Note: In countries outside of the U.S., some formulations of Tylenol® with Codeine (eg, Tylenol® No. 3) include caffeine.

Limit total acetaminophen dose to <4 g/day. May cause severe hepatic toxicity on acute overdose; in addition, chronic daily dosing in adults has resulted in liver damage in some patients. Use with caution in patients with alcoholic liver disease; consuming 3 alcoholic drinks/day may increase the risk of liver damage. Use caution in patients with known G6PD deficiency.

This combination should be used with caution in elderly or debilitated patients, hypotension, adrenocortical insufficiency, thyroid disorders, prostatic hyperplasia, urethral stricture, seizure disorder, CNS depression, head injury or increased intracranial pressure. Causes sedation; caution must be used in performing tasks which require alertness (eg, operating machinery or driving). Safety and efficacy in pediatric patients have not been established.

Note: Some non-U.S. formulations (including most Canadian formulations) may contain caffeine as an additional ingredient. Caffeine may cause CNS and cardiovascular stimulation, as well as GI irritation in high doses. Use with caution in patients with a history of peptic ulcer or GERD; avoid in patients with symptomatic cardiac arrhythmias.

>10%:

Central nervous system: Lightheadedness, dizziness, sedation

Gastrointestinal: Nausea, vomiting

Respiratory: Dyspnea

1% to 10%:

Central nervous system: Euphoria, dysphoria

Dermatologic: Pruritus

Gastrointestinal: Constipation, abdominal pain

Miscellaneous: Histamine release

<1%: Palpitations, hypotension, bradycardia, peripheral vasodilation, increased intracranial pressure, antidiuretic hormone release, biliary tract spasm, urinary retention, miosis, respiratory depression, physical and psychological dependence

Symptoms of overdose include hepatic necrosis, blood dyscrasias, respiratory depression.

Acetylcysteine 140 mg/kg orally (loading) followed by 70 mg/kg every 4 hours for 17 doses; therapy should be initiated based upon laboratory analysis suggesting high probability of hepatotoxic potential.

Naloxone 2 mg I.V. (0.01 mg/kg for children) with repeat administration as necessary up to a total of 10 mg; can also be used to reverse the toxic effects of the opiate.

Activated charcoal is effective at binding certain chemicals, and this is especially true for acetaminophen (use within 2 hours of ingestion).

Increased toxicity: CNS depressants, phenothiazines, tricyclic antidepressants, guanabenz, MAO inhibitors (may also decrease blood pressure); effect of warfarin may be enhanced

Children: Analgesic:

Codeine: 0.5-1 mg codeine/kg/dose every 4-6 hours

Acetaminophen: 10-15 mg/kg/dose every 4 hours up to a maximum of 2.6 g/24 hours for children <12 years; alternatively, the following can be used:

3-6 years: 5 mL 3-4 times/day as needed of elixir

7-12 years: 10 mL 3-4 times/day as needed of elixir

>12 years: 15 mL every 4 hours as needed of elixir

Adults:

Antitussive: Based on codeine (15-30 mg/dose) every 4-6 hours (maximum: 360 mg/24 hours based on codeine component)

Analgesic: Based on codeine (30-60 mg/dose) every 4-6 hours (maximum: 4000 mg/24 hours based on acetaminophen component)

Dosing adjustment in renal impairment: See individual monographs for Acetaminophen and Codeine

A study by Hylek, et al, suggested that the combination of acetaminophen with warfarin (Coumadin®) may cause enhanced anticoagulation. The following recommendations have been made by Hylek, et al, and supported by an editorial in JAMA by Bell.

Dose and duration of acetaminophen should be as low as possible, individualized and monitored.

The study by Hylek reported the following:

For patients who reported taking the equivalent of at least 4 regular strength (325 mg) tablets for longer than a week, the odds of having an INR >6.0 were increased 10-fold above those not taking acetaminophen. Risk decreased with lower intakes of acetaminophen reaching a background level of risk at a dose of 6 or fewer 325 mg tablets per week.

