INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
MACRODANTIN CAPSULES 50 mg (capsule)
MACRODANTIN CAPSULES 100 mg (capsule)

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

MACRODANTIN CAPSULES 50 mg (capsule)
MACRODANTIN CAPSULES 100 mg (capsule)

COMPOSITION:
Each MACRODANTIN capsule contains 50 mg or 100 mg nitrofurantoin macrocrystals, a synthetic chemical of controlled crystal size. The chemical name is 1[(5-nitrofur-furylidene)amino] hydantoin.

PHARMACOLOGICAL CLASSIFICATION:
A 18 5 Urinary tract antiseptics

PHARMACOLOGICAL ACTION:
MACRODANTIN is an antibacterial agent for specific urinary tract infections.
Nitrofurantoin is rapidly and completely absorbed from the gastro-intestinal tract. Anti-bacterial concentrations are not achieved in plasma following ingestion of recommended doses because of rapid elimination.
MACRODANTIN exerts bacteriostatic activity against many strains of:
        Escherichia coli
        Enterococci
Anti-bacterial activity is higher in acidic urine.
Many strains of Enterobacter species and Klebsiella species are resistant to MACRODANTIN. It is not active against most strains of Proteus and Pseudomonas species.

INDICATIONS:
MACRODANTIN is indicated for the treatment and prevention of recurrence of uncomplicated lower urinary tract infections, e.g. pyelonephritis, pyelitis and cystitis. (It is not indicated for the treatment of associated renal, cortical or perinephric abscesses).

CONTRA-INDICATIONS:
Anuria, oliguria and renal impairment are contra-indications to therapy with this agent. Treatment of this type of patient carries an increased risk of toxicity because of impaired excretion of the drug.
Pregnant women at term, as well as infants under one month of age, because of the possibility of haemolytic anaemia due to immature enzyme systems (glutathione instability).
Safe use in earlier pregnancy has not been established.
Contra-indicated in those patients with known sensitivity to MACRODANTIN (nitrofurantoin macrocrystals) and in those patients with a deficiency of glucose-6-phosphate dehydrogenase or nursing mothers of infants with this defiency.

WARNINGS:
A course of therapy should not exceed 14 days and repeated courses should be separated by rest periods.
Patients with a history of asthma may experience acute asthmatic attacks.
Elderly patients and patients undergoing prolonged therapy should be monitored for changes in pulmonary function.
Cases of haemolytic anaemia of the primaquine sensitivity type have been induced by MACRODANTIN. The haemolysis appears to be linked to a glucose-6-phosphate dehydrogenase deficiency in the red blood cells of the affected patients. Any sign of haemolysis is an indication to discontinue the agent.
Pseudomonas is the organism most commonly impiclated in superinfections in patients treated with MACRODANTIN.

DOSAGE AND DIRECTIONS FOR USE:
Adults

Acute urinary tract infections:	50-100 mg four times a day, with meals and at bedtime.
To prevent recurrences:	50-100 mg per day.

Children

Acute urinary tract infections.	Should be calculated on the basis of 5-7 mg/kg of body mass per 24 hours to be given in divided doses four times a day (contra-indicated for children under one month).
To prevent recurrences:	1 mg/kg/day for long term therapy.

