9.6.4 Vitamin D
Note The term Vitamin D is used for a range of compounds which possess the property of preventing or curing rickets. They include ergocalciferol (calciferol, vitamin D2), colecalciferol (vitamin D3), dihydrotachysterol, alfacalcidol (1α-hydroxycholecalciferol), and calcitriol (1,25-dihydroxycholecalciferol).
Simple vitamin D deficiency can be prevented by taking an oral supplement of only 10 micrograms (400 units) of ergocalciferol (calciferol, vitamin D2) or colecalciferol (vitamin D3) daily. Vitamin D deficiency can occur in people whose exposure to sunlight is limited and in those whose diet is deficient in vitamin D. In these individuals, ergocalciferol or colecalciferol in a dose of 20 micrograms (800 units) daily by mouth may be given to treat vitamin D deficiency; higher doses may be necessary for severe deficiency. Patients who do not respond should be referred to a specialist.
Preparations containing calcium with colecalciferol are available for the management of combined calcium and vitamin D deficiency, or for those at high risk of deficiency (see also Osteoporosis and Calcium Supplements).
Vitamin D deficiency caused by intestinal malabsorption or chronic liver disease usually requires vitamin D in pharmacological doses, such as ergocalciferol tablets up to 1 mg (40 000 units) daily; the hypocalcaemia of hypoparathyroidism often requires doses of up to 2.5 mg (100 000 units) daily in order to achieve normocalcaemia.
Vitamin D requires hydroxylation by the kidney to its active form, therefore the hydroxylated derivatives alfacalcidol or calcitriol should be prescribed if patients with severe renal impairment require vitamin D therapy. Calcitriol is also licensed for the management of postmenopausal osteoporosis.
Paricalcitol, a synthetic vitamin D analogue, is licensed for the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure (section 9.5.1.2).
Important. All patients receiving pharmacological doses of vitamin D should have their plasma-calcium concentration checked at intervals (initially once or twice weekly) and whenever nausea or vomiting occur.
ERGOCALCIFEROL
(Calciferol, Vitamin D2)
Indications see notes above
Cautions take care to ensure correct dose in infants; monitor plasma-calcium concentration in patients receiving high doses and in renal impairment (see notes above); interactions: Appendix 1 (vitamins)
Contra-indications hypercalcaemia; metastatic calcification
Pregnancy high doses teratogenic in animals but therapeutic doses unlikely to be harmful
Breast-feeding caution with high doses; may cause hypercalcaemia in infant — monitor serum-calcium concentration
Side-effects symptoms of overdosage include anorexia, lassitude, nausea and vomiting, diarrhoea, constipation, weight loss, polyuria, sweating, headache, thirst, vertigo, and raised concentrations of calcium and phosphate in plasma and urine
With calcium
For prescribing information on calcium, see section 9.5.1.1
Calcium and Ergocalciferol (Non-proprietary)
(Calcium and Vitamin D)
Tablets, calcium lactate 300 mg, calcium phosphate 150 mg (calcium 97 mg or Ca2+ 2.4 mmol), ergocalciferol 10 micrograms (400 units). Net price 28-tab pack = £11.26. Counselling, crush before administration or may be chewed
Pharmacological strengths
Note The BP directs that when calciferol is prescribed or demanded, colecalciferol or ergocalciferol should be dispensed or supplied
Ergocalciferol (Non-proprietary)
Tablets, ergocalciferol 250 micrograms (10 000 units), net price 100 = £21.99; 1.25 mg (50 000 units), 100 = £30.34
Note May be difficult to obtain
Important When the strength of the tablets ordered or prescribed is not clear, the intention of the prescriber with respect to the strength (expressed in micrograms or milligrams per tablet) should be ascertained.
Injection, for intramuscular use only, ergocalciferol, 7.5 mg (300 000 units)/mL in oil, net price 1-mL amp = £9.35, 2-mL amp = £10.84
Note Other formulations of ergocalciferol are available from ‘special-order’ manufacturers or specialist importing companies
ALFACALCIDOL
(1α-Hydroxycholecalciferol)
Indications see notes above
Cautions see under Ergocalciferol; also nephrolithiasis
Contra-indications see under Ergocalciferol
Pregnancy see under Ergocalciferol
Breast-feeding see under Ergocalciferol
Side-effects see under Ergocalciferol; also rarely nephrocalcinosis, pruritus, rash, and urticaria
Dose
By mouth or by intravenous injection over 30 seconds, ADULT and CHILD over 20 kg, initially 1 microgram daily (elderly 500 nanograms), adjusted to avoid hypercalcaemia; maintenance, usually 0.25–1 microgram daily; NEONATE and PRETERM NEONATE initially 50–100 nanograms/kg daily, CHILD under 20 kg initially 50 nanograms/kg daily
Alfacalcidol (Non-proprietary) 
Capsules, alfacalcidol 250 nanograms, net price 30-cap pack = £2.67; 500 nanograms 30-cap pack = £5.80; 1 microgram 30-cap pack = £5.87
One-Alpha® (LEO) 
Capsules, alfacalcidol 250 nanograms (white), net price 30-cap pack = £3.37; 500 nanograms (red), 30-cap pack = £6.27; 1 microgram (brown), 30-cap pack = £8.75
Excipients include sesame oil
Oral drops, sugar-free, alfacalcidol 2 micrograms/mL (1 drop contains approx. 100 nanograms), net price 10 mL = £21.30
Excipients include alcohol
Note The concentration of alfacalcidol in One-Alpha® drops is 10 times greater than that of the former preparation One-Alpha® solution.
Injection, alfacalcidol 2 micrograms/mL, net price 0.5-mL amp = £2.16, 1-mL amp = £4.11
Excipients include alcohol, propylene glycol (caution in neonates, see Excipients)
Note Shake ampoule for at least 5 seconds before use
CALCITRIOL
(1,25-Dihydroxycholecalciferol)
Indications see notes above
Cautions see under Ergocalciferol; monitor plasma calcium, phosphate, and creatinine during dosage titration
Contra-indications see under Ergocalciferol
Pregnancy see under Ergocalciferol
Breast-feeding see under Ergocalciferol
Side-effects see under Ergocalciferol
Dose
By mouth, renal osteodystrophy, initially 250 nanograms daily, or on alternate days (in patients with normal or only slightly reduced plasma-calcium concentration), increased if necessary in steps of 250 nanograms at intervals of 2–4 weeks; usual dose 0.5–1 microgram daily; CHILD not established
Established postmenopausal osteoporosis, 250 nanograms twice daily (monitor plasma-calcium concentration and creatinine, consult product literature)
Calcitriol (Non-proprietary) 
Capsules, calcitriol 250 nanograms, net price 30-cap pack = £5.41, 100-cap pack = £19.15; 500 nanograms, 30-cap pack = £9.68, 100-cap pack = £25.76
COLECALCIFEROL
(Cholecalciferol, vitamin D3)
Indications see notes above
Cautions see under Ergocalciferol
Contra-indications see under Ergocalciferol
Pregnancy see under Ergocalciferol
Breast-feeding see under Ergocalciferol
Side-effects see under Ergocalciferol
Fultium-D3® (Internis) 
Capsules, colecalciferol 20 micrograms (800 units) (blue), net price 30-cap pack = £3.60, 90-cap pack = £10.80; 80 micrograms (3200 units) (green), 30-cap pack = £13.32, 90-cap pack = £39.96. Label: 25
Excipients include arachis (peanut) oil
InVita D3® (Consilient) 
Oral solution, colecalciferol 625 micrograms (25 000 units)/mL, net price 3 × 1-mL unit amp = £4.45. Label: 21
Note May be mixed with a small amount of cold or lukewarm food immediately before administration
Colecalciferol
Various formulations available from ‘special-order’ manufacturers or specialist importing companies
With calcium
For prescribing information on calcium, see section 9.5.1.1
Accrete D3® (Internis)
Tablets, f/c, calcium carbonate 1.5 g (calcium 600 mg or Ca2+ 15 mmol), colecalciferol 10 micrograms (400 units), net price 60-tab pack = £2.95
Adcal-D3® (ProStrakan)
Tablets (chewable) (lemon or tutti-frutti flavour), calcium carbonate 1.5 g (calcium 600 mg or Ca2+ 15 mmol), colecalciferol 10 micrograms (400 units), net price 56-tab pack = £3.65, 112-tab pack = £7.49. Label: 24
Dissolve (effervescent tablets), lemon flavour, calcium carbonate 1.5 g (calcium 600 mg or Ca2+ 15 mmol), colecalciferol 10 micrograms (400 units), net price 56-tab pack = £5.99. Label: 13
