qanastek/EMEA-V3 huggingface dataset:
According to several international guidelines, doxycycline is also commonly recommended for the treatment of rosacea but is only approved in a few EU countries; consequently the off-label use of doxycycline is widely prescribed in clinical practice for long-term treatment (months to up to several years) of acne vulgaris, with dosages generally higher (100 mg daily) than the proposed dosage for Oracea (40 mg daily).
Skond diversi linji ta ’ gwida internazzjonali, doxycycline huwa wkoll irrakkomandat b’ mod komuni għall- kura ta ’ rosacea iżda huwa biss approvat fi ftit pajjiżi ta ’ l - UE; konsegwentement l- użu mingħajr tikketta ta ’ doxycycline li jingħata b’ mod komuni b’ riċetta ta ’ tabib fil- prattika klinika għal kura fit- tul (xhur sa diversi snin) ta ’ acne vulgaris, b’ dożaġġi ġeneralment iktar għoljin (100 mg kuljum) milli d- doża proposta għal Oracea (40 mg kuljum).
This probably leading to a higher risk for adverse reactions, such as development of resistance in the commensal microflora.
Dan probabbilment iwassal għal riskju iktar għoli ta ’ reazzjonijiet avversi, bħalma huwa l- iżvilupp ta ’ reżistenza fil- mikroflora kommensali.
Thus, the present application for Oracea (doxycycline 40 mg tablets) is not for a New Chemical Entity but aims to develop a formulation designed for once a day oral administration that could provide steady state doxycycline plasma concentrations at the anti-inflammatory level but not at the antimicrobial level.
Għalhekk, l- applikazzjoni preżenti għal Oracea (pilloli ta ’ doxycycline 40 mg) mhijiex għal Entità Kimika Ġdida iżda timmira biex tiżviluppa formulazzjoni ddisinnjata għal għoti orali ta ’ darba kuljum li tista ’ tipprovdi konċentrazzjonijiet fil- plażma ta ’ doxycycline fi stat fiss fil- livell anti- infjammatorju iżda mhux fil- livell antimikrobjali.
The procedure was referred to the CHMP, who raised a number of issues through a List of Questions and a subsequent List of Outstanding Issues, which were addressed by the Applicant.
Il- proċedura ġiet riferuta lis- CHMP, li qajjem numru ta ’ argumenti permezz ta ’ Lista ta ’ Mistoqsijiet u Lista ta ’ Kwistjonijiet Pendenti, li ġew indirizzati mill- Applikant.
The CHMP considered that the safety of doxycycline (100-200 mg daily) has been established over many decades of clinical use, providing re-assurance on the tolerability of the lower dose of Oracea.
Is- CHMP ikkunsidra li s- sigurtà ta ’ doxycycline (100- 200 mg kuljum) ġiet stabbilita fuq bosta għexieren ta ’ snin ta ’ użu kliniku, u dan jipprovdi serħan il- moħħ fuq it- tollerabbiltà tad- doża iktar baxxa ta ’ Oracea.
The clinical studies showed no treatment-related serious AEs and tolerability seems to be unaffected by gender, age or disease severity.
L- istudji kliniċi ma wrew l- ebda AEs serji relatati mal- kura u t- tollerabbiltà tidher li mhijiex effettwata mis- sess, età jew severità tal- marda.
In contrast to higher, antimicrobial doses of doxycycline that may lead to the development of resistance and opportunistic overgrowth, long-term clinical trial experience with doxycycline 40 mg/ day confirms the good tolerability of doxycycline at this dose level during prolonged treatment.
B’ kuntrast ma ’ dożi antimikrobjali, iktar għoljin ta ’ doxycycline li jistgħu jwasslu għall- iżvilupp ta ’ reżistenza u tikbir żejjed opportunistiku, esperjenza ta ’ provi kliniċi fit- tul b’ doxycycline 40 mg/ day tikkonferma t- tollerabbiltà tajba ta ’ doxycycline f’ dan il- livell ta ’ doża waqt kura fit- tul.
Post-marketing experience has not identified any new safety concerns.
Esperjenza ta ’ wara t- tqegħid fis- suq ma identifikatx xi tħassib ġdid ta ’ sigurtà.
Overall it is estimated that, since authorization, more than 400,000 prescriptions for Oracea were filled at pharmacies in the USA up to November 2007 and the post-marketing experience identified no new safety concerns.
B’ kollox ma ’ kollox huwa stmat li, sa mill- awtorizzazzjoni, iktar minn 400, 000 riċetta għal Oracea minn tobba mtlew fl- ispiżeriji fil- USA sa Novembru 2007 u l - esperjenza ta ’ wara t- tqegħid fis- suq ma identifikat l- ebda tħassib ġdid għas- sigurtà.
Regarding efficacy, the Applicant demonstrated the clinical efficacy of Oracea as monotherapy in reducing the papulo-pustular lesion count, through two Phase III double-blinded, randomized, placebo-controlled studies, including over 530 patients.
Rigward l- effikaċja, l- Applikant wera li l- effikaċja klinika ta ’ Oracea bħala monoterapija fit- tnaqqis ta ’ l- għadd ta ’ leżjonijiet papulo- pustulari, permezz ta ’ żewġ studji ta ’ Fażi III ikkontrollati bi plaċebo, irrandomizzati, double- blinded li inkludew aktar fuq minn 530 pazjent.
Both studies showed significant superiority of Oracea compared with placebo.
Iż- żewġ studji wrew superjorità sinifikattiva ta ’ Oracea meta mqabbla ma ’ plaċebo.
Since no formal dose-response studies have been conducted, Phase III data were analyzed to investigate the existence of a dose– efficacy relationship.
Minħabba li ma sar l- ebda studju formali fir- rigward tad- doża- reazzjoni, tagħrif ta ’ Fażi III ġie analizzat biex tkun investigata l - eżistenza ta ’ relazzjoni bejn id- doża- effikaċja.
The applicant concluded that higher mg/ kg doses led to higher plasma concentrations, but did not lead to increased clinical efficacy and that anti-inflammatory– dose doxycycline (40-mg formulation) conferred peak anti-inflammatory efficacy in the treatment of rosacea.
L- applikant ikkonkluda li dożi mg/ kg iktar għoljin wasslu għal konċentrazzjonijiet fil- plażma iktar għoljin, iżda ma wasslux għal żieda fl- effikaċja klinika u li doża anti- infjammatorja ta ’ doxycycline (formulazzjoni 40- mg) tat effikaċja massima anti - infjammatorja fil- kura ta ’ rosacea.
In addition, the preliminary results of a study comparing Oracea (40 mg doxycycline) to 100 mg doxycycline daily, both in conjunction with topical metronidazole, support the non-inferiority hypothesis of the Oracea dosing regimen.
Barra minn hekk, ir- riżultati preliminari ta ’ studju li qabbel Oracea (40 mg doxycycline) ma ’ 100 mg doxycycline kuljum, it- tnejn li huma flimkien ma ’ metronidazole topikali, jappoġġjaw l- ipoteżi ta ’ nuqqas ta ’ inferjorità tar- reġimen tad- dożaġġ ta ’ Oracea.
