Domina

Composition:

Each 5ml oral suspension contains 25mg Nitrofurantoin.

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:

The Nitrofurantoin macrocrystals are specially formulated ,the controlled crystal size is designed to control the speed of absorption and thus reduce the incidence of nausea.
Orally administered Nitrofurantoin is readily absorbed in the upper gastrointestinal tract at a slower rate when compared to microcrystalline Nitrofurantoin. Blood concentrations at therapeutic dosage are usually low with an elimination half-life of about 30 minutes or less.
Maximum urinary excretion usually occurs 4-5 hours after administration of macrocrystalline Nitrofurantoin. Urinary drug dose recoveries of about 25-30% are obtained.

Indications:

For the treatment of and prophylaxis against acute or recurrent, uncomplicated lower urinary tract infections or pyelitis either spontaneous or following surgical procedures.
It is specifically indicated for the treatment of infections when due to susceptible strains of Escherichia coli, enterococci, and staphylococci, Citrobacter, Klebsiellaand Enterobacter.

Dosage and Administration:

Adults:

50 to 100mg four times a day - the lower dosage level is recommended for uncomplicated urinary tract infections.

Pediatric Patients:

5 to 7mg/kg of body weight per 24 hours, given in four divided doses (contraindicated under one month of age).

Weight in kg	Pediatric Doses (ml) and Frequency
7 kg to 11 kg	2.5 mL Four times Daily
12 kg to 21 kg	5 mL Four times Daily
22 kg to 30 kg	7.5 mL Four times Daily
31 kg to 41 kg	10 mL Four times Daily
42 kg or greater	See Adult Dose

Elderly:

Provided there is no significant renal impairment, in which Nitrofurantoin is contraindicated, the dosage should be that for any normal adult.

Overdose:

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

Contraindications:

Patients with known hypersensitivity to nitrofurantoin or other nitrofurans.
Patients suffering from renal dysfunction with an eGFR of less than 45 ml/minute. Nitrofurantoin may be used with caution as short-course therapy only for the treatment of uncomplicated lower urinary tract infection in individual cases with an eGFR between 30-44 ml/min to treat resistant pathogens, when the benefits are expected to outweigh the risks.
G6PD enzyme deficiency
Acute porphyria.
In infants under three months of age as well as pregnant patients at term (during labour and delivery) because of the theoretical possibility of haemolyticanaemia in the foetus or in the newborn infant due to immature erythrocyte enzyme systems.

Undesirable effects:

Respiratory: If any of the following reactions occur the drug should be discontinued.

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. 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. 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 recognize symptoms as early as possible. Pulmonary function may be impaired permanently, even after cessation of therapy.

Hepatic: Hepatic reactions including cholestatic jaundice and chronic active hepatitis occur rarely.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. 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, haemolyticanaemia, thrombocytopenia and megaloblasticanaemia, 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 angioneuroticoedema, maculopapular, erythematous or eczematous eruptions, urticaria, and pruritus have occurred.Lupus-like syndrome associated with pulmonary reaction to Nitrofurantoin has been reported. Exfoliative dermatitis and erythema multiforme (including Stevens - Johnson syndrome) have been reported rarely.
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 genito-urinary tract because suppression of normal bacterial flora does not occur elsewhere in the body.

Warnings and precautions:

Acute, subacute, or chronic pulmonary reactions have been observed in patients treated with nitrofurantoin. if these reactions occur, nitrofurantoin (macrocrystals) should be discontinued andappropriate measures taken. reports have cited pulmonary reactions as a contributing cause of death.

close monitoring of the pulmonary condition of patients receiving longterm therapy is warranted and requires that the benefits of therapy be weighed against potential risks

Nitrofurantoin is not effective for the treatment of parenchymal infections of unilaterally nonfunctioning 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.
Urine may be coloured yellow or brown after taking Nitrofurantoin.
Patients on Nitrofurantoin are susceptible to false positive urinary glucose.
Gastrointestinal reactions may be minimized by taking the drug with food or milk, or by adjustment of dosage.
For long-term treatment, the patients should be monitored closely for evidence of hepatitis or pulmonary symptoms or other evidence of toxicity.
Discontinue treatment with Nitrofurantoin if unexplained pulmonary, hepatic, haematological or neurological syndromes occur.
Hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely. Fatalities have been reported.
Cases of hemolytic anemia of the primaquine-sensitivity type have been induced by nitrofurantoin. Hemolysis appears to be linked to a glucose-6-phosphate dehydrogenase deficiency in the red blood cells of the affected patients.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including nitrofurantoin, and may range in severity from mild diarrhea to fatal colitis.
Patients should be advised to take nitrofurantoin (macrocrystals) with food to further enhance tolerance and improve drug absorption.

Drug Interactions:

Increased absorption with food or agents delaying gastric emptying.
Decreased absorption with magnesium trisilicate.
Decreased renal excretion of Nitrofurantoin by probenecid and sulphinpyrazone.
Decreased anti-bacterial activity by carbonic anhydrase inhibitors and urine alkalisation.
Anti-bacterial antagonism by quinolone anti-infective.
Interference with some tests for glucose in urine.
As Nitrofurantoin belongs to the group of Antibacterials, it will have the following interactions:
- Oestrogens: 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.

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.

Use in Pregnancy and Lactation:

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.Nitrofurantoin is however contraindicated in infants less than three months of age and in pregnant women during labour and delivery, because of the 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.

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