Active ingredients: Calcitriol (Vitamin D)
Rocaltrol 0.25 mcg soft capsules
Rocaltrol 0.50 mcg soft capsules
Why is Rocaltrol used? What is it for?
Pharmacotherapeutic group
Vitamin D and analogues.
Therapeutic indications
Renal osteodystrophy in patients with chronic renal failure, particularly in those undergoing hemodialysis. Hypoparathyroidism, both idiopathic and surgical. Pseudohypoparathyroidism. Vitamin D-resistant hypophosphatemic rickets. Pseudo-dependent vitamin D familial rickets. Postmenopausal osteoporosis: the differential diagnosis should carefully exclude conditions with similar skeletal symptoms, such as multiple myeloma and tumor osteolysis, for which treatment with Rocaltrol is not indicated.
Contraindications When Rocaltrol should not be used
Hypersensitivity to the active substance or to any of the excipients
- Diseases associated with hypercalcemia;
- Presence of signs of vitamin D toxicity
Precautions for use What you need to know before taking Rocaltrol
There is a close correlation between calcitriol treatment and the development of hypercalcemia.
A sudden increase in calcium intake as a result of a change in diet (for example, in the case of a greater increase in the consumption of dairy products) or the uncontrolled intake of preparations containing calcium can lead to the onset of hypercalcaemia.
It is essential to communicate to patients and their families the need to strictly adhere to the prescribed diet and to explain to them how to recognize the symptoms of hypercalcemia.
As soon as serum calcium levels exceed normal values (9-11 mg / 100 ml or 2250-2750 mcmol / l) by 1 mg / 100 ml (250 mcmol / l) or serum creatinine exceeds 120 mcmol / l, Rocaltrol treatment should be stopped immediately until normocalcaemia is restored (see Dose, method and time of administration).
Immobilized patients, for example those undergoing surgery, are particularly exposed to the risk of hypercalcemia.
Calcitriol increases serum levels of inorganic phosphate.
This effect is desirable in patients with hypophosphataemia, while it requires attention in patients with renal insufficiency due to the risk of ectopic calcification. In these cases, the plasma phosphate concentration should be maintained at the normal level (2-5 mg / 100 ml or 0.65-1.62 mmol / l) by oral administration of appropriate phosphate-binding agents and a low-fat diet. phosphate content.
The serum calcium-phosphate product (Ca x P) must not exceed the threshold of 70 mg2 / dl2.
Patients with vitamin D-resistant rickets (familial hypophosphataemia) treated with Rocaltrol should continue oral phosphate therapy.
However, the possible increase in intestinal phosphate absorption by Rocaltrol should be taken into account, as this effect could modify the need for phosphate supplementation.
Calcitriol is an active metabolite of vitamin D, therefore no other vitamin D preparations should be taken during treatment with Rocaltrol, in order to avoid the development of hypervitaminosis D.
If the patient has switched from ergocalciferol (vitamin D2) to calcitriol, it may take several months for the blood concentration of ergocalciferol to return to baseline (see Interactions).
Patients with normal renal function treated with Rocaltrol should avoid dehydration. Maintain adequate fluid intake.
In patients with normal renal function, chronic hypercalcaemia may be associated with an increase in serum creatinine.
In patients with postmenopausal osteoporosis, careful monitoring of renal function and blood calcium is essential before starting therapy and at regular intervals during treatment with Rocaltrol (see Dose, method and time of administration).
Interactions Which drugs or foods can modify the effect of Rocaltrol
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Since calcitriol is an active metabolite of vitamin D, no other preparations containing vitamin D or its derivatives should be taken during treatment with calcitriol to avoid the development of hypervitaminosis D.
Dietary instructions should be strictly followed, especially with regard to calcium supplements, and uncontrolled intake of additional calcium preparations should be avoided.
Concomitant treatment with a thiazide diuretic increases the risk of hypercalcaemia. Calcitriol dosage should be carefully determined in patients treated with digitalis because hypercalcaemia may precipitate cardiac arrhythmias in these individuals (see Special Warnings).
