natgillin/translations-raw huggingface dataset:
The reconstituted solution should be inspected for particulate matter and/or discolouration prior to administration.
Rekonstituirano zdravilo je treba pred dajanjem vizualno pregledati glede prisotnosti delcev in/ali obarvanja.
Based on what is known about the disposition kinetics of native FXa, andexanet alfa is likely rapidly broken down in plasma by endogenous proteases, consistent with its relatively short effective half-life (one hour).
endogene proteaze verjetno hitro razgradijo andeksanet alfa v plazmi, kar se sklada z njegovim razmeroma kratkim efektivnim razpolovnim časom (ena ura).
In prospective, randomized, placebo-controlled, dose-ranging studies in healthy subjects, the dose and dose regimen of andexanet alfa required to reverse anti-FXa activity and restore thrombin generation for FXa inhibitors (apixaban or rivaroxaban) were determined.
V prospektivni, randomizirani, s placebom nadzorovani študiji razpona odmerkov pri zdravih prostovoljcih so določili odmerek in shemo odmerjanja andeksaneta alfa, potrebna za odpravo aktivnosti proti FXa in obnovo tvorbe trombina pri zaviralcih FXa (apiksaban ali rivaroksaban).
Reversal of FXa inhibitor anticoagulation in patients with acute major bleeding In Study 14-505 (ANNEXA-4), a Phase IIIb/IV multinational, prospective, single-arm, open-label study, Ondexxya was administered to 352 patients on FXa inhibitors who presented with acute major bleeding.
Odprava antikoagulacije zaradi zaviralca FXa pri bolnikih z večjo akutno krvavitvijo V večnacionalni, prospektivni odprti študiji 14-505 (ANNEXA-4) z enim krakom faze IIIb/IV so zdravilo Ondexxya dali 352 bolnikom, zdravljenim z zaviralci FXa, ki so imeli večjo akutno krvavitev.
Andexanet alfa is a specific reversal agent for FXa inhibitors.
Andeksanet alfa je specifično zdravilo za odpravo učinka zaviralcev FXa.
Table 1: Dosing regimens
Preglednica 1: Sheme odmerjanja
Very common (may affect more than 1 in 10 people)
Pogosti (pojavijo se lahko pri največ 1 bolniku od 10 bolnikov):
Administration using an intravenous bag
Dajanje z uporabo vrečke za infuzijo
Cardiovascular causes of death (n=27) included: haemorrhagic stroke (n=6), ischaemic stroke (n=5), sudden cardiac death (including unwitnessed) (n=5), cardiomechanical/pump failure (n=4), myocardial infarction (n=2), bleeding other than haemorrhagic stroke (n=1), and other cardiovascular causes (n=4).
Srčno-žilni vzroki smrti (n = 27) so zajemali: hemoragično možgansko kap (n = 6), ishemično možgansko kap (n = 5), nenadno srčno smrt (vključno s smrtjo brez prič) (n = 5), kardiomehansko odpoved/odpoved črpalke (n = 4), miokardni infarkt (n = 2), krvavitev, ki ni bila hemoragična možganska kap (n = 1), in druge srčno-žilne vzroke (n = 4).
Treatment of patients with more severe ICH with andexanet alfa has not been studied.
Zdravljenja bolnikov s hujšo intrakranialno krvavitvijo z andeksanetom alfa niso proučevali.
In order to further substantiate correlation of the biomarker (antiFXa-activity) with haemostatic efficacy and clarify the risk of thromboses and thromboembolic events, the MAH should submit the results of ANNEXA-4, an interventional non-randomized, multicentre, prospective, open-label, single-group study in patients with acute major bleeding.
Za nadaljnjo utemeljitev korelacije med biološkim označevalcem (delovanjem proti FXa) in hemostatsko učinkovitostjo ter razjasnitev tveganja za tromboze in trombembolične dogodke mora imetnik dovoljenja za promet z zdravilom predložiti rezultate intervencijske nerandomizirane multicentrične prospektivne odprte študije z eno skupino ANNEXA-4 pri bolnikih z večjo akutno krvavitvijo.
In a study comparing andexanet alfa pharmacokinetics in elderly (65-69 years) and younger (26-42 years) healthy subjects who had received apixaban, the pharmacokinetics of andexanet alfa in the elderly subjects were not statistically different than those in the younger subjects.
(26-42 let) zdravih osebah, ki so prejele apiksaban, se farmakokinetika andeksaneta alfa pri starejših osebah ni statistično razlikovala od tiste pri mlajših osebah.