Caplets (= tablets), f/c, calcium carbonate 750 mg (calcium 300 mg or Ca2+ 7.5 mmol), colecalciferol 5 micrograms (200 units), net price 112-tab pack = £3.65
Cacit® D3 (Warner Chilcott)
Granules, effervescent, lemon flavour, calcium carbonate 1.25 g (calcium 500 mg or Ca2+ 12.5 mmol), colecalciferol 11 micrograms (440 units)/sachet, net price 30-sachet pack = £4.06. Label: 13
Calceos® (Galen)
Tablets (chewable), lemon flavour, calcium carbonate 1.25 g (calcium 500 mg or Ca2+ 12.5 mmol), colecalciferol 10 micrograms (400 units), net price 60-tab pack = £3.58. Label: 24
Calcichew-D3® (Takeda)
Calcichew-D3® Tablets (chewable), orange flavour, calcium carbonate 1.25 g (calcium 500 mg or Ca2+ 12.5 mmol), colecalciferol 5 micrograms (200 units), net price 100-tab pack = £7.68. Label: 24
Excipients include aspartame (section 9.4.1)
Calcichew-D3® Forte Tablets (chewable), lemon flavour, calcium carbonate 1.25 g (calcium 500 mg or Ca2+ 12.5 mmol), colecalciferol 10 micrograms (400 units), net price 60-tab pack = £4.24, 100-tab pack = £7.08. Label: 24
Excipients include aspartame (section 9.4.1)
Calcichew-D3® 500 mg/400 unit caplets, f/c, lemon flavour, calcium carbonate providing calcium 500 mg (Ca2+ 12.5 mmol), colecalciferol 10 micrograms (400 units), net price 100-tab pack = £7.43
Excipients include propylene glycol, see Excipients
Calfovit D3® (Menarini)
Powder, lemon flavour, calcium phosphate 3.1 g (calcium 1.2 g or Ca2+ 30 mmol), colecalciferol 20 micrograms (800 units), net price 30-sachet pack = £4.32. Label: 13, 21
Kalcipos-D® (Meda) 
Tablets (chewable), calcium carbonate providing calcium 500 mg (Ca2+ 12.5 mmol), colecalciferol 20 micrograms (800 units), net price 30-tab pack = £4.21. Label: 24
Natecal D3® (Chiesi)
Tablets (chewable), (aniseed, peppermint, and molasses flavour), calcium carbonate 1.5 g (calcium 600 mg or Ca2+ 15 mmol), colecalciferol 10 micrograms (400 units), net price 60-tab pack = £3.63. Label: 24
Excipients include aspartame (section 9.4.1)
Colecalciferol formulations [unlicensed]
Available from ‘special-order’ manufacturers or specialist importing companies
DIHYDROTACHYSTEROL
Indications see notes above
Cautions see under Ergocalciferol
Contra-indications see under Ergocalciferol
Pregnancy see under Ergocalciferol
Breast-feeding see under Ergocalciferol
Side-effects see under Ergocalciferol
AT 10® (Intrapharm)
Oral solution, dihydrotachysterol 250 micrograms/mL. Net price 15-mL dropper bottle = £22.87
Excipients include arachis (peanut) oil
Dose acute, chronic, and latent forms of hypocalcaemic tetany due to hypoparathyroidism, consult product literature
PARICALCITOL
Indications see under preparations below
Cautions monitor plasma calcium and phosphate during dose titration and at least monthly when stabilised; monitor parathyroid hormone concentration; interactions: Appendix 1 (vitamins)
Contra-indications see under Ergocalciferol
Pregnancy toxicity in animal studies — manufacturer advises avoid unless potential benefit outweighs risk; see also under Ergocalciferol
Breast-feeding manufacturer advises caution — no information available; see also under Ergocalciferol
Side-effects see under Ergocalciferol; also dyspepsia, taste disturbance, breast tenderness, acne, pruritus, and rash
Dose
Consult product literature
Zemplar® (AbbVie) 
Capsules, paricalcitol 1 microgram (grey), net price 28-cap pack = £69.44; 2 micrograms (orange-brown), 28-cap pack = £138.88; 4 micrograms (gold), 28-cap pack = £277.76
For prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure
Injection, paricalcitol 5 micrograms/mL, net price 1-mL amp = £12.40, 2-mL amp = £24.80. For injection via haemodialysis access
Excipients include propylene glycol, see Excipients
For prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure in patients on haemodialysis
9.6.5 Vitamin E
(Tocopherols)
The daily requirement of vitamin E has not been well defined but is probably about 3 to 15 mg daily. There is little evidence that oral supplements of vitamin E are essential in adults, even where there is fat malabsorption secondary to cholestasis. In young children with congenital cholestasis, abnormally low vitamin E concentrations may be found in association with neuromuscular abnormalities, which usually respond only to the parenteral administration of vitamin E.
