drugs

Tamsulosin

Tamsulosin is a α1-selective alpha blocker, used to treat the symptoms of benign prostatic hyperplasia. Tamsulosin works by binding selectively and competitively to alpha1A postsynaptic adrenergic receptors (which innervate almost all smooth muscle), thus causing smooth muscle relaxation, including that of prostate and urethra. The relaxation of the smooth muscles of these two anatomical structures determines an increase in the maximum speed of the urinary flow and a considerable reduction in the obstruction. Tamsulosin also improves the symptoms of irritation of the lower urinary tract caused by the contraction of smooth muscles.

One of the most serious drawbacks of tamsulosin is the lowering of blood pressure; since most patients with benign prostatic hyperplasia are at an advanced age, it is also one of the most frequent drawbacks. The lowering of blood pressure occurs because tamsulosin - also releasing the smooth muscles surrounding the larger vessels of the circulatory system - causes an enlargement of the blood vessels, consequently a decrease in peripheral resistance. Although studies conducted by administering the drug to people with normal blood pressure have not demonstrated any clinically significant reduction in blood pressure, it is advisable to be careful while treating elderly people or those who tend to have low blood pressure.

Tamsulosin was developed by the pharmaceutical company Yamanuchi Pharmaceuticals (now part of the pharmaceutical company Astellas Pharma), and is marketed by various companies such as Boehringer-Ingelheim or CLS, but still under the Astellas Pharma license. Tamsulosin was first marketed in the United States under the registered name of Flomax, while in some European countries such as Italy and Iceland, Astellas Pharma Europe marketed the drug under the registered name of Ominic. In 2009, however, the patent of the pharmaceutical company Astellas Pharma for the Flomax expired, so in March 2010 the Food and Drug Administration (FDA) approved the sale of the generic preparation. Now in Italy tamsulosin is also marketed as a generic drug under different names, such as Antunes, Pradif, Tamsulosina, Lura, Tamlic, Probena and Botam.

Tamsulosin is a drug rapidly absorbed from the intestine, thus also boasting a very high bioavailability. Absorption of tamsulosin may be slowed down in cases where the drug is administered concurrently or close to meals; therefore, to optimize its absorption it is recommended to administer it after breakfast. On average, after six hours from the intake, the plasma concentration peak of the drug is reached, which can however vary from one patient to another, both after a single dose and after repeated doses over time, based on individual metabolic characteristics. The distribution of tamsulosin in the circulatory system occurs through the binding of the drug with plasma proteins in a very high percentage, which exceeds 99%. Since tamsulosin is metabolized slowly, the effect of the first hepatic passage is almost nil; consequently, most of the tamsulosin is found unchanged in the plasma.

The metabolites of tamsulosin show a different efficacy compared to the unaltered drug; both tamsulosin and its metabolites are eliminated mainly via the urine.

Posology and method of use

The recommended dose of tamsulosin for the treatment of benign prostatic hyperplasia symptoms is 0.4 mg / day, taken as a single daily dose, about three quarters of an hour after breakfast. In patients with severely impaired hepatic and / or renal function, dose adjustment may be necessary, as tamsulosin is almost completely eliminated via the kidneys.

If the desired clinical effects are not observed within three or four weeks of starting treatment, it is necessary to increase the daily dose to 0.8 mg, always taken in a single daily dose. In the event of discontinuation of tamsulosin treatment, if the drug is resumed, it is advisable to take it at a dose of 0.4 mg / day, regardless of the dose used before the therapy was interrupted; only later can the dose be increased if necessary.

Tamsulosin capsules should be swallowed whole, without breaking, chewing, opening or damaging them in any way.

Contraindications and warnings for use

Before starting treatment with tamsulosin, it is advisable to subject the patient to various prostate tests to rule out the presence of a prostate cancer of a malignant nature or other pathological conditions that can manifest themselves with the same symptoms as benign prostatic hyperplasia. Apart from prostate control by digital examination, it is recommended to also perform prostate specific antigen (PSA) test, both before and during treatment with tamsulosin.

The use of the drug can cause a lowering of blood pressure due to its vasodilator effect, which in some cases, especially in subjects complaining of low blood pressure, can cause dizziness, weakness and even fainting; in these cases the patient should lie down on a bed, lying down, until the symptoms disappear.

