Zemplar Soft Capsules

/ AbbVie

This drug can be taken with or without food.
Chronic Kidney Disease (CKD) Stages 3 and 4: This drug should be administered once a day, either daily or three times a week taken every other day.
Initial Dose: The initial dose is based on baseline intact parathyroid hormone (iPTH) levels.
Dose Titration: Dosing must be individualised based on serum or plasma iPTH levels, with monitoring of serum calcium and serum phosphorus.
Chronic Kidney Disease (CKD), Stage 5: Should be administered three times a week every other day.
Initial Dose: The initial dose of this drug  in micrograms is based on a baseline ipth level (pg/ml)/60 [(pmol/l)/7], up to an initial maximum dose of 32 micrograms.
Dose Titration: Subsequent dosing should be individualised and based on iPTH, serum calcium and phosphorus levels. A suggested dose titration of paricalcitol capsules is based on the following formula:
Titration dosage (micrograms) =most recent iPTU level (pg/ml)/60 or Titration dosage (micrograms) =most recent iPTU level (pmol/L)/7 Serum calcium and phosphorus levels should be closely monitored after initiation, during dose titration periods, and with co-administration of strong P450 3A inhibitors. If an elevated serum calcium or elevated Ca x P is observed and the patient is on a calcium-based phosphate binder, the binder dose may be decreased or withheld, or the patient may be switched to a non-calcium-based phosphate binder.If serum calcium > 11.0 mg/dL (2.8 mmol/L) or Ca x P > 70 mg2/dL2 (5.6 mmol2/L2) or iPTH 150 pg/mL, the dose should be decreased by 2 to 4 micrograms with respect to that calculated by the most recent iPTH/60 (pg/mL) [iPTH/7 (pmol/L)]. If further adjustment is required, the dose of paricalcitol capsules should be reduced or interrupted until these parameters are normalised.As iPTH approaches the target range (150-300 pg/mL), small, individualised dose adjustments may be necessary in order to achieve a stable iPTH. In situations where monitoring of iPTH, Ca or P occurs less frequently than once per week, a more modest initial and dose titration ratio may be warranted.
Special Populations
Hepatic Impairment: No dose adjustment is required in patients with mild to moderate hepatic impairment. There is no experience in patients with severe hepatic impairment.
Pediatric population: Safety and efficacy in paediatric patients have not been established.
Elderly: No overall differences in safety and effectiveness were observed between elderly patients (65 – 75 years) with regard to younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Prevention and treatment of secondary hyperparathyroidism associated with chronic renal insufficiency (chronic kidney disease Stages 3 and 4) patients and chronic renal failure (chronic kidney disease Stage 5) patients on haemodialysis or peritoneal dialysis.

Paricalcitol should not be given to patients with evidence of vitamin D toxicity, hypercalcaemia, or hypersensitivity to paricalcitol or any of the excipients in this medicinal product.      

Over suppression of parathyroid hormone may result in elevations of serum calcium levels and may lead to low-turnover bone disease. Patient monitoring and individualised dose titration is required to reach appropriate physiological endpoints.
If clinically significant hypercalcaemia develops and the patient is receiving a calcium-based phosphate binder, the dose of the calcium-based phosphate binder should be reduced or interrupted. Chronic hypercalcaemia may be associated with generalized vascular calcification and other soft tissue calcification. Phosphate or vitamin D-related medicinal products should not be taken concomitantly with paricalcitol due to an increased risk of hypercalcaemia and Ca x P product elevation. In pre-dialysis patients, paricalcitol, like other vitamin D receptor activators, may increase serum creatinine (and therefore decrease the estimated GFR [eGFR]) without changing true glomerular filtration rate (GFR).
See prescribing information for full details.

Pruritus, hypoparathyrodism, hypercalcaemia, hyperphosphataemia, headache, dysgeusia.
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Ketoconazole: Ketoconazole is known to be a nonspecific inhibitor of several cytochrome P450enzymes. The available in vivo and in vitrodata suggest that ketoconazole may interact with enzymes that are responsible for the metabolism of paricalcitol and other vitamin D analogs. Caution should be taken while dosing paricalcitol with ketoconazole.The effect of multiple doses of ketaconazole administered as 200 mg, twice daily (BID) for 5 days on the pharmacokinetics of paricalcitol capsulehas been studied in healthy subjects. The Cmax of paricalcitol was minimally affected, but AUC0- approximately doubled in the presence of ketoconazole. The mean half-life of paricalcitol was 17.0 hours in the presence of ketoconazole as compared to 9.8 hours, when paricalcitol was administered alone. The results of this study indicate that following either oral or intravenous administration of paricalcitol the maximum amplification of the paricalcitol AUCINF from a drug interaction with ketoconazole is not likely to be greater than about two-fold.
Specific interaction studies were not performed. Digitalis toxicity is potentiated by hypercalcaemia of any cause, so caution should be applied when digitalis is prescribed concomitantly with paricalcitol. Phosphate or vitamin D-related medicinal products should not be taken concomitantly with paricalcitol due to an increased risk of hypercalcaemia and Ca x P product elevation. High doses of calcium-containing preparation or thiazide diuretics may increase the risk of hypercalcaemia. Magnesium-containing preparations (e.g. antacids) should not be taken concomitantly with vitamin D preparations, because hypermagnesemia may occur. Aluminium-containing preparations (e.g. antacids, phosphate-binders) should not be administered chronically with Vitamin D medicinal products, as increased blood levels of aluminium and aluminium bone toxicity may occur. Drugs that impair intestinal absorption of fat-soluble vitamins, such as cholestyramine, may interfere with the absorption of Paricalcitol.
See prescribing information for full details. 

Pregnancy: There is no adequate data on the use of Paricalcitol in pregnant women.
Lactation: It is not known whether Paricalcitol is excreted in human milk.
See prescribing information for full details.                  

Excessive administration of Paricalcitol capsules can cause hypercalcaemia, hypercalciuria, hyperphosphataemia, and over suppression of parathyroid hormone. High intake of calcium and phosphate concomitant with Paricalcitol capsules may lead to similar abnormalities.
Treatment of patients with clinically significant hypercalcaemia consists of immediate dose reduction or interruption of Paricalcitol therapy and includes a low calcium diet, withdrawal of calcium supplements, patient mobilisation, attention to fluid and electrolyte imbalances, assessment of electrocardiographic abnormalities (critical in patients receiving digitalis), and haemodialysis or peritoneal dialysis against a calcium-free dialysate, as warranted.
Signs and symptoms of vitamin D intoxication associated with hypercalcaemia include: Early: Weakness, headache, somnolence, nausea, vomiting, dry mouth, constipation, muscle pain, bone pain and metallic taste.
Late: Anorexia, weight loss, conjunctivitis (calcific), pancreatitis, photophobia, rhinorrhoea, pruritis, hyperthermia, decreased libido, elevated BUN, hypercholesterolaemia, elevated AST and ALT, ectopic calcification, hypertension, cardiad arrhythmias, somnolence, death and rarely, overt psychosis. Serum calcium levels should be monitored frequently until normocalcaemia ensues. Paricalcitol is not significantly removed by dialysis.