"Vemurafenib (Zelboraf, Roche/Genentech), a BRAF inhibitor marketed for use in the treatment of melanoma, has now shown activity in patients with refractory papillary thyroid cancer.
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The effects of administered vitamin D can persist for two or more months after cessation of treatment.
Hypervitaminosis D is characterized by:
- Hypercalcemia with anorexia, nausea, weakness, weight loss, vague aches and stiffness, constipation, mental retardation, anemia, and mild acidosis.
- Impairment of renal function with polyuria, nocturia, polydipsia, hypercalciuria, reversible azotemia, hypertension, nephrocalcinosis, generalized vascular calcification, or irreversible renal insufficiency which may result in death.
- Widespread calcification of the soft tissues, including the heart, blood vessels, renal tubules, and lungs. Bone demineralization (osteoporosis) in adults occurs concomitantly.
- Decline in the average rate of linear growth and increased mineralization of bones in infants and children (dwarfism).
The treatment of hypervitaminosis D with hypercalcemia consists in immediate withdrawal of the vitamin, a low calcium diet, generous intake of fluids, along with symptomatic and supportive treatment. Hypercalcemic crisis with dehydration, stupor, coma, and azotemia requires more vigorous treatment. The first step should be hydration of the patient. Intravenous saline may quickly and significantly increase urinary calcium excretion. A loop diuretic (furosemide or ethacrynic acid) may be given with the saline infusion to further increase renal calcium excretion. Other reported therapeutic measures include dialysis or the administration of citrates, sulfates, phosphates, corticosteroids, EDTA (ethylenediaminetetraacetic acid), and mithramycin via appropriate regimens. With appropriate therapy, recovery is the usual outcome when no permanent damage has occurred. Deaths via renal or cardiovascular failure have been reported.
The LD50 in animals is unknown. The toxic oral dose of ergocalciferol in the dog is 4 mg/kg.
Last reviewed on RxList: 5/7/2009
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