Copyright 1978-2006 Lexi-Comp, Inc. All rights reserved.
(For additional information see "Acetaminophen and diphenhydramine: Patient drug information")
U.S. BRAND NAMES — Excedrin® P.M. [OTC]; Goody's PM® [OTC]; Legatrin PM® [OTC]; Percogesic® Extra Strength [OTC]; Tylenol® PM [OTC]; Tylenol® Severe Allergy [OTC]
PHARMACOLOGIC CATEGORY Analgesic, Miscellaneous
DOSING: ADULTS — Insomnia and pain: Oral: Adults: 50 mg of diphenhydramine HCl (76 mg diphenhydramine citrate) at bedtime or as directed by physician; do not exceed recommended dosage
DOSING: PEDIATRIC — Not for use in children <12 years of age.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy is usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg Excedrin® P.M.: Acetaminophen 500 mg and diphenhydramine citrate 38 mg Legatrin PM®: Acetaminophen 500 mg and diphenhydramine hydrochloride 50 mg Percogesic® Extra Strength: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg Tylenol® PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg [also available in vanilla caplets] Tylenol® Severe Allergy: Acetaminophen 500 mg and diphenhydramine hydrochloride 12.5 mg
Gelcap: Tylenol® PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg
Geltab: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg Excedrin® P.M.: Acetaminophen 500 mg and diphenhydramine citrate 38 mg Tylenol® PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg
Liquid: Tylenol® PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg per 15 mL (240 mL) [contains sodium benzoate; vanilla flavor]
Powder for oral solution: Goody's PM®: Acetaminophen 500 mg and diphenhydramine citrate 38 mg [contains potassium 41.9 mg and sodium 3.15 mg per powder]
Tablet: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg Excedrin® P.M.: Acetaminophen 500 mg and diphenhydramine citrate 38 mg
DOSAGE FORMS: CONCISE Caplet: Acetaminophen 500 mg and diphenhydramine 25 mg Excedrin® P.M. [OTC]: Acetaminophen 500 mg and diphenhydramine 38 mg Legatrin PM® [OTC]: Acetaminophen 500 mg and diphenhydramine 50 mg Percogesic® Extra Strength [OTC], Tylenol® PM [OTC]: Acetaminophen 500 mg and diphenhydramine 25 mg Tylenol® Severe Allergy [OTC]: Acetaminophen 500 mg and diphenhydramine 12.5 mg
Gelcap: Tylenol® PM [OTC]: Acetaminophen 500 mg and diphenhydramine 25 mg
Geltab: Acetaminophen 500 mg and diphenhydramine 25 mg Excedrin® P.M. [OTC]: Acetaminophen 500 mg and diphenhydramine 38 mg Tylenol® PM [OTC]: Acetaminophen 500 mg and diphenhydramine 25 mg
Liquid: Tylenol® PM [OTC]: Acetaminophen 500 mg and diphenhydramine 25 mg per 15 mL
Powder for oral solution: Goody's PM® [OTC]: Acetaminophen 500 mg and diphenhydramine 38 mg
Tablet: Acetaminophen 500 mg and diphenhydramine 25 mg Excedrin® P.M. [OTC]: Acetaminophen 500 mg and diphenhydramine 38 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes gelcap, powder, and liquid
USE — Aid in the relief of insomnia accompanied by minor pain
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
DRUG INTERACTIONS Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Diphenhydramine: Inhibits CYP2D6 (moderate)
Also see individual agents.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
PHARMACODYNAMICS / KINETICS — See individual agents.
Wednesday, January 16, 2008
Acetaminophen and diphenhydramine: Drug information
Copyright 1978-2006 Lexi-Comp, Inc. All rights reserved.
(For additional information see "Acetaminophen and diphenhydramine: Patient drug information")
U.S. BRAND NAMES — Excedrin® P.M. [OTC]; Goody's PM® [OTC]; Legatrin PM® [OTC]; Percogesic® Extra Strength [OTC]; Tylenol® PM [OTC]; Tylenol® Severe Allergy [OTC]
PHARMACOLOGIC CATEGORY Analgesic, Miscellaneous
DOSING: ADULTS — Insomnia and pain: Oral: Adults: 50 mg of diphenhydramine HCl (76 mg diphenhydramine citrate) at bedtime or as directed by physician; do not exceed recommended dosage
DOSING: PEDIATRIC — Not for use in children <12 years of age.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy is usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg Excedrin® P.M.: Acetaminophen 500 mg and diphenhydramine citrate 38 mg Legatrin PM®: Acetaminophen 500 mg and diphenhydramine hydrochloride 50 mg Percogesic® Extra Strength: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg Tylenol® PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg [also available in vanilla caplets] Tylenol® Severe Allergy: Acetaminophen 500 mg and diphenhydramine hydrochloride 12.5 mg
Gelcap: Tylenol® PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg
Geltab: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg Excedrin® P.M.: Acetaminophen 500 mg and diphenhydramine citrate 38 mg Tylenol® PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg
Liquid: Tylenol® PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg per 15 mL (240 mL) [contains sodium benzoate; vanilla flavor]
Powder for oral solution: Goody's PM®: Acetaminophen 500 mg and diphenhydramine citrate 38 mg [contains potassium 41.9 mg and sodium 3.15 mg per powder]
Tablet: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg Excedrin® P.M.: Acetaminophen 500 mg and diphenhydramine citrate 38 mg
DOSAGE FORMS: CONCISE Caplet: Acetaminophen 500 mg and diphenhydramine 25 mg Excedrin® P.M. [OTC]: Acetaminophen 500 mg and diphenhydramine 38 mg Legatrin PM® [OTC]: Acetaminophen 500 mg and diphenhydramine 50 mg Percogesic® Extra Strength [OTC], Tylenol® PM [OTC]: Acetaminophen 500 mg and diphenhydramine 25 mg Tylenol® Severe Allergy [OTC]: Acetaminophen 500 mg and diphenhydramine 12.5 mg
Gelcap: Tylenol® PM [OTC]: Acetaminophen 500 mg and diphenhydramine 25 mg
Geltab: Acetaminophen 500 mg and diphenhydramine 25 mg Excedrin® P.M. [OTC]: Acetaminophen 500 mg and diphenhydramine 38 mg Tylenol® PM [OTC]: Acetaminophen 500 mg and diphenhydramine 25 mg
Liquid: Tylenol® PM [OTC]: Acetaminophen 500 mg and diphenhydramine 25 mg per 15 mL
Powder for oral solution: Goody's PM® [OTC]: Acetaminophen 500 mg and diphenhydramine 38 mg
Tablet: Acetaminophen 500 mg and diphenhydramine 25 mg Excedrin® P.M. [OTC]: Acetaminophen 500 mg and diphenhydramine 38 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes gelcap, powder, and liquid
USE — Aid in the relief of insomnia accompanied by minor pain
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
DRUG INTERACTIONS Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Diphenhydramine: Inhibits CYP2D6 (moderate)
Also see individual agents.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
PHARMACODYNAMICS / KINETICS — See individual agents.
(For additional information see "Acetaminophen and diphenhydramine: Patient drug information")
U.S. BRAND NAMES — Excedrin® P.M. [OTC]; Goody's PM® [OTC]; Legatrin PM® [OTC]; Percogesic® Extra Strength [OTC]; Tylenol® PM [OTC]; Tylenol® Severe Allergy [OTC]
PHARMACOLOGIC CATEGORY Analgesic, Miscellaneous
DOSING: ADULTS — Insomnia and pain: Oral: Adults: 50 mg of diphenhydramine HCl (76 mg diphenhydramine citrate) at bedtime or as directed by physician; do not exceed recommended dosage
DOSING: PEDIATRIC — Not for use in children <12 years of age.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy is usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg Excedrin® P.M.: Acetaminophen 500 mg and diphenhydramine citrate 38 mg Legatrin PM®: Acetaminophen 500 mg and diphenhydramine hydrochloride 50 mg Percogesic® Extra Strength: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg Tylenol® PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg [also available in vanilla caplets] Tylenol® Severe Allergy: Acetaminophen 500 mg and diphenhydramine hydrochloride 12.5 mg
Gelcap: Tylenol® PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg
Geltab: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg Excedrin® P.M.: Acetaminophen 500 mg and diphenhydramine citrate 38 mg Tylenol® PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg
Liquid: Tylenol® PM: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg per 15 mL (240 mL) [contains sodium benzoate; vanilla flavor]
Powder for oral solution: Goody's PM®: Acetaminophen 500 mg and diphenhydramine citrate 38 mg [contains potassium 41.9 mg and sodium 3.15 mg per powder]
Tablet: Acetaminophen 500 mg and diphenhydramine hydrochloride 25 mg Excedrin® P.M.: Acetaminophen 500 mg and diphenhydramine citrate 38 mg
DOSAGE FORMS: CONCISE Caplet: Acetaminophen 500 mg and diphenhydramine 25 mg Excedrin® P.M. [OTC]: Acetaminophen 500 mg and diphenhydramine 38 mg Legatrin PM® [OTC]: Acetaminophen 500 mg and diphenhydramine 50 mg Percogesic® Extra Strength [OTC], Tylenol® PM [OTC]: Acetaminophen 500 mg and diphenhydramine 25 mg Tylenol® Severe Allergy [OTC]: Acetaminophen 500 mg and diphenhydramine 12.5 mg
Gelcap: Tylenol® PM [OTC]: Acetaminophen 500 mg and diphenhydramine 25 mg
Geltab: Acetaminophen 500 mg and diphenhydramine 25 mg Excedrin® P.M. [OTC]: Acetaminophen 500 mg and diphenhydramine 38 mg Tylenol® PM [OTC]: Acetaminophen 500 mg and diphenhydramine 25 mg
Liquid: Tylenol® PM [OTC]: Acetaminophen 500 mg and diphenhydramine 25 mg per 15 mL
Powder for oral solution: Goody's PM® [OTC]: Acetaminophen 500 mg and diphenhydramine 38 mg
Tablet: Acetaminophen 500 mg and diphenhydramine 25 mg Excedrin® P.M. [OTC]: Acetaminophen 500 mg and diphenhydramine 38 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes gelcap, powder, and liquid
USE — Aid in the relief of insomnia accompanied by minor pain
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
DRUG INTERACTIONS Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Diphenhydramine: Inhibits CYP2D6 (moderate)
Also see individual agents.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
PHARMACODYNAMICS / KINETICS — See individual agents.
Acetaminophen and codeine: Drug information
Copyright 1978-2006 Lexi-Comp, Inc. All rights reserved.
(For additional information see "Acetaminophen and codeine: Patient drug information" and see "Acetaminophen and codeine: Pediatric drug information")
U.S. BRAND NAMES — Capital® and Codeine; Tylenol® With Codeine
PHARMACOLOGIC CATEGORY Analgesic, Opioid
DOSING: ADULTS — Doses should be adjusted according to severity of pain and response of the patient. Adult doses 60 mg codeine fail to give commensurate relief of pain but merely prolong analgesia and are associated with an appreciably increased incidence of side effects.
Cough (Antitussive): Oral: Based on codeine (15-30 mg/dose) every 4-6 hours (maximum: 360 mg/24 hours based on codeine component)
Pain (Analgesic): Oral: Based on codeine (30-60 mg/dose) every 4-6 hours (maximum: 4000 mg/24 hours based on acetaminophen component) 1-2 tablets every 4 hours to a maximum of 12 tablets/24 hours
DOSING: PEDIATRIC
(For additional information see "Acetaminophen and codeine: Pediatric drug information")Analgesic: Oral: 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>12 years: 15 mL every 4 hours as needed of elixir
DOSING: ELDERLY — Doses should be titrated to appropriate analgesic effect.
1 Tylenol® [#3] or 2 Tylenol® [#2] tablets every 4 hours; do not exceed 4 g/day acetaminophen.
DOSING: RENAL IMPAIRMENT — See individual agents.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy is usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product; [CAN] = Canadian brand name
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]
DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name
Caplet: ratio-Lenoltec No. 1 [CAN], Tylenol No. 1 [CAN]: Acetaminophen 300 mg, codeine 8 mg, and caffeine 15 mg [not available in the U.S.] Tylenol No. 1 Forte [CAN]: Acetaminophen 500 mg, codeine 8 mg, and caffeine 15 mg [not available in the U.S.]
Elixir, oral [C-V]: Acetaminophen 120 mg and codeine 12 mg per 5 mL Tylenol Elixir with Codeine [CAN]: Acetaminophen 160 mg and codeine 8 mg per 5 mL [not available in the U.S.]
