Calcitriol
From DrugPedia: A Wikipedia for Drug discovery
| Calcitriol
| |
| Systematic (IUPAC) name | |
| (1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecycl
ohexane-1,3-diol | |
| Identifiers | |
| CAS number | ? |
| ATC code | ? |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C27H44O3 |
| Mol. mass | 416.64 |
| SMILES | & |
| Synonyms | Rocaltrol |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status | |
| Routes | ? |
Calcitriol is a form of Vitamin D3 with three alcohol groups. It increases gastrointestinal Calcium absorption, stimulates osteoclastic Calcium resorption from bone, facilitates the effect Parathyroid Hormone (PTH) has on bone resorption, and increases renal tubular absorption of Calcium. Production of Calcitriol by the cells of the Proximal Tubule of the nephron in the kidney is stimulated by hypocalcemia and hypophospatemia. Pronouncation: (Kal-si-TRYE-ole)
Contents |
[edit] General Properties
Class: Fat-soluble vitamin
Trade Names:
Calcijex
- Injection 1 mcg/mL
Trade Names:
Rocaltrol
- Capsules 0.25 mcg
- Capsules 0.5ߙmcg
- Oral solution 1 mcg/mL
Trade Names:
Calcitriol Injection
- Injection 2 mcg/mL
[edit] Pharmacology
Supply of vitamin D depends mainly on exposure to ultraviolet rays of the sun for conversion of 7-dehydrocholesterol in the skin to vitamin D 3 (cholecalciferol). Vitamin D 3 is activated in the liver and kidney before fully active as a regulator of calcium and phosphorus metabolism at target tissues.
[edit] Pharmacokinetics
Absorption
Oral
Rapidly absorbed from the intestine. T max is 3 to 6 h.
Distribution
Approximately 99.9% protein bound. Excreted in breast milk in low levels.
Metabolism
The first pathway involves 24-hydroxylase to produce calcitroic acid; the second pathway involves hydroxylation and cyclization. Calcitrol also undergoes enterohepatic recycling.
Elimination
The t ½ is about 5 to 8 h. About 27% is excreted in the feces and 7% in the urine within 24 h.
Special Populations
Renal Function Impairment
The t ½ is increased by at least 2-fold.
Children
The t ½ is prolonged.
[edit] Indications and Usage
Dialysis (Oral, IV)
Hypocalcemia and resultant metabolic bone disease in patients on chronic renal dialysis.
Predialysis (Oral)
Secondary hyperparathyroidism and resultant metabolic bone disease in patients with moderate to severe chronic renal failure (Ccr 15ߙto 55 mL/min) not yet on dialysis.
Hypoparathyroidism (Oral)
Hypocalcemia in patients with postsurgical hypoparathyroidism, idiopathic hypoparathyroidism, and pseudohypoparathyroidism.
Unlabeled Uses
Decreased severity of psoriatic lesions with an initial oral dose of 0.25 mcg twice daily and topically 0.1 to 0.5 mcg/g petrolatum.
[edit] Contraindications
Hypercalcemia or patients with vitamin D toxicity; hypersensitivity to any component of this product.
[edit] Dosage and Administration
Dialysis
PO 0.25 mcg/day. Unsatisfactory response, increase dose by 0.25 mcg/day at 4- to 8-wk intervals. Obtain serum calcium levels at least twice weekly during this titration. Normal or only slightly reduced calcium levels may respond to doses of 0.25 mcg every other day.
IV 0.02 mcg/kg (1 to 2 mcg) 3 times/wk, every other day. May increase 0.5 to 1 mcg, every 2 to 4 wk. During this titration, obtain serum calcium levels twice weekly.
Hypoparathyroidism
PO Initial dose is 0.25 mcg/day in the morning. Unsatisfactory response, increase dose at 2- to 4-wk intervals. During this titration, obtain serum calcium levels 2 times/wk.
Adults and children (6 yr of age and older)
PO 0.5ߙto 2ߙmcg daily.
Children (1 to 5 yr of age)
PO Have usually been given 0.25 to 0.75 mcg daily.
Discontinue if hypercalcemia or serum calcium times phosphate product (Ca × P) totals more than 70.
Predialysis
PO Initial dose is 0.25 mcg/day in adults and children older than 3 yr of age. Dosage may be increased up to 0.5 mcg/day. In patients younger than 3 yr of age, dosage is 10 to 15 ng/kg/day.
General Advice
- Oral
- Administer prescribed dose without regard to meals, but administer with food if GI upset occurs.
- Administer dose in the morning to patient with hypoparathyroidism.
