Schedule H

Oral, Intravenous

Formulation Strength

Capsule 0.25 mcg

Capsule 0.5 mcg

Oral Drops 0.1 mcg/mL (15 mL bottle)

Injection 1 mcg/mL (1 mL ampoule)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Renal Osteodystrophy / CKD-related Secondary Hyperparathyroidism

A. Adults on Dialysis

Parameter Details

Starting dose 0.25–0.5 mcg/day PO or IV (post-dialysis)

Titration Increase by 0.25 mcg every 4–8 weeks based on PTH, serum calcium, and phosphate

Usual maintenance dose 0.5–1 mcg/day

Maximum dose 2 mcg/day

B. Adults with CKD Not on Dialysis

Parameter Details

Starting dose 0.25 mcg once daily PO

Titration Increase by 0.25 mcg every 4–8 weeks based on PTH and calcium levels

Usual maintenance dose 0.25–0.5 mcg/day

Maximum dose 1 mcg/day

Clinical notes:

• Monitor serum calcium and phosphate at least every 4 weeks during titration

• IV administration preferred post-dialysis for better control

• Target PTH reduction of 30–50% from baseline

1. Hypocalcaemia due to Hypoparathyroidism or Pseudohypoparathyroidism

Parameter Details

Starting dose 0.25–0.5 mcg once daily PO

Titration Increase by 0.25 mcg every 2–4 weeks based on serum calcium levels

Usual maintenance dose 0.5–1 mcg/day

Maximum dose 2 mcg/day

Clinical notes:

• Often requires concurrent oral calcium supplementation (1–2 g elemental calcium/day)

• Target serum calcium at low-normal range (8.0–8.5 mg/dL) to avoid hypercalciuria

• Monitor 24-hour urinary calcium periodically

1. Vitamin D-Resistant Rickets and Osteomalacia (Hepatic Origin)

Parameter Details

Starting dose 0.25 mcg once daily PO

Titration Adjust every 4 weeks based on clinical response and calcium/phosphorus levels

Usual maintenance dose 0.25–0.75 mcg/day

Maximum dose 1 mcg/day

Clinical notes:

• Reserved for vitamin D-resistant forms only

• Nutritional rickets should be treated with cholecalciferol, not alfacalcidol

• X-linked hypophosphatemic rickets requires additional oral phosphate supplementation

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Corticosteroid-induced osteoporosis 0.25–0.5 mcg/day PO Long-term maintenance OFF-LABEL; Specialist only; Evidence: RCTs showing benefit in preventing bone loss

Osteoporosis in CKD patients 0.25–0.5 mcg/day PO Long-term OFF-LABEL; Specialist only; Evidence: Indian nephrology practice, small RCTs

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Paediatric Renal Osteodystrophy / CKD-MBD

Body Weight Starting Dose Usual Maintenance Maximum Dose

<10 kg 0.05 mcg/day PO 0.05–0.1 mcg/day 0.25 mcg/day

10–20 kg 0.1 mcg/day PO 0.1–0.25 mcg/day 0.5 mcg/day

20 kg 0.25 mcg/day PO 0.25–0.5 mcg/day 1 mcg/day

Titration: Increase by 0.05–0.1 mcg every 2–4 weeks based on serum calcium, phosphate, and PTH levels

Clinical notes:

• Start at lower range in infants

• IV administration for children on haemodialysis (post-dialysis dosing)

• Oral drops formulation preferred for accurate dosing in young children

1. Vitamin D-Resistant Rickets (Hereditary)

Parameter Details

Starting dose 0.05–0.1 mcg/kg/day PO

Titration Increase every 2–4 weeks based on clinical and biochemical response

Usual maintenance dose 0.1–0.2 mcg/kg/day

Maximum dose 2 mcg/day

Clinical notes:

• X-linked hypophosphatemic rickets requires concurrent oral phosphate supplementation

