Balacet Side Effects
Generic Name: acetaminophen / propoxyphene
Note: This document contains side effect information about acetaminophen / propoxyphene. Some of the dosage forms listed on this page may not apply to the brand name Balacet.
Nervous system side effects of propoxyphene have included dizziness, sedation, stupor, delirium, somnolence, ataxia, coma, syncope, and respiratory depression. The sedative effects of propoxyphene have been associated with a 60% increased risk of hip fracture in elderly patients.[Ref]
Other side effects including propoxyphene dependence have been reported (although the abuse liability of propoxyphene is less than that of some other narcotic analgesics). Withdrawal symptoms (after either abrupt cessation or fast tapering) have been reported to include agitation, restlessness, anxiety, insomnia, tremor, tachycardia, hallucinations, psychosis, abdominal cramps, vomiting, sweating, and seizures.
Drug toxicity, multiple drug overdose, and narcotic overdose have also been reported with propoxyphene.
Sensorineural deafness has been reported following chronic abuse and/or large doses of propoxyphene-containing compounds. Optic atrophy has been reported following overdose.[Ref]
Gastrointestinal side effects of acetaminophen are rare, except in alcoholics and after overdose. Cases of acute pancreatitis have been reported rarely with acetaminophen use. Nausea, vomiting, and constipation are relatively common effects of propoxyphene. Gastrointestinal bleeding and acute pancreatitis have also been reported with the use of propoxyphene.[Ref]
One study has suggested that acetaminophen may precipitate acute biliary pain and cholestasis. The mechanism of this effect may be related to inhibition of prostaglandin and alterations in the regulation of the sphincter of Oddi.
Cardiovascular side effects of propoxyphene have included arrhythmia, bradycardia, cardiac/respiratory arrest, congestive arrest, congestive heart failure (CHF), tachycardia, myocardial infarction (MI), hypotension, decreased blood pressure, elevated heart rate, abnormal heart rate, and dizziness. A variety of arrhythmias (including heart block) have been reported most often in association with overdose.[Ref]
Some of the cardiotoxic effects reported in association with propoxyphene may be attributable to its major active metabolite, norpropoxyphene.[Ref]
Renal side effects of acetaminophen have been rare and have included acute tubular necrosis and interstitial nephritis. Cases of severe hypoglycemia have been reported in patients with chronic renal failure who received propoxyphene.[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.
A single case of nephrogenic diabetes insipidus has been reported following overdose of propoxyphene (however, other causes of diabetes insipidus in that patient were not rigorously excluded).
The adverse effects of propoxyphene may be more likely and more severe in patients with renal insufficiency.[Ref]
Hypersensitivity side effects to acetaminophen have been reported rarely.
Hypersensitivity side effects to propoxyphene have also been reported.[Ref]
Genitourinary side effects have included a case of retroperitoneal fibrosis in association with propoxyphene therapy.[Ref]
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. Cases of hemolytic anemia, pancytopenia, and disseminated intravascular coagulation after administration (or abuse) of propoxyphene-containing compounds have been reported rarely.[Ref]
Dermatologic side effects including rashes have been reported in association with both propoxyphene and acetaminophen. Itch has also been reported with the use of propoxyphene.[Ref]
Respiratory side effects including a case of acetaminophen-induced eosinophilic pneumonia have been reported.
Musculoskeletal side effects including myopathy and rhabdomyolysis have been reported after chronic oral use. Fibrous myopathy has also been reported in propoxyphene-abusing patients who administer the drug via intramuscular injection.[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.
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.
In the 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 including metabolic acidosis have been reported following a massive overdose of acetaminophen.
Metabolic side effects including metabolic acidosis have been reported with the use of propoxyphene. Cases of severe hypoglycemia have been reported in patients with chronic renal failure.
Ocular side effects including eye swelling and vision blurred have been reported with the use of propoxyphene.
General side effects including drug tolerance and influenza type illness have been reported with the use of propoxyphene.
Psychiatric side effects including abnormal behavior, confusional state, hallucinations, and mental status change have been reported with the use of propoxyphene.
