Tamsulosin dosing

In a placebo-controlled study in 6 hypertensive men with blood pressure well controlled by enalapril, the addition of tamsulosin 400 micrograms daily for 7 days then 800 mierograms daily for a further 7 days had no clinically relevant effects on blood pressure (assessed after 6 and 14 days of tamsulosin). In addition, no first-dose hypotensive effect was seen on the day tamsulosin was started, or on the day the tamsulosin dose was increased. ... 

No important interaction occurs between cimetidine and either alfuzosin or doxazosin. Tamsulosin does not appear to have a clinically significant interaction with cimetidine, but caution is recommended with high tamsulosin doses. 

Requirement for up-titration of dose Yes (for terazosin and doxazosin immediate-release) no (for alfuzosin possibly for doxazosin extended-release and tamsulosin) No... 

Pharmacologic and functional uroselectivity are dose-related phenomena. Large daily doses of tamsulosin or alfu-zosin may cause loss of uroselectivity with resultant hypotension and dizziness in some patients. 

Need for up-titration of daily dose. Up-titration is required for terazosin and immediate-release doxazosin. It is minimally required for extended-release doxazosin and tamsulosin. It is not required for extended-release alfuzosin. 

Dosage formulation. Immediate-release formulations of terazosin and doxazosin are quickly absorbed and produce high peak plasma levels. Modified- or extended-release formulations of doxazosin, alfuzosin, and tamsulosin produce lower peak levels, but more sustained therapeutic plasma levels, than immediate-release formulations and have less potential for producing hypotensive episodes, thereby allowing initiation of treatment with a therapeutic dose and once daily dosing.25-27... 

Tamsulosin is a good choice for patients who cannot tolerate hypotension have severe coronary artery disease, volume depletion, cardiac arrhythmias, severe orthostasis, or liver failure or are taking multiple antihypertensives. Tamsulosin is also suitable for patients who want to avoid the delay of dose titration. 

First-dose effect Prazosin, terazosin, doxazosin, alfuzosin, and tamsulosin,... 

Use caution when using tamsulosin in combination with cimetidine, particularly at doses higher than 0.4 mg. 

Contraindications Concurrent use of alpha-adrenergic blockers (other than the minimum dose tamsulosin), concurrent use of sodium nitroprusside or nitrates in any form, severe hepatic impairment... 

Prazosin, doxazosin, and terazosin are all efficacious in patients with BPH. These drugs are particularly useful in patients who also have hypertension. Considerable interest has focused on which -receptor subtype is most important for smooth muscle contraction in the prostate subtype-selective K1A-receptor antagonists might lead to improved efficacy and safety in treating this disease. As indicated above, tamsulosin is also efficacious in BPH and has relatively minor effects on blood pressure at a low dose. This drug may be preferred in patients who have experienced orthostatic hypotension with other -receptor... 

Tadalafil has also been extensively evaluated in patients with cardiovascular disease and has a similar safety and efficacy profile to sildenafil (45). Studies have shown no adverse effects on cardiac contraction, ventricular repolarization, or ischemic threshold. A similar hypotensive effect has been recorded with a dose of doxazosin 8 mg so caution is needed. As hypotension does not occur in the supine position and as tadalafil has a long half-life it is suggested that tadalafil is taken in the morning and doxazosin in the evening. There is no interaction of tadalafil with the selective a-adrenoceptor antagonist tamsulosin, which can, therefore, be prescribed as an alternative to doxazosin for symptomatic benign prostate hypertrophy (46). 

Tamsulosin is an alphai-adrenoceptor antagonist that was specially designed for the treatment of benign prostatic hjrperplasia, since it is highly selective for the urinary tract alphaiA-adrenoceptors (1). Indeed, it produces little or no cardiovascnlar effects, no first-dose effect, and much less dizziness. In clinical trials, adverse effects included dizziness, weakness, headache, and nasal congestion. Abnormal ejacnlation was the most frequent adverse effect, in 8% of the patients at 0.4 mg/day, and in 18% at 0.8 mg/day (2,3). 

Clinical studies have reported very few adverse effects that are of a mild nature (usually gastric distress or headache) following saw palmetto administration at normal doses. One randomized, double-blind study of finasteride, tamsulosin, and saw palmetto for 3 months observed no differences among the three treatments in terms of the effectiveness measures and no change in sexual function in those individuals receiving saw palmetto, though ejaculation disorders were noted as the most common side effect in those individuals receiving either tamsulosin or finasteride (26). 

