Rocaltrol
Rocaltrol Medication Information:
Rocaltrol medication comes in several different strengths; click on the strength you need to view prices from pharmacies competing to earn your business.
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Rocaltrol 0.250 mcg
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Rocaltrol 0.500 mcg
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Rocaltrol Oral Solution 1MCG/ML 1 mcg/mL
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Pharmacology
The supply of vitamin D in man depends on dietary intake and/or exposure to the ultraviolet rays of the sun for conversion of 7-dehydrocholesterol to vitamin D3 (cholecalciferol). Vitamin D3 must be metabolized in the liver and the kidney before it is fully active on its target tissues. The initial transformation is catalyzed by a vitamin D3-25-hydroxylase enzyme (25-OHase) present in the liver, and the product of this reaction is 25-hydroxy-vitamin D3 (25-OH-D3). The latter undergoes hydroxylation in the mitochondria of kidney tissue. This reaction is activated by the renal 25-hydroxy-vitamin D3-1 alphahydroxylase (alpha-OHase) to produce 1,25-(OH)2D3 (calcitriol).
The 2 known sites of action of calcitriol are intestine and bone, but additional evidence suggests that it also acts on the kidney and the parathyroid gland.
In acutely uremic rats, calcitriol has been shown to stimulate calcium absorption. It is the most active known form of vitamin D3 in stimulating intestinal calcium transport. This agent also promotes the intestinal absorption of phosphorus through stimulation of an active transport system distinct from the calcium transport process.
Calcitriol stimulates bone resorption which serves to mobilize calcium for the circulation, when an intestinal source of calcium is absent. This effect is related to the role of vitamin D in maintaining the homeostasis of calcium and phosphorus in plasma. In addition, calcitriol may interact directly with osteoblasts.
Calcitriol's effects on the renal transport of calcium and phosphate appear to be influenced by the presence or absence of the parathyroid glands, vitamin D status, volume expansion and the dose of vitamin D metabolite used. With the available information it is not possible to determine which vitamin D metabolite, if any, influences divalent ion transport by the renal tubule under physiologic conditions or if so, whether an interaction with parathyroid hormone is required.
The presence of a direct negative feedback effect of calcitriol on the parathyroid gland has been suspected. Some investigators have postulated that calcitriol may exert a direct influence on the parathyroids. Although inhibition of PTH secretion by calcitriol has been demonstrated in vitro, the data obtained from in vivo studies are more equivocal.
Indications
Rocaltrol (calcitriol) is indicated in the management of:
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Hypocalcemia and osteodystrophy in patients with chronic renal failure undergoing dialysis.
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Hypocalcemia and its clinical manifestations associated with:
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Post surgical hypoparathyroidism
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Idiopathic hypoparathyroidism
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Pseudohypoparathyroidism
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Vitamin D resistant rickets (familial hypophosphatemia).
Precautions
Supplied
Capsules
0.50 µg
Each brown-orange to red-orange, opaque, oval soft gelatin capsule contains: calcitriol 0.50 µg. Nonmedicinal ingredients: butylated hydroxyanisole, butylated hydroxytoluene, fractioned coconut oil, gelatin, glycerol 85%, hydrogenated products of partially hydrolysed starch, red iron oxide, titanium dioxide E 171 and yellow iron oxide. Blister packages of 100. Store at 15-25°C, store in the original container. Protect from light and moisture. Keep blister in the outer carton.
Solution
Each mL of clear, colourless oily solution contains: calcitriol 1.0 µg. Nonmedicinal ingredients: butylated hydroxyanisole, butylated hydroxytoluene and medium chain triglyceride. Bottles of 10 mL. Store at 15-30°C, store in the original container. Protect from light.
0.25 µg
Each brown-orange to red-orange, opaque (first-half)/white to grey-yellow or grey-orange, opaque (second half), oval soft gelatin capsule contains: calcitriol 0.25 µg. Nonmedicinal ingredients: butylated hydroxyanisole, butylated hydroxytoluene, fractioned coconut oil, gelatin, glycerol 85%, hydrogenated products of partially hydrolysed starch, red iron oxide, titanium dioxide E 171 and yellow iron oxide. Blister packages of 100. Store at 15-25°C, store in the original container. Protect from light and moisture. Keep blister in the outer carton.
Contraindications
Rocaltrol (calcitriol) should not be given to patients with hypercalcemia or with a known hypersensitivity to calcitriol, vitamin D or its analogues and derivatives. It should not be administered if there is evidence of vitamin D overdosage.
