Distal Ureteral Calculi: Recommended Dose: 0.4 mg once daily after meals. For patients who fail to pass calculi confirmed by X-ray (KUB) observation after the treatment for 4-weeks, consultation with specialist physician should be considered.

Children: There is no relevant indication for use of Harnal OCAS 0.4 mg tablets in children.

Renal Impariment: No dose adjustment is warranted in renal impairment and in patients with mild to moderate hepatic insufficiency.

Administration: Harnal OCAS 0.4 mg tablets can be taken independently of food. The tablet must be swallowed whole and not be crunched or chewed as this interferes with the prolonged release of the active substance.

As with other α1-adrenoceptor antagonists, a reduction in blood pressure can occur in individual cases during treatment with Harnal/OCAS, 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.

Harnal/OCAS does not eliminate the cause of benign prostatic hyperplasia, but gives symptomatic relief. If the expected response does not result, surgical therapy or other alternative procedures should be considered.

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.

Before the start of treatment, patients should be asked whether they are taking any antihypertensive drugs. If any such drugs are used, blood pressure during treatment should be monitored closely. If a decrease in blood pressure is observed, the treatment should be discontinued or other appropriate measures taken.

Intraoperative floppy iris syndrome (IFIS, a variant of small pupil syndrome) considered to be due to α1-blocking action has been observed during cataract surgery in some patients on or previously treated with tamsulosin. Ophthalmologist should be aware of possible occurrence of IFIS during cataract surgery.

Effects on the Ability to Drive or Operate Machinery: Since Harnal/OCAS may produce dizziness, patients should be cautioned against performing hazardous activities eg, working at altitudes or driving a car.

Use in pregnancy & lactation: Not applicable, as Harnal/OCAS is intended for male patients only.

Safety in female patients has not been established. In the patient with distal ureteral calculi, Harnal/OCAS should be used in male patients.

Gastrointestinal disorders: Uncommon: Constipation, diarrhoea, nausea, vomiting.

General Disorders and Administration Site Conditions: Uncommon: Asthenia.

Nervous System Disorders: Common: Dizziness (1.3%). Uncommon: Headache. Rare: Syncope.

Reproductive System and Breast Disorders: Uncommon: Abnormal ejaculation. Very Rare: Priapism.

Respiratory, Thoracic and Mediastinal Disorders: Uncommon: Rhinitis.

Skin and Subcutaneous Tissue Disorders: Uncommon: Rash, pruritus, urticaria. Rare: Angioedema.

Vascular Disorders: Uncommon: Postural hypotension.

During cataract surgery, a small pupil situation known as Intraoperative Floppy Iris Syndrome (IFIS) has been reported during post-marketing surveillance (see Precautions).

In vitro, neither diazepam nor propranolol, trichlomethiazide, 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.

No interactions at the level of hepatic metabolism have been seen during in vitro studies with liver microsomal fractions (representative of the cytochrome P-450-linked drug metabolising enzyme system), involving amitryptyline, salbutamol, glibenclamide and finasteride. Diclofenac and warfarin, however, may increase the elimination rate of tamsulosin.

Concurrent administration of other α1-adrenoceptor antagonists could lead to hypotensive effects.

Incompatibilities: Not applicable.

Pharmacology: Mechanism of Action: Tamsulosin binds selectively and competitively to the post-synaptic α1-adrenoceptors, in particular to subtypes α1A and α1D. It brings about the relaxation of prostatic and urethral smooth muscle.

Pharmacodynamic Effects: Harnal/OCAS 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 catheterisation is significantly delayed.

Alpha1-adrenoceptor antagonists can reduce blood pressure by lowering peripheral resistance. No reduction in blood pressure of any clinical significance was observed during studies with Harnal/OCAS.

Pharmacokinetics: Absorption: Harnal OCAS is a prolonged-release tablet of the non-ionic gel matrix type. The OCAS formulation provides consistent slow release of tamsulosin, resulting in an adequate exposure, with little fluctuation, over 24 hrs.

Tamsulosin administered as Harnal OCAS is absorbed from the intestine, of the administered dose, approximately 57% is estimated to be absorbed.

The rate and extent of absorption of tamsulosin administered as Harnal OCAS are not affected by food.

Tamsulosin shows linear pharmacokinetics.

After a single dose of Harnal OCAS in the fasted state, plasma concentrations of tamsulosin peak at a median time of 6 hrs. In steady state, which is reached by day 4 of multiple dosing, plasma concentrations of tamsulosin peak at 4-6 hrs in the fasted and fed state. Peak plasma concentrations increase from approximately 6 ng/mL after the 1st dose to 11 ng/mL in steady state.

As a result of the prolonged-release characteristics of Harnal OCAS, the trough concentration of tamsulosin in plasma amounts to 40% of the peak plasma concentration under fasted and fed conditions.

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. The volume of distribution is small (about 0.2 L/kg).

Metabolism: Tamsulosin has a low first-pass effect, being metabolised slowly. Most tamsulosin is present in plasma in the form of unchanged active substance. 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 is more active than the original compound.

Excretion: Tamsulosin and its metabolites are mainly excreted in the urine. The amount excreted as unchanged active substance is estimated to be about 4-6% of the dose, administered as Harnal OCAS.

After a single dose of Harnal OCAS and in steady state, elimination half-lives (t1/2) of about 19 and 15 hrs, respectively, have been measured.

Toxicolgy: Preclinical Safety Data: 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 α1-adrenoceptor 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.