warnings and cautions
5 WARNINGS AND PRECAUTIONS Hypercalcemia : The risk may be increased when Paricalcitol Injection is used concomitantly with high dose calcium preparations, thiazide diuretics, or metabolically inactive or active forms of vitamin D. Monitor serum calcium when using Paricalcitol Injection and adjust dose accordingly. ( 5.1 ) Digitalis Toxicity : Hypercalcemia increases the risk of digitalis toxicity. In patients using Paricalcitol Injection concomitantly with digitalis compounds, monitor both serum calcium and patients for signs and symptoms of digitalis toxicity and increase frequency of monitoring when initiating or adjusting the dose of Paricalcitol Injection. ( 5.2 ) Risk of Increased Paricalcitol Levels With Concomitant Use of Strong CYP3A Inhibitors : Use of Paricalcitol Injection with strong CYP3A inhibitors increases the concentration of paricalcitol in the blood. In patients on Paricalcitol Injection who are initiating or discontinuing drugs known to be strong CYP3A inhibitors, monitor serum calcium and PTH more frequently and adjust Paricalcitol Injection dose as required. ( 5.3 ) Adynamic Bone Disease : May develop if PTH levels are suppressed to abnormally low levels. Monitor PTH levels and adjust Paricalcitol Injection accordingly. ( 5.4 ) 5.1 Hypercalcemia Hypercalcemia may occur during Paricalcitol Injection treatment and may be exacerbated by concomitant administration of high doses of calcium containing preparations, thiazide diuretics, or vitamin D (i.e., all forms). Acute hypercalcemia may exacerbate tendencies for cardiac arrhythmias and seizures and may potentiate the effect of digitalis on the heart. Chronic hypercalcemia can lead to generalized vascular calcification and other soft-tissue calcification. Hypercalcemia may be so severe as to require emergency attention. High intake of calcium and phosphate concomitantly with vitamin D compounds may lead to hypercalcemia, hypercalciuria, and hyperphosphatemia. Prevention of such adverse reactions requires frequent serum calcium monitoring and careful Paricalcitol Injection dose adjustments. Concomitant use with other active vitamin D analogues should be avoided during Paricalcitol Injection treatment to prevent hypercalcemia. Patients also should be informed about the symptoms of elevated calcium, which include feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination and weight loss. 5.2 Digitalis Toxicity Hypercalcemia of any cause increases the risk of digitalis toxicity. In patients using Paricalcitol Injection concomitantly with digitalis compounds, monitor both serum calcium and patients for signs and symptoms of digitalis toxicity and increase frequency of monitoring when initiating or adjusting the dose of Paricalcitol Injection [see Dosage and Administration ( 2 ) ]. 5.3 Risk of Increased Paricalcitol Levels With Concomitant Use of Strong CYP3A Inhibitors Concomitant use of Paricalcitol Injection with strong CYP3A inhibitors will increase the levels of paricalcitol in the blood. In patients on Paricalcitol Injection who are initiating or discontinuing therapy with drugs known to be strong CYP3A inhibitors, monitor serum calcium and PTH more frequently and adjust Paricalcitol Injection dose as required [see Drug Interactions ( 7.1 ), Clinical Pharmacology ( 12.3 ) ]. 5.4 Adynamic Bone Disease Adynamic bone disease with subsequent increased risk of fractures may develop if PTH levels are suppressed to abnormally low levels. Monitor PTH levels and adjust Paricalcitol Injection dose [see Dosage and Administration ( 2 ) ].