Tamsulosin Hydrochloride 400mcg Modified-Release Capsules Taj Pharma

  1. Name of the medicinal product

Tamsulosin Hydrochloride 400mcg Modified-Release Capsules Taj Pharma

  1. Qualitative and quantitative composition

Each hard modified-release capsule contains:
Tamsulosin Hydrochloride USP          400mcg
Excipients                                                 q.s.

  1. Pharmaceutical form

Modified-release capsule, hard.

Orange body/olive-green cap. The capsules contain white to off-white spheres.

  1. Clinical particulars

4.1 Therapeutic indications

Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).

4.2 Posology and method of administration

Posology

One capsule a day to be taken after breakfast or the first meal of the day.

Patients with renal impairment

No dose adjustment is warranted in renal impairment.

Patients with hepatic impairment

No dose adjustment is warranted in patients with mild to moderate hepatic insufficiency (see also section 4.3, Contraindications).

Paediatric population

The safety and efficacy of tamsulosin in children < 18 years have not been established. Currently available data are described in section 5.1.

Method of administration

For oral use.

The capsule must be swallowed whole and must not be crunched or chewed as this interferes with the modified release of the active ingredient.

4.3 Contraindications

  • Hypersensitivity to the active substance, including drug-induced angioedema, or to any of the excipients listed in section 6.1.
  • A history of orthostatic hypotension.
  • Severe hepatic insufficiency.

4.4 Special warnings and precautions for use

As with other α1-adrenoceptor antagonists, a reduction in blood pressure can occur in individual cases during treatment with tamsulosin, 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 tamsulosin 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 severely renal impaired patients (creatinine clearance of <10 ml/min) should be approached with caution as these patients have not been studied.

Angioedema has been rarely reported after the use of tamsulosin. Treatment should be discontinued immediately, the patient should be monitored until disappearance of the oedema, and tamsulosin should not be re-administered.

The ‘Intraoperative Floppy Iris Syndrome’ (IFIS, a variant of small pupil syndrome) has been observed during cataract or glaucoma surgery in some patients on or previously treated with tamsulosin. IFIS may increase the risk of eye complications during and after the operation.

Discontinuing tamsulosin 1-2 weeks prior to cataract or glaucoma surgery is anecdotally considered helpful, but the benefit of treatment discontinuation has not yet been established. IFIS has also been reported in patients who had discontinued tamsulosin for a longer period prior to cataract or glaucoma surgery.

The initiation of therapy with tamsulosin in patients for whom cataract or glaucoma surgery is scheduled is not recommended. During pre-operative assessment, cataract surgeons and ophthalmic teams should consider whether patients scheduled for cataract or glaucoma surgery are being or have been treated with tamsulosin in order to ensure that appropriate measures will be in place to manage the IFIS during surgery.

Tamsulosin should not be given in combination with strong inhibitors of CYP3A4 in patients with poor metaboliser CYP2D6 phenotype.

Tamsulosin should be used with caution in combination with strong and moderate inhibitors of CYP3A4 such as erythromycin (see section 4.5).

4.5 Interaction with other medicinal products and other forms of interaction

Interaction studies have only been performed in adults.

No interactions have been seen when tamsulosin was given concomitantly with either atenolol, enalapril, or theophylline.

Concomitant cimetidine brings about a rise in plasma levels of tamsulosin, whereas 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.

Diclofenac and warfarin may increase the elimination rate of tamsulosin.

Tamsulosin has not been found to interact with amitriptyline, salbutamol, glibenclamide or finasteride during in vitro studies with liver microsomal fractions (representing the cytochrome P450-linked metabolising enzyme system).

Concomitant administration of tamsulosin with strong inhibitors of CYP3A4 may lead to increased exposure to tamsulosin. Concomitant administration with ketoconazole (a known strong CYP3A4 inhibitor) resulted in an increase in AUC and Cmax of tamsulosin by a factor of 2.8 and 2.2, respectively.

Tamsulosin hydrochloride should not be given in combination with strong inhibitors of CYP3A4 in patients with poor metaboliser CYP2D6 phenotype.

Tamsulosin should be used with caution in combination with strong and moderate inhibitors of CYP3A4.

Concomitant administration of tamsulosin with paroxetine, a strong inhibitor of CYP2D6, resulted in a Cmax and AUC of tamsulosin that had increased by a factor of 1.3 and 1.6, respectively, but these increases are not considered clinically relevant.

Concurrent administration with another α1-adrenoreceptor antagonist can lead to hypotensive effects.

4.6 Fertility, pregnancy and lactation

Pregnancy and breast-feeding

Tamsulosin hydrochloride is not indicated for use in women.

Fertility

Ejaculation disorders have been observed in short and long term clinical studies with tamsulosin. Events of ejaculation disorder, retrograde ejaculation and ejaculation failure have been reported in the post authorisation phase.

4.7 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 can occur.

4.8 Undesirable effects

Common

(≥1/100 to <1/10)

Uncommon

(≥1/1,000 to <1/100)

Rare

(≥1/10,000 to <1/1,000)

Very rare

(<1/10,000)

Not known

(cannot be estimated from the available data)

Nervous system disorders Dizziness (1.3%) Headache Syncope
Eye disorders Blurred vision*, Impaired vision*
Cardiac disorders Palpitations
Vascular disorders Orthostatic hypotension
Respiratory, thoracic and mediastinal disorders Rhinitis Epistaxis*
Gastro-intestinal disorders Constipation, Diarrhoea, Nausea, Vomiting Dry mouth*
Skin and subcutaneous tissue disorders Rash, Pruritus, Urticaria Angioedema Stevens- Johnson syndrome Erythema multiform, Dermatitis exfoliative
Reproductive system and breast disorders Ejaculation disorders including Retrograde ejaculation, Ejaculation failure Priapism
General disorders and administration site conditions Asthenia

*Observed in the post-marketing period

During cataract and glaucoma surgery a small pupil situation, known as Intraoperative Floppy Iris Syndrome (IFIS), has been associated with therapy of tamsulosin during post-marketing surveillance (see also section 4.4).

Post-marketing experience: In addition to the adverse events listed above, atrial fibrillation, arrhythmia, tachycardia and dyspnoea have been reported in association with tamsulosin use. Because these spontaneously reported events are from the worldwide post marketing experience, the frequency of events and the role of tamsulosin in their causation cannot be reliably determined.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

4.9 Overdose

Symptoms

Overdosage with tamsulosin can potentially result in severe hypotensive effects. Severe hypotensive effects have been observed at different levels of overdosing. The largest dose of tamsulosin that was administered to an individual patient accidentally was 12 mg. The patient developed a headache, but did not require hospital treatment.

Management

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.

If large quantities of the medicinal product are involved, gastric lavage may be performed and activated charcoal and an osmotic laxative, such as sodium sulphate, may be given.

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs used in benign prostatic hypertrophy, alpha adrenoreceptor antagonists.

Mechanism of action

Tamsulosin binds selectively and competitively to postsynaptic α1 adrenoreceptors, in particular to subtypes α 1A and α 1D, which convey smooth muscle contractionthereby relaxing the prostatic and urethral smooth muscle.

Pharmacodynamic effects

Tamsulosin increases the maximum urinary flow rate by relaxing prostatic and urethral smooth muscle, thus relieving obstruction.

The medicinal product also improves the irritative and obstructive symptoms in which the contraction of smooth muscle in the lower urinary tract plays an important role. Alpha-blockers can reduce blood pressure by lowering peripheral resistance. No reduction in blood pressure of any clinical significance was observed during studies with tamsulosin in normotensive patients.

The medicinal product’s effect on storage and voiding symptoms are also maintained during long-term therapy, as a result of which the need for surgical treatment is significantly postponed.

Paediatric population

A double-blind, randomised, placebo-controlled, dose ranging study was performed in children with neuropathic bladder. A total of 161 children (with an age of 2 to 16 years) were randomised and treated at 1 of 3 dose levels of tamsulosin (low [0.001 to 0.002 mg/kg], medium [0.002 to 0.004 mg/kg], and high [0.004 to 0.008 mg/kg]), or placebo. The primary endpoint was number of patients who decreased their detrusor leak point pressure (LPP) to <40 cm H2O based upon two evaluations on the same day. Secondary endpoints were: Actual and percent change from baseline in detrusor leak point pressure, improvement or stabilisation of hydronephrosis and hydroureter and change in urine volumes obtained by catheterisation and number of times wet at time of catheterisation as recorded in catheterisation diaries. No statistically significant difference was found between the placebo group and any of the 3 tamsulosin dose groups for either the primary or any secondary endpoints. No dose response was observed for any dose level.