Vitamin E has been tried for various other conditions but there is little scientific evidence of its value.
ALPHA TOCOPHERYL ACETATE
Cautions predisposition to thrombosis; increased risk of necrotising enterocolitis in neonate weighing less than 1.5 kg; interactions: Appendix 1 (vitamins)
Pregnancy no evidence of safety of high doses
Breast-feeding excreted in milk; minimal risk, although caution with large doses
Side-effects diarrhoea and abdominal pain with doses more than 1 g daily
Vitamin E Suspension (Non-proprietary)
Suspension, alpha tocopheryl acetate 500 mg/5 mL. Net price 100 mL = £42.12
Dose malabsorption in cystic fibrosis, 100–200 mg daily; CHILD 1 month–1 year 50 mg daily; 1–12 years, 100 mg daily
Malabsorption in abetalipoproteinaemia, ADULT and CHILD 50–100 mg/kg daily
Malabsorption in chronic cholestasis and severe liver disease, CHILD see BNF for Children
Note Tablets containing tocopheryl acetate are available from ‘special-order’ manufacturers or specialist importing companies
ALPHA TOCOPHEROL
Indications vitamin E deficiency because of malabsorption in congenital or hereditary chronic cholestasis
Cautions predisposition to thrombosis; interactions: Appendix 1 (Vitamin E)
Contra-indications preterm neonates
Hepatic impairment manufacturer advises caution and monitor closely — no information available
Renal impairment manufacturer advises caution and monitor closely; risk of renal toxicity due to polyethylene glycol content
Pregnancy manufacturer advises caution, no evidence of harm in animal studies
Breast-feeding manufacturer advises use only if potential benefit outweighs risk — no information available
Side-effects diarrhoea; less commonly asthenia, headache, disturbances in serum-potassium and serum-sodium concentrations, alopecia, pruritus, and rash
Vedrop® (Orphan Europe) 
Oral solution, yellow, D-alpha tocopherol (as tocofersolan) 50 mg/mL, net price 20 mL = £54.55, 60 mL = £163.65 (all with oral syringe)
Note Tocofersolan is a water-soluble form of D-alpha tocopherol
Dose CHILD under 18 years, 17 mg/kg daily, adjusted as necessary
9.6.6 Vitamin K
Vitamin K is necessary for the production of blood clotting factors and proteins necessary for the normal calcification of bone.
Because vitamin K is fat soluble, patients with fat malabsorption, especially in biliary obstruction or hepatic disease, may become deficient. Menadiol sodium phosphate is a water-soluble synthetic vitamin K derivative that can be given orally to prevent vitamin K deficiency in malabsorption syndromes.
Oral coumarin anticoagulants act by interfering with vitamin K metabolism in the hepatic cells and their effects can be antagonised by giving vitamin K; for advice on the use of vitamin K in haemorrhage, see section 2.8.2.
Vitamin K deficiency bleeding Neonates are relatively deficient in vitamin K and those who do not receive supplements of vitamin K are at risk of serious bleeding including intracranial bleeding. The Chief Medical Officer and the Chief Nursing Officer have recommended that all newborn babies should receive vitamin K to prevent vitamin K deficiency bleeding (previously termed haemorrhagic disease of the newborn). An appropriate regimen should be selected after discussion with parents in the antenatal period.
Vitamin K (as phytomenadione) 1 mg may be given by a single intramuscular injection at birth; this prevents vitamin K deficiency bleeding in virtually all babies. For preterm neonates, see BNF for Children.
Alternatively, in healthy babies who are not at particular risk of bleeding disorders, vitamin K may be given by mouth, and arrangements must be in place to ensure the appropriate regimen is followed. Two doses of a colloidal (mixed micelle) preparation of phytomenadione 2 mg should be given by mouth in the first week, the first dose being given at birth and the second dose at 4–7 days. For exclusively breast-fed babies, a third dose of colloidal phytomenadione 2 mg is given by mouth at 1 month of age; the third dose is omitted in formula-fed babies because formula feeds contain adequate vitamin K. An alternative regimen is to give one dose of phytomenadione 1 mg by mouth at birth (using the contents of a phytomenadione capsule, see preparation below) to protect from the risk of vitamin K deficiency bleeding in the first week; for exclusively breast-fed babies, further doses of phytomenadione 1 mg are given by mouth (using the contents of a phytomenadione capsule) at weekly intervals for 12 weeks.
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