Furamag

INSTRUCTIONS for medical use of the medicinal product FURAMAG® (FURAMAG)

Composition:

Active substance: soluble nitrofurantoin;

1 capsule contains 50 mg of soluble nitrofurantoin;

Excipients: magnesium hydroxycarbonate, potassium carbonate, talc; capsule shell: titanium dioxide (E 171), quinoline yellow dye (E 104), gelatin.

Pharmaceutical form. Capsules.

Main physicochemical properties: hard gelatin capsules №3 of yellow color. Contents of the capsules: powder ranging from orange-brown to reddish-brown. The presence of particles of white, yellow, orange, and orange-brown colors is permissible.

Pharmacotherapeutic group.

Antibacterial agents for systemic use. Nitrofuran derivatives. ATC code J01XE.

Pharmacological Properties

Pharmacodynamics

Furamag® is a complex compound of soluble furazidin and magnesium hydroxycarbonate in a 1:1 ratio, which has fundamentally different pharmacological properties compared to plain furazidin (after administration, in the acidic environment of the stomach, soluble furazidin is not converted into poorly soluble furazidin; therefore, the bioavailability of Furamag® is 3 times higher than that of conventional furazidin).

The drug exhibits a broad antibacterial spectrum of activity against both gram-positive and gram-negative microorganisms. Furamag® is effective against gram-positive cocci (streptococci and staphylococci) and gram-negative rods (Escherichia coli, Salmonella, Shigella, Proteus, Klebsiella, Enterobacter). It is also active against protozoa (Giardia lamblia). Compared to other nitrofurans, Furamag® demonstrates higher activity against staphylococci, Escherichia coli, Aerobacter aerogenes, Bact. Citrovorum, Proteus mirabilis, and Proteus morganii. Furamag® is also more effective against Enterococcus faecalis and Staphylococcus spp. compared to other groups of antimicrobial agents.

Microbial resistance to soluble furazidin develops slowly and does not reach clinically significant levels.

Furamag® does not alter the pH of urine and circulates in high concentrations in the kidneys.

For the majority of microorganisms, the bacteriostatic concentration of furazidin ranges from 1:100,000 to 1:200,000. As a result of nitrofuran action, microorganisms produce fewer toxins, which may lead to clinical improvement even before pronounced inhibition of microbial growth. The bactericidal concentration is approximately twice as high. Nitrofurans inhibit cellular respiration and the Krebs cycle, as well as other biochemical processes in microorganisms, leading to disruption of the cell wall or cytoplasmic membrane. Unlike many other antimicrobial agents, nitrofurans do not suppress the body's immune system; on the contrary, they stimulate it (increasing complement titers and enhancing leukocyte phagocytic activity). Nitrofurans, at therapeutic doses, stimulate leukopoiesis.

Pharmacokinetics

After oral administration of Furamag® capsules, in the acidic environment of the stomach, soluble furazidin is not converted into insoluble furazidin, thereby significantly enhancing its bacteriostatic and bactericidal effects. After absorption from the gastrointestinal tract (mainly from the small intestine via passive diffusion) into the portal venous system of the liver, a bacteriostatic concentration of the drug is achieved.

Absorption of nitrofurans from the distal segment of the small intestine exceeds that from the proximal and middle segments by 2 and 4 times, respectively. Nitrofurans are poorly absorbed in the large intestine.

Clinically significant high concentrations of the active substance are found in lymph (which helps limit the spread of infection via lymphatic pathways). The drug concentration in bile is several times higher than in blood serum, while in cerebrospinal fluid (CSF), it is several times lower than in blood serum. The concentration of soluble furazidin in saliva amounts to 30% of its concentration in blood serum. The concentration of soluble furazidin in blood and tissues is relatively low due to its rapid elimination, whereas its concentration in urine is significantly higher than in blood. Maximum blood concentration persists from 3 to 8 hours; the drug appears in urine 3–4 hours after administration. Renal excretion of soluble furazidin occurs via glomerular filtration and tubular secretion (85%), with partial tubular reabsorption. Biotransformation (less than 10%) occurs in the liver and kidneys. In cases of impaired renal excretory function, the intensity of metabolism increases. At low concentrations of soluble furazidin in urine, filtration and secretion predominate; at high concentrations, secretion decreases and reabsorption increases.

Four hours after administration, the concentration of the drug in urine is significantly higher than after administration of an equivalent dose of furazidin. Absorption of Furamag® is notably improved when taken after food.

Clinical characteristics.

Indications.