MACRODANTIN may be given with food or milk to further minimise gastric upset.
Therapy should be continued for at least one week and for at least 3 days after sterility of the urine is obtained.
Continued infection indicates need for re-evaluation. Nitrofurantoin is highly soluble in urine, to which it may impart a brown colour.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Gastro-intestinal reactions:
Anorexia, nausea, and vomiting are the most frequent reactions; less frequently abdominal pain and diarrhoea.
Hypersensitivity reactions:
Skin rashes and fever may occur.
Anaphylaxis, erythema multiforme, exfoliative dermatitis, pancreatitis, a lupus-like syndrome, myalgia and anthralgia have been reported.
Pulmonary sensitivity reactions may occur, which can be acute, subacute or chronic.
Acute pulmonary sensitivity reaction is commonly manifested by sudden onset of fever, chills, eosinophilia, cough, chest pain, dyspnoea, pulmonary infiltration or consolidation and pleural effusion. The acute reactions usually occur within the first week of treatment and resolve with discontinuation of the medicine.
More insidious subacute reactions have also been reported.
Interstitial pulmonary fibrosis can occur in patients on chronic medication.
Subacute or chronic pulmonary reaction is associated with prolonged therapy. Insidious onset of malaise, dyspnoea on exertion, cough, altered pulmonary function, and röentgenographic and histologic findings of diffuse interstitial pneumonitis or fibrosis or both are common manifestations.
Impaired pulmonary function may result even after cessation of the drug therapy.
Dermatological reactions:
Maculopapular, erythematous, or eczematous eruption, pruritus, urticaria and angioedema.
Other sensitivity reactions:
Hepatotoxicity including cholestatic jaundice and hepatitis may develop. Chronic active hepatitis and hepatocellular damage have been reported.
Haematological reactions:
Haemolytic anaemia, granulocytopenia or agranulocytosis, eosinophilia and megaloblastic anaemia, leucopenia, thrombocytopenia in persons with a genetic deficiency of glucose-6-phosphate dehydrogenase.
Neurological reactions:
Peripheral neuropathy, reversible headache, dizziness, nystagmus and drowsiness. Severe polyneuropathies with demyelination and degeneration of both sensory and motor nerves have been reported. Patients should be warned to report early signs of peripheral neuropathy such as paraesthesia.
Miscellaneous reactions:
Transient alopecia. As with other antimicrobial agents, superinfection by resistant organisms may occur. With MACRODANTIN, however, these are limited to the genitourinary tract because suppression of normal bacterial flora elsewhere in the body does not occur. Nitrofurantoin colours the urine brown.
Precautions:
Patients should be warned to report early signs of peripheral neuropathy. If peripheral neuropathy occurs the treatment should be discontinued. Care is required in patients with predisposing pulmonary, hepatic, neurological or allergic disorders and in those with conditions (such as anaemia, diabetes mellitus, electrolyte imbalance, debility or vitamin B deficiency) which may predispose to peripheral neuropathy.
Elderly patients are especially susceptible to the pulmonary intoxication of nitrofurantoin.
Acute, subacute or chronic pulmonary reaction has been observed in patients treated with MACRODANTIN. If these reactions occur, the drug should be withdrawn and appropriate measures should be taken.
Interactions:
Probenecid or sulphinpyrazone may reduce the excretion of nitrofurantoin and should not be given concomitantly.
Magnesium trisilicate may reduce the absorption of nitrofurantoin.
Nitrofurantoin may cause false positive reactions in urine tests for glucose using copper reduction methods.
Antagonism between nitrofurantoin and nalidixic acid, and nitrofurantoin and oxolinic acid has been demonstrated in vitro and nitrofurantoin should not be given concomitantly with quinolines.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See Side-effects and Special Precautions.
Treatment is symptomatic and supportive.

IDENTIFICATION:
MACRODANTIN is available in opaque, yellow capsules of 100 mg (imprinted "100" in black), and in opaque, yellow and white capsules of 50 mg (imprinted "50" in black).

PRESENTATION:
MACRODANTIN capsules are available in 50 mg and 100 mg strengths. Both strengths are available in containers containing 50 and 250 capsules.

STORAGE INSTRUCTIONS:
The capsules should be stored in light-resistant and preferably, moisture-proof containers. Store at temperatures below 25°C.
KEEP OUT OF REACH OF CHILDREN

REGISTRATION NUMBERS:
MACRODANTIN CAPSULES 50 mg: G/18.5/160
MACRODANTIN CAPSULES 100 mg: G/18.5/161

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
SmithKline Beecham Pharmaceuticals (Pty) Ltd
6 Carey Street,
Wynberg Ext. 6,
Johannesburg, 2090

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
13.03.1991

P2216

Current: May 2004
Source: Community Pharmacy
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