natgillin/translations-raw huggingface dataset:
Pre- and postnatal development studies in rats conducted with sacubitril at high doses up to 750 mg/kg/day (2.2-fold the MRHD on the basis of AUC) and valsartan at doses up to 600 mg/kg/day (0.86-fold the MRHD on the basis of AUC) indicate that treatment with Neparvis during organogenesis, gestation and lactation may affect pup development and survival. 
Ispitivanja pred- i postnatalnog razvoja u štakora provedena sa sakubitrilom u visokim dozama do 750 mg/kg/dan (2,2 puta MRHD-a na temelju AUC-a) i valsartanom u dozama do 600 mg/kg/dan (0,86 puta MRHD-a na temelju AUC-a) ukazuju na to da liječenje Neparvisom tijekom organogeneze, gestacije i laktacije može utjecati na razvoj i preživljenje mladunčadi.
If a dose is missed, the patient should take the next dose at the scheduled time. 
Ako bolesnik propusti dozu Neparvisa, sljedeću dozu treba uzeti prema rasporedu.
Time to first occurrence of CV death or heart failure hospitalisations in PARADIGM-HF 
Vrijeme do prve pojave KV smrti ili hospitalizacije zbog zatajenja srca u PARADIGM-HF-u
In PARADIGM-HF study, Neparvis was administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other angiotensin II receptor blocker (ARB) (see section 5.1). 
U PARADIGM-HF ispitivanju, Neparvis je primijenjen zajedno s drugim terapijama za liječenje zatajenja srca, umjesto ACE inhibitora ili drugog blokatora receptora angiotenzina II (ARB) (vidjeti dio 5.1).
Patients were required to discontinue their existing ACE inhibitor or ARB therapy and enter a sequential single-blind run-in period during which they received treatment with enalapril 10 mg twice daily, followed by single-blind treatment with Neparvis 100 mg twice daily, increasing to 200 mg twice daily (see section 4.8 for discontinuations during this period). 
Bolesnici su trebali prekinuti postojeću terapiju ACE inhibitorom ili ARB-om te ući u uzastopno jednostruko slijepo ulazno razdoblje tijekom kojeg su primali terapiju enalaprilom 10 mg dvaput na dan, nakon čega je slijedilo jednostruko slijepo liječenje Neparvisom 100 mg dvaput na dan, povećano na 200 mg dvaput na dan (vidjeti dio 4.8 za prekide tijekom tog razdoblja).
In vitro metabolism studies indicate that potential for CYP 450-based drug interactions is low since there is limited metabolism of Neparvis via CYP450 enzymes. 
In vitro ispitivanja metabolizma upućuju na to da je potencijal za interakcije s lijekovima na temelju CYP 450 nizak budući da je metabolizam
Exposure to ARBs therapy during the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). 
Poznato je da izloženost terapiji ARB-ovima tijekom drugog i trećeg tromjesečja u ljudi izaziva fetotoksičnost (smanjenu funkciju bubrega, oligohidramnion, retardaciju okoštavanja lubanje) i neonatalnu toksičnost (zatajenje bubrega, hipotenziju, hiperkalijemiju).
Neparvis should be used with caution in these patients and the recommended starting dose is 24 mg/26 mg twice daily (see sections 4.4 and 5.2). 
Neparvis treba primjenjivati s oprezom u tih bolesnika te se preporučuje početna doza od 24 mg/26 mg dvaput na dan (vidjeti dijelove 4.4 i 5.2).
NPs exert their effects by activating membrane-bound guanylyl cyclase-coupled receptors, resulting in increased concentrations of the second messenger cyclic guanosine monophosphate (cGMP), which could result in vasodilation, natriuresis and diuresis, increased glomerular filtration rate and renal blood flow, inhibition of renin and aldosterone release, reduction of sympathetic activity, and anti-hypertrophic and anti-fibrotic effects. 
NP-i ostvaruju svoje učinke aktiviranjem za membranu vezanih receptora sparenih s guanilil ciklazom, što rezultira povišenim koncentracijama drugog glasnika cikličkog guanozin monofosfata (cGMP), što bi moglo rezultirati vazodilatacijom, natriurezom i diurezom, povećanjem glomerularne filtracije i protoka krvi kroz bubrege, inhibicijom otpuštanja renina i aldosterona, smanjenjem simpatičke aktivnosti te antihipertrofičnim i antifibrotičkim učincima.
Neparvis may therefore increase the systemic exposure of OATP1B1 and OATP1B3 substrates such as statins. 
Neparvis stoga može povećati sistemsku izloženost supstratima OATP1B1 i OATP1B3 kao što su statini.
As there is very limited clinical experience in patients with severe renal impairment (eGFR <30 ml/min/1.73 m2) (see section 5.1) Neparvis should be used with caution and a starting dose of 24 mg/26 mg twice daily is recommended. 
Budući da postoji vrlo ograničeno kliničko iskustvo u bolesnika s teškim oštećenjem bubrega (eGFR <30 ml/min/1,73 m2) (vidjeti dio 5.1) Neparvis treba primjenjivati s oprezom te se preporučuje početna doza od 24 mg/26 mg dvaput na dan.
A hydroxyl metabolite of valsartan has been identified in plasma at low concentrations (<10%). 
Utvrđen je hidroksilni metabolit valsartana u plazmi pri niskim koncentracijama
Treatment should not be initiated in patients with serum potassium level >5.4 mmol/l or with SBP <100 mmHg (see section 4.4). 
Liječenje se ne smije započeti u bolesnika s razinom kalija u serumu >5,4 mmol/l ili sa SKT-om <100 mmHg (vidjeti dio 4.4).
Patients with mild and moderate renal impairment are more at risk of developing hypotension (see section 4.2). 
Bolesnici s blagim i umjerenim oštećenjem bubrega izloženi su većem riziku od razvoja hipotenzije (vidjeti dio 4.2).
• The other ingredients in the tablet core are microcrystalline cellulose, low-substituted hydroxypropylcellulose, crospovidone, magnesium stearate, talc and silica colloidal anhydrous. 
• Drugi sastojci u jezgri tablete su mikrokristalična celuloza, niskosupstituirana hidroksipropilceluloza, krospovidon, magnezijev stearat, talk i silicijev dioksid koloidni bezvodni.
You can take Neparvis with or without food. 
Neparvis uz hranu ili bez nje.
• low blood pressure (dizziness, light-headedness) 
• niski krvni tlak (omaglica, ošamućenost)
Combination of Neparvis with aliskiren is potentially associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) (see sections 4.3 and 4.4). 
Kombinacija Neparvisa s aliskirenom je potencijalno povezana s višom učestalošću nuspojava kao što su hipotenzija, hiperkalijemija i smanjena funkcija bubrega (uključujući akutno zatajenje bubrega) (vidjeti dijelove 4.3 i 4.4).
No dose adjustment is required when administering Neparvis to patients with mild hepatic impairment (Child-Pugh A classification). 
Nije potrebno prilagođavanje doze kada se Neparvis primjenjuje u bolesnika s blagim oštećenjem jetre (stupanj A prema Child-Pugh klasifikaciji).
There is very limited clinical experience in patients with severe renal impairment (estimated GFR <30 ml/min/1.73m2) and these patients may be at greatest risk of hypotension (see section 4.2). 
Postoji vrlo ograničeno iskustvo s bolesnicima s teškim oštećenjem bubrega (procijenjeni GFR <30 ml/min/1,73m2) te bi ti bolesnici mogli biti izloženi najvećem riziku od hipotenzije (vidjeti dio 4.2).
Neparvis was superior to enalapril, reducing the risk of cardiovascular death or heart failure hospitalisations to 21.8% compared to 26.5% for enalapril treated patients. 
Neparvis je bio superioran u odnosu na enalapril, smanjujući rizik od kardiovaskularne smrti ili hospitalizacija zbog zatajenja srca na 21,8% u usporedbi s 26,5% kod bolesnika liječenih enalaprilom.
The effects of Neparvis on amyloid-β concentrations in CSF and brain tissue were assessed in young (2-4 years old) cynomolgus monkeys treated with Neparvis (24 mg sacubitril/26 mg valsartan/kg/day) for two weeks. 
Neparvisa na koncentracije amiloida-β u cerebrospinalnoj tekućini i moždanom tkivu ocijenjeni su u mladih (2-4 godine starosti) cynomolgus majmuna liječenih Neparvisom (24 mg sakubitrila/26 mg valsartana/kg/dan) tijekom dva tjedna.
In a thorough QTc clinical study in healthy male subjects, single doses of Neparvis 194 mg sacubitril/206 mg valsartan and 583 mg sacubitril/617 mg valsartan had no effect on cardiac repolarisation. 
U temeljitom kliničkom ispitivanju QTc intervala u zdravih muških ispitanika, jednokratne doze Neparvisa od 194 mg sakubitrila/206 mg valsartana te 583 mg sakubitrila/617 mg valsartana nisu imale učinak na srčanu repolarizaciju.
In the Neparvis group, 76% of patients remained on the target dose of 200 mg twice daily at the end of the study (mean daily dose of 375 mg). 
U skupini koja je primala Neparvis, 76% bolesnika ostalo je na ciljnoj dozi od 200 mg dvaput na dan na kraju ispitivanja (srednja dnevna doza od 375 mg).
In juvenile rats treated with valsartan (postnatal days 7 to 70), doses as low as 1 mg/kg/day produced persistent irreversible kidney changes consisting of tubular nephropathy (sometimes accompanied by tubular epithelial necrosis) and pelvic dilatation. 
U juvenilnih štakora liječenih valsartanom (postnatalni dani od 7. do 70.), doze već od 1 mg/kg/dan proizvele su trajne ireverzibilne promjene na bubrezima koje su odgovarale tubularnoj nefropatiji (ponekad popraćene nekrozom tubularnog epitela) i dilataciju zdjelice.
Pump failure accounted for 26% of cardiovascular deaths and was reduced by 21% in Neparvis-treated patients compared to enalapril-treated patients (HR 0.79, p=0.0338). 
Zatajenje srca kao pumpe predstavljalo je 26% kardiovaskularnih smrti i bilo je smanjeno za 21% u bolesnika liječenih Neparvisom u usporedbi s bolesnicima liječenima enalaprilom (HR 0,79, p=0,0338).
In PARADIGM-HF, angioedema was reported in 0.5% of patients treated with Neparvis, compared with 0.2% of patients treated with enalapril. 
U ispitivanju PARADIGM-HF, angioedem je bio zabilježen u 0,5% bolesnika liječenih Neparvisom, u usporedbi s 0,2% bolesnika liječenih enalaprilom.
Non-steroidal anti-inflammatory agents (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors 
Nesteroidni protuupalni lijekovi (NSAID), uključujući selektivne inhibitore ciklooksigenaze-2 (COX-2)
Patients with a prior history of angioedema were not studied. 
Bolesnici s angioedemom u anamnezi nisu bili ispitivani.
The risk may be further increased by dehydration or concomitant use of non-steroidal anti-inflammatory agents (NSAIDs) (see section 4.5). 
Ovaj se rizik može dodatno povećati dehidracijom ili istodobnom primjenom nesteroidnih protuupalnih lijekova (NSAID) (vidjeti dio 4.5).
Use of Neparvis may be associated with decreased renal function. 
Primjena Neparvisa može biti povezana sa smanjenom bubrežnom funkcijom.
The most commonly reported adverse reactions during treatment with Neparvis were hypotension, hyperkalaemia and renal impairment (see section 4.4). 
