qanastek/EMEA-V3 huggingface dataset:
This applies particularly when losartan is given in the presence of other conditions (fever, dehydration) likely to impair renal function.
Dan japplika b’ mod partikolari meta losartan jingħata fil- preżenza ta ’ kundizzjonijiet oħra (deni, deidrazzjoni) li x’ aktarx jistgħu jimpedixxu l- funzjoni renali.
Concomitant use of losartan and ACE-inhibitors has shown to impair renal function.
L- użu konkomitanti ta ’ losartan u impedituri ACE intweriet li timpedixxi l- funzjoni renali.
Therefore, concomitant use is not recommended.
Għalhekk l- użu konġunt mhux rakkomandat.
Therefore, the use of Losartan tablets is not recommended.
Għalhekk, it- teħid ta ’ pilloli ta ’ losartan mhuwiex rakkomandat.
Coronary heart disease and cerebrovascular disease As with any antihypertensive agents, excessive blood pressure decrease in patients with ischaemic cardiovascular and cerebrovascular disease could result in a myocardial infarction or stroke.
Mard tal- qalb koronarju u mard ċerebrovaskulari Bħal fil- każ ta ’ mediċini ta ’ kontra l- pressjoni oħra, tnaqqis fil- pressjoni ta ’ demm eċċessiva f’ pazjenti b’ mard kardjovaskulari u ċerebrovaskulari iskaemiku jistgħu jirriżultaw f’ infart mijokardikjaku jew puplesija.
Heart failure In patients with heart failure, with or without renal impairment, there is - as with other drugs acting on the renin-angiotensin system - a risk of severe arterial hypotension, and (often acute) renal impairment.
F’ pazjenti li għandhom insuffiċjenza tal- qalb, bi jew mingħajr indeboliment renali - bħal fil- każ ta ’ mediċini oħra li jaħdmu fuq is- sistema renin- angiotensin - hemm riskju ta ’ pressjoni baxxa fl- arterji severa, u indeboliment renali (ta ’ spiss akuta).
There is no sufficient therapeutic experience with losartan in patients with heart failure and concomitant severe renal impairment, in patients with severe heart failure (NYHA class IV) as well as in patients with heart failure and symptomatic life threatening cardiac arrhythmias.
Hemm esperjenza terapewtika ristretta b’ losartan f’ pazjenti b’ insuffiċjenza kardijaka flimkien ma ’ indeboliment renali sever f’ pazjenti b’ insuffiċjenza kardijaka severa (NYHA klassi IV) kif ukoll f’ pazjenti b’ insuffiċjenza kardijaka u b’ arritmiji kardijaċi sintomatiċi li huma ta ’ theddida għal ħajja.
Therefore, losartan should be used with caution in these patient groups.
Għalhekk, losartan għandu jintuża b’ kawtela f’ dawn il- gruppi ta ’ pazjenti.
The combination of losartan with a beta-blocker should be used with caution (see section 5.1).
Il- kombinazzjoni ta ’ losartan ma ’ beta- blocker għandha tintuża b’ kawtela (ara sezzjoni 5. 1)
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy As with other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.
Bħal fil- każ ta ’ vażodilaturi oħra, kawtela speċjali hija indikata f’ pazjenti li jbatu minn stenosi aortika jew mitrali jew kardjomijopatija ipertrofika ostruttiva.
Galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorbtion Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose- galactose malabsorption should not take this medicine.
Pazjenti li għandhom problemi ereditarji rari ta ’ intolleranza ta ’ gallatosju, id- defiċjenza ta ’ Lapp Lactase jew malassorbiment ta ’ glukosju- gallatosju m’ għandhomx jieħdu din il- mediċina.
28 Pregnancy Losartan should not be initiated during pregnancy.
Tqala Losartan m’ għandux jiġi mibdi waqt it- tqala.
Unless continued losartan therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy.
Għajr meta t- terapija b’ Cozaar hi konsidrata essenzjali, pazjenti li jippjanaw tqala, għandhom jinqalbu fuq trattamenti altermattivi ta ’ kontra l- pressjoni li għandhom profil ta ’ sigurtà stabbilit għal użu fi tqala.
When pregnancy is diagnosed, treatment with losartan should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).
Meta tqala tiġi dijanjonizzata, it- trattament b’ Cozaar għandu jitwaqqaf immedjatament, u jekk jixraq, terapija alternattiva għandha tiġi mibdija (ara sezzjonijiet 4. 3 u 4. 6).
Other warnings and precautions As observed for angiotensin converting enzyme inhibitors, losartan and the other angiotensin antagonists are apparently less effective in lowering blood pressure in black people than in non-blacks, possibly because of higher prevalence of low-renin states in the black hypertensive population.
Twissijiet oħra u prekawzjonijiet Kif kien osservat għal impedituri ta ’ enżimi li jikkonvertu angiotensin, losartan u l- antagonisti oħra ta ’ angiotensin jidhru li huma inqas effettivi biex ibaxxu l- pressjoni għolja f’ persuni suwed milli f’ persuni mhux suwed, possibilment minħabba l- prevalenza ogħla ta ’ stati baxxi ta ’ renin fil- popolazzjoni sewda li tbati bi pressjoni għolja.
Other antihypertensive agents may increase the hypotensive action of Losartan.
Mediċini ta ’ kontra l- pressjoni għolja oħrajn jistgħu jżidu l- azzjoni ta ’ tnaqqis fil- pressjoni ta ’ Losartan.
Other substances inducing hypotension like tricyclic antidepressants, antipsychotics, baclofene, amifostine:
Sustanzi oħra li jissensitizzaw l- pressjoni baxxa bħal mediċini kontra d- dipressjoni triċikliċi, antipsikotiċi, baclofene, amifostene:
Concomitant use with these drugs that lower blood pressure, as main or side-effect, may increase the risk of hypotension.
