Prostulax

Each prolonged-release capsule contains Tamsulosin Hydrochloride BP 400 mcg (as modified-release pellets).
Tamsulosin, a selective alpha-1A adrenoceptor blocking agent, exhibits selectivity for alpha-1A receptors in the human prostate. At least, three discrete alpha-1 adrenoceptor subtypes have been identified: alpha-1A, Alpha-1B and alpha-1D; their distribution differs between human organs and tissues. Approximately 70% of the alpha-1 receptors in human prostate are of the alpha-1A subtype.

Alpha-1-Adrenoceptor Antagonist.
Pharmacology: Mechanism of Action: Tamsulosin binds selectively and competitively to postsynaptic alpha 1-receptors, in particular to the subtype alpha 1A, which bring about relaxation of the smooth muscle of the prostate, whereby tension is reduced.
Pharmacodynamic Effects: Prostulax (Tamsulosin HCl) increases maximum urinary flow rate by reducing smooth muscle tension in prostate and urethra and 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. Alpha 1-blockers can reduce blood pressure by lowering peripheral resistance.
Pharmacokinetics: Absorption: 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 Tamsulosin Hydrochloride after the same meal each day. Tamsulosin shows linear kinetics. After single dose of Prostulax (Tamsulosin HCl) 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. C_max in patients is about two third higher that reached after 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.
Distribution: In man, Tamsulosin is about 99% bound to plasma proteins and volume of distribution is small (about 0.21/kg).
Biotransformation: Tamsulosin and its metabolites have a low first pass effect, being metabolized slowly. Most Tamsulosin is present in plasma in the form of unchanged drug. It is metabolized in the liver. No dose adjustment is warranted in hepatic insufficiency. None of the metabolites are more active than the original compound.
Elimination: Tamsulosin and its metabolites are mainly excreted in the urine with about 9% of a dose being present in the form of unchanged drug. After as single dose of Prostulax (Tamsulosin HCl) in the fed state, and in the steady state in patients, elimination half-lives of about 10 and 13 hours respectively have been measured. The presence of renal impairment does not warrant lowering the dose.

Treatment of functional symptoms of benign prostatic hyperplasia (BPH).

For oral use. One capsule daily, to be taken after breakfast or the first meal of the day. The capsule must be swallowed whole and must not be crunched or chewed as this interferes with the prolonged release of the active substance.
Pediatric population: The safety and efficacy of tamsulosin in children <18 years have not been established.
Use in renal impairment: No dose adjustment is warranted in patients with mild to moderate hepatic insufficiency.

If overdose of Tamsulosin HCl 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 this 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 HCl is 94% to 99% protein bound; therefore, dialysis is unlikely to be of benefit. One patient reported an overdose of thirty 0.4 mg Tamsulosin HCl capsules. Following the ingestion of the capsules, the patient reported a severe headache. Measures, such as emesis can be taken to impede absorption. When large quantities are involved, gastric lavage can be applied and activated charcoal and an osmotic laxative, such as sodium sulfate, can be administered.

Hypersensitivity to tamsulosin, including drug-induced angioedema, or to any of the excipients.
History of orthostatic hypotension.
Severe hepatic insufficiency.

As with other Alpha-1 adrenoceptor antagonists, a reduction in blood pressure can occur individual cases during treatment with tamsulosin as a result of which, rarely, syncope can occur. At the first signs of orthostatic hypotension (dizziness, weakness), the patient should sit or lie down until the symptoms have disappeared. Before the therapy with tamsulosin is initiated, the patient should be examined in order to exclude the presence of other conditions, which can cause the same symptoms as benign prostatic hyperplasia.
Digital rectal examination and, when necessary, determination of prostate specific antigen (PSA) should be performed before treatment and at regular intervals afterwards. The treatment of patients with severe renal impairment (creatinine clearance of <10 mL/min) should be approached with caution, as these patients have not been studied. Angioedema has been rarely reported after the use of tamsulosin. Treatment should be discontinued immediately, patient should be monitored until disappearance of the edema, and tamsulosin should not be re-administered. The "Intraoperative Floppy Iris Syndrome" (IFIS, a variant of small pupil syndrome) has been observed during cataract 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 for whom cataract surgery is not recommended.
Discontinuing tamsulosin 1-2 weeks prior to cataract surgery is anecdotally considered helpful, but the benefit and duration of stopping of therapy prior to cataract surgery has not yet been established. During pre-operative assessment, cataract surgeons and ophthalmic teams should consider whether patients scheduled for cataract 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.

Prostulax 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.

Interaction studies have only been performed in adults. No interactions have been seen when tamsulosin was given concomitantly with atenolol, enalapril, nifedipine or theophylline. Concomitant cimetidine brings about a rise in plasma levels of tamsulosin, whereas furosemide a fall, but as levels remain within the normal range posology need not be adjusted. In vitro, neither diazepam nor propranolol, trichlormethiazide, chlormadinone, amitriptyline, 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 chlormadinone. Diclofenac and warfarin, however, may increase the elimination rate of tamsulosin. Concomitant administration of tamsulosin hydrochloride with strong inhibitors of CYP3A4 in patients with poor metabolizer CYP2D6 phenotype. Tamsulosin hydrochloride should be used with caution in combination with strong and moderate inhibitors of CYP3A4. Concomitant administration of tamsulosin hydrochloride 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. Concurrent administration of other α1-adrenoceptor antagonist could lead to hypotensive effects.

Store at temperatures not exceeding 30°C. Protect from light and moisture.

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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