Harnal® D 0.2 mg Tablet
DESCRIPTION
Tamsulosin hydrochloride is a white crystal. It is freely soluble in formic acid, sparingly soluble in water, slightly soluble in acetic acid (100), and very slightly soluble in ethanol (99.5)
PHARMACOLOGY
| 1 | Pharmacological Effects | ||||
| (1) | Effects in humans In a receptor binding assay using human prostate preparations, tamsulosin hydrochloride was 2.2 times more potent than prazosin hydrochloride and 40 times more so than phentolamine mesylate in α1-receptor blocking activity. | ||||
| (2) | Effects in animals | ||||
| 1) | Blockade of α-adrenergic receptors In a receptor binding assay using isolated rat cerebral membrane and an in vitro experiment using isolated rabbit aorta, tamsulosin hydrochloride inhibited α1-receptors selectively and competitively. Its action was 1/2.2 to 22 times more potent than prazosin hydrochloride and 45 to 140 times more potent than phentolamine mesylate. In vitro experiments using isolated rabbit aorta, isolated rat vas deferens and isolated guinea pig intestine, tamsulosin hydrochloride proved to be 5,400 to 24,000 times more selective for α1-receptors than for α2-receptors. | ||||
| 2) | Effect on the lower urinary tract (urethra and urinary bladder) and prostate In a receptor binding assay using isolated smooth muscle from the rabbit urethra, prostate and urinary bladder base, tamsulosin hydrochloride was 23 to 98 times more potent than prazosin hydrochloride in α1-receptor blocking activity, and 87 to 320 times more potent than phentolamine mesylate. In anesthetized dogs, the drug inhibited the α1-agonist (phenylephrine)-induced increase in intrauretheral pressure with 13 times greater potency than the increase in diastolic blood pressure. | ||||
| 3) | Improvement of bladder outlet obstruction In anesthetized male dogs, tamsulosin hydrochloride decreased urethral pressure in the prostatic zone of the intraurethral pressure curve. In anesthetized rats, however, the drug did not affect rhythmic bladder contraction or threshold intravesical pressure. | ||||
| 2. | Mechanism of action Tamsulosin hydrochloride decreases urethral pressure in the prostatic zone of the intraurethral pressure curve by inhibiting α1-receptors in the urethra and prostate, thus improving bladder outlet obstruction associated with benign prostatic hyperplasia. | ||||
PHARMACOKINETICS
Metabolism and excretion
Single doses of Tamsulosin hydrochloride at 0.1 to 0.6 mg were orally administered to healthy male adults. The excretion rate of the unchanged drug in the urine up to 30 h after administration remained almost constant at 12 to 14%. No significant changes in the excretion rate after repeated administrations were observed.
INDICATIONS
Bladder outlet disturbance associated with benign prostatic hyperplasia.
CONTRA-INDICATIONS
Harnal® D Tablet are contraindicated in the following patients:
- Patients with a history of hypersensitive reactions to this drug.
- Patients who take vardenafil HCl hydrate (See "Drug Interactions")
- Severe hepatic insufficiency
- Severe impaired renal function (An excessive increase in plasma drug concentration may be induced in patients with impaired renal function, but complete pharmacokinetic data in such patients are not yet available. Therefore, patients with severe impaired renal function should not use this drug.)
PRECAUTIONS
- Careful Administration (Harnal® D Tablet should be administered with caution in the following patients.)
- Patients with orthostatic hypotension [Symptoms may be exacerbated.]
- Patients with hepatic dysfunctions [Plasma drug concentrations may be increased.]
- Patients with mild to moderate renal dysfunction [An increase in plasma drug concentrations may result.]
- The elderly patients [See "Geriatric Use"]
- Important Precautions
- The tablets disintegrate in the mouth, but are not absorbed through the oral mucosa. Therefore, the patients should be instructed to swallow the dissolved tablet with saliva or a drink of water.
- Use with caution concerning dosage and administration. Overdosage may cause a decrease in blood pressure.
- Blood pressure in the orthostatic position may decrease. Patients must be watched for any changes in blood pressure occurring with postural change.
- The drug does not eliminate the cause of the disease, but gives symptomatic relief. If the expected response does not result, surgical therapy or other alternative procedures should be considered.
- Since the drug may produce dizziness, patients should be cautioned about driving, operating machinery or performing hazardous tasks.
- Before the start 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 dose should be reduced, the treatment discontinued, or other appropriate measures taken.
- Intraoperative Floppy Iris Syndrome (IFIS, a variant of small pupil syndrome) considered to be due to alpha-1 blocking action has been observed during cataract surgery in some patients on or previously treated with tamsulosin. Opthalmologist should be aware of possible occurrence of IFIS during cataract surgery.
- Use in patients with micturition syncope is not advised
- Geriatric Use; The elderly are more likely to have a renal dysfunction. Such patients should be carefully monitored. If efficacy is not noted at 0.2 mg, the dose should not be increased further, and other appropriate measures must be taken.
- Cautions in Use
- Caution in dispensing: Patients should be instructed to press the tablet out of a press-through package (PTP) and take it. [It has been reported that, if the PTP sheet is swallowed, the sharp corners of the sheet may puncture the esophageal mucosa, resulting in severe complications such as mediastinitis.]
