Tadalafil Actavis 10 mg Filmdragerad tablett

Sverige - svenska - Läkemedelsverket (Medical Products Agency)

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Bipacksedel Bipacksedel (PIL)

11-12-2020

Produktens egenskaper Produktens egenskaper (SPC)

27-04-2018

Aktiva substanser:
tadalafil
Tillgänglig från:
Actavis Group PTC ehf.
ATC-kod:
G04BE08
INN (International namn):
tadalafil
Dos:
10 mg
Läkemedelsform:
Filmdragerad tablett
Sammansättning:
laktosmonohydrat Hjälpämne; natriumlaurilsulfat Hjälpämne; tadalafil 10 mg Aktiv substans
Receptbelagda typ:
Receptbelagt
Produktsammanfattning:
Förpacknings: Blister, 4 tabletter; Blister, 8 tabletter; Blister, 12 tabletter
Bemyndigande status:
Godkänd
Godkännandenummer:
52884
Tillstånd datum:
2016-07-20

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26-10-2020

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20-07-2016

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Bipacksedel: Information till användaren

Tadalafil Actavis 10 mg filmdragerade tabletter

tadalafil

Läs noga igenom denna bipacksedel innan du börjar ta detta läkemedel. Den innehåller

information som är viktig för dig.

Spara denna information, du kan behöva läsa den igen.

Om du har ytterligare frågor vänd dig till läkare eller apotekspersonal.

Detta läkemedel har ordinerats enbart åt dig. Ge det inte till andra. Det kan skada dem, även om

de uppvisar sjukdomstecken som liknar dina.

Om du får biverkningar, tala med läkare eller apotekspersonal. Detta gäller även eventuella

biverkningar som inte nämns i denna information. Se avsnitt 4.

I denna bipacksedel finns information om följande

Vad Tadalafil Actavis är och vad det används för

Vad du behöver veta innan du tar Tadalafil Actavis

Hur du tar Tadalafil Actavis

Eventuella biverkningar

Hur Tadalafil Actavis ska förvaras

Förpackningens innehåll och övriga upplysningar

1.

Vad Tadalafil Actavis är och vad det används för

Tadalafil Actavis är en behandling för vuxna män med erektil dysfunktion. Detta innebär att en man

inte kan få, eller bibehålla, en hård, erigerad penis, tillräcklig för sexuellt umgänge. Tadalafil Actavis

har visat sig signifikant förbättra förmågan att få en hård, erigerad penis, tillräcklig för sexuellt

umgänge.

Tadalafil Actavis innehåller den aktiva substansen tadalafil som tillhör en grupp läkemedel som kallas

fosfodiesteras typ 5-hämmare. Tadalafil Actavis verkar vid sexuell stimulering genom att blodkärlen i

penis slappnar av, så att blod kan strömma in. Detta resulterar i förbättrad erektil funktion. Om du inte

har erektil dysfunktion hjälper inte Tadalafil Actavis.

Det är viktigt att komma ihåg att Tadalafil Actavis inte har någon effekt, om du inte är sexuellt

stimulerad. Behovet av förspel för dig och din partner är detsamma som när du inte har tagit något

läkemedel för erektil dysfunktion.

Tadalafil som finns i Tadalafil Actavis kan också vara godkänd för att behandla andra sjukdomar som

inte nämns i denna produktinformation. Fråga läkare, apoteks- eller annan hälso- och

sjukvårdspersonal om du har ytterligare frågor och följ alltid deras instruktion.

2.

Vad du behöver veta innan du tar Tadalafil Actavis

Ta inte Tadalafil Actavis om du:

är allergisk mot tadalafil eller något annat innehållsämne i detta läkemedel (anges i avsnitt 6).

tar läkemedel som innehåller organiska nitrater eller kväveoxid-donatorer som t ex amylnitrit.

Dessa läkemedel (”nitrater”) används för att behandla kärlkramp (bröstsmärta). Tadalafil

Actavis har visat sig öka effekten av dessa läkemedel. Om du tar någon form av nitrater eller

om du är osäker, tala med din läkare.

har en allvarlig hjärtsjukdom eller nyligen har haft en hjärtattack inom de senaste 90 dagarna.

nyligen har haft slaganfall (stroke) inom de senaste 6 månaderna.

har lågt blodtryck eller okontrollerat högt blodtryck.

någonsin tidigare har förlorat synen på grund av icke-arteritisk främre ischemisk

optikusneuropati (NAION), så kallad ”stroke i ögat”.

tar riociguat. Detta läkemedel används för att behandla pulmonell arteriell hypertension (dvs

högt blodtryck i lungorna) och kronisk tromboembolisk pulmonell hypertension (dvs högt

blodtryck i lungorna till följd av blodproppar). PDE5-hämmare, såsom Tadalafil Actavis, har

visats öka den blodtryckssänkande effekten av detta läkemedel. Om du tar riociguat eller om

du är osäker, tala med din läkare.

Varningar och försiktighet

Tala med läkare innan du tar Tadalafil Actavis.

Tänk på att sexuellt umgänge utgör en möjlig risk för patienter med hjärtsjukdom, eftersom det

anstränger hjärtat mer än vanligt. Om du har problem med hjärtat ska du tala om det för din läkare.

Innan du tar tabletterna, tala om för din läkare om du har:

sicklecellanemi (onormala röda blodkroppar).

multipelt myelom (cancer i benmärgen).

leukemi (blodcellscancer).

deformerad penis.

allvarlig leversjukdom.

allvarlig njursjukdom.

Det är inte känt om Tadalafil Actavis är effektivt hos patienter som har genomgått:

bäckenoperation.

operation där delar av, eller hela, prostatakörteln avlägsnas och där nerverna inte bevaras

(radikal icke-nervsparande prostatektomi).

