Aci Kestomal

Dimethicone:

• Aci Kestomal (Dimethicone) reviews

This medication is used as a moisturizer to treat or prevent dry, rough, scaly, itchy skin and minor skin irritations (e.g., diaper rash, skin burns from radiation therapy). Emollients are substances that soften and moisturize the skin and decrease itching and flaking. Some products (e.g., zinc oxide, white petrolatum ) are used mostly to protect the skin against irritation (e.g., from wetness). Dry skin is caused by a loss of water in the upper layer of the skin. Emollients/moisturizers work by forming an oily layer on the top of the skin that traps water in the skin. Petrolatum, lanolin, mineral oil and Aci Kestomal (Dimethicone) are common emollients. Humectants, including glycerin, lecithin, and propylene glycol, draw water into the outer layer of skin. Many products also have ingredients that soften the horny substance (keratin) that holds the top layer of skin cells together (e.g., urea, alpha hydroxy acids such as lactic/citric/glycolic acid, and allantoin ). This helps the dead skin cells fall off, helps the skin keep in more water, and leaves the skin feeling smoother and softer.

Magnesium Carbonate:

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• References
• Aci Kestomal (Magnesium Carbonate) reviews

Aci Kestomal (Magnesium Carbonate) Sulfate

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

Aci Kestomal (Magnesium Carbonate) Sulfate Injection, USP is a sterile solution of Aci Kestomal (Magnesium Carbonate) 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.

Aci Kestomal (Magnesium Carbonate) 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

Aci Kestomal (Magnesium Carbonate) (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 Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate). While there are large stores of Aci Kestomal (Magnesium Carbonate) present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral Aci Kestomal (Magnesium Carbonate) therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.

Aci Kestomal (Magnesium Carbonate) prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) levels range from 1.5 to 2.5 mEq/liter.

As plasma Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate). Serum Aci Kestomal (Magnesium Carbonate) concentrations in excess of 12 mEq/L may be fatal.

Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) 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. Aci Kestomal (Magnesium Carbonate) is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.

INDICATIONS AND USAGE

Aci Kestomal (Magnesium Carbonate) Sulfate Injection, USP is suitable for replacement therapy in Aci Kestomal (Magnesium Carbonate) deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum Aci Kestomal (Magnesium Carbonate) (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), Aci Kestomal (Magnesium Carbonate) sulfate may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.

Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) 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. Aci Kestomal (Magnesium Carbonate) sulfate should be used during pregnancy only if clearly needed. If Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate), their dosage should be adjusted with caution because of additive CNS depressant effects of Aci Kestomal (Magnesium Carbonate).

Because Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) should be given until they return. Serum Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) intoxication in eclampsia.

50% Aci Kestomal (Magnesium Carbonate) 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

Aci Kestomal (Magnesium Carbonate) sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate), their dosage should be adjusted with caution because of additive CNS depressant effects of Aci Kestomal (Magnesium Carbonate). CNS depression and peripheral transmission defects produced by Aci Kestomal (Magnesium Carbonate) may be antagonized by calcium.

Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral Aci Kestomal (Magnesium Carbonate) sulfate and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.

Cardiac Glycosides - Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) toxicity.

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) sulfate for more than 5 to 7 days.^1-10 Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).

Labor and Delivery

Continuous administration of Aci Kestomal (Magnesium Carbonate) sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) is distributed into milk during parenteral Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) should be monitored in such patients.

ADVERSE REACTIONS

The adverse effects of parenterally administered Aci Kestomal (Magnesium Carbonate) usually are the result of Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) sulfate therapy for eclampsia has been reported.

OVERDOSAGE

Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of Aci Kestomal (Magnesium Carbonate).

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 Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) Deficiency

In the treatment of mild Aci Kestomal (Magnesium Carbonate) deficiency, the usual adult dose is 1 gram, equivalent to 8.12 mEq of Aci Kestomal (Magnesium Carbonate) (2 mL of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) sulfate is 20 grams/48 hours and frequent serum Aci Kestomal (Magnesium Carbonate) concentrations must be obtained. Continuous use of Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) 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, Aci Kestomal (Magnesium Carbonate) 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

Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) 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

Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) sulfate tocolysis. Acta Obstet Gynecol Scan. 2006;85(9):1099-103.
• Malaeb SN, Rassi A, Haddad MC. Bone mineralization in newborns whose mothers received Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) sulfate therapy on neonatal calcium metabolism and bone mineral content. Gynecol Obstet Invest. 1997;43(4):236-41.
• Santi MD, Henry GW, Douglas GL. Aci Kestomal (Magnesium Carbonate) 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. Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) sulfate infusion for tocolysis. J Pediatr. 1988; 113(6):1078-82.
• McGuinness GA, Weinstein MM, Cruikshank DP, et al. Effects of Aci Kestomal (Magnesium Carbonate) 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 Aci Kestomal (Magnesium Carbonate) 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% Aci Kestomal (Magnesium Carbonate) Sulfate 5 g/10 mL (500 mg/mL)

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% Aci Kestomal (Magnesium Carbonate) Sulfate Injection, USP

5 g/10 mL (500 mg/mL) (4 mEq Mg++/mL)

MUST BE DILUTED FOR INTRAVENOUS USE.

For Intravenous or Intramuscular Use. Sterile. 4.06 mOsmol/mL (calc.).

Contains no more than 75 mcg/L of aluminum.

Hospira, Inc., Lake Forest, IL 60045 USA

Hospira

RL-6891

Magnesium Oxide:

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• References
• Aci Kestomal (Magnesium Oxide) reviews

Aci Kestomal (Magnesium Oxide) Sulfate

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

Aci Kestomal (Magnesium Oxide) Sulfate Injection, USP is a sterile solution of Aci Kestomal (Magnesium Oxide) 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.

Aci Kestomal (Magnesium Oxide) 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

Aci Kestomal (Magnesium Oxide) (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 Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide). While there are large stores of Aci Kestomal (Magnesium Oxide) present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral Aci Kestomal (Magnesium Oxide) therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.

Aci Kestomal (Magnesium Oxide) prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) levels range from 1.5 to 2.5 mEq/liter.

As plasma Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide). Serum Aci Kestomal (Magnesium Oxide) concentrations in excess of 12 mEq/L may be fatal.

Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) 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. Aci Kestomal (Magnesium Oxide) is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.

INDICATIONS AND USAGE

Aci Kestomal (Magnesium Oxide) Sulfate Injection, USP is suitable for replacement therapy in Aci Kestomal (Magnesium Oxide) deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum Aci Kestomal (Magnesium Oxide) (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), Aci Kestomal (Magnesium Oxide) sulfate may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.

Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) 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. Aci Kestomal (Magnesium Oxide) sulfate should be used during pregnancy only if clearly needed. If Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide), their dosage should be adjusted with caution because of additive CNS depressant effects of Aci Kestomal (Magnesium Oxide).

Because Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) should be given until they return. Serum Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) intoxication in eclampsia.

50% Aci Kestomal (Magnesium Oxide) 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

Aci Kestomal (Magnesium Oxide) sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide), their dosage should be adjusted with caution because of additive CNS depressant effects of Aci Kestomal (Magnesium Oxide). CNS depression and peripheral transmission defects produced by Aci Kestomal (Magnesium Oxide) may be antagonized by calcium.

Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral Aci Kestomal (Magnesium Oxide) sulfate and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.

Cardiac Glycosides - Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) toxicity.

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) sulfate for more than 5 to 7 days.^1-10 Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).

Labor and Delivery

Continuous administration of Aci Kestomal (Magnesium Oxide) sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) is distributed into milk during parenteral Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) should be monitored in such patients.

ADVERSE REACTIONS

The adverse effects of parenterally administered Aci Kestomal (Magnesium Oxide) usually are the result of Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) sulfate therapy for eclampsia has been reported.

OVERDOSAGE

Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of Aci Kestomal (Magnesium Oxide).

