Drugs List

Therapeutic Indications

Uses

Correction of calcium and phosphate metabolism in renal osteodystrophy
Osteoporosis - postmenopausal

Unlicensed Uses

Hypocalcaemia due to hypoparathyroidism
Treatment of rickets

Contraindications

Hypervitaminosis D
Hereditary fructose intolerance
Hypercalcaemia
Metastatic calcification

Precautions and Warnings

Children under 18 years
Immobilisation
Tissue calcification
Breastfeeding
Haemodialysis
Hyperparathyroidism
Pregnancy
Renal impairment

Regular haemodialysis increases risk of hypercalcaemia
Renal failure increases risk of hypercalcaemia
Tertiary hyperparathyroidism increases risk of hypercalcaemia
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Ensure patient has adequate fluid intake
Breastfeeding: Hypercalcaemia of infant possible if mother taking vitamin D
Breastfeeding: Monitor infant for systemic effects of treating the mother
Monitor serum calcium levels
Monitor serum creatinine
Monitor serum phosphate levels
Discontinue if hypercalcaemia occurs
Discontinue if serum creatinine rises to > 120 micro mol/l
Dosage of phosphate binding agents may need to be modified
Avoid other sources of vitamin D
Dietary restrictions should be maintained
Adequate daily intake of calcium essential

During dose titration serum calcium should be determined twice weekly.

Discontinue therapy if calcium levels rise to 1 mg/100 ml (250 micromol/l) above normal (9 to 11 mg/100 ml or 2250 to 2750 micromol/l) and do not resume until normal calcaemia ensues.

Plasma phosphate levels should be monitored in patients with renal failure because of the danger of ectopic calcification. Plasma phosphate levels should be maintained at the normal level (2 to 5 mg/100 ml or 0.65 to 1.62 mmol/l) by the oral administration of appropriate phosphate-binding agents and low phosphate diet.

The serum calcium times phosphate (Ca x P) product should not be allowed to exceed 70 mg squared/dl squared.

Patients with vitamin D-resistant rickets who are being treated with calcitriol must continue their oral phosphate therapy.

Possible stimulation of intestinal absorption of phosphate by calcitriol should be taken into account since this effect may modify the need for phosphate supplementation.

In patients that are switched from a long acting vitamin D preparation (e.g. ergocalciferol, colecalciferol) to calcitriol it may take several months for the level in the blood to return to the baseline value, so increasing the risk of hypercalcaemia.

Pregnancy and Lactation

Pregnancy

Calcitriol should be used with caution in pregnancy.

Reproductive toxicity studies in rats and dogs indicated that calcitriol at an oral dose of twice the usual human dosage for up to 6 months produced no or minimal adverse effects. A dose of 8 times the usual human dosage for up to 6 months produced moderate adverse effects, primarily due to prolonged hypercalcaemia. There is no evidence to suggest that vitamin D is teratogenic in humans even at very high doses.

Schaefer concludes that very high doses of vitamin D are contraindicated in pregnancy due to the risk of hypercalcaemia but where there is a documented maternal vitamin D deficiency, supplementation should be administered until maternal plasma concentrations return to normal levels. In such instances however, maternal and neonatal calcium and phosphate levels should be monitored regularly.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Calcitriol should be used with caution in breastfeeding.

Calcitriol is excreted in human breast milk. A direct relationship exists between maternal serum levels and the concentration in breast milk. Excessive maternal doses of calcitriol can cause hypercalcaemia and hypervitaminosis D in the breast-fed infant. If breast feeding is continued where the mother is taking calcitriol, the serum calcium levels of the mother and infant should be monitored.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Apathy
Cardiac arrhythmias
Constipation
Decreased appetite
Dehydration
Erythema
Growth retardation (children)
Headache
Hypercalcaemia
Hypersensitivity reactions
Muscle weakness
Nausea
Nocturia
Paralytic ileus
Polydipsia
Polyuria
Pruritus
Psychiatric disorders
Pyrexia
Rash
Sensory disturbances
Serum creatinine increased
Soft tissue calcification
Somnolence
Thirst
Urinary tract infections
Urticaria
Vomiting
Weight loss

Presentation

Oral formulations containing calcitriol

Drugs List

Therapeutic Indications

Uses

Correction of calcium and phosphate metabolism in renal osteodystrophy
Osteoporosis - postmenopausal

Unlicensed Uses

Hypocalcaemia due to hypoparathyroidism
Treatment of rickets

Dosage

Dose should be determined individually according to biological response, to prevent hypercalcaemia.

