Menstrual Pain/Dysmenorrhea

A randomized crossover study (unpublished) in primary dysmenorrhea compared the effect of acetaminophen 1000 mg four times daily, ibuprofen 400 mg three times daily, and placebo in patients with a history of recurrent moderate to severe dysmenorrhea. The two active drugs were comparable in the treatment of primary symptoms of dysmenorrhea, and both were superior to placebo.

Post-Immunization Muscle Aches and Pain

Aoki and associates⁷⁶ evaluated the effect of acetaminophen on the incidence of adverse effects and immunogenicity of whole-virus influenza vaccine in healthcare workers. Hospital personnel volunteers were randomly assigned to acetaminophen 325 mg, acetaminophen 650 mg, or placebo. Capsules were taken at the time of the vaccination, and 4, 8, and 12 hours after vaccination. Acetaminophen 650 mg significantly reduced the incidence of sore arm and nausea without affecting antibody response.

Cancer Pain

Wallenstein and Houde⁷⁷ found 600 mg of acetaminophen or aspirin to be approximately equivalent and significantly superior to salicylamide and placebo for pain relief in patients with cancer. Moertel and colleagues⁷⁸ compared acetaminophen 650 mg, codeine 65 mg, aspirin 650 mg, pentazocine 50 mg, propoxyphene 65 mg, and ethoheptazine 75 mg in the treatment of cancer pain. On the basis of mean pain relief scores, neither propoxyphene nor ethoheptazine was statistically superior to placebo. Acetaminophen was superior to placebo and comparable to codeine, aspirin, and pentazocine for pain relief.

Sore Throat

The analgesic efficacy of acetaminophen also has been demonstrated in pain associated with tonsillectomy, tonsillitis, and sore throat.^79-81

Toxicology

A number of acute, subacute, and chronic toxicity studies in animals show that the toxic effects of acetaminophen appear only at extremely high doses.

Acute Toxicity (Multiple Animal Models)

See Table 5.

Subacute Toxicity (Rats)

Oral doses of up to 1000 mg/kg/d or intramuscular doses of up to 100 mg/kg/d were given to rats for 13 days or 30 days, respectively. No drug-related changes were seen in mortality rate or necropsy findings compared with controls.

Subacute Toxicity (Dogs)

After acetaminophen (20 and 63 mg/kg/d) was given intramuscularly for 4 weeks to dogs, mortality rate, laboratory determinations, and gross necropsy observations were not significantly different from control values. Slight thyroid hyperplasia was seen on histopathologic examinations in the six high-dose dogs, slight renal tubular cell cloudy swelling was noted in three high-dose and one low-dose dog, and slight liver glycogen depletion was found in one control, three high-dose, and two low-dose animals.¹⁵⁶

Chronic Toxicity (Rats)

Acetaminophen, 200 mg/kg/d, given to rats once a day by gavage for 28 weeks produced no changes in weight gain, gross pathology, or histologic findings in liver, kidney, heart, or lungs.¹⁵⁷ Acetaminophen incorporated into the diet of rats for 100 days showed that the minimum dose that caused death in all rats was 1060 mg/kg/d, the dose that caused death in 50% of rats was 765 mg/kg/d, and the maximum dose that caused no deaths was 413 mg/kg/d. At or near the LD₅₀ (100 days), histologic findings included areas of hepatic necrosis, some renal tubular degeneration, and testicular atrophy.¹⁵⁸

TABLE 5. Acute toxicity (LD₅₀ mg/kg) of acetaminophen

Acute Nephrotoxicity (Rats)

Bookmark this page: