Schedule H

Oral

• Tablets: 5 mg, 10 mg, 35 mg, 70 mg

• Combination Tablet: Alendronate 70 mg + Cholecalciferol 5600 IU

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Postmenopausal Osteoporosis — Treatment and Prevention

Parameter Recommendation

Starting dose 70 mg orally once weekly OR 10 mg orally once daily

Titration Not applicable

Usual maintenance dose 70 mg once weekly OR 10 mg once daily

Maximum dose 70 mg weekly (equivalent to 10 mg daily)

Clinical Notes:

• Take in the morning on an empty stomach with a full glass of plain water (200–250 mL)

• Wait at least 30 minutes before first food, drink, or other medications

• Remain upright (sitting or standing) for at least 30 minutes after taking to reduce oesophageal irritation

• Ensure adequate calcium (1000–1200 mg/day) and vitamin D (800–1000 IU/day) intake

• Weekly dosing preferred for better adherence

1. Glucocorticoid-Induced Osteoporosis

Parameter Recommendation

Starting dose 5 mg orally once daily (postmenopausal women not on oestrogen: 10 mg daily)

Titration Not applicable

Usual maintenance dose 5–10 mg once daily

Maximum dose 10 mg daily

Clinical Notes:

• Indicated for patients on glucocorticoids ≥7.5 mg prednisolone equivalent expected for ≥3 months

• Continue treatment duration based on glucocorticoid use and BMD assessment

• Ensure calcium and vitamin D supplementation throughout

1. Osteoporosis in Men — Treatment

Parameter Recommendation

Starting dose 70 mg orally once weekly OR 10 mg orally once daily

Titration Not applicable

Usual maintenance dose 70 mg once weekly OR 10 mg once daily

Maximum dose 70 mg weekly

Clinical Notes:

• Consider in men with fragility fracture or BMD T-score ≤−2.5

• Bone density improvement typically noted by 6–12 months

• Same administration instructions as postmenopausal osteoporosis

1. Paget's Disease of Bone

Parameter Recommendation

Starting dose 40 mg orally once daily

Titration Not applicable

Usual maintenance dose 40 mg once daily for 6 months

Maximum dose 40 mg daily

Clinical Notes:

• Single 6-month treatment course

• Retreatment may be considered after minimum 6-month observation period if relapse occurs

• Ensure normal calcium and vitamin D status before initiating

• Monitor serum alkaline phosphatase (ALP) for response

Secondary Indications – Adults (Off-label, if any)

Indication Dose Duration Notes

Bone Loss Prevention in Early Breast Cancer (on Aromatase Inhibitors) 70 mg weekly During aromatase inhibitor therapy OFF-LABEL; Specialist only; Evidence: International RCTs; IV bisphosphonates often preferred

Note: For metastatic bone disease, IV bisphosphonates (zoledronic acid) or denosumab are preferred over oral alendronate.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

NOT APPROVED for routine use in children in India.

• No approved paediatric indications

• Indian regulatory sources (CDSCO) do not list paediatric indications

Secondary Indications – Paediatrics (Off-label, if any)

1. Osteogenesis Imperfecta — Age ≥4 Years

Parameter Recommendation

Starting dose 1 mg/kg/week orally (may divide into 1–2 doses per week)

Titration Adjust based on BMD response and tolerability

Usual maintenance dose 1–2 mg/kg/week

Maximum dose 2 mg/kg/week or 70 mg/week (whichever lower)

Clinical Notes:

• OFF-LABEL use; Specialist only (Paediatric Endocrinology)

• Evidence: International RCTs; Indian tertiary centre practice

• IV pamidronate often preferred over oral alendronate in severe cases

1. Juvenile Idiopathic Osteoporosis — Age ≥4 Years

Parameter Recommendation

Starting dose 5 mg orally once daily

Titration May increase to 10 mg daily based on response

Usual maintenance dose 5–10 mg once daily

Maximum dose 10 mg daily

Clinical Notes:

• OFF-LABEL use; Specialist only

• Evidence: Indian tertiary centre practice extrapolated from adult data

• Treatment cycles of 6–12 weeks with reassessment

Safety Monitoring in Paediatric Use:

• Growth velocity monitoring at each visit

• BMD assessment every 6–12 months

• Serum calcium, phosphate, vitamin D

• Dental health assessment

• Renal function

Not recommended below 4 years of age under any circumstances. Use above 4 years only under paediatric endocrinology specialist supervision in tertiary centres.