No clinical evaluation for apixabantreated subjects with high-dose andexanet alfa and no evaluation for rivaroxaban-treated subjects with low-dose andexanet alfa was performed in these studies.
Klinična ocena pri osebah, zdravljenih z apiksabanom, pri velikih odmerkih andeksaneta alfa, in ocena pri osebah, zdravljenih z rivaroksabanom, pri majhnih odmerkih andeksaneta alfa, v teh študijah nista bili izdelani.
Among the apixaban-treated subjects in Study 14-503, the percent change in anti-FXa activity was -92.34% (± 2.809%) for the andexanet alfa group and -32.70% (± 5.578%) for the placebo group (p < 0.0001), the latter reflecting the intrinsic clearance of the anticoagulant.
Med osebami, zdravljenimi z apiksabanom v študiji 14-503, je odstotna sprememba aktivnosti proti FXa znašala -92,34 % (± 2,809 %) v skupini, zdravljeni z andeksanetom alfa, in -32,70 % (± 5,578 %) v skupini, zdravljeni s placebom (p < 0,0001), pri čemer je zadnja odražala intrinzični očistek antikoagulanta.
Table 4: List of adverse reactions in healthy subjects and bleeding patients System organ class/ Preferred term
Preglednica 4: Seznam neželenih učinkov pri zdravih osebah in bolnikih s krvavitvijo
Once all required vials are reconstituted, the reconstituted solution is withdrawn from each vial, using the large volume (60 mL or larger) syringe equipped with a 20 gauge (or larger) needle.
Po rekonstituciji vseh potrebnih vial je treba iz vsake viale povleči rekonstituirano raztopino z veliko injekcijsko brizgo (60 ml ali večjo), opremljeno z iglo velikosti 20 (ali večjo).
Administration using a syringe pump
Dajanje z uporabo črpalke za brizgo
In order to substantiate correlation of the biomarker (antiFXa-activity) with haemostatic efficacy and clarify the risk of thromboses and thromboembolic events, the MAH should submit the results of a global randomised controlled clinical trial to investigate the use of andexanet versus standard of care treatment in patients with intracranial haemorrhage (ICH) taking apixaban, rivaroxaban, or edoxaban (study 18-513).
Za utemeljitev korelacije med biološkim označevalcem (delovanjem proti FXa) in hemostatsko učinkovitostjo ter razjasnitev tveganja za tromboze in trombembolične dogodke mora imetnik dovoljenja za promet z zdravilom predložiti rezultate globalnega randomiziranega nadzorovanega kliničnega preskušanja za raziskavo uporabe andeksaneta v primerjavi s standardnim zdravljenjem pri bolnikih z intrakranialno krvavitvijo (ICH), ki jemljejo apiksaban, rivaroksaban ali edoksaban
Reversing FXa inhibitor therapy exposes patients to the thrombotic risk of their underlying disease.
Odprava učinka zdravljenja z zaviralci FXa izpostavi bolnike tveganju za trombozo zaradi osnovne bolezni.
High dose
Velik odmerek
Once all required vials are reconstituted, withdraw the reconstituted solution from each vial, using the large volume (60 mL or larger) syringe equipped with a 20 gauge (or larger) needle.
Po rekonstituciji vseh potrebnih vial iz vsake viale povlecite rekonstituirano raztopino z veliko injekcijsko brizgo (60 ml ali večjo), opremljeno z iglo velikosti 20 G (ali večjo).
At the time of the event 10/36 (27.8%) patients were on antithrombotic therapy.
Ob času dogodka je 10 bolnikov od 36 bolnikov (27,8 %) prejemalo antikoagulacijsko zdravljenje.
Patients being treated with FXa inhibitor therapy have underlying disease states that predispose them to thromboembolic events.
Bolniki, zdravljeni z zaviralci FXa, imajo osnovna bolezenska stanja, zaradi katerih so nagnjeni k trombotičnim dogodkom.
Attach ancillary equipment (i.e., extension tubing, air filters, syringe driver) in preparation for administration.
Med pripravo na dajanje zdravila priključite pomožno opremo (npr. cevne podaljške, zračne filtre, črpalko za infuzijo).
Administer the reconstituted solution at the appropriate rate.
Z ustrezno hitrostjo aplicirajte rekonstituirano raztopino.
While it is permissible to combine the bolus and infusion into a single IV bag, to ensure the correct administration rate, it is recommended that the bolus and infusion are split into two separate bags.
