Unitro 50/100 50 mg. 100 mg Capsule

UNITRO 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.

Adults
Acute urinary tract infections: 50 mg to 100 mg four times a day, with meals and at bedtime. To prevent recurrences: 50 mg to 100 mg per day. UNITRO may be given with food or milk to further minimise gastric upset. Therapy should be discontinued 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.

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

Method of administration
UNITRO is administered orally.

UNITRO is contraindicated:
u2022 In patients with known sensitivity to nitrofurantoin microcrystals and any of the excipients of UNITRO.
u2022 In patients with a deficiency of glucose 6-phosphate dehydrogenase or nursing mothers of infants with this deficiency.
u2022 Anuria, oliguria and renal impairment are contraindications to therapy with UNITRO. Treatment of this type of patient carries an increased risk of toxicity because of impaired excretion of nitrofurantoin.
u2022 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).
u2022 Acute porphyria
u2022 Patients suffering from renal impairment with an eGFR of less than 45 mL/min.

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 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).

u2022 Probenecid or sulphinpyrazone may reduce the excretion of UNITRO and should not be given concomitantly.
u2022 Magnesium trisilicate may reduce the absorption of UNITRO.
u2022 UNITRO may cause false positive reactions in urine tests for glucose using copper reduction methods.
u2022 Antagonism between nitrofurantoin and nalidixic acid, and nitrofurantoin and oxolinic acid has been demonstrated in vitro.
u2022 UNITRO should not be given concomitantly with quinolones.
The effect of other medicines on nitrofurantoin:
u2022 Food or medicines that delays gastric emptying increase the bioavailability of UNITRO.
u2022 Carbonic anhydrase inhibitors and alkalising medicines can reduce the antibacterial activity of UNITRO.
u2022 Magnesium trisilicate, co-administered with UNITRO, reduces the absorption of UNITRO.
u2022 There may be an antagonism between quinolones and UNITRO: simultaneous administration is not recommended.
u2022 Probenecid and sulfinpyrazone can reduce the renal clearance of UNITRO.
The effect of nitrofurantoin on other medicines / laboratory tests:
u2022 Typhoid fever vaccine (oral): antibacterial medicines make the oral typhoid fever vaccine ineffective.
u2022 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-phosphate 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:
Reported adverse reactions for nitrofurantoin are listed below according to organ systems.

System organ class Frequency
Infections and infestations
Superinfections by fungi or resistant organisms such as Pseudomonas. However, these are limited to the genitourinary tract. Frequency unknown
Blood and Lymphatic system disorders
Aplastic anemia Frequent
Agranulocytosis, leucopenia, granulocytopenia, haemolytic anemia, thrombocytopenia, glucose -6- phosphate dehydrogenase deficiency anemia, megaloblastic anemia and eosinophilia. Frequency unknown
Immune system disorders
Allergic skin reactions, Angioneurotic oedema and anaphylaxis. Frequency unknown
Psychiatric disorders
Depression, euphoria, confusion, psychotic reactions. Frequency unknown
Nervous system disorders
Peripheral neuropathy including optic neuritis (sensory as well as motor involvement), nystagmus, vertigo, dizziness, headache and drowsiness. Benign intracranial hypertension. Frequency unknown
Cardiac disorders
Collapse and cyanosis. Frequent
Respiratory, thoracic and mediastinal disorders
Acute pulmonary reactions, Subacute pulmonary reactions*, Chronic pulmonary reactions, Cough, Dyspnoea, Pulmonary fibrosis; possible association with lupus-erythematous-like syndrome. Frequency unknown
Gastrointestinal disorders
Sialadenitis, Pancreatitis, Nausea, Anorexia, Emesis, Abdominal pain and Diarrhoea. Frequency unknown
Hepatobiliary disorders
Cholestatic jaundice, Chronic active hepatitis (fatalities have been reported), Hepatic necrosis, autoimmune hepatitis. Frequency unknown
Skin and subcutaneous tissue disorders
Transient alopecia Exfoliative dermatitis and erythema multiforme (including Stevens-Johnson Syndrome), maculopapular, erythematous or eczematous eruptions, urticaria, rash, and pruritus. Lupus-like syndrome associated with pulmonary reaction. Medicine Rash With Eosinophilia And Systemic Symptoms (DRESS syndrome), cutaneous vasculitis. Frequency unknown
Renal and urinary disorders
Yellow or brown discoloration of urine, interstitial nephritis. Frequency unknown
General disorders and administration site conditions
Asthenia, fever, chills, fever and arthralgia. Frequency unknown
Investigations
False positive urinary glucose test results Frequency unknown

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 u20186.04 Adverse Drug Reactions Reporting Formu2019. Found under SAHPRAu2019s publications: https://www/sahpra.org.za/Publications/Index/8.

Symptoms and signs of overdose include gastric irritation, nausea and vomiting. Treatment is symptomatic and supportive (see section 4.7).