- Name of the medicinal product
Normirama 400 microgram Capsules
- Qualitative and quantitative composition
One capsule contains 400 micrograms tamsulosin hydrochloride.
For the full list of excipients, see section 6.1.
- Pharmaceutical form
Hard gelatin capsules filled with white to off-white pellets.
- Clinical particulars
4.1 Therapeutic indications
Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).
4.2 Posology and method of administration
Oral use.
One capsule a day after breakfast or the first meal of the day.
The capsule is swallowed whole with a glass of water while standing or sitting (not lying down). The capsule should not be broken or pulled apart as this may have an effect on the release of the long-acting active ingredient.
No dose adjustment is warranted in renal impairment. No dose adjustment is warranted in patients with mild to moderate hepatic insufficiency (see section 4.3).
Paediatric Population
There is no relevant indication for use of tamsulosin hydrochloride in children.
The safety and efficacy of tamsulosin hydrochloride in children < 18 years have not been established. Currently available data are described in section 5.1
4.3 Contraindications
- Hypersensitivity to the active substance including drug-induced angioedema, or to any of the excipients listed in section 6.1.
- Orthostatic hypotension observed earlier (history of orthostatic hypotension).
- Severe hepatic insufficiency.
4.4 Special warnings and precautions for use
As with other α1 adrenoceptors antagonists, a reduction in blood pressure can occur in individual cases during treatment with tamsulosin hydrochloride 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 hydrochloride 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.
Angio-oedema 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 surgery in some patients on or previously treated with tamsulosin hydrochloride. IFIS may increase the risk of eye complications during and after the operation.
Discontinuing tamsulosin hydrochloride 1-2 weeks prior to cataract 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 surgery.
The initiation of therapy with tamsulosin hydrochloride in patients for whom cataract surgery is scheduled is not recommended. During pre-operative assessment, cataract surgeons and ophthalmic teams should consider whether patients scheduled for cataract 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 hydrochloride should not be given in combination with strong inhibitors of CYP3A4 in patients with poor metaboliser CYP2D6 phenotype.
Tamsulosin hydrochloride should be used with caution in combination with strong and moderate inhibitors of CYP3A4 (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 hydrochloride 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, chlormadinon, 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 chlormadinon.
Diclofenac and Warfarin, however, may increase the elimination rate of tamsulosin.
Concomitant administration of tamsulosin hydrochloride with strong inhibitors of CYP3A4 may lead to increased exposure to tamsulosin hydrochloride. Concomitant administration with ketoconazole (a known strong CYP3A4 inhibitor) resulted in an increase in AUC and Cmax of tamsulosin hydrochloride 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 hydrochloride should be used with caution in combination with strong and moderate inhibitors of CYP3A4.
Concomitant administration of tamsulosin hydrochloride 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 of other α1adrenoreceptor antagonists could lead to hypotensive effects.
4.6 Fertility, pregnancy and lactation
Tamsulosin is not indicated for use in women.
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 authorization 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
| System Organ Class | Common (> 1/100; < 1/10) | Uncommon (> 1/1,000; < 1/100) | Rare (> 1/10,000; < 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 | ||
| Cardiac disorders | Palpitations | ||||
| Vascular disorders | Orthostatic hypotension | ||||
| Eye disorders | Vision blurred, visual impairment | ||||
| Respiratory, thoracic and mediastinal disorders | Rhinitis | Epistaxis | |||
| Gastrointestinal disorders | Constipation, diarrhoea, nausea, vomiting | Dry mouth | |||
| Skin and subcutaneous tissue disorders | Rash, pruritus, urticaria | Angio-oedema | Stevens-Johnson syndrome | Erythema multiforme, dermatitis exfoliative | |
| Reproductive system and breast disorders | Priapism | Ejaculation disorder, retrograde ejaculation, ejaculation failure | |||
| General disorders and administration site conditions | Asthenia |
During cataract surgery a small pupil situation, known as Intraoperative Floppy Iris Syndrome (IFIS), has been associated with therapy of tamsulosin during post-marketing surveillance
4.9 Overdose
Symptoms
Overdosage with tamsulosin hydrochloride can potentially result in severe hypotensive effects. Severe hypotensive effects have been observed at different levels of overdosing.
Treatment
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.
- Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: urologicals, alpha-adrenoreceptor antagonist;
ATC code: G04CA02.
Mechanism of action
Tamsulosin binds selectively and competitively to postsynaptic α1A adrenoreceptors, which convey smooth muscle contraction by relaxing 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
No dose response was observed for any dose level of Tamsulosin in paediatric population.
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 breakfast.
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.
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.
- Pharmaceutical particulars
6.1 List of excipients
Content of capsule
Microcrystalline cellulose
Methacrylic acid-ethyl acrylate copolymer
Triacetin
Magnesium Stearate
Talc
Capsule body
Gelatin
Titanium dioxide
Erythrosine
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 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
Carton box containing 1 ( Transparent PVC/ Aluminium ) blister each of 10 hard gelatin capsules.
6.6 Special precautions for disposal and other handling
No special requirements.
- Marketing authorisation holder
RamaPharma for pharmaceutical Industries.
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