Najčešće prijavljene nuspojave tijekom liječenja Neparvisom bile su hipotenzija, hiperkalijemija i oštećenje bubrega (vidjeti dio 4.4).
The primary endpoint was the composite of cardiovascular (CV) death or hospitalisation for heart failure (HF). 
Primarni kompozitni ishod obuhvatio je kardiovaskularnu (KV) smrt ili hospitalizaciju zbog zatajenja srca.
The complementary cardiovascular benefits of Neparvis in heart failure patients are attributed to the enhancement of peptides that are degraded by neprilysin, such as natriuretic peptides (NP), by LBQ657 and the simultaneous inhibition of the effects of angiotensin II by valsartan. 
Komplementarne kardiovaskularne koristi Neparvisa u bolesnika sa zatajenjem srca pripisuju se povećanju količine peptida koje neprilizin razgrađuje, kao što su natriuretski peptidi (NP), pomoću LBQ657 i istodobnoj inhibiciji učinaka angiotenzina II od strane valsartana.
BNP is not a suitable biomarker of heart failure in patients treated with Neparvis because BNP is a neprilysin substrate (see section 4.4). 
BNP nije prikladan biomarker zatajenja srca u bolesnika liječenih Neparvisom zato što je BNP supstrat neprilizina (vidjeti dio 4.4).
The embryo-foetal no-observed adverse effect level (NOAEL) for sacubitril was at least 750 mg/kg/day in rats and 200 mg/kg/day in rabbits (2.2-fold the MRHD on the basis of LBQ657 AUC). 
Embriofetalna razina bez opaženih štetnih učinaka (NOAEL) za sakubitril bila je najmanje 750 mg/kg/dan u štakora i 200 mg/kg/dan u zečeva (2,2 puta MRHD-a na temelju AUC-a LBQ657).
Patients with SBP <100 mmHg, severe renal impairment (eGFR <30 ml/min/1.73 m2) and severe hepatic impairment were excluded at screening and therefore not prospectively studied. 
Bolesnici koji su imali SKT <100 mmHg, teško oštećenje bubrega (eGFR <30 ml/min/1,73 m2) i teško oštećenje jetre bili su isključeni kod probira i stoga nisu bili prospektivno ispitivani.
Nervous system disorders 
Poremećaji živčanog sustava Omaglica
Furosemide 
Furosemid
168 film-coated tablets 
168 filmom obloženih tableta
In PARADIGM-HF, hyperkalaemia and serum potassium concentrations >5.4 mmol/l were reported in 11.6% and 19.7% of Neparvis-treated patients and 14.0% and 21.1% of enalapril-treated patients, respectively. 
U ispitivanju PARADIGM-HF, hiperkalijemija i koncentracije kalija u serumu >5.4 mmol/l bile su prijavljene u 11,6% i 19,7% bolesnika liječenih Neparvisom, odnosno u 14,0% i 21,1% bolesnika liječenih enalaprilom.
Animal studies with Neparvis have shown reproductive toxicity (see section 5.3). 
Ispitivanja Neparvisa u životinja su pokazala reproduktivnu toksičnost (vidjeti dio 5.3).
Hypotension* 
Hipotenzija*
This prevents sustained activation of the renin-angiotensin-aldosterone system that would result in vasoconstriction, renal sodium and fluid retention, activation of cellular growth and proliferation, and subsequent maladaptive cardiovascular remodelling. 
To sprječava održanu aktivaciju renin-angiotenzin-aldosteronskog sustava koja bi rezultirala vazokonstrikcijom, zadržavanjem natrija i tekućine putem bubrega, aktivacijom staničnog rasta i proliferacije te naknadnim maladaptivnim kardiovaskularnim remodeliranjem.
The tablets are supplied in PVC/PVDC/Aluminium blister packs of 14, 20, 28 tablets or 56 tablets and in multipacks of 196 tablets (7 packs of 28 tablets). 
Tablete se isporučuju u PVC/PVDC/aluminij blister pakiranjima od 14, 20, 28 ili 56 tableta i u višestrukim pakiranjima od 196 tableta (7 pakiranja od po 28 tableta).
However, in patients with mild to moderate hepatic impairment, the exposures of free concentrations of LBQ657 increased by 1.47- and 3.08-fold, respectively, and the exposures of free concentrations of valsartan increased by 1.09-fold and 2.20-fold, respectively, compared to matching healthy subjects. 
Međutim, u bolesnika s blagim do umjerenim oštećenjem jetre izloženosti slobodnih koncentracija LBQ657 povećale su se za 1,47 odnosno 3,08 puta, a izloženosti slobodnih koncentracija valsartana povećale su se za 1,09 odnosno 2,20 puta, u usporedbi s odgovarajućim zdravim ispitanicima.
≤ eGFR <90 ml/min/1.73 m2), the largest group of patients enrolled in 
≤ eGFR <90 ml/min/1,73 m2) koji su bili najveća skupina bolesnika uključena u PARADIGM-HF.
Co-administration of Neparvis increased the Cmax of atorvastatin and its metabolites by up to 2-fold and AUC by up to 1.3-fold. 
Istodobna primjena Neparvisa povećala je Cmax atorvastatina i njegovih metabolita za do 2 puta te AUC za do 1,3 puta.
During the enalapril run-in period, 1,102 patients (10.5%) permanently discontinued from the study, 5.6% because of an adverse reaction, most commonly renal dysfunction (1.7%), hyperkalemia (1.7%) and hypotension (1.4%). 
Tijekom ulaznog razdoblja s enalaprilom, 1102 bolesnika (10,5%) trajno je prekinulo sudjelovanje u ispitivanju, 5,6% zbog nuspojave, najčešće bubrežne disfunkcije (1,7%), hiperkalijemije (1,7%) i hipotenzije (1,4%).
• metformin, a medicine used to treat diabetes. 
• metformin, lijek koji se koristi za liječenje šećerne bolesti.
Following twice daily dosing of Neparvis, steady-state levels of sacubitril, LBQ657 and valsartan are reached in three days. 
Nakon doziranja Neparvisa dvaput na dan, razine sakubitrila, LBQ657 i valsartana u stanju dinamičke ravnoteže postižu se za tri dana.
Tablet core 
Jezgra tablete
Hyperkalaemia and serum potassium 
Hiperkalijemija i kalij u serumu
• The active substances are sacubitril and valsartan. 
• Djelatne tvari su sakubitril i valsartan.
Neparvis exhibits the mechanism of action of an angiotensin receptor neprilysin inhibitor by simultaneously inhibiting neprilysin (neutral endopeptidase; NEP) via LBQ657, the active metabolite of the prodrug sacubitril, and by blocking the angiotensin II type-1 (AT1) receptor via valsartan. 
Neparvis pokazuje mehanizam djelovanja inhibitora angiotenzinskog receptora i neprilizina tako što istodobno inhibira neprilizin (neutralna endopeptidaza; NEP) putem LBQ657, aktivnog metabolita prolijeka sakubitrila, te blokira receptor angiotenzina II tip 1 (AT1) putem valsartana.
There are no data from the use of Neparvis in pregnant women. 
Ne postoje podaci o primjeni Neparvisa u trudnica.
Sacubitril treatment during organogenesis resulted in embryo-foetal lethality and embryo-foetal toxicity (decreased foetal body weights and skeletal malformations) in rabbits at doses associated with maternal toxicity (500 mg/kg/day; 5.7-fold the MRHD on the basis of LBQ657 AUC). 
Liječenje sakubitrilom tijekom organogeneze rezultiralo je embriofetalnom smrtnošću i embriofetalnom toksičnošću (smanjena fetalna tjelesna težina i malformacije skeleta) u zečeva pri dozama povezanima s maternalnom toksičnošću (500 mg/kg/dan; 5,7 puta MRHD-a na temelju AUC-a LBQ657).
