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Avodart Soft Capsules 0.5mg

*
Pharmacy Only: Prescription

  • Company:

    GlaxoSmithKline (Ireland) Ltd

  • Status:

    No Recent Update

  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)

  • Active Ingredient(s):

    Dutasteride

    *Additional information is available within the SPC or upon request to the company

Updated on 08 July 2022

File name

ie-pl-avodart-issue5draft1 clean.pdf

Reasons for updating

  • Change to section 6 - manufacturer

Updated on 13 December 2017

Reasons for updating

  • New SPC for new product

Legal category:Product subject to medical prescription which may not be renewed (A)

Updated on 13 December 2017

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

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SPC:
Section 4.8: Change from 'depressed mood' to 'depression'
Section 4.8: Clarification that 'ejaculation disorders' includes 'semen volume decreased'
Section 5.1: Addition of paragraph on effects on sexual function

Updated on 12 December 2017

File name

PIL_10207_886.pdf

Reasons for updating

  • New PIL for new product

Updated on 12 December 2017

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 15 August 2017

Reasons for updating

  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text

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Corrected the renewal date in section 9 of the Avodart SPC for Ireland, in line with the correct date on the HPRA SPC.

Updated on 19 July 2017

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text
  • Improved presentation of SPC

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Section 4.4 updated with information regarding prostate cancer and high grade tumours, cardiovascular adverse events and breast neoplasia.
Section 4.8: Formatting of frequencies updated.
Section 5.1: Updated with information regarding studies on breast neoplasia, prostate cancer and cardiovascular events.
Section 5.2: Updated biotransformation and elimination headings

Updated on 18 July 2017

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 3 - how to take/use
  • Change to section 4 - how to report a side effect
  • Change to section 6 - date of revision
  • Improved presentation of PIL

Updated on 15 July 2015

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

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Section 7 - change to Ireland MAH address

Updated on 15 July 2015

Reasons for updating

  • Change to date of revision
  • Change to MA holder contact details

Updated on 24 October 2014

Reasons for updating

  • Change to section 9 - Date of renewal of authorisation

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Section 9 - Update to common renewal date.

Updated on 22 October 2014

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.3 - Contraindications
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text

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Section 2 - Addition of the following statement: Each capsule contains lecithin (which may contain soya oil).
Section 4.8 - the addition of HPRA adverse event contact information in section 4.8.

Also, minor editorial changes throughout in the following sections:
4.3 Contraindications
4.6 Fertility, pregnancy and lactation
5.1 Pharmacodynamic properties
6.6 Special precautions for disposal and other handling

Updated on 21 October 2014

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to instructions about missed dose
  • Change to storage instructions
  • Change to date of revision
  • Addition of information on reporting a side effect.

Updated on 20 November 2013

Reasons for updating

  • Change to section 6.1 - List of excipients
  • Change to Section 4.8 – Undesirable effects - how to report a side effect

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Changes to:

 

 

Section 4.8 - Undesirable effects,
Section 6.1 - List of excipients

 

Updated on 20 November 2013

Reasons for updating

  • Change of inactive ingredient
  • Change to side-effects

Updated on 30 July 2012

Reasons for updating

  • Change to warnings or special precautions for use

Updated on 10 April 2012

Reasons for updating

  • Change to section 3 - Pharmaceutical form
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.1 - List of excipients

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Chages to the following:

Section 3 - PHARMACEUTICAL FORM,
Section 4.3 - Contraindications,
Section 4.4 - Special warnings and precautions for use,
Section 4.6 - Pregnancy and lactation,
Section 4.8 - Undesirable effects,
Section 5.1 - Pharmacodynamic properties,
Section 6.1 - List of excipients

Updated on 02 April 2012

Reasons for updating

  • Change to, or new use for medicine
  • Change to warnings or special precautions for use

Updated on 21 February 2012

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects

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Change to Section 4.4 & 4.8

Updated on 17 February 2012

Reasons for updating

  • Change to side-effects

Updated on 02 November 2011

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to appearance of the medicine

Updated on 20 October 2011

Reasons for updating

  • Change to section 3 - Pharmaceutical form
  • Change to section 4.3 - Contraindications
  • Change to section 4.8 - Undesirable effects
  • Change to section 6.1 - List of excipients

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Changes to the following Sections:

3
4.3
4.8
6.1

Updated on 15 April 2011

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

1.         NAME OF THE MEDICINAL PRODUCT

 

Avodart 0.5 mg soft capsules.