5.2 Pharmacokinetic properties

Absorption

Tamsulosin is rapidly absorbed from the intestines and its bioavailability is almost complete. Absorption is slowed down if a meal has been eaten before taking the medicinal product. Uniformity of absorption can be assured by always taking tamsulosin after the same daily meal.

Tamsulosin shows linear kinetics.

Peak plasma levels are achieved at approximately six hours after a single dose of tamsulosin taken after a full meal. The steady state is reached by day five of multiple dosing when Cmax in patients is about two-thirds higher than that reached after a single dose. Although this has been demonstrated only in the elderly, the same result would also be expected in younger patients.

There are huge inter-patient variations in plasma levels of tamsulosin, both after single as well as multiple dosing.

Distribution

In humans, tamsulosin is more than 99% bound to plasma proteins and the volume of distribution is small (about 0.2 l/kg).

Biotransformation

Tamsulosin has a low first pass metabolic effect. Most tamsulosin is found unaltered in plasma. The substance is metabolised in the liver.

In studies on rats, tamsulosin was found to cause only a slight induction of microsomal liver enzymes.

In vitro results suggest that CYP3A4 and also CYP2D6 are involved in metabolism, with possible minor contributions to tamsulosin hydrochloride metabolism by other CYP isozymes. Inhibition of CYP3A4 and CYP2D6 drug metabolizing enzymes may lead to increased exposure to tamsulosin hydrochloride (see sections 4.4 and 4.5).

The metabolites are not as effective and toxic as the active medicinal product itself.

Elimination

Tamsulosin and its metabolites are mainly excreted in the urine with about 9% of the dose being present in unchanged form.

The elimination half-life of tamsulosin in patients is approximately 10 hours (when taken after a meal) and 13 hours in the steady state.

5.3 Preclinical safety data

Toxicity after a single dose and multiple dosing has been investigated in mice, rats and dogs. Reproductive toxicity has also been investigated in rats, carcinogenicity in mice and rats, and genotoxicity in vivo and in vitro.

The common toxicity profile found with large doses of tamsulosin is equivalent to the pharmacological effect associated with alpha adrenergic antagonists.

Changes in ECG readings were found with very large doses in dogs. This is not, however, assumed to be of any clinical significance. Tamsulosin has not been found to have any significant genotoxic properties.

Greater proliferative changes in the mammary glands of female rats and mice have been discovered on exposure to tamsulosin. These findings, which are probably indirectly linked to hyperprolactinaemia and only occur as a result of large doses having been taken, are considered clinically insignificant.

  1. Pharmaceutical particulars

6.1 List of excipients

Content of capsule

Cellulose microcrystalline, Methacrylic acid-ethyl acrylate copolymer (1:1) dispersion 30 per cent

Polysorbate, Sodium laurilsulfate, Triethyl citrate and Talc.

Capsule shell: Gelatin, Indigo carmine, Titanium dioxide, Yellow iron oxide, Red iron oxide, Black iron oxide.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Blister packs: Store in the original package.

Capsule containers: Keep the container tightly closed.

6.5 Nature and contents of container

PVC/PE/PVDC/Aluminium blister packs in cardboard boxes containing 10, 14, 20, 28, 30, 50, 56, 60, 90, 100 and 500 modified-release capsules.

HDPE capsule containers with PP child-resistant closures containing 10, 14, 20, 28, 30, 50, 56, 60, 90, 100 or 500 modified-release capsules.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Tamsulosin Hydrochloride 400mcg Modified-Release Capsules Taj Pharma
(Tamsulosin Hydrochloride)

Package leaflet: Information for the patient

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

–Keep this leaflet. You may need to read it again.

–If you have any further questions, ask your doctor or pharmacist.

–This medicine has been prescribed for you only. Do not pass it on to others. It may harm them even if their signs of illness are the same as yours.

