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Aspirin / codeine Side Effects

Applies to aspirin / codeine: oral tablet

General

In general, many of the side effects noted with aspirin use have been dose related.[Ref]

Nervous system

Central nervous system side effects from 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.

Central nervous system side effects in patients receiving aspirin have included agitation, cerebral edema, coma, confusion, dizziness, headache, cranial hemorrhage, lethargy and seizures. Tinnitus and subjective hearing loss (or both) may occur. Some investigators have reported that modest doses may result in decreased frequency selectivity and may therefore impair hearing performance, particularly in the setting of background noise.[Ref]

Opioids may result in psychotic symptoms in some patients.

One retrospective study of elderly patients who sustained a hip fracture suggested that the relative risk of hip fracture was 1.6 in patients using codeine compared to age matched nonusers.

Regarding the use of aspirin, some investigators have suggested that tinnitus may be a less reliable indicator of salicylate toxicity than previously believed. Patients with high frequency hearing loss may have difficulty perceiving tinnitus. In a study of rheumatoid arthritis patients, those with tinnitus had no greater salicylate levels than those without tinnitus. Elderly patients may be less likely to perceive tinnitus than younger patients.[Ref]

Other

Other side effects have included withdrawal symptoms. Withdrawal symptoms have been reported after either abrupt cessation or fast tapering of narcotic analgesics, and have included agitation, restlessness, anxiety, insomnia, tremor, abdominal cramps, blurred vision, vomiting, and sweating.

Reye's syndrome, although rare, has been associated with aspirin use in children with an acute viral illness. Reye's syndrome has also been reported even more rarely in adults.[Ref]

Reye's syndrome typically involves vomiting, neurologic dysfunction, and hepatic dysfunction during or shortly after an acute viral infection.[Ref]

Cardiovascular

Hypotension is rare with codeine use and has been reported most frequently with high doses.[Ref]

Cardiovascular side effects of codeine have included hypotension and dizziness.

Cardiovascular side effects of aspirin have been reported rarely and include salicylate induced variant angina, ventricular ectopy, conduction abnormalities, and hypotension, particularly during salicylate toxicity.[Ref]

Gastrointestinal

Gastrointestinal side effects are common and have included epigastric distress (in as many as 83% of patients treated with regular aspirin), abdominal discomfort or pain, endoscopically identifiable gastric mucosal lesions, nausea, and vomiting. More serious gastrointestinal effects include hemorrhage, peptic ulcers, perforation, and esophageal ulcerations.

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]

Endoscopically identifiable gastric mucosal lesions occur in most patients who receive a single dose of aspirin. Clinically evident gastrointestinal bleeding has been reported in as many as 3% of treated elderly patients. Anorectal ulceration and rectal stenosis have been reported in patients who abuse aspirin containing rectal suppositories. One case controlled study has suggested that an association between aspirin (and other NSAID) consumption and appendicitis may exist.[Ref]

Dermatologic

Dermatologic side effects from the use of aspirin have been reported rarely and include Stevens-Johnson syndrome and a lichenoid eruption.

Codeine induced rashes have been reported rarely. Codeine induced rashes may be related to direct stimulation of histamine release. Case reports of severe scarlatiniform eruptions have also been reported.[Ref]

Renal

The mechanism of an aspirin induced decrease in renal function may be related to inhibition of renal prostaglandin synthesis with consequent decreases in renal blood flow. Vasodilating renal prostaglandins may be particularly important in patients who exhibit arterial underfilling (i.e. heart failure, cirrhosis). The administration of high doses of NSAIDs to such patients has produced acute renal failure in rare instances.[Ref]

Renal side effects of aspirin have included reduction in glomerular filtration rate (particularly in patients who are sodium restricted or who exhibit diminished effective arterial blood volume, such as patients with advanced heart failure or cirrhosis), interstitial nephritis, papillary necrosis, elevations in serum creatinine, elevations in blood urea nitrogen, proteinuria, hematuria, and renal failure.

