Risedronate Sodium + Calcium Carbonate

Approved:

• Postmenopausal Osteoporosis: To reduce vertebral and non-vertebral fracture risk when dietary calcium is inadequate.
• Glucocorticoid‑Induced Osteoporosis: In adults on ≥7.5 mg prednisone (or equivalent) daily for ≥3 months.
• Osteopenia (off-label): For low bone mineral density with increased fracture risk, typically postmenopausal women or men.

Off‑Label/Clinically Accepted:

• Male Osteoporosis
• Premenopausal Secondary Osteoporosis: Under specialized clinical oversight.

• Risedronate Sodium: 35 mg once weekly or 150 mg once monthly, swallowed with 180–240 mL plain water on an empty stomach. Patients must remain upright for ≥30 minutes post-dose.
• Calcium Carbonate: 500–1000 mg elemental calcium daily, divided with meals.

Special Populations:

• Elderly: Standard adult dosing; assess renal function.
• Pediatrics: Not established.
• Renal Impairment: Contraindicated for risedronate if CrCl <30 mL/min; calcium with caution.
• Hepatic Impairment: No adjustment, but monitor closely.

• Risedronate inhibits osteoclasts by binding to hydroxyapatite, interfering with the mevalonate pathway, leading to apoptosis and decreased bone resorption.
• Calcium Carbonate supplies elemental calcium, essential for bone mineralization and aiding risedronate’s efficacy.

• Risedronate:
• Oral bioavailability ~0.6%; Tmax ~1 hour; not metabolized; excreted largely unchanged; half-life ≈ 480 hours.
• Calcium Carbonate:
• Absorption ~20–40%, enhanced by acidity; peak serum calcium in 1–2 hours; renal excretion via homeostatic mechanisms.

• Pregnancy:
• Risedronate: Category C — only if benefits outweigh risks.
• Calcium: Acceptable as dietary supplementation.
• Lactation:
• Risedronate: Excreted in breast milk; not recommended.
• Calcium: Safe and supported for nursing mothers.

• Class: Antiresorptive Agent + Mineral Supplement
• Subclass: Bisphosphonate (third generation) + Calcium Salt Supplement

• Hypersensitivity to either component.
• Hypocalcemia.
• Esophageal motility disorders or inability to sit upright.
• Severe renal impairment (CrCl <30 mL/min for risedronate).
• Hypercalcemia or disorders affecting calcium metabolism.

• Esophageal injury: Adherence to posture and timing instructions is essential.
• Osteonecrosis of the jaw & atypical femur fractures: Rare; consider dental evaluation.
• Hypocalcemia: Must be corrected prior; monitor calcium levels.
• Kidney stones: Monitor calcium intake in high-risk patients.
• Drug holiday: Review after 3–5 years to assess ongoing need.

Common:

• Gastrointestinal issues (pain, dyspepsia, constipation), musculoskeletal pain

Serious (rare):

• Esophagitis, osteonecrosis, atypical fractures, severe hypocalcemia

Notes:

• GI effects often appear early; musculoskeletal pain may occur anytime.

• Calcium and cation-containing products: Decrease risedronate absorption; separate doses by ≥30 minutes.
• NSAIDs: May heighten GI risk.
• Thiazide diuretics: Could increase serum calcium.
• Corticosteroids: Combined osteoporosis risk; supportive calcium is advised.
• No CYP450 metabolism interactions.

• Guidelines: Emphasize adequate calcium intake with bisphosphonate use; dental assessment recommended before initiation.
• Regulatory alerts: Highlight rare risks (jaw osteonecrosis/anomalies) requiring monitoring.
• Therapy review: Recommended after 3–5 years based on fracture risk.

• Temperature: Store below 25 °C (77 °F); brief excursions to 15–30 °C allowed.
• Humidity/Light: Keep in dry, tightly sealed containers away from direct light.
• Handling: Do not crush or chew tablets; store calcium in original packaging.
• Reconstitution: Not required.