qanastek/EMEA-V3 huggingface dataset:
The following medicines may increase the effects of Rapinyl: • Certain types of antifungal medicines containing e. g. ketoconazole or itraconazole (used to treat fungal infections). • Certain types of antibiotic medicines used to treat infections (called macrolides, containing e. g. erythromycin). • Certain types of antiviral medicines used to treat infections caused by viruses (called protease inhibitors, containing e. g. ritonavir). • Medicines containing alcohol • Medicines called monoamine-oxidase (MAO) inhibitors, which are used for severe depression and Parkinson’ s disease.
Il- mediċini li ġejjin jistgħu jħarrxu l- effetti ta ’ Rapinyl: • Ċertu tipi ta ’ mediċini kontra l- moffa li fihom eż. ketoconazole jew itraconazole (użati biex jittrattaw infezzjonijiet tal- moffa). • Ċertu tipi ta ’ mediċini antibijotiċi użati biex jittrattaw infezzjonijiet (imsejħa makrolidi, li jkun fihom eż. erythromycin). • Ċertu tipi ta ’ mediċini antivirali użati biex jittrattaw infezzjonijiet kontra l- vajrusis (imsejħa protease inhibitors, li fihom eż. ritonavir). • Mediċini li fihom l- alkoħol • Mediċini li jissejħu impedituri tal- monoamine- oxidase (MAO), li jintużaw għal dipressjoni severa u l- marda ta ’ Parkinson.
Tell your doctor if you have taken this type of medicine within the last two weeks
Għarraf lit- tabib tiegħek jekk ħadt din iit- tip ta ’ mediċina fl- aħħar ġimagħtejn
The following medicines may reduce the effects of Rapinyl: • Certain types of strong pain killers containing e. g. buprenorphine or pentazocine
Il- mediċini li ġejjin jistgħu jdgħajfu l- effetti ta ’ Rapinyl: • Ċertu tipi ta ’ mediċini qawwija li jaġixxu kontra l- uġigħ li fihom eż. buprenorphine jew pentazocine
Rapinyl may add to the effect of medicines that make you feel sleepy, including: • other strong pain-relieving medicines (opioid-type medicines e. g. for pain and cough) • general anaesthetics (used to make you sleep during operations) • muscle relaxants • sleeping tablets • medicines used to treat
Rapinyl jista ’ jżid l- effett ta ’ mediċini li jagħmluk bi ngħas, li jinkludu: • mediċini qawwija oħra li jaġixxu kontra l- uġigħ (mediċini tat- tip opjojdi eż. għal uġigħ u sogħla) • loppju ġenerali (użat biex jagħmlek torqod waqt l- operazzjonijiet) • rilassaturi tal- muskoli • pilloli ta ’ l- irqad • mediċini użati biex jittrattaw id- dipressjoni o l- allerġiji o l- ansjetà u l- psikosi o • mediċini li fihom clonidine (użati biex jittrattaw il- pressjoni għolja tad- demm).
depression allergies anxiety and psychosis
Meta tieħu Rapinyl ma ’ l- ikel u x- xorb
• medicines containing clonidine (used to treat high blood pressure).
Rapinyl jista ’ jagħmel lil xi persuni iħossuhom bi ngħas.
Do not consume alcohol without consulting your doctor as it might make you feel more drowsy than usual.
M’ għandekx tieħu alkoħol mingħajr ma tikkonsulta mat- tabib tiegħek peress li jista ’ jkun li tħossok aktar bi ngħas mis- soltu.
Do not drink grapefruit juice while you are prescribed Rapinyl treatment as it may increase the side effects of Rapinyl.
36 M’ għandekx tixrob grejpfrut meta tingħata it- trattament ta ’ Rapinyl bir- riċetta peress li jistgħu jiħraxu l- effetti kollaterali ta ’ Rapinyl.
34 Pregnancy and breast-feeding
Tqala u Treddigħ
You must not use Rapinyl during pregnancy unless you have been specifically told to by your doctor.
M’ għandekx tuża Rapinyl waqt it- tqala għajr meta t- tabib tiegħek qallek tagħmel mod ieħor.
Fentanyl is passed on into breast milk and may cause extreme drowsiness and shallow breathing in the breastfed child.
Fentanyl jgħaddi fil- ħalib ta ’ l- omm u jista ’ jikkawża ngħas qawwi u teħid ta ’ nifs baxx fit- tarbija li qed tittredda ’.
Consult your doctor and do not use Rapinyl during breast-feeding unless your doctor considers that the benefits for you are greater than the risks to the child.
Ikkonsulta mat- tabib tiegħek u tużax Rapinyl waqt li tkun qed tredda ’ għajr meta t- tabib tiegħek jikkonsidra li l- benefiċċji biex tagħmel hekk jisbqu r- riskji għat- tarbija.
Ask your doctor or pharmacist for advice before taking any medicine when pregnant or breast-feeding.
Itlob il- parir tat- tabib jew ta’ l- ispiżjar tiegħek qabel tieħu xi mediċina meta tkun tqila jew qed tredda ’.
Rapinyl may impair your mental and/ or physical ability to perform potentially hazardous tasks such as driving or operating machinery.
Rapinyl jista ’ jfixkel il- abilita mentali u/ jew fiżiċi tiegħek biex twettaq doveri li huma potenzjalment perikolużi bħal sewqan jew it- tħaddim ta ’ magni.
If you feel dizzy, sleepy or have blurred vision when you take Rapinyl, do not drive or use machinery.
Jekk tħossok stordut, bi ngħas jew għandek vista mċajpra meta tieħu Rapinyl, m’ għandekx issuq jew tħaddem inġenji.
HOW TO TAKE RAPINYL
KIF GĦANDEK TIEĦU RAPINYL
Before taking Rapinyl for the first time your doctor will explain how Rapinyl should be taken to effectively treat your breakthrough pain.
Qabel ma tieħu Rapinyl l- ewwel darba, it- tabib tiegħek ser jispjegalek kif Rapinyl għandu jittieħed sabiex jittratta b’ mod effettiv l- uġigħ sfondat tiegħek.
Always take Rapinyl exactly as your doctor has told you.
Dejjem għandek tieħu Rapinyl skond il- parir tat- tabib.
This product should ONLY be used by you according to your doctor’ s instructions.
Dan il- prodott għandu jintuża BISS kif preskritt.
It should not be used by anyone else as it could present a SERIOUS risk to their health, especially in children.
Jekk il- prodott jintuża minn xi ħadd ieħor jista ’ jkun hemm riskju SERJU għas- saħħa tagħhom, speċjalment fit- tfal.
Initial Phase – Finding the most appropriate dose
Fażi tal- Bidu – Biex issib l- aktar doża adattata
For Rapinyl to work successfully, your doctor will need to identify the most appropriate dose for treating a single episode of breakthrough pain.
Sabiex Rapinyl ikun jista ’ jaħdem b’ suċċess, it- tabib tiegħek ikun irid jidentifika l- aktar doża xierqa biex jittratta episodju waħdieni ta ’ uġigħ sfondat.
Rapinyl sublingual tablets are available in a range of strengths.
Il- pilloli għal taħt l- ilsien ta ’ Rapinyl jiġu f’ diversi qawwiet.