L- użu konġunt ta ’ dawn il- mediċini li jbaxxu l- pressjoni, bħala l- effett prinċipali jeew bħala effett kollaterali, jistgħu jżidu r- riskju ta ’ pressjoni baxxa.
Losartan is predominantly metabolised by cytochrome P450 (CYP) 2C9 to the active carboxy-acid metabolite.
Losartan huwa prinċipalment metabolizzat b’ cytochrome P450 (CYP) 2C9 għal metabolit attiv ta ’ carboxy- acid.
In a clinical trial it was found that fluconazole (inhibitor of CYP2C9) decreases the exposure to the active metabolite by approximately 50%.
Fi prova klinika nstab li fluconazole (impeditur ta ’ CYP2C9) inaqqas l- espożizzjoni għal metabolit attiv b’ madwar 50%.
It was found that concomitant treatment of losartan with rifampicine (inducer of matabolism enzymes) gave a 40% reduction in plasma concentration of the active metabolite.
Instab li trattament fl- istess ħin b’ losartan b’ rifampicin (sensitizzatur ta ’ enżimi metaboliċi) wassal għal tnaqqis ta’ 40% fil- konċentrazzjoni tal- metabolit attiv fil- plażma.
The clinical relevance of this effect is unknown.
Ir- rilevanza klinika ta ’ dan l- effett mhix magħrufa.
No difference in exposure was found with concomitantly treatment with fluvastatin (weak inhibitor of CYP2C9).
Ma nstabet l- ebda differenza fl- espożizzjoni bi trattament flimkien ma ’ fluvastatin (impeditur ħafif ta ’ CYP2C9).
As with other drugs that block angiotensin II or its effects, concomitant use of other drugs which retain potassium (e. g. potassium-sparing diuretics: amiloride, triamterene, spironolactone) or may increase potassium levels (e. g. heparin), potassium supplements or salt substitutes containing potassium may lead to increases in serum potassium.
Bħal fil- każ ta ’ mediċini oħra li jimblokkaw angiotensin II jew l- effetti tiegħu, l- użu fl- istess ħin ta ’ mediċini oħra li jiristrinġu l- potassju (eż. dijuretiċi li ma jinkoraġixxux it- tnixxija ta ’ potassju fl- urina: amiloride, triamteren, spironolactone) jew li jistgħu jżidu l- livelli ta ’ potassju (eż. eparina), supplimenti tal- potassju jew sostituti ta ’ l- imluħa li fihom il- potassju jistgħu jwasslu għal żieda tal- potassju fis- serum.
Co-medication is not advisable.
L- għoti ta ’ mediċini flimkien mhux rakkomandat
Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors.
Żjidiet riversibbli fil- konċentrazzjonijiet tal- litju fis- serum u tossiċità ġew irrapportati waqt it- teħid ta ’ litju u impedituri ACE flimkien.
Very rare cases have also been reported with antiotensin II receptor antagonists.
Każijiet rari ħafna ġew irrapportati wkoll b’ antagonisti tar- riċettatur angiotensin II.
Co-administration of lithium and losartan should be undertaken with caution.
L- għoti flimkien tal- litju u losartan għandu jsir b’ kawtela.
If this combination proves essential, serum lithium level monitoring is recommended during concomitant use.
Jekk din il- kombinazzjoni tinstab li hija essenzjali, huwa rakkomandat li jkun hemm monitoraġġ tal- livell tal- litju fis- serum waqt l- użu konkomitanti.
When angiotensin II antagonists are administered simultaneously with NSAIDs (i. e. selective COX-2 inhibitors, acetylsalicylic acid at anti-inflammatory doses and non-selective NSAIDs), attenuation of the antihypertensive effect may occur.
Meta antagonisti ta ’ angiotensin II jiġu amministrati b’ mod simultaneju ma ’ mediċini mhux sterojdi li jaġixxu kontra l- infjammazzjoni, NSAIDs (i. e. impedituri silettivi ta ’ COX- 2, acetylsalicylic acid f’ dożi ta ’ kontra l- infjammazzjoni u NSAIDs mhux silettivi), jista ’ jkun hemm attenwazzjoni ta ’ l- effett ta ’ kontra l- pressjoni għolja.
Concomitant use of angiotensin II antagonists or diuretics and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure, and an increase in serum potassium, especially in patients with poor pre-existing renal function.
L- użu flimkien ta ’ antagonisti ta ’ angiotensin II jew dijuretiċi u NSAIDs jista ’ jwassal għal riskju ogħla jew tiħżin tal- funzjoni renali, li jinkludi l- possibilità ta ’ insuffiċjenza renali akuta, u żieda ta ’ potassju fis- serum, speċjalment f’ pazjenti b’ funzjoni renali eżistenti minn qabel dgħajfa.
The combination should be administered with caution, especially in the elderly.
Il- kombinazzjoni għandha tingħata b’ attenzjoni speċjalment fl- anzjani.
Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy, and periodically thereafter.
Il- pazjenti għandhom ikunu idratati sew u konsiderazzjoni għandha tingħata sabiex il- funzjoni renali tibqa ’ tiġi monitorata wara l- bidu ta ’ terapija konkomitanti, u perijodikament wara din.
4.6 Pregnancy and lactation
25 4. 6 Tqala u Treddigħ
Pregnancy The use of losartan is not recommended during the first trimester of pregnancy (see section 4.4).
Tqala L- użu ta ’ losartan mhux rakkomandat waqt l- ewwel tliet xhur ta ’ tqala (ara sezzjoni 4. 4).
