acetaminophen
Acephen, Anacin Aspirin Free, Feverall, Neopap, Panadol, Tempra, Tylenol

Available forms
Available without a prescription
Caplets: 160 mg, 500 mg, 650 mg
Capsules: 325 mg, 500 mg
Gelcaps: 500 mg
Solution: 48 mg/ml, 80 mg/0.8 ml, 80 mg/ml ◆, 80 mg/1.66 ml, 80 mg/2.5 ml, 80 mg/5 ml, 100 mg/ml, 120 mg/5 ml, 160 mg/5 ml, 500 mg/15 ml
Sprinkle capsules: 80 mg, 160 mg
Suppositories: 80 mg, 120 mg, 125 mg, 300 mg, 325 mg, 650 mg
Suspension: 80 mg/ml ◆, 100 mg/ml, 80 mg/ 5 ml ◆, 160 mg/5 ml
Syrup: 16 mg/ml
Tablets: 160 mg, 325 mg, 500 mg, 650 mg
Tablets (chewable): 80 mg

Indications and dosages
 Mild pain, fever. Adults and children older than age 12: 325 to 650 mg P.O. or P.R. q 4 to 6 hours p.r.n. Maximum dose shouldn’t exceed 4 g daily. Maximum dose for long-term therapy is 2.6 g daily; alternatively, two 650-mg extended-release tablets every 8 hours p.r.n., not to exceed 4 g per day.
Children: 10 to 15 mg/kg/dose. Or, the following guidelines can be used:
Children ages 11 to 12: 480 mg P.O. or P.R. q 4 to 6 hours p.r.n.
Children ages 9 to 10: 400 mg P.O. or P.R. q 4 to 6 hours p.r.n.
Children ages 6 to 8: 320 mg P.O. or P.R. q 4 to 6 hours p.r.n.
Children ages 4 to 5: 240 mg P.O. or P.R. q 4 to 6 hours p.r.n.
Children ages 2 to 3: 160 mg P.O. or P.R. q 4 to 6 hours p.r.n.
Children ages 12 to 23 months: 120 mg P.O. or P.R. q 4 to 6 hours p.r.n.
Children ages 4 to 11 months: 80 mg P.O. or P.R. q 4 to 6 hours p.r.n.
Children age 3 months or less: 40 mg P.O. or P.R. q 4 to 6 hours p.r.n.
 Osteoarthritis. Adults: Up to 1 g P.O. q.i.d.; doses of 3 to 4 g per day common in these patients.
≡ Dosage adjustment. For chronic alcoholics, dose should not exceed 2 g daily.

Pharmacodynamics
Mechanism and site of action may be related to inhibition of prostaglandin synthesis in CNS.
Analgesic action: Analgesic effect may be related to an elevation of the pain threshold.
Antipyretic action: Drug may exert antipyretic effect by direct action on hypothalamic heat-regulating center to block effects of endogenous pyrogen. This results in increased heat dissipation through sweating and vasodilation.

Pharmacokinetics
Absorption: Absorbed rapidly and completely via the GI tract.
Distribution: 25% protein-bound. Plasma levels don’t correlate well with analgesic effect, but they do correlate with toxicity.
Metabolism: About 90% to 95% is metabolized in the liver.
Excretion: Excreted in urine. Average elimination half-life ranges from 1 to 4 hours. In acute overdose, prolongation of elimination half-life is correlated with toxic effects. Half-life longer than 4 hours is linked to hepatic necrosis; longer than 12 hours is linked to coma.

Contraindications and precautions
No known contraindications. Use cautiously in patients with history of chronic alcohol abuse because hepatotoxicity has occurred after therapeutic doses. Also use cautiously in patients with hepatic or CV disease, renal function impairment, or viral infection.

Interactions
Drug-drug. Antacids: Delay and decrease absorption of acetaminophen. Separate administration times.
Anticoagulants, thrombolytics: May potentiate effects of these drugs. This appears to be clinically insignificant.
Anticonvulsants, isoniazid: Increase risk of hepatotoxicity. Use together cautiously.
Phenothiazines: May cause hypothermia if used with acetaminophen in large doses. Use together cautiously.
Drug-herb. Feverfew, ginkgo biloba: May increase risk of bleeding. Discourage use together.
Red clover: Coumarin effects may enhance anticoagulation. Discourage use together. If use together is unavoidable, monitor PT and INR closely.
Watercress: May inhibit oxidative metabolism of acetaminophen. Discourage use together.
Drug-food. Any food: Delays and decreases absorption of acetaminophen. Advise taking drug on an empty stomach.
Caffeine: May enhance therapeutic effect of acetaminophen. Discourage use together.
Drug-lifestyle. Alcohol use: Increases risk of liver toxicity. Discourage alcohol use.

Adverse reactions
Hematologic: hemolytic anemia, neutropenia, leukopenia, pancytopenia, thrombocytopenia.
Hepatic: jaundice, severe liver damage.
Metabolic: hypoglycemia.
Skin: rash, urticaria.

Effects on lab test results
• May decrease glucose level.
• May decrease hemoglobin and neutrophil, WBC, RBC, and platelet counts.