Suspension, oral [C-V]: Acetaminophen 120 mg and codeine 12 mg per 5 mL Capital® and Codeine [C-V]: Acetaminophen 120 mg and codeine 12 mg per 5 mL
Tablet [C-III]: Acetaminophen 300 mg and codeine 15 mg; acetaminophen 300 mg and codeine 30 mg; acetaminophen 300 mg and codeine 60 mg ratio-Emtec [CAN], Triatec-30 [CAN]: Acetaminophen 300 mg and codeine 30 mg [not available in the U.S.] ratio-Lenoltec No. 1 [CAN]: Acetaminophen 300 mg, codeine 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 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 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 60 mg [not available in the U.S.] Triatec-8 [CAN]: Acetaminophen 325 mg, codeine 8 mg, and caffeine 30 mg [not available in the U.S.] Triatec-8 Strong [CAN]: Acetaminophen 500 mg, codeine 8 mg, and caffeine 30 mg [not available in the U.S.] Tylenol® with Codeine No. 3: Acetaminophen 300 mg and codeine 30 mg Tylenol® with Codeine No. 4: Acetaminophen 300 mg and codeine 60 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of mild-to-moderate pain
ADVERSE REACTIONS SIGNIFICANT >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% (Limited to important or life-threatening): Antidiuretic hormone release, biliary tract spasm, bradycardia, hypotension, intracranial pressure increased, physical and psychological dependence, respiratory depression, urinary retention
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, codeine, or any component of the formulation; significant respiratory depression (in unmonitored settings); acute or severe bronchial asthma; hypercapnia; paralytic ileus
WARNINGS / PRECAUTIONS Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Hepatotoxicity: May cause severe hepatic toxicity on acute overdose; in addition, chronic daily dosing in adults has resulted in liver damage in some patients. Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).
Disease-related concerns: Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions. Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison's disease. CNS depression/coma: Use with caution in patients with CNS depression or coma. Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Ethanol use: Use with caution in patients with alcoholic liver disease; consuming 3 alcoholic drinks/day may increase the risk of liver damage. G6PD deficiency: Use with caution in patients with known G6PD deficiency. Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. Hepatic impairment: Use with caution in patients with severe hepatic impairment. Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture. Renal impairment: Use with caution in patients with renal impairment. Respiratory disease: Use with caution in patients with pre-existing respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function; critical respiratory depression may occur, even at therapeutic dosages. Seizure disorder: Use with caution in patients with a history of seizure disorder. Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations: Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Decrease initial dose.
Dosage form specific issues: Metabisulfite: Tablets contain metabisulfite which may cause allergic reactions. Non-U.S. formulations: 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.
Other warnings/precautions: Dosage limit: Limit total acetaminophen dose to <4 g/day. Withdrawal: Concurrent use of agonist/antagonist analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Abrupt discontinuation following prolonged use may also lead to withdrawal symptoms.
RESTRICTIONS — C-III; C-V
Note: In countries outside of the U.S., some formulations of Tylenol® with Codeine (eg, Tylenol® No. 3) include caffeine.
DRUG INTERACTIONS — Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Increased toxicity: CNS depressants, phenothiazines, tricyclic antidepressants, guanabenz, MAO inhibitors (may also decrease blood pressure); effect of warfarin may be enhanced.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
PREGNANCY RISK FACTOR — C (show table)
LACTATION — Enters breast milk/use caution
DIETARY CONSIDERATIONS — May be taken with food.
PRICING — (data from drugstore.com)Solution (Acetaminophen-Codeine) 120-12 mg/5 mL (118): $8.99 120-12 mg/5 mL (240): $8.98
Tablets (Acetaminophen-Codeine #2) 300-15 mg (30): $7.99
Tablets (Acetaminophen-Codeine #3) 300-30 mg (30): $7.99
Tablets (Acetaminophen-Codeine #4) 300-60 mg (30): $11.99
Tablets (Tylenol/Codeine #3) 300-30 mg (30): $17.69
Tablets (Tylenol/Codeine #4) 300-60 mg (30): $30.54
MONITORING PARAMETERS — Relief of pain, respiratory and mental status, blood pressure, bowel function
TOXICOLOGY / OVERDOSE COMPREHENSIVE Symptoms 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).
CANADIAN BRAND NAMES — ratio-Emtec; ratio-Lenoltec; Triatec-30; Triatec-8 Strong; Triatec-8; Tylenol Elixir with Codeine; Tylenol No. 1 Forte; Tylenol No. 1; Tylenol No. 2 with Codeine; Tylenol No. 3 with Codeine; Tylenol No. 4 with Codeine
INTERNATIONAL BRAND NAMES — Algesidal (FR); Algimide (CO); Algimide F (CO); Chemists Own Dolased Day Pain Relief (AU); Claradol Codeine (FR); Co-Cadamol (SG); Cod-Acamol Forte (IL); Codabrol (IL); Codalgin (AU, NZ); Codapane (AU); Codeidol (CO); Codeidol F (CO); Codeipar (CL); Codicet (TH); Codilprane Enfant (FR); Codipar (GB, IE); Coditam (ID); Codoliprane (FR); Codoliprane Enfant (FR); Codral Pain Relief (AU); Dafalgan Codeine (FR); Dolorol Forte (ZA); Dymadon Co (AU, NZ); Dymadon Forte (AU); Efferalgan Codeine (PY); Febricod (AU); Liquigesic Co (AU); Maxadol (ZA); Nasa w/codeine (TH); Paceco (MY, SG); Panadeine (AN, AU, BB, BM, BS, BZ, CZ, GY, HK, HU, JM, MY, NZ, SR, TT); Panadeine Co (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Panadeine Forte (AU); Panadiene (AN, AU, BB, BM, BS, BZ, CZ, GY, HK, HU, JM, JP, MY, NZ, SR, TT); Panado-Co Caplets (ZA); Panadol Ultra (HK); Panamax (AU); Paracodol (ZA); Paradine (MY); Paramax (EE); Parcono (TH); Parcoten (HK); Perdolan codeine (BE); Prodeine Forte (AU); Prodeine-15 (AU); ratio-Emtec (CA); ratio-Lenoltec (CA); Rokamol Plus (IL); Solpadeine (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Solpadol (GB, IE); Triatec-30 (CA); Triatec-8 (CA); Triatec-8 Strong (CA); TWC 30 (IN); Tylenol Elixir with Codeine (CA); Tylenol No. 1 (CA); Tylenol No. 1 Forte (CA); Tylenol No. 2 with Codeine (CA); Tylenol No. 3 with Codeine (CA); Tylenol No. 4 with Codeine (CA); Tylex CD (CR, DO, GT, HN, MX, NI, PA, SV); Winadol Forte (CO); Zapain (GB, IE)
MECHANISM OF ACTION — Inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center; binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; causes cough supression by direct central action in the medulla; produces generalized CNS depression. Caffeine (contained in some non-U.S. formulations) is a CNS stimulant; use with acetaminophen and codeine increases the level of analgesia provided by each agent.
PHARMACODYNAMICS / KINETICS — See individual agents.
(For additional information see "Acetaminophen and codeine: Patient drug information" and see "Acetaminophen and codeine: Pediatric drug information")
U.S. BRAND NAMES — Capital® and Codeine; Tylenol® With Codeine
PHARMACOLOGIC CATEGORY Analgesic, Opioid
DOSING: ADULTS — Doses should be adjusted according to severity of pain and response of the patient. Adult doses 60 mg codeine fail to give commensurate relief of pain but merely prolong analgesia and are associated with an appreciably increased incidence of side effects.
Cough (Antitussive): Oral: Based on codeine (15-30 mg/dose) every 4-6 hours (maximum: 360 mg/24 hours based on codeine component)
Pain (Analgesic): Oral: Based on codeine (30-60 mg/dose) every 4-6 hours (maximum: 4000 mg/24 hours based on acetaminophen component) 1-2 tablets every 4 hours to a maximum of 12 tablets/24 hours
DOSING: PEDIATRIC
(For additional information see "Acetaminophen and codeine: Pediatric drug information")Analgesic: Oral: 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>12 years: 15 mL every 4 hours as needed of elixir
DOSING: ELDERLY — Doses should be titrated to appropriate analgesic effect.
1 Tylenol® [#3] or 2 Tylenol® [#2] tablets every 4 hours; do not exceed 4 g/day acetaminophen.
DOSING: RENAL IMPAIRMENT — See individual agents.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy is usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product; [CAN] = Canadian brand name
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]
DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name
Caplet: ratio-Lenoltec No. 1 [CAN], Tylenol No. 1 [CAN]: Acetaminophen 300 mg, codeine 8 mg, and caffeine 15 mg [not available in the U.S.] Tylenol No. 1 Forte [CAN]: Acetaminophen 500 mg, codeine 8 mg, and caffeine 15 mg [not available in the U.S.]
Elixir, oral [C-V]: Acetaminophen 120 mg and codeine 12 mg per 5 mL Tylenol Elixir with Codeine [CAN]: Acetaminophen 160 mg and codeine 8 mg per 5 mL [not available in the U.S.]
Suspension, oral [C-V]: Acetaminophen 120 mg and codeine 12 mg per 5 mL Capital® and Codeine [C-V]: Acetaminophen 120 mg and codeine 12 mg per 5 mL
Tablet [C-III]: Acetaminophen 300 mg and codeine 15 mg; acetaminophen 300 mg and codeine 30 mg; acetaminophen 300 mg and codeine 60 mg ratio-Emtec [CAN], Triatec-30 [CAN]: Acetaminophen 300 mg and codeine 30 mg [not available in the U.S.] ratio-Lenoltec No. 1 [CAN]: Acetaminophen 300 mg, codeine 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 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 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 60 mg [not available in the U.S.] Triatec-8 [CAN]: Acetaminophen 325 mg, codeine 8 mg, and caffeine 30 mg [not available in the U.S.] Triatec-8 Strong [CAN]: Acetaminophen 500 mg, codeine 8 mg, and caffeine 30 mg [not available in the U.S.] Tylenol® with Codeine No. 3: Acetaminophen 300 mg and codeine 30 mg Tylenol® with Codeine No. 4: Acetaminophen 300 mg and codeine 60 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of mild-to-moderate pain
ADVERSE REACTIONS SIGNIFICANT >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% (Limited to important or life-threatening): Antidiuretic hormone release, biliary tract spasm, bradycardia, hypotension, intracranial pressure increased, physical and psychological dependence, respiratory depression, urinary retention
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, codeine, or any component of the formulation; significant respiratory depression (in unmonitored settings); acute or severe bronchial asthma; hypercapnia; paralytic ileus
WARNINGS / PRECAUTIONS Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Hepatotoxicity: May cause severe hepatic toxicity on acute overdose; in addition, chronic daily dosing in adults has resulted in liver damage in some patients. Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).
Disease-related concerns: Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions. Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison's disease. CNS depression/coma: Use with caution in patients with CNS depression or coma. Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Ethanol use: Use with caution in patients with alcoholic liver disease; consuming 3 alcoholic drinks/day may increase the risk of liver damage. G6PD deficiency: Use with caution in patients with known G6PD deficiency. Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. Hepatic impairment: Use with caution in patients with severe hepatic impairment. Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture. Renal impairment: Use with caution in patients with renal impairment. Respiratory disease: Use with caution in patients with pre-existing respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function; critical respiratory depression may occur, even at therapeutic dosages. Seizure disorder: Use with caution in patients with a history of seizure disorder. Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations: Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Decrease initial dose.
Dosage form specific issues: Metabisulfite: Tablets contain metabisulfite which may cause allergic reactions. Non-U.S. formulations: 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.
Other warnings/precautions: Dosage limit: Limit total acetaminophen dose to <4 g/day. Withdrawal: Concurrent use of agonist/antagonist analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Abrupt discontinuation following prolonged use may also lead to withdrawal symptoms.
RESTRICTIONS — C-III; C-V
Note: In countries outside of the U.S., some formulations of Tylenol® with Codeine (eg, Tylenol® No. 3) include caffeine.
DRUG INTERACTIONS — Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Increased toxicity: CNS depressants, phenothiazines, tricyclic antidepressants, guanabenz, MAO inhibitors (may also decrease blood pressure); effect of warfarin may be enhanced.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
PREGNANCY RISK FACTOR — C (show table)
LACTATION — Enters breast milk/use caution
DIETARY CONSIDERATIONS — May be taken with food.
PRICING — (data from drugstore.com)Solution (Acetaminophen-Codeine) 120-12 mg/5 mL (118): $8.99 120-12 mg/5 mL (240): $8.98
Tablets (Acetaminophen-Codeine #2) 300-15 mg (30): $7.99
Tablets (Acetaminophen-Codeine #3) 300-30 mg (30): $7.99
Tablets (Acetaminophen-Codeine #4) 300-60 mg (30): $11.99
Tablets (Tylenol/Codeine #3) 300-30 mg (30): $17.69
Tablets (Tylenol/Codeine #4) 300-60 mg (30): $30.54
MONITORING PARAMETERS — Relief of pain, respiratory and mental status, blood pressure, bowel function
TOXICOLOGY / OVERDOSE COMPREHENSIVE Symptoms 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).
CANADIAN BRAND NAMES — ratio-Emtec; ratio-Lenoltec; Triatec-30; Triatec-8 Strong; Triatec-8; Tylenol Elixir with Codeine; Tylenol No. 1 Forte; Tylenol No. 1; Tylenol No. 2 with Codeine; Tylenol No. 3 with Codeine; Tylenol No. 4 with Codeine
INTERNATIONAL BRAND NAMES — Algesidal (FR); Algimide (CO); Algimide F (CO); Chemists Own Dolased Day Pain Relief (AU); Claradol Codeine (FR); Co-Cadamol (SG); Cod-Acamol Forte (IL); Codabrol (IL); Codalgin (AU, NZ); Codapane (AU); Codeidol (CO); Codeidol F (CO); Codeipar (CL); Codicet (TH); Codilprane Enfant (FR); Codipar (GB, IE); Coditam (ID); Codoliprane (FR); Codoliprane Enfant (FR); Codral Pain Relief (AU); Dafalgan Codeine (FR); Dolorol Forte (ZA); Dymadon Co (AU, NZ); Dymadon Forte (AU); Efferalgan Codeine (PY); Febricod (AU); Liquigesic Co (AU); Maxadol (ZA); Nasa w/codeine (TH); Paceco (MY, SG); Panadeine (AN, AU, BB, BM, BS, BZ, CZ, GY, HK, HU, JM, MY, NZ, SR, TT); Panadeine Co (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Panadeine Forte (AU); Panadiene (AN, AU, BB, BM, BS, BZ, CZ, GY, HK, HU, JM, JP, MY, NZ, SR, TT); Panado-Co Caplets (ZA); Panadol Ultra (HK); Panamax (AU); Paracodol (ZA); Paradine (MY); Paramax (EE); Parcono (TH); Parcoten (HK); Perdolan codeine (BE); Prodeine Forte (AU); Prodeine-15 (AU); ratio-Emtec (CA); ratio-Lenoltec (CA); Rokamol Plus (IL); Solpadeine (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Solpadol (GB, IE); Triatec-30 (CA); Triatec-8 (CA); Triatec-8 Strong (CA); TWC 30 (IN); Tylenol Elixir with Codeine (CA); Tylenol No. 1 (CA); Tylenol No. 1 Forte (CA); Tylenol No. 2 with Codeine (CA); Tylenol No. 3 with Codeine (CA); Tylenol No. 4 with Codeine (CA); Tylex CD (CR, DO, GT, HN, MX, NI, PA, SV); Winadol Forte (CO); Zapain (GB, IE)
MECHANISM OF ACTION — Inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center; binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; causes cough supression by direct central action in the medulla; produces generalized CNS depression. Caffeine (contained in some non-U.S. formulations) is a CNS stimulant; use with acetaminophen and codeine increases the level of analgesia provided by each agent.
PHARMACODYNAMICS / KINETICS — See individual agents.
Acetaminophen and codeine: Drug information
Copyright 1978-2006 Lexi-Comp, Inc. All rights reserved.
(For additional information see "Acetaminophen and codeine: Patient drug information" and see "Acetaminophen and codeine: Pediatric drug information")
U.S. BRAND NAMES — Capital® and Codeine; Tylenol® With Codeine
PHARMACOLOGIC CATEGORY Analgesic, Opioid
DOSING: ADULTS — Doses should be adjusted according to severity of pain and response of the patient. Adult doses 60 mg codeine fail to give commensurate relief of pain but merely prolong analgesia and are associated with an appreciably increased incidence of side effects.
Cough (Antitussive): Oral: Based on codeine (15-30 mg/dose) every 4-6 hours (maximum: 360 mg/24 hours based on codeine component)
Pain (Analgesic): Oral: Based on codeine (30-60 mg/dose) every 4-6 hours (maximum: 4000 mg/24 hours based on acetaminophen component) 1-2 tablets every 4 hours to a maximum of 12 tablets/24 hours
DOSING: PEDIATRIC
(For additional information see "Acetaminophen and codeine: Pediatric drug information")Analgesic: Oral: 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>12 years: 15 mL every 4 hours as needed of elixir
DOSING: ELDERLY — Doses should be titrated to appropriate analgesic effect.
1 Tylenol® [#3] or 2 Tylenol® [#2] tablets every 4 hours; do not exceed 4 g/day acetaminophen.
DOSING: RENAL IMPAIRMENT — See individual agents.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy is usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product; [CAN] = Canadian brand name
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]
DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name
Caplet: ratio-Lenoltec No. 1 [CAN], Tylenol No. 1 [CAN]: Acetaminophen 300 mg, codeine 8 mg, and caffeine 15 mg [not available in the U.S.] Tylenol No. 1 Forte [CAN]: Acetaminophen 500 mg, codeine 8 mg, and caffeine 15 mg [not available in the U.S.]
Elixir, oral [C-V]: Acetaminophen 120 mg and codeine 12 mg per 5 mL Tylenol Elixir with Codeine [CAN]: Acetaminophen 160 mg and codeine 8 mg per 5 mL [not available in the U.S.]
Suspension, oral [C-V]: Acetaminophen 120 mg and codeine 12 mg per 5 mL Capital® and Codeine [C-V]: Acetaminophen 120 mg and codeine 12 mg per 5 mL
Tablet [C-III]: Acetaminophen 300 mg and codeine 15 mg; acetaminophen 300 mg and codeine 30 mg; acetaminophen 300 mg and codeine 60 mg ratio-Emtec [CAN], Triatec-30 [CAN]: Acetaminophen 300 mg and codeine 30 mg [not available in the U.S.] ratio-Lenoltec No. 1 [CAN]: Acetaminophen 300 mg, codeine 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 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 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 60 mg [not available in the U.S.] Triatec-8 [CAN]: Acetaminophen 325 mg, codeine 8 mg, and caffeine 30 mg [not available in the U.S.] Triatec-8 Strong [CAN]: Acetaminophen 500 mg, codeine 8 mg, and caffeine 30 mg [not available in the U.S.] Tylenol® with Codeine No. 3: Acetaminophen 300 mg and codeine 30 mg Tylenol® with Codeine No. 4: Acetaminophen 300 mg and codeine 60 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of mild-to-moderate pain
ADVERSE REACTIONS SIGNIFICANT >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% (Limited to important or life-threatening): Antidiuretic hormone release, biliary tract spasm, bradycardia, hypotension, intracranial pressure increased, physical and psychological dependence, respiratory depression, urinary retention
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, codeine, or any component of the formulation; significant respiratory depression (in unmonitored settings); acute or severe bronchial asthma; hypercapnia; paralytic ileus
WARNINGS / PRECAUTIONS Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Hepatotoxicity: May cause severe hepatic toxicity on acute overdose; in addition, chronic daily dosing in adults has resulted in liver damage in some patients. Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).
Disease-related concerns: Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions. Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison's disease. CNS depression/coma: Use with caution in patients with CNS depression or coma. Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Ethanol use: Use with caution in patients with alcoholic liver disease; consuming 3 alcoholic drinks/day may increase the risk of liver damage. G6PD deficiency: Use with caution in patients with known G6PD deficiency. Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. Hepatic impairment: Use with caution in patients with severe hepatic impairment. Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture. Renal impairment: Use with caution in patients with renal impairment. Respiratory disease: Use with caution in patients with pre-existing respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function; critical respiratory depression may occur, even at therapeutic dosages. Seizure disorder: Use with caution in patients with a history of seizure disorder. Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations: Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Decrease initial dose.
Dosage form specific issues: Metabisulfite: Tablets contain metabisulfite which may cause allergic reactions. Non-U.S. formulations: 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.
Other warnings/precautions: Dosage limit: Limit total acetaminophen dose to <4 g/day. Withdrawal: Concurrent use of agonist/antagonist analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Abrupt discontinuation following prolonged use may also lead to withdrawal symptoms.
RESTRICTIONS — C-III; C-V
Note: In countries outside of the U.S., some formulations of Tylenol® with Codeine (eg, Tylenol® No. 3) include caffeine.
DRUG INTERACTIONS — Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Increased toxicity: CNS depressants, phenothiazines, tricyclic antidepressants, guanabenz, MAO inhibitors (may also decrease blood pressure); effect of warfarin may be enhanced.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
PREGNANCY RISK FACTOR — C (show table)
LACTATION — Enters breast milk/use caution
DIETARY CONSIDERATIONS — May be taken with food.
PRICING — (data from drugstore.com)Solution (Acetaminophen-Codeine) 120-12 mg/5 mL (118): $8.99 120-12 mg/5 mL (240): $8.98
Tablets (Acetaminophen-Codeine #2) 300-15 mg (30): $7.99
Tablets (Acetaminophen-Codeine #3) 300-30 mg (30): $7.99
Tablets (Acetaminophen-Codeine #4) 300-60 mg (30): $11.99
Tablets (Tylenol/Codeine #3) 300-30 mg (30): $17.69
Tablets (Tylenol/Codeine #4) 300-60 mg (30): $30.54
MONITORING PARAMETERS — Relief of pain, respiratory and mental status, blood pressure, bowel function
TOXICOLOGY / OVERDOSE COMPREHENSIVE Symptoms 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).
CANADIAN BRAND NAMES — ratio-Emtec; ratio-Lenoltec; Triatec-30; Triatec-8 Strong; Triatec-8; Tylenol Elixir with Codeine; Tylenol No. 1 Forte; Tylenol No. 1; Tylenol No. 2 with Codeine; Tylenol No. 3 with Codeine; Tylenol No. 4 with Codeine
INTERNATIONAL BRAND NAMES — Algesidal (FR); Algimide (CO); Algimide F (CO); Chemists Own Dolased Day Pain Relief (AU); Claradol Codeine (FR); Co-Cadamol (SG); Cod-Acamol Forte (IL); Codabrol (IL); Codalgin (AU, NZ); Codapane (AU); Codeidol (CO); Codeidol F (CO); Codeipar (CL); Codicet (TH); Codilprane Enfant (FR); Codipar (GB, IE); Coditam (ID); Codoliprane (FR); Codoliprane Enfant (FR); Codral Pain Relief (AU); Dafalgan Codeine (FR); Dolorol Forte (ZA); Dymadon Co (AU, NZ); Dymadon Forte (AU); Efferalgan Codeine (PY); Febricod (AU); Liquigesic Co (AU); Maxadol (ZA); Nasa w/codeine (TH); Paceco (MY, SG); Panadeine (AN, AU, BB, BM, BS, BZ, CZ, GY, HK, HU, JM, MY, NZ, SR, TT); Panadeine Co (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Panadeine Forte (AU); Panadiene (AN, AU, BB, BM, BS, BZ, CZ, GY, HK, HU, JM, JP, MY, NZ, SR, TT); Panado-Co Caplets (ZA); Panadol Ultra (HK); Panamax (AU); Paracodol (ZA); Paradine (MY); Paramax (EE); Parcono (TH); Parcoten (HK); Perdolan codeine (BE); Prodeine Forte (AU); Prodeine-15 (AU); ratio-Emtec (CA); ratio-Lenoltec (CA); Rokamol Plus (IL); Solpadeine (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Solpadol (GB, IE); Triatec-30 (CA); Triatec-8 (CA); Triatec-8 Strong (CA); TWC 30 (IN); Tylenol Elixir with Codeine (CA); Tylenol No. 1 (CA); Tylenol No. 1 Forte (CA); Tylenol No. 2 with Codeine (CA); Tylenol No. 3 with Codeine (CA); Tylenol No. 4 with Codeine (CA); Tylex CD (CR, DO, GT, HN, MX, NI, PA, SV); Winadol Forte (CO); Zapain (GB, IE)
MECHANISM OF ACTION — Inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center; binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; causes cough supression by direct central action in the medulla; produces generalized CNS depression. Caffeine (contained in some non-U.S. formulations) is a CNS stimulant; use with acetaminophen and codeine increases the level of analgesia provided by each agent.
PHARMACODYNAMICS / KINETICS — See individual agents.
(For additional information see "Acetaminophen and codeine: Patient drug information" and see "Acetaminophen and codeine: Pediatric drug information")
U.S. BRAND NAMES — Capital® and Codeine; Tylenol® With Codeine
PHARMACOLOGIC CATEGORY Analgesic, Opioid
DOSING: ADULTS — Doses should be adjusted according to severity of pain and response of the patient. Adult doses 60 mg codeine fail to give commensurate relief of pain but merely prolong analgesia and are associated with an appreciably increased incidence of side effects.
Cough (Antitussive): Oral: Based on codeine (15-30 mg/dose) every 4-6 hours (maximum: 360 mg/24 hours based on codeine component)
Pain (Analgesic): Oral: Based on codeine (30-60 mg/dose) every 4-6 hours (maximum: 4000 mg/24 hours based on acetaminophen component) 1-2 tablets every 4 hours to a maximum of 12 tablets/24 hours
DOSING: PEDIATRIC
(For additional information see "Acetaminophen and codeine: Pediatric drug information")Analgesic: Oral: 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>12 years: 15 mL every 4 hours as needed of elixir
DOSING: ELDERLY — Doses should be titrated to appropriate analgesic effect.
1 Tylenol® [#3] or 2 Tylenol® [#2] tablets every 4 hours; do not exceed 4 g/day acetaminophen.
DOSING: RENAL IMPAIRMENT — See individual agents.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy is usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product; [CAN] = Canadian brand name
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]
DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name
Caplet: ratio-Lenoltec No. 1 [CAN], Tylenol No. 1 [CAN]: Acetaminophen 300 mg, codeine 8 mg, and caffeine 15 mg [not available in the U.S.] Tylenol No. 1 Forte [CAN]: Acetaminophen 500 mg, codeine 8 mg, and caffeine 15 mg [not available in the U.S.]
Elixir, oral [C-V]: Acetaminophen 120 mg and codeine 12 mg per 5 mL Tylenol Elixir with Codeine [CAN]: Acetaminophen 160 mg and codeine 8 mg per 5 mL [not available in the U.S.]
Suspension, oral [C-V]: Acetaminophen 120 mg and codeine 12 mg per 5 mL Capital® and Codeine [C-V]: Acetaminophen 120 mg and codeine 12 mg per 5 mL
Tablet [C-III]: Acetaminophen 300 mg and codeine 15 mg; acetaminophen 300 mg and codeine 30 mg; acetaminophen 300 mg and codeine 60 mg ratio-Emtec [CAN], Triatec-30 [CAN]: Acetaminophen 300 mg and codeine 30 mg [not available in the U.S.] ratio-Lenoltec No. 1 [CAN]: Acetaminophen 300 mg, codeine 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 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 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 60 mg [not available in the U.S.] Triatec-8 [CAN]: Acetaminophen 325 mg, codeine 8 mg, and caffeine 30 mg [not available in the U.S.] Triatec-8 Strong [CAN]: Acetaminophen 500 mg, codeine 8 mg, and caffeine 30 mg [not available in the U.S.] Tylenol® with Codeine No. 3: Acetaminophen 300 mg and codeine 30 mg Tylenol® with Codeine No. 4: Acetaminophen 300 mg and codeine 60 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of mild-to-moderate pain
ADVERSE REACTIONS SIGNIFICANT >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% (Limited to important or life-threatening): Antidiuretic hormone release, biliary tract spasm, bradycardia, hypotension, intracranial pressure increased, physical and psychological dependence, respiratory depression, urinary retention
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, codeine, or any component of the formulation; significant respiratory depression (in unmonitored settings); acute or severe bronchial asthma; hypercapnia; paralytic ileus
WARNINGS / PRECAUTIONS Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Hepatotoxicity: May cause severe hepatic toxicity on acute overdose; in addition, chronic daily dosing in adults has resulted in liver damage in some patients. Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).
Disease-related concerns: Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions. Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison's disease. CNS depression/coma: Use with caution in patients with CNS depression or coma. Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Ethanol use: Use with caution in patients with alcoholic liver disease; consuming 3 alcoholic drinks/day may increase the risk of liver damage. G6PD deficiency: Use with caution in patients with known G6PD deficiency. Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. Hepatic impairment: Use with caution in patients with severe hepatic impairment. Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture. Renal impairment: Use with caution in patients with renal impairment. Respiratory disease: Use with caution in patients with pre-existing respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function; critical respiratory depression may occur, even at therapeutic dosages. Seizure disorder: Use with caution in patients with a history of seizure disorder. Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations: Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Decrease initial dose.
Dosage form specific issues: Metabisulfite: Tablets contain metabisulfite which may cause allergic reactions. Non-U.S. formulations: 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.
Other warnings/precautions: Dosage limit: Limit total acetaminophen dose to <4 g/day. Withdrawal: Concurrent use of agonist/antagonist analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Abrupt discontinuation following prolonged use may also lead to withdrawal symptoms.
RESTRICTIONS — C-III; C-V
Note: In countries outside of the U.S., some formulations of Tylenol® with Codeine (eg, Tylenol® No. 3) include caffeine.
DRUG INTERACTIONS — Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Increased toxicity: CNS depressants, phenothiazines, tricyclic antidepressants, guanabenz, MAO inhibitors (may also decrease blood pressure); effect of warfarin may be enhanced.
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
PREGNANCY RISK FACTOR — C (show table)
LACTATION — Enters breast milk/use caution
DIETARY CONSIDERATIONS — May be taken with food.
PRICING — (data from drugstore.com)Solution (Acetaminophen-Codeine) 120-12 mg/5 mL (118): $8.99 120-12 mg/5 mL (240): $8.98
Tablets (Acetaminophen-Codeine #2) 300-15 mg (30): $7.99
Tablets (Acetaminophen-Codeine #3) 300-30 mg (30): $7.99
Tablets (Acetaminophen-Codeine #4) 300-60 mg (30): $11.99
Tablets (Tylenol/Codeine #3) 300-30 mg (30): $17.69
Tablets (Tylenol/Codeine #4) 300-60 mg (30): $30.54
MONITORING PARAMETERS — Relief of pain, respiratory and mental status, blood pressure, bowel function
TOXICOLOGY / OVERDOSE COMPREHENSIVE Symptoms 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).
CANADIAN BRAND NAMES — ratio-Emtec; ratio-Lenoltec; Triatec-30; Triatec-8 Strong; Triatec-8; Tylenol Elixir with Codeine; Tylenol No. 1 Forte; Tylenol No. 1; Tylenol No. 2 with Codeine; Tylenol No. 3 with Codeine; Tylenol No. 4 with Codeine
INTERNATIONAL BRAND NAMES — Algesidal (FR); Algimide (CO); Algimide F (CO); Chemists Own Dolased Day Pain Relief (AU); Claradol Codeine (FR); Co-Cadamol (SG); Cod-Acamol Forte (IL); Codabrol (IL); Codalgin (AU, NZ); Codapane (AU); Codeidol (CO); Codeidol F (CO); Codeipar (CL); Codicet (TH); Codilprane Enfant (FR); Codipar (GB, IE); Coditam (ID); Codoliprane (FR); Codoliprane Enfant (FR); Codral Pain Relief (AU); Dafalgan Codeine (FR); Dolorol Forte (ZA); Dymadon Co (AU, NZ); Dymadon Forte (AU); Efferalgan Codeine (PY); Febricod (AU); Liquigesic Co (AU); Maxadol (ZA); Nasa w/codeine (TH); Paceco (MY, SG); Panadeine (AN, AU, BB, BM, BS, BZ, CZ, GY, HK, HU, JM, MY, NZ, SR, TT); Panadeine Co (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Panadeine Forte (AU); Panadiene (AN, AU, BB, BM, BS, BZ, CZ, GY, HK, HU, JM, JP, MY, NZ, SR, TT); Panado-Co Caplets (ZA); Panadol Ultra (HK); Panamax (AU); Paracodol (ZA); Paradine (MY); Paramax (EE); Parcono (TH); Parcoten (HK); Perdolan codeine (BE); Prodeine Forte (AU); Prodeine-15 (AU); ratio-Emtec (CA); ratio-Lenoltec (CA); Rokamol Plus (IL); Solpadeine (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Solpadol (GB, IE); Triatec-30 (CA); Triatec-8 (CA); Triatec-8 Strong (CA); TWC 30 (IN); Tylenol Elixir with Codeine (CA); Tylenol No. 1 (CA); Tylenol No. 1 Forte (CA); Tylenol No. 2 with Codeine (CA); Tylenol No. 3 with Codeine (CA); Tylenol No. 4 with Codeine (CA); Tylex CD (CR, DO, GT, HN, MX, NI, PA, SV); Winadol Forte (CO); Zapain (GB, IE)
MECHANISM OF ACTION — Inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center; binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; causes cough supression by direct central action in the medulla; produces generalized CNS depression. Caffeine (contained in some non-U.S. formulations) is a CNS stimulant; use with acetaminophen and codeine increases the level of analgesia provided by each agent.
PHARMACODYNAMICS / KINETICS — See individual agents.
Acenocoumarol: Drug information
(For additional information see "Acenocoumarol: Patient drug information")
PHARMACOLOGIC CATEGORY Anticoagulant, Coumarin Derivative
DOSING: ADULTS — Note: Dosage must be individualized. The following information is based on the manufacturer's labeling in Canada.
Oral: Initial: 8-12 mg on day 1, followed by 4-8 mg on day 2. Subsequent dosage should be based on PT/INR measurements. Usual range of maintenance doses: 1-10 mg/day. Tapering of dosage is recommended prior to discontinuation.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [CAN] = Canadian brand name
Tablet: Sintrom® [CAN]: 1 mg, 4 mg [not available in the U.S.]
DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name
Tablet: Sintrom® [CAN]: 1 mg, 4 mg [not available in the U.S.]
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer at the same time each day.
USE — Prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders; atrial fibrillation with risk of embolism; adjunct in the prophylaxis of coronary occlusion and transient ischemic attacks
ADVERSE REACTIONS SIGNIFICANT — As with all anticoagulants, bleeding is the major adverse effect of acenocoumarol. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the intensity of anticoagulation and patient susceptibility.
Frequency not defined. Cardiovascular: Hemorrhagic shock Central nervous system: Fever, headache, stroke (hemorrhagic) Dermatologic: Rash, urticaria, skin necrosis Skin necrosis/gangrene, due to paradoxical local thrombosis, is a known but rare risk of oral anticoagulant therapy. Its onset is usually within the first few days of therapy and is frequently localized to the limbs, breast, or penis. The risk of this effect is increased in patients with protein C or S deficiency.
Additional adverse reactions associated with warfarin, but likely to also occur with indanediones, include priapism and skin necrosis ("purple toe" syndrome or cutaneous gangrene). Gastrointestinal: Gastrointestinal bleeding, melena Genitourinary: Hematuria Hematologic: Hemorrhage, retroperitoneal hematoma, unrecognized bleeding sites (eg, colon cancer) may be uncovered by anticoagulation. Other hematologic reactions reported with coumarin derivatives include agranulocytosis, red cell aplasia, anemia, thrombocytopenia, eosinophilia. Hepatic: Hepatitis, hepatotoxicity, hematobilia Ocular: Ocular hemorrhage Respiratory: Epistaxis, hemoptysis, pulmonary hemorrhage Miscellaneous: Hypersensitivity/allergic reactions
CONTRAINDICATIONS — Hypersensitivity to acenocoumarol or any component of the formulation; hemorrhagic tendencies; hemophilia; thrombocytopenia purpura; leukemia; recent or potential surgery of the eye or CNS; major regional lumbar block anesthesia or surgery resulting in large, open surfaces; bleeding from the GI, respiratory, or GU tract; threatened abortion; aneurysm; prolonged dietary insufficiencies (vitamin K deficiency); ascorbic acid deficiency; history of bleeding diathesis; prostatectomy; continuous tube drainage of the small intestine; polyarthritis; diverticulitis; emaciation; malnutrition; cerebrovascular hemorrhage; eclampsia/pre-eclampsia; blood dyscrasias; severe uncontrolled or malignant hypertension; severe hepatic disease; pericarditis or pericardial effusion; subacute bacterial endocarditis; visceral carcinoma; following spinal puncture and other diagnostic or therapeutic procedures with potential for significant bleeding; history of warfarin-induced necrosis; an unreliable, noncompliant patient; alcoholism; patient who has a history of falls or is a significant fall risk; pregnancy
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Anaphylaxis/hypersensitivity: May cause hypersensitivity reactions, including anaphylaxis; use with caution in patients with anaphylactic disorders. Bleeding: May cause major or fatal bleeding. Risk factors for bleeding include high intensity anticoagulation (INR >4), age (>65 years), variable INRs, history of GI bleeding, hypertension, cerebrovascular disease, serious heart disease, anemia, severe diabetes, malignancy, trauma, renal insufficiency, polycythemia vera, vasculitis, open wound, history of PUD, indwelling catheters, menstruating and postpartum women, drug-drug interactions and long duration of therapy. Patient must be instructed to report bleeding, accidents, or falls as well as any new or discontinued medications, herbal or alternative products used, significant changes in smoking or dietary habits. Skin necrosis/gangrene: Necrosis or gangrene of the skin and other tissues can occur (rarely) due to early hypercoagulability; risk is increased in patients with protein C deficiency. "Purple toe" syndrome, due to cholesterol microembolization, has been described with coumarin-type anticoagulants.
Disease-related concerns: Infection: Use with caution in patients with acute infection or active TB; antibiotics and fever may alter response to acenocoumarol. Renal impairment: Use with caution in patients with renal impairment. Thyroid disease: Use with caution in patients with thyroid disease.
Special populations: Elderly: The elderly may be more sensitive to anticoagulant therapy. Ovulating women: May be at risk of developing ovarian hemorrhage at the time of ovulation. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Patient selection: Use care in the selection of patients appropriate for this treatment; ensure patient cooperation especially from the alcoholic, illicit drug user, demented, or psychotic patient.
RESTRICTIONS — Not available in U.S.
DRUG INTERACTIONS Substrate of CYP1A2 (major), 2C9 (major), 2C19 (minor)
Note: As an oral coumarin derivative, acenocoumarol is likely subject to the same pharmacodynamic drug-drug interactions as warfarin.
Acetaminophen: May increase the effects of acenocoumarol.
Amiodarone: May increase the level/effects of acenocoumarol.
Anticoagulants: May increase the effects of acenocoumarol.
Antiplatelet agents: May increase the effects of acenocoumarol.
CYP1A2 inducers may decrease the levels/effects of acenocoumarol. Example inducers include aminoglutethimide, carbamazepine, phenobarbital, and rifampin.
CYP1A2 inhibitors may increase the levels/effects of acenocoumarol. Example inhibitors include ciprofloxacin, fluvoxamine, ketoconazole, norfloxacin, ofloxacin, and rofecoxib.
CYP2C9 inducers may decrease the levels/effects of acenocoumarol. Example inducers include carbamazepine, phenobarbital, phenytoin, rifampin, rifapentine, and secobarbital.
CYP2C9 inhibitors may increase the levels/effects of acenocoumarol. Example inhibitors include delavirdine, fluconazole, gemfibrozil, ketoconazole, nicardipine, NSAIDs, pioglitazone, and sulfonamides.
Miconazole: May increase the level/effects of acenocoumarol.
NSAIDs: May increase the level/effects of acenocoumarol.
Salicylates: May increase the effects of acenocoumarol.
Sulfamethoxazole: May increase the effects of acenocoumarol.
Sulfinpyrazone: May increase the effects of acenocoumarol.
Tetracycline antibiotics: May increase the effects of acenocoumarol.
Trimethoprim: May increase the effects of acenocoumarol.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Avoid ethanol. Acute ethanol ingestion (binge drinking) decreases the metabolism of oral anticoagulants and increases PT/INR. Chronic daily ethanol use increases the metabolism of oral anticoagulants and decreases PT/INR.
Food: The anticoagulant effects of acenocoumarol may be decreased if taken with foods rich in vitamin K. Vitamin E may increase anticoagulant effect.
Herb/Nutraceutical: St John's wort may decrease oral anticoagulant levels. Alfalfa contains large amounts of vitamin K as do many enteral products. Coenzyme Q10 may decrease response to oral anticoagulants. Avoid cat's claw, dong quai, evening primrose, feverfew, red clover, horse chestnut, garlic, green tea, ginseng, and ginkgo (all have additional antiplatelet activity).
PREGNANCY IMPLICATIONS — Oral anticoagulants cross the placenta and produce fetal abnormalities. Fatal hemorrhage in the fetus has been reported even when the mother's acenocoumarol levels were in the therapeutic range. Acenocoumarol should not be used during pregnancy because of significant risks. Adjusted-dose heparin can be given safely throughout pregnancy in patients with venous thromboembolism. Women of childbearing potential are advised to use effective contraception during treatment.
LACTATION — Enters breast milk/not recommended (per manufacturer)
DIETARY CONSIDERATIONS — Foods high in vitamin K (eg, beef liver, pork liver, green tea, and leafy green vegetables) inhibit anticoagulant effect. Do not change dietary habits once stabilized on acenocoumarol therapy. A balanced diet with a consistent intake of vitamin K is essential. Avoid large amounts of alfalfa, asparagus, broccoli, Brussels sprouts, cabbage, cauliflower, green teas, kale, lettuce, spinach, turnip greens, watercress; these decrease efficacy of oral anticoagulants. It is recommended that the diet contain a CONSISTENT vitamin K content of 70-140 mcg/day. Check with healthcare provider before changing diet. Avoid using multivitamins that contain vitamin K.
MONITORING PARAMETERS — PT/INR; hepatic function, CBC, urinalysis (for albuminuria/proteinuria)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms of overdose include internal or external hemorrhage and hematuria. Avoid emesis and lavage to avoid possible trauma and incidental bleeding. When an overdose occurs, the drug should be immediately discontinued and vitamin K1 (phytonadione) may be administered, up to 40 mg I.V. for adults. When hemorrhage occurs, fresh frozen plasma transfusions can help control bleeding by replacing clotting factors. In urgent bleeding, prothrombin complex concentrates may be needed.
CANADIAN BRAND NAMES — Sintrom®
INTERNATIONAL BRAND NAMES — Acenocoumarol (PL); Acenocumarol (PL); Acenox (CL); Acitrom (IN); Coarol (CL); Isquelium (CL); Mini-Sintrom (FR); Neo-Sintrom (CL); Sinthrome (GB); Sintrom (AR, AT, BE, CA, CH, ES, FR, GR, IL, IT, MX, NL, PL, PT); Syncumar (PL)
MECHANISM OF ACTION — Interferes with hepatic synthesis of vitamin K-dependent coagulation factors (II, VII, IX, X)
PHARMACODYNAMICS / KINETICS Onset of action: Peak anticoagulant effect: Oral: 36-48 hours
Absorption: Oral: 60%
Protein binding: 99%
Metabolism: Hepatic, via oxidation (possibly by CYP1A2, 2C9, and 2C19) to inactive metabolites
Half-life elimination: 8-11 hours
Time to peak, plasma: 1-3 hours
Excretion: Urine (60%) and feces (29%) as metabolites
PHARMACOLOGIC CATEGORY Anticoagulant, Coumarin Derivative
DOSING: ADULTS — Note: Dosage must be individualized. The following information is based on the manufacturer's labeling in Canada.
Oral: Initial: 8-12 mg on day 1, followed by 4-8 mg on day 2. Subsequent dosage should be based on PT/INR measurements. Usual range of maintenance doses: 1-10 mg/day. Tapering of dosage is recommended prior to discontinuation.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [CAN] = Canadian brand name
Tablet: Sintrom® [CAN]: 1 mg, 4 mg [not available in the U.S.]
DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name
Tablet: Sintrom® [CAN]: 1 mg, 4 mg [not available in the U.S.]
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer at the same time each day.
USE — Prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders; atrial fibrillation with risk of embolism; adjunct in the prophylaxis of coronary occlusion and transient ischemic attacks
ADVERSE REACTIONS SIGNIFICANT — As with all anticoagulants, bleeding is the major adverse effect of acenocoumarol. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the intensity of anticoagulation and patient susceptibility.
Frequency not defined. Cardiovascular: Hemorrhagic shock Central nervous system: Fever, headache, stroke (hemorrhagic) Dermatologic: Rash, urticaria, skin necrosis Skin necrosis/gangrene, due to paradoxical local thrombosis, is a known but rare risk of oral anticoagulant therapy. Its onset is usually within the first few days of therapy and is frequently localized to the limbs, breast, or penis. The risk of this effect is increased in patients with protein C or S deficiency.
Additional adverse reactions associated with warfarin, but likely to also occur with indanediones, include priapism and skin necrosis ("purple toe" syndrome or cutaneous gangrene). Gastrointestinal: Gastrointestinal bleeding, melena Genitourinary: Hematuria Hematologic: Hemorrhage, retroperitoneal hematoma, unrecognized bleeding sites (eg, colon cancer) may be uncovered by anticoagulation. Other hematologic reactions reported with coumarin derivatives include agranulocytosis, red cell aplasia, anemia, thrombocytopenia, eosinophilia. Hepatic: Hepatitis, hepatotoxicity, hematobilia Ocular: Ocular hemorrhage Respiratory: Epistaxis, hemoptysis, pulmonary hemorrhage Miscellaneous: Hypersensitivity/allergic reactions
CONTRAINDICATIONS — Hypersensitivity to acenocoumarol or any component of the formulation; hemorrhagic tendencies; hemophilia; thrombocytopenia purpura; leukemia; recent or potential surgery of the eye or CNS; major regional lumbar block anesthesia or surgery resulting in large, open surfaces; bleeding from the GI, respiratory, or GU tract; threatened abortion; aneurysm; prolonged dietary insufficiencies (vitamin K deficiency); ascorbic acid deficiency; history of bleeding diathesis; prostatectomy; continuous tube drainage of the small intestine; polyarthritis; diverticulitis; emaciation; malnutrition; cerebrovascular hemorrhage; eclampsia/pre-eclampsia; blood dyscrasias; severe uncontrolled or malignant hypertension; severe hepatic disease; pericarditis or pericardial effusion; subacute bacterial endocarditis; visceral carcinoma; following spinal puncture and other diagnostic or therapeutic procedures with potential for significant bleeding; history of warfarin-induced necrosis; an unreliable, noncompliant patient; alcoholism; patient who has a history of falls or is a significant fall risk; pregnancy
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Anaphylaxis/hypersensitivity: May cause hypersensitivity reactions, including anaphylaxis; use with caution in patients with anaphylactic disorders. Bleeding: May cause major or fatal bleeding. Risk factors for bleeding include high intensity anticoagulation (INR >4), age (>65 years), variable INRs, history of GI bleeding, hypertension, cerebrovascular disease, serious heart disease, anemia, severe diabetes, malignancy, trauma, renal insufficiency, polycythemia vera, vasculitis, open wound, history of PUD, indwelling catheters, menstruating and postpartum women, drug-drug interactions and long duration of therapy. Patient must be instructed to report bleeding, accidents, or falls as well as any new or discontinued medications, herbal or alternative products used, significant changes in smoking or dietary habits. Skin necrosis/gangrene: Necrosis or gangrene of the skin and other tissues can occur (rarely) due to early hypercoagulability; risk is increased in patients with protein C deficiency. "Purple toe" syndrome, due to cholesterol microembolization, has been described with coumarin-type anticoagulants.
Disease-related concerns: Infection: Use with caution in patients with acute infection or active TB; antibiotics and fever may alter response to acenocoumarol. Renal impairment: Use with caution in patients with renal impairment. Thyroid disease: Use with caution in patients with thyroid disease.
Special populations: Elderly: The elderly may be more sensitive to anticoagulant therapy. Ovulating women: May be at risk of developing ovarian hemorrhage at the time of ovulation. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Patient selection: Use care in the selection of patients appropriate for this treatment; ensure patient cooperation especially from the alcoholic, illicit drug user, demented, or psychotic patient.
RESTRICTIONS — Not available in U.S.
DRUG INTERACTIONS Substrate of CYP1A2 (major), 2C9 (major), 2C19 (minor)
Note: As an oral coumarin derivative, acenocoumarol is likely subject to the same pharmacodynamic drug-drug interactions as warfarin.
Acetaminophen: May increase the effects of acenocoumarol.
Amiodarone: May increase the level/effects of acenocoumarol.
Anticoagulants: May increase the effects of acenocoumarol.
Antiplatelet agents: May increase the effects of acenocoumarol.
CYP1A2 inducers may decrease the levels/effects of acenocoumarol. Example inducers include aminoglutethimide, carbamazepine, phenobarbital, and rifampin.
CYP1A2 inhibitors may increase the levels/effects of acenocoumarol. Example inhibitors include ciprofloxacin, fluvoxamine, ketoconazole, norfloxacin, ofloxacin, and rofecoxib.
CYP2C9 inducers may decrease the levels/effects of acenocoumarol. Example inducers include carbamazepine, phenobarbital, phenytoin, rifampin, rifapentine, and secobarbital.
CYP2C9 inhibitors may increase the levels/effects of acenocoumarol. Example inhibitors include delavirdine, fluconazole, gemfibrozil, ketoconazole, nicardipine, NSAIDs, pioglitazone, and sulfonamides.
Miconazole: May increase the level/effects of acenocoumarol.
NSAIDs: May increase the level/effects of acenocoumarol.
Salicylates: May increase the effects of acenocoumarol.
Sulfamethoxazole: May increase the effects of acenocoumarol.
Sulfinpyrazone: May increase the effects of acenocoumarol.
Tetracycline antibiotics: May increase the effects of acenocoumarol.
Trimethoprim: May increase the effects of acenocoumarol.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Avoid ethanol. Acute ethanol ingestion (binge drinking) decreases the metabolism of oral anticoagulants and increases PT/INR. Chronic daily ethanol use increases the metabolism of oral anticoagulants and decreases PT/INR.
Food: The anticoagulant effects of acenocoumarol may be decreased if taken with foods rich in vitamin K. Vitamin E may increase anticoagulant effect.
Herb/Nutraceutical: St John's wort may decrease oral anticoagulant levels. Alfalfa contains large amounts of vitamin K as do many enteral products. Coenzyme Q10 may decrease response to oral anticoagulants. Avoid cat's claw, dong quai, evening primrose, feverfew, red clover, horse chestnut, garlic, green tea, ginseng, and ginkgo (all have additional antiplatelet activity).
PREGNANCY IMPLICATIONS — Oral anticoagulants cross the placenta and produce fetal abnormalities. Fatal hemorrhage in the fetus has been reported even when the mother's acenocoumarol levels were in the therapeutic range. Acenocoumarol should not be used during pregnancy because of significant risks. Adjusted-dose heparin can be given safely throughout pregnancy in patients with venous thromboembolism. Women of childbearing potential are advised to use effective contraception during treatment.
LACTATION — Enters breast milk/not recommended (per manufacturer)
DIETARY CONSIDERATIONS — Foods high in vitamin K (eg, beef liver, pork liver, green tea, and leafy green vegetables) inhibit anticoagulant effect. Do not change dietary habits once stabilized on acenocoumarol therapy. A balanced diet with a consistent intake of vitamin K is essential. Avoid large amounts of alfalfa, asparagus, broccoli, Brussels sprouts, cabbage, cauliflower, green teas, kale, lettuce, spinach, turnip greens, watercress; these decrease efficacy of oral anticoagulants. It is recommended that the diet contain a CONSISTENT vitamin K content of 70-140 mcg/day. Check with healthcare provider before changing diet. Avoid using multivitamins that contain vitamin K.
MONITORING PARAMETERS — PT/INR; hepatic function, CBC, urinalysis (for albuminuria/proteinuria)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms of overdose include internal or external hemorrhage and hematuria. Avoid emesis and lavage to avoid possible trauma and incidental bleeding. When an overdose occurs, the drug should be immediately discontinued and vitamin K1 (phytonadione) may be administered, up to 40 mg I.V. for adults. When hemorrhage occurs, fresh frozen plasma transfusions can help control bleeding by replacing clotting factors. In urgent bleeding, prothrombin complex concentrates may be needed.