• Vitamin D-dependent rickets type I responds well

• Regular monitoring of growth, calcium, phosphate, and alkaline phosphatase

1. Hypoparathyroidism in Children

Parameter Details

Starting dose 0.25 mcg once daily PO

Titration Increase by 0.25 mcg every 2–4 weeks based on calcium levels

Usual maintenance dose 0.5–1 mcg/day

Maximum dose 2 mcg/day

Safety Monitoring:

• Serum calcium: Weekly during titration, then monthly

• Serum phosphate: Every 2–4 weeks during titration

• PTH levels: Every 3 months in CKD-MBD

• Growth monitoring: Height velocity assessment every 6 months

• Urinary calcium: Periodically to detect hypercalciuria

Secondary Indications — Paediatric (Off-label)

Indication Dose Duration Notes

Neonatal hypocalcaemia (refractory) 0.05 mcg/kg/day PO Short course; reassess after 1–2 weeks OFF-LABEL; Specialist only; Evidence: Indian NICU practice

Age Restrictions:

• Not recommended below corrected gestational age of 28 weeks except under neonatologist supervision

• Oral drops formulation should be used for accurate dosing in children <5 years

Mild-to-moderate CKD (eGFR 30–89) No dose reduction; alfacalcidol is activated in liver, not kidney

Severe CKD (eGFR <30) No dose reduction; monitor closely for hypercalcaemia

Haemodialysis IV preferred post-dialysis; monitor calcium/phosphate frequently

Peritoneal dialysis Oral dosing acceptable; standard monitoring

• Hypercalcaemia (serum calcium >10.5 mg/dL)

• Hyperphosphataemia with concurrent hypercalcaemia

• Evidence of vitamin D toxicity

• Known hypersensitivity to alfacalcidol or any excipients

• Metastatic calcification

• History of nephrolithiasis or nephrocalcinosis

• Concurrent digitalis therapy (hypercalcaemia increases risk of digoxin toxicity)

• Prolonged immobilisation (increased risk of hypercalcaemia)

• Sarcoidosis or other granulomatous diseases (increased sensitivity to vitamin D)

• Concurrent thiazide diuretic therapy

• Adynamic bone disease (may worsen with oversuppression of PTH)

• Patients on calcium supplements (monitor total calcium intake)

Parameter Details

Risk category Not formally categorised in India; limited human data available

Use recommendation Avoid unless clearly indicated; use only if benefit outweighs risk

Preferred alternatives Cholecalciferol for uncomplicated vitamin D deficiency

When may be used Hypoparathyroidism or CKD requiring active vitamin D — under specialist supervision

Monitoring Maternal serum calcium (hypercalcaemia may cause fetal growth retardation, supravalvular aortic stenosis); fetal growth parameters

Parameter Details

Compatibility Generally compatible with breastfeeding at doses ≤1 mcg/day

Drug levels in milk Low (at therapeutic doses)

Preferred alternatives Cholecalciferol for routine maternal vitamin D supplementation

Infant monitoring Signs of hypercalcaemia: poor feeding, vomiting, constipation, excessive thirst, failure to thrive

Parameter Recommendation

Recommended starting dose 0.25 mcg once daily PO

Titration Slower than standard — increase at 4–8 week intervals with frequent monitoring

Extra risks Increased sensitivity to hypercalcaemia; reduced renal calcium clearance; higher risk of nephrocalcinosis

Additional considerations Falls risk if hypercalcaemia causes weakness; cardiac arrhythmia risk in those on digoxin; assess renal function before initiation

Interacting Drug Mechanism/Effect Recommendation

Thiazide diuretics Reduced renal calcium excretion; increased risk of hypercalcaemia Avoid combination or monitor calcium closely; consider dose reduction

Digoxin Hypercalcaemia enhances digoxin toxicity and arrhythmia risk Monitor calcium levels strictly; adjust digoxin if needed

Magnesium-containing antacids Risk of hypermagnesaemia, especially in renal impairment Avoid in CKD patients

Aluminium-containing phosphate binders Increased aluminium absorption and toxicity Avoid; use calcium-based or non-aluminium binders

