Contact Us    Contact Us     |     Feedback
MOBILE VIEW  | 

ANTACIDS

Export To Excel

Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) This management deals with aluminum, calcium, and magnesium containing antacids. Bismuth salts are covered under another specific management.
    B) SODIUM BICARBONATE is no longer recommended as an antacid due to the risk of systemic alkalosis.

Specific Substances

    A) CONSTITUENTS OF THE GROUP
    1) ALUMINUM
    a) Aluminum carbonate
    b) Aluminum hydroxide
    c) Aluminum phosphate
    d) Dihydroxyaluminum aminoacetate
    2) CALCIUM
    a) Calcium Carbonate
    3) MAGNESIUM
    a) Magnesium carbonate
    b) Magnesium hydroxide
    c) Magnesium oxide
    d) Magnesium trisilicate
    4) SODIUM BICARBONATE
    5) COMBINATION
    a) Dihydroxyaluminum sodium carbonate
    b) Magaldrate
    6) GENERAL TERMS
    a) Antacid
    b) Antacids

Available Forms Sources

    A) FORMS
    1) Formulations (Am Pharm Assoc, 1986):
    1) Chewing gums
    2) Liquids
    3) Lozenges
    4) Powders
    5) Tablets
    B) USES
    1) Antacids are indicated for the following gastric conditions:
    a) Acute gastritis and stress ulceration (Hastings et al, 1978; Lehmann et al, 1984; Martin et al, 1980; McElwee et al, 1979; Morrissey & Barreras, 1974; Peterson & Richardson, 1985; Priebe et al, 1980) Zinner et al, 1989)
    b) Gastroesophageal reflux (Rhodes, 1982)
    c) Non-ulcer dyspepsia (Petersen, 1982; Robinson, 1984)
    d) Peptic ulcer disease (Butler & Gersh, 1975; Christensen et al, 1977; Gotthard et al, 1975; Grossman, 1980; Hollander & Harlan, 1973; Ippoliti, 1982; Isenberg et al, 1983; Lam, 1988; Littman et al, 1977; McCarthy, 1979; Meyer et al, 1977) Morris & Rhodes, 1979; (Peterson et al, 1977; Rune & Zachariassen, 1980; Rune et al, 1984; Soll, 1989; Sturdevant et al, 1977; Walan, 1984)
    e) Gastrointestinal bleeding (Hastings et al, 1978; Priebe et al, 1980)
    f) Esophagitis (Morrissey & Barreras, 1974)
    g) Prior neutralization of gastric acid during anesthesia, coma, cesarian section, or endoscopy to protect against aspiration pneumonitis (Hardman et al, 1996).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Antacids are used for the treatment of heartburn, dyspepsia, gastritis, and gastroesophageal reflux.
    B) PHARMACOLOGY: These agents work by buffering hydrochloric acid in the stomach and increasing gastric pH.
    C) TOXICOLOGY: Toxicity can result from excessive bicarbonate absorption causing systemic alkalosis, or from excessive absorption of the cations in the alkaline salts (eg, calcium, magnesium, aluminum, sodium).
    D) EPIDEMIOLOGY: Exposure is common; significant toxicity is rare and generally develops from chronic excessive use rather than acute overdose.
    E) WITH THERAPEUTIC USE
    1) Constipation or diarrhea are the most common adverse effects.
    F) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Diarrhea or constipation can develop. Asymptomatic hypermagnesemia, hypernatremia, hypercalcemia, elevations in serum aluminum concentrations or mild volume overload may also develop after chronic excessive use.
    2) SEVERE TOXICITY: With prolonged administration and/or excessively large doses, dysrhythmias, hypo- and hypertension, encephalopathy, acute renal failure, gastrointestinal obstruction and/or perforation, metabolic alkalosis, fluid, electrolyte, and mineral derangements, and myopathies and osteodystrophies have been reported. Distention and/or obstruction with perforation and hypergastrinemia have been observed with prolonged or excessive antacid administration.
    0.2.20) REPRODUCTIVE
    A) A series of 458 pregnancies showed more congenital malformations in women taking antacids in the first trimester of pregnancy than in a control group. A study of 48 pregnancies showed no malformations from antacid use. Negative reports were published for specific antacids including dihydroxyaluminum sodium carbonate and potassium citrate.

Laboratory Monitoring

    A) No routine laboratory studies are needed in patients with acute exposure.
    B) In patients with chronic excessive use, monitor vital signs and evaluate for clinical evidence of volume overload.
    C) Monitor fluids, serum electrolytes (including calcium, magnesium, and phosphorus), ECG, and renal function tests in symptomatic patients and those with chronic excessive use.
    D) Monitor serum aluminum concentrations in patients with encephalopathy after chronic use of aluminum containing antacids, particularly patients with renal failure.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TOXICITY
    1) No treatment is generally necessary beyond supportive care and cessation of antacid use.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Evaluate for electrolyte abnormalities (hypernatremia, hypermagnesemia, hypercalcemia, hypophosphatemia) and volume overload and treat as necessary. Monitor ECG.
    C) DECONTAMINATION
    1) GI decontamination is not necessary because of the poor absorption from the gastrointestinal tract and lack of systemic toxicity after acute overdose.
    D) HYPERCALCEMIA
    1) Treat with intravenous hydration; add diuretics if hypercalcemia persists.
    E) HYPERMAGNESEMIA
    1) Treat with intravenous fluids. Monitor ECG and neurologic exam (particularly deep tendon reflexes). Hemodialysis can be used to treat severe hypermagnesemia.
    F) ALUMINUM INTOXICATION
    1) Generally no treatment is required beyond cessation of exposure. Deferoxamine can be used for severe aluminum intoxication, primarily in patients with renal failure.
    G) HYPERNATREMIA
    1) Treat with intravenous hydration.
    H) CONGESTIVE HEART FAILURE
    1) Treat with nitrates and diuretics.
    I) ENHANCED ELIMINATION PROCEDURE
    1) Hemodialysis can be used to correct severe hypermagnesemia or hypercalcemia but is rarely necessary.
    J) PATIENT DISPOSITION
    1) HOME CRITERIA: Patients with minimal GI symptoms after inadvertent exposure can be managed at home.
    2) OBSERVATION CRITERIA: Patients with deliberate self-harm exposures, persistent symptoms or long-term excessive ingestion should be sent to a healthcare facility for evaluation.
    3) ADMISSION CRITERIA: Patients with persistent electrolyte abnormalities or volume overload should be admitted.
    K) PITFALLS
    1) Acute toxicity is extremely rare; avoid overly aggressive treatment.
    L) PHARMACOKINETICS
    1) Antacids are poorly absorbed from the GI tract and are largely excreted renally.
    M) PREDISPOSING CONDITIONS
    1) Patients with renal insufficiency and congestive heart failure are predisposed to developing toxicity from chronic overuse.
    N) DIFFERENTIAL DIAGNOSIS
    1) Other causes of electrolyte abnormalities or volume overload such as diuretic use, congestive heart failure, renal failure.