Om du får en plötslig synnedsättning eller synförlust ska du avbryta behandlingen med Tadalafil

Actavis och omedelbart ta kontakt med din läkare.

Försämrad hörsel eller plötslig hörselnedsättning har noterats hos några patienter som tar tadalafil.

Fastän det inte är känt om händelserna har ett samband med tadalafil, bör du kontakta läkare

omedelbart om du får försämrad hörsel eller plötslig hörselnedsättning.

Tadalafil Actavis är inte avsett för användning av kvinnor

Barn och ungdomar

Tadalafil Actavis är inte avsett för användning av barn och ungdomar under 18 år.

Andra läkemedel och Tadalafil Actavis

Tala alltid om för din läkare om du tar, nyligen har tagit eller kan tänkas ta andra läkemedel.

Ta inte Tadalafil Actavis om du redan tar nitrater.

Vissa läkemedel kan påverkas av Tadalafil Actavis eller påverka hur väl Tadalafil Actavis kommer att

fungera. Tala om för din läkare eller apotekspersonal om du redan tar:

alfa-blockerare (används för att behandla högt blodtryck eller urinvägssymtom relaterade till

benign prostatahyperplasi).

något annat läkemedel för att behandla högt blodtryck.

riociguat.

en 5-alfa reduktashämmare (som används för att behandla benign prostatahyperplasi).

läkemedel så som ketokonazoltabletter (för att behandla svampinfektioner) och

proteashämmare för behandling av AIDS eller HIV infektion.

fenobarbital, fenytoin och karbamazepin (antiepileptiska läkemedel).

rifampicin, erytromycin, klaritromycin eller itrakonazol.

andra behandlingar för erektil dysfunktion.

Tadalafil Actavis med dryck och alkohol

För information om påverkan av alkohol, se avsnitt 3. Grapefruktjuice kan påverka hur väl Tadalafil

Actavis kommer att fungera och skall intas med försiktighet. Tala med din läkare för ytterligare

information.

Fertilitet

När hundar behandlades sågs en minskning av sperma. Minskning av sperma har setts hos några män.

Det är osannolikt att denna minskning av sperma skulle leda till infertilitet.

Körförmåga och användning av maskiner

Yrsel har rapporterats av några av de män som tagit Tadalafil Actavis i de kliniska studierna. Känn

efter hur du reagerar på tabletterna innan du kör bil eller använder maskiner.

Du är själv ansvarig för att bedöma om du är i kondition att framföra motorfordon eller utföra arbeten

som kräver skärpt uppmärksamhet. En av faktorerna som kan påverka din förmåga i dessa avseenden

är användning av läkemedel på grund av deras effekter och/eller biverkningar. Beskrivning av dessa

effekter och biverkningar finns i andra avsnitt. Läs därför all information i denna bipacksedel för

vägledning. Diskutera med din läkare eller apotekspersonal om du är osäker.

Tadalafil Actavis innehåller laktos och natrium:

Om du inte tål vissa sockerarter, bör du kontakta din läkare innan du tar detta läkemedel.

Detta läkemedel innehåller mindre än 1 mmol (23 mg) per filmdragerad tablett, d.v.s. är nästintill

”natriumfritt”.

3.

Hur du tar Tadalafil Actavis

Ta alltid detta läkemedel enligt läkarens anvisningar. Rådfråga läkare eller apotekspersonal om du är

osäker.

Tadalafil Actavis tabletter intas genom munnen och är endast avsedda för män. Svälj tabletten hel med

lite vatten. Tabletten kan tas oberoende av måltid.

Den rekommenderade dosen

är en 10 mg före sexuell aktivitet. Om effekten är för svag av

denna dos kan läkaren öka dosen till 20 mg. Tadalafil Actavis tabletter intas genom munnen.

Tadalafil Actavis kan tas ända fram till 30 minuter före sexuell aktivitet. Effekten av Tadalafil Actavis

kan kvarstå upp till 36 timmar efter tablettintag.

Ta inte Tadalafil Actavis mer än en gång per dag. Tadalafil Actavis 10 mg och 20 mg är avsett att

användas före förväntad sexuell aktivitet och rekommenderas inte att användas kontinuerligt varje dag.

Det är viktigt att komma ihåg att Tadalafil Actavis inte har någon effekt, om du inte är sexuellt

stimulerad. Behovet av förspel för dig och din partner är detsamma som när du inte har tagit något

läkemedel för erektil dysfunktion.

Alkoholintag kan påverka din förmåga att få erektion och kan tillfälligt sänka ditt blodtryck. Undvik

intag av stora mängder alkohol (0,8 promille eller mer i blodet) när du har tagit eller planerar att ta

Tadalafil Actavis eftersom detta kan öka risken för yrsel när man står upp.

Om du har tagit för stor mängd av Tadalafil Actavis

Kontakta din läkare. Du kan få biverkningar beskrivna i avsnitt 4.

Om du fått i dig för stor mängd läkemedel eller om t.ex. ett barn fått i sig läkemedlet av misstag

kontakta läkare, sjukhus eller Giftinformationscentralen (tel. 112) för bedömning av risken samt

rådgivning.

Om du har ytterligare frågor om detta läkemedel vänd dig till din läkare eller apotekspersonal.

4.

Eventuella biverkningar

Liksom alla läkemedel kan detta läkemedel orsaka biverkningar men alla användare behöver inte få

dem. Biverkningarna är vanligen milda eller måttliga till sin natur.

