4. Possible side effects

Reporting of Side effects

United Kingdom (Northern Ireland): Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

 

6. Contents of the pack and other information

Marketing Authorisation Holder and Manufacturer

Ireland and United Kingdom (Northern Ireland)

Eli Lilly and Company (Ireland) Limited

Tel: + 353-(0) 1 661 4377

 

United Kingdom

Eli Lilly and Company Limited

Tel: + 44-(0) 1256 315000

 

This leaflet was revised in July 2020 September 2021

Changes

Added (underline) deleted (strikethrough)

Formatting changes made throughout the document.

4.4          Special warnings and precautions for use

[…]

Sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

[…]

4.8          Undesirable effects

[…]

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via United Kingdom: Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard or Ireland: HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie. Malta: ADR Reporting, Website: www.medicinesauthority.gov.mt/adportal.

[…]

8.         MARKETING AUTHORISATION NUMBER(S)

 

Ireland, Malta and United Kingdom (Northern Ireland)

EU/1/08/476/005                Adcirca 20 mg 28 tablets

EU/1/08/476/006                Adcirca 20 mg 56 tablets

 

United Kingdom (Great Britain)

PLGB 14895/0229

 

10.       DATE OF REVISION OF THE TEXT

23 March 201728 January 2021

[…]

 

AD123M

Changes

Added (underline) deleted (strikethrough)

Title

ADCIRCA^® 20 mg film-coated tablets

tTadalafil

 

2.         What you need to know before you take ADCIRCA

[…]

ADCIRCA contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium‑free’.

 

4.         Possible side effects

[…]

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via

United Kingdom: Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store; Ireland: HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.; Malta: ADR Reporting, Website: www.medicinesauthority.gov.mt/adrportal.  By reporting side effects you can help provide more information on the safety of this medicine.

 

6.         Contents of the pack and other information

[…]

Malta

Charles de Giorgio Ltd.

Tel: + 356 25600 500

[…]

 

This leaflet was last revised in February January 2021

Changes

Added (bold), Deleted (strikethrough):

 

4.2       Posology and method of administration

Paediatric population

The safety and efficacy of ADCIRCA in individuals below 18 years of agethe paediatric population has not yet been established.  No data are availableCurrently available data are described in section 5.1.

 

5.1          Pharmacodynamic properties

Paediatric population

A single study has been performed in paediatric patients with Duchenne Muscular Dystrophy (DMD) in which no evidence of efficacy was seen. The randomised, double‑blind, placebo‑controlled, parallel, 3‑arm study of tadalafil was conducted in 331 boys aged 7‑14 years with DMD receiving concurrent corticosteroid therapy. The study included a 48‑week double-blind period where patients were randomised to tadalafil 0.3 mg/kg, tadalafil 0.6 mg/kg, or placebo daily. Tadalafil did not show efficacy in slowing the decline in ambulation as measured by the primary 6 minute walk distance (6MWD) endpoint: least squares (LS) mean change in 6MWD at 48 weeks was ‑51.0 meters (m) in the placebo group, compared with ‑64.7 m in the tadalafil 0.3 mg/kg group (p = 0.307) and ‑59.1 m in the tadalafil 0.6 mg/kg group (p = 0.538). In addition, there was no evidence of efficacy from any of the secondary analyses performed in this study. The overall safety results from this study were generally consistent with the known safety profile of tadalafil and with adverse events (AEs) expected in a paediatric DMD population receiving corticosteroids.

The European Medicines Agency has deferred the obligation to submit the results of studies with ADCIRCA in one or more subsets of the paediatric population in the treatment of pulmonary arterial hypertension (see section 4.2 for information on paediatric use).

 

6.6       Special precautions for disposal

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

 

10.          DATE OF REVISION OF THE TEXT

23 MarchFebruary 2017     

 

*ADCIRCA (tadalafil) is a trademark of Eli Lilly and Company.                                                                                    AD112M

Added (bold), Deleted (strikethrough):

 

4.2       Posology and method of administration

 

 

Paediatric population

The safety and efficacy of ADCIRCA in individuals below 18 years of agethe paediatric population has not yet been established.  No data are availableCurrently available data are described in section 5.1.

