Posology : מינונים

4.2 Posology and method of administration                            shaft fracture. Poor healing of these fractures has also been
Clodronate is eliminated mainly via the kidneys. Therefore,          reported. Discontinuation of bisphosphonate therapy in adequate fluid intake must be maintained during clodronate           patients suspected to have an atypical femur fracture should treatment.                                                           be considered pending evaluation of the patient, based on an Pediatric patients: Safety and efficacy in children have not been    individual benefit/risk assessment.
established.                                                         During bisphosphonate treatment patients should be advised to Elderly patients: There are no special dosage recommendations        report any thigh, hip or groin pain and any patient presenting for the elderly. Clinical trials have included patients over 65      with such symptoms should be evaluated for an incomplete years, and no adverse effects specific to this age group have        femur fracture.
been reported.                                                       4.5 Interaction with other medicinal products and other Adequate hydration must be ensured, and renal function and                  forms of interaction serum calcium levels should be monitored before and during           Concomitant use with other bisphosphonates is contraindicated.
treatment.                                                           Clodronate has been reported to be associated with renal The length of time that a clinically acceptable serum calcium        dysfunction when used simultaneously with non-steroidal anti- level is maintained after infusion of clodronate varies              inflammatory analgesics (NSAIDs), most often diclofenac.
considerably from patient to patient. The infusion may be            Due to increased risk of hypocalcemia, caution should be taken repeated if necessary to control the serum calcium level             when using clodronate together with aminoglycosides.
or, alternatively, treatment with oral clodronate may be             Concomitant use of estramustine phosphate with clodronate appropriate.                                                         has been reported to increase the serum concentration of orally Adult patients with normal renal function                            administered estramustine phosphate by up to 80%.
The normal dose is 300 mg (one 5-ml ampule) clodronate daily,        Clodronate forms poorly soluble complexes with divalent diluted into 500 ml of either glucose (50 mg/ml) or sodium           cations. Therefore, clodronate should not be administered chloride (9 mg/ml) solution.                                         intravenously with solutions containing divalent cations (e.g.
The prepared solution will be infused over a period of a             Ringer's solution).
minimum of two hours on successive days until normocalcemia          4.6 Fertility, pregnancy and lactation is achieved, which usually happens within five days. Such            Fertility therapy should normally not be continued for more than seven         In animal studies, clodronate did not cause fetal damage, but days.                                                                large doses decreased male fertility.
Alternatively, the dose of 1500 mg clodronate can be given as        No clinical data on the effect of clodronate on fertility in a single dose, diluted in a volume of 500 ml as recommended          humans is available.
above, with an infusion time of 4 hours.
Pregnancy
Patients with renal failure
It is not known if clodronate passes into the fetus in humans.
It is recommended that the clodronate dose to be infused be          In animal studies, clodronate did pass through the placental reduced as follows:                                                  barrier into the fetus. Furthermore, it is not known if clodronate Renal failure         Creatinine            Reduction in dose        can affect reproduction or cause fetal damage in humans. There clearance, ml/min     (%)                      are only limited amount of data from the use of clodronate in pregnant women. Bonefos is not recommended during
Mild                  50–80                 25 pregnancy and in women of childbearing potential not using
Moderate              12–50                 25–50                    effective contraception.
Severe                < 12                  50                       Lactation It is recommended that 300 mg clodronate be infused prior to         It is unknown whether clodronate is excreted in human milk.
hemodialysis and that the dose be reduced by 50% on non-             A risk to the suckling child cannot be excluded. Breast-feeding dialysis days. In such a case, the treatment schedule must be        should be discontinued during treatment with Bonefos.
limited to 5 days. It should be noted that peritoneal dialysis       4.7 Effects on ability to drive and use machines removes clodronate poorly from the circulation.
Not known.