Om du får någon av följande biverkningar, sluta använda läkemedlet och uppsök läkare

omedelbart:

allergiska reaktioner med utslag (frekvens mindre vanlig).

bröstsmärta – använd inte nitrater men uppsök läkare omedelbart.

priapism, förlängd och möjligtvis smärtsam erektion efter att ha tagit Tadalafil Actavis

(frekvens sällsynt). Om du får erektion som varar kontinuerligt i över 4 timmar, ska du

omedelbart kontakta läkare.

plötslig synförlust (frekvens sällsynt).

Andra biverkningar har rapporterats:

Vanliga (kan förekomma hos upp till 1 av 10 användare):

huvudvärk, ryggsmärta, muskelvärk, smärta i armar och ben, ansiktsrodnad, nästäppa och

matsmältningsbesvär.

Mindre vanliga (kan förekomma hos upp till 1 av 100 användare):

yrsel, magsmärta, illamående, kräkningar, reflux, dimsyn, smärta i ögonen,

andningssvårigheter, förekomst av blod i urinen, förlängd erektion, hjärtklappning, snabba

hjärtslag, högt blodtryck, lågt blodtryck, näsblod, tinnitus (ljud i öronen utan yttre ljudkälla),

svullna händer, fötter eller anklar och trötthet.

Sällsynta (kan förekomma hos upp till 1 av 1000 användare):

svimning, krampanfall och tillfällig minnesförlust, svullna ögonlock, röda ögon, plötslig

försämring eller förlust av hörsel, utslag (kliande röda små blåsor på huden), blödning från

penis, förekomst av blod i sperma och ökad svettning.

Hjärtattack och slaganfall har rapporterats sällsynt hos män som intagit Tadalafil Actavis. De flesta

hade kända problem med hjärtat innan de tog läkemedlet.

Partiell, tillfällig eller varaktig synnedsättning eller synförlust på ett eller båda ögonen har rapporterats

sällsynt.

Ytterligare några sällsynta biverkningar

som inte observerades i de kliniska prövningarna, har

rapporterats av män som tar Tadalafil Actavis. Dessa är:

migrän, ansiktssvullnad, allvarlig allergisk reaktion som orsakar svullnad av ansikte och svalg,

allvarliga hudutslag, störningar i blodflödet till ögonen, oregelbundna hjärtslag, kärlkramp och

plötslig hjärtdöd.

Biverkningen yrsel har rapporterats oftare hos män över 75 år som tar Tadalafil Actavis. Diarré har

rapporterats oftare hos män över 65 år som tar Tadalafil Actavis.

Rapportering av biverkningar

Om du får biverkningar, tala med läkare eller apotekspersonal. Detta gäller även eventuella

biverkningar som inte nämns i denna information. Du kan också rapportera biverkningar direkt (se

detaljer nedan). Genom att rapportera biverkningar kan du bidra till att öka informationen om

läkemedels säkerhet.

Läkemedelsverket

Box 26

751 03 Uppsala

www.lakemedelsverket.se.

5.

Hur Tadalafil Actavis ska förvaras

Förvara detta läkemedel utom syn- och räckhåll för barn.

Används före utgångsdatum som anges på kartongen och blisterkartan efter EXP.

Utgångsdatumet är den sista dagen i angiven månad.

Inga särskilda förvaringsanvisningar.

Läkemedel ska inte kastas i avloppet eller bland hushållsavfall. Fråga apotekspersonalen hur man

kastar läkemedel som inte längre används. Dessa åtgärder är till för att skydda miljön.

6.

Förpackningens innehåll och övriga upplysningar

Innehållsdeklaration

Den aktiva substansen är tadalafil. En tablett innehåller 10 mg tadalafil.

Övriga innehållsämnen är:

Tablettkärna

: laktosmonohydrat, pregelatiserad stärkelse, kolloidal vattenfri kiseldioxid

kroskarmellosnatrium, natriumlaurilsulfat, magnesiumstearat.

Filmdragering

: hypromellos, laktosmonohydrat, titandioxid (E171), triacetin, talk E553b), gul

järnoxid (E172), röd järnoxid (E172).

Läkemedlets utseende och förpackningsstorlekar

En tablett innehåller 10 mg tadalafil.

10 mg filmdragerade tabletter är: ljust gula, ovala, filmdragerade tabletter, märkta med ”10” på ena

sidan. Tabletterna är 11 mm x 6,6 mm i diameter och 3,9 – 4,5 mm tjocka.

Förpackningsstorlekar

Tadalafil Actavis 10 mg finns i blisterförpackningar med 4, 8 och 12 tabletter.

Eventuellt kommer inte alla förpackningsstorlekar att marknadsföras.

Innehavare av godkännande för försäljning

Actavis Group PTC ehf.

Reykjavikurvegi 76-78

220 Hafnarfjördur

Island

Tillverkare

Actavis Ltd.

BLB016 Bulebel Industrial Estate

Zejtun ZTN 3000

Malta

Balkanpharma Dupnitsa AD

3 Samokovsko Shosse Str.

Dupnitsa 2600

Bulgarien

Specifar SA

1, 28 Octovriou Str.

12351 Agia Varvara

Grekland

Denna bipacksedel ändrades senast

2020-12-11

Ytterligare information om detta läkemedel finns på Läkemedelsverkets webbplats

www.lakemedelsverket.se

Läs hela dokumentet

SUMMARY OF PRODUCT CHARACTERISTICS

1.

NAME OF THE MEDICINAL PRODUCT

Tadalafil Actavis 10 mg film-coated tablets

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 10 mg tadalafil.

Excipient with known effect

Each film-coated tablet contains 177 mg lactose (as monohydrate).

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Film-coated tablet (tablet).

10 mg film-coated tablets are: Pale yellow, oval shape, film-coated tablets, debossed with ‘10’ on one side

and plain on the other side. The tablet is 11 mm x 6.6 mm in diameter and 3.9 – 4.5 mm in thickness.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Treatment of erectile dysfunction in adult males.

