PHARMACEUTICAL FORM
Each prolonged release film-coated tablet contains 0.4 mg tamsulosin hydrochloride.
Approximately 9 mm in diameter, round, bi-convex, yellow, film-coated and debossed with the code '04'.
INDICATIONS
Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).
CONTRA-INDICATIONS
Hypersensitivity to tamsulosin hydrochloride including drug-induced angiodema or to any of the excipients. A history of orthostatic hypotension.
Severe hepatic insufficiency.
SPECIAL WARNINGS AND SPECIAL PRECAUTIONS FOR USE
As with other alpha-1 adrenoceptor antagonists, a reduction in blood pressure can occur in individual cases during treatment with Harnal® OCAS 0.4 mg, 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 therapy with Harnal® OCAS 0.4 mg 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.
Intraoperative Floppy Iris Syndrome (IFIS, a variant of small pupil syndrome) considered to be due to alpha1 blocking action has been observed during cataract surgery in some patients on or previously treated with tamsulosin. Ophthalmologists should be aware of possible occurrence of IFIS during cataract surgery. The initiation of therapy with tamsulosin in patients for whom cataract surgery is scheduled is not recommended.
It is possible that a remnant of the tablet is observed in the faeces.
INTERACTION WITH OTHER MEDICAL PRODUCTS AND OTHER FORMS OF INTERACTION
Interaction studies have only been performed in adults. No interactions have been seen when tamsulosin hydrochloride was given concomitantly with either atenolol, enalapril, nifedipine or theophylline.
Concomitant cimetidine brings about a rise in plasma levels of tamsulosin, while 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.
No interactions at the level of hepatic metabolism have been seen during in vitro studies with liver microsomal fractions (representative of the cytochrome P450-linked drug metabolising enzyme system), involving amitriptyline, 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.
PREGNANCY AND LACTATION
Not applicable, as Harnal® OCAS 0.4 mg is intended for male patients only.
However, patients should be aware of the fact that dizziness, drowsiness, blurred vision and syncope can occur.
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 dizziness, drowsiness, blurred vision and syncope can occur.
UNDESIRABLE EFFECTS
| MedDRA system organ class | Common (›1%, ‹10%) | Uncommon (›0.1%, ‹1%) | Rare (›0.01%, ‹0.1%) | Very rare (‹0.01%) |
Cardiac disorders
| Palpitations | |||
| Gastro-intestinal disorders | Constipation, diarrhoea, nausea, vomiting | |||
| General disorders and administration site conditions | Asthenia | |||
| Nervous systems disorders | Dizziness (1.3%) | Headache | Syncope | |
| Reproductive system and breast disorders | Abnormal ejaculation | Priapism | ||
| Respiratory, thoracic and mediastinal disorders | Rhinitis | |||
| Skin and subcutaneous tissue disorders | Rash, pruritus, urticaria | Angioedema | ||
| Vascular disorders | Postural hypotension |
During cataract surgery a small pupil situation, known as Intraoperative Floppy Iris Syndrome (IFIS). has been reported during post-marketing surveillance.
As with other alpha-blockers, drowsiness and blurred vision can occur.
OVERDOSE
Acute overdose with 5mg of tamsulosin hydrochloride has been reported. Acute hypotension [systolic blood pressure 70 mmHg), vomiting and diarrhoea were observed, which were treated with fluid replacement and the patient could be discharged the same day.
In case of acute hypotension occurring after overdosage cardiovascular support should be given. Blood pressure can be restored and heart rate brought back to normal by lying the patient down. If this does not help then volume expanders and, when necessary, vasopressors could be employed. Renal function should be monitored and general supportive measures applied.
Dialysis is unlikely to be of help as tamsulosin is very highly bound to plasma proteins.
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 sulphate, can be administered.
POSOLOGY AND METHOD OF ADMINISTRATION
One tablet daily.
Harnal® OCAS 0.4 mg 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.
PHARMACODYNAMIC PROPERTIES
- Pharmacotherapeutic group; α1-adrenoceptor antagonists.
- Mechanism of action; Tamsulosin binds selectively and competitively to the postsynaptic α1-adrenoceptors, in particular to subtypes a 1A and a 1D. It brings about relaxation of prostatic and urethral smooth muscle.
- Pharmacodynamic effects; Harnal® OCAS 0.4 mg increases the maximum urinary flow rate. It relieves obstruction by relaxing smooth muscle in prostate and urethra thereby improving voiding symptoms.
These effects on storage and voiding symptoms are maintained during long-term therapy. The need for surgery or catheterisation is significantly delayed.
α1-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 0.4 mg.
PHARMACOKINETIC PROPERTIES
1) Absorption
Harnal® OCAS 0.4 mg 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 hours.
Tamsulosin administered as Harnal® OCAS 0.4 mg 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 0.4 mg are not affected by food.
Tamsulosin shows linear pharmacokinetics.
After a single dose of Harnal® OCAS 0.4 mg in the fasted state, plasma concentrations of tamsulosin
peak at a median time of 6 hours. In steady state, which is reached by day 4 of multiple dosing, plasma concentrations of tamsulosin peak at 4 to 6 hours, in the fasted and fed state. Peak plasma concentrations increase from approximately 6 ng/ml after the first 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 lasted and fed conditions.
There is a considerable inter-patient variation in plasma levels both alter single and multiple dosing.
2) Distribution
In man, tamsulosin is about 99% bound to plasma proteins. The volume of distribution is small (about 0.2 l/kg).
3) 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.
No dose adjustment is warranted in hepatic insufficiency.
None of the metabolites is more active than the original compound.
4) 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 0.4 mg.
After a single dose of Harnal® OCAS 0.4 mg and in steady state, elimination half-lives of about 19 and 15 hours, respectively, have been measured.
No dose adjustment is warranted in renal impairment.
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 viva 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-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.
PACKAGING
Harnal® OCAS 0.4 mg Tablet:
3 blisters x 10 tablets
Store below 30°C
Shelf Life: 3 years
"Harus dengan resep dokter"
Reg. No.: DKI1120100414A1
Manufactured by:
ASTELLAS PHARMA EUROPE B.V.
THE NETHERLANDS
Imported by:
PT Combiphar, Bandung, Indonesia
0 Komentar
Penulisan markup di komentar