterial concentrations of nitrofurantoin in urine are not achieved, while the frequency of adverse effects increases. Nitrofurantoin crosses the placental and blood-brain barriers and is excreted into breast milk. Elimination half-life is 0.3–1 hour.

Clinical characteristics.

Indications.

Bacterial infections of the urinary tract (pyelitis, pyelonephritis, cystitis, urethritis), including treatment of recurrent infections, as well as prevention of infection during urological surgeries, catheterization, and cystoscopy.

Contraindications.

• Hypersensitivity to nitrofurantoin or to excipients of the medicinal product;
• hypersensitivity to other nitrofurans;
• pulmonary fibrosis;
• pyelonephritis in the presence of concomitant renal parenchymal inflammation or perinephric abscess;
• anuria;
• oliguria;
• porphyria;
• renal failure (creatinine clearance less than 45 ml/min);
• liver cirrhosis;
• chronic hepatitis;
• chronic heart failure;
• hemodialysis;
• glucose-6-phosphate dehydrogenase deficiency (risk of hemolytic anemia);
• neuritis and polyneuropathy;
• pregnancy and breastfeeding;
• children under 12 years of age.

Interaction with other medicinal products and other types of interactions.

The use of nitrofurantoin should not be combined with drugs that impair kidney function.

Antacids and adsorbents reduce the absorption of the drug and therefore should not be used concomitantly with nitrofurantoin.

Uricosuric agents (probenecid and sulfinpyrazone) reduce the excretion of nitrofurantoin (increasing nitrofurantoin blood concentration, decreasing efficacy, and increasing the risk of toxicity); therefore, they should not be used concomitantly with the drug.

Carbonic anhydrase inhibitors reduce the antibacterial activity of the drug.

Nitrofurantoin reduces the reabsorption of estrogens.

When used concomitantly with contraceptives, a reduction in contraceptive effect is possible.

Nitrofurantoin inactivates the oral typhoid vaccine.

In vitro, nitrofurantoin reduces the antibacterial activity of quinolone group drugs (nalidixic acid, fluoroquinolones). Simultaneous use of these drugs should be avoided.

Concomitant use with ristomycin, chloramphenicol, and sulfonamides should be avoided due to possible suppression of hematopoietic processes.

In renal failure, concomitant use of nitrofurantoin with aminoglycosides is not recommended.

When used concomitantly with antibiotics (penicillins and cephalosporins), antibacterial activity is significantly enhanced. The drug combines well with tetracycline and erythromycin.

The antibacterial activity of nitrofurantoin is reduced in alkaline urine; therefore, it should not be combined with drugs that increase urine pH.

Alcoholic beverages should not be consumed during treatment, as they may exacerbate adverse reactions (e.g., headache, nausea, vomiting).

Special precautions for use

According to individual published data, nitrofurantoin has been associated with acute attacks of porphyria; therefore, the use of this medicinal product is contraindicated in patients with porphyria.

Nitrofurantoin should be administered with caution in patients with impaired renal function. When excretion of nitrofurantoin in urine is reduced, its antibacterial concentration in urine may not be achieved, thus increasing plasma concentrations and the risk of toxicity (administration is contraindicated if creatinine clearance is less than 45 mL/min).

No significant differences in response to nitrofurantoin treatment have been observed between elderly individuals (over 65 years of age) and younger patients; however, caution is recommended due to the potential for impaired renal function in elderly patients.

Cases of pseudomembranous colitis have been reported during nitrofurantoin therapy. The possibility of this adverse reaction should be considered in patients who develop diarrhea resulting from suppression of the normal colonic microflora during antibacterial therapy. In mild cases of pseudomembranous colitis, discontinuation of the antibacterial agent may be sufficient; in moderate to severe cases, appropriate treatment is required.

The drug should be used with caution in patients with anemia, diabetes mellitus, electrolyte imbalance, debilitated patients, patients with vitamin B complex or folic acid deficiency, pulmonary diseases, hepatic insufficiency, and in those predisposed to peripheral neuropathies.

If signs of peripheral neuropathy occur, the drug should be discontinued.

During prolonged therapy, pulmonary function should be monitored, especially in elderly patients, in whom pulmonary reactions may worsen. The drug should be discontinued at the first signs of lung injury.

During long-term therapy, blood counts and liver function tests should be monitored regularly. Nitrofurantoin may cause false-positive glucose reactions in urine when using copper reduction methods.

If an enzymatic method is used to determine glucose in urine, nitrofurantoin does not interfere with test results.

The medicinal product may color urine dark yellow or brown.

Hepatotoxicity

Hepatic reactions, including hepatitis, autoimmune hepatitis, cholestatic jaundice, and chronic active hepatitis, may have an insidious onset; therefore, periodic biochemical tests should be performed in patients to monitor liver function. If hepatitis occurs, the drug should be immediately discontinued and appropriate measures taken.

Nitrofurantoin should not be used for the treatment of cortical renal diseases, pyelonephritis, or prostatitis.

The use of this medicinal product may lead to diarrhea caused by Clostridium difficile. Treatment with this drug alters the normal colonic flora and may promote overgrowth of Clostridium difficile. If Clostridium difficile-associated diarrhea is suspected or confirmed, nitrofurantoin therapy should be discontinued and appropriate treatment initiated.

In some cases, during nitrofurantoin therapy (particularly with prolonged use), bacterial resistance may develop. In such cases, nitrofurantoin should be discontinued and an alternative antibacterial agent selected for further treatment.

Use during pregnancy or breastfeeding

The medicinal product is contraindicated during pregnancy or breastfeeding.

