Cipladantin 50 mg/100 mg Capsules

CIPLADANTIN is indicated for 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.

Posology
Therapy should be continued for at least one week and for at least three days after sterility of the urine is obtained. Continued infection indicates need for re-evaluation. CIPLADANTIN is highly soluble in urine, to which it may impart a brown colour.

Adults
u2022 To treat acute urinary tract infections: 50 to 100 mg four times a day, with meals and at bedtime.
u2022 To prevent recurrences: 50 to 100 mg per day.

Special populations
Paediatric population
u2022 To treat acute urinary tract infections: should be calculated on the basis 5 to 7 mg/kg of body mass per 24 hours to be given in divided doses four times a day.
u2022 To prevent recurrences: 1 mg/kg per day for long term therapy.
u2022 CIPLADANTIN must not be given to children less than a month old.

Method of administration
CIPLADANTIN may be taken with food or milk (e.g. at mealtimes) to further minimise gastric upset (see section 5.2).

CIPLADANTIN is contraindicated in the following patients:
u2022 Patients with known hypersensitivity to nitrofurantoin or any of the excipients of CIPLADANTIN listed in section 6.1.
u2022 Anuria, oliguria and renal impairment. Treatment of this type of patients carry an increased risk of toxicity because of impaired excretion of the medicine.
u2022 Pregnant women at term (during labour and delivery).
u2022 Infants under three months of age because of the possibility of haemolytic anaemia due to immature enzyme systems (glutathione instability).
u2022 Patients with a deficiency of glucose 6-phosphate dehydrogenase (G6PD).
u2022 Nursing mothers of infants with a deficiency of glucose 6-phosphate dehydrogenase.
u2022 Acute porphyria.

CIPLADANTIN is not effective for the treatment of parenchymal infections of unilaterally non-functioning kidney. A surgical cause for infection should be excluded in recurrent or severe cases. CIPLADANTIN should 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 to 40 mL/min to treat resistant pathogens. A course of therapy should not exceed 14 days and repeated courses should be separated by rest periods. Since pre-existing conditions may mask adverse reactions, CIPLADANTIN should be used caution in patients with pulmonary disease, hepatic dysfunction, neurological disorders and allergic diathesis. Treatment must be discontinued if otherwise unexplained pulmonary, hepatic, haematological or neurological reactions occur.
Caution is advised in patients with anaemia, diabetes mellitus, electrolyte imbalance, debilitating conditions and folic acid deficiency. Patients should be warned to report early signs of peripheral neuropathy. If peripheral neuropathy occurs (paraesthesiae), the treatment should be discontinued. Acute, subacute or chronic pulmonary reaction has been observed in patients treated with CIPLADANTIN. If these reactions occur, the CIPLADANTIN should be withdrawn and appropriate measures should be taken. Chronic pulmonary reaction (including pulmonary fibrosis and diffuse interstitial pneumonitis) can develop insidiously and may occur frequently in elderly patients. Close monitoring of the pulmonary conditions of patients receiving long-term therapy is warranted (especially in the elderly). Patients with a history of asthma may experience acute asthmatic attacks. Cases of haemolytic anaemia of the primaquine sensitivity type have been induced by CIPLADANTIN. The haemolysis appears to be linked to a G6PD deficiency in the red blood cells of the affected patients. Any sign of haemolysis is an indication to discontinue the medicine. CIPLADANTIN should not be given to patients with renal impairment since antibacterial concentrations in the urine may not be attained and toxic concentrations in the plasma can occur.
Although hepatic reactions such as hepatitis, cholestatic jaundice, and hepatic necrosis rarely occur, fatalities have been reported. Patients should be monitored, and treatment be stopped immediately if hepatitis occurs. CIPLADANTIN may cause false positive reactions in urine tests for glucose using copper reduction methods. For long-term treatment, patients must be monitored for evidence of toxicity including hepatitis and pulmonary effects. Gastrointestinal reactions may be minimised by taking CIPLADANTIN with food or milk, or by adjusting the dose. Pseudomonas is the organism most implicated in superinfections in patients treated with CIPLADANTIN. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Probenecid or sulphinpyrazone
Probenecid or sulphinpyrazone may reduce the excretion of nitrofurantoin and should not be given concomitantly.
Magnesium trisilicate
Magnesium trisilicate may reduce the absorption of nitrofurantoin.
Copper reduction methods
Nitrofurantoin may cause false positive reactions in urine tests for glucose using copper reduction methods.
Quinolones
Antagonism between nitrofurantoin and nalidixic acid and nitrofurantoin and oxolinic acid has been demonstrated in vitro. Therefore, CIPLADANTIN should not be given concomitantly with quinolines as there is antibacterial antagonism.
Carbonic anhydrase inhibitors (e.g. acetazolamide) and urine alkalinisers (e.g. potassium citrate mixture)
Decreased anti-bacterial activity by carbonic anhydrase inhibitors and urine alkalisation.
Food and medicines delaying gastric emptying (e.g. atropine, hyoscine)
There is an increased absorption with food or medicines delaying gastric emptying.
Oestrogens
In common with other antibiotics, nitrofurantoin may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of oestrogen-containing contraceptive medicines. Therefore, patients should be warned appropriately, and extra contraceptive precautions be taken.
Typhoid vaccine (oral)
CIPLADANTIN belongs to a group of antibacterial medicines that inactivate oral typhoid vaccine.

