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Drug Details

CALCIJEX

• Drug Class Description
  Vitamin D analogues (vitamins).
• Generic Name
  Calcitriol
• Presentation
  Solution for Injection
• Description
  Calcijex 1 microgram/ml Solution for Injection
• Indications
  Calcijex is indicated in the management of hypocalcaemia in patients undergoing dialysis for chronic renal failure. It has been shown to significantly reduce elevated parathyroid hormone (PTH) levels. Reduction of PTH has been shown to result in an improvement in renal osteodystrophy.
• Adult Dosage
  

  The optimal dose of Calcijex must be carefully determined for each patient.

  The effectiveness of Calcijex therapy is predicted on the assumption that each patient is receiving an adequate and appropriate daily intake of calcium. To ensure that each patient receives an adequate daily intake of calcium, the physician should either prescribe a calcium supplement, or instruct the patient in proper dietary measures.

  The recommended initial dose of Calcijex is 0.50 microgram (approximately 0.01 microgram/kg) administered three times weekly, approximately every other day. Calcijex can be administered as a bolus dose intravenously through the catheter at the end of haemodialysis. If a satisfactory response in the biochemical parameters and clinical manifestations of the disease state is not observed, the dose may be increased by 0.25 to 0.50 microgram increments at two to four week intervals. During this titration period, serum calcium and phosphate levels should be obtained at least twice weekly, and if hypercalcaemia is noted, or a serum calcium times phosphate greater than 7-8 mmol/l is noted, the drug should be immediately discontinued until these parameters are normal. Then the Calcijex dose should be reinitiated at a lower dose. Most patients undergoing haemodialysis respond to doses of between 0.5 and 3.0 microgram three times per week. Incremental dosing must be individualised and commensurate with PTH, serum calcium and phosphorus levels.

  Dialysis patients with moderate to severe secondary hyperparathyroidism

  Based on limited data from clinical trials with dialysis patients with moderate to severe secondary hyperparathyroidism, an initial dose, depending on the severity of secondary hyperparathyroidism, of 1.0 to 2.0 microgram administered three times weekly approximately every other day may be considered in this group of patients. Doses as small as 0.5 microgram and as large as 4.0 microgram thrice weekly have been used as an initial dose in this group, depending on the severity of the hyperparathyroidism. If a satisfactory response in the biochemical parameters and clinical manifestations of the disease state is not observed, the dose may be increased by 0.25 to 0.5 microgram at two to four week intervals. Incremental dosing from 0.25 microgram to 2.0 microgram has been used and maximal doses up to 8 microgram three times per week have been reported in a small number of patients with severe secondary hyperparathyroidism. Close biochemical monitoring and other advice detailed above are essential during therapy, in particular during dose titration. Doses may need to be reduced as the PTH levels decrease in response to the therapy. Parathyroidectomy may be considered in patients with severe secondary hyperparathroidism, refractory to all standard treatment.

  Higher doses of Calcijex may be required for patients taking barbiturates or anticonvulsants as these may reduce its effects. The effects of Calcijex may be counteracted by corticosteroids.

  Parenteral drug products such as Calcijex should be inspected visually for particulate matter prior to administration. Although calcitriol itself is a colourless, crystalline compound, the sodium ascorbate added as an antioxidant in Calcijex is white or very faintly yellow, and can turn yellow as it combines with oxygen.

  Calcijex should be drawn up into a plastic 1ml tuberculin syringe and administered at a bolus dose intravenously at the end of dialysis. It may be administered through the catheter at the end of haemodialysis.

• Child Dosage
  

  Safety and efficacy of Calcijex in children have not be established.

  The use of Calcijex in paediatric patients aged between 9 and 18 years of age was investigated in a clinical trial in paediatric end stage renal disease patients on haemodialysis.

• Contra Indications
  

  Calcijex should not be given to patients with hypercalcaemia or evidence of vitamin D toxicity.