In order for tadalafil to be effective, sexual stimulation is required.

Tadalafil Actavis is not indicated for use by women.

4.2

Posology and method of administration

Posology

Adult men

In general, the recommended dose is 10 mg taken prior to anticipated sexual activity and with or without

food. In those patients in whom tadalafil 10 mg does not produce an adequate effect, 20 mg might be tried. It

may be taken at least 30 minutes prior to sexual activity.

The maximum dose frequency is once per day.

Tadalafil 10 and 20 mg is intended for use prior to anticipated sexual activity and it is not recommended for

continuous daily use.

In patients who anticipate a frequent use of Tadalafil Actavis (i.e., at least twice weekly) a once daily

regimen with the lowest doses of Tadalafil Actavis might be considered suitable, based on patient choice and

the physician’s judgement.

In these patients the recommended dose is 5 mg taken once a day at approximately the same time of day. The

dose may be decreased to 2.5 mg once a day based on individual tolerability.

The appropriateness of continued use of the daily regimen should be reassessed periodically.

Special populations

Elderly men

Dose adjustments are not required in elderly patients.

Men with renal impairment

Dose adjustments are not required in patients with mild to moderate renal impairment. For patients with

severe renal impairment 10 mg is the maximum recommended dose. Once-a-day dosing of tadalafil is not

recommended in patients with severe renal impairment (see sections 4.4 and 5.2)

Men with hepatic impairment

The recommended dose of Tadalafil Actavis is 10 mg taken prior to anticipated sexual activity and with or

without food. There is limited clinical data on the safety of tadalafil in patients with severe hepatic

impairment (Child-Pugh Class C); if prescribed, a careful individual benefit/risk evaluation should be

undertaken by the prescribing physician. There are no available data about the administration of doses higher

than 10 mg of tadalafil to patients with hepatic impairment. Once-a-day dosing has not been evaluated in

patients with hepatic impairment; therefore if prescribed, a careful individual benefit/risk evaluation should

be undertaken by the prescribing physician (see sections 4.4 and 5.2).

Men with diabetes

Dose adjustments are not required in diabetic patients.

Paediatric population

There is no relevant use of Tadalafil Actavis in the paediatric population with regard to the treatment of

erectile dysfunction.

Method of administration

For oral use.

4.3

Contraindications

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

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 Actavis to patients who are using any form of organic nitrate is contraindicated

(see section 4.5).

Tadalafil Actavis must not be used in men with cardiac disease for whom sexual activity is inadvisable.

Physicians should consider the potential cardiac risk of sexual activity in patients with pre-existing

cardiovascular disease.

The following groups of patients with cardiovascular disease were not included in clinical trials and the use

of tadalafil is therefore contraindicated:

patients with myocardial infarction within the last 90 days,

patients with unstable angina or angina occurring during sexual intercourse,

patients with New York Heart Association Class 2 or greater heart failure in the last 6 months,

patients with uncontrolled arrhythmias, hypotension (< 90/50 mm Hg), or uncontrolled hypertension,

patients with a stroke within the last 6 months.

Tadalafil Actavis is contraindicated in 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).

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).

4.4

Special warnings and precautions for use

Before treatment with Tadalafil Actavis

A medical history and physical examination should be undertaken to diagnose erectile dysfunction and

determine potential underlying causes, before pharmacological treatment is considered.

Prior to initiating any treatment for erectile dysfunction, physicians should consider the cardiovascular status

of their patients, since there is a degree of cardiac risk associated with sexual activity. Tadalafil has

vasodilator properties, resulting in mild and transient decreases in blood pressure (see section 5.1) and as

such potentiates the hypotensive effect of nitrates (see section 4.3).

The evaluation of erectile dysfunction should include a determination of potential underlying causes and the

identification of appropriate treatment following an appropriate medical assessment. It is not known if

Tadalafil Actavis is effective in patients who have undergone pelvic surgery or radical non-nerve-sparing

prostatectomy.

Cardiovascular

Serious cardiovascular events, including myocardial infarction, sudden cardiac death, unstable angina

pectoris, ventricular arrhythmia, stroke, transient ischemic attacks, chest pain, palpitations and tachycardia,

have been reported either post marketing and/or in clinical trials. Most of the patients in whom these events

have been reported had pre-existing cardiovascular risk factors. However, it is not possible to definitively

determine whether these events are related directly to these risk factors, to Tadalafil Actavis, to sexual

activity, or to a combination of these or other factors.

In patients who are taking alpha

blockers, concomitant administration of tadalafil may lead to symptomatic

hypotension in some patients (see section 4.5). The combination of tadalafil and doxazosin is not

recommended.

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, the patient should be advised that in case of sudden visual defect, he should

stop taking Tadalafil Actavis and consult a physician immediately (see section 4.3).

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.

Hepatic impairment

There is limited clinical data on the safety of single-dose administration of tadalafil in patients with severe

hepatic insufficiency (Child-Pugh Class C). If Tadalafil Actavis is prescribed, a careful individual

benefit/risk evaluation should be undertaken by the prescribing physician.

Priapism and anatomical deformation of the penis

Patients who experience erections lasting 4 hours or more should be instructed to seek immediate medical

assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency may

result.

Tadalafil Actavis should be used with caution in patients with anatomical deformation of the penis (such as

angulation, cavernosal fibrosis or Peyronie's disease), or in patients who have conditions which may

predispose them to priapism (such as sickle cell anaemia, multiple myeloma or leukaemia).

