Omnexel

Change address of MAH Astellas Pharm Co., Ltd.

Change of address of MAH Astellas Pharma Co., Ltd.

4.8 Undesirable effects

4.6 Fertility, pregnancy and lactation

Omnexel is not indicated for use in women.

Omnexel

4.4 Special warnings and precautions for use

The ‘Intraoperative Floppy Iris Syndrome’ (IFIS, a variant of small pupil syndrome) has been observed during cataract and glaucoma 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 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 the surgery.

The initiation of therapy with tamsulosin hydrochloride in patients for whom cataract or glaucoma surgery is scheduled is not recommended. During pre-operative assessment, 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.

4.8 Undesirable effects

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).

7     Marketing authorisation holder

Astellas Pharma Co. Ltd.

5 Waterside

Citywest Business Campus

Naas Road

Dublin 24

Ireland

4.4 Special warnings and precautions for use

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 lead to increased the risk of eye procedural complications during and after the operation. The initiation of therapy with tamsulosin in patients for whom cataract surgery is scheduled is not recommended. Discontinuing tamsulosin hydrochloride 1-2 weeks prior to cataract surgery is anecdotally considered helpful, but the benefit of treatment discontinuation and duration of stopping of therapy prior to cataract surgery 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).

 It is possible that a remnant of the tablet is observed in the faeces.

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, nifedipine 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.

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 metabolising enzyme system), involving amitriptyline, salbutamol, glibenclamide and finasteride. 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 α₁‑adrenoceptor antagonists could lead to hypotensive effects.

4.8 Undesirable effects

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 (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.

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.

5. PHARMACOLOGICAL PROPERTIES

Absorption

Omnic Ocas 0,4 is a prolonged release tablet of the non‑ionic gel matrix type. The Ocas formulation provides consistent slow release of tamsulosin, resulting in an adequate exposure over 24 hours, with little fluctuation, over 24 hours.

Tamsulosin hydrochloride administered as Omnic Ocas 0,4 mgprolonged release tablets is absorbed from the intestine. Under fasting conditions approximately 57% Oof the administered dose, approximately 57%  is estimated to be absorbed.

The rate and extent of absorption of tamsulosin hydrochloride administered as Omnic Ocas 0,4prolonged release tablets are not affected by fooda low fat meal. The extent of absorption is increased by 64% and 149% (AUC and C_max respectively) by a high-fat meal compared to fasted.

Biotransformation

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 section 4.4 and 4.5).

10. Date of revision of the text

August 2011

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

400 micrograms tamsulosin hydrochloride changed to 0.4 mg tamsulosin hydrochloride

6.3     Shelf life

Increased from 2 years to 3 years

10.     DATE OF REVISION OF THE TEXT

Changed from October 2006 to May 2009

Omnexel SPC Changes

(October 2005 v October 2006)

Section 2 Qualitative and Quantitative Composition

Insertion of a reference to the excipients in section 6.1.

Section 4.2 Posology and method of administration

“Oral Use.”

“No dose adjustment is warranted in renal impairment.

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

There is no relevant indication for use of Omnexel^®, 400 micrograms, in children.”

Section 4.3 Contraindications

Insertion of new text (highlighted in red below) to the end of the following sentence:

“Hypersensitivity to tamsulosin hydrochloride or to any of the excipients, including drug-induced angioedema.”

Section 4.4 Special warnings and precautions for use

Insertion of the following new text:

“The 'Intra-operative 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.  IFIS may lead to increased procedural complications during the operation.  The initiation of therapy with tamsulosin in patients for whom cataract surgery is scheduled is not recommended. Discontinuing tamsulosin 1-2 weeks prior to cataract surgery is anecdotally considered helpful, but the benefit and duration of stopping therapy prior to cataract surgery has not yet been established.

During preoperative 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.

It is possible that a remnant of the tablet is observed in the faeces.”

Section 4.5 Interaction with other medicinal products and other forms of interaction

Insertion of the following new text: “Interaction studies have only been performed in adults”

Section 4.8      Undesirable effects

Description of the frequency of the undesirable effects changed from percentages to fractions.

Insertion of the following new text:

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

Section 4.9      Overdose

Insertion of the following new text:

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

Section 5.2      Pharmacokinetic properties

The heading “Metabolism” has been changed to “Biotransformation”

Deletion of the following text:

“No dose adjustment is warranted in hepatic insufficiency”

“No dose adjustment is warranted in renal impairment”.

Section 6.5      Nature and contents of container

Insertion of two new pack sizes: “..18,..45,..”

Section 9 Date of First Authorisation/Renewal of the Authorisation

Updated to: 18^th March 2005/12^th July 2006

Section 10 Date of Revision of the Text

Updated to: October 2006

Section 7: Marketing Authorisation Holder changed from Yamanouchi to Astellas Pharma Co. Ltd

Section 8: Marketing Authorisation Number changed to 1241/6/1

Section 10: Date of Revision of the Text changed to October 2005