Note: Alendronate is excreted unchanged by kidneys; accumulation occurs in renal impairment. Not significantly removed by haemodialysis.

Note: Alendronate is not metabolised hepatically; excreted unchanged in urine or deposited in bone.

• Oesophageal abnormalities that delay oesophageal emptying (stricture, achalasia)

• Inability to stand or sit upright for at least 30 minutes after taking

• Hypocalcaemia (must be corrected before initiating therapy)

• Severe renal impairment (eGFR <35 mL/min)

• Known hypersensitivity to alendronate or other bisphosphonates

• Pregnancy

• Active upper gastrointestinal disorders (gastritis, peptic ulcer disease, GERD, dysphagia) — increased risk of oesophageal adverse events

• Vitamin D deficiency — must correct before starting to avoid hypocalcaemia

• Risk of atypical femoral fractures with long-term use (>3–5 years) — reassess periodically

• Risk of osteonecrosis of the jaw (ONJ) — especially with dental disease, invasive dental procedures, or poor oral hygiene

• Active dental infections or planned invasive dental surgery — consider completing dental work before initiating

• Malabsorption syndromes — may reduce efficacy

• Patients unable to follow strict dosing instructions — therapy may be ineffective and risky

• Long-term glucocorticoid use — may exacerbate GI adverse effects

Parameter Details

Risk Category Contraindicated during pregnancy

Known Risks Animal studies show fetal skeletal abnormalities and reduced ossification; bisphosphonates accumulate in bone and may be released during pregnancy

Recommendation Do not use during pregnancy

Preferred Alternatives Calcium and vitamin D supplementation; if anti-resorptive therapy essential, specialist obstetric-endocrine input mandatory

Women of Childbearing Potential Counsel regarding long bone half-life (bisphosphonates persist in bone for years after discontinuation)

Parameter Details

Compatibility Not recommended during breastfeeding

Drug Levels in Milk Unknown; likely very low due to minimal systemic absorption and high bone affinity

Potential Infant Risks Theoretical risk to infant skeletal development

Recommendation Defer bisphosphonate therapy until after breastfeeding if clinically appropriate

Preferred Alternatives Calcium and vitamin D; address modifiable risk factors

Parameter Recommendation

Starting dose Standard adult dosing (70 mg weekly or 10 mg daily)

Titration Not applicable

Special Risks Higher risk of oesophageal adverse events; age-related decline in renal function (check eGFR before starting); increased falls risk

Administration Strict adherence to upright posture for ≥30 minutes; ensure adequate hydration; take with full glass of plain water

Monitoring Renal function before initiation; calcium and vitamin D status; falls risk assessment

Interacting Drug Mechanism / Effect Recommendation

Calcium supplements Calcium binds alendronate in GI tract; markedly reduces absorption Do not take together; separate by at least 30–60 minutes (alendronate must be taken first)

Antacids (aluminium, magnesium, calcium-containing) Reduce alendronate absorption Separate by at least 30–60 minutes after alendronate

Iron supplements Reduce alendronate absorption Separate by at least 30–60 minutes after alendronate

IV Aminoglycosides Additive hypocalcaemic effect Monitor serum calcium closely if concurrent use essential

Interacting Drug Mechanism / Effect Recommendation

NSAIDs (aspirin, ibuprofen, naproxen) Additive GI mucosal irritation; increased risk of GI ulceration Use with caution; avoid if history of GI disease; consider gastroprotection

Proton Pump Inhibitors (omeprazole, pantoprazole) May reduce bisphosphonate absorption; associated with increased fracture risk Monitor; long-term PPI use should be reviewed periodically

Glucocorticoids Additive bone loss if glucocorticoids used without alendronate; increased GI adverse effects when combined Appropriate indication for alendronate; monitor for GI symptoms

Loop Diuretics (furosemide) Potential for additive hypocalcaemia Monitor serum calcium

H2 Receptor Antagonists (ranitidine) May increase alendronate bioavailability (clinical significance uncertain) Monitor for adverse effects

Gastrointestinal (most common):

• Abdominal pain / Dyspepsia

• Acid reflux / Heartburn

• Nausea

• Flatulence

• Constipation or diarrhoea

• Abdominal distension

Musculoskeletal:

• Bone, muscle, or joint pain

• Muscle cramps

Other:

• Headache

• Dizziness

Note: GI adverse effects are often related to improper administration technique.

