部份中文骨化三醇处方资料（仅供参考）
英文名：calcitriol
商品名：Rocaltrol
中文名：骨化三醇口服溶液
生产商：Validus Pharmaceuticals LLC
药理作用
骨化三醇是维生素D3的最重要活性代谢产物之一，通常在肾脏内由其前体25-羟基维生素D3（25-HCC）转化而成，正常生理性每日生成量为0.5~1.0ug，并在骨质合成增加期内（如生长期或妊娠期）其生长量稍有增加。骨化三醇促进肠道对钙的吸收并调节骨的矿化。单剂量骨化三醇的药理作用大约可持续3~5天。骨化三醇在调节钙平衡方面的关键作用，包括对骨骼中成骨细胞活性的刺激作用，为治疗骨质疏松症提供充分的药理基础。肾性骨营养不良的患者，口服本品使肠道吸收钙的能力恢复正常，纠正低血钙，及过高的血碱性磷酶和血甲状旁腺素浓度。本品能减轻骨与肌肉疼痛，并矫正发生在纤维性骨炎和其他矿化不足病人中的组织学改变。维生素D依赖性佝偻病人，血中骨化三醇水平降低或缺失，由于肾脏内生产骨化三醇不足，可考虑本品作为一种替代性治疗。维生素D抵抗性佝偻病病人和低磷血症的病人中，血钙水平降低，本品治疗能降低磷的管式消除，并结合磷制剂的治疗，恢复骨的生长。即使在很高剂量，无证据表明维生素D对人具有致畸作用。
适应证
1、绝经后骨质疏松；
2、慢性肾功能低下；
3、术后甲状腺功能低下；
4、特发性甲状旁腺功能低下；
5、假性甲状腺功能低下；
6、维生素D依赖性佝偻病；
7、低血磷性维生素D抵抗型佝偻病等。
用法用量
应根据每个病人血钙水平小心制定本品的每日最佳剂量。开始以本品治疗时，应尽可能使用最小剂量，并且不能在没有监测血钙水平的情况下增加用量。确定了本品的最佳剂量后，应每月复查一次血钙水平（或参照下面有关个别适应症之详细说明）。采集血钙标本时，不能使用止血带。若血钙超过正常范围（9~11mg/100ml或2250~2750u mol/l）1mg/100ml（250umol/l ），或血肌酐大于120umol/l，则必须减少剂量或完全中止治疗直至血钙正常。在血钙增高期间，必须每日测定血钙及血磷水平，血钙正常后可服用本品，但日剂量应低于前剂量0.25ug。每日应估计钙摄入量并酌情进行调整。本平最佳疗效的先决条件是足够但不过量的钙摄入量（成人：每日约800毫克），治疗开始时，补钙是必要的。
因为胃肠道对钙的吸收的改善，有些病人可能宜保持较低的钙摄入量。有高血钙倾向的病人，可能只需要小剂量补钙或完全不需要补钙。每日钙总摄取量（如从食物和药物）平均大约为800mg，不应超过1000mg。
口服，具体方法如下：
1、绝经后骨质疏松：推荐剂量为每次0.25ug，每日三次。服药后分别于第4周、第3个月、第6个月监测血钙和血肌酐浓度，以后每六个月监测一次。
2、肾习性骨营养不良（包括透析病人）：起始阶段的每日剂量为0.25ug血钙正常或略有降低的病人隔日0.25ug即可。如2~4周内生化指标及病情未见明显改善，则每隔2~4周将本品的每日用量增加0.25ug，在此期间至少每周测定血钙两次。大多数病人最佳用量为每日0.5至1.0ug之间。
3、甲状腺功能低下和佝偻病：推荐起始剂量为每日0.25ug，晨服。如生化指标和病情未见明显改善，则每隔2~4周增加剂量。在此期间，每捉至少测定血钙浓度两次。甲状旁腺功能低下者，偶见吸收不佳现象，因此这种病人需要较大剂量或遵医嘱.
