75．罗钙全

出处：按学科分类—医药、卫生 军事医学科学出版社《临床常用进口药物手册》第422页（12704字）

【中文释文】：

(骨化三醇)维生素D₃的生物活性药物

〔成分〕

罗钙全的活性成分是骨化三醇的合成物：1_α，25-二羟胆钙化醇：(5Z，7F)-9，10-开环胆甾-5，10(19)-三烯-1_α，3β，25-三醇。罗钙全有0．25μg及0．5μg的胶囊制剂。

〔性质〕

骨化三醇是维生素D₃的最重要活性代谢物之一。此代谢物通常是在肾脏内形成的其前体是25-骨化二醇。骨化三醇具有促进小肠吸收钙并调节骨的无机盐代谢等作用。

在有明显肾功能不全的病人，特别是需要长期血液透析的病人，内源性骨化三醇的合成会大幅度下降，甚至几乎停止合成，此种缺乏导致肾性骨营养不良。

减轻骨与肌肉的疼痛，有助于调节正常或降低已增高的血清碱性磷酸酶，调节正常或降低已增高的血清甲状旁腺素浓度。

在术后甲状旁腺功能低下，自发性甲状旁腺功能低下，假性甲状旁腺功能低下，低钙血症的病人，经罗钙全治疗后能减轻其临床症状。

在维生素D依赖性佝偻病的病人，血清骨化三醇水平低下或缺乏，因为其肾脏内源性骨化三醇缺乏所致。罗钙全则可起替代治疗。

罗钙全对维生素D抗性佝偻病和低磷酸盐血症的病人也有疗效。虽然长期的疗效未得以证实，但在一些病人，罗钙全可改善低磷酸盐血症。罗钙全的治疗也适用于新生儿肝炎，胆道闭锁、胱氨酸病和缺乏钙及维生素D饮食所致的佝偻病病人。

〔药代动力学〕

在正常人，氚标记及无标记的骨化三醇实验指出，口服后骨化三醇很快便会被吸收，3～6h内达峰值。

最快可在口服7h便使钙水平增加，这是由于迅速吸收的结果。每天两次0．5μg及1．0μg的剂量所引起的尿钙排泄反映出生物反应是和剂量有关的。每天两次0．5μg或1．0μg的剂量所达到的稳定状态水平会在停药后(药物半衰期为3．5h)下降至基线值。

〔适应证〕

慢性肾功能衰竭病人的肾性骨营养不良，特别是需要长期血液透析的病人。

手术后甲状旁腺功能低下，自发性甲状旁腺功能低下，假性甲状旁腺功能低下。

维生素D依赖性佝偻病，血磷酸盐过少，维生素D抗性佝偻病。

〔禁忌证〕

凡与高血钙有关的疾病。

〔备注〕

鉴于骨化三醇是维生素D₃的重要代谢产物之一，因此，在罗钙全治疗期间，不能同时给予维生素D制剂及其衍生物，以免可能增加作用和引起高钙血症。

〔妊娠期应用〕

孕妇应用罗钙全的安全性未被确立。因此必须仔细权衡用药的利弊，即药物带来的好处及可能给孕妇和胎儿带来的危险。

〔儿童应用〕

因为3岁以下及进行透析的儿童应用罗钙全的经验不足，所以必须权衡药物的利弊。

〔剂量与用法〕

罗钙全的最合适日剂量应该根据每个病人血清钙的水平仔细地予以测定。肾性骨营养不良(透析病人)：首次剂量是0．25μg／d。如病人血清钙水平正常或略低，则隔天给予0．25μg已足够。如果在2～4周，病情及生化指标等方面均无明显的改善，那么可在2～4周的期间内把剂量增加0．25μg／d。在此期间应每周至少2次测定病人的血钙浓度。大部分病人在剂量为0．5～1．0μg／d的范围有内良好反应。如病人同时服用巴比妥类药物或抗惊厥剂则可能需要较大剂量。

给予病人足量的钙片(成人的剂量约为800～1000mg／d)是罗钙全发挥更大疗效的一个先决条件。如有需要，可再给予额外的钙片。

因为改善胃肠道吸收钙的功能，所以在一些病人维持服用基础剂量的钙片即可。那些有高钙血症倾向的病人只需服用低剂量钙片甚至不服用钙片。

甲状旁腺功能低下和佝偻病：首次剂量是0．25μg，晨服，如果病情及生化指标等方面改善不明显，那么在2～4周的期间内可增加日剂量。在剂量确定期间，应每周至少2次测定血钙浓度。

在甲状旁腺功能低下的病人，偶然会有吸收障碍，此时应给予大剂量的罗钙全。

一般病人：当罗钙全的最合适剂量确定后，血清钙的浓度必须每月复查一次。一旦血清钙浓度比正常值高出10mg／l(平均为90～110mg／l)，此时罗钙全的剂量必须大大减低或停止治疗直到血钙正常为止。如病人服用其他的钙制剂亦应停止，此有助于促使血清钙恢复正常水平。还必须给于低钙饮食。