Adverse Effect Clinical Action

Oesophagitis / Oesophageal Ulceration / Erosion May cause severe retrosternal pain, dysphagia, odynophagia; discontinue immediately; GI referral; do not rechallenge

Oesophageal Stricture (rare) Discontinue permanently; surgical intervention may be required

Osteonecrosis of the Jaw (ONJ) Higher risk with dental disease, invasive dental procedures, poor oral hygiene; discontinue and refer to maxillofacial surgery if suspected

Atypical Femoral Fractures (subtrochanteric/diaphyseal) Associated with long-term use (>3–5 years); investigate prodromal thigh/groin pain; consider drug holiday if low fracture risk

Hypocalcaemia Especially if pre-existing vitamin D deficiency or hypoparathyroidism; correct before starting; monitor

Severe Musculoskeletal Pain May occur days to years after starting; may warrant discontinuation

Uveitis / Scleritis / Episcleritis (rare) Ophthalmology referral; may require discontinuation

Hypersensitivity Reactions (rare) Urticaria, angioedema; discontinue

1–2 Weeks Post-Initiation Serum calcium (in high-risk patients: elderly, vitamin D deficient, malnourished)

Every 6–12 Months Clinical assessment; GI symptoms; adherence to administration instructions

Every 12–24 Months BMD (DEXA scan) to assess response

Long-term (>3–5 Years) Reassess need for continued therapy vs drug holiday; monitor for prodromal symptoms of atypical femoral fracture (thigh/groin pain); annual dental review if ongoing therapy

Monotherapy:

• Fosamax (MSD) — Originator

• Osteofos (Cipla)

• Alenta (Sun Pharma)

• Bonmax (Zydus)

• Osteobon (Torrent)

• Alenost (Intas)

• Dronal (Dr. Reddy's)

Fixed-Dose Combination with Vitamin D:

• Osteofos-D70 (Cipla)

• Fosamax Plus (MSD)

• Included in NLEM 2022; pricing NPPA-controlled for scheduled formulations

• Significant price variation between brands

• Government supply available through public healthcare facilities

• Weekly dosing (70 mg once weekly) provides equivalent efficacy to daily dosing with significantly better adherence — preferred regimen for most patients

• Strict administration instructions are critical for both efficacy and safety: empty stomach, full glass of plain water only (not juice, coffee, or milk), upright posture for ≥30 minutes — non-compliance leads to both treatment failure and increased oesophageal adverse events

• Always correct vitamin D deficiency before starting therapy — failure to do so increases risk of hypocalcaemia and may reduce treatment efficacy

• Complete necessary invasive dental procedures before initiating long-term therapy in high-risk patients (cancer, immunosuppression) — ONJ is rare in osteoporosis patients but devastating when it occurs

• Consider drug holiday after 3–5 years in patients at lower fracture risk — atypical femoral fractures are associated with prolonged use; reassess fracture risk vs continued therapy

• Combination tablet with vitamin D (Alendronate 70 mg + Cholecalciferol 5600 IU) offers convenience for weekly dosing while ensuring vitamin D adequacy

Alendronate; osteoporosis; bisphosphonate; postmenopausal; Paget's disease; glucocorticoid-induced osteoporosis; bone health; oral weekly; oesophageal irritation; atypical fracture; renal-contraindication; NLEM India; Schedule H

RxIndia v1.0 — 04 May 2025

• CDSCO approved product information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• National List of Essential Medicines (NLEM) 2022

• API Textbook of Medicine — Endocrinology chapter

• AIIMS Standard Treatment Guidelines — Osteoporosis

• Indian Menopause Society Guidelines for Osteoporosis Management

• ICMR Guidance on Bone Health

• Goodman & Gilman's: The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• International RCTs (for off-label paediatric indications — marked accordingly)