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DRUGS & SUPPLEMENTS
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Adcal Syrup
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Adcal Syrup uses
Adcal Syrup consists of Calcium, Vitamin B12, Vitamin D3.Calcium:
- Indications and usage
- Dosage and administration
- Dosage forms and strengths
- Contraindications
- Warnings and precautions
- Adverse reactions
- Drug interactions
- Use in specific populations
- Overdosage
- Description
- Clinical pharmacology
- Nonclinical toxicology
- Clinical studies
- How supplied/storage and handling
- Patient counseling information
1 INDICATIONS AND USAGE
Adcal Syrup (Calcium) acetate is a phosphate binder indicated to reduce serum phosphorus in patients with end stage renal disease (ESRD).
- Calcium acetate is a phosphate binder indicated for the reduction of serum phosphorus in patients with end stage renal disease. (1)
2 DOSAGE AND ADMINISTRATION
The recommended initial dose of Adcal Syrup (Calcium) acetate for the adult dialysis patient is 2 capsules with each meal. Increase the dose gradually to lower serum phosphorus levels to the target range, as long as hypercalcemia does not develop. Most patients require 3 to 4 capsules with each meal.
- Starting dose is 2 capsules with each meal. (2)
- Titrate the dose every 2 to 3 weeks until acceptable serum phosphorus level is reached. Most patients require 3 to 4 capsules with each meal. (2)
3 DOSAGE FORMS AND STRENGTHS
Capsule: 667 mg Adcal Syrup (Calcium) acetate capsule.
- Capsule: 667 mg Adcal Syrup (Calcium) acetate capsule. (3)
4 CONTRAINDICATIONS
Patients with hypercalcemia.
- Hypercalcemia. (4)
5 WARNINGS AND PRECAUTIONS
- Treat mild hypercalcemia by reducing or interrupting Adcal Syrup acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of Adcal Syrup (Calcium) acetate. (5.1)
- Hypercalcemia may aggravate digitalis toxicity. (5.2)
5.1 Hypercalcemia
Patients with end stage renal disease may develop hypercalcemia when treated with Adcal Syrup (Calcium), including Adcal Syrup (Calcium) acetate. Avoid the use of Adcal Syrup (Calcium) supplements, including Adcal Syrup (Calcium) based nonprescription antacids, concurrently with Adcal Syrup (Calcium) acetate.
An overdose of Adcal Syrup (Calcium) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum Adcal Syrup (Calcium) levels twice weekly. Should hypercalcemia develop, reduce the Adcal Syrup (Calcium) acetate dosage, or discontinue the treatment, depending on the severity of hypercalcemia
More severe hypercalcemia (Ca >12 mg/dL) is associated with confusion, delirium, stupor and coma. Severe hypercalcemia can be treated by acute hemodialysis and discontinuing Adcal Syrup (Calcium) acetate therapy.
Mild hypercalcemia (10.5 to 11.9 mg/dL) may be asymptomatic or manifest as constipation, anorexia, nausea, and vomiting. Mild hypercalcemia is usually controlled by reducing the Adcal Syrup (Calcium) acetate dose or temporarily discontinuing therapy. Decreasing or discontinuing Vitamin D therapy is recommended as well.
Chronic hypercalcemia may lead to vascular calcification and other soft-tissue calcification. Radiographic evaluation of suspected anatomical regions may be helpful in early detection of soft tissue calcification. The long term effect of Adcal Syrup (Calcium) acetate on the progression of vascular or soft tissue calcification has not been determined.
Hypercalcemia (>11 mg/dL) was reported in 16% of patients in a 3 month study of solid dose formulation of Adcal Syrup (Calcium) acetate; all cases resolved upon lowering the dose or discontinuing treatment.
Maintain the serum calcium-phosphorus (Ca x P) product below 55 mg2/dL2.
5.2 Concomitant Use with Medications
Hypercalcemia may aggravate digitalis toxicity.
6 ADVERSE REACTIONS
Hypercalcemia is discussed elsewhere [see Warnings and Precautions ].
- The most common (>10%) adverse reactions are hypercalcemia, nausea and vomiting. (6.1)
- In clinical studies, patients have occasionally experienced nausea during Adcal Syrup (Calcium) acetate therapy. (6)
To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1 Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In clinical studies, Adcal Syrup (Calcium) acetate has been generally well tolerated.
Adcal Syrup (Calcium) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of Adcal Syrup (Calcium) acetate was studied in a two week double-blind, placebo-controlled, cross-over study with 69 enrolled ESRD hemodialysis patients. Adverse reactions (>2% on treatment) from these trials are presented in Table 1.
| Preferred Term | Total adverse reactions reported for Adcal Syrup (Calcium) acetate N=167 N (%) | 3 month, open label study of Adcal Syrup (Calcium) acetate N=98 N (%) | Double blind, placebo-controlled, cross-over study of liquid Adcal Syrup (Calcium) acetate N=69 | |
| Adcal Syrup (Calcium) acetate N (%) | Placebo N (%) | |||
| Nausea | 6 (3.6) | 6 (6.1) | 0 (0) | 0 (0) |
| Vomiting | 4 (2.4) | 4 (4.1) | 0 (0) | 0 (0) |
| Hypercalcemia | 21 (12.6) | 16 (16.3) | 5 (7.2) | 0 (0) |
Mild hypercalcemia may be asymptomatic or manifest itself as constipation, anorexia, nausea, and vomiting. More severe hypercalcemia is associated with confusion, delirium, stupor, and coma. Decreasing dialysate Adcal Syrup (Calcium) concentration could reduce the incidence and severity of Adcal Syrup (Calcium) acetate-induced hypercalcemia. Isolated cases pruritus have been reported, which may represent allergic reactions.
6.2 Postmarketing Experience
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or to establish a causal relationship to drug exposure.
The following additional adverse reactions have been identified during post-approval of Adcal Syrup (Calcium) acetate: dizziness, edema, and weakness.
7 DRUG INTERACTIONS
The drug interaction of Adcal Syrup acetate is characterized by the potential of Adcal Syrup (Calcium) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). Adcal Syrup (Calcium) acetate may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism.
There are no empirical data on avoiding drug interactions between Adcal Syrup (Calcium) acetate and most concomitant drugs. When administering an oral medication with Adcal Syrup (Calcium) acetate where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, administer the drug one hour before or three hours after Adcal Syrup (Calcium) acetate. Monitor blood levels of the concomitant drugs that have a narrow therapeutic range. Patients taking anti-arrhythmic medications for the control of arrhythmias and anti-seizure medications for the control of seizure disorders were excluded from the clinical trials with all forms of Adcal Syrup (Calcium) acetate.
- Calcium acetate may decrease the bioavailability of tetracyclines or fluoroquinolones. (7)
- When clinically significant drug interactions are expected, administer the drug at least one hour before or at least three hours after Adcal Syrup (Calcium) acetate or consider monitoring blood levels of the drug. (7)
7.1 Ciprofloxacin
In a study of 15 healthy subjects, a co-administered single dose of 4 Adcal Syrup (Calcium) acetate tablets, approximately 2.7g, decreased the bioavailability of ciprofloxacin by approximately 50%.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C:
Adcal Syrup acetate capsules contains Adcal Syrup (Calcium) acetate. Animal reproduction studies have not been conducted with Adcal Syrup (Calcium) acetate, and there are no adequate and well controlled studies of Adcal Syrup (Calcium) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with Adcal Syrup (Calcium) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum Adcal Syrup (Calcium) levels is important for maternal and fetal well being. Hypercalcemia during pregnancy may increase the risk for maternal and neonatal complications such as stillbirth, preterm delivery, and neonatal hypocalcemia and hypoparathyroidism. Adcal Syrup (Calcium) acetate treatment, as recommended, is not expected to harm a fetus if maternal Adcal Syrup (Calcium) levels are properly monitored during and following treatment.
8.2 Labor and Delivery
The effects of Adcal Syrup (Calcium) acetate on labor and delivery are unknown.
8.3 Nursing Mothers
Adcal Syrup Acetate Capsules contains Adcal Syrup (Calcium) acetate and is excreted in human milk. Human milk feeding by a mother receiving Adcal Syrup (Calcium) acetate is not expected to harm an infant, provided maternal serum Adcal Syrup (Calcium) levels are appropriately monitored.
8.4 Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
8.5 Geriatric Use
Clinical studies of Adcal Syrup (Calcium) acetate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
10 OVERDOSAGE
Administration of Adcal Syrup (Calcium) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].
11 DESCRIPTION
Adcal Syrup (Calcium) acetate acts as a phosphate binder. Its chemical name is Adcal Syrup (Calcium) acetate. Its molecular formula is C4H6CaO4, and its molecular weight is 158.17. Its structural formula is:
Each white opaque/blue opaque capsule contains 667 mg of Adcal Syrup (Calcium) acetate USP (anhydrous; Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) Adcal Syrup (Calcium), polyethylene glycol 8000 and magnesium stearate. Each capsule shell contains: black monogramming ink, FD&C Blue #1, FD&C Red #3, gelatin and titanium dioxide. The black monogramming ink contains: ammonium hydroxide, iron oxide black, isopropyl alcohol, n-butyl alcohol, propylene glycol and shellac glaze.
Adcal Syrup (Calcium) Acetate Capsules are administered orally for the control of hyperphosphatemia in end-stage renal failure.
12 CLINICAL PHARMACOLOGY
Patients with ESRD retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum Adcal Syrup resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.
12.1 Mechanism of Action
Adcal Syrup (Calcium) acetate, when taken with meals, combines with dietary phosphate to form an insoluble Adcal Syrup (Calcium) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.
12.2 Pharmacodynamics
Orally administered Adcal Syrup (Calcium) acetate from pharmaceutical dosage forms is systemically absorbed up to approximately 40% under fasting conditions and up to approximately 30% under nonfasting conditions. This range represents data from both healthy subjects and renal dialysis patients under various conditions.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No carcinogenicity, mutagenicity, or fertility studies have been conducted with Adcal Syrup (Calcium) acetate.
14 CLINICAL STUDIES
Effectiveness of Adcal Syrup (Calcium) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Adcal Syrup (Calcium) acetate solid oral dosage form.
Ninety-one patients with end-stage renal disease who were undergoing hemodialysis and were hyperphosphatemic (serum phosphorus >5.5 mg/dL) following a 1 week phosphate binder washout period contributed efficacy data to an open-label, non-randomized study.
The patients received Adcal Syrup (Calcium) acetate 667 mg tablets at each meal for a period of 12 weeks. The initial starting dose was 2 tablets per meal for 3 meals a day, and the dose was adjusted as necessary to control serum phosphorus levels. The average final dose after 12 weeks of treatment was 3.4 tablets per meal. Although there was a decrease in serum phosphorus, in the absence of a control group the true magnitude of effect is uncertain.
The data presented in Table 2 demonstrate the efficacy of Adcal Syrup (Calcium) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Adcal Syrup (Calcium) levels are also presented.
| * Ninety-one patients completed at least 6 weeks of the study. † ANOVA of difference in values at pre-study and study completion. ‡ Values expressed as mean ± SE. | |||||
| Parameter | Pre-Study | Week 4* | Week 8 | Week 12 | p-value† |
| Phosphorus (mg/dL)‡ | 7.4 ± 0.17 | 5.9 ± 0.16 | 5.6 ± 0.17 | 5.2 ± 0.17 | ≤0.01 |
| Adcal Syrup (Calcium) (mg/dL)‡ | 8.9 ± 0.09 | 9.5 ± 0.10 | 9.7 ± 0.10 | 9.7 ± 0.10 | ≤0.01 |
There was a 30% decrease in serum phosphorus levels during the 12 week study period (p<0.01). Two-thirds of the decline occurred in the first month of the study. Serum Adcal Syrup (Calcium) increased 9% during the study mostly in the first month of the study.
Treatment with the phosphate binder was discontinued for patients from the open-label study, and those patients whose serum phosphorus exceeded 5.5 mg/dL were eligible for entry into a double-blind, placebo-controlled, cross-over study. Patients were randomized to receive Adcal Syrup (Calcium) acetate or placebo, and each continued to receive the same number of tablets as had been individually established during the previous study. Following 2 weeks of treatment, patients switched to the alternative therapy for an additional 2 weeks.
The phosphate binding effect of Adcal Syrup (Calcium) acetate is shown in the Table 3.
| * ANOVA of Adcal Syrup (Calcium) acetate vs. placebo after 2 weeks of treatment. † Values expressed as mean ± SEM. | ||||
| Parameter | Pre-Study | Post-Treatment | p-value* | |
| Adcal Syrup (Calcium) Acetate | Placebo | |||
| Phosphorus (mg/dL)† | 7.3 ± 0.18 | 5.9 ± 0.24 | 7.8 ± 0.22 | <0.01 |
| Adcal Syrup (Calcium) (mg/dL)† | 8.9 ± 0.11 | 9.5 ± 0.13 | 8.8 ± 0.12 | <0.01 |
Overall, 2 weeks of treatment with Adcal Syrup (Calcium) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum Adcal Syrup (Calcium) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.
16 HOW SUPPLIED/STORAGE AND HANDLING
Adcal Syrup (Calcium) Acetate Capsules
667 mg capsule is supplied as a white opaque/blue opaque capsule, imprinted with “54 215” on the cap and body.
NDC 0615-2303-39: Blistercards of 30 Capsules
NDC 0615-2303-30: Unit-dose Boxes of 30 Capsules
STORAGE
Store at 20° to 25°C (68° to 77°F).
17 PATIENT COUNSELING INFORMATION
Inform patients to take Adcal Syrup (Calcium) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Adcal Syrup (Calcium) supplements including nonprescription antacids. Inform the patients about the symptoms of hypercalcemia [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ].
Advise patients who are taking an oral medication where reduction in the bioavailability of that medication would have clinically significant effect on its safety or efficacy to take the drug one hour before or three hours after Adcal Syrup (Calcium) acetate capsules.
Distr. by: West-Ward
Pharmaceuticals Corp.
Eatontown, NJ 07724
10003705/05
Revised April 2016
Vitamin B12:
Pharmacological action
Adcal Syrup refers to a group of water-soluble vitamins. It has high biological activity. Adcal Syrup (Vitamin B12) is necessary for normal hematopoiesis (promotes maturation of erythrocytes). Involved in the processes of transmethylation, hydrogen transport, synthesis of methionine, nucleic acids, choline, creatine. Contributes to the accumulation in erythrocytes of compounds containing sulfhydryl groups. Has a beneficial effect on liver function and the nervous system. Activates the coagulation of blood in high doses causes an increase in the activity of thromboplastin and prothrombin.
Pharmacokinetics
After oral administration Adcal Syrup (Vitamin B12) absorbed from the gastrointestinal tract. Metabolized in the tissues, becoming a co-enzyme form - adenosylcobalamin which is the active form of cyanocobalamin. Excreted in bile and urine.
Why is Adcal Syrup prescribed?
Anemia due to B12-deficiency conditions; in the complex therapy for iron and posthemorrhagic anemia; aplastic anemia caused by toxic substances and drugs; liver disease (hepatitis, cirrhosis); funicular myelosis; polyneuritis, radiculitis, neuralgia, amyotrophic lateral sclerosis; children cerebral palsy, Down syndrome, peripheral nerve injury; skin diseases (psoriasis, photodermatosis, herpetiformis dermatitis, neurodermatitis); to prevent and treat symptoms of deficiency of Adcal Syrup (Vitamin B12) (including the application of biguanide, PASA, vitamin C in high doses); radiation sickness.
Dosage and administration
Adcal Syrup is used as injections SC, IV, IM, intralumbar, and also oral. With anemia associated with Adcal Syrup (Vitamin B12) deficiency is introduced on 100-200 mcg in 2 days. In anemia with symptoms of funicular myelosis and megalocytic anemia with diseases of the nervous system - 400-500 micrograms in the first 7 days daily, then 1 time every 5-7 days. In the period of remission in the absence of events funicular myelosis maintenance dose - 100 mcg 2 times a month, in the presence of neurological symptoms - at 200-400 mcg 2-4 times a month. In acute post-hemorrhagic anemia and iron anemia by 30-100 mcg 2-3 times a week. When aplastic anemia (especially in children) - 100 micrograms before clinical improvement. When nutritional anemia in infants and preterm - 30 mcg / day during 15 days.
In diseases of the central and peripheral nervous system and neurological diseases with a pain syndrome is administered in increasing doses - 200-500 mcg, with the improvement in the state - 100 mcg / day. The course of treatment with Adcal Syrup (Vitamin B12) is 2 weeks. In traumatic lesions of peripheral nervous system - at 200-400 mcg every other day for 40-45 days.
When hepatitis and cirrhosis - 30-60 mcg / day or 100 mg every other day for 25-40 days.
Dystrophy in young children, Down syndrome and cerebral palsy - by 15-30 mcg every other day.
When funicular myelosis, amyotrophic lateral sclerosis can be introduced into the spinal canal at 15-30 mcg, gradually increasing the dose of 200-250 micrograms.
In radiation sickness, diabetic neuropathy, sprue - by 60-100 mcg daily for 20-30 days.
When deficiency of Adcal Syrup (Vitamin B12) to prevent - IV or IM for 1 mg 1 time a month; for treatment - IV or IM for 1 mg daily for 1-2 weeks, the maintenance dose is 1-2 mg IV or IM from 1 per week, up to 1 per month. Duration of treatment is determined individually.
Adcal Syrup (Vitamin B12) side effects, adverse reactions
CNS: rarely - a state of arousal.
Cardiovascular system: rarely - pain in the heart, tachycardia.
Allergic reactions: rarely - urticaria.
Adcal Syrup contraindications
Thromboembolism, erythremia, erythrocytosis, increased sensitivity to cyanocobalamin.
Adcal Syrup using during pregnancy and breastfeeding
Cyanocobalamin can be used in pregnancy according to prescriptions.
Special instructions
When stenocardia should be used with caution in a single dose of Adcal Syrup 100 mcg. During treatment should regularly monitor the blood picture and coagulation. It is unacceptable to enter in the same syringe with cyanocobalamin solutions of thiamine and pyridoxine.
Adcal Syrup (Vitamin B12) drug interactions
In an application of Adcal Syrup (Vitamin B12) with hormonal contraceptives for oral administration may decrease the concentration of cyanocobalamin in plasma.
In an application with anticonvulsant drugs decreased cyanocobalamin absorption from the gut.
In an Adcal Syrup (Vitamin B12) application with neomycin, aminosalicylic acid, colchicine, cimetidine, ranitidine, drugs potassium decreased cyanocobalamin absorption from the gut.
Cyanocobalamin may exacerbate allergic reactions caused by thiamine.
When parenteral application of chloramphenicol may decrease the hematopoietic effects of cyanocobalamin with anemia.
Pharmaceutical incompatibility
Contained in the molecule of cyanocobalamin cobalt ion contributes to the destruction of ascorbic acid, thiamine bromide, riboflavin in one solution.
Adcal Syrup pharmaceutical active ingredients containing related brand and generic drugs:
Adcal Syrup available forms, composition, doses:
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.