Drugs

Acetaminophen/codeine

Definition

Acetaminophen with codeine is a drug that combines acetaminophen, a nonprescription painkiller (analgesic), with codeine, an opium-based painkiller. It belongs to the family of drugs called opioid analgesics.

Purpose

Acetaminophen with codeine is used to treat mild to moderately severe pain that is not relieved by nonprescription painkillers alone.

Description

Acetaminophen / codeineAcetaminophen with codeine is a white, diskshaped tablet 10 millimeters (mm) in diameter. The strength of the tablet (rated 2, 3, or 4) is embossed on one side. The pill is to be taken whole by mouth with or without food. In the United States, acetaminophen with codeine is a Schedule III controlled substance. This means that:

  • The drug has the potential for abuse at a lower level than Schedule I or Schedule II drugs.
  • The drug has legitimate medical uses.
  • Prolonged use of the drug can cause low to moderate physical dependence or high psychological dependence.

Acetaminophen with codeine tablets come in three strengths:

  • 300 mg acetaminophen with 15 mg codeine (strength 2)
  • 300 mg acetaminophen with 30 mg codeine (strength 3)
  • 300 mg acetaminophen with 60 mg codeine (strength 4)

Acetaminophen with codeine is sold in the United States by several generic manufacturers and under various brand names, including:

  • Capital & Codeine
  • Tylenol (#2, #3, #4)
  • Fioricet with codeine
  • Phrenilin with caffeine
  • codeine containing added caffeine and butalbital

Canadian brand names

In Canada, a formulation containing 325 milligrams (mg) acetaminophen, 8 mg of codeine, and 15 mg caffeine is available without a prescription. It is sold as Tylenol #1 and under other names.

In Canada, acetaminophen with codeine is sold under the names Acet codeine, Procet-30, ratio-Emtec-30, ratio-Lenoltec No. 4, Triacet-30, and Tylenol #4. Many other formulations include acetaminophen, codeine, and caffeine, including Atasol, Exdol, and Tylenol. These brand names are available in varying strengths from 8 mg to 35 mg of codeine.

International brand names

Internationally, acetaminophen is known as paracetamol. There are dozens of brand names for the combination of paracetamol and codeine, depending on the country of origin. For example, in countries such as India, other drugs are added to the paracetamol-codeine combination or another analgesic such as aspirin or ibuprofen is substituted for paracetamol. Internationally, the combination of paracetamol and codeine is also available in capsule form.

Recommended dosage

The dosage should always be the lowest dosage needed to control pain and within the acceptable limitations listed in Precautions. Usual adult doses range from 15 to 60 mg codeine and 300 to 1,000 mg acetaminophen. Doses may be repeated every 4 hours, with a maximum 24-hour dosage of 360 mg codeine and 4,000 mg acetaminophen.

This drug is not recommended for use in children under three years old. The usual dosage for children is 0.5mg per kilogram(kg, or 2.2 lb.) of body weight, repeated every four hours.

Precautions

The U.S. Food and Drug Administration (FDA) requires a boxed warning for this drug indicating that acetaminophen has been associated with cases of acute liver failure, usually at doses greater than 4,000 mg per day. An additional warning indicates that acetaminophen with codeine should not be used in children who have had a tonsillectomy or adenoidectomy.

Other precautions include the warning that codeine can be physically and psychologically addictive if used for a long time and that tolerance can develop. Individuals with a history of substance abuse are at higher risk for addiction. In addition, this drug may not be appropriate or the usual dosage may need to be reduced in individuals who have severe renal (kidney) or hepatic (liver) impairment, head injuries, elevated intracranial pressure, hypothyroidism, Addison’s disease, constriction of the urethra, or enlarged prostate.

Codeine crosses into breast milk. Women who are ultra-high metabolizers of codeine may have levels of codeine in breast milk high enough to cause respiratory depression or death in the nursing infant. However, acetaminophen with codeine is considered compatible with breastfeeding by the American Academy of Pediatrics.

Long-term heavy alcohol abusers are at increased risk of liver damage from acetaminophen use beyond the standard dosage.

In January 2014, the FDA recommended that healthcare professionals cease prescribing or dispensing drug products that contained more than 325 mg of acetaminophen per dose. There is no evidence that higher doses of acetaminophen (more than 325 mg) provide benefits that outweigh the risks to the liver, and limiting the dosage helps reduce the risk of liver injury. Accidental acetaminophen overdose can result in liver failure, the need for liver transplant, and death.

Cases of severe liver damage have occurred in patients who:

  • exceeded the prescribed dose of acetaminophen within a 24-hour period
  • took more than one product that contained acetaminophen
  • consumed alcohol while taking acetaminophen

Pediatric

Acetaminophen with codeine is not recommended for children under age three. Children should not be given acetaminophen with codeine after having tonsils or adenoids removed, especially if this was a treatment for sleep apnea. In addition, children who are ultra-high metabolizers of codeine are at high risk for respiratory depression and death.

Geriatric

All individuals, but especially older individuals who have decreased liver or kidney function may not clear acetaminophen or codeine from the body as rapidly as individuals with fully functioning kidneys and livers. This can allow the drug to build up in the blood, causing more liver damage. Dosage must be adjusted in these individuals.

Pregnant or breastfeeding

Acetaminophen with codeine is a pregnancy category C drug. Codeine crosses the placenta. The newborn may show withdrawal effects if the mother has taken codeine even at low doses as little as ten days before delivery. Acetaminophen with codeine should be given only if benefits outweigh risks.

Codeine crosses into breast milk. Women who are ultra-high metabolizers of codeine may have levels of codeine in breast milk high enough to cause respiratory depression or death in the nursing infant. However, acetaminophen with codeine is considered compatible with breastfeeding by the American Academy of Pediatrics.

Side effects

Rarely acetaminophen may cause a serious skin reaction that can be fatal. At the first sign of any rash or sign of hypersensitivity, individuals should stop taking the drug. Hypersensitivity reactions include swelling of the face, mouth, or throat; difficulty breathing; rash or skin eruptions; and vomiting.

Common but less serious side effects include dizziness, lightheadedness, drowsiness, nausea, and constipation. Mental abilities and physical responses may be delayed. Other side effects are possible. Individuals should report to their healthcare provider any unusual, unexpected, or troubling side effects.

Laboratory tests for serum amylase and urinary 5-hydroxyindoleacetic acid may be altered by this drug.

Interactions

Drugs

All drugs that depress the central nervous system enhance the effect of codeine. These include other narcotics and sleep medicines. Buprenorphine, naltrexone, and quinidine may decrease the effectiveness of acetaminophen with codeine. This drug may increase the chance of side effects in individuals taking anticoagulants such as warfarin (Coumadin). Certain chemotherapy drugs and drugs to treat human immunodeficiency virus (HIV) can increase liver damage. Other drugs not listed here may interact with acetaminophen with codeine. Individuals should review all medications they are taking with their doctor or pharmacist before starting this drug.

Herbs and supplements

As of early 2015, there was no definitive research on which drugs and supplements may interact with acetaminophen with codeine. Individuals should review all herbs and supplements with their doctor or pharmacist before starting this drug.

Food and other substances

Both alcohol and codeine are central nervous system depressants. Taken together, they can cause respiratory depression or death. Acetaminophen is more likely to cause liver damage in individuals who are heavy consumers of alcohol.