Acetaminophen / caffeine / dihydrocodeine Side Effects
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:
Seek medical attention right away if any of these SEVERE side effects occur while taking acetaminophen / caffeine / dihydrocodeine:
Constipation; dizziness; drowsiness; headache; light-headedness; mild itching; nausea; sweating; tiredness; vomiting.
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.[Ref]
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.[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.[Ref]
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.[Ref]
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.[Ref]
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.[Ref]
Metabolic side effects of acetaminophen have included metabolic acidosis following a massive overdose of acetaminophen.[Ref]
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.[Ref]
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.[Ref]
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.[Ref]
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.[Ref]
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.[Ref]
Hematologic side effects of acetaminophen have included thrombocytopenia, thrombocytopenia purpura, leukopenia, pancytopenia, neutropenia, and agranulocytosis.[Ref]
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.[Ref]
Musculoskeletal side effects of caffeine have included tenseness and tremor.[Ref]
Psychiatric side effects of caffeine have included anxiety and anxiety neurosis.
Psychiatric side effects of dihydrocodeine have included severe narcosis, hallucinations, and vivid dreams.[Ref]
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.[Ref]
Endocrine side effects of caffeine have rarely included alterations in serum glucose such as hypoglycemia and hyperglycemia.[Ref]
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.[Ref]
Ocular side effects of caffeine have included scintillating scotoma.[Ref]
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.[Ref]
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.[Ref]
1. "Product Information. Panlor SS (APAP/caffeine/dihydrocodeine)." Pamlab LLC, Mandeville, LA.
2. Kondo K, Inoue Y, Hamada H, Yokoyama A, Kohno N, Hiwada K "Acetaminophen-induced eosinophilic pneumonia." Chest 104 (1993): 291-2
3. Kurtovic J, Riordan SM "Paracetamol-induced hepatotoxicity at recommended dosage." J Intern Med 253 (2003): 240-3
4. Gursoy M, Haznedaroglu IC, Celik I, Sayinalp N, Ozcebe OI, Dundar SV "Agranulocytosis, plasmacytosis, and thrombocytosis followed by a leukemoid reaction due to acute acetaminophen toxicity." Ann Pharmacother 30 (1996): 762-5
5. Vitols S "Paracetamol hepatotoxicity at therapeutic doses." J Intern Med 253 (2003): 95-8
6. Zimmerman HJ, Maddrey WC "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology 22 (1995): 767-73
7. Vlachopoulos C, Hirata K, Stefanadis C, Toutouzas P, O'Rourke MF "Caffeine increases aortic stiffness in hypertensive patients." Am J Hypertens 16 (2003): 63-6
8. Pfeiffer M, Stanojevic S, Feuchtinger T, et al. "Rituximab mediates in vitro antileukemic activity in pediatric patients after allogeneic transplantation." Bone Marrow Transplant (2005):
9. "Product Information. Cafcit (caffeine)" Roxane Laboratories Inc, Columbus, OH.