There is a relationship of functional antagonism between vitamin D analogues, which promote calcium absorption, and corticosteroids, which inhibit it.
Medicines containing magnesium (e.g. antacids) can cause hypermagnesemia, therefore their intake during treatment with Rocaltrol should be avoided by patients on chronic renal dialysis.
Since Rocaltrol also has an effect on the transport of phosphate in the intestine, kidneys and bones, the dosage of the phosphate binding agents must be corrected according to the phosphatemia (normal values: 2-5 mg / 100 ml or 0.65- 1.62 mmol / l).
Patients with vitamin D-resistant rickets (familial hypophosphataemia) should continue oral phosphate therapy. However, the possible increase in intestinal absorption of phosphate exerted by calcitriol should be taken into account as this effect could modify the need for phosphate supplementation.
Administration of enzyme inducers such as phenytoin or phenobarbital may lead to increased metabolism of calcitriol and thus to a reduction in its serum concentrations. Therefore, if these drugs are administered concomitantly, higher doses of calcitriol may be required.
Bile acid sequestrants, including cholestyramine and sevelamer can reduce intestinal absorption of fat-soluble vitamins and, therefore, impair intestinal absorption of calcitriol.
Warnings It is important to know that:
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine
Pregnancy
Administration of near-lethal oral doses of vitamin D to pregnant rabbits resulted in the development of supravalvular aortic stenosis in fetuses. There is no evidence to suggest a teratogenic effect of vitamin D in humans, even at very high doses. Rocaltrol should only be administered during pregnancy if the benefits outweigh the potential risk to the fetus.
Feeding time
It is assumed that exogenous calcitriol is secreted in breast milk. In light of the potential risk of hypercalcaemia in the mother and adverse reactions to Rocaltrol in breastfed infants, mothers may continue to breastfeed while taking Rocaltrol provided that maternal and neonate serum calcium levels are monitored. .
Effects on ability to drive and use machines
Based on the pharmacodynamic profile of reported adverse events, it is considered unlikely that this medicinal product will have adverse effects on the ability to drive or use machines.
Important information about some of the ingredients
Rocaltrol contains sorbitol. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
Dosage and method of use How to use Rocaltrol: Dosage
The optimal daily dose of Rocaltrol should be carefully established in each patient on the basis of the calcium values.
Renal osteodystrophy:
the efficacy of the treatment is conditioned by the simultaneous intake of calcium: in adults the supplementary intake of calcium must be 600-1000 mg per day.
The recommended starting dose of Rocaltrol is 0.25 mcg per day: in patients with normal or only slightly reduced calcium, starting doses of 0.25 mcg every 2 days are sufficient. If no improvement in clinical picture and biochemical parameters is observed after 2-4 weeks, the dose of Rocaltrol should be increased by 0.25 micrograms per day at intervals of 2-4 weeks. During this period, the calcium should be checked at least twice a week and, if hypercalcemia is found, the administration of Rocaltrol and the additional calcium should be stopped immediately until the calcium is within normal limits. Therapy will then be resumed with a daily dosage 0.25 mcg lower than the previous one. The optimal daily dose of Rocaltrol, to be established in the manner indicated above, is in most patients between 0.5 mcg and 1 mcg. Higher dosages may be necessary in case of concomitant administration of barbiturates or anticonvulsants.
Hypoparathyroidism and rickets:
the recommended starting dose of Rocaltrol is 0.25 micrograms per day, given in the morning. If no improvement in clinical and biochemical parameters is noted, the dose can be increased every 2-4 weeks. During this interval, calcium should be determined at least twice a week. In patients with hypoparathyroidism, a malabsorption syndrome can sometimes be observed: in these cases higher doses of Rocaltrol may be required.
Postmenopausal osteoporosis:
it is recommended to start with the administration of 0.5 micrograms twice daily and, if the calcium levels do not show significant changes, continue with this dosage. Unlike renal osteodystrophy, it is absolutely necessary to avoid an additional supply of calcium.