Ability to influence reaction rate while driving or operating machinery

Nitrofurantoin does not affect reaction speed while driving or operating machinery; however, individuals who experience dizziness, headache, or other central nervous system adverse effects during treatment should exercise caution.

Method of Administration and Dosage

Nitrofurantoin is taken orally, immediately after meals, with a large amount of water.

Acute infections: adults − 100 mg twice daily for 7 days.

Severe chronic recurrent infections: adults − 100 mg 3−4 times daily for 7 days.

If nausea occurs, the dose should be reduced or the medication discontinued.

For prophylaxis of urinary tract infections: the recommended dose is 100 mg at bedtime.

For adults, the maximum single dose is 300 mg; the maximum daily dose is 600 mg.

Children aged 12 years and older: adult doses may be used in cases of acute uncomplicated urinary tract infections.

Patients with impaired liver and/or kidney function, elderly patients

There are no data on dosing in patients with impaired liver and/or kidney function or in elderly patients. However, the medication should be used with caution. Nitrofurantoin is contraindicated in patients with renal insufficiency.

Surgical prophylaxis: 100 mg twice daily on the day of the procedure and for 3 days after the procedure.

If a dose has been missed, continue treatment according to the previously prescribed regimen.

Children

The medication may be used in children aged 12 years and older.

Overdose

Symptoms: nausea, vomiting, headache, dizziness.

Neurological disturbances indicate elevated plasma concentrations of nitrofurantoin. Development of polyneuritis results from accumulation of nitrofurantoin and its metabolites; therefore, the risk of polyneuritis is increased in renal insufficiency.

Treatment: discontinue the medication; increased fluid intake to promote urinary excretion of nitrofurantoin; use of enterosorbents, antihistamines, and B-complex vitamins. Treatment is symptomatic. There is no specific antidote.

In cases of acute overdose, gastric lavage should be performed.

Nitrofurantoin is removed by hemodialysis.

Side effects

The medicinal product may cause side effects, which do not occur in all individuals.

Side effects are listed according to the MedDRA organ system classification and by frequency of occurrence: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare (< 1/10,000); not known (cannot be estimated from available data).

Infections and infestations

Pseudomembranous colitis has been reported during nitrofurantoin therapy. In mild cases of pseudomembranous colitis, discontinuation of the medicinal product is sufficient. In moderate to severe cases, appropriate treatment must be initiated.

Blood and lymphatic system disorders: Rare – megaloblastic anemia, leukopenia, granulocytopenia or agranulocytosis, thrombocytopenia, hemolytic anemia may develop in patients with glucose-6-phosphate dehydrogenase deficiency.

*Immune system disorders: Not known – cutaneous vasculitis.

In isolated cases, autoimmune reactions have been observed, primarily associated with chronic changes in the lungs or liver. The main symptoms of this lupus-like syndrome include fever, transient rash, arthralgia, and eosinophilia. Increased serum levels of antinuclear antibodies, antibodies to smooth muscle, or to renal glomeruli, as well as a positive Coombs test, may also occur.

**Nervous system disorders: Common – headache; rare – drowsiness, dizziness, depression, euphoria, nystagmus, confusion, psychotic reactions, restlessness (excitement), asthenia, increased intracranial pressure, benign intracranial hypertension, peripheral neuropathy, the first symptoms of which are paresthesia, burning sensation in the heels, and muscle weakness. If the first symptoms of peripheral neuropathy occur, the medicinal product should be discontinued.

Respiratory system, thoracic organs and mediastinum disorders

Acute and chronic pulmonary hypersensitivity reactions are characterized by sudden fever, eosinophilia, cough, chest pain, and dyspnea. Within several hours or days after the start of therapy, pulmonary infiltrates or opacities and pleural effusion may appear, which resolve after discontinuation of the medicinal product. During prolonged therapy, acute and subacute pulmonary symptoms, including pulmonary fibrosis, may develop insidiously in patients. Pulmonary fibrosis may be irreversible, especially if therapy continues after the onset of symptoms. If the first symptoms of pulmonary hypersensitivity reaction occur, the medicinal product should be discontinued and appropriate treatment initiated.

*Gastrointestinal disorders: Common – nausea, vomiting, loss of appetite, anorexia (frequency and severity depend on the dose); rare – diarrhea, pancreatitis.

Side effects occur less frequently if the medicinal product is taken with food and a large amount of liquid.

*Hepatobiliary disorders: Rare – hepatitis, cholestatic jaundice (independent of dose and resolves after discontinuation of the medicinal product), cholestatic liver function disorders; not known – autoimmune hepatitis.

*Skin and subcutaneous tissue disorders: Common – hypersensitivity reactions (skin rashes, maculopapular eruptions, urticaria, pruritus); rare – reversible hair loss; in isolated cases, angioedema, salivary gland inflammation, exfoliative dermatitis, erythema multiforme (Stevens-Johnson syndrome), lupus-like syndrome may occur.

*Vascular disorders: Rare – hyperemia, circulatory collapse.

*Renal and urinary disorders: Not known – interstitial nephritis.

*Musculoskeletal and connective tissue disorders: Rare – gout, myalgia, joint pain.

*Eye disorders: Very rare – visual disturbances.

*Reproductive system and breast disorders: Very rare – transient disturbances in spermatogenesis.

*Other: Not known – possible resistance development in microorganisms such as Pseudomonas.

Shelf life.

5 years.

Storage conditions.

Store in a dry, protected from light place at a temperature not exceeding 25°C.

Keep out of reach of children.

Packaging.

10 tablets in a blister pack. 2 blisters in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

JSC "Olpha" / Olpha AS.

Manufacturer's address and place of business.

Rupnicu iela 5, Olaine, Olaines novads, LV-2114, Latvia.