Provided that the proposed indication mirrors the primary endpoint in the pivotal studies, as currently suggested, the CHMP considered that efficacy could be regarded as sufficiently demonstrated in the presently studied populations in the submitted phase 3 studies.
Diment li l - indikazzjoni proposta tirrifletti l- punt ta ’ tmiem primarju fl- istudji ewlenin, kif qiegħed jiġi ssuġġerit fil- preżent, is- CHMP ikkunsidra li l- effikaċja tista ’ titqies li tkun intweriet biżżejjed fil - popolazzjonijiet studjati fil- preżent fl- istudji ta ’ fażi 3 sottomessi.
The Applicant
L- Applikant indirizza t- tħassib li l- ebda studju ta ’ tqabbil ma kien ipprovdut billi argumenta li prova klinika kkontrollata bl- użu ta ’ mediċina ta ’ tqabbil attiva bħalma hija doxycycline sistemiku ma kinitx meħtieġa, minħabba li l- programm ta ’ żvilupp kien konformi ma ’ numru ta ’ linji gwida ta ’ l- ICH CPMP/ ICH/ 291/ 95 u CPMP/ ICH/ 135/ 95 li ma jeħtiġux mediċina ta ’ tqabbil attiva u mal- Gwida E10
4 considered that studies against other active treatments were not practical or warranted, in the case of Oracea.
L- Applikant ikkunsidra li studji kontra kuri attivi oħrajn ma kinux prattiċi jew garantiti, fil- każ ta ’ Oracea.
In addition, there is a lack of well-characterized comparator as very few EU countries have the indication rosacea approved for doxycycline (100 mg daily), which would present additional challenges studying two unapproved drugs (100 mg doxycycline and Oracea) in one clinical trial.
Barra minn hekk, hemm nuqqas ta ’ mediċina ta ’ tqabbil ikkaratterizzata sewwa minħabba li ftit wisq pajjiżi ta ’ l- UE għandhom l- indikazzjoni rosacea approvata għal doxycycline (100 mg kuljum), li tippreżenta sfidi addizzjonali li jistudjaw żewġ mediċini mhux approvati (100 mg doxycycline u Oracea) fi prova klinika waħda.
However, studies were conducted to evaluate the efficacy and safety of Oracea in conjunction to active treatment such as metronidazole, showing that Oracea, given as an adjunct to metronidazole, is far superior to metronidazole alone and that no difference in efficacy was found between low and high doses of doxycycline.
Madankollu, saru studji biex jevalwaw l- effikaċja u s- sigurtà ta ’ Oracea flimkien ma ’ kura attiva bħalma hija metronidazole, li wrew li Oracea, mogħtija miżjuda ma ’ metronidazole, hija bil- bosta superjuri għal metronidazole waħdu u li ma nstabet l- ebda differenza fl- effikaċja bejn dożi baxxi u għoljin ta ’ doxycycline.
The CHMP agreed with the ICH guidelines, stating that an active comparator is not required if it is considered ethically and practically feasible to use placebo in the control group.
Is- CHMP qabel mal- linji gwidi ta ’ l- ICH, billi ddikjara li mediċina attiva ta ’ tqabbil ma tkunx meħtieġa jekk ikun ikkunsidrat etikament u prattikament fattibbli li jintuża plaċebo fil- grupp ta ’ kontroll.
The indication rosacea as defined by the study inclusion criteria was regarded to fulfil these criteria.
L- indikazzjoni rosacea kif iddefinita bil- kriterji ta ’ inklużjoni ta ’ l - istudju kienet meqjusa bħala waħda li tissodisfa dawn il- kriterji.
Consequently, the CHMP considered the clinical efficacy of Oracea to be sufficiently demonstrated in the two placebo-controlled phase 3 studies and the issue to be resolved.
Konsegwentement, is- CHMP ikkunsidra li l- effikaċja klinika ta ’ Oracea intweriet biżżejjed f’ żewġ studji ta ’ fażi 3 ikkontrollati bi plaċebo u qies li l- kwistjoni ġiet solvuta.
Regarding the risk of resistance induction, the Applicant provided data from several studies demonstrating that the 100 mg doxycycline dose leads to marked emergence of resistant strains in the oral and intestinal micro flora.
Rigward ir- riskju ta ’ induzzjoni ta ’ reżistenza, l- Applikant ipprovda tagħrif minn diversi studji li wera li doża ta ’ 100 mg doxycycline twassal għal tfaċċar qawwi ta ’ speċi reżistenti fil- mikro flora orali u intestinali.
Six studies addressed the emergence issue in low dose doxycycline (40 mg daily), focusing on the effects on the intestinal microflora, on subgingival microflora and saliva and on the skin flora.
Sitt studji indirizzaw il- problema ta ’ tfaċċar f’ doxycycline f’ doża baxxa (40 mg kuljum), li ffukkaw fuq l- effetti ta ’ mikroflora intestinali, mikroflora sottoġinġivali u bżieq u fuq il- flora tal - ġilda.
A double-blind, placebo controlled study by Walker et al, 2005 studying the effect of 20 mg doxycycline bid did not show any statistically significant differences between the active group and the placebo group in terms of emergence of doxycycline- or multidrug-resistant bacteria in faecal or vaginal samples.
Studju double- blind, ikkontrollat bi plaċebo minn Walker et al, 2005 li studja l- effett ta ’ 20 mg doxycycline bid ma wera l- ebda differenza statistikament sinjifikanti bejn il- grupp attiv u l- grupp plaċebo f’ termini ta ’ tfaċċar ta ’ batterji reżistenti għal doxycycline jew mediċini multipli f’ kampjuni ta ’ ppurgar jew vaġinali.
With regard to target site exposure of bacteria to doxycycline, the Applicant referred to several publications stating that the resulting concentrations of antibacterially-active drug will be very low, leading to a very low risk of resistance pressure.
Fir- rigward ta ’ espożizzjoni tas- sit fil- mira tal- batterji għal doxycycline, l - Applikant irrefera għal diversi pubblikazzjonijiet li iddikjaraw li l- konċentrazzjonijiet ta ’ mediċina antibatterikament attivi li jirriżultaw sejrin ikunu baxxi ħafna, li jwasslu għal riskju baxx ħafna ta ’ pressjoni ta ’ reżistenza.
Following the administration of the 40 mg modified release formulation of doxycycline, the maximum excreted concentrations of doxycycline will be between 0.03 – 0.16 mg/ L for all excretion mechanisms.
Wara l- għoti ta ’ formulazzjoni ta ’ tnixxija mmodifikata ta ’ 40 mg ta ’ doxycycline, il- konċentrazzjonijiet massimi eliminati ta ’ doxycycline ikunu bejn 0. 03 – 0. 16 mg/ L għall- mekkaniżmi kollha ta ’ eliminazzjoni.
