natgillin/translations-raw huggingface dataset:
By blocking their re-uptake, desvenlafaxine increases the amount of these neurotransmitters in the spaces between certain nerve cells, increasing the level of communication between the cells.
Desvenlafaksin z blokiranjem ponovnega privzemanja poveča količino teh nevrotransmiterjev v prostorih med posameznimi živčnimi celicami, zaradi česar se poveča raven komunikacije med celicami.
In relation to its parent substance, venlafaxine, desvenlafaxine seemed to be less effective with no advantages in terms of safety and tolerability.
Videti je, da je desvenlafaksin v primerjavi s starševsko učinkovino, venelafaksinom, manj učinkovit in brez prednosti glede varnosti in prenašanja pri bolnikih.
Ellefore is a medicine that contains the active substance desvenlafaxine.
Ellefore je zdravilo, ki vsebuje zdravilno učinkovino desvenlafaksin.
What is Ellefore?
Kaj je zdravilo Ellefore?
Based on the review of the data, at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Ellefore could not have been approved for the treatment of major depressive disorder.
Na podlagi pregleda podatkov je CHMP v času umika vloge izrazil določene zadržke in je začasno menil, da zdravilo Ellefore ne more biti odobreno za zdravljenje hude depresivne motnje.
The CHMP was concerned that, overall, the effectiveness of Ellefore had not been shown convincingly.
CHMP je menil, da učinkovitost zdravila Ellefore ni bila prepričljivo dokazana.
The active substance in Ellefore, desvenlafaxine, is a ‘serotonin-noradrenaline re-uptake inhibitor' (SNRI).
Zdravilna učinkovina v zdravilu Ellefore, desvenlafaksin, je inhibitor ponovnega privzema serotonina in noradrenalina (SNRI).
One long-term study looked at how long it took for symptoms to return in a total of 376 patients who had already shown a response to an initial 12 weeks of Ellefore treatment.
V eni od dolgoročnih študij so pri vsega skupaj 376 bolnikih, ki so se že odzvali na začetno 12tedensko zdravljenje z zdravilom Ellefore, opazovali čas, potreben za ponoven pojav simptomov.
The company informed the CHMP that there are no consequences for patients currently included in clinical trials with Ellefore and that there are no compassionate use programmes ongoing.
Družba je obvestila CHMP, da umik nima nobenih posledic za bolnike, ki trenutno sodelujejo v kliničnih preskušanjih ali programih sočutne uporabe zdravila Ellefore.
What was Ellefore expected to be used for?
Za kaj naj bi se zdravilo Ellefore bilo uporabljalo?
Therefore, at the time of the withdrawal, the CHMP's view was that a benefit of Ellefore had not been sufficiently demonstrated and any benefits did not outweigh the identified risks.
CHMP je v času umika menil, da koristi zdravila Ellefore niso bile zadostno dokazane in da ne odtehtajo znanih tveganj.
How is Ellefore expected to work?
Kako naj bi zdravilo Ellefore delovalo?
• if you are taking medicines for high blood pressure.
· če jemljete zdravila za visok krvni tlak.
In-use storage times and conditions prior to use are the responsibility of the user.
Čas in pogoji shranjevanja pred uporabo so odgovornost uporabnika.
Median TTP:
mediana TTP:
• if you think you may need any vaccinations in the near future, including vaccinations needed to travel to other countries.
· če menite, da boste v kratkem potrebovali katero koli cepljenje, vključno s cepljenji, ki bi jih potrebovali za potovanje v druge države.
• Keep this card with you all the time - such as in your wallet or purse.
· Kartico imejte vedno pri sebi, na primer v denarnici ali torbici.
If not used immediately, preparation should take place in controlled and validated aseptic conditions.
Če ni uporabljeno takoj, mora priprava potekati v kontroliranih in preverjenih aseptičnih pogojih.
• What to do if you think you might be getting an infection.
· Kaj storite, če menite, da imate morda okužbo
In total: 8 cycles.
Skupaj: 8 ciklov.
The corresponding AUCτ ratios were 1.66, 1.17 and 1.32.
Ustrezna razmerja AUCτ so bila 1,66, 1,17 in 1,32.
