Professional Drug Information > Acetaminophen, Sodium Bicarbonate, and Citric Acid

Acetaminophen, Sodium Bicarbonate, and Citric Acid (Systemic)

INN:
Acetaminophen—Paracetamol

VA CLASSIFICATION
Primary: CN103

Commonly used brand name(s): Bromo-Seltzer.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

^†Not commercially available in Canada.

Category:


Analgesic-antacid—

Indications

Accepted

Pain and upset stomach (treatment)—Acetaminophen, sodium bicarbonate, and citric acid combination is indicated for relief of mild to moderate pain, primarily when an upset stomach is also present ^{04}. However, it is recommended that this medication be used only on an occasional or short-term basis; long-term use is not recommended because of the high sodium bicarbonate content ^{06}.


Pharmacology/Pharmacokinetics

Mechanism of action/Effect:


Analgesic:

The mechanism of acetaminophen's analgesic action has not been fully determined. Acetaminophen may act predominantly by inhibiting prostaglandin synthesis in the central nervous system (CNS) and, to a lesser extent, through a peripheral action by blocking pain-impulse generation. The peripheral action may also be due to inhibition of prostaglandin synthesis or to inhibition of the synthesis or actions of other substances that sensitize pain receptors to mechanical or chemical stimulation. ^{01}



Antacid:

The antacid action is produced by the sodium citrate that is formed, along with carbon dioxide, when the effervescent granules are dissolved in water ^{04}. The antacid citrate reacts chemically to neutralize or buffer existing quantities of stomach acid but has no direct effect on its output. This action results in increased pH of stomach contents, thus providing relief of hyperacidity symptoms. Also, the acid concentration within the lumen of the esophagus is reduced; the resultant increase in intra-esophageal pH and decrease in pepsin activity aid in the control of gastroesophageal reflux ^{{02} {03}}.


Distribution:




Acetaminophen:

In breast milk: Peak concentrations of 10 to 15 mcg per mL (66.2 to 99.3 micromoles/L) of acetaminophen have been measured 1 to 2 hours following maternal ingestion of a single 650-mg dose. The half-life in breast milk is 1.35 to 3.5 hours. ^{01}


Protein binding:




Acetaminophen:

Not significant with doses producing plasma concentrations below 60 mcg per mL (397.2 micromoles/L); may reach moderate levels with high or toxic doses ^{01}.


Biotransformation:




Acetaminophen:

Approximately 90 to 95% of a dose is metabolized in the liver, primarily by conjugation with glucuronic acid, sulfuric acid, and cysteine. An intermediate metabolite, which may accumulate in overdosage after the primary metabolic pathways become saturated, is hepatotoxic and possibly nephrotoxic. ^{01}


Half-life:


Acetaminophen:

1 to 4 hours; does not change with renal failure but may be prolonged in acute overdosage, in some forms of hepatic disease, in the elderly, and in the neonate; may be somewhat shortened in children ^{01}.

In breast milk—1.35 to 3.5 hours.


Time to peak effect:


Acetaminophen:

1 to 3 hours ^{01}.


Duration of action:


Acetaminophen:

3 to 4 hours ^{01}.


Elimination:


Acetaminophen—
        Renal, as metabolites, primarily conjugates; 3% of a dose may be excreted unchanged ^{01}.



In dialysis—
        Hemodialysis—120 mL per minute (for unmetabolized acetaminophen); metabolites are also cleared rapidly ^{01}.
        Hemoperfusion—200 mL per minute ^{01}.
        Peritoneal dialysis—<10 mL per minute ^{01}.



Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to aspirin may not be sensitive to acetaminophen; however, acetaminophen has produced mild bronchospastic reactions in some aspirin-sensitive asthmatics (less than 5% of those tested) ^{01}.

Pregnancy/Reproduction
Fertility—

Acetaminophen

Chronic toxicity studies in animals have shown that high doses of acetaminophen cause testicular atrophy and inhibition of spermatogenesis; the relevance of this finding to use in humans is not known ^{01}.


Pregnancy—

Acetaminophen

Problems in humans have not been documented. Although controlled studies have not been done, it has been shown that acetaminophen crosses the human placenta ^{01}.



Sodium bicarbonate

Problems in humans have not been documented. However, risk-benefit must be considered because chronic use may lead to systemic alkalosis. Also, ingestion of substantial quantities of sodium may cause edema and weight gain. ^{03}


Breast-feeding


Acetaminophen:

Problems in humans have not been documented. Although peak concentrations of 10 to 15 mcg per mL (66.2 to 99.3 micromoles/L) have been measured in breast milk 1 to 2 hours following maternal ingestion of a single 650-mg dose, neither acetaminophen nor its metabolites were detected in the urine of the nursing infants. The half-life in breast milk is 1.35 to 3.5 hours. ^{01}



Sodium bicarbonate:

Problems in humans have not been documented ^{03}.


Pediatrics


Acetaminophen:

Appropriate studies performed to date with acetaminophen have not demonstrated pediatrics-specific problems that would limit the usefulness of the analgesic in children ^{01}.



Sodium bicarbonate:

Antacids should not be given to young children (up to 6 years of age) who complain of stomach upset unless prescribed by a physician. Because young children usually are not able to describe their symptoms precisely, proper diagnosis is necessary to rule out the presence of a medical problem (e.g., appendicitis) that requires other treatment. ^{03}



Geriatrics



Acetaminophen:

Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of acetaminophen in the elderly. ^{01}



Sodium bicarbonate:

Elderly patients are more likely to have age-related renal function impairment; ingestion of significant quantities of sodium may be hazardous to these patients ^{03}. Use of this analgesic-antacid combination should preferably be limited to 5 days at a time, because of the very high sodium content, unless more prolonged therapy is prescribed and monitored by a physician ^{06}.


Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

^{01}{02}{03}The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Note: Not all interactions between sodium bicarbonate and other oral medications have been identified in this monograph. Because the antacid may increase or reduce the rate and/or extent of absorption of other oral medications, patients should be advised not to take any other oral medication within 1 to 2 hours of sodium bicarbonate.
Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Acidifiers, urinary, such as:
Ammonium chloride
Ascorbic acid
Potassium or sodium phosphates    (the acetaminophen and antacid combination medication contains sufficient sodium bicarbonate to alkalinize the urine and counteract the effect of urinary acidifiers; frequent use of sodium bicarbonate, especially in high doses, is best avoided by patients receiving therapy to acidify the urine ^{09})


» Alcohol, especially chronic abuse of or
Hepatic enzyme inducers (See Appendix II ) or
Hepatotoxic medications, other (See Appendix II )    (risk of hepatotoxicity with single toxic doses or prolonged use of high doses of acetaminophen may be increased in alcoholics or in patients regularly taking other hepatotoxic medications or hepatic enzyme inducers)

    (chronic use of barbiturates [except butalbital] or primidone has been reported to decrease the therapeutic effects of acetaminophen, probably because of increased metabolism resulting from induction of hepatic microsomal enzyme activity; the possibility should be considered that similar effects may occur with other hepatic enzyme inducers)


Alkalizers, urinary, other, such as:
Antacids, calcium and/or magnesium-containing
Carbonic anhydrase inhibitors
Citrates
Sodium bicarbonate    (frequent use of the sodium bicarbonate in this combination medication by patients receiving other urinary alkalizers may increase the risk of additive effects, including an unacceptably high degree of urinary alkalinization and, except with the carbonic anhydrase inhibitors, systemic alkalosis ^{10})

    (concurrent use of sodium citrate with sodium bicarbonate may promote the development of calcium stones in patients with uric acid stones, due to sodium ion opposition to the hypocalciuric effect of the alkaline load; may also cause hypernatremia)


Amphetamines or
» Mecamylamine or
Quinidine    (antacid-induced alkalinization of the urine may inhibit urinary excretion of these medications, possibly causing increases in half-life, duration of action, and/or toxicity; although the clinical significance of this effect is probably minimal with occasional low-dose use of this acetaminophen and antacid combination, concurrent use with mecamylamine is not recommended)


Anticholinergics or other medications with anticholinergic activity (See Appendix II )    (antacids may decrease absorption of anticholinergics, thereby reducing their effectiveness; it is recommended that the 2 medications be taken at least 1 hour apart)

    (antacid-induced alkalinization of the urine may also delay urinary excretion, and thereby potentiate the side effects, of anticholinergics; however, the clinical significance of this effect is probably minimal with occasional low-dose use of this combination medication)


Anticoagulants, coumarin- or indandione-derivative    (concurrent chronic, high-dose administration of acetaminophen may increase the anticoagulant effect, possibly by decreasing hepatic synthesis of procoagulant factors; anticoagulant dosage adjustment based on increased monitoring of prothrombin time may be necessary when chronic, high-dose acetaminophen therapy is initiated or discontinued; however, this does not apply to occasional use, or to chronic use of doses below 2 grams per day, of acetaminophen)


Aspirin or other salicylates or
Nonsteroidal anti-inflammatory drugs (NSAIDs)    (prolonged concurrent use of acetaminophen and a salicylate is not recommended because chronic, high-dose administration of the combined analgesics [1.35 grams daily, or cumulative ingestion of 1 kg annually, for 3 years or longer] significantly increases the risk of analgesic nephropathy, renal papillary necrosis, end-stage renal disease, and cancer of the kidney or urinary bladder; also, it is recommended that for short-term use, the combined dose of acetaminophen plus salicylate not exceed that recommended for acetaminophen or a salicylate given individually)

    (prolonged concurrent use of acetaminophen and NSAIDs other than aspirin may also increase the risk of adverse renal effects; it is recommended that patients be under close medical supervision while receiving such combined therapy)

    (diflunisal may increase the plasma concentration of acetaminophen by 50%, leading to increased risk of acetaminophen-induced hepatotoxicity)

    (antacid-induced alkalinization of the urine may increase renal salicylate excretion and lower serum salicylate concentrations; to prevent fluctuations in salicylate concentration, frequent or high-dose use of antacid-containing products should be avoided in patients receiving chronic, high-dose salicylate therapy, e.g., patients with arthritis or rheumatic fever)


Calcium-containing medications or
Milk or milk products    (prolonged concurrent use with sodium bicarbonate may result in the milk-alkali syndrome)


Ciprofloxacin or
Norfloxacin    (antacid-induced alkalinization of the urine may reduce the solubility of these medications in urine, thereby increasing the risk of crystalluria and nephrotoxicity; however, the clinical significance of this effect is probably minimal with occasional low-dose use of an acetaminophen and antacid combination)


Diuretics, potassium-depleting, such as:
Diuretics, loop
Diuretics, thiazide    (concurrent use with sodium bicarbonate may increase the possibility of hypochloremic alkalosis)


Enteric-coated medications    (antacids increase intragastric pH, which may cause early dissolution, and loss of the protective effect, of enteric coatings; gastric or duodenal irritation may result; the medications should be taken several hours apart)


Histamine H ₂-receptor antagonists, such as:
Cimetidine
Famotidine
Nizatidine
Ranitidine    (antacids may decrease absorption of histamine H ₂-receptor antagonists when ingested simultaneously; the medications should be taken at least 30 to 60 minutes apart)


Iron supplements, oral    (antacids may decrease absorption of orally administered iron; administration of the medications should be separated by the largest possible interval)


» Methenamine    (antacid-induced alkalinization of the urine reduces the efficacy of methenamine by inhibiting its conversion to the active substance, formaldehyde; although the clinical significance of this effect with occasional low-dose use of an acetaminophen and antacid combination has not been determined, concurrent use is best avoided)


Mexiletine    (marked antacid-induced alkalinization of the urine may retard renal excretion of mexiletine)


Other medications, oral, especially:
» Ciprofloxacin^{12}
» Enoxacin^{13}
» Itraconazole^{14}
» Ketoconazole^{11}
» Lomefloxacin^{15}
» Norfloxacin^{16}
» Ofloxacin^{17}
» Tetracyclines^{11}    (antacids present as buffering agents in analgesic products may interfere with the absorption of many other orally administered medications; if used concurrently, a buffered analgesic product should be taken at least 6 hours before or 2 hours after ciprofloxacin or lomefloxacin, 8 hours before or 2 hours after enoxacin, 2 hours after itraconazole, 2 hours before or after ketoconazole, 2 hours before or after norfloxacin or ofloxacin, 1 to 3 hours before or after tetracycline, and at least 1 to 2 hours before or after other orally administered medications)


Sucralfate    (antacids may interfere with binding of sucralfate to the mucosa when ingested simultaneously; the 2 medications should be taken at least one-half hour apart)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
» Gastric acid secretion test    (antacids may antagonize the effect of pentagastrin and histamine in the evaluation of gastric acid secretory function and should not be administered on the morning of the test)


Glucose, blood, determinations    (acetaminophen may produce falsely decreased values when the glucose oxidase/peroxidase method is used, but probably not when the hexokinase/glucose-6-phosphate dehydrogenase [G6PD] method is used)

    (values may be falsely increased when certain instruments are used in glucose analysis if high acetaminophen concentrations are present; instrument manufacturer's instruction manual should be consulted)


5-Hydroxyindoleacetic acid (5-HIAA), urine, determinations    (acetaminophen may produce false-positive results with qualitative screening tests using nitrosonaphthol reagent; the quantitative test is unaffected)


Pancreatic function test using bentiromide    (administration of acetaminophen prior to the bentiromide test will invalidate test results because acetaminophen is also metabolized to an arylamine and will thus increase the apparent quantity of para-aminobenzoic acid [PABA] recovered; it is recommended that acetaminophen be discontinued at least 3 days prior to administration of bentiromide)


Uric acid, serum, determinations    (acetaminophen may produce falsely increased values when the phosphotungstate uric acid test method is used)

With physiology/laboratory test values
Bilirubin concentrations, serum and
Lactate dehydrogenase (LDH) activity, serum and
Prothrombin time and
Transaminase activity, serum    (may be increased indicating hepatotoxicity, especially in alcoholics, patients taking other hepatic enzyme inducers, or patients with pre-existing hepatic disease, when single toxic doses [> 8 to 10 grams] of acetaminophen are taken or with prolonged use of lower doses [> 3 to 5 grams a day])


Gastrin concentrations, serum and
Systemic and urinary pH    (may be increased by antacids, especially with frequent and/or high-dose administration)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Alcoholism, active or
» Hepatic disease or
» Viral hepatitis    (increased risk of acetaminophen-induced hepatotoxicity)


» Any condition in which administration of substantial quantities of sodium may be detrimental, such as:
Congestive heart failure
Edema
Hepatic cirrhosis
Hypertension
Toxemia of pregnancy
Any condition in which administration of antacids may mask symptoms, delay diagnosis, or produce other complications, such as:
» Appendicitis or symptoms of
Bleeding, gastrointestinal or rectal
» Intestinal obstruction
Intolerance to acetaminophen, sodium bicarbonate, or citric acid    (increased risk of allergic reaction)


» Renal function impairment    (ingestion of significant quantities of sodium increases the risk of hypernatremia, edema, and hypertension)

    (risk of adverse renal effects may be increased with prolonged use of high doses of acetaminophen in patients with severe renal function impairment; occasional use is acceptable)



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Hepatic function determinations    (may be required at periodic intervals during high-dose or long-term acetaminophen therapy, especially in patients with pre-existing hepatic disease ^{01})


Renal function determinations    (may be required during long-term high-dose use of this medication, especially in patients with pre-existing renal function impairment ^{03})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive: ^{{01} {02} {03}}

Those indicating need for medical attention
Incidence unknown—dependent on dosage and on frequency and duration of sodium bicarbonate administration
    
Edema (swelling of face, fingers, ankles, feet, or lower legs; weight gain)
    
hypercalcemia associated with milk-alkali syndrome (frequent urge to urinate ; continuing headache; continuing loss of appetite; nausea or vomiting; unusual tiredness or weakness)
    
increased blood pressure
    
metabolic alkalosis (mood or mental changes; muscle pain or twitching; nervousness or restlessness ; slow breathing; unpleasant taste ; unusual tiredness or weakness)—more likely in patients with renal function impairment

Incidence rare
For acetaminophen only
    
Agranulocytosis (fever with or without chills; sores, ulcers, or white spots on lips or in mouth; sore throat)
    
anemia (unusual tiredness or weakness)
    
dermatitis, allergic (skin rash, hives, or itching)
    
hepatitis (yellow eyes or skin)
    
renal colic (pain, severe and/or sharp, in lower back and/or side)—with prolonged use of high doses in patients with severe renal function impairment
    
renal failure (sudden decrease in amount of urine)
    
sterile pyuria (cloudy urine)
    
thrombocytopenia (usually asymptomatic; rarely, unusual bleeding or bruising; black, tarry stools; blood in urine or stools; pinpoint red spots on skin)
Note: Acetaminophen-induced renal function impairment may be sufficiently severe to result in uremia, especially with prolonged use of high doses in patients with pre-existing renal impairment ^{01}. Also, although a causal association has not been established, a retrospective study has suggested that long-term daily use of acetaminophen may be associated with an increased risk of chronic renal failure (analgesic nephropathy) in individuals without pre-existing renal function impairment ^{07}.






Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent
    
Increased thirst
    
stomach cramps





Overdose
For specific information on the agents used in the management of Acetaminophen, Sodium Bicarbonate, and Citric Acid overdose, see:
   • Acetylcysteine (Systemic) monograph; and/or
   • Charcoal, Activated (Oral-Local) monograph.
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute
    
Gastrointestinal upset (diarrhea; loss of appetite; nausea or vomiting; stomach cramps or pain)
    
increased sweating
Note: Although these early signs and symptoms often do not occur, they sometimes occur within 6 to 14 hours after ingestion and persist for about 24 hours.



Chronic
    
Hepatotoxicity (pain, tenderness, and/or swelling in upper abdominal area)—may occur 2 to 4 days after the overdose is ingested
Note: The first indications of overdosage may be signs and symptoms of possible liver damage and abnormalities in liver function tests, which may not occur until 2 to 4 days after ingestion of the overdose. Maximal changes in liver function tests usually occur 3 to 5 days after ingestion of the overdose.
Overt hepatic disease or failure may occur 4 to 6 days after ingestion of the overdose. Hepatic encephalopathy (with mental changes, confusion, agitation, or stupor), convulsions, respiratory depression, coma, cerebral edema, coagulation defects, gastrointestinal bleeding, disseminated intravascular coagulation, hypoglycemia, metabolic acidosis, renal tubular necrosis leading to renal failure (signs include bloody or cloudy urine and sudden decrease in amount of urine), cardiac arrhythmias, and cardiovascular collapse may occur.





Treatment of overdose


For sodium bicarbonate-induced alkolosis ^{03}:
Specific treatment—May include parenteral administration of calcium gluconate. See the package insert or Calcium Gluconate in Calcium Supplements (Systemic) monograph.

Supportive care—Rebreathing of expired air from a paper bag or mask. Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.



For acetaminophen overdose ^{01}:
To decrease absorption—May include emptying the stomach via induction of emesis or gastric lavage.

Removing activated charcoal (if used) by gastric lavage may be advisable. Although activated charcoal is recommended in cases of mixed drug overdose, it may interfere with absorption of orally administered acetylcysteine (antidote used to protect against acetaminophen-induced hepatotoxicity) and decrease its efficacy.

To enhance elimination—Instituting hemodialysis or hemoperfusion to remove acetaminophen from the circulation may be beneficial if acetylcysteine administration cannot be instituted within 24 hours following ingestion of a massive acetaminophen overdose. However, the efficacy of such treatment in preventing acetaminophen-induced hepatotoxicity is not known.

Specific treatment—Use of acetylcysteine. It is recommended that acetylcysteine administration be instituted as soon as possible after ingestion of an overdose has been reported, without waiting for the results of plasma acetaminophen determinations or other laboratory tests. Acetylcysteine is most effective if treatment is started within 10 to 12 hours after ingestion of the overdose; however, it may be of some benefit if treatment is started within 24 hours. See package insert or Acetylcysteine (Systemic) monograph for specific dosing guidelines for use of this product.