Overdose and treatment
In all cases of suspected acetaminophen overdose, a regional poison center or the Rocky Mountain Poison and Drug Center (1-800-525-5042) may be called for assistance. In acute overdose, plasma levels of 300 mcg/ml 4 hours after ingestion or 50 mcg/ml 12 hours after ingestion are linked to hepatotoxicity. Signs and symptoms of overdose include cyanosis, anemia, jaundice, skin eruptions, fever, emesis, CNS stimulation, delirium, methemoglobinemia progressing to depression, coma, vascular collapse, seizures, and death. During an overdose, patient may have increased AST, ALT, bilirubin, and prothrombin levels.
 Acetaminophen poisoning develops in stages:
Stage 1 (12 to 24 hours after ingestion): nausea, vomiting, diaphoresis, anorexia
Stage 2 (24 to 48 hours after ingestion): clinically improved but elevated liver function test results
Stage 3 (72 to 96 hours after ingestion): peak hepatotoxicity
Stage 4 (7 to 8 days after ingestion): recovery
 To treat toxic overdose of acetaminophen, empty stomach immediately by inducing emesis with ipecac syrup (if patient is conscious) or by performing gastric lavage. Administer activated charcoal by way of nasogastric tube. Oral acetylcysteine (Mucomyst) is a specific antidote for acetaminophen poisoning and is most effective if started within 10 to 12 hours after ingestion, but it can help if started within 24 hours after ingestion. Administer a Mucomyst loading dose of 140 mg/kg P.O., followed by maintenance doses of 70 mg/kg P.O. every 4 hours for an additional 17 doses. Doses vomited within 1 hour of administration must be repeated. Remove charcoal before giving acetylcysteine because it may interfere with absorption of this antidote.
 Hemodialysis may be helpful to remove acetaminophen from the body. Monitor laboratory parameters and vital signs closely. Provide symptomatic and supportive measures (respiratory support, correction of fluid and electrolyte imbalances). Determine plasma acetaminophen levels at least 4 hours after overdose. If plasma acetaminophen levels indicate hepatotoxicity, perform liver function tests every 24 hours for at least 96 hours.

Special considerations
• Acetaminophen doesn’t have a significant anti-inflammatory effect. Even so, studies have shown substantial benefit in patients with osteoarthritis of the knee. Therapeutic benefits may stem from the analgesic effects of the drug.
• Many OTC products contain acetaminophen. Be aware of this when recommending this drug.
 ALERT Be aware of patient’s total daily intake of acetaminophen, especially if he is also taking other prescribed drugs containing this component, such as Percocet. Toxicity can occur. Researchers advise limiting daily acetaminophen to four extra-strength pills or 2 g total from all medicines to decrease the incidence of liver poisoning with toxic doses of the drug.
• Patients unable to tolerate aspirin may be able to tolerate acetaminophen.
• When buffered acetaminophen effervescent granules are prescribed, consider sodium content for sodium-restricted patients.
• Advise patients with phenylketonuria that many preparations contain aspartame.
• Many acetaminophen preparations contain sulfites.
• The extended-release tablet shouldn’t be crushed, chewed, or dissolved in liquid.
• Address patient’s level of pain and response before and after drug administration.
• Monitor vital signs, especially temperature, to evaluate effectiveness of drug.
• Monitor PT and INR values in patients receiving oral anticoagulants and sustained acetaminophen therapy.
• Store rectal acetaminophen suppositories in refrigerator.
• Acetaminophen may cause a false-positive test result for urinary 5-hydroxyindoleacetic acid.
Breast-feeding patients
• Drug appears in breast milk in low concentrations. No adverse effects have been reported.
Pediatric patients
• Children shouldn’t take more than five doses per day or take drug for longer than 5 days unless prescribed. Instruct caregivers on weight-based acetaminophen dosing, to use the provided calibrated measuring device with the preparation, and not to give more than the recommended dose. Also, caution caregivers not to use other OTC preparations that contain acetaminophen.
Geriatric patients
• Geriatric patients are more sensitive to drug. Use with caution.

Patient education
• Instruct patient in proper administration of prescribed form of drug.
• Advise patient on long-term high-dose drug therapy to arrange for monitoring of laboratory parameters, especially BUN, serum creatinine, liver function tests, and CBC.
• Warn patient with current or past rectal bleeding to avoid using rectal acetaminophen suppositories. If they’re used, they must be retained in the rectum for at least 1 hour.
• Warn patient that high doses or unsupervised long-term use of acetaminophen can cause liver damage. Use of alcoholic beverages increases the risk of liver toxicity.
• Tell patient to avoid use if body temperature is above 103° F (39° C), if fever persists longer than 3 days, or if fever recurs.
• Tell patient not to take NSAIDs with acetaminophen on a regular basis.
• Warn patient to avoid taking tetracycline antibiotics within 1 hour after taking buffered acetaminophen effervescent granules.
• Tell patient not to use drug for arthritic or rheumatic conditions without medical approval. Drug may relieve pain but not other symptoms.
• Advise adult patient not to take drug for longer than 10 days without medical approval.
• Tell patient on high-dose or long-term therapy that regular follow-up visits are essential.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use