Drug Class Description
Bisphosphonates.

Generic Name
Sodium clodronate

Drug Description
Bonefos Capsules: yellow capsules. Bonefos Tablets: white f-c oval scored tablets marked L134. Bonefos Injection: solution in ampoules.

Presentation
Bonefos Capsules: Sodium clodronate 400 mg . Bonefos Tablets: Sodium clodronate 800 mg . Bonefos Injection: Sodium clodronate 60 mg /mL.

Indications
Bonefos Capsules and Tablets: Osteolytic lesions, hypercalcaemia and bone pain associated with skeletal metastases in breast cancer or multiple myeloma. Hypercalcaemia of malignancy. Bonefos Injection: Hypercalcaemia

Adult Dosage
The recommended daily dose of BONEFOS is 1600 mg sodium clodronate taken as a single dose or in two divided doses (800 mg bd). The capsules should be taken with a little fluid, but not milk, at least 1 hour before or 1 hour after food. If necessary, the dose may be increased but should not exceed a maximum of 3200 mg sodium clodronate daily.The oral bioavailability of bisphosphonates is poor. Bioequivalence studies have shown appreciable differences in bioavailability between different oral formulations of sodium clodronate, as well as marked inter- and intra-patient variability. Dose adjustment may be required if the formulation is changed.Dose adjustment is not recommended when switching between BONEFOS capsule and tablet formulations.Renal impairment:In patients with moderate renal impairment (creatinine clearance between 10 and 30 ml/min), the daily dose should be reduced to half the adult dose, i.e. 800 mg sodium clodronate. Sodium clodronate is contra-indicated in patients with creatinine clearance below 10 ml/min.

Child Dosage
BONEFOS has not been eva luated in children

Elderly Dosage
There are no special dosage recommendations in the elderly. Clinical trials have included patients over 65 years and no adverse reactions specific to this age group have been reported.

Contra Indications
BONEFOS Capsules are contraindicated in patients with known hypersensitivity to bisphosphonates, in patients with moderate to severe renal failure (serum creatinine greater than 440 micromol/l or creatinine clearance below 10 ml/min), in children, in pregnant and lactating women, and in patients receiving other bisphosphonates.

Special Precautions
BONEFOS Capsules should be administered with care to patients with renal insufficiency. It is recommended that appropriate monitoring of hydration status and renal function with serum creatinine measurement be carried out during treatment. Serum calcium should be monitored periodically.Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including osteomyelitis) has been reported in patients with cancer receiving treatment regimens including primarily intravenously administered bisphosphonates. Many of these patients were also receiving chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with osteoporosis receiving oral bisphosphonates.A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene).While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw.Clinical judgement of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.

Interactions
Concomitant use of other bisphosphonates is contraindicated. Patients receiving NSAIDs in addition to sodium clodronate have developed renal dysfunction. However, a synergistic action has not been established. As aminoglycosides can cause hypocalcaemia concomitant clodronate should be administered with caution. There is no evidence from clinical experience that sodium clodronate interacts with other medication such as steroids, diuretics, analgesics or chemotherapeutic agents.Bonefos forms complexes with divalent metal ions, and therefore simultaneous administration with food, antacids and mineral supplements may impair absorption.

Adverse Reactions
Side-effects include gastrointestinal disturbances, for example nausea, vomiting and diarrhoea may occur during oral treatment, but these are usually mild. If these symptoms occur, use of the divided dose regimen rather than a single daily dose may improve gastro-intestinal tolerance. Hypersensitivity reactions have been mainly confined to the skin: pruritus, urticaria, exfoliative dermatitis. Bronchospasm has been precipitated rarely in patients with and without a previous history of asthma. Renal dysfunction, including failure, has been reported.Reversible elevations of serum creatinine, parathyroid hormone, lactic acid dehydrogenase, transaminase and alkaline phosphatase have been reported. Asymptomatic hypocalcaemia has been noted infrequently, symptomatic hypocalcaemia is rare.Isolated cases of osteonecrosis of the jaw have been reported, primarily in patients who were previously treated with amino-bisphosphonates like zoledronate and pamidronate

Manufacturer
Boehringer Ingelheim

Drug Availability
(POM)

Updated
14 April 2009