 

**************************************************************

 

4.6.            Fertility, Pregnancy and Lactation

 

**************************************************************

 

4.7.            Undesirable Effects

 

 

AVODART IN COMBINATION WITH THE ALPHA-BLOCKER TAMSULOSIN

 

Data Year 2 data from the 4 year CombAT Study, comparing dutasteride 0.5 mg (n=1623) and tamsulosin 0.4 mg (n=1611) once daily alone and in combination (n=1610) have shown that the incidence of any investigator-judged drug-related adverse event during the first, and second, third and fourth years of treatment respectively was 22%, 6%, 4% and 52% for dutasteride/tamsulosin combination therapy, 15%, 6%, 3% and 2%14% and 5% for dutasteride monotherapy and 13%, 5%, 2% and 24% for tamsulosin monotherapy. The higher incidence of adverse events in the combination therapy group in the first year of treatment was due to a higher incidence of reproductive disorders, specifically ejaculation disorders, observed in this group.

 

The following investigator-judged drug-related adverse events have been reported with an incidence of greater than or equal to 1% during the first year of treatment in the Year 2 analysis of the CombAT Study; the incidence of these events during the four yearsfirst and second year of treatment is shown in the table below:

 

 

System Organ Class

Adverse Reaction

Incidence during treatment period

Year 1

Year 2

Year 3

Year 4

    Combinationa (n)

(n=1610)

(n=1428)

(n=1283)

(n=1200)

    Dutasteride

(n=1623)

(n=1464)

(n=1325)

(n=1200)

    Tamsulosin

(n=1611)

(n=1468)

(n=1281)

(n=1112)

Reproductive system and breast disorders, Psychiatric disorders, Investigations

Impotence

 

 

 

 

    Combinationa

6.3%

1.8%

0.9%

0.4%

    Dutasteride

5.1%

1.6%

0.6%

0.3%

    Tamsulosin

3.3%

1.0%

0.6%

1.1%

Altered (decreased) libido

 

 

 

 

    Combinationa

5.3%

0.8%

0.2%

0%

    Dutasteride

3.8%

1.0%

0.2%

0%

    Tamsulosin

2.5%

0.7%

0.2%

<0.1%

Ejaculation disorders

 

 

 

 

    Combinationa

9.0%

1.0%

0.5%

<0.1%

    Dutasteride

1.5%

0.5%

0.2%

0.3%

    Tamsulosin

2.7%

0.5%

0.2%

0.3%

Breast disordersb

 

 

 

 

    Combinationa

2.1%

0.8%

0.9%

0.6%

    Dutasteride

1.7%

1.2%

0.5%

0.7%

    Tamsulosin

0.8%

0.4%

0.2%

0%

Nervous system disorders

Dizziness

 

 

 

 

    Combinationa

1.4%

0.1%

<0.1%

0.2%

    Dutasteride

0.7%

0.1%

<0.1%

<0.1%

    Tamsulosin

1.3%

0.4%

<0.1%

0%

 

a           Combination = dutasteride 0.5 mg once daily plus tamsulosin 0.4 mg once daily.

b           Includes breast tenderness and breast enlargement.

 

**************************************************************

 

5.       PHARMACOLOGICAL PROPERTIES

 

5.1.            Pharmacodynamic Properties

 

AVODART IN COMBINATION WITH THE ALPHA-BLOCKER TAMSULOSIN

 

Avodart 0.5 mg/day (n = 1,623), tamsulosin 0.4 mg/day (n = 1,611) or the combination of Avodart 0.5 mg plus tamsulosin 0.4 mg (n = 1,610) were evaluated in male subjects with moderate to severe symptoms of BPH who had prostates ≥30ml and a PSA value within the range 1.5 - 10 ng/mL in a multicentre, multinational, randomized double-blind, parallel group study. Approximately 5352% of subjects had previous exposure to 5-alpha reductase inhibitor or alpha-blocker treatment. The primary efficacy endpointEfficacy endpoints during the first 2 years of treatment waswere change in International Prostate Symptom Score (IPSS), maximum urine flow rate (Qmax) and prostate volume. IPSS is an 8-item instrument based on AUA-SI with an additional question on quality of life. Secondary efficacy endpoints at 2 years included maximum urine flow rate (Qmax) and prostate volume. The combination achieved significance for IPSS from Month 3 compared to Avodart and from Month 9 compared to tamsulosin. For Qmax combination achieved significance from Month 6 compared to both Avodart and tamsulosin.

