( N-acetyl-p-aminophenol ; APAP )

Pronunciation: a-SEET-a-MIN-oh-fen
Class: Analgesic, Antipyretic

Trade Names

Acephen
- Suppositories, rectal 120 mg
- Suppositories, rectal 325 mg
- Suppositories, rectal 650 mg

Aminofen
- Tablets, oral 325 mg
- Tablets, oral 500 mg

Anacin AF
- Tablets, oral 500 mg

Apra Children's
- Elixir, oral 160 mg/5 mL

Beta Temp Children's
- Suspension 160 mg/5 mL

Chloraseptic Sore Throat
- Liquid, oral 1,000 mg/30 mL

Ed-Apap Children's
- Solution, oral 160 mg/5 mL

ElixSure Children's Fever Reducer/Pain Reliever
- Solution, oral 160 mg/5 mL

Febrol
- Solution, oral 325 mg/5 mL

Feverall
- Suppositories, rectal 80 mg
- Suppositories, rectal 120 mg
- Suppositories, rectal 325 mg
- Suppositories, rectal 650 mg

Infantaire Drops
- Solution, concentrate, oral 100 mg/mL

Little Fevers Fever-Pain Relief
- Solution, concentrate, oral 80 mg/mL

Mapap
- Tablets, oral 325 mg
- Tablets, oral 500 mg
- Tablets, chewable, oral 80 mg
- Capsules, oral 500 mg
- Liquid, oral 160 mg/5 mL

Mapap Arthritis Pain
- Tablets, ER, oral 650 mg

Mapap Children's
- Tablets, chewable, dispersible, oral 80 mg
- Tablets, chewable, dispersible, oral 160 mg
- Suspension, oral 160 mg/5 mL

Mapap Drops
- Solution, concentrate, oral 80 mg/0.8 mL

Mapap Extra Strength
- Liquid, oral 500 mg/15 mL

Maxapap
- Tablets, oral 325 mg
- Tablets, oral 500 mg

Nortemp
- Solution/Suspension, oral 160 mg/5 mL

Nortemp Infants
- Suspension, oral 80 mg/0.8 mL

Ofirmev
- Injection, solution 10 mg/mL

Pharbetol
- Tablets, oral 325 mg
- Tablets, oral 500 mg

Q-Pap
- Tablets, oral 325 mg
- Tablets, oral 500 mg
- Liquid, oral 160 mg/5 mL

Q-Pap Children's
- Liquid, oral 160 mg/5 mL
- Suspension, oral 160 mg/5 mL

Q-Pap Infants Drops
- Solution, concentrate, oral 80 mg/0.8 mL

Silapap Children's
- Liquid, oral 160 mg/5 mL

Silapap Infants
- Solution, concentrate, oral 100 mg/mL

Standback Aspirin Free
- Powder, oral 950 mg

Tactinal
- Tablets, chewable, oral 80 mg
- Tablets, oral 325 mg
- Tablets, oral 500 mg

Triaminic Fever Reducer
- Syrup, oral 160 mg/5 mL

Triaminic Infants' Drops
- Suspension, oral 80 mg/0.8 mL

Tylenol 8 Hour
- Tablets, ER, oral 650 mg

Tylenol Arthritis Pain
- Tablets, oral 500 mg
- Tablets, ER, oral 650 mg

Tylenol Children's Meltaways
- Tablets, chewable, dispersible, oral 80 mg

Tylenol Children's
- Suspension, oral 160 mg/5 mL

Tylenol Children's with Flavor Creator
- Suspension, oral 160 mg/5 mL

Tylenol Extra Strength
- Liquid, oral 166.6 mg/5 mL

Tylenol Extra Strength Caplets
- Tablets, oral 500 mg

Tylenol Extra Strength GoTabs
- Tablets, chewable, oral 500 mg

Tylenol Extra Strength Rapid Release Gels
- Tablets, immediate-release, oral 500 mg

Tylenol Infants' Drops
- Solution, concentrate, oral 80 mg/0.8 mL

Tylenol Jr. Meltaways
- Tablets, chewable, dispersible, oral 160 mg

Tylenol Regular Strength
- Tablets, oral 325 mg

Tylenol Sore Throat Daytime
- Liquid, oral 500 mg/15 mL

UN-Aspirin Extra Strength
- Tablets, oral 500 mg

Apo-Acetaminophen (Canada)
Atasol (Canada)
Pediatrix (Canada)
Tempra (Canada)
Tylenol Junior Strength Tablets “Meltaways” (Canada)

Pharmacology

Inhibits prostaglandins in CNS, but lacks anti-inflammatory effects in periphery; reduces fever through direct action on hypothalamic heat-regulating center.

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Pharmacokinetics

Absorption

Rapid and complete from the GI tract. T _max is 0.5 to 2 h (15 min for IV); 4 h after overdosage.

Distribution

Distributed throughout most body fluids and tissues, except fat. Binding to plasma proteins is low (10% to 25%).

Metabolism

Primarily metabolized by hepatic conjugation (94%), and approximately 4% is metabolized by CYP-450 oxidase to toxic metabolite.

Elimination

The half-life is approximately 2 h. Approximately 90% to 100% is recovered in the urine within the first day, primarily as inactive metabolites. 5% is excreted as unchanged drug.

Special Populations

Hepatic Function Impairment

The half-life may increase 2-fold or more in patients with liver disease.

Children

Pharmacokinetic exposure of acetaminophen IV observed in children and adolescents is similar to that of adults, but higher in neonates and infants.

Neonates and cirrhotic patients

The half-life is slightly prolonged.

Indications and Usage

Temporary relief of minor aches and pains due to common cold or flu, backache, headache, arthritis, menstrual and premenstrual cramps, muscular aches, sore throat, toothache (PO/PR); management of mild to moderate pain and management of moderate to severe pain with adjunctive opioid analgesics (IV); temporary reduction of fever.

Unlabeled Uses

Pain and fever prophylaxis after vaccination.

Contraindications

Hypersensitivity to acetaminophen or any component of the formulation; severe hepatic impairment or severe active liver disease (IV).

Dosage and Administration

If possible, use the patient's weight to determine the dose; otherwise, use age.

IV Adults and Children 13 y and older 50 kg or more

IV 1,000 mg every 6 h or 650 mg every 4 h (max, 1,000 mg [single dose] and 4,000 mg [daily dose]).

Less than 50 kg

IV 15 mg/kg every 6 h or 12.5 mg/kg every 4 h (max, 15 mg/kg, up to 750 mg [single dose] and 75 mg/kg, up to 3,750 mg [daily dose]).

Children 2 to 12 years of age

IV 15 mg/kg every 6 h or 12.5 mg/kg every 4 h (max, 15 mg/kg [single dose] and 75 mg/kg [daily dose]).

PO Adults and Children older than 12 y

PO 325 to 1,000 mg every 4 to 6 h (immediate-release) or 1,300 mg every 8 h (ER). Do not exceed 4 g in 24 h.

Children

If possible, use the patient's weight to determine the dose; otherwise, use age.

12 y of age or 43.6 kg (96 lb) or more

PO 640 mg every 4 to 6 h (max, 5 doses/day [3.2 g in 24 h]).

11 y of age or 32.7 to 42.3 kg (72 to 95 lb)

PO 480 mg every 4 to 6 h (max, 5 doses/day [2.4 g in 24 h]).

9 to 10 y of age or 27.3 to 32.3 kg (60 to 71 lb)

PO 400 mg every 4 to 6 h (max, 5 doses/day [2 g in 24 h]).

6 to 8 y of age or 21.8 to 26.8 kg (48 to 59 lb)

PO 320 mg every 4 to 6 h (max, 5 doses/day [1.6 g in 24 h]).

4 to 5 y of age or 16.4 to 21.4 kg (36 to 47 lb)

PO 240 mg every 4 h (max, 5 doses/day [1.2 g in 24 h]).

2 to 3 y of age or 10.9 to 15.9 kg (24 to 35 lb)

PO 160 mg every 4 h (max, 5 doses/day [800 mg in 24 h])

PR Adults and Children 12 y of age and older

PR Two 325 mg suppositories or one 650 mg suppository every 4 to 6 h carefully inserted well up into rectum while symptoms persist (max, 3,900 mg in 24 h).

Children 6 to 12 y of age

PR One 325 mg suppository every 4 to 6 h carefully inserted well up into rectum while symptoms last (max, 1,900 mg in 24 h).

3 to 6 y of age

PR One 120 mg suppository carefully inserted well up into rectum every 4 to 6 h while symptoms persist (max, 720 mg in 24 h).

12 to 36 months of age

PR One 80 mg suppository carefully inserted well up into rectum every 4 h (max, 480 mg in 24 h).

3 to 11 months of age

PR One 80 mg suppository carefully inserted well up into rectum every 6 h.

Renal function impairment Severe renal impairment (CrCl 30 mL/min or less)

IV May need longer dosing interval and reduced total daily dose.

Hepatic function impairment

IV Reduced total daily dose may be warranted.

General Advice

• IV
• Administer IV over 15 min. May be administered without further dilution.
• Small-volume pediatric doses of up to 60 mL should be placed in a syringe and administered using a syringe pump.
• Do not add other medications to the acetaminophen vial or infusion device. Diazepam and chlorpromazine are physically incompatible with acetaminophen and should not be administered simultaneously.
• Vials are for single use only; discard unused portion.

• PO
• Adult extra-strength formulation should not be used in children younger than 12 y of age.
• Shake elixirs, infant drops, and suspensions well before using.
• Chewable tablets should be chewed before swallowing.
• Dissolve disintegrating tablets in mouth before swallowing; tablets should not be chewed or swallowed whole.
• Instruct patients to swallow ER tablets whole; do not crush, break, or chew.

• PR
• Suppositories are for rectal use only.
• Remove suppository wrapper before inserting.

Storage/Stability

Injection

Store between 68° and 77°F. Use within 6 h of penetration of the vacuum seal or transfer of the contents to another container. Do not refrigerate or freeze.

Oral doseforms

Store between 59° and 80°F. Avoid high humidity.