Use with CYP3A4 inhibitors

Caution should be exercised when prescribing Tadalafil Actavis to patients using potent CYP3A4 inhibitors

(ritonavir, saquinavir, ketoconazole, itraconazole, and erythromycin) as increased tadalafil exposure (AUC)

has been observed if the medicinal products are combined (see section 4.5).

Tadalafil Actavis and other treatments for erectile dysfunction

The safety and efficacy of combinations of tadalafil and other PDE5 inhibitors or other treatments for

erectile dysfunction have not been studied. The patients should be informed not to take Tadalafil Actavis in

such combinations.

Excipients

Lactose

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose

malabsorption should not take this medicinal product.

Sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say

essentially ‘sodium-free’.

4.5

Interaction with other medicinal products and other forms of interaction

Interaction studies were conducted with 10 mg and/or 20 mg tadalafil, as indicated below. With regard to

those interaction studies where only the 10 mg tadalafil dose was used, clinically relevant interactions at

higher doses cannot be completely ruled out.

Effects of other substances on tadalafil

Cytochrome P450 inhibitors

Tadalafil is principally metabolised by CYP3A4. A selective inhibitor of CYP3A4, ketoconazole (200 mg

daily), increased tadalafil (10 mg) exposure (AUC) 2-fold and C

by 15  %, relative to the AUC and C

values for tadalafil alone. Ketoconazole (400 mg daily) increased tadalafil (20 mg) exposure (AUC) 4-fold

and C

by 22 %. Ritonavir, a protease inhibitor (200 mg twice daily), which is an inhibitor of CYP3A4,

CYP2C9, CYP2C19, and CYP2D6, increased tadalafil (20 mg) exposure (AUC) 2-fold with no change in

. Although specific interactions have not been studied, other protease inhibitors, such as saquinavir, and

other CYP3A4 inhibitors, such as erythromycin, clarithromycin, itraconazole and grapefruit juice should be

co-administered with caution as they would be expected to increase plasma concentrations of tadalafil (see

section 4.4). Consequently the incidence of the adverse reactions listed in section 4.8 might be increased.

Transporters

The role of transporters (for example p-glycoprotein) in the disposition of tadalafil is not known. Therefore

there is the potential of drug interactions mediated by inhibition of transporters.

Cytochrome P450 inducers

A CYP3A4 inducer, rifampicin, reduced tadalafil AUC by 88 %, relative to the AUC values for tadalafil

alone (10 mg). This reduced exposure can be anticipated to decrease the efficacy of tadalafil; the magnitude

of decreased efficacy is unknown. Other inducers of CYP3A4 such as phenobarbital, phenytoin and

carbamazepine, may also decrease plasma concentrations of tadalafil.

Effects of tadalafil on other medicinal products

Nitrates

In clinical studies, tadalafil (5, 10 and 20 mg) was shown to augment the hypotensive effects of nitrates.

Therefore, administration of Tadalafil Actavis to patients who are using any form of organic nitrate is

contraindicated (see section 4.3). Based on the results of a clinical study in which 150 subjects receiving

daily doses of tadalafil 20 mg for 7 days and 0.4 mg sublingual nitroglycerin at various times, this interaction

lasted for more than 24 hours and was no longer detectable when 48 hours had elapsed after the last tadalafil

dose. Thus, in a patient prescribed any dose of Tadalafil Actavis (2.5 mg-20 mg), where nitrate

administration is deemed medically necessary in a life-threatening situation, at least 48 hours should have

elapsed after the last dose of Tadalafil Actavis before nitrate administration is considered. In such

circumstances, nitrates should only be administered under close medical supervision with appropriate

haemodynamic monitoring.

Anti-hypertensives (including calcium channel blockers)

The co-administration of doxazosin (4 and 8 mg daily) and tadalafil (5 mg daily dose and 20 mg as a single

dose) increases the blood pressure-lowering effect of this alpha-blocker in a significant manner. This effect

lasts at least twelve hours and may be symptomatic, including syncope. Therefore this combination is not

recommended (see section 4.4).

In interaction studies performed in a limited number of healthy volunteers, these effects were not reported

with alfuzosin or tamsulosin. However, caution should be exercised when using tadalafil in patients treated

with any alpha-blockers, and notably in the elderly. Treatments should be initiated at minimal dosage and

progressively adjusted.

In clinical pharmacology studies, the potential for tadalafil to augment the hypotensive effects of

antihypertensive medicinal products was examined. Major classes of antihypertensive medicinal products

were studied, including calcium channel blockers (amlodipine), angiotensin converting enzyme (ACE)

inhibitors (enalapril), beta-adrenergic receptor blockers (metoprolol), thiazide diuretics (bendrofluazide), and

angiotensin II receptor blockers (various types and doses, alone or in combination with thiazides, calcium

channel blockers, beta-blockers, and/or alpha-blockers). Tadalafil (10 mg except for studies with angiotensin

II receptor blockers and amlodipine in which a 20 mg dose was applied) had no clinically significant

interaction with any of these classes. In another clinical pharmacology study tadalafil (20 mg) was studied in

combination with up to 4 classes of antihypertensives. In subjects taking multiple antihypertensives, the

ambulatory-blood-pressure changes appeared to relate to the degree of blood-pressure control. In this regard,

study subjects whose blood pressure was well controlled, the reduction was minimal and similar to that seen

in healthy subjects. In study subjects whose blood pressure was not controlled, the reduction was greater

although this reduction was not associated with hypotensive symptoms in the majority of subjects. In patients

receiving concomitant antihypertensive medicinal products, tadalafil 20 mg may induce a blood pressure

decrease, which (with the exception of alpha blockers, see above) is, in general, minor and not likely to be

clinically relevant. Analysis of phase 3 clinical trial data showed no difference in adverse events in patients

taking tadalafil with or without antihypertensive medicinal products. However, appropriate clinical advice

should be given to patients regarding a possible decrease in blood pressure when they are treated with

antihypertensive medicinal products.