The use of losartan is contra-indicated during the 2nd and 3rd trimester of pregnancy (see section 4.3 and 4.4).
L- użu ta ’ losartan hu kontra- indikat waqt it- 2ni u t- 3et tliet xhur ta ’ tqala (ara sezzjonijiet 4. 3 u 4. 4).
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk 29 cannot be excluded.
Evidenza epidemjoloġika dwar ir- riskju ta ’ teratoġeniċità wara espożizzjoni għal impedituri ACE waqt l- ewwel tliet xhur ta ’ tqala għadha mhix konklusiva; madankollu żieda żgħira fir- riskju ma tistax tiġi eskluża.
Whilst there is no controlled epidemiological data on the risk with Angiotensin II Receptor Inhibitors (AIIRAs), similar risks may exist for this class of drugs.
Filwaqt li mhemmx tagħrif epidemjoloġiku b’ kontrolli fuq ir- riskju b’ Impedituri għar - Riċettaturi ta ’ Amgiotensin II (AIIRAs), riskji bħal dawn jistgħu jeżistu għal din il- klassi ta ’ mediċini.
Unless continued ARB therapy is considered essential, patients planning pregnancy should be changed to alternative anti- hypertensive treatments which have an established safety profile for use in pregnancy.
Għajr meta jissokta, it- terapija b’ ARB hi konsidrata essenzjali, pazjenti li qed jippjanaw tqala, għandhom jinqalbu fuq trattamenti altermattivi ta ’ kontra l- pressjoni li għandhom profil ta ’ sigurtà stabbilit għal użu fi tqala.
When pregnancy is diagnosed, treatment with losartan should be stopped immediately and, if appropriate, alternative therapy should be started.
Meta tqala tiġi dijanjonizzata, it- trattament b’ losartan għandu jitwaqqaf minnufih, u jekk jixraq, terapija alternattiva għandha tinbeda.
Losartan therapy exposure during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia) (see also 5.3'Preclinical safety data ').
L- espożizzjoni għat- terapija b’ losartan waqt it- tieni u t- tielet trimestri hi magħrufa li tinduċi tossiċità fil- fetu uman (tnaqqis fil- funzjoni tal- kliewi, oligoħidramnios, dewmien għal ossifikazzjoni tal- kranju) u tossiċità lit- tarbija għadha titwieled (insuffiċjenza renali, pressjoni baxxa, iperkalemja) (ara wkoll 5. 3 ‘ Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina ’).
Should exposure to losartan have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Jekk l- espożizzjoni għal losartan tkun seħħet mit- tieni trimestru ta ’ tqala, verifiċi bl- ultrasawnd għal funzjoni renali u l- kranju huma rakkomandati.
Infants whose mothers have taken losartan should be closely observed for hypotension (see also section 4.3 and 4.4).
Trabi li ommhom tkun ħadet losartan għandhom jiġu osservati għal pressjoni baxxa (ara wkoll sezzjonijiet 4. 3 u 4. 4).
Because of the potential for adverse effects on the nursing infant, losartan is contraindicated during breast-feeding (see section 4.3).
Minħabba l- potenzjal għal effetti avversi fuq it- trabi mredda ’, losartan hu kontra- indikat waqt it- treddigħ (ara sezzjoni 4. 3).
The frequency of adverse events listed below is defined using the following convention: very common (≥ 1/ 10); common (≥ 1/ 100, < 1/ 10); uncommon (≥ 1/ 1,000, < 1/ 100); rare (≥ 1/ 10,000, < 1/ 1,000); very rare (< 1/ 10,000), not known (cannot be estimated from the available data).
Il- frekwenza ta ’ każijiet avversi elenkati hawn isfel hija mfissra bil- konvenzjoni li ġejja: komuni ħafna (≥ 1/ 10); komuni (≥ 1/ 100, < 1/ 10); mhux komuni (≥ 1/ 1, 000, < 1/ 100); rari (≥ 1/ 10, 000, < 1/ 1, 000); rari ħafna (< 1/ 10, 000), mhux magħruf (ma tistax tittieħed stima mid- data disponibbli).
In controlled clinical trials for essential hypertension, hypertensive patients with left ventricular hypertrophy, chronic heart failure as well as for hypertension and type 2 diabetes mellitus with renal disease, the most common adverse event was dizziness.
Fi provi kliniċi b’ kontrolli għal pressjoni essenzjali għolja, pazjenti bil- pressjoni għolja b’ ipertrofija fil- ventrikula tax- xellug, insuffiċjenza tal- qalb kronika kif ukoll pressjoni għolja u dijabete melittus tat- tip 2 bil- mard tal- kliewi, l- isturdament kien l- aktar reazzjoni avversa komuni.
Hypertension In controlled clinical trials for essential hypertension with losartan the following adverse events were reported
Pressjoni għolja Fil- provi kliniċi b’ kontrolli għal pressjoni essenzjali għolja b’ losartan, ir- reazzjonijiet avversi li ġejjin ġew irraportati:
Common: dizziness, vertigo Uncommon: somnolence, headache, sleep disorders
Komuni: sturdament, vertiġini Mhux komuni: ngħas, uġigħ ta ’ ras, disturbi ta ’ l- irqadt
Cardiac disorder:
Disturbi fil- qalb:
Uncommon: palpitations, angina pectoris
Mhux komuni: palpitazzjonijiet, anġina pectoris
Vascular disorders:
26 Disturbi vaskulari:
Uncommon: symptomatic hypotension (especially in patients with intravascular volume depletion, e. g. patients with severe heart failure or under treatment with high dose diuretics), dose-related orthostatic effects, rash.