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 Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) Deficiency

In the treatment of mild Aci Kestomal (Magnesium Oxide) deficiency, the usual adult dose is 1 gram, equivalent to 8.12 mEq of Aci Kestomal (Magnesium Oxide) (2 mL of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) sulfate is 20 grams/48 hours and frequent serum Aci Kestomal (Magnesium Oxide) concentrations must be obtained. Continuous use of Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) 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, Aci Kestomal (Magnesium Oxide) 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

Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) 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

Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) sulfate tocolysis. Acta Obstet Gynecol Scan. 2006;85(9):1099-103.
• Malaeb SN, Rassi A, Haddad MC. Bone mineralization in newborns whose mothers received Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) sulfate therapy on neonatal calcium metabolism and bone mineral content. Gynecol Obstet Invest. 1997;43(4):236-41.
• Santi MD, Henry GW, Douglas GL. Aci Kestomal (Magnesium Oxide) 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. Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) sulfate infusion for tocolysis. J Pediatr. 1988; 113(6):1078-82.
• McGuinness GA, Weinstein MM, Cruikshank DP, et al. Effects of Aci Kestomal (Magnesium Oxide) 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 Aci Kestomal (Magnesium Oxide) 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% Aci Kestomal (Magnesium Oxide) Sulfate 5 g/10 mL (500 mg/mL)

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% Aci Kestomal (Magnesium Oxide) 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

Metoclopramide Hydrochloride:

• 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
• How supplied/storage and handling
• Patient counseling information
• Aci Kestomal (Metoclopramide Hydrochloride) reviews

1 INDICATIONS AND USAGE

Aci Kestomal (Metoclopramide Hydrochloride) tablets are indicated for the:

• Treatment for 4 to 12 weeks of symptomatic, documented gastroesophageal reflux in adults who fail to respond to conventional therapy.
• Relief of symptoms in adults with acute and recurrent diabetic gastroparesis.

Limitations of Use:

Aci Kestomal (Metoclopramide Hydrochloride) tablets are not recommended for use in pediatric patients due to the risk of developing tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates [see Use in Specific Populations ( 8.4 ) ].

Aci Kestomal (Metoclopramide Hydrochloride) tablets are indicated for the:

• Treatment for 4 to 12 weeks of symptomatic, documented gastroesophageal reflux in adults who fail to respond to conventional therapy. (1)
• Relief of symptoms in adults with acute and recurrent diabetic gastroparesis. (1)

Limitations of Use:

Aci Kestomal (Metoclopramide Hydrochloride) tablets are not recommended for use in pediatric patients due to the risk of tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates. (1, 8.4)

2 DOSAGE AND ADMINISTRATION

Gastroesophageal Reflux

• Administer Aci Kestomal (Metoclopramide Hydrochloride) continuously or intermittently:
  • Continuous: Administer 10 to 15 mg, 30 minutes before each meal and at bedtime (maximum of 60 mg per day) for 4 to 12 weeks.
  • Intermittent: Single doses up to 20 mg prior to provoking situation.

Acute and Recurrent Diabetic Gastroparesis (2.3)

• Administer 10 mg, 30 minutes before each meal and at bedtime (maximum of 40 mg per day) for 2 to 8 weeks

Dosage Adjustment in Specific Populations (2.2, 2.3)

• For gastroesophageal reflux and acute and recurrent diabetic gastroparesis, see Full Prescribing Information for recommended dosage reductions for elderly patients, in patients with moderate or severe hepatic or renal impairment, and cytochrome P450 2D6 (CYP2D6) poor metabolizers.

2.1 Important Administration Instructions

Avoid treatment with Aci Kestomal (Metoclopramide Hydrochloride) for longer than 12 weeks because of the increased risk of developing TD with longer-term use [see Dosage and Administration (2.2, 2.3), Warnings and Precautions (5.1)].

2.2 Dosage for Gastroesophageal Reflux

Aci Kestomal tablets may be administered continuously or intermittently in patients with symptomatic gastroesophageal reflux who fail to respond to conventional therapy:

Continuous Dosing

The recommended adult dosage of Aci Kestomal (Metoclopramide Hydrochloride) is 10 to 15 mg four times daily for 4 to 12 weeks. The treatment duration is determined by endoscopic response. Administer the dosage thirty minutes before each meal and at bedtime. The maximum recommended daily dosage is 60 mg.

Table 1 displays the recommended daily dosage and maximum daily dosage for adults and dosage adjustments for patients with moderate or severe hepatic impairment (Child-Pugh B or C), in patients with creatinine clearance less than 60 mL/minute, in cytochrome P450 2D6 (CYP2D6) poor metabolizers, and with concomitant use with strong CYP2D6 inhibitors.

Intermittent Dosing

If symptoms only occur intermittently or at specific times of the day, administer Aci Kestomal (Metoclopramide Hydrochloride) in single dose up to 20 mg prior to the provoking situation. Consider dosage reductions for the populations and situations in Table 1.

	Recommended Dosage	Maximum Recommended Daily Dosage
Adult patients	10 to 15 mg four times daily (thirty minutes before each meal and at bedtime)	60 mg
Mild hepatic impairment (Child-Pugh A)
Elderly patients [see Use in Specific Populations (8.5)]	5 mgElderly patients may be more sensitive to the therapeutic or adverse effects of Aci Kestomal (Metoclopramide Hydrochloride); therefore, consider a lower starting dosage of 5 mg four times daily with titration to the recommended adult dosage of 10 to 15 mg four times daily based upon response and tolerability. four times daily (thirty minutes before each meal and at bedtime)
Moderate or severe hepatic impairment (Child-Pugh B or C) [see Use in Specific Populations (8.7)]	5 mg four times daily (thirty minutes before each meal and at bedtime), or 10 mg taken three times daily	30 mg
CYP2D6 poor metabolizers [see Use in Specific Populations (8.9)]
Concomitant use with strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine) [see Drug Interactions (7.1)]
Moderate or severe renal impairment (creatinine clearance less than or equal to 60 mL/minute) [see Use in Specific Populations (8.6)]
Patients with End-Stage Renal Disease (ESRD) including those treated with hemodialysis and continuous ambulatory peritoneal dialysis [see Use in Specific Populations (8.6)]	5 mg four times daily (thirty minutes before each meal and at bedtime) or 10 mg twice daily	20 mg

2.3 Dosage for Acute and Recurrent Diabetic Gastroparesis

The recommended adult dosage for the treatment of acute and recurrent diabetic gastroparesis is 10 mg four times daily for 2 to 8 weeks, depending on symptomatic response. Avoid Aci Kestomal (Metoclopramide Hydrochloride) treatment for greater than 12 weeks [see Warnings and Precautions (5.1)]. Administer the dosage thirty minutes before each meal and at bedtime. The maximum recommended daily dosage is 40 mg.

Table 2 displays the recommended daily dosage and maximum daily dosage for adults and dosage adjustments for patients with moderate or severe hepatic impairment (Child-Pugh B or C), in patients with creatinine clearance less than 60 mL/minute, in cytochrome P450 2D6 (CYP2D6) poor metabolizers, and with concomitant use with strong CYP2D6 inhibitors.

If patients with diabetic gastroparesis have severe nausea or vomiting and are unable to take oral Aci Kestomal (Metoclopramide Hydrochloride) tablets, consider starting therapy with Aci Kestomal (Metoclopramide Hydrochloride) injection given intramuscularly or intravenously for up to 10 days injection). After patients are able to take oral therapy, switch to Aci Kestomal (Metoclopramide Hydrochloride) tablets.

	Recommended Dosage	Maximum Recommended Daily Dosage
Adult Patients	10 mg four times daily (30 minutes before each meal and at bedtime)	40 mg
Mild hepatic impairment (Child-Pugh A)
Elderly patients [see Use in Specific Populations (8.5)]	5 mgElderly patients may be more sensitive to the therapeutic or adverse effects of Aci Kestomal (Metoclopramide Hydrochloride); therefore, consider a lower dosage of 5 mg four times daily with titration to the recommended adult dosage of 10 mg four time daily based upon response and tolerability. four times daily (30 minutes before each meal and at bedtime)
Moderate or severe hepatic impairment (Child-Pugh B or C) [see Use in Specific Populations (8.7)]	5 mg four times daily (30 minutes before each meal and at bedtime)	20 mg
CYP2D6 poor metabolizers [see Use in Specific Populations (8.9)]
Concomitant use with strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine) [see Drug Interactions (7.1)]
Moderate or severe renal impairment (creatinine clearance less than 60 mL/minute) [see Use in Specific Populations (8.6)]
Patients with End-Stage Renal Disease (ESRD) including those treated with hemodialysis and continuous ambulatory peritoneal dialysis [see Use in Specific Populations (8.6)]	5 mg twice daily	10 mg

3 DOSAGE FORMS AND STRENGTHS

Tablets:

• 5 mg Aci Kestomal (Metoclopramide Hydrochloride): white, round, unscored, debossed “TV” on one side and “2204” on the other side.
• 10 mg Aci Kestomal (Metoclopramide Hydrochloride): white, round, scored, debossed “TEVA” on one side and “2203” above the score on the other side.

Tablets: 5 mg and 10 mg Aci Kestomal (Metoclopramide Hydrochloride) (3)

4 CONTRAINDICATIONS

Aci Kestomal (Metoclopramide Hydrochloride) is contraindicated:

• In patients with a history of tardive dyskinesia (TD) or a dystonic reaction to Aci Kestomal (Metoclopramide Hydrochloride) [see Warnings and Precautions ( 5.1, 5.2 ) ].
• When stimulation of gastrointestinal motility might be dangerous (e.g., in the presence of gastrointestinal hemorrhage, mechanical obstruction, or perforation).
• In patients with pheochromocytoma or other catecholamine-releasing paragangliomas. Aci Kestomal (Metoclopramide Hydrochloride) may cause a hypertensive/pheochromocytoma crisis, probably due to release of catecholamines from the tumor [see Warnings and Precautions (5.5)].
• In patients with epilepsy. Aci Kestomal (Metoclopramide Hydrochloride) may increase the frequency and severity of seizures [see Adverse Reactions (6)].
• In patients with hypersensitivity to Aci Kestomal (Metoclopramide Hydrochloride). Reactions have included laryngeal and glossal angioedema and bronchospasm [see Adverse Reactions (6)].

• History of TD or dystonic reaction to Aci Kestomal (Metoclopramide Hydrochloride) (4)
• When stimulation of gastrointestinal motility might be dangerous (4)
• Pheochromocytoma, catecholamine-releasing paragangliomas (4)
• Epilepsy (4)
• Hypersensitivity to Aci Kestomal (Metoclopramide Hydrochloride) (4)

5 WARNINGS AND PRECAUTIONS

• Tardive Dyskinesia, Other Extrapyramidal Symptoms (EPS), and Neuroleptic Malignant Syndrome (NMS): Avoid concomitant use of other drugs known to cause TD/EPS/NMS and avoid use in patients with Parkinson’s Disease. If symptoms occur, discontinue Aci Kestomal (Metoclopramide Hydrochloride) and seek immediate medical attention. (5.1, 5.2, 5.3, 7.1, 7.2)
• Depression and suicidal ideation/suicide: Avoid use. (5.4)

5.1 Tardive Dyskinesia

Aci Kestomal (Metoclopramide Hydrochloride) can cause tardive dyskinesia (TD), a syndrome of potentially irreversible and disfiguring involuntary movements of the face or tongue, and sometimes of the trunk and/or extremities. Movements may be choreoathetotic in appearance. The risk of developing TD and the likelihood that TD will become irreversible increases with duration of treatment and total cumulative dosage. Additionally, the risk of developing TD is increased among the elderly, especially elderly women [see Use in Specific Populations (8.5)], and in patients with diabetes mellitus. Due to the risk of developing TD, avoid treatment with Aci Kestomal (Metoclopramide Hydrochloride) for longer than 12 weeks and reduce the dosage in elderly patients [see Dosage and Administration (2.2, 2.3)].

Discontinue Aci Kestomal (Metoclopramide Hydrochloride) immediately in patients who develop signs and symptoms of TD. There is no known effective treatment for established cases of TD, although in some patients TD may remit, partially or completely, within several weeks to months after Aci Kestomal (Metoclopramide Hydrochloride) is withdrawn.

Aci Kestomal (Metoclopramide Hydrochloride) itself may suppress, or partially suppress, the signs of TD, thereby masking the underlying disease process. The effect of this symptomatic suppression upon the long-term course of TD is unknown. Aci Kestomal (Metoclopramide Hydrochloride) is contraindicated in patients with a history of TD [see Contraindications (4)]. Avoid Aci Kestomal (Metoclopramide Hydrochloride) in patients receiving other drugs that are likely to cause TD (e.g., antipsychotics).

5.2 Other Extrapyramidal Symptoms

In addition to TD, Aci Kestomal may cause other extrapyramidal symptoms (EPS), parkinsonian symptoms, and motor restlessness. Advise patients to seek immediate medical attention if such symptoms occur and to discontinue Aci Kestomal (Metoclopramide Hydrochloride).

• Extrapyramidal symptoms (EPS), such as acute dystonic reactions, occurred in patients treated with Aci Kestomal (Metoclopramide Hydrochloride) dosages of 30 mg to 40 mg daily. Such reactions occurred more frequently in adults less than 30 years of age and at higher than recommended dosages. EPS occurred more frequently in pediatric patients compared to adults (metoclopramide is not approved for use in pediatric patients). Symptoms can occur in the first 24 to 48 hours after starting Aci Kestomal (Metoclopramide Hydrochloride). Symptoms included involuntary movements of limbs and facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of tongue, bulbar type of speech, trismus, or dystonic reactions resembling tetanus. Rarely, dystonic reactions were present as stridor and dyspnea, possibly due to laryngospasm. Diphenhydramine hydrochloride or benztropine mesylate may be used to treat these adverse reactions. Avoid Aci Kestomal (Metoclopramide Hydrochloride) in patients receiving other drugs that can cause EPS (e.g., antipsychotics).
• Parkinsonian symptoms (bradykinesia, tremor, cogwheel rigidity, mask-like facies) have occurred after starting Aci Kestomal (Metoclopramide Hydrochloride), more commonly within the first 6 months, but also after longer periods. Symptoms generally have subsided within 2 to 3 months after discontinuation of Aci Kestomal (Metoclopramide Hydrochloride). Avoid Aci Kestomal (Metoclopramide Hydrochloride) in patients with Parkinson’s disease and other patients being treated with antiparkinsonian drugs due to potential exacerbation of symptoms. Avoid treatment with Aci Kestomal (Metoclopramide Hydrochloride) for more than 12 weeks [see Dosage and Administration (2.2, 2.3), Warnings and Precautions (5.1)].
• Motor restlessness (akathisia) has developed and consisted of feelings of anxiety, agitation, jitteriness, and insomnia, as well as inability to sit still, pacing, and foot tapping. If symptoms resolve, consider restarting at a lower dosage.

5.3 Neuroleptic Malignant Syndrome

Aci Kestomal (Metoclopramide Hydrochloride) may cause a potentially fatal symptom complex called neuroleptic malignant syndrome (NMS). NMS has been reported in association with Aci Kestomal (Metoclopramide Hydrochloride) overdosage and concomitant treatment with another drug associated with NMS. Avoid Aci Kestomal (Metoclopramide Hydrochloride) in patients receiving other drugs associated with NMS, including typical and atypical antipsychotics.

Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and manifestations of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac arrhythmias). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Patients with such symptoms should be evaluated immediately.

In the diagnostic evaluation, consider the presence of other serious medical conditions (e.g., pneumonia, systemic infection) and untreated or inadequately treated extrapyramidal signs and symptoms. Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, malignant hyperthermia, drug fever, serotonin syndrome, and primary central nervous system pathology.

Management of NMS includes:

• Immediate discontinuation of Aci Kestomal (Metoclopramide Hydrochloride) and other drugs not essential to concurrent therapy [see Drug Interactions (7.1)].
• Intensive symptomatic treatment and medical monitoring.
• Treatment of any concomitant serious medical problems for which specific treatments are available.

5.4 Depression

Depression has occurred in metoclopramide-treated patients with and without a history of depression. Symptoms have included suicidal ideation and suicide. Avoid Aci Kestomal use in patients with a history of depression.