Infections caused by microorganisms sensitive to Furagin soluble: urogenital infections (acute and chronic cystitis, urethritis, pyelonephritis, prostatitis), gynecological infections.

As anti-relapse therapy for urinary tract infections.

For prevention of infectious complications during urological surgeries, cystoscopy, catheterization, etc.

Contraindications.

• Hypersensitivity to furazidin, nitrofuran derivatives, or excipients of the medicinal product;
• severe renal impairment (creatinine clearance less than 30 mL/min);
• severe hepatic impairment;
• polyneuropathy (including diabetic);
• glucose-6-phosphate dehydrogenase deficiency (risk of hemolysis);
• porphyria (disorders caused by impaired metabolism of hemoglobin breakdown products);
• undergoing hemodialysis or peritoneal dialysis;
• pregnancy and breastfeeding.

Interaction with other medicinal products and other types of interactions.

Agents that alkalinize urine reduce the therapeutic effect of Furamag® (accelerate elimination of Furamag® with urine).

Agents that acidify urine (acids, including ascorbic acid, as well as calcium chloride) increase the concentration of Furamag® in urine, enhancing the therapeutic effect of the drug, but at the same time increasing the risk of increased toxicity.

Concomitant use with chloramphenicol, ristomycin, and sulfonamides enhances suppression of hematopoiesis.

In vitro, nitrofurans are antagonists of quinolones (nalidixic acid, oxolinic acid, norfloxacin). However, in vivo clinical significance of this interaction has not been studied, therefore, concomitant use with quinolones should be avoided.

Concomitant use of probenecid and sulfinpyrazone reduces elimination of furazidin, increasing the risk of adverse reactions and toxicity.

Simultaneous administration of Furamag® and antacids (containing magnesium trisilicate) reduces absorption of Furamag®.

In renal impairment, concomitant use of Furamag® with aminoglycosides is not recommended.

Antibacterial action of Furamag® is significantly enhanced when used concomitantly with antibiotics (penicillins and cephalosporins), and it combines well with tetracycline and erythromycin.

Alcohol consumption should be avoided during treatment, as alcohol may intensify adverse effects (palpitations, chest pain, headache, nausea, vomiting, seizures, hypotension, fever, anxiety).

Special precautions for use.

The medicinal product should be used with caution in the following cases:

• Renal function impairment (contraindicated in severe renal insufficiency);
• Anemia;
• Deficiency of B-group vitamins and folic acid;
• Lung diseases.

The use of Furamag® is not recommended in cases of urosepsis and parenchymal kidney infection.

Peripheral neuropathy (pain, sensory disturbances in the area innervated by the affected nerve) may develop during prolonged use of Furamag®.

Experimental studies and clinical observations in patients have shown that nitrofurans adversely affect testicular function, manifested as decreased sperm and ejaculate volume, reduced sperm motility, and pathological changes in sperm morphology.

In patients with diabetes mellitus, the drug may cause polyneuropathy.

If symptoms of neuropathy develop, the drug should be discontinued.

During prolonged use of prophylactic doses of Furamag®, clinically significant microbial resistance does not develop.

There have been no reports of pseudomembranous colitis during treatment with Furamag®, although such data exist for almost all antibacterial agents, including nitrofuran derivatives. However, the possibility of this adverse effect should be considered in patients who develop diarrhea during antibacterial therapy due to suppression of the natural microflora of the rectum. In contrast to antibiotics, Furamag® has virtually no effect on intestinal microflora. In mild cases of pseudomembranous colitis, discontinuation of the antibacterial agent is sufficient.

Laboratory testing of patients who have taken Furamag® has shown that the drug may cause false-positive results for glucose in urine when the copper reduction method is used. Furamag® does not affect the results of glucose testing in urine when the enzymatic method is used.

During prolonged treatment, monitoring of renal and liver function parameters is necessary, as well as monitoring of lung function, especially in patients over 65 years of age.

To prevent neuritis, concomitant use of antihistamines and B-group vitamins (nicotinamide, thiamine) is recommended.

Use during pregnancy or breastfeeding.

Pregnancy

The medicinal product is contraindicated during pregnancy. There are no adequate and well-controlled safety studies in pregnant women. Nitrofurans cross the placental barrier, but their concentration is many times lower than that in maternal blood.

Breastfeeding

Nitrofurans are excreted in breast milk. The medicinal product is contraindicated during breastfeeding due to the risk of hemolytic anemia in infants.

Ability to affect reaction speed when driving or operating machinery.

The drug generally does not affect reaction speed when driving or operating machinery. However, patients who experience dizziness, drowsiness, or other central nervous system side effects during treatment should exercise caution when driving or operating machinery.