CANADIAN BRAND NAMES — Sintrom®
INTERNATIONAL BRAND NAMES — Acenocoumarol (PL); Acenocumarol (PL); Acenox (CL); Acitrom (IN); Coarol (CL); Isquelium (CL); Mini-Sintrom (FR); Neo-Sintrom (CL); Sinthrome (GB); Sintrom (AR, AT, BE, CA, CH, ES, FR, GR, IL, IT, MX, NL, PL, PT); Syncumar (PL)
MECHANISM OF ACTION — Interferes with hepatic synthesis of vitamin K-dependent coagulation factors (II, VII, IX, X)
PHARMACODYNAMICS / KINETICS Onset of action: Peak anticoagulant effect: Oral: 36-48 hours
Absorption: Oral: 60%
Protein binding: 99%
Metabolism: Hepatic, via oxidation (possibly by CYP1A2, 2C9, and 2C19) to inactive metabolites
Half-life elimination: 8-11 hours
Time to peak, plasma: 1-3 hours
Excretion: Urine (60%) and feces (29%) as metabolites
Acenocoumarol: Drug information
(For additional information see "Acenocoumarol: Patient drug information")
PHARMACOLOGIC CATEGORY Anticoagulant, Coumarin Derivative
DOSING: ADULTS — Note: Dosage must be individualized. The following information is based on the manufacturer's labeling in Canada.
Oral: Initial: 8-12 mg on day 1, followed by 4-8 mg on day 2. Subsequent dosage should be based on PT/INR measurements. Usual range of maintenance doses: 1-10 mg/day. Tapering of dosage is recommended prior to discontinuation.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [CAN] = Canadian brand name
Tablet: Sintrom® [CAN]: 1 mg, 4 mg [not available in the U.S.]
DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name
Tablet: Sintrom® [CAN]: 1 mg, 4 mg [not available in the U.S.]
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer at the same time each day.
USE — Prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders; atrial fibrillation with risk of embolism; adjunct in the prophylaxis of coronary occlusion and transient ischemic attacks
ADVERSE REACTIONS SIGNIFICANT — As with all anticoagulants, bleeding is the major adverse effect of acenocoumarol. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the intensity of anticoagulation and patient susceptibility.
Frequency not defined. Cardiovascular: Hemorrhagic shock Central nervous system: Fever, headache, stroke (hemorrhagic) Dermatologic: Rash, urticaria, skin necrosis Skin necrosis/gangrene, due to paradoxical local thrombosis, is a known but rare risk of oral anticoagulant therapy. Its onset is usually within the first few days of therapy and is frequently localized to the limbs, breast, or penis. The risk of this effect is increased in patients with protein C or S deficiency.
Additional adverse reactions associated with warfarin, but likely to also occur with indanediones, include priapism and skin necrosis ("purple toe" syndrome or cutaneous gangrene). Gastrointestinal: Gastrointestinal bleeding, melena Genitourinary: Hematuria Hematologic: Hemorrhage, retroperitoneal hematoma, unrecognized bleeding sites (eg, colon cancer) may be uncovered by anticoagulation. Other hematologic reactions reported with coumarin derivatives include agranulocytosis, red cell aplasia, anemia, thrombocytopenia, eosinophilia. Hepatic: Hepatitis, hepatotoxicity, hematobilia Ocular: Ocular hemorrhage Respiratory: Epistaxis, hemoptysis, pulmonary hemorrhage Miscellaneous: Hypersensitivity/allergic reactions
CONTRAINDICATIONS — Hypersensitivity to acenocoumarol or any component of the formulation; hemorrhagic tendencies; hemophilia; thrombocytopenia purpura; leukemia; recent or potential surgery of the eye or CNS; major regional lumbar block anesthesia or surgery resulting in large, open surfaces; bleeding from the GI, respiratory, or GU tract; threatened abortion; aneurysm; prolonged dietary insufficiencies (vitamin K deficiency); ascorbic acid deficiency; history of bleeding diathesis; prostatectomy; continuous tube drainage of the small intestine; polyarthritis; diverticulitis; emaciation; malnutrition; cerebrovascular hemorrhage; eclampsia/pre-eclampsia; blood dyscrasias; severe uncontrolled or malignant hypertension; severe hepatic disease; pericarditis or pericardial effusion; subacute bacterial endocarditis; visceral carcinoma; following spinal puncture and other diagnostic or therapeutic procedures with potential for significant bleeding; history of warfarin-induced necrosis; an unreliable, noncompliant patient; alcoholism; patient who has a history of falls or is a significant fall risk; pregnancy
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Anaphylaxis/hypersensitivity: May cause hypersensitivity reactions, including anaphylaxis; use with caution in patients with anaphylactic disorders. Bleeding: May cause major or fatal bleeding. Risk factors for bleeding include high intensity anticoagulation (INR >4), age (>65 years), variable INRs, history of GI bleeding, hypertension, cerebrovascular disease, serious heart disease, anemia, severe diabetes, malignancy, trauma, renal insufficiency, polycythemia vera, vasculitis, open wound, history of PUD, indwelling catheters, menstruating and postpartum women, drug-drug interactions and long duration of therapy. Patient must be instructed to report bleeding, accidents, or falls as well as any new or discontinued medications, herbal or alternative products used, significant changes in smoking or dietary habits. Skin necrosis/gangrene: Necrosis or gangrene of the skin and other tissues can occur (rarely) due to early hypercoagulability; risk is increased in patients with protein C deficiency. "Purple toe" syndrome, due to cholesterol microembolization, has been described with coumarin-type anticoagulants.
Disease-related concerns: Infection: Use with caution in patients with acute infection or active TB; antibiotics and fever may alter response to acenocoumarol. Renal impairment: Use with caution in patients with renal impairment. Thyroid disease: Use with caution in patients with thyroid disease.
Special populations: Elderly: The elderly may be more sensitive to anticoagulant therapy. Ovulating women: May be at risk of developing ovarian hemorrhage at the time of ovulation. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Patient selection: Use care in the selection of patients appropriate for this treatment; ensure patient cooperation especially from the alcoholic, illicit drug user, demented, or psychotic patient.
RESTRICTIONS — Not available in U.S.
DRUG INTERACTIONS Substrate of CYP1A2 (major), 2C9 (major), 2C19 (minor)
Note: As an oral coumarin derivative, acenocoumarol is likely subject to the same pharmacodynamic drug-drug interactions as warfarin.
Acetaminophen: May increase the effects of acenocoumarol.
Amiodarone: May increase the level/effects of acenocoumarol.
Anticoagulants: May increase the effects of acenocoumarol.
Antiplatelet agents: May increase the effects of acenocoumarol.
CYP1A2 inducers may decrease the levels/effects of acenocoumarol. Example inducers include aminoglutethimide, carbamazepine, phenobarbital, and rifampin.
CYP1A2 inhibitors may increase the levels/effects of acenocoumarol. Example inhibitors include ciprofloxacin, fluvoxamine, ketoconazole, norfloxacin, ofloxacin, and rofecoxib.
CYP2C9 inducers may decrease the levels/effects of acenocoumarol. Example inducers include carbamazepine, phenobarbital, phenytoin, rifampin, rifapentine, and secobarbital.
CYP2C9 inhibitors may increase the levels/effects of acenocoumarol. Example inhibitors include delavirdine, fluconazole, gemfibrozil, ketoconazole, nicardipine, NSAIDs, pioglitazone, and sulfonamides.
Miconazole: May increase the level/effects of acenocoumarol.
NSAIDs: May increase the level/effects of acenocoumarol.
Salicylates: May increase the effects of acenocoumarol.
Sulfamethoxazole: May increase the effects of acenocoumarol.
Sulfinpyrazone: May increase the effects of acenocoumarol.
Tetracycline antibiotics: May increase the effects of acenocoumarol.
Trimethoprim: May increase the effects of acenocoumarol.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Avoid ethanol. Acute ethanol ingestion (binge drinking) decreases the metabolism of oral anticoagulants and increases PT/INR. Chronic daily ethanol use increases the metabolism of oral anticoagulants and decreases PT/INR.
Food: The anticoagulant effects of acenocoumarol may be decreased if taken with foods rich in vitamin K. Vitamin E may increase anticoagulant effect.
Herb/Nutraceutical: St John's wort may decrease oral anticoagulant levels. Alfalfa contains large amounts of vitamin K as do many enteral products. Coenzyme Q10 may decrease response to oral anticoagulants. Avoid cat's claw, dong quai, evening primrose, feverfew, red clover, horse chestnut, garlic, green tea, ginseng, and ginkgo (all have additional antiplatelet activity).
PREGNANCY IMPLICATIONS — Oral anticoagulants cross the placenta and produce fetal abnormalities. Fatal hemorrhage in the fetus has been reported even when the mother's acenocoumarol levels were in the therapeutic range. Acenocoumarol should not be used during pregnancy because of significant risks. Adjusted-dose heparin can be given safely throughout pregnancy in patients with venous thromboembolism. Women of childbearing potential are advised to use effective contraception during treatment.
LACTATION — Enters breast milk/not recommended (per manufacturer)
DIETARY CONSIDERATIONS — Foods high in vitamin K (eg, beef liver, pork liver, green tea, and leafy green vegetables) inhibit anticoagulant effect. Do not change dietary habits once stabilized on acenocoumarol therapy. A balanced diet with a consistent intake of vitamin K is essential. Avoid large amounts of alfalfa, asparagus, broccoli, Brussels sprouts, cabbage, cauliflower, green teas, kale, lettuce, spinach, turnip greens, watercress; these decrease efficacy of oral anticoagulants. It is recommended that the diet contain a CONSISTENT vitamin K content of 70-140 mcg/day. Check with healthcare provider before changing diet. Avoid using multivitamins that contain vitamin K.
MONITORING PARAMETERS — PT/INR; hepatic function, CBC, urinalysis (for albuminuria/proteinuria)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms of overdose include internal or external hemorrhage and hematuria. Avoid emesis and lavage to avoid possible trauma and incidental bleeding. When an overdose occurs, the drug should be immediately discontinued and vitamin K1 (phytonadione) may be administered, up to 40 mg I.V. for adults. When hemorrhage occurs, fresh frozen plasma transfusions can help control bleeding by replacing clotting factors. In urgent bleeding, prothrombin complex concentrates may be needed.
CANADIAN BRAND NAMES — Sintrom®
INTERNATIONAL BRAND NAMES — Acenocoumarol (PL); Acenocumarol (PL); Acenox (CL); Acitrom (IN); Coarol (CL); Isquelium (CL); Mini-Sintrom (FR); Neo-Sintrom (CL); Sinthrome (GB); Sintrom (AR, AT, BE, CA, CH, ES, FR, GR, IL, IT, MX, NL, PL, PT); Syncumar (PL)
MECHANISM OF ACTION — Interferes with hepatic synthesis of vitamin K-dependent coagulation factors (II, VII, IX, X)
PHARMACODYNAMICS / KINETICS Onset of action: Peak anticoagulant effect: Oral: 36-48 hours
Absorption: Oral: 60%
Protein binding: 99%
Metabolism: Hepatic, via oxidation (possibly by CYP1A2, 2C9, and 2C19) to inactive metabolites
Half-life elimination: 8-11 hours
Time to peak, plasma: 1-3 hours
Excretion: Urine (60%) and feces (29%) as metabolites
PHARMACOLOGIC CATEGORY Anticoagulant, Coumarin Derivative
DOSING: ADULTS — Note: Dosage must be individualized. The following information is based on the manufacturer's labeling in Canada.
Oral: Initial: 8-12 mg on day 1, followed by 4-8 mg on day 2. Subsequent dosage should be based on PT/INR measurements. Usual range of maintenance doses: 1-10 mg/day. Tapering of dosage is recommended prior to discontinuation.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [CAN] = Canadian brand name
Tablet: Sintrom® [CAN]: 1 mg, 4 mg [not available in the U.S.]
DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name
Tablet: Sintrom® [CAN]: 1 mg, 4 mg [not available in the U.S.]
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer at the same time each day.
USE — Prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders; atrial fibrillation with risk of embolism; adjunct in the prophylaxis of coronary occlusion and transient ischemic attacks
ADVERSE REACTIONS SIGNIFICANT — As with all anticoagulants, bleeding is the major adverse effect of acenocoumarol. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the intensity of anticoagulation and patient susceptibility.
Frequency not defined. Cardiovascular: Hemorrhagic shock Central nervous system: Fever, headache, stroke (hemorrhagic) Dermatologic: Rash, urticaria, skin necrosis Skin necrosis/gangrene, due to paradoxical local thrombosis, is a known but rare risk of oral anticoagulant therapy. Its onset is usually within the first few days of therapy and is frequently localized to the limbs, breast, or penis. The risk of this effect is increased in patients with protein C or S deficiency.