5.5 Hypertension

Aci Kestomal (Metoclopramide Hydrochloride) may elevate blood pressure. In one study in hypertensive patients, intravenously administered Aci Kestomal (Metoclopramide Hydrochloride) was shown to release catecholamines; hence, avoid use in patients with hypertension or in patients taking monoamine oxidase inhibitors [see Drug Interactions (7.1)].

There are also clinical reports of hypertensive crises in patients with undiagnosed pheochromocytoma. Aci Kestomal (Metoclopramide Hydrochloride) is contraindicated in patients with pheochromocytoma or other catecholamine-releasing paragangliomas [see Contraindications (4)]. Discontinue Aci Kestomal (Metoclopramide Hydrochloride) in any patient with a rapid rise in blood pressure.

5.6 Fluid Retention

Because Aci Kestomal produces a transient increase in plasma aldosterone, patients with cirrhosis or congestive heart failure may be at risk of developing fluid retention and volume overload. Discontinue Aci Kestomal (Metoclopramide Hydrochloride) if any of these adverse reactions occur.

5.7 Hyperprolactinemia

As with other dopamine D₂ receptor antagonists, Aci Kestomal (Metoclopramide Hydrochloride) elevates prolactin levels.

Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported with prolactin-elevating drugs, including Aci Kestomal (Metoclopramide Hydrochloride).

Hyperprolactinemia may potentially stimulate prolactin-dependent breast cancer. However, some clinical studies and epidemiology studies have not shown an association between administration of dopamine D₂ receptor antagonists and tumorigenesis in humans [see Nonclinical Toxicology ( 13.1 ) ].

5.8 Effects of the Ability to Drive and Operate Machinery

Aci Kestomal (Metoclopramide Hydrochloride) may impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a motor vehicle. Concomitant use of central nervous system (CNS) depressants or drugs associated with EPS may increase this effect (e.g., alcohol, sedatives, hypnotics, opiates, and anxiolytics). Avoid Aci Kestomal (Metoclopramide Hydrochloride) or the interacting drug, depending on the importance of the drug to the patient [see Drug Interactions (7.1)].

6 ADVERSE REACTIONS

The following adverse reactions are described, or described in greater detail, in other sections of the labeling:

• Tardive dyskinesia [see Boxed Warning and Warnings and Precautions (5.1)]
• Other extrapyramidal effects [see Warnings and Precautions (5.2)]
• Neuroleptic malignant syndrome [see Warnings and Precautions (5.3)]
• Depression [see Warnings and Precautions (5.4)]
• Hypertension [see Warnings and Precautions (5.5)]
• Fluid retention [see Warnings and Precautions (5.6)]
• Hyperprolactinemia [see Warnings and Precautions (5.7)]
• Effects on the ability to drive and operate machinery [see Warnings and Precautions (5.8)]

The following adverse reactions have been identified from clinical studies or postmarketing reports of Aci Kestomal (Metoclopramide Hydrochloride). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The most common adverse reactions (in approximately 10% of patients receiving 10 mg of Aci Kestomal (Metoclopramide Hydrochloride) four times daily) were restlessness, drowsiness, fatigue, and lassitude. In general, the incidence of adverse reactions correlated with the dosage and duration of Aci Kestomal (Metoclopramide Hydrochloride) administration.

Adverse reactions, especially those involving the nervous system, occurred after stopping Aci Kestomal (Metoclopramide Hydrochloride) including dizziness, nervousness, and headaches.

Central Nervous System Disorders

• Tardive dyskinesia, acute dystonic reactions, drug-induced parkinsonism, akathisia, and other extrapyramidal symptoms
• Convulsive seizures
• Hallucinations
• Restlessness, drowsiness, fatigue, and lassitude occurred in approximately 10% of patients who received 10 mg four times daily. Insomnia, headache, confusion, dizziness, or depression with suicidal ideation occurred less frequently.
• Neuroleptic malignant syndrome, serotonin syndrome (in combination with serotonergic agents).

Endocrine Disorders: Fluid retention secondary to transient elevation of aldosterone. Galactorrhea, amenorrhea, gynecomastia, impotence secondary to hyperprolactinemia

Cardiovascular Disorders: Acute congestive heart failure, possible atrioventricular block, hypotension, hypertension, supraventricular tachycardia, bradycardia, fluid retention

Gastrointestinal Disorders: Nausea, bowel disturbances (primarily diarrhea)

Hepatic Disorders: Hepatotoxicity, characterized by, e.g., jaundice and altered liver function tests, when Aci Kestomal (Metoclopramide Hydrochloride) was administered with other drugs with known hepatotoxic potential

Renal and Urinary Disorders: Urinary frequency, urinary incontinence

Hematologic Disorders: Agranulocytosis, neutropenia, leukopenia, methemoglobinemia, sulfhemoglobinemia

Hypersensitivity Reactions: Bronchospasm (especially in patients with a history of asthma), urticaria; rash; angioedema, including glossal or laryngeal edema

Eye Disorders: Visual disturbances

Metabolism Disorders: Porphyria

• Most common adverse reactions (> 10%) are restlessness, drowsiness, fatigue, and lassitude. (6)

To report SUSPECTED ADVERSE REACTIONS, contact TEVA USA, PHARMACOVIGILANCE at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

7 DRUG INTERACTIONS

• Antipsychotics: Potential for additive effects, including TD, EPS, and NMS; avoid concomitant use.
• CNS depressants: Increased risk of CNS depression. Avoid concomitant use and monitor for adverse reactions. (7.1)
• Strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine): See Full Prescribing Information for recommended dosage reductions. (2.2, 2.3, 7.1)
• MAO inhibitors: Increased risk of hypertension; avoid concomitant use. (5.5, 7.1)
• Additional drug interactions: See Full Prescribing Information. (7.1, 7.2)

7.1 Effects of Other Drugs on Aci Kestomal (Metoclopramide Hydrochloride)

Table 3 displays the effects of other drugs on Aci Kestomal (Metoclopramide Hydrochloride).

Antipsychotics
Clinical Impact	Potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS).
Intervention	Avoid concomitant use [see Warnings and Precautions (5.1, 5.2, 5.3)].
Strong CYP2D6 Inhibitors, not Included in Antipsychotic Category Above
Clinical Impact	Increased plasma concentrations of Aci Kestomal (Metoclopramide Hydrochloride); risk of exacerbation of extrapyramidal symptoms [see Clinical Pharmacology (12.3)].
Intervention	Reduce the Aci Kestomal (Metoclopramide Hydrochloride) dosage [see Dosage and Administration (2.2, 2.3)].
Examples	quinidine, bupropion, fluoxetine, and paroxetine
Monoamine Oxidase Inhibitors
Clinical Impact	Increased risk of hypertension [see Warnings and Precautions (5.5)].
Intervention	Avoid concomitant use.
Central Nervous System (CNS) Depressants
Clinical Impact	Increased risk of CNS depression [see Warnings and Precautions (5.8)].
Intervention	Avoid Aci Kestomal (Metoclopramide Hydrochloride) or the interacting drug, depending on the importance of the drug to the patient.
Examples	alcohol, sedatives, hypnotics, opiates and anxiolytics
Drugs that Impair Gastrointestinal Motility
Clinical Impact	Decreased systemic absorption of Aci Kestomal (Metoclopramide Hydrochloride).
Intervention	Monitor for reduced therapeutic effect.
Examples	antiperistaltic antidiarrheal drugs, anticholinergic drugs, and opiates
Dopaminergic Agonists and Other Drugs that Increase Dopamine Concentrations
Clinical Impact	Decreased therapeutic effect of Aci Kestomal (Metoclopramide Hydrochloride) due to opposing effects on dopamine.
Intervention	Monitor for reduced therapeutic effect.
Examples	apomorphine, bromocriptine, cabergoline, levodopa, pramipexole, ropinirole, and rotigotine

7.2 Effects of Aci Kestomal on Other Drugs

Table 4 displays the effects of Aci Kestomal (Metoclopramide Hydrochloride) on other drugs.

