ZODORAY Capsule Ref.[50532] Active ingredients: Alfacalcidol

1α-OHD₃ should be given with care to patients with impaired renal function. If hypercalcaemia is induced by 1α-OHD₃ it can be rapidly corrected by stopping treatment Throughout treatment, regular plasma calcium determinations are essential. Facilities for monitoring regular corrected plasma calcium and other appropriate biochemical parameters should be available when 1α-OHD₃ is used.

Early symptoms include polyuria, polydipsia, weakness, headache, nausea, constipation, dry mouth, muscle and bone pain, metallic taste. If hypercalcaemia occurs, 1α-OHD₃ should be stopped until the plasma calcium returns to normal (about one week) and then restarted at half the last dose used.

The risk of hypercalcaemia depends on such factors as the degree of any mineralisation defect, renal function, and the dose of 1α-OHD₃ that is used. Thus, hypercalcaemia is less likely in osteomalacia and more likely in renal failure. Hypercalcaemia will occur when there is biochemical evidence of bone healing (e.g. a return towards normal in the level of plasma alkaline phosphatase) and the dose of 1α-OHD₃ is not reduced appropriately. Prolonged hypercalcaemia should be avoided, particularly in chronic renal failure. Plasma calcium levels should be measured at weekly to monthly intervals depending on the progress of the patient. Frequent estimations are necessary in the early stages of treatment and later when there is evidence of bone healing. Plasma calcium levels should also be estimated regularly during the initial treatment of disorders without significant bone involvement, e.g. hypoparathyroidism.

Hypercalcaemia in conjunction with hyperphosphataemia increases the risk of metastatic calcifications. In diseases where hyperphosphataemia may occur, e.g. reduced kidney function, phosphate binding medicines should be used.

Patients concurrently taking barbiturates and other anticonvulsant medicines may require larger doses of 1α-OHD₃ to produce the desired effect, as these substances may induce the hepatic metabolising enzymes.

1α-OHD₃ should only be used during pregnancy and lactation if considered essential by the doctor.

ZODORAY contains arachis oil (peanut oil). Arachis oil may cause a severe allergic reaction in patients that are allergic to peanuts.

Patients with rare hereditary problems of fructose intolerance should not take ZODORAY. ZODORAY contains 1 mg of alcohol (ethanol) in each dosage unit which is equivalent to 1% v/v. The small amount of alcohol in ZODORAY will not have any noticeable effects.

Thiazide diuretics and calcium containing preparations: Concurrent use of thiazide diuretics or calcium containing preparations may enhance the risk of hypercalcaemia. Calcium levels should be monitored.

Other vitamin D containing preparations: Concurrent use of other vitamin D containing preparations may enhance the risk of hypercalcaemia. Use of multiple vitamin D analogues should be avoided.

Anticonvulsants: Anticonvulsants (e.g. barbiturates, phenytoin, carbamazepine or primidone) have enzyme-inducing effects resulting in an increased metabolism of alfacalcidol. Patients taking anticonvulsants may require larger doses of ZODORAY.

Magnesium-containing antacids and laxatives: Absorption of magnesium-containing antacids may be enhanced by ZODORAY, increasing the risk of hypermagnesaemia.

Aluminium-containing preparations: ZODORAY may increase the serum concentration of aluminium. Patients taking aluminium-containing preparations (e.g. aluminium hydroxide, sucralfate) should be monitored for signs of aluminium related toxicities.

Bile acid sequestrants: Concomitant oral administration of bile acid sequestrants such as cholestyramine may impair the intestinal absorption of ZODORAY. ZODORAY should be administered at least 1 hour before, or 4 to 6 hours after the intake of the bile acid sequestrant in order to minimise the potential risk of interaction.

Alfacalcidol should be used with caution for:

a) Patients concomitantly treated with digoxin as hypercalcaemia may lead to dysrhythmia in such patients.

b) Patients with nephrolithiasis

Pregnancy

ZODORAY should not be used in pregnancy. ZODORAY should not be used in the first trimester of pregnancy.

Hypercalcaemia may produce congenital disorders.

There are no adequate data from the use of ZODORAY in pregnant women. Studies in animals have shown reproductive toxicity. The potential risks for humans are unknown.

Breastfeeding

Women using ZODORAY should not breastfeed their babies. ZODORAY is suspected to be excreted into breast milk. Hypercalcaemia in the infant cannot be excluded. Because of inadequate data, breastfeeding is advised against during treatment with ZODORAY.

Fertility

There are no clinical studies on the effect of ZODORAY on fertility. A pre-clinical study did not show an effect on fertility in rats.

ZODORAY has no or negligible influence on the ability to drive or use machines.

a. Summary of the safety profile

The most frequently reported undesirable effects are hypercalcaemia and various skin reactions such as pruritus and rash, gastrointestinal pain/discomfort and hyperphosphataemia.

b. Tabulated summary of adverse reactions

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 “6.04 Adverse Drug Reactions Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8.

Not applicable.