Caloxa 50 mg Tablets

Treatment of advanced prostate cancer in combination with luteinizing hormone releasing hormone (LHRH) analogue therapy or surgical castration.

Posology
Adult males including the elderly: One tablet (50 mg) once a day. Treatment with Caloxa 50 mg should be started at least three days before commencing treatment with a LHRH analogue, or at the same time as surgical castration.
Renal Impairment: No dosage adjustment is necessary for patients with renal impairment.
Hepatic Impairment: No dosage adjustment is necessary for patients with mild hepatic impairment. Increased accumulation may occur in patients with moderate to severe hepatic impairment (see section 4.4).

Females and children, pregnant women or breastfeeding mothers. Caloxa 50 mg must not be given to any patient who has shown a hypersensitivity reaction to its use.

Hepatic function impairment: Caloxa 50 mg is extensively metabolised in the liver. Data suggests that its elimination may be slower in subjects with severe hepatic impairment and this could lead to increased accumulation of Caloxa 50 mg. Metabolism of Caloxa 50 mg may be delayed in patients with moderate to severe hepatic function impairment, resulting in a prolonged elimination half-life and increased risk of toxicity. Therefore, Caloxa 50 mg should be used with caution in patients with moderate to severe hepatic impairment. Periodic liver function testing should be considered during long-term use of Caloxa 50 mg, due to the possibility of hepatic changes. Severe hepatic changes have been observed infrequently with Caloxa 50 mg (see section 4.8). Caloxa 50 mg therapy should be discontinued if changes are severe.
Medicines metabolised by cytochrome P450: Although clinical studies using antipyrine as a marker of Cytochrome P450 (CYP) activity showed no evidence of a drug interaction potential with Caloxa 50 mg, midazolam exposure (AUC) was increased by up to 80 %, after co-administration with Caloxa 50 mg for 28 days. This rise is comparable to that seen in other studies after administration of grapefruit juice. Caution should be exercised with the co-administration of Caloxa 50 mg with compounds such as these.

Luteinising Hormone Releasing Hormone (LHRH): There is no evidence of any pharmacodynamic or pharmacokinetic interactions between Caloxa 50 mg and LHRH analogues.
Ketoconazole and Cimetidine: Formal interaction studies have not been undertaken, but caution should be exercised when prescribing Caloxa 50 mg with other medicines, e.g. ketoconazole and cimetidine, which may inhibit oxidation of Caloxa 50 mg. It could result in increased plasma concentrations of Caloxa 50 mg which could lead to an increase in side-effects.
Medicines Metabolised by Cytochrome P450: Although clinical studies using antipyrine as a marker of Cytochrome P450 (CYP) activity showed no evidence of a drug interaction potential with Caloxa 50 mg, midazolam exposure (AUC) was increased by up to 80 %, after co-administration with Caloxa 50 mg for 28 days. This rise is comparable to that seen in other studies after administration of grapefruit juice. Caution should be exercised with the co-administration of Caloxa 50 mg with compounds such as these. (see section 4.4).
Coumarin Anticoagulants: Caloxa 50 mg can displace the coumarin anticoagulant, warfarin, from its protein binding sites. It is therefore recommended that if Caloxa 50 mg is started in patients who are already receiving coumarin anticoagulants, prothrombin time should be closely monitored.

Safety and efficacy of Caloxa 50 mg during pregnancy and lactation have not been established, (see section 4.3).

During treatment with Bicalutamide, somnolence has been reported and those patients who experience this symptom should not drive or use machines.

Blood and lymphatic system disorders
Frequent: Anaemia
The following side effects have been reported but the frequencies are unknown: Leucopenia, neutropenia, thrombocytopenia
Immune system disorders
Less frequent: Hypersensitivity reactions (including angioneurotic oedema and urticaria)
Metabolism and nutrition disorders
Frequent: Anorexia, decreased appetite
The following side effects have been reported but the frequencies are unknown: Diabetes mellitus, hyperglycaemia.
Psychiatric disorders
Frequent: depression, decreased libido
Nervous system disorders
Frequent: Dizziness, somnolence, insomnia
Less frequent: Reversible neurological reactions such as nervousness, drowsiness and confusion
Cardiac disorders
Frequent: Myocardial infarction (fatal outcomes have been reported), cardiac failure
Vascular disorders
Frequent: Hypertension, Hot flush
Respiratory, thoracic and mediastinal disorders
Frequent: Upper respiratory tract infection, cough or hoarseness, shortness of breath, sore throat and sneezing
Less frequent: Interstitial lung disease and dyspnoea. Fatal outcomes have been reported.
Gastrointestinal disorders
Frequent: Abdominal pain, constipation, nausea, dyspepsia, flatulence, diarrhoea
Less frequent: Gastro-intestinal or rectal bleeding, vomiting
Hepato-biliary disorders
Frequent: Hepatic changes (including elevated levels of transaminases, jaundice), hepatitis
Less frequent: Hepatic failure. The following side effects have been reported but the frequencies are unknown: Methaemoglobinaemia
Skin and subcutaneous tissue disorders
Frequent: Alopecia, hirsuitism/hair re-growth, dry skin, pruritis, rash, sweating
Renal and urinary disorders
Frequent: Haematuria
The following side effects have been reported but the frequencies are unknown: Nocturia
Reproductive system and breast disorders
Frequent: Gynaecomastia and breast tenderness, impotence, decreased libido, erectile dysfunction
General disorders and administration site conditions
Frequent: Asthenia, oedema, chest pain, fever, chills, flu-like syndrome
Investigations
Frequent: Weight gain
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. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

There is no human experience of overdosage. There is no specific antidote; treatment should be symptomatic. Dialysis may not be helpful, since Caloxa 50 mg is highly protein bound and is not recovered unchanged in the urine. General supportive care, including frequent monitoring of vital signs, is indicated.