不良反应
由于骨化三醇能产生维生素D的作用，所以可能发生的不良反应与维生素D过量相似。如高血钙综合症或钙中毒（取决于高钙的严重程度及持续时间）。偶见的急性症状包括食欲减退、头痛、呕吐和便秘。慢性症状包括营养不良、感觉障碍，拌有口渴的发热、尿多、脱水、情感谈漠，发育停止及泌尿道感染。
长达15年临床使用本品治疗所有适应症。结果显示不良反应发生率很低，包括高钙血症在内的发生率为0.111%或更低。并发高钙和高磷血症的病人（浓度大于6mg/100mmol/l）可能发生软组织钙化，这些表现可通过放射学检查而观察到。
肾功能正常的病人，慢性高钙血症也许与血肌酐增高有关。
由于骨化三醇的生物半衰期较短，其药代动力学研究表明，停药或减量数天后升高的血钙即回复正常范围，这一过程要比维生素D3快许多。对敏感体质的病人可能会发生过敏反应。
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ROCALTROL 0.25MCG CAP 30  CALCITRIOL  VALIDUS PHARMACEUTICALS LLC. 30698014323
ROCALTROL 1MCG/ML SOL 15ML  CALCITRIOL  VALIDUS PHARMACEUTICALS LLC. 30698091115
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Rocaltrol(Calcitriol)
ROCALTROL®
Roche
Calcitriol
Vitamin D3 Metabolite
Action And Clinical 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 (cholecalciferol) must be metabolized in the liver and the kidneys before it is fully active on its target tissues. The initial transformation is catalyzed by a vitamin D3-25-hydroxylase enzyme (25-OH-ase) 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-OH-ase) to produce 1,25-(OH)2D3 (calcitriol).
Calcitriol’s two known sites of action are intestine and bone, but additional evidence suggests that it also acts on the kidney and the parathyroid gland.
In acutely uremic rats, calcitriol stimulates 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 And Clinical Uses: The management of hypocalcemia and osteodystrophy in patients with chronic renal failure undergoing dialysis. Hypocalcemia and its clinical manifestations associated with: postsurgical hypoparathyroidism, idiopathic hypoparathyroidism, pseudohypoparathyroidism. Vitamin D resistant rickets (familial hypophosphatemia).
Contra-Indications: Hypersensitivity to calcitriol, vitamin D or its analogues and derivatives; hypercalcemia; evidence of vitamin D overdosage.
Manufacturers’ Warnings In Clinical States: Since calcitriol is a potent cholecalciferol derivative with profound effects on intestinal absorption of dietary calcium and inorganic phosphate, it should not be used concomitantly with other vitamin D products or their derivatives.
Calcitriol therapy should only be considered when adequate laboratory facilities for monitoring of blood and urine chemistries are available. During treatment, progressive hypercalcemia, either due to hyper-responsiveness or overdosage, may become so severe as to require emergency treatment.
Chronic hypercalcemia can lead to generalized vascular calcification, nephrocalcinosis, calcifications of the cornea or other soft tissues. During calcitriol treatment, the serum total calcium (mg/dL) times serum inorganic phosphate product (CaxP) should not exceed 70.
Dialysate calcium level of 7 mg % or above in addition to excessive dietary calcium supplements may lead to frequent episodes of hypercalcemia.
In patients on digitalis, hypercalcemia may precipitate cardiac arrhythmias; in such patients, use calcitriol with extreme caution.
To control serum inorganic phosphate levels and dietary phosphate absorption in patients undergoing dialysis, oral aluminum carbonate or aluminum hydroxide gel must be used. Magnesium containing antacids may contribute towards hypermagnesemia in patients on chronic renal dialysis and should be avoided during calcitriol therapy.
Pregnancy: Safety in women who are or may become pregnant has not been established; use of calcitriol in these cases may be considered only when the potential benefits have been weighed against possible hazards to mother and fetus.
Lactation: Since calcitriol may be excreted in human milk, avoid breast feeding during treatment.
Precautions: Patient selection and follow-up: Patients with renal osteodystrophy and hypocalcemia, poorly managed by conventional vitamin D therapy are likely to respond to calcitriol. The desired therapeutic margin of calcitriol is narrow; therefore, determine the optimal daily dose carefully for each patient by dose titration to obtain satisfactory response in the biochemical parameters and clinical manifestations (see Dosage).