Dopaminergic Agonists and Drugs Increasing Dopamine Concentrations
Clinical Impact	Opposing effects of Aci Kestomal (Metoclopramide Hydrochloride) and the interacting drug on dopamine. Potential exacerbation of symptoms (e.g., parkinsonian symptoms).
Intervention	Avoid concomitant use [see Warnings and Precautions (5.2)].
Examples	Apomorphine, bromocriptine, cabergoline, levodopa, pramipexole, ropinirole, rotigotine
Succinylcholine, Mivacurium
Clinical Impact	Aci Kestomal (Metoclopramide Hydrochloride) inhibits plasma cholinesterase leading to enhanced neuromuscular blockade.
Intervention	Monitor for signs and symptoms of prolonged neuromuscular blockade
Drugs with Absorption Altered due to Increased Gastrointestinal Motility
Clinical Impact	The effect of Aci Kestomal (Metoclopramide Hydrochloride) on other drugs is variable. Increased gastrointestinal (GI) motility by Aci Kestomal (Metoclopramide Hydrochloride) may impact absorption of other drugs leading to decreased or increased drug exposure.
Intervention	Drugs with Decreased Absorption (e.g., digoxin, atovaquone, posaconazole oral suspension Interaction does not apply to posaconazole delayed-release tablets, fosfomycin): Monitor for reduced therapeutic effect of the interacting drug. For digoxin monitor therapeutic drug concentrations and increase the digoxin dose as needed. Drugs with Increased Absorption (e.g., sirolimus, tacrolimus, cyclosporine): Monitor therapeutic drug concentrations and adjust the dose as needed. See prescribing information for the interacting drug.
Insulin
Clinical Impact	Increased GI motility by Aci Kestomal (Metoclopramide Hydrochloride) may increase delivery of food to the intestines and increase blood glucose.
Intervention	Monitor blood glucose and adjust insulin dosage regimen as needed.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Published studies, including retrospective cohort studies, national registry studies, and meta-analyses, do not report an increased risk of adverse pregnancy-related outcomes with use of Aci Kestomal during pregnancy.

There are potential risks to the neonate following exposure in utero to Aci Kestomal (Metoclopramide Hydrochloride) during delivery [see Clinical Considerations]. In animal reproduction studies, no adverse developmental effects were observed with oral administration of Aci Kestomal (Metoclopramide Hydrochloride) to pregnant rats and rabbits at exposures about 6 and 12 times the maximum recommended human dose (MRHD) [see Data].

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Aci Kestomal (Metoclopramide Hydrochloride) crosses the placental barrier and may cause extrapyramidal signs and methemoglobinemia in neonates with maternal administration during delivery. Monitor neonates for extrapyramidal signs [see Warnings and Precautions (5.1, 5.2), Use in Specific Populations (8.4)].

Data

Animal Data

Reproduction studies have been performed following administration of oral Aci Kestomal (Metoclopramide Hydrochloride) during organogenesis in pregnant rats at about 6 times the MRHD calculated on body surface area and in pregnant rabbits at about 12 times the MRHD calculated on body surface area. No evidence of adverse developmental effects due to Aci Kestomal (Metoclopramide Hydrochloride) were observed.

8.2 Lactation

Risk Summary

Limited published data report the presence of Aci Kestomal (Metoclopramide Hydrochloride) in human milk in variable amounts. Breastfed infants exposed to Aci Kestomal (Metoclopramide Hydrochloride) have experienced gastrointestinal adverse reactions, including intestinal discomfort and increased intestinal gas formation [see Data]. Aci Kestomal (Metoclopramide Hydrochloride) elevates prolactin levels [see Warnings and Precautions (5.7)]; however, the published data are not adequate to support drug effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Aci Kestomal (Metoclopramide Hydrochloride) and any potential adverse effects on the breastfed child from Aci Kestomal (Metoclopramide Hydrochloride) or from the underlying maternal condition.

Clinical Considerations

Monitor breastfeeding neonates because Aci Kestomal (Metoclopramide Hydrochloride) may cause extrapyramidal signs (dystonias) and methemoglobinemia [see Warnings and Precautions (5.1, 5.2), Use in Specific Populations (8.4)].

Data

In published clinical studies, the estimated amount of Aci Kestomal (Metoclopramide Hydrochloride) received by the breastfed infant was less than 10% of the maternal weight-adjusted dose. In one study, the estimated daily amount of Aci Kestomal (Metoclopramide Hydrochloride) received by infants from breast milk ranged from 6 to 24 mcg/kg/day in early puerperium (3 to 9 days postpartum) and from 1 to 13 mcg/kg/day at 8 to 12 weeks postpartum.

8.4 Pediatric Use

Aci Kestomal is not recommended for use in pediatric patients due to the risk of tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates. The safety and effectiveness of Aci Kestomal (Metoclopramide Hydrochloride) in pediatric patients have not been established.

Dystonias and other extrapyramidal symptoms associated with Aci Kestomal (Metoclopramide Hydrochloride) are more common in pediatric patients than in adults [see Warnings and Precautions (5.1, 5.2)]. In addition, neonates have reduced levels of NADH-cytochrome b₅ reductase, making them more susceptible to methemoglobinemia, a possible adverse reaction of Aci Kestomal (Metoclopramide Hydrochloride) use in neonates [see Use in Specific Populations (8.8)].

8.5 Geriatric Use

Aci Kestomal (Metoclopramide Hydrochloride) is known to be substantially excreted by the kidney, and the risk of adverse reactions, including tardive dyskinesia (TD), may be greater in patients with impaired renal function [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)]. Elderly patients are more likely to have decreased renal function and may be more sensitive to the therapeutic or adverse effects of Aci Kestomal (Metoclopramide Hydrochloride); therefore, consider a reduced dosage of Aci Kestomal (Metoclopramide Hydrochloride) in elderly patients [see Boxed Warning, Dosage and Administration (2.2, 2.3), Warnings and Precautions (5.1)].

8.6 Renal Impairment

The clearance of Aci Kestomal is decreased and the systemic exposure is increased in patients with moderate to severe renal impairment compared to patients with normal renal function, which may increase the risk of adverse reactions. Reduce the Aci Kestomal (Metoclopramide Hydrochloride) dosage in patients with moderate and severe renal impairment (creatinine clearance less than or equal to 60 mL/minute), including those receiving hemodialysis and continuous ambulatory peritoneal dialysis [see Dosage and Administration (2.2, 2.3), Clinical Pharmacology (12.3)].

8.7 Hepatic Impairment

Patients with severe hepatic impairment (Child-Pugh C) have reduced systemic Aci Kestomal (Metoclopramide Hydrochloride) clearance (by approximately 50%) compared to patients with normal hepatic function. The resulting increase in Aci Kestomal (Metoclopramide Hydrochloride) blood concentrations increases the risk of adverse reactions. There is no pharmacokinetic data in patients with moderate hepatic impairment (Child-Pugh B). Reduce Aci Kestomal (Metoclopramide Hydrochloride) dosage in patients with moderate or severe (Child-Pugh B or C) hepatic impairment [see Dosage and Administration (2.2, 2.3)]. There is no dosage adjustment required for patients with mild hepatic impairment (Child-Pugh A).

In addition, Aci Kestomal (Metoclopramide Hydrochloride), by producing a transient increase in plasma aldosterone, may increase the risk of fluid retention in patients with hepatic impairment [see Warnings and Precautions (5.6)].

Monitor patients with hepatic impairment for the occurrence of fluid retention and volume overload.

8.8 NADH-Cytochrome b₅ Reductase Deficiency

Metoclopramide-treated patients with NADH-cytochrome b₅ reductase deficiency are at an increased risk of developing methemoglobinemia and/or sulfhemoglobinemia. For patients with glucose-6-phosphate dehydrogenase deficiency with metoclopramide-induced methemoglobinemia, methylene blue treatment is not recommended. Methylene blue may cause hemolytic anemia in patients with G6PD deficiency, which may be fatal [see Overdosage (10)].