10. Brown G "Acetaminophen-induced hypotension." Heart Lung 25 (1996): 137-40
11. Hartley TR, Lovallo WR, Whitsett TL "Cardiovascular effects of caffeine in men and women." Am J Cardiol 93 (2004): 1022-6
12. Sondermeijer H, van Marle A, Kamen P, Krum H "Acute effects of caffeine on heart rate variability." Am J Cardiol 90 (2002): 906
13. Koulouris Z, Tierney MG, Jones G "Metabolic acidosis and coma following a severe acetaminophen overdose." Ann Pharmacother 33 (1999): 1191-4
14. 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
15. Halevi A, BenAmitai D, Garty BZ "Toxic epidermal necrolysis associated with acetaminophen ingestion." Ann Pharmacother 34 (2000): 32-4
16. "Multum Information Services, Inc. Expert Review Panel"
17. Filipe PL, Freitas JP, Decastro JC, Silva R "Drug eruption induced by acetaminophen in infectious mononucleosis." Int J Dermatol 34 (1995): 220-1
18. Thomas RH, Munro DD "Fixed drug eruption due to paracetamol." Br J Dermatol 115 (1986): 357-9
19. Nelson EB, Temple AR "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
20. Cheung L, Potts RG, Meyer KC "Acetaminophen treatment nomogram." N Engl J Med 330 (1994): 1907-8
21. Bray GP "Liver failure induced by paracetamol." BMJ 306 (1993): 157-8
22. Johnson GK, Tolman KG "Chronic liver disease and acetaminophen." Ann Intern Med 87 (1977): 302-4
23. Wong V, Daly M, Boon A, Heatley V "Paracetamol and acute biliary pain with cholestasis." Lancet 342 (1993): 869
24. Shriner K, Goetz MB "Severe hepatotoxicity in a patient receiving both acetaminophen and zidovudine." Am J Med 93 (1992): 94-6
25. Bonkovsky HL, Kane RE, Jones DP, Galinsky RE, Banner B "Acute hepatic and renal toxicity from low doses of acetaminophen in the absence of alcohol abuse or malnutrition - evidence for increased susceptibility to drug toxicity due to cardiopulmonary and renal insufficiency." Hepatology 19 (1994): 1141-8
26. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med 104 (1986): 399-404
27. Smilkstein MJ, Douglas Dr, Daya MR "Acetaminophen poisoning and liver function." N Engl J Med 331 (1994): 1310-1
28. Whitcomb DC "Acetaminophen poisoning and liver function." N Engl J Med 331 (1994): 1311
29. Brotodihardjo AE, Batey RG, Farrell GC, Byth K "Hepatotoxicity from paracetamol self-poisoning in Western Sydney: a continuing challenge." Med J Aust 157 (1992): 382-5
30. Rumore MM, Blaiklock RG "Influence of age-dependent pharmacokinetics and metabolism on acetaminophen hepatotoxicity." J Pharm Sci 81 (1992): 203-7
31. Cheung L, Meyer KC "Acetaminophen poisoning and liver function." N Engl J Med 331 (1994): 1311-2
32. Whitcomb DC, Block GD "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA 272 (1994): 1845-50
33. Lee WM "Acute liver failure." Am J Med 96 (1994): 3-9
34. Mofenson HC, Caraccio TR, Nawaz H, Steckler G "Acetaminophen induced pancreatitis." Clin Toxicol 29 (1991): 223-30
35. Bonkovsky HL "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
36. Block R, Jankowski JA, Lacoux P, Pennington CR "Does hypothermia protect against the development of hepatitis in paracetamol overdose?" Anaesthesia 47 (1992): 789-91
37. Debruyne D, Tartiere J, Albessard F, Samba D, Deshayes JP, Moulin M "Clinical pharmacokinetics of propofol in postoperative sedation after orthotopic liver transplantation." Clin Drug Invest 9 (1995): 8-15
38. Kaysen GA, Pond SM, Roper MH, Menke DJ, Marrama MA "Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen." Arch Intern Med 145 (1985): 2019-23
39. O'Dell JR, Zetterman RK, Burnett DA "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA 255 (1986): 2636-7
40. Keays R, Harrison PM, Wendon JA, et al "Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial." BMJ 303 (1991): 1026-9
41. Block R "Liver failure induced by paracetamol." BMJ 306 (1993): 457
42. McJunkin B, Barwick KW, Little WC, Winfield JB "Fatal massive hepatic necrosis following acetaminophen overdose." JAMA 236 (1976): 1874-5