Adults

Children

Additional Dosage Information

Contraindications

Hypervitaminosis D
Hereditary fructose intolerance
Hypercalcaemia
Metastatic calcification

Precautions and Warnings

Children under 18 years
Immobilisation
Tissue calcification
Breastfeeding
Haemodialysis
Hyperparathyroidism
Pregnancy
Renal impairment

Regular haemodialysis increases risk of hypercalcaemia
Renal failure increases risk of hypercalcaemia
Tertiary hyperparathyroidism increases risk of hypercalcaemia
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Ensure patient has adequate fluid intake
Breastfeeding: Hypercalcaemia of infant possible if mother taking vitamin D
Breastfeeding: Monitor infant for systemic effects of treating the mother
Monitor serum calcium levels
Monitor serum creatinine
Monitor serum phosphate levels
Discontinue if hypercalcaemia occurs
Discontinue if serum creatinine rises to > 120 micro mol/l
Dosage of phosphate binding agents may need to be modified
Avoid other sources of vitamin D
Dietary restrictions should be maintained
Adequate daily intake of calcium essential

During dose titration serum calcium should be determined twice weekly.

Discontinue therapy if calcium levels rise to 1 mg/100 ml (250 micromol/l) above normal (9 to 11 mg/100 ml or 2250 to 2750 micromol/l) and do not resume until normal calcaemia ensues.

Plasma phosphate levels should be monitored in patients with renal failure because of the danger of ectopic calcification. Plasma phosphate levels should be maintained at the normal level (2 to 5 mg/100 ml or 0.65 to 1.62 mmol/l) by the oral administration of appropriate phosphate-binding agents and low phosphate diet.

The serum calcium times phosphate (Ca x P) product should not be allowed to exceed 70 mg squared/dl squared.

Patients with vitamin D-resistant rickets who are being treated with calcitriol must continue their oral phosphate therapy.

Possible stimulation of intestinal absorption of phosphate by calcitriol should be taken into account since this effect may modify the need for phosphate supplementation.

In patients that are switched from a long acting vitamin D preparation (e.g. ergocalciferol, colecalciferol) to calcitriol it may take several months for the level in the blood to return to the baseline value, so increasing the risk of hypercalcaemia.

Pregnancy and Lactation

Pregnancy

Calcitriol should be used with caution in pregnancy.

Reproductive toxicity studies in rats and dogs indicated that calcitriol at an oral dose of twice the usual human dosage for up to 6 months produced no or minimal adverse effects. A dose of 8 times the usual human dosage for up to 6 months produced moderate adverse effects, primarily due to prolonged hypercalcaemia. There is no evidence to suggest that vitamin D is teratogenic in humans even at very high doses.

Schaefer concludes that very high doses of vitamin D are contraindicated in pregnancy due to the risk of hypercalcaemia but where there is a documented maternal vitamin D deficiency, supplementation should be administered until maternal plasma concentrations return to normal levels. In such instances however, maternal and neonatal calcium and phosphate levels should be monitored regularly.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Calcitriol should be used with caution in breastfeeding.

Calcitriol is excreted in human breast milk. A direct relationship exists between maternal serum levels and the concentration in breast milk. Excessive maternal doses of calcitriol can cause hypercalcaemia and hypervitaminosis D in the breast-fed infant. If breast feeding is continued where the mother is taking calcitriol, the serum calcium levels of the mother and infant should be monitored.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Apathy
Cardiac arrhythmias
Constipation
Decreased appetite
Dehydration
Erythema
Growth retardation (children)
Headache
Hypercalcaemia
Hypersensitivity reactions
Muscle weakness
Nausea
Nocturia
Paralytic ileus
Polydipsia
Polyuria
Pruritus
Psychiatric disorders
Pyrexia
Rash
Sensory disturbances
Serum creatinine increased
Soft tissue calcification
Somnolence
Thirst
Urinary tract infections
Urticaria
Vomiting
Weight loss

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: March 2015.

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Summary of Product Characteristics: Rocaltrol 0.25mcg and 0.5mcg capsules. Roche Products Limited. Revised June 2014.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 22 August 2017