Sections 2, 4.2, 4.3, 4.4, 4.6, 4.8, 4.9, 5.1, 5.2 updated inline with QRD template$0$0$0$0Section 4.2 - method of administration - for oral use only included$0$0Section 4.3: Following wording added: • Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.$0$0• Patients with a history of micturition syncope.$0$0• History of postural hypotension (in benign prostatic hyperplasia)  $0$0Section 4.4 - Following wording included: As with all alpha-1 receptor blockers, terazosin should be used with caution in patients with congestive heart failure. $0$0Section 5.2 Following wording added Absorption$0$0Terazosin is rapidly and almost completely absorbed from the gastrointestinal tract after oral doses. The bioavailability of oral terazoscin is approximately 90%. The plasma concentration of the parent drug is a maximum about 1 hour post administration and declines with a half-life of approximately 12 hours. Food has little or no effect on bioavailability.  $0$0Distribution$0$0The drug is highly bound to plasma proteins. Approximately 90-94% of terazosin is bound to plasma proteins. $0$0Biotransformation$0$0It is metabolised in the liver. Hepatic metabolism is extensive with major biliary elimination $0$0Elimination$0$0Approximately 40% of the administered dose is eliminated in the urine and 60% in the faeces.  The drug is highly bound to plasma proteins.$0

Sections 2, 4.2, 4.3, 4.4, 4.6, 4.8, 4.9, 5.1, 5.2 updated inline with QRD template$0$0$0$0Section 4.2 - method of administration - for oral use only included$0$0Section 4.3: Following wording added: • Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.$0$0• Patients with a history of micturition syncope.$0$0• History of postural hypotension (in benign prostatic hyperplasia)  $0$0Section 4.4 - Following wording included: As with all alpha-1 receptor blockers, terazosin should be used with caution in patients with congestive heart failure. $0$0Section 5.2 Following wording added Absorption$0$0Terazosin is rapidly and almost completely absorbed from the gastrointestinal tract after oral doses. The bioavailability of oral terazoscin is approximately 90%. The plasma concentration of the parent drug is a maximum about 1 hour post administration and declines with a half-life of approximately 12 hours. Food has little or no effect on bioavailability.  $0$0Distribution$0$0The drug is highly bound to plasma proteins. Approximately 90-94% of terazosin is bound to plasma proteins. $0$0Biotransformation$0$0It is metabolised in the liver. Hepatic metabolism is extensive with major biliary elimination $0$0Elimination$0$0Approximately 40% of the administered dose is eliminated in the urine and 60% in the faeces.  The drug is highly bound to plasma proteins.$0

Section 4.1 Therapeutic indications
Section 4.6 Pregnancy and lactation
Section 4.8 Undesirable effects
Section 6.6 Special precautions for disposal and other handling
Section 10. DATE OF REVISION OF THE TEXT

Section 4.1 Therapeutic indications
Section 4.6 Pregnancy and lactation
Section 4.8 Undesirable effects
Section 6.6 Special precautions for disposal and other handling
Section 10. DATE OF REVISION OF THE TEXT

Changes in bold below: Section 4.8 following PSUR submission and Section 10 to show current date.

 

4.8.      Undesirable Effects

 

Post marketing experience:  

 

Thrombocytopenia, priapism and angioedema have been reported.  Atrial fibrillation has been reported: however, a cause and effect relationship has not been established.

 

 

10.       Date of Revision of the Text

 

June 2010

 

Changes in bold below: Section 4.8 following PSUR submission and Section 10 to show current date.

 

4.8.      Undesirable Effects

 

Post marketing experience:  

 

Thrombocytopenia, priapism and angioedema have been reported.  Atrial fibrillation has been reported: however, a cause and effect relationship has not been established.

 

 

10.       Date of Revision of the Text

 

June 2010

 

Implementation of warnings concerning additional hypotensive effects following co-administration of non-selective alpha-blockers and phosphodiesterase-5-inhibitors. Changes were made to sections 4.4, 4.5, and 10 below in bold.

 

4.4.      Special warnings and precautions for use

 

Pharmacokinetic studies indicate that patients with impaired renal function need no alteration in recommended dosage.  There is no evidence that terazosin aggravates renal dysfunction.

 

There is as yet insufficient experience of use of terazosin in children under the age of 12 years.

 

An excessive hypotensive effect may occur in some patients following soon after the initial doses.  This is usually self limiting and in most cases does not recur after the initial period of therapy or during subsequent dose titration. Please also see Section 4.7 Effects on Ability to Drive and Use Machines.

 

The usual half life of terazosin is 10-12 hours.  This may be significantly prolonged in patients with congestive cardiac failure (by up to 7-8 hours), usually with reduction on clinical improvement.

 

In certain patients with left ventricular failure, the decrease in left ventricular filling consequent to vigorous therapy may result in a significant fall in cardiac output and systemic blood pressure after administration of terazosin.  These effects should be kept in mind when introducing therapy and continuous titration of dose used.

Since the drug is metabolised in the liver it should only be used with care in patients with existing hepatic dysfunction.

 

As with other alpha-1-adrenoreceptor antagonists, terazosin is not recommended in patients with history of micturition syncope.

 

Laboratory Tests:  Small but statistically significant decreases in haematocrit, haemoglobin, white blood cells, total protein and albumin were observed in controlled clinical trials.  These laboratory findings suggest the possibility of haemodilution.  Treatment with terazosin for up to 24 months had no significant effect on Prostate Specific Antigen (PSA) levels.

 

In clinical trials, the incidence of postural hypotension was greater in BPH patients than those with hypertension.

 

If administration is discontinued for more than several days, therapy should be re-instituted using the initial dosing regimen.

