Tylenol with Codeine #4 Side Effects

Generic Name: acetaminophen / codeine

Note: This page contains side effects data for the generic drug acetaminophen / codeine. It is possible that some of the dosage forms included below may not apply to the brand name Tylenol with Codeine #4.

It is possible that some side effects of Tylenol with Codeine #4 may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

For the Consumer

Applies to acetaminophen / codeine: oral capsule, oral elixir, oral solution, oral suspension, oral tablet

As well as its needed effects, acetaminophen / codeine may cause unwanted side effects that require medical attention.

If any of the following side effects occur while taking acetaminophen / codeine, check with your doctor immediately:

More common
  • Difficult or troubled breathing
  • irregular, fast or slow, or shallow breathing
  • pale or blue lips, fingernails, or skin
  • shortness of breath
Incidence not known
  • Black, tarry stools
  • bleeding gums
  • blood in the urine or stools
  • cough or hoarseness
  • difficulty with swallowing
  • dizziness
  • fast heartbeat
  • fever with or without chills
  • general feeling of tiredness or weakness
  • hives
  • itching
  • lower back or side pain
  • painful or difficult urination
  • pinpoint red spots on the skin
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • skin rash
  • sore throat
  • sores, ulcers, or white spots on the lips or in the mouth
  • tightness in the chest
  • unusual bleeding or bruising
  • unusual tiredness or weakness

If any of the following symptoms of overdose occur while taking acetaminophen / codeine, get emergency help immediately:

Symptoms of overdose
  • Abdominal or stomach pain
  • bloody or cloudy urine
  • chills
  • constricted, pinpoint, or small pupils (black part of the eye)
  • convulsions
  • dark urine
  • headache
  • increased sweating
  • light-colored stools
  • loss of appetite
  • loss of consciousness
  • nausea
  • sudden decrease in amount of urine
  • unpleasant breath odor
  • vomiting
  • vomiting of blood
  • yellow eyes or skin

Some acetaminophen / codeine side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

More common
  • Drowsiness
  • lightheadedness
  • relaxed and calm
  • sleepiness
Incidence not known
  • Difficulty having a bowel movement (stool)
  • false or unusual sense of well-being

For Healthcare Professionals

Applies to acetaminophen / codeine: oral capsule, oral liquid, oral suspension, oral tablet

Nervous system

Nervous system side effects of codeine have included mental and respiratory depression, stupor, delirium, somnolence, and dysphoria. An increased risk of falls and hip fractures has been associated with codeine therapy, particularly in the elderly.[Ref]

Other

Other side effects such as withdrawal symptoms (after either abrupt cessation or fast tapering of narcotic analgesics) have included agitation, restlessness, anxiety, insomnia, tremor, abdominal cramps, blurred vision, vomiting and sweating.[Ref]

Gastrointestinal

One study has suggested that acetaminophen may precipitate acute biliary pain and cholestasis. The mechanism for this side effect may be related to inhibition of prostaglandin and alterations in the regulation of the sphincter of Oddi.[Ref]

Gastrointestinal side effects of acetaminophen are rare except in alcoholics and after overdose. Cases of acute pancreatitis have been reported rarely in association with acetaminophen.

Nausea, vomiting, and constipation have been reported frequently with the use of codeine. Severe constipation and ileus resulting in colonic perforation have been also reported. Four cases of acute pancreatitis have been reported.[Ref]

Hepatic

Hepatic side effects of acetaminophen including severe and sometimes fatal dose dependent hepatitis have been reported in alcoholic patients. Hepatotoxicity has been increased during fasting. Several cases of hepatotoxicity from chronic acetaminophen therapy at therapeutic doses have also been reported despite a lack of risk factors for toxicity.[Ref]

Alcoholic patients may develop hepatotoxicity after even modest doses of acetaminophen. In healthy patients, approximately 15 grams of acetaminophen is necessary to deplete liver glutathione stores by 70% in a 70 kg person. However, hepatotoxicity has been reported following smaller doses. Glutathione concentrations may be repleted by the antidote N-acetylcysteine. One case report has suggested that hypothermia may also be beneficial in decreasing liver damage during overdose.

In a recent retrospective study of 306 patients admitted for acetaminophen overdose, 6.9% had severe liver injury but all recovered. None of the 306 patients died.

A 19-year-old female developed hepatotoxicity, reactive plasmacytosis and agranulocytosis followed by a leukemoid reaction after acute acetaminophen toxicity.

The adverse effects of acetaminophen-codeine may be more likely and more severe in patients with liver disease.[Ref]

Cardiovascular

Cardiovascular side effects of codeine have included hypotension and dizziness.[Ref]

Renal

Renal side effects of acetaminophen including acute tubular necrosis and interstitial nephritis have been reported rarely.[Ref]

Acute tubular necrosis associated with acetaminophen usually occurs in conjunction with liver failure, but has been observed as an isolated finding in rare cases. Adverse acetaminophen renal effects are most often observed after overdose, after chronic abuse (often with multiple analgesics), or in association with acetaminophen-related hepatotoxicity. A possible increase in the risk of renal cell carcinoma has been associated with chronic acetaminophen use as well. Acute renal failure (which responded to naloxone therapy) has also been reported in association with codeine therapy.

The adverse effects of codeine may be more likely and more severe in patients with renal insufficiency.[Ref]

Hypersensitivity

Hypersensitivity side effects including anaphylaxis and fixed drug eruptions have been reported rarely in association with acetaminophen use.[Ref]

Genitourinary

Genitourinary side effects including urinary retention have been reported in association with codeine use.[Ref]

Hematologic

Hematologic side effects including rare cases of thrombocytopenia associated with acetaminophen have been reported. Acute thrombocytopenia has also been reported as having been caused by sensitivity to acetaminophen glucuronide, the major metabolite of acetaminophen. Methemoglobinemia with resulting cyanosis has also been observed in the setting of acute overdose.[Ref]

Dermatologic

Dermatologic side effects including rashes have been reported in association with both codeine and acetaminophen. A case of henoch-schonlein purpura has been reported in a patient receiving acetaminophen with codeine. Acetaminophen has been associated with a risk of rare but potentially fatal serious skin reactions know as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP).[Ref]

Codeine-induced rashes may be related to direct stimulation of histamine release. Case reports of severe scarlatiniform eruptions have also been reported in association with codeine. General erythematous skin rashes associated with acetaminophen have been reported, but are rare. A rare case of bullous erythema associated with acetaminophen has been reported.[Ref]

Respiratory

Respiratory side effects have included a case of acetaminophen-induced eosinophilic pneumonia.[Ref]

Immunologic

Immunologic side effects have been reported. One study of a patient with exercise-induced anaphylaxis and three control subjects has found a correlation between codeine wheal size and recent exercise.[Ref]

References

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49. Doan T, Greenberger PA "Nearly fatal episodes of hypotension, flushing, and dyspnea in a 47- year-old woman." Ann Allergy 70 (1993): 439-44

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53. Bougie DW, Benito AI, Sanchez-Abarca LI, Torres R, Birenbaum J, Aster RH "Acute thrombocytopenia caused by sensitivity to the glucuronide conjugate of acetaminophen." Blood 109 (2007): 3608-9

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56. Thomas RH, Munro DD "Fixed drug eruption due to paracetamol." Br J Dermatol 115 (1986): 357-9

57. Guccione JL, Zemtsov A, Cobos E, Neldner KH "Acquired purpura fulminans induced by alcohol and acetaminophen - successful treatment with heparin and vitamin-k." Arch Dermatol 129 (1993): 1267-9

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