 

 

5.1          Pharmacodynamic properties

 

Paediatric population

A single study has been performed in paediatric patients with Duchenne Muscular Dystrophy (DMD) in which no evidence of efficacy was seen. The randomised, double‑blind, placebo‑controlled, parallel, 3‑arm study of tadalafil was conducted in 331 boys aged 7‑14 years with DMD receiving concurrent corticosteroid therapy. The study included a 48‑week double-blind period where patients were randomised to tadalafil 0.3 mg/kg, tadalafil 0.6 mg/kg, or placebo daily. Tadalafil did not show efficacy in slowing the decline in ambulation as measured by the primary 6 minute walk distance (6MWD) endpoint: least squares (LS) mean change in 6MWD at 48 weeks was ‑51.0 meters (m) in the placebo group, compared with ‑64.7 m in the tadalafil 0.3 mg/kg group (p = 0.307) and ‑59.1 m in the tadalafil 0.6 mg/kg group (p = 0.538). In addition, there was no evidence of efficacy from any of the secondary analyses performed in this study. The overall safety results from this study were generally consistent with the known safety profile of tadalafil and with adverse events (AEs) expected in a paediatric DMD population receiving corticosteroids.

 

The European Medicines Agency has deferred the obligation to submit the results of studies with ADCIRCA in one or more subsets of the paediatric population in the treatment of pulmonary arterial hypertension (see section 4.2 for information on paediatric use).

 

 

6.6       Special precautions for disposal

 

No special requirements.

 

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

 

 

10.          DATE OF REVISION OF THE TEXT

 

23 MarchFebruary 2017

               

 

 

*ADCIRCA (tadalafil) is a trademark of Eli Lilly and Company.                                                                                    AD112M

Added (bold), Deleted (strikethrough):

 

4.4       Special warnings and precautions for use

 

 

Vision

Visual defects and cases of NAION have been reported in connection with the intake of tadalafil and other PDE5 inhibitors. Analyses of observational data suggest an increased risk of acute NAION in men with erectile dysfunction following exposure to tadalafil or other PDE5 inhibitors. As this may be relevant for all patients exposed to tadalafil, tThe patient should be advised that in case of sudden visual defect, he should stop taking ADCIRCA andto consult a physician immediately (see section 4.3). Patients with known hereditary degenerative retinal disorders, including retinitis pigmentosa, were not included in the clinical studies, and use in these patients is not recommended.

 

Changes

 

Added (bold), Deleted (strikethrough):

 

4.4       Special warnings and precautions for use

 

 

Decreased or sudden hearing loss

Cases of sudden hearing loss have been reported after the use of tadalafil. Although other risk factors were present in some cases (such as age, diabetes, hypertension and previous hearing loss history) patients should be advised to stop taking tadalafil and seek prompt medical attention in the event of sudden decrease or loss of hearing.

 

Renal and hepatic impairment

 

 

10.       DATE OF REVISION OF THE TEXT

 

01 January 201623 February 2017

Changes

 

Added (bold), Deleted (strikethrough):

 

 

 

7.         MARKETING AUTHORISATION HOLDER

 

Eli Lilly Nederland B.V.

Papendorpseweg 83, 3528 BJ Utrecht Grootslag 1-5, NL-3991 RA, Houten
The Netherlands

 

 

10.       DATE OF REVISION OF THE TEXT

 

20 August 201501 January 2016

*ADCIRCA (tadalafil) is a trademark of Eli Lilly and Company. AD78M

Changes

 

Added (bold), Deleted (strikethrough):

 

4.3          Contraindications

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

 

Acute myocardial infarction within the last 90 days.

 

Severe hypotension (<90/50 mm Hg).

 

-          In clinical studies, tadalafil was shown to augment the hypotensive effects of nitrates. This is thought to result from the combined effects of nitrates and tadalafil on the nitric oxide/cGMP pathway. Therefore, administration of tadalafil to patients who are using any form of organic nitrate is contraindicated (see section 4.5).

 

The co-administration of PDE5 inhibitors, including tadalafil, with guanylate cyclase stimulators, such as riociguat, is contraindicated as it may potentially lead to symptomatic hypotension (see section 4.5).

 

Patients who have loss of vision in one eye because of non-arteritic anterior ischaemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure (see section 4.4).

 

4.5          Interaction with other medicinal products and other forms of interaction

 

Riociguat

Preclinical studies showed an additive systemic blood pressure lowering effect when PDE5 inhibitors were

combined with riociguat.  In clinical studies, riociguat has been shown to augment the hypotensive effects of PDE5

inhibitors. There was no evidence of favourable clinical effect of the combination in the population studied.

