Tramadol and hyperacusis
Tramadol and hyperacusis was identified as a potential signal in a screening of VigiBase, the WHO global database of individual case safety reports, focusing on patient reports. As of June 2019, there were 20 reports for the combination. Overall, they support an association between tramadol and hyperacusis with all cases reporting tramadol as the only suspect drug, and with a consistent time-to- onset of up to two days among all cases that provided it.
Hyperacusis can be described as experiencing “sounds of everyday life as intrusively loud, uncomfortable, and sometimes painful”. It can either develop suddenly or over time. To avoid noise, some people may withdraw from normal daily activities and may therefore become isolated.
From the data six cases reported a positive dechallenge and two a positive rechallenge. κ-opioid receptor-mediated facilitation of NMDA receptor sensitivity to glutamate has been suggested as a mechanism for hyperacusis in rodents. Hyperacusis is not listed as an adverse reaction in the label for tramadol, and while changes in sensorial capacity is, this might not be specific enough for the patients, who would benefit from more precise labelling.
Midostaurin – photosensitivity reaction
Midostaurin is a protein kinase inhibitor indicated as monotherapy for the treatment of adult patients with aggressive systemic mastocytosis, systemic mastocytosis with associated haematological neoplasm or mast cell leukaemia.
Reports in the French pharmacovigilance database, the Base Nationale de Pharmacovigilance (BNPV) as well as in VigiBase, the WHO global database of individual case safety reports (ICSRs), indicate that midostaurin can cause photosensitivity reactions while interacting with sunlight in certain patients.
All cases found were marked as serious and the treatment in most cases continued, in some with recorded advice of sun protection. In one case the drug was permanently withdrawn, and the treating physician issued a contraindication for the drug for the patient following a photosensitivity test with a very strong reaction to the drug. There is no mention of photosensitivity in the product labels for midostaurin, but in a French compassionate use programme involving 28 patients, 25% of the patients reported an occurrence of photosensitivity reactions following treatment with midostaurin, strengthening the suspicion based on the reports found in BNPV and VigiBase.
Agomelatine and Increased Blood Pressure
Agomelatine is a non-selective melatonin receptor MT1 and MT2 agonist plus a neutral serotonergic 5- HT2C antagonist indicated for the treatment of major depressive episodes. Of the 24 reports from eight countries on increased blood pressure and agomelatine in the WHO global database of individual case safety reports (VigiBase), twelve were eligible for assessment. Of these, six revealed a consistent pattern of a short time to onset and nine reported recovery on dechallenge, with a positive rechallenge in two of them. Although data on the mechanism of action of agomelatine, as well as a former signal, suggest a mild hypo- rather than hypertensive action, it is also true that melatonin, which is structurally closely related to agomelatine, has hypertension as a labelled adverse effect. Thus, despite the presence of additional risk factors for hypertension in a considerable proportion of these cases, a contributory role of agomelatine to the events cannot be excluded.
Referance: Uppsala Monitoring Centre. WHO Pharm. Newsletter 2020(2): 14-24.
Leave a Reply