Drug Class Description
Vitamin D analogues (vitamins).

Generic Name
Calcitriol - nutrition

Drug Description
Each capsule contains either 0.25 or 0.5 microgram of calcitriol.

Presentation
Soft capsules.0.25 microgram: One length brown-orange to red-orange opaque and the other white to grey-yellow or grey-orange opaque.0.5 microgram: Both lengths brown-orange to red-orange opaque.

Indications
Rocaltrol is indicated for the correction of the abnormalities of calcium and phosphate metabolism in patients with renal osteodystrophy.Rocaltrol is also indicated for the treatment of established post-menopausal osteoporosis.

Adult Dosage
The dose of Rocaltrol should be carefully adjusted for each patient according to the biological response so as to avoid hypercalcaemia.The effectiveness of treatment depends in part on an adequate daily intake of calcium, which should be augmented by dietary changes or supplements if necessary. The capsules should be swallowed with a little water.AdultsRenal OsteodystrophyThe initial daily dose is 0.25 mcg of Rocaltrol. In patients with normal or only slightly reduced calcium levels, doses of 0.25 mcg every other day are sufficient. If no satisfactory response in the biochemical parameters and clinical manifestations of the disease is observed within 2 - 4 weeks, the daily dosage may be increased by 0.25 mcg at 2 - 4 week intervals. During this period, serum calcium levels should be determined at least twice weekly. Should the serum calcium levels rise to 1 mg/ 100ml (250 µmol/l) above normal (9 to 11 mg/100 ml or 2250 - 2750 µmol/l), or serum creatinine rises to > 120 µmol/l, treatment with Rocaltrol should be stopped immediately until normocalcaemia ensues. Most patients respond to between 0.5 mcg and 1.0 mcg daily. See section 4.5 for details of dose adjustments related to drug interactions.An oral Rocaltrol pulse therapy with an initial dosage of 0.1 mcg/kg/week split into two or three equal doses given at the end of the dialysis has been shown to be effective in patients with osteodystrophy refractory to continuous therapy. A maximum total cumulative dosage of 12 mcg per week should not be exceeded.Post-menopausal OsteoporosisThe recommended dose of Rocaltrol is 0.25 mcg twice daily.Serum calcium and creatinine levels should be determined at 1, 3 and 6 months and at 6 monthly intervals thereafter.

Child Dosage
Dosage in children has not been established.Rocaltrol capsules are for oral administration only.

Elderly Dosage
Clinical experience with Rocaltrol in elderly patients indicates that the dosage recommended for use in younger adults may be given without apparent ill-consequence.

Contra Indications
Rocaltrol should not be given to patients with hypercalcaemia or evidence of metastatic calcification. The use of Rocaltrol in patients with known hypersensitivity to calcitriol (or drugs of the same class) and any of the constituent excipients is contraindicated.Rocaltrol is contraindicated if there is evidence of vitamin D toxicity.Owing to the presence of sorbitol, patients with rare hereditary problems of fructose intolerance should not take this medicine.

Special Precautions
All other vitamin D compounds and their derivatives, including proprietary compounds or foodstuffs which may be “fortified” with vitamin D, should be withheld during treatment with Rocaltrol.If the patient is switched from a long acting vitamin D preparation (e.g. ergocalciferol or colecalciferol) to calcitriol, it may take several months for the level in the blood to return to the baseline value, thereby increasing the risk of hypercalcaemia.An abrupt increase in calcium intake as a result of changes in diet (e.g. increased consumption of dairy products) or uncontrolled intake of calcium preparations may trigger hypercalcaemia. Patients and families should be advised that strict adherence to prescribed diets is mandatory and they should be instructed on how to recognise the symptoms of hypercalcaemia.In patients with end-stage renal failure, treatment does not obviate the need to control plasma phosphate with phosphate-binding agents. Since Rocaltrol affects phosphate transport in the gut and bone, the dose of phosphate-binding agent may need to be modified. The value for serum calcium multiplied by phosphorus (Ca x P) should not be allowed to exceed 70 mg2/dl2 or 5.6 mmol2/l2.Immobilised patients, e.g. those who have undergone surgery, are particularly exposed to the risk of hypercalcaemia.Patients with normal renal function who are taking Rocaltrol should avoid dehydration. Adequate fluid intake should be maintained.

Interactions
Concomitant treatment with a thiazide diuretic increases the risk of hypercalcaemia. Calcitriol dosage must be determined with care in patients undergoing treatment with digitalis, as hypercalcaemia in such patients may precipitate cardiac arrhythmias.Vitamin D derivatives can increase magnesium absorption, although magnesium balance is generally not affected, owing to a compensatory increase in urinary excretion. It is therefore recommended that magnesium-containing drugs (e.g. antacids) are not taken by patients with chronic renal failure on dialysis during therapy with Rocaltrol since, under these circumstances, hypermagnesaemia could occur.Administration of enzyme inducers such as phenytoin or phenobarbital may lead to increased metabolism and hence reduced serum concentrations of calcitriol. Therefore higher doses of calcitriol may be necessary if these drugs are administered simultaneously.A relationship of functional antagonism exists between vitamin D analogues, which promote calcium absorption, and corticosteroids, which inhibit it.Colestyramine can reduce intestinal absorption of fat-soluble vitamins and therefore may impair intestinal absorption of calcitriol.

Adverse Reactions
The number of adverse effects reported from clinical use of Rocaltrol over a period of 15 years in all indications is very low with each individual effect, including hypercalcaemia, occurring rarely ( 0.001%).Hypercalcaemia and hypercalcuria are the major side effects of Rocaltrol and indicate excessive dosage. Patients with tertiary hyperparathyroidism, renal failure, or on regular haemodialysis are particularly prone to develop hypercalcaemia. The clinical features of hypercalcaemia include anorexia, constipation, nausea, vomiting, headache, weakness, apathy and somnolence. More severe manifestations may include fever, thirst/polydipsia, dehydration, polyuria, nocturia, abdominal pain, paralytic ileus, cardiac arrhythmias and psychiatric disturbances. Rarely, overt psychosis and metastatic calcification (particularly nephrocalcinosis and renal stones) may occur. The relatively short biological half-life of Rocaltrol permits rapid elimination of the compound when treatment is stopped and hypercalcaemia will recede within 2 - 7 days. This rate of reversal of biological effects is more rapid than when other vitamin D derivatives are used.In patients with normal renal function, chronic hypercalcaemia may be associated with an increase in serum creatinine.Mild, non-progressive and reversible elevations in levels of liver enzymes (SGOT, SGPT) have been noted in a few patients treated with Rocaltrol, but no pathological changes in the liver have been reported.Hypersensitivity reactions (pruritus, rash, urticaria and, very rarely, severe erythematous skin disorders) may occur in susceptible individuals.

Manufacturer
Roche Products Limited

Drug Availability
(POM)

Updated
21 May 2009