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DRUGS & SUPPLEMENTS
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ActiCal
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ActiCal uses
ActiCal consists of Calcium (Calcium Carbonate), Calcium (Calcium Citrate), Magnesium (Magnesium Amino Acid Chelate), Magnesium (Magnesium Citrate), Silicon (Silicon Amino Acid Chelate), Vitamin D3 (Cholecalciferol).Calcium (Calcium Carbonate):
- 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
ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) acetate capsule.
- Capsule: 667 mg ActiCal (Calcium (Calcium Carbonate)) acetate capsule. (3)
4 CONTRAINDICATIONS
Patients with hypercalcemia.
- Hypercalcemia. (4)
5 WARNINGS AND PRECAUTIONS
- Treat mild hypercalcemia by reducing or interrupting ActiCal ) acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)), including ActiCal (Calcium (Calcium Carbonate)) acetate. Avoid the use of ActiCal (Calcium (Calcium Carbonate)) supplements, including ActiCal (Calcium (Calcium Carbonate)) based nonprescription antacids, concurrently with ActiCal (Calcium (Calcium Carbonate)) acetate.
An overdose of ActiCal (Calcium (Calcium Carbonate)) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum ActiCal (Calcium (Calcium Carbonate)) levels twice weekly. Should hypercalcemia develop, reduce the ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) 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, ActiCal (Calcium (Calcium Carbonate)) acetate has been generally well tolerated.
ActiCal (Calcium (Calcium Carbonate)) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) acetate N=167 N (%) | 3 month, open label study of ActiCal (Calcium (Calcium Carbonate)) acetate N=98 N (%) | Double blind, placebo-controlled, cross-over study of liquid ActiCal (Calcium (Calcium Carbonate)) acetate N=69 | |
| ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) concentration could reduce the incidence and severity of ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) acetate: dizziness, edema, and weakness.
7 DRUG INTERACTIONS
The drug interaction of ActiCal ) acetate is characterized by the potential of ActiCal (Calcium (Calcium Carbonate)) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). ActiCal (Calcium (Calcium Carbonate)) acetate may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism.
There are no empirical data on avoiding drug interactions between ActiCal (Calcium (Calcium Carbonate)) acetate and most concomitant drugs. When administering an oral medication with ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) acetate tablets, approximately 2.7g, decreased the bioavailability of ciprofloxacin by approximately 50%.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C:
ActiCal ) acetate capsules contains ActiCal (Calcium (Calcium Carbonate)) acetate. Animal reproduction studies have not been conducted with ActiCal (Calcium (Calcium Carbonate)) acetate, and there are no adequate and well controlled studies of ActiCal (Calcium (Calcium Carbonate)) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with ActiCal (Calcium (Calcium Carbonate)) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum ActiCal (Calcium (Calcium Carbonate)) 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. ActiCal (Calcium (Calcium Carbonate)) acetate treatment, as recommended, is not expected to harm a fetus if maternal ActiCal (Calcium (Calcium Carbonate)) levels are properly monitored during and following treatment.
8.2 Labor and Delivery
The effects of ActiCal (Calcium (Calcium Carbonate)) acetate on labor and delivery are unknown.
8.3 Nursing Mothers
ActiCal ) Acetate Capsules contains ActiCal (Calcium (Calcium Carbonate)) acetate and is excreted in human milk. Human milk feeding by a mother receiving ActiCal (Calcium (Calcium Carbonate)) acetate is not expected to harm an infant, provided maternal serum ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].
11 DESCRIPTION
ActiCal (Calcium (Calcium Carbonate)) acetate acts as a phosphate binder. Its chemical name is ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) acetate USP (anhydrous; Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) ActiCal (Calcium (Calcium Carbonate)), 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.
ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal ) resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.
12.1 Mechanism of Action
ActiCal (Calcium (Calcium Carbonate)) acetate, when taken with meals, combines with dietary phosphate to form an insoluble ActiCal (Calcium (Calcium Carbonate)) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.
12.2 Pharmacodynamics
Orally administered ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) acetate.
14 CLINICAL STUDIES
Effectiveness of ActiCal (Calcium (Calcium Carbonate)) acetate in decreasing serum phosphorus has been demonstrated in two studies of the ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum ActiCal (Calcium (Calcium Carbonate)) 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 |
| ActiCal (Calcium (Calcium Carbonate)) (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 ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) acetate is shown in the Table 3.
| * ANOVA of ActiCal (Calcium (Calcium Carbonate)) acetate vs. placebo after 2 weeks of treatment. † Values expressed as mean ± SEM. | ||||
| Parameter | Pre-Study | Post-Treatment | p-value* | |
| ActiCal (Calcium (Calcium Carbonate)) Acetate | Placebo | |||
| Phosphorus (mg/dL)† | 7.3 ± 0.18 | 5.9 ± 0.24 | 7.8 ± 0.22 | <0.01 |
| ActiCal (Calcium (Calcium Carbonate)) (mg/dL)† | 8.9 ± 0.11 | 9.5 ± 0.13 | 8.8 ± 0.12 | <0.01 |
Overall, 2 weeks of treatment with ActiCal (Calcium (Calcium Carbonate)) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum ActiCal (Calcium (Calcium Carbonate)) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.
16 HOW SUPPLIED/STORAGE AND HANDLING
ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of ActiCal (Calcium (Calcium Carbonate)) 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 ActiCal (Calcium (Calcium Carbonate)) acetate capsules.
Distr. by: West-Ward
Pharmaceuticals Corp.
Eatontown, NJ 07724
10003705/05
Revised April 2016
Calcium (Calcium Citrate):
- 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
ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) acetate capsule.
- Capsule: 667 mg ActiCal (Calcium (Calcium Citrate)) acetate capsule. (3)
4 CONTRAINDICATIONS
Patients with hypercalcemia.
- Hypercalcemia. (4)
5 WARNINGS AND PRECAUTIONS
- Treat mild hypercalcemia by reducing or interrupting ActiCal ) acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)), including ActiCal (Calcium (Calcium Citrate)) acetate. Avoid the use of ActiCal (Calcium (Calcium Citrate)) supplements, including ActiCal (Calcium (Calcium Citrate)) based nonprescription antacids, concurrently with ActiCal (Calcium (Calcium Citrate)) acetate.
An overdose of ActiCal (Calcium (Calcium Citrate)) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum ActiCal (Calcium (Calcium Citrate)) levels twice weekly. Should hypercalcemia develop, reduce the ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) 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, ActiCal (Calcium (Calcium Citrate)) acetate has been generally well tolerated.
ActiCal (Calcium (Calcium Citrate)) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) acetate N=167 N (%) | 3 month, open label study of ActiCal (Calcium (Calcium Citrate)) acetate N=98 N (%) | Double blind, placebo-controlled, cross-over study of liquid ActiCal (Calcium (Calcium Citrate)) acetate N=69 | |
| ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) concentration could reduce the incidence and severity of ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) acetate: dizziness, edema, and weakness.
7 DRUG INTERACTIONS
The drug interaction of ActiCal ) acetate is characterized by the potential of ActiCal (Calcium (Calcium Citrate)) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). ActiCal (Calcium (Calcium Citrate)) acetate may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism.
There are no empirical data on avoiding drug interactions between ActiCal (Calcium (Calcium Citrate)) acetate and most concomitant drugs. When administering an oral medication with ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) acetate tablets, approximately 2.7g, decreased the bioavailability of ciprofloxacin by approximately 50%.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C:
ActiCal ) acetate capsules contains ActiCal (Calcium (Calcium Citrate)) acetate. Animal reproduction studies have not been conducted with ActiCal (Calcium (Calcium Citrate)) acetate, and there are no adequate and well controlled studies of ActiCal (Calcium (Calcium Citrate)) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with ActiCal (Calcium (Calcium Citrate)) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum ActiCal (Calcium (Calcium Citrate)) 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. ActiCal (Calcium (Calcium Citrate)) acetate treatment, as recommended, is not expected to harm a fetus if maternal ActiCal (Calcium (Calcium Citrate)) levels are properly monitored during and following treatment.
8.2 Labor and Delivery
The effects of ActiCal (Calcium (Calcium Citrate)) acetate on labor and delivery are unknown.
8.3 Nursing Mothers
ActiCal ) Acetate Capsules contains ActiCal (Calcium (Calcium Citrate)) acetate and is excreted in human milk. Human milk feeding by a mother receiving ActiCal (Calcium (Calcium Citrate)) acetate is not expected to harm an infant, provided maternal serum ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].
11 DESCRIPTION
ActiCal (Calcium (Calcium Citrate)) acetate acts as a phosphate binder. Its chemical name is ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) acetate USP (anhydrous; Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) ActiCal (Calcium (Calcium Citrate)), 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.
ActiCal (Calcium (Calcium Citrate)) 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 ActiCal ) resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.
12.1 Mechanism of Action
ActiCal (Calcium (Calcium Citrate)) acetate, when taken with meals, combines with dietary phosphate to form an insoluble ActiCal (Calcium (Calcium Citrate)) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.
12.2 Pharmacodynamics
Orally administered ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) acetate.
14 CLINICAL STUDIES
Effectiveness of ActiCal (Calcium (Calcium Citrate)) acetate in decreasing serum phosphorus has been demonstrated in two studies of the ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum ActiCal (Calcium (Calcium Citrate)) 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 |
| ActiCal (Calcium (Calcium Citrate)) (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 ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) acetate is shown in the Table 3.
| * ANOVA of ActiCal (Calcium (Calcium Citrate)) acetate vs. placebo after 2 weeks of treatment. † Values expressed as mean ± SEM. | ||||
| Parameter | Pre-Study | Post-Treatment | p-value* | |
| ActiCal (Calcium (Calcium Citrate)) Acetate | Placebo | |||
| Phosphorus (mg/dL)† | 7.3 ± 0.18 | 5.9 ± 0.24 | 7.8 ± 0.22 | <0.01 |
| ActiCal (Calcium (Calcium Citrate)) (mg/dL)† | 8.9 ± 0.11 | 9.5 ± 0.13 | 8.8 ± 0.12 | <0.01 |
Overall, 2 weeks of treatment with ActiCal (Calcium (Calcium Citrate)) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum ActiCal (Calcium (Calcium Citrate)) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.
16 HOW SUPPLIED/STORAGE AND HANDLING
ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of ActiCal (Calcium (Calcium Citrate)) 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 ActiCal (Calcium (Calcium Citrate)) acetate capsules.
Distr. by: West-Ward
Pharmaceuticals Corp.
Eatontown, NJ 07724
10003705/05
Revised April 2016
Magnesium (Magnesium Amino Acid Chelate):
- Description
- Clinical pharmacology
- Indications and usage
- Contraindications
- Warnings
- Precautions
- Adverse reactions
- Overdosage
- Dosage and administration
- How supplied
- References
ActiCal (Magnesium (Magnesium Amino Acid Chelate)) Sulfate
Injection, USP
Ansyr Plastic Syringe
Rx only
DESCRIPTION
ActiCal (Magnesium (Magnesium Amino Acid Chelate)) Sulfate Injection, USP is a sterile solution of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate heptahydrate in Water for Injection, USP administered by the intravenous or intramuscular routes as an electrolyte replenisher or anticonvulsant. Must be diluted before intravenous use. May contain sulfuric acid and/or sodium hydroxide for pH adjustment. The pH is 5.5 to 7.0. The 50% concentration has an osmolarity of 4.06 mOsmol/mL (calc.).
The solution contains no bacteriostat, antimicrobial agent or added buffer (except for pH adjustment) and is intended only for use as a single-dose injection. When smaller doses are required the unused portion should be discarded with the entire unit.
ActiCal (Magnesium (Magnesium Amino Acid Chelate)) Sulfate, USP heptahydrate is chemically designated MgSO4 - 7H2O with molecular weight of 246.48 and occurs as colorless crystals or white powder freely soluble in water.
The plastic syringe is molded from a specially formulated polypropylene. Water permeates from inside the container at an extremely slow rate which will have an insignificant effect on solution concentration over the expected shelf life. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the syringe material.
CLINICAL PHARMACOLOGY
ActiCal (Magnesium (Magnesium Amino Acid Chelate)) (Mg++) is an important cofactor for enzymatic reactions and plays an important role in neurochemical transmission and muscular excitability.
As a nutritional adjunct in hyperalimentation, the precise mechanism of action for ActiCal (Magnesium (Magnesium Amino Acid Chelate)) is uncertain. Early symptoms of hypomagnesemia (less than 1.5 mEq/liter) may develop as early as three to four days or within weeks.
Predominant deficiency effects are neurological, e.g., muscle irritability, clonic twitching and tremors. Hypocalcemia and hypokalemia often follow low serum levels of ActiCal (Magnesium (Magnesium Amino Acid Chelate)). While there are large stores of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral ActiCal (Magnesium (Magnesium Amino Acid Chelate)) therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.
ActiCal (Magnesium (Magnesium Amino Acid Chelate)) prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. ActiCal (Magnesium (Magnesium Amino Acid Chelate)) is said to have a depressant effect on the central nervous system (CNS), but it does not adversely affect the woman, fetus or neonate when used as directed in eclampsia or pre-eclampsia. Normal plasma ActiCal (Magnesium (Magnesium Amino Acid Chelate)) levels range from 1.5 to 2.5 mEq/liter.
As plasma ActiCal (Magnesium (Magnesium Amino Acid Chelate)) rises above 4 mEq/liter, the deep tendon reflexes are first decreased and then disappear as the plasma level approaches 10 mEq/liter. At this level respiratory paralysis may occur. Heart block also may occur at this or lower plasma levels of ActiCal (Magnesium (Magnesium Amino Acid Chelate)). Serum ActiCal (Magnesium (Magnesium Amino Acid Chelate)) concentrations in excess of 12 mEq/L may be fatal.
ActiCal (Magnesium (Magnesium Amino Acid Chelate)) acts peripherally to produce vasodilation. With low doses only flushing and sweating occur, but larger doses cause lowering of blood pressure. The central and peripheral effects of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) poisoning are antagonized to some extent by intravenous administration of calcium.
Pharmacokinetics
With intravenous administration the onset of anticonvulsant action is immediate and lasts about 30 minutes. Following intramuscular administration the onset of action occurs in about one hour and persists for three to four hours. Effective anticonvulsant serum levels range from 2.5 to 7.5 mEq/liter. ActiCal (Magnesium (Magnesium Amino Acid Chelate)) is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.
INDICATIONS AND USAGE
ActiCal (Magnesium (Magnesium Amino Acid Chelate)) Sulfate Injection, USP is suitable for replacement therapy in ActiCal (Magnesium (Magnesium Amino Acid Chelate)) deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum ActiCal (Magnesium (Magnesium Amino Acid Chelate)) (Mg++) level is usually below the lower limit of normal (1.5 to 2.5 mEq/liter) and the serum calcium (Ca++) level is normal (4.3 to 5.3 mEq/liter) or elevated.
In total parenteral nutrition (TPN), ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.
ActiCal (Magnesium (Magnesium Amino Acid Chelate)) Sulfate Injection, USP is also indicated for the prevention and control of seizures (convulsions) in pre-eclampsia and eclampsia, respectively.
CONTRAINDICATIONS
Parenteral administration of the drug is contraindicated in patients with heart block or myocardial damage.
WARNINGS
FETAL HARM: Continuous administration of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate beyond 5 to 7 days to pregnant women can lead to hypocalcemia and bone abnormalities in the developing fetus. These bone abnormalities include skeletal demineralization and osteopenia. In addition, cases of neonatal fracture have been reported. The shortest duration of treatment that can lead to fetal harm is not known. ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate should be used during pregnancy only if clearly needed. If ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate is given for treatment of preterm labor, the woman should be informed that the efficacy and safety of such use have not been established and that use of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate beyond 5 to 7 days may cause fetal abnormalities.
ALUMINUM TOXICITY: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.
Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.
Parenteral use in the presence of renal insufficiency may lead to ActiCal (Magnesium (Magnesium Amino Acid Chelate)) intoxication. Intravenous use in the eclampsia should be reserved for immediate control of life-threatening convulsions.
PRECAUTIONS
General
Administer with caution if flushing and sweating occurs. When barbiturates, narcotics or other hypnotics (or systemic anesthetics) are to be given in conjunction with ActiCal (Magnesium (Magnesium Amino Acid Chelate)), their dosage should be adjusted with caution because of additive CNS depressant effects of ActiCal (Magnesium (Magnesium Amino Acid Chelate)).
Because ActiCal (Magnesium (Magnesium Amino Acid Chelate)) is removed from the body solely by the kidneys, the drug should be used with caution in patients with renal impairment. Urine output should be maintained at a level of 100 mL or more during the four hours preceding each dose. Monitoring serum ActiCal (Magnesium (Magnesium Amino Acid Chelate)) levels and the patient's clinical status is essential to avoid the consequences of overdosage in toxemia. Clinical indications of a safe dosage regimen include the presence of the patellar reflex (knee jerk) and absence of respiratory depression (approximately 16 breaths or more/minute). When repeated doses of the drug are given parenterally, knee jerk reflexes should be tested before each dose and if they are absent, no additional ActiCal (Magnesium (Magnesium Amino Acid Chelate)) should be given until they return. Serum ActiCal (Magnesium (Magnesium Amino Acid Chelate)) levels usually sufficient to control convulsions range from 3 to 6 mg/100 mL (2.5 to 5 mEq/liter). The strength of the deep tendon reflexes begins to diminish when ActiCal (Magnesium (Magnesium Amino Acid Chelate)) levels exceed 4 mEq/liter. Reflexes may be absent at 10 mEq magnesium/liter, where respiratory paralysis is a potential hazard. An injectable calcium salt should be immediately available to counteract the potential hazards of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) intoxication in eclampsia.
50% ActiCal (Magnesium (Magnesium Amino Acid Chelate)) Sulfate Injection, USP must be diluted to a concentration of 20% or less prior to intravenous infusion. Rate of administration should be slow and cautious, to avoid producing hypermagnesemia. The 50% solution also should be diluted to 20% or less for intramuscular injection in infants and children.
Laboratory Tests
ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) is monitored. The normal serum level is 1.5 to 2.5 mEq/L.
Drug Interactions
CNS Depressants - When barbiturates, narcotics or other hypnotics (or systemic anesthetics), or other CNS depressants are to be given in conjunction with ActiCal (Magnesium (Magnesium Amino Acid Chelate)), their dosage should be adjusted with caution because of additive CNS depressant effects of ActiCal (Magnesium (Magnesium Amino Acid Chelate)). CNS depression and peripheral transmission defects produced by ActiCal (Magnesium (Magnesium Amino Acid Chelate)) may be antagonized by calcium.
Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.
Cardiac Glycosides - ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate should be administered with extreme caution in digitalized patients, because serious changes in cardiac conduction which can result in heart block may occur if administration of calcium is required to treat ActiCal (Magnesium (Magnesium Amino Acid Chelate)) toxicity.
Pregnancy
Teratogenic Effects
Pregnancy Category D (See WARNINGS and PRECAUTIONS )
See WARNINGS and PRECAUTIONS .
ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate can cause fetal abnormalities when administered beyond 5 to 7 days to pregnant women. There are retrospective epidemiological studies and case reports documenting fetal abnormalities such as hypocalcemia, skeletal demineralization, osteopenia and other skeletal abnormalities with continuous maternal administration of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate for more than 5 to 7 days.1-10 ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate injection should be used during pregnancy only if clearly needed. If this drug is used during pregnancy, the woman should be apprised of the potential harm to the fetus.
Nonteratogenic Effects
When administered by continuous intravenous infusion (especially for more than 24 hours preceding delivery) to control convulsions in a toxemic woman, the newborn may show signs of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).
Labor and Delivery
Continuous administration of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate outside of its approved indication in pregnant women should be by trained obstetrical personnel in a hospital setting with appropriate obstetrical care facilities.
Nursing Mothers
Since ActiCal (Magnesium (Magnesium Amino Acid Chelate)) is distributed into milk during parenteral ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate administration, the drug should be used with caution in nursing women.
Geriatrics
Geriatric patients often require reduced dosage because of impaired renal function. In patients with severe impairment, dosage should not exceed 20 grams in 48 hours. Serum ActiCal (Magnesium (Magnesium Amino Acid Chelate)) should be monitored in such patients.
ADVERSE REACTIONS
The adverse effects of parenterally administered ActiCal (Magnesium (Magnesium Amino Acid Chelate)) usually are the result of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) intoxication. These include flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system depression proceeding to respiratory paralysis. Hypocalcemia with signs of tetany secondary to ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate therapy for eclampsia has been reported.
OVERDOSAGE
ActiCal (Magnesium (Magnesium Amino Acid Chelate)) intoxication is manifested by a sharp drop in blood pressure and respiratory paralysis. Disappearance of the patellar reflex is a useful clinical sign to detect the onset of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of ActiCal (Magnesium (Magnesium Amino Acid Chelate)).
For Treatment of Overdose
Artificial respiration is often required. Intravenous calcium, 10 to 20 mL of a 5% solution (diluted if desirable with isotonic sodium chloride for injection) is used to counteract effects of hypermagnesemia. Subcutaneous physostigmine, 0.5 to 1 mg may be helpful.
Hypermagnesemia in the newborn may require resuscitation and assisted ventilation via endotracheal intubation or intermittent positive pressure ventilation as well as intravenous calcium.
DOSAGE AND ADMINISTRATION
Dosage of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate must be carefully adjusted according to individual requirements and response, and administration of the drug should be discontinued as soon as the desired effect is obtained.
Both intravenous and intramuscular administration are appropriate. Intramuscular administration of the undiluted 50% solution results in therapeutic plasma levels in 60 minutes, whereas intravenous doses will provide a therapeutic level almost immediately. The rate of intravenous injection should generally not exceed 150 mg/minute (1.5 mL of a 10% concentration or its equivalent), except in severe eclampsia with seizures. Continuous maternal administration of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate in pregnancy beyond 5 to 7 days can cause fetal abnormalities.
Solutions for intravenous infusion must be diluted to a concentration of 20% or less prior to administration. The diluents commonly used are 5% Dextrose Injection, USP and 0.9% Sodium Chloride Injection, USP. Deep intramuscular injection of the undiluted (50%) solution is appropriate for adults, but the solution should be diluted to a 20% or less concentration prior to such injection in children.
In ActiCal (Magnesium (Magnesium Amino Acid Chelate)) Deficiency
In the treatment of mild ActiCal (Magnesium (Magnesium Amino Acid Chelate)) deficiency, the usual adult dose is 1 gram, equivalent to 8.12 mEq of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) (2 mL of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) per 24 hours). For severe hypomagnesemia, as much as 250 mg (approximately 2 mEq) per kg of body weight (0.5 mL of the 50% solution) may be given intramuscularly within a period of four hours if necessary. Alternatively, 5 grams, (approximately 40 mEq) can be added to one liter of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP for slow intravenous infusion over a three-hour period. In the treatment of deficiency states, caution must be observed to prevent exceeding the renal excretory capacity.
In Hyperalimentation
In total parenteral nutrition, maintenance requirements for ActiCal (Magnesium (Magnesium Amino Acid Chelate)) are not precisely known. The maintenance dose used in adults ranges from 8 to 24 mEq (1 gram to 3 grams) daily; for infants, the range is 2 to 10 mEq (0.25 gram to 1.25 grams) daily.
In Pre-eclampsia or Eclampsia
In severe pre-eclampsia or eclampsia, the total initial dose is 10 grams to 14 grams of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate. Intravenously, a dose of 4 grams to 5 grams in 250 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP may be infused. Simultaneously, intramuscular doses of up to 10 grams (5 grams or 10 mL of the undiluted 50% solution in each buttock) are given. Alternatively, the initial intravenous dose of 4 grams may be given by diluting the 50% solution to a 10 or 20% concentration; the diluted fluid (40 mL of a 10% solution or 20 mL of a 20% solution) may then be injected intravenously over a period of three to four minutes. Subsequently, 4 grams to 5 grams (8 to 10 mL of the 50% solution) are injected intramuscularly into alternate buttocks every four hours as needed, depending on the continuing presence of the patellar reflex and adequate respiratory function. Alternatively, after the initial intravenous dose, some clinicians administer 1 gram to 2 grams/hour by constant intravenous infusion. Therapy should continue until paroxysms cease. A serum ActiCal (Magnesium (Magnesium Amino Acid Chelate)) level of 6 mg/100 mL is considered optimal for control of seizures. A total daily (24 hr) dose of 30 grams to 40 grams should not be exceeded. In the presence of severe renal insufficiency, the maximum dosage of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate is 20 grams/48 hours and frequent serum ActiCal (Magnesium (Magnesium Amino Acid Chelate)) concentrations must be obtained. Continuous use of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate in pregnancy beyond 5 to 7 days can cause fetal abnormalities.
Other Uses
In counteracting the muscle-stimulating effects of barium poisoning, the usual dose of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate is 1 gram to 2 grams given intravenously.
For controlling seizures associated with epilepsy, glomerulonephritis or hypothyroidism, the usual adult dose is 1 gram administered intramuscularly or intravenously.
In paroxysmal atrial tachycardia, ActiCal (Magnesium (Magnesium Amino Acid Chelate)) should be used only if simpler measures have failed and there is no evidence of myocardial damage. The usual dose is 3 grams to 4 grams (30 to 40 mL of a 10% solution) administered intravenously over 30 seconds with extreme caution.
For reduction of cerebral edema, 2.5 grams (25 mL of a 10% solution) is given intravenously.
Incompatibilities
ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate in solution may result in a precipitate formation when mixed with solutions containing:
Alcohol (in high Heavy Metals
concentrations) Hydrocortisone sodium
Alkali carbonates and succinate
bicarbonates Phosphates
Alkali hydroxides Polymixin B sulfate
Arsenates Procaine hydrochloride
Barium Salicylates
Calcium Strontium
Clindamycin phosphate Tartrates
The potential incompatibility will often be influenced by the changes in the concentration of reactants and the pH of the solutions.
It has been reported that ActiCal (Magnesium (Magnesium Amino Acid Chelate)) may reduce the antibiotic activity of streptomycin, tetracycline and tobramycin when given together.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
HOW SUPPLIED
ActiCal (Magnesium (Magnesium Amino Acid Chelate)) Sulfate Injection, USP is supplied in single-dose containers as follows:
| NDC No. | Container | Total Amount | Concentration | mEq Mg++/mL |
| 0409-1754-10 | Ansyr Plastic Syringe | 5 g/10 mL | 50% | 4 mEq/mL |
Do not administer unless solution is clear and container is undamaged. Discard unused portion.
Store at 20 to 25°C (68 to 77°F).
REFERENCES
- Yokoyama K, Takahashi N, Yada Y. Prolonged maternal ActiCal (Magnesium (Magnesium Amino Acid Chelate)) administration and bone metabolism in neonates. Early Hum Dev. 2010;86(3):187-91. Epub 2010 Mar 12.
- Wedig KE, Kogan J, Schorry EK et al. Skeletal demineralization and fractures caused by fetal ActiCal (Magnesium (Magnesium Amino Acid Chelate)) toxicity. J. Perinatol. 2006; 26(6):371-4.
- Nassar AH, Sakhel K, Maarouf H, et al. Adverse maternal and neonatal outcome of prolonged course of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate tocolysis. Acta Obstet Gynecol Scan. 2006;85(9):1099-103.
- Malaeb SN, Rassi A, Haddad MC. Bone mineralization in newborns whose mothers received ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulphate for tocolysis of premature labor. Pediatr Radiol. 2004;34(5):384-6. Epub 2004 Feb 18.
- Matsuda Y, Maeda Y, Ito M, et al. Effect of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate treatment on neonatal bone abnormalities. Gynecol Obstet Invest. 1997;44(2):82-8.
- Schanler RJ, Smith LG, Burns PA. Effects of long-term maternal intravenous ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate therapy on neonatal calcium metabolism and bone mineral content. Gynecol Obstet Invest. 1997;43(4):236-41.
- Santi MD, Henry GW, Douglas GL. ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate treatment of preterm labor as a cause of abnormal neonatal bone mineralization. J Pediatr Orthrop. 1994;14(2):249-53.
- Holcomb WL, Shackelford GD, Petrie RH. ActiCal (Magnesium (Magnesium Amino Acid Chelate)) tocolysis and neonatal bone abnormalities; a controlled study. Obstet Gynecol. 1991; 78(4):611-4.
- Cumming WA, Thomas VJ. Hypermagnesemia: a cause of abnormal metaphyses in the neonate. Am J Roentgenol. 1989; 152(5):1071-2.
- Lamm CL, Norton KL, Murphy RJ. Congenital rickets associated with ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate infusion for tocolysis. J Pediatr. 1988; 113(6):1078-82.
- McGuinness GA, Weinstein MM, Cruikshank DP, et al. Effects of ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate treatment on perinatal calcium metabolism. II. Neonatal responses. Obstet Gynecol. 1980; 56(5): 595-600.
- Riaz M, Porat R, Brodsky NL, et al. The effects of maternal ActiCal (Magnesium (Magnesium Amino Acid Chelate)) sulfate treatment on newborns: a prospective controlled study. J. Perinatol. 1998;18(6 pt 1):449-54.
Hospira, Inc., Lake Forest, IL 60045 USA
LAB-1024-1.0
April 2017
Hospira Logo
50% ActiCal (Magnesium (Magnesium Amino Acid Chelate)) Sulfate 5 g/10 mL (500 mg/mL)
Rx only
NDC 0409-1754-10
10 mL Single-dose syringe
50% ActiCal (Magnesium (Magnesium Amino Acid Chelate)) Sulfate Injection, USP
5 g/10 mL (500 mg/mL) (4 mEq Mg++/mL)
MUST BE DILUTED FOR INTRAVENOUS USE.
For Intravenous or Intramuscular Use. Sterile. 4.06 mOsmol/mL (calc.).
Contains no more than 75 mcg/L of aluminum.
Hospira, Inc., Lake Forest, IL 60045 USA
Hospira
RL-6891
Magnesium (Magnesium Citrate):
- Description
- Clinical pharmacology
- Indications and usage
- Contraindications
- Warnings
- Precautions
- Adverse reactions
- Overdosage
- Dosage and administration
- How supplied
- References
ActiCal (Magnesium (Magnesium Citrate)) Sulfate
Injection, USP
Ansyr Plastic Syringe
Rx only
DESCRIPTION
ActiCal (Magnesium (Magnesium Citrate)) Sulfate Injection, USP is a sterile solution of ActiCal (Magnesium (Magnesium Citrate)) sulfate heptahydrate in Water for Injection, USP administered by the intravenous or intramuscular routes as an electrolyte replenisher or anticonvulsant. Must be diluted before intravenous use. May contain sulfuric acid and/or sodium hydroxide for pH adjustment. The pH is 5.5 to 7.0. The 50% concentration has an osmolarity of 4.06 mOsmol/mL (calc.).
The solution contains no bacteriostat, antimicrobial agent or added buffer (except for pH adjustment) and is intended only for use as a single-dose injection. When smaller doses are required the unused portion should be discarded with the entire unit.
ActiCal (Magnesium (Magnesium Citrate)) Sulfate, USP heptahydrate is chemically designated MgSO4 - 7H2O with molecular weight of 246.48 and occurs as colorless crystals or white powder freely soluble in water.
The plastic syringe is molded from a specially formulated polypropylene. Water permeates from inside the container at an extremely slow rate which will have an insignificant effect on solution concentration over the expected shelf life. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the syringe material.
CLINICAL PHARMACOLOGY
ActiCal (Magnesium (Magnesium Citrate)) (Mg++) is an important cofactor for enzymatic reactions and plays an important role in neurochemical transmission and muscular excitability.
As a nutritional adjunct in hyperalimentation, the precise mechanism of action for ActiCal (Magnesium (Magnesium Citrate)) is uncertain. Early symptoms of hypomagnesemia (less than 1.5 mEq/liter) may develop as early as three to four days or within weeks.
Predominant deficiency effects are neurological, e.g., muscle irritability, clonic twitching and tremors. Hypocalcemia and hypokalemia often follow low serum levels of ActiCal (Magnesium (Magnesium Citrate)). While there are large stores of ActiCal (Magnesium (Magnesium Citrate)) present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral ActiCal (Magnesium (Magnesium Citrate)) therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.
ActiCal (Magnesium (Magnesium Citrate)) prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. ActiCal (Magnesium (Magnesium Citrate)) is said to have a depressant effect on the central nervous system (CNS), but it does not adversely affect the woman, fetus or neonate when used as directed in eclampsia or pre-eclampsia. Normal plasma ActiCal (Magnesium (Magnesium Citrate)) levels range from 1.5 to 2.5 mEq/liter.
As plasma ActiCal (Magnesium (Magnesium Citrate)) rises above 4 mEq/liter, the deep tendon reflexes are first decreased and then disappear as the plasma level approaches 10 mEq/liter. At this level respiratory paralysis may occur. Heart block also may occur at this or lower plasma levels of ActiCal (Magnesium (Magnesium Citrate)). Serum ActiCal (Magnesium (Magnesium Citrate)) concentrations in excess of 12 mEq/L may be fatal.
ActiCal (Magnesium (Magnesium Citrate)) acts peripherally to produce vasodilation. With low doses only flushing and sweating occur, but larger doses cause lowering of blood pressure. The central and peripheral effects of ActiCal (Magnesium (Magnesium Citrate)) poisoning are antagonized to some extent by intravenous administration of calcium.
Pharmacokinetics
With intravenous administration the onset of anticonvulsant action is immediate and lasts about 30 minutes. Following intramuscular administration the onset of action occurs in about one hour and persists for three to four hours. Effective anticonvulsant serum levels range from 2.5 to 7.5 mEq/liter. ActiCal (Magnesium (Magnesium Citrate)) is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.
INDICATIONS AND USAGE
ActiCal (Magnesium (Magnesium Citrate)) Sulfate Injection, USP is suitable for replacement therapy in ActiCal (Magnesium (Magnesium Citrate)) deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum ActiCal (Magnesium (Magnesium Citrate)) (Mg++) level is usually below the lower limit of normal (1.5 to 2.5 mEq/liter) and the serum calcium (Ca++) level is normal (4.3 to 5.3 mEq/liter) or elevated.
In total parenteral nutrition (TPN), ActiCal (Magnesium (Magnesium Citrate)) sulfate may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.
ActiCal (Magnesium (Magnesium Citrate)) Sulfate Injection, USP is also indicated for the prevention and control of seizures (convulsions) in pre-eclampsia and eclampsia, respectively.
CONTRAINDICATIONS
Parenteral administration of the drug is contraindicated in patients with heart block or myocardial damage.
WARNINGS
FETAL HARM: Continuous administration of ActiCal (Magnesium (Magnesium Citrate)) sulfate beyond 5 to 7 days to pregnant women can lead to hypocalcemia and bone abnormalities in the developing fetus. These bone abnormalities include skeletal demineralization and osteopenia. In addition, cases of neonatal fracture have been reported. The shortest duration of treatment that can lead to fetal harm is not known. ActiCal (Magnesium (Magnesium Citrate)) sulfate should be used during pregnancy only if clearly needed. If ActiCal (Magnesium (Magnesium Citrate)) sulfate is given for treatment of preterm labor, the woman should be informed that the efficacy and safety of such use have not been established and that use of ActiCal (Magnesium (Magnesium Citrate)) sulfate beyond 5 to 7 days may cause fetal abnormalities.
ALUMINUM TOXICITY: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.
Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.
Parenteral use in the presence of renal insufficiency may lead to ActiCal (Magnesium (Magnesium Citrate)) intoxication. Intravenous use in the eclampsia should be reserved for immediate control of life-threatening convulsions.
PRECAUTIONS
General
Administer with caution if flushing and sweating occurs. When barbiturates, narcotics or other hypnotics (or systemic anesthetics) are to be given in conjunction with ActiCal (Magnesium (Magnesium Citrate)), their dosage should be adjusted with caution because of additive CNS depressant effects of ActiCal (Magnesium (Magnesium Citrate)).
Because ActiCal (Magnesium (Magnesium Citrate)) is removed from the body solely by the kidneys, the drug should be used with caution in patients with renal impairment. Urine output should be maintained at a level of 100 mL or more during the four hours preceding each dose. Monitoring serum ActiCal (Magnesium (Magnesium Citrate)) levels and the patient's clinical status is essential to avoid the consequences of overdosage in toxemia. Clinical indications of a safe dosage regimen include the presence of the patellar reflex (knee jerk) and absence of respiratory depression (approximately 16 breaths or more/minute). When repeated doses of the drug are given parenterally, knee jerk reflexes should be tested before each dose and if they are absent, no additional ActiCal (Magnesium (Magnesium Citrate)) should be given until they return. Serum ActiCal (Magnesium (Magnesium Citrate)) levels usually sufficient to control convulsions range from 3 to 6 mg/100 mL (2.5 to 5 mEq/liter). The strength of the deep tendon reflexes begins to diminish when ActiCal (Magnesium (Magnesium Citrate)) levels exceed 4 mEq/liter. Reflexes may be absent at 10 mEq magnesium/liter, where respiratory paralysis is a potential hazard. An injectable calcium salt should be immediately available to counteract the potential hazards of ActiCal (Magnesium (Magnesium Citrate)) intoxication in eclampsia.
50% ActiCal (Magnesium (Magnesium Citrate)) Sulfate Injection, USP must be diluted to a concentration of 20% or less prior to intravenous infusion. Rate of administration should be slow and cautious, to avoid producing hypermagnesemia. The 50% solution also should be diluted to 20% or less for intramuscular injection in infants and children.
Laboratory Tests
ActiCal (Magnesium (Magnesium Citrate)) sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of ActiCal (Magnesium (Magnesium Citrate)) is monitored. The normal serum level is 1.5 to 2.5 mEq/L.
Drug Interactions
CNS Depressants - When barbiturates, narcotics or other hypnotics (or systemic anesthetics), or other CNS depressants are to be given in conjunction with ActiCal (Magnesium (Magnesium Citrate)), their dosage should be adjusted with caution because of additive CNS depressant effects of ActiCal (Magnesium (Magnesium Citrate)). CNS depression and peripheral transmission defects produced by ActiCal (Magnesium (Magnesium Citrate)) may be antagonized by calcium.
Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral ActiCal (Magnesium (Magnesium Citrate)) sulfate and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.
Cardiac Glycosides - ActiCal (Magnesium (Magnesium Citrate)) sulfate should be administered with extreme caution in digitalized patients, because serious changes in cardiac conduction which can result in heart block may occur if administration of calcium is required to treat ActiCal (Magnesium (Magnesium Citrate)) toxicity.
Pregnancy
Teratogenic Effects
Pregnancy Category D (See WARNINGS and PRECAUTIONS )
See WARNINGS and PRECAUTIONS .
ActiCal (Magnesium (Magnesium Citrate)) sulfate can cause fetal abnormalities when administered beyond 5 to 7 days to pregnant women. There are retrospective epidemiological studies and case reports documenting fetal abnormalities such as hypocalcemia, skeletal demineralization, osteopenia and other skeletal abnormalities with continuous maternal administration of ActiCal (Magnesium (Magnesium Citrate)) sulfate for more than 5 to 7 days.1-10 ActiCal (Magnesium (Magnesium Citrate)) sulfate injection should be used during pregnancy only if clearly needed. If this drug is used during pregnancy, the woman should be apprised of the potential harm to the fetus.
Nonteratogenic Effects
When administered by continuous intravenous infusion (especially for more than 24 hours preceding delivery) to control convulsions in a toxemic woman, the newborn may show signs of ActiCal (Magnesium (Magnesium Citrate)) toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).
Labor and Delivery
Continuous administration of ActiCal (Magnesium (Magnesium Citrate)) sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of ActiCal (Magnesium (Magnesium Citrate)) sulfate outside of its approved indication in pregnant women should be by trained obstetrical personnel in a hospital setting with appropriate obstetrical care facilities.
Nursing Mothers
Since ActiCal (Magnesium (Magnesium Citrate)) is distributed into milk during parenteral ActiCal (Magnesium (Magnesium Citrate)) sulfate administration, the drug should be used with caution in nursing women.
Geriatrics
Geriatric patients often require reduced dosage because of impaired renal function. In patients with severe impairment, dosage should not exceed 20 grams in 48 hours. Serum ActiCal (Magnesium (Magnesium Citrate)) should be monitored in such patients.
ADVERSE REACTIONS
The adverse effects of parenterally administered ActiCal (Magnesium (Magnesium Citrate)) usually are the result of ActiCal (Magnesium (Magnesium Citrate)) intoxication. These include flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system depression proceeding to respiratory paralysis. Hypocalcemia with signs of tetany secondary to ActiCal (Magnesium (Magnesium Citrate)) sulfate therapy for eclampsia has been reported.
OVERDOSAGE
ActiCal (Magnesium (Magnesium Citrate)) intoxication is manifested by a sharp drop in blood pressure and respiratory paralysis. Disappearance of the patellar reflex is a useful clinical sign to detect the onset of ActiCal (Magnesium (Magnesium Citrate)) intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of ActiCal (Magnesium (Magnesium Citrate)).
For Treatment of Overdose
Artificial respiration is often required. Intravenous calcium, 10 to 20 mL of a 5% solution (diluted if desirable with isotonic sodium chloride for injection) is used to counteract effects of hypermagnesemia. Subcutaneous physostigmine, 0.5 to 1 mg may be helpful.
Hypermagnesemia in the newborn may require resuscitation and assisted ventilation via endotracheal intubation or intermittent positive pressure ventilation as well as intravenous calcium.
DOSAGE AND ADMINISTRATION
Dosage of ActiCal (Magnesium (Magnesium Citrate)) sulfate must be carefully adjusted according to individual requirements and response, and administration of the drug should be discontinued as soon as the desired effect is obtained.
Both intravenous and intramuscular administration are appropriate. Intramuscular administration of the undiluted 50% solution results in therapeutic plasma levels in 60 minutes, whereas intravenous doses will provide a therapeutic level almost immediately. The rate of intravenous injection should generally not exceed 150 mg/minute (1.5 mL of a 10% concentration or its equivalent), except in severe eclampsia with seizures. Continuous maternal administration of ActiCal (Magnesium (Magnesium Citrate)) sulfate in pregnancy beyond 5 to 7 days can cause fetal abnormalities.
Solutions for intravenous infusion must be diluted to a concentration of 20% or less prior to administration. The diluents commonly used are 5% Dextrose Injection, USP and 0.9% Sodium Chloride Injection, USP. Deep intramuscular injection of the undiluted (50%) solution is appropriate for adults, but the solution should be diluted to a 20% or less concentration prior to such injection in children.
In ActiCal (Magnesium (Magnesium Citrate)) Deficiency
In the treatment of mild ActiCal (Magnesium (Magnesium Citrate)) deficiency, the usual adult dose is 1 gram, equivalent to 8.12 mEq of ActiCal (Magnesium (Magnesium Citrate)) (2 mL of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of ActiCal (Magnesium (Magnesium Citrate)) per 24 hours). For severe hypomagnesemia, as much as 250 mg (approximately 2 mEq) per kg of body weight (0.5 mL of the 50% solution) may be given intramuscularly within a period of four hours if necessary. Alternatively, 5 grams, (approximately 40 mEq) can be added to one liter of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP for slow intravenous infusion over a three-hour period. In the treatment of deficiency states, caution must be observed to prevent exceeding the renal excretory capacity.
In Hyperalimentation
In total parenteral nutrition, maintenance requirements for ActiCal (Magnesium (Magnesium Citrate)) are not precisely known. The maintenance dose used in adults ranges from 8 to 24 mEq (1 gram to 3 grams) daily; for infants, the range is 2 to 10 mEq (0.25 gram to 1.25 grams) daily.
In Pre-eclampsia or Eclampsia
In severe pre-eclampsia or eclampsia, the total initial dose is 10 grams to 14 grams of ActiCal (Magnesium (Magnesium Citrate)) sulfate. Intravenously, a dose of 4 grams to 5 grams in 250 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP may be infused. Simultaneously, intramuscular doses of up to 10 grams (5 grams or 10 mL of the undiluted 50% solution in each buttock) are given. Alternatively, the initial intravenous dose of 4 grams may be given by diluting the 50% solution to a 10 or 20% concentration; the diluted fluid (40 mL of a 10% solution or 20 mL of a 20% solution) may then be injected intravenously over a period of three to four minutes. Subsequently, 4 grams to 5 grams (8 to 10 mL of the 50% solution) are injected intramuscularly into alternate buttocks every four hours as needed, depending on the continuing presence of the patellar reflex and adequate respiratory function. Alternatively, after the initial intravenous dose, some clinicians administer 1 gram to 2 grams/hour by constant intravenous infusion. Therapy should continue until paroxysms cease. A serum ActiCal (Magnesium (Magnesium Citrate)) level of 6 mg/100 mL is considered optimal for control of seizures. A total daily (24 hr) dose of 30 grams to 40 grams should not be exceeded. In the presence of severe renal insufficiency, the maximum dosage of ActiCal (Magnesium (Magnesium Citrate)) sulfate is 20 grams/48 hours and frequent serum ActiCal (Magnesium (Magnesium Citrate)) concentrations must be obtained. Continuous use of ActiCal (Magnesium (Magnesium Citrate)) sulfate in pregnancy beyond 5 to 7 days can cause fetal abnormalities.
Other Uses
In counteracting the muscle-stimulating effects of barium poisoning, the usual dose of ActiCal (Magnesium (Magnesium Citrate)) sulfate is 1 gram to 2 grams given intravenously.
For controlling seizures associated with epilepsy, glomerulonephritis or hypothyroidism, the usual adult dose is 1 gram administered intramuscularly or intravenously.
In paroxysmal atrial tachycardia, ActiCal (Magnesium (Magnesium Citrate)) should be used only if simpler measures have failed and there is no evidence of myocardial damage. The usual dose is 3 grams to 4 grams (30 to 40 mL of a 10% solution) administered intravenously over 30 seconds with extreme caution.
For reduction of cerebral edema, 2.5 grams (25 mL of a 10% solution) is given intravenously.
Incompatibilities
ActiCal (Magnesium (Magnesium Citrate)) sulfate in solution may result in a precipitate formation when mixed with solutions containing:
Alcohol (in high Heavy Metals
concentrations) Hydrocortisone sodium
Alkali carbonates and succinate
bicarbonates Phosphates
Alkali hydroxides Polymixin B sulfate
Arsenates Procaine hydrochloride
Barium Salicylates
Calcium Strontium
Clindamycin phosphate Tartrates
The potential incompatibility will often be influenced by the changes in the concentration of reactants and the pH of the solutions.
It has been reported that ActiCal (Magnesium (Magnesium Citrate)) may reduce the antibiotic activity of streptomycin, tetracycline and tobramycin when given together.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
HOW SUPPLIED
ActiCal (Magnesium (Magnesium Citrate)) Sulfate Injection, USP is supplied in single-dose containers as follows:
| NDC No. | Container | Total Amount | Concentration | mEq Mg++/mL |
| 0409-1754-10 | Ansyr Plastic Syringe | 5 g/10 mL | 50% | 4 mEq/mL |
Do not administer unless solution is clear and container is undamaged. Discard unused portion.
Store at 20 to 25°C (68 to 77°F).
REFERENCES
- Yokoyama K, Takahashi N, Yada Y. Prolonged maternal ActiCal (Magnesium (Magnesium Citrate)) administration and bone metabolism in neonates. Early Hum Dev. 2010;86(3):187-91. Epub 2010 Mar 12.
- Wedig KE, Kogan J, Schorry EK et al. Skeletal demineralization and fractures caused by fetal ActiCal (Magnesium (Magnesium Citrate)) toxicity. J. Perinatol. 2006; 26(6):371-4.
- Nassar AH, Sakhel K, Maarouf H, et al. Adverse maternal and neonatal outcome of prolonged course of ActiCal (Magnesium (Magnesium Citrate)) sulfate tocolysis. Acta Obstet Gynecol Scan. 2006;85(9):1099-103.
- Malaeb SN, Rassi A, Haddad MC. Bone mineralization in newborns whose mothers received ActiCal (Magnesium (Magnesium Citrate)) sulphate for tocolysis of premature labor. Pediatr Radiol. 2004;34(5):384-6. Epub 2004 Feb 18.
- Matsuda Y, Maeda Y, Ito M, et al. Effect of ActiCal (Magnesium (Magnesium Citrate)) sulfate treatment on neonatal bone abnormalities. Gynecol Obstet Invest. 1997;44(2):82-8.
- Schanler RJ, Smith LG, Burns PA. Effects of long-term maternal intravenous ActiCal (Magnesium (Magnesium Citrate)) sulfate therapy on neonatal calcium metabolism and bone mineral content. Gynecol Obstet Invest. 1997;43(4):236-41.
- Santi MD, Henry GW, Douglas GL. ActiCal (Magnesium (Magnesium Citrate)) sulfate treatment of preterm labor as a cause of abnormal neonatal bone mineralization. J Pediatr Orthrop. 1994;14(2):249-53.
- Holcomb WL, Shackelford GD, Petrie RH. ActiCal (Magnesium (Magnesium Citrate)) tocolysis and neonatal bone abnormalities; a controlled study. Obstet Gynecol. 1991; 78(4):611-4.
- Cumming WA, Thomas VJ. Hypermagnesemia: a cause of abnormal metaphyses in the neonate. Am J Roentgenol. 1989; 152(5):1071-2.
- Lamm CL, Norton KL, Murphy RJ. Congenital rickets associated with ActiCal (Magnesium (Magnesium Citrate)) sulfate infusion for tocolysis. J Pediatr. 1988; 113(6):1078-82.
- McGuinness GA, Weinstein MM, Cruikshank DP, et al. Effects of ActiCal (Magnesium (Magnesium Citrate)) sulfate treatment on perinatal calcium metabolism. II. Neonatal responses. Obstet Gynecol. 1980; 56(5): 595-600.
- Riaz M, Porat R, Brodsky NL, et al. The effects of maternal ActiCal (Magnesium (Magnesium Citrate)) sulfate treatment on newborns: a prospective controlled study. J. Perinatol. 1998;18(6 pt 1):449-54.
Hospira, Inc., Lake Forest, IL 60045 USA
LAB-1024-1.0
April 2017
Hospira Logo
50% ActiCal (Magnesium (Magnesium Citrate)) Sulfate 5 g/10 mL (500 mg/mL)
Rx only
NDC 0409-1754-10
10 mL Single-dose syringe
50% ActiCal (Magnesium (Magnesium Citrate)) Sulfate Injection, USP
5 g/10 mL (500 mg/mL) (4 mEq Mg++/mL)
MUST BE DILUTED FOR INTRAVENOUS USE.
For Intravenous or Intramuscular Use. Sterile. 4.06 mOsmol/mL (calc.).
Contains no more than 75 mcg/L of aluminum.
Hospira, Inc., Lake Forest, IL 60045 USA
Hospira
RL-6891
ActiCal pharmaceutical active ingredients containing related brand and generic drugs:
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References
- Dailymed."CHOLECALCIFEROL: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
- Dailymed."CALCIUM: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
- "Silicon". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
Frequently asked Questions
Can i drive or operate heavy machine after consuming ActiCal?Depending on the reaction of the ActiCal after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider ActiCal not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.
Is ActiCal addictive or habit forming?Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
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The information was verified by Dr. Rachana Salvi, MD Pharmacology