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).

5-alpha reductase inhibitors

In a clinical trial that compared tadalafil 5 mg co-administered with finasteride 5 mg to placebo plus

finasteride 5 mg in the relief of BPH symptoms, no new adverse reactions were identified. However, as a

formal drug-drug interaction study evaluating the effects of tadalafil and 5-alpha reductase inhibitors (5-

ARIs) has not been performed, caution should be exercised when tadalafil is co-administered with 5-ARIs.

CYP1A2 substrates (e.g. theophylline)

When tadalafil 10 mg was administered with theophylline (a non-selective phosphodiesterase inhibitor) in a

clinical pharmacology study, there was no pharmacokinetic interaction. The only pharmacodynamic effect

was a small (3.5 bpm) increase in heart rate. Although this effect is minor and was of no clinical significance

in this study, it should be considered when co-administering these medicinal products.

Ethinylestradiol and terbutaline

Tadalafil has been demonstrated to produce an increase in the oral bioavailability of ethinylestradiol; a

similar increase may be expected with oral administration of terbutaline, although the clinical consequence

of this is uncertain.

Alcohol

Alcohol concentrations (mean maximum blood concentration 0.08 %) were not affected by co-administration

with tadalafil (10 mg or 20 mg). In addition, no changes in tadalafil concentrations were seen 3 hours after

co-administration with alcohol. Alcohol was administered in a manner to maximise the rate of alcohol

absorption (overnight fast with no food until 2 hours after alcohol). Tadalafil (20 mg) did not augment the

mean blood pressure decrease produced by alcohol (0.7 g/kg or approximately 180 ml of 40 % alcohol

[vodka] in an 80-kg male) but in some subjects, postural dizziness and orthostatic hypotension were

observed. When tadalafil was administered with lower doses of alcohol (0.6 g/kg), hypotension was not

observed and dizziness occurred with similar frequency to alcohol alone. The effect of alcohol on cognitive

function was not augmented by tadalafil (10 mg).

Cytochrome P450 metabolised medicinal products

Tadalafil is not expected to cause clinically significant inhibition or induction of the clearance of medicinal

products metabolised by CYP450 isoforms. Studies have confirmed that tadalafil does not inhibit or induce

CYP450 isoforms, including CYP3A4, CYP1A2, CYP2D6, CYP2E1, CYP2C9 and CYP2C19.

CYP2C9 substrates (e.g. R-warfarin)

Tadalafil (10 mg and 20 mg) had no clinically significant effect on exposure (AUC) to S-warfarin or R-

warfarin (CYP2C9 substrate), nor did tadalafil affect changes in prothrombin time induced by warfarin.

Aspirin

Tadalafil (10 mg and 20 mg) did not potentiate the increase in bleeding time caused by acetyl salicylic acid.

Antidiabetic medicinal products

Specific interaction studies with antidiabetic medicinal products were not conducted.

4.6

Fertility, pregnancy and lactation

Tadalafil Actavis is not indicated for use by women.

Pregnancy

There are limited data from the use of tadalafil in pregnant women. Animal studies do not indicate direct or

indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal

development (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Tadalafil

Actavis during pregnancy.

Breastfeeding

Available pharmacodynamic/toxicological data in animals have shown excretion of tadalafil in milk. A risk

to the suckling child cannot be excluded. Tadalafil Actavis should not be used during breast feeding.

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

Tadalafil has negligible influence on the ability to drive or use machines. Although the frequency of reports

of dizziness in placebo and tadalafil arms in clinical trials was similar, patients should be aware of how they

react to tadalafil, before driving or using machines.

4.8

Undesirable effects

Summary of the safety profile

The most commonly reported adverse reactions in patients taking tadalafil for the treatment of erectile

dysfunction or benign prostatic hyperplasia were headache, dyspepsia, back pain and myalgia, in which the

incidences increase with increasing dose of tadalafil. The adverse reactions reported were transient, and

generally mild or moderate. The majority of headaches reported with tadalafil once-a-day dosing are

experienced within the first 10 to 30 days of starting treatment.

Tabulated summary of adverse reactions

The table below lists the adverse reactions observed from spontaneous reporting and in placebo- controlled

clinical trials (comprising a total of 8022 patients on tadalafil and 4422 patients on placebo) for on-demand

and once-a-day treatment of erectile dysfunction and the once-a-day treatment of benign prostatic

hyperplasia.

Frequency convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100),

rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000) and not known (cannot be estimated from the

available data).

Very common

Common

Uncommon

Rare

Immune system disorders

Hypersensitivity

reactions

Angioedema

Nervous system disorders

Headache

Dizziness

Stroke

(including

haemorrhagic events),

syncope, transient

ischaemic attacks

migraine

, seizures,

transient amnesia

Eye disorders

Blurred vision,

sensations described as

eye pain

Visual field defect,

swelling of eyelids,

conjunctival

hyperaemia, non-

arteritic anterior

ischemic optic

neuropathy (NAION)

retinal vascular

occlusion

Ear and labyrinth disorders

Tinnitus

Sudden hearing loss

Cardiac disorders

1

Tachycardia,

palpitations

Myocardial infarction,

unstable angina

pectoris

, ventricular

arrhythmia

Vascular disorders

Flushing

Hypotension

hypertension

Very common

Common

Uncommon

Rare

Respiratory, thoracic and mediastinal disorders

Nasal congestion

Dyspnoea,

epistaxis

Gastrointestinal disorders

Dyspepsia

Abdominal pain,

Vomiting, Nausea,

Gastro-oesophageal

reflux

Skin and subcutaneous tissue disorders

Rash

Urticaria, Stevens-

Johnson syndrome

exfoliative dermatitis

hyperhydrosis

(sweating)

Musculoskeletal, connective tissue and bone disorders

Back pain, myalgia,

pain in extremity

Renal and urinary disorders

Haematuria

Reproductive system and breast disorders

Prolonged erections

Priapism, Penile

haemorrhage,

Haematospermia

General disorders and administration site conditions

Chest pain

, Peripheral

oedema, Fatigue

Facial oedema

, sudden

cardiac death

Most of the patients had pre-existing cardiovascular risk factors (see section 4.4).

