Clodronate
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Clodronate is relatively safe, nontoxic drug. Safety has now been evaluated in fifty-nine published clinical trials. The side effects that do occur are usually mild, of short duration, and easy to manage.
Gastrointestinal disturbances, including nausea, vomiting, and diarrhea, have been reported in 2 percent to 10 percent of patients taking clodronate orally. In most cases this problem was mild and transient. Hypocalcemia occasionally develops, which is easily reversed by lowering the dosage. Three cases of fatal kidney failure have been reported in connection with clodronate therapy. A few patients have shown a rise in serum LDH, a liver enzyme, while taking clodronate, but this may be attributed to other advancing cancer activity, unrelated to the bone involvement.
Clodronate therapy is usually begun with the intravenous infusion of 300 mg (1 ampule) daily. Usually three to five days is sufficient to produce normal calcium levels, and the patient can then be maintained with oral clodronate. In my clinical experience, occasionally patients whose bone cancer is very advanced may be slow to respond and require five additional days of intravenous clodronate treatment.
After intravenous treatment is completed, the recommended oral dose of clodronate is from 1,600 mg to 2,400 mg daily, in two or three equal doses. In cases of highly advanced bone cancer, the initial dose may be increased to 3,200 mg daily. When starting the treatment of mild to moderate cases by oral dose only, the initial dose is 3,200 mg daily, which is reduced as the patient responds. In my experience an oral dosage level of 1,200 mg daily (1 400-mg capsule thirty minutes before each meal) is almost always sufficient for successful maintenance.
Therapy must be continued uninterrupted. Clinical trials with clodronate reveal that regression and relapse occur within days or weeks after discontinuation of treatment. (2, 14) Therapy with clodronate actually allows the cancerous bone lesions to heal.
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