Drug-related side effects and adverse reactions
Drug-related side effects and adverse reactions, also called adverse drug reaction (ADR), adverse drug event (ADE) or drug toxicity, is defined as the "manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning..." The meaning of this expression differs from the meaning of "side effect", as this last expression might also imply that the effects can be beneficial.
The World Health Organization defines it as:
An adverse drug reaction (ADR) is ‘a response to a medicine which is
noxious and unintended, and which occurs at doses normally used in man’. In this description it is of importance that it concerns the response of a patient, in which individual factors may play an important role, and that the phenomenon is noxious (an unexpected therapeutic
response, for example, may be a side effect but not an adverse reaction).
6% of hospital admissions and 2.5% of emergency department visits for injuries or poisonings may be due to adverse drug reactions. Adverse drug reactions also occur among ambulatory outpatients and among inpatients. A minority of drug toxicity is recognized by health care providers.
- Type A: Dose-related; pharmacologically predictable. In a study of older adults, this type was the most common with the most common offending drugs being warfarin, insulin, and digoxin.
- Type B: Non-dose related; bizarre and unpredictable.
- Type C: Dose-related and time-related. This is related to duration and dosage of exposure. An example is hypothalamic-pituitary-adrenal suppression from glucocorticoid therapy.
- Type D: Time-related; delayed reaction. An example is tardive dyskinesia.
- Type E: Withdrawal; end of dose reaction. An example is narcotic or beta-blocker withdrawal.
- Type F: Unexpected failure of therapy. This may be caused by drug interactions. An example is failure of oral contraceptives due to induction of enzymes by a second drug.
Drug-induced liver injury
Drug reaction with eosinophilia and systemic symptoms
Drug reaction with eosinophilia and systemic symptoms (DRESS) may be caused by medications including allopurinol, phenytoin, dapsone, carbamazepine, trimethoprim-sulfamethoxazole, penicillin, and non-steroidal anti-inflammatory agents. About half of cases have eosinophilia.
Some interactions are due to the system of cytochrome P-450 enzymes used to clear drugs from the body. These interactions can be complex, involving either increasing or decreasing the activity of a given cytochrome pathway, or preferentially (i.e., competitive inhibition) using the pathway rather than other drugs. As one example, theophylline and ciprofloxacin up-regulate the cytochrome pathway that also clears estrogen and phenytoin. As a result, oral contraceptives and anticonvulsants may fail because the pathway clears them too quickly and an adequate blood level cannot be maintained.
Monoamine oxidase inhibitors can cause fatal hypertension in patients who have also consumed food containing high concentrations of tyramine. The suspect foods form an odd assortment, such as Chianti wine, some smoked fish and aged cheese.
QT interval prolongation
ADRs may be described by their frequency and severity
The World Health Organization recommends standardization of descriptions of frequency. Although the WHO document is not currently available online, their recommendations have been summarized by others.
- very common (>1/10 patients)
- common (>1/100)
- uncommon (>1/1000)
- rare (>1/10,000)
- very rare (<1/100,000)
- Hospitalization (initial or prolonged)
- Disability - significant, persistent, or permanent change, impairment, damage or disruption in the patient's body function/structure, physical activities or quality of life.
- Congenital Anomaly
- - or -
- Requires Intervention to Prevent Permanent Impairment or Damage
Etiology / cause
As research better explains the biochemistry of drug use, less ADRs are Type B ('idiosyncratic') and more are Type A (pharmacologically predictable). Common mechanisms are:
- Abnormal pharmacokinetics due to
- genetic factors
- comorbid disease states
- Synergistic effects between either
- a drug and a disease
- two drugs
Risk factors are:
- The number of drugs
- History of prior drug toxicity
- Presence of heart failure
- Presence of liver disease
- Presence of renal failure
- Presence of 4 or more medical conditions
Comorbid disease states
Various diseases, especially those that cause renal or hepatic insufficiency, may alter drug metabolism. Resources are available that report changes in a drug's metabolism due to disease states. However, heavy physician workload may reduce the ability of the physician to use these resources.
