Drug Interaction:
CYP450 System-
Invitro studies inducates that paricalcitrol is not an inhibitor of the system.
Hence paricalcitrol is not expected to inhibit or induce the clearance of drugs metabolized
by these system
Digoxin- digitalis toxicity is initiated by hypercalcemia of any cause, so excercise caution
when digitalis compounds are prescribed concomittantly with paricalcitrol capsules
Omeprazole- the pharmacokinetics of paricalitrol were unaffected when omiprazole was
administered approximately 2 hours prior to paricacitrol dose.
Ketoconazole-the mean half-life was 17 hours in the presence of ketoconazole compared
with 9.8 hrs when paricalitrol was administered alone.
Cholestyramine- drug that impair intestinal absorption of fat-soluble vitamins such as
chloestyramine may intrerfere with absorption of paricalcitrol.
Indication:
Hyperparathyroidism
Adverse Reaction:
Adverse reactions-
Cardiovascular system - 25%
Hypertension 7%, hypotension5%, syncope3%
CNS system- 17%
Dizziness 5%,headache 5%, vertigo 5%
Dermatologic system- 16%
Rash 6%, pruritus 3%, skin ulcer 3%
GI system- 27%
Diarrrhea 7%, gastroenteritis 3%, nausea 6% vomiting 6%, constipation 4%,
abdominal pain 4%
GU system- 9%
Urinary tract infection 3%, abnormal kidney function 2%
Hematological system- 4%
Ecchymosis 2%
Metabolic/nutritional system -22%
Edema 7%, Gout 4%, Uremia 7%
Musculoskeletal system- 11%
Arthiritis 5%, leg cramps 3% myalgia 2%
Respiratory system- 24%
Pharyngitis 10% rhinitis 5%, sinusitis 3%
Special senses- 8%
Amblyopia 2%, retinal disorder 2%
Miscellaneous- 46%
Accidental injury 9%, allergic reaction 6%, pain 7%, viral infection 7%,
asthenia 3%, chest pain 3%, infection 4%, fever 3%, back pain 4%
Contra-Indications:
Do not give paricalcitrol to patients with evidence of vitamin D toxicity, hypercalcemia,
or sensitivity to any of the ingredient in this product.
Warning/precautions-
Excessive administration of vitamin D compounds including paricalcitrol can cause
oversuppression of PTH, hypercalcemia, hypercalcuria, hyperphosphatemia, and
adynamic bone disease
Acute hypercalcemia may exacerbate tendencies for cardiac arrhyhthmias and seizures,
and it may potententiate the action of digitalis.
Concomittant vitamin D intake- withhold pharmacologic doses of vitamin D and its
derivatives during paricalcitrol treatment to avoid hypercalcemia
Pregnancy-
Use paricalcitrol during pregnancy only if potential benefit to the mother justifies
the potential risk to the fetus
Lactation-
Decide whether to discontinue breast-feeding or th drug taking into account the
importance of the drug to the mother
Children-
Safety and efficacy of paricalcitrol in children have not been established
Monitoring-
During the initial dosing or following any dosage adjustments , monitor serum
calcium, serum phosphorus, and serum or plasma iPTH at least every 2 weeks
for 3 months, then monthly for 3 months, and every 3 months thereafter.
closely monitor serum calcium and phosporus levels during coadministration
with CYP3A inhibitors
Dosages/ Overdosage Etc:
Hyperparathyroidism
Dosage-
Paricalcitrol may be administered daily or 3 times a week.
When dosing 3 times a week, the dose should be administered no more frequently
than every other day. The average weekly doses for daily and 3 times -a-week dosage
regimen are similar.
Initial dose- the initial dose of paricalcitrol is based on baseline intact parathyroid
hormone (iPTH) levels
Base line iPTH level Daily dose 3 times weekly dose
<500 pg/mL 1mcg 2mcg
more than 500 pg/mL 2mcg 4mcg
Pharmacology/ Pharmacokinetics:
Pharmacology-
Paricalcitrol is a synthetic biologically active vitamin D analog of calcitrol with modifications
to the side chain D2 and A (19-nor) ring.
Preclinical and in vitro studies have demonstrated that paricalcitrol bilogical actions
are mediated through binding of he VDR which results in the selective activation of
vitamin-D response pathways. Vitamin D and paricalcitrol have been shown to reduce
PTH levels by inhibiting PTH synthesis and secretion
Pharmacokinetics-
Following oral administration of paricalcitrol at 0.24mcg/kg
Mean absolute bioavailability was 72%
Mean plasma concentration
Cmax , time to Cmax Tmax, and area under the curve AUC were
0.63ng/mL, 3 hours, and 5.25ngh/mL respy
A food-effect study on healthy subjects indcated that Cmax and AUC were unchanged
when paricalcitrol was administered with a high fat meal compared to fasting.
Food delays Tmax about 2 hours.
Excretion-
In healthy subjects the mean elimination half-life of paricalcitrol is 4 to 6 hours over the
studied range of 0.06 to 0.48mcg/kg.
Pharmcokinetics of paricalcitrol capsules have been studied in chronic kidney disease
stage 3 and stage 4 patients.
Administration of paricalcitrol 4mcg capsules in chronic kidney stage 3 patients the
mean half life of paricaltriol is 17 hours
The mean half life of paricalcitrol is 20 hours in chronic kidney disease when given a
paricaltrol capsules 2mcg per capsule
Interaction with Food:
A food-effect study on healthy subjects indcated that Cmax and AUC were unchanged
when paricalcitrol was administered with a high fat meal compared to fasting.
Food delays Tmax about 2 hours.
Pregnancy and lactation:
Pregnancy-
Use paricalcitrol during pregnancy only if potential benefit to the mother justifies
the potential risk to the fetus
Lactation-
Decide whether to discontinue breast-feeding or th drug taking into account the
importance of the drug to the mother
Children-
safety and efficacy of paricalcitrol in children have not been established
Manufacturer Details