Parkal

/ Unipharm Trading Ltd

Initial Dose should be calculated based on baseline parathyroid hormone (PTH) levels, administered as an intravenous (IV) bolus dose no more frequently then every other day at any time during dialysis.
The initial dose of paricalcitol is based on the following formula:
Initial dose (micrograms)=baseline intact PTH level (pmol/l) / 8
Or
Initial dose (micrograms)=baseline intact PTH level (pg/mL) / 80
The maximum dose safely administered in clinical studies was as high as 40 micrograms.
Titration Dose:
The currently accepted target range for PTH levels in end-stage renal failure subjects undergoing dialysis is no more than 1.5 to 3 times the non-uremic upper limit of normal, 15.9 to 31.8 pmol/l (150-300 pg/ml), for intact PTH.
Close monitoring and individual dose titration are necessary to reach appropriate physiological endpoints. If hypercalcaemia or a persistently elevated corrected Ca x P product greater than 5.2 mmol²/l² (65 mg²/dl²) is noted, the dosage should be reduced or interrupted until these parameters are normalised. Then, paricalcitol administration should be reinitiated at a lower dose. Doses may need to be decreased as the PTH levels decrease in response to therapy.
The following table is a suggested approach for dose titration: Once dosage has been established, serum calcium and phosphate should be measured at least monthly. Serum intact PTH measurements are recommended every three months. During dose adjustment with paricalcitol, laboratory tests may be required more frequently.
See prescribing information for full details.

For the prevention and treatment in adults of secondary hyperparathyroidism in patients with chronic renal failure who are undergoing haemodialysis.

Over suppression of parathyroid hormone may result in elevations of serum calcium levels and may lead to metabolic bone disease. Patient monitoring and individualized dose titration is required to reach appropriate physiological endpoints.
If clinically significant hypercalcemia 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.
Digitalis toxicity is potentiated by hypercalcaemia of any cause, so caution should be applied when digitalis is prescribed concomitantly with paricalcitol.
Caution should be exercised if co-administering paricalcitol with ketoconazole.
This medicine contains 100 mg of ethanol (alcohol) per ml of solution (100 mg per ampoule) which is equivalent to 12.7% v/v of ethanol. The amount in a 40 micrograms dose (8 ml volume) of this medicine is equivalent to 20 ml beer or 8 ml wine. The small amount of alcohol in this medicine will not have any noticeable effects.
See prescribing information for full details.

The most common adverse reaction associated with paricalcitol therapy was hypercalcaemia, occurring in 4.7% of patients. Hypercalcaemia is dependent on the level of PTH oversuppression and can be minimised by proper dose titration.
Common: Headache, Dysgeusia, Pruritus, Hypoparathyroidism, Hypercalcaemia, Hyperphosphataemia.
See prescribing information for full details.

No interaction studies have been performed with paricalcitol injection. However, an interaction study between ketoconazole and paricalcitol has been performed with the capsule formulation.
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 preparations or thiazide diuretics may increase the risk of hypercalcaemia.
Aluminium-containing preparations (e.g., antacids, phosphate-binders) should not be administered chronically with Vitamin D medicinal products, as increased blood levels of aluminum and aluminum bone toxicity may occur.
Magnesium-containing preparations (e.g. antacids) should not be taken concomitantly with vitamin D preparations, because hypermagnesaemia may occur.
Ketoconazole is known to be a non-specific inhibitor of several cytochrome P450 enzymes. The available in vivo and in vitro data 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 ketoconazole administered as 200 mg, twice daily (BID) for 5 days on the pharmacokinetics of paricalcitol capsule has 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 oral administration of paricalcitol the maximum amplification of the paricalcitol AUC ∞ from a drug interaction with ketoconazole is not likely to be greater than about two-fold.
Digitalis toxicity is potentiated by hypercalcaemia of any cause, so caution should be applied when digitalis is prescribed concomitantly with paricalcitol.

Pregnancy:
There are no adequate data from the use of paricalcitol in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. Parkal should not be used in pregnancy unless clearly necessary.
Breast-feeding:
Animal studies have shown excretion of paricalcitol or its metabolites in breast milk, in small amounts.
A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with paricalcitol should be made taking into account the benefit of breast-feeding to the child and the benefit of paricalcitol therapy to the woman.

No case of overdose has been reported.
Overdosage of paricalcitol may lead to hypercalcaemia, hypercalciuria, hyperphosphatemia, and over suppression of PTH.
In the event of an overdose, signs and symptoms of hypercalcemia (serum calcium levels) should be monitored and reported to a physician. Treatment should be initiated as appropriate.
Paricalcitol is not significantly removed by dialysis. 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.
When serum calcium levels have returned to within normal limits, paricalcitol may be reinitiated at a lower dose. If persistent and markedly elevated serum calcium levels occur, there are a variety of therapeutic alternatives that may be considered. These include the use of drugs such as phosphates and corticosteroids as well as measures to induce diuresis.
This product contains 38.6% v/v of propylene glycol as an excipient. Isolated cases of Central Nervous System depression, haemolysis and lactic acidosis have been reported as toxic effect associated with propylene glycol administration at high doses. Although they are not expected to be found with administration as propylene glycol is eliminated during the dialysis process, the risk of toxic effect in overdosing situations has to be taken into account.

Paricalcitol may have minor influence on the ability to drive and use machines. Dizziness may occur following administration of paricalcitol.
Product contains: Ethanol (12.7% v/v) and propylene glycol (38.6% v/v).
Propylene glycol interacts with heparin and neutralises its effect. This product contains propylene glycol as an excipient and should be administered through a different injection port than heparin.
See prescribing information for full details.