UNITRO Hard gelatin capsule Ref.[115190] Active ingredients: Nitrofurantoin

Prolonged use of UNITRO is not recommended. 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 UNITRO. 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 UNITRO.

Pseudomonas is the organism most commonly implicated in super infections in patients treated with UNITRO. During UNITRO treatments there are lung and liver complications that can be life-threatening (see section 4.8). The treatment should be stopped immediately and the necessary measures should be taken.

Acute, subacute and chronic pulmonary reactions have been observed in patients treated with UNITRO. If these reactions occur, UNITRO must be discontinued immediately.

Chronic pulmonary reactions (including pulmonary fibrosis and diffuse interstitial pneumonitis) can develop insidiously, and can often occur in elderly patients. Close monitoring of the pulmonary conditions of patients receiving long-term therapy is indicated (especially in the elderly).

Patients with hepatic impairment

Patients should be closely monitored for signs of hepatitis (especially in the long term use). Existing conditions can mask pulmonary and hepatic side effects, there is caution provided when UNITRO is used in patients with pulmonary diseases, disturbed hepatic function, neurological disorders and allergic diathesis.

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.

Hepatotoxicity

Hepatic reactions, including hepatitis, autoimmune hepatitis, cholestatic jaundice, chronic active hepatitis and hepatic necrosis, can occur. 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, UNITRO should be withdrawn immediately and appropriate measures should be taken.

Urine can be coloured yellow or brown after taking UNITRO. Patients who taking UNITRO can test false positive for urine glucose (if tested for urine reducing substances).

UNITRO is not effective for the treatment of parenchymal infections of unilateral non- functioning kidney. A surgical cause for infection should be excluded in recurrent or severe cases.

• Probenecid or sulphinpyrazone may reduce the excretion of UNITRO and should not be given concomitantly.
• Magnesium trisilicate may reduce the absorption of UNITRO.
• UNITRO 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.
• UNITRO should not be given concomitantly with quinolones.

The effect of other medicines on nitrofurantoin:

• Food or medicines that delays gastric emptying increase the bioavailability of UNITRO.
• Carbonic anhydrase inhibitors and alkalising medicines can reduce the antibacterial activity of UNITRO.
• Magnesium trisilicate, co-administered with UNITRO, reduces the absorption of UNITRO.
• There may be an antagonism between quinolones and UNITRO: simultaneous administration is not recommended.
• Probenecid and sulfinpyrazone can reduce the renal clearance of UNITRO.

The effect of nitrofurantoin on other medicines/laboratory tests:

• Typhoid fever vaccine (oral): antibacterial medicines make the oral typhoid fever vaccine ineffective.
• Nitrofurantoin can affect certain laboratory tests. False positive results or incorrect high reading can occur with urinary glucose tests based on the reduction of copper sulphate, such as Benedict’s reagent and Clinitest (Ames). However, there is no interference with the Clinistix test.

Pregnancy

Data in pregnant women indicate no teratogenicity or fetal/neonatal toxicity. Animal studies do not show reproductive toxicity as clinically relevant doses. Therefore, UNITRO can be used during pregnancy, except in 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).

Breastfeeding

UNITRO is excreted in breast milk. UNITRO can be used during breastfeeding, but it is contraindicated in those patients with a deficiency of glucose 6-phospahte dehydrogenase or nursing mothers of infants with this deficiency

Fertility

In men, at supra-therapeutic doses, a temporary stoppage in spermatogenesis and reduced sperm counts. Clinical doses are not associated with male infertility. No reduced fertility was observed in animal studies. In rats, at high doses observed a temporary stoppage in spermatogenesis.

UNITRO can cause dizziness and drowsiness. Patient should be advised not to drive or operate machines until the symptoms disappear.

A tabulated list of undesirable effects is outlined below.

a. Tabulated list of adverse reactions

Reported adverse reactions for nitrofurantoin are listed below according to organ systems.

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.

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 to SAHPRA via The ‘6.04 Adverse Drug Reactions Reporting Form’. Found under SAHPRA’s publications: https://www/sahpra.org.za/Publications/Index/8.

Not applicable.