Postmarketing surveillance reported adverse reactions not observed in placebo-controlled clinical

trials.

More commonly reported when tadalafil is given to patients who are already taking antihypertensive

medicinal products.

Description of selected adverse reactions

A slightly higher incidence of ECG abnormalities, primarily sinus bradycardia, has been reported in patients

treated with tadalafil once a day as compared with placebo. Most of these ECG abnormalities were not

associated with adverse reactions.

Other special populations

Data in patients over 65 years of age receiving tadalafil in clinical trials, either for the treatment of erectile

dysfunction or the treatment of benign prostatic hyperplasia, are limited. In clinical trials with tadalafil taken

on demand for the treatment of erectile dysfunction, diarrhoea was reported more frequently in patients over

65 years of age. In clinical trials with tadalafil 5mg taken once a day for the treatment of benign prostatic

hyperplasia, dizziness and diarrhoea were reported more frequently in patients over 75 years of age.

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 the national reporting system listed in Appendix V.

4.9

Overdose

Single doses of up to 500 mg have been given to healthy subjects, and multiple daily doses up to 100 mg

have been given to patients. Adverse events were similar to those seen at lower doses. In cases of overdose,

standard supportive measures should be adopted as required. Haemodialysis contributes negligibly to

tadalafil elimination.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

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

Mechanism of action

Tadalafil is a selective, reversible inhibitor of cyclic guanosine monophosphate (cGMP)-specific

phosphodiesterase type 5 (PDE5). When sexual stimulation causes the local release of nitric oxide, inhibition

of PDE5 by tadalafil produces increased levels of cGMP in the corpus cavernosum. This results in smooth

muscle relaxation and inflow of blood into the penile tissues, thereby producing an erection. Tadalafil has no

effect in the absence of sexual stimulation.

Pharmacodynamic effects

Studies

in vitro

have shown that tadalafil is a selective inhibitor of PDE5. PDE5 is an enzyme found in

corpus cavernosum smooth muscle, vascular and visceral smooth muscle, skeletal muscle, platelets, kidney,

lung, and cerebellum. The effect of tadalafil is more potent on PDE5 than on other phosphodiesterases.

Tadalafil is > 10,000-fold more potent for PDE5 than for PDE1, PDE2 and PDE4 enzymes which are found

in the heart, brain, blood vessels, liver, and other organs. Tadalafil is > 10,000-fold more potent for PDE5

than for PDE3, an enzyme found in the heart and blood vessels. This selectivity for PDE5 over PDE3 is

important because PDE3 is an enzyme involved in cardiac contractility. Additionally, tadalafil is

approximately 700-fold more potent for PDE5 than for PDE6, an enzyme which is found in the retina and is

responsible for phototransduction. Tadalafil is also > 10,000-fold more potent for PDE5 than for PDE7

through PDE10.

Clinical efficacy and safety

Three clinical studies were conducted in 1054 patients in an at-home setting to define the period of

responsiveness to tadalafil. Tadalafil demonstrated statistically significant improvement in erectile function

and the ability to have successful sexual intercourse up to 36 hours following dosing, as well as patients’

ability to attain and maintain erections for successful intercourse compared to placebo as early as 16 minutes

following dosing.

Tadalafil administered to healthy subjects produced no significant difference compared to placebo in supine

systolic and diastolic blood pressure (mean maximal decrease of 1.6/0.8 mm Hg, respectively), in standing

systolic and diastolic blood pressure (mean maximal decrease of 0.2/4.6 mm Hg, respectively), and no

significant change in heart rate.

In a study to assess the effects of tadalafil on vision, no impairment of colour discrimination (blue/green)

was detected using the Farnsworth-Munsell 100-hue test. This finding is consistent with the low affinity of

tadalafil for PDE6 compared to PDE5. Across all clinical studies, reports of changes in colour vision were

rare (< 0.1 %).

Three studies were conducted in men to assess the potential effect on spermatogenesis of tadalafil 10 mg

(one 6-month study) and 20 mg (one 6-month and one 9-month study) administered daily. In two of these

studies decreases were observed in sperm count and concentration related to tadalafil treatment of unlikely

clinical relevance. These effects were not associated with changes in other parameters such as motility,

morphology and FSH.

Tadalafil at doses of 2 to 100 mg has been evaluated in 16 clinical studies involving 3250 patients, including

patients with erectile dysfunction of various severities (mild, moderate, severe), etiologies, ages (range 21-86

years), and ethnicities. Most patients reported erectile dysfunction of at least 1 year in duration. In the

primary efficacy studies of general populations, 81 % of patients reported that tadalafil improved their

erections as compared to 35 % with placebo. Also, patients with erectile dysfunction in all severity

categories reported improved erections whilst taking tadalafil (86 %, 83 %, and 72 % for mild, moderate, and

severe, respectively, as compared to 45 %, 42 %, and 19 % with placebo). In the primary efficacy studies, 75

% of intercourse attempts were successful in tadalafil treated patients as compared to 32 % with placebo.

