Tamulsin

Each film-coated tablet contains: Tamsulosin Hydrochloride 400 mcg.
White coloured, oval shaped, biconvex film coated tablets, plain on both sides.

Pharmacology: Pharmacodynamics: Alpha-adrenoceptor antagonist.
Preparations for the exclusive treatment of prostatic disease.
Mechanism of action: Tamsulosin binds selectively and competitively to postsynaptic alpha1-receptors, in particular to the subtype alpha1A, resulting in relaxation of the smooth muscle of the prostate, whereby tension is reduced.
Pharmacodynamic effects: Tamsulosin increases maximum urinary flow rate by reducing smooth muscle tension in the prostate and urethra, thereby relieving obstruction.
It also improves the complex of irritative and obstructive symptoms in which bladder instability and tension of the smooth muscles of the lower urinary tract play an important role. Alpha1-blockers can reduce blood pressure by lowering peripheral resistance. No reduction in blood pressure of any clinical significance was observed during studies with Tamsulosin.
Paediatric population: 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 wet times 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.
Pharmacokinetics: Absorption: Tamsulosin administered as a prolonged-release tablet is absorbed from the intestine and its bioavailability is approximately 55-59%. A consistent slow release of Tamsulosin is maintained over the whole pH range encountered in the gastrointestinal tract with little fluctuation over 24 hours. The rate and extent of absorption of Tamsulosin administered as a prolonged release-tablet is not affected by food intake.
Tamsulosin shows linear kinetics.
Following administration of a single dose of Tamsulosin in fasting state, plasma levels of Tamsulosin peak at a median time of 6 hours. At steady state, which is reached by day 4 of multiple dosing, plasma levels of Tamsulosin peak at 4 to 6 hours in fasting and fed state. Peak plasma levels increase from approximately 6 ng/mL after the first dose to 11 ng/mL at steady state.
As a result of the prolonged release characteristics of the tablet the trough concentration of Tamsulosin in plasma amounts to 40% of the peak plasma concentration under fasting and fed conditions. There is a considerable inter-patient variation in plasma levels, both after single and multiple dosing.
Distribution: In male patients, Tamsulosin is about 99% bound to plasma proteins and the volume of distribution is small (about 0.2l/kg).
Biotransformation: Tamsulosin has a low first pass effect, being metabolised slowly. Most Tamsulosin is present in plasma in the form of unchanged drug. It is metabolised in the liver.
In rats, hardly any induction of microsomal liver enzymes was seen to be caused by Tamsulosin.
None of the metabolites are more active than the original compound.
Elimination: Tamsulosin and its metabolites are mainly excreted in the urine. The urinary recovery of unchanged drug is estimated to be about 4-6% of the dose, administered as a prolonged release tablet.
After a single dose of Tamsulosin, and at steady state, elimination half-life of about 19 and 15 hours, respectively, has been measured.

It is used for the treatment of functional symptoms of benign prostatic hyperplasia (BPH).

For oral use: One tablet daily can be taken independently of food.
The tablet should be swallowed whole and should not be crushed or chewed as this will interfere with the prolonged release of the active ingredient.
Special populations: Renal impairment: No dose adjustment is required in patients with renal impairment.
Hepatic impairment: No dose adjustment is required in patients with mild to moderate hepatic impairment.
Paediatric population: The safety and efficacy of Tamsulosin in children <18 years have not been established. Currently available data are described in Pharmacology: Pharmacodynamics under Actions.

Should overdosage of Tamsulosin hydrochloride capsule lead to hypotension, support of the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplished by keeping the patient in the supine position. If these measure is inadequate, then administration of intravenous fluids should be considered. If necessary vasopressors should then be used and renal function should be monitored and supported as needed. Laboratory data indicate that Tamsulosin hydrochloride is 94% to 99% protein bound; therefore, dialysis is unlikely to be of benefit.
One patient reported an overdose of thirty 400 mcg Tamsulosin hydrochloride capsule. Following the ingestion of the capsules, the patient reported a severe headache.

Hypersensitivity to Tamsulosin, including drug-induced angioedema, or to any component of this products.
A history of orthostatic hypotension.
Severe hepatic insufficiency.

As with other alpha1-blockers, a reduction in blood pressure can occur in individual cases during treatment with Tamsulosin, leading in rare cases of syncope. At the first signs of orthostatic hypotension (dizziness, weakness), the patient should sit or lie down until the symptoms have disappeared. Prior to commencement of therapy with Tamsulosin, the patient should be examined in order to exclude the presence of other conditions which may produce similar symptoms to those of benign prostatic hyperplasia. Digital rectal examination and, when necessary, determination of prostate specific antigen (PSA) should be performed prior to commencement of treatment and at regular intervals afterwards. The treatment of patients with severe renal impairment (creatinine clearance less than 10 mL/min) should be approached with caution as these patients have not been studied.
The 'Intraoperative Floppy Iris Syndrome' (IFIS, a variant of small pupil syndrome) has been observed during cataract and glaucoma surgery in some patients on or previously treated with Tamsulosin. IFIS may lead to increased procedural complications during the operation. The initiation of therapy with Tamsulosin in patients scheduled for cataract or glaucoma surgery is not recommended.
Discontinuing Tamsulosin 1-2 weeks prior to cataract or glaucoma surgery is anecdotally considered helpful, but the benefit of treatment discontinuation has not been established.
IFIS has also been reported in patients who had discontinued Tamsulosin for a longer period prior to surgery.
During pre-operative assessment, surgeons and ophthalmic teams should consider whether patients scheduled for cataract or glaucoma surgery are being or have been treated with Tamsulosin in order to ensure that appropriate measures will be in place to manage the IFIS during surgery.
Tamsulosin prolonged-release tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Tamsulosin should not be given in combination with strong inhibitors of CYP3A4 in patients with poor metaboliser CYP2D6 phenotype.
Tamsulosin should be used with caution in combination with strong and moderate inhibitors of CYP3A4.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed. However patients should be aware of the fact that drowsiness, blurred vision, dizziness and syncope can occur.
Use in Pregnancy & Lactation: See Use in Pregnancy & Lactation for further information.

Fertility, Pregnancy and Lactation: Tamsulosin is not indicated for use in women.
Ejaculation disorders have been observed in short and long term clinical studies with Tamsulosin. Events of ejaculation disorder, retrograde ejaculation and ejaculation failure have been reported in the post authorization phase.

Tabulated list of adverse reactions: (See table.)

Click on icon to see table/diagram/image

Observed post-marketing: As with other alpha-blockers, drowsiness, blurred vision or oedema can occur.
During cataract and glaucoma surgery a small pupil situation, known as Intraoperative Floppy Iris Syndrome (IFIS), has been associated with therapy of Tamsulosin during post-marketing surveillance.
Post-marketing experience: In addition to the adverse events listed previously, atrial fibrillation, arrhythmia, tachycardia and dyspnoea have been reported in association with Tamsulosin use. Because these spontaneously reported events are from the worldwide post marketing experience, the frequency of events and the role of Tamsulosin in their causation cannot be reliably determined.

Interaction studies have only been performed in adults.
No interactions have been seen when Tamsulosin was given concomitantly with atenolol, enalapril or theophylline.
Concomitant cimetidine increases and concomitant furosemide lowers plasma levels of Tamsulosin, however, as levels remain within the normal range, posology need not be changed.
In vitro, neither diazepam nor propranolol, trichlormethiazide, chlormadinon, amitryptyline, diclofenac, glibenclamide, simvastatin and warfarin change the free fraction of Tamsulosin in human plasma. Neither does Tamsulosin change the free fractions of diazepam, propranolol, trichlormethiazide, and chlormadinon. Diclofenac and warfarin, however, may increase the elimination rate of Tamsulosin. Concomitant administration of Tamsulosin with strong inhibitors of CYP3A4 may lead to increased exposure to Tamsulosin.
Concomitant administration with ketoconazole (a known strong CYP3A4 inhibitor) resulted in an increase in AUC and Cmax of Tamsulosin by a factor of 2.8 and 2.2, respectively.
Tamsulosin should not be given in combination with strong inhibitors of CYP3A4 in patients that are poor metaboliser CYP2D6 phenotype.
Tamsulosin should be used with caution in combination with strong and moderate inhibitors of CYP3A4.
Concomitant administration of Tamsulosin with paroxetine, a strong inhibitor of CYP2D6, resulted in a Cmax and AUC of Tamsulosin that had increased by a factor of 1.3 and 1.6, respectively, but these increases are not considered clinically relevant.
There is a theoretical risk of enhanced hypotensive effect when given concomitantly with drugs which may reduce blood pressure, including anaesthetic agents and other alpha1-adrenoreceptors antagonists.

Store at temperatures not exceeding 30°C.

Drugs for Bladder & Prostate Disorders

G04CA02 - tamsulosin ; Belongs to the class of alpha-adrenoreceptor antagonists. Used in the treatment of benign prostatic hypertrophy.

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