43. Kumar S, Rex DK "Failure of physicians to recognize acetaminophen hepatotoxicity in chronic alcoholics." Arch Intern Med 151 (1991): 1189-91
44. Hartleb M "Do thyroid hormones promote hepatotoxicity to acetaminophen?" Am J Gastroenterol 89 (1994): 1269-70
45. Minton NA, Henry JA, Frankel RJ "Fatal paracetamol poisoning in an epileptic." Hum Toxicol 7 (1988): 33-4
46. Sawynok J "Pharmacological rationale for the clinical use of caffeine." Drugs 49 (1995): 37-50
47. Clementz GL, Dailey JW "Psychotropic effects of caffeine." Am Fam Physician 37 (1988): 167-72
48. Drenth JP, Frenken LA, Wuis EW, Van der Meer JW "Acute renal failure associated with paracetamol ingestion in an alcoholic patient." Nephron 67 (1994): 483-5
49. Duchene A, Chadenas D, Marneffe-Lebrequier H "Insuffisance renale aigue isolee apres intoxication volontaire par le paracetamol." Presse Med 20 (1991): 1684-5
50. Boyer TD, Rouff SL "Acetaminophen-induced hepatic necrosis and renal failure." JAMA 218 (1971): 440-1
51. Curry RW, Robinson JD, Sughrue MJ "Acute renal failure after acetaminophen ingestion." JAMA 247 (1982): 1012-4
52. Keaton MR "Acute renal failure in an alcoholic during therapeutic acetaminophen ingestion." South Med J 81 (1988): 1163-6
53. Segasothy M, Suleiman AB, Puvaneswary M, Rohana A "Paracetamol: a cause for analgesic nephropathy and end-stage renal disease." Nephron 50 (1988): 50-4
54. Perneger TV, Whelton PK, Klag MJ "Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs." N Engl J Med 331 (1994): 1675-79
55. Eguia L, Materson BJ "Acetaminophen-related acute renal failure without fulminant liver failure." Pharmacotherapy 17 (1997): 363-70
56. Vanchieri C "Australian study links certain analgesics to renal cancers." J Natl Cancer Inst 85 (1993): 262-3
57. Goldberg M "Analgesic nephropathy in 1981: which drug is responsible?" JAMA 247 (1982): 64-5
58. McCredie M, Stewart JH, Day NE "Different roles for phenacetin and paracetamol in cancer of the kidney and renal pelvis." Int J Cancer 53 (1993): 245-9
59. Shoenfeld Y, Shaklai M, Livni E, Pinkhas J "Thrombocytopenia from acetaminophen." N Engl J Med 303 (1980): 47
60. Settipane RA, Stevenson DD "Cross sensitivity with acetaminophen in aspirin-sensitive subjects with asthma." J Allergy Clin Immunol 84 (1989): 26-33
61. Doan T "Acetaminophen hypersensitivity and other analgesics - response." Ann Allergy 72 (1994): 285
62. Kalyoncu AF "Acetaminophen hypersensitivity and other analgesics." Ann Allergy 72 (1994): 285
63. Leung R, Plomley R, Czarny D "Paracetamol anaphylaxis." Clin Exp Allergy 22 (1992): 831-3
64. Van Diem L, Grilliat JP "Anaphylactic shock induced by paracetamol." Eur J Clin Pharmacol 38 (1990): 389-90
65. Kawada A, Hiruma M, Noguchi H, Ishibashi A "Fixed drug eruption induced by acetaminophen in a 12-year-old girl." Int J Dermatol 35 (1996): 148-9
66. Doan T, Greenberger PA "Nearly fatal episodes of hypotension, flushing, and dyspnea in a 47- year-old woman." Ann Allergy 70 (1993): 439-44
67. Watson J, Deary I, Kerr D "Central and peripheral effects of sustained caffeine use: tolerance is incomplete." Br J Clin Pharmacol 54 (2002): 400-6
68. Keijzers GB, De Galan BE, Tack CJ, Smits P "Caffeine can decrease insulin sensitivity in humans." Diabetes Care 25 (2002): 364-9
69. "Summaries for patients. Coffee drinkers at lower risk for type 2 diabetes." Ann Intern Med 140 (2004): I17
70. Poirier L, Cleroux J, Nadeau A, Lacourciere Y "Effects of nebivolol and atenolol on insulin sensitivity and haemodynamics in hypertensive patients." J Hypertens 19 (2001): 1429-35
71. Boyle CA, Berkowitz GS, LiVolsi VA, Ort S, Merino MJ, White C, Kelsey JL "Caffeine consumption and fibrocystic breast disease: a case-control epidemiologic study." J Natl Cancer Inst 72 (1984): 1015-9
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.
More about acetaminophen/caffeine/dihydrocodeine
- Acetaminophen Caffeine Dihydrocodeine (FDA)
- Acetaminophen, Caffeine, and Dihydrocodeine (Wolters Kluwer)
Related treatment guides
Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.