Acetaminophen

Name: Acetaminophen

Is acetaminophen safe to take if I'm pregnant or breastfeeding?

Acetaminophen is excreted in breast milk in small quantities. However, acetaminophen use by the nursing mother appears to be safe.

Introduction

Synthetic nonopiate derivative of p-aminophenol; produces analgesia and antipyresis.198 207 222

Interactions for Acetaminophen

Drugs Affecting Hepatic Microsomal Enzymes

Drugs that induce or regulate CYP2E1 may alter metabolism of acetaminophen and increase its hepatotoxic potential.300 (See Metabolism under Pharmacokinetics.) Clinical importance not established.300

Specific Drugs

Drug

Interaction

Comments

Alcohol

Increased risk of acetaminophen-induced hepatotoxicity101 102 103 104 105 107 108 109 110 111 112 113 115 116 117 120 122 123 124 125 126 127 128 129 130 131 132

Complex effects on acetaminophen pharmacokinetics; excessive alcohol use can induce hepatic cytochromes, but alcohol also competitively inhibits acetaminophen metabolism300

Avoid regular or excessive use of acetaminophen; alternatively, avoid chronic ingestion of alcohol128 129 147 222 (see Prescribing Limits: Adults, under Dosage and Administration)

Anticonvulsants (barbiturates, carbamazepine, phenytoin)

Increased conversion of acetaminophen to hepatotoxic metabolites; increased risk of hepatotoxicity152 157 160 162 163 164 165

Limit acetaminophen self-medication;165 dosage adjustment not required162 163 164

Anticoagulants, oral

Possible increased PT168 176

Effects of IV acetaminophen not established300

Clinical importance questioned;a monitor anticoagulant activity if large doses of acetaminophen used168 169

Manufacturer of acetaminophen injection states more frequent INR monitoring also may be appropriate during short-term concomitant IV acetaminophen use300

Aspirin

No inhibition of antiplatelet effect of aspirin144

Isoniazid

Possible increased risk of hepatotoxicity166

Limit acetaminophen self-medication166

Phenothiazines

Possible increased risk of severe hypothermiaa

Acetaminophen Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration, with peak plasma concentration attained within 10–60 minutes (immediate-release preparations) or 60–120 minutes (extended-release preparations).a

Poor or variable absorption following rectal administration; considerable variation in peak plasma concentrations attained; time to reach peak plasma concentration is substantially longer than after oral administration.226 227 228

Pharmacokinetics of IV acetaminophen are dose proportional at doses of 0.5–1 g.300

Systemic exposure is similar following IV or oral administration, but peak plasma concentration at end of 15-minute IV infusion is up to 70% higher than peak concentration following oral administration of same dose.300

Following single-dose IV administration in pediatric patients (15-mg/kg dose) or adults (1-g dose), systemic exposure in children and adolescents is similar to that in adults, but exposure is higher in neonates and infants.300 Simulations suggest that dose reductions of 33% in infants 1 month to <2 years of age and 50% in neonates up to 28 days of age, with a minimum dosing interval of 6 hours, would result in systemic exposures similar to those observed in children ≥2 years of age.300

Food

Food may delay absorption following administration as extended-release tablets.148

Distribution

Extent

Rapidly distributed to most body tissues except fat.300 a Crosses placenta198 293 and is distributed into breast milk in small quantities.198 293 300

Plasma Protein Binding

10–25%.300 a

Elimination

Metabolism

Metabolized principally by sulfate and glucuronide conjugation; 226 small amounts (5–10%) oxidized by CYP-dependent pathways (mainly CYP2E1) to a toxic metabolite, N-acetyl-p-benzoquinoneimine (NAPQI).226 300 NAPQI is detoxified by glutathione and eliminated; any remaining toxic metabolite may bind to hepatocytes and cause cellular necrosis.121 226

Elimination Route

Mainly excreted in urine as conjugates.300 a

Half-life

Reportedly 1.25–3 hours.a

Following IV administration, 2.4 hours in adults, 2.9–3 hours in children and adolescents, 4.2 hours in infants, and 7 hours in neonates.300

Special Populations

Following toxic doses or in patients with liver damage, plasma half-life may be prolonged.a

In patients with moderate to severe renal impairment, acetaminophen conjugates may accumulate.a

Brand Names U.S.