During the first month of therapy, calcium should be checked at least once a week. In case of hypercalcaemia (> 11.5 mg / 100 ml), the administration of Rocaltrol should be suspended until normocalcaemia is restored. In the opinion of the physician it is possible the association with calcitonin (especially in the case of high turnover osteoporosis).
General information: once the optimal dosage has been established, a control of calcium once a month is sufficient. In the event that the serum calcium level exceeds normal values by 1 mg per 100 ml (9-11 mg / 100 ml), the dose of Rocaltrol should be considerably reduced or the treatment stopped until normal calcium has been restored. . To favor the rapid normalization of serum calcium values, the supplementary administration of calcium, which is foreseen in the treatment of renal osteodystrophy, hypoparathyroidism and rickets, can also be discontinued. The amount of calcium introduced in the diet must also be limited. In the period of hypercalcemia, it is necessary to carry out daily control of serum levels of calcium and phosphorus. Once normal values have been restored, Rocaltrol treatment can be resumed with a daily dose 0.25 mcg lower than the previous one.
Pediatric population
The safety and efficacy of calcitriol capsules in children have not been sufficiently studied to allow for dosing recommendations. Limited data are available on the use of calcitriol capsules in pediatric patients.
Overdose What to do if you have taken too much Rocaltrol
Since calcitriol is a derivative of vitamin D, the symptoms of overdose are the same as for an overdose of vitamin D. Taking high doses of calcium and phosphate together with Rocaltrol can induce similar symptoms. The calcium-phosphate product (Ca x Serum P) must not exceed the threshold of 70 mg2 / dl2. An elevated level of calcium in the dialysate can contribute to the development of hypercalcemia. Acute symptoms of vitamin D intoxication: anorexia, headache, vomiting, constipation.
Chronic symptoms: dystrophy (weakness, weight loss), sensory disturbances, possible fever with thirst, polyuria, dehydration, apathy, growth arrest and urinary tract infections; hypercalcemia, with metastatic calcification of the renal cortex, myocardium, lungs and of the pancreas.
Treatment
For the treatment of asymptomatic hypercalcemia.
In the treatment of accidental overdose, the following measures should be considered: immediate gastric lavage or induction of vomiting to prevent further absorption. Administration of liquid paraffin to promote faecal excretion. Repeated measurements of serum calcium are advisable. If elevated serum calcium levels persist, phosphates and corticosteroids may be administered and measures instituted to induce adequate diuresis.
Hypercalcaemia to higher levels (> 3.2 mmol / L) can cause renal failure, particularly if blood phosphate levels are normal or elevated due to impaired renal function.
In case of accidental overdose of Rocaltrol notify your doctor immediately or go to the nearest hospital. If you have any questions about the use of Rocaltrol, ask your doctor or pharmacist
Side Effects What are the side effects of Rocaltrol
Like all medicines, Rocaltrol can cause side effects, although not everybody gets them.
The adverse reactions listed below reflect clinical trial experience and post-marketing experience. The most commonly reported adverse reaction was hypercalcaemia.
Clinical studies
The adverse reactions listed in Table 1 are presented by system organ class and frequency categories, defined according to the following convention: very common (≥ 1/10), common (≥ 1/100,
Table 1 Summary of adverse reactions occurring in patients treated with Rocaltrol (calcitriol)
Because calcitriol exerts a "vitamin D-like activity, adverse events similar to those seen when taking too much vitamin D may occur, such as hypercalcaemia syndrome or calcium intoxication (depending on the severity and duration of the" hypercalcemia)
Occasionally acute symptoms such as decreased appetite, headache, nausea, vomiting, abdominal pain or upper abdominal pain and constipation may be observed. Due to the short biological half-life of calcitriol, pharmacokinetic investigations have shown the normalization of calcium within a few days of discontinuing treatment, i.e. more rapidly than treatment with preparations containing vitamin D3.
Chronic effects may include muscle weakness, weight loss, sensory disturbances, pyrexia, thirst, polydipsia, polyuria, dehydration, apathy, growth retardation and urinary tract infections.
For signs and symptoms of acute or chronic calcitriol poisoning, see "Overdose".
In case of concomitant hypercalcaemia and hyperphosphataemia> 6 mg / 100 ml or> 1.9 mmol / l, calcinosis may occur, which can be observed radiographically.
Sensitive individuals may experience hypersensitivity reactions including rash, erythema, itching and hives.
Laboratory anomalies
In patients with normal renal function, chronic hypercalcaemia may be associated with an increase in blood creatinine.
A few cases of abnormal increases in neutrophils and lymphopenia have been described
Post-marketing experience
The number of adverse events reported during clinical use of Rocaltrol over a 15-year period in all indications is very low and for any single event, including hypercalcaemia, the incidence is 0.001% or less.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Side effects can also be reported directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on safety of this medicine.
Expiry and Retention
Store at a temperature not exceeding 30 ° C.
Store in the original package and keep the bottle tightly closed to protect from light and moisture.
Expiry: see the expiry date indicated on the package.
The expiry date indicated refers to the product in intact packaging, correctly stored.
Warning: do not use the medicine after the expiry date indicated on the package.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Keep this medicine out of the sight and reach of children.
Composition
Rocaltrol 0.25 mcg soft capsules: one capsule contains: active ingredient: calcitriol 0.25 mcg.
Rocaltrol 0.50 mcg soft capsules: one capsule contains: active ingredient: calcitriol 0.50 mcg.
Excipients: medium chain saturated triglycerides, butylhydroxyanisole, butylhydroxytoluene. The capsule shell contains gelatin, glycerol 85%, Karion 83 (sorbitol, mannitol, hydrogenated hydrolyzed starch), titanium dioxide (E 171), yellow iron oxide (E 172) and red iron oxide (E 172).
Pharmaceutical form and content
Rocaltrol 0.25 mcg soft capsules: 30 capsules.
Rocaltrol 0.50 mcg soft capsules: 30 capsules.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
ROCALTROL SOFT CAPSULES
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Rocaltrol 0.25 mcg capsules soft.
One capsule contains: calcitriol 0.25 mcg.
Rocaltrol 0.50 mcg capsules soft.
One capsule contains: calcitriol 0.50 mcg.
Excipients with known effects: sorbitol.
For the full list of excipients, see 6.1.
03.0 PHARMACEUTICAL FORM
Rocaltrol is available in soft capsules for oral use.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Renal osteodystrophy in patients with chronic renal failure, particularly in those undergoing hemodialysis. Hypoparathyroidism, both idiopathic and surgical. Pseudohypoparathyroidism. Vitamin D-resistant hypophosphatemic rickets. Pseudo-dependent vitamin D familial rickets. Postmenopausal osteoporosis: the differential diagnosis should carefully exclude conditions with similar skeletal symptoms, such as multiple myeloma and tumor osteolysis, for which treatment with Rocaltrol is not indicated.
04.2 Posology and method of administration
The optimal daily dose of Rocaltrol should be carefully established in each patient on the basis of the calcium values.
Renal osteodystrophy:
the efficacy of the treatment is conditioned by the simultaneous intake of calcium: in adults the supplementary intake of calcium must be 600-1000 mg per day.
The recommended starting dose of Rocaltrol is 0.25 mcg per day: in patients with normal or only slightly reduced calcium, starting doses of 0.25 mcg every 2 days are sufficient. If no improvement in clinical picture and biochemical parameters is observed after 2-4 weeks, the dose of Rocaltrol should be increased by 0.25 micrograms per day at intervals of 2-4 weeks. During this period, calcium should be checked at least twice a week and, if hypercalcaemia is found, the administration of Rocaltrol and additional calcium should be stopped immediately until the calcium level is within normal limits. Therapy will then be resumed with a daily dosage 0.25 mcg lower than the previous one. The optimal daily dose of Rocaltrol, to be established in the manner indicated above, is in most patients between 0.5 mcg and 1 mcg. Higher dosages may be necessary in case of concomitant administration of barbiturates or anticonvulsants.