† Outcome at 24 weeks
† Izid po 24 tednih
Three cases had no reported adverse event.
treh primerih niso poročali o nobenem neželenem dogodku.
How much and how often you will receive your treatment
Koliko zdravila boste dobili in kako pogosto
In addition, central volume was slightly (9%) lower in females compared to males.
Poleg tega je bil centralni volumen nekoliko (9 %) nižji pri ženskah kot pri moških.
The most frequent reported or observed serious adverse drug reactions were:
Najpogosteje zabeleženi ali opaženi resni neželeni učinki so bili:
Date of latest renewal: 2 June 2008
Datum prve odobritve: 2. junij 1998 Datum zadnjega podaljšanja: 2. junij 2008
• Changes in laboratory tests carried out by your doctor.
· spremembe rezultatov laboratorijskih preiskav, ki jih naroči vaš zdravnik.
If an injection is interrupted it can be resumed at the same site or another location may be used, if appropriate.
Če se injiciranje prekine, ga je mogoče nadaljevati na istem mestu, lahko pa se uporabi tudi drugo mesto, če je to primerno.
Proportion with PFS event
Delež z dogodkom PFS
Overall survival
celokupno preživetje
1 Antibody Way Oceanside, CA 92056 5802 USA
1 Antibody Way Oceanside, CA 92056 5802 ZDA
• Additional risk minimisation measures
· Dodatni ukrepi za zmanjševanje tveganj
Available data suggest that clinical response is usually achieved within 16 - 24 weeks of an initial treatment course.
Podatki, ki so na voljo, kažejo, da je klinični odziv ponavadi dosežen v roku 16-24 tednov po začetnem ciklu zdravljenja.
All IRRs were CTC Grade 1 or 2.
Vse IRR so bile 1. ali 2. stopnje po CTC.
This is usually given every 3 weeks up to 8 times.
Ta se po navadi daje na 3 tedne, do 8-krat.
You must tell your doctor or nurse if you are pregnant, think that you might be pregnant or are planning to become pregnant.
Zdravniku ali medicinski sestri morate povedati, če ste noseči, menite, da ste noseči, ali načrtujete zanositev.
Proportion of patients with no radiographic change
Delež bolnikov brez radioloških sprememb
Do not have MabThera if you have an active infection or a serious problem with your immune system.
Zdravila MabThera ne smete prejeti, če imate aktivno okužbo ali resno težavo s svojim imunskim sistemom.
Take this into account if you are on a low-sodium diet.
To količino upoštevajte, če ste na dieti z nizkim vnosom natrija.
All patients n=99
Vsi bolniki n = 99
95.1%b CI (−3.2%, 24.3%) a
95,1 %b IZ (-3,2 %, 24,3 %) a
Results from trial BP22333 are presented in section 5.2.
Izsledki preskušanja BP22333 so predstavljeni v poglavju 5.2.
Date of most recent infusion: ____________ Date of first infusion: ___________________ Patient's Name:________________________ Doctor's Name:________________________ Doctor's contact details:_________________
Bolnikovo ime:________________________ Zdravnikovo ime:______________________ Zdravnikov telefon:_________________
Your doctor may decide to treat you longer with MabThera (up to 5 years), depending on how you respond to the medicine.
Zdravnik se lahko odloči, da vas bo z zdravilom MabThera zdravil dlje (do 5 let), odvisno od tega, kako se odzovete na zdravilo.
+myocardial infarction4 and 6,
+miokardni infarkt4 in 6,
The gender- related pharmacokinetic differences are not considered to be clinically relevant and dose adjustment is not required.
S spolom povezane razlike v farmakokinetiki ne štejemo za klinično pomembne in prilagajanje odmerkov ni potrebno.
− CI = confidence interval.
IZ = interval zaupanja.
Your doctor may decide to stop your MabThera treatment if these reactions are serious.
Zdravnik se lahko odloči za prenehanje zdravljenja z zdravilom MabThera, če so te reakcije resne.
Binet stage A Binet stage B Binet stage C
stopnja po Binetu A stopnja po Binetu B stopnja po Binetu C
9/L as clinical experience in this population is limited.
Kliničnih izkušenj v tej populaciji je namreč malo.