You may need to try different strengths of Rapinyl sublingual tablets over a number of episodes of breakthrough pain to find the most appropriate dose.
Għandu mnejn ikollok bżonn tipprova diversi qawwiet differenti tal- pilloli Rapinyl għal taħt l- ilsien f’ għadd ta ’ episodji differenti ta ’ uġigħ sfondat sabiex tinstab l- aktar doża adattata għalik.
Your doctor will help you do this and will work with you to find the best strength of tablet to use.
It- tabib tiegħek ser jgħinek tasal għal dan u ser jaħdem miegħek sabiex tkun tista ’ tieħu l- aħjar qawwa ta ’ pillola.
If you do not get adequate pain relief from one tablet your doctor may ask you to take two tablets to treat an episode of breakthrough pain.
Jekk ma jkollokx l- aħjar serħan mill- uġigħ minn pillola waħda, it- tabib tiegħek għandu mnejn jistaqsik tieħu żewġ pilloli sabiex tittratta episodju wieħed ta ’ uġigħ sfondat.
Do not take a second tablet unless your doctor tells you to as this may result in overdose.
Tieħux pillola oħra jekk it- tabib tiegħek jgħidlek tagħmel hekk għax inkella tista ’ tirriżulta b’ doża eċċessiva.
Your doctor will advise you which strength of tablet to use.
It- tabib tiegħek ser jagħtik parir dwar liema qawwa ta ’ pillola għandek tieħu.
Rapinyl is a different type of medicine from other medicines you may have used to treat your breakthrough pain.
Rapinyl hija mediċina differenti minn mediċini oħra li għandek mnejn użajt biex tittratta l- uġigħ sfondat tiegħek.
You must always use the dose of Rapinyl as prescribed by your doctor – this may be a different dose from that which you have used with other medicines for breakthrough pain.
Dejjem għandek tuża d- doża ta ’ Rapinyl li kitiblek fuq ir- riċetta t- tabib tiegħek – din taf tkun doża differenti min dik li użajt għal mediċini oħra għal uġigħ sfondat.
Maintenance Phase - Once you have found the most appropriate dose
Fażi ta ’ Manteniment - Ġaladarba sibt l- aktar doża adattata
Once you and your doctor have found a dose of Rapinyl tablets that controls your breakthrough pain you should take this dose no more than four times a day.
Ġaladarba inti u t- tabib tiegħek sibtu l- aħjar doża tal- pilloli Rapinyl li tikkontrolla l- uġigħ sfondat tiegħek, inti għandek tieħu din id- doża mhux aktar minn erba ’ darbiet kuljum.
A dose of Rapinyl may consist of more than one tablet.
Doża ta ’ Rapinyl tsta ’ tikkonsisti minn aktar minn pillola waħda.
If you think that the dose of Rapinyl that you are using is not controlling your breakthrough pain satisfactorily tell your doctor, as he may need to adjust your dose.
Peress li jkollu bżonn jaġġusta d- doża tiegħek.
You must not change your dose of Rapinyl unless directed by your doctor.
M’ għandekx tibdel id- doża tiegħek ta ’ Rapinyl għajr meta jgħidlek mod ieħor it- tabib tiegħek.
35 Taking the medicine
Meta tieħu l- mediċina
Rapinyl should be used sublingually.
Rapinyl għandu jittieħed minn taħt l- ilsien.
This means that the tablet should be placed under the tongue where it dissolves rapidly in order to allow fentanyl to be absorbed across the lining of the mouth.
Dan ifisser li l- pillola trid titqiegħed taħt l- ilsien fejn tinħall malajr sabiex tippermetti lil fentanyl biex jiġi assorbit mir- riti tal- ħalq.
Once absorbed, fentanyl starts to work to relieve pain.
Ġaladarba ikun assorbit, fentanyl jibda jaġixxi biex isserraħ mill- uġigħ.
When you get an episode of breakthrough pain, take the dose advised by your doctor as follows:
Meta jkollok episodju ta ’ uġigħ sfondat, ħu d- doża li t- tabib tiegħek irrakomandalek tieħu kif ġej:
• If your mouth is dry, take a sip of water to moisten it.
• Jekk ħalqek hu xott, ħu boqqa ilma biex tumdah.
Spit out or swallow the water.
Obżoq jew ibla ’ l- ilma.
• Remove the tablet(s) from the blister pack immediately before use.
• Neħħi l- pillola (/ i) mill- pakkett tal- folja eżatt qabel ser tehodha.
• Peel back the tab of the foil top of one blister and gently remove the tablet.
• Qaxxar in- naħa ta ’ wara tar- ras tal- fojl ta ’ folja waħda u b’ ġentilezza neħħi l- pillola.
Do not try to push Rapinyl sublingual tablets through the foil top, like a normal tablet
Tipprovax tombotta l- pillola għal taħt l- ilsien mill- qoxra tal- fojl, bħal ma jsir f’ pilloli normali
• Place the tablet under your tongue as far back as you can and let it dissolve completely.
• Poġġi l- pillola taħt l- ilsien kemm jista ’ jkun fuq in- naħa ta ’ wara u ħalliha tinħall kollha.
• Rapinyl will dissolve rapidly under the tongue and be absorbed in order to provide pain relief.
• Rapinyl ser jinħall malajr taħt l- ilsienu jiġi assorbit sabiex jagħti serħan mill- uġigħ.
It is therefore important that you do not suck, chew or swallow the tablet.
Huwa għalhekk importanti li ma terdgħax, tomgħod jew tibla ’ l- pillola.
• You should not drink or eat anything until the tablet has completely dissolved under your tongue.
• M’ għandek la tixrob u lanqas tiekol xejn sakemm il- pillola tkun inħallet kollha taħt ilsienek.
If you take more Rapinyl than you should • remove any remaining tablets from your mouth • tell your carer or another person in your house what has happened • you or your carer should immediately contact your doctor, pharmacist or local hospital and discuss what action to take • while waiting for the doctor, keep the person awake by talking to or shaking her/ him now and then
• neħħi kull pillola li għad baqa minn ħalqek • għid lil min jieħu ħsiebek jew persuna oħra li tinsab fid- dar tiegħek xi ġralek • inti jew l- persuna li tieħu ħsiebek għandkom immedjatament tikkuntattja lit- tabib jew l- ispiżjar tiegħek jew l- isptar lokali sabiex tiddiskuti x’ azzjoni għandha tittieħed • waqt li qed tistenna t- tabib, żomm il- persuna mqajma billi toqgħod titħadded miegħu/ magħha jew iċċaqilqu/ iċċaqlaqha kull tant ħin
Symptoms of overdose include: • extreme drowsiness • slow, shallow breathing If these occur, seek emergency medical help immediately.
Sintomi ta ’ doża eċċessiva jinkludu: • ngħas qawwi ħafna • teħid ta ’ nifs bil- mod u baxx Jekk dawn iseħħu, fittex għal għajnuna medika u ta ’ emerġenza minnufih.
If you think someone has taken Rapinyl by accident seek emergency medical help immediately.
Jekk taħseb li xi ħadd ħa Rapinyl b ’ aċċident fittex għal għajnuna t’ emerġenza minnufih.