8.9 CYP2D6 Poor Metabolizers

Aci Kestomal (Metoclopramide Hydrochloride) is a substrate of CYP2D6. The elimination of Aci Kestomal (Metoclopramide Hydrochloride) may be slowed in patients who are CYP2D6 poor metabolizers (compared to patients who are CYP2D6 intermediate, extensive, or ultra-rapid metabolizers); possibly increasing the risk of dystonic and other adverse reactions to Aci Kestomal (Metoclopramide Hydrochloride) [see Clinical Pharmacology (12.3)]. Reduce the Aci Kestomal (Metoclopramide Hydrochloride) dosage in patients who are poor CYP2D6 metabolizers [see Dosage and Administration (2.2, 2.3)].

10 OVERDOSAGE

Manifestations of Aci Kestomal (Metoclopramide Hydrochloride) overdosage included drowsiness, disorientation, extrapyramidal reactions, other adverse reactions associated with Aci Kestomal (Metoclopramide Hydrochloride) use (including, e.g., methemoglobinemia), and sometimes death. Neuroleptic malignant syndrome (NMS) has been reported in association with Aci Kestomal (Metoclopramide Hydrochloride) overdose and concomitant treatment with another drug associated with NMS [see Warnings and Precautions (5.1, 5.2, 5.3)].

There are no specific antidotes for Aci Kestomal (Metoclopramide Hydrochloride) overdosage. If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.

Methemoglobinemia can be reversed by the intravenous administration of methylene blue. However, methylene blue may cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, which may be fatal.

Hemodialysis and continuous ambulatory peritoneal dialysis do not remove significant amounts of Aci Kestomal (Metoclopramide Hydrochloride).

11 DESCRIPTION

Aci Kestomal (Metoclopramide Hydrochloride) hydrochloride, USP, the active ingredient of Aci Kestomal (Metoclopramide Hydrochloride) tablets, is a dopamine-2 receptor antagonist. Aci Kestomal (Metoclopramide Hydrochloride) hydrochloride (metoclopramide monohydrochloride monohydrate) is a white or practically white, crystalline, odorless or practically odorless powder. It is very soluble in water, freely soluble in alcohol, sparingly soluble in chloroform and practically insoluble in ether. Chemically, it is 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxy benzamide monohydrochloride monohydrate. Its structural formula is as follows:

C₁₄H₂₂ClN₃O₂-HCl-H₂O M.W. 354.3

Aci Kestomal (Metoclopramide Hydrochloride) tablets are for oral administration. Aci Kestomal (Metoclopramide Hydrochloride) tablets are available in 5 mg and 10 mg tablets.

• Each Aci Kestomal (Metoclopramide Hydrochloride) tablet, 5 mg contains 5 mg Aci Kestomal (Metoclopramide Hydrochloride) (equivalent to 5.91 mg of Aci Kestomal (Metoclopramide Hydrochloride) hydrochloride, USP).
• Each Aci Kestomal (Metoclopramide Hydrochloride) tablet, 10 mg contains 10 mg Aci Kestomal (Metoclopramide Hydrochloride) (equivalent to 11.82 mg of Aci Kestomal (Metoclopramide Hydrochloride) hydrochloride, USP).

Inactive Ingredients

Corn starch, dibasic calcium phosphate, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate.

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12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Aci Kestomal stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary, or pancreatic secretions. The exact mechanism of action of Aci Kestomal (Metoclopramide Hydrochloride) in the treatment of gastroesophageal reflux and acute and recurrent diabetic gastroparesis has not been fully established. It seems to sensitize tissues to the action of acetylcholine. The effect of Aci Kestomal (Metoclopramide Hydrochloride) on motility is not dependent on intact vagal innervation, but it can be abolished by anticholinergic drugs.

Aci Kestomal (Metoclopramide Hydrochloride) increases the tone and amplitude of gastric (especially antral) contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. It increases the resting tone of the lower esophageal sphincter. It has little, if any, effect on the motility of the colon or gallbladder.

12.2 Pharmacodynamics

Gastroesophageal Reflux

In patients with gastroesophageal reflux and low lower esophageal sphincter pressure (LESP), single oral doses of Aci Kestomal (Metoclopramide Hydrochloride) produced dose-related increases in LESP. Effects began at about 5 mg and increased through 20 mg. The increase in LESP from a 5 mg dose lasted about 45 minutes and that of 20 mg lasted between 2 and 3 hours. Increased rate of stomach emptying was observed with single oral doses of 10 mg.

12.3 Pharmacokinetics

Absorption

Relative to an intravenous dose of 20 mg, the absolute bioavailability of oral Aci Kestomal (Metoclopramide Hydrochloride) is 80% ± 15.5% as demonstrated in a crossover study of 18 subjects. Peak plasma concentrations occurred at about 1 to 2 hours after a single oral dose. Similar time to peak was observed after individual doses at steady state.

In a single dose study of 12 subjects, the area under the drug concentration-time curve increased linearly with doses from 20 to 100 mg (5 times the maximum recommended single dose). Peak concentrations increased linearly with dose; time to peak concentrations remained the same; whole body clearance was unchanged; and the elimination rate remained the same. The mean elimination half-life in subjects with normal renal function was 5 to 6 hours. Linear kinetic processes adequately describe the absorption and elimination of Aci Kestomal (Metoclopramide Hydrochloride).

Distribution

Aci Kestomal (Metoclopramide Hydrochloride) is not extensively bound to plasma proteins (about 30%). The whole body volume of distribution is high (about 3.5 L/kg), which suggests extensive distribution of drug to the tissues.

Elimination

Metabolism: Aci Kestomal (Metoclopramide Hydrochloride) undergoes enzymatic metabolism via oxidation as well as glucuronide and sulfate conjugation reactions in the liver. Monodeethylmetoclopramide, a major oxidative metabolite, is formed primarily by CYP2D6, an enzyme subject to genetic variability [see Dosage and Administration (2.2, 2.3), Use in Specific Populations (8.9)].

Excretion: Approximately 85% of the radioactivity of an orally administered dose appeared in the urine within 72 hours. After oral administration of 10 or 20 mg, a mean of 18% and 22% of the dose, respectively, was recovered as free Aci Kestomal (Metoclopramide Hydrochloride) in urine within 36 hours.

Specific Populations

Patients with Renal Impairment: In a study of 24 patients with varying degrees of renal impairment (moderate, severe, and end-stage renal disease (ESRD) requiring dialysis), the systemic exposure (AUC) of Aci Kestomal (Metoclopramide Hydrochloride) in patients with moderate to severe renal impairment was about 2-fold the AUC in subjects with normal renal function. The AUC of Aci Kestomal (Metoclopramide Hydrochloride) in patients with ESRD on dialysis was about 3.5-fold the AUC in subjects with normal renal function [see Dosage and Administration (2.2, 2.3) and Use in Specific Populations (8.6)].

Patients with Hepatic Impairment: In a group of 8 patients with severe hepatic impairment (Child-Pugh C), the average Aci Kestomal (Metoclopramide Hydrochloride) clearance was reduced by approximately 50% compared to patients with normal hepatic function [see Dosage and Administration (2.2, 2.3) and Use in Specific Populations (8.7)].

Drug Interaction Studies

Effect of Aci Kestomal (Metoclopramide Hydrochloride) on CYP2D6 Substrates

Although in vitro studies suggest that Aci Kestomal (Metoclopramide Hydrochloride) can inhibit CYP2D6, Aci Kestomal (Metoclopramide Hydrochloride) is unlikely to interact with CYP2D6 substrates in vivo at therapeutically relevant concentrations.

Effect of CYP2D6 Inhibitors on Aci Kestomal (Metoclopramide Hydrochloride)

In healthy subjects, 20 mg of Aci Kestomal (Metoclopramide Hydrochloride) and 60 mg of fluoxetine (a strong CYP2D6 inhibitor) were administered, following prior exposure to 60 mg fluoxetine orally for 8 days. The patients who received concomitant Aci Kestomal (Metoclopramide Hydrochloride) and fluoxetine had a 40% and 90% increase in Aci Kestomal (Metoclopramide Hydrochloride) C_max and AUC_0-∞, respectively, compared to patients who received Aci Kestomal (Metoclopramide Hydrochloride) alone [see Drug Interactions (7.1)].