The binding of doxycycline to plasma proteins, epidermal tissue and faeces must be taken into account as only the free fraction (10%) of doxycycline is antibacterially active following the oral administration of 40 mg doxycycline.
L- irbit ta ’ doxycycline ma ’ proteini fil- plażma, tessuti epidermali u ippurgar għandu jiġu kkunsidrat minħabba li l- frazzjoni ħielsa biss (10%) ta ’ doxycycline hija antibatterikament attiva wara l- għoti orali ta ’ 40 mg doxycycline.
The Applicant also presented data from six placebo- controlled studies conducted in over 400 patients, showing no evidence of increase in resistance of the microbiological flora of the gastrointestinal tract (faeces), vagina, skin, saliva or dental plaque after long-term treatment with doxycycline 40 mg/ day for 6 to 18 months, which is in line with pharmacokinetic investigations on target site exposure.
L- Applikant ippreżenta wkoll tagħrif minn sitt studji kkontrollati bi plaċebo fuq aktar minn 400 pazjent, li ma wrew l- ebda evidenza ta ’ żieda fir- reżistenza tal- flora mikrobijoloġika tal- passaġġ gastrointestinali (ippurgar), vaġina, ġilda, bżieq jew plakka dentali wara kura fit- tul b’ doxycycline 40 mg/ kuljum għal 6 sa 18- il xahar, u dan jaqbel ma ’ investigazzjonijiet farmakokinetiċi fuq espożizzjoni tas- sit fil- mira.
Based on these findings it is scientifically reasonable to conclude that the effect of low dose doxycycline on the normal residential flora including E coli, Enterococci, Staphylococci and Streptococci to be almost non-existent and concluded that the risk of inducing resistance development is negligible.
Abbażi ta ’ dawn is- sejbiet, huwa xjentifikament raġjonevoli li jiġi konkluż li l- effett ta ’ doxycycline f’ doża baxxa fuq il- flora residenzjali normali inklużi E coli, Enterococci, Staphylococci u Streptococci huwa kważi mhux eżistenti u kkonkluda li r- riskju ta ’ induzzjoni ta ’ żvilupp ta ’ reżistenza huwa negliġibbli.
The CHMP acknowledges that available studies and pharmacokinetic data indicate that Oracea (40 mg doxycycline daily) is less likely to induce resistance in the normal micro biota than 100 mg doxycycline daily, and thus does not consider this issue to be a major objection that should preclude an approval of the product.
Is- CHMP irrikonoxxa li l- istudji u t- tagħrif farmakokinetiku disponibbli jindikaw li Oracea (40 mg doxycycline kuljum) x’ aktarx tinduċi inqas reżistenza fil- mikro bijota normali milli 100 mg doxycycline kuljum, u b’ hekk ma jikkunsidrax li din il- kwistjoni hija oġġezzjoni maġġura li għandha tipprekludi approvazzjoni tal- prodott.
However, increased knowledge of the ecological effects of long-term administration of low-dose doxycycline is highly desirable, and the Applicant is requested to commit to submitting a study protocol for a well designed post-marketing clinical study investigating emergence of resistance in relevant bacterial groups in the intestinal and upper respiratory tract for validation and to carry out a study accordingly within 3 months of approval.
Madankollu, żieda fl- għarfien ta ’ l- effetti ekoloġiċi ta ’ għoti fit - tul ta ’ doża baxxa ta ’ doxycycline hija mixtieqa bil- bosta, u l- Applikant huwa mitlub li jimpenja ruħu li jissottometti protokoll ta ’ studju għal studju kliniku ddisinnjat sewwa ta ’ wara t- tqegħid fis- suq li jistħarreġ il- feġġa ta ’ reżistenza fi gruppi batteriċi relevanti fil- passaġġ intestinali u respiratorju tan - naħa ta ’ fuq għal validazzjoni u li jwettaq studju bix- xieraq fi żmien 3 xhur mill- approvazzjoni.
The data resulting from this study should be provided to the relevant national competent authorities for assessment.
Id - dejta li tirriżulta minn dan l- istudju għandha tkun ipprovduta lill- awtoritajiet kompetenti nazzjonali relevanti għal valutazzjoni.
The Applicant was also requested to reflect information on this issue in sections 4.4 and 5.1 of the SPC.
L- Applikant intalab ukoll biex jirrifletti tagħrif fuq din il- kwistjoni f’ sezzjoniet 4. 4 u 5. 1 tal- SPC.
Finally, the CHMP also acknowledged the difficulty in breaking down the different subgroups of rosacea since symptoms often overlap between the different subtypes and recognised that Oracea is aimed towards the treatment of papules and pustules rather than treatment of rosacea as a whole or treatment of a specific subtype.
Finalment, is- CHMP għaraf ukoll id- diffikultà fl- analiżi tas- sottogruppi differenti ta ’ rosacea minħabba li s- sintomi ta ’ spiss jitrikkbu bejn is- sottotipi differenti u rrikonoxxa li Oracea hija mmirata lejn il- kura ta ’ papuli u pustuli milli l- kura ta ’ rosacea in ġenerali jew kura ta ’ sottotip speċifiku.
The CHMP was also satisfied with the explanation on the exclusion criteria of nodule numbers, as no effect on nodules is claimed in the proposed indication.
Is- CHMP kien ukoll sodisfatt bl- ispjega tal- kriterji ta ’ esklużjoni tan- numru ta ’ għoqiedi,
Regarding erythema, the CHMP considered that despite the absence of evidence of a positive effect on erythema, there are no indications of any risk of worsening of erythema during Oracea therapy.
Fir- rigward ta ’ eritima, is- CHMP ikkunsidra li minkejja n- nuqqas ta ’ evidenza ta ’ effett pożittiv fuq eritima, ma hemm l- ebda indikazzjoni ta ’ xi riskju ta ’ aggravar ta ’ eritima waqt terapija b’ Oracea.
Furthermore, the CHMP was of the opinion that although the efficacy of doxycycline 40mg daily has not been demonstrated in patients with ocular rosacea, the literature data combined with the results from the
Barra minn hekk, is- CHMP kien ta ’ l- opinjoni li għalkemm ma ntwerietx l- effikaċja ta ’ doxycycline 40mg kuljum f’ pazjenti b’ rosacea okulari, id- dejta tal- letteratura kkumbinata ma ’ riżultati minn żewġ studji kkontrollati bi plaċebo sottomessa ma indikat l- ebda tħassib fir- rigward tas- sigurtà f’ dan is - sottogrupp.
The CHMP proposed the amendment of section 4.4 of the SPC, in order to minimise the risk for withholding treatment from patients with ocular rosacea.
Is- CHMP ippropona l- emenda ta ’ sezzjoni 4. 4 tal- SPC, sabiex jiminimizza r- riskju għaż - żamma ta ’ kura f’ pazjenti b’ rosacea okulari.
The CHMP also considered that the survey referred to by the Applicant, showing that papulopustular lesions are readily recognized and rated by dermatologists providing a qualitative as well as quantitative measurement, was relevant; therefore the currently proposed indication was considered clinically applicable and practical.