Caplet:

ratio-Lenoltec No. 1 [CAN], Tylenol No. 1 [CAN]: Acetaminophen 300 mg, codeine phosphate, 8 mg and caffeine 15 mg [not available in the U.S.]

Tylenol No. 1 Forte [CAN]: Acetaminophen 500 mg, codeine phosphate 8 mg, and caffeine 15 mg [not available in the U.S.]

Elixir, oral [C-V]: Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (5 mL, 10 mL, 12.5 mL, 15 mL, 120 mL, 480 mL) [contains alcohol 7%]

Tylenol® with Codeine [DSC]: Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (480 mL) [contains alcohol 7%; cherry flavor]

Tylenol Elixir with Codeine [CAN]: Acetaminophen 160 mg and codeine phosphate 8 mg per 5 mL (500 mL) [contains alcohol 7%, sucrose 31%; cherry flavor; not available in the U.S.]

Suspension, oral [C-V] (Capital® and Codeine): Acetaminophen 120 mg and codeine phosphate 12 mg per 5 mL (480 mL) [alcohol free; fruit punch flavor]

Tablet [C-III]: Acetaminophen 300 mg and codeine phosphate 15 mg; acetaminophen 300 mg and codeine phosphate 30 mg; acetaminophen 300 mg and codeine phosphate 60 mg

ratio-Emtec [CAN], Triatec-30 [CAN]: Acetaminophen 300 mg and codeine phosphate 30 mg [not available in the U.S.]

ratio-Lenoltec No. 1 [CAN]: Acetaminophen 300 mg, codeine phosphate 8 mg, and caffeine 15 mg [Not available in the U. S.]

ratio-Lenoltec No. 2 [CAN], Tylenol No. 2 with Codeine [CAN]: Acetaminophen 300 mg, codeine phosphate 15 mg, and caffeine 15 mg [not available in the U.S.]

ratio-Lenoltec No. 3 [CAN], Tylenol No. 3 with Codeine [CAN]: Acetaminophen 300 mg, codeine phosphate 30 mg, and caffeine 15 mg [not available in the U.S.]

ratio-Lenoltec No. 4 [CAN], Tylenol No. 4 with Codeine [CAN]: Acetaminophen 300 mg and codeine phosphate 60 mg [not available in the U.S.]

Triatec-8 [CAN]: Acetaminophen 325 mg, codeine phosphate 8 mg, and caffeine 30 mg [not available in the U.S.]

Triatec-8 Strong [CAN]: Acetaminophen 500 mg, codeine phosphate 8 mg, and caffeine 30 mg [not available in the U.S.]

Tylenol® with Codeine No. 3: Acetaminophen 300 mg and codeine phosphate 30 mg [contains sodium metabisulfite]

Tylenol® with Codeine No. 4: Acetaminophen 300 mg and codeine phosphate 60 mg [contains sodium metabisulfite]

Dionne RA, "New Approaches to Preventing and Treating Postoperative Pain,"J Am Dent Assoc, 1992, 123(6):26-34.

Dionne RA, Campbell RA, Cooper SA, et al, "Suppression of Postoperative Pain by Preoperative Administration of Ibuprofen in Comparison to Placebo, Acetaminophen, and Acetaminophen Plus Codeine,"J Clin Pharmacol, 1983, 23(1):37-43.

Mokhlesi B, Leikin JB, Murray P, et al, "Adult Toxicology in Critical Care: Part II: Specific Poisonings,"Chest, 2003, 123(3):897-922.

Forbes JA, Butterworth GA, Burchfield WH, et al, "Evaluation of Ketorolac, Aspirin, and an Acetaminophen-Codeine Combination in Postoperative Oral Surgery Pain,"Pharmacotherapy, 1990, 10(6 Pt 2):77S-93S.

Gobetti JP, "Controlling Dental Pain,"J Am Dent Assoc, 1992, 123(6):47-52.