Trial BO22334 (SABRINA)
Preskušanje BO22334 (SABRINA)
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 °C - 8 °C, unless dilution has taken place in controlled and validated aseptic conditions.
Če je ne uporabimo takoj, je za čas in pogoje shranjevanja pred uporabo odgovoren uporabnik; čas običajno ne sme presegati 24 ur pri temperaturi od 2 °C do 8 °C, razen če je bila raztopina pripravljena v nadzorovanih in validiranih aseptičnih pogojih.
Figure 3: Cumulative incidence over time of first major relapse
Slika 3: Kumulativna incidenca glede na čas prvega hujšega recidiva
• if you have ever taken medicines which affect your immune system - such as chemotherapy or immune-suppressive medicines.
· če ste kdaj jemali zdravila, ki vplivajo na imunski sistem - na primer kemoterapijo ali imunosupresivna zdravila.
• Show this card to any doctor, nurse or dentist you see - not just the specialist who prescribes your MabThera.
· Pokažite jo vsem zdravnikom, medicinskim sestram in zobozdravnikom, ki jih obiščete - ne samo specialistu, ki vam predpiše zdravilo MabThera.
Treatment, N
Zdravljenje (n)
Twenty nine (0.48%) post-dose observations (all from trial BP22333) were below the quantification limit.
Devetindvajset (0,48 %) vrednosti po odmerku (vse iz preskušanja BP22333) je bilo pod mejo kvantifikacije.
MabThera will be given to you by a doctor or nurse who is experienced in the use of this treatment.
Zdravilo MabThera vam bo dal zdravnik ali medicinska sestra, ki ima izkušnje z uporabo takšnih zdravil.
It remains unknown if early detection of PML and suspension of MabThera therapy may lead to similar stabilisation or improved outcome.
Ni znano, ali lahko zgodnje odkritje PML in ukinitev zdravljenja z zdravilom MabThera doseže podobno stabilizacijo ali izboljšanje izida.
Patients who have ever had hepatitis B infection will be carefully checked by their doctor for signs of this infection
Bolnike, ki so kdaj imeli okužbo z virusom hepatitisa B, bo zdravnik skrbno spremljal glede znakov te okužbe;
If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the same time.
Kadar predložitev PSUR in posodobitev RMP sovpadata, se ju lahko predloži istočasno.
Patients should receive MabThera for at least 24 months after achievement of remission (absence of clinical signs and symptoms).
MabThera prejemati vsaj 24 mesecev po doseženi remisiji (odsotnost kliničnih znakov in simptomov).
No data are available on performing the injection in other sites of the body, therefore injections should be restricted to the abdominal wall.
Podatkov o injiciranju v druge dele telesa ni, zato mora biti injiciranje omejeno na trebušno steno.
If you can get pregnant, you and your partner must use an effective method of contraception while using MabThera.
Če bi lahko zanosili, morate vi in vaš partner med uporabo zdravila MabThera uporabljati učinkovito kontracepcijsko zaščito.
The risk of disease progression was reduced by 46 % and the risk of relapse by 51 %.
Tveganje za napredovanje bolezni je bilo manjše za 46 %, tveganje za ponovitev bolezni pa za 51 %.
Your doctor will decide when to start MabThera injections.
Vaš zdravnik bo presodil, kdaj začeti z injekcijami zdravila MabThera.
• if you think you may have an infection, even a mild one like a cold.
· če menite, da bi lahko imeli okužbo, četudi blago, kot je prehlad.
Non-oncology indications:
Neonkološke indikacije:
Depending on the signs and symptoms of your disease, your doctor will decide when you should receive more MabThera.
Glede na znake in simptome vaše bolezni se bo zdravnik odločil, kdaj boste ponovno zdravljeni z zdravilom MabThera.
The “primary” statistical test for “response” was the trend test of CR versus PR versus non-response (p < 0.0001)
“Primarni” statistični test za “odgovor” je bil test trenda CR v primerjavi s PR v primerjavi z neodzivnimi (p < 0,0001).
MabThera may also cause changes in laboratory tests carried out by your doctor.
Zdravilo MabThera lahko vpliva tudi na spremembe laboratorijskih preiskav, ki jih naroči vaš zdravnik.
You may be asked not to take these other medicines 12 hours before you are given MabThera.
