Vitamin D (cholecalciferol) is the sunshine vitamin, essential for absorbing calcium and keeping bones strong. Deficiency causes rickets in children and osteomalacia/osteoporosis in adults.
Also known as: Colecalciferol, Vitamina D3
Calcitriol + cholecalciferol: additive vitamin D effect with risk of hypercalcaemia.
Calcitriol (1,25-dihydroxycholecalciferol) is the active form of vitamin D; cholecalciferol (D3) is converted in the body to calcitriol. Concomitant use sums the effects on intestinal calcium absorption and can cause hypercalcaemia, hypercalciuria and, if prolonged, nephrocalcinosis and renal impairment. In patients receiving both (e.g., chronic kidney disease with maintenance D3 and active calcitriol), monitor serum calcium, urinary calcium and renal function, and reduce or stop one form if serum calcium rises above the limit.
Calcitriol + vitamin D3: additive vitamin D effect with risk of hypercalcaemia. Monitor serum calcium.
Both raise serum calcium; the combination may exceed the therapeutic threshold.
Serum calcium (Ca × P).
Symptomatic hypercalcaemia (nausea, confusion, nephrolithiasis).
Avoid the combination unless clinically needed; if used, monitor calcium.
DailyMed (FDA) — approved Calcitriol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cdcaffc6-e14e-4607-b77b-fc78a8382f60 ; approved Cholecalciferol (vitamin D3) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3822c324-e22a-4ac4-ac1c-9b63983b516a — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Thiazide + vitamin D3: additive hypercalcaemia.
Hydrochlorothiazide reduces renal calcium excretion and vitamin D3 increases intestinal calcium absorption; together the two effects add up and can cause hypercalcaemia, especially in patients with renal impairment, prolonged immobilisation or additional calcium supplementation. The risk is particularly relevant when starting vitamin D in patients already on thiazides, or when increasing the dose. Monitor serum calcium (and urinary calcium) after starting or adjusting vitamin D in patients on thiazides, and reduce supplementation if serum calcium rises.
Thiazide + vitamin D3: additive hypercalcaemia. Monitor serum calcium.
The thiazide reduces calcium excretion and vitamin D increases its absorption; together they raise serum calcium.
Serum calcium.
Polyuria, constipation, weakness.
Monitor serum calcium during prolonged supplementation.
DailyMed (FDA) — approved Hydrochlorothiazide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0789baef-3424-43ab-a3fb-4908172da565 ; approved Cholecalciferol (vitamin D3) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3822c324-e22a-4ac4-ac1c-9b63983b516a — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Phenytoin + vitamin D3: phenytoin increases vitamin D metabolism.
Phenytoin (and other enzyme inducers such as carbamazepine and phenobarbital) induces hepatic cytochrome P450 enzymes (CYP3A4, CYP2C9) that hydroxylate vitamin D, accelerating its catabolism and reducing 25-hydroxyvitamin D levels. Long-term, this loss can cause hypocalcaemia, secondary hyperparathyroidism, reduced bone density and osteomalacia in epileptic patients on prolonged therapy. Monitor vitamin D levels and serum calcium, consider preventive vitamin D (and calcium) supplementation and assess bone density in patients on chronic phenytoin.
Phenytoin + vitamin D3: phenytoin accelerates vitamin D metabolism — risk of deficiency and osteomalacia.
Phenytoin enzyme induction (CYP450) accelerates vitamin D degradation.
25(OH)D and calcium.
Vitamin D deficiency and bone changes in chronic use.
Monitor 25(OH)D in at-risk patients; supplement if needed.
DailyMed (FDA) — approved Phenytoin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ef4e97a7-cd18-47a9-a016-2eca5481a87e ; approved Cholecalciferol (vitamin D3) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3822c324-e22a-4ac4-ac1c-9b63983b516a — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Digoxin + vitamin D3: vitamin D-induced hypercalcaemia may increase digoxin toxicity.
Digitalis toxicity is potentiated by electrolyte disturbances, including hypercalcaemia (and hypokalaemia and hypomagnesaemia). Vitamin D3, especially at high doses or with simultaneous calcium supplementation, can raise serum calcium and increase myocardial sensitivity to digoxin, with risk of arrhythmias. In digitalised patients starting vitamin D (or increasing the dose), monitor serum calcium and signs of digitalis toxicity (nausea, bradycardia, arrhythmias, visual disturbances) and consider measuring digoxin levels; correct any hypercalcaemia promptly.
Digoxin + vitamin D3: vitamin D-induced hypercalcaemia may increase digitalis toxicity.
Vitamin D increases calcium absorption; in digitalised patients hypercalcaemia sensitises the myocardium.