Parameter	Aci Kestomal (Metoclopramide Hydrochloride) alone (mean SD)	Aci Kestomal (Metoclopramide Hydrochloride) with fluoxetine (mean SD)
Cmax (ng/mL)	44 ± 15	62.7 ± 9.2
AUC0-∞ (ng∙h/mL)	313 ± 113	591 ± 140
t1/2 (h)	5.5 ± 1.1	8.5 ± 2.2

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

A 77-week study was conducted in rats with oral Aci Kestomal (Metoclopramide Hydrochloride) doses up to 40 mg/kg/day (about six times the maximum recommended human dose on body surface area basis). Aci Kestomal (Metoclopramide Hydrochloride) elevated prolactin levels and the elevation persisted during chronic administration. An increase in mammary neoplasms was found in rodents after chronic administration of Aci Kestomal (Metoclopramide Hydrochloride) [see Warnings and Precautions (5.7)]. In a rat model for assessing the tumor promotion potential, a 2-week oral treatment with Aci Kestomal (Metoclopramide Hydrochloride) at a dose of 260 mg/kg/day (about 35 times the maximum recommended human dose based on body surface area) enhanced the tumorigenic effect of N-nitrosodiethylamine.

Mutagenesis

Aci Kestomal (Metoclopramide Hydrochloride) was positive in the in vitro Chinese hamster lung cell/HGPRT forward mutation assay for mutagenic effects and in the in vitro human lymphocyte chromosome aberration assay for clastogenic effects. It was negative in the in vitro Ames mutation assay, the in vitro unscheduled DNA synthesis assay with rat and human hepatocytes, and the in vivo rat micronucleus assay.

Impairment of Fertility

Aci Kestomal (Metoclopramide Hydrochloride) at intramuscular doses up to 20 mg/kg/day (about three times the maximum recommended human dose based on body surface area) was found to have no effect on fertility and reproductive performance of male and female rats.

16 HOW SUPPLIED/STORAGE AND HANDLING

Each white, round, unscored, debossed “TV” on one side and “2204” on the other side, compressed Aci Kestomal (Metoclopramide Hydrochloride) tablet, USP contains Aci Kestomal (Metoclopramide Hydrochloride) hydrochloride, USP equivalent to 5 mg Aci Kestomal (Metoclopramide Hydrochloride). Available in bottles of 100 (NDC 0093-2204-01) and 500 (NDC 0093-2204-05).

Each white, round, scored, debossed “TEVA” on one side and “2203” above the score on the other side, compressed Aci Kestomal (Metoclopramide Hydrochloride) tablet, USP contains Aci Kestomal (Metoclopramide Hydrochloride) hydrochloride, USP equivalent to 10 mg Aci Kestomal (Metoclopramide Hydrochloride). Available in bottles of 100 (NDC 0093-2203-01), 500 (NDC 0093-2203-05), and 1000 (NDC 0093-2203-10).

Dispense in a tight, light-resistant container. Store tablets at 20° to 25°C (68° to 77°F).

This product is light sensitive. It should be inspected before use and discarded if either color or particulate is observed.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Inform patients or their caregivers that Aci Kestomal (Metoclopramide Hydrochloride) can cause serious adverse reactions. Instruct patients to discontinue Aci Kestomal (Metoclopramide Hydrochloride) and contact a healthcare provider immediately if the following serious reactions occur:

• Tardive dyskinesia and other extrapyramidal reactions [see Warnings and Precautions (5.1, 5.2)]
• Neuroleptic malignant syndrome [see Warnings and Precautions (5.3)]
• Depression and/or possible suicidal ideation [see Warnings and Precautions (5.4)]

Inform patients or their caregivers that concomitant treatment with numerous other medications can precipitate or worsen serious adverse reactions such as tardive dyskinesia or other extrapyramidal reactions, neuroleptic malignant syndrome, and CNS depression [see Drug Interactions (7.1, 7.2)]. Explain that the prescriber of any other medication must be made aware that the patient is taking Aci Kestomal (Metoclopramide Hydrochloride).

Inform patients or their caregivers that Aci Kestomal (Metoclopramide Hydrochloride) can cause drowsiness or dizziness, or otherwise impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a motor vehicle [see Warnings and Precautions (5.8)].

Manufactured In Croatia By:

Pliva Hrvatska d.o.o.

Zagreb, Croatia

Manufactured For:

Teva Pharmaceuticals USA, Inc.

North Wales, PA 19454

Rev. Q 8/2017

MEDICATION GUIDE Aci Kestomal (Metoclopramide Hydrochloride) TABLETS, USP (MET-oh-KLOE-pra-mide), oral use

Read this Medication Guide before you start taking Aci Kestomal (Metoclopramide Hydrochloride) tablets and each time you get a refill. There may be new information. If you take another product that contains Aci Kestomal (Metoclopramide Hydrochloride) (such as Aci Kestomal (Metoclopramide Hydrochloride) injection, Aci Kestomal (Metoclopramide Hydrochloride) orally disintegrating tablets, or Aci Kestomal (Metoclopramide Hydrochloride) oral solution), you should read the Medication Guide that comes with that product. Some of the information may be different. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about Aci Kestomal (Metoclopramide Hydrochloride) tablets? Aci Kestomal (Metoclopramide Hydrochloride) tablets can cause serious side effects, including: Tardive dyskinesia (abnormal muscle movements). These movements happen mostly in the face muscles. You cannot control these movements. They may not go away even after stopping Aci Kestomal (Metoclopramide Hydrochloride) tablets. There is no treatment for tardive dyskinesia, but symptoms may decrease or go away over time after you stop taking Aci Kestomal (Metoclopramide Hydrochloride) tablets. Your chances for getting tardive dyskinesia increase: the longer you take Aci Kestomal (Metoclopramide Hydrochloride) tablets and the more Aci Kestomal (Metoclopramide Hydrochloride) tablets you take. You should not take Aci Kestomal (Metoclopramide Hydrochloride) tablets for more than 12 weeks. if you are older, especially if you are an older woman. if you have diabetes. It is not possible for your healthcare provider to know if you will get tardive dyskinesia if you take Aci Kestomal (Metoclopramide Hydrochloride) tablets. Call your healthcare provider right away if you get movements you cannot stop or control, such as: lip smacking, chewing, or puckering up your mouth frowning or scowling sticking out your tongue blinking and moving your eyes shaking of your arms and legs See the section “What are the possible side effects of Aci Kestomal (Metoclopramide Hydrochloride) tablets?” for more information about side effects.

What are Aci Kestomal (Metoclopramide Hydrochloride) tablets? Aci Kestomal (Metoclopramide Hydrochloride) tablets are a prescription medicine used in adults: for 4 to 12 weeks to relieve heartburn symptoms with gastroesophageal reflux when certain other treatments do not work. to relieve the symptoms of slow stomach emptying in people with diabetes. Aci Kestomal (Metoclopramide Hydrochloride) tablets are not recommended for use in children.

Do not take Aci Kestomal (Metoclopramide Hydrochloride) tablets if you: have a history of tardive dyskinesia or have a problem controlling your muscles and movements after taking Aci Kestomal (Metoclopramide Hydrochloride) tablets or a medicine that works like Aci Kestomal (Metoclopramide Hydrochloride) tablets. have stomach or intestine problems that could get worse with Aci Kestomal (Metoclopramide Hydrochloride) tablets, such as bleeding, blockage or a tear in the stomach or bowel wall. have a type of tumor that can cause high blood pressure such as pheochromocytoma. have epilepsy (seizures). Aci Kestomal (Metoclopramide Hydrochloride) tablets can increase your chance for seizures and make them worse. are allergic to Aci Kestomal (Metoclopramide Hydrochloride). Aci Kestomal (Metoclopramide Hydrochloride) tablets can cause serious allergic reactions. Stop taking Aci Kestomal (Metoclopramide Hydrochloride) tablets right away and get emergency help if you have any of these symptoms: swelling of your tongue, throat, lips, eyes or face. trouble swallowing or breathing. skin rash, hives, sores in your mouth, or skin blisters.