Is- CHMP ikkunsidra wkoll li l- istħarriġ li saret referenza għalih mill- Applikant, li juri li leżjonijiet papulopustulari huma diġà rikonoxxuti u vvalutati mid - dermatologi li jipprovdi kejl kwalitattiv kif ukoll kwantitattiv, kien relevanti; għaldaqstant l - indikazzjoni proposta fil- preżent kienet ikkunsidrata klinikament applikabbli u prattika.
In conclusion, the CHMP considers the efficacy of Oracea to reduce papulopustular lesions in adult patients with facial rosacea to be sufficiently demonstrated.
Bħala konklużjoni, is- CHMP jikkunsidra li l- effikaċja ta ’ Oracea li tnaqqas leżjonijiet papulopustulari f’ pazjenti adulti b’ rosacea tal- wiċċ intweriet biżżejjed.
The extensive clinical experience of long- term treatment with doxycycline at higher dosages (100-200 mg daily) and the fact that all Phase 3 studies indicate that Oracea is well tolerated and demonstrates a safety profile comparable to placebo was considered reassuring.
L- esperjenza klinika estensiva ta ’ kura fit- tul b’ doxycycline f’ dożaġġi iktar għoljin (100- 200 mg kuljum) u l- fatt li l- istudji ta ’ Fażi 3 kollha jindikaw li Oracea hija ttollerata sewwa u turi profil ta ’ sigurtà li jaqbel ma ’ plaċebo kienet ikkunsidrata ta ’ serħan il- moħħ.
However, the studies submitted concerning the absence of risk for selection of antibiotic resistance in the normal microbiota were not considered as fully convincing, due to limitations in the methods used.
Madankollu, l- istudji sottomessi li jikkonċernaw in- nuqqas ta ’ riskju għal għażla ta ’ reżistenza antibijotika fil- mikrobijota normali ma kinux ikkunsidrati konvinċenti, minħabba limitazzjonijiet fil- metodi wżati.
Consequently, the CHMP required a commitment from the Applicant to perform an appropriate post-marketing study in order to further elucidate the risk for emergence of resistance in the intestinal and upper respiratory microflora associated with the long- term use of Oracea.
Konsegwentement, is- CHMP ħtieġ impenn mill- Applikant li jagħmel studju ta ’ wara t- tqegħid fis- suq addattat sabiex jitfa ’ dawl aħjar fuq ir- riskju għall- feġġa ta ’ reżistenza fil- mikroflora intestinali u respiratorja tan- naħa ta ’ fuq assoċjati ma ’ użu fit- tul ta ’ Oracea.
The scope, design and endpoints of the study should be in line with similar trials published in the literature and the study protocol should be validated by and submitted to the National Competent Authority of the Reference Member State within three months of approval.
L- iskop, disinn u punt ta ’ tmiem għandhom ikunu konformi ma ’ provi simili ppubblikati fil - letteratura u l- protokoll ta ’ l- istudju għandu jkun ivvalidat u sottomess lill- Awtorità Nazzjonali Kompetenti fi żmien tliet xhur mill- approvazzjoni.
2 years) from the date of approval.
L- Applikant għandu jkompli dan l- istudju u jippreżenta rapport fi żmien perijodu rageonevoli (per eżempju sentejn) mid- data ta ’ l- approvazzjoni.
The Applicant was also requested to revise the SPC for Oracea, in sections 4.4 and 5.1 due to the lack of experience in patients with ocular rosacea, as seen in the adopted revised Product Information.
L- Applikant kien ukoll mitlub jirrevedi l- SPC għal Oracea, f’ sezzjonijiet 4. 4 u 5. 1 minħabba nuqqas ta ’ esperjenza f’ pazjenti b’ rosacea okulari, kif jidher fit- Tagħrif dwar il- Prodott rivedut adottat.
In assessing the benefit/ risk of Oracea, the current situation of limited treatment options for rosacea was taken into consideration, as well as the fact that Oracea is expected to provide an alternative to the international guidelines recommending off-label use of doxycycline (or other tetracycline derivates) for the treatment of rosacea, with the associated decrease in risk for adverse events.
Fil- valutazzjoni ta ’ benefiċċju/ riskju ta ’ Oracea, tqieset is- sitwazzjoni attwali ta ’ għażliet ta ’ kura limitata għal rosacea, kif ukoll il- fatt li Oracea hija mistennija tipprovdi alternattiva għal- linji gwida internazzjonali li jirakkomandaw użu mingħajr tikketta ta ’ doxycycline (jew derivattivi tetracycline oħrajn) għall- kura ta ’ rosacea, bit- tnaqqis assoċjat fir- riskju għal episodji avversi.
Thus, the CHMP considers that the benefits of marketing a systemic drug such as Oracea in the present indication outweighs the risk for potential harmful effects related to resistance development and therefore consider the benefit-risk ratio to be positive.
Għalhekk, is - CHMP jikkunsidra li l- benefiċċji li tpoġġi fis- suq mediċina sistemika bħalma hija Oracea fl - indikazzjoni preżenti jegħlbu r- riskju għal effetti potenżjali ta ’ ħsara relatati ma ’ żvilupp ta ’ reżistenza u għaldaqstant jikkunsidra l- proporzjon benefiċċju- riskju bħala wieħed pożittiv.
GROUNDS FOR AMENDMENT OF THE SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET
RAĠUNIJIET GĦAL EMENDA TAS- SOMMARJI TAL- KARATTERISTIĊI TAL - PRODOTT, TIKKETTA U FULJETT TA ’ TAGĦRIF
- The CHMP considers the efficacy of Oracea to reduce papulopustular lesions in adult patients with
- Is- CHMP jikkunsidra li l- effikaċja ta ’ Oracea biex tnaqqas leżjonijiet papulopustulari f’ pazjenti
facial rosacea to be sufficiently demonstrated,
adulti b’ rosacea tal- wiċċ intweriet biżżejjed,
- The CHMP considers that Oracea is well tolerated and is satisfied with the safety profile when in
- Is- CHMP jikkunsidra li Oracea hija ttollerata tajjeb u huwa sodisfatt bil- profil ta ’ sigurtà meta
conjunction with the commitment to carry out a post-marketing study as set out in Annex IV and the revision of the Summary of Product Characteristics as set out in Annex III,
jitqies flimkien ma ’ l- impenn li jsir studju ta ’ wara t- tqegħid fis- suq kif stabbilit fl- Anness IV u r - reviżjoni tas- Sommarju tal- Karatteristiċi tal- Prodott kif stabbilit fl- Anness III,
- The CHMP considers that the benefits of marketing a systemic drug such as Oracea in the present
- Is- CHMP jikkunsidra li l- benefiċċji tat- tqegħid fis- suq ta ’ mediċina sistemika bħalma hija Oracea fl -
indication outweigh the risk for potential harmful effects related to resistance development and therefore considers the benefit-risk ratio to be positive,
indikazzjoni preżenti jegħlbu r- riskju għal effetti potenzjali ta ’ ħsara relatati ma ’ żvilupp ta ’ reżistenza u għaldaqstant jikkunsidra li l- proporzjon benefiċċju- riskju huwa wieħed pożittiv.
the CHMP has recommended the granting of the Marketing Authorisations for which the Summary of Product Characteristics, labelling and package leaflet are set out in Annex III for Oracea.