Hypoparathyroidism and rickets:
the recommended starting dose of Rocaltrol is 0.25 micrograms per day, given in the morning. If no improvement in clinical and biochemical parameters is noted, the dose can be increased every 2-4 weeks. During this interval, calcium should be determined at least twice a week. In patients with hypoparathyroidism, a malabsorption syndrome can sometimes be observed: in these cases higher doses of Rocaltrol may be required.
Postmenopausal osteoporosis:
it is recommended to start with the administration of 0.5 micrograms twice daily and, if the calcium levels do not show significant changes, continue with this dosage. Unlike renal osteodystrophy, it is absolutely necessary to avoid an additional supply of calcium.
During the first month of therapy, calcium should be checked at least once a week. In case of hypercalcaemia (> 11.5 mg / 100 ml), the administration of Rocaltrol should be suspended until normocalcaemia is restored. In the opinion of the physician it is possible the association with calcitonin (especially in the case of high turnover osteoporosis).
General information:
once the optimal dosage has been established, a control of calcium once a month is sufficient. In the event that the serum calcium level exceeds normal values by 1 mg per 100 ml (9-11 mg / 100 ml), the dose of Rocaltrol should be considerably reduced or the treatment stopped until normal calcium has been restored. . To favor the rapid normalization of serum calcium values, the supplementary administration of calcium, which is foreseen in the treatment of renal osteodystrophy, hypoparathyroidism and rickets, can also be discontinued. The amount of calcium introduced in the diet must also be limited. In the period of hypercalcemia, it is necessary to carry out daily control of serum levels of calcium and phosphorus. Once normal values have been restored, Rocaltrol treatment can be resumed with a daily dose 0.25 mcg lower than the previous one.
Pediatric population
The safety and efficacy of calcitriol capsules in children have not been sufficiently studied to allow for dosing recommendations. Limited data are available on the use of calcitriol capsules in pediatric patients.
04.3 Contraindications
Hypersensitivity to the active substance (or to active substances belonging to the same class) or to any of the excipients listed in section 6.1.
Diseases associated with hypercalcemia;
Presence of signs of vitamin D toxicity.
04.4 Special warnings and appropriate precautions for use
There is a close correlation between calcitriol treatment and the development of hypercalcemia.
A sudden increase in calcium intake due to a change in diet (for example, in the case of a greater increase in the consumption of dairy products) or to the uncontrolled intake of preparations containing calcium can lead to the onset of hypercalcaemia.
It is essential to communicate to patients and their families the need to strictly adhere to the prescribed diet and to explain to them how to recognize the symptoms of hypercalcemia.
As soon as serum calcium levels exceed normal values (9-11 mg / 100 ml or 2250-2750 mcmol / l) by 1 mg / 100 ml (250 mcmol / l) or serum creatinine exceeds 120 mcmol / l, Rocaltrol treatment should be stopped immediately until normocalcaemia is restored (see section 4.2).
Immobilized patients, for example those undergoing surgery, are particularly exposed to the risk of hypercalcemia.
Calcitriol increases serum levels of inorganic phosphate.
This effect is desirable in patients with hypophosphataemia, while it requires attention in patients with renal insufficiency due to the risk of ectopic calcification. In these cases, the plasma phosphate concentration should be maintained at the normal level (2-5 mg / 100 ml or 0.65-1.62 mmol / l) by oral administration of appropriate phosphate-binding agents and a low-fat diet. phosphate content.
The serum calcium-phosphate product (Ca x P) must not exceed the threshold of 70 mg2 / dl2.
Patients with vitamin D-resistant rickets (familial hypophosphataemia) treated with Rocaltrol should continue oral phosphate therapy.
However, the possible increase in intestinal phosphate absorption by Rocaltrol should be taken into account, as this effect could modify the need for phosphate supplementation.
Calcitriol is an active metabolite of vitamin D, therefore no other vitamin D preparations should be taken during treatment with Rocaltrol, in order to avoid the development of hypervitaminosis D.
If the patient has switched from ergocalciferol (vitamin D2) to calcitriol treatment, it may take several months for the blood concentration of ergocalciferol to return to baseline (see section 4.5).
