Pocket Oncology (Pocket Notebook Series), 1st Ed.

BONE-MODIFYING AGENTS

Thu Oanh Dang

Alendronate (Fosamax)

Dosing/dose adjustments: Ppx: 35 mg oral weekly or 5 mg oral daily. Tx: 70 mg oral weekly or 10 mg oral daily. CrCl < 35 mL/min: Use not recommended. No hepatic dose adjustments recommended.

PK/PD: Poor bioavailability (fasting 0.6%, ↓ up to 60% w/food), 78% protein bound, fecal & urinary excretion (unabsorbed drug), T1/2 10 y

Adverse effects: ONJ, ↓ Ca, GI irritation & esophageal erosion (pts should remain upright ≥ 30 min post dose), & muscle pain

DDI: Antacid/PPI/mineral-containing medications (↓ absorption of oral bisphosphonate), NSAIDs & aspirin (↑ GI irritation)

Clinical pearls: Take w/water in AM, ≥30 min prior to medications or food & do not lie down ≥30 min post dose. Not indicated for malignant hypercalcemia. Use concurrent Ca & vit D supplements for indications other than hypercalcemia. Ensure good oral health before starting Rx.

Etidronate (Didronel)

Dosing/dose adjustments: 5–20 mg/kg/d orally. Use w/caution & consider dose reduction in renal & hepatic impairment.

PK/PD: 3% oral absorption, fecal & urinary excretion

Adverse effect: GI upset, ONJ, ↓ Ca, esophageal erosion (pts should remain upright ≥30 min post dose), muscle pain

DDI: Antacid/PPI/mineral-containing medications (↓ absorption of oral bisphosphonate), NSAIDs & aspirin (↑ GI irritation), warfarin (↑ bleeding risk)

Clinical pearls: Take w/water in AM, ≥30 min prior to medications or food & do not lie down ≥30 min post dose. Not indicated for malignant hypercalcemia. Use concurrent Ca & vit D supplements for indications other than hypercalcemia. Ensure good oral health prior to Rx.

Ibandronate (Boniva)

Dosing/dose adjustments: Osteoporosis: 150 mg oral monthly or 3 mg IV every 3 mos. Hypercalcemia (unlabeled use): 2–6 mg IV infused over 1–2 h once or every 3–4 wks for bone met in breast CA. CrCl < 30 mL/min: Use is not recommended. No hepatic dose adjustments recommended.

PK/PD: Min. absorption (90% ↓ post breakfast), 86–99.5% protein bound, fecal & urinary excretion, T1/2 (IV) 5–25 h, (oral) 37–157 h

Adverse effects: GI, back pain (<14%), ONJ, esophageal erosion (pts should remain upright ≥30 min post dose)

DDI: Antacid/PPI/mineral-containing medications (↓ absorption of oral bisphosphonate), NSAIDs, & aspirin (↑ GI irritation)

Clinical pearls: Oral form not indicated for malignant hypercalcemia. IV can be used off label in oncology. Take w/water in AM, ≥30 min prior to medications or food & do not lie down ≥30 min post dose. Use concurrent Ca & vit D supplements for indications other than hypercalcemia.

Risedronate (Actonel)

Dosing/dose adjustments: 5 mg oral daily or 35 mg weekly or 150 mg monthly. CrCl < 30 mL/min: Use not recommended. No hepatic dose adjustments recommended.

PK/PD: Poor bioavailability, 24% protein bound, fecal & urinary excretion, T1/2 up to 456 h

Adverse effects: HTN (11%), HA (<18%), rash (<12%), peripheral edema (8%), GI, arthralgia (<33%), UTI (11%), other infxn ≤ 31%, ONJ, esophageal erosion (pts should remain upright ≥30 min post dose)

DDI: Antacid/PPI/mineral-containing medications (↓ absorption of oral bisphosphonate), NSAIDs, & aspirin (↑ GI irritation)

Clinical pearls: Take w/water in AM, ≥30 min prior to medications or food & do not lie down ≥30 min post dose. Not indicated for malignant hypercalcemia. Use concurrent Ca & vit D supplements for indications other than hypercalcemia. Ensure good oral health before starting Rx.

Pamidronate (Aredia)

Dosing/dose adjustments: Hypercalcemia: 60–90 mg IV once, may repeat every 7 d. Myeloma & breast CA: 90 mg IV over 2 h monthly. CrCl < 30 mL/min or SCr > 3 mg/dL: Myeloma: Infuse over 4–6 h and/or use ↓ dose. Other indications: Not recommended or use w/extreme caution.

PK/PD: Up to 24 h for ↓ in albumin-corrected serum Ca; max effect up to 7 d, urinary excretion w/in 120 h, T1/2 21–35 h

Adverse effects: Acute renal tox (esp in myeloma pts), electrolyte imbalances (↓ K, phos, Mg, Ca), fevers (<39%), HA, fatigue, ONJ

DDI: Thalidomide (↑ nephrotoxicity), other nephrotoxic agents

Clinical pearls: Check SCr before each dose. Longer infusion (>2 h) may ↓ risk of renal tox. Ensure good oral health prior to Rx.

Zoledronate (Zometa, Reclast)

Dosing/dose adjustments: Zometa (Oncology): Malignant hypercalcemia 4 mg IV once, may repeat after 7 d. Myeloma: 4 mg IV monthly. Reclast(Osteoporosis): 5 mg IV yearly or every 2 y. Nononcology use: CrCl < 35 mL/min: Use is not recommended. Myeloma or bone mets: CrCl 50–60mL/min: 3.5 mg; 40–49 mL/min: 3.3 mg; 30–39 mL/min: 3 mg; <30 mL/min: Use not recommended. Malignant hypercalcemia: Sev. renal impairment (SCr > 4 mg/dL): Use w/extreme caution.

PK/PD: Low protein binding (28–53%), urinary excretion w/in 24 h, T1/2 146 h

Adverse effects: Acute infusion rxn (flu-like sx) w/in 3 d post infusion (up to 44%), acute renal tox (esp in myeloma pts), alopecia, ONJ, electrolyte disturbances (↓ K, phos, Mg, Ca)

DDI: Thalidomide (↑ nephrotoxicity), other nephrotoxic agents

Clinical pearls: Check SCr before each dose. ↑ infusion time may ↓ renal tox. APAP prior & 72 h post infusion may ↓ incidence of infusion rxn. Ensure good oral health prior to Rx.

Denosumab (Xgeva, Prolia)

Dosing/dose adjustments: Prev of skeletal events in solid tumors (Xgeva): 120 mg SC every 4 wks. Prev of bone loss (Prolia): 60 mg SC every 6 mos. Prolia: No renal dose adjustment. Xgeva: Not studied in renal impaired pts. Hepatic impairment: Not studied.

PK/PD: 60% SC bioavailability, T1/2 25–28 d

Adverse effects: ONJ, rash, fatigue, ↓ calcium, GI tox, infxn, & peripheral edema

DDI: No formal studies have been conducted

Clinical pearls: Oral exam prior to Rx. Monitor for sign/sx of infxn. May cause fetal harm.

Info. based on publicly available drug inserts from: Merck, Procter & Gamble, Genetech, Warner Chilcott, Novartis, & Amgen. Accessed 2/17/13.