Čeprav je dovoljeno bolus in infuzijo združiti v isti vrečki za infuzijo, se priporoča, da za zagotovitev pravilne hitrosti infundiranja bolus in infuzijo ločite v dve vrečki.
FXa inhibitors did not affect andexanet alfa pharmacokinetics at therapeutic levels.
Zaviralci FXa pri terapevtskih ravneh niso vplivali na farmakokinetiko andeksaneta alfa.
After an appropriate number of vials of Ondexxya has been reconstituted, the reconstituted solution (10 mg/mL) is transferred to a suitable empty intravenous bag comprised of polyolefin (PO) or polyvinyl chloride (PVC) material without further dilution (see section 6.6) prior to administration by IV infusion using a 0.2 or 0.22 micron in-line polyethersulfone (PES) or equivalent low proteinbinding filter.
Po rekonstituciji ustreznega števila vial zdravila Ondexxya se rekonstituirana raztopina (10 mg/ml) brez nadaljnjega redčenja prenese v primerno prazno vrečko za intravensko infuzijo, izdelano iz poliolefina (PO) ali polivinilklorida (PVC) (glejte poglavje 6.6), čemur sledi i.v.
Reporting suspected adverse reactions after authorisation of the medicinal product is important, as it allows continued monitoring of the benefit/risk balance of the medicinal product.
Omogoča namreč stalno spremljanje razmerja med koristmi in tveganji zdravila.
Ondexxya is supplied in glass vials as a white to off-white powder for solution for infusion, which is reconstituted (dissolved) before use.
Izgled zdravila Ondexxya in vsebina pakiranja Zdravilo Ondexxya je na voljo v steklenih vialah v obliki belega do umazano belega praška za raztopino za infundiranje, ki ga je treba pred uporabo rekonstituirati (raztopiti).
Using a 20 mL (or larger) syringe and a 20 gauge (or larger) needle, withdraw 20 mL of water for injections.
V 20-ml (ali večjo) injekcijsko brizgo z iglo velikosti 20 G (ali večjo) povlecite 20 ml vode za injekcije.
Bolus strengths of andexanet alfa being necessary to achieve mean unbound apixaban (400 mg bolus) and unbound rivaroxaban concentrations (800 mg bolus) below the anticipated respective threshold for no anticoagulant effect were twice as high for rivaroxaban (20 mg QD) compared to apixaban (5 mg BID), due to the differential PK characteristics and dose levels of respective FXa inhibitor.
Bolusni odmerki andeksaneta alfa, potrebni za znižanje povprečnih koncentracij nevezanega apiksabana (400-mg bolus) in nevezanega rivaroksabana (800-mg bolus) pod ustrezno pričakovano mejno vrednost za odsotnost antikoagulacijskega učinka, so bili pri rivaroksabanu dvakrat večji
Andexanet alfa binds direct FXa inhibitors with high affinity, making them unavailable to exert their anticoagulant effects.
Andeksanet alfa z veliko afiniteto veže neposredne zaviralce FXa in jim s tem prepreči antikoagulacijsko delovanje.
• disturbance of taste
• motnje okušanja,
Submission of the final CSR by 30
Predložitev končnega poročila klinične študije do
Among the rivaroxaban-treated subjects in Study 14-504, the percent change in anti-FXa activity was -96.72% (± 1.838%) for the andexanet alfa group and -44.75% (± 11.749%) for the placebo group (p < 0.0001 ), the latter reflecting the intrinsic clearance of the anticoagulant.
FXa znašala -96,72 % (± 1,838 %) v skupini, zdravljeni z andeksanetom alfa, in -44,75 % (± 11,749 %) v skupini, zdravljeni s placebom (p < 0,0001), pri čemer je zadnja odražala intrinzični očistek antikoagulanta.
Powder for solution for infusion 4 x 1 vial of 200 mg
4 × 1 viala z 200 mg
No thromboembolic events were observed in 223 healthy volunteers who received FXa inhibitors and were treated with andexanet alfa.
Pri 223 zdravih prostovoljcih, ki so prejeli zaviralce FXa in zdravljenje z andeksanetom alfa, niso opazili trombemboličnih dogodkov.
The 30-day mortality rates were 16.2% (37/229) in patients presenting with ICH, 12.8% (12/94) with GI bleeding, and 17.9% (5/28) with other types of bleeding.