Additional adverse reactions associated with warfarin, but likely to also occur with indanediones, include priapism and skin necrosis ("purple toe" syndrome or cutaneous gangrene). Gastrointestinal: Gastrointestinal bleeding, melena Genitourinary: Hematuria Hematologic: Hemorrhage, retroperitoneal hematoma, unrecognized bleeding sites (eg, colon cancer) may be uncovered by anticoagulation. Other hematologic reactions reported with coumarin derivatives include agranulocytosis, red cell aplasia, anemia, thrombocytopenia, eosinophilia. Hepatic: Hepatitis, hepatotoxicity, hematobilia Ocular: Ocular hemorrhage Respiratory: Epistaxis, hemoptysis, pulmonary hemorrhage Miscellaneous: Hypersensitivity/allergic reactions
CONTRAINDICATIONS — Hypersensitivity to acenocoumarol or any component of the formulation; hemorrhagic tendencies; hemophilia; thrombocytopenia purpura; leukemia; recent or potential surgery of the eye or CNS; major regional lumbar block anesthesia or surgery resulting in large, open surfaces; bleeding from the GI, respiratory, or GU tract; threatened abortion; aneurysm; prolonged dietary insufficiencies (vitamin K deficiency); ascorbic acid deficiency; history of bleeding diathesis; prostatectomy; continuous tube drainage of the small intestine; polyarthritis; diverticulitis; emaciation; malnutrition; cerebrovascular hemorrhage; eclampsia/pre-eclampsia; blood dyscrasias; severe uncontrolled or malignant hypertension; severe hepatic disease; pericarditis or pericardial effusion; subacute bacterial endocarditis; visceral carcinoma; following spinal puncture and other diagnostic or therapeutic procedures with potential for significant bleeding; history of warfarin-induced necrosis; an unreliable, noncompliant patient; alcoholism; patient who has a history of falls or is a significant fall risk; pregnancy
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Anaphylaxis/hypersensitivity: May cause hypersensitivity reactions, including anaphylaxis; use with caution in patients with anaphylactic disorders. Bleeding: May cause major or fatal bleeding. Risk factors for bleeding include high intensity anticoagulation (INR >4), age (>65 years), variable INRs, history of GI bleeding, hypertension, cerebrovascular disease, serious heart disease, anemia, severe diabetes, malignancy, trauma, renal insufficiency, polycythemia vera, vasculitis, open wound, history of PUD, indwelling catheters, menstruating and postpartum women, drug-drug interactions and long duration of therapy. Patient must be instructed to report bleeding, accidents, or falls as well as any new or discontinued medications, herbal or alternative products used, significant changes in smoking or dietary habits. Skin necrosis/gangrene: Necrosis or gangrene of the skin and other tissues can occur (rarely) due to early hypercoagulability; risk is increased in patients with protein C deficiency. "Purple toe" syndrome, due to cholesterol microembolization, has been described with coumarin-type anticoagulants.
Disease-related concerns: Infection: Use with caution in patients with acute infection or active TB; antibiotics and fever may alter response to acenocoumarol. Renal impairment: Use with caution in patients with renal impairment. Thyroid disease: Use with caution in patients with thyroid disease.
Special populations: Elderly: The elderly may be more sensitive to anticoagulant therapy. Ovulating women: May be at risk of developing ovarian hemorrhage at the time of ovulation. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Patient selection: Use care in the selection of patients appropriate for this treatment; ensure patient cooperation especially from the alcoholic, illicit drug user, demented, or psychotic patient.
RESTRICTIONS — Not available in U.S.
DRUG INTERACTIONS Substrate of CYP1A2 (major), 2C9 (major), 2C19 (minor)
Note: As an oral coumarin derivative, acenocoumarol is likely subject to the same pharmacodynamic drug-drug interactions as warfarin.
Acetaminophen: May increase the effects of acenocoumarol.
Amiodarone: May increase the level/effects of acenocoumarol.
Anticoagulants: May increase the effects of acenocoumarol.
Antiplatelet agents: May increase the effects of acenocoumarol.
CYP1A2 inducers may decrease the levels/effects of acenocoumarol. Example inducers include aminoglutethimide, carbamazepine, phenobarbital, and rifampin.
CYP1A2 inhibitors may increase the levels/effects of acenocoumarol. Example inhibitors include ciprofloxacin, fluvoxamine, ketoconazole, norfloxacin, ofloxacin, and rofecoxib.
CYP2C9 inducers may decrease the levels/effects of acenocoumarol. Example inducers include carbamazepine, phenobarbital, phenytoin, rifampin, rifapentine, and secobarbital.
CYP2C9 inhibitors may increase the levels/effects of acenocoumarol. Example inhibitors include delavirdine, fluconazole, gemfibrozil, ketoconazole, nicardipine, NSAIDs, pioglitazone, and sulfonamides.
Miconazole: May increase the level/effects of acenocoumarol.
NSAIDs: May increase the level/effects of acenocoumarol.
Salicylates: May increase the effects of acenocoumarol.
Sulfamethoxazole: May increase the effects of acenocoumarol.
Sulfinpyrazone: May increase the effects of acenocoumarol.
Tetracycline antibiotics: May increase the effects of acenocoumarol.
Trimethoprim: May increase the effects of acenocoumarol.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Avoid ethanol. Acute ethanol ingestion (binge drinking) decreases the metabolism of oral anticoagulants and increases PT/INR. Chronic daily ethanol use increases the metabolism of oral anticoagulants and decreases PT/INR.
Food: The anticoagulant effects of acenocoumarol may be decreased if taken with foods rich in vitamin K. Vitamin E may increase anticoagulant effect.
Herb/Nutraceutical: St John's wort may decrease oral anticoagulant levels. Alfalfa contains large amounts of vitamin K as do many enteral products. Coenzyme Q10 may decrease response to oral anticoagulants. Avoid cat's claw, dong quai, evening primrose, feverfew, red clover, horse chestnut, garlic, green tea, ginseng, and ginkgo (all have additional antiplatelet activity).
PREGNANCY IMPLICATIONS — Oral anticoagulants cross the placenta and produce fetal abnormalities. Fatal hemorrhage in the fetus has been reported even when the mother's acenocoumarol levels were in the therapeutic range. Acenocoumarol should not be used during pregnancy because of significant risks. Adjusted-dose heparin can be given safely throughout pregnancy in patients with venous thromboembolism. Women of childbearing potential are advised to use effective contraception during treatment.
LACTATION — Enters breast milk/not recommended (per manufacturer)
DIETARY CONSIDERATIONS — Foods high in vitamin K (eg, beef liver, pork liver, green tea, and leafy green vegetables) inhibit anticoagulant effect. Do not change dietary habits once stabilized on acenocoumarol therapy. A balanced diet with a consistent intake of vitamin K is essential. Avoid large amounts of alfalfa, asparagus, broccoli, Brussels sprouts, cabbage, cauliflower, green teas, kale, lettuce, spinach, turnip greens, watercress; these decrease efficacy of oral anticoagulants. It is recommended that the diet contain a CONSISTENT vitamin K content of 70-140 mcg/day. Check with healthcare provider before changing diet. Avoid using multivitamins that contain vitamin K.
MONITORING PARAMETERS — PT/INR; hepatic function, CBC, urinalysis (for albuminuria/proteinuria)
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms of overdose include internal or external hemorrhage and hematuria. Avoid emesis and lavage to avoid possible trauma and incidental bleeding. When an overdose occurs, the drug should be immediately discontinued and vitamin K1 (phytonadione) may be administered, up to 40 mg I.V. for adults. When hemorrhage occurs, fresh frozen plasma transfusions can help control bleeding by replacing clotting factors. In urgent bleeding, prothrombin complex concentrates may be needed.
CANADIAN BRAND NAMES — Sintrom®
INTERNATIONAL BRAND NAMES — Acenocoumarol (PL); Acenocumarol (PL); Acenox (CL); Acitrom (IN); Coarol (CL); Isquelium (CL); Mini-Sintrom (FR); Neo-Sintrom (CL); Sinthrome (GB); Sintrom (AR, AT, BE, CA, CH, ES, FR, GR, IL, IT, MX, NL, PL, PT); Syncumar (PL)
MECHANISM OF ACTION — Interferes with hepatic synthesis of vitamin K-dependent coagulation factors (II, VII, IX, X)
PHARMACODYNAMICS / KINETICS Onset of action: Peak anticoagulant effect: Oral: 36-48 hours
Absorption: Oral: 60%
Protein binding: 99%
Metabolism: Hepatic, via oxidation (possibly by CYP1A2, 2C9, and 2C19) to inactive metabolites
Half-life elimination: 8-11 hours
Time to peak, plasma: 1-3 hours
Excretion: Urine (60%) and feces (29%) as metabolites
Acebutolol: Drug information
(For additional information see "Acebutolol: Patient drug information")
U.S. BRAND NAMES — Sectral®
PHARMACOLOGIC CATEGORY Antiarrhythmic Agent, Class IIBeta Blocker With Intrinsic Sympathomimetic Activity
DOSING: ADULTS Angina, ventricular arrhythmia: Oral: 400 mg/day in divided doses; maintenance: 600-1200 mg/day in divided doses; maximum: 1200 mg/day
Hypertension: Oral: 400-800 mg/day (larger doses may be divided); maximum: 1200 mg/day; usual dose range (JNC 7): 200-800 mg/day in 2 divided doses
DOSING: ELDERLY — Oral: Initial: 200-400 mg/day; dose reduction due to age-related decrease in Clcr will be necessary; do not exceed 800 mg/day.
DOSING: RENAL IMPAIRMENT Clcr 25-49 mL/minute/1.73 m2: Reduce dose by 50%.
Clcr <25 mL/minute/1.73 m2: Reduce dose by 75%.
DOSING: HEPATIC IMPAIRMENT — Use with caution.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, as hydrochloride: 200 mg, 400 mg Sectral®: 200 mg, 400 mg
DOSAGE FORMS: CONCISE Capsule, as hydrochloride: 200 mg, 400 mg Sectral®: 200 mg, 400 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — To discontinue therapy, taper dose gradually. May be administered without regard to meals.
USE — Treatment of hypertension, ventricular arrhythmias, angina
ADVERSE REACTIONS SIGNIFICANT >10%: Central nervous system: Fatigue (11%)
1% to 10%: Cardiovascular: Chest pain (2%), edema (2%), bradycardia, hypotension, CHF Central nervous system: Headache (6%), dizziness (6%), insomnia (3%), depression (2%), abnormal dreams (2%), anxiety, hyperesthesia, hypoesthesia, impotence Dermatologic: Rash (2%), pruritus Gastrointestinal: Constipation (4%), diarrhea (4%), dyspepsia (4%), nausea (4%), flatulence (3%), vomiting, abdominal pain Genitourinary: Micturition frequency (3%), dysuria, nocturia, impotence (2%) Neuromuscular & skeletal: Arthralgia (2%), myalgia (2%), back pain, joint pain Ocular: Abnormal vision (2%), conjunctivitis, dry eyes, eye pain Respiratory: Dyspnea (4%), rhinitis (2%), cough (1%), pharyngitis, wheezing
<1% (Limited to important or life-threatening): AV block, exacerbation of pre-existing renal insufficiency, hepatotoxic reaction, impotence, lichen planus, pleurisy, pneumonitis, pulmonary granulomas, systemic lupus erythematosus, urinary retention, ventricular arrhythmia
Potential adverse effects (based on experience with other beta-blocking agents) include reversible mental depression, disorientation, catatonia, short-term memory loss, emotional lability, slightly clouded sensorium, laryngospasm, respiratory distress, allergic reactions, erythematous rash, agranulocytosis, purpura, thrombocytopenia, mesenteric artery thrombosis, ischemic colitis, alopecia, Peyronie's disease, claudication
CONTRAINDICATIONS — Hypersensitivity to beta-blocking agents; uncompensated congestive heart failure; cardiogenic shock; bradycardia or second- and third-degree heart block (except in patients with a functioning artificial pacemaker); sinus node dysfunction; pregnancy (2nd and 3rd trimesters)
WARNINGS / PRECAUTIONS Disease-related concerns: Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring. CHF: Use with caution in patients with compensated heart failure and monitor for a worsening of the condition (beta-blockers with intrinsic sympathomimetic activity have not been demonstrated to be of value in CHF). Conduction ABNL: Consider pre-existing conditions such as sick sinus syndrome before initiating. Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms. Hepatic impairment: Use with caution in patients with hepatic impairment. Myasthenia gravis: Use with caution in patients with myasthenia gravis. Peripheral vascular disease (PVD): Use with caution in patients with PVD (including Raynaud's). Pheochromocytoma (untreated): Adequate alpha-blockade is required prior to use of any beta-blocker. Psychiatric disease: Use with caution in patients with a history of psychiatric illness; may cause or exacerbate CNS depression. Renal impairment: Use with caution in patients with renal impairment, especially the elderly.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Abrupt withdrawal: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia.
DRUG INTERACTIONS — Inhibits CYP2D6 (weak)
Alpha-blockers (prazosin, terazosin): Concurrent use of beta-blockers may increase risk of orthostasis.
Clonidine: Hypertensive crisis after or during withdrawal of either agent.
Drugs which slow AV conduction (digoxin): Effects may be additive with beta-blockers.
Glucagon: Acebutolol may blunt the hyperglycemic action of glucagon.
Insulin and oral hypoglycemics: Acebutolol masks the tachycardia from hypoglycemia.
NSAIDs (ibuprofen, indomethacin, naproxen, piroxicam) may reduce the antihypertensive effects of beta-blockers.
Salicylates may reduce the antihypertensive effects of beta-blockers.
Sulfonylureas: Beta-blockers may alter response to hypoglycemic agents.
Verapamil or diltiazem may have synergistic or additive pharmacological effects when taken concurrently with beta-blockers.
ETHANOL / NUTRITION / HERB INTERACTIONS Food: Peak serum acebutolol levels may be slightly decreased if taken with food.
Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid yohimbe, ginseng (may worsen hypertension).
