Source: Web Search Revision Year: 2019 Publisher: Astellas Pharmaceuticals A.E.B.E., 6-8 Agisilaou Str., 15123 Marousi, Athens-Greece Tel: +30 210 8189900 Fax: +30 216 8008998
Pharmacotherapeutic group: α1-adrenoceptor antagonist
ATC code: GO4CAO2
Preparations for the exclusive treatment of prostatic disease.
Tamsulosin binds selectively and competitively to the postsynaptic α1-adrenoceptors, in particular to subtypes α1A and α1D. It brings about relaxation of prostatic and urethral smooth muscle.
Omnic 0,4 increases the maximum urinary flow rate. It relieves obstruction by relaxing smooth muscle in prostate and urethra thereby improving voiding symptoms.
It also improves the storage symptoms in which bladder instability plays an important role.
These effects on storage and voiding symptoms are maintained during long-term therapy. The need for surgery or catheterization is significantly delayed.
α1-adrenoceptors antagonists can reduce blood pressure by lowering peripheral resistance. No reduction in blood pressure of any clinical significance was observed during studies with Omnic 0,4.
A double-blind, randomized, placebo-controlled, dose ranging study was performed in children with neuropathic bladder. A total of 161 children (with an age of 2 to 16 years) were randomized and treated at 1 of 3 dose levels of tamsulosin (low [0.001 to 0.002 mg/kg], medium [0.002 to 0.004 mg/kg], and high [0.004 to 0.008 mg/kg]), or placebo. The primary endpoint was number of patients who decreased their detrusor leak point pressure (LPP) to <40 cm H2O based upon two evaluations on the same day. Secondary endpoints were: Actual and percent change from baseline in detrusor leak point pressure, improvement or stabilization of hydronephrosis and hydroureter and change in urine volumes obtained by catheterisation and number of times wet at time of catheterisation as recorded in catheterisation diaries. No statistically significant difference was found between the placebo group and any of the 3 tamsulosin dose groups for either the primary or any secondary endpoints. No dose response was observed for any dose level.
Tamsulosin hydrochloride is absorbed from the intestine and is almost completely bioavailable. Absorption of tamsulosin hydrochloride is reduced by a recent meal. Uniformity of absorption can be promoted by the patient always taking Omnic 0.4 mg after the same meal. Tamsulosin shows linear kinetics.
After a single dose of Omnic 0.4 mg in the fed state, plasma levels of tamsulosin peak at around 6 hours and, in the steady state, which is reached by day 5 of multiple dosing, Cmax in patients is about two thirds higher than that reached after a single dose. Although this was seen in elderly patients, the same finding would also be expected in young ones.
There is a considerable inter-patient variation in plasma levels both after single and multiple dosing.
In man, tamsulosin is about 99% bound to plasma proteins. The volume of distribution is small (about 0.2 l/kg).
Tamsulosin has a low first pass effect, being metabolized slowly. Most tamsulosin is present in plasma in the form of unchanged active substance. It is metabolized in the liver.
In rats, hardly any induction of microsomal liver enzymes was seen to be caused by tamsulosin.
In vitro results suggest that CYP3A4 and also CYP2D6 are involved in metabolism, with possible minor contributions to tamsulosin hydrochloride metabolism by other CYP isozymes. Inhibition of CYP3A4 and CYP2D6 drug metabolizing enzymes may lead to increased exposure to tamsulosin hydrochloride (see section 4.4 and 4.5).
None of the metabolites are more active than the original compound.
Tamsulosin and its metabolites are mainly excreted in the urine with about 9% of a dose being present in the form of unchanged active substance.
After a single dose of Omnic 0.4 mg in the fed state, and in the steady state in patients, elimination half-lives of about 10 and 13 hours respectively have been measured.
Single and repeat dose toxicity studies were performed in mice, rats and dogs. In addition, reproduction toxicity in rats, carcinogenicity in mice and rats and in vivo and in vitro genotoxicity were examined.
The general toxicity profile, as seen with high doses of tamsulosin, is consistent with the known pharmacological actions of the α 1-adrenoceptors antagonists.
At very high dose levels the ECG was altered in dogs. This response is considered to be not clinically relevant. Tamsulosin showed no relevant genotoxic properties.
Increased incidences of proliferative changes of mammary glands of female rats and mice have been reported. These findings, which are probably mediated by hyperprolactinemia and only occurred at high dose levels, are regarded as irrelevant.
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