Mepafuran for the treatment of prophylaxis against acute or recurrent and uncomplicated lower urinary tract infections

Mepafuran 50 mg and 100 mg
Hard gelatin capsules

COMPOSITION :

Each hard gelatin capsule contains:
Active ingredients :
Mepafuran                      50 mg
Nitrofurantoin               50 mg
Mepafuran                      100 mg
Nitrofurantoin               100 mg
Inactive ingredients :
Magnesium stearate. Avicel and Maize starch.

THERAPEUTIC INDICATIONS :

For the treatment of and prophylaxis against acute or recurrent, uncomplicated lower urinary tract infections or pyelitis either spontaneous or following surgical procedures. Nitrofurantoin is specifically indicated for the treatment of infections due to susceptible strains of Escherichia coli, Enterococci, Staphylococci, Citrobacter, Klebsiella and Enterobacter.

POSOLOGY AND METHOD OF ADMtNtSTRATION
Dosage:

Adults
Acute Uncomplicated Urinary Tract Infections: 50 mg four times daily for seven days. Severe Chronic Recurrence: 100 mg four times day for seven cays.
Long Term Suppression: 50 mg – 100 mg once a day.
Pophylaxis: 50 mg four times daily for the duration of procedure and 3 days thereafter.
Children and Infants over three months of age
Acute Urinary Tract Infections: 3 mg/kg/day in four divided doses for seven days. Suppressive: 1 mg/kg, once a day.
For children under 25 Kg bodyweight consideration should be given to the use of nitrofurantoin suspension.
Elderty
Provided there is no significant renal impairment, in which Nitrofurantoin is contraindicated, the dosage should be that for any normal adult. See precaution and risks to elderly patients associated
with lonq- term therapy.

CONTRAINDICATIONS :

⦁ Patients with known hypersensitivity to nitrofurantoin or other nitrofurans.
⦁ Patients suffering from renal dysfunction with a creatinine clearance of less than 60 ml/minute or elevated serum creatinine.
⦁ G6PD deficiency.
⦁ Acute porphyria.
⦁ In infants less than 3 months and at the end of pregnancy (during labour and delivery) because of the theoretical possibility of hemolytic anemia in the fetus or newborn (under 3 months) due to immature erythrocyte enzyme system.
⦁ Products containing nitrofurantoin are contraindicated in patients with previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin.

SPECIAL WARNINGS AND PRECAUTIONS :
Nitrofurantoin is not effective for the treatment of parenchymal infections of unilaterally non-functioning kidney. A surgical cause for infection should be excluded in recurrent or severe cases.
Since pre-existing conditions may mask adverse reactions, Nitrofurantoin should be used with caution in patients with pulmonary disease, hepatic dysfunction, neurological disorders, and allergic diathesis.
Peripheral neuropathy and susceptibility to peripheral neuropathy, which may become severe or irreversible, has occurred and may be life threatening. Therefore, treatment should be stopped at the first signs of neural involvement (paraesthesiae).
Nitrofurantoin should be used in caution with patients with anaemia, diabetes mellitus, electrolyte imbalance, debilitating conditions and vitamin B (particularly folate) deficiency.
Acute, subacute and chronic pulmonary reactions have been observed in patients treated with nitrofurantoin. If these reactions occur, nitrofurantoin should be discontinued immediately.
Chronic pulmonary reactions (including pulmonary fibrosis and diffuse interstitial pneumonitis) can develop insidiously, and may occur commonly in elderty patients.
Close monitoring of the pulmonary condition of patients receiving long-term therapy is warranted (especially in the elderly).
Patients should be monitored closely for signs of hepatitis (particularly in long-term use). Urine may be coloured yellow or brown after taking Nitrofurantoin. Patients on Nitrofurantoin are susceptible to false positive urinary glucose (If tested for reducing substances) Nitrofurantoin should be discontinued at any sign of haemolysis in those with suspected glucose-6-phosphate dehydogenase deficiency.
Gastrointestinal reactions may be minimised by taking the drug with food or milk, or by adjustment of dosage.
For long-term treatment, monitor patients closely for evidence of hepatitis or pulmonary symptoms or other evidence of toxicity.
Discontinue treatment with Nitrofurantoin if otherwise unexplained pulmonary, hepatic, haematological or neurological syndromes occur.

DRUG INTERACTION :
1. Increased absorption with food or agents delaying gastric emptying.
2. Decreased absorption with magnesium tnsilicate.
3. Decreased renal excretion of Nitrofurantoin by probenecid and sulphinpyrazone.
4. Decreased anti-bacterial activity by carbonic anhydrase inhibitors and urine alkalisation.
5. Anti-bacterial antagonism by quinolone anti-infectives.
6. Interference with some tests for glucose in urine
7. As Nitrofurantoin belongs to the group of Antibacterials, it will have the following resulting interactions:
• Oestrogens: In common with other antibiotics, nitrofurantoin may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of oestrogen-containing contraceptive products.
Therefore, patients should be warned appropriately and extra contraceptive precautions taken .
• Typhoid Vaccine (oral): Antibacterials inactivate oral typhoid vaccine.

PREGNANCY AND LACTATION :

Nitrofurantoin has been in extensive clinical use since 1952, and its suitability in human pregnancy has been well documented. However, as with all other drugs, the maternal side effects may
adversely affect course of pregnancy. The drug should be used at the lowest dose as appropriate for a specific indication, only after careful assessment.
Nitrofurantoirn is however contraindicated in infants under three months of age and in pregnant women during labour and delivery, because of Ihe possible risk of haemolysis of the infants’immature red cells. Breast feeding an infant known or suspected to have an erythrocyte enzyme deficiency (including G6PD deficiency), must be temporarily avoided, since Nitrofurantoin is detected in trace amounts in breast milk.
Nitrofurantoin is contraindicated during the last trimester of pregnancy ( risk of hemolytic anemia in the newborn). In the first 6 months of pregnancy nitrofurantoin must not be used unless it is clearly necessary.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES :

Nitrofurantoin may cause dizziness and drowsiness and the patient should not drive or operate machinery if affected this way.