Pregnancy
Maternal side effects associated with CIPLADANTIN may adversely affect the course of pregnancy. Therefore, CIPLADANTIN should be used at the lowest possible dose, only after careful assessment. CIPLADANTIN is contraindicated in weeks 38-42 of pregnancy, during labour and delivery.
Breastfeeding
CIPLADANTIN is contraindicated in infants less than three months old (see section 4.3) because of the possible risk of haemolysis of the infantsu2019 immature red blood cells. Therefore, nursing mothers should not breastfeed their infants while being treated with CIPLADANTIN.
Fertility
There are no data on fertility in humans.

Patients should be informed that dizziness and drowsiness has been reported during treatment with nitrofurantoin and should not drive or operate machinery if affected.

Infections and infestations: Frequency not known: superinfections by fungi or resistant organisms such as Pseudomonas
Blood and lymphatic system disorders: Less frequent: aplastic anaemia. Frequency not known: agranulocytosis, leukopenia, granulocytopenia, haemolytic anaemia, thrombocytopenia and megaloblastic anaemia, G6PD deficiency anaemia, eosinophilia.
Immune system disorders: Frequency not known: allergic skin reactions, angioedema and anaphylaxis.
Psychiatric disorders: Frequency not known: depression, euphoria, confusion, psychotic reactions.
Nervous system disorders: Less frequent: peripheral neuropathy including optical neuritis with symptoms of sensory and motor involvement, nystagmus, vertigo, dizziness, headache, drowsiness, benign intercranial hypertension.
Cardiac disorders: Less frequent: collapse and cyanosis.
Respiratory, thoracic and mediastinal disorders: Frequency not known: acute pulmonary reactions, subacute pulmonary reactions*, chronic pulmonary reactions, cough, dyspnoea, pulmonary fibrosis; possible association with lupus-erythematous-like syndrome.
Gastrointestinal disorders: Frequency not known: sialadenitis, anorexia, nausea, vomiting, pancreatitis, emesis, abdominal pain, diarrhoea.
Hepato-biliary disorders: Frequency not known: cholestatic jaundice, chronic active hepatitis (fatalities have been reported), hepatic necrosis, autoimmune hepatitis.
Skin and subcutaneous tissue disorders: Less frequent: transient alopecia, exfoliative dermatitis, erythema multiforme (including Steven-Johnson syndrome), rash, maculopapular, erythematous or eczematous eruptions, urticaria, pruritus, lupus-like syndrome associated with pulmonary reaction, drug rash with eosinophilia and systemic symptom (DRESS syndrome), cutaneous vasculitis.
Renal and urinary disorders: Frequency not known: yellow or brown discolouration of the urine.
General disorders and administrative side disorders: Frequency not known: asthenia, fever, chills, drug fever and arthralgia.
Investigations: Frequency not known: false positive urinary glucose.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reaction Reporting 359 Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8 and to Cipla Medpro (Pty) Ltd. (by e-mail: [email protected]) or telephone 080 222 6662 (toll free).

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. Treatment is symptomatic and supportive. Monitoring of full blood count, liver function and pulmonary function tests are recommended. A high fluid intake should be maintained to promote urinary excretion.