Product characteristics and clinical use

Vitamin D compounds are used in the treatment and prevention of vitamin D deficiency states and hypocalcaemia in disorders such as hypoparathyroidism and secondary hyperparathyroidism.

The term vitamin D is used for a range of compounds including:

• ergocalciferol (vitamin D2)
• colecalciferol (vitamin D3)
• alfacalcidol (1α-hydroxycholecalciferol)
• calcitriol (1,25- dihydroxycholecalciferol)

Available formulations

Many forms and analogues of vitamin D are available. The Electronic Medicines Compendium (eMC) provides a list of Vitamin D products available in the UK and details associated licensed indications. Other products containing vitamin D are available without a UK licence.

Choice of formulation

Choice of product depends on the indication and the relative properties of the available agents.

Diet or cultural requirements

Patients may be on a specific product because of diet or cultural requirements. Information on choosing an oral vitamin D preparation for vegetarians or vegans is available.

Renal impairment

Vitamin D requires hydroxylation by the kidney to its active form; alfacalcidol and calcitriol are active metabolites of vitamin D which do not require hydroxylation by the kidney.  Considerations related to the individuals renal impairment will need to be made when choosing a vitamin D product.

Risk

The number of available products has resulted in variability of clinical guidance in recommended reference sources and clinical use.  Inconsistent practice across the UK leads to a risk of confusion among prescribers regarding the most appropriate product to prescribe; which in turn could lead to inadvertent over administration or sub optimal therapy.

Mitigation

Rationalise the products used in local/regional guidelines and formularies to limit the risk of confusion between products.

Ensure clear documentation of the clinical use and approved medicinal product name at the point of prescribing and at all transfers of care to limit the risk of incorrect formulations being inadvertently chosen.

Units of measurement

The active ingredient of vitamin D in products may be expressed either as metric or international units.  Alfacalcidol may be expressed as both micrograms and nanograms in reference sources and clinical guidelines.

Risk

Potential confusion around the unit of measurement (IU or metric) for vitamin D preparations.

Potential confusion in the unit of measurement (microgram or nanogram) used for alfacalcidol

Mitigation

Ensure local clinical guidelines/protocols, prescribing systems and formularies are consistent in the units used to express vitamin D.

When prescribing, validating or dispensing vitamin D, in particular alfacalcidol, be aware of differences in how the product is expressed.

When prescribing or documenting the strength of Vitamin D avoid the use of abbreviations, particularly if handwritten, and write the word units in full

When the strength of the product prescribed or ordered is not clear, the intention of instruction with  respect to the strength should be ascertained.

Dose, duration and frequency

Dosage should be individualised for each patient based on indication, patent specific parameters and response.

There is a wide range of doses used for different clinical indications and a number of different treatment regimens recommended in literature. Treatment regimens include both daily, weekly and monthly administration frequencies.

Key reference sources may not include all prescribing regimens

Upper limit

There are upper limits for daily intake considered safe for most individuals which are detailed in the NHS Health A-Z document for Vitamin D

These upper limits may not apply to individuals with medical disorders that predispose to hypercalcaemia.

Doses higher than the recommended upper limit may be used in patients with Vitamin D deficiency caused by intestinal malabsorption or chronic liver disease and in the treatment of hypocalcaemia of hypoparathroidism.

Loading dose regimens

Where rapid correction of vitamin D deficiency is required, treatment may be based on fixed loading doses (high dose) for a limited duration of time, followed by regular maintenance (low dose) therapy.  Daily doses used in loading dose regimens are higher than the recommended upper limit, but are used for a short defined duration.

Loading dose regimens for treatment of vitamin D deficiency vary in recommended doses and durations.  Example regimens given in the NICE guidance Vitamin D deficiency in adults for colecalciferol and ergocalciferol do not exceed a cumulative total of 300,000 International Units. NICE guidance Vitamin D deficiency in children provide example loading dose regimens for children and infants

Risk

Confusion related to the indication, clinical guidance and therapeutic goals of vitamin D may lead to incorrect doses or frequencies being used, which in turn could lead to inadvertent over administration with associated toxicity, or sub optimal therapy.

