Ibandronate
Ibandronate
Generic Name
Ibandronate
Mechanism
- High‑affinity binding to hydroxyapatite crystals in bone, localizing the drug at sites of active resorption.
- Inhibition of farnesyl pyrophosphate synthase in the mevalonate pathway → decreased prenylation of small GTPases essential for osteoclast function.
- Result: ↓ osteoclast activity → ↓ bone resorption, ↑ bone mineral density (BMD), and reduced fracture risk.
Pharmacokinetics
| Parameter | Key Points |
| Absorption | Oral absorption ~0.7‑1.4 % (low & food‑sensitive). |
| First‑pass | Minimal hepatic metabolism; little systemic distribution. |
| Distribution | Strong bone affinity; >90 % bound to bone mineral. |
| Half‑life | Skeletal 20–86 days; plasma <1 hr (rapid clearance). |
| Elimination | Renal excretion; dose‑adjusted for CrCl <30 mL/min. |
Indications
- Postmenopausal osteoporosis (oral 150 mg weekly).
- Glucocorticoid‑induced osteoporosis (oral 150 mg weekly).
- Paget disease of bone (IV 5 mg monthly, up to 3 years).
- Preventing fractures in high‑risk patients (e.g., bone‑protective indication in breast cancer on aromatase inhibitors).
Contraindications
- Absolute: esophageal or gastric ulcer, impaired esophageal motility, active esophagitis, pregnancy, lactation.
- Renal impairment: eGFR <30 mL/min → contraindicated IV; dose reduction for oral.
- Hypocalcemia (untreated) → monitor Ca⁺²⁺ before initiation.
- Osteonecrosis of the jaw (ONJ): avoid in patients with recent dental surgery or poor oral hygiene.
- Atypical femoral fractures: rare but reported with prolonged use.
Dosing
- Oral: 150 mg once weekly (no more than 5 days apart).
- Take on an empty stomach with 4–8 oz of plain water.
- Remain upright for 30 min; do not eat or drink for 30 min before the next dose.
- IV (Paget disease): 5 mg by slow infusion over 8 min, once monthly for up to 3 years.
- Renal dose adjustment (oral):
- eGFR 30–49 mL/min: 150 mg every 2 weeks.
- eGFR <30 mL/min: avoid; consider alternative bisphosphonate.
Adverse Effects
- GI: dyspepsia, esophagitis, abdominal pain, nausea.
- Musculoskeletal: back pain, arthralgia, myalgia.
- Hypocalcemia → tetany, paresthesia (especially post‑transplant).
- Osteonecrosis of the jaw (rare).
- Atypical femoral fractures (rare).
- Infusion‑related (IV): fever, chills, back pain.
Monitoring
- Baseline: serum Ca⁺²⁺, phosphate, creatinine, eGFR, 24‑h urine calcium.
- Ongoing:
- Calcium & creatinine every 6–12 months (long‑term therapy).
- Bone turnover markers (e.g., CTX) if monitoring efficacy or withdrawal.
- Dental exam before initiating therapy and periodically thereafter.
Clinical Pearls
- Empty‑stomach rule is critical: non‑compliance >30 % of doses leads to 30–50 % loss of efficacy.
- Switching bisphosphonates: for patients on alendronate, switch to ibandronate only after a 1‑month break to avoid overlapping bone‑binding.
- “Bisphosphonate holiday”: consider 1–2 year break after 3–5 years in low‑risk patients; reassess BMD before resuming.
- Paget management: maintain IV 5 mg monthly until ALP normalizes for 1–2 months; then switch to oral for long‑term suppression.
- Renal safety: patients with eGFR 30–49 mL/min should receive oral every‑other‑week dosing, not IV.
- Patient education: emphasize strict hydration, upright posture, and avoidance of large meals immediately before/after dosing to prevent esophagitis.
- Onset of effect: BMD improvements seen after 2–3 years; early benefit reflected by reduced vertebral fracture risk.
*This drug card summarizes key pharmacological facts and practical guidance for using ibandronate in clinical practice.*