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Logo ‘FURADANTIN’Tablets 50 mg
‘FURADANTIN’Tablets 100 mg
‘FURADANTIN’Suspension 25 mg/ mL

SCHEDULING STATUS:
S4

PROPRIETARY NAMES
(and dosage form):

‘FURADANTIN’Tablets 50 mg
‘FURADANTIN’Tablets 100 mg
‘FURADANTIN’Suspension 25 mg/ mL

COMPOSITION:
Each ‘Furadantin’Tablet contains 50 mg or 100 mg
nitrofurantoin. The chemical name is 1[(5-nitrofur-furylidene)amino]hydantoin.

Each 5 mL of suspension curtains 25 mg nitrofurantoin. The suspension also contains methyl p-hydroxy benzoate 0,10% m/v and propyl P-hydroxybenzoate 0,02% m/v as preservatives.

PHARMACOLOGICAL CLASSIFICATION:
A.18.5 Urinary tract antiseptics.

PHARMACOLOGICAL ACTION:
Clinical Pharmacology:
Orally administered ‘Furadantin’is readily absorbed and rapidly excreted in urine. During therapeutic drug dosage, only low blood concentrations are usually present. It is highly soluble in urine, to which it may impart a brown colour. Following a therapeutic dose regimen (100 mg four times a day for 7 days) average urinary drug recoveries (0 - 24 hours) on day 1 and day 7 were 42,7% and 43,6% respectively, for ‘Furadantin’.

Microbiology:
‘Furadantin’is an antibacterial agent for specific urinary tract infections. It is bacteriostatic in low concentrations (10 µg/mL to 5 µg/mL) and in vitro is considered to be bactericidal in higher concentrations. Its presumed mode of action is based upon its interference with several bacterial enzyme systems. Bacteria develop only a limited resistance to furan derivatives clinically. ‘Furadantin’is usually active against the following organisms in vitro: Escherichia coli, enterococci (e.g. Streptococcus faecalis), Staphylococcus aureus.

NOTE: Some strains ofEnterobacter species and Klebsiella species are resistant to ‘Furadantin’. It is not active against most strains ofProteus species, and Serratia species. It has no activity against Pseudomonas species.

Susceptibility Tests:
Quantitative methods that require measurement of zone diameters give the most precise estimates of antimicrobial susceptibility. One recommended procedure* uses a disc containing 300 micrograms for testing susceptibility; interpretations correlate zone diameters of this disc test with MIC values for nitrofurantoin. Reports from the laboratory should be interpreted according to the following criteria:

Susceptible organisms produce zones of 17 mm or greater, indicating that the tested organism is likely to respond to therapy.

Organisms of intermediate susceptibility produce zones of 15 to 16 mm, indicating that the tested organism would be susceptible if a high dosage is used.

Resistance organisms produce zones of 14 mm or less, indicting that other therapy should be selected.

A bacterial isolate may be considered susceptible if the MIC value for nitrofurantoin is not more than 25 micrograms per mL. Organisms are considered resistant if the MIC is not less than 100 micrograms per mL.

INDICATIONS:
‘Furadantin’is indicated for the treatment of urinary tract infections when due to susceptible strains of E. coli, enterococci, S. aureus (it is not indicated for the treatment of associated renal cortical or perinephric abscesses), and certain susceptible strains of Klebsiella species, Enterobacter species and Proteus species.

NOTE: Specimens for culture and susceptibility testing should be obtained prior to and during drug administration.

CONTRA-INDICATIONS:
Anuria, oliguria, or significant impairment of renal function (creatinine clearance under 40 mL per minute) are contra-indications to therapy with this drug. Treatment of this type of patient carries an increased risk of toxicity because of impaired excretion of the drug. For the same reason, this drug is much less effective under these circumstances.

The drug is contra-indicated in pregnant patients at term as well as in infants under one month of age because of the possibility of haemolytic anaemia due to immature enzyme systems (glutathione instability).

The drug is also contra-indicated in those patients with known hypersensitivity to ‘Furadantin’, ‘Macrodantin’(nitrofurantoin macrocrystals), and other nitrofurantoin preparations.

WARNINGS:
Acute, subacute and chronic pulmonary reactions have been observed in patients treated with nitrofurantoin products. If these reactions occur, the drug should be withdrawn and appropriate measures should be taken.

An insidious onset of pulmonary reactions (diffuse interstitial pneumonitis or pulmonary fibrosis, or both) in patients on long-term therapy warrants close monitoring of these patients.

There have been isolated reports giving pulmonary reactions as a contributing cause of death. (See Hypersensitivity reactions).

Cases of haemolytic anaemia of the primaquine sensitivity type have been induced by ‘Furadantin. The haemolysis appears to be linked to a glucose-6-phosphate dehydrogenase deficiency in the red blood cells of the affected patients. This deficiency is found in 10 percent of Negroes and a small percentage of ethnic groups of Mediterranean and Near Eastern origin. Any signs of haemolysis is an indication to discontinue the drug. Haemolysis ceases when the drug is withdrawn.

Pseudomonas is the organism most commonly implicated in superinfections in patients treated with ‘Furadantin’.

DOSAGE AND DIRECTIONS FOR USE:
Tablets and Oral Suspension:
Adults:
50 - 100 mg four times a day.

Children:
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 under one month).

Average dose for children:
‘Furadantin’(nitrofurantoin) Oral Suspension (5 mg/mL).

Body Weight:   No. of Teaspoonfuls
Pounds Kilograms (4 Times Daily)
15 to 26 7 to 11 ½ (2,5 mL)
27 to 46 12 to 21 l (5 mL)
47 to 68 22 to 30 1½ (7,5 mL)
69 to 91 31 to 41 2 (10 mL)

Administration:
‘Furadantin’may be given with food or milk to 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 the need for re-evaluation.

If the drug is to be used for long-term suppressive therapy, reduction of dosage should be considered.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Gastrointestinal Reactions:
Anorexia, nausea and emesis are the most frequent reactions; abdominal pain and diarrhoea occur less frequently. These dose-related toxicity reactions can be minimised by reduction of dosage, especially in the female patient. Hepatitis occurs rarely.

Hypersensitivity Reactions:
Pulmonary sensitivity reactions may occur, which can be acute, subacute or chronic.

Acute reactions are commonly manifested by fever, chills cough chest pain, dyspnoea, pulmonary infiltration with consolidated or pleural effusion on X-ray, and eosinophilia. The acute reactions usually occur within the first week of treatment and are reversible with cessation of therapy. Resolution may be dramatic.

In subacute reactions, fever, and eosinophilia are observed less often. Recovery is somewhat slower, perhaps as long as several months. If the symptoms are not recognised as being drug related and nitrofurantoin is not withdrawn, symptoms may become more severe.

Chronic pulmonary reactions are more likely to occur in patients who have been on continuous nitrofurantoin therapy for six months or longer. The insidious onset of malaise, dyspnoea on exertion, cough and altered pulmonary function are common manifestations. Röntgenographic and histologic findings of diffuse interstitial pneumonitis or fibrosis, or both, are also common manifestations. Fever is rarely prominent.

The severity of these chronic pulmonary reactions and the degree of their resolution appear to be related to the duration of therapy after the first clinical signs appear. Pulmonary function may be permanently impaired even after cessation of nitrofurantoin therapy. This risk is greater when pulmonary reactions are not recognised early.

Dermatologic Reactions:
Maculopapular, erythematous, or eczematous eruption, pruritus, urticaria and angioedema.

Other Sensitivity Reactions:
Anaphylaxis, asthmatic attack in patients with history of asthma, cholestatic jaundice, drug fever and arthralgia.

Haematologic Reactions:
Haemolytic anaemia, granulocytopenia, leucopenia, eosinophilia, and megaloblastic anaemia. Return of the blood picture to normal has followed cessation of therapy.

Neurological Reactions:
Peripheral neuropathy, headache, dizziness, nystagmus and drowsiness.

Miscellaneous Reactions:
Transient alopecia. As with other antimicrobial agents, superinfections by resistant organisms may occur. With ‘Furadantin’, however, these are limited to the genito-urinary tract because suppression of normal bacterial flora elsewhere in the body does not occur.

Precautions:
Peripheral neuropathy may occur with ‘Furadantin’ therapy, this may become severe or irreversible. Fatalities have been reported. Predisposing conditions such as renal impairment, anaemia, diabetes, electrolyte imbalance, vitamin B deficiency and debilitating disease may enhance such occurrence.

Use in Pregnancy:
The safety of ‘Furadantin’ during pregnancy and lactation has not been established. Use of this drug in women of childbearing potential requires that the anticipated benefit be weighed against the possible risks.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Excessive intake would probably cause vomiting. Should overdosage occur, stomach wash-out is recommended.

There is no known specific antidote to nitrofurantoin.

IDENTIFICATION:
‘Furadantin’Tablets are yellow in colour and have a pentagonal shape.
Each tablet has a break line on one face and the tablet strength is shown on the opposite face, (50 mg and 100 mg).

‘Furadantin’Suspension is a yellow suspension.

PRESENTATION:
‘Furadantin’Tablets are available in 50 mg and 100 mg strengths.
Both strengths are available in containers containing 50 tablets.

‘Furadantin’Suspension is available in bottles of 100 mL.

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

REFERENCE NUMBERS:
‘Furadantin’Tablets 50 mg:        H.1638 (Act 101/1965)
‘Furadantin’Tablets 100 mg:        H.1951 (Act 101/1965)
‘Furadantin’Suspension 25 mg/5 mL:        H.1637 (Act 101/1965)

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

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
28.05.1991

*        National Committee for Clinical Laboratory Standards. Approved Standard: ASM-2, Performance Standards for Antimicrobial Disc Susceptibility Tests, July 1975

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