Range Of Toxicity

    A) Toxicity is very unlikely following a single acute overdose.

Clinical Effects

Summary Of Exposure

    A) USES: Antacids are used for the treatment of heartburn, dyspepsia, gastritis, and gastroesophageal reflux.
    B) PHARMACOLOGY: These agents work by buffering hydrochloric acid in the stomach and increasing gastric pH.
    C) TOXICOLOGY: Toxicity can result from excessive bicarbonate absorption causing systemic alkalosis, or from excessive absorption of the cations in the alkaline salts (eg, calcium, magnesium, aluminum, sodium).
    D) EPIDEMIOLOGY: Exposure is common; significant toxicity is rare and generally develops from chronic excessive use rather than acute overdose.
    E) WITH THERAPEUTIC USE
    1) Constipation or diarrhea are the most common adverse effects.
    F) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: Diarrhea or constipation can develop. Asymptomatic hypermagnesemia, hypernatremia, hypercalcemia, elevations in serum aluminum concentrations or mild volume overload may also develop after chronic excessive use.
    2) SEVERE TOXICITY: With prolonged administration and/or excessively large doses, dysrhythmias, hypo- and hypertension, encephalopathy, acute renal failure, gastrointestinal obstruction and/or perforation, metabolic alkalosis, fluid, electrolyte, and mineral derangements, and myopathies and osteodystrophies have been reported. Distention and/or obstruction with perforation and hypergastrinemia have been observed with prolonged or excessive antacid administration.

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) Hypotension and ECG changes do not usually occur until there is severe hypermagnesemia (10 to 15 mEq/L) in the presence of depressed renal function (Am Pharm Assoc, 1986).
    b) CASE REPORT (INFANT): A 4-week-old infant presented with lethargy and hypotension (68/44 mmHg) following overdose administration of a magnesium-containing antacid, 1 teaspoonful every other day for 1 week (approximately 3.5 times his estimated normal daily requirement). Serum magnesium level was 3.9 mmol/L (normal, 0.6 to 0.8 mmol/L). Following supportive care, the child recovered within 4 days after hospital admission (Sullivan & Berman, 2000).
    B) BRADYCARDIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Junctional bradyarrhythmia occurred in a patient with chronic renal failure and a magnesium blood level of 4.7 mEq/L while receiving 30 mL of a magnesium-aluminum combination antacid every 2 hours (Berns & Kollmeyer, 1976).
    C) RIGHT HEART FAILURE
    1) WITH POISONING/EXPOSURE
    a) CONGESTIVE HEART FAILURE may occur secondary to fluid retention following excessive doses of sodium-containing antacids (Rimer & Franklin, 1960).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) PULMONARY ASPIRATION
    1) WITH POISONING/EXPOSURE
    a) Aspiration pneumonia was reported in seriously ill patients treated with antacids believed to facilitate colonization of upper airway (Driks et al, 1987; DuMoulin et al, 1982).
    B) ACUTE RESPIRATORY INSUFFICIENCY
    1) WITH POISONING/EXPOSURE
    a) Respiratory depression has been reported with severe hypermagnesemia (Jenny et al, 1978; Outerbridge et al, 1973).
    b) CASE REPORT: A 16-week-old infant who received 16 doses of one third of a teaspoon of magnesium hydroxide suspension (550 mg magnesium/10 mL) over 48 hours presented with lethargy and apneic episodes (Alison & Bulugahapitiya, 1990).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) TOXIC ENCEPHALOPATHY
    1) WITH POISONING/EXPOSURE
    a) Elevated aluminum levels were found in the brain gray matter of uremic patients who died of a neurologic syndrome of unknown cause after 3 or more years of aluminum hydroxide ingestion for phosphate binding (Alfrey et al, 1976; Nathan & Pedersen, 1980).
    b) Seizures, myoclonus, confusion, and coma were reported in women with renal failure and metabolic acidosis requiring oral solutions of citrate (Shohl's solution) in combination with aluminum hydroxide gel (Bakir et al, 1989; Kirschbaum & Schoolwerth, 1989).
    B) CENTRAL NERVOUS SYSTEM DEFICIT
    1) WITH POISONING/EXPOSURE
    a) CNS depression can occur with magnesium antacid overdose (Am Pharm Assoc, 1986; Wilson et al, 1986; Sullivan & Berman, 2000), or from severe metabolic alkalosis.
    b) CASE REPORT: A 35-year-old man presented comatose (Glasgow coma score 3/15), with metabolic alkalosis (pH 7.54, HCO3 50.6 mmol/L (50.6 meq/L)), pO2 of 11 kPa (82.5 mmHg), pCO2 of 8 kPa (60 mmHg), and base excess +22), hyponatremia (sodium 127 mmol/L), hypokalemia (potassium 1.6 mmol/L), hypochloremia (chloride 66 mmol/L), and hypercalcemia. He was treated with intravenous 0.9% saline and potassium, regained consciousness an hour after presentation, and his metabolic abnormalities resolved over 4 days. He admitted to consuming 4 bottles of 500 mL each of an antacid that contains sodium alginate 520 mg, sodium bicarbonate 133.5 mg, and calcium carbonate 80 mg per 5 mL over the 48 hours prior to admission (Gawarammana et al, 2007).
    c) CASE REPORT: A 16-year-old girl with a history of acute lymphoblastic leukemia who had received a bone marrow transplant 45 days previously was admitted with epigastric pain. Two days after admission she began taking 15 mL of aluminum magnesium gel every 2 hours (1 mL contains Al(OH)3 paste 240 mg, Mg(OH)2 paste 30% 133 mg, sucrose 40 mg). Three days after initiating this therapy she was unresponsive, with isocoric unreactive pupils, absent deep tendon reflexes, flaccid hypotonic extremities, hypotensive (70/46 mmHg) and hypothermic (temperature 34.8 degrees C). Laboratory studies were significant for hypermagnesemia (serum magnesium concentration 5.6 mmol/L (normal: 0.53–1.07 mmol/L)), hyponatremia (serum sodium 128 mEq/L) and acute renal failure (creatinine 3 mg/dL (270 micromol/L, BUN 77 mg/dL (27.5 mmol/L). She was treated with intravenous fluids, vasopressors and diuretics and gradually recovered over 12 days (Jaing et al, 2002).
    C) ALZHEIMER'S DISEASE
    1) WITH POISONING/EXPOSURE
    a) Alzheimer's disease and its possible association with antacids (odds ratio, 3.1; 95% confidence interval, 1.2 to 7.9) was inferred in an inconclusive case-control study of 130 matched pairs (Graves et al, 1990). This was contrary to earlier inferences based on review of death certificates in a long-term follow-up study on cimetidine (Colin-Jones et al, 1989).
    D) DECREASED MUSCLE TONE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT (INFANT): A 4-week-old infant developed hypotonia with minimal movement of his extremities despite stimulation, after administration of a magnesium-containing antacid, 1 teaspoonful every other day for 1 week (approximately 3.5 times his estimated normal daily requirement). Serum magnesium level was 3.9 mmol/L (normal, 0.6 to 0.8 mmol/L). Following supportive care, the child's hypotonia resolved within 4 days after hospital admission (Sullivan & Berman, 2000).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) SWOLLEN ABDOMEN
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Gastric distention and flatulence with perforation due to the effervescent sodium bicarbonate was believed to be the cause of a 6-cm tear on the lesser curve of the stomach. This was observed in a 70-year-old man who suddenly became dyspneic and in pain with distended abdomen after taking 12 g of sodium bicarbonate in water (Downs & Stonebridge, 1989).
    B) DIARRHEA
    1) WITH POISONING/EXPOSURE
    a) Diarrhea was noted with use of calcium carbonate, magnesium antacids, and magnesium-aluminum hydroxides (Fordtran, 1973; (Strom, 1982; Stewart et al, 1983).
    b) Excessive ingestion of magnesium containing antacids can be an unrecognized cause of chronic diarrhea (Fine et al, 1991).
    C) CONSTIPATION
    1) WITH POISONING/EXPOSURE
    a) Constipation is the main side effect of aluminum antacids (Am Pharm Assoc, 1986).
    D) INTESTINAL OBSTRUCTION
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Small bowel obstructions due to concretions were reported in 2 patients receiving 1000 to 1400 mL/day of aluminum hydroxide suspension for 5 days. A third patient developed colonic obstruction after ingesting 120 mL/day for 40 days.
    1) All were bedridden patients with diminished bowel motility and dehydration due to hemodialysis and fluid restriction (Townsend et al, 1973).
    b) Other reports of fecal antacid concretions reinforced this predisposition in hemodialysis patients and emphasized risk of peritonitis secondary to pressure necrosis (Adams et al, 1982; Korenmen et al, 1978; Moh & Gold, 1987; Salmon et al, 1978; Welch et al, 1980).
    c) Antacid bezoars have also been reported in infants.
    1) CASE REPORT: A newborn infant who inadvertently received 12.5 mL of Gaviscon(R) developed a gastric bezoar (Hewitt & Benham, 1976).
    2) CASE REPORT: Antacid bezoar was also reported in a 1-kg infant 8 days after receiving magaldrate 2 mL every 3 hours. The bezoar was relieved with hourly nasogastric saline instillation and discontinuation of the antacid (Rosenberg, 1982).
    3) CASE REPORT: Ileal perforation with multiple fecaliths believed to be antacid bezoars was reported in an 880-g boy who received 2 mL of aluminum and magnesium hydroxides every 3 hours for gastrointestinal bleeding (Brand & Greer, 1990).
    E) HYPERGASTRINEMIA
    1) WITH POISONING/EXPOSURE
    a) Excess gastrin may be seen with chronic antacid use (Frommer, 1986; Peterson et al, 1986).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) KIDNEY STONE
    1) WITH POISONING/EXPOSURE
    a) NEPHROLITHIASIS has been reported with long-term use of calcium- and magnesium-containing antacids (Morrissey & Barreras, 1974).
    B) ACUTE RENAL FAILURE SYNDROME
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Acute renal failure associated with magnesium-ammonium-phosphate kidney stone occurred in a 51-year-old man who ingested twenty-five to fifty (25 to 50) magnesium trisilicate-aluminum hydroxide (Gelusil(R)) tablets daily for several years for gastritis (Millette & Snodgrass, 1981).
    C) DIALYSIS DEMENTIA
    1) WITH POISONING/EXPOSURE
    a) DIALYSIS ENCEPHALOPATHY SYNDROME, characterized by dysarthria, apraxia, asterixis, myoclonus, dementia, and focal seizures and vitamin D-resistant osteomalacia, has been reported in men with elevated aluminum levels in bone, brain, and muscle (Alfrey et al, 1976; Berlyne, 1980).

Acid-Base

    3.11.2) CLINICAL EFFECTS
    A) ALKALOSIS
    1) WITH POISONING/EXPOSURE
    a) Systemic alkalosis may occur with large doses or prolonged therapy with sodium bicarbonate (Korenmen et al, 1978).
    b) CASE REPORT: A 35-year-old man presented comatose (Glasgow coma score 3/15), with metabolic alkalosis (pH 7.54, HCO3 50.6 mmol/L (50.6 meq/L)), pO2 of 11 kPa (82.5 mmHg), pCO2 of 8 kPa (60 mmHg), and base excess +22), hyponatremia (sodium 127 mmol/L), hypokalemia (potassium 1.6 mmol/L), hypochloremia (chloride 66 mmol/L), and hypercalcemia. He was treated with intravenous 0.9% saline and potassium, regained consciousness an hour after presentation, and his metabolic abnormalities resolved over 4 days. He admitted to consuming 4 bottles of 500 mL each of an antacid that contains sodium alginate 520 mg, sodium bicarbonate 133.5 mg, and calcium carbonate 80 mg per 5 mL over the 48 hours prior to admission (Gawarammana et al, 2007).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) OSTEOPOROSIS
    1) WITH POISONING/EXPOSURE
    a) OSTEOMALACIA AND OSTEOPOROSIS may occur with phosphate depletion following aluminum hydroxide therapy (Andreoli et al, 1984; Saadeh et al, 1987; Spencer & Lender, 1979).
    1) CASE REPORT: Phosphate depletion resulted in bilateral hip fractures in a 40-year-old woman who consumed a daily average of 12 g magnesium oxide and 60 g aluminum aminoacetate over several months for dyspepsia (Neumann & Jensen, 1989).
    B) TOXIC MYOPATHY
    1) WITH POISONING/EXPOSURE
    a) PROXIMAL MYOPATHY AND OSTEODYSTROPHY may be exacerbated or initiated with long-term administration of aluminum antacids in persons with renal impairments (Hardman et al, 1996; Ravid & Robson, 1976).

Reproductive

    3.20.1) SUMMARY
    A) A series of 458 pregnancies showed more congenital malformations in women taking antacids in the first trimester of pregnancy than in a control group. A study of 48 pregnancies showed no malformations from antacid use. Negative reports were published for specific antacids including dihydroxyaluminum sodium carbonate and potassium citrate.
    3.20.2) TERATOGENICITY
    A) MALFORMATIONS
    1) CASE SERIES: A series of 458 pregnancies showed more congenital malformations in women taking antacids in the first trimester of pregnancy than in a control group (Nelson & Forfar, 1971).
    B) LACK OF EFFECT
    1) Antacids have not been seriously implicated as teratogens in the humans (Schardein, 1985).
    2) Negative reports were published for specific antacids including dihydroxyaluminum sodium carbonate and potassium citrate (Dordevic & Beric, 1972; Mellin, 1964).
    3) A study of 48 pregnancies showed no malformations from antacid use (Jacobs, 1975).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No routine laboratory studies are needed in patients with acute exposure.
    B) In patients with chronic excessive use, monitor vital signs and evaluate for clinical evidence of volume overload.
    C) Monitor fluids, serum electrolytes (including calcium, magnesium, and phosphorus), ECG, and renal function tests in symptomatic patients and those with chronic excessive use.
    D) Monitor serum aluminum concentrations in patients with encephalopathy after chronic use of aluminum containing antacids, particularly patients with renal failure.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Serum aluminum, calcium, and magnesium in patients with renal impairment. Monitor serum electrolytes as well.
    a) Normal serum aluminum levels are less than 15 mcg/L (Monteagudo et al, 1989).
    b) Normal total serum calcium levels are 9 to 10.4 mg/dL (4.5 to 5.2 mEq/L). Symptoms may appear when plasma calcium reaches 6.6 mEq/L (JEF Reynolds , 1990).
    c) Normal serum magnesium levels range from 1.3 to 2.6 mEq/L (Baselt & Cravey, 1989).
    B) ACID/BASE
    1) Monitor pH.
    4.1.3) URINE
    A) Urine electrolytes and pH in symptomatic patients (Gibaldi et al, 1974)
    4.1.4) OTHER
    A) OTHER
    1) STOOL
    a) Stool magnesium concentrations can be used to identify patients with diarrhea related to excessive use of magnesium containing antacids. In a volunteer study, stool magnesium concentration was 45 mmol/L in subjects with diarrhea induced by magnesium antacids, compared with 14.6 mmol/day in normal subjects. The authors also found that 15 of 359 patients with unexplained chronic diarrhea (4.2%) had biochemical and/or clinical evidence that magnesium ingestion was a significant cause of the diarrhea (Fine et al, 1991).

Radiographic Studies

    A) RADIOGRAPHIC, OTHER
    1) Radiologic features of aluminum-related bone disease are osteopenia, pathologic fractures, Looser's zones, and subperiosteal resorption which are hard to distinguish from the features of osteitis fibrosa cystica (Monteagudo et al, 1989; Sherrard, 1986).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with persistent electrolyte abnormalities or volume overload should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Patients with minimal GI symptoms after inadvertent exposure can be managed at home.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with deliberate self-harm exposures, persistent symptoms or long-term excessive ingestion should be sent to a healthcare facility for evaluation.

Monitoring

    A) No routine laboratory studies are needed in patients with acute exposure.
    B) In patients with chronic excessive use, monitor vital signs and evaluate for clinical evidence of volume overload.
    C) Monitor fluids, serum electrolytes (including calcium, magnesium, and phosphorus), ECG, and renal function tests in symptomatic patients and those with chronic excessive use.
    D) Monitor serum aluminum concentrations in patients with encephalopathy after chronic use of aluminum containing antacids, particularly patients with renal failure.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) GI decontamination is not necessary because of the poor absorption from the gastrointestinal tract and lack of systemic toxicity after acute overdose.
    6.5.2) PREVENTION OF ABSORPTION
    A) GI decontamination is not necessary because of the poor absorption from the gastrointestinal tract and lack of systemic toxicity after acute overdose.
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TOXICITY: No treatment is generally necessary beyond supportive care and cessation of antacid use.
    2) MANAGEMENT OF SEVERE TOXICITY: Evaluate for electrolyte abnormalities (hypernatremia, hypermagnesemia, hypercalcemia, hypophosphatemia) and volume overload and treat as necessary. Monitor ECG.
    B) MONITORING OF PATIENT
    1) No routine laboratory studies are needed in patients with acute exposure.
    2) In patients with chronic excessive use, monitor vital signs and evaluate for clinical evidence of volume overload.
    3) Monitor fluids, serum electrolytes (including calcium, magnesium, and phosphorus), ECG, and renal function tests in symptomatic patients and those with chronic excessive use.
    4) Monitor serum aluminum concentrations in patients with encephalopathy after chronic use of aluminum containing antacids, particularly patients with renal failure.
    C) ALUMINUM INTOXICATION
    1) Generally no treatment is required beyond cessation of exposure. Deferoxamine can be used for severe aluminum intoxication, primarily in patients with renal failure.
    2) Excessive aluminum tissue deposits can be mobilized with deferoxamine prior to hemodialysis (Wills & Savory, 1983).
    D) HYPERCALCEMIA
    1) Symptomatic hypercalcemia in chronic ingestion may require fluids and diuretic therapy.
    E) HYPERMAGNESEMIA
    1) Treat with intravenous fluids. Monitor ECG and neurologic exam (particularly deep tendon reflexes). Hemodialysis can be used to treat severe hypermagnesemia but is rarely necessary.
    2) Calcium can displace magnesium from cell membranes and thus antagonize respiratory depression caused by hypermagnesemia (Gilman et al, 1990).
    3) Correct hypotension with fluids and/or pressor agents.

Enhanced Elimination

    A) HEMODIALYSIS
    1) Hemodialysis and peritoneal dialysis can reduce serum aluminum, calcium, and magnesium concentrations, but are rarely necessary after acute ingestion (Ferdinandus et al, 1981; Wills & Savory, 1983).

Range Of Toxicity

Summary

    A) Toxicity is very unlikely following a single acute overdose.

Therapeutic Dose

    7.2.1) ADULT
    A) SPECIFIC SUBSTANCE
    1) ALUMINUM HYDROXIDE/MAGNESIUM HYDROXIDE ORAL LIQUID
    a) 2 to 4 teaspoonfuls between meals or at bedtime for treatment of indigestion, heartburn, upset stomach (Prod Info aluminum hydroxide, magnesium hydroxide oral liquid, 2005).
    2) CALCIUM CARBONATE
    a) 4 chewable tablets (1040 mg), in 2 divided doses, administered in the morning and at night (Prod Info calcium carbonate chewable oral tablets, 2007).
    3) MAGNESIUM HYDROXIDE ORAL LIQUID
    a) 1 to 3 teaspoonfuls (400 to 1200 mg) up to 4 times daily (Prod Info MILK OF MAGNESIA oral liquid, 2007).
    4) SODIUM BICARBONATE
    a) Less than 60 years of age: 1 to 4 tablets (each tablet containing 650 mg) every 4 hours, not to exceed 24 tablets/24 hours, up to a maximum duration of therapy of 2 weeks (Prod Info sodium bicarbonate oral tablets, 2008).
    b) 60 years and older: 1 to 2 tablets (each tablet containing 650 mg) every 4 hours, not to exceed 12 tablets/24 hours, up to a maximum duration of therapy of 2 weeks.
    7.2.2) PEDIATRIC
    A) SPECIFIC SUBSTANCE
    1) ALUMINUM HYDROXIDE/MAGNESIUM HYDROXIDE ORAL LIQUID
    a) 12 years and older: 2 to 4 teaspoonfuls between meals or at bedtime for treatment of indigestion, heartburn, upset stomach (Prod Info aluminum hydroxide, magnesium hydroxide oral liquid, 2005).
    2) CALCIUM CARBONATE
    a) 2 to 5 years (11 to 21 kg): 1 chewable tablet (400 mg) and repeat as needed; MAX dose is 3 tablets in a 24-hour-period (Prod Info CHILDREN'S MYLANTA(R) oral chewable tablet, 2006).
    b) 6 to 11 years (22 to 43 kg): 2 chewable tablets (400 mg) and repeat as needed; MAX dose is 6 tablets in a 24-hour-period (Prod Info CHILDREN'S MYLANTA(R) oral chewable tablet, 2006).
    3) MAGNESIUM HYDROXIDE ORAL LIQUID
    a) 12 years and older: 1 to 3 teaspoonfuls (400 to 1200 mg) up to 4 times daily (Prod Info MILK OF MAGNESIA oral liquid, 2007).

Maximum Tolerated Exposure

    A) SPECIFIC SUBSTANCE
    1) ALUMINUM: A maximum daily dose of elemental aluminum has been estimated to be 30 mg/kg; however, a safe dose has yet to be determined (Committee on Nutrition, 1986).
    2) CALCIUM: Chronic administration of calcium carbonate given at a dose of 4 to 60 g/day for 2 to 60 days and combined with sodium bicarbonate can cause milk-alkali syndrome. Cases where doses have been lower (5 to 10 g/day) have involved predisposing factors such as renal impairment (Ginsberg et al, 1973).
    3) SODIUM BICARBONATE: The suggested daily maximum intake is 200 mEq of sodium bicarbonate for patients under 60 years old and 100 mEq for those 60 years of age and older (Schmidt, 1974).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) CASE REPORTS
    a) INFANT: A 4-week-old infant developed hypermagnesemia with lethargy and hypotonia following overdose administration of a magnesium-containing antacid, 1 teaspoonful every other day for 1 week (approximately 3.5 times his estimated normal daily requirement). On presentation, the child's serum magnesium concentration was 3.9 mmol/L (normal, 0.6 to 0.8 mmol/L) (Sullivan & Berman, 2000).

Pharmacology Toxicology

Pharmacologic Mechanism

    A) EFFECTS ON ACID SECRETION:
    1) The primary action of antacid is to neutralize gastric acid, thereby, increasing the pH in the stomach and duodenal bulb (Hannibal et al, 1980).
    2) Elevation of the pH in the gastric antrum increases the secretion of gastrin and causes a compensatory secretion of acid and pepsin.
    3) This rebound secretion is brief and of a low degree with aluminum hydroxide, magnesium hydroxide, or sodium bicarbonate but is prolonged and intense with calcium carbonate (Hardman et al, 1996).
    B) ANTIPEPTIC EFFECTS: The anti-pepsin effect of antacids have been attributed to the following mechanisms:
    1) An increase in the pH to above 4 resulting in inhibition of pepsinogen conversion to pepsin (Piper & Fenton, 1964).
    2) Adsorption of pepsin by the antacid (Berstad, 1982; Kuruvilla, 1971; Piper & Fenton, 1961).
    3) Possible stimulation of endorphin release or prostaglandin formation (Johansson, 1987).
    C) ESOPHAGEAL SPHINCTER: Raising the intragastric pH can increase the lower esophageal sphincter tone (Feurle, 1975).
    D) MUCOSAL BARRIER: A possible protective effect of antacids is the tightening of the mucosal barrier without actually coating the mucosal lining (Dill, 1972).
    E) CYTOPROTECTIVE EFFECTS: Of antacids were demonstrated in studies with rats.
    1) Antacids may cause local hyperosmolality that can stimulate prostaglandin synthesis (Szelenyi et al, 1983).
    2) Antacids can increase the depth of the gastric mucosa layer which is the site of hydrochloric acid neutralization (James & Marriott, 1982).
    3) The cytoprotective effect of aluminum hydroxide in alcohol-induced gastric mucosal damage can be due to normalization of vascular permeability via release of endogenous prostaglandin E2 and involvement of sulfhydryl compounds (Szelenyi & Brune, 1986).
    F) ALUMINUM:
    1) Aluminum-containing antacids can delay gastric emptying time in animals and, in humans, this effect is related to the aluminum concentration in the gastric contents (Hurwitz & Sheehan, 1971; Hurwitz et al, 1976).
    2) Aluminum binds with and decreases dietary phosphate absorption in the gut causing release of calcium from the bone with resulting osteomalacia and osteoporosis (Spencer & Lender, 1979).
    3) Aluminum hydroxide can be potentially therapeutic for gastric ulcers with bile salt reflux because this antacid has a strong affinity for bile salts and lysolecithin (Clain et al, 1977; Kivilaakso, 1982).
    4) Solubilization of aluminum-containing antacids in acidic medium enhances their mucosal protective activity, probably by releasing an activated aluminum ion, the hexaaquoaluminum cation (DiJoseph et al, 1989).
    G) CALCIUM AND MAGNESIUM can cause pancreatic enzyme secretion and gallbladder emptying (Holtermuller & Dehdaschti, 1982).
    1) Calcium carbonate reacts with gastric acid to form carbon dioxide, water, and calcium chloride (Malagelada & Carlson, 1982). It can induce gastric hypersecretion, especially in the presence of food (Barreras, 1973; Case, 1973; Fordtran, 1968).
    2) Magnesium salts cause duodenal secretion of cholecystokinin which may stimulate motility and fluid secretion (Hardman et al, 1996).
    H) SODIUM BICARBONATE reacts with gastric acid to form sodium chloride, water, and carbon dioxide (Malagelada & Carlson, 1982).

Physicochemical

Molecular Weight

    A) Varies

References

General Bibliography

    1) Adams PL, Rutsky EA, & Rostand SG: Lower gastrointestinal tract dysfunction in patients receiving long-term hemodialysis. Arch Intern Med 1982; 142:303-306.
    2) Alfrey AC, LeGendre, & Kaehny WD: The dialysis encephalopathy syndrome. N Engl J Med 1976; 294:184-188.
    3) Alison LH & Bulugahapitiya D: Laxative-induced magnesium poisoning in a 6-week-old infant (letter). Br Med J 1990; 300:126.
    4) Am Pharm Assoc: Handbook of Nonprescription Drugs, 8th ed, The National Professional Society of Pharmacists, Washington, DC, 1986.
    5) Andreoli SP, Bergstein JM, & Sherrard DJ: Aluminum intoxication from aluminum-containing phosphate binders in children with azotemia not undergoing dialysis. N Engl J Med 1984; 310:1079-1084.
    6) Bakir AA, Hryhorczuk DO, & Ahmed S: Hyperaluminemia in renal failure: the influence of age and citrate intake. Clin Nephrol 1989; 31:40-44.
    7) Barreras RF: . Calcium and gastric secretion. Gastroenterol 1973; 64:1168-1184.
    8) Baselt RC & Cravey RH: Disposition of Toxic Drugs and Chemicals in Man, 3rd ed. Year Book Medical Publishers, Chicago, IL, 1989.
    9) Berlyne GM: Aluminum toxicity in renal failure. Int J Artif Organs 1980; 3:60-61.
    10) Berns AS & Kollmeyer KR: Magnesium-induced bradycardia (letter). Ann Intern Med 1976; 85:760-761.
    11) Berstad A: Antacids and pepsin. Scand J Gastroenterol 1982; 17(Suppl 75):13-15.
    12) Brand JM & Greer FR: Hypermagnesemia and intestinal perforation following antacid administration in a premature infant. Pediatrics 1990; 85:121-124.
    13) Burnett CH, Commons RR, & Albright F: Hypercalcemia without hypercalciuria or hypophosphatemia, calcinosis, and renal insufficiency. New Engl J Med 1949; 240:787-794.
    14) Butler ML & Gersh H: Antacid versus placebo in hospitalized gastric ulcer patients: A controlled therapeutic study. Am J Dig Dis 1975; 20:803-807.
    15) Canning G & Slater SD: Failure to diagnose the milk-alkali syndrome. Scot Med J 1987; 32:056-057.
    16) Case RM: Calcium and gastrointestinal secretion. Digestion 1973; 8:269-288.
    17) Christensen E, Juhl E, & Tygstrup N: Treatment of duodenal ulcer. Randomized clinical trials of a decade (1964 to 1974). Gastroenterol 1977; 73:1170-1178.
    18) Clain JE, Malagelada JR, & Chadwick VS: Binding properties in vitro of antacids for conjugated bile acids. Gastroenterol 1977; 73:556-559.
    19) Colin-Jones D, Langman MJS, & Lawson DH: Alzheimer's disease in antacid users. Lancet 1989; 1:1453.
    20) Committee on Nutrition: Aluminum toxicity in infants and children. Pediatrics 1986; 78:1150-1154.
    21) D'Arcy PF & McElnay C: Drug-antacid interactions: assessment of clinical importance. Drug Intelligence Clin Pharmacy 1987; 21:607-617.
    22) DiJoseph JF, Borella LE, & Nabi Mir G: Activated aluminum complex from solubilized antacids exhibits enhanced cytoprotective activity in the rat. Gastroenterol 1989; 96:730-735.
    23) Dill JE: Antacid therapy and the gastric mucosal barrier. Gastroenterol 1972; 62:697.
    24) Dordevic M & Beric B: Our experience in the treatment of pyrosis in pregnancy with Kompensan. Med Pregl 1972; 25:277-279.
    25) Downs NM & Stonebridge PA: Gastric rupture due to excessive sodium bicarbonate ingestion. Scot Med J 1989; 34:534-535.
    26) Driks MR, Craven DE, & Celli BR: Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. N Engl J Med 1987; 317:1376-1382.
    27) DuMoulin GC, Hedley-White J, & Paterson DG: Aspiration of gastric bacteria in antacid-treated patients: a frequent cause of postoperative colonization of the airway. Lancet 1982; 1:242-245.
    28) Faraj JH: Hyperosmolality due to antacid treatment. Anesthesia 1989; 44:911-912.
    29) Ferdinandus J, Pederson JA, & Whang R: Hypermagnesemia as a cause of refractory hypotension, respiratory depression, and coma. Arch Intern Med 1981; 141:669-670.
    30) Feurle GE: Effect of rising intragastric pH induced by several antacids on serum gastrin concentration in duodenal ulcer patients and in a control group. Gastroenterol 1975; 68:1-7.
    31) Fine KD, Sant Ana CA, & Fordtran JS: Diagnosis of magnesium-induced diarrhea.. N Engl J Med 1991; 324:1012-1017.
    32) Fleming LW, Prescott A, & Stewat WK: Bioavailability of aluminum. Lancet 1989; 1:433.
    33) Fordtran JS: Acid rebound. N Engl J Med 1968; 279:900-905.
    34) French JK, Holdaway IM, & Williams LC: Milk alkali syndrome following over-the-counter antacid self-medication. N Zealand Med J 1986; 99:322-323.
    35) Frommer D: Antacid-induced hypergastrinemia (letter). Gastroenterology 1986; 91:788-789.
    36) Gawarammana IB , Coburn J , Greene S , et al: Severe hypokalaemic metabolic alkalosis following ingestion of gaviscon. Clin Toxicol (Phila) 2007; 45(2):176-178.
    37) Gibaldi M, Grundhofer B, & Levy G: Effect of antacids on pH of urine. Clin Pharmacol Ther 1974; 16:520-525.
    38) Gilman AG, Goodman LS, & Rall TW: The Pharmacological Basis of Therapeutics, 8th ed, MacMillan Publishing Company, New York, NY, 1990.
    39) Ginsberg DS, Kaplan EL, & Katz AI: Hypercalcaemia after oral calcium carbonate therapy in patients on chronic hemodialysis. Lancet 1973; 1:1271-1274.
    40) Gotthard R, Strom M, & Bodemar G: Treatment of active prepyloric and duodenal ulcers with antacid/anticholinergic cimetidine and placebo. Scand J Gastroenterol 1975; 17(Suppl 75):86-96.
    41) Graves AB, White E, & Koepsell TD: The association between aluminum-containing products and Alzheimer's disease. J Clin Epidemiol 1990; 43:35-44.
    42) Grossman MI: The use of antacids in the treatment of peptic ulcer. Scand J Gastroenterol 1980; 15:37-40.
    43) Hannibal S, Remvig L, & Rune SJ: The effect of antacid on gastric and duodenal bulb acidity. Scand J Gastroenterol 1980; 15:29-36.
    44) Hardman JG, Limbird LE, & Molinoff PB: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, McGraw-Hill, New York, NY, 1996.
    45) Hastings PR, Skillman JJ, & Bushnell LS: Antacid titration in the prevention of acute gastrointestinal bleeding. N Engl J Med 1978; 298:1041-1045.
    46) Hewitt GJ & Benham ES: A complication of Gaviscon(R) in a neonate - The Gavisconoma. Aust Paediatr J 1976; 12:47-48.
    47) Hollander D & Harlan J: Antacids versus placebos in peptic ulcer therapy. A controlled double-blind investigation. JAMA 1973; 226:1181-1185.
    48) Holtermuller KH & Dehdaschti M: Antacids and hormones. Scand J Gastroenterol 1982; 17(Suppl 75):24-31.
    49) Hurwitz A & Sheehan MB: The effects of antacids on the absorption of orally administered pentobarbital in the rat. J Pharmacol Exp Ther 1971; 179:124-131.
    50) Hurwitz A, Robinson RG, & Vats TS: Effects of antacids on gastric emptying. Gastroenterol 1976; 71:268-273.
    51) Insogna KL, Bordley DR, & Caro JF: Osteomalacia and weakness from excessive antacid ingestion. JAMA 1980; 244:2544-2546.
    52) Ippoliti AF: Antacid therapy for duodenal and gastric ulcer: the experience in the United States. Scand J Gastroenterol 1982; 17(Suppl 75):82-85.
    53) Isenberg JI, Peterson WL, & Elashoff JD: Healing of benign gastric ulcer with low-dose antacid or cimetidine: a double-blind, randomized, placebo-controlled trial. N Eng J Med 1983; 308:1319-1324.
    54) JEF Reynolds : Martindale: The Extra Pharmacopoeia (electronic version). The Pharmaceutical Press. London, UK (Internet Version). Edition expires 1990; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    55) Jacobs D: Maternal drug ingestion and congenital malformations. S Afr Med J 1975; 49:2073-2080.
    56) Jaing TH, Hung IJ, Chung HT, et al: Acute hypermagnesemia: a rare complication of antacid administration after bone marrow transplantation. Clin Chim Acta 2002; 326(1-2):201-203.
    57) James SL & Marriott C: An investigation of the effect of an antacid mucosal protective on gastric mucus. Pharm Acta Helv 1982; 57:265-267.
    58) Jameson S: Magnesium-containing antacids to patients with uremia. Scand J Urol & Nephrol 1972; 6:260-264.
    59) Jenkins JK, Best TR, & Nicks SA: Milk-alkali syndrome with a serum calcium level of 22 mg/dL and J waves on the ECG. Southern Med J 1987; 80:1444-1449.
    60) Jenny DB, Goris GB, & Urwiller RD: Hypermagnesemia following irrigation of renal pelvis. JAMA 1978; 240:1378-1379.
    61) Johansson C: Ulcerogenic drugs and antiulcer compounds: effects on gastroduodenal mucosa. Scand J Gastroenterology 1987; 22(suppl 128):24-32.
    62) Kapsner P, Langsdorf L, & Marcus R: Milk-alkali syndrome in patients treated with calcium carbonate after cardiac transplantation. Arch Intern Med 1986; 146:1965-1968.
    63) Kirschbaum BB & Schoolwerth AC: Acute aluminum toxicity associated with oral citrate and aluminum-containing antacids. Am J Med Sci 1989; 297:9-11.
    64) Kivilaakso E: Antacids and bile salts. Scand J Gastroenterol 1982; 17(Suppl 75):16-23.
    65) Korenmen MD, Stubbs MB, & Fish JC: Intestinal obstruction from medication bezoars. JAMA 1978; 240:54-55.
    66) Kuruvilla JT: Antipeptic activity. Gut 1971; 12:897-898.
    67) Lam SK: Antacids: the past, the present, and the future. Baillieres Clin Gastroenterol 1988; 2:641-654.
    68) Lehmann L, Duesel W, & Klaue P: pH control via secretin or antacid: prophylaxis of stress ulcers in high-risk surgical patients. Int Care Med 1984; 10:239-243.
    69) Levy Y, Bansal M, & Zackson DA: Phosphate depletion syndrome: case report with bone and muscle histology findings and review of the literature. J Parenter Enter Nutr 1988; 12:313-317.
    70) Littman A, Welch R, & Fruin RC: Controlled trials of aluminum hydroxide gels for peptic ulcer. Gastroenterol 1977; 73:6-10.
    71) Lotz M, Zisman E, & Bartter FC: Evidence for a phosphorus-depletion syndrome in man. N Engl J Med 1968; 275:409-415.
    72) Mackway-Jones K, Cove-Smith R, & Lawler P: Prophylactic aluminum hydroxide and hyperaluminemia in intensive care. Intensive Care Med 1987; 13:293-294.
    73) Malagelada JR & Carlson GL: Antacids and hydrochloric acid. Scand J Gastroenterl 1982; 17(Suppl 75):10-12.
    74) Martin LF, May MH, & Polk HC: Failure of gastric pH control by antacids or cimetidine in the critically ill: a valid sign of sepsis. Surgery 1980; 88:59-68.
    75) McCarthy DM: Peptic ulcer: antacids or cimetidine?. Hosp Pract 1979; 14:52-64.
    76) McElwee HP, Sirinek KR, & Levine BA: Cimetidine offers protection equal to antacids in prevention of stress ulceration following thermal injury. Surgery 1979; 86:620-624.
    77) Mellin GW: Drugs in the first trimester of pregnancy and fetal life of Homo sapiens. Am J Obstet Gynecol 1964; 90:1169-1180.
    78) Meyer JH, Schwabe A, & Isenberg JI: Treatment of peptic ulcer disease - a symposium. West J Med 1977; 126:273-287.
    79) Millette CH & Snodgrass GL: Acute renal failure associated with chronic antacid ingestion. Am J Hosp Pharm 1981; 38:1352-1355.
    80) Moh P & Gold B: Gastric antacid bezoar in a patient with chronic renal failure. State J Med 1987; 87:235-236.
    81) Monteagudo FSE, Cassidy MJD, & Folb PI: Recent developments in aluminum toxicology. Med Toxicol 1989; 4:1-16.
    82) Morrissey JF & Barreras RF: Antacid therapy. N Engl J Med 1974; 290:550-554.
    83) Nathan E & Pedersen SE: Dialysis encephalopathy in a non-dialyzed uremic boy treated with aluminum hydroxide orally. Acta Paediatr Scand 1980; 69:793-796.
    84) Nelson NM & Forfar JO: Associations between drugs administered during pregnancy and congenital malformations of the fetus. Br Med J 1971; 1:523-527.
    85) Neumann L & Jensen BG: Osteomalacia from Al and Mg antacids: report of a case of bilateral hip fracture. Acta Orthop Scand 1989; 60:361-362.
    86) Outerbridge EW, Papageorgiou A, & Stern L: Magnesium sulfate enema in a newborn: fatal systemic magnesium absorption. JAMA 1973; 224:1392.
    87) Petersen H: Antacids in non-ulcer dyspepsia. Scand J Gastroenterol 1982; 17(Suppl 75):77-78.
    88) Peterson WL & Richardson CT: Sustained fasting achlorhydria: a comparison of medical regimen. Gastroenterol 1985; 88:666-669.
    89) Peterson WL, Sturdevant RAL, & Frank HD: Healing of duodenal ulcer with an antacid regimen. N Engl J Med 1977; 297:341-345.
    90) Peterson WL, Walsh JH, & Richardson CT: Cimetidine blocks antacid-induced hypergastrinemia. Gastroenterology 1986; 90:48-52.
    91) Piper DW & Fenton BH: The absorption of pepsin. Am J Dig Dis 1961; 6:134.
    92) Piper DW & Fenton BH: pH stability and activity curves of pepsin with special reference to their clinical importance. Gut 1964; 5:506-508.
    93) Priebe HJ, Skillman JJ, & Bushnell LS: Antacids versus cimetidine in preventing acute gastrointestinal bleeding. N Engl J Med 1980; 302:426-430.
    94) Product Information: CHILDREN'S MYLANTA(R) oral chewable tablet, calcium carbonate oral chewable tablet. Merck Consumer Pharmaceuticals Co, Ft. Washington, PA, 2006.
    95) Product Information: MILK OF MAGNESIA oral liquid, magnesium hydroxide oral liquid. Humco, Texarkana, TX, 2007.
    96) Product Information: aluminum hydroxide, magnesium hydroxide oral liquid, aluminum hydroxide, magnesium hydroxide oral liquid. Goldline Laboratories,Inc, Miami, FL, 2005.
    97) Product Information: calcium carbonate chewable oral tablets, calcium carbonate chewable oral tablets. Freeda Vitamins,Inc, New York, NY, 2007.
    98) Product Information: sodium bicarbonate IV injection, sodium bicarbonate IV injection. Hospira,Inc, Lake Forest, IL, 2006.
    99) Product Information: sodium bicarbonate oral tablets, sodium bicarbonate oral tablets. Rugby Laboratories,Inc, Duluth, GA, 2008.
    100) Puntis JWL, Ballantine NE, & Durbin GM: Raised plasma aluminum in an infant on antacid. Lancet 1989; 2:923.
    101) Ravid M & Robson ML: Proximal myopathy caused by iatrogenic phosp depletion. JAMA 1976; 236:1380.
    102) Rhodes J: Oesophagitis and the role of antacid therapy. Scand J Gastroenterol 1982; 17(Suppl 75):74-76.
    103) Rimer DG & Franklin M: Sodium content of antacids. JAMA 1960; 173:995.
    104) Robinson MG: Review of peptic ulcer maintenance trials. Am J Med 1984; 77(Suppl 5B):23-29.
    105) Rosenberg HK: Antacid bezoar in a premature infant. Clin Pediatr 1982; 21:503-504.
    106) Rune SJ & Zachariassen A: Acute relief of epigastric pain by antacid in duodenal ulcer patients. Scand J Gastroenterol 1980; 15:41-45.
    107) Rune SJ, Jensen WG, & Wulff HR: Additional antacid does not increase the effect of cimetidine in gastric ulcer disease. Scand J Gastroenterol 1984; 19:56-58.
    108) Saadeh G, Bauer T, & Licata A: Antacid-induced osteomalacia. Cleve Clin J Med 1987; 54:214-216.
    109) Salmon R, Aubert P, & David R: Aluminum gel causing large-bowel perforation. Lancet 1978; 1:875.
    110) Schardein JL: Chemically Induced Birth Defects, Marcel Dekker Inc, Inc, New York, 1985.
    111) Schmidt AM: Monograph for antacids and antiflatulants. Fed Register 1974; 39:19862.
    112) Sherrard DJ: Aluminum and renal osteodystrophy. Semin Nephrol 1986; 6(Suppl 1):5-11.
    113) Shields HM: Rapid fall of serum phosphorus secondary to antacid therapy. Gastroenterol 1978; 75:1137-1141.
    114) Soll AH: Duodenal ulcer and drug therapy. In Gastrointestinal Disease, 4th ed. Sleisenger MH & Fordtran JS (Eds), WB Saunders Co, Philadelphia, PA, 1989.
    115) Spencer H & Kramer L: Antacid-induced calcium loss (editorial). Arch Int Med 1983; 143:657-659.
    116) Spencer H & Lender M: Adverse effects of aluminum-containing antacids on mineral metabolism. Gastroenterol 1979; 76:603-606.
    117) Spencer H, Kramer L, & Norris C: Effects of small doses of aluminum-containing antacids on calcium and phosphorus metabolism. Am J Clin Nutr 1982; 36:32-40.
    118) Stewart RB, Hale WE, & Marks RG: Antacid use in an ambulatory elderly population. A report from Dunedin program. Dig Dis Sci 1983; 28:1062-1069.
    119) Stiel J, Mitchell CA, & Radcliff FJ: Hypercalcemia in patients with peptic ulceration receiving large doses of calcium carbonate. Gastroenterol 1967; 53:900.
    120) Strom M: Antacid side-effects on bowel habits. Scand J Gastroenterol 1982; 17(Suppl 75):54-55.
    121) Sturdevant RAL, Isenberg JI, & Secrist D: Antacid and placebo produced similar pain relief in duodenal ulcer patients. Gastroenterol 1977; 72:1-5.
    122) Sullivan JE & Berman BW: Hypermagnesemia with lethargy and hypotonia due to administration of magnesium hydroxide to a 4-week-old infant. Arch Pediatr Adolesc Med 2000; 154:1272-1274.
    123) Sutton RAL & Dirks JH: Calcium and magnesium: renal handling and disorders of metabolism. In: Brenner BM, Rector FC (Eds): The Kidney, 3rd ed, WB Saunders, Philadelphia, PA, 1986.
    124) Szelenyi I & Brune K: Possible role of sulfhydryls in mucosal protection induced by aluminum hydroxide. Dig Dis Sci 1986; 31:1207-1210.
    125) Szelenyi I, Postius SI, & Engler H: Evidence for a functional protective effect produced by antacids in the rat stomach. Eur J Pharmacol 1983; 88:403-406.
    126) Townsend CM Jr, Remmers AR Jr, & Sarles HE: Intestine: obstruction from medication bezoar in patients with renal failure. N Engl J Med 1973; 288:1058.
    127) Valli C, Schulthess HK, & Asper R: Interaction of nutrients with antacids: a complication during enteral tube feeding. Lancet 1986; 1:747-748.
    128) VanKalmthout PM, Engels LGJ, & Bakker HH: Severe copper deficiency due to excessive use of an antacid combined with pyloric stenosis. Dig Dis Sci 1982; 27:859-861.
    129) Walan A: Antacid and anticholinergics in the treatment of duodenal ulcer. Clin Gastroenterol 1984; 13:473-479.
    130) Welch JP, Schweizer RT, & Bartus SA: Management of antacid impactions in hemodialysis and renal transplant patients. Am J Surg 1980; 139:561-568.
    131) Williams JW, Vera SR, & Peters TG: Biliary excretion of aluminum in aluminum osteodystrophy with liver disease. Ann Intern Med 1986; 104:782-785.
    132) Wills MR & Savory J: Aluminum poisoning: dialysis encephalopathy, osteomalacia, and anemia. Lancet 1983; 29-33.
    133) Wilson C, Azmy AF, & Beattie TJ: Hypermagnesemia and progression of renal failure associated with renacidin therapy. Clin Nephrol 1986; 25:266-267.