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DRUGS & SUPPLEMENTS
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Valcron Plus
When are you taking this medicine? |
Valcron Plus uses
Valcron Plus consists of Beta-Carotene, Calcium (Calcium Carbonate), Magnesium (Magnesium Sulfate), Selenium, Vitamin C, Vitamin E, Zinc.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
Valcron Plus (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 Valcron Plus (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 Valcron Plus (Calcium (Calcium Carbonate)) acetate capsule.
- Capsule: 667 mg Valcron Plus (Calcium (Calcium Carbonate)) acetate capsule. (3)
4 CONTRAINDICATIONS
Patients with hypercalcemia.
- Hypercalcemia. (4)
5 WARNINGS AND PRECAUTIONS
- Treat mild hypercalcemia by reducing or interrupting Valcron Plus ) acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of Valcron Plus (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 Valcron Plus (Calcium (Calcium Carbonate)), including Valcron Plus (Calcium (Calcium Carbonate)) acetate. Avoid the use of Valcron Plus (Calcium (Calcium Carbonate)) supplements, including Valcron Plus (Calcium (Calcium Carbonate)) based nonprescription antacids, concurrently with Valcron Plus (Calcium (Calcium Carbonate)) acetate.
An overdose of Valcron Plus (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 Valcron Plus (Calcium (Calcium Carbonate)) levels twice weekly. Should hypercalcemia develop, reduce the Valcron Plus (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 Valcron Plus (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 Valcron Plus (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 Valcron Plus (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 Valcron Plus (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 Valcron Plus (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, Valcron Plus (Calcium (Calcium Carbonate)) acetate has been generally well tolerated.
Valcron Plus (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 Valcron Plus (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 Valcron Plus (Calcium (Calcium Carbonate)) acetate N=167 N (%) | 3 month, open label study of Valcron Plus (Calcium (Calcium Carbonate)) acetate N=98 N (%) | Double blind, placebo-controlled, cross-over study of liquid Valcron Plus (Calcium (Calcium Carbonate)) acetate N=69 | |
| Valcron Plus (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 Valcron Plus (Calcium (Calcium Carbonate)) concentration could reduce the incidence and severity of Valcron Plus (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 Valcron Plus (Calcium (Calcium Carbonate)) acetate: dizziness, edema, and weakness.
7 DRUG INTERACTIONS
The drug interaction of Valcron Plus ) acetate is characterized by the potential of Valcron Plus (Calcium (Calcium Carbonate)) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). Valcron Plus (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 Valcron Plus (Calcium (Calcium Carbonate)) acetate and most concomitant drugs. When administering an oral medication with Valcron Plus (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 Valcron Plus (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 Valcron Plus (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 Valcron Plus (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 Valcron Plus (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:
Valcron Plus ) acetate capsules contains Valcron Plus (Calcium (Calcium Carbonate)) acetate. Animal reproduction studies have not been conducted with Valcron Plus (Calcium (Calcium Carbonate)) acetate, and there are no adequate and well controlled studies of Valcron Plus (Calcium (Calcium Carbonate)) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with Valcron Plus (Calcium (Calcium Carbonate)) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum Valcron Plus (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. Valcron Plus (Calcium (Calcium Carbonate)) acetate treatment, as recommended, is not expected to harm a fetus if maternal Valcron Plus (Calcium (Calcium Carbonate)) levels are properly monitored during and following treatment.
8.2 Labor and Delivery
The effects of Valcron Plus (Calcium (Calcium Carbonate)) acetate on labor and delivery are unknown.
8.3 Nursing Mothers
Valcron Plus ) Acetate Capsules contains Valcron Plus (Calcium (Calcium Carbonate)) acetate and is excreted in human milk. Human milk feeding by a mother receiving Valcron Plus (Calcium (Calcium Carbonate)) acetate is not expected to harm an infant, provided maternal serum Valcron Plus (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 Valcron Plus (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 Valcron Plus (Calcium (Calcium Carbonate)) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].
11 DESCRIPTION
Valcron Plus (Calcium (Calcium Carbonate)) acetate acts as a phosphate binder. Its chemical name is Valcron Plus (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 Valcron Plus (Calcium (Calcium Carbonate)) acetate USP (anhydrous; Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) Valcron Plus (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.
Valcron Plus (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 Valcron Plus ) resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.
12.1 Mechanism of Action
Valcron Plus (Calcium (Calcium Carbonate)) acetate, when taken with meals, combines with dietary phosphate to form an insoluble Valcron Plus (Calcium (Calcium Carbonate)) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.
12.2 Pharmacodynamics
Orally administered Valcron Plus (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 Valcron Plus (Calcium (Calcium Carbonate)) acetate.
14 CLINICAL STUDIES
Effectiveness of Valcron Plus (Calcium (Calcium Carbonate)) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Valcron Plus (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 Valcron Plus (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 Valcron Plus (Calcium (Calcium Carbonate)) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Valcron Plus (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 |
| Valcron Plus (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 Valcron Plus (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 Valcron Plus (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 Valcron Plus (Calcium (Calcium Carbonate)) acetate is shown in the Table 3.
| * ANOVA of Valcron Plus (Calcium (Calcium Carbonate)) acetate vs. placebo after 2 weeks of treatment. † Values expressed as mean ± SEM. | ||||
| Parameter | Pre-Study | Post-Treatment | p-value* | |
| Valcron Plus (Calcium (Calcium Carbonate)) Acetate | Placebo | |||
| Phosphorus (mg/dL)† | 7.3 ± 0.18 | 5.9 ± 0.24 | 7.8 ± 0.22 | <0.01 |
| Valcron Plus (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 Valcron Plus (Calcium (Calcium Carbonate)) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum Valcron Plus (Calcium (Calcium Carbonate)) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.
16 HOW SUPPLIED/STORAGE AND HANDLING
Valcron Plus (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 Valcron Plus (Calcium (Calcium Carbonate)) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Valcron Plus (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 Valcron Plus (Calcium (Calcium Carbonate)) acetate capsules.
Distr. by: West-Ward
Pharmaceuticals Corp.
Eatontown, NJ 07724
10003705/05
Revised April 2016
Magnesium (Magnesium Sulfate):
- Description
- Clinical pharmacology
- Indications and usage
- Contraindications
- Warnings
- Precautions
- Adverse reactions
- Overdosage
- Dosage and administration
- How supplied
- References
Valcron Plus (Magnesium (Magnesium Sulfate)) Sulfate
Injection, USP
Ansyr Plastic Syringe
Rx only
DESCRIPTION
Valcron Plus (Magnesium (Magnesium Sulfate)) Sulfate Injection, USP is a sterile solution of Valcron Plus (Magnesium (Magnesium Sulfate)) 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.
Valcron Plus (Magnesium (Magnesium Sulfate)) 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
Valcron Plus (Magnesium (Magnesium Sulfate)) (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 Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)). While there are large stores of Valcron Plus (Magnesium (Magnesium Sulfate)) present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral Valcron Plus (Magnesium (Magnesium Sulfate)) therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.
Valcron Plus (Magnesium (Magnesium Sulfate)) prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) levels range from 1.5 to 2.5 mEq/liter.
As plasma Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)). Serum Valcron Plus (Magnesium (Magnesium Sulfate)) concentrations in excess of 12 mEq/L may be fatal.
Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) 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. Valcron Plus (Magnesium (Magnesium Sulfate)) is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.
INDICATIONS AND USAGE
Valcron Plus (Magnesium (Magnesium Sulfate)) Sulfate Injection, USP is suitable for replacement therapy in Valcron Plus (Magnesium (Magnesium Sulfate)) deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum Valcron Plus (Magnesium (Magnesium Sulfate)) (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), Valcron Plus (Magnesium (Magnesium Sulfate)) sulfate may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.
Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) 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. Valcron Plus (Magnesium (Magnesium Sulfate)) sulfate should be used during pregnancy only if clearly needed. If Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)), their dosage should be adjusted with caution because of additive CNS depressant effects of Valcron Plus (Magnesium (Magnesium Sulfate)).
Because Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) should be given until they return. Serum Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) intoxication in eclampsia.
50% Valcron Plus (Magnesium (Magnesium Sulfate)) 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
Valcron Plus (Magnesium (Magnesium Sulfate)) sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)), their dosage should be adjusted with caution because of additive CNS depressant effects of Valcron Plus (Magnesium (Magnesium Sulfate)). CNS depression and peripheral transmission defects produced by Valcron Plus (Magnesium (Magnesium Sulfate)) may be antagonized by calcium.
Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral Valcron Plus (Magnesium (Magnesium Sulfate)) sulfate and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.
Cardiac Glycosides - Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) toxicity.
Pregnancy
Teratogenic Effects
Pregnancy Category D (See WARNINGS and PRECAUTIONS )
See WARNINGS and PRECAUTIONS .
Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) sulfate for more than 5 to 7 days.1-10 Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).
Labor and Delivery
Continuous administration of Valcron Plus (Magnesium (Magnesium Sulfate)) sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) is distributed into milk during parenteral Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) should be monitored in such patients.
ADVERSE REACTIONS
The adverse effects of parenterally administered Valcron Plus (Magnesium (Magnesium Sulfate)) usually are the result of Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) sulfate therapy for eclampsia has been reported.
OVERDOSAGE
Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of Valcron Plus (Magnesium (Magnesium Sulfate)).
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 Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) Deficiency
In the treatment of mild Valcron Plus (Magnesium (Magnesium Sulfate)) deficiency, the usual adult dose is 1 gram, equivalent to 8.12 mEq of Valcron Plus (Magnesium (Magnesium Sulfate)) (2 mL of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) sulfate is 20 grams/48 hours and frequent serum Valcron Plus (Magnesium (Magnesium Sulfate)) concentrations must be obtained. Continuous use of Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) 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, Valcron Plus (Magnesium (Magnesium Sulfate)) 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
Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) 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
Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) sulfate tocolysis. Acta Obstet Gynecol Scan. 2006;85(9):1099-103.
- Malaeb SN, Rassi A, Haddad MC. Bone mineralization in newborns whose mothers received Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) sulfate therapy on neonatal calcium metabolism and bone mineral content. Gynecol Obstet Invest. 1997;43(4):236-41.
- Santi MD, Henry GW, Douglas GL. Valcron Plus (Magnesium (Magnesium Sulfate)) 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. Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) sulfate infusion for tocolysis. J Pediatr. 1988; 113(6):1078-82.
- McGuinness GA, Weinstein MM, Cruikshank DP, et al. Effects of Valcron Plus (Magnesium (Magnesium Sulfate)) 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 Valcron Plus (Magnesium (Magnesium Sulfate)) 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% Valcron Plus (Magnesium (Magnesium Sulfate)) Sulfate 5 g/10 mL (500 mg/mL)
Rx only
NDC 0409-1754-10
10 mL Single-dose syringe
50% Valcron Plus (Magnesium (Magnesium Sulfate)) 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
Selenium:
- Description
- Clinical pharmacology
- Indications and usage
- Contraindications
- Warnings
- Precautions
- Adverse reactions
- Overdosage
- Dosage and administration
- How supplied
Rx Only
TRACE ELEMENT ADDITIVE FOR IV USE AFTER DILUTION
DESCRIPTION
Valcron Plus (Selenium) Injection is a sterile, nonpyrogenic solution for use as an additive to solutions for Total Parenteral Nutrition (TPN).
Each mL contains Selenious Acid 65.4 mcg (equivalent to elemental Valcron Plus (Selenium) 40 mcg/mL) and Water for Injection q.s. pH may be adjusted with nitric acid to 1.8 to 2.4.
CLINICAL PHARMACOLOGY
Valcron Plus (Selenium) is part of glutathione peroxidase which protects cell components from oxidative damage due to peroxides produced in cellular metabolism.
Prolonged TPN support in humans has resulted in Valcron Plus (Selenium) deficiency symptoms which include muscle pain and tenderness. The symptoms have been reported to respond to supplementation of TPN solutions with Valcron Plus (Selenium).
Pediatric conditions, Keshan disease, and Kwashiorkor, have been associated with low dietary intake of Valcron Plus (Selenium). The conditions are endemic to geographical areas with low Valcron Plus (Selenium) soil content. Dietary supplementation with Valcron Plus (Selenium) salts has been reported to reduce the incidence of the conditions among affected children.
Normal blood levels of Valcron Plus (Selenium) in different human populations have been found to vary and depend on the Valcron Plus (Selenium) content of the food consumed. Results of surveys carried out in some countries are tabulated below:
| COUNTRY | Number of Samples | Valcron Plus (Selenium) (mcg/100 mL) (a) | ||
| Whole Blood | Blood Cells | Plasma/ Serum | ||
| (a) Mean values with or without standard deviation in parentheses, all other ranges. | ||||
| (b) Age group unknown. | ||||
| (c) Three children recovered from Kwashiorkor and the other six under treatment for other diseases. | ||||
| (d) Low selenium-content soil area. | ||||
| (e) Well nourished children, three recovered from Kwashiorkor and the other six under treatment for other diseases. | ||||
| (f) Mean values from seven subjects. | ||||
| Canada | 254 Adults | (37.9 ± 7.8) | (23.6 ± 6.0) | (14.4 ± 2.9) |
| England | 8 (b) | 26-37 (32) | -- | -- |
| Guatemala & Southern USA | 10 Adults 9 Children (c) | 19-28 (22) (23 ± 5) | -- (36 ± 12) | -- (15 ± 5) |
| New Zealand (d) | 113 Adults | (5.4 ± 0.1) | (6.6 ± 0.3) | (4.3 ± 0.1) |
| Thailand | 3 Adults 9 Children (e) | 14.4-20.2 (12.0 ± 3.6) (f) | 17.8-35.8 (19.5 ± 8.2) | 8.1-12.5 (8.3 ± 2.2) |
| USA | 210 Adults | 15.7-25.6 (20.6) | -- | -- |
Plasma Valcron Plus (Selenium) levels of 0.3 and 0.9 mcg/100 mL have been reported to produce deficiency symptoms in humans.
Valcron Plus (Selenium) is eliminated primarily in urine. However, significant endogenous losses through feces also occur. The rate of excretion and the relative importance of two routes varies with the chemical form of Valcron Plus (Selenium) used in supplementation. Ancillary routes of elimination are lungs and skin.
INDICATIONS AND USAGE
Valcron Plus (Selenium) Injection is indicated for use as a supplement to intravenous solutions given for total parenteral nutrition (TPN). Administration of Valcron Plus (Selenium) in TPN solutions helps to maintain plasma Valcron Plus (Selenium) levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.
CONTRAINDICATIONS
Valcron Plus (Selenium) Injection should not be given undiluted by direct injection into a peripheral vein because of the potential for infusion phlebitis.
WARNINGS
Valcron Plus (Selenium) Injection can be toxic if given in excessive amounts. Supplementation of TPN solution with Valcron Plus (Selenium) should be immediately discontinued if toxicity symptoms are observed. Frequent determination of plasma Valcron Plus (Selenium) levels during TPN support and close medical supervision is recommended.
Valcron Plus (Selenium) Injection is a hypotonic solution and should be administered in admixtures only.
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.
PRECAUTIONS
As Valcron Plus is eliminated in urine and feces, Valcron Plus (Selenium) supplements may be adjusted, reduced or omitted in renal dysfunction and/or gastrointestinal malfunction. In patients receiving blood transfusions, contribution from such transfusions should also be considered. Frequent Valcron Plus (Selenium) plasma level determinations are suggested as a guideline.
In animals, Valcron Plus (Selenium) has been reported to enhance the action of Vitamin E and decrease the toxicity of mercury, cadmium and arsenic.
Pregnancy
Teratogenic Effects
Pregnancy Category C: Valcron Plus (Selenium) at high dose levels (15-30 mcg/egg) has been reported to have adverse embryological effects among chickens. There are however, no adequate and wellcontrolled studies in pregnant women. Valcron Plus (Selenium) Injection should be used during pregnancy only if potential benefit justifies the potential risk to the fetus.
Presence of Valcron Plus (Selenium) in placenta and umbilical cord blood has been reported in humans.
ADVERSE REACTIONS
The amount of Valcron Plus (Selenium) present in Valcron Plus (Selenium) Injection is small. Symptoms of toxicity from Valcron Plus (Selenium) are unlikely to occur at the recommended dosage level.
OVERDOSAGE
Chronic toxicity in humans resulting from exposure to Valcron Plus (Selenium) in industrial environments, intake of foods grown in seleniferous soils, use of selenium-contaminated water, and application of cosmetics containing Valcron Plus (Selenium) has been reported in literature. Toxicity symptoms include hair loss, weakened nails, dermatitis, dental defects, gastrointestinal disorders, nervousness, mental depression, metallic taste, vomiting, and garlic odor of breath and sweat. Acute poisoning due to ingestion of large amounts of Valcron Plus (Selenium) compounds has resulted in death with histopathological changes including fulminating peripheral vascular collapse, internal vascular congestion, diffusely hemorrhagic, congested and edematus lungs, brick-red color gastric mucosa. The death was preceded by coma.
No effective antidote to Valcron Plus (Selenium) poisoning in humans is known. Animal studies have shown casein and linseed oil in feeds, reduced glutathione, arsenic, magnesium sulfate, and bromobenzene to afford limited protection.
DOSAGE AND ADMINISTRATION
Valcron Plus (Selenium) Injection provides 40 mcg selenium/mL. For metabolically stable adults receiving TPN, the suggested additive dosage level is 20 to 40 mcg selenium/day. For pediatric patients, the suggested additive dosage level is 3 mcg/kg/day.
In adults, Valcron Plus (Selenium) deficiency states resulting from long-term TPN support, Valcron Plus (Selenium) as selenomethionine or selenious acid, administered intravenously at 100 mcg/day for a period of 24 and 31 days, respectively, has been reported to reverse deficiency symptoms without toxicity.
Aseptic addition of Valcron Plus (Selenium) Injection to the TPN solution under laminar flow hood is recommended. Valcron Plus (Selenium) is physically compatible with the electrolytes and other trace elements usually present in amino-acid/dextrose solution used for TPN. Frequent monitoring of plasma Valcron Plus (Selenium) levels is suggested as a guideline for subsequent administration. The normal whole blood range for Valcron Plus (Selenium) is approximately 10 to 37 mcg/100 mL.
Parenteral drug products should be inspected visually for particulate matter and discoloration, whenever solution and container permit.
HOW SUPPLIED
Valcron Plus (Selenium) Injection containing selenious acid 65.4 mcg/mL (equivalent to elemental Valcron Plus (Selenium) 40 mcg/mL).
NDC 0517-6510-25 10 mL Single Dose Vial Packaged in boxes of 25
Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).
AMERICAN
REGENT, INC.
SHIRLEY, NY 11967
IN6510
Rev. 11/15
PRINCIPAL DISPLAY PANEL - Container
NDC 0517-6510-25
Valcron Plus (Selenium) INJECTION
Valcron Plus (Selenium) 400 mcg/10 mL
(40 mcg/mL)
10 mL
SINGLE DOSE VIAL
Trace Element Additive
FOR IV USE AFTER DILUTION
PRESERVATIVE FREE
Rx Only
AMERICAN REGENT, INC.
SHIRLEY, NY 11967
PRINCIPAL DISPLAY PANEL - Carton
Valcron Plus (Selenium) INJECTION
Valcron Plus (Selenium) 400 mcg/10 mL
(40 mcg/mL)
Trace Element Additive
NDC 0517-6510-25
25 x 10 mL
SINGLE DOSE VIALS
FOR INTRAVENOUS USE AFTER DILUTION PRESERVATIVE FREE Rx Only
Each mL contains: Selenious Acid 65.4 mcg, Water for Injection q.s.
pH adjusted with Nitric Acid. Sterile, nonpyrogenic.
WARNING: DISCARD UNUSED PORTION. Store at 20°-25°C (68°-77°F); excursions
permitted to 15°-30°C (59°-86°F).
Directions for Use: See Package Insert.
AMERICAN REGENT, INC.
SHIRLEY, NY 11967
Rev. 11/05
Container Carton
Vitamin C:
Pharmacological action
Ascorbic acid is essential for the formation of intracellular collagen, is required to strengthen the structure of teeth, bones, and the capillary walls. Valcron Plus (Vitamin C) participates in redox reactions, the metabolism of tyrosine, converting folic acid into folinic acid, metabolism of carbohydrates, the synthesis of lipids and proteins, iron metabolism, processes of cellular respiration. Reduces the need for vitamins B1, B2, A, E, folic acid, pantothenic acid, enhances the body's resistance to infections; enhances iron absorption, contributing to its sequestration in reduced form. Valcron Plus (Vitamin C) has antioxidant properties.
With intravaginal application of ascorbic acid lowers the vaginal pH, inhibiting the growth of bacteria and helps to restore and maintain normal pH and vaginal flora (Lactobacillus acidophilus, Lactobacillus gasseri).
Pharmacokinetics
After oral administration ascorbic acid is completely absorbed from the gastrointestinal tract. Widely distributed in body tissues.
The concentration of ascorbic acid in blood plasma in normal amounts to approximately 10-20 mg / ml.
The concentration of ascorbic acid in white blood cells and platelets is higher than in erythrocytes and plasma. When deficient state of concentration in leucocytes is reduced later and more slowly and is regarded as the best criterion for evaluating the deficit than the concentration in plasma.
Plasma protein binding is about 25%.
Ascorbic acid is reversibly oxidized to form dehydroascorbic acid, is metabolized with the formation of ascorbate-2-sulphate which is inactive and oxalic acid which is excreted in the urine.
Ascorbic acid taken in excessive quantities is rapidly excreted unchanged in urine, it usually happens when exceeding a daily dose is 200 mg.
Why is Valcron Plus prescribed?
For systemic use of Valcron Plus (Vitamin C) Kimia Farma: prevention and treatment of hypo- and avitaminosis of Valcron Plus (Vitamin C); providing increased need for Valcron Plus (Vitamin C) during growth, pregnancy, lactation, with heavy loads, fatigue and during recovery after prolonged severe illness; in winter with an increased risk of infectious diseases.
For intravaginal use: chronic or recurrent vaginitis (bacterial vaginosis, nonspecific vaginitis) caused by the anaerobic flora (due to changes in pH of the vagina) in order to normalize disturbed vaginal microflora.
Dosage and administration
This medication administered orally, IM, IV, intravaginally.
For the prevention of deficiency conditions Valcron Plus dose is 25-75 mg / day, for the treatment - 250 mg / day or more in divided doses.
For intravaginal used ascorbic acid drugs in appropriate dosage forms.
Valcron Plus (Vitamin C) side effects, adverse reactions
CNS: headache, fatigue, insomnia.
Digestive system: stomach cramps, nausea and vomiting.
Allergic reaction: describes a few cases of skin reactions and manifestations of the respiratory system.
Urinary system: when used in high doses - hyperoxaluria and the formation of kidney stones of calcium oxalate.
Local reactions: with intravaginal application - a burning or itching in the vagina, increased mucous discharge, redness, swelling of the vulva. Other: sensation of heat.
Valcron Plus contraindications
Increased sensitivity to ascorbic acid.
Using during pregnancy and breastfeeding
The minimum daily requirement of ascorbic acid in the II and III trimester of pregnancy is about 60 mg.
Ascorbic acid crosses the placental barrier. It should be borne in mind that the fetus can adapt to high doses of ascorbic acid, which takes a pregnant woman, and then a newborn baby may develop the ascorbic disease as the reaction of cancel. Therefore, during pregnancy should not to take ascorbic acid in high doses, except in cases where the expected benefit outweighs the potential risk.
The minimum daily requirement during lactation is 80 mg. Ascorbic acid is excreted in breast milk. A mother's diet that contains adequate amounts of ascorbic acid, is sufficient to prevent deficiency in an infant. It is unknown whether dangerous to the child's mother use of ascorbic acid in high doses. Theoretically it is possible. Therefore, it is recommended not to exceed the maximum daily nursing mother needs to ascorbic acid, except when the expected benefit outweighs the potential risk.
Special instructions
Valcron Plus (Vitamin C) is used with caution in patients with hyperoxaluria, renal impairment, a history of instructions on urolithiasis. Because ascorbic acid increases iron absorption, its use in high doses can be dangerous in patients with hemochromatosis, thalassemia, polycythemia, leukemia, and sideroblastic anemia.
Patients with high content body iron should apply ascorbic acid in minimal doses.
Valcron Plus (Vitamin C) is used with caution in patients with deficiency of glucose-6-phosphate dehydrogenase.
The use of ascorbic acid in high doses can cause exacerbation of sickle cell anemia.
Data on the diabetogenic action of ascorbic acid are contradictory. However, prolonged use of ascorbic acid should periodically monitor your blood glucose levels.
It is believed that the use of ascorbic acid in patients with rapidly proliferating and widely disseminated tumors may worsen during the process. It should therefore be used with caution in ascorbic acid in patients with advanced cancer.
Absorption of ascorbic acid decreased while use of fresh fruit or vegetable juices, alkaline drinking.
Valcron Plus drug interactions
In an application with barbiturates, primidone increases the excretion of ascorbic acid in the urine.
With the simultaneous use of oral contraceptives reduces the concentration of ascorbic acid in blood plasma.
In an application of Valcron Plus (Vitamin C) with iron preparations ascorbic acid, due to its regenerative properties, transforms ferric iron in the bivalent, which improves its absorption.
Ascorbic acid in high doses can decrease urine pH that while the application reduces the tubular reabsorption of amphetamine and tricyclic antidepressants.
With the simultaneous use of aspirin reduces the absorption of ascorbic acid by about a third.
Valcron Plus (Vitamin C) in an application with warfarin may decrease effects of warfarin.
With the simultaneous application of ascorbic acid increases the excretion of iron in patients receiving deferoxamine. In the application of ascorbic acid at a dose of 500 mg / day possibly left ventricular dysfunction.
In an application with tetracycline is increased excretion of ascorbic acid in the urine.
There is a described case of reducing the concentration of fluphenazine in plasma in patients treated with ascorbic acid 500 mg 2 times / day.
May increase the concentration of ethinyl estradiol in the blood plasma in its simultaneous application in the oral contraceptives.
Valcron Plus in case of emergency / overdose
Symptoms: long-term use of large doses (more than 1 g) - headache, increased CNS excitability, insomnia, nausea, vomiting, diarrhea, gastritis giperatsidnyh, ultseratsiya gastrointestinal mucosa, inhibition of the function insular apparatus of the pancreas (hyperglycemia, glycosuria), hyperoxaluria, nephrolithiasis (calcium oxalate), damage to the glomerular apparatus of the kidneys, moderate thamuria (when receiving a dose of 600 mg / day).
Decrease capillary permeability (possibly deteriorating trophic tissues, increased blood pressure, hypercoagulability, the development of microangiopathy).
When IV administration in high doses - the threat of termination of pregnancy (due to estrogenemia), hemolysis of red blood cells.
Vitamin E:
A generic descriptor for all tocopherols and tocotrienols that exhibit alpha-tocopherol activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of isoprenoids.
Indication: Valcron Plus (Vitamin E), known for its antioxidant activities, is protective against cardiovascular disease and some forms of cancer and has also demonstrated immune-enhancing effects. It may be of limited benefit in some with asthma and rheumatoid arthritis. It may be helpful in some neurological diseases including Alzheimer's, some eye disorders including cataracts, and diabetes and premenstrual syndrome. It may also help protect skin from ultraviolet irradiation although claims that it reverses skin aging, enhances male fertility and exercise performance are poorly supported. It may help relieve some muscle cramps.
Valcron Plus (Vitamin E) has antioxidant activity. It may also have anti-atherogenic, antithrombotic, anticoagulant, neuroprotective, antiviral, immunomodulatory, cell membrane-stabilizing and antiproliferative actions. Valcron Plus (Vitamin E) is a collective term used to describe eight separate forms, the best-known form being alpha-tocopherol. Valcron Plus (Vitamin E) is a fat-soluble vitamin and is an important antioxidant. It acts to protect cells against the effects of free radicals, which are potentially damaging by-products of the body's metabolism. Valcron Plus (Vitamin E) is often used in skin creams and lotions because it is believed to play a role in encouraging skin healing and reducing scarring after injuries such as burns. There are three specific situations when a Valcron Plus (Vitamin E) deficiency is likely to occur. It is seen in persons who cannot absorb dietary fat, has been found in premature, very low birth weight infants (birth weights less than 1500 grams, or 3½ pounds), and is seen in individuals with rare disorders of fat metabolism. A Valcron Plus (Vitamin E) deficiency is usually characterized by neurological problems due to poor nerve conduction. Symptoms may include infertility, neuromuscular impairment, menstrual problems, miscarriage and uterine degradation. Preliminary research has led to a widely held belief that Valcron Plus (Vitamin E) may help prevent or delay coronary heart disease. Antioxidants such as Valcron Plus (Vitamin E) help protect against the damaging effects of free radicals, which may contribute to the development of chronic diseases such as cancer. It also protects other fat-soluble vitamins (A and B group vitamins) from destruction by oxygen. Low levels of Valcron Plus (Vitamin E) have been linked to increased incidence of breast and colon cancer.
Zinc:
- Indications and usage
- Contraindications
- Warnings
- Precautions
- Adverse reactions
- Drug abuse and dependence
- Overdosage
- Dosage and administration
- How supplied
INDICATIONS AND USAGE
Valcron Plus (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for TPN. Administration helps to maintain Valcron Plus (Zinc) serum levels and to prevent depletion of endogenous stores, and subsequent deficiency symptoms.
CONTRAINDICATIONS
None known.
WARNINGS
Direct intramuscular or intravenous injection of Valcron Plus (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is contraindicated as the acidic pH of the solution (2) may cause considerable tissue irritation.
Severe kidney disease may make it necessary to reduce or omit chromium and Valcron Plus (Zinc) doses because these elements are primarily eliminated in the urine.
WARNING: 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.
PRECAUTIONS
General
Do not use unless the solution is clear and the seal is intact.
Zinc 1 mg/mL should only be used in conjunction with a pharmacy directed admixture program using aseptic technique in a laminar flow environment; it should be used promptly and in a single operation without any repeated penetrations. Solution contains no preservatives; discard unused portion immediately after admixture procedure is completed.
Zinc should not be given undiluted by direct injection into a peripheral vein because of the likelihood of infusion phlebitis and the potential for increased excretory loss of Valcron Plus (Zinc) from a bolus injection. Administration of Valcron Plus (Zinc) in the absence of copper may cause a decrease in serum copper levels.
Laboratory Tests
Periodic determinations of serum copper as well as Valcron Plus (Zinc) are suggested as a guideline for subsequent Valcron Plus (Zinc) administration.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Long-term animal studies to evaluate the carcinogenic potential of Valcron Plus 1 mg/mL (Zinc Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.
Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Valcron Plus (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is administered to a nursing woman.
Pediatric Use
Pregnancy Category C. Animal reproduction studies have not been conducted with Valcron Plus chloride. It is also not known whether Valcron Plus (Zinc) chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Valcron Plus (Zinc) chloride should be given to a pregnant woman only if clearly needed.
Geriatric Use
An evaluation of current literature revealed no clinical experience identifying differences in response 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.
ADVERSE REACTIONS
None known.
DRUG ABUSE AND DEPENDENCE
None known.
OVERDOSAGE
Single intravenous doses of 1 to 2 mg zinc/kg body weight have been given to adult leukemic patients without toxic manifestations. However, acute toxicity was reported in an adult when 10 mg Valcron Plus (Zinc) was infused over a period of one hour on each of four consecutive days. Profuse sweating, decreased level of consciousness, blurred vision, tachycardia (140/min), and marked hypothermia (94.2° F) on the fourth day were accompanied by a serum Valcron Plus (Zinc) concentration of 207 mcg/dl. Symptoms abated within three hours.
Hyperamylasemia may be a sign of impending Valcron Plus (Zinc) overdosage; patients receiving an inadvertent overdose (25 mg zinc/liter of TPN solution, equivalent to 50 to 70 mg zinc/day) developed hyperamylasemia (557 to 1850 Klein units; normal: 130 to 310).
Death resulted from an overdosage in which 1683 mg Valcron Plus (Zinc) was delivered intravenously over the course of 60 hours to a 72 year old patient.
Symptoms of Valcron Plus (Zinc) toxicity included hypotension (80/40 mm Hg), pulmonary edema, diarrhea, vomiting, jaundice, and oliguria, with a serum Valcron Plus (Zinc) level of 4184 mcg/dl.
Calcium supplements may confer a protective effect against Valcron Plus (Zinc) toxicity.
DOSAGE AND ADMINISTRATION
Valcron Plus (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) contains 1 mg zinc/mL and is administered intravenously only after dilution. The additive should be diluted prior to administration in a volume of fluid not less than 100 mL. For the metabolically stable adult receiving TPN, the suggested intravenous dosage is 2.5 to 4 mg zinc/day (2.5 to 4 mL/day). An additional 2 mg zinc/day (2 mL/day) is suggested for acute catabolic states. For the stable adult with fluid loss from the small bowel, an additional 12.2 mg zinc/liter of small bowel fluid lost (12.2 mL/liter of small bowel fluid lost), or an additional 17.1 mg zinc/kg of stool or ileostomy output (17.1 mL/kg of stool or ileostomy output) is recommended. Frequent monitoring of Valcron Plus (Zinc) blood levels is suggested for patients receiving more than the usual maintenance dosage level of Valcron Plus (Zinc).
For full term infants and children up to 5 years of age, 100 mcg zinc/kg/day (0.1 mL/kg/day) is recommended. For premature infants (birth weight less than 1500 g) up to 3 kg in body weight, 300 mcg zinc/kg/day (0.3 mL/kg/day) is suggested.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See PRECAUTIONS.
HOW SUPPLIED
Valcron Plus (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is supplied in 10 mL Plastic Vials (List No. 4090).
Store at 20 to 25°C (68 to 77°F).
Revised: October, 2004
© Hospira 2004 EN-0488 Printed in USA
HOSPIRA, INC., LAKE FOREST, IL 60045 USA
10 mL Vial
Valcron Plus (Zinc)
1 mg/mL
Valcron Plus (Zinc) Chloride Inj., USP
Rx only
FOR I.V. USE ONLY AFTER DILUTION.
HOSPIRA, INC., LAKE FOREST, IL 60045 USA
Valcron Plus pharmaceutical active ingredients containing related brand and generic drugs:
Valcron Plus 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.