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DRUGS & SUPPLEMENTS
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BNPH HP
How often in a day do you take medicine? How many times? |
BNPH HP uses
BNPH HP consists of Calcium (Oyster Shells), Calcium Fluoride, Calcium Phosphate Tribasic, Hecla Lava, Hydrogen Fluoride, Poison Ivy.Calcium (Oyster Shells):
- 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
BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) acetate capsule.
- Capsule: 667 mg BNPH HP (Calcium (Oyster Shells)) acetate capsule. (3)
4 CONTRAINDICATIONS
Patients with hypercalcemia.
- Hypercalcemia. (4)
5 WARNINGS AND PRECAUTIONS
- Treat mild hypercalcemia by reducing or interrupting BNPH HP ) acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)), including BNPH HP (Calcium (Oyster Shells)) acetate. Avoid the use of BNPH HP (Calcium (Oyster Shells)) supplements, including BNPH HP (Calcium (Oyster Shells)) based nonprescription antacids, concurrently with BNPH HP (Calcium (Oyster Shells)) acetate.
An overdose of BNPH HP (Calcium (Oyster Shells)) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum BNPH HP (Calcium (Oyster Shells)) levels twice weekly. Should hypercalcemia develop, reduce the BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) 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, BNPH HP (Calcium (Oyster Shells)) acetate has been generally well tolerated.
BNPH HP (Calcium (Oyster Shells)) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) acetate N=167 N (%) | 3 month, open label study of BNPH HP (Calcium (Oyster Shells)) acetate N=98 N (%) | Double blind, placebo-controlled, cross-over study of liquid BNPH HP (Calcium (Oyster Shells)) acetate N=69 | |
| BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) concentration could reduce the incidence and severity of BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) acetate: dizziness, edema, and weakness.
7 DRUG INTERACTIONS
The drug interaction of BNPH HP ) acetate is characterized by the potential of BNPH HP (Calcium (Oyster Shells)) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). BNPH HP (Calcium (Oyster Shells)) acetate may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism.
There are no empirical data on avoiding drug interactions between BNPH HP (Calcium (Oyster Shells)) acetate and most concomitant drugs. When administering an oral medication with BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) acetate tablets, approximately 2.7g, decreased the bioavailability of ciprofloxacin by approximately 50%.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C:
BNPH HP ) acetate capsules contains BNPH HP (Calcium (Oyster Shells)) acetate. Animal reproduction studies have not been conducted with BNPH HP (Calcium (Oyster Shells)) acetate, and there are no adequate and well controlled studies of BNPH HP (Calcium (Oyster Shells)) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with BNPH HP (Calcium (Oyster Shells)) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum BNPH HP (Calcium (Oyster Shells)) 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. BNPH HP (Calcium (Oyster Shells)) acetate treatment, as recommended, is not expected to harm a fetus if maternal BNPH HP (Calcium (Oyster Shells)) levels are properly monitored during and following treatment.
8.2 Labor and Delivery
The effects of BNPH HP (Calcium (Oyster Shells)) acetate on labor and delivery are unknown.
8.3 Nursing Mothers
BNPH HP ) Acetate Capsules contains BNPH HP (Calcium (Oyster Shells)) acetate and is excreted in human milk. Human milk feeding by a mother receiving BNPH HP (Calcium (Oyster Shells)) acetate is not expected to harm an infant, provided maternal serum BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].
11 DESCRIPTION
BNPH HP (Calcium (Oyster Shells)) acetate acts as a phosphate binder. Its chemical name is BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) acetate USP (anhydrous; Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) BNPH HP (Calcium (Oyster Shells)), 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.
BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP ) resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.
12.1 Mechanism of Action
BNPH HP (Calcium (Oyster Shells)) acetate, when taken with meals, combines with dietary phosphate to form an insoluble BNPH HP (Calcium (Oyster Shells)) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.
12.2 Pharmacodynamics
Orally administered BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) acetate.
14 CLINICAL STUDIES
Effectiveness of BNPH HP (Calcium (Oyster Shells)) acetate in decreasing serum phosphorus has been demonstrated in two studies of the BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum BNPH HP (Calcium (Oyster Shells)) 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 |
| BNPH HP (Calcium (Oyster Shells)) (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 BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) acetate is shown in the Table 3.
| * ANOVA of BNPH HP (Calcium (Oyster Shells)) acetate vs. placebo after 2 weeks of treatment. † Values expressed as mean ± SEM. | ||||
| Parameter | Pre-Study | Post-Treatment | p-value* | |
| BNPH HP (Calcium (Oyster Shells)) Acetate | Placebo | |||
| Phosphorus (mg/dL)† | 7.3 ± 0.18 | 5.9 ± 0.24 | 7.8 ± 0.22 | <0.01 |
| BNPH HP (Calcium (Oyster Shells)) (mg/dL)† | 8.9 ± 0.11 | 9.5 ± 0.13 | 8.8 ± 0.12 | <0.01 |
Overall, 2 weeks of treatment with BNPH HP (Calcium (Oyster Shells)) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum BNPH HP (Calcium (Oyster Shells)) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.
16 HOW SUPPLIED/STORAGE AND HANDLING
BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of BNPH HP (Calcium (Oyster Shells)) 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 BNPH HP (Calcium (Oyster Shells)) acetate capsules.
Distr. by: West-Ward
Pharmaceuticals Corp.
Eatontown, NJ 07724
10003705/05
Revised April 2016
Calcium Fluoride:
- 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
BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) acetate capsule.
- Capsule: 667 mg BNPH HP (Calcium Fluoride) acetate capsule. (3)
4 CONTRAINDICATIONS
Patients with hypercalcemia.
- Hypercalcemia. (4)
5 WARNINGS AND PRECAUTIONS
- Treat mild hypercalcemia by reducing or interrupting BNPH HP acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride), including BNPH HP (Calcium Fluoride) acetate. Avoid the use of BNPH HP (Calcium Fluoride) supplements, including BNPH HP (Calcium Fluoride) based nonprescription antacids, concurrently with BNPH HP (Calcium Fluoride) acetate.
An overdose of BNPH HP (Calcium Fluoride) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum BNPH HP (Calcium Fluoride) levels twice weekly. Should hypercalcemia develop, reduce the BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) 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, BNPH HP (Calcium Fluoride) acetate has been generally well tolerated.
BNPH HP (Calcium Fluoride) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) acetate N=167 N (%) | 3 month, open label study of BNPH HP (Calcium Fluoride) acetate N=98 N (%) | Double blind, placebo-controlled, cross-over study of liquid BNPH HP (Calcium Fluoride) acetate N=69 | |
| BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) concentration could reduce the incidence and severity of BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) acetate: dizziness, edema, and weakness.
7 DRUG INTERACTIONS
The drug interaction of BNPH HP acetate is characterized by the potential of BNPH HP (Calcium Fluoride) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). BNPH HP (Calcium Fluoride) acetate may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism.
There are no empirical data on avoiding drug interactions between BNPH HP (Calcium Fluoride) acetate and most concomitant drugs. When administering an oral medication with BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) acetate tablets, approximately 2.7g, decreased the bioavailability of ciprofloxacin by approximately 50%.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C:
BNPH HP acetate capsules contains BNPH HP (Calcium Fluoride) acetate. Animal reproduction studies have not been conducted with BNPH HP (Calcium Fluoride) acetate, and there are no adequate and well controlled studies of BNPH HP (Calcium Fluoride) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with BNPH HP (Calcium Fluoride) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum BNPH HP (Calcium Fluoride) 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. BNPH HP (Calcium Fluoride) acetate treatment, as recommended, is not expected to harm a fetus if maternal BNPH HP (Calcium Fluoride) levels are properly monitored during and following treatment.
8.2 Labor and Delivery
The effects of BNPH HP (Calcium Fluoride) acetate on labor and delivery are unknown.
8.3 Nursing Mothers
BNPH HP Acetate Capsules contains BNPH HP (Calcium Fluoride) acetate and is excreted in human milk. Human milk feeding by a mother receiving BNPH HP (Calcium Fluoride) acetate is not expected to harm an infant, provided maternal serum BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].
11 DESCRIPTION
BNPH HP (Calcium Fluoride) acetate acts as a phosphate binder. Its chemical name is BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) acetate USP (anhydrous; Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) BNPH HP (Calcium Fluoride), 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.
BNPH HP (Calcium Fluoride) 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 BNPH HP resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.
12.1 Mechanism of Action
BNPH HP (Calcium Fluoride) acetate, when taken with meals, combines with dietary phosphate to form an insoluble BNPH HP (Calcium Fluoride) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.
12.2 Pharmacodynamics
Orally administered BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) acetate.
14 CLINICAL STUDIES
Effectiveness of BNPH HP (Calcium Fluoride) acetate in decreasing serum phosphorus has been demonstrated in two studies of the BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum BNPH HP (Calcium Fluoride) 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 |
| BNPH HP (Calcium Fluoride) (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 BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) acetate is shown in the Table 3.
| * ANOVA of BNPH HP (Calcium Fluoride) acetate vs. placebo after 2 weeks of treatment. † Values expressed as mean ± SEM. | ||||
| Parameter | Pre-Study | Post-Treatment | p-value* | |
| BNPH HP (Calcium Fluoride) Acetate | Placebo | |||
| Phosphorus (mg/dL)† | 7.3 ± 0.18 | 5.9 ± 0.24 | 7.8 ± 0.22 | <0.01 |
| BNPH HP (Calcium Fluoride) (mg/dL)† | 8.9 ± 0.11 | 9.5 ± 0.13 | 8.8 ± 0.12 | <0.01 |
Overall, 2 weeks of treatment with BNPH HP (Calcium Fluoride) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum BNPH HP (Calcium Fluoride) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.
16 HOW SUPPLIED/STORAGE AND HANDLING
BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of BNPH HP (Calcium Fluoride) 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 BNPH HP (Calcium Fluoride) acetate capsules.
Distr. by: West-Ward
Pharmaceuticals Corp.
Eatontown, NJ 07724
10003705/05
Revised April 2016
Calcium Phosphate Tribasic:
Active Ingredients: BNPH HP (Calcium Phosphate Tribasic) 19%, Colloidal Silicon Dioxide 2.5%
Purpose: Anticavity
Keep out of reach of children under 6 years old
- Supervise children as necessary until being capable of using without supervision
- Instruct children under 6 years old in good brushing and rinsing habits
If more than used for brushing is accidentally swallowed, get medical help or contact a Poison Control Center right away
Inactive Ingredients: Xylitol, Erythritol, Chitosan, D-Sorbitol Solution, L-Menthol, Lactic Acid
- Brush teeth twice daily or after each meal as directed by a dentist or doctor
Hydrogen Fluoride:
KEEP OUT OF REACH OF CHILDREN
NOT FOR HUMAN USE
WARNING
Causes eye irritation
Wash skin thoroughly after handling. Do not mix with bleach or other chlorinated products – will cause chlorine gas.
DIRECTIONS:
IMPORTANT: Do not further dilute with water or mix with any other teat dips. If product in dip cup becomes visibly dirty, discard contents and replenish with fresh product. Do not reuse or return any unused product to the original container.
Udder Prep: When using an udder wash step before milking, make sure to wash teats with appropriate udder wash solution using proper cleaning procedures. Teats should then be dried with single-service towels.
Directions for Teat Dipping
Pre-Milk Dipping: Before each cow is milked, and using fresh BNPH HP (Hydrogen Fluoride), dip each teat full-length into the teat dip cup. Wipe teats after dipping using single-service towels to avoid contamination of milk.
Post-Milk Dipping: Using fresh BNPH HP (Hydrogen Fluoride), dip each teat full-length into the teat dip cup. Do not wipe. Allow to air dry. Do not turn cows out in freezing weather until the product is completely dry.
Directions for Teat Spraying
Pre-Milk Spraying: Before each cow is milked, and using fresh BNPH HP (Hydrogen Fluoride), spray entire teat. Wipe teats after dipping using single-service towels to avoid contamination of milk.
Post-Milk Spraying: Using fresh BNPH HP (Hydrogen Fluoride), spray entire teat immediately after each milking. Do not wipe. Allow to air dry. Do not turn cows out in freezing weather until the product is completely dry.
Expanded Usage: When freshening cows, begin dipping teats twice daily for about 10 days before calving.
PRECAUTION: BNPH HP (Hydrogen Fluoride) is not intended to cure or help the healing of chapped or irritated teats. As with any germicide, irritation or sensitization may occur in sensitive animals. In case of teat irritation or chapping, have the condition examined and, if necessary, treated by a veterinarian.
READ SAFETY DATA SHEET (SDS) BEFORE USING THIS PRODUCT
EMERGENCY HEALTH INFORMATION: 1 800 328 0026. If located outside the United States and Canada, call collect 1 651 222 5352 (number is in the US).
208 L (55 US GAL)
6301947
Sanitizing Teat Dip
CHEM-STAR
ACTIVE INGREDIENTS:
BNPH HP (Hydrogen Fluoride) Peroxide... 0.5%
Lactic Acid... 1.7%
Dodecyl Benzene Sulfonic Acid... 0.5%
INERT INGREDIENTS:... 97.3%
(contains sorbitol, glycerin)
TOTAL:... 100.0%
MEDA
S12274 Liegel Court
Spring Green, Wisconsin 53588
Made in U.S.A. - 766651/5300/1016
MANUFACTURED FOR AND DISTRIBUTED BY MILKING EQUIPMENT DEALERS ASSOCIATION, INC.
BNPH HP pharmaceutical active ingredients containing related brand and generic drugs:
BNPH HP 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.