Concomitant use of riociguat with PDE5 inhibitors, including tadalafil, is contraindicated (see section 4.3).

 

4.8          Undesirable effects

 

Description of selected adverse reactions

 

1 Events not reported in registration studies and cannot be estimated from the available data.  The adverse

reactions have been included in the table as a result of postmarketing or clinical study data from the use of

tadalafil in the treatment of erectile dysfunction.

2 Most of the patients in whom these events have been reported had pre-existing cardiovascular risk factors.

 

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows

continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to

report any suspected adverse reactions via UK: www.mhra.gov.uk/yellowcard or Ireland: HPRA

Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website:

www.hpra.ie; E-mail: medsafety@hpra.ie.

 

10.          DATE OF REVISION OF THE TEXT

 

20 August 2015

Note: document re-ordered throughout due to QRD template changes affecting placement, alternative wording and layout throughout document

 

 

2.         QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Added (bold) deleted (strikethrough):

 

Each film-coated tablet contains 20 mg tadalafil.

 

Excipient with known effect:
Each film-coated tablet contains 245 233 mg lactose (as monohydrate).

 

 

 

3.         PHARMACEUTICAL form

 

Added (bold):

Orange and almond shaped film-coated tablets, marked "4467" on one side.

 

 

 

4.         Clinical particulars

4.6       Fertility, pregnancy and lactation

 

Added:

 

Fertility

Effects were seen in dogs that might indicate impairment of fertility. Two subsequent clinical studies suggest that this effect is unlikely in humans, although a decrease in sperm concentration was seen in some men (see sections 5.1 and 5.3).

 

4.7       Effects on ability to drive and use machines

 

Added (bold) deleted (strikethrough):

 

ADCIRCA has negligible influence on the ability to drive or use machines. No studies on the effect on the ability to drive and use machines have been performed.

 

4.8       Undesirable effects

 

Deleted:

Cardiac disorders
	Chest pain2 Palpitations2, 5	Sudden cardiac death2, 5, Tachycardia2, 5		Unstable angina pectoris, Ventricular arrhythmia, Myocardial Infarction2

 

 

5.         PHARMACOLOGICAL PROPERTIES

 

5.1       Pharmacodynamic properties

 

Added (bold):

 

Pharmacotherapeutic group: Urologicals, drugs used in erectile dysfunction, ATC code: G04BE08.

 

 

Added :

 

Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of studies with ADCIRCA in one or more subsets of the paediatric population in the treatment of pulmonary arterial hypertension (see section 4.2 for information on paediatric use).

 

 

 

9.         DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

 

Added:

Date of latest renewal: 1 October 2013

 

 

10.          DATE OF REVISION OF THE TEXT

 

New date

               

22 May 2013

 

                Added:

 

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu.

 

4.         Clinical particulars

4.8       Undesirable effects

 

Added (bold) deleted (strikethrough):

 

Very common (≥1/10)	Common (≥1/100 to <1/10)	Uncommon (≥1/1000 to <1/100)	Rare (≥1/10,000 to <1/1000)		Not known1
Nervous System disorders
Headache67	Syncope, Migraine5	Seizures5, Transient amnesia5			Stroke2 (including haemorrhagic events)
Ear and labyrinth disorders
		Tinnitus			Sudden hearing loss6
Renal and urinary disorders
		Haematuria
Reproductive system and breast disorders
	Increased uterine bleeding4	Priapism5, Penile haemorrhage, Haematospermia			Prolonged erections

 

(6) Sudden decrease or loss of hearing has been reported in a small number of postmarketing and clinical trial cases with the use of all PDE5 inhibitors, including tadalafil.

(7) (6) See section c)

 

 

10.          DATE OF REVISION OF THE TEXT

 

New date

               

                17 January 2013

4.         Clinical particulars

4.8       Undesirable effects

 

Added (bold):

 

Very common (≥1/10)	Common (≥1/100 to <1/10)	Uncommon (≥1/1000 to <1/100)	Rare (≥1/10,000 to <1/1000)	Not known1
Immune system disorders
	Hypersensitivity reactions5			Angioedema
Nervous System disorders
Headache7	Syncope, Migraine5	Seizures5, Transient amnesia5		Stroke2 (including haemorrhagic events)

 

 

 

10.          DATE OF REVISION OF THE TEXT

 

New date

               

                23 August 2012

None provided