Method of Administration and Dosage

The medicinal product should be taken orally after meals. Swallow the capsule whole with a large amount of water.

Adults: 50–100 mg three times daily.

The treatment course lasts from 5 to 7–10 days.

If necessary, repeat the course after 10–15 days.

Children with body weight of 30 kg or more: 50 mg three times daily.

The maximum daily dose for adults is 300 mg.

For prophylaxis of recurrent urinary tract infections: in adults and children, administer 1/3–1/4 of the daily dose (50–100 mg) at bedtime for 3–6 months.

For prophylaxis of infection during urological surgeries, cystoscopy, catheterization, etc., the drug should be administered as follows:
Adults: 50 mg three times daily;
Children: 25 mg three times daily (use the product Furamag®, 25 mg capsules). The duration of administration is determined by the physician.

If a dose is missed, the next dose should be taken as soon as the patient remembers.

Do not take a double dose to make up for a missed dose.

Children

The drug can be used in children with body weight exceeding 30 kg.

Overdose

Toxic effects usually occur in patients with impaired renal function.

Symptoms: In case of overdose, neurotoxic symptoms may occur, including ataxia and tremor.

Treatment: In case of poisoning, discontinue the drug and drink large amounts of fluid. In the event of acute symptoms, antihistamine agents should be used. For prevention of neuritis, administration of B-group vitamins (thiamine bromide) may be considered.

Adverse Reactions

Furamag®, like other medicinal products, may cause adverse reactions, which do not occur in all patients.

Frequency of adverse reactions according to the MedDRA classification system: very common (≥ 1/10); common (≥ 1/100 to <1/10); uncommon (≥ 1/1000 to <1/100); rare (≥ 1/10000 to <1/1000); very rare (<1/10000), including isolated cases; frequency not known (cannot be estimated from available data).

Blood and lymphatic system disorders: very rare – disturbances in hematopoiesis (agranulocytosis, thrombocytopenia, aplastic anemia).

Immune system disorders: rare – hypersensitivity reactions, including pruritus, rash; very rare – urticaria, angioedema.

Nervous system disorders: common – headache; uncommon – dizziness, somnolence; rare – peripheral neuropathy, neuritis, polyneuritis.

Eye disorders: rare – visual disturbances.

Ear and labyrinth disorders: very rare – tinnitus.

Respiratory, thoracic and mediastinal disorders: very rare – acute and chronic pulmonary hypersensitivity reactions. Skin rash, pruritus, urticaria, angioedema, and myalgia have been reported concurrently with acute pulmonary reactions. Acute pulmonary reaction is a hypersensitivity reaction that may develop within several hours, rarely minutes, and is characterized by chills, eosinophilia, cough (with or without sputum), chest pain, and severe dyspnea. Acute pulmonary reaction usually resolves after discontinuation of the drug.

Chronic pulmonary reactions may occur over a prolonged period after discontinuation of nitrofuran therapy and are characterized by progressively worsening dyspnea, tachypnea, chills, eosinophilia, progressive cough, interstitial pneumonia, and/or pulmonary fibrosis.

Nasal disorders, hoarseness of voice.

Gastrointestinal disorders: uncommon – nausea, flatulence; rare – vomiting, loss of appetite, diarrhea, dyspepsia, constipation, abdominal pain; very rare – pancreatitis.

The frequency of adverse effects decreases when the drug is taken with food.

Skin and subcutaneous tissue disorders: rare – papular rash, pruritus; very rare – angioedema, urticaria, exfoliative dermatitis, erythema multiforme, reversible alopecia.

Musculoskeletal and connective tissue disorders: very rare – arthralgia, rib pain, cramps.

Vascular disorders: very rare – mild intracranial hypertension.

Hepatobiliary disorders: very rare – cholestatic jaundice, hepatitis, right upper quadrant abdominal pain, liver function abnormalities.

General disorders and administration site conditions: very rare – fever, weakness, sensation of a foreign body in the throat.

Investigations: very rare – albuminuria, erythrocyturia.

To reduce adverse effects, it is recommended to take vitamin B complex (in case of polyneuropathy), antihistamines (for allergic reactions), and to maintain high fluid intake.

In case of severe adverse effects, the dose should be reduced or the drug discontinued.

Furamag® may darken urine, turning it yellow-brown or brown.

If adverse reactions not listed in this instruction occur during treatment with Furamag®, they should be reported to a physician.

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 capsules in a blister. 3 blisters per 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.