PREGNANCY RISK FACTOR — B (show table) (manufacturer); D (2nd and 3rd trimesters - expert analysis)
PREGNANCY IMPLICATIONS — Acebutolol crosses the placenta. Beta-blockers have been associated with persistent bradycardia, hypotension, and IUGR; IUGR is probably related to maternal hypertension. Available evidence suggests beta-blockers are generally safe during pregnancy (JNC 7). Cases of neonatal hypoglycemia have been reported following maternal use of beta-blockers at parturition or during breast-feeding. Monitor breast-fed infant for symptoms of beta-blockade.
LACTATION — Enters breast milk/use caution
BREAST-FEEDING CONSIDERATIONS — Hypotension, bradycardia, and tachypnea have been reported in nursing infants.
DIETARY CONSIDERATIONS — May be taken without regard to meals.
PRICING — (data from drugstore.com)Capsules (Acebutolol HCl) 200 mg (60): $32.99 400 mg (30): $21.99
Capsules (Sectral) 200 mg (60): $169.99 400 mg (30): $124.99
MONITORING PARAMETERS — Blood pressure, orthostatic hypotension, heart rate, CNS effects, ECG
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include cardiac disturbances, CNS toxicity, bronchospasm, hypoglycemia, and hyperkalemia. The most common cardiac symptoms include hypotension and bradycardia. Atrioventricular block, intraventricular conduction disturbances, cardiogenic shock, and asystole may occur with severe overdose, especially with membrane-depressant drugs (eg, propranolol). CNS effects include convulsions, coma, and respiratory arrest is commonly seen with propranolol and other membrane-depressant and lipid-soluble drugs. Treatment is symptomatic for seizures, hypotension, hyperkalemia, and hypoglycemia. Bradycardia and hypotension resistant to atropine, isoproterenol or pacing, may respond to glucagon. Wide QRS defects caused by membrane-depressant poisoning may respond to hypertonic sodium bicarbonate. Repeat-dose charcoal, hemoperfusion, or hemodialysis may be helpful.
CANADIAN BRAND NAMES — Apo-Acebutolol®; Gen-Acebutolol; Monitan®; Novo-Acebutolol; Nu-Acebutolol; Rhotral; Rhoxal-acebutolol; Sandoz-Acebutolol; Sectral®
INTERNATIONAL BRAND NAMES — Abutol (PL); ACB (NZ, SG); Acebutolol (PL); Acecor (PL); Apo-Acebutolol (CA); Beloc (CL); Cetolol (PL); Diasectral (DK, FI); Flebutol (VE); Gen-Acebutolol (CA); Grifobutol (CL); Monitan (CA); Novo-Acebutolol (CA); Nu-Acebutolol (CA); Prent (DE, IT, PT); Rhotral (CA); Rhoxal-acebutolol (CA); Sandoz-Acebutolol (CA); Sectral (AE, AN, BB, BE, BG, BH, BM, BS, BZ, CA, CH, CY, CZ, EG, ES, FR, GB, GY, HK, IE, IL, IQ, IR, IT, JM, JO, KW, LB, LY, MY, NL, OM, PL, QA, SA, SR, SY, TT, TW, YE, ZA); Sectral LP (FR)
MECHANISM OF ACTION — Competitively blocks beta1-adrenergic receptors with little or no effect on beta2-receptors except at high doses; exhibits membrane stabilizing and intrinsic sympathomimetic activity
PHARMACODYNAMICS / KINETICS Onset of action: 1-2 hours
Duration: 12-24 hours
Absorption: Oral: 40%
Protein binding: 5% to 15%
Metabolism: Extensive first-pass effect
Half-life elimination: 6-7 hours
Time to peak: 2-4 hours
Excretion: Feces (~55%); urine (35%)
PATIENT INFORMATION — Do not discontinue abruptly. Consult pharmacist or prescriber before taking with other adrenergic drugs (eg, cold medications). Take at the same time each day. May be taken without regard to meals. Use with caution while driving or performing tasks requiring alertness. Notify prescriber if CHF symptoms become worse or if other side effects occur. May mask signs of hypoglycemia in diabetics.
(For additional information see "Acebutolol: Patient drug information")
U.S. BRAND NAMES — Sectral®
PHARMACOLOGIC CATEGORY Antiarrhythmic Agent, Class IIBeta Blocker With Intrinsic Sympathomimetic Activity
DOSING: ADULTS Angina, ventricular arrhythmia: Oral: 400 mg/day in divided doses; maintenance: 600-1200 mg/day in divided doses; maximum: 1200 mg/day
Hypertension: Oral: 400-800 mg/day (larger doses may be divided); maximum: 1200 mg/day; usual dose range (JNC 7): 200-800 mg/day in 2 divided doses
DOSING: ELDERLY — Oral: Initial: 200-400 mg/day; dose reduction due to age-related decrease in Clcr will be necessary; do not exceed 800 mg/day.
DOSING: RENAL IMPAIRMENT Clcr 25-49 mL/minute/1.73 m2: Reduce dose by 50%.
Clcr <25 mL/minute/1.73 m2: Reduce dose by 75%.
DOSING: HEPATIC IMPAIRMENT — Use with caution.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, as hydrochloride: 200 mg, 400 mg Sectral®: 200 mg, 400 mg
DOSAGE FORMS: CONCISE Capsule, as hydrochloride: 200 mg, 400 mg Sectral®: 200 mg, 400 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — To discontinue therapy, taper dose gradually. May be administered without regard to meals.
USE — Treatment of hypertension, ventricular arrhythmias, angina
ADVERSE REACTIONS SIGNIFICANT >10%: Central nervous system: Fatigue (11%)
1% to 10%: Cardiovascular: Chest pain (2%), edema (2%), bradycardia, hypotension, CHF Central nervous system: Headache (6%), dizziness (6%), insomnia (3%), depression (2%), abnormal dreams (2%), anxiety, hyperesthesia, hypoesthesia, impotence Dermatologic: Rash (2%), pruritus Gastrointestinal: Constipation (4%), diarrhea (4%), dyspepsia (4%), nausea (4%), flatulence (3%), vomiting, abdominal pain Genitourinary: Micturition frequency (3%), dysuria, nocturia, impotence (2%) Neuromuscular & skeletal: Arthralgia (2%), myalgia (2%), back pain, joint pain Ocular: Abnormal vision (2%), conjunctivitis, dry eyes, eye pain Respiratory: Dyspnea (4%), rhinitis (2%), cough (1%), pharyngitis, wheezing
<1% (Limited to important or life-threatening): AV block, exacerbation of pre-existing renal insufficiency, hepatotoxic reaction, impotence, lichen planus, pleurisy, pneumonitis, pulmonary granulomas, systemic lupus erythematosus, urinary retention, ventricular arrhythmia
Potential adverse effects (based on experience with other beta-blocking agents) include reversible mental depression, disorientation, catatonia, short-term memory loss, emotional lability, slightly clouded sensorium, laryngospasm, respiratory distress, allergic reactions, erythematous rash, agranulocytosis, purpura, thrombocytopenia, mesenteric artery thrombosis, ischemic colitis, alopecia, Peyronie's disease, claudication
CONTRAINDICATIONS — Hypersensitivity to beta-blocking agents; uncompensated congestive heart failure; cardiogenic shock; bradycardia or second- and third-degree heart block (except in patients with a functioning artificial pacemaker); sinus node dysfunction; pregnancy (2nd and 3rd trimesters)
WARNINGS / PRECAUTIONS Disease-related concerns: Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring. CHF: Use with caution in patients with compensated heart failure and monitor for a worsening of the condition (beta-blockers with intrinsic sympathomimetic activity have not been demonstrated to be of value in CHF). Conduction ABNL: Consider pre-existing conditions such as sick sinus syndrome before initiating. Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms. Hepatic impairment: Use with caution in patients with hepatic impairment. Myasthenia gravis: Use with caution in patients with myasthenia gravis. Peripheral vascular disease (PVD): Use with caution in patients with PVD (including Raynaud's). Pheochromocytoma (untreated): Adequate alpha-blockade is required prior to use of any beta-blocker. Psychiatric disease: Use with caution in patients with a history of psychiatric illness; may cause or exacerbate CNS depression. Renal impairment: Use with caution in patients with renal impairment, especially the elderly.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Abrupt withdrawal: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia.
DRUG INTERACTIONS — Inhibits CYP2D6 (weak)
Alpha-blockers (prazosin, terazosin): Concurrent use of beta-blockers may increase risk of orthostasis.
Clonidine: Hypertensive crisis after or during withdrawal of either agent.
Drugs which slow AV conduction (digoxin): Effects may be additive with beta-blockers.
Glucagon: Acebutolol may blunt the hyperglycemic action of glucagon.
Insulin and oral hypoglycemics: Acebutolol masks the tachycardia from hypoglycemia.
NSAIDs (ibuprofen, indomethacin, naproxen, piroxicam) may reduce the antihypertensive effects of beta-blockers.
Salicylates may reduce the antihypertensive effects of beta-blockers.
Sulfonylureas: Beta-blockers may alter response to hypoglycemic agents.
Verapamil or diltiazem may have synergistic or additive pharmacological effects when taken concurrently with beta-blockers.
ETHANOL / NUTRITION / HERB INTERACTIONS Food: Peak serum acebutolol levels may be slightly decreased if taken with food.
Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid yohimbe, ginseng (may worsen hypertension).
PREGNANCY RISK FACTOR — B (show table) (manufacturer); D (2nd and 3rd trimesters - expert analysis)
PREGNANCY IMPLICATIONS — Acebutolol crosses the placenta. Beta-blockers have been associated with persistent bradycardia, hypotension, and IUGR; IUGR is probably related to maternal hypertension. Available evidence suggests beta-blockers are generally safe during pregnancy (JNC 7). Cases of neonatal hypoglycemia have been reported following maternal use of beta-blockers at parturition or during breast-feeding. Monitor breast-fed infant for symptoms of beta-blockade.
LACTATION — Enters breast milk/use caution
BREAST-FEEDING CONSIDERATIONS — Hypotension, bradycardia, and tachypnea have been reported in nursing infants.
DIETARY CONSIDERATIONS — May be taken without regard to meals.
PRICING — (data from drugstore.com)Capsules (Acebutolol HCl) 200 mg (60): $32.99 400 mg (30): $21.99
Capsules (Sectral) 200 mg (60): $169.99 400 mg (30): $124.99
MONITORING PARAMETERS — Blood pressure, orthostatic hypotension, heart rate, CNS effects, ECG
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include cardiac disturbances, CNS toxicity, bronchospasm, hypoglycemia, and hyperkalemia. The most common cardiac symptoms include hypotension and bradycardia. Atrioventricular block, intraventricular conduction disturbances, cardiogenic shock, and asystole may occur with severe overdose, especially with membrane-depressant drugs (eg, propranolol). CNS effects include convulsions, coma, and respiratory arrest is commonly seen with propranolol and other membrane-depressant and lipid-soluble drugs. Treatment is symptomatic for seizures, hypotension, hyperkalemia, and hypoglycemia. Bradycardia and hypotension resistant to atropine, isoproterenol or pacing, may respond to glucagon. Wide QRS defects caused by membrane-depressant poisoning may respond to hypertonic sodium bicarbonate. Repeat-dose charcoal, hemoperfusion, or hemodialysis may be helpful.
CANADIAN BRAND NAMES — Apo-Acebutolol®; Gen-Acebutolol; Monitan®; Novo-Acebutolol; Nu-Acebutolol; Rhotral; Rhoxal-acebutolol; Sandoz-Acebutolol; Sectral®
INTERNATIONAL BRAND NAMES — Abutol (PL); ACB (NZ, SG); Acebutolol (PL); Acecor (PL); Apo-Acebutolol (CA); Beloc (CL); Cetolol (PL); Diasectral (DK, FI); Flebutol (VE); Gen-Acebutolol (CA); Grifobutol (CL); Monitan (CA); Novo-Acebutolol (CA); Nu-Acebutolol (CA); Prent (DE, IT, PT); Rhotral (CA); Rhoxal-acebutolol (CA); Sandoz-Acebutolol (CA); Sectral (AE, AN, BB, BE, BG, BH, BM, BS, BZ, CA, CH, CY, CZ, EG, ES, FR, GB, GY, HK, IE, IL, IQ, IR, IT, JM, JO, KW, LB, LY, MY, NL, OM, PL, QA, SA, SR, SY, TT, TW, YE, ZA); Sectral LP (FR)
MECHANISM OF ACTION — Competitively blocks beta1-adrenergic receptors with little or no effect on beta2-receptors except at high doses; exhibits membrane stabilizing and intrinsic sympathomimetic activity
PHARMACODYNAMICS / KINETICS Onset of action: 1-2 hours
Duration: 12-24 hours
Absorption: Oral: 40%
Protein binding: 5% to 15%
Metabolism: Extensive first-pass effect
Half-life elimination: 6-7 hours
Time to peak: 2-4 hours
Excretion: Feces (~55%); urine (35%)
PATIENT INFORMATION — Do not discontinue abruptly. Consult pharmacist or prescriber before taking with other adrenergic drugs (eg, cold medications). Take at the same time each day. May be taken without regard to meals. Use with caution while driving or performing tasks requiring alertness. Notify prescriber if CHF symptoms become worse or if other side effects occur. May mask signs of hypoglycemia in diabetics.
(For additional information see "Acebutolol: Patient drug information")
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