Monitoring—May include determining plasma acetaminophen concentration at least 4 hours following ingestion of the overdose. Determinations performed prior to this time are not reliable for assessing potential hepatotoxicity. Initial plasma concentrations above 150 mcg per mL (993 micromoles/L) at 4 hours, 100 mcg per mL (662 micromoles/L) at 6 hours, 70 mcg per mL (463.4 micromoles/L) at 8 hours, 50 mcg per mL (331 micromoles/L) at 10 hours, 20 mcg per mL (132.4 micromoles/L) at 15 hours, 8 mcg per mL (53 micromoles/L) at 20 hours, or 3.5 mcg per mL (23.2 micromoles/L) at 24 hours postingestion indicate possible hepatotoxicity and the need for completing the full course of acetylcysteine treatment. If the initial determination indicates a plasma concentration below those listed at the times indicated, cessation of acetylcysteine therapy can be considered. However, some clinicians advise that more than one determination should be performed to ascertain peak absorption and half-life of acetaminophen prior to considering discontinuation of acetylcysteine.

Performing liver function tests (serum aspartate aminotransferase [AST; SGOT], serum alanine aminotransferase [ALT; SGPT], prothrombin time, and bilirubin) at 24-hour intervals for at least 96 hours postingestion if the plasma acetaminophen concentration indicates potential hepatotoxicity. If no abnormalities are detected within 96 hours, further determinations are not needed.

Monitoring renal and cardiac function and administering appropriate therapy as required.

Supportive care—May include maintaining fluid and electrolyte balance, correcting hypoglycemia, and administering vitamin K ₁(if prothrombin time ratio exceeds 1.5) and fresh frozen plasma or clotting factor concentrate (if prothrombin time ratio exceeds 3.0). Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Acetaminophen, Sodium Bicarbonate, and Citric Acid (Systemic). ^{{01} {02} {03}}

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Allergic reaction to acetaminophen, aspirin, or sodium bicarbonate, history of

Pregnancy—Acetaminophen crosses the placenta; sodium may cause edema and weight gain




Use in the elderly— Because of the very high sodium content, use of this acetaminophen and antacid combination should preferably be limited to 5 days at a time, unless more prolonged therapy is prescribed and monitored by a physician
Other medications, especially alcohol (especially chronic abuse of), mecamylamine, methenamine, oral ciprofloxacin, enoxacin, itraconazole, ketoconazole, lomefloxacin, norfloxacin, ofloxacin, and tetracyclines
Other medical problems, especially alcoholism (active), symptoms of appendicitis or, hepatic disease or viral hepatitis, conditions in which sodium may be detrimental, and intestinal obstruction.

Proper use of this medication
» Following physician's or manufacturer's directions; not taking more medication than the amount recommended because acetaminophen may cause liver damage with long-term use or greater-than-recommended doses and because of the very high sodium content of this medication

Proper administration: ^{04}

Dissolving granules in water prior to ingestion: Pouring measured dose into glass, then adding 1/2 glass (120 mL) cool water

Drinking while solution is still effervescing, or after it has settled

Drinking entire amount, then rinsing glass with a little more water and drinking that, to ensure receiving full dosage

» Proper dosing
Missed dose (if on scheduled dosing): Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
Regular visits to physician to check progress if long-term therapy is prescribed

Checking with physician, because additional treatment may be needed, if symptoms persist for longer than 10 days, condition becomes worse, new symptoms occur, or the painful area is red or swollen

» Not taking this medication within:

   —6 hours before or 2 hours after ciprofloxacin or lomefloxacin
   —8 hours before or 2 hours after enoxacin
   —2 hours after itraconazole
   —3 hours before or after ketoconazole
   —2 hours before or after norfloxacin or ofloxacin
   —3 to 4 hours before or after an oral tetracycline
   —1 or 2 hours before or after any other oral medication


» Caution if other medications containing acetaminophen or significant quantities of sodium are used

Not using a salicylate or a nonsteroidal anti-inflammatory drug together with acetaminophen for longer than a few days, unless otherwise directed by physician

If taking more than an occasional 1 or 2 doses of this medication:

» Avoiding alcoholic beverages; increased risk of liver toxicity, especially in alcoholics, with high doses or prolonged use of acetaminophen