Serum calcium and ECG.
Nausea, arrhythmias, confusion.
Monitor serum calcium and signs of digoxin toxicity, especially when thiazides are also used.
DailyMed (FDA) — approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e61d2108-d871-44c0-b12a-2e61fbb56967 ; approved Cholecalciferol (vitamin D3) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3822c324-e22a-4ac4-ac1c-9b63983b516a — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Carbamazepine + vitamin D3: carbamazepine accelerates vitamin D metabolism, risking deficiency.
Carbamazepine is an enzyme inducer (CYP3A4 and others) that accelerates vitamin D catabolism, reducing 25-hydroxyvitamin D levels and, long-term, serum calcium and bone density — with risk of osteomalacia and fractures in patients on prolonged antiepileptic therapy. Monitor vitamin D and serum calcium, supplement vitamin D preventively (and calcium when indicated) and consider bone density assessment in chronic carbamazepine patients, especially older people and postmenopausal women.
Carbamazepine + vitamin D3: carbamazepine accelerates vitamin D metabolism — risk of deficiency.
Enzyme-inducing antiepileptics increase vitamin D and calcium catabolism.
25(OH)D, calcium and bone density in chronic use.
Vitamin D deficiency, osteomalacia, fractures.
Consider a higher vitamin D dose and monitor levels/25(OH)D in at-risk patients.
DailyMed (FDA) — approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=97e6e175-75e8-437b-b457-ddb1ae4e857d ; approved Cholecalciferol (vitamin D3) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3822c324-e22a-4ac4-ac1c-9b63983b516a — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Fat-rich meals increase cholecalciferol absorption.
Take vitamin D3 with the main meal.
EMC-UK (MHRA) — approved Cholecalciferol (vitamin D3) SmPC: https://www.medicines.org.uk/emc/product/7263/smpc
Vitamin D is fat-soluble — absorption improves when taken with a meal containing fat.
Take with the largest meal of the day (ideally containing fat).
Prontuário Terapêutico INFARMED, 8 (fat-soluble vitamins); literature (colecalciferol with main meal ↑ 30–50%).
In sarcoidosis there is extra-renal calcitriol production, increasing hypercalcaemia risk.
Use with caution and monitor serum calcium.
EMC-UK (MHRA) — approved Cholecalciferol (vitamin D3) SmPC: https://www.medicines.org.uk/emc/product/7263/smpc
Vitamin D increases calcium absorption — contraindicated in hypercalcaemia and hypercalciuria.
Monitor serum calcium and 25-OH-D in prolonged treatment (site monograph).
Site monograph (vitamin D — monitor serum calcium).
In CKD renal activation of vitamin D is reduced — use active forms only under supervision (hypercalcaemia and bone disease risk).
In CKD, prefer calcitriol/alfacalcidol with monitoring (site monograph).
Site monograph (vitamin D — in CKD use active forms only under supervision).
Prefer drugs that do not require renal hydroxylation (calcitriol or alfacalcidol).
Prefer calcitriol or alfacalcidol in renal impairment.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 4, Drugs and renal impairment: Prefer drugs that do not require renal hydroxylation (calcitriol or alfacalcidol).
Annex 1 records the vitamin D entry with a note on vitamin A excess and the limit: "the pregnant woman should not take more than 2000 IU daily" (of vitamin D; l. 42019-21). Maternal vitamin D deficiency is associated with neonatal rickets — supplementation at 400–2000 IU/day is safe and recommended in at-risk women.
Compatible within the 2000 IU/day limit; overdose causes fetal hypercalcaemia (aortic stenosis, retinopathy — l. 39833-36 under cholecalciferol).
Compatible; Annex 2 records "monitor infant calcium if the mother receives high doses" (l. 42425, under cholecalciferol).
No specific additional contraception.
Prontuário Terapêutico INFARMED — Annex 1: "Vitamin D" (l. 42019-21) and "Cholecalciferol" (l. 39833-36); Annex 2 (l. 42425).
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Raised serum 25-OH-D; improved calcium absorption and bone mineralisation.
Hepatic hydroxylation (CYP2R1) to 25-OH-D (stored form) and renal (CYP27B1) to active 1,25-(OH)2-D; calcitriol binds the VDR receptor and regulates calcium absorption genes (TRPV6, calbindin).
Intestinal absorption with bile (fat-soluble); bioavailability 50–80%, better with a fatty meal.
Sequential hepatic and renal hydroxylation; inactivation by CYP24A1 (24-hydroxylase); biliary excretion.
Cholecalciferol ~ 2–3 weeks (adipose storage); calcitriol ~ 4–6 h.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
