Adult: 300 mg daily via infusion over at least 2 hr until normocalcaemia is achieved. Max duration of treatment: 7 days. Alternatively, 1,500 mg as a single infusion over at least 4 hr.
Oral Osteolytic bone metastases
Adult: Initially, 1,600 mg daily as a single or in 2 divided doses, increased as necessary. Max: 3,200 mg daily.
Oral Hypercalcaemia of malignancy
Adult: Maintenance following Ca normalisation w/ IV therapy: 1,600-2,400 mg as a single or in 2 divided doses. Max: 3,200 mg daily.
Renal Impairment
Oral Daily doses >1,600
mg should not be used continuously.
CrCl (mL/min)
Dosage
<10
Contraindicated.
10-<30
Reduce dose by 50%.
30-<50
Reduce dose by 25%.
Intravenous
CrCl (mL/min)
Dosage
<10
Contraindicated.
10-49
Reduce dose by 25-50%.
50-80
Reduce dose by up to 25%.
Administration
Should be taken on an empty stomach. Take w/ a glass of plain water at least 1 hr before or after food. Remain in an upright position for at least 30 min. Do not take w/ milk, food or products containing Ca or other polyvalent cations. Tab may be divided only along the score-line. Swallow cap/tab whole or divided halves of tab, do not chew/crush.
Monitor hepatic and renal function, CBC; serum Ca, K, Mg, and phosphate levels.
Overdosage
Symptoms: Increased serum creatinine, renal dysfunction. Acute renal failure and liver injury may occur. Theoretically, hypocalcaemia may develop up to 2-3 days following the overdose. Management: Symptomatic treatment. Ensure adequate hydration. Oral or parenteral Ca supplementation may be needed.
Drug Interactions
Decreased effect and absorption w/ antacids or iron preparations. Increased risk of severe hypocalcaemia w/ aminoglycosides. Increases serum level of estamustine phosphate. May potentiate the hypocalcaemic effect w/ corticosteroids, phosphate, calcitonin, mithramycin and loop diuretics. Risk of renal dysfunction w/ NSAIDs.
Food Interaction
Food, beverage and dairy products may interfere w/ absorption.
Lab Interference
May interfere w/ diagnostic imaging agent such as technetium-99m-diphosphonate in bone scans.
Action
Description: Mechanism of Action: Clodronic acid lowers serum Ca through inhibition of bone resorption via actions on osteoclasts or osteoclast precursors. Onset: Ca-lowering effect: W/in 48 hr (IV). Duration: Ca-lowering effect: 5 days to 3 wk following discontinuation. Pharmacokinetics: Absorption: Poorly absorbed (oral). Decreased absorption when given w/ food, esp Ca-containing products. Bioavailability: 1-4% (oral). Time to peak plasma concentration: 30 min (oral). Distribution: Volume of distribution: Approx 20 L. Plasma protein binding: Low; strongly bound to bone. Excretion: Via urine (60-80% as unchanged drug) and faeces (as unabsorbed drug). Terminal elimination half-life: Oral: Approx 6 hr. IV 13 hr (serum).
Chemical Structure
Clodronic acid Source: National Center for Biotechnology Information. PubChem Database. Clodronic Acid, CID=25419, https://pubchem.ncbi.nlm.nih.gov/compound/Clodronic-Acid (accessed on Jan. 21, 2020)
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