Avozaq SR 0,4mg Capsules

AVOZAQ SR 0,4 mg is indicated for the treatment of functional symptoms of benign prostatic hyperplasia (BPH) in adult males. Efficacy in children with neurogenic bladder has not been demonstrated.

Posology
One capsule to be taken daily after breakfast, or after the first daily meal.
Special populations
Renal impairment
No dose adjustment is warranted in renal impairment.
Hepatic impairment
In patients with mild to moderate hepatic insufficiency, no dose adjustment is warranted (see section 4.3).
Paediatric population
AVOZAQ SR 0,4 mg is not indicated in children. The safety and efficacy of tamsulosin hydrochloride in children under the age of 18 have not been established.
Method of administration
AVOZAQ SR 0,4 mg is to be taken orally, swallowed whole, without crushing or chewing, as this will affect the sustained release properties of the active ingredient.

• hypersensitivity to tamsulosin hydrochloride or to any of the ingredients of AVOZAQ SR 0,4 mg (see section 6.1)
• patients with a history of orthostatic hypotension
• patients with hepatic insufficiency
• combination therapy with strong inhibitors of CYP3A4 such as ketoconazole (see section 4.5)

A decrease in blood pressure can occur in individual cases during AVOZAQ SR 0,4 mg therapy, as a result of which orthostatic hypotension and syncope can occur. At the first signs of orthostatic hypotension (dizziness, weakness), the patient should sit or lie down until the symptoms have disappeared. Prior to initiating therapy with AVOZAQ SR 0,4 mg, 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 with AVOZAQ SR 0,4 mg and at regular intervals afterwards. Treatment should be approached with caution in patients with severe renal impairment (creatinine clearance of <10 mL/min), as this patient group has not been studied.

In some patients previously treated with tamsulosin as in AVOZAQ SR 0,4 mg, the u201cIntraoperative Floppy Iris Syndromeu201d (IFIS, a variant of small pupil syndrome) has been observed during cataract and glaucoma surgery. IFIS may increase the risk of eye complications during and after the operation. Although the discontinuation of AVOZAQ SR 0,4 mg 1 to 2 weeks prior to cataract or glaucoma surgery is anecdotally considered helpful, the benefit of treatment discontinuation has not yet been established as IFIS has also been reported in patients who had discontinued AVOZAQ SR 0,4 mg for a longer period prior to eye surgery. In patients for whom cataract or glaucoma surgery is scheduled, initiation of therapy with AVOZAQ SR 0,4 mg 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 AVOZAQ SR 0,4 mg in order to ensure that appropriate measures will be in place to manage the IFIS during surgery. Combination therapy with strong inhibitors of CYP3A4 in patients with poor metaboliser CYP2D6 phenotype, is not recommended. Caution is recommended when AVOZAQ SR 0,4 mg is taken in combination with strong and moderate inhibitors of CYP3A4 (see section 4.5). AVOZAQ SR 0,4 mg is intended for adult male patients only.

Priapism
Tamsulosin 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.
Sulphur Allergy
In patients with sulphur allergy, allergic reaction to tamsulosin as in AVOZAQ SR 0,4 mg has been rarely reported. If a patient reports a serious or life-threatening sulphur allergy, caution is warranted when administering AVOZAQ SR 0,4 mg capsules.

No interactions have been seen when tamsulosin as in AVOZAQ SR 0,4 mg was given concomitantly with either atenolol, enalapril, nifedipine, digoxin or theophylline. When AVOZAQ SR 0,4 mg is taken concomitantly with cimetidine, a rise in plasma levels of tamsulosin occur. In vitro, neither diazepam, propranolol, trichlormethiazide, chlormadinone, amitriptyline, diclofenac, glibenclamide, simvastatin or warfarin change the free fraction of tamsulosin in human plasma. Tamsulosin does not change the free fractions of diazepam, propranolol, trichlormethiazide and chlormadinone.