1. Ng B, Alvear M "Dextropropoxyphene addiction--a drug of primary abuse." Am J Drug Alcohol Abuse 19 (1993): 153-8
2. Critchley J, Illingworth RN, Pottage A, Proudfoot AT, Prescott L "Acute poisoning with distalgesic." Br Med J 1 (1979): 342-3
3. Rosenow EC 3d "The spectrum of drug-induced pulmonary disease." Ann Intern Med 77 (1972): 977-91
4. Shorr RI, Griffin MR, Daugherty JR, Ray WA "Opioid analgesics and the risk of hip fracture in the elderly: codeine and propoxyphene." J Gerontol 47 (1992): M111-5
5. Owen M, Hills LJ "How safe is dextropropoxyphene?." Med J Aust 1 (1980): 617-8
6. Whittington RM "Dextropropoxyphene addiction." Lancet 2 (1979): 743-4
7. Strode SW "Propoxyphene dependence and withdrawal." Am Fam Physician 32 (1985): 105-8
8. Claghorn JL, Schoolar JC "Propoxyphene hydrochloride, a drug of abuse." JAMA 196 (1966): 1089-91
9. Collins GB, Kiefer KS "Propoxyphene dependence: an update." Postgrad Med 70 (1981): 57-61
10. Harris B, Harper M "Psychosis after dextropropoxyphene." Lancet 2 (1979): 743
11. Wall R, Linford SM, Akhter MI "Addiction to Distalgesic (dextropropoxyphene)." Br Med J 280 (1980): 1213-4
12. Salguero CH, Villarreal JE, Hug CC Jr, Domino EF "Propoxyphene dependence." JAMA 210 (1969): 135-6
13. Wong V, Daly M, Boon A, Heatley V "Paracetamol and acute biliary pain with cholestasis." Lancet 342 (1993): 869
14. 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
15. Bray GP "Liver failure induced by paracetamol." BMJ 306 (1993): 157-8
16. Ford MJ, Kellett RJ, Busuttil A, Finlayson ND "Dextropropoxyphene and jaundice." Br Med J 2 (1977): 674
17. Klein NC, Magida MG "Propoxyphene (Darvon) hepatotoxicity." Am J Dig Dis 16 (1971): 467-9
18. Johnson GK, Tolman KG "Chronic liver disease and acetaminophen." Ann Intern Med 87 (1977): 302-4
19. "Product Information. Darvocet N-100 (acetaminophen-propoxyphene)." Lilly, Eli and Company, Indianapolis, IN.
20. Keaton MR "Acute renal failure in an alcoholic during therapeutic acetaminophen ingestion." South Med J 81 (1988): 1163-6
21. 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
22. Shriner K, Goetz MB "Severe hepatotoxicity in a patient receiving both acetaminophen and zidovudine." Am J Med 93 (1992): 94-6
23. Gillette JR "An integrated approach to the study of chemically reactive metabolites of acetaminophen." Arch Intern Med 141 (1981): 375-9
24. "Dextropropoxyphene." Med J Aust 2 (1979): 494
25. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med 104 (1986): 399-404
26. Bassendine MF, Woodhouse KW, Bennett M, James OF "Dextropropoxyphene induced hepatotoxicity mimicking biliary tract disease." Gut 27 (1986): 444-9
27. Daikos GK, Kosmidis JC "Propoxyphene jaundice." JAMA 232 (1975): 835
28. Lee WM "Acute liver failure." Am J Med 96 (1994): 3-9
29. Minton NA, Henry JA, Frankel RJ "Fatal paracetamol poisoning in an epileptic." Hum Toxicol 7 (1988): 33-4
30. Kumar S, Rex DK "Failure of physicians to recognize acetaminophen hepatotoxicity in chronic alcoholics." Arch Intern Med 151 (1991): 1189-91
31. O'Dell JR, Zetterman RK, Burnett DA "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA 255 (1986): 2636-7
32. 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
33. Briggs RS, Barrand KG, Levene M "Ischaemic colitis and drug abuse." Br Med J 2 (1977): 1478
34. Block R "Liver failure induced by paracetamol." BMJ 306 (1993): 457
35. Lee TH, Rees PJ "Hepatotoxicity of dextropropoxyphene." Br Med J 2 (1977): 296-7
36. Rumore MM, Blaiklock RG "Influence of age-dependent pharmacokinetics and metabolism on acetaminophen hepatotoxicity." J Pharm Sci 81 (1992): 203-7
37. Block R, Jankowski JA, Lacoux P, Pennington CR "Does hypothermia protect against the development of hepatitis in paracetamol overdose?" Anaesthesia 47 (1992): 789-91
