Sandra R. Knowles

Frequency, type and clinical importance of medication history errors at admission to hospital: a systematic review

Background: Over a quarter of hospital prescribing errors are attributable to incomplete medication histories being obtained at the time of admission. We undertook a systematic review of studies describing the frequency, type and clinical importance of medication history errors at hospital admission. Methods: We searched MEDLINE, EMBASE and CINAHL for articles published from 1966 through April 2005 and bibliographies of papers subsequently retrieved from the search. We reviewed all published studies with quantitative results that compared prescription medication histories obtained by physicians at the time of hospital admission with comprehensive medication histories. Three reviewers independently abstracted data on methodologic features and results. Results: We identified 22 studies involving a total of 3755 patients (range 33–1053, median 104). Errors in prescription medication histories occurred in up to 67% of cases: 10%– 61% had at least 1 omission error (deletion of a drug used before admission), and 13%– 22% had at least 1 commission error (addition of a drug not used before admission); 60%– 67% had at least 1 omission or commission error. Only 5 studies (n = 545 patients) explicitly distinguished between unintentional discrepancies and intentional therapeutic changes through discussions with ordering physicians. These studies found that 27%– 54% of patients had at least 1 medication history error and that 19%– 75% of the discrepancies were unintentional. In 6 of the studies (n = 588 patients), the investigators estimated that 11%–59% of the medication history errors were clinically important. Interpretation: Medication history errors at the time of hospital admission are common and potentially clinically important. Improved physician training, accessible community pharmacy databases and closer teamwork between patients, physicians and pharmacists could reduce the frequency of these errors.

Idiosyncratic drug reactions: the reactive metabolite syndromes

Idiosyncratic drug reactions are unpredictable reactions that can result in significant morbidity and mortality. Severe reactions are often characterised by fever and internal organ involvement. Despite progress in the identification of reactive metabolites believed to be the cause of idiosyncratic reactions, the basic mechanisms remain elusive. Furthermore, because of the lack of consensus regarding definition of these syndromes, reporting, and therefore epidemiological data, are often unreliable. Research is needed to explore further the pathophysiology of these reactions, so that better diagnostic tests and treatment methods can be developed.

Anticonvulsant hypersensitivity syndrome: incidence, prevention and management.

Although the anticonvulsant hypersensitivity syndrome was first described in 1950, confusion still abounds regarding the syndrome. The triad of fever, rash and internal organ involvement occurring 1 to 8 weeks after exposure to an anticonvulsant heralds this rare (1 in 1000 to 10 000 exposures) but serious reaction. Aromatic anticonvulsants [phenytoin, phenobarbital (phenobarbitone) and carba-mazepine] are the most frequently involved drugs; however, there have also been several cases of anticonvulsant hypersensitivity syndrome associated with lamotrigine.Fever, in conjunction with malaise and pharyngitis, is often the first sign. This is followed by a rash which can range from a simple exanthem to toxic epidermal necrolysis. Internal organ involvement usually involves the liver, although other organs such as the kidney, CNS or lungs may be involved. Hypothyroidism may be a complication in these patients approximately 2 months after occurrence of symptoms.The aromatic anticonvulsants are metabolised to hydroxylated aromatic compounds, such as arene oxides. If detoxification of this toxic metabolite is insufficient, the toxic metabolite may bind to cellular macromolecules causing cell necrosis or a secondary immunological response. Cross-reactivity among the aromatic anticonvulsants may be as high as 75%. In addition, there is a familial tendency to hypersensitivity to anticonvulsants.Discontinuation of the anticonvulsant is essential in patients who develop symptoms compatible with anticonvulsant hypersensitivity syndrome. A minimum battery of laboratory tests, such as liver transaminases, complete blood count and urinalysis and serum creatinine, should be performed. Corticosteroids are usually administered if symptoms are severe. Patients with anticonvulsant hypersensitivity syndrome should avoid all aromatic anticonvulsants; benzo-diazepines, valproic acid (sodium valproate) or one of the newer anticonvulsants can be used for seizure control. However, valproic acid should be used very cautiously in the presence of hepatitis. There is no evidence that lamotrigine cross-reacts with aromatic anticonvulsants. In addition, family counselling is a vital component of patient management.

Clinical and immunogenetic correlates of abacavir hypersensitivity

A patch test (PT) may be useful in defining true abacavir hypersensitivity syndrome (AHS). Seven previously PT-positive patients remote from the original AHS were shown to have robust 24 h responses, supporting PT durability. HLA-B*5701 was present in all seven PT-positive versus one of 11 controls tolerating abacavir (P < 0.001). Five of seven PT (71%) versus one of 11 controls (9%) (P = 0.005) showed significant abacavir-specific CD8 proliferation, suggesting a direct role for HLA-B*5701-restricted CD8 cells in the pathophysiology of AHS.

Utility of patch testing in patients with hypersensitivity syndromes associated with abacavir.

A diagnostic test would be useful to help eliminate the associated morbidity and mortality after full-dose rechallenge with abacavir in patients with suspected hypersensitivity. We describe seven patients with syndromes compatible with abacavir hypersensitivity who had positive patch tests. Immunohistochemistry on skin biopsies from the acute prospectively identified patients with rash (n = 3) matched those from positive-patch patients (n = 7), suggesting an identical pathophysiological process. No patients developed systemic symptoms or signs during patch testing.

Should celecoxib be contraindicated in patients who are allergic to sulfonamides? Revisiting the meaning of 'sulfa' allergy.

Celecoxib, a selective cyclo-oxygenase-2 inhibitor, is a diaryl-substituted pyrazole derivative containing a sulfonamide substituent. Because of this structural component, celecoxib is contraindicated for use in patients who have demonstrated allergic reactions to sulfonamides. However, there is a lack of data demonstrating cross-reactivity among sulfonamide medications.A sulfonamide is any compound with an SO2NH2 moiety. The major difference between sulfonamide antimicrobials and other sulfonamide-containing medications such as furosemide, thiazide diuretics and celecoxib, is that sulfonamide antimicrobials contain an aromatic amine group at the N4 position. This allows for division of the sulfonamides into 2 groups: aromatic amines (i.e., sulfonamide antimicrobials) and nonaromatic amines. In addition, sulfonamide antimicrobials contain a substituted ring at the N1-position; this group is not found with nonaromatic amine-containing sulfonamides.Adverse reactions to sulfonamide antimicrobials include type I, or immunoglobulin (Ig) E-mediated reactions, hypersensitivity syndrome reactions, and severe skin reactions such as toxic epidermal necrolysis. The aromatic amine portion of the sulfonamide antimicrobial is considered to be critical in the development of latter 2 reactions. In susceptible individuals, the hydroxylamine metabolite is unable to be detoxified leading to a cascade of cytotoxic and immunological events that eventually results in the adverse reaction. Since celecoxib does not contain the aromatic amine, adverse reactions such as hypersensitivity syndrome reactions and toxic epidermal necrolysis would not be expected to occur at the same frequency as they do with sulfonamide antimicrobials. Similarly, for IgE-mediated reactions, the N1-substituent and not the sulphonamide moiety is important in determining specificity to antibodies. Celecoxib and other nonaromatic amine-containing sulfonamide medications do not contain the N1-substituent.Cross-reactivity among the various sulfonamide-containing medications has also not been substantiated by published case reports. In fact, conflicting information exists in the literature. Reports showing lack of cross-reactivity balance the few case reports suggesting cross-reactivity.Cross-reactivity between sulfonamide medications should be based on scientific data, including chemistry, metabolism, immune responses and clinical data. Based on the current information, there is no documentation for cross-reactivity between sulfonamide antimicrobials and other sulfonamide medications, such as celecoxib.

Lamotrigine-associated anticonvulsant hypersensitivity syndrome

We systematically reviewed and analyzed published and unpublished cases of lamotrigine-associated adverse drug reactions consistent with the features of the anticonvulsant hypersensitivity syndrome (AHS) to identify characteristics of the syndrome. We identified 26 cases (mean age, 28 ± 18 years; range, 3.5 to 74 years; 54% female), of which nine were published. The characteristics of the syndrome associated with lamotrigine are comparable to AHS induced by older aromatic anticonvulsants.

Terbinafine therapy may be associated with the development of psoriasis de novo or its exacerbation: Four case reports and a review of drug-induced psoriasis

Adverse effects may occur in 10.4% of patients receiving terbinafine therapy, with cutaneous reactions in 2.7%. We describe the development of psoriasis in four patients who took oral terbinafine. Two patients had plaque-type psoriasis that flared 12 and 17 days, respectively, after starting terbinafine. Another patient developed pustular-type psoriasis de novo after 27 days of terbinafine therapy. The fourth patient was a psoriatic with stable plaque disease who experienced a pustular flare after taking terbinafine for 21 days. We are aware of only one report in the literature in which a patient developed pustular psoriasis de novo after 5 days of terbinafine therapy. In all patients the psoriasis cleared or lessened after discontinuation of terbinafine and institution of antipsoriatic therapy.

Evaluation of the Extent of Under-Reporting of Serious Adverse Drug Reactions The Case of Toxic Epidermal Necrolysis

AbstractIntroduction: Toxic epidermal necrolysis (TEN) is a life-threatening adverse drug reaction (ADR) that is primarily the result of drug exposure (incidence 0.4–1.3 per million person-years). Life-threatening ADRs such as TEN should be reported to ADR monitoring programmes, which collect reports for suspected ADRs and alert the public and medical practitioners to new drug hazards. In Canada, reports are made to the Canadian Adverse Drug Reaction Monitoring Program (CADRMP). Objective: To examine the extent of under-reporting for TEN in Canada. Design: A retrospective case series design was used to collect all TEN cases for the period January 1995 to December 2000. Methods: The CADRMP and 22 burn centres across Canada were contacted for all TEN patients treated during the specified time period. Patient Groups Studied: The study population consisted of patients admitted to burn treatment sites across Canada, patient cases reported to the CADRMP and patient cases recorded by the Canadian Institute for Health Information (CIHI) hospital discharge summaries as the International Classification of Diseases Version 9 Clinical Modification (ICD-9-CM) code 695.1. Results: Twenty-five TEN cases (six fatal) were reported to CADRMP from January 1995 to December 2000. During this period, 14 (63.6%) burn treatment sites reported admission of 250 TEN cases. Hospital discharge summaries using the ICD-9-CM code 695.1 indicated that 4349 cases were admitted to hospital during this time period and it was estimated that 15.5% (n = 674) of these cases were TEN. Using the burn facility data as the denominator, 10% (25 of 250) of TEN cases were reported to CADRMP. Using CIHI data as a denominator, only 4% (25 of 674) of TEN cases were reported to CADRMP. Conclusions: There is serious under-reporting of TEN. Lack of reporting of life-threatening ADRs can compromise population safety. There is a need to increase awareness of ADR reporting programmes.

Common adverse events associated with the use of ribavirin for severe acute respiratory syndrome in Canada

Abstract Although information on efficacy and adverse drug reactions is lacking, ribavirin has been used empirically for the treatment of severe acute respiratory syndrome (SARS). We report common adverse events in 110 patients with suspected or probable SARS who were treated with ribavirin. Sixty-one percent of the patients had evidence of hemolytic anemia, and hypocalcemia and hypomagnesmia were reported in 58% and 46% of patients, respectively.