» Avoiding large amounts of milk or milk products

Possible need for sodium restriction

Possible interference with some laboratory tests; preferably checking with laboratory 3 to 4 days ahead of time; if this is not possible, informing physician in charge if acetaminophen taken within the past 3 or 4 days

Diabetics: Possible false results with blood glucose tests; checking with physician, nurse, or pharmacist if changes in test results noted

» Suspected overdose: Getting emergency help at once even if no symptoms apparent; symptoms of severe acetaminophen overdosage may be delayed, but treatment must be begun as soon as possible; treatment started 24 hours or more after the overdose may be ineffective in preventing liver damage or fatality


Side/adverse effects
Signs of potential side effects, especially edema, hypercalcemia associated with milk-alkali syndrome, increased blood pressure, metabolic alkalosis, agranulocytosis, anemia, allergic dermatitis, hepatitis, renal colic, renal failure, sterile pyuria, and thrombocytopenia


General Dosing Information
One retrospective study has suggested that long-term daily use of acetaminophen may be associated with an increased risk of chronic renal disease. The results of this study are not considered conclusive, and further investigation is required to establish a causal association. ^{07} However, until more definitive information is available, prolonged daily administration of acetaminophen should probably be limited to patients who are receiving appropriate medical supervision. ^{08}


Oral Dosage Forms

ACETAMINOPHEN FOR EFFERVESCENT ORAL SOLUTION USP

Usual adult and adolescent dose
Analgesics-antacid
Oral, 325 to 650 mg of acetaminophen every four hours as needed. ^{04}


Note: It is recommended that a physician be consulted if symptoms are not relieved within ten days ^{01}. However, geriatric patients should preferably not self-medicate with this product for longer than five days at a time, because of the very high sodium content ^{06}.


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


325 mg of acetaminophen with 2.781 grams of sodium bicarbonate and 2.224 grams of citric acid per 3/4-capful measured dose (OTC) [Bromo-Seltzer (sodium 761 mg [33.08 mmol] per 325-mg dose)]^{04}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Preparation of dosage form:
The measured dose is to be dissolved in 120 mL of cool water just prior to administration.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • Keep container tightly closed.

Revised: 07/12/1994

References

1. Acetaminophen (Systemic) monograph, 1990 revision.
   

2. Antacids (Oral-Local) monograph, 1990 revision.
   

3. Sodium Bicarbonate (Systemic) monograph, 1990 revision.
   

4. Bromo-Seltzer product label (Warner-Lambert—US), Rec 3/90.
   

5. Krogh C, editor. Self-Medication. 3rd ed. Ottawa: Canadian Pharmaceutical Association, 1989: M33.
   

6. Panel consensus, Acetaminophen (Systemic) monograph, draft 1982.
   

7. Sandler DP, Smith JC, Weinberg CR, et al. Analgesic use and chronic renal disease. N Engl J Med 1989 May 11; 320: 1238–43.
   

8. Reviewers' responses to ballot 11/3/89.
   

9. Reviewers' responses to monograph draft 1/91.
   

10. Reviewers' responses to monograph draft 1/91.
    

11. Panel response to Sodium Bicarbonate (Systemic) monograph revision 1982.
    

12. Hoffken G, et al. Pharmacokinetics and bioavailability of ciprofloxacin and ofloxacin: effects of food and antacid intake. Rev Infect Dis 1988; 19(suppl 1): S138-S139.
    

13. Penetrex (Rhone-Poulenc Rorer). In: PDR Physicians' desk reference. 48th ed. 1994. Montvale, NJ: Medical Economics Data Production Company, 1994: 1861-3.
    

14. Panel response to Itraconazole monograph revision 1993.
    

15. Shimada J, et al. Effect of antacid on absorption of the quinolone lomefloxacin. Antimicrob Agents Chemother 1992; 36(6): 1219-24.
    

16. Nix DE, et al. Inhibition of norfloxacin absorption by antacids. Antimicrob Agent Chemother 1990; 34(3): 432-5.
    

17. Flor S, et al. Effects of magnesium-aluminum hydroxide and calcium carbonate antacids on bioavailability of ofloxacin. Antimicrob Agents Chemother 1990; 34(12): 2436-8.
    
    
    

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