38. Zimmerman HJ, Maddrey WC "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology 22 (1995): 767-73
39. McJunkin B, Barwick KW, Little WC, Winfield JB "Fatal massive hepatic necrosis following acetaminophen overdose." JAMA 236 (1976): 1874-5
40. Mofenson HC, Caraccio TR, Nawaz H, Steckler G "Acetaminophen induced pancreatitis." Clin Toxicol 29 (1991): 223-30
41. Heaney RM "Left bundle branch block associated with propoxyphene hydrochloride poisoning." Ann Emerg Med 12 (1983): 780-2
42. Wiederholt IC, Genco M, Foley JM "Recurrent episodes of hypoglycemia induced by propoxyphene." Neurology 17 (1967): 703-6
43. Duchene A, Chadenas D, Marneffe-Lebrequier H "Insuffisance renale aigue isolee apres intoxication volontaire par le paracetamol." Presse Med 20 (1991): 1684-5
44. Singer I, Forrest JN Jr "Drug-induced states of nephrogenic diabetes insipidus." Kidney Int 10 (1976): 82-95
45. Curry RW, Robinson JD, Sughrue MJ "Acute renal failure after acetaminophen ingestion." JAMA 247 (1982): 1012-4
46. Kleinman JG, Breitenfield RV, Roth DA "Transient cholestatic hepatitis in a neonate associated with carbamazepine exposure during pregnancy and breast-feeding." Clin Nephrol 14 (1980): 201-5
47. Segasothy M, Suleiman AB, Puvaneswary M, Rohana A "Paracetamol: a cause for analgesic nephropathy and end-stage renal disease." Nephron 50 (1988): 50-4
48. Boyer TD, Rouff SL "Acetaminophen-induced hepatic necrosis and renal failure." JAMA 218 (1971): 440-1
49. Goldberg M "Analgesic nephropathy in 1981: which drug is responsible?" JAMA 247 (1982): 64-5
50. Vanchieri C "Australian study links certain analgesics to renal cancers." J Natl Cancer Inst 85 (1993): 262-3
51. 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
52. Almirall J, Montoliu J, Torras A, Revert L "Propoxyphene-induced hypoglycemia in a patient with chronic renal failure." Nephron 53 (1989): 273-5
53. Doan T, Greenberger PA "Nearly fatal episodes of hypotension, flushing, and dyspnea in a 47- year-old woman." Ann Allergy 70 (1993): 439-44
54. Doan T "Acetaminophen hypersensitivity and other analgesics - response." Ann Allergy 72 (1994): 285
55. Leung R, Plomley R, Czarny D "Paracetamol anaphylaxis." Clin Exp Allergy 22 (1992): 831-3
56. Settipane RA, Stevenson DD "Cross sensitivity with acetaminophen in aspirin-sensitive subjects with asthma." J Allergy Clin Immunol 84 (1989): 26-33
57. Kalyoncu AF "Acetaminophen hypersensitivity and other analgesics." Ann Allergy 72 (1994): 285
58. Critchley JA, Smith MF, Prescott LF "Distalgesic abuse and retroperitoneal fibrosis." Br J Urol 57 (1985): 486-7
59. Fulton JD, McGonigal G "Steroid responsive haemolytic anaemia due to dextropropoxyphene paracetamol combination." J R Soc Med 82 (1989): 228
60. Shoenfeld Y, Shaklai M, Livni E, Pinkhas J "Thrombocytopenia from acetaminophen." N Engl J Med 303 (1980): 47
61. 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
62. Webster GK "Pancytopenia after administration of distalgesic." Br Med J 3 (1973): 353
63. Fisch HP, Wands J, Yeung J, Davis PJ "Pulmonary edema and disseminated intravascular coagulation after intravenous abuse of d-propoxyphene (darvon)." South Med J 65 (1972): 493-5
64. 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
65. Thomas RH, Munro DD "Fixed drug eruption due to paracetamol." Br J Dermatol 115 (1986): 357-9
66. Kondo K, Inoue Y, Hamada H, Yokoyama A, Kohno N, Hiwada K "Acetaminophen-induced eosinophilic pneumonia." Chest 104 (1993): 291-2
67. Dalakas MC "Subacute painful myopathy from chronic propoxyphene napsylate abuse." JAMA 255 (1986): 1709
68. Restrepo JF, Guzman R, Pena MA, Lizarazo H, Mendez O, Rondon F, Iglesias A "Fibrous myopathy induced by propoxyphene injections." J Rheumatol 20 (1993): 596-7
69. 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
Some side effects may not be reported. You may report them to the FDA.