Abnormal drug metabolism may be due to inherited factors of either Phase I oxidation or Phase II conjugation. Pharmacogenomics is the study on the inherited basis of drug reactions. Among drugs frequently cited in adverse drug reactions, 60% are metabolized by enzymes with genetic variations in metabolism. 7% to 22% of randomly selected have such variation.
Phase I reactions
Phase II reactions
Impaired hepatic function
Impaired renal function
|Group||Description||Estimated creatinine clearance (ml/min)|
|1||Normal renal function||> 80 mL/min|
|2||Mild renal function||> 50-80 mL/min|
|3||Moderate renal function||> 30-50 mL/min|
|4||Severe renal function||<30 mL/min|
The National Kidney Disease Education Program provides guidance on dosing drugs in patients with reduced glomerular filtration rate. Food and Drug Administration provides guidance on the labeling of prescription medications to guide dosing for patients with impaired renal function. Although this categorization uses estimated creatinine clearance, using estimated glomerular filtration yields similar recommendations for dosing adjustments.
Interactions with other drugs
An example of synergism is two drugs that both prolong the cardiac QT interval.
Other factors that my increase ADRs
Fragmented health care
When controlled for other factors such as the number of prescribing physicians, the number of medicatations may not be a risk factor for adverse drug reactions.
- "A clinical event, including a laboratory test abnormality, that occurs in a plausible time relation to drug administration, and which cannot be explained by concurrent disease or other drugs or chemicals"
- "The response to withdrawal of the drug (dechallenge) should be clinically plausible"
- "The event must be definitive pharmacologically or phenomenologically, using a satisfactory rechallenge procedure if necessary"
- "A clinical event, including a laboratory test abnormality, with a reasonable time relation to administration of the drug, unlikely to be attributed to concurrent disease or other drugs or chemicals, and which follows a clinically reasonable response on withdrawal (dechallenge)"
- "Rechallenge information is not required to fulfil this definition"
- "A clinical event, including a laboratory test abnormality, with a reasonable time relation to administration of the drug, but which could also be explained by concurrent disease or other drugs or chemicals"
- "Information on drug withdrawal may be lacking or unclear"
- "A clinical event, including a laboratory test abnormality, with a temporal relation to administration of the drug, which makes a causal relation improbable, and in which other drugs, chemicals, or underlying disease provide plausible explanations"
- "A clinical event, including a laboratory test abnormality, reported as an adverse reaction, about which more data are essential for a proper assessment or the additional data are being examined"
- "A report suggesting an adverse reaction that cannot be judged, because information is insufficient or contradictory and cannot be supplemented or verified"
An alternative scale is the Naranjo algorithm.
Intolerance to multiple drugs
Detection of toxicity in individual patients
The question "In the past XX months, have you noticed any side effects, unwanted reactions, or other problems with medications you have taken?" may help detect toxic reactions.
Detection of previously unrecognized toxicity in populations
Unfortunately, more drug toxicity is not reported. Reports of more than three cases of a rare disease associated with a drug suggests the drug may be causing the disease. More complicated rules for signals are available.
News of previously unrecognized drug toxicity may be first published in scientific journals. Published reports may be more helpful than spontaneous reports although drug toxicity is more likely to be spontaneously reported than published. However, published reports may be lacking in quality.
Many countries have official bodies that monitor drug safety and reactions. On an international level, the World Health Organization (WHO) runs the Uppsala Monitoring Centre, and the European Union runs the European Medicines Agency (EMEA). In the United States, the Food and Drug Administration (FDA) is responsible for monitoring post-marketing studies. However, the book, Physicians' Desk Reference, which is a collection of FDA approved drug labels, may contribute to adverse drug effects by systematically underreporting the lowest effect dose of drugs.
Computerized provider order entry
The role of computerized provider order entry (CPOE) may prevent ADRs according to a systematic review. However, individual studies have been inconsistent with both positive and negative effects on process measures. CPOE has difficulty in precision of alerting.
Non-physicians may be able to successfully use CPOE.
Overriding of alerts may decrease patient safety.
Medication reconciliation may help.
Lists of high risk medications
The Beers list has been developed for predictable adverse drug reactions and thus provide a list of medications to avoid. After the original list of medications was not associated with clinical outcomes, the list is periodically revised with a Delphi method. The current list is online. The Beers list has become a clinical measure of quality assurance.
- National Library of Medicine. Drug toxicity. Retrieved on 2007-11-23.
- Nebeker JR, Barach P, Samore MH (2004). "Clarifying adverse drug events: a clinician's guide to terminology, documentation, and reporting". Ann. Intern. Med. 140 (10): 795-801. PMID 15148066.
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- World Health Organization (2002), Safety of Medicines: A guide to detecting and reporting adverse drug reactions; Why health professionals need to take action, WHO/EDM/QSM/2002.2, p. 5
- Pirmohamed M, James S, Meakin S, et al (2004). "Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients". BMJ 329 (7456): 15–9. DOI:10.1136/bmj.329.7456.15. PMID 15231615. Research Blogging.
- Budnitz DS, Pollock DA, Weidenbach KN, Mendelsohn AB, Schroeder TJ, Annest JL (2006). "National surveillance of emergency department visits for outpatient adverse drug events". JAMA 296 (15): 1858–66. DOI:10.1001/jama.296.15.1858. PMID 17047216. Research Blogging.
- Gandhi TK, Weingart SN, Borus J, et al (2003). "Adverse drug events in ambulatory care". N. Engl. J. Med. 348 (16): 1556–64. DOI:10.1056/NEJMsa020703. PMID 12700376. Research Blogging.
- Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP (1997). "Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality". JAMA 277 (4): 301–6. PMID 9002492.
- Gurwitz JH, Field TS, Harrold LR, Rothschild J, Debellis K, Seger AC et al. (2003). "Incidence and preventability of adverse drug events among older persons in the ambulatory setting.". JAMA 289 (9): 1107-16. PMID 12622580.
- Edwards IR, Aronson JK (2000). "Adverse drug reactions: definitions, diagnosis, and management". Lancet 356 (9237): 1255–9. DOI:10.1016/S0140-6736(00)02799-9. PMID 11072960. Research Blogging.
- Budnitz DS, Shehab N, Kegler SR, Richards CL (2007). "Medication use leading to emergency department visits for adverse drug events in older adults". Ann. Intern. Med. 147 (11): 755–65. PMID 18056659.
- Rawlins MD, Thompson JW. Pathogenesis of adverse drug reactions. In: Davies DM, ed. Textbook of adverse drug reactions. Oxford: Oxford University Press, 1977:10.
- Aronson JK. Drug therapy. In: Haslett C, Chilvers ER, Boon NA, Colledge NR, Hunter JAA, eds. Davidson's principles and practice of medicine 19th ed. Edinburgh: Elsevier Science, 2002:147-63. ISBN 0-44307-035-0.
- Macy, Eric; Eunis W. Ngor (2013-05). "Safely Diagnosing Clinically Significant Penicillin Allergy Using Only Penicilloyl-Poly-Lysine, Penicillin, and Oral Amoxicillin". The Journal of Allergy and Clinical Immunology: In Practice 1 (3): 258-263. DOI:10.1016/j.jaip.2013.02.002. ISSN 2213-2198. Retrieved on 2013-07-13. Research Blogging.
- Messaad D, Sahla H, Benahmed S, Godard P, Bousquet J, Demoly P (2004). "Drug provocation tests in patients with a history suggesting an immediate drug hypersensitivity reaction.". Ann Intern Med 140 (12): 1001-6. PMID 15197017.
- Chen YC, Chiu HC, Chu CY (2010). "Drug reaction with eosinophilia and systemic symptoms: a retrospective study of 60 cases.". Arch Dermatol 146 (12): 1373-9. DOI:10.1001/archdermatol.2010.198. PMID 20713773. Research Blogging.
- Dereure O (2001). "Drug-induced skin pigmentation. Epidemiology, diagnosis and treatment.". Am J Clin Dermatol 2 (4): 253-62. PMID 11705252.
- Levantine A, Almeyda J (1973). "Drug induced changes in pigmentation.". Br J Dermatol 89 (1): 105-12. PMID 4132858.
- Council for International Organizations of Medical Sciences. Guidelines for preparing core clinical safety information on drugs. Geneva: CIOMS, 1995.
- Hoes JN, Jacobs JW, Boers M, et al (2007). "EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases". Ann. Rheum. Dis. 66 (12): 1560–7. DOI:10.1136/ard.2007.072157. PMID 17660219. Research Blogging.
- MedWatch - What Is A Serious Adverse Event?. Retrieved on 2007-09-18.
- Onder G, Petrovic M, Tangiisuran B, Meinardi MC, Markito-Notenboom WP, Somers A et al. (2010). "Development and validation of a score to assess risk of adverse drug reactions among in-hospital patients 65 years or older: the GerontoNet ADR risk score.". Arch Intern Med 170 (13): 1142-8. DOI:10.1001/archinternmed.2010.153. PMID 20625022. Research Blogging.
- Clinical Drug Use. Retrieved on 2007-09-18.
- Sheen SS, Choi JE, Park RW, Kim EY, Lee YH, Kang UG (2008). "Overdose rate of drugs requiring renal dose adjustment: data analysis of 4 years prescriptions at a tertiary teaching hospital". J Gen Intern Med 23 (4): 423-8. DOI:10.1007/s11606-007-0336-8. PMID 18373140. Research Blogging.
- Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W (2001). "Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review". JAMA 286 (18): 2270–9. PMID 11710893.
- Goldstein DB (2003). "Pharmacogenetics in the laboratory and the clinic". N. Engl. J. Med. 348 (6): 553–6. DOI:10.1056/NEJMe020173. PMID 12571264. Research Blogging.
- Drug-Interactions.com. Retrieved on 2007-09-18.
- Weinshilboum R (2003). "Inheritance and drug response". N. Engl. J. Med. 348 (6): 529–37. DOI:10.1056/NEJMra020021. PMID 12571261. Research Blogging.
- Evans WE, McLeod HL (2003). "Pharmacogenomics--drug disposition, drug targets, and side effects". N. Engl. J. Med. 348 (6): 538–49. DOI:10.1056/NEJMra020526. PMID 12571262. Research Blogging.
- Food and Drug Administration, Guidance for Industry: [http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093606.htm Pharmacokinetics in Patients with Impaired Hepatic Function: Study Design, Data Analysis, and Impact on Dosing and Labeling], US Department of Health and Human Services, Rockville, MD (1998) May.
- Food and Drug Administration, Guidance for Industry: Pharmacokinetics in Patients With Impaired Renal Function—Study Design, Data Analysis, and Impact on Dosing and Labeling, US Department of Health and Human Services, Rockville, MD (1998) May.
- The National Kidney Disease Education Program. (2009) Chronic Kidney Disease and Drug Dosing: Information for Providers National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), U.S. Department of Health & Human Services (DHHS).
- Stevens LA, Nolin TD, Richardson MM, Feldman HI, Lewis JB, Rodby R et al. (2009). "Comparison of drug dosing recommendations based on measured GFR and kidney function estimating equations.". Am J Kidney Dis 54 (1): 33-42. DOI:10.1053/j.ajkd.2009.03.008. PMID 19446939. PMC PMC2756662. Research Blogging.
- Guthrie, B.; C. McCowan, P. Davey, C. R. Simpson, T. Dreischulte, K. Barnett (2011-06). "High risk prescribing in primary care patients particularly vulnerable to adverse drug events: cross sectional population database analysis in Scottish general practice". BMJ 342 (jun21 1): d3514-d3514. DOI:10.1136/bmj.d3514. ISSN 0959-8138. Retrieved on 2011-06-23. Research Blogging.
- Green JL, Hawley JN, Rask KJ (2007). "Is the number of prescribing physicians an independent risk factor for adverse drug events in an elderly outpatient population?". Am J Geriatr Pharmacother 5 (1): 31–9. DOI:10.1016/j.amjopharm.2007.03.004. PMID 17608245. Research Blogging.
- UMC Causality Assessment of Suspected Adverse Reactions. World Health Organization. Retrieved on 2008-01-14.
- Davies SJ, Jackson PR, Ramsay LE, Ghahramani P (2003). "Drug intolerance due to nonspecific adverse effects related to psychiatric morbidity in hypertensive patients". Arch. Intern. Med. 163 (5): 592-600. PMID 12622606.
- Gex-Collet C, Helbling A, Pichler WJ (2005). "Multiple drug hypersensitivity--proof of multiple drug hypersensitivity by patch and lymphocyte transformation tests". J Investig Allergol Clin Immunol 15 (4): 293–6. PMID 16433211.
- Hohl CM, Yu E, Hunte GS, Brubacher JR, Hosseini F, Argent CP et al. (2012). "Clinical decision rules to improve the detection of adverse drug events in emergency department patients.". Acad Emerg Med 19 (6): 640-9. DOI:10.1111/j.1553-2712.2012.01379.x. PMID 22687179. Research Blogging.
- Steinman MA et al. Managing Medications in Clinically Complex Elders: "There's Got to Be a Happy Medium" JAMA. 2010;304(14):1592-1601 DOI:10.1001/jama.2010.1482
- Hazell L, Shakir SA (2006). "Under-reporting of adverse drug reactions : a systematic review.". Drug Saf 29 (5): 385-96. PMID 16689555.
- Moride Y, Haramburu F, Requejo AA, Bégaud B (1997). "Under-reporting of adverse drug reactions in general practice.". Br J Clin Pharmacol 43 (2): 177-81. PMID 9131950. PMC PMC2042725.
- Scott HD, Rosenbaum SE, Waters WJ, Colt AM, Andrews LG, Juergens JP et al. (1987). "Rhode Island physicians' recognition and reporting of adverse drug reactions.". R I Med J 70 (7): 311-6. PMID 3476980.
- Begaud B, Moride Y, Tubert-Bitter P, Chaslerie A, Haramburu F (1994). "False-positives in spontaneous reporting: should we worry about them?". Br J Clin Pharmacol 38 (5): 401-4. PMID 7893579. PMC PMC1364871.
- Tubert P, Bégaud B, Haramburu F, Péré JC (1991). "Spontaneous reporting: how many cases are required to trigger a warning?". Br J Clin Pharmacol 32 (4): 407-8. PMID 1958431. PMC PMC1368597.
- Haramburu F, Bégaud B, Péré JC (1990). "Comparison of 500 spontaneous and 500 published reports of adverse drug reactions.". Eur J Clin Pharmacol 39 (3): 287-8. PMID 2257868.
- Liu BA, Mittmann N, Knowles SR, Shear NH (1996). "Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone associated with the use of selective serotonin reuptake inhibitors: a review of spontaneous reports.". CMAJ 155 (5): 519-27. PMID 8804257. PMC PMC1335030. Review in: J Fam Pract. 1993 Mar;36(3):341-3
- Loke YK, Price D, Derry S, Aronson JK (2006). "Case reports of suspected adverse drug reactions--systematic literature survey of follow-up.". BMJ 332 (7537): 335-9. DOI:10.1136/bmj.38701.399942.63. PMID 16421149. PMC PMC1363912. Research Blogging.
- Golder S, Loke Y (2009). "Search strategies to identify information on adverse effects: a systematic review.". J Med Libr Assoc 97 (2): 84-92. DOI:10.3163/1536-5050.97.2.004. PMID 19404498. PMC PMC2670220. Research Blogging.
- Cohen JS (2001). "Dose discrepancies between the Physicians' Desk Reference and the medical literature, and their possible role in the high incidence of dose-related adverse drug events". Arch. Intern. Med. 161 (7): 957–64. PMID 11295958.
- Shamliyan TA, Duval S, Du J, Kane RL (2008). "Just what the doctor ordered. Review of the evidence of the impact of computerized physician order entry system on medication errors.". Health Serv Res 43 (1 Pt 1): 32-53. DOI:10.1111/j.1475-6773.2007.00751.x. PMID 18211517. PMC PMC2323150. Research Blogging.
- Bates DW, Leape LL, Cullen DJ, Laird N, Petersen LA, Teich JM et al. (1998). "Effect of computerized physician order entry and a team intervention on prevention of serious medication errors.". JAMA 280 (15): 1311-6. PMID 9794308.
- Raebel MA, Charles J, Dugan J, et al (2007). "Randomized trial to improve prescribing safety in ambulatory elderly patients". J Am Geriatr Soc 55 (7): 977–85. DOI:10.1111/j.1532-5415.2007.01202.x. PMID 17608868. Research Blogging.