–If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

  1. What Tamsulosin Hydrochloride is and what it is used for
  2. What you need to know before you take Tamsulosin Hydrochloride
  3. How to take Tamsulosin Hydrochloride
  4. Possible side effects
  5. How to store Tamsulosin Hydrochloride
  6. Contents of the pack and other information

 

  1. What Tamsulosin Hydrochloride is and what it is used for

Tamsulosin Hydrochloride contains the active ingredient tamsulosin hydrochloride which belongs to a group of medicines called alpha-adrenoreceptor antagonists (alpha1A-blockers). These medicines are used to reduce muscle contraction in the prostate and urethra. This facilitates the flow of urine through the urethra and aids urination.

Tamsulosin Hydrochloride is used for the treatment of lower urinary tract symptoms caused by an enlarged prostate, known as benign prostatic hyperplasia (BPH).

  1. What you need to know before you take Tamsulosin Hydrochloride

Do not take Tamsulosin Hydrochloride:

  • If you are allergic to tamsulosin or any of the other ingredients of this medicine (listed in section 6). Allergy to tamsulosin can express itself as sudden swelling of hands or feet, difficulties in breathing and/or itch and rash, swollen lips, tongue or throat (angioedema).
  • If you have experienced dizziness or have fainted due to lowered blood pressure (e.g. when suddenly sitting or standing up).
  • If you have severe liver problems.

Warnings and precautions

Talk to your doctor or pharmacist before taking Tamsulosin Hydrochloride:

  • If you have severe kidney problems.
  • If you are undergoing or about to have an operation on your eye for cloudiness of the lens (cataract) or increased pressure in the eye (glaucoma).An eye condition called Intraoperative Floppy Iris Syndrome may occur (see section 4 ‘Possible side effects’). Please tell your eye specialist that you have previously taken, are taking, or are planning to take tamsulosin. The specialist can then take appropriate precautions with respect to medication and surgical techniques to be used. Ask your doctor whether or not you should postpone or temporarily stop taking this medicine when undergoing eye surgery because of a cloudy lens (cataract) or increased pressure in the eye (glaucoma).

During treatment

Talk to your doctor or pharmacist:

  • If you experience dizziness or fainting during the use of tamsulosin. If you experience these signs of orthostatic hypotension, please sit or lie down straight away until the symptoms disappear.
  • If you experience sudden swelling of hands or feet, swollen lips, tongue or throat, difficulties in breathing and/or itch and rash, caused by an allergic reaction (angioedema) during the use of tamsulosin.

You should have your prostate or urinary system examined by a doctor before taking Tamsulosin Hydrochloride and at regular intervals thereafter.

Children and adolescents

Do not give this medicine to children or adolescents under the age of 18 years because it does not work in this population.

Other medicines and Tamsulosin Hydrochloride

Tell your doctor if you are taking, have recently taken or might take any other medicines.

  • tamsulosin may lower blood pressure when taken with other alpha1A-blockers e.g. doxazosin, prazosin and indoramin.
  • diclofenac (an anti-inflammatory painkiller) and warfarin (used to prevent blood clotting) may have an influence on how fast tamsulosin is removed from the body.
  • medicines which lower your blood pressure such as verapamil and diltiazem.
  • medicines which are used to suppress your immune system e.g ciclosporin.
  • antibiotics to treat infection e.g. erythromycin, clarithromycin.
  • medicines to treat fungal infections e.g. ketoconazole, itraconazole, fluconazole, voriconazole.
  • medicines used to treat HIV e.g. ritonavir, saquinavir.

Please note that these statements may also apply to products used some time ago or at some time in the future.

Pregnancy, breast-feeding and fertility

Tamsulosin is not indicated for use in women.

Tamsulosin may cause ejaculation disorders including ejaculation of the semen into the urinary bladder (retrograde ejaculation) and inability to ejaculate (ejaculation failure).

Driving and using machines

No studies on the effects of tamsulosin on the ability to drive or use machines have been performed.

However, patients should be aware that dizziness may occur.

  1. How to take Tamsulosin Hydrochloride

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

The recommended dose is one capsule a day after breakfast or the first meal of the day.

The capsule should be swallowed whole.