12,8-odstotna (12/94) in pri bolnikih z drugimi vrstami krvavitev 17,9-odstotna (5/28).
Andexanet alfa is administered as an intravenous bolus at a target rate of approximately 30 mg/min over 15 minutes (low dose) or 30 minutes (high dose), followed by administration of a continuous infusion of 4 mg/min (low dose) or 8 mg/min (high dose) for 120 minutes (see table 1).
Andeksanet alfa se daje v obliki intravenskega bolusa s ciljno hitrostjo približno 30 mg/min v trajanju 15 minut (majhen odmerek) ali 30 minut (velik odmerek), ki mu sledi aplikacija kontinuirane infuzije 4 mg/min (majhen odmerek) ali 8 mg/min (velik odmerek) v trajanju 120 minut (glejte preglednico 1).
In clinical trials of patients with life-threatening bleeding, fever and stroke may affect up to 1 in 10 people; transient ischaemic attack (TIA), heart attack, and blood clots in the legs or lungs may affect up to 1 in 100 people (uncommon side effects).
Prehodni ishemični napad (TIA), srčni napad in krvni strdki v nogah ali pljučih se lahko pojavijo pri največ 1 bolniku od 100 bolnikov (občasni neželeni učinki).
No dose-limiting toxicities have been observed during clinical trials.
Med kliničnimi preskušanji niso opazili toksičnosti, ki bi omejevale odmerek.
Your doctor may decide to give you Ondexxya to rapidly reverse the effects of the anticoagulant in case of a life-threatening or uncontrolled bleeding situation.
Zdravnik se bo v primeru smrtno nevarne ali neobvladane krvavitve morda odločil, da vam da zdravilo Ondexxya za hitro odpravo učinkov antikoagulanta.
Portola Netherlands B.V. Prins Bernhardplein 200 1097 JB Amsterdam Netherlands
1097 JB Amsterdam Nizozemska
Apixaban
Dojenje
Medical judgement should balance the benefits of anticoagulation with the risks of re-bleeding (see section 4.4).
Pri medicinski presoji je treba ustrezno upoštevati koristi antikoagulacije in tveganja ponovne krvavitve
How Ondexxya is used
Kako uporabljati zdravilo Ondexxya
Ondexxya 200 mg powder for solution for infusion
IME ZDRAVILA Ondexxya 200 mg prašek za raztopino za infundiranje
• nausea (feeling sick)
• siljenje na bruhanje (navzea),
FXa inhibitor
Zaviralec FXa
Ondexxya 200 mg powder for solution for infusion andexanet alfa
IME ZDRAVILA Ondexxya 200 mg prašek za raztopino za infundiranje andeksanet alfa
Andexanet alfa is administered as an intravenous (IV) bolus at a target rate of approximately 30 mg/min over 15 (low dose) or 30 minutes (high dose), immediately followed by administration of a continuous infusion of 4 mg (low dose) or 8 mg (high dose) per minute for 120 minutes (see table 1).
bolus s ciljno hitrostjo približno 30 mg/min v trajanju 15 minut (majhen odmerek) ali 30 minut (velik odmerek), ki mu takoj sledi aplikacija kontinuirane infuzije s hitrostjo 4 mg/min (majhen odmerek) ali 8 mg/min (velik odmerek) v trajanju 120 minut
Andexanet alfa is to be reconstituted and the 10 mg/mL solution then transferred to a suitable IV bag comprised of polyolefin (PO) or polyvinyl chloride (PVC) material without further dilution prior to administration by IV infusion using a 0.2 or 0.22 micron in-line polyethersulfone (PES) or equivalent low protein-binding filter.
Andeksanet alfa je treba rekonstituirati, rekonstituirana raztopina (10 mg/ml) pa se brez nadaljnjega redčenja prenese v primerno vrečko za intravensko infuzijo, izdelano iz poliolefina (PO) ali polivinilklorida (PVC), čemur sledi dajanje z i.v.
Mannitol
Apiksaban
It reverses the effects of certain anticoagulants called factor Xa inhibitors (apixaban or rivaroxaban).
imenovanih zaviralci faktorja Xa (apiksaban ali rivaroksaban).