If you stop taking Rapinyl You should only stop taking Rapinyl sublingual tablets on the advice of your doctor.
Għandek twaqqaf il- pilloli għal taħt l- ilsien ta ’ Rapinyl fuq il- parir tat- tabib tiegħek biss.
You must continue to take/ use your regular opioid pain relieving medicine for persistent pain as advised by your doctor.
Għandek tibqa ’ tieħu/ tuża l- mediċina opjojdi li sserħek mill- uġigħ għal uġigħ persistenti kif irrakomandalek it - tabib.
There should be no noticeable effects if you stop taking Rapinyl, but possible symptoms of withdrawal are anxiety, tremor, sweating, paleness, nausea and vomiting.
M’ għandux ikun hemm effetti notevoli jekk tieqaf tieħu Rapinyl, imma sintomi possibbli ta ’ waqfien jinkludu ansjetà, rogħda, tagħriq, sfurija, tqalligħ u remettar.
However, if you are concerned about your pain relief, you should talk to your doctor.
Madankollu, jekk inti mħasseb dwar is- serħan mill- uġigħ, għandek tkellem lit- tabib tiegħek.
Like all medicines, Rapinyl can cause side-effects, although not everybody gets them.
Bħal kull mediċina oħra, Rapinyl jista ’ jkollu effetti sekondarji, għalkemm ma jidhrux fuq kulħadd
36 If you start to feel unusually or extremely sleepy or your breathing becomes slow or shallow, you or your carer should immediately contact your doctor or local hospital for emergency help (see also section 3 “ If you take more Rapinyl than you should”).
Jekk tibda tħossok li għandek ngħas mhux tas- soltu jew tħossok estremament imħeddel jew jekk in- nifs tiegħek jibda jkun bil- mod jew fil- baxx, int jew il- persuna li tieħu ħsiebek għandkom tikkuntattjaw lit- tabib jew lill- isptar tiegħek għal għajnuna t’ emerġenza (ara wkoll sezzjoni 3 “ Jekk tieħu Rapinyl aktar milli suppost ”).
Very common side effects (affects more than 1 user in 10) include: • nausea, headache, sleepiness/ tiredness, dizziness.
Effetti sekondarji komuni ħafna (jaffettwaw aktar minn utent 1 f’ kull 10) jinkludu: • tqalligħ, uġigħ ta ’ ras, ngħas/ għeja, sturdament.
Common side effects (affects 1 to 10 users in 100) include: • vomiting, diarrhoea, constipation, stomach ache, bloated feeling, indigestion, loss of appetite • depression, difficulty in concentrating, excessive feeling of well being • increased sensitivity to sound and noise, blurred or double vision • low blood pressure, flushing/ feeling hot, slow shallow breathing, feeling weak, feeling faint, reduced sensitivity to touch, numbness or tingling • runny or blocked nose, dry mouth, sore throat, itching of the skin, skin rash, irritation under the tongue
Effetti sekondarji komuni (jaffettwaw minn 1 sa 10 f’ 100 utent) jinkludu: • remettar, dijarea, stitikezza, uġigħ fl- istonku, tħossok minfuħ, indiġestjoni, nuqqas t’ aptit • dipressjoni, diffiċli tikkonċentra, tħossok tassew tajjeb • sensittività ogħla għal ħsejjes u l- istorbju, vista mċajpra jew doppja • pressjoni baxxa tad- demm, fwawar/ tħossok sħun, tieħu nifs bil- mod u fil- baxx, tħossok debboli, tħossok ser tistordi, sensittività mnaqqsa meta tħoss, tirżiħ jew tgħarriex • imnieħer iqattar jew imblokkat, ħalq xott, griżmejn jweġgħuk, ħakk fuq il- ġilda, raxx tal- ġilda, irritazzjoni taħt l- ilsien
Other known side effects associated with fentanyl products include: • Very common side effects (affects more than 1 user in 10 people): excessive sweating • Common side effects (affects 1 to 10 users in 100): feeling confused, feeling anxious or nervous, hallucinations, abnormal thinking, muscle twitching, difficulty sleeping, strange dreams, tongue or taste problems, flushing, mouth ulcers/ blisters, blockage of the gut, difficulty swallowing, being accident-prone • Uncommon side effects (affects 1 to 10 users in 1,000): feeling restless, feeling detached, moodswings, trembling, difficulty speaking, being forgetful, loss of coordination, vertigo, slow or fast heartbeat, high blood pressure, difficulty breathing, slow or shallow breathing, asthma, bloating, wind, thirst, difficulty going to the toilet, change in frequency of going to the toilet, feeling unwell • Rare side effects (affects 1 to 10 users in 10,000): hiccups • Very rare side effects (affects less than 1 user in 10,000): irregular heartbeat, stopping breathing, blood in the saliva, decrease in amount of urine, painful contraction of the bladder
Qalb tħabbat b’ mod irregolari, tieqaf tieħu n- nifs, demm fir- rieq, tnaqqis fl- ammont ta ’ urina, kontrazzjoni bl- uġigħ fil- borza
HOW TO STORE RAPINYL
KIF TAĦŻEN RAPINYL
The pain-relieving medicine in Rapinyl is very strong and could be life-threatening if taken accidentally by a child.
Il- mediċina li sserraħ mill- uġigħ f’ Rapinyl hi qawwija ħafna u tista ’ tkun ta ’ periklu għal ħajja fit- tfal.
Rapinyl must be kept out of the reach and sight of children.
Rapinyl għandu jinżamm fejn ma jintaħaqx u ma jidhirx mit- tfal.
Do not use Rapinyl after the expiry date which is stated on the carton after EXP.
Tużax Rapinyl wara d- data ta ’ skadenza li tidher fuq il- kartuna wara EXP.
Store in the original blister in order to protect from moisture.
Aħżen fil- pakkett ta ’ folji oriġinali sabiex tilqa ’ mill- umdità.
It is recommended to keep Rapinyl in a locked storage space.
Huwa rakkomandat li Rapinyl jinżamm f’ post magħluq.
Any unused product should be taken, if possible, to your pharmacist to be disposed of safely.
39 Kull prodott mhux użat għandu, jekk possibbli, jittieħed għand l- ispiżjar tiegħek biex jintrema b’ mod sikur.
What Rapinyl contains
X’ fih Rapinyl
The active substance is fentanyl.
Is- sustanza attiva hi fentanyl.
One sublingual tablet contains 50 micrograms fentanyl (as citrate) 100 micrograms fentanyl (as citrate) 200 micrograms fentanyl (as citrate) 300 micrograms fentanyl (as citrate) 400 micrograms fentanyl (as citrate) 600 micrograms fentanyl (as citrate) 800 micrograms fentanyl (as citrate)
50 mikrogramma fentanyl (bħala citrate) 100 mikrogramma fentanyl (bħala citrate) 200 mikrogramma fentanyl (bħala citrate) 300 mikrogramma fentanyl (bħala citrate) 400 mikrogramma fentanyl (bħala citrate) 600 mikrogramma fentanyl (bħala citrate) 800 mikrogramma fentanyl (bħala citrate)
The other ingredients are mannitol (E421), silicified microcrystalline cellulose, croscarmellose sodium and magnesium stearate.