How to store Neparvis 
Kako čuvati Neparvis
• if you have liver disease. 
• ako imate bolest jetre.
Table 1 List of adverse reactions 
Tablica 1 Popis nuspojava
The pharmacodynamic effects of Neparvis were evaluated after single and multiple dose administrations in healthy subjects and in patients with heart failure, and are consistent with simultaneous neprilysin inhibition and RAAS blockade. 
Neparvisa ocjenjivani su nakon primjene jednokratne i višekratnih doza u zdravih ispitanika i u bolesnika sa zatajenjem srca, te su u skladu s istodobnom inhibicijom neprilizina i blokadom RAAS-a.
Cardiovascular abnormalities (mainly cardiomegaly) were observed in rabbit foetuses at a maternally non-toxic dose (1.46 mg sacubitril/1.54 mg valsartan/kg/day). 
Kardiovaskularne abnormalnosti (uglavnom kardiomegalija) uočene su u fetusa zečeva pri dozama koje nisu toksične za majku (1,46 mg sakubitrila/1,54 mg valsartana/kg/dan).
• if you have low blood pressure or are taking any other medicines that reduce your blood pressure (for example, a diuretic) or are suffering from vomiting or diarrhoea, especially if you are aged 65 years or more, or if you have kidney disease and low blood pressure. 
diuretik) ili ako patite od povraćanja ili proljeva, posebno ako imate 65 godina ili više, ili ako imate bolest bubrega i niski krvni tlak.
In PARADIGM-HF, hypotension and clinically relevant low systolic blood pressure (<90 mmHg and decrease from baseline of >20 mmHg) were reported in 17.6% and 4.76% of Neparvis-treated patients compared with 11.9% and 2.67% of enalapril-treated patients, respectively. 
U ispitivanju PARADIGM-HF, hipotenzija i klinički značajan niski sistolički krvni tlak (<90 mmHg i smanjenje od početne vrijednosti >20 mmHg) bili su prijavljeni u 17,6% i 4,76% bolesnika liječenih Neparvisom, odnosno u 11,9% i 2,67% bolesnika liječenih enalaprilom.
A starting dose of 24 mg/26 mg twice daily should be considered in patients with moderate renal impairment (eGFR 30-60 ml/min/1.73 m2). 
Početna doza od 24 mg/26 mg dvaput na dan se treba razmotriti u bolesnika s umjerenim oštećenjem bubrega (eGFR 30-60 ml/min/1,73 m2).
OATP1B1 and OATP1B3 substrates, e.g. statins 
Supstrati OATP1B1 i OATP1B3, npr. statini
Microcrystalline cellulose Low-substituted hydroxypropylcellulose Crospovidone, type A Magnesium stearate 
Celuloza, mikrokristalična Niskosupstituirana hidroksipropilceluloza Krospovidon, tip A
Symptomatic hypotension is more likely to occur if the patient has been volume-depleted, e.g. by diuretic therapy, dietary salt restriction, diarrhoea or vomiting. 
Veća je vjerojatnost da će se pojaviti simptomatska hipotenzija u bolesnika sa smanjenim volumenom tekućine, npr. zbog liječenja diureticima, ograničenja unosa soli, proljeva ili povraćanja.
Neparvis is contraindicated in patients with a known history of angioedema related to previous ACE inhibitor or ARB therapy or with hereditary or idiopathic angioedema (see section 4.3). 
Neparvis je kontraindiciran u bolesnika s angioedemom u anamnezi povezanim s prethodnom terapijom ACE inhibitorom ili ARB-om ili s nasljednim ili idiopatskim angioedemom (vidjeti dio 4.3).
The combination of Neparvis with direct renin inhibitors such as aliskiren is not recommended (see section 4.4). 
Kombinacija Neparvisa s izravnim inhibitorima renina kao što je aliskiren nije preporučena (vidjeti dio 4.4).
The relative risk reduction was 20% versus enalapril (see Table 2). 
