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Urology
Tamflo

TAMFLO

The active ingredient of TAMFLO is Tamsulosin Hydrochloride, a α1-adrenoceptor blocking agent.

PRESENTATION

Each capsules contains 0.4 mg Tamsulosin Hydrochloride.
Pack size: 10*10 Blisters.

CLINICAL PHARMACOLOGY

PHARMACODYNAMIC PROPERTIES

 

  • Mechanism of Action

    The tone of the human prostate smooth muscle is maintained primarily by Noradrenaline released from adrenergic nerves and stimulating post-junctional α1-Adrenoceptors. This provides the rationale for the use of α1-Adrenoceptor antagonists for lower urinary tract symptoms associated with Benign Prostatic Hyperplasia (BPH).
    Pharmacological studies have established that Tamsulosin is a selective, potent and competitive α1- Adrenoceptor antagonist and that it has a greater affinity for the α1a-receptor subtype, predominantly present in the human prostate. α1-adrenoceptor antagonists generally can reduce blood pressure by lowering peripheral resistance. The binding of Tamsulosin to α1-Adrenoceptors in the prostate results in relaxation of prostate smooth muscle followed by improvements in urodynamic. 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.

 

PHARMACOKINETIC PROPERTIES

 

  • Absorption

    Tamsulosin is a prolonged release tablet of the non-ionic gel matrix type. The Tamsulosin 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 Tamsulosin 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 Hydrochloride administered as Tamsulosin tablets are only slightly affected by food, but this is unlikely to be clinically significant.
    Tamsulosin Hydrochloride administered as Tamsulosin tablets exhibits near linear pharmacokinetics (plasma concentrations Cmax and AUC vs. dose) over the dosage range 0.4 mg through 0.8 mg to 1.2 mg once daily. Steady state is reached by day 4 of multiple dosing. The pharmacokinetics of a 400 µg once daily dose of Tamsulosin hydrochloride as tablets. As a result of the prolonged release characteristic of, the trough concentrations – at steady state, of Tamsulosin hydrochloride in plasma amount to approximately 40% of the peak plasma concentrations, under fasted and fed conditions.
    There is a considerable inter-patient variation in the plasma concentrations of Tamsulosin Hydrochloride, after both 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

    There is a considerable inter-patient variation in the plasma concentrations of Tamsulosin Hydrochloride, after both single and multiple dosing.
    Tamsulosin 400µg 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. In vitro results suggest that CYP3A4 and also CYP2D6 are involved in metabolism, with possible minor contributions to Tamsulosin metabolism by other CYP isozymes.
    Inhibition of Hepatic drug metabolizing enzymes may lead to increased exposure to Tamsulosin 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.

  • Excretion

    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 as Tamsulosin. No dose adjustment is warranted in Renal Impairment.

 

DRUG-DRUG INTERACTION

 

  • Drugs known to interact with Tamsulosin

    Concomitant Cimetidine leads to a rise in plasma levels of Tamsulosin, while Furosemide leads to a fall (about 12% following a single 20 mg intravenous dose). However, as levels remain within the normal range, dosage need not be adjusted. Concurrent administration of Tamsulosin with other α1-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 0.5 mg. No interactions have been seen when Tamsulosin Hydrochloride was given concomitantly with either Atenolol, Enalapril, Nifedipine or Theophylline.

 

THERAPEUTIC INDICATIONS

For the relief of Lower Urinary Tract Symptoms (LUTS) associated with Benign Prostatic Hyperplasia (BPH).

DOSAGE AND METHOD OF 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. Tamsulosin can be taken on an empty stomach, or before, with or after food.

SIDE- EFFECTS

Common

  • Retrograde Ejaculation

    When this happens the ejaculation fluid is not squirted out, most of it runs back into the bladder. Retrograde ejaculation is painless.

  • Dizziness

 

Uncommon

  • Headache
  • Skin rash (red spots or patches), itching, and hives.
  • Weakness
  • Dizziness on standing
  • Nausea, vomiting, diarrhoea, constipation
  • Fast heart beats
  • Blocked nose

 

Rare

  • Faintness

 

SPECIAL WARNINGS AND PRECAUTIONS FOR USE

 

  • 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.

  • Myocardial Ischemia

    Patients with myocardial infarction or angina pectoris within the preceding six months were excluded from the Phase III clinical studies. Dizziness: 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 and glaucoma surgery in some patients taking or who have previously been treated with α1-adrenoceptor antagonists, including Tamsulosin.

  • Sulfa Allergy

    Cases of allergic reaction to Tamsulosin in patients with a past history of sulphonamide allergy have been reported. If a patient reports a sulfa allergy, caution is warranted when administering

  • Use in Hepatic Impairment

    Since the type of formulation will not affect the disposition of Tamsulosin no dose adjustment for is expected in patients with mild to moderate hepatic impairment. Severe hepatic impairment

  • Use in Renal Impairment

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

  • Pediatrics use is not indicated for use in children.
  • Effects on Fertility

    The no effect dose on male rat fertility was associated with plasma Tamsulosin levels (AUC) at least 50% of those expected in human males treated with Tamsulosin.

  • Use in Pregnancy

    Pregnancy Category B2 Tamsulosin is intended for use only in males, there is some evidence for impairment of offspring reproductive capacity when maternal treatment with Tamsulosin is started before pregnancy.

  • Use in Lactation

    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.

 

CONTRAINDICATIONS

  • Hypersensitivity, including drug-induced Angioedema, to Tamsulosin Hydrochloride 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 1-adrenoceptor inhibitor.