在高钙血症期间，血清钙及磷酸盐的浓度必须逐日测定。当血清钙水平恢复正常后，可继续用罗钙全治疗，剂量应比前次剂量低0．25μg／d。

〔副作用〕

如果剂量不超过许可范围，罗钙全没有副作用。由于罗钙全具有维生素D的作用，因此其副反应类似维生素D过量后的副作用，例如：高钙血综合征或钙中毒(这取决于高钙血的持续时间及严重程度)，由于骨化三醇的生物半衰期短，药代动力学研究表明在减量或停药后的几天内，血清钙即可恢复正常，和维生素D或其衍生物治疗相比，罗钙全血清钙恢复正常的时间要快得多。

〔注意事项〕

由于罗钙全能影响肠、胃与骨内磷酸盐的转运，因此，凡同时服用与磷酸盐的结合的药物，其剂量必须根据血清磷酸盐的浓度加以调节(正常浓度：20～50mg／l)。如同时发生高钙血与血磷酸盐过多(＞60mg／l)，病人会发生软组织钙化，这可以通过X线摄片显示。

在肾功能正常的病人，慢性高钙血症可能与血清肌酐的升高有关，这通常是可逆的，这些病人最重要的是要注意那些可致高钙血症的因素。

罗钙全的治疗开始必须是最低剂量，在没有严密监测血清钙水平时不能随意增加剂量。必须估计每天从饮食中吸收的钙，并调整剂量。

肾功能正常的病人，服用罗钙全时，必须避免脱水，必须持续服用足够的液体。在慢性肾脏透析的病人，服用罗钙全时不应同时服有含镁的制剂(例如止酸剂)，因为可引起高镁血症。

患维生素D抗性佝偻病的病人(家族性低磷酸盐血症)必须继续日服磷酸盐。然而罗钙全的作用可能减少磷酸盐的需要，所以应该考虑罗钙全可能刺激小肠吸收磷酸盐。

〔包装〕

胶囊(红色与白色)0．25μg，有30粒及100粒装。

胶囊(红色)0．5μg，有30粒及100粒装。

〔生产厂家〕

瑞士巴塞尔豪夫迈氏罗氏公司

(附本品别名：钙三醇，R021-5535)

【外文释文】：

Trade Mark

Biologically active form of vitamin D₃

Composition

The active ingredient of Rocaltrol is synthetic calcitriol：1a，25-di-hydroxycholecalciferol；(5Z，7E)-9，10-secocholesta-5，10(19)-triene-1a，3β，25-triol．Rocaltrol is available as 0．25-μg and 0．5-μg capsules．

Properties

Calcitriol is one of the most important active metabolites of vitamin D3．This metabolite is normally formed in the kidney from its precursor，25-hydroxycholecalciferol(25-HCC)．Calcitriol promotes intestinal absorption of calcium and regulates bone mineralization．

In patients with marked renal insufficiency，particularly those who are undergoing long term haemodialysis，synthesis of endogenous calcitriol decreases to an ever greater extent and may even cease altogether．This deficiency plays a key role in the development of renal osteodystrophy．

In patients with renal osteodystrophy，oral administration of Rocaltrol normalizes impaired intestinal absorption of calcium，corrects hypocalcaemia，alleviates bone and muscle pain and contributes towards normalization or reduction of the increased serum alkaline phosphatase activty，normalization or reduction of the increased parathyroid hormone concentrations in serum．

In patients with postsurgical hypoparathyroidism，idiopathic hypoparathyroidism，and pseudohypoparathyroidism，hypocalcaemia and its clinical manifestations are alleviated by Rocaltrol therapy．

In patients with vitamin D dependency rickets the serum levels of calcitriol are low or absent．As the endogenous production of calcitriol in the kidney is insufficient，Rocaltrol is considered replacement therapy．

Patients with vitamin D resistant rickets and hypophosphataemia may benefit from Rocaltrol，although long-term benefits have not been established．However，rocaltrol may improve hypophosphataemia in some patients．

Patients with rickets due to neonatal hepatitis，biliary atresia，cystinosis，and dietary lack of calcium and vitamin D have benefited from Rocaltrol therapy．

Pharmacokinetics

In the normal man，studies with both tritium-labelled and unlabelled calcitriol indicate that it is rapidly absorbed after oral administration with peak levels being reached after three to six hours．

Rapid absorption is consistent with the significant increases in urinary calcium detected as early as seven hours after ingestion．

A dose-related biological response is reflected in increases in urinary calcium excretion with doses of 0．5μg and 1．0μg given twice daily．The steady-state levels attained after dosing with 0．5μg or 1．0μg twice daily fall to basal values upon withdrawal of the drug with a half-life of about 3．5 hours．

Indications

Renal osteodystrophy in patients with chronic renal failure，particularly those undergoing haemodialysis．