Conclusions presented by the European Medicines Agency on: • Conditional marketing authorisation
Sklepne ugotovitve, ki jih je predstavila Evropska agencija za zdravila, o:
Musculoskeletal and connective tissue disorders
Bolezni mišično-skeletnega sistema in vezivnega tkiva bolečine v hrbtu pogosti mišični krči pogosti
Immune system disorders
Bolezni imunskega sistema urtikarija pogosti
Excipients: Tris base, Tris hydrochloride, L-arginine hydrochloride, sucrose, mannitol, polysorbate 80
L-argininijev klorid saharoza manitol polisorbat 80
Restoration of thrombin generation to within normal ranges (defined as one standard deviation from baseline levels) within two minutes and maintained for 20 hours was achieved with bolus only and bolus plus infusion for low-dose andexanet alfa in subjects on apixaban.
Ponovno tvorbo trombina znotraj normalnih mejnih vrednosti (opredeljenih z enim standardnim odklonom od izhodiščne ravni) v dveh minutah, ki se je ohranila 20 ur, so dosegli z dajanjem samo bolusa ter dajanjem bolusa in infuzije pri majhnih odmerkih andeksaneta alfa pri osebah, zdravljenih z placebo: bolus + 2-uri infuzije (n = 8) zdravilo ONDEXXYA: bolus 400 mg + 480 mg × 2-uri infuzije (n = 23)
Reversal of apixaban
Odprava učinka apiksabana
• dizziness
• srbenje,
Animal studies are insufficient with respect to reproductive toxicity (see section 5.3).
Podatkov o uporabi andeksaneta alfa pri nosečnicah ni. Ni dovolj študij na živalih o vplivu zdravila na sposobnost razmnoževanja (glejte poglavje 5.3).
Package Leaflet: Information for the patient and user Ondexxya 200 mg powder for solution for infusion andexanet alfa
IME ZDRAVILA IN POT(I) UPORABE Ondexxya 200 mg prašek za raztopino za infundiranje andeksanet alfa intravenska uporaba
The recommended dose regimen of Ondexxya is based on the dose of rivaroxaban the patient is taking at the time of anticoagulation reversal, as well as on the time since the patient's last dose of rivaroxaban (see table 3).
Priporočena shema odmerjanja zdravila Ondexxya temelji na odmerku rivaroksabana, ki ga bolnik jemlje v času, ko je potrebna odprava antikoagulacije, in času, ki je pretekel od bolnikovega zadnjega odmerka rivaroksabana (glejte preglednico 3).
The recommended dose regimen of andexanet alfa is based on the dose of rivaroxaban the patient is taking at the time of anticoagulation reversal, as well as on the time since the patient's last dose of rivaroxaban (see table 3).
Priporočena shema odmerjanja andeksaneta alfa temelji na odmerku rivaroksabana, ki ga bolnik jemlje v času, ko je potrebna odprava antikoagulacije, ter času, ki je pretekel od bolnikovega zadnjega odmerka rivaroksabana (glejte preglednico 3).
Flushing very common
zelo pogosti
No trials have been conducted to investigate the pharmacokinetics of andexanet alfa in patients with hepatic impairment.
Preskušanj za raziskavo farmakokinetike andeksaneta alfa pri bolnikih z okvaro ledvic niso izvedli.
Reversal of anticoagulation in healthy subjects aged 50-75 (Studies 14-503 and 14-504) In a prospective, randomized, placebo-controlled study, healthy subjects with a median age of 56.5 years on apixaban 5 mg twice daily received andexanet alfa (n=24) administered as a 400 mg IV bolus immediately followed by a 4 mg per minute IV infusion for 120 minutes (480 mg) or placebo (n=8).
Odprava antikoagulacije pri zdravih osebah, starih 50-75 let (študiji 14-503 in 14-504) V prospektivni, randomizirani, s placebom nadzorovani študiji so zdrave osebe z mediano starostjo
The recommended dose regimen of Ondexxya is based on the dose of apixaban the patient is taking at the time of anticoagulation reversal, as well as on the time since the patient's last dose of apixaban (see table 2).
Priporočena shema odmerjanja zdravila Ondexxya temelji na odmerku apiksabana, ki ga bolnik jemlje v času, ko je potrebna odprava antikoagulacije, in času, ki je pretekel od bolnikovega zadnjega odmerka apiksabana (glejte preglednico 2).
Nervous system disorders
Organski sistem/
The recommended dose regimen of andexanet alfa is based on the dose of apixaban the patient is taking at the time of anticoagulation reversal, as well as on the time since the patient's last dose of apixaban (see table 2).
Priporočena shema odmerjanja andeksaneta alfa temelji na odmerku apiksabana, ki ga bolnik jemlje v času, ko je potrebna odprava antikoagulacije, ter času, ki je pretekel od bolnikovega zadnjega odmerka apiksabana (glejte preglednico 2).