Is- sustanzi l- oħra huma mannitol (E421), silicified microcrystalline cellulose, croscarmellose sodium u magnesium stearate.
What Rapinyl looks like and contents of the pack
Id- Dehra ta ’ Rapinyl u l- kontenut tal- pakkett
Rapinyl is a small white sublingual tablet to be inserted under the tongue.
Rapinyl hi pillola bajda għal taħt l- ilsien li trid toqgħod taħt l- ilsien.
It comes in a range of different strengths and shapes.
Hi tiġi f’ għadd ta ’ qawwiet u forom differenti.
Your doctor will prescribe the strength (shape) and number of tablets suitable for you.
It- tabib tiegħek ser jippreskrivi l- qawwa (forma) u l- għadd ta ’ pilloli li huma adattati għalik.
The 50 microgram tablet is a white pentagon-shaped tablet.
Il- pillola ta ’ 50 mikrogramma hi pillola bajda f’ għamla ta ’ pentagonu Il- pillola ta ’ 100 mikrogramma hi pillola bajda u tonda.
The 100 microgram tablet is a white round tablet The 200 microgram tablet is a white oval-shaped tablet The 300 microgram tablet is a white triangle-shaped tablet The 400 microgram tablet is a white diamond-shaped tablet The 600 microgram tablet is a white “ D” -shaped tablet The 800 microgram tablet is a white capsule-shaped tablet
Il- pillola ta ’ 200 mikrogramma hi pillola bajda f’ forma ovali Il- pillola ta ’ 300 mikrogramma hi pillola bajda f’ forma triangolari Il- pillola ta ’ 400 mikrogramma hi pillola bajda f’ forma ta ’ djamant Il- pillola ta ’ 600 mikrogramma hi pillola bajda f’ forma ta ’ D Il- pillola ta ’ 800 mikrogramm hi pillola bajda f’ forma ta ’ kapsula
Rapinyl tablets are contained in blisters, available in cartons of 10 or 30 tablets.
Il- pilloli Rapinyl jiġu f’ kartuni ta ’ 10 pilloli jew 30 pillola.
[See Annex I - To be completed nationally] {Name and address }< {tel }> < {fax }> < {e-mail }>
[Ara Anness I - Biex jitlesta fil- pajjiż partikolari] {Isem u indirizz} < {tel} > < {faks} > < {posta elettronika} >
Recip AB Lagervägen 7 136 50 Haninge Sweden Tel. +46 8 6025200
Recip AB Lagervägen 7 136 50 Haninge L- Iżvezja Tel. +46 8 6025200
38 ANNEX IV
40 ANNESS IV
CONDITIONS OF THE MARKETING AUTHORISATIONS
KUNDIZZJONIJIET TA 'L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
39 The National Competent Authorities, coordinated by the Reference Member State, shall ensure that the following conditions are fulfilled by the Marketing Authorisation Holders:
41 L- Awtoritajiet Nazzjonali Kompetenti, ikkoordinati mill- Istat Membru ta 'Referenza, għandhom jiżguraw li l- kundizzjonijiet li ġejjin jiġu sodisfatti mid- Detenturi ta' l- Awtorizzazzjoni għat- Tqegħid fis- Suq:
The Applicant commits to provide the following information to the National Competent Authority of the Reference Member State:
L- applikant jimpenja ruħu li jipprovdi l- informazzjoni segwenti lill- Awtorità Nazzjonali Kompetenti ta 'l- Istat Membru ta' Referenza:
Analysis of the 30% and 50% responder rates at 10 and 15 minutes for the study EN-3267- 005,
analiżi tar- rati ta 'dawk li rrispondew 30% u 50% wara 10 u 15- il minuta għall- istudju EN - o 3267- 005,
Final results of studies EN3267-005 and 3267-007, including detailed exposure of patients and full safety analysis.
ir- riżultati finali ta 'l- istudji EN3267- 005 u 3267- 007, fosthom l- esponiment dettaljat tal - o pazjenti u analiżi sħiħa dwar is- sigurtà.
London, 12 September 2008 EMEA/ CHMP/ 495857/ 2008
Londra, 12 ta ’ Settembru 2008 EMEA/ CHMP/ 495849/ 2008
OPINION FOLLOWING AN ARTICLE 29(4)1 REFERRAL FOR
OPINJONI WARA RIFERIMENT SKOND L- ARTIKOLU 29( 4) 1 GĦAL
Rapinyl and associated names
Rapinyl u ismijiet assoċjati
International Non-Proprietary Name (INN): fentanyl citrate
Denominazzjoni Komuni Internazzjonali (DKI): fentanyl citrate
Rapinyl and associated names, 50µg, 100µg, 200µg, 300µg, 400µg, 600µg, 800µg, sublingual tablets is indicated for the management of breakthrough pain in adult patients using opioid therapy for chronic cancer pain.
Rapinyl u ismijiet assoċjati, 50µg, 100µg, 200µg, 300µg, 400µg, 600µg, 800µg, pilloli għal taħt l- ilsien huwa indikat għall- ġestjoni ta ’ uġigħ penetranti f’ pazjenti adulti li jużaw kura opjode għal uġigħ kroniku ikkawżat minn kanċer.
ProStrakan Ltd submitted applications for Rapinyl and associated names, 50µg, 100µg, 200µg, 300µg, 400µg, 600µg, 800µg, sublingual tablets.
ProStrakan Ltd issottomettiet applikazzjonijiet għal Rapinyl u ismijiet assoċjati, 50µg, 100µg, 200µg, 300µg, 400µg, 600µg, 800µg, pilloli għal taħt l- ilsien.
The Decentralised Procedure, SE/ H/ 575/ 07/ DC, started on 1 September 2006.
Il- Proċedura Deċentralizzata, SE/ H/ 575/ 07/ DC, bdiet fl- 1 ta ’ Settembru 2006.
The Reference Member State was Sweden and the Concerned Member States were Austria, Belgium, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Norway, Poland, Portugal, Slovak Republic, Slovenia, Spain and United Kingdom.
L- Istat Membru tar- Riferiment kien l- Iżvezja u l- Istati Membri Konċernati kienu l- Awstrija, il- Belġju, Ċipru, ir- Repubblika Ċeka, id- Danimarka, l- Estonja, il- Finlandja, Franza, il- Ġermanja, il- Greċja, l - Ungerija, l- Iżlanda, l- Irlanda, l- Italja, il- Latvja, il- Litwanja, il- Lussemburgu, in- Norveġja, il- Polonja, il - Portugall, ir- Repubblika Slovakka, is- Slovenja, Spanja u r- Renju Unit.
These Member States were not able to reach an agreement and Sweden referred the reasons for disagreement to the EMEA on 27 September 2007.
Dawn l- Istati Membri ma setgħux jilħqu ftehim u l- Iżvezja rriferiet ir- raġunijiet għan- nuqqas ta ’ ftehim lill - EMEA fis- 27 ta ’ Settembru 2007.
Significant difference has been identified with regard to the need for further clinical efficacy and safety data for the evaluation of the benefit/ risk and the lack of PK data under normal conditions of use of the product.