Mhux komuni: pressjoni baxxa sintomatika (speċjalment f’ pazjenti bi żvojtar ta ’ volumi intravaskulari eż. pazjenti b’ insuffiċjenza tal- qalb severa jew taħt trattament b’ dożi għolja ta ’ dijuretiċi), effetti ortostatiċi relatati mad- doża, raxx.
Uncommon: abdominal pain, obstipation 30 General disorders and administration site conditions:
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata:
Uncommon: asthenia, fatigue, oedema
Komuni: astenja, għeja, edema
Hypertensive patients with left ventricular hypertrophy In a controlled clinical trial in hypertensive patients with left ventricular hypertrophy the following adverse events were reported:
Pazjenti bil- pressjoni għolja b’ ipertrofija fil- ventrikola tax- xellug Fi prova klinika b’ kontrolli b’ pazjenti bi pressjoni għolja u b’ ipertrofija fil- ventrikola tax- xellug, l- effetti avversi li ġejjin kienu rapportati:
Nervous system disorders: common: dizziness
Disturbi fis- sistema nervuża: komuni: sturdament
Ear and labyrinth disorders: common: vertigo
Disturbi fil- widnejn u fis- sistema labirintika: komuni: vertiġini
General disorders and administration site conditions: common: asthenia/ fatigue
Komuni: astenja/ għeja
Chronic heart failure
Insuffiċjenza kardijaka kronika
In a controlled clinical trial in patients with cardiac insufficiency the following adverse events were reported:
Fi prova klinika b’ kontrolli f’ pazjenti b’ insuffiċjenza kardijaka l- effetti avversi li ġejjin ġew irrapportati:
Nervous system disorders: uncommon: dizziness, headache rare: paraesthesia
Mhux komuni: sturdament, uġigħ ta ’ ras rari: paraestesija
Cardiac disorders: rare: syncope, artrial fibrillation, cerebrovascular accident
Disturbi tal- qalb: rari: sinkope, fibrillazzjoni atrijali, aċċident ċerebrovaskulari
Vascular disorders: uncommon: hypotension, including orthostatic hypotension
Disturbi vaskulari: komuni: pressjoni baxxa, li tinkludi pressjoni ortostatika baxxa
Respiratory, thoracic and mediastinal disorders: uncommon: dyspnoea
Disturbi respiratorji, toraċiċi u medjastinali: komuni: dispnea
Gastrointestinal disorders: uncommon: diarrhoea, nausea, vomiting
Mhux komuni: dijarea, tqalligħ, remettar
Skin and subcutanous tissue disorders: uncommon: urticaria, pruritus, rash
Disturbi tal- ġilda u fit- tessuti ta ’ taħt il- ġilda: mhux komuni: urtikarja, ħakk, raxx
General disorders and administration site conditions: uncommon: asthenia/ fatigue
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata: komuni: astenja/ għeja
Hypertension and type 2 diabetes with renal disease
Pazjenti bi pressjoni għolja u dijabete ta ’ tip II ma ’ mard tal- kliewi
In a controlled clinical trial in type 2 diabetic patients with proteinuria (RENAAL study, see section 5.1) the most common drug-related adverse events which were reported for losartan are as follows:
Fi prova klinika b’ kontrolli b’ pazjenti li għandhom dijabete ta ’ tip 2 bi protejnurja (studju RENAAL, ara sezzjoni 5. 1) l- aktar każijiet avversi marbutin mal- mediċina li ġew rapportati għal losartan huma dawn li ġejjin:
Nervous system disorders: common: dizziness
27 Disturbi fis- sistema nervuża: komuni: sturdamenti
Vascular disorders: common: hypotension
Disturbi vaskulari: komuni: pressjoni baxxa
General disorders and administration site conditions: common: asthenia/ fatigue 31 Investigations: common: hypoglycaemia, hyperkalaemia
Investigazzjonijiet: komuni: ipogliċemija, iperkalemija
The following adverse events occurred more often in patients receiving losartan than placebo:
Il- każijiet avversi li ġejjin seħħew aktar ta ’ spiss f’ pazjenti li rċevew losartan milli l- plaċebo
Blood and lymphatic system disorders: not known: anaemia
Disturbi tad- demm u tas- sistema limfatika: mhux magħruf: anemija
Cardiac disorders: not known: syncope, palpitations
Disturbi kardijaċi: mhux magħruf: sinkope, palpitazzjonijiet
Vascular disorders: not known: orthostatic hypotension
Mhux magħruf: pressjoni ortostatika baxxa
Gastrointestinal disorders: not known: diarrhoea
Disturbi gastro- intestinali: mhux magħruf: dijarea
Muscoskeletal and connective tissue disorders: not known: back pain
Mhux magħruf: uġigħ fid- dahar
Renal and urinary disorders: not known: urinary tract infections
Disturbi fil- kliewi u fis- sistema urinarja: mhux magħruf: infezzjonijiet fl- apparat urinarju
General disorders and administration site conditions: not known: flu-like symptoms
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata: mhux magħruf: sintomi bħal ta ’ l- influwenza
Post-marketing experience
Esperjenza ta ’ wara t- tqegħid fis- suq
The following adverse events have been reported in post-marketing experience:
Il- każijiet avversi li ġejjin ġew irraportati wara t- tqegħid fis- suq:
Blood and lymphatic system disorders: not known:
Disturbi tad- demm u tas- sistema limfatika: mhux magħruf:
Anaemia, thrombocytopenia
Anemija, tromboċitopenija
Immune system disorders: rare: hypersensitivity: anaphylactic reactions, angiooedema including swelling of the larynx and glottis causing airway obstruction and/ or swelling of the face, lips, pharynx, and/ or tongue; in some of these patients angiooedema had been reported in the past in connection with the administration of other medicines, including ACE inhibitors; vasculitis, including Henoch-Schonlein purpura.