Each vial contains 200 mg of andexanet alfa.
NAVEDBA ENE ALI VEČ UČINKOVIN Ena viala vsebuje 200 mg andeksaneta alfa.
• muscle spasms
• suha usta,
How Ondexxya is stored
Shranjevanje zdravila Ondexxya
• chest discomfort
• neugodje v prsih,
NAME OF THE MEDICINAL PRODUCT
Navodila za ravnanje z zdravilom
Skin and subcutaneous tissue disorders
Bolezni kože in podkožja srbenje pogosti generalizirani pruritus pogosti
Ondexxya contains the active ingredient andexanet alfa.
Kaj je zdravilo Ondexxya in za kaj ga uporabljamo Zdravilo Ondexxya vsebuje učinkovino andeksanet alfa.
PHARMACEUTICAL PARTICULARS 6.1 List of excipients
FARMACEVTSKI PODATKI 6.1 Seznam pomožnih snovi tris (hidroksimetil) aminometan tris hidroklorid
• itching
• omotica,
In a similar study, subjects with a median age of 57 years on rivaroxaban 20 mg daily received andexanet alfa (n=26) administered as an 800 mg IV bolus immediately followed by an 8 mg per minute IV infusion for 120 minutes (960 mg) or placebo (n=13).
konec infuzije konec bolusa placebo: bolus + 2-uri infuzije (n = 13) zdravilo ONDEXXYA: bolus 800 mg + 960 mg × 2-uri infuzije (n = 26)
• excessive sweating
• povečano potenje,
METHOD AND ROUTE(S) OF ADMINISTRATION
anti-FXa (ng/ml)
§ Measles virus1 Enders' Edmonston strain (live, attenuated)
Virus ošpic1, sev Enders' Edmonston (živ, oslabljen)
Varicella virus3 Oka/Merck strain (live, attenuated)
Virus varicella-zoster3, sev Oka/Merck (živ, oslabljen)
Mumps virus1 Jeryl Lynn™ (Level B) strain (live, attenuated) not less than 4.30 log10 CCID50* Rubella virus2 Wistar RA 27/3 strain (live, attenuated)
najmanj 3,99 log10 PFU** * 50-odstotni infektivni odmerek na celični kulturi (CCID = cell culture infectious dose) ** enote, ki tvorijo plak (PFU = plaque-forming units) (1) pridobljen iz celic piščančjih zarodkov (2) pridobljen iz humanih diploidnih pljučnih (WI-38) fibroblastov (3) pridobljen iz humanih diploidnih (MRC-5) celic
10 vials + 10 pre-filled syringes with attached needle
10 vial + 10 napolnjenih injekcijskih brizg z iglo
1 vial + 1 pre-filled syringe without needle
1 viala + 1 napolnjena injekcijska brizga brez igle
1 vial + 1 pre-filled syringe with attached needle
1 viala + 1 napolnjena injekcijska brizga z iglo
In such case, treatment must be stopped immediately.
V takih primerih je treba zdravljenje takoj prekiniti.
Given the
Ob upoštevanju naslednjega:
The PRAC noted that others studies will become available.
Odbor PRAC je izpostavil, da bodo na voljo druge študije;
• The PRAC noted that some of the studies have methodological limitations.
• odbor PRAC je ugotovil, da imajo nekatere študije metodološke omejitve.
The studies and their limitations were considered together with the overall evidence available to date.
Odbor je študije in njihove omejitve obravnaval skupaj s celotnimi dokazi, ki so bili na voljo.
However, the CMDh considered that an amendment was required in the package leaflet to improve clarity for patients that should tell their doctor if they have high blood pressure but also if they are being treated for high blood pressure.
Vendar je skupina CMDh menila, da je potrebna sprememba navodila za uporabo, da se izboljša jasnost za bolnike, ki se morajo posvetovati z zdravnikom, če imajo visok krvni tlak oziroma če se zdravijo zaradi visokega krvnega tlaka.
Some studies show an increased risk while others do not suggest a risk and therefore have not corroborated the signal.
Nekatere študije so pokazale povečano tveganje, druge pa ne, zato niso podprle pomislekov;
In addition, there is limited experience on the safety and efficacy of the use of testosterone in patients over 65 years of age.
Poleg tega so izkušnje glede varnosti in učinkovitosti uporabe testosterona pri bolnikih, starejših od 65 let, omejene.