Is- CHMP irrakkomanda l- għoti ta ’ Awtorizzazzjonijiet għat- Tqegħid fis- Suq, li s- Sommarju tal - Karatteristiċi tal- Prodott, tikketta u fuljett ta ’ tagħrif għalihom jinsabu fl- Anness III għal Oracea.
The conditions of the Marketing Authorisation are set out in Annex IV.
Il - kondizzjonijiet ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq jinsabu fl- Anness IV.
7 A.
7 ANNESS III
ORACEA 40 mg modified-release hard capsules
ORACEA kapsuli iebsa ta ’ 40 mg li jerħu l- mediċina b' mod modifikat
Each capsule contains 40 mg doxycycline (as monohydrate).
Kull kapsula fiha 40 mg doxycycline (bħala monohydrate).
Excipient:
Sustanzi mhux attiva:
Each hard capsule contains 102 – 150 mg of sucrose.
Kull kapsula iebsa fiha 102 – 150 mg ta ’ sucrose.
Modified-release hard capsule
Kapsula iebsa li terħi l- mediċina b' mod modifikat
Beige capsule, No.
Kapsula kannella fl- isfar, daqs No.
2 size, bear the marking “ CGPI 40”.
2, li għandha l- marka “ CGPI 40 ”.
ORACEA is indicated to reduce papulopustular lesions in adult patients with facial rosacea.
ORACEA huwa indikat biex inaqqas il- feriti ta ’ nfafet u ponot f’ pazjenti adulti b’ rosaċeja fil- wiċċ.
Adults, including the elderly:
Adulti, inkluż l- anzjani:
The daily dose is 40 mg (1 capsule).
Id- doża ta ’ kuljum hija 40 mg (kapsula waħda).
The capsule should be taken in the morning with adequate amounts of water in order to reduce the risk of oesophageal irritation and ulceration (see section 4.4).
Il- kapsula għandha tittieħed fil- għodu ma ’ ammonti adegwati ta ’ ilma sabiex jitnaqqas ir- riskju ta ’ irritazzjoni u ulċerazzjoni ta ’ l- esofagu (ara sezzjoni 4. 4).
Patients should be evaluated after 6 weeks and, if no effect is seen, consideration should be given to stopping treatment.
Il- pazjenti għandhom jiġu eżaminati wara 6 ġimgħat, u jekk ma jkun osservat l- ebda effett, wieħed għandu jikkunsidra t- twaqqif tal- kura.
In clinical trials patients were treated for 16 weeks.
Fi provi kliniċi l- pazjenti kienu kkurati għal 16- il ġimgħa.
Upon discontinuation, lesions tended to reappear at 4 weeks follow-up.
Mat - twaqqif, kien hemm tendenza li l- feriti jerġgħu jidrhu fil- vista ta ’ wara 4 ġimgħat.
Therefore it is recommended that patients should be assessed 4 weeks after stopping treatment.
Għalhekk huwa rrakkomandat li l- pazjenti għandhom jiġu eżaminati 4 ġimgħat wara t- twaqqif tal- kura.
No dosage adjustment is necessary in patients with renal impairment.
Ma hemm bżonn ta ’ l- ebda aġġustament fid- dożaġġ f’ pazjenti b’ indeboliment tal- kliewi.
Hepatic impairment ORACEA should be administered with caution to patients with hepatic impairment or to those receiving potentially hepatotoxic medicinal products (see section 4.4)
Indeboliment tal- fwied ORACEA għandu jingħata b’ kawtela lill- pazjenti b’ indeboliment tal- fwied jew lil dawk li qed jirċievu prodotti mediċinali potenzjalment epatotossiċi (ara sezzjoni 4. 4)
Doxycycline is contraindicated in children below age 12 (see section 4.3).
Doxycycline huwa kontra- indikat fit- tfal taħt l- età ta ’ 12- il sena (ara sezzjoni 4. 3).
9 4.3 Contraindications
4. 3 Kontra- indikazzjonijiet
Hypersensitivity to the active substance, to other tetracyclines or to any of the excipients.
Sensittività eċċessiva għas- sustanza attiva, għal tetracyclines oħra jew għal xi sustanzi mhux attivi.
Infants and children up to 12 years of age.
Trabi u tfal b’ età sa 12- il sena.
Second and third trimesters of pregnancy (see section 4.6).
10 It- tieni u t- tielet trimestru tat- tqala (ara sezzjoni 4. 6).
Patients known to have, or suspected to have, achlorhydria or who have had surgery that bypasses or excludes the duodenum must not be prescribed doxycycline.
Pazjenti magħrufa li għandhom, jew suspettati li għandhom, aklorħajdra jew li kellhom kirurġija li taqbeż jew teskludi d- duwodenu m’ għandhomx jiġu preskritti doxycycline.
ORACEA contains doxycycline in a formulation designed to yield plasma levels below the antimicrobial threshold.
ORACEA fih doxycycline f’ formulazzjoni ddisinjata biex tagħti livelli fil- plażma taħt il- limitu effettiv kontra l- mikrobi.
ORACEA must not be used to treat infections caused by organisms susceptible (or suspected to be susceptible) to doxycycline.
ORACEA m’ għandux jintuża għall- kura ta ’ infezzjonijiet ikkawżati minn organiżmi suxxettibli (jew suspettati li huma suxxettiblie) għal doxycycline.
Solid dosage forms of the tetracyclines may cause oesophageal irritation and ulceration.
Forom ta ’ dożaġġ solidi ta ’ tetracyclines jistgħu jikkawżaw irritazzjoni u ulċerazzjoni ta ’ l- esofagu.
To avoid oesophageal irritation and ulceration, adequate fluids (water) should be taken with this medicinal product (see section 4.2).
Biex jiġi evitat irritazzjoni u ulċerazzjoni ta ’ l- esofagu, għandhom jittieħdu biżżejjed fluwidi (ilma) ma ’ dan il- prodott mediċinali (ara sezzjoni 4. 2).
ORACEA should be swallowed whilst in an upright sitting or standing posture.
ORACEA għandu jinbela ’ waqt li f’ pożizzjoni bilqiegħda jew wieqfa.
Whilst no overgrowth by opportunistic microorganisms such as yeasts were noted during the clinical studies with ORACEA, therapy with tetracyclines at higher doses may result in overgrowth of non- susceptible microorganisms including fungi.
Filwaqt li matul l- istudji kliniċi b’ ORACEA ma kien innutat l- ebda tkabbir żżejjed minn mikro - organiżmi opportunistiċi bħall- fungi b’ ċellula waħda, terapija b’ dożi ogħla ta ’ tetracyclines tista ’ twassal għal tkabbir żżejjed ta ’ mikro- organiżmi mhux suxxettibli inkluż fungi.