UNDESIRABLE EFFECTS :

Respiratory If any of the following respiratory reactions occur the drug should be discontinued. Acute, subacute or chronic pulmonary reactions (reports have cited pulmonary reactions as contributing cause of death). Pulmonary toxicity should be considered when treatment is extended for >6 months especially if the patient is elderly.
Acute pulmonary reactions usually occur within the first week of treatment and are reversible with cessation of therapy.                         Acute pulmonary reactions are commonly manifested by fever, chills, cough, chest pain, dyspnoea, pulmonary infiltration with consolidation or pleural effusion on chest x-ray, and eosinophilia. In subacute pulmonary reactions, fever and eosinophilia occur less often than in the acute form.
Chronic pulmonary reactions occur rarely in patients who have received continuous therapy for six months or longer and are more common in elderly patients. Changes in ECG have occurred,
associated with pulmonary reactions.
Minor symptoms such as fever, chills, cough and dyspnoea may be significant. Collapse and cyanosis have been reported rarely. The severity of chronic pulmonary reactions and their degree of resolution appear to be related to the duration of therapy after the first clinical signs appear. It is important to recognise symptoms as early as possible. Pulmonary function may be impaired permanently, even after cessation of therapy.
Hepatic  Hepatic reactions including cholestatic jaundice, chronic active hepatitis, hepatic failure and hepatic biliary reactions. Fatalities have been reported. Cholestatic jaundice is generally associated with short-term therapy (usually up to two weeks). Chronic active hepatitis, occasionally leading to hepatic necrosis is generally associated with long-term therapy (usually after six months). The onset may be insidious. Treatment should be stopped at the first sign of hepatotoxicity.
Neurological  Peripheral neuropathy (including optical neuritis) with symptoms of sensory as well as motor involvement, which may become severe or irreversible, has been reported infrequently, Less
frequent reactions of unknown causal relationship are depression. euphoria. confusion. psychotic reactions, nystagmus, vertigo, dizziness, asthenia, headache and drowsiness. Treatment should be stopped at the first sign of neurological involvement.
Gastrointestinal Nausea and anorexia have been reported. Emesis, abdominal pain and diarrhoea are less common gastrointestinal reactions.
Haematological Agranulocytosis, leucopenia, granulocytopenia. haemolytic anaemia, thrombocytopenia, megaloblastic anaemia, glucose-6-phosphate dehydrogenase deficiency anaemia, and eosinophilia have been reported. Aplastic anaemia has been reported rarely. Cessation of therapy has generally returned the blood picture to normal.
Hypersensitivity Allergic skin reactions manifesting as angioneurotic oedema, maculopapular, erythematous or
eczematous eruptions, urticaria, rash, and pruritis have occurred.
Lupus-like syndrome associated with pulmonary reactions to Nitrofurantoin has been reported. Exfoliative dermatitis and erythema multiforme (including Stevens- Johnson Syndrome) have been reported rarely.
Other hypersensitivity reactions include anaphylaxis, sialadenitis, pancreatitis, drug fever and arthralgia.
Miscellaneous Transient alopecia and benign intracranial hypertension. As with other antimicrobial agents, superinfections by fungi or resistant organisms such as Pseudomonas may occur.
However, these are limited to the genitourinary tract because suppression of normal bacterial flora does not occur elsewhere in the body.

OVERDOSE :

Symptoms and signs of overdosage include gastric irritation, nausea and vomiting. There is no known specific antidote. Nitrofurantoin can be haemodialysed. Standard treatment is by induction
of emesis or by gastric lavage in cases of recent ingestion. Monitoring of full blood count, liver function tests and pulmonary function, are recommended. A high fluid intake should be maintained to promote urinary excretion of the drug.

PHARMACOLOGICAL PROPERTIES :

Pharmacodynamic properties
Nitrofurantoin is a broad spectrum antibacterial agent, active against the majority of urinary pathogens. The wide range of organisms sensitive to the bactericidal activity include:
Escherichia coli.
Enterococcus Faecalis.
Klebsiella Species.
Enterobacter Species.
Staphylococcus Species, e.g. S.Aureus, S.Saprophyticus, S.Epidermidis.
Citrobacter Species.
Clinically most common urinary pathogens are sensitive to Nitrofurantoin. Most strains of Proteus and Serratia are resistant. All pseudomonas strains are resistant.
Pharmacokinetic properties
Orally administered Nitrofurantoin is readily absorbed in the upper gastrointestinal tract and is rapidly excreted in the urine. Blood concentrations at therapeutic dosages are usually low with an
elimination half-life of about 30 minutes. Maximum urinary excretion usually occurs 2-4 hours after administration of Nitrofurantoin. Urinary drug dose recoveries of about 40-45% are obtained.

PACKAGE AND STORAGE :

Mepafuran 50 mg :A carton box containing 20 capsules and inner leaflet.
Mepafuran 100 mg :A carton box containing 20 capsules and inner leaflet.
Store in a dry place at temperature not exceeding 30’C.
Keep out of reach of children

Produced by :

Arab Company for Pharmaceuticals & Medicinal plants
(MEPACO – MEDIFOOD)
Enshas EI Rami – Sharkeya – Egypt

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