Relativno smanjenje rizika iznosilo je 20% u odnosu na enalapril (vidjeti Tablicu 2).
The adverse embryofoetal effects of Neparvis are attributed to the angiotensin receptor antagonist activity (see section 4.6). 
Neparvisa pripisuju se antagonističkoj aktivnosti prema angiotenzinskom receptoru (vidjeti dio 4.6).
ACE inhibitor therapy must not be started until 36 hours after the last dose of Neparvis (see sections 4.2 and 4.3). 
Terapija ACE inhibitorom ne smije se započinjati do 36 sati nakon zadnje doze Neparvisa (vidjeti dijelove 4.2 i 4.3).
Multipack: 168 (3 packs of 56) film-coated tablets Multipack: 196 (7 packs of 28) film-coated tablets 
Višestruko pakiranje: 168 (3 pakiranja od 56) filmom obloženih tableta Višestruko pakiranje: 196 (7 pakiranja od 28) filmom obloženih tableta
BNP is not a suitable biomarker of heart failure in patients treated with Neparvis because it is a neprilysin substrate (see section 5.1). 
BNP nije odgovarajući biomarker zatajenja srca u bolesnika liječenih Neparvisom zato što je supstrat neprilizina (vidjeti dio 5.1).
196 film-coated tablets 
196 filmom obloženih tableta
Angioedema has been reported in patients treated with Neparvis. 
Angioedem je prijavljen u bolesnika liječenih Neparvisom.
Hyperkalaemia* 
Hiperkalijemija*
It is teratogenic based on a low incidence of foetal hydrocephaly, associated with maternally toxic doses, which was observed in rabbits at an Neparvis dose of ≥4.9 mg sacubitril/5.1 mg valsartan/kg/day. 
On je teratogen na temelju niske incidencije fetalne hidrocefalije, povezano s toksičnim dozama za majku, što je bilo uočeno u zečeva uz dozu Neparvisa ≥4,9 mg sakubitrila/5,1 mg valsartana/kg/dan.
• The combination of Neparvis with direct renin inhibitors such as aliskiren is not recommended (see section 4.5). 
• Kombinacija Neparvisa s direktnim inhibitorima renina kao što je aliskiren nije preporučljiva (vidjeti dio 4.5).
If any of the above applies to you, tell your doctor or pharmacist before you take Neparvis. 
Ako se bilo što od navedenoga odnosi na Vas, obratite se svom liječniku ili ljekarniku prije uzimanja Neparvisa.
Neparvis is contraindicated in patients with severe hepatic impairment, biliary cirrhosis or cholestasis (Child-Pugh C classification) (see section 4.3). 
Neparvis je kontraindiciran u bolesnika s teškim oštećenjem jetre, bilijarnom cirozom ili kolestazom (Child-Pugh stupanj C) (vidjeti dio 4.3).
Primary composite endpoint of CV death and heart failure hospitalisations* 
Primarni kompozitni ishod KV smrti i hospitalizacija zbog zatajenja srca*
If treatment with Neparvis is stopped, ACE inhibitor therapy must not be initiated until 36 hours after the last dose of Neparvis (see sections 4.2, 4.3 and 4.5). 
Ako se prekine liječenje Neparvisom, terapija ACE inhibitorom ne smije se započinjati do 36 sati nakon zadnje doze Neparvisa (vidjeti dijelove 4.2, 4.3 i 4.5).
• (acute) renal failure (severe kidney disorder) 
• (akutno) zatajenje bubrega (teški poremećaj bubrega)
• Known history of angioedema related to previous ACE inhibitor or ARB therapy (see section 4.4). 
• Angioedem u anamnezi povezan s prethodnom terapijom ACE inhibitorom ili ARB-om (vidjeti dio 4.4).
Monitoring of serum potassium is recommended if Neparvis is co-administered with these agents (see section 4.4). 
Preporučuje se praćenje kalija u serumu ako se Neparvis primjenjuje istodobno s tim tvarima (vidjeti dio 4.4).