Excessive dosage of calcitriol induces hypercalcemia and hypercalciuria; therefore, early in treatment during dosage adjustment determine serum calcium at least twice weekly. A fall in serum alkaline phosphatase values may indicate impending hypercalcemia. Should hypercalcemia develop, discontinue the drug immediately until the serum calcium has normalized. This may take several days to a week.
In patients with normal renal function, chronic hypercalcemia may be associated with an increase in serum creatinine. While the elevation of serum creatinine is usually reversible, it is important in such patients to pay careful attention to those factors which may lead to hypercalcemia. Therapy should always be started at the lowest possible dose and increased with careful monitoring of serum calcium concentrations. An estimate of daily dietary calcium intake should be made and the intake adjusted when indicated.
Patients with normal renal function should avoid dehydration. Adequate fluid intake should be maintained.
Patients with vitamin D resistant rickets (familial hypophosphatemia) should pursue their oral phosphate therapy. However, the possible stimulation of intestinal phosphate absorption should be taken into account since this effect may modify the requirement for phosphate supplements.
Essential laboratory tests: Serum calcium, inorganic phosphorus, magnesium, alkaline phosphatase as well as 24 hour urinary calcium and phosphorus should be determined periodically during calcitriol maintenance therapy. During the initial phase of the medication, determine serum calcium more frequently (at least twice weekly). Periodic ophthalmological examinations and radiological eva luation of suspected anatomical regions for early detection of ectopic calcifications are advisable.
Drug Interactions: Hypercalcemia in patients on digitalis may precipitate cardiac arrhythmias. Intestinal absorption of calcitriol may be impaired by resins such as cholestyramine and by use of mineral oil as a laxative. Although the precise mechanism involved is unknown, long-term anticonvulsant treatment, particularly with phenytoin and barbiturates, may interfere with the actions of vitamin D. Patients under concurrent treatment with such agents may require slightly higher doses of calcitriol.
Information for the Patient: Inform the patient and his or her immediate relatives about the need for compliance with dosage instructions, strict adherence to prescribed calcium intake, dietary and supplementary, and avoidance of unapproved nonprescription drugs or medications. Patients should also be made aware of the symptoms of hypercalcemia and should seek medical attention if such symptoms are noted (see Adverse Effects).
Adverse Reactions: Most frequent: hypercalcemia (20 to 30%).
Less frequent: headache, nausea, vomiting, constipation, abdominal cramps, pruritus, 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 adverse effects of 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:
a. Early: weakness, headache, somnolence, nausea, cardiac arrhythmias, excessive thirst, vomiting, dry mouth, constipation, muscle pain, bone pain, metallic taste.
b. Late: polyuria, polydipsia, 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.
Symptoms And Treatment Of Overdose: Symptoms: Calcitriol administration to patients in excess of their daily requirements can cause hypercalcemia, hypercalciuria and hyperphosphatemia. Conversely, high calcium and phosphate intake concomitantly with therapeutic doses of calcitriol may cause similar abnormalities. In dialysis patients, high levels of calcium in the dialysis bath may contribute to hypercalcemia.
Treatment: Accidental Overdosage: Employ 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, mineral oil administration may promote fecal elimination. Obtain serial serum electrolyte determinations (especially calcium ion), rate of urinary calcium excretion and assessment of ECG abnormalities due to hypercalcemia. 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 concentrations occur, a variety of therapeutic alternatives 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. Peritoneal dialysis has been used against a calcium-free dialysate.
Treatment of Hypercalcemia in Patients undergoing Hemodialysis: General treatment of hypercalcemia (more than 1 mg/dL or 0.25 mmol/L above the upper limit of the normal range) consists of immediate discontinuation of calcitriol therapy, institution of a low calcium diet and withdrawal of calcium supplements.