  This drug is contraindicated in patients with previous hypersensitivity to calcitriol or any of its excipients.

• Special Precautions
  

  General

  Excessive dosage of Calcijex induces hypercalcaemia, and in some instances hypercalciuria; therefore, early in treatment during dosage adjustment, serum calcium and phosphate should be determined at least twice weekly. Should hypercalcaemia develop, the drug should be discontinued immediately.

  Calcijex should be given cautiously to patients on digitalis, because hypercalcaemia in such patients may precipitate cardiac arrhythmias.

  Adynamic bone disease may develop if PTH levels are suppressed to abnormal levels. Monitoring of the development of adynamic bone disease can be performed using bone biopsies, or more simply via measurement of PTH levels. The use of bone biopsies to monitor the development of adynamic bone disease is appropriate if the biopsies are being performed primarily for other diagnostic reasons. Otherwise PTH levels may replace a bone biopsy for this purpose. It PTH levels fall below the recommended target range in patients treated with Calcijex, the Calcijex dose should be reduced or therapy discontinued. Discontinuation of Calcijex therapy may result in rebound effect, therefore, appropriate titration downward to a maintenance dose is recommended.

  Since calcitriol is the most potent metabolite of vitamin D available, vitamin D and its derivatives should be withheld during treatment.

  In patients undergoing dialysis who have high serum phosphate levels, appropriate serum phosphate binders should be used. Aluminium containing phosphate binders should not be used except in exceptional circumstances.

  Low calcium dialysis fluids may be helpful in patients who develop hypercalcaemia whilst taking calcium-based phosphate binders in combination with vitamin D analogues.

  Overdosage of any form of vitamin D is dangerous. Progressive hypercalcaemia due to overdosage of vitamin D and its metabolites may be so severe as to require emergency attention. Chronic hypercalcaemia can lead to generalised vascular calcification, nephrocalcinosis and other soft tissue calcification. The serum calcium times phosphate (Ca x P) product should not be allowed to exceed 7 - 8. Radiographic evaluation of suspects anatomical regions may be useful in the early detection of this condition.

  Information for the Patient

  The patient should be informed about adherence to instructions about diet and calcium supplementation and avoidance of the use of unapproved non-prescription drugs, including magnesium-containing antacids. Patients should be also be carefully informed about the symptoms of hypercalcaemia.

  Essential Laboratory Tests

  Serum calcium, phosphate, magnesium and alkaline phosphatase and 24-hour urinary calcium and phosphate should be determined periodically. During the initial phase of the medication, serum calcium and phosphate should be determined more frequently (twice weekly).

  Renal Transplantation

  The rate of bone loss can be excessive and may exceed 5% per year in the immediate post-transplant period. Recommendations for treating post-transplant bone loss with calcitriol have not been established.

• Interactions
  

  Magnesium-containing antacids and Calcijex should not be used concomitantly, because such use may lead to the development of hypermagnesaemia.

  Concurrent use of vitamin D analogs and cardiac glycosides may result in cardiac arrhythmias.

  The effects of vitamin D may be reduced in patients taking barbiturates or anticonvulsants.

  Corticosteroids may counteract the effect of vitamin D analogs.

• Adverse Drug Reactions
  

  Adverse effects of Calcijex are, in general, similar to those encountered with excessive vitamin D intake. The early and late signs and symptoms of vitamin D intoxication associated with hypercalcaemia include :

  Early

  Weakness, headaches, somnolence, nausea, vomiting, dry mouth, constipation, muscle pain, bone pain and metallic taste.

  Late

  Polyuria, polydipsia, anorexia, weight loss, nocturia, conjunctivitis (calcific), pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolaemia, elevated SGOT and SGPT, ectopic calcification, hypertension, cardiac arrhythmias and, rarely, overt psychosis.

  Rare cases of hypersensitivity reactions have been reported including anaphylaxis and localised redness at the injection site.