Acetaminophen / caffeine / dihydrocodeine Side Effects

Not all side effects for acetaminophen / caffeine / dihydrocodeine may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to acetaminophen / caffeine / dihydrocodeine: capsules, tablets

Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Constipation; dizziness; drowsiness; headache; light-headedness; mild itching; nausea; sweating; tiredness; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur while taking acetaminophen / caffeine / dihydrocodeine:

Severe allergic reactions (rash; hives; itching; difficulty breathing or swallowing; tightness in the chest; swelling of the mouth, face, lips, throat, or tongue); change in the amount of urine produced; confusion; fainting; fast, slow, or irregular heartbeat; fever, chills, or persistent sore throat; hallucinations; mental or mood changes (eg, agitation, anxiety, depression); red, swollen, blistered, or peeling skin; ringing in the ears; seizures; severe or persistent constipation; severe or persistent dizziness, drowsiness, headache, or light-headedness; shortness of breath; slow, shallow, or difficult breathing; symptoms of liver problems (eg, yellowing of the eyes or skin, dark urine, pale stools, loss of appetite, unusual or severe stomach pain); trouble urinating; unusual bruising or bleeding; unusual tiredness or weakness; vision changes.

For Healthcare Professionals

Applies to acetaminophen / caffeine / dihydrocodeine: oral capsule, oral tablet


Respiratory side effects of dihydrocodeine have included respiratory depression and cough suppression.


Hepatic side effects of acetaminophen have included severe and sometimes fatal dose dependent hepatitis 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.

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.


Two cases of hypotension have been reported following the administration of acetaminophen. Both patients experienced significant decreases in blood pressure. One of the two patients required pressor agents to maintain adequate mean arterial pressures. Neither episode was associated with symptoms of anaphylaxis. Neither patient was rechallenged after resolution of the initial dose.

Cardiovascular side effects of acetaminophen have included two cases of hypotension.

Cardiovascular side effects of caffeine have included extrasystole, palpitation, and tachycardia.

Cardiovascular side effects of dihydrocodeine have included orthostatic hypotension.


In a case of metabolic acidosis, causality is uncertain as more than one drug was ingested. The case of metabolic acidosis followed the ingestion of 75 grams of acetaminophen, 1.95 grams of aspirin, and a small amount of a liquid household cleaner. The patient also had a history of seizures which the authors reported may have contributed to an increased lactate level indicative of metabolic acidosis.

Metabolic side effects of acetaminophen have included metabolic acidosis following a massive overdose of acetaminophen.


Dermatologic side effects of acetaminophen have rarely included erythematous skin rashes. Acetaminophen associated bullous erythema and purpura fulminans have been reported. One case of toxic epidermal necrolysis associated with acetaminophen administered to a pediatric patient has been reported. 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).

Dermatologic side effects of caffeine have included urticaria.


Gastrointestinal side effects of acetaminophen have rarely included acute pancreatitis in alcoholics and after overdose.

Gastrointestinal side effects of caffeine have included nausea, diarrhea, stomach pain, and vomiting.

Gastrointestinal side effects of dihydrocodeine have included nausea, vomiting, constipation, diarrhea, abdominal pain, dry mouth, indigestion, and anorexia.


In general, acetaminophen is well tolerated when administered in therapeutic doses.

General side effects of caffeine have included irritability and restlessness. Consumption of higher doses of caffeine (less than 600 mg/day) has been reported to have lead to caffeinism. Caffeinism is a syndrome characterized by anxiety, restlessness, and sleep disorders (similar to anxiety states). It has also been reported that chronic, heavy caffeine ingestion may be associated with depression. Caffeine may cause anxiety and panic in panic disorder patients and may aggravate premenstrual syndrome (PMS).

General side effects of dihydrocodeine have included sweating and tolerance.


Acute tubular necrosis usually occurs in conjunction with liver failure, but has been observed as an isolated finding in rare cases of acetaminophen use. A possible increase in the risk of renal cell carcinoma has been associated with chronic acetaminophen use as well.

One case-controlled study of patients with end-stage renal disease suggested that long term consumption of acetaminophen may significantly increase the risk of end-stage renal disease particularly in patients taking multiple doses per day.

However, a cohort study of analgesia use in initially healthy men concluded that moderate use of analgesics including acetaminophen was not associated with increased risk of renal disease.

Renal side effects of acetaminophen have rarely included acute renal failure, acute tubular necrosis, and interstitial nephritis. Adverse renal effects are most often observed after overdose, after chronic abuse (often with multiple analgesics), or in association with acetaminophen-related hepatotoxicity.

Renal side effects of caffeine have included increased urine flow rate, creatinine clearance, sodium and calcium excretion.

Renal side effects of dihydrocodeine have included granulomatous interstitial nephritis and acute renal failure.


Hematologic side effects of acetaminophen have included thrombocytopenia, thrombocytopenia purpura, leukopenia, pancytopenia, neutropenia, and agranulocytosis.


Hypersensitivity side effects of acetaminophen have rarely included urticaria, erythematous skin reaction, laryngeal edema, angioedema, and anaphylaxis.

Hypersensitivity side effects of dihydrocodeine have included anaphylaxis.


Musculoskeletal side effects of caffeine have included tenseness and tremor.


Psychiatric side effects of caffeine have included anxiety and anxiety neurosis.

Psychiatric side effects of dihydrocodeine have included severe narcosis, hallucinations, and vivid dreams.


Several studies report a decrease in insulin sensitivity in individuals following caffeine consumption. The mechanism leading to this effect is unknown but may be related to elevated serum epinephrine levels.

A few studies report a possible decreased risk of type 2 diabetes mellitus in individuals who consume coffee.

Endocrine side effects of caffeine have rarely included alterations in serum glucose such as hypoglycemia and hyperglycemia.

Nervous system

Nervous system side effects of caffeine have included central nervous system stimulation such as irritability, restlessness, jitteriness, headache, insomnia, and lightheadedness.

Nervous system side effects of dihydrocodeine have included lightheadedness, dizziness, drowsiness, headache, sedation, and confusion.


Ocular side effects of caffeine have included scintillating scotoma.


Other side effects of caffeine have included fibrocystic breast disease in women. One study has reported that while favorable subjective and performance-enhancing stimulant effects occur at low to intermediate caffeine doses, the unfavorable subjective and somatic effects, as well as performance disruption from high doses of caffeine may intrinsically limit the doses of caffeine used in the general population.

In one study of 634 women with fibrocystic breast disease (compared to 1066 women without the disease), the occurrence of fibrocystic breast disease was positively associated with average daily consumption of caffeine. Women who consumed 31 to 250 mg/day of caffeine were reported to have a 1.5 times increase in odds to have the disease. Women who consumed over 500 mg/day of caffeine were reported to have a 2.3 times increase in odds.

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