Ġiet identifikata differenza sinifikanti fir- rigward tal- ħtieġa għal aktar effikaċja klinika u dejta dwar is - sigurtà għall- evalwazzjoni tal- benefiċċju/ riskju u n- nuqqas ta ’ dejta tal- PK f’ kundizzjonijiet normali ta ’ użu tal- prodott.
This refers to the bridging strategy of the Applicant and was considered to be a serious public health concern.
Din tirreferi għall- istrateġija ta ’ bridging tal- Applikant u tqieset bħala ta ’ tħassib serju għas- saħħa pubblika.
The arbitration procedure started on 18 October 2007 with the adoption of a list of questions.
Il- proċedura ta ’ arbitraġġ bdiet fit- 18 ta ’ Ottubru 2007 bl- adozzjoni ta ’ lista ta ’ mistoqsijiet.
The Rapporteur was Dr Tomas Salmonson (SE) and Dr Pierre Demolis (FR) was Co-Rapporteur.
Ir- Rapporteur kien Dr Tomas Salmonson (SE) u Dr Pierre Demolis (FR) kien il- Ko- Rapporteur.
The Applicant provided written explanations on 7 April 2008.
L- Applikant ta spjegazzjonijiet bil- miktub fis- 7 ta ’ April 2008.
During their June 2008 meeting, the CHMP, in the light of the overall data submitted and the scientific discussion within the Committee, was of the opinion that the benefit/ risk ratio is favourable for Rapinyl and associated names, that the objections raised by Germany, France, Norway and United Kingdom should not prevent the granting of a Marketing Authorisation and that the Summary of Product Characteristics, Labelling and Package Leaflet of the Reference Member State should be amended.
Matul il- laqgħa tiegħu ta ’ Ġunju 2008, is- CHMP, fid- dawl tad- dejta ġenerali ippreżentata u tad- diskussjoni xejntifika fi ħdan il- Kumitat, kien tal- opinjoni li l- proporzjon bejn il- benefiċċju/ riskju kien wieħed favorevoli għal Rapinyl u ismijiet assoċjati, li l- oġġezzjonijiet imqajma mill- Ġermanja, Franza, in - Norveġja u r- Renju Unit ma għandhomx jimpedixxu l- għoti tal- Awtorizzazzjoni għat- Tqegħid fis- Suq u li s- Sommarju tal- Karatteristiċi tal- Prodott, Tikketta u Fuljett ta ’ Tagħrif tal- Istat Membru ta ’ Riferiment għandhom jiġu emendati.
A positive opinion was adopted by consensus on 26 June 2008
Fis- 26 ta ’ Ġunju 2008 ġiet adottata opinjoni pożittiva b’ konsensus.
1 Member State
1 Stat membru
Marketing Authorisation INN Holder
Detentur tal - Awtorizzazzjoni għat - Tqegħid fuq is- Suq
Invented Name
Isem ivvintat
Content (concentration)
Il- Kontenut > (Konċentrat)
Remeron SolTab 15 mg Schmelztabletten
Remeron SolTab Schmelzpillolaten
Orodispersible tablets
Pilloli li jinħallu fil- ħalq
Remeron SolTab 30 mg Schmelztabletten
Remeron SolTab Schmelzpillolaten
Remeron SolTab 45 mg Schmelztabletten
Remeron SolTab Schmelzpillolaten
Film-coated tablets Film-coated tablets Film-coated tablets Orodispersible tablets Orodispersible tablets
Użu orali
Orodispersible tablets
Pilloli miksija b’ rita
Film-coated Tablets
Pilloli miksija b’ rita
REMERON 15 MG REMERON 30 MG REMERON 45 MG REMERON SOLTAB 15 MG
REMERON 30 30 mg MG
15 mg 30 mg 45 mg 15 mg
Pilloli miksija b’ rita
Oral use Oral use Oral use Oral use
Użu orali
2 Member State
2 Stat membru
Orodispersible tablets Orodispersible tablets Orodispersible tablets
Pilloli li jinħallu fil- ħalq
Film-coated tablets Film-coated tablets Film-coated tablets
Pilloli miksija b’ rita
Orodispersible tablets Orodispersible tablets
Pilloli li jinħallu fil- ħalq
Film-coated tablets Film-coated tablets
Pilloli miksija b’ rita
Oral Solution Film-coated tablets
Soluzzjoni orali Pilloli miksija b’ rita
Oral use Oral use
Użu orali Użu orali
Strength
Pilloli li jinħallu fil- ħalq
Pharmaceutical Form
Użu orali
Maistraatinportti 2 00240 Helsinki, Finland
Pilloli li jinħallu fil- ħalq
Mirtazapine Mirtazapine Mirtazapine
Użu orali
Film-coated tablets Film-coated tablets Orodispersible tablets
Pilloli miksija b’ rita
Mirtazapine
Użu orali
Orodispersible tablets
Pilloli li jinħallu Użu orali fil- ħalq
Oral use
5 Stat membru
4 Member State
Detentur tal - Awtorizzazzjoni għat - Tqegħid fuq is- Suq
Orodispersible tablets Orodispersible tablets Oral Solution
Pilloli li jinħallu fil- ħalq
Iceland
Iżlanda
Film-coated tablets
Pilloli miksija
Mirtazapine Mirtazapine
Għamla Farmaċewtika
Remeron Remeron
Mnjen jingħata
Ireland
Użu orali
Remeron Zispin® tablets
Remeron
Oral Solution Film-coated tablets
Soluzzjoni orali
Zispin® tablets
Zispin® miksija
film-coated
Pilloli b’ rita
Organon (Ireland) Limited, Mirtazapine
Organon (Ireland) Limited, PO Box 2857,
Zispin®
Zispin® Pilloli
Soltab®
Soltab® li jinħallu
PO Box 2857,
Drynam Road,
Strength
fil- ħalq
Zispin® Soltab® orodispersible tablets
Zispin® Soltab® Pilloli li jinħallu fil- ħalq
Zispin® oral solution
Zispin® Soluzzjoni orali
Oral Solution
Soluzzjoni orali Użu orali
Film-coated tablets
Pilloli miksija Użu orali b’ rita
Film-coated tablets Film-coated tablets
Pilloli miksija Użu orali b’ rita
Mirtazapine Mirtazapine Mirtazapine Mirtazapine Mirtazapine Mirtazapine
Detentur tal - Awtorizzazzjoni għat - Tqegħid fuq is- Suq
Remeron Remeron Remeron Mirtazapina Organon Mirtazapina Organon Mirtazapina Organon
Il- Kontenut > (Konċentrat)
Orodispersible tablets Orodispersible tablets Orodispersible tablets Orodispersible tablets Orodispersible tablets Orodispersible tablets
Użu orali
Organon, Kloosterstraat 6, P. O.