In a 12-week study performed in 186 patients (142 tadalafil, 44 placebo) with erectile dysfunction secondary

to spinal cord injury, tadalafil significantly improved the erectile function leading to a mean per-subject

proportion of successful attempts in patients treated with tadalafil 10 or 20 mg (flexible-dose, on demand) of

48 % as compared to 17 % with placebo.

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 waived the obligation to submit the results of studies with tadalafil in

all subsets of the paediatric population in the treatment of the erectile dysfunction (see section 4.2 for

information on paediatric use).

5.2

Pharmacokinetic properties

Absorption

Tadalafil is readily absorbed after oral administration and the mean maximum observed plasma

concentration (C

) is achieved at a median time of 2 hours after dosing. Absolute bioavailability of tadalafil

following oral dosing has not been determined.

The rate and extent of absorption of tadalafil are not influenced by food, thus tadalafil may be taken with or

without food. The time of dosing (morning versus evening) had no clinically relevant effects on the rate and

extent of absorption.

Distribution

The mean volume of distribution is approximately 63 L, indicating that tadalafil is distributed into tissues. At

therapeutic concentrations, 94 % of tadalafil in plasma is bound to proteins. Protein binding is not affected

by impaired renal function. Less than 0.0005 % of the administered dose appeared in the semen of healthy

subjects.

Biotransformation

Tadalafil is predominantly metabolised by the cytochrome P450 (CYP) 3A4 isoform. The major circulating

metabolite is the methylcatechol glucuronide. This metabolite is at least 13,000-fold less potent than tadalafil

for PDE5. Consequently, it is not expected to be clinically active at observed metabolite concentrations.

Elimination

The mean oral clearance for tadalafil is 2.5 l/h and the mean half-life is 17.5 hours in healthy subjects.

Tadalafil is excreted predominantly as inactive metabolites, mainly in the faeces (approximately 61 % of the

dose) and to a lesser extent in the urine (approximately 36 % of the dose).

Linearity/non-linearity

Tadalafil pharmacokinetics in healthy subjects are linear with respect to time and dose. Over a dose range of

2.5 to 20 mg, exposure (AUC) increases proportionally with dose. Steady-state plasma concentrations are

attained within 5 days of once-daily dosing.

Pharmacokinetics determined with a population approach in patients with erectile dysfunction are similar to

pharmacokinetics in subjects without erectile dysfunction.

Special populations

Elderly

Healthy elderly subjects (65 years or over), had a lower oral clearance of tadalafil, resulting in 25 % higher

exposure (AUC) relative to healthy subjects aged 19 to 45 years. This effect of age is not clinically

significant and does not warrant a dose adjustment.

Renal insufficiency

In clinical pharmacology studies using single-dose tadalafil (5 to 20 mg), tadalafil exposure (AUC)

approximately doubled in subjects with mild (creatinine clearance 51 to 80 ml/min) or moderate (creatinine

clearance 31 to 50 ml/min) renal impairment and in subjects with end-stage renal disease on dialysis. In

haemodialysis patients, C

was 41 % higher than that observed in healthy subjects. Haemodialysis

contributes negligibly to tadalafil elimination.

Hepatic insufficiency

Tadalafil exposure (AUC) in subjects with mild and moderate hepatic impairment (Child-Pugh Class A and

B) is comparable to exposure in healthy subjects when a dose of 10 mg is administered. There is limited

clinical data on the safety of tadalafil in patients with severe hepatic insufficiency (Child- Pugh Class C). If

tadalafil is prescribed, a careful individual benefit/risk evaluation should be undertaken by the prescribing

physician. There are no available data about the administration of doses higher than 10 mg of tadalafil to

patients with hepatic impairment.

Patients with diabetes

Tadalafil exposure (AUC) in patients with diabetes was approximately 19 % lower than the AUC value for

healthy subjects. This difference in exposure does not warrant a dose adjustment.

5.3

Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology,

repeated dose toxicity, genotoxicity, carcinogenic potential and toxicity to reproduction.

There was no evidence of teratogenicity, embryotoxicity or foetotoxicity in rats or mice that received up to

1000 mg/kg/day tadalafil. In a rat prenatal and postnatal development study, the no observed effect dose was

30 mg/kg/day. In the pregnant rat the AUC for calculated free drug at this dose was approximately 18 times

the human AUC at a 20 mg dose.

There was no impairment of fertility in male and female rats. In dogs given tadalafil daily for 6 to 12 months

at doses of 25 mg/kg/day (resulting in at least a 3-fold greater exposure [range 3.7-18.6] than seen in humans

given a single 20 mg dose) and above, there was regression of the seminiferous tubular epithelium that

resulted in a decrease in spermatogenesis in some dogs. See also section 5.1.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Tablet core

Lactose monohydrate

Pregelatinised starch

Colloidal anhydrous silica

Croscarmellose sodium

Sodium laurilsulfate

Magnesium stearate

Film-coat

Hypromellose (E464)

Lactose monohydrate

Titanium dioxide (E171)

Triacetin

Talc (E553b)

Iron oxide yellow (E172)

Iron oxide red (E172)

6.2

Incompatibilities

Not applicable.

6.3

Shelf life

3 years

6.4

Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5

Nature and contents of container

The tablets are packaged in PVC/PCTFE/Aluminium blisters.

4, 8 and 12 film-coated tablets

Not all pack sizes may be marketed.

6.6

Special precautions for disposal

No special requirements.

7.

MARKETING AUTHORISATION HOLDER

[To be completed nationally]

8.

MARKETING AUTHORISATION NUMBER(S)

[To be completed nationally]

9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

[To be completed nationally]

10.

DATE OF REVISION OF THE TEXT

10/2020[To be completed nationally]

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