Patients with normal renal function treated with Rocaltrol should avoid dehydration. Maintain adequate fluid intake.
In patients with normal renal function, chronic hypercalcaemia may be associated with an increase in serum creatinine.
In patients with postmenopausal osteoporosis, careful monitoring of renal function and blood calcium is essential before starting therapy and at regular intervals during treatment with Rocaltrol (see section 4.2).
Important information about some of the ingredients
Rocaltrol contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Since calcitriol is an active metabolite of vitamin D, no other preparations containing vitamin D or its derivatives should be prescribed during treatment with calcitriol to ensure that the development of hypervitaminosis D is avoided. If the patient switches from ergocalciferol (vitamin D2 ) to that with calcitriol, it may take a few months for the blood level of ergocalciferol to return to baseline.
Dietary instructions should be strictly followed, especially with regard to calcium supplements, and uncontrolled intake of additional calcium preparations should be avoided.
Concomitant treatment with a thiazide diuretic increases the risk of hypercalcaemia. Calcitriol dosage should be carefully determined in patients treated with digitalis because hypercalcaemia in these patients may precipitate cardiac arrhythmias (see section 4.4).
There is a relationship of functional antagonism between vitamin D analogues, which promote calcium absorption, and corticosteroids, which inhibit it.
Medicines containing magnesium (e.g. antacids) can cause hypermagnesemia, therefore their intake during treatment with Rocaltrol should be avoided by patients on chronic renal dialysis.
Since Rocaltrol also has an effect on the transport of phosphate in the intestine, kidneys and bones, the dosage of the phosphate binding agents must be corrected according to the phosphatemia (normal values: 2-5 mg / 100 ml or 0.65- 1.62 mmol / l).
Patients with vitamin D-resistant rickets (familial hypophosphataemia) should continue oral phosphate therapy. However, the possible increase in intestinal absorption of phosphate by calcitriol must be taken into account as this effect could modify the need for phosphate supplementation.
Administration of enzyme inducers such as phenytoin or phenobarbital may lead to increased metabolism of calcitriol and thus to a reduction in its serum concentrations. Therefore, if these drugs are administered concomitantly, higher doses of calcitriol may be required.
Bile acid sequestrants, including cholestyramine, and sevelamer can reduce intestinal absorption of fat-soluble vitamins and, therefore, impair intestinal absorption of calcitriol.
04.6 Pregnancy and lactation
Pregnancy
Administration of near-lethal oral doses of vitamin D to pregnant rabbits resulted in the development of supravalvular aortic stenosis in fetuses. There is no evidence to suggest a teratogenic effect of vitamin D in humans, even at very high doses. Rocaltrol should only be administered during pregnancy if the benefits outweigh the potential risk to the fetus.
Feeding time
It is assumed that exogenous calcitriol is secreted in breast milk. In light of the potential risk of hypercalcaemia in the mother and adverse reactions to Rocaltrol in breastfed infants, mothers may continue to breastfeed while taking Rocaltrol provided that maternal and neonate serum calcium levels are monitored. .
04.7 Effects on ability to drive and use machines
Based on the pharmacodynamic profile of reported adverse events, it is considered unlikely that this medicinal product will have adverse effects on the ability to drive or use machines.
04.8 Undesirable effects
The adverse reactions listed below reflect clinical trial experience and post-marketing experience. The most commonly reported adverse reaction was hypercalcaemia.
Clinical studies
The adverse reactions listed in Table 1 are presented by system organ class and frequency categories, defined according to the following convention: very common (≥ 1/10), common (≥ 1/100,
Table 1 Summary of adverse reactions occurring in patients treated with Rocaltrol (calcitriol)
Since calcitriol exerts a "vitamin D-like activity, adverse events similar to those seen when taking too much vitamin D may occur, such as hypercalcaemia syndrome or calcium intoxication (depending on the severity and duration of the" hypercalcaemia) (see sections 4.2 and 4.4).
Occasionally acute symptoms such as decreased appetite, headache, nausea, vomiting, abdominal pain or upper abdominal pain and constipation may be observed.
Due to the short biological half-life of calcitriol, pharmacokinetic investigations have shown the normalization of calcium within a few days of discontinuing treatment, i.e. more rapidly than treatment with preparations containing vitamin D3.
Chronic effects may include muscle weakness, weight loss, sensory disturbances, pyrexia, thirst, polydipsia, polyuria, dehydration, apathy, growth retardation and urinary tract infections.
For signs and symptoms of acute or chronic calcitriol intoxication, see section 4.9.
In case of concomitant hypercalcaemia and hyperphosphataemia> 6 mg / 100 ml or> 1.9 mmol / l, calcinosis may occur, which can be observed radiographically.
Sensitive individuals may experience hypersensitivity reactions including rash, erythema, itching and hives.
Laboratory anomalies
In patients with normal renal function, chronic hypercalcaemia may be associated with an increase in blood creatinine.
A few cases of abnormal increases in neutrophils and lymphopenia have been described.
Post-marketing experience
The number of adverse events reported during clinical use of Rocaltrol over a 15-year period in all indications is very low and for any single event, including hypercalcaemia, the incidence is 0.001% or less.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
Signs and symptoms
Since calcitriol is a derivative of vitamin D, the symptoms of overdose are the same as for an overdose of vitamin D. Taking high doses of calcium and phosphate together with Rocaltrol can induce similar symptoms. The calcium-phosphate product (Ca x Serum P) should not exceed the threshold of 70 mg2 / dl2 An elevated level of calcium in the dialysate may contribute to the development of hypercalcemia.
Acute symptoms of vitamin D intoxication: anorexia, headache, vomiting, constipation.
Chronic symptoms: dystrophy (weakness, weight loss), sensory disturbances, possible fever with thirst, polyuria, dehydration, apathy, stunting and urinary tract infections; hypercalcemia, with metastatic calcification of the renal cortex, myocardium, lungs and pancreas.
Treatment
For the treatment of asymptomatic hypercalcaemia, see section 4.2.
In the treatment of accidental overdose, the following measures should be considered: immediate gastric lavage or induction of vomiting to prevent further absorption. Administration of liquid paraffin to promote excretion with faeces.
It is advisable to carry out repeated measurements of calcium. If elevated serum calcium levels persist, phosphates and corticosteroids may be administered and measures instituted to induce adequate diuresis.
Hypercalcaemia to higher levels (> 3.2 mmol / L) can cause renal failure, particularly if blood phosphate levels are normal or elevated due to impaired renal function.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Vitamin D and analogues.
ATC code: A11CC04.
Calcitriol is one of the main active metabolites of vitamin D3 which is formed in the kidney from its precursor, 25-hydroxycholecalciferol (25-HCC).
Rocaltrol promotes intestinal absorption of calcium and regulates bone mineralization.
In patients with severe renal insufficiency, particularly in those who have been undergoing periodic hemodialysis for some time, the formation of endogenous calcitriol is progressively reduced and may even cease altogether: this deficiency plays a primary role in the onset of renal osteodystrophy. In patients with osteodystrophy. renal, oral administration of Rolcatrol:
• normalizes the intestinal absorption of calcium;
• corrects hypocalcemia;
• relieves bone and muscle pain.
Administration also favors:
- normalization or reduction of serum levels of alkaline phosphatase;
- normalization or reduction of parathyroid hormone serum levels.
In patients with hypoparathyroidism, both idiopathic and surgical, Rocaltrol corrects the hypocalcemia secondary to parathyroid hormone deficiency. In pseudohypoparathyroidism it allows to restore normal intestinal calcium absorption, to correct hypocalcemia and to reduce parathyroid hormone levels. circulating. In vitamin D-resistant hypophosphatemic rickets, administration of Rocaltrol leads to an improvement in the clinical picture and a normalization of circulating phosphates. In family vitamin D-dependent rickets Rocaltrol determines the remission of bone lesions and the normalization of calcemic and phosphate values and intestinal calcium absorption. In patients suffering from postmenopausal osteoporosis, estrogen deficiency causes a reduced endogenous synthesis of calcitriol , with consequent decrease of intestinal calcium absorption and bone mineralization processes. The administration of Rocaltrol determines a significant increase in intestinal calcium absorption. In this way the calcium balance, negative in these patients, returns to being positive.
05.2 Pharmacokinetic properties
Studies carried out in healthy subjects, with both tritium-labeled and unlabeled calcitriol, show that drug absorption occurs rapidly after oral administration, reaching maximum levels in the space of 3-6 hours. Rapid absorption is confirmed by rapid increase of calcium in the urine, verifiable as early as seven hours after administration. A dose-related biological response is evidenced in the increase of calcium excretion in the urine with doses of 0.5 and 1.0 mcg administered twice a day. Steady-state values, achieved with doses of 0.5 mcg twice a day, drop to baseline levels following drug discontinuation, with a half-life of approximately three and a half hours.
05.3 Preclinical safety data
The acute toxicity of calcitriol was evaluated in mice and rats. After oral administration the LD50 in mice is 2 mg / kg, in rats it is> 5 mg / kg.
Subchronic toxicity studies in rats and dogs indicated that calcitriol at an oral dose of 20 ng / kg / day (twice the usual human dosage) administered for up to 6 months produced minimal adverse effects. dose of 80 ng / kg / day (8 times the usual human dosage) administered for up to 6 months produced adverse effects of moderate intensity; the observed alterations seemed to result mainly from a prolonged hypercalcemia.
Chronic toxicity of calcitriol was evaluated in rats and dogs. Three groups of rats and dogs were given the compound orally, for a duration of 26 weeks, at dosages of 0.02, 0.08 and 0.30 mcg / kg / day. In the groups of rats receiving medium and high dosages there was a reduction in body weight, decreased food intake, increased serum calcium; these changes were absent or less marked in the group receiving the lowest doses. Dogs given the high and medium doses presented with marked anorexia, severe weight loss, deterioration in physical condition, increased calcium, metastatic soft tissue calcification and bone changes. In the dogs of the group receiving 0.02 mcg / kg / day these findings were attenuated.
Reproductive toxicity studies conducted in rats indicated that oral doses up to 300 ng / kg / day (30 times the usual human dose) produced no adverse reproductive effects. Multiple fetal abnormalities were observed in rabbits. two litters at a mother-toxic oral dose of 300 ng / kg / day and in one litter at 80 ng / kg / day, but not 20 ng / kg / day (twice the usual human dose). Despite the absence of statistically significant differences between the treated groups and the control groups in the number of litters or fetuses that exhibited abnormalities, the possibility that these findings were due to the administration of calcitriol cannot be ruled out.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Medium-chain saturated triglycerides, butylhydroxyanisole, butylhydroxytoluene.
The capsule shell contains gelatin, glycerol 85%, Karion 83 (sorbitol, mannitol, hydrogenated hydrolyzed starch), titanium dioxide (E 171), yellow iron oxide (E 172) and red iron oxide (E 172).
06.2 Incompatibility
No specific incompatibilities are known to date.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Store at a temperature not exceeding 30 ° C.
Store in the original package and keep the bottle tightly closed to protect from light and moisture.
06.5 Nature of the immediate packaging and contents of the package
The soft capsules are contained in a dark glass bottle, closed with a high-density polythene screw cap which, internally, has a truncated conical relief to guarantee a perfect seal.
The bottle is enclosed in a cardboard box together with the package leaflet.
06.6 Instructions for use and handling
No special instructions for disposal.
Unused medicine and wastes derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
Roche S.p.A. - Piazza Durante 11 - 20131 Milan
08.0 MARKETING AUTHORIZATION NUMBER
"0.25 mcg soft capsules" 30 capsules AIC n ° 024280012
"0.50 mcg soft capsules" 30 capsules AIC n ° 024280024
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Renewal: June 2010
10.0 DATE OF REVISION OF THE TEXT
AIFA Determination of October 2015