Postsurgical hypoparathyroidism．

Idiopathic hypoparathyroidism．

Pseudohypoparathyroidism．

Vitamin D dependency rickets．

Hypophosphataemic vitamin D resistant rickets．

Contraindications

All diseases associated with hypercalcaemia．

Warnings：since calcitriol is one of the most important active metabolites of vitamin D₃，pharmacologic doses of vitamin D and its derivatives should be withheld during treatment with Rocaltrol)to avoid possible additive effects and hypercalcaemia．

Use in pregnancy

The safety of Rocaltrol in women who are or may become pregnant has not yet been established；the potential benefits should therefore be weighed against the possible risk to moth er and child．

Use in children

Since insufficient experience has so far been gained on the use of Rocaltrol in children under three years old and those undergoing dialysis，the potential benefits must be individually weighed against the possible risk．

Dosage and administration

The optimal daily dose of Rocaltrol must be carefully determined for each patient on the basis of the serum calcium level．

Renal osteodystrophy(dialysis patients)：the initial daily dose is 0．25μg．In patients with normal or only slightly reduced serum calcium levels，doses of 0．25μg every other day are sufficient．If no satisfactory response in the biochemical parameters and clinical manifestion of the disease is observed within two to four weeks，the dosage may be increased by 0．25μg per day at two-to four-week intervals．During this period，serum calcium levels should be determined at least twice weekly．Most patients respond to between 0．5μg and 1．0μg daily．Higher doses may be necessary if barbiturates or anticonvulsant drugs are administered simultaneously．

A prerequisite for the optimal efficacy of Rocaltrol is an adequate calcium intake(in adults，approximately 800-1000mg daily)．Additional calcium should be prescribed if necessary．

Because of improved calcium absorption from the gastrointestinal tract，some patients on Rocaltrol may be maintained on lower calcium intake．Patients who tend to develop hypercalcaemia may require only low doses of calcium or no supplementation at all．

Hypoparathyroidism and rickets：the recommended initial dose of Rocaltrol is 0．25μg per day given in the morning．If a satisfactory response in the biochemical parameters and clinical manifestations of the disease are not observed，the dose may calcium levels should be obtained at least twice weekly．

Malabsorption is occasionally noted in patients with hypoparathyroidism；hence，larger doses of Rocaltrol may be needed．

Generally：when the optimal dosage of Rocaltrol has been determined，the serum calcium levels should be checked every month．As soon as serum calcium levels rise to 1 mg per 100ml above normal(9-11mg per 100ml on average)，the dosage of Rocaltrol，should be substantially reduced or treatment stopped altogether until normocalcaemia ensues．Withdrawal of additional doses of calcium can also be of benefit in bringing about rapid normalization of serum calcium levels．Careful consideration should also be given to lowering the dietary calcium intake．

During the period of hypercalacmia，serum calcium and phosphate levels must be determined daily．When normal levels have been attained，the treatment with Rocaltrol can be continued，at a daily dose 0．25μg lower than that previously used．

Side effects

Rocaltrol causes no side effects provided the dosage does not exceed individual requirements．Since Rocaltrol exerts vitamin D activity，‘side effects’are similar to those found when an excessive dosage of vitamin D3 is given，i．e．hypercalcaemia syndrome or calcium intoxication(depending on the severity and duration of hypercalcaemia)．

Because of the short biologicial half-life of calcitrol，pharmacokinetic investigations have shown normalization of serum calcium to ensure within a few days of treatment withdrawal or of dosage reduction，i．e．much faster than in treatment with vitamin D₃ or its derivatives．

Precautions

Since Rocaltrol also has an effect on phosphate transport in the intestine，kidneys and bones，the dosage of phosphate-binding agents must be adjusted in accordance with the serum phosphate concentration(normal levels：2-5mg per 100ml)．

In concurrent hypercalcaemia and hyperphosphtaemia(＞6 mg per 100 ml)，soft-tissue calcification may occur；this can be seen radiographically．

In patients with normal renal function，chronic hypercalcaemia may be associated with an increase in serum creatinine．While this is usually reversible，it is important in such patients to pay careful attention to those factors which may lead to hypercalcaemia．Rocaltrol therapy should always be started at the lowest possible dose and should not be increased without careful monitoring of the serum calcium．An estimate of daily dietary calcium intake should be made and the intake adjusted when indicated．

Patients with normal renal function taking Rocaltrol should avoid dehydration．Adequate fluid intake should be maintained．

Magnesium-containing drugs(e．g．antacids)should not be taken during therapy with Rocaltrol in patients on chronic renal dialysis since they may cause hypermagnesaemia．

Patients with vitamin D resistant rickets(familial hypophosphataemia)should pursue their oral phosphate therapy．However，the possible stimulation of intestinal phosphate absorption by Rocaltrol should be taken into account since this effect may modify the requirement for phosphate supplements．

Packs

Capsules(red and white)0．25μg 30and 100

Capsules(red)0．5μg 30and 100

Medicine：keep out of reach of children

Manufacturer

F．Hoffmann-La Roche，Ltd．，Basle，Switzerland