Disturbi fis- sistema immuni: rari: sensittività eċċessiva: reazzjonijiet anafilattiċi, anġjodema li tinkludi tinfiħ tal- larinġi u l- glottide li tikkawża impediment fil- passaġġ ta ’ l- arja u/ jew nefħa fil- wiċċ, ix- xofftejn, il- farinġi u/ jew l- ilsien. f’ xi wħud minn dawn il- pazjenti anġjodema kienet irrapportata fil- passat u marbuta ma ’ l- għoti ta ’ mediċini oħra li jinkludu impedituri ACE; vaskulite, li tinkludi purpura ta ’ Henoch- Schoenlein.
Nervous system disorders: not known: migraine
Disturbi fis- sistema nervuża: mhux magħruf: emikranja
Respiratory, thoracic and mediastinal disorders: not known: cough
Mhux magħruf: sogħla
Hepatobiliary disorders: rare: hepatitis not known: liver function abnormalities
28 Disturbi fil- fwied u fil- marrara: rari: epatite mhux magħruf: abnormalitajiet fil- funzjonament tal- fwied
Skin and subcutaneous tissue disorders: not known: urticaria, pruritus, rash
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda: mhux magħruf: urtikarja, ħakk, raxx
32 not known: myalgia, arthralgia
Disturbi muskolu- skeletriċi u tat- tessut konnettiv: mhux magħruf: uġigħ fil- muskoli, uġigħ fil- ġogi
Renal disorders:
Disturbi fil- kliewi:
As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function including renal failure have been reported in patients at risk; these changes in renal function may be reversible upon discontinuation of therapy (see section 4.4)
Bħala konsegwenza għall- impediment tas- sistema renin- angiotensin- aldosterone, bidliet fil- funzjoni renali, li jinkludi insuffiċjenza renali ġew irrapportati f’ pazjenti li jinsabu f’ riskju; dawn il- bidliet fil- funzjoni renali jistgħu jkunu riversibbli mat- twaqqif tat- terapija (ara sezzjoni 4. 4).
In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of Losartan tablets.
Investigazzjonijiet Fi provi kliniċi b’ kontrolli, bidliet klinikament importanti f’ parametri tal- laboratorju standard rarement kienu assoċjati ma ’ l- għoti ta ’ pilloli Losartan.
Elevations of ALT occurred rarely and usually resolved upon discontinuation of therapy.
Żidiet f’ ALT rarement seħħew u ġeneralment irriżolvew ruħom malli t- terapija twaqqfet.
Hyperkalaemia (serum potassium > 5.5 mmol/ l) occurred in 1.5% of patients in hypertension clinical trials.
Iperkalemja (> 5. 5 mmol/ l potassju fis- serum) seħħet f’ 1. 5% tal- pazjenti li kellhom pressjoni għolja fil- provi kliniċi.
In a clinical study conducted in type 2 diabetic patients with nephropathy, 9.9% of patients treated with Losartan tablets developed hyperkalaemia > 5.5 mEq/ l and 3.4% of patients treated with placebo (see section 4.4, ‘ Electrolyte imbalances’).
Fi studju kliniku li sar fuq pazjenti li kellhom dijabete ta ’ tip 2 b’ nefropatija, iperkalemija > 5. 5 mEq/ l żviluppat f’ 9. 9% ta ’ pazjenti ttrattati bil- pilloli Losartan u fi 3. 4% ta ’ pazjenti trattati bi plaċebo (ara sezzjoni 4. 4, ‘ Żbilanċi elettrolitiċi ’).
In a controlled clinical trial on patients with cardiac insufficiency, increase in blood urea, serum creatinine and serum potassium has been reported.
Fi prova klinika b’ kontrolli, fuq pazjenti b’ insuffiċjenza kardijaka, ġew rapportati każijiet ta ’ żieda fl- urea fid- demm, kreatinina fis- serum u potassju fis- serum.
The adverse experience profile for pediatric patients appears to be similar to that seen in adult patients.
Il- profil ta ’ esperjenzi avversi għal pazjenti tfal jidher li hu l- istess bħal dak ta ’ pazjenti adulti.
Data in the pediatric population are limited.
Tagħrif dwar il- popolazzjoni tat- tfal hu ristrett.
Symptoms of intoxication No experience with overdose in man is available so far.
Sintomi ta ’ intossikazzjoni L- ebda każ ta ’ doża eċċessiva ma ġie rrappurtat fuq il- bniedem s’ issa.
The most likely symptoms, depending on the extent of overdose, are hypotension, tachycardia, possibly bradycardia.
Is- sintomi li x’ aktarx jimmanifestaw irwieħhom, skond is- severità tad- doża eċċessiva, huma pressjoni baxxa, takikardja u possibilment bradikarja.
Treatment of intoxication Measures are depending on the time of drug intake and kind and severity of symptoms.
Trattament ta ’ l- intossikazzjoni Il- miżuri jiddependu mill- ħin tat- teħid tal- mediċina u l- mod u s- severità tas- sintomi.
Stabilisation of the circulatory system should be given priority.
L- istabbilità tas- sistema ċirkolatorja għandha tingħata prijorità.
After oral intake the administration of a sufficient dose of activated charcoal is indicated.
Wara t- teħid mill- ħalq, huwa indikat li għandha tingħata doża adattata ta ’ charcoal attivat.
Afterwards, close monitoring of the vital parameters should be performed.
Wara dan, għandu jkun hemm monitoraġġ mill- qrib tal- parametri vitali.
Vital parameters should be corrected if necessary.
Il- parametri vitali għandhom jiġu kkoreġuti jekk meħtieġ.