Before taking Aci Kestomal (Metoclopramide Hydrochloride) tablets, tell your healthcare provider about all of your medical conditions, including if you: have diabetes. Your dose of insulin may need to be changed. had problems controlling your muscle movements after taking any medicine. have Parkinson’s disease. have a type of tumor that can cause high blood pressure (pheochromoctyoma). have kidney or liver disease. have or had depression or mental illness. have high blood pressure. have heart failure or heart rhythm problems. have breast cancer. drink alcohol. have seizures are pregnant or plan to become pregnant. Aci Kestomal (Metoclopramide Hydrochloride) tablets may harm your unborn baby if taken during the end of pregnancy. Talk to your healthcare provider if you become pregnant while taking Aci Kestomal (Metoclopramide Hydrochloride) tablets. are breastfeeding or plan to breastfeed. Aci Kestomal (Metoclopramide Hydrochloride) can pass into your breast milk and may harm your baby. You and your healthcare provider should decide if you will take Aci Kestomal (Metoclopramide Hydrochloride) tablets or breastfeed. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Aci Kestomal (Metoclopramide Hydrochloride) tablets may affect the way other medicines work, and other medicines may affect how Aci Kestomal (Metoclopramide Hydrochloride) tablets work. Tell your healthcare provider before you start or stop other medicines. Especially tell your healthcare provider if you take: another medicine that contains Aci Kestomal (Metoclopramide Hydrochloride), such as Aci Kestomal (Metoclopramide Hydrochloride) injection or Aci Kestomal (Metoclopramide Hydrochloride) oral solution a medicine for Parkinson’s disease a blood pressure medicine a medicine for depression, especially a Monoamine Oxidase Inhibitor (MAOI) an anti-psychotic medicine, used to treat mental illness such as schizophrenia insulin medicines that can make you sleepy, such as anti-anxiety medicines, sleep medicines, and narcotics If you are not sure if your medicine is one listed above, ask your healthcare provider or pharmacist. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I take Aci Kestomal (Metoclopramide Hydrochloride) tablets? Take Aci Kestomal (Metoclopramide Hydrochloride) tablets exactly as your healthcare provider tells you. Do not change your dose unless your healthcare provider tells you to. Aci Kestomal (Metoclopramide Hydrochloride) comes as a tablet you take by mouth. You should not take Aci Kestomal (Metoclopramide Hydrochloride) tablets for more than 12 weeks. Take Aci Kestomal (Metoclopramide Hydrochloride) tablets at least 30 minutes before each meal and at bedtime. If you take too many Aci Kestomal (Metoclopramide Hydrochloride) tablets, call your poison control center at 1-800-222-1222 or go to the nearest emergency room right away.

What should I avoid while taking Aci Kestomal (Metoclopramide Hydrochloride) tablets? Do not drink alcohol while taking Aci Kestomal (Metoclopramide Hydrochloride) tablets. Alcohol may make some side effects of Aci Kestomal (Metoclopramide Hydrochloride) tablets worse, such as feeling sleepy. Do not drive, operate machinery, or do other dangerous activities until you know how Aci Kestomal (Metoclopramide Hydrochloride) tablets affect you. Aci Kestomal (Metoclopramide Hydrochloride) tablets may cause sleepiness or dizziness.

What are the possible side effects of Aci Kestomal (Metoclopramide Hydrochloride) tablets? Tardive dyskinesia (abnormal muscle movements). See “What is the most important information I need to know about Aci Kestomal (Metoclopramide Hydrochloride) tablets?” Other changes in muscle control and movement, such as: Uncontrolled spasms of your face and neck muscles, or muscles of your body, arms, and legs (dystonia). These muscle spasms can cause abnormal movements and body positions, and speech problems. These spasms usually start within the first 2 days of treatment. Rarely, these muscle spasms may cause trouble breathing. These spasms happen more often in adults less than 30 years of age. Parkinsonism. Symptoms include slight shaking, body stiffness, trouble moving or keeping your balance. If you already have Parkinson's Disease, your symptoms may become worse while you are taking Aci Kestomal (Metoclopramide Hydrochloride) tablets. Being unable to sit still or feeling you need to move your hands, feet, or body (akathisia). Symptoms can include feeling jittery, anxious, irritated or unable to sleep (insomnia), feeling the need to walk around (pacing) and tapping your feet. Neuroleptic Malignant Syndrome (NMS). NMS is a very rare but very serious condition that can happen with Aci Kestomal (Metoclopramide Hydrochloride) tablets. NMS can cause death and must be treated in a hospital. Symptoms of NMS include: high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating. Depression, thoughts about suicide, and suicide. Some people who take Aci Kestomal (Metoclopramide Hydrochloride) tablets become depressed, even if they have no history of depression. You may have thoughts about hurting or killing yourself. Some people who have taken Aci Kestomal (Metoclopramide Hydrochloride) tablets have ended their own lives (suicide). High blood pressure. Aci Kestomal (Metoclopramide Hydrochloride) tablets can cause your blood pressure to increase. Too much body water. People who have certain liver problems or heart failure and take Aci Kestomal (Metoclopramide Hydrochloride) tablets may hold too much water in their body (fluid retention). Tell your doctor right away if you have sudden weight gain, or swelling of your hands, legs, or feet. Increased prolactin. Tell your doctor if your menstrual periods stop, your breasts get larger and make milk, or you cannot have sex (impotence). These symptoms go away when you stop taking Aci Kestomal (Metoclopramide Hydrochloride) tablets. Call your healthcare provider and get medical help right away if you: feel depressed or have thoughts about hurting or killing yourself have high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating have muscle movements you cannot stop or control have muscle movements that are new or unusual The most common side effects of Aci Kestomal (Metoclopramide Hydrochloride) tablets include: restlessness drowsiness tiredness lack of energy You may have more side effects the longer you take Aci Kestomal (Metoclopramide Hydrochloride) tablets and the more Aci Kestomal (Metoclopramide Hydrochloride) tablets you take. You may still have side effects after stopping Aci Kestomal (Metoclopramide Hydrochloride) tablets. You may have symptoms from stopping Aci Kestomal (Metoclopramide Hydrochloride) tablets such as headaches, and feeling dizzy or nervous. Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of Aci Kestomal (Metoclopramide Hydrochloride) tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Aci Kestomal (Metoclopramide Hydrochloride) tablets? Store Aci Kestomal (Metoclopramide Hydrochloride) tablets at room temperature between 68°F to 77°F (20°C to 25°C). Keep Aci Kestomal (Metoclopramide Hydrochloride) tablets in the bottle it comes in and away from light. Keep the bottle closed tightly. Keep Aci Kestomal (Metoclopramide Hydrochloride) tablets and all medicines out of the reach of children.

General information about the safe and effective use of Aci Kestomal (Metoclopramide Hydrochloride) tablets. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Aci Kestomal (Metoclopramide Hydrochloride) tablets for a condition for which they were not prescribed. Do not give Aci Kestomal (Metoclopramide Hydrochloride) tablets to other people, even if they have the same symptoms that you have. They may harm them. You can ask your pharmacist or healthcare provider for information about Aci Kestomal (Metoclopramide Hydrochloride) tablets that is written for health professionals. For more information, call 1-888-838-2872.

What are the ingredients in Aci Kestomal (Metoclopramide Hydrochloride) tablets, USP? Active ingredient: Aci Kestomal (Metoclopramide Hydrochloride) hydrochloride, USP Inactive ingredients: corn starch, dibasic calcium phosphate, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured In Croatia By:

Pliva Hrvatska d.o.o.

Zagreb, Croatia

Manufactured For:

Teva Pharmaceuticals USA, Inc.

North Wales, PA 19454

Rev. D 8/2017

NDC 0093-2204-01

Aci Kestomal (Metoclopramide Hydrochloride)

Tablets, USP

5mg

PHARMACIST: Dispense the accompanying

Medication Guide to each patient.

Rx only

100 TABLETS

TEVA

NDC 0093-2203-01

Aci Kestomal (Metoclopramide Hydrochloride)

Tablets, USP

10 mg

PHARMACIST: Dispense the accompanying

Medication Guide to each patient.

Rx only

100 TABLETS

TEVA