During cataract surgery, in some patients previously treated with tamsulosin, the appearance of the Intra-operative Floppy Iris Syndrome occurred, which consists in narrowing the iris and shrinking the pupil; in most cases, patients had recently discontinued treatment with tamsulosin, 2 to 14 days before surgery, but in some very rare cases patients had stopped treatment for more than 5 months. Therefore, if the patient already knows that he must undergo surgery to remove the cataract, it is not advisable to start treatment with tamsulosin. Furthermore, during the pre-operative assessment, it is recommended that the ophthalmologist and the surgeon ascertain whether the patient has been treated with tamsulosin, in order to have all the information and means necessary (such as the ring that it is used for the enlargement of the iris) in order to perform the best surgical intervention.

Like most drugs, tamsulosin is metabolised by the large CYP450 family of enzymes, especially by the CYP3A4 and CYP2D6 isoenzymes. Therefore all inhibitors of the CYP450 enzyme system, in particular inhibitors of the isoenzymes CYP3A4 and CYP2D6, may cause changes in the plasma concentration of tamsulosin. Not surprisingly, the joint administration of tamsulosin and ketoconazole, which is a strong inhibitor of CYP3A4, causes a noticeable increase in the plasma concentration of tamsulosin; for this reason the concomitant administration of these two drugs is not recommended. Other moderate inhibitors of the CYP3A4 isoenzyme, such as erythromycin, have not yet been studied, but joint administration to tamsulosine is thought to result in pharmacologically non-significant concentration changes. Another drug to consider is paroxetine, which is a strong inhibitor of the CYP2D6 isoenzyme. Administration of paroxetine concomitantly with tamsulosin, due to its metabolism inhibition, causes a significant increase in the plasma concentration of tamsulosin, so it is not recommended to use these two drugs simultaneously. Also cimetidine, if it is administered together with tamsulosin, can decrease the clearence of the latter and increase its concentration. Another category of drugs for which the combined administration of tamsulosin is not recommended is that of PDE5 inhibitors, such as sildenafil (Viagra) or tadalafil (Cialis), since both cause vasodilation and contribute to amplifying tamsulosin-induced hypotension, thus being able to cause the patient to faint. Furthermore warfarin and diclofenac may increase the elimination rate of tamsulosin.

In the event of an overdose, lowering of blood pressure can occur until fainting, preceded by vomiting and diarrhea; to lower the levels of tamsulosin it is recommended to subject the patient to gastric lavage to decrease the absorption of the drug, and to administer vasoconstrictors to counteract the lowering of blood pressure.

Pregnancy and breastfeeding

So far, animal studies have shown no risk of fetal toxicity related to the use of tamsulosin, even in very high doses that exceeded about 50 times those used in therapy. Despite this, the use of tamsulosin in women in general, especially if pregnant, is contraindicated.

However, the data collected from the same animal studies have shown a significant reduction in male and female fertility when administered at doses about 50 times higher than those used to treat the symptoms of benign prostatic hyperplasia. The mechanism of these effects is not yet completely clear but it is thought to have to do with the problems related to ejaculation, the number of spermatozoa contained in the semen and the impediment of proper fertilization. However, the effect of fertility reduction is reversible; in the case of administration of a single dose of tamsulosine (about 50 times higher than the therapeutic dose), it took three days for the male's reproductive capacity to return to normal, while in the case of administrations of multi-mega-doses it can be used from four to nine weeks before everything returns to the desired levels. A treatment with multiple doses of tamsulosine, about 16 times greater than the therapeutic doses, always conducted on animals, has not shown any kind of side effects either on male fertility or on female fertility.

There are still no data regarding tamsulosin secretion in breast milk therefore the use of tamsulosin during breastfeeding is contraindicated.

Side and unwanted effects

Like all medicines, tamsulosin can also cause a number of side effects, although most patients do not experience any type of disorder. The most common side effects of tamsulosin are those related to vasodilation and lowering of blood pressure: headache, which is complained about 20% of patients, dizziness, complained about 15% of patients, drowsiness, insomnia and decreased libido, complained by about 1% of patients; however, with regard to this last point it is interesting to note that even in the control group treated with placebo, the same percentage of patients, equal to about 1.2%, complained of a decrease in libido. Other side effects are those related to the urogenital system, such as retrograde ejaculation, ejaculate volume reduction and painful ejaculation. Retrograde ejaculation is thought to be caused by inhibition of the prostatic sphincter. Although tamsulosin is associated with ejaculation disorders, it has been confirmed that it is not responsible for erectile dysfunction.

Another side effect of tamsulosin, which occurs during cataract surgery, is the flag iris syndrome (Intraoperative Floppy Iris Syndrome).