ABSTRACT
Title
Safety profile of antiviral analogues: a case/non case study using the Italian spontaneous reporting database
Authors
A. Pugi1,2, R. Bonaiuti1,2, M. Tuccori1,3, M. Moschini1,2, V. Maggini1,2, L. Sottosanti4, S. Potenza4, F. Ferrazin4, A. Mugelli1,2, A. Vannacci1,2, F. Lapi1,2.
1 Tuscan Regional Centre of Pharmacovigilance, Italy
2 Department of Pharmacology, University of Florence
3 Unit of Pharmacology, University Hospital of Pisa
4 Pharmacovigilance Unit, Italian Medicines Agency, Rome
1 Tuscan Regional Centre of Pharmacovigilance, Italy
2 Department of Pharmacology, University of Florence
3 Unit of Pharmacology, University Hospital of Pisa
4 Pharmacovigilance Unit, Italian Medicines Agency, Rome
Abstract
Worldwide a high percentage of people suffers from serious illnesses of viral etiology. Although the available antivirals possess a demonstrated efficacy, their use is associated with serious Adverse Drug Reaction (ADRs). Gastrointestinal and cutaneous reactions, as well as neuropathy, hematological, renal, metabolic disorders have been in fact described during therapy with antiviral analogues.
The aim of our study was to evaluate the “signal alarms” likely due to antivirals-induced ADRs, using the Italian spontaneous reporting database (January 2001-September 2010). We analyzed the spontaneous reports according to a case/non-case design by estimating the Reporting Odds Ratio (ROR) and 95% Confidence Intervals (CI) as a measure of disproportionality. Reports with a causality assessment defined at least as “possible” entered the analysis.
Those ADRs reported for antiviral analogues, such as kidney failure, depression, anemia which counted more than 10 reports, were considered as ‘cases’ while all other events as ‘non-cases’. Herein, antivirals were compared with other drugs if more disproportionally reported among ‘cases’ than ‘non cases’.
Herein, 947 reports of ADRs induced by antivirals and 42346 reports due to other drugs entered in the final analysis. Among schemes related to antivirals, 41.8% were female and the majority of patients’ age ranged from 36 to 65 years old. Moreover 71.9% of patients were exposed to a monotherapy regimen with antivirals or with a single add-on medication; among the reports, 42.1% was concurrently treated with interferon.
Renal reactions [(renal colic (ROR=23.0; 95% CI 11.8-44.9) and acute kidney injury (ROR=3.9; 95% CI 2.4-6.5)] likely due to antivirals were reported with an higher frequency when compared with other medications. Among hematological events, only anemia showed a significant ROR (13.5; 95% CI 10.5-17.4). Hypertriglyceridemia and lactic acidosis were described with 10.3 and 16-fold higher risk of being reported than the other drugs (95% CI 4.1-25.8 and 7.9-32.2, respectively). Hallucinations (ROR=4.1; 95% CI 2.5-6.7) and depression (ROR=14.9; 95% CI 9.5-23.4) were the neuropsychiatric events whose disproportionality was significantly higher for antivirals. The occurrence of cutaneous reactions (i.e. dermatitis, urticaria, pruritus, exanthema erythematosus) did not show significant differences when compared with all other drugs.
Our results confirmed the heterogeneity of antivirals safety profiles. Because of the clinical burden of the observed ADRs (e.g. kidney disorders), patients should be monitored carefully during this therapy. Further pharmacoepidemiology surveys should be carried out with the aim of assessing the risk of ADRs likely due to any single antiviral molecule.
The aim of our study was to evaluate the “signal alarms” likely due to antivirals-induced ADRs, using the Italian spontaneous reporting database (January 2001-September 2010). We analyzed the spontaneous reports according to a case/non-case design by estimating the Reporting Odds Ratio (ROR) and 95% Confidence Intervals (CI) as a measure of disproportionality. Reports with a causality assessment defined at least as “possible” entered the analysis.
Those ADRs reported for antiviral analogues, such as kidney failure, depression, anemia which counted more than 10 reports, were considered as ‘cases’ while all other events as ‘non-cases’. Herein, antivirals were compared with other drugs if more disproportionally reported among ‘cases’ than ‘non cases’.
Herein, 947 reports of ADRs induced by antivirals and 42346 reports due to other drugs entered in the final analysis. Among schemes related to antivirals, 41.8% were female and the majority of patients’ age ranged from 36 to 65 years old. Moreover 71.9% of patients were exposed to a monotherapy regimen with antivirals or with a single add-on medication; among the reports, 42.1% was concurrently treated with interferon.
Renal reactions [(renal colic (ROR=23.0; 95% CI 11.8-44.9) and acute kidney injury (ROR=3.9; 95% CI 2.4-6.5)] likely due to antivirals were reported with an higher frequency when compared with other medications. Among hematological events, only anemia showed a significant ROR (13.5; 95% CI 10.5-17.4). Hypertriglyceridemia and lactic acidosis were described with 10.3 and 16-fold higher risk of being reported than the other drugs (95% CI 4.1-25.8 and 7.9-32.2, respectively). Hallucinations (ROR=4.1; 95% CI 2.5-6.7) and depression (ROR=14.9; 95% CI 9.5-23.4) were the neuropsychiatric events whose disproportionality was significantly higher for antivirals. The occurrence of cutaneous reactions (i.e. dermatitis, urticaria, pruritus, exanthema erythematosus) did not show significant differences when compared with all other drugs.
Our results confirmed the heterogeneity of antivirals safety profiles. Because of the clinical burden of the observed ADRs (e.g. kidney disorders), patients should be monitored carefully during this therapy. Further pharmacoepidemiology surveys should be carried out with the aim of assessing the risk of ADRs likely due to any single antiviral molecule.