 

The primary efficacy endpoint at 4 years of treatment was time to first event of AUR or BPH-related surgery. After 4 years of treatment, combination therapy statistically significantly reduced the risk of AUR or BPH-related surgery (65.8% reduction in risk p<0.001 [95% CI 54.7% to 74.1%]) compared to tamsulosin monotherapy. The incidence of AUR or BPH-related surgery by Year 4 was 4.2% for combination therapy and 11.9% for tamsulosin (p<0.001). Compared to Avodart monotherapy, combination therapy reduced the risk of AUR or BPH-related surgery by 19.6% (p=0.18 [95% CI -10.9% to 41.7%]). The incidence of AUR or BPH-related surgery by Year 4 was 4.2% for combination therapy and 5.2% for Avodart.

 

Secondary efficacy endpoints after 4 years of treatment included time to clinical progression (defined as a composite of: IPSS deterioration by ³4 points, BPH-related events of AUR, incontinence, urinary tract infection (UTI), and renal insufficiency) change in International Prostate Symptom Score (IPSS), maximum urine flow rate (Qmax) and prostate volume. IPSS is an 8-item instrument based on the AUA-SI with an additional question on quality of life. Results following 4 years of treatment are presented below:

 

Results following 2 years of treatment are presented below:

 

Parameter

 

Time-point

Combination

Avodart

Tamsulosin

AUR or BPH related surgery (5)

Incidence at Month 48

4.2

5.2

11.9a

Clinical progression* (%)

Month 48

12.6

17.8b

21.5a

IPSS (units)

[Baseline]

Month 4824 (Change from Baseline)

[16.6]

-6.32

[16.4]

-5.3b4.9a

[16.4]

-3.8a4.3b

Qmax (mL/sec)

[Baseline]

Month 4824 (Change from Baseline)

[10.9]

2.4

[10.6]

2.01.9c*

[10.7]

0.7a9d*

Prostate Volume (ml)

[Baseline](ml)

Month 4824 (% Change from Baseline)

[54.7]

-27.36.9

[54.6]

-28.0

[55.8]

+4.6a0.0*

Prostate Transition Zone Volume (ml)#

[Baseline](ml)

Month 4824 (% Change from Baseline)

[27.7]

-17.923.4

[30.3]

-26.52.8

[30.5]

18.2a8.8*

BPH Impact Index (BII) (units)

[Baseline]

Month 4824 (Change from Baseline)

[5.3]

-2.21

[5.3]

-1.8b7*

[5.3]

-1.2a5*

IPSS Question 8 (BPH-related Health Status) (units)

 

[Baseline]

Month 4824 (Changes from Baseline)

[3.6]

-1.54

[3.6]

-1.3b1*

[3.6]

-1.1a*

Baseline values are mean values and changes from baseline are adjusted mean changes.

* Clinical progression was defined as a composite of: IPSS deterioration by ³4 points, BPH-related events of AUR, incontinence, UTI, and renal insufficiency.

# Measured at selected sites (13% of randomized patients)

a. Combination achieved significance (p<0.001) vs. tamsulosin at Month 48

b. Combination achieved significance (p<0.001) vs. Avodart at Month 48

a. Combination achieved significance (p<0.001) vs. Avodart from Month 3

b. Combination achieved significance (p<0.001) vs. tamsulosin from Month 9

c. Combination achieved significance (p<=0.006) vs. Avodart from Month 6

d. Combination achieved significance (p<0.001) vs. tamsulosin from Month 6

* p<0.01

 

Cardiac failure:

 

In this 4 year BPH study the incidence of the composite term cardiac failure in the combination group (14/1610, 0.9%) was higher than in either monotherapy group:  Avodart, (4/1623, 0.2%) and tamsulosin, (10/1611, 0.6%) (see section 4.4).