Renal side effects including urinary retention and acute renal failure have been reported in association with codeine therapy.[Ref]

Immunologic

Immunologic side effects may occur. 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]

Hematologic

Hematologic side effects of aspirin (in addition to predictable antiplatelet effects which may result in hemorrhage) include increased blood fibrinolytic activity. In addition, hypoprothrombinemia, thrombocytopenia, thrombocyturia, megaloblastic anemia, and pancytopenia have been reported rarely. Aplastic anemia has also been reported.[Ref]

Hypersensitivity

Hypersensitivity side effects include bronchospasm, rhinitis, conjunctivitis, urticaria, angioedema, and anaphylaxis with the use of aspirin. Approximately 10% to 30% of asthmatics are aspirin-sensitive (with the clinical triad of aspirin sensitivity, bronchial asthma, and nasal polyps).[Ref]

The mechanism of aspirin induced hypersensitivity may be related to an up regulation of the 5-lipoxygenase pathway of arachidonic acid metabolism with a resulting increase in the products of 5-lipoxygenase (such as leukotrienes).[Ref]

Hepatic

Hepatic side effects including cases of aspirin induced hepatotoxicity and cholestatic hepatitis, particularly at high doses, have been reported rarely.[Ref]

Oncologic

Oncologic side effects may be beneficial ones. Several epidemiologic studies have suggested that chronic aspirin use may decrease the risk of large bowel neoplasms. Other studies have not found such a beneficial effect.[Ref]

Metabolic

Metabolic side effects of aspirin have included dehydration and hyperkalemia. Respiratory alkalosis and metabolic acidosis, particularly during salicylate toxicity, have been reported. A case of hypoglycemia has been reported in a patient on hemodialysis. Salicylates have also been reported to displace triiodothyronine (T3) and thyroxine (T4) from protein binding sites. The initial effect is an increase in serum free T4 concentrations.[Ref]

Musculoskeletal

Musculoskeletal side effects including rhabdomyolysis have occurred in patients receiving aspirin.[Ref]

Respiratory

Respiratory side effects including hyperpnea, pulmonary edema, and tachypnea have occurred in patients receiving aspirin.[Ref]

Endocrine

Endocrine side effects of aspirin use have been reported to include hypoglycemia (children) and hyperglycemia.[Ref]

Ocular

Ocular side effects including cases of localized periorbital edema have been reported rarely in patients receiving aspirin.[Ref]

References

1. Dickinson JP, Prentice CRM "Aspirin: benefit and risk in thromboprophylaxis." Qjm Mon J Assoc Physician 91 (1998): 523-38

2. "Multum Information Services, Inc. Expert Review Panel"

3. He J, Whelton PK, Vu B, Klag MJ "Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials." JAMA 280 (1998): 1930-35

4. Lanas A, Serrano P, Bajador E, Esteva F, Benito R, Sainz R "Evidence of aspirin use in both upper and lower gastrointestinal perforation." Gastroenterology 112 (1997): 683-9

5. Petty GW, Brown RD, Whisnant JP, Sicks JD, O'Fallon WM, Wiebers DO "Frequency of major complications of aspirin, warfarin, and intravenous heparin for secondary stroke prevention: a population study." Ann Intern Med 130 (1999): 14-22

6. Boissel JP "Individualizing aspirin therapy for prevention of cardiovascular events." JAMA 280 (1998): 1949-50

7. "Product Information. Bayer aspirin (aspirin)." Bayer, West Haven, CT.

8. Max MB, Schafer SC, Culnane M, et al "Association of pain relief with drug side effects in postherpeticneuralgia: a single-dose study of clonidine, codeine, ibuprofen, and placebo." Clin Pharmacol Ther 43 (1988): 363-71

9. 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

10. de Groot AC, Conemans J "Allergic urticarial rash from oral codeine." Contact Dermatitis 14 (1986): 209-14

11. "Product Information. Calcidrine (codeine)." Abbott Pharmaceutical, Abbott Park, IL.

12. Cox RG "Hypoxaemia and hypotension after intravenous codeine phosphate." Can J Anaesth 41 (1994): 1211-3

13. Parke TJ, Nandi PR, Bird KJ, Jewkes DA "Profound hypotension following intravenous codeine phosphate: three case reports and some recommendations." Anaesthesia 47 (1992): 852-4

14. Hastier P, Buckley MJM, Peten EP, Demuth N, Dumas R, Demarquay JF, CaroliBosc FX, Delmont JP "A new source of drug-induced acute pancreatitis: Codeine." Am J Gastroenterol 95 (2000): 3295-8

15. Gonzalogarijo MA, Revengaarranz F "Fixed drug eruption due to codeine." Br J Dermatol 135 (1996): 498-9

16. Hill SA, Quinn K, Shelly MP, Park GR "Reversible renal failure following opioid administration." Anaesthesia 46 (1991): 938-9

17. Lin RY, Barnard M "Skin testing with food, codeine, and histamine in exercise-induced anaphylaxis." Ann Allergy 70 (1993): 475-8

18. Surks MI, Sievert R "Drugs and thyroid function." N Engl J Med 333 (1995): 1688-94

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

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