Morda vam bo naročil, da ne jemljite teh drugih zdravil 12 ur, preden boste dobili zdravilo MabThera.
The information provided in this section pertains to the use of MabThera in oncology.
Informacije v tem poglavju se nanašajo na uporabo zdravila MabThera v onkologiji.
The Physician information, Patient information and Patient Alert Card must be agreed with the National Competent Authorities prior to distribution.
Vsebina in oblika izobraževalnega gradiva za zdravnike in bolnike ter opozorilne kartice za bolnika morata biti pred razdeljevanjem dogovorjeni s pristojnim nacionalnim organom.
• painful joints or back
· boleči sklepi ali hrbet,
The overall proportion of patients found to have anti-rHuPH20 antibodies remained generally constant over the follow-up period in both cohorts.
Celotni delež bolnikov, pri katerih so ugotovili protitelesa proti rHuPH20, je ostal med obdobjem spremljanja v obeh kohortah na splošno stalen.
In clinical trials more than 3100 patients received at least one treatment course and were followed for periods ranging from 6 months to over 5 years; approximately 2400 patients received two or more courses of treatment with over 1000 having received 5 or more courses.
V kliničnih preskušanjih je več kot 3100 bolnikov prejelo najmanj en cikel zdravljenja, po tem so jih spremljali od 6 mesecev do več kot 5 let; približno 2400 bolnikov je prejelo dva ali več ciklov zdravljenja, od teh pa več kot 1000 bolnikov 5 ali več ciklov zdravljenja.
• tremors (shakiness, often in the hands)
· tremor (tresenje, pogosto tresenje rok),
• The need for close supervision during administration in an environment where full resuscitation facilities are immediately available
· informacije o nujnosti skrbnega nadzora med aplikacijo v okolju, kjer so nemudoma na voljo vsi pripomočki za oživljanje,
At minimum this should include HBsAg-status and HBcAb-status.These can be complemented with other appropriate markers as per local guidelines.
To vključuje najmanj določanje statusa HBsAg in HBcAb, ki ju lahko dopolnimo z ostalimi primernimi označevalci v skladu z lokalnimi smernicami.
For storage conditions after first opening see section 6.3.
Za pogoje shranjevanja po prvem odprtju glejte poglavje 6.3.
ACR20 ACR50 ACR70 EULAR Response (Good/Moderate) Mean Change in DAS
ACR20 ACR50 ACR70 Odziv po EULAR (dober/zmeren)
Based on popPK analysis an absolute bioavailability of 71% was estimated.
Na podlagi populacijske farmakokinetične analize je bila ocenjena absolutna biološka uporabnost 71 %.
The incidence of infections that were serious or required IV antibiotics was approximately 4 per 100 patient years.
Incidenca okužb, ki so bile resne ali so zahtevale uporabo intravenskega antibiotika, je bila približno 4 na 100 bolnik-let.
Based on popPK analysis of study BO25341 (SAWYER) an absolute bioavailability of 68.4% was estimated.
Na podlagi populacijske farmakokinetične analize študije BO25341 (SAWYER) je bila ocenjena absolutna biološka uporabnost 68,4 %.
• What the signs of an infection are
· Kateri so znaki okužbe
Higher time-dependenet clearance in subjects with higher disease burden would lead to lower initial exposure and longer time needed to achieve the same exposure as in subjects with lower burden of the disease.
Večji od-časa-odvisen-očistek pri bolnikih z višjim bremenom bolezni je povzročil nižjo začetno izpostavljenost zdravilu in podaljšanje časa, potrebnega za doseganje enake izpostavljenosti kot pri bolnikih z nižjim bremenom bolezni.
For these reasons MabThera should not be administered to pregnant women unless the possible benefit outweighs the potential risk.
Zato nosečnice ne smejo prejemati zdravila MabThera, razen če je pričakovana korist večja od možnega tveganja.
The response rates for the analysis of 176 patients in SAWYER Part 2 are shown in Table 2.
Deleži odgovorov analize 176 bolnikov v 2. delu preskušanja SAWYER so prikazani v preglednici 2.
When should I not have MabThera?
Kdaj ne smete prejeti zdravila MabThera?