Pilloli li jinħallu fil- ħalq
Box 20, NL 5340 AB Oss,
Użu orali
Film-coated tablets Orodispersible tablets Orodispersible tablets
Pilloli li jinħallu fil- ħalq
Oral use Oral use Oral use
Mirtazapina Organon
The Netherlands
Użu orali
Lithuania
Latvja
Marketing Authorisation INN Holder
Pilloli li jinħallu fil- ħalq
Invented Name
Użu orali
Content (concentration)
Pilloli li jinħallu fil- ħalq
Remergon Remergon Remergon
Pilloli miksija b’ rita
15 mg 30 mg 45 mg
8 Stat membru
Film-coated tablets Film-coated tablets Film-coated tablets
Detentur tal - Awtorizzazzjoni għat - Tqegħid fuq is- Suq
Oral use Oral use Oral use
Għamla Farmaċewtika
The Netherlands Delegation of power:
Il- Kontenut > (Konċentrat)
Mirtazapine Mirtazapine
5349AB Oss, The Netherlands
Orodispersible tablets Orodispersible tablets
Pilloli miksija b’ rita
Oral solution
Soluzzjoni orali Pilloli li jinħallu fil- ħalq
Oral use
Użu orali Użu orali
Orodispersible Tablets Orodispersible Tablets Orodispersible Tablets Orodispersible Tablets
Pilloli li jinħallu fil- ħalq
Oral use Oral use Oral use Oral use
Mirtazapine Mirtazapine
15 mg per tablet 30 mg per tablet 45 mg per tablet 15 mg per tablet
orodiskullgeerbare pillolaten
Mirtazapine orodispergeerbare tabletten
Mirtazapine orodiskullgeerbare pillolaten
Orodispersible Tablets
Pilloli li jinħallu Użu orali fil- ħalq
Oral use
9 Stat membru
30 mg per tablet
Isem ivvintat
Mirtazapine
Qawwa
Mirtazapine orodispergeerbare tabletten
Għamla Farmaċewtika
45 mg
Mnjen jingħata
Orodispersible Tablets
Il- Kontenut > (Konċentrat)
Film-coated tablets Film-coated tablets Orodispersible tablets
Pilloli miksija Użu orali b’ rita
30 mg per tablet 45 mg per tablet 15 mg per tablet
Mirtazapine
7
Remeron
Member State
45 mg
Marketing Authorisation INN Holder
Pilloli miksija b’ rita
Route of administration
Remeron- S smeltepillolater
Remeron-S smeltetabletter
Remeron- S smeltepillolater
Portugal
Użu orali
Oral use Oral use Oral use
Pilloli miksija b’ rita
1070-159 Lisboa
Użu orali
Mirtazapine Mirtazapine Mirtazapine
Il- Kontenut > (Konċentrat)
30 mg 45 mg 15 mg/ ml
15 mg/ ml 15 mg
Orodispersible tablets Orodispersible tablets Oral solution
Soluzzjoni orali Pilloli li jinħallu fil- ħalq
Oral use Oral use Oral use
Użu orali Użu orali
Romania
Rumanija
Slovak Republic
Republikka Slovakka
De Hospitalet, 147- 149 Cityparc Ronda de Dalt Edificio Amsterdam
De Hospitalet, 147 -
Film coated tablets Film coated tablets Film coated tablets
Film coated
Oral use Oral use Oral use
149 Cityparc Ronda de Dalt
08940 Cornellá de
Edificio Amsterdam 08940 Cornellá de
Oral use Oral use Oral use Oral use Oral use Oral use
Pilloli li jinħallu fil- ħalq
990 mg/ 66 ml
Użu orali
Mirtazapine Mirtazapine Mirtazapine
Mirtazapine Rexer Flas
Tablets Tablets Tablets
Pilloli li jinħallu fil- ħalq
Oral use Oral use Oral use
Organon,
Mirtazapine Mirtazapine
Mirtazapine Rexer Mirtazapine Mirtazapina
Oral solution Orodispersible tablets
Soluzzjoni orali Pilloli li jinħallu
Marketing Authorisation INN Holder
Kloosterstraat 6, P. O.
Invented Name
Box
Strength
Organon
30 mg 45 mg 15 mg
fil- ħalq
Tablets
Użu orali
Tablets
Pilloli li jinħallu fil- ħalq
United Kingdom
Svezja
Oral Solution
Soluzzjoni orali Pilloli li jinħallu fil- ħalq
Zispin SolTab 15mg orodispersible tablet
Pilloli li jinħallu fil- ħalq
10 ANNEX II
Użu orali
SCIENTIFIC CONCLUSIONS AND GROUNDS PRESENTED BY THE EMEA
Mirtazapine 15mg/ ml Soluzzjoni orali
11 SCIENTIFIC CONCLUSIONS
Soluzzjoni orali
Remeron tablets 15, 30 and 45 mg Remeron orodispersible tablets 15, 30 and 45 mg Remeron oral solution 15 mg/ ml
Zispin SolTab 15mg orodiskullsible pillola
The SPC proposals by the company were mainly based upon this MRP.
Pilloli li jinħallu Użu orali fil- ħalq
The following sections of the Product Information were addressed during this harmonisation procedure.
Zispin SolTab 30mg orodiskullsible pillola
SPC Section 4.1 Therapeutic Indications
Pilloli li jinħallu Użu orali fil- ħalq
In section 4.1 Therapeutic Indications of the SPC, the CHMP considered that the indication should be amended to:
Zispin SolTab 45mg orodiskullsible pillola
Episodes of major depression (or treatment of episodes of major depression) in accordance with the wording agreed for this indication for other products of which the SPC is harmonised in Europe.
45 mg
The CHMP considered that the addition of “ in adults” was not acceptable.
Pilloli li jinħallu Użu orali fil- ħalq
This proposal was adopted by the applicant/ MAH and the issue was resolved.
KONKLUŻJONIJIET XJENTIFIĊI U RAĠUNIJIET IPPREŻENTATI MILL- EMEA
SPC Section 4.2 Posology and Method of Administration
14 KONKLUŻJONIJIET XJENTIFIĊI
The proposal was adopted by the applicant/ MAH and the issue was resolved.
SOMMARJU ĠENERALI TA ’ L- EVALWAZZJONI XJENTIFIKA TA ’ REMERON U TA ’ L - ISMIJIET ASSOĊJATI (ARA ANNESS I)
Additionally, the CHMP considered that the clearance of mirtazapine may be decreased in patients with moderate to severe renal impairment (creatinine clearance < 40 ml/ min).
Remeron (mirtazapine) ġie riferut għall- armonizzazzjoni tas- Sommarju tal- Karatteristiċi tal- Prodott, skond l- Artikolu 30( 1) tad- Direttiva 2001/ 83/ KE.
This should be taken into account when prescribing Remeron to this category of patients (see section 4.4).
Mirtazapine huwa indikat għal episodji ta ’ depressjoni kbira.
The applicant/ MAH was therefore asked to provide support for the cut-off at 40 ml/ min as the range is normally defined as 30- 50 ml/ min (moderate renal impairment).
Ir- riferiment sar mill- applikant u għandu l- mira li jarmonizza oqsma prinċipali ta ’ diskrepanza bejn l- Istati Membri ta ’ l- UE, fir- rigward tas- Sommarju tal- Karatteristiċi tal- Prodott (SPCs), il- Fuljetti ta ’ Tagħrif (PLs), it- Tikketti u Modulu 3 tal- prodotti segwenti li fihom is- sustanza attiva mirtazapine:
In this study, subjects were divided into 4 categories using the following cut-off values:
Remeron pilloli 15, 30 u 45 mg Remeron pilloli li jinħallu fil- ħalq 15, 30 u 45 mg Remeron soluzzjoni orali 15 mg/ ml
12 At that time, in 1989, the cut-off values for the level of renal impairment were in line with FDA draft Guidance for Industry on “ Pharmacokinetics and Pharmacodynamics in patients with Impaired renal function: study design, data analysis, and impact on dosing and labelling”.
Fl- 14 ta ’ Frar 2007 ġie konkluż tiġdid kombinat permezz tal- MRP għal Remeron pilloli miksijin b’ rita 45 mg, Remeron 15, 30, 45 mg, Remeron soluzzjoni orali 15 mg/ ml, Mirtazapine pilloli li jinħallu fil - ħalq 15, 30, 45 mg., li b’ kollox kien jinvolvi 8 Stati Membri, fosthom l- Istat Membru ta ’ Referenza (RMS).
This FDA Guidance was superseded in 1998.
Il- proposti għall- SPC mill- kumpanija kienu bbażati prinċipalment fuq dan il- MRP.
In addition, the most recent EU Guideline was only established in 1994 (Note for Guidance on the evaluation on the pharmacokinetics of medicinal products in patients with impaired renal function, CHMP/ EWP/ 225/ 02).
Barra minn hekk ġew implimentati r- rakkomandazzjonijiet mill- Grupp ta ’ Ħidma għall- Farmakoviġilanza fir- rigward tal- SPC prinċipali għall- antidipressanti.
Importantly, patients with renal impairment and their doctors should be aware of the fact that in subjects with impaired renal function exposure to mirtazapine may be increased and that there is a positive correlation between severity and exposure.
Fl- aħħarnett, l- SPCs ta ’ referenza ġew riveduti skond il- Linja gwida tal- Kummissjoni Ewropea (KE) dwar l- SPC, ta ’ Ottubru 2005.
The CHMP considered this explanation to be acceptable and the issue was resolved.
Matul din il - proċedura ta ’ armonizzazzjoni ġew indirizzati s- sezzjonijiet li ġejjin ta ’ l- Informazzjoni dwar il - Prodott.
SPC Section 4.3 Contraindications
SPC Sezzjoni 4. 1 Indikazzjonijiet Terapewtiċi
The applicant/ MAH restricted the contra-indication to hypersensitivity only, in accordance with the EC Guideline on SPC, as only absolute contraindications should be mentioned and relative contra- indications should move to the warning section 4.3 or section.
Episodji ta ’ depressjoni qawwija (jew trattament ta ’ episodji ta ’ depressjoni qawwija) skond il- kliem miftiehem għal din l- indikazzjoni għal prodotti oħra li l- SPC tagħhom hija armonizzata fl- Ewropa.
However, the CHMP did not consider this explanation acceptable and requested that the applicant/ MAH should argue why these contra- indications are not absolute.
Is- CHMP ħass li ż- żieda ta ’ “ fl- adulti ” ma kinetx aċċettabbli.
The CHMP was of the opinion that Phenylketonuria, MAO inhibitors, and pathological alterations of blood count are considered absolute contra-indications.
Din il- proposta ġiet adottata mill- applikant/ id- Detentur ta ’ l- Awtorizzazzjoni g] at- Tqeg] id fis- Suq u l- kwistjoni ġiet solvuta.
Phenylketonuria The applicant/ MAH argued that, according to the Guideline on SPC (October 2005) contraindications “ arising from the presence of certain excipients (under reference to the Guideline on excipients in the label and package leaflet of medicinal products for human use )” should be included.
Fis- Sezzjoni 4. 2 ta ’ l- SPC, Pożoloġija u metodu ta ’ kif għandu jingħata, is- CHMP ħass li s- sentenza “ It- trattament għandu preferibbilment jitkompla sakemm il- pazjent ikun ħeles mis- sintomi għal 4- 6 xhur ” għandha tiġi sostitwita bi “ Il- pazjenti b’ depressjoni għandhom jiġu kkurati għal perjodu suffiċjenti ta ’ mill- anqas 6 xhur biex ikun żgurat li ħelsu mis- sintomi. ” (skond il- kliem ta ’ antidipressanti oħra).
The Guideline on excipients in the dossier for application for marketing authorisation of a medicinal product (EMEA/ CHMP/ QWP/ 396951/ 2006) and the above mentioned guideline (CHMP/ 463/ 00) indicate which excipients and information should appear in the labelling.
Barra minn hekk, is- CHMP ħass li t- tneħħija ta ’ mirtazapine tista ’ tkun imnaqqsa f’ pazjenti li jkollhom indeboliment moderat għal serju tal- kliewi (tneħħija tal- kreatinina < 40 ml/ min).
The Annex explicitly mentions those excipients that require to be mentioned as a contraindication (e. g. hypersensitivity to peanut or soya oil).
Dan għandu jiġi kkunsidrat meta wieħed jordna Remeron lil din il- kategorija ta ’ pazjenti (ara sezzjoni 4. 4).
These do not include hereditary deficiencies of amino acid (phenylalanine) metabolism, such as phenylketonuria.
Għalhekk l- applikant/ Detentur ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq intalab għalhekk sabiex jipprovdi sostenn għall- cut- off ta ’ 40 ml/ min billi l- medda ġeneralment hija definita bħala 30- 50 ml/ min (indeboliment moderat tal- kliewi).
Since it is indicated in the Annex that aspartame, containing a source of phenylalanine may be harmful for people with phenylketonuria (and no comment is included in the Annex that a contraindication should be included in the SPC, such as done for peanut oil), this is not considered to be an absolute contraindication.
Biex jinvestiga l- impatt ta ’ indeboliment tal- kliewi fuq il- farmakokinetiċi ta ’ mirtazapine, l - applikant/ Detentur ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq għamlu riferenza għal prova klinika li kienet imfassla speċifikament għal dak il- għan (prova 22503).
The amount of phenylalanine is low in Remeron orodispersible tablets.
F’ dan l- istudju, l- individwi kienu maqsuma f’ 4 kategoriji billi ntużaw il- valuri ta ’ qtugħ il- linja li ġejjin:
Patients who are sensitive to phenylalanine are usually aiming for low phenylalanine levels (e. g. through diet), not complete abstinence of this source.
Grupp 1 Kontrolli normali b’ saħħithom b’ rata ta ’ filtrazzjoni glomerulari (GFR) ta ’ > 80 ml/ min/ 1. 73 m2
The use of aspartame as presented in these amounts in Remeron orodispersible tablets is not an absolute contraindication.
Dik hija r- raġuni għall- valur ta ’ qtugħ il- linja ta ’ 40 ml/ min/ 1. 73 m2.
It is therefore proposed to keep this warning in the corresponding section, section 4.4.
Din il- Gwida tal- FDA kienet sostitwita fl- 1998.
Aspartame may be/ is considered contraindicated in infants, but mirtazapine is not to be used in this age category and, consequently, requires no further warning.
Importanti li l- pazjenti b’ indeboliment renali u t- tobba tagħhom għandhom ikunu konxji tal- fatt li l- esponiment għal mirtazapine, f’ individwi li jkollhom indeboliment fil- funzjoni tal- fwied, jista ’ jkun akbar u li hemm korrelazzjoni pożittiva bejn il- gravità u l- esponiment.