 

**************************************************************

 

10.     DATE OF REVISION OF THE TEXT

 

May 2010March 2011

Updated on 09 July 2010

Reasons for updating

  • Change to drug interactions

Updated on 02 June 2010

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 5.1 - Pharmacodynamic properties

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……………..

 

 

4.1.            Special Warnings and Special Precautions for Use

 

Combination therapy should be prescribed after careful benefit risk assessment due to the potential increased risk of adverse events and after consideration of alternative treatment options including monotherapies (see section 4.2).

 

In a 4-year clinical study, the incidence of cardiac failure (a composite term of reported events, primarily cardiac failure and congestive cardiac failure) was higher among subjects taking the combination of Avodart and an alpha blocker tamsulosin, than it was among subjects not taking the combination.  No causal relationship between Avodart (alone or in combination with an alpha blocker) and cardiac failure has been established (see section 5.1).

 

……………….

 

Section 5.1 Pharmacodynamic Properties

 

 

……………….

 

AVODART IN COMBINATION WITH THE ALPHA-BLOCKER TAMSULOSIN

 

Avodart 0.5 mg/day (n = 1,623), tamsulosin 0.4 mg/day (n = 1,611) or the combination of Avodart 0.5 mg plus tamsulosin 0.4 mg (n = 1,610) were evaluated in male subjects with moderate to severe symptoms of BPH who had prostates ³30ml and a PSA value within the range 1.5 - 10 ng/mL in a multicentre, multinational, randomized double‑blind, parallel group study. Approximately 52% of subjects had previous exposure to 5-alpha reductase inhibitor or alpha-blocker treatment. Efficacy endpoints during the first 2 years of treatment were change in International Prostate Symptom Score (IPSS), maximum urine flow rate (Qmax) and prostate volume. IPSS is an 8-item instrument based on AUA-SI with an additional question on quality of life.

 

Results following 2 years of treatment are presented below:

 

 

Parameter

 

Time-point

Combination

Avodart

Tamsulosin

IPSS (units)

[Baseline]

Month 24 (Change from Baseline)

[16.6]

-6.2

[16.4]

-4.9a

[16.4]

-4.3b

Qmax (mL/sec)

[Baseline]

Month 24 (Change from Baseline)

[10.9]

2.4

[10.6]

1.9c*

[10.7]

0.9d*

Prostate Volume

[Baseline] (ml)

Month 24 (% Change from Baseline)

[54.7]

-26.9

[54.6]

-28.0

[55.8]

0.0*

Prostate Transition Zone Volume

[Baseline] (ml)

Month 24 (% Change from Baseline)

[27.7]

-23.4

[30.3]

-22.8

[30.5]

8.8*

BPH Impact Index (BII) (units)

[Baseline]

Month 24 (Change from Baseline)

[5.3]

-2.1

[5.3]

-1.7*

[5.3]

-1.5*

IPSS Question 8 (BPH-related Health Status)

 

[Baseline]

Month 24 (Change from Baseline)

[3.6]

-1.4

[3.6]

-1.1*

[3.6]

-1.1*

a. Combination achieved significance (p<0.001) vs. Avodart from Month 3

b. Combination achieved significance (p<0.001) vs. tamsulosin from Month 9

c. Combination achieved significance (p<=0.006) vs. Avodart from Month 6

d. Combination achieved significance (p<0.001) vs. tamsulosin from Month 6

* p<0.01

 

Cardiac failure:

 

In this 4 year BPH study the incidence of the composite term cardiac failure in the combination group (14/1610, 0.9%) was higher than in either monotherapy group:  Avodart, (4/1623, 0.2%) and tamsulosin, (10/1611, 0.6%) (see section 4.4).

 

Updated on 07 December 2009

Reasons for updating

  • Improved electronic presentation

Updated on 22 October 2009

Reasons for updating

  • Change of manufacturer

Updated on 02 December 2008

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to dosage and administration

Updated on 26 August 2008

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 10 - Date of revision of the text

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4.1.            Posology and Method of Administration

 

Avodart can be administered alone or in combination with the alpha-blocker tamsulosin (0.4 mg) (see sections 4.4, 4.8 and 5.1).