Although not observed in clinical trials with ORACEA, the use of tetracyclines at higher doses may increase the incidence of vaginal candidiasis.
Għalkemm mhux osservat fil- provi kliniċi b’ ORACEA, l- użu ta ’ tetracyclines f’ dożi ogħla jista ’ jżid l- inċidenza ta ’ kandidajasi vaġinali.
ORACEA should be used with caution in patients with a history of predisposition to candidiasis overgrowth.
ORACEA għandu jintuża b’ kawtela f’ pazjenti b’ passat ta ’ predispożizzjoni ta ’ tkabbir żżejjed ta ’ kandidajasi.
If superinfection is suspected, appropriate measures should be taken, including consideration of discontinuing ORACEA.
Jekk hemm suspett ta ’ superinfezzjoni, għandhom jittieħdu miżuri xierqa, inkluż kunsiderazzjoni għal waqfien ta ’ ORACEA.
Treatment with higher doses of tetracyclines is associated with emergence of resistant intestinal bacteria, such as enterococci and enterobacteria.
Kura b’ dożi ogħla ta ’ tetracyclines hija assoċjata ma ’ l- itfaċċar ta ’ batterja tal- musrana reżistenti, bħal enterococci u enterobacteria.
Although not observed during clinical studies with low dose doxycycline (40 mg/ day), the risk for development of resistance in the normal microflora cannot be excluded in patients treated with ORACEA.
Għalkemm mhux osservat waqt l- istudji kliniċi b’ doża baxxa ta ’ doxycycline (40 mg/ jum), ir- riskju ta ’ l- iżvilupp ta ’ reżistenza fil- mikroflora normali ma tistax tiġi eskluża f’ pazjenti kkurati b’ ORACEA.
Doxycycline blood levels in patients treated with ORACEA are lower than in those treated with conventional antimicrobial formulations of doxycycline.
Livelli fid- demm ta ’ doxycycline f’ pazjenti kkurati b’ ORACEA huma aktar baxxi minn dawk ikkurati b’ formulazzjonijiet konvenzjonali kontra l- mikrobi ta ’ doxycycline.
However, as there are no data to support safety in hepatic impairment at this lower dose, ORACEA should be administered with caution to patients with hepatic impairment or to those receiving potentially hepatotoxic medicinal products.
Iżda, minħabba li m’ hemmx tagħrif li jsostni s- sigurtà f’ indeboliment tal- fwied f’ din id- doża aktar baxxa, ORACEA għandu jingħata b’ kawtela lill- pazjenti b’ indeboliment tal- fwied jew lil dawk li qed jirċievu prodotti mediċinali potenzjalment epatotossiċi.
The antianabolic action of tetracyclines may cause an increase in BUN.
L- azzjoni anti- anabolika ta ’ tetracyclines tista ’ tikkawża żjieda fil- BUN.
Studies to date indicate that this does not occur with the use of doxycycline in patients with impaired renal function.
Sa llum studji jindikaw li dan ma jseħħx bl- użu ta ’ doxycycline f’ pazjenti b’ funzjoni tal - kliewi mdgħajjfa.
Caution should be observed in the treatment of patients with myasthenia gravis who may be at risk of worsening of the condition.
Għandha tiġi osservata kawtela fil- kura ta ’ pazjenti b’ mijastenja gravis li jistgħu jkunu f’ riskju li l - kundizzjoni tmur għall- agħar.
All patients receiving doxycycline, including ORACEA, should be advised to avoid excessive sunlight or artificial ultraviolet light whilst receiving doxycycline and to discontinue therapy if phototoxicity (eg skin eruption etc) occurs.
Il- pazjenti kollha li qed jirċievu doxycycline, inkluż ORACEA, għandhom jiġu avżati biex jevitaw dawl tax- xemx eċċessiv jew dawl ultravjola artifiċjali waqt li qed jirċievu doxycycline u biex iwaqqfu t- terapija jekk ikun hemm fototossiċità (e. ż. nfafet fil- ġilda etc).
Use of sunscreen or sunblock should be considered.
Għandu jiġi kkunsidrat l- użu ta ’ protezzjoni għax- xemx jew ta ’ sunblock.
Treatment should cease at the first sign of photosensitivity.
Il- kura għandha titwaqqaf ma ’ l- ewwel sinjali ta ’ fotosensittività.
In common with the use of antimicrobial medicinal products in general, there is a risk of the development of pseudomembranous colitis with doxycycline treatment.
Bħall- użu ta ’ prodotti mediċinali kontra l- mikrobi b’ mod ġenerali, hemm riskju ta ’ l- iżvilupp ta ’ kolite psewdomembranuża bil- kura b’ doxycycline.
This may include the discontinuation
F’ każ ta ’ żvilupp ta ’ dijarea waqt kura b’ ORACEA, il - possibbiltà ta ’ kolite psewdomembranuża għandha tiġi kkunsidrata u għandha tinbeda terapija xierqa.
10 of doxycycline and the institution of specific antibiotic therapy.
Din tista ’ tinkludi t- twaqqif ta ’ doxycycline u l- bidu ta ’ terapija antibijotika speċifika.
Agents inhibiting peristalsis should not be employed in this situation.
Sustanzi li jinibixxu l- peristalsi m’ għandhomx jintużaw f’ din is- sitwazzjoni.
ORACEA should not be used in patients with ocular manifestations of rosacea (such as ocular rosacea and/ or blepharitis/ meibomianitis) as there are limited efficacy and safety data in this population.
ORACEA m’ għandux jintuża f’ pazjenti b’ manifestazzjonijiet ta ’ rosaċeja fl- għajnejn (bħal rosaċeja okulari u/ jew blefarite/ mejbomajenajtis) peress li hemm tagħrif limitat dwar l- effikaċja u s- sigurtà f’ din il- popolazzjoni.
If these manifestations appear during the course of the treatment Oracea should be discontinued and the patient should be referred to an ophthalmologist.
Jekk dawn il- manifestazzjonijiet jidru waqt il- kors ta ’ kura, Oracea għandu
In humans, the use of tetracyclines during tooth development may cause permanent discolouration of the teeth (yellow-grey-brown).
Fil- bnedmin, l- użu ta ’ tetracyclines waqt l- iżvilupp tas- snien jista ’ jikkawża bidla permanenti fil- kulur tas- snien (isfar- griż- kannella).
This reaction is more common during long-term use of the medicinal product but has been observed following repeated short-term courses.
Din ir- reazzjoni hija iktar komuni waqt l- użu fit- tul tal- prodott mediċinali iżda kienet osservata wara korsijiet qosra ripetuti.
Enamel hypoplasia has also been reported.
Kienet irrapportata wkoll ipoplasja ta ’ l - enamel.
As for other tetracyclines, doxycycline forms a stable calcium complex in any bone- forming tissue.