The CHMP considered that the explanations provided appear scientifically sound and justified, noting that the aspartame content of the product is adequately addressed in the proposed form
Is- CHMP kien ta ’ l- opinjoni li l - Fenilketonurja, l- inibituri MAO, u l- bidliet patoloġiċi fl- għadd tad- demm huma kkunsidrati bħala kontra- indikazzjonijiet assoluti.
MAO-inhibitors The applicant/ MAH argues that it does not have data from clinical trials evaluating interactions between MAO inhibitors (MAO-Is) and mirtazapine.
Fenilketonurja L- applikant/ Detentur ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq argumenta li, skond il- Linja gwida dwar l- SPC (Ottubru 2005), il- kontra- indikazzjonijiet li “ jirriżultaw mill- preżenza ta ’ ċerti sustanzi mhux attivi (b’ referenza għal- Linja gwida dwar is- sustanza mhux attivi fit- tikketta u l- fuljett ta ’ tagħrif ta ’ prodotti mediċinali għall- użu mill- bniedem) għandhom jiġu inklużi.
As explained in the referral application dossier, animal studies have shown that mirtazapine induces only a small and temporary increase in noradrenalin and serotonin levels in the hippocampus (data available on request).
Il- Linja gwida dwar is - sustanzi mhux attivi fil- faxxiklu għall- applikazzjoni għall- awtorizzazzjoni għat- tqegħid fis- suq ta ’ prodott mediċinali (EMEA/ CHMP/ QWP/ 396951/ 2006) u l- linja gwida msemmija qabel (CHMP/ 463/ 00) jindikaw liema sustanzi mhux attivi u informazzjoni għandhom jidhru fit- tikketti.
Since the mechanism of interaction is different for MAO-Is with mirtazapine compared to MAO-Is and SSRIs, it is unlikely that the risk of serotonin syndrome is as high as with other serotonergic antidepressants, such as SSRIs.
L - Anness isemmi b’ mod espliċitu dawk is- sustanzi mhux attivi li jridu jissemmew bħala kontra - indikazzjoni (eż. sensittività eċċessiva għaż- żejt tal- karawett jew tas- soja).
MAO-inhibitors are therefore relatively contra-indicated with Remeron.
Dawn ma jinkludux defiċjenzi ereditarji tal- metaboliżmu ta ’ l- aċidu amminiku (phenylalanine), bħall- fenilketonurja.
The low number of post-marketing reports suggests that this interaction does not occur frequently and do not warrant any change to the location in the SPC where the warning for concomitant use of Remeron with MAO-Is is provided.
Billi fl- Anness hemm indikat li l- aspartame, li fih sors ta ’ phenylalanine, jista ’ jagħmel ħsara lil persuni b’ fenilketonurja (u m’ hemm ebda kumment fl- Anness li għandha tiġi inkluża kontra- indikazzjoni fl - SPC, bħalma jsir għaż- żejt tal- karawett), din mhijiex ikkunsidrata bħala kontra- indikazzjoni assoluta.
The warning at section 4.5 seems sufficient for its purpose.
L- ammont ta ’ phenylalanine f’ Remeron pilloli li jinħallu fil- ħalq huwa wieħed baxx.
Hence it is proposed not to include MAO-inhibitors as absolute contraindication in section 4.3.
Il- pazjenti li huma sensittivi għal phenylalanine ġeneralment jimmiraw għal livelli baxxi ta ’ phenylalanine (eż. permezz ta ’ dieta), u mhux astinenza totali ta ’ dan is- sors.
13 The CHMP considered that a contraindication is acceptable, given the marginal influence on noradrenaline and serotonin levels and the post-marketing experience available to date.
L- użu ta ’ l- aspartame kif ippreżentat f’ dawn l- ammonti f’ Remeron pilloli li jinħallu fil- ħalq m’ huwiex kontra- indikazzjoni assoluta.
Pathological alterations of blood count The applicant/ MAH stated that there are no data indicating that mirtazapine aggravates conditions where blood count is altered.
Għalhekk huwa propost li din it- twissija tinżamm fis- sezzjoni korrispondenti, is- sezzjoni 4. 4.
Given the very low incidence of the most serious condition, i. e. agranulocytosis (independent from the question of causality or whether it surpasses the background incidence), this is not an absolute contraindication and should not be included in section 4.3
L- aspartame jista ’ jiġi/ huwa kkunsidrat bħala kontra- indikat fit- tfal żgħar, iżda mirtazapine m’ għandux jintuża f’ din il - kategorija ta ’ età u, għalhekk, m’ għandux bżonn ta ’ iżjed twissijiet.
With regards to the pathological alterations of blood count, the CHMP considered that proposed wording is acceptable, based on the meta-analysis report provided in the applicant/ MAH’ s responses.
Is- CHMP ħass li l- ispjegazzjonijiet mogħtija jidhru xjentifikament sodi u ġustifikati, u nnota li l - kontenut ta ’ aspartame fil- prodott huwa indirizzat b’ mod adegwat fil- forma proposta.
In Sections 4.3 (Contra-indications) and 4.5 (Interaction with other medicinal products and forms of interaction) of the SPC, the interaction with MAOIs concerns an absolute contra-indication in accordance with the SPCs for SSRIs and SNRIs.
Inibituri MAO L- applikant/ Detentur ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq jgħid li m’ għandux informazzjoni minn provi kliniċi li jevalwaw l- interazzjonijiet bejn l- inibituri MAO (MAO- Is) u mirtazapine.
The CHMP considered that the arguments provided by the applicant/ MAH were insufficient to justify that mirtazapine would act different from SSRIs and SNRIs (e. g. venlafaxine).
Kif spjegat fil- faxxiklu ta ’ l- applikazzjoni għal referenza, l- istudji fuq l- annimali wrew li mirtazapine 16 jikkawża biss żieda żgħira u temporanja fil- livelli ta ’ noradrenalin u serotonin fil- hippocampus (id - dejta tinsab disponibbli fuq rikjesta).
Moreover, the CHMP was of the opinion that the mechanism of interaction with MAOIs with mirtazapine is different from SSRIs.
Billi l- mekkaniżmu ta ’ l- interazzjoni huwa differenti għal MAO - Is flimkien ma ’ mirtazapine meta mqabbel ma ’ MAO- Is u SSRIs, huwa improbabbli li r- riskju tas - sindrome ta ’ serotonin ikun għoli daqs b’ antidipressanti serotonerġiċi oħra, bħas- SSRIs.
The low number of post-marketing reports does not justify this either.
L- inibituri MAO għalhekk huma relattivament kontra- indikati ma ’ Remeron.
Therefore, the addition of a cross reference to section 4.3 of the SPC in section 4.5 (after the wording related to the interaction with MAOIs) was recommended, in line with the harmonised SPC for SSRIs and in line with the SPC for venlafaxine - a SNRI.
In- numru baxx ta ’ rapporti wara t - tqegħid fis- suq tal- prodott jissuġġerixxi li din l- interazzjoni ma sseħħx b’ mod frekwenti u ma titlobx li jinbidel il- post fl- SPC fejn hija pprovduta t- twissija dwar l- użu simultanju ta ’ Remeron ma ’ MAO- Is.