TAMFAST is a film-coated, prolonged release tablet containing 0.4mg Tamsulosin HCl, an a1-adrenoceptor blocking agent. It has a high affinity for the a1A-receptor subtype predominantly present in the human prostate.

The chemical name of Tamsulosin HCl is (R)-5-[2-[[2-(2-ethoxyphenoxy) ethyl] amino] propyl]-2- methoxybenzenesulfonamide, monoHCl. The molecular weight is 444.98. Tamsulosin HCl is sparingly soluble in water (1:85) and slightly soluble in alcohol. It is stable in an acidic environment

Composition

Each film coated tablet of TAMFAST prolonged release tablet contains 0.4mg Tamsulosin HCl

Pharmacology

The tone of the human prostate smooth muscle is maintained primarily by noradrenaline released from adrenergic nerves and stimulating post-junctional a1-adrenoceptors. This provides the rationale for the use of a1-adrenoceptor antagonists for lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH).

Pharmacodynamics

Pharmacological studies have established that Tamsulosin is a selective, potent and competitive a1-adrenoceptor antagonist and that it has a greater affinity for the a1A-receptor subtype, predominantly present in the human prostate. a1-adrenoceptor antagonists generally can reduce blood pressure by lowering peripheral resistance.

The binding of Tamsulosin to a1-adrenoceptors in the prostate results in relaxation of prostate smooth muscle followed by improvements in urodynamics. Thus, Tamsulosin increases maximum urinary flow rate by reducing smooth muscle tension in the prostate and urethra and thereby relieving obstruction. It also improves the symptoms related to bladder instability and tension of the smooth muscle of the lower urinary tract. These effects on urinary storage and voiding symptoms are maintained during long-term therapy. The need for surgery or catheterization is significantly delayed.

Pharmacokinetics

Absorption and distribution

TAMFAST is a prolonged release tablet of Tamsulosin HCl. The TAMFAST formulation provides consistent slow release of Tamsulosin, which is maintained over the whole pH range encountered in the gastro-intestinal tract, resulting in an adequate exposure, with little fluctuation, over 24 hours. Tamsulosin administered as TAMFAST is absorbed from the intestine. Of the administered dose, approximately 55 to 59% is estimated to be absorbed. The rate and extent of absorption of Tamsulosin administered as TAMFAST tablets are only slightly affected by food, but this is unlikely to be clinically significant.

There is a considerable inter-patient variation in the plasma concentrations of Tamsulosin, after both single and multiple dosing. In man, Tamsulosin is about 99% bound to plasma proteins. The volume of distribution is small (about 0.2 l/kg).

Metabolism and Excretion

TAMFAST contains Tamsulosin as the R (-) isomer. In humans, there is no in vivo conversion to the less active S(+) isomer. Tamsulosin has a low first pass effect, being metabolized slowly. Most Tamsulosin is present in plasma in the form of unchanged drug. Tamsulosin is metabolized in the liver, but the specific cytochrome P450 isoenzymes responsible for this metabolism have not have been identified. In rats, Tamsulosin was seen to cause minimal induction of microsomal liver enzymes. No dose adjustment is warranted in hepatic insufficiency.

None of the metabolites is more active than the original precursor compound. Tamsulosin and its metabolites are mainly excreted in the urine. The amount excreted as unchanged drug is estimated to be about 4 - 6% of the dose administered

No dose adjustment is warranted in renal impairment

Indications and Usage

For the relief of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).

Contraindications

  • Hypersensitivity to Tamsulosin or any other component of the product.
  • A history of orthostatic hypotension.
  • Severe hepatic impairment (Child-Pugh scores >9).
  • Severe renal impairment with creatinine clearance of less than 10mL/min.
  • Concurrent use of another a1-adrenoceptor inhibitor.

Warnings

The signs and symptoms of orthostasis (postural hypotension, dizziness and vertigo) were detected more frequently in Tamsulosin -treated patients than in placebo recipients. As with other alpha-adrenergic blocking agents there is a potential risk of syncope.

Patients beginning treatment with Tamsulosin should be cautioned to avoid situations where injury could result should syncope occur.

Rarely (probably less than one in fifty thousand patients), Tamsulosin, like other alpha1 antagonists, has been associated with Priapism (persistent painful penile erection unrelated to sexual activity). Because this condition can lead to permanent impotence if not properly treated, patients must be advised about the seriousness of the condition

Precautions

Syncope and Postural hypotension

Patients beginning treatment with Tamsulosin tablets should be cautioned to avoid situations where injury could result should syncope occur. Postural hypotension can occur during treatment with Tamsulosin, but rarely results in syncope. However, the patient should be warned of this possibility and advised to sit or lie down if symptoms of hypotension should occur.

Exclusion of prostatic carcinoma and other urological conditions

Carcinoma of the prostate and other conditions which can cause the same symptoms as benign prostatic hyperplasia should be excluded before starting therapy with Tamsulosin. Digital rectal examination and, as considered appropriate, determination of prostate specific antigen should be performed before treatment and at regular intervals afterwards.

Myocardial ischaemia

Patients with myocardial infarction or angina pectoris within the preceding six months were excluded from the Phase III clinical studies. As a result, the safety of Tamsulosin in these patients has not been formally assessed.

Dizziness

As Tamsulosin may cause dizziness, patients should be warned to take care whilst operating machinery or driving.

Intra-operative Floppy Iris Syndrome

Intra-operative Floppy Iris Syndrome' (IFIS) has been observed during cataract surgery in some patients taking or who have previously been treated with a1-adrenoceptor antagonists. This variant of small pupil syndrome is characterized by the combination of a flaccid iris that billows in response to intra-operative irrigation currents, progressive intra-operative miosis despite pre-operative dilation with standard mydriatic drugs, and potential prolapse of the iris toward the phaco-emulsification incisions. The patient's ophthalmologist should be prepared for possible modifications to their surgical technique, such as the utilization of iris hooks, iris dilator rings, or visco-elastic substances. There does not appear to be a benefit of stopping a1-adrenoceptor antagonist therapy prior to cataract surgery.

Use in pregnancy

Tamsulosin is intended for use only in males. Tamsulosin, at oral doses causing maternal toxicity, was not embryotoxic or teratogenic when administered during gestation in rats (doses up to 300 mg/kg/day) or rabbits (doses up to 50 mg/kg/day). However, administration of Tamsulosin during the peri-/post-natal period was associated with a higher incidence of stillbirths and reduced pup weight gain after birth. No adverse effects on development or reproductive performance were observed on surviving pups; however, there is some evidence for impairment of offspring reproductive capacity when maternal treatment with Tamsulosin is started before pregnancy.

Use in lactation

Tamsulosin is intended for use only in males. In female rats, Tamsulosin and/or its metabolites were shown to pass into milk after oral administration of the drug during lactation. The effect on the newborn is not known.

Renal impairment

Severe renal impairment, with creatinine clearance of less than 10mL/min. is a CONTRAINDICATION, as these patients have not been studied.

Hepatic impairment

Severe hepatic impairment (Child-Pugh scores >9) is a CONTRAINDICATION.

Interactions with other drugs

Drugs known to interact with Tamsulosin

Concomitant cimetidine leads to a rise in plasma levels of Tamsulosin, while frusemide leads to a fall (about 12% following a single 20mg intravenous dose). However, as levels remain within the normal range, dosage need not be adjusted. Concurrent administration of Tamsulosin with other ?1-adrenoceptor antagonists is contraindicated because of the potential for hypotensive effects

Drugs which may interact with Tamsulosin

Tamsulosin binds extensively to plasma proteins and may displace other protein-bound drugs. Clinical trial data are not available. 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 metabolizing enzyme system), involving amitriptyline, salbutamol, glibenclamide and finasteride. Diclofenac and warfarin, however, may increase the elimination rate of Tamsulosin.

Drugs which do not interact significantly with Tamsulosin

Tamsulosin did not affect the pharmacokinetics of a single intravenous dose of digoxin 0.5mg. No interactions have been seen when Tamsulosin was given concomitantly with either atenolol, enalapril, nifedipine or theophylline.

General

Limited clinical data are available on interactions between Tamsulosin and other drugs. Tamsulosin is metabolized in the liver, and may be expected to interact with other hepatically-metabolised drugs. However, the specific cytochrome P450 isoenzymes responsible for Tamsulosin metabolism have not been identified. Tamsulosin should therefore be used with caution in patients who are taking other drugs, particularly those which undergo hepatic metabolism.

Other in vitro findings

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.

An in vitro study using human liver microsomal fractions showed no effect of amitriptyline, salbutamol, glibenclamide and finasteride on the rate of disappearance of Tamsulosin. The clinical relevance of these findings is uncertain.

Side Effects & Adverse Reactions

Priapism

Rarely, Tamsulosin, like other alpha-1 antagonists, has been associated with priapism (persistent painful penile erection unrelated to sexual activity). Patients should be informed that this reaction is extremely rare, but if not brought to immediate medical attention, can lead to permanent erectile dysfunction.

Abnormal ejaculation

Patients should be advised on the potential for abnormal ejaculation to occur upon commencement of Tamsulosin treatment. Retrograde ejaculation is the most commonly reported abnormal ejaculation event associated with the use of Tamsulosin

Cardiac disorders

Uncommon: palpitations.

Gastro-intestinal disorders

Uncommon: constipation, diarrhea, nausea, vomiting.

General disorders

Uncommon: asthenia.

Nervous system disorders

Common: dizziness (1.3%). Uncommon: headache. Rare: syncope.

Reproductive system 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 variant of small pupil syndrome known as Intra-operative Floppy Iris Syndrome (IFIS) has been reported during post-marketing surveillance in association with a1-adrenoceptor antagonist therapy)

Dosage and Administration

One tablet daily. The tablet must be swallowed whole and not be broken, crunched or chewed, as this compromises the prolonged release properties of the tablet for the active ingredient. TAMFAST can be taken on an empty stomach, or before, with or after food.

Overdosage

Acute overdose with 5 mg Tamsulosin has been reported. Acute hypotension (systolic blood pressure 70 mm Hg), vomiting and diarrhea were observed, which were treated with fluid replacement and the patient could be discharged the same day.

If acute hypotension occurs after overdosage, cardiovascular support should be given and maintained. Blood pressure can be restored and heart rate brought back to normal by lying the patient down. If this is insufficient then volume expanders and, when necessary, vasopressors could be administered. 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 to impede absorption, such as emesis, can be taken. When large quantities of Tamsulosin are involved, gastric lavage can be applied and activated charcoal and an osmotic laxative, such as sodium sulphate, can be administered.

TAMFAST is a sustained release formulation. The signs and symptoms of overdose may be delayed or prolonged from the time of ingestion.

Storage

Store in a cool, dry place. Protect from light and moisture

Presentation

TAMFAST is a film-coated, prolonged release tablet containing 0.4mg of Tamsulosin HCl supplied in aluminum foil blister strips of 10 tablets and 20 such strips in a box.