Warnings
Lactation
Rocaltrol may be excreted in human milk. In view of the potential for hypercalcemia in the mother and for adverse reactions from Rocaltrol in nursing infants, mothers may breastfeed while taking Rocaltrol, provided that the serum calcium levels of the mother and infant are monitored.
Pregnancy
The safety of Rocaltrol in women who are or may become pregnant has not been established; use of Rocaltrol in these cases may be considered only when the potential benefits have been weighed against possible hazards to mother and fetus.
Adverse Effects
The following adverse reactions, based on clinical studies, have been reported in association with Rocaltrol treatment:
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Most frequent: hypercalcemia (20-30%).
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Less frequent: headache, nausea, vomiting, constipation, abdominal cramp, pruritis, conjunctivitis, agitation, extremity pain, apprehension, polyuria, insomnia, elevated AST and/or ALT, elevated alkaline phosphatase, hypercalciuria, hypermagnesemia, hyperphosphatemia, elevated lymphocytes, elevated hematocrit, elevated neutrophils, elevated hemoglobin.
The number of adverse effects reported from clinical use of Rocaltrol over a period of 15 years in all indications is very low with each individual effect, including hypercalcemia, occurring at a rate of 0.001% or less.
Hypersensitivity reactions (pruritus, rash, urticaria, and very rarely severe erythematous skin disorders) may occur in susceptible individuals. The adverse effects of Rocaltrol (calcitriol) are, in general, similar to those encountered with excessive vitamin D intake. The early and late signs and symptoms associated with vitamin D intoxication and hypercalcemia are:
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Early: weakness, headache, somnolence, nausea, cardiac arrhythmias, excessive thirst, vomiting, dry mouth, constipation, muscle pain, bone pain, metallic taste, abdominal pain or stomach ache.
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Late: polyuria, polydipsia, urinary tract infections, anorexia, weight loss, nocturia, conjunctivitis (calcific), pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolemia, elevated AST and ALT, ectopic calcification, hypertension, cardiac arrhythmias, and rarely, overt psychosis.
Overdose
Symptoms
Administration of Rocaltrol (calcitriol) to patients in excess of their daily requirements can cause hypercalcemia, hypercalciuria and hyperphosphatemia. Conversely, high intake of calcium and phosphate concomitantly with therapeutic doses of Rocaltrol may cause similar abnormalities. In dialysis patients, high levels of calcium in the dialysis bath may contribute to hypercalcemia. The serum calcium times phosphate (Ca x P) product should not be allowed to exceed 70 mg2/dL2.
Treatment of Accidental Overdosage
The treatment of acute accidental overdosage with Rocaltrol should consist of general supportive measures. If drug ingestion is discovered within a relatively short time, induction of emesis or gastric lavage may be of benefit in preventing further absorption. If the drug has passed through the stomach, the administration of mineral oil may promote its fecal elimination. Serial serum electrolyte determinations (especially calcium ion) rate of urinary calcium excretion and assessment of electrocardiographic abnormalities due to hypercalcemia should be obtained. Such monitoring is critical in patients receiving digitalis. Discontinuation of supplemental calcium and low calcium diet are also indicated in accidental overdosage. Due to the relatively short pharmacological action of calcitriol, further measures are probably unnecessary. Should, however, persistent and markedly elevated serum calcium levels occur, there are a variety of therapeutic alternatives which may be considered, depending on the patient's underlying condition. These include the use of drugs such as phosphates and corticosteroids as well as measures to induce an appropriate forced diuresis. The use of peritoneal dialysis against a calcium-free dialysate has also been reported.
Dosage
The optimal daily dose of Rocaltrol (calcitriol) must be carefully determined for each patient. The effectiveness of calcitriol therapy is predicated on the assumption that each patient is receiving an adequate daily intake of calcium. The recommended daily intake for calcium is in the order of 800 mg for adults and 350 mg for infants during the first 6 months of life.
To ensure that each patient receives an adequate daily intake of calcium, the physician should either prescribe a calcium supplement or instruct the patient in appropriate dietary measures.
However, because of improved calcium absorption from the gastrointestinal tract, some patients on Rocaltrol may be maintained on a lower calcium intake or no supplementation at all.
Dialysis Patients: Adults: Titration: The recommended initial dose of Rocaltrol is 0.25 µg/day. If a satisfactory response in the biochemical parameters and clinical manifestations of the disease state are not observed, dosage may be increased by 0.25 µg/day at 2- to 4-week intervals. During this titration period, serum calcium levels should be obtained at least twice weekly, and if hypercalcemia is noted, the drug should be immediately discontinued until normocalcemia ensues.
Maintenance: Patients with normal or only slightly reduced serum calcium levels may respond to Rocaltrol doses of 0.25 µg every other day. Most patients undergoing hemodialysis respond to between 0.5 and 1 µg/day.
In order to decrease the risk of hypercalcemic episodes, a downward adjustment of the dose of Rocaltrol may be advisable once a reduction in serum alkaline phosphatase has been achieved.
Hypoparathyroidism and Vitamin D Resistant Rickets: Adults: The recommended initial dose of Rocaltrol is 0.25 µg/day. If a satisfactory response in the biochemical parameters and clinical manifestations of the disease are not observed, the dose may be increased by 0.25 µg/day at 2- to 4-week intervals. During the dosage titration period, serum calcium levels should be measured at least twice weekly and, if hypercalcemia is present, Rocaltrol should be immediately discontinued until normocalcemia ensues. Consideration should also be given to lowering the calcium intake.
Malabsorption is occasionally noted in patients with hypoparathyroidism; hence, larger doses of Rocaltrol may be needed.
Children: Initiation of Treatment: X linked hypophosphatemic rickets: 0.01 to 0.02 µg/kg/day (mean 0.018 µg/kg/day).
Vitamin D dependency rickets type 1: 0.010 to 0.025 µg/kg/day (mean 0.017 µg/kg/day).
Hypoparathyroidism: 0.03 to 0.05 µg/kg/day (mean 0.04 µg/kg/day).
Response is checked after 2 weeks to ascertain that the dose has not produced hypercalcemia. Biochemical evaluation should include serum calcium (total and ionized if available), phosphate, alkaline phosphatase, and creatinine. If satisfactory biochemical improvement has not occurred, the dose is increased by about 25% and the effect re-evaluated in 2 weeks. Until the desired response to treatment is achieved, the dose is gradually increased or decreased in this manner. Improvement in the radiographic lesions of rickets takes several weeks to become apparent.
For severely hypocalcemic or symptomatic patients, an initial dose as high as 0.05 µg/kg/day may be used to treat the hypocalcemia. In this situation, the serum calcium concentration should be monitored very closely (hospitalization recommended) and, as soon as the patient is out of danger from hypocalcemia, the dose reduced.
Maintenance: X linked hypophosphatemic rickets: 0.01 to 0.05 µg/kg/day (mean 0.022 µg/kg/day).
Vitamin D dependency rickets type 1: 0.0046 to 0.015 µg/kg/day.
Hypoparathyroidism: 0.014 to 0.040 µg/kg/day (mean 0.025 µg/kg/day).
Assessment of serum calcium (total and ionized), phosphate, alkaline phosphatase and creatinine should be made at 3 to 4 month intervals once treatment has been established and for as long as the medication is administered.
Hypercalcemia can occur at any time while the patient is treated with Rocaltrol (even if the dose has not been changed). Patients with rachitic or osteomalacic bone changes may become hypercalcemic as the bones become remineralized and therefore take up less calcium from the blood. To decrease the risk of hypercalcemia, a downward adjustment of the Rocaltrol dose may be advisable once a reduction in serum alkaline phosphatase has been achieved.
The single most important indicator of calcitriol overdose appears to be hypercalcemia as determined by accurate and frequent measurement of the serum calcium concentration. Signs of hypercalcemia such as polyuria, nocturia, polydipsia, nausea, vomiting, anorexia, weight loss, and constipation should be watched for but are less sensitive indicators of toxicity. Most hypercalcemic patients are asymptomatic.
If hypercalcemia occurs, Rocaltrol is discontinued for 1 to 2 weeks or until hypercalcemia disappears. Hypercalcemia frequently resolves in 2 to 7 days. Therapy is then resumed with a dose about 25% lower than that which caused intoxication. If the dose has been increased or decreased for any reason, the calcium level should be re-evaluated at 2-week intervals.
Fasting urine samples for measurement of calcium/creatinine ratio may be used to monitor the development of hypercalciuria.
Kidney ultrasounds may be indicated yearly during Rocaltrol therapy. However, the clinical significance of the finding of nephrocalcinosis is not known.
Rocaltrol solution must be measured accurately and can be administered directly into the mouth of the infant. The bottle should be closed tightly each time after use, and when stored between 15 and 30°C and protected from light, the solution is stable for 6 weeks after opening.
Intermittent (pulse) Therapy: Oral intermittent (pulse) therapy with Rocaltrol 2 or 3 times weekly has been shown to be effective even in patients refractory to continuous therapy. Serum calcium levels should be monitored during therapy.
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