Known examples of harm include:

• Prescribing daily high doses instead of the intended weekly/monthly frequency or twice daily instead of twice weekly
• Prescribing loading dose regimen higher than a cumulative total of 300,000 International Units of colecalciferol or ergocalciferol in adults
• Poor communication of intended duration of therapy, particularly at transfers of care, leading to loading doses being continued for longer than intended
• Inadvertent prescribing of acute regimens (high dose) rather than maintenance (low dose) regimens at transfers of care, or vice versa.  Failure to perform adequate medicines reconciliation may contribute to this risk
• Prescribing oral doses in addition to intramuscular therapy.
• Unclear documentation of the intended frequency on medicines administration charts leading e.g. not crossing off the days a dose is not to be given leading to over administration
• A reliance on templates in electronic dispensing systems for frequency instructions leading to errors on the medication label at the dispensing stage
• Transcribing errors with new medication charts or at transfers of care

Mitigation

Where possible standardise practice for vitamin D therapy; rationalise product range and dose regimens used within prescribing systems and local/regional treatment protocols.

Ensure prescriptions for vitamin D are reviewed and consideration given to the indication, duration and where possible plasma calcium levels to provide assurance that the dose and frequency is appropriate for the individual patient.  Any concerns, in particular doses above the usual upper limit, should be queried with the prescriber.

Ensure clear documentation and communication of intended dose, frequency and duration of treatment at the point of prescribing and at all transfers of care.  This includes:

• intended “stop dates” for loading regimens documented and communicated. Use of electronic medication records can support clear communication.
• intended review date for patients administered an annual depot vitamin D dose
• where a review/stop date for a loading dose is not clear this should be clarified and documented
• intended frequency when using medication administration charts; days where a dose is not to be administered should be clearly crossed off
• prudent use of electronic prescribing functionality; use of order sets to identify and support loading regimens vs maintenance regimens

Ensure dispensing systems are set up to support users in choosing the correct dose and frequency.

Ensure the patient/carer is involved where possible; counsel the patient/carer on the intended duration of loading regimens and when a switch to a lower maintenance dose should be undertaken.  Patients/carers should be aware of the indication for their vitamin D therapy.

Monitoring

All patients receiving pharmacological doses of vitamin D should have their plasma-calcium concentration checked at appropriate intervals relative to the indication and dosage, or where clinical symptoms indicate.

Symptoms of toxicity

Vitamin D is the most likely of all vitamins to cause overt toxicity; this is rarely seen unless the vitamin D dose is very high.

Excessive intake leads to hypercalcaemia and its associated effects including apathy, anorexia, constipation, diarrhoea, dry mouth, headache, nausea, vomiting, thirst, and weakness. Later symptoms are often associated with calcification of soft tissues and include bone pain, cardiac arrhythmias, hypertension, renal damage, psychosis (rare) and weight loss.

Treatment of toxicity

Treatment of toxicity requires stopping all intake of supplementary vitamin D and clinical assessment by an appropriate medical professional.

Risk

Failure to recognise the associated risk of vitamin D toxicity and awareness of actions required when patients on vitamin D therapy present with high plasma calcium levels may lead to patient harm.

Mitigation

Ensure patients on vitamin D therapy receive adequate monitoring. Clear documentation and communication of a clinically appropriate monitoring frequency may support early recognition of toxicity.

Counselling patients on the symptoms of vitamin D toxicity may promote early identification of toxicity.

Ensure healthcare professionals responsible for clinical reviews of patients on vitamin D therapy are aware of acceptable plasma calcium levels for their patient and recommended actions to take following identification of elevated calcium levels.

Acknowledgments

Information on prevalent risks associated with using vitamin D was provided by the Patient Safety Team at NHS England.

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