- Administer prescribed dose of oral solution using disposable graduated oral dispensers supplied with medication.
- Injection
- For IV bolus injection only. Not for intradermal, subcutaneous, IM, or intra-arterial administration.
- Do not administer if particulate matter, cloudiness, or discoloration noted.
- Discard any unused solution. Do not save for future use.
[edit] Storage/Stability
Oral
Store capsules and oral solution at controlled room temperature (59° to 86°F). Protect from light.
Injection
Store injection at controlled room temperature (59° to 86°F).
[edit] Drug Interactions
Calcium supplements
Avoid uncontrolled intake of additional calcium-containing preparations.
Cholestyramine
May reduce intestinal absorption of fat soluble vitamins.
Ketoconazole
May reduce endogenous calcitriol concentrations.
Magnesium
Magnesium-containing products may cause hypermagnesemia and should be avoided during calcitriol administration to patients on chronic renal dialysis.
Phenytoin/Phenobarbital
Inhibits endogenous synthesis of calcitriol, therefore may require higher doses if given simultaneously.
Phosphate-binding agents
Because phosphate transport in the intestine, kidneys, and bones may be affected, the dosage of phosphate-binding agents must be adjusted based on serum phosphate concentration.
Thiazides
Known to induce hypercalcemia by the reduction of calcium excretion.
Vitamin D
To avoid possible additive effects and hypercalcemia, withhold pharmacologic doses of vitamin D and its derivatives.
Laboratory Test Interactions
None well documented.
[edit] Adverse Reactions
See overdosage section.
[edit] Precautions
Monitor
Calcium intake
Ensure that patient is receiving an adequate daily intake of calcium. Consider adding a calcium supplement if dietary calcium intake is less than 600 mg/day.
Dialysis patients
Ensure that serum calcium, phosphorous, magnesium, and alkaline phosphatase are determined periodically in patient on dialysis.
Hypercalcemia symptoms
Frequently assess patient for signs and symptoms of hypercalcemia (eg, weakness, headache, drowsiness, nausea, vomiting, bone pain, metallic taste, appetite loss, weight loss, polyuria, polydipsia, nocturia, photophobia, mental status change). Immediately inform health care provider if noted.
Hypercalcemic patients
Ensure that serum calcium and phosphorous are evaluated daily during periods of hypercalcemia.
Hypoparathyroid patients
Ensure that serum calcium, phosphorous, and 24-h urinary calcium are determined periodically in hypoparathyroid patient.
Predialysis patients
Ensure that serum calcium, phosphorous, alkaline phosphatase, creatinine, and intact parathyroid hormone (iPTH) are determined before starting therapy in predialysis patient. Thereafter, serum calcium, phosphorous, alkaline phosphatase, and creatinine should be determined monthly for 6 mo and then periodically thereafter. The iPTH should be determined every 3 to 4 mo.
Serum calcium levels
Ensure that serum calcium is evaluated before starting therapy, twice weekly during dosage adjustment, and then periodically thereafter, and that blood samples are taken without a tourniquet. If hypercalcemia is noted or if the serum calcium times phosphate product (Ca × P) is greater than 70, immediately discontinue therapy and notify health care provider.
Pregnancy
Category C .
Lactation
May be excreted in breast milk.
Children
Safety and efficacy not established in dialysis patients.
Elderly
Dose selection should be cautious, starting at the low end of the dosage range.
[edit] Overdosage
Symptoms
Adverse reactions are associated with excessive intake. The early stage of toxicity includes the following: weakness, headache, somnolence, nausea, vomiting, dry mouth, constipation, muscle pain, bone pain, metallic taste. The late stage symptoms of toxicity include the following: cardiac arrhythmias, hypertension, pruritus, conjunctivitis (calcific), anorexia, weight loss, pancreatitis, polyuria, polydipsia, nocturia, elevated BUN, nephrocalcinosis, hypercholesterolemia, elevated AST/ALT, albuminia, decreased libido, hyperthermia, photophobia, rhinorrhea, ectopic calcification, overt psychosis, dystrophy, sensory disturbances, dehydration, apathy, arrested growth, UTI.
[edit] Patient Information
- Instruct patient to carefully follow the diet and calcium supplementation instructions supplied by health care provider.
- Advise patient to take prescribed dose without regard to meals but to take with food if GI upset occurs.
- Advise patient or caregiver using oral solution to use disposable graduated oral dispensers supplied with medication.
- Instruct dialysis patient to avoid using any magnesium-containing products (eg, antacids).
- Educate patient regarding signs and symptoms of hypercalcemia. Instruct patient to immediately inform health care provider if they occur.
