Clodronic acid


Thông tin thuốc gốc
Chỉ định và Liều dùng
Intravenous
Hypercalcaemia of malignancy
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%.
Cách dùng
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.
Hướng dẫn pha thuốc
Dilute dose in 500 mL of NaCl 0.9% or glucose 5%.
Tương kỵ
Incompatible w/ Ca-containing soln (e.g. Ringer’s soln).
Chống chỉ định
Acute GI inflammatory conditions. Severe renal failure (CrCl <10mL/min). Pregnancy and lactation. Patients receiving other bisphosphonates.
Thận trọng
Renal impairment.
Phản ứng phụ
Osteonecrosis of the jaw and external auditory canal, skin reactions (e.g. pruritus, urticaria, exfoliative dermatitis), bronchospasm, diarrhoea, nausea, vomiting, moderate leucopenia, renal dysfunction (including renal failure), hypocalcaemia; elevated serum creatinine, lactic acid dehydrogenase, parathyroid hormone, transaminase and alkaline phosphatase; transient proteinuria (IV). Rarely, atypical femoral fractures.
Thông tin tư vấn bệnh nhân
Maintain adequate fluid intake.
MonitoringParameters
Monitor hepatic and renal function, CBC; serum Ca, K, Mg, and phosphate levels.
Quá liều
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.
Tương tác
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.
Tác dụng
Description: 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).
Đặc tính

Chemical Structure Image
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)

Bảo quản
Store between 15-30˚C.
Phân loại ATC
M05BA02 - clodronic acid ; Belongs to the class of bisphosphonates. Used in the treatment of bone diseases.
References
Anon. Clodronate. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 16/06/2016.

Buckingham R (ed). Clodronate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 16/06/2016.

Disodium Clodronate 60 mg/ml Concentrate for Solution for Infusion (SINDAN Ltd.). MHRA. https://products.mhra.gov.uk/. Accessed 16/06/2016.

Joint Formulary Committee. Sodium Clodronate. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 16/06/2016.

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