Treatment Difference (MabTheraCyclophosphamide)
razlika zdravljenj (MabTheraciklofosfamid)
If you respond well to treatment, you may be given MabThera as a maintenance treatment.
Če se boste na zdravilo dobro odzvali, boste lahko zdravilo MabThera prejemali kot vzdrževalno zdravljenje.
MabThera is not indicated for these patients, since the safety data about long-term MabThera treatment are insufficient, in particular concerning the risk of development of malignancies and PML.
Zdravilo MabThera ni indicirano za uporabo pri teh bolnikih zaradi nezadostnih podatkov o varnosti dolgoročnega zdravljenja z zdravilom MabThera, še posebej v zvezi s tveganjem za razvoj malignih bolezni ter PML.
• infections such as herpes infections and eye infection
· okužbe, kot so okužbe z virusom herpes in očesne okužbe,
Medicines given before each MabThera administration Before you are given MabThera, you will be given other medicines (pre-medication) to prevent or reduce possible side effects.
Zdravila, ki jih boste dobili pred vsakim dajanjem zdravila MabThera Preden boste dobili zdravilo MabThera, boste dobili druga zdravila (to imenujemo premedikacija) za preprečitev ali zmanjšanje možnih neželenih učinkov.
Your doctor will check if you should have any vaccines before you receive MabThera.
Vaš zdravnik bo preveril, ali bi morali biti cepljeni, preden boste dobili zdravilo MabThera.
Patients reporting signs and symptoms of infection following MabThera therapy should be promptly evaluated and treated appropriately.
Bolnike, pri katerih se pojavijo znaki in simptomi okužbe po zdravljenju z zdravilom MabThera, je treba nemudoma pregledati in primerno zdraviti.
The rate of all ADRs following first MabThera exposure was highest during the first 6 months and declined thereafter.
Delež vseh neželenih učinkov, ki so se pojavili po prvi izpostavitvi zdravilu MabThera, je bil najvišji v prvih 6 mesecih in se je potem zmanjševal.
This analysis suggests that dose adjustment of MabThera with any of the tested covariates is not expected to result in a meaningful reduction in its pharmacokinetic variability.
Te analize kažejo, da prilagoditev odmerka zdravila MabThera s katerokoli od testiranih spremenljivk verjetno ne bo pomembno zmanjšala njegove farmakokinetične variabilnosti.
Part 2 N = 176
2. del n = 176
Before giving a subsequent course of MabThera treatment, patients should be re-evaluated for any potential risk for infections.
Pred dajanjem nadaljnjega cikla zdravila MabThera je treba bolnike ponovno oceniti glede možnega tveganja za okužbe.
Following subcutaneous administration, the absorption of rituximab is slow, reaching maximal concentrations about 3 days after administration.
Po podkožni uporabi se rituksimab absorbira počasi in doseže največjo koncentracijo približno 3 dni po uporabi.
Table 14 Physical Function and Quality of Life outcomes at week 24 in Trial 1
Funkcijska zmogljivost in vpliv na kakovost življenja po 24 tednih v preskušanju 1 Izid†
• tight or painful muscles
· napete ali boleče mišice,
The overall trial design was identical among both stages and patients were randomized into the following two treatment groups:
Celotna zasnova preskušanja je bila v obeh stopnjah enaka in bolniki so bili randomizirani v naslednji terapevtski skupini:
key efficacy results for the pooled analysis of 410 patients in SABRINA stages 1 and 2 are shown in table 2.
Ključni rezultati učinkovitosti za združeno analizo 410 bolnikov iz 1. in 2. stopnje preskušanja SABRINA so prikazani v preglednici 2.
Figure 2: ACR responses for 4 treatment courses (24 weeks after each course (within patient, within visit) in patients with an inadequate response to TNF-inhibitors (n=146)
Slika 2: Odzivi ACR za 4 cikle zdravljenja 24 tednov po vsakem ciklu (intraindividualno, znotraj pregledov) pri bolnikih, ki niso zadostno odgovorili zdravljenje z zaviralci TNF (n = 146)
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product Characteristics, section 4.2).
B. POGOJI ALI OMEJITVE GLEDE OSKRBE IN UPORABE Predpisovanje in izdaja zdravila je le na recept s posebnim režimom (Glejte Prilogo I: Povzetek glavnih značilnosti zdravila, poglavje 4.2).