Suppositories

Store between 36° and 80°F.

Drug Interactions

Barbiturates, carbamazepine, hydantoins, sulfinpyrazone

May decrease therapeutic effect of acetaminophen; concomitant long-term use may increase risk of hepatotoxicity. At usual therapeutic doses, no special precautions are needed.

Charcoal

As an antidote, charcoal can decrease the absorption of acetaminophen when given as soon as possible after overdosage.

Ethanol

Long-term excessive use of alcohol may increase risk of hepatotoxicity. Use with caution in patients with a history of chronic alcohol ingestion.

Lamotrigine

Acetaminophen may reduce plasma concentration. If an interaction is suspected, adjust the lamotrigine dose accordingly.

Warfarin

Possible increased risk of bleeding, especially with dosages of more than 325 mg/day. More frequent assessment of INR is warranted. Adjust the warfarin dose as needed.

Adverse Reactions

Cardiovascular

IV

Hypertension, hypotension, tachycardia (at least 1%).

CNS

IV

Headache (10%); insomnia (7%); agitation (at least 5%); anxiety, fatigue (at least 1%).

Dermatologic

IV

Pruritus (at least 5%); rash (at least 1%).

GI

IV

Nausea (34%); vomiting (15%); constipation (at least 5%); abdominal pain, diarrhea (at least 1%).

Hematologic

Hemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia.

IV

Anemia (at least 1%).

Hepatic

Jaundice.

IV

Hepatic enzyme increase (at least 1%).

Local

IV

Infusion-site pain (at least 1%).

Metabolic

IV

Hypervolemia, hypoalbuminemia, hypokalemia, hypomagnesemia, hypophosphatemia, peripheral edema (at least 1%).

Musculoskeletal

IV

Muscle spasms, pain in extremity, trismus (at least 1%).

Respiratory

IV

Atelectasis (at least 5%); abnormal breath sounds, dyspnea, hypoxia, pleural effusion, pulmonary edema, stridor, wheezing (at least 1%).

Miscellaneous

Allergic skin eruptions, hypoglycemia, fever.

IV

Pyrexia (5%); oliguria, periorbital edema (at least 1%).

Precautions

Pregnancy

Category B (PO/PR); Category C (IV).

Lactation

Excreted in breast milk. The American Academy of Pediatrics classifies oral acetaminophen as compatible with breast-feeding. Exercise caution when IV acetaminophen is administered to a breast-feeding woman.

Children

The safety and effectiveness of acetaminophen injection have not been established in children younger than 2 y of age.

Hypersensitivity

Hypersensitivity reactions (including pruritus, rash, respiratory distress, urticaria, and swelling of the face, mouth, and throat) have been reported. There have also been infrequent reports of life-threatening anaphylaxis requiring emergent medical attention.

Renal Function

Reduce dosage in patients with severe renal function impairment.

Hepatic Function

Chronic alcoholic patients should not exceed 2 g/day. Acetaminophen injection is contraindicated in patients with severe hepatic impairment or severe active liver disease. Use with caution in patients with hepatic impairment or active liver disease.

Special Risk Patients

Use with caution in patients with alcoholism, chronic malnutrition, or severe hypovolemia.

Hepatic effects

Can cause liver damage, including severe hepatotoxicity and death, especially when recommended dose is exceeded.

Persistent pain or fever

May indicate serious illness.

Overdosage

Symptoms

Abdominal pain, acute renal failure, anorexia, cardiac arrhythmias, confusion, diaphoresis, diarrhea, hepatic necrosis, hypoglycemic coma, jaundice, liver failure, low BP, malaise, nausea, renal tubular necrosis, thrombocytopenia, vomiting.

Patient Information

• Advise patient not to use with other products containing acetaminophen.
• Advise patients that using higher than recommended doses may result in hepatic injury, including severe hepatotoxicity and death. The maximum recommended dose should not be exceeded.
• In case of an overdose, instruct patient or caregiver to contact health care provider or a poison control center immediately. Prompt medical attention is critical even if no signs or symptoms are present.
• Instruct patients to inform health care provider if they experience swelling of the face, mouth, and throat; respiratory distress; urticaria; rash; and/or pruritus.

• PO/PR
• Instruct family to consult health care provider for use in children younger than 3 y of age, and not to continue giving drug for more than 5 days unless advised by health care provider.
• Instruct adult patients not to continue taking drug more than 10 days for pain or 3 days for fever.
• Instruct patients to contact health care provider if new symptoms occur, redness or swelling is present, pain gets worse or lasts for longer than 10 days, or fever gets worse or lasts for longer than 3 days.
• Advise patient that if a measuring cup is provided for oral liquids, to use it to determine child's dose.
• Advise patients to shake suspensions well before using.
• Advise patients that if a sore throat is severe, persists for longer than 2 days, or is accompanied or followed by fever, headache, nausea, rash, or vomiting, to consult health care provider promptly.
• Advise patients that if they consume 3 or more alcoholic drinks per day, to ask health care provider whether they should take acetaminophen or another pain reliever or fever reducer.
• Advise patients with diabetes to use sugar-free form of drug.

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