Bħal b’ tetracyclines oħra, doxycycline jifforma kumpless stabbli mal- calcium f’ kull tessut li jifforma l- għadam.
A decrease in fibula growth has been observed in premature infants given oral tetracycline in doses of 25 mg/ kg every 6 hours.
Kien osservat tnaqqis fit- tkabbir tal- fibula fi trabi prematuri li ngħataw tetracycline orali f’ dożi ta ’ 25 mg/ kg kull 6 sigħat.
This reaction was shown to be reversible when the medicinal product was discontinued.
Intweriet li din ir- reazzjoni hija riversibbli meta l - prodott mediċinali jitwaqqaf.
In the event of a severe acute hypersensitivity reaction (eg anaphylaxis), treatment with ORACEA must be stopped at once and the usual emergency measures taken (eg administration of antihistamines, corticosteroids, sympathomimetics and, if necessary, artificial respiration).
F’ każ ta ’ reazzjoni ta ’ sensittività eċċessiva severa u akuta (e. ż. anafilassi), kura b’ ORACEA għandha titwaqqaf minnufih u għandhom jittieħdu l- miżuri ta ’ emerġenza neċessarji tas- soltu (e. ż. għoti ta ’ antistamini, kortikosterojdi, simpatomimetiċi u, jekk hemm bżonn, respirazzjoni artifiċjali).
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product.
Pazjenti bi problemi ereditarji rari ta ’ intolleranza għal fructose, assorbiment ħażin ta ’ glucose - galactose jew insuffiċjenza ta ’ sucrase- isomaltase m’ għandhomx jieħdu dan il- prodott mediċinali.
The recommendations below regarding the potential interactions between doxycycline and other medicinal products are based upon experience with the larger doses generally used in antimicrobial formulations of doxycycline rather than with ORACEA.
Ir- rakkomandazzjonijiet hawn taħt dwar l- interazzjonijiet potenzjali bejn doxycycline u prodotti mediċinali oħra huma bbażati fuq esperjenza b’ dożi akbar ta ’ doxycycline li ġeneralment huma wżati f’ formulazzjonijiet kontra l- mikrobi u mhux fuq esperjenza b’ ORACEA.
However, at the present time, insufficient data exist for reassurance that the interactions described with higher doses of doxycycline will not occur with ORACEA.
Iżda, fil- preżent, ma jeżistix biżżejjed tagħrif biex jassikura li l- interazzjonijiet deskritti b’ dożi ogħla ta ’ doxycycline ma jseħħux b’ ORACEA.
Interactions affecting doxycycline:
Interazzjonijiet li jaffettwaw lil doxycycline:
The absorption of doxycycline from the gastro-intestinal tract may be inhibited by bi- or tri-valent ions such as aluminium, zinc, calcium (found for example in milk, dairy products and calcium- containing fruit juices), by magnesium (found for example in antacids) or by iron preparations, activated charcoal, cholestyramine, bismuth chelates and sucralfate.
L- assorbiment ta ’ doxycycline mill- apparat gastro- intestinali jista ’ jiġi inibit minn ijoni bivalenti jew trivalenti bħal aluminium, zinc, calcium (jinstab per eżempju fil- ħalib, prodotti mill- ħalib u meraq tal - frott li fihom il- calcium), minn magnesium (jinstab per eżempju fl- antaċidi) jew minn preparazzjonijiet ta ’ l- iron, faħam attivat, cholestyramine, kelati ta ’ bismuth u sucralfate.
Therefore such medicinal products or foodstuffs should be taken after a period of 2 to 3 hours following ingestion of doxycycline.
Għalhekk prodotti mediċinali jew ta ’ l- ikel bħal dawn għandhom jittieħdu wara perijodu ta ’ sagħtejn sa ’ 3 sigħat wara t- teħid mill- ħalq ta ’ doxycycline.
Medicinal products which increase gastric pH may reduce the absorption of doxycycline, and should be taken at least 2 hours after doxycycline.
Prodotti mediċinali li jżidu l- pH gastrika jistgħu jnaqqsu l- assorbiment ta ’ doxycycline, u għandhom jittieħdu ta ’ l- inqas sagħtejn wara doxycycline.
Quinapril may reduce the absorption of doxycycline due to the high magnesium content in quinapril tablets.
Quinapril jista ’ jnaqqas l- assorbiment ta ’ doxycycline minħabba l- kontenut ogħli ta ’ magnesium fil - pilloli quinapril.
Rifampicin, barbiturates, carbamazepine, diphenylhydantoin, primidone, phenytoin and chronic alcohol abuse may accelerate the decomposition of doxycycline due to enzyme induction in the liver thereby decreasing its half-life.
Rifampicin, barbiturates, carbamazepine, diphenylhydantoin, primidone, phenytoin u abbuż kroniku ta ’ alkoħol jistgħu jaċċeleraw id- dekompożizzjoni ta ’ doxycycline minħabba l- induzzjoni ta ’ enżimi fil- fwied b’ hekk inaqqsu il- half- life tiegħu.
Sub-therapeutic doxycycline concentrations may result.
Jistgħu jirriżultaw konċentrazzjonijiet sotto- terapewtiċi ta ’ doxycycline.
Concurrent use of cyclosporin has been reported to decrease the half-life of doxycycline.
L- użu fl- istess waqt ta ’ cyclosporin kien irrapportat li jnaqqas il- half- life ta ’ doxycycline.
Interactions affecting other medicinal products:
Interazzjonijiet li jaffettwaw prodotti mediċinali oħra:
Concomitant use not recommended:
L- użu fl- istess waqt mhux irrakkomandat:
11 When doxycycline is administered shortly before, during or after courses of isotretinoin, there is the possibility of potentiation between the medicinal products to cause reversible pressure increase in the intracranial cavity (pseudotumour cerebri).
Meta doxycycline jingħata ftit qabel, waqt jew wara korsijiet ta ’ isotretinoin, hemm il - possibbiltà ta ’ żjieda fil- qawwa tal- prodotti mediċinali biex b’ hekk jikkawżaw żjieda riversibbli fil- pressjoni intrakranjali (pseudotumour cerebri).
Concomitant administration should therefore be avoided.
Għalhekk l- għoti fl- istess ħin għandu jiġi evitat.
Bacteriostatic medicinal products including doxycycline may interfere with the bacteriocidal action of penicillin and beta-lactam antibiotics.
12 Prodotti mediċinali batterjostatiċi inkluż doxycycline jistgħu jinterferixxu ma ’ l- azzjoni batteriċida tal- peniċillina u antibijotiċi beta- lactam.
It is advisable that doxycycline and beta-lactam antibiotics should not therefore be used in combination.
Għalhekk huwa rrakkomandat li doxycycline u antibijotiċi beta- lactam m’ għandhomx jiġu wżati flimkien.
Tetracyclines and methoxyflurane used in combination have been reported to result in fatal renal toxicity.
Tetracyclines u methoxyflurane wżati flimkien kienu rrapportati li wasslu għal tossiċità renali fatali.