Interacting Drug Mechanism/Effect Recommendation

Phenytoin / Phenobarbital / Carbamazepine Increased vitamin D metabolism via CYP450 induction; reduced efficacy May need higher alfacalcidol doses; monitor response

Glucocorticoids Oppose vitamin D effects on calcium absorption May require higher doses of alfacalcidol

Cholestyramine / Colestipol Reduced oral absorption of alfacalcidol Administer alfacalcidol 1 hour before or 4 hours after bile acid sequestrants

Calcium supplements Additive effect; risk of hypercalcaemia Monitor total calcium intake; adjust supplementation

Rifampicin Increased vitamin D metabolism May require dose adjustment; monitor response

• Mild hypercalcaemia (thirst, polyuria, nausea)

• Hyperphosphataemia

• Headache

• Nausea and metallic taste

• Fatigue

• Muscle weakness (if calcium elevated)

• Abdominal discomfort

• Pruritus

Adverse Effect Clinical Action

Severe hypercalcaemia (confusion, cardiac arrhythmia, coma) Discontinue immediately; IV fluids; loop diuretics; hospitalisation

Nephrocalcinosis Discontinue; renal imaging; nephrology consultation

Acute pancreatitis (rare) Discontinue; supportive management

Metastatic calcification (soft tissue/vascular) Discontinue; assess calcium-phosphate product

Progressive renal impairment Discontinue; evaluate for nephrocalcinosis

Phase Parameters

Baseline Serum calcium, phosphate, alkaline phosphatase, PTH; renal function (eGFR); 25-hydroxyvitamin D levels

During titration Serum calcium and phosphate: weekly for first month, then every 2 weeks

Long-term Serum calcium, phosphate: every 1–2 months; PTH (in CKD patients): every 3–6 months; 24-hour urinary calcium: if hypercalciuria suspected; renal ultrasound: annually for long-term use

Alfa D Pfizer Capsules, Drops

One Alpha Leo Pharma Capsules, Injection

Alphadol Sun Pharma Capsules

Alfacip Cipla Capsules

Calfasyn RPG LifeSciences Capsules

Alfaferol Abbott Capsules

Note: FDC combinations with calcium carbonate available from some manufacturers

• NPPA status: Not under NLEM price control

• Government supply: Available in tertiary nephrology centres

1. Preferred in CKD: Unlike cholecalciferol, alfacalcidol does not require renal 1α-hydroxylation — preferred choice in CKD stages 3–5 and dialysis patients.

1. Titrate slowly: Hypercalcaemia develops insidiously — always titrate at 4–8 week intervals with regular calcium monitoring; faster titration risks toxicity.

1. Monitor calcium AND phosphate together: Evaluating a single marker is misleading; high calcium-phosphate product (>55 mg²/dL²) increases metastatic calcification risk.

1. IV for dialysis: Post-dialysis IV administration provides better control and avoids absorption variability in uraemic patients.

1. Not for nutritional deficiency: Nutritional rickets and simple vitamin D deficiency should be treated with cholecalciferol, not alfacalcidol — reserve for resistant or CKD-related conditions.

1. Avoid over-suppression of PTH: In CKD-MBD, target 30–50% PTH reduction from baseline; complete suppression causes adynamic bone disease.

Alfacalcidol; vitamin D analogue; CKD-MBD; renal osteodystrophy; secondary hyperparathyroidism; hypoparathyroidism; rickets; hypocalcaemia; nephrology; pregnancy-caution

RxIndia v1.0 — 05 May 2025

• CDSCO-approved product inserts

• Indian Pharmacopoeia (IP)

• API Textbook of Medicine (Chronic Kidney Disease section)

• AIIMS Renal Drug Handbook

• ICMR CKD-MBD management guidelines

• Hospital protocols (AIIMS, PGI Chandigarh)

• IAP Guidelines (paediatric dosing)

• WHO Essential Medicines List (supportive paediatric data)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics