MACROBID Prolonged-release capsule Ref.[7490] Active ingredients: Nitrofurantoin

Nitrofurantoin is not effective for the treatment of parenchymal infections of a unilaterally functioning kidney. A surgical cause for infection should be excluded in recurrent or severe cases.

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.

Since pre-existing conditions may mask hepatic or pulmonary 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 (paraesthesia).

Nitrofurantoin should be used with caution in 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 elderly patients. Close monitoring of the pulmonary conditions of patients receiving long-term therapy is warranted (especially in the elderly).

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 signs of haemolysis in those with suspected glucose-6-phosphate dehydrogenase deficiency.

Gastrointestinal reactions may be minimised by taking the drug with food or milk, or by adjustment of dosage.

Hepatotoxicity

Hepatic reactions, including hepatitis, autoimmune hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely. Fatalities have been reported. The onset of chronic active hepatitis may be insidious, and patients should be monitored periodically for changes in biochemical tests that would indicate liver injury. If hepatitis occurs, the drug should be withdrawn immediately and appropriate measures should be taken.

For long term treatment monitor the patient closely for appearance of hepatic or pulmonary symptoms and other evidence of toxicity.

Discontinue treatment with nitrofurantoin if otherwise unexplained pulmonary, hepatotoxic, haematological or neurological syndromes occur.

1. Increased absorption with food or agents delaying gastric emptying.
2. Decreased absorption with magnesium trisilicate.
3. Decreased renal excretion of Nitrofurantoin by probenecid and sulfinpyrazone.
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:
   • Typhoid Vaccine (oral): Antibacterials inactivate oral typhoid vaccine.

Pregnancy

Animal studies with nitrofurantoin have shown no teratogenic effects. 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.

Nitrofurantoin is however contraindicated in infants under 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

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.

Macrobid may cause dizziness and drowsiness. Patients should be advised not to drive or operate machinery if affected in this way until such symptoms go away.

A tabulated list of undesirable effects is outlined below:

The undesirable effects are listed according to organ systems and following frequencies: Rare (≥1/10,000 to <1/1,000), Not known (cannot be estimated from the available data).

Infections and infestations

Not known: Superinfections by fungi or resistant organisms such as Pseudomonas. However, these are limited to the genitourinary tract.

Blood and lymphatic system disorders

Rare: Aplastic anaemia

Not known: Agranulocytosis, leucopenia, granulocytopenia, haemolytic anaemia, thrombocytopenia,glucose-6-phosphatedehydrogenase deficiency anaemia, megaloblasticanaemia and eosinophilia

Immune system disorders

Not known: Allergic skin reactions, angioneuroticoedema and anaphylaxis. Cutaneous vasculitis.

Psychiatric disorders

Not known: depression, euphoria, confusion, psychotic reactions

Nervous system disorders

Not known: Peripheral neuropathy including optic neuritis (sensory as well as motor involvement), nystagmus, vertigo, dizziness, headache and drowsiness. Benign intracranial hypertension.

Cardiac disorders

Rare: Collapse and cyanosis

Respiratory, thoracic and mediastinal disorders

Not known: Acute pulmonary reactions, Subacute pulmonary reactions*, Chronic pulmonary reactions, Cough, Dyspnoea, Pulmonary fibrosis; possible association with lupus-erythematous-like syndrome.

Gastrointestinal disorders

Not known: Sialadenitis, Pancreatitis, Nausea, Anorexia, Emesis, Abdominal pain and Diarrhea.

Hepatobiliary disorders

Not known: Cholestatic jaundice, Chronic active hepatitis**, Hepatic necrosis, Autoimmune hepatitis

Skin and subcutaneous tissue disorders

Not known: Transient alopecia, Exfoliative dermatitis and erythema multiforme (including Stevens-Johnson Syndrome), maculopapular, erythematous or eczematous eruptions,urticaria, rash, and pruritis. Lupus-like syndrome associated with pulmonary reaction, Drug Rash With Eosinophilia And Systemic Symptoms (DRESS syndrome), cutaneous vasculitis

Renal and urinary disorders

Not known: Yellow or brown discolouration of urine. Interstitial nephritis.

General disorders and administration site conditions

Not known: Asthenia, fever, chills, drug fever and arthralgia

Investigations

Not known: False positive urinary glucose

* 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.
** Can be fatal.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the MHRA yellow card scheme website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Not applicable.