Doxycycline has been shown to potentiate the hypoglycaemic effect of sulphonylurea oral antidiabetic agents.
Doxycycline intwera li jsaħħaħ l- effett ipogliċemiku ta ’ sustanzi antidijabetiċi orali ta ’ sulphonylurea.
If administered in combination with these medicinal products, blood glucose levels should be monitored and, if necessary, the doses of the sulphonylureas should be reduced.
Jekk mogħti flimkien ma ’ dawn il- prodotti mediċinali, l- livelli ta ’ glucose fid- demm għandhom jiġu sorveljati u jekk meħtieġ, id- dożi ta ’ sulphonylureas għandhom jiġu mnaqqsa.
Doxycycline has been shown to depress plasma prothrombin activity thereby potentiating the effect of anticoagulants of the dicoumarol type.
Doxycycline intwera li jnaqqas l- attività ta ’ prothrombin fil- plażma u b’ hekk isaħħaħ l- effett ta ’ sustanzi kontra l- koagulazzjoni tad- demm tat- tip dicoumarol.
If administered in combination with these agents, coagulation parameters including INR should be monitored and, if necessary, the doses of the anticoagulant medicinal products reduced.
Jekk mogħti flimkien ma ’ dawn is - sustanzi, il- parametri ta ’ koagulazzjoni inkluż l- INR għandhom jiġu sorvejlati, u jekk meħtieġ, għandhom jitnaqqsu d- dożi tal- prodotti mediċinali kontra l- koagulazzjoni tad- demm.
The possibility of an increased risk of bleeding events should be borne in mind.
Il- possibbiltà ta ’ riskju miżjud ta ’ episodji ta ’ fsad għandha tittieħed f’ kunsiderazzjoni.
Tetracyclines used concurrently with oral contraceptives have in a few cases resulted in either breakthrough bleeding or pregnancy.
Tetracyclines użati fl- istess waqt ma ’ kontraċettivi orali fi ftit każijiet wasslu għal fsad mhux mistenni jew tqala.
Studies in animals have not demonstrated a teratogenic effect.
Studji fuq bhejjem ma wrewx effett teratoġeniku.
In humans, the use of tetracyclines during a limited number of pregnancies has not revealed any specific malformation to date.
Fil- bnedmin, s’ issa, l- użu ta ’ tetracyclines f’ numru limitat ta ’ nisa tqal ma wera l- ebda maformazzjoni speċifika.
The administration of tetracyclines during the second and the third trimesters results in permanent discolouration of the deciduous teeth in the offspring.
L- għoti ta ’ tetracyclines waqt it- tieni u t- tielet trimestru wassal għal bidla permanenti fil- kulur tas - snien tal- ħalib tat- tarbija.
As a consequence, doxycycline is contraindicated during the second and third trimesters of pregnancy (see section 4.3).
Bħala konsegwenza, doxycycline huwa kontra- indikat waqt it- tieni u t- tielet trimestru tat- tqala (ara sezzjoni 4. 3).
Low levels of tetracyclines are secreted into the milk of lactating women.
Livelli baxxi ta ’ tetracyclines jinħelsu fil- ħalib ta ’ nisa li qed ireddgħu.
Doxycycline can be used by breast-feeding mothers for short term use only.
Doxycycline jista ’ jintuża minn ommijiet li qed ireddgħu għall- perijodu ta ’ użu qasir biss.
Long term use of doxycycline may result in significant absorption by the suckling infant and is therefore not recommended because of a theoretical risk of dental discolouration and decreased bone growth of the suckling child.
L- użu fit- tul ta ’ doxycycline jista ’ jwassal għal assorbiment sinifikanti mit- tarbija li qed terda ’ u għalhekk mhux irrakkomandat minħabba r- riskju teoretiku ta ’ bidla fil- kulur tas- snien u tnaqqis fit- tkabbir ta ’ l- għadam tat- tarbija li qed terda ’.
Doxycycline has no or negligible influence on the ability to drive and use machines.
Doxycycline m’ għandu l- ebda effett jew għandu influwenza żgħira ħafna fuq il- ħila biex issuq u tħaddem magni.
In the pivotal placebo-controlled studies with ORACEA in rosacea, 269 patients were treated with ORACEA 40 mg once daily and 268 patients were treated with placebo for 16 weeks.
Fl- istudji pivitali kkontrollati bil- plaċebo b’ ORACEA f’ rosaċeja, 269 pazjent kienu kkurati b’ ORACEA 40 mg darba kuljum u 268 pazjent kienu kkurati bil- plaċebo għal 16- il ġimgħa.
Gastrointestinal adverse reactions overall occurred in a higher proportion of patients on ORACEA (13.4%) than on placebo (8.6%).
Reazzjonijiet gastro- intestinali avversi seħħew f’ proporzjon ogħla f’ pazjenti fuq ORACEA (13. 4%) meta mqabbel mal- plaċebo (8. 6%).
The most commonly reported adverse reactions in patients treated with ORACEA, ie those which occurred with ≥ 3% frequency on ORACEA and with a frequency at least 1% higher than on placebo, were nasopharyngitis, diarrhoea and hypertension.
L- aktar reazzjonijiet avversi rrapportati b’ mod komuni f’ pazjenti kkurati b’ ORACEA, ie dawk li seħħew bi frekwenza ta ’ ≥ 3% b’ ORACEA u bi frekwenza ta ’ mill - inqas 1% ogħla mill- plaċebo, kienu nasofarinġite, dijarea u pressjoni għolja.
The table below lists adverse reactions on ORACEA in the pivotal clinical trials, ie adverse reactions for which the frequency on ORACEA was greater than the frequency on placebo (by ≥ 1%).
It- tabella taħt telenka reazzjonijiet avversi b’ ORACEA fil- provi kliniċi pivitali, ie reazzjonijiet avversi li kellhom frekwenza ogħla b’ ORACEA minn dik bil- plaċebo (b’ ≥ 1%).
Common:
Reazzjonijiet avversi rrapportati għall- antibijotiċi tetracycline bħala klassi huma elenkati fit- tabella li ġejja.
≥ 1/ 100 to < 1/ 10
Il- kategoriji ta ’ frekwenza wżati huma: ≥ 1/ 100 sa < 1/ 10 Komuni:
Uncommon: ≥ 1/ 1,000 to < 1/ 100 Rare: ≥ 1/ 10,000 to < 1/ 1,000 Very rare:
Rari ħafna:
< 1/ 10,000
< 1/ 10, 000
Adverse reactionsa on ORACEA in pivotal placebo-controlled studies in rosacea:
Reazzjonijiet avversia b’ ORACEA fl- istudji pivitali kkontrollati bil- plaċebo f’ rosaċeja:
MedDRA system organ class
Sistema tal- klassifika tal- organi MedDRA
Frequency ≥ 1/ 100, < 1/ 10
Frekwenza ≥ 1/ 100, < 1/ 10
Nasopharyngitis Sinusitis Fungal infection
Nasofarinġite Sinusite Infezzjoni mill- moffa