Diclofenac and warfarin, however, may increase the elimination rate of tamsulosin, as in AVOZAQ SR 0,4 mg. A definitive medicine interaction study between tamsulosin hydrochloride and warfarin was not conducted. Results from limited in vitro and in vivo studies are inconclusive. Caution should be exercised with concomitant administration of warfarin and AVOZAQ SR 0,4 mg capsules. Concomitant administration of AVOZAQ SR 0,4 mg 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 C max of tamsulosin hydrochloride by a factor of 2,8 and 2,2, respectively. Since CYP2D6 poor metabolisers cannot be readily identified and the potential for significant increase in tamsulosin hydrochloride exposure exists when AVOZAQ SR 0,4 mg is co-administered with strong CYP3A4 inhibitors in CYP2D6 poor metabolisers, AVOZAQ SR 0,4 mg should not be given in combination with strong inhibitors of CYP3A4 (see section 4.3). AVOZAQ SR 0,4 mg should be given with caution in combination with moderate inhibitors of CYP3A4. AVOZAQ SR 0,4 mg capsules should be used with caution in combination with moderate inhibitors of CYP3A4 (e.g., erythromycin). Concomitant administration of AVOZAQ SR 0,4 mg with paroxetine, a strong inhibitor of CYP2D6, resulted in an increased C max and AUC by a factor of 1,3 and 1,6, respectively. These increases are not considered clinically relevant.

Other Alpha Adrenergic Blocking medicines
Concurrent administration of other alpha 1-adrenoceptor antagonists could lead to hypotensive effects. The pharmacokinetic and pharmacodynamic interactions between AVOZAQ SR 0,4 mg and other alpha adrenergic blocking medicines have not been determined; however, interactions between AVOZAQ SR 0,4 mg capsules and other alpha adrenergic blocking agents may be expected.

PDE5 Inhibitors
Caution is advised when alpha adrenergic blocking medicines including AVOZAQ SR 0,4 mg are co-administered with PDE5 inhibitors. Alpha-adrenergic blockers and PDE5 inhibitors are both vasodilators that can lower blood pressure. Concomitant use of these two medicine classes can potentially cause symptomatic hypotension.

Furosemide
AVOZAQ SR 0,4 mg had no effect on the pharmacodynamics (excretion of electrolytes) of furosemide. While furosemide produced an 11% to 12% reduction in tamsulosin hydrochloride C max and AUC, these changes are expected to be clinically insignificant and do not require adjustment of the dosage. Concomitant use with furosemide brings about a fall, but as levels remain within the normal range dosages need not to be changed.

AVOZAQ SR 0,4 mg is not indicated for use in women.
Fertility
Ejaculation disorders have been observed in short- and long-term clinical studies with tamsulosin, as in AVOZAQ SR 0,4 mg. Events of ejaculation disorder, retrograde ejaculation and ejaculation failure may occur.

No data is available on whether AVOZAQ SR 0,4 mg adversely affects the ability to drive or operate machinery. However, patients should be aware of the fact that dizziness, blurred vision, visual impairment, or Intraoperative Floppy Iris Syndrome (IFIS) may occur and should not engage in these activities until they know how AVOZAQ SR 0,4 mg affects them.

a). Tabulated summary of adverse reactions

System Organ Class
Frequency
Side effects

Nervous system disorders
Frequent
Dizziness, somnolence, insomnia
Less frequent
Headache, syncope

Eye disorders
Frequency unknown
Blurred vision, visual impairment, intraoperative floppy iris syndrome (IFIS)

Cardiac disorders
Less frequent
Frequency unknown
Palpitations
Atrial fibrillation, dysrhythmia, tachycardia

Vascular disorders
Less frequent
Orthostatic hypotension

Respiratory, thoracic, and mediastinal disorders
Less frequent
Frequency unknown
Rhinitis, pharyngitis, cough increased, sinusitis
Epistaxis, dyspnoea

Gastrointestinal disorders
Less frequent
Frequency unknown
Constipation, diarrhoea, nausea, vomiting, tooth disorder
Dry mouth

Skin and subcutaneous tissue disorders
Less frequent
Frequency unknown
Rash, pruritus, urticaria, angioedema, Stevens-Johnson Syndrome
Erythema multiforme, exfoliative dermatitis, skin desquamation

Reproductive system and breast disorders
Frequent
Less frequent
Ejaculation disorders, retrograde ejaculation, ejaculation failure, libido decreased
Priapism

General disorders and administrative site conditions
Less frequent
Asthenia, infection, back pain, chest pain

Signs and symptoms:
Overdosage with AVOZAQ SR 0,4 mg may result in severe hypotensive effects. Severe hypotensive effects have been observed at different levels of overdosing. The highest dose of tamsulosin as in AVOZAQ SR 0,4 mg accidentally given to a single patient was 12 mg, resulting in headache but not requiring hospitalisation.
Management of overdose:
Cardiovascular support should be given in cases of acute hypotension occurring after overdosage. By lying the patient down, blood pressure can be restored, and heart rate brought back to normal. 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, activated charcoal and an osmotic laxative, such as sodium sulphate, can be administered.