- Caution in oral administration:
- Patients should be instructed not to chew the Harnal® D Tablet. [Prolonged release particles of tamsulosin hydrochloride are contained in the tablets. Crushing or chewing the tablets may destroy the prolonged release particles and may cause changes in pharmacokinetics.]
- The tablets can be soaked in saliva on the tongue, lightly mashed between the tongue and hard palate, and then swallowed with saliva alone.
- The tablets should not be taken without water if the patient is lying down.
ADVERSE REACTIONS
Adverse reactions (including abnormal clinical laboratory values) appeared in 104 cases (2.2%) out of 4,724 used for the analysis of safety at the time of approval and during post-marketing surveillance for Harnal® Capsules. The most frequently observed adverse reactions were dizziness and stomach discomfort (at the end of the Harnal® Capsules reexamination period).
- Clinically significant adverse reactions
- Syncope unconsciousness (Incidence unknown): As transient unconsciousnesses or etc. may appear with the decrease of blood pressure, the patient should be observed carefully. If such reactions are observed during treatment, discontinue treatment and institute appropriate medical therapy.
- Hepatic dysfunction or jaundice (Incidence unknown): As increases of AST (GOT), AL T (GPT), or jaundice may appear, the patient should be observed carefully. If such reactions are observed during treatment, appropriate measures such as drug discontinuation should be taken.
- Other adverse reactions
5% ≥ 0.1%
|
‹ 0.1%
|
Incidence unknown
| |
| Nervous system/ Psychiatric | Dizziness Giddiness | Dizziness on standing up, headache, sleepiness | Nervousness |
| Cardiovascular | Blood pressure dropped, orthostatic hypotension. tachycardia, palpitation | Arrhythmia | |
| Hypersensitivity* | Itching, rash | Urticaria | |
| Gastrointestinal | Stomach discomfort | Nausea/vomiting, dipsosis, obstipation, stomach heaviness, stomachache. appetite decreased, diarrhea, dysphagia | |
| Others | Nasal obstruction, edema, urinary incontinence, burning sensation of pharynx, generalized fatigue | Dysgeusia, gynaecomastia, priapism Intraoperative Floppy Iris Syndrome (IFIS)** |
** During cataract surgery, a variant of small pupil syndrome known as Intraoperative Floppy Iris Syndrome (IFIS) has been reported (see Important Precautions).
DRUG INTERACTIONS
[Contraindications for co-administration] (Harnal® D Tablet should not be co-administered with the following drugs.)
| Drugs | Signs, Symptoms, and Treatment | Mechanism and Risk Factors |
| Vardenafil HCl hydrate | It has been reported that concomitant use of vardenafil HCl hydrate and Tamsulosin Hydrochloride may cause hypotension or orthostatic hypotension. | Since Tamsulosin Hydrochloride exhibits an α-blocking activity, the vasodilatory hypotensive action of vardenafil HCl hydrate may be enhanced by concomitant use. |
[Precautions for coadministration] (Harnal® D Tablet should be administered with care when coadministered with the following drugs.)
| Drugs | Signs, Symptoms, and Treatment | Mechanism and Risk Factors |
| Antihypertensives | Take precautions by decreasing doses as orthostatic hypotension may occur. | Patients who take antihypertensives may experience a decrease in blood pressure when they stand up. |
| Sildenafil citrate | It has been reported that concomitant use of sildenafil citrate and other α-blockers may cause hypotension accompanied by subjective symptoms such as dizziness. | Since Tamsulosin Hydrochloride exhibits an α-blocking activity, the vasodilatory hypotensive action of sildenafil citrate may be enhanced by concomitant use. |
OVERDOSE
No cases of acute overdosage have been reported. However, acute hypotension is likely to occur after overdosage in which case cardiovascular support should be given. Blood pressure can be restored and the heart rate brought back to normal by lying the patient down.
If this does not help then volume expanders. when necessary, vasopressors could be employed. Renal function should be monitored and general supportive measures applied. Dialysis is unlikely to be 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 administrative.
DOSAGE AND ADMINISTRATION
The usual adult dosage for oral use is 0.2 mg - 0.4 mg of tamsulosin hydrochloride once daily after meals.
The dosage may be adjusted depending on the patient's age and symptoms.
PHYSICOCHEMISTRY
Nonproprietary name:
Tamsulosin hydrochloride
Chemical name:
(-)-(R)-5-[2-[[2-(o-ethoxyphenoxy)ethyl]amino]propyl]-2-methoxybenzenesulfonamide hydrochloride
Molecular formula:
C20H28N2O5S HCl Molecular weight: 444.97
Melting point:
About 230°C (decomposition)
Structural formula:
PACKAGING
Harnal® D Tablet:
Box of 2 x 14 Tablets
Store below 30°C
"Harus dengan resep dokter"
Reg. No.: DKI0829000281A1
Manufactured by:
Astellas Tokai Co., Ltd. Shizuoka, Japan
Licenced from:
Astellas Pharma Inc., Tokyo, Japan
Packed by: Interthai Pharmaceutical Manufacturing Ltd., Bangkok, Thailand
Imported by: P.T. Astellas Pharma Indonesia, Jakarta, Indonesia
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