On the basis of limited experience with MabThera in rheumatoid arthritis patients (see section 4.8) the present data do not seem to suggest any increased risk of malignancy.
Na osnovi omejenih izkušenj z zdravilom MabThera pri zdravljenju revmatoidnega artritisa (glejte poglavje 4.8) sedanji podatki ne kažejo kakršnegakoli povečanega tveganja za razvoj malignih bolezni.
Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease (see section 4.4 regarding other cardiovascular diseases).
Hudo srčno popuščanje (IV. razred po klasifikaciji Newyorškega združenja za srce NYHA) ali huda, neobvladljiva bolezen srca (glejte poglavje 4.4 glede drugih srčno-žilnih bolezni).
MabThera will be given to you once a week for 4 weeks.
ga boste prejeli enkrat na teden 4 tedne.
A total of 176 patients with CLL were randomized into the following two treatment groups:
Skupno so randomizirali 176 bolnikov s KLL v naslednji terapevtski skupini:
In patients where the treatment is working, MabThera may be used as a maintenance treatment for 2 years after completing the initial treatment.
Pri bolnikih, pri katerih takšno zdravljenje deluje, je mogoče zdravilo MabThera uporabljati kot vzdrževalno zdravljenje še dve leti po dokončanju začetnega zdravljenja.
MabThera was given in combination with intravenous glucocorticoids which may reduce the incidence and severity of these events.
Zdravilo MabThera so dajali v kombinaciji z intravenskimi glukokortikoidi, ki lahko zmanjšajo incidenco in izrazitost teh učinkov.
Rarely, some of these side effects have been fatal.
Redko so bili nekateri od teh neželenih učinkov smrtni.
• high or low blood pressure (low blood pressure especially when standing upright)
· visok ali nizek krvni tlak (nizek krvni tlak zlasti po hitrem vstajanju)
Patients could receive 1000 mg IV at the time of relapse (see section 5.1).
Bolniki so lahko dobili 1000 mg intravensko ob času recidiva (glejte poglavje 5.1).
This compares favourably with the TTP achieved after the prior course of MabThera (12.4 months).
To je lepo primerljivo s časom do napredovanja bolezni, ki je bil dosežen po predhodnem zdravljenju z zdravilom MabThera (12,4 meseca).
Abbreviations: NA, not available; ORR: overall response rate; CR: complete response; PR: partial response
Okrajšave: NA: ni na voljo; ORR: celokupni odgovor (overall response rate); CR: popolni odgovor (complete response); PR: delni odgovor (partial response).
• hearing loss, loss of other senses.
· poslabšanje sluha, poslabšanje drugih čutov.
In a long-term observational safety study, 97 GPA/MPA patients received treatment with MabThera (mean of 8 infusions [range 1-28]) for up to 4 years, according to their physician's standard practice and discretion.
V dolgoročni opazovalni študiji varnosti je 97 bolnikov z GPA/MPA prejemalo zdravljenje z zdravilom MabThera (v povprečju 8 infuzij [razpon od 1 do 28]) do 4 leta, v skladu s standardno prakso in presojo njihovega zdravnika.
Of 356 patients evaluated for ADA, 1.1 % (4 patients) were positive.
Od 356 bolnikov, pri katerih so ocenjevali ADA, so bili pozitivni 4 bolniki (1,1 %).
Other medicines and MabThera
Druga zdravila in zdravilo MabThera
Key results from all four trials are summarized in table 3.
Ključni rezultati vseh štirih preskušanj so povzeti v preglednici 3.
The cells that are affected by MabThera help to fight infection and you should wait until the infection has passed before you are given MabThera.
Celice, ki jih zdravilo MabThera uniči, pomagajo pri borbi proti okužbam, zato morate počakati, da se okužba pozdravi, preden prejmete zdravilo MabThera.
Therefore, the switch to MabThera subcutaneous formulation can only occur at the second or subsequent cycles of treatment.
Zato je mogoče prehod na podkožno obliko zdravila MabThera opraviti le v drugem ali nadaljnjih ciklih zdravljenja.
No dose reductions of MabThera are recommended.
Odmerka zdravila MabThera ni priporočljivo zmanjšati.