Tamsulosin s selectivity for aiA-receptors has multiple implications. Dose titration is minimal therefore patients can begin therapy with the lowest effective maintenance dose, 0.4 mg orally once a day. Patients can be instructed to take the dose anytime during the day, unlike terazosin and doxazosin, which should be taken at bedtime. Eor best effect, tamsulosin should be taken on an empty stomach, as food decreases its bioavailability. The onset of peak action is quicker, in the range of 2 weeks, because only a minority of patients will... 

Lee E, Lee C. Clinical comparison of selective and non-selective a -adrenoreceptor antagonists in benign prostatic hyperplasia Studies on tamsulosin in a fixed dose and terazosin in increasing doses. Br J Urol... 

The most recently introduced a, antagonist for BPH, tamsulosin, has selectivity for a and adrenoceptors, vs. a,0 (Table 2). Tamsulosin shows either no selectivity (Kenny et al., 1994 Blue et al., 1997) or slight urethral selectivity (Brune et al., 1996 Testa et al., 1997) in conscious or anesthetized dogs. A small study comparing tamsulosin and terazosin showed a lower incidence of side effects with tamsulosin (Lee and Lee, 1997), although a similar comparison between tamsulosin and alfuzosin showed a similar incidence (Wilde and McTavish, 1996). Unlike most of the a [-antagonists, tamsulosin does not require dose-titration, since blood pressure is not significantly reduced at doses effective for BPH. However, this may be a consequence of the delayed-release preparation used, since early studies with standard formulations in normal volunteers showed a hypotensive effect (Tsunoo et al., 1990). 

Prazosin, terazosin, doxazosin, tamsulosin, and alfuzosin have been studied extensively and used widely in patients with benign prostatic hyperplasia. With the exception of tamsulosin, the comparative efficacies of each of these drugs, especially in comparison with relative adverse effects such as postural hypotension, appear similar, although direct comparisons are limited. Tamsulosin at the recommended dose of 0.4 mg daily is less likely to cause orthostatic hypotension than the other drugs. There is growing evidence that the predominant a,-receptor subtype expressed in the human prostate is the a,-receptor. Developments in this area will provide the basis for the selection of Ct receptor antagonists with specificity for the relevant subtype of aj-receptor. However, the possibility remains that some of the symptoms of BPH are due to aj-receptors in other sites, such as bladder, spinal cord, or brain. 

Tamsulosin (Flomax), a benzenesulfonamide, is an a receptor antagonist with some selectivity for a,A (and a,D) subtypes compared to ajg subtype. This selectivity may favor blockade of receptors in prostate. Tamsulosin is efficacious in the treatment of BPH with little effect on blood pressure. Tamsulosin is well absorbed and has a half-fife of 5 to 10 hours. It is extensively metabolized by CYPs. Tamsulosin may be administered at a 0.4-mg starting dose a dose of 0.8 mg ultimately will be more efficacious in some patients. Abnormal ejaculation is an adverse effect of tamsulosin. 

Thus, tamsulosin and alfuzosin are first-line drugs for the treatment of BPH and have no utility in treating hypertension, because they have fewer cardiovascular effects than terazosin and doxazosin. Their clinical profiles are related to their pharmacokinetic differences (Table 45.3). Improvements in urine flow occur 4 to 8 hours after the first dose and in BPH symptoms after 1 week. 

It is unclear whether there are any real differences between the alpha blockers in their propensity to cause this first-dose effect. With the exception of indoramin, postural hypotension, syncope, and dizziness are listed as adverse effects of the alpha blockers available in the UK and for most it is recommended that they should be started with a low dose and titrated as required. Tamsulosin is reported to have some selectivity for the alpha receptor 1A subtype, which are found mostly in the prostate, and therefore have less effect on blood pressure an initial titration of the dose is therefore not considered to be necessary. Nevertheless, it would be prudent to exercise caution with all the drugs in this class. 

Severe first-dose hypotension, and synergistic hypotensive effects that occurred when a patient taking enalapril was given bnna-zosin have been replicated in healthy subjects. The first-dose effect seen with other alpha blockers (particularly alfuzosin, prazosin and terazosin) is also likely to be potentiated by ACE inhibitors. In one small study tamsulosin did not have any clinically relevant effects on blood pressure that was already well controlled by enalapril. 

---