Determine serum calcium concentrations daily until normocalcemia ensues. Hypercalcemia frequently resolves in 2 to 7 days. When serum calcium concentrations have returned to within normal limits, calcitriol therapy may be reinstituted at a dose of 0.25 µg/day less than prior therapy. Monitor serum calcium concentrations carefully (at least twice weekly) during this period of dosage adjustment and subsequent dosage titration. Correct persistent or markedly elevated serum calcium concentrations by dialysis against a calcium-free dialysate.
Dosage And Administration: Determine the optimum daily dose carefully for each patient. The effectiveness of calcitriol therapy is predicated on the assumption that each patient is receiving an adequate daily calcium intake. 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 an adequate daily calcium intake, instruct patients regarding appropriate dietary measures or prescribe a calcium supplement. However, because of improved calcium absorption from the gastrointestinal tract, some patients may be maintained on a lower calcium intake or no supplementation at all.
Dialysis Patients: Adults: Titration: Initial calcitriol dose is 0.25 g/day. If a satisfactory response in the biochemical parameters and clinical manifestations of the disease state is not observed, dosage may be increased by 0.25 g/day at 2 to 4 week intervals. During this titration period, obtain serum calcium levels at least twice weekly, and if hypercalcemia is noted, discontinue the drug immediately until normocalcemia ensues.
Maintenance: Patients with normal or only slightly reduced serum calcium levels may respond to calcitriol at doses of 0.25 g every other day. Most patients undergoing hemodialysis respond to between 0.5 and 1 g/day.
In order to decrease the risk of hypercalcemic episodes, a downward adjustment of the calcitriol dose may be advisable once a reduction in serum alkaline phosphatase has been achieved.
Hypoparathyroidism and Vitamin D Resistant Rickets:
Adults: Initial dose: 0.25 g/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 g/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, calcitriol 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 may be needed.
Children: Initiation of Treatment: x-linked hypophosphatemic rickets: 0.01 to 0.02 g/kg/day (mean 0.018 g/kg/day).
Vitamin D dependency rickets type 1: 0.010 to 0.025 g/kg/day (mean 0.017 g/kg/day).
Hypoparathyroidism: 0.03 to 0.05 g/kg/day (mean 0.04 g/kg/day).
Response is checked after 2 weeks to ascertain that the dose has not produced hypercalcemia. Biochemical eva luation 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-eva luated 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 g/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 g/kg/day (mean 0.022 g/kg/day).
Vitamin D dependency rickets type 1=0.0046 to 0.015 g/kg/day.
Hypoparathyroidism=0.014 to 0.040 g/kg/day (mean 0.025 g/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 Calcitriol (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 calcitriol 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, calcitriol 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-eva luated 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 calcitriol therapy. However, the clinical significance of the finding of nephrocalcinosis is not known.
Calcitriol 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.
Availability And Storage: Capsules: 0.25 g: Each white/brownish-red oval soft gelatin capsule contains: calcitriol 0.25 g. Energy: 6.5 kJ (1.5 kcal). Nonmedicinal ingredients: butylated hydroxyanisole, butylated hydroxytoluene, canthaxanthin, fractionated coconut oil, gelatin, glycerin hydrogenated partially hydrolyzed starch and titanium dioxide. Alcohol-, gluten-, lactose-, sulfite- and tartrazine-free. Bottles of 100.
0.50 g: Each brownish-red oval soft gelatin capsule contains: calcitriol 0.50 g. Energy: 6.5 kJ (1.5 kcal). Nonmedicinal ingredients: butylated hydroxyanisole, butylated hydroxytoluene, canthaxanthin, fractionated coconut oil, gelatin, glycerin hydrogenated partially hydrolyzed starch and titanium dioxide. Alcohol-, gluten-, lactose-, sulfite- and tartrazine-free. Bottles of 100.
Solution: Each mL of clear, colorless, oily solution contains: calcitriol 1.0 g. Nonmedicinal ingredients: butylated hydroxyanisole, butylated hydroxytoluene and fractionated coconut oil. Bottles of 10 mL, boxes of 5.
Store capsules and solution at 15 to 30°C and protect from light. Discard solution 6 weeks after first opening the bottle.