- Raebel MA, Carroll NM, Kelleher JA, Chester EA, Berga S, Magid DJ (2007). "Randomized trial to improve prescribing safety during pregnancy". J Am Med Inform Assoc 14 (4): 440–50. DOI:10.1197/jamia.M2412. PMID 17460126. Research Blogging.
- Glassman PA, Belperio P, Lanto A, et al (2007). "The utility of adding retrospective medication profiling to computerized provider order entry in an ambulatory care population". J Am Med Inform Assoc 14 (4): 424–31. DOI:10.1197/jamia.M2313. PMID 17460134. Research Blogging.
- Judge J, Field TS, DeFlorio M, et al (2006). "Prescribers' responses to alerts during medication ordering in the long term care setting". J Am Med Inform Assoc 13 (4): 385–90. DOI:10.1197/jamia.M1945. PMID 16622171. Research Blogging.
- Kazemi A, Fors UG, Tofighi S, Tessma M, Ellenius J (2010). "Physician order entry or nurse order entry? Comparison of two implementation strategies for a computerized order entry system aimed at reducing dosing medication errors.". J Med Internet Res 12 (1): e5. DOI:10.2196/jmir.1284. PMID 20185400. PMC PMC2855204. Research Blogging.
- Nanji KC, Slight SP, Seger DL, Cho I, Fiskio JM, Redden LM et al. (2014). "Overrides of medication-related clinical decision support alerts in outpatients.". J Am Med Inform Assoc 21 (3): 487-91. DOI:10.1136/amiajnl-2013-001813. PMID 24166725. PMC PMC3994856. Research Blogging.
- Schnipper JL, Hamann C, Ndumele CD, Liang CL, Carty MG, Karson AS et al. (2009). "Effect of an electronic medication reconciliation application and process redesign on potential adverse drug events: a cluster-randomized trial.". Arch Intern Med 169 (8): 771-80. DOI:10.1001/archinternmed.2009.51. PMID 19398689. Research Blogging.
- Beers MH (1997). "Explicit criteria for determining potentially inappropriate medication use by the elderly. An update". Arch. Intern. Med. 157 (14): 1531–6. PMID 9236554.
- Hanlon JT, Fillenbaum GG, Kuchibhatla M, Artz MB, Boult C, Gross CR et al. (2002). "Impact of inappropriate drug use on mortality and functional status in representative community dwelling elders.". Med Care 40 (2): 166-76. PMID 11802089.
- American Geriatrics Society 2012 Beers Criteria Update Expert Panel (2012). "American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults.". J Am Geriatr Soc 60 (4): 616-31. DOI:10.1111/j.1532-5415.2012.03923.x. PMID 22376048. PMC PMC3571677. Research Blogging.
- Fick DM, Cooper JW, Wade WE, Waller JL, Maclean JR, Beers MH (2003). "Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts". Arch. Intern. Med. 163 (22): 2716–24. DOI:10.1001/archinte.163.22.2716. PMID 14662625. Research Blogging.
- Use of high-risk medications in the elderly: percentage of Medicare members 66 years of age and older who received at least one high-risk medication.
- Hamilton H, Gallagher P, Ryan C, Byrne S, O'Mahony D (2011). "Potentially inappropriate medications defined by STOPP criteria and the risk of adverse drug events in older hospitalized patients.". Arch Intern Med 171 (11): 1013-9. DOI:10.1001/archinternmed.2011.215. PMID 21670370. Research Blogging.
- Gallagher P, O'Mahony D (2008). "STOPP (Screening Tool of Older Persons' potentially inappropriate Prescriptions): application to acutely ill elderly patients and comparison with Beers' criteria.". Age Ageing 37 (6): 673-9. DOI:10.1093/ageing/afn197. PMID 18829684. Research Blogging.
- Mallal S, Phillips E, Carosi G, et al (February 2008). "HLA-B*5701 screening for hypersensitivity to abacavir". N. Engl. J. Med. 358 (6): 568–79. DOI:10.1056/NEJMoa0706135. PMID 18256392. Research Blogging.