  • Acephen [OTC]
  • Aspirin Free Anacin Extra Strength [OTC]
  • Cetafen Extra [OTC]
  • Cetafen [OTC]
  • FeverAll Adult [OTC]
  • FeverAll Children's [OTC]
  • FeverAll Infants' [OTC]
  • FeverAll Junior Strength [OTC]
  • Little Fevers [OTC]
  • Mapap Arthritis Pain [OTC]
  • Mapap Children's [OTC]
  • Mapap Extra Strength [OTC]
  • Mapap Infants' [OTC] [DSC]
  • Mapap [OTC]
  • Non-Aspirin Pain Reliever [OTC]
  • Nortemp Children's [OTC]
  • Ofirmev
  • Pain & Fever Children's [OTC]
  • Pain Eze [OTC]
  • Pharbetol Extra Strength [OTC]
  • Pharbetol [OTC]
  • Q-Pap Children's [OTC] [DSC]
  • Q-Pap Extra Strength [OTC] [DSC]
  • Q-Pap Infants' [OTC] [DSC]
  • Q-Pap [OTC] [DSC]
  • Silapap Children's [OTC]
  • Silapap Infants' [OTC] [DSC]
  • Triaminic Children's Fever Reducer Pain Reliever [OTC]
  • Tylenol 8 HR Arthritis Pain [OTC]
  • Tylenol 8 HR [OTC] [DSC]
  • Tylenol Children's [OTC]
  • Tylenol Extra Strength [OTC]
  • Tylenol Infants' [OTC]
  • Tylenol Jr. Meltaways [OTC] [DSC]
  • Tylenol [OTC]
  • Valorin Extra [OTC]
  • Valorin [OTC]

Pharmacology

Although not fully elucidated, believed to inhibit the synthesis of prostaglandins in the central nervous system and work peripherally to block pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center

Absorption

Primarily absorbed in small intestine (rate of absorption dependent upon gastric emptying); minimal absorption from stomach; varies by dosage form

Distribution

~1 L/kg at therapeutic doses

Metabolism

At normal therapeutic dosages, primarily hepatic metabolism to sulfate and glucuronide conjugates, while a small amount is metabolized by CYP2E1 to a highly reactive intermediate, N-acetyl-p-benzoquinone imine (NAPQI), which is conjugated rapidly with glutathione and inactivated to nontoxic cysteine and mercapturic acid conjugates. At toxic doses (as little as 4 g daily) glutathione conjugation becomes insufficient to meet the metabolic demand causing an increase in NAPQI concentrations, which may cause hepatic cell necrosis. Oral administration is subject to first pass metabolism.

Excretion

Urine (<5% unchanged; 60% to 80% as glucuronide metabolites; 20% to 30% as sulphate metabolites; ~8% cysteine and mercapturic acid metabolites)

Onset of Action

Oral: <1 hour

IV: Analgesia: 5 to 10 minutes; Antipyretic: Within 30 minutes

Peak effect: IV: Analgesic: 1 hour

Time to Peak

Serum: Oral: Immediate release: 10 to 60 minutes (may be delayed in acute overdoses); IV: 15 minutes

Dosing Geriatric

Refer to adult dosing.

Dosing Renal Impairment

Oral (Aronoff 2007):

Adults:

GFR ≥50 mL/minute: No dosage adjustment necessary.

GFR 10 to 50 mL/minute: Administer every 6 hours.

GFR <10 mL/minute: Administer every 8 hours.

CRRT: Administer every 6 hours.

Infants, Children, and Adolescents:

GFR ≥10 mL/minute/1.73 m2: No dosage adjustment necessary.

GFR <10 mL/minute/1.73 m2: Administer every 8 hours.

Intermittent hemodialysis or peritoneal dialysis: Administer every 8 hours.

CRRT: No dosage adjustment necessary.

IV: Children, Adolescents, and Adults:

CrCl >30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling.

CrCl ≤30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling. Use with caution; consider decreasing daily dose and extending dosing interval.

Administration

Oral: May administer without regard to food; may administer with food to decrease possible GI upset; shake drops and suspension well before use; do not crush or chew extended release products

Injection: For IV infusion only. Administer undiluted over 15 minutes.

For doses <1,000 mg (<50 kg): Withdraw appropriate dose and place into separate empty, sterile container (eg, glass bottle, plastic IV container, syringe) for administration. Small volume pediatric doses (up to 600 mg [60 mL]) may be placed in a syringe and infused via syringe pump.

For 1,000 mg doses (≥50 kg): Insert a vented IV set through vial stopper or a non-vented IV set through the administration spike port of the bag.

Rectal: Remove wrapper; insert suppository well up into the rectum.

Description

Active Ingredient

Acetaminophen Regular Strength

Drug Facts

Active Ingredient (in each caplet) Acetaminophen 325 mg

Uses of Acetaminophen

Acetaminophen is a prescription medication used to treat mild to moderate pain and reduce fever.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Side Effects of Acetaminophen

Serious side effects have been reported with acetaminophen. See the “Acetaminophen Precautions” section.

Common side effects of acetaminophen include nausea, vomiting, headache, and insomnia in adults and nausea, vomiting, constipation, itching, and agitation in children.

This is not a complete list of acetaminophen side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Acetaminophen Precautions

Serious side effects have been reported with acetaminophen including the following:

  • Liver injury. Acetaminophen should be used cautiously in patients with liver impairment or disease, alcoholism, malnutrition, dehydration or severe blood loss, or severe kidney injury. Tell your healthcare provider right away if you have some or all of the following symptoms of liver injury.
    • vomiting
    • nausea
    • fatigue
    • abdominal pain
  • Serious skin reactions. Tell your healthcare provider right away if you have red, peeling, or blistering skin.
  • Allergy and hypersensitivity reaction. Tell your healthcare provider right away if you have some or all of the following symptoms of an allergic-type reaction:
    • hives
    • itching
    • swelling of the face, throat, tongue, eyes, hands, feet, ankles, or lower legs
    • hoarseness
    • difficulty breathing or swallowing

Do not take acetaminophen if you:

  • are allergic to acetaminophen or to any of its ingredients
  • have severe liver impairment or active liver disease

Acetaminophen FDA Warning

WARNING: RISK OF MEDICATION ERRORS AND HEPATOTOXICITY

Take care when prescribing, preparing, and administering OFIRMEV Injection to avoid dosing errors which could result in accidental overdose and death. In particular, be careful to ensure that:

the dose in milligrams (mg) and milliliters (mL) is not confused;

the dosing is based on weight for patients under 50 kg;

infusion pumps are properly programmed; and

the total daily dose of acetaminophen from all sources does not exceed maximum daily limits.

Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed the maximum daily limits, and often involve more than one acetaminophen-containing product.

How should I take acetaminophen?

Use acetaminophen exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended.

Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death.

  • Adults and teenagers who weigh at least 110 pounds (50 kilograms): Do not take more than 1000 milligrams (mg) at one time. Do not take more than 4000 mg in 24 hours.

  • Children younger than 12 years old: Do not take more than 5 doses of acetaminophen in 24 hours. Use only the number of milligrams per dose that is recommended for the child's weight and age. Use exactly as directed on the label.

  • Avoid also using other medicines that contain acetaminophen, or you could have a fatal overdose.

If you are treating a child, use a pediatric form of acetaminophen. Use only the special dose-measuring dropper or oral syringe that comes with the specific pediatric form you are using. Carefully follow the dosing directions on the medicine label.

Measure liquid medicinewith the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Acetaminophen made for infants is available in two different dose concentrations, and each concentration comes with its own medicine dropper or oral syringe. These dosing devices are not equal between the different concentrations. Using the wrong device may cause you to give your child an overdose of acetaminophen. Never mix and match dosing devices between infant formulations of acetaminophen.

You may need to shake the liquid before each use. Follow the directions on the medicine label.

The chewable tablet must be chewed thoroughly before you swallow it.

Make sure your hands are dry when handling the acetaminophen disintegrating tablet. Place the tablet on your tongue. It will begin to dissolve right away. Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing.

To use the acetaminophen effervescent granules, dissolve one packet of the granules in at least 4 ounces of water. Stir this mixture and drink all of it right away. To make sure you get the entire dose, add a little more water to the same glass, swirl gently and drink right away.

Stop taking acetaminophen and call your doctor if:

  • you still have a fever after 3 days of use;

  • you still have pain after 7 days of use (or 5 days if treating a child);

  • you have a skin rash, ongoing headache, or any redness or swelling; or

  • if your symptoms get worse, or if you have any new symptoms.

This medication can cause unusual results with certain lab tests for glucose (sugar) in the urine. Tell any doctor who treats you that you are using acetaminophen.

Store at room temperature away from heat and moisture.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of acetaminophen can be fatal.

The first signs of an acetaminophen overdose include loss of appetite, nausea, vomiting, stomach pain, sweating, and confusion or weakness. Later symptoms may include pain in your upper stomach, dark urine, and yellowing of your skin or the whites of your eyes.

How it works

  • Acetaminophen is used to relieve pain. Experts aren't sure exactly how acetaminophen works, but suspect it blocks a specific type of cyclo-oxygenase (COX) enzyme, located mainly in the brain.
  • Acetaminophen belongs to the class of medicines called analgesics (pain relievers); it is specifically a non-narcotic analgesic. It may also be called an antipyretic because it will bring down a fever.
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