 

Adults (including elderly):

 

The recommended dose of Avodart is one capsule (0.5 mg) taken orally once a day.  The capsules should be swallowed whole and not chewed or opened as contact with the capsule contents may result in irritation of the oropharyngeal mucosa. The capsules may be taken with or without food.  Although an improvement may be observed at an early stage, it can take up to 6 months before a response to the treatment can be achieved. No dose adjustment is necessary in the elderly.

 

Renal impairment

 

The effect of renal impairment on dutasteride pharmacokinetics has not been studied. No adjustment in dosage is anticipated for patients with renal impairment (see section 5.2).

 

Hepatic impairment

 

The effect of hepatic impairment on dutasteride pharmacokinetics has not been studied so caution should be used in patients with mild to moderate hepatic impairment (see section 4.4 and section 5.2). In patients with severe hepatic impairment, the use of dutasteride is contraindicated (See section 4.3 Contraindications).

10.     DATE OF REVISION OF THE TEXT

 

June 2008

Updated on 30 June 2008

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties

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Changes due to approval of the indication for co-administration of Avodart with alpha-blocker Tamsulosin.

Relevant amendments to sections 4.1, 4.2, 4.4, 4.8, & 5.1 of the SPC.

Updated on 20 June 2008

Reasons for updating

  • Change of manufacturer
  • Change to, or new use for medicine
  • Change to side-effects

Updated on 04 March 2008

Reasons for updating

  • Correction of spelling/typing errors

Legal category:Product subject to medical prescription which may not be renewed (A)

Updated on 08 February 2008

Reasons for updating

  • Change to section 4.8 - Undesirable effects

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4.8.      Undesirable Effects

Approximately 19% of the 2167 patients who received dutasteride in the Phase III placebo-controlled trials developed adverse reactions. The majority of events were mild to moderate and occurred in the reproductive system.

 

The following table shows adverse reactions from controlled clinical trials and post-marketing experience. The listed adverse events from clinical trials have been reported with a higher incidence in patients treated with dutasteride compared with placebo during the first year of treatment. Adverse events from post-marketing experience were identified from spontaneous post-marketing reports; therefore the true incidence is unknown:

 

 

 

 

Organ system

Adverse reaction       

Incidence

 

*Reproductive system and breast disorders

Impotence        

6.0%   

Altered (decreased) libido

3.7%

Ejaculation disorders

1.8%   

Gynecomastia (includes breast enlargement and/or breast tenderness)

1.3%   

**Immune system disorders

Allergic reactions including rash, pruritus, urticaria, localised oedema, and angioedema

Unknown

* Incidence from clinical trial data

** Adverse events from post-marketing data

Updated on 14 December 2007

Reasons for updating

  • Change to improve clarity and readability

Updated on 29 November 2007

Reasons for updating

  • Improved electronic presentation

Legal category:Product subject to medical prescription which may not be renewed (A)

Updated on 28 August 2007

Reasons for updating

  • Improved electronic presentation

Legal category:Product subject to medical prescription which may not be renewed (A)

Updated on 20 December 2006

Reasons for updating

  • Change to section 6.5 - Nature and contents of container

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6.5. Nature and Contents of Container

Blisters of opaque PVC/PVDC film containing 10 soft gelatin capsules packed into containers of 10, 30, 50, 60 and 90 capsules. Not all pack sizes may be marketed.

Updated on 13 November 2006

Reasons for updating

  • Change to warnings or special precautions for use

Updated on 02 March 2006

Reasons for updating

  • Improved electronic presentation

Updated on 13 February 2006

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 5.1 - Pharmacodynamic properties

Legal category:Product subject to medical prescription which may not be renewed (A)

Updated on 31 January 2006

Reasons for updating

  • Improved electronic presentation

Updated on 04 August 2005

Reasons for updating

  • New PIL for medicines.ie

Updated on 07 January 2005

Reasons for updating

  • New SPC for new product

Legal category:Product subject to medical prescription which may not be renewed (A)