Tamsulosin has been marketed as a major innovation among alpha-blockers due to a lower frequency of orthostatic hypotension than other drugs in this class. It is now the market leader in the treatment of benign prostatic hyperplasia (BPH) and the most commonly prescribed treatment for lower urinary tract symptoms worldwide. However, it is not known whether it induces a first dose phenomenon in clinical practice and confers increased risk for hypotension, requiring admission to hospital immediately after initiating or restarting drug treatment.
This population based retrospective cohort study using healthcare claims data from the IMS Lifelink database in the US and self controlled case series aimed to characterise the risk of severe hypotension at different time intervals during the course of tamsulosin treatment in men aged 40-85 years with BPH.
There were 2562 admissions to hospital for severe hypotension among 383,567 new users of study drugs (tamsulosin, n=297,596; 5-alpha reductase inhibitor [5ARI], n=85 ,971). The incidence for hypotension was higher for tamsulosin than for 5ARIs (42.4 vs. 31.3/10 000 person years). After start of tamsulosin, the cohort analysis identified an increased rate of hypotension during weeks 1-4 (rate ratio 2.12; 95% CI, 1.29 to 3.04) and weeks 5-8 (1.51; 1.04 to 2.18), and no significant increase at weeks 9-12. The rate ratio for hypotension also increased at weeks 1-4 (1.84; 1.46 to 2.33) and weeks 5-8 (1.85; 1.45 to 2.36) after restarting tamsulosin, as did maintenance treatment (1.19; 1.07 to 1.32). The self controlled case series gave similar results.
The researchers note that clinical trials reported a 12% incidence of orthostatic hypotension among patients taking 0.4 mg tamsulosin vs. 6% in patients taking placebo between 4 to 8 hours after dosing, however, no treatment emergent hypotensive events were observed. In these trials, patients were kept at the treating site for 8 hours after the first dose and received counseling on the effects of orthostatic hypotension; a setting that may not apply to treatment practice in the real world. They conclude that their data add to the current literature to better define and quantify the risk of hypotension with tamsulosin, and advise that clinicians focus on improved counselling strategies to warn patients about this risk.
An accompanying editorial calls for improved postmarketing surveillance of alpha-blockers considered to have minimal risks of orthostatic hypotension.