Neither Losartan nor the active metabolite can be removed by haemodialysis.
La losartan u lanqas il- metabolit attiv ma jistgħu jiġu eliminati b’ emodijaliżi.
Angiotensin II Receptor Antagonists, ATC code:
Antagonisti tar- riċettatur ta ’ Angiotensin II, komuni, Kodiċi ATC:
Losartan is a synthetic oral angiotensin-II receptor (type AT1) antagonist.
Losartan huwa riċettatur antagonista sintetiku u orali tar- riċettatur angiotensin- II (tip AT1).
Angiotensin II, a potent vasoconstrictor, is the primary active hormone of the renin/ angiotensin system and an important determinant of the pathophysiology of hypertension.
Angiotensin II, li jdejjaq b’ mod qawwi l- arterji u l- vini, huwa l- ormon prinċipali attiv tas- sistema renin/ anġiotensin u fattur determinanti tal- patofiżjoloġija tal- pressjoni għolja.
Angiotensin II binds to the AT1 receptor found in many tissues (e. g. vascular smooth muscle, adrenal gland, kidneys and the heart) and elicits several important biological actions, including vasoconstriction and the release of aldosterone.
Angiotensin II jintrabat mar- riċettatur AT1 li jinstab f’ ħafna tessuti (eż. il- muskoli vaskulari lixxi, il- glandoli adrenali, il- kliewi u l- qalb) u jissensitizza diversi azzjonijiet bijoloġiċi importanti li jinkludu t- tidjiq tal- vażi tad- demm u
Angiotensin II also stimulates smooth muscle cell proliferation.
Angiotensin II jissensitizza wkoll il- proliferazzjoni taċ- ċelloli lixxi tal- muskoli.
Furthermore Losartan does not inhibit ACE (kininase II), the enzyme that degrades bradykinin.
Barraminhekk Losartan ma jimpeddixxiex ACE (kininase II), l- enżima li tiddegrada bradykinin.
Consequently, there is no potentiation of undesirable bradykinin- mediated effects.
Konsegwentement, m’ hemmx effetti potenzjali mhux mixtieqa li jistgħu jsiru b’ bradykinin.
33 During administration of Losartan, removal of the angiotensin II negative feedback on renin secretion leads to increased plasma renin activity (PRA).
Waqt l- għoti ta ’ Losartan, it- tneħħija tar- rispons negattiv ta ’ angiotensin II fuq t- tnixxija ta ’ renin għandha twassal għal żieda fl- attività ta ’ renin fil- plażma (PRA - plasma renin activity).
Despite these increases, antihypertensive activity and suppression of plasma aldosterone concentration are maintained, indicating effective angiotensin II receptor blockade.
Minkejja dawn iż- żidied, l- attività kontra l- pressjoni għolja u t- trażżin tal- konċentrazzjoni ta ’ aldosterone fil- plażma huma mantenuti, li jindika impediment effettiv għar- riċettatur ta ’ angiotensin II.
After discontinuation of Losartan, PRA and angiotensin II values fell within three days to the baseline values.
Wara li losartan twaqqaf, il- valuri ta ’ PRA u angiotensin II waqgħu fi żmien tliet ijiem għal valuri ta ’ riferiment.
Both Losartan and its principal active metabolite have a far greater affinity for the AT1-receptor than for the AT2-receptor.
Kemm Losartan u anke l- metabolit prinċipali attiv tiegħu għandhom affinità akbar għal riċettatur AT1 milli għar- riċettatur AT2.
The active metabolite is 10- to 40- times more active than Losartan on a weight for weight basis.
Il- metabolit attiv huwa minn 10 darbiet sa 40 darba aktar attiv minn losartan fuq bażi ta ’ piż għal piż.
Hypertension Studies
Studji dwar il- Pressjoni Għolja
In controlled clinical studies, once-daily administration of Losartan to patients with mild to moderate essential hypertension produced statistically significant reductions in systolic and diastolic blood pressure.
Fi studji kliniċi b’ kontrolli, l- għoti darba fil- ġimgħa ta ’ Losartan lil pazjenti bi pressjoni essenzjali għolja minn ħafifa sa moderata ikkaġunat tnaqqis statistikament sinifikanti fil- pressjoni tad- demm sistolika u dijastolika.
Measurements of blood pressure 24 hours post-dose relative to 5 – 6 hours post-dose demonstrated blood pressure reduction over 24 hours; the natural diurnal rhythm was retained.
Il- kejl tal- pressjoni tad- demm 24 siegħa wara d- doża imqabbel ma ’ 5 - 6 sigħat wara d- doża wera tnaqqis fil- pressjoni fuq 24 siegħa; bir- ritmu diurnali naturali jibqa ’ jinżamm.
Blood pressure reduction at the end of the dosing interval was 70 – 80% of the effect seen 5-6 hours post- dose.
It- tnaqqis fil- pressjoni tad- demm fl- aħħar ta ’ l- intervall dożat kien ta ’ 70 – 80% ta ’ l- effett li deher 5 - 6 sigħat wara d- doża.
Losartan is equally effective in males and females, and in younger (below the age of 65 years) and older hypertensive patients.
Losartan huwa effettiv ugwalment kemm fin- nisa u kemm fl- irġiel, u f’ pazjenti iżgħar (taħt il- 65 sena) u anzjani li għandhom il- pressjoni għolja.
LIFE-Study The Losartan Intervention For Endpoint Reduction in Hypertension [LIFE] study was a randomised, triple-blind, active-controlled study in 9193 hypertensive patients aged 55 to 80 years with ECG- documented left-ventricular hypertrophy.
Studju LIFE L- istudju ta ’ Intervent b’ Losartan għal Tnaqqis fil- Punt ta ’ Riferiment Aħħari [LIFE] kien studju randomizzat, triple- blind, b’ kontrolli attivi li sar fuq 9, 193 pazjent bi pressjoni għolja fl- etajiet ta ’ bejn 55 sa 80 sena u b’ ipertrofija fil- ventrikula tax- xellug iddokumentata b’ ECG.
Patients were randomised to once daily Losartan 50 mg or once daily atenolol 50 mg.
Il- pazjenti kienu randomizzati għal doża ta ’ Losartan 50 mg darba kuljum u atenolol 50 mg darba kuljum.
If goal blood pressure (< 140/ 90 mmHg) was not reached, hydrochlorothiazide (12.5 mg) was added first and, if needed, the dose of Losartan or atenolol was then increased to 100 mg once daily.
Jekk il- pressjoni tad- demm bersalljata (< 140/ 90 mmHg) ma ntlaħqitx, ingħatat doża ta ’ hydrochlorothiazide (12. 5 mg) l- ewwel u, jekk meħtieġ id- doża ta ’ Losartan jew atenolol ġiet miżjuda sa 100 mg darba kuljum.
Other antihypertensives, with the exception of ACE-inhibitors, angiotensin II antagonists or beta-blockers were added if necessary to reach the goal blood pressure.
Mediċini kontra l- pressjoni għolja addizzjonali oħra, bl- eċċezzjoni ta ’ impedituri ACE, antagonisti ta ’ angiotensin II jew beta- blockers ġew magħduda jekk meħtieġ sabiex jintlaħaq l- għan li titnaqqas il- pressjoni tad- demm bersalljata.
The mean length of follow up was 4.8 years.
Iż- żmien medju ta ’ follow- up kien ta ’ 4. 8 snin
The primary endpoint was the composite of cardiovascular morbidity and mortality as measured by a reduction in the combined incidence of cardiovascular death, stroke and myocardial infarction.
Il- punt ta ’ riferiment aħħari prinċipali kien il- kompost ta ’ morbidità u mortalità kardjovaskulari kif imkejla bi tnaqqis fl- inċidenza kkombinata ta ’ mewt kardjovaskulari, puplesija u infart mijokardijaku.
Treatment with losartan resulted in a 13.0% risk reduction (p=0.021, 95% confidence interval 0.77-0.98) compared with atenolol for patients reaching the primary composite endpoint.
Dan kien
This was mainly attributable to a reduction of the incidence of stroke.
30 prinċipalment attribwit għall- inċidenza ta ’ puplesija.
Race In the LIFE-Study black patients treated with Losartan had a higher risk of suffering the primary combined endpoint, i. e. a cardiovascular event (e. g. cardiac infarction, cardiovascular death) and especially stroke, than the black patients treated with atenolol.
Razza Fl- istudju LIFE, il- pazjenti suwed ittrattati b’ Losartan kienu f’ riskju ogħla li jbatu minn punt prinċipali ta ’ riferiment kompost i. e. inċident kardjovaskulari (e. g. infart kardijaku, mewt kardjovaskulari) u speċjalment puplesija milli mill- pazjenti suwed ittrattati b’ atenolol.
Therefore the results observed with losartan in comparison with atenolol in the LIFE study with regard to cardiovascular morbidity/ mortality do not apply for black patients with hypertension and left ventricular hypertrophy.
Għalhekk, ir- riżultati osservati b’ losartan meta mqabbla ma ’ atenolol fl- istudju LIFE in konessjoni ma ’ morbidità/ mortalità kardjovaskulari ma japplikawx għal pazjenti suwed bi pressjoni għolja b’ ipertrofija fil- ventrikula tax - xellug.
34 RENAAL-Study The Reduction of Endpoints in NIDDM with the Angiotensin II Receptor Antagonist Losartan RENAAL study was a controlled clinical study conducted worldwide in 1513 Type 2 diabetic patients with proteinuria, with or without hypertension.
Studju RENAAL L- istudju kliniku b’ kontrolli magħruf bħala RENAAL, “ The Reduction of Endpoints in NIDDM with the Angiotensin II Receptor Antagonist Losartan ”, sar madwar id- dinja kollha fuq 1513- il pazjent dijabetiku ta ’ Tip 2 u bi protejnurja, bi jew mingħajr pressjoni għolja.
751 Patients were treated with Losartan The objective of the study was to demonstrate a nephroprotective effect of Losartan potassium over and above the benefit of a blood lowering pressure.
L- għan ta ’ l- istudju kien li juri l- effett nefroprotettiv ta ’ Losartan potassium lil hinn mill- benefiċċju ta ’ tnaqqis fil- pressjoni tad- demm.
Patients with proteinuria and a serum creatinine of 1.3 – 3.0 mg/ dl were randomised to receive Losartan 50 mg once a day, titrated if necessary, to achieve blood pressure response, or to placebo, on a background of conventional antihypertensive therapy excluding ACE-inhibitors and angiotension II antagonists.
Pazjenti bi protejnurja u b’ livelli ta ’ 1. 3 – 3. 0 mg/ dl ta ’ kreatinina fis- serum kienu randomizzati biex jirċievu Losartan 50 mg darba kuljum, b’ mod iddożat jekk meħtieġ, sabiex jintlaħaq rispons għal pressjoni tad- demm, jew għal plaċebo, fi sfond ta ’ terapija ta ’ kontra l- pressjoni konvenzjonali li teskludi impedituri ACE u antagonisti ta ’ angiotensin II.
Investigators were instructed to titrate the study medication to 100 mg daily as appropriate; 72% of patients were taking the 100 mg daily dose for the majority of the time.
Ir- riċerkaturi ngħataw struzzjonijiet biex ikunu jistgħu jiddożaw il- mediċina studjata għal 100 mg kuljum kif meħtieġ; 72% ta ’ pazjenti kienu qed jieħdu d- doża ta ’ 100 mg kuljum fil- maġġoranza tal- ħin.
Other antihypertensive agents (diuretics, calcium antagonists, alpha- and beta-receptor blockers and also centrally acting antihypertensives) were permitted as supplementary treatment depending on the requirement in both groups.
Mediċini ta ’ kontra l- pressjoni għolja (dijuretiċi, antagonisti tal- kalċju, impedituri ta ’ riċettaturi alfa u beta u wkoll mediċini ta ’ kontra l- pressjoni li jaġixxu b’ mod ċentrali) kienu permessi bħala trattament supplimentari skond il- ħtieġa ta ’ żewġ gruppi.
Patients were followed up for up to 4.6 years (3.4 years on average).
Pazjenti kienu segwiti għal sa 4. 6 snin (medja ta ’ 3. 4 snin).
The primary endpoint of the study was a composite endpoint of doubling of the serum creatinine end- stage renal failure (need for dialysis or transplantation) or death.
Il- punt ta ’ riferiment aħħari prinċipali ta ’ l- istudju kien punt ta ’ riferiment kompost ta ’ irdoppjar fil- livell ta ’ kreatinina fis- serum f’ insuffiċjenza renali ta ’ l- aħħar stadju (ħtieġa ta ’ dijaliżi jew trapjant) jew mewt.
The results showed that the treatment with Losartan (327 events) as compared with placebo (359 events) resulted in a 16.1% risk reduction (p = 0.022) in the number of patients reaching the primary composite endpoint.
Ir- riżultati wrew li t- trattament b’ Losartan (327 każ) meta mqabbel mal- plaċebo (359 każ) irriżulta fi tnaqqis fir- riskju ta ’ 16. 1% (p = 0. 022) fl- għadd ta ’ pazjenti li jilħqu l- punt ta ’ riferiment aħħari prinċipali kompost.
25.3% risk reduction for doubling of the serum creatinine (p = 0.006); 28.6% risk reduction for end-stage renal failure (p = 0.002); 19.9% risk reduction for end-stage renal failure or death (p = 0.009); 21.0% risk reduction for doubling of serum creatinine or end-stage renal failure (p = 0.01).
Għall- komposti kkombinati u individwali li ġejjin, ir- riżultati fil- punt ta ’ riferiment aħħari prinċipali wrew tnaqqis fir- riskju sinifikanti fil- grupp trattat b’ Losartan: tnaqqis fir- riskju bi 25. 3% għall- irdoppjar ta’ kreatinina fis- serum (p = 0. 006); tnaqqis ta ’ riskju bi 28. 6% għal insuffiċjenza fil- kliewi fl- aħħar stadju (p = 0. 002); tnaqqis ta ’ riskju ta ’ 19. 9% għal insuffiċjenza renali ta ’ l- aħħar stadju jew mewt (p = 0. 009); tnaqqis ta ’ riskju ta ’ 21. 0% għall- irdoppjar ta ’ kreatinina tas- serum jew insuffiċjenza renali ta ’ l- aħħar stadju (p = 0. 01).
All-cause mortality rate was not significantly different between the two treatment groups.
Ir- rata ta ’ mortalità għal kull kawża ma kinetx sinifikament differenti bejn iż- żewġ gruppi ta ’ trattament.
In this study losartan was generally well tolerated, as shown by a therapy discontinuation rate on account of adverse events that was comparable to the placebo group.
F’ dan l- istudju losartan kien ġeneralment ittollerat sew, kif muri b’ rata ta ’ waqfien ta ’ terapija dovuti għal każijiet avversi li kienet komparabbli mal- grupp ta ’ plaċebo.
ELITE I and ELITE II Study In the ELITE Study carried out over 48 weeks in 722 patients with heart failure (NYHA Class II-IV), no difference was observed between the patients treated with Losartan and those treated with captopril was observed with regard to the primary endpoint of a long-term change in renal function.
Studju ELITE I u ELITE II Fl- istudju ELITE li dam sejjer 48 ġimgħa fuq 722 pazjent b’ insuffiċjenza kardijaka (NYHA Klassi II- IV), ma kien hemm ebda differenza osservata bejn pazjenti trattati b’ Losartan u dawk trattati b ’ captopril dwar il- punt ta ’ riferiment aħħari prinċipali ta ’ bidla fuq perijodu ta ’ żmien fit- tul fil- funzjoni renali.
The observation of the ELITE I Study, that, compared with captopril, Losartan reduced the mortality risk, was not confirmed in the subsequent ELITE II Study, which is described in the following.
L- osservazzjoni ta ’ l- Istudju ELITE, li, mqabbel ma ’ captopril, Losartan naqqas ir- riskju ta ’ mortalità, ma ġiex ikkonfermat fl- Istudju sussegwenti ELITE II, li hu deskritt hawn isfel.
In the ELITE II Study Losartan 50 mg once daily (starting dose 12.5 mg, increased to 25 mg, then 50 mg once daily) was compared with captopril 50 mg three times daily (starting dose 12.5 m, increased to 25 mg and then to 50 mg three times daily).
Fl- Istudju ELITE II Losartan 50 mg li ngħata darba kuljum (b’ doża inizjali ta ’ 12. 5 mg, miżjuda għal 25 mg, imbagħad għal 50 mg darba kuljum) kien imqabbel ma ’ captopril 50 mg li ngħata tliet darbiet kuljum (doża tal- bidu ta ’ 12. 5 mg, miżjuda għal 25 mg u mbagħad għal 50 mg tliet darