Acid-X

Acetaminophen:

• Pharmacological action
• Why is Acid-X (Acetaminophen) prescribed?
• Acid-X dosage and administration
• Acid-X side effects, adverse reactions
• Contraindications
• Using during pregnancy and breastfeeding
• Special Instructions
• Acid-X (Acetaminophen) Drug Interactions
• Acid-X in case of emergency / overdose
• Acid-X (Acetaminophen) reviews

Pharmacological action

Acid-X is an analgesic-antipyretic. It has analgesic, antipyretic and weak anti-inflammatory action. The mechanism of action is associated with inhibition of prostaglandin synthesis, the predominant influence on the thermoregulation center in the hypothalamus, enhances heat transfer.

Why is Acid-X (Acetaminophen) prescribed?

Pain weak and moderate intensity of different genesis (including headache, migraine, toothache, neuralgia, myalgia, algomenorrhea; pain in trauma, burns). Fever in infectious and inflammatory diseases.

Acid-X dosage and administration

Oral or rectally adults and adolescents with a body weight over 60 kg is used in a single dose of 500 mg, the multiplicity of admission - up to 4 times / Maximum duration of treatment - 5-7 days.

Maximum dose: single - 1 g, daily - 4 g.

Single dose for oral administration for children aged 6-12 years - 250-500 mg, 1-5 years - 120-250 mg, from 3 months to 1 year - 60-120 mg, up to 3 months - 10 mg / kg. Single dose rectal in children aged 6-12 years - 250-500 mg, 1-5 years - 125-250 mg.

Multiplicity - 4 at intervals of not less than 4 h. The maximum duration of treatment - 3 days.

Maximum dose: 4 single dose per day.

Acid-X side effects, adverse reactions

Digestive system: rarely - dyspepsia; long-term use at high doses - hepatotoxic effects, methemoglobinemia, renal dysfunction and liver, hypochromic anemia. Hemopoietic system: rarely - thrombocytopenia, leukopenia, pancytopenia, neutropenia, agranulocytosis. Allergic reactions: rarely - skin rash, itching, hives.

Contraindications

Chronic active alcoholism, increased sensitivity to Acid-X, marked disturbances of liver function and / or kidney disease, anemia, pregnancy (I term).

Using during pregnancy and breastfeeding

Acid-X (Acetaminophen) crosses the placental barrier. So far, no observed adverse effects of Acid-X (Acetaminophen) on the fetus in humans.

Acid-X (Acetaminophen) is excreted in breast milk: the content in milk was 0.04-0.23% of the dose adopted mother.

If necessary, use of Acid-X (Acetaminophen) during pregnancy and lactation (breastfeeding) should carefully weigh the potential benefits of therapy for the mother and the potential risk to the fetus or child.

In experimental studies found no embryotoxic, teratogenic and mutagenic action of Acid-X (Acetaminophen).

Special Instructions

Acid-X is used with caution in patients with disorders of the liver and kidneys, with benign hyperbilirubinemia, as well as in elderly patients.

With prolonged use of Acid-X (Acetaminophen) is necessary to monitor patterns of peripheral blood and functional state of the liver.

Used for treatment of premenstrual tension syndrome in combination with pamabrom (diuretic, a derivative of xanthine) and mepyramine (Histamine H1-receptors blocker).

Acid-X (Acetaminophen) Drug Interactions

With the simultaneous use with inducers of microsomal liver enzymes, means having hepatotoxic effect, increasing the risk of hepatotoxic action of Acid-X (Acetaminophen).

With the simultaneous use of anticoagulants may be slight to moderate increase in prothrombin time.

With the simultaneous use of anticholinergics may decrease absorption of Acid-X (Acetaminophen).

With the simultaneous use of oral contraceptives accelerated excretion of Acid-X (Acetaminophen) from the body and may reduce its analgesic action.

With the simultaneous use with urological means reduced their effectiveness.

With the simultaneous use of activated charcoal reduced bioavailability of Acid-X (Acetaminophen).

When Acid-X (Acetaminophen) applied simultaneously with diazepam may decrease excretion of diazepam.

There have been reports about the possibility of enhancing mielodepression effect of zidovudine while applying with Acid-X (Acetaminophen). A case of severe toxic liver injury.

Described cases of toxic effects of Acid-X (Acetaminophen), while the use of isoniazid.

When applied simultaneously with carbamazepine, phenytoin, phenobarbital, primidonom decreases the effectiveness of Acid-X (Acetaminophen), which is caused by an increase in its metabolism and excretion from the body. Cases of hepatotoxicity, while the use of Acid-X (Acetaminophen) and phenobarbital.

In applying cholestyramine a period of less than 1 h after administration of Acid-X (Acetaminophen) may decrease of its absorption.

At simultaneous application with lamotrigine moderately increased excretion of lamotrigine from the body.

With the simultaneous use of metoclopramide may increase absorption of Acid-X (Acetaminophen) and its increased concentration in blood plasma.

When applied simultaneously with probenecid may decrease clearance of Acid-X (Acetaminophen), with rifampicin, sulfinpyrazone - may increase clearance of Acid-X (Acetaminophen) due to increasing its metabolism in the liver.

At simultaneous application of Acid-X (Acetaminophen) with ethinylestradiol increases absorption of Acid-X (Acetaminophen) from the gut.

Enhances the effect of indirect anticoagulants (coumarin derivatives and indandione). Antipyretic and analgesic activity of caffeine increases, reduce - rifampicin, phenobarbital and alcohol (accelerated biotransformation, inducing microsomal liver enzymes).

Acid-X in case of emergency / overdose

At a reception in toxic doses (10-15 g in adults) may develop liver necrosis.

Symptoms of overdose may include: nausea, vomiting, loss of appetite, sweating, extreme tiredness, unusual bleeding or bruising, pain in the upper right part of the stomach, yellowing of the skin or eyes, flu-like symptoms

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
• Acid-X (Calcium Carbonate) reviews

1 INDICATIONS AND USAGE

Acid-X (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 Acid-X (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 Acid-X (Calcium Carbonate) acetate capsule.

- Capsule: 667 mg Acid-X (Calcium Carbonate) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

- Treat mild hypercalcemia by reducing or interrupting Acid-X acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of Acid-X (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 Acid-X (Calcium Carbonate), including Acid-X (Calcium Carbonate) acetate. Avoid the use of Acid-X (Calcium Carbonate) supplements, including Acid-X (Calcium Carbonate) based nonprescription antacids, concurrently with Acid-X (Calcium Carbonate) acetate.

An overdose of Acid-X (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 Acid-X (Calcium Carbonate) levels twice weekly. Should hypercalcemia develop, reduce the Acid-X (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 Acid-X (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 Acid-X (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 Acid-X (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 Acid-X (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 Acid-X (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, Acid-X (Calcium Carbonate) acetate has been generally well tolerated.

Acid-X (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 Acid-X (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.

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 Acid-X (Calcium Carbonate) concentration could reduce the incidence and severity of Acid-X (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 Acid-X (Calcium Carbonate) acetate: dizziness, edema, and weakness.

7 DRUG INTERACTIONS

The drug interaction of Acid-X acetate is characterized by the potential of Acid-X (Calcium Carbonate) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). Acid-X (Calcium Carbonate) acetate may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism.

There are no empirical data on avoiding drug interactions between Acid-X (Calcium Carbonate) acetate and most concomitant drugs. When administering an oral medication with Acid-X (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 Acid-X (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 Acid-X (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 Acid-X (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 Acid-X (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:

Acid-X acetate capsules contains Acid-X (Calcium Carbonate) acetate. Animal reproduction studies have not been conducted with Acid-X (Calcium Carbonate) acetate, and there are no adequate and well controlled studies of Acid-X (Calcium Carbonate) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with Acid-X (Calcium Carbonate) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum Acid-X (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. Acid-X (Calcium Carbonate) acetate treatment, as recommended, is not expected to harm a fetus if maternal Acid-X (Calcium Carbonate) levels are properly monitored during and following treatment.

8.2 Labor and Delivery

The effects of Acid-X (Calcium Carbonate) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

Acid-X Acetate Capsules contains Acid-X (Calcium Carbonate) acetate and is excreted in human milk. Human milk feeding by a mother receiving Acid-X (Calcium Carbonate) acetate is not expected to harm an infant, provided maternal serum Acid-X (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 Acid-X (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 Acid-X (Calcium Carbonate) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].

11 DESCRIPTION

Acid-X (Calcium Carbonate) acetate acts as a phosphate binder. Its chemical name is Acid-X (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 Acid-X (Calcium Carbonate) acetate USP (anhydrous; Ca(CH₃COO)₂; MW=158.17 grams) equal to 169 mg (8.45 mEq) Acid-X (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.

Acid-X (Calcium Carbonate) Acetate Capsules are administered orally for the control of hyperphosphatemia in end-stage renal failure.

Chemical Structure

12 CLINICAL PHARMACOLOGY

Patients with ESRD retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum Acid-X resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.

12.1 Mechanism of Action

Acid-X (Calcium Carbonate) acetate, when taken with meals, combines with dietary phosphate to form an insoluble Acid-X (Calcium Carbonate) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.

12.2 Pharmacodynamics

Orally administered Acid-X (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 Acid-X (Calcium Carbonate) acetate.

14 CLINICAL STUDIES

Effectiveness of Acid-X (Calcium Carbonate) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Acid-X (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 Acid-X (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 Acid-X (Calcium Carbonate) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Acid-X (Calcium Carbonate) levels are also presented.

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 Acid-X (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 Acid-X (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 Acid-X (Calcium Carbonate) acetate is shown in the Table 3.

Overall, 2 weeks of treatment with Acid-X (Calcium Carbonate) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum Acid-X (Calcium Carbonate) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.

16 HOW SUPPLIED/STORAGE AND HANDLING

Acid-X (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 Acid-X (Calcium Carbonate) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Acid-X (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 Acid-X (Calcium Carbonate) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016