 

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

 

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.  Isolated reports have also been received with other alpha-1 blockers and the possibility of a class effect cannot be excluded.  An IFIS may lead to increased procedural complications during the cataract operation current or past use of alpha-1 blockers should be made known to the ophthalmic surgeon in advance of surgery.

 

Concomitant use of phosphodiesterase-5-inhibitors (e.g. sildenafil, tadalafil, vardenafil) and terazosin may lead to symptomatic hypotension in some patients.  In order to minimise the risk for developing postural hypotension the patient should be stable on the alpha-blocker therapy before initiating use of phosphodiesterase-5-inhibitors.

 

4.5.      Interactions with other medicinal products and other forms of interaction

 

Terazosin is highly protein bound.  There is a theoretical potential for interaction with such drugs as anticoagulants and nonsteroidal anti-inflammatory drugs leading to higher plasma levels of drug.

 

Except for angiotension converting enzyme (ACE) inhibitors and diuretics, no clinically significant interactions have been observed with Hytrin in BPH.  In BPH patients the adverse events profile of patients treated concurrently with non-steroidal anti-inflammatory drugs (NSAIDs), theophylline, antianginal agents, oral hypoglycaemic agents, ACE inhibitors or diuretics was compared to the profile in the general treated population.

 

In the small subset of patients who were treated with Hytrin and ACE inhibitors or diuretics, the percent reporting dizziness or other dizziness-related adverse events appears to be greater than in the total population of terazosin patients from double-blind placebo-controlled studies.

 

Caution should be observed when Hytrin is administered concomitantly with other antihypertensive agents (e.g. calcium antagonists) to avoid the possibility of significant hypotension.  When adding Hytrin to a diuretic or other antihypertensive agent, dosing reduction and retitration of these agents may be necessary.

 

Phosphodiesterase-5-inhibitors (e.g. sildenafil, tadalafil, vardenafil) (see section 4.4).

 

10.        Date of Revision of the Text

 

December 2009

 

 

 

Implementation of warnings concerning additional hypotensive effects following co-administration of non-selective alpha-blockers and phosphodiesterase-5-inhibitors. Changes were made to sections 4.4, 4.5, and 10 below in bold.

 

4.4.      Special warnings and precautions for use

 

Pharmacokinetic studies indicate that patients with impaired renal function need no alteration in recommended dosage.  There is no evidence that terazosin aggravates renal dysfunction.

 

There is as yet insufficient experience of use of terazosin in children under the age of 12 years.

 

An excessive hypotensive effect may occur in some patients following soon after the initial doses.  This is usually self limiting and in most cases does not recur after the initial period of therapy or during subsequent dose titration. Please also see Section 4.7 Effects on Ability to Drive and Use Machines.

 

The usual half life of terazosin is 10-12 hours.  This may be significantly prolonged in patients with congestive cardiac failure (by up to 7-8 hours), usually with reduction on clinical improvement.

 

In certain patients with left ventricular failure, the decrease in left ventricular filling consequent to vigorous therapy may result in a significant fall in cardiac output and systemic blood pressure after administration of terazosin.  These effects should be kept in mind when introducing therapy and continuous titration of dose used.

Since the drug is metabolised in the liver it should only be used with care in patients with existing hepatic dysfunction.

 

As with other alpha-1-adrenoreceptor antagonists, terazosin is not recommended in patients with history of micturition syncope.

 

Laboratory Tests:  Small but statistically significant decreases in haematocrit, haemoglobin, white blood cells, total protein and albumin were observed in controlled clinical trials.  These laboratory findings suggest the possibility of haemodilution.  Treatment with terazosin for up to 24 months had no significant effect on Prostate Specific Antigen (PSA) levels.

 

In clinical trials, the incidence of postural hypotension was greater in BPH patients than those with hypertension.

 

If administration is discontinued for more than several days, therapy should be re-instituted using the initial dosing regimen.

 

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

 

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.  Isolated reports have also been received with other alpha-1 blockers and the possibility of a class effect cannot be excluded.  An IFIS may lead to increased procedural complications during the cataract operation current or past use of alpha-1 blockers should be made known to the ophthalmic surgeon in advance of surgery.

 

Concomitant use of phosphodiesterase-5-inhibitors (e.g. sildenafil, tadalafil, vardenafil) and terazosin may lead to symptomatic hypotension in some patients.  In order to minimise the risk for developing postural hypotension the patient should be stable on the alpha-blocker therapy before initiating use of phosphodiesterase-5-inhibitors.

 

4.5.      Interactions with other medicinal products and other forms of interaction

 

Terazosin is highly protein bound.  There is a theoretical potential for interaction with such drugs as anticoagulants and nonsteroidal anti-inflammatory drugs leading to higher plasma levels of drug.

 

Except for angiotension converting enzyme (ACE) inhibitors and diuretics, no clinically significant interactions have been observed with Hytrin in BPH.  In BPH patients the adverse events profile of patients treated concurrently with non-steroidal anti-inflammatory drugs (NSAIDs), theophylline, antianginal agents, oral hypoglycaemic agents, ACE inhibitors or diuretics was compared to the profile in the general treated population.

 

In the small subset of patients who were treated with Hytrin and ACE inhibitors or diuretics, the percent reporting dizziness or other dizziness-related adverse events appears to be greater than in the total population of terazosin patients from double-blind placebo-controlled studies.

 

Caution should be observed when Hytrin is administered concomitantly with other antihypertensive agents (e.g. calcium antagonists) to avoid the possibility of significant hypotension.  When adding Hytrin to a diuretic or other antihypertensive agent, dosing reduction and retitration of these agents may be necessary.

 

Phosphodiesterase-5-inhibitors (e.g. sildenafil, tadalafil, vardenafil) (see section 4.4).

 

10.        Date of Revision of the Text

 

December 2009