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Thus, there was no increase in the number of reports after the tadalafil OTC switch in Poland (Tables 10 and 11).

Side Effect Frequency Severity Advice Notes
Headache Common Mild Take pain relief Usually transient
Flushing Common Mild Stay cool Temporary
Indigestion Uncommon Mild Avoid spicy foods
Ear ringing Rare Mild Seek medical help Persistent symptoms

Table 10: EVDAS, Tadalafil, Poland: Number of relevant ICSRs retrieved, by seriousness.

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Table 11: FAERS, Tadalafil, Poland: Number of relevant ICSRs retrieved, by seriousness. In view of the low total number of cases and the high number of probable duplicates, ICSR reporting rates were not calculated.

Aspect OTC Tadalafil Prescribed Tadalafil
Average Cost £8 - £20 per pack £20 - £50+ per consultation + medication
Insurance Coverage Usually not covered Often covered or subsidized
Convenience Purchase directly, quick access Requires doctor visit

The ADRs included in the ICSRs retrieved from EVDAS and FAERS respectively.

Aspect OTC Tadalafil Prescription Tadalafil
Dispensing Authority Pharmacist with license (if allowed) Prescribed by doctor
Cost Usually lower Higher due to consultation
Availability Limited, often online with caution Widely available in clinics/hospitals
Packaging Discreet, and sometimes generic Original branded packaging

The listings reflect the repetitive reporting in particular of a single literature report primarily describing the occurrence of back pain in a patient with depression that was reported together with a number of additional events including tachycardia, tachypnoea and various neuropsychiatric events.

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Two of the 8 cases reporting ‘Subarachnoid haemorrhage’ were identified as probable duplicates of a case initially reported in 2009 and further 5 cases were probable duplicates of a single case occurring in 2019. Since 2018, there has been a notable increase in Adverse Drug Reactions (ADRs) reported within the System Organ Class (SOC) of Vascular disorders from FAERS. This rise was attributed to reports of known undesirable effects, ‘Flushing’, ‘Orthostatic hypotension’, ‘Hypotension’ and ‘Hot flush’. In FAERS, 32 cases reported AE of Flushing, 15 cases reported orthostatic hypotension, 13 cases reported hypotension and 12 cases reported for hot flush. More than half of these above mentioned cases were probable duplicates.

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(22 out of 32 cases reporting Flushing were duplicates, 12 out of 15 cases reporting Orthostatic hypotension were duplicates, 9 out of 13 cases reporting Hypotension were duplicates and buy tadalafil 9 out of 12 cases reporting Hot flush were duplicates). Review of a cluster of reports of ‘Cardiac arrest’ (14 ADRs in FAERS in 2021) revealed that 11 of these 14 cases are probable duplicates referring to the same patient. The case describes a lifethreatening suspected drug-drug interaction with an alpha receptor agonist and a beta blocker, which are listed drug interactions where particular caution is advised. Further information on this case is not available. Of the other 3 ICSRs, one is a literature report where exposure to sildenafil predated the non-Rx/OTC switch and one is a published report from the Netherlands describing death primarily attributed to illicit use of 3-methylmethcathinone; both cases are thus unrelated to the non-Rx switch in the UK.

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In the remaining third article, radiological and clinical findings of HIV associated pneumonia and patient being a heavy smoker are risk factor for cardiac arrest leading to fatality. Patient age was reported for 541 of the 770 cases retrieved from FAERS and ranged from 22 to 91 years (median, 59 years). No contraindicated medicines were reported as concomitant or cosuspect drugs in any of the ED cases from the UK retrieved from either database. Sildenafil is available as non-prescription medicine for treatment of ED in Norway since August, 2019. Number of ICSRs and reporting rates over time: ICSR numbers and reporting rates over time for cases retrieved from EVDAS and FAERS are shown in Figures 8 and 9, respectively. No other noteworthy ADR clusters or trends over time were observed.

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No contraindicated medicines were reported as concomitant or cosuspect drugs in any of the tadalafil cases from Poland retrieved from either database.

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Otherwise, no noteworthy ADR clusters or trends over time were observed. Patient age was reported in 32 of the 54 cases retrieved for Poland from FAERS and ranged from 30 to 71 years (median, 64 years). No contraindicated medicines were reported as concomitant or cosuspect drugs in any of the ED cases from Poland retrieved from either database. Sildenafil is available as non-prescription medicine for treatment of ED in the UK since March, 2018. Number of ICSRs and reporting rates over time: Consistent with high exposure estimates for sildenafil in the UK as well as a traditionally high spontaneous ADR reporting rate, the majority of the ICSRs selected from EVDAS and FAERS (71.93% and 87.30%, respectively) were received from the UK (5).

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An increase in ICSR numbers over time was observed. This trend coincided with an approximately 75% increase in exposure between 2014 and 2022 and also needs to be seen against the backdrop of a general increase in spontaneous ADR reporting observed in Europe in recent years. Annual exposure-adjusted ICSR reporting rates were consistently very low (<4 to 5 ICSRs per million sold tablets per year) but showed a transient increase for non-serious cases in 2018- 2019 and increase for serious cases in 2023 (Figure 6). In FAERs, this increase was found to predate the non-Rx/OTC switch and to be mostly explained by reporting of probable duplicates (Figure 7). There was no indication of a trend towards a greater proportion of fatal cases after the switch to non-prescription status in either database.

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Figure 6: EVDAS/Sildenafil/UK – Number of ICSRs and reporting rates, by seriousness. Figure 7: FAERS/Sildenafil/UK – Number of ICSRs and reporting rates, by duplicate classification. Possible clusters of individual ADRs (MedDRA PTs) after 2018 were consistently found to be artefacts, mostly due to probable case duplicates: A possible trend towards higher numbers of ADRs from the SOC “Nervous system disorders” was observed in both databases which was primarily attributed to a higher incidence of specific adverse events such as ‘Headache’, ‘Loss of consciousness’, ‘Syncope’, ‘Dizziness’ and ‘Subarachnoid haemorrhage’. Review of the corresponding cases in FAERS revealed that most of the cases reported in or after 2018 were duplicates (16 of the 29 cases reporting Headache were duplicates, 17 of the 23 cases reporting Syncope were duplicates, 16 of the 17 cases reporting Loss of consciousness were duplicates and 12 of the 21 cases reporting dizziness were duplicates). This high proportion of duplicate reports suggests that the actual number of unique adverse events may be considerably lower than initially indicated by the raw data. Tadalafil is available as non-Rx medicine for treatment of ED in UK since June, 2023.

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Number of ICSRs and reporting rates over time (EVDAS): The number of ICSRs reported overtime for tadalafil in UK is presented in Table 12.

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From the tadalafil 60mg uk limited number of ICSRs reported in EVDAS and FAERS, no noteworthy ADR clusters or trends over time were observed. Patient age was reported for 18 of the 20 cases retrieved from FAERS and ranged from 28 to 69 years (median, 59 years). No contraindicated medicines were reported as concomitant or cosuspect drugs in any of the ED cases from Ireland retrieved from either database. Tadalafil is available as OTC medicine for treatment of ED in Poland since March, 2022. The query of EVDAS for cases concerning tadalafil resulted in a total of 13 946 ICSRs with an EV Gateway receipt date ≥ 01 Jan, 2010 of which 15 ICSRs originated from Poland (Figure 11).

Incidence not known

The query of FAERS yielded 27,569 ICSRs concerning tadalafil with FDA receipt date ≥ 01 Jan, 2010 of which 23 ICSRs originated from Poland. All cases retrieved from EVDAS and FAERS for Poland treated for ED or unknown indications and were included in the analysis. Figure 11: EVDAS, Tadalafil, Poland: Number of ICSRs and Reporting rate. Number of ICSRs and reporting rates over time: Almost all cases in both databases were reported in 2022. Case review in FAERS suggested that 17 of the 23 cases were probable duplicates, of which 13 probable duplicates created from a single literature report that was published in February 2022 (prior to tadalafil becoming available as non-prescription medicine). The higher RR from 2023-2024 was observed in serious ICSRs, of which majority accounted for the fatal outcome (N=41).

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In these fatal ICSRs, majority of the ICSRs (N=39; 95.1%) reported unspecified cause of death (PT-Death), with no relevant information reported.

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Based on small case numbers, a possible trend towards higher in case numbers in EVDAS is apparent; however, this trend started several years before the non-Rx switch in Norway and was mostly due to non-serious cases. Figure 8: EVDAS/Sildenafil/Norway – Number of ICSRs and reporting rates, by seriousness. Figure 9: FAERS/Sildenafil/Norway – Number of ICSRs and reporting rates, by duplicate classification. No fatal cases were retrieved for Norway from either database since non-Rx switch (August, 2019). Case characteristics: The ADRs included in the ICSRs retrieved from EVDAS and FAERS.

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No noteworthy ADR clusters or trends over time were observed. Patient age was reported for 17 of the 22 cases retrieved from FAERS and ranged from 31 to 81 years (median, 63 years). No contraindicated medicines were reported as concomitant or cosuspect drugs in any of the ED cases from Norway retrieved from either database. Sildenafil is available as non-prescription medicine for treatment of ED in Ireland since January, 2021. Number of ICSRs and reporting rates over time: The annual number of relevant cases and corresponding annual reporting rates for ICSRs retrieved from EVDAS, stratified by seriousness, are shown in Figure 10.

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There was no increase in case numbers or reporting rates during the limited period since non-Rx switch in Ireland. Figure 10: EVDAS/Sildenafil/Ireland – Number of ICSRs and reporting rates, by seriousness. Of the 17 cases retrieved for Ireland from FAERS for Ireland (Table 6), 4 cases were classified as probable duplicates. In view of the low case numbers, ICSR reporting rates for cases retrieved from FAERS for Ireland were not calculated. Case characteristics: The ADRs included in the ICSRs retrieved from EVDAS and FAERS respectively. And among these 39 fatal cases, majority (N=25; 64.1%) of the cases were reported in elderly group patients (Table 12 and Figure 12).

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Table 12: Pattern of cases reported overtime from EVDAS in UK. Figure 12: EVDAS/Tadalafil/United Kingdom – Number of ICSRs, by seriousness and reporting rate.