The capsule must not be crunched or chewed as this will affect how the medicine gets into the body.

If you take more Tamsulosin Hydrochloride than you should

If you may have taken more tamsulosin than you should, talk to your doctor or pharmacist immediately. You may get symptoms of low blood pressure such as dizziness, lightheadedness, fainting, blurred vision, irregular heartbeat, confusion, or being weak. If any of these symptoms occur, you should sit or lie down.

If you forget to take Tamsulosin Hydrochloride

If you have forgotten to take Tamsulosin Hydrochloride after the first meal of the day, it can be taken later the same day after food. If you have missed a day, just continue to take your daily capsule as prescribed. Do not take a double dose to make up for a forgotten individual capsule.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

  1. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects:

If you have any of the following symptoms, stop taking this medicine and tell your doctor immediately or go to the casualty department at your nearest hospital:

Rare (may affect up to 1 in 1,000 people)

  • sudden swelling of hands or feet, difficulties in breathing and/or itch and rash, swollen lips, tongue or throat (angioedema)

Very rare (may affect up to 1 in 10,000 people)

  • a widespread rash with severe blisters, peeling skin and bleeding in the lips, eyes, mouth, nose and genitals (Stevens-Johnson syndrome)

Not known (frequency cannot be estimated from the available data)

  • irregular and abnormal fast heartbeat (atrial fibrillation)

Other possible side effects:

Common (may affect up to 1 in 10 people)

  • dizziness
  • ejaculation disorders including inability to ejaculate and ejaculation of semen into the urinary bladder (retrograde ejaculation).

Uncommon (may affect up to 1 in 100 people)

  • headache
  • a sensation of abnormal heart beat (palpitations)
  • dizziness especially when suddenly sitting or standing up (orthostatic hypotension)
  • runny or blocked nose (rhinitis)
  • constipation
  • diarrhoea
  • feeling sick
  • being sick
  • rash
  • itching
  • feeling of weakness (asthenia)

Rare (may affect up to 1 in 1,000 people)

  • fainting

Very rare (may affect up to 1 in 10,000 people)

  • painful, prolonged, unwanted erection (priapism)

Not known (frequency cannot be estimated from the available data)

  • widespread inflammation of the skin with pale-red, pale centred blotches known as erythema multiforme
  • abnormal heart rhythm (arrhythmia)
  • accelerated heart beat (tachycardia)
  • shortness of breath (dyspnoea)
  • blurred or reduced vision (impaired vision)
  • nose bleed
  • scaly skin rash (dermatitis exfoliative)
  • dry mouth.

In some occasions, possible complications in connection to cataract or glaucoma operations have been observed. During eye surgery a condition called Floppy Iris Syndrome (IFIS) may occur: the pupil may dilate poorly and the iris (the coloured circular part of the eye) may become floppy during surgery. For more information, see section 2 ‘Warnings and precautions’.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

  1. How to store Tamsulosin Hydrochloride

Keep this medicine out of the sight and reach of children.

Store in the original package.

Keep the container tightly closed.

Do not use this medicine after the expiry date which is stated on the label and carton after ‘EXP’. The expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

  1. Contents of the pack and other information

What Tamsulosin Hydrochloride contains:

The active substance is tamsulosin hydrochloride.

Each hard modified-release capsule contains:
Tamsulosin Hydrochloride USP          400mcg
Excipients                                                 q.s.

The other ingredients are: microcrystalline cellulose, methacrylic acid-ethyl acrylate copolymer (1:1) dispersion, polysorbate, sodium laurilsulfate, triethyl citrate and talc.

The capsule shell ingredients are gelatin, Indigo carmine, titanium dioxide, yellow iron oxide, red iron oxide and black iron oxide.

What Tamsulosin Hydrochloride looks like and contents of the pack

Modified-release capsule, hard.

PVC/PE/PVDC/Aluminium blister packs in cardboard boxes containing 10, 14, 20, 28, 30, 50, 56, 60, 90, 100 and 500 modified-release capsules.

HDPE capsule containers with PP child-resistant closures containing 10, 14, 20, 28, 30, 50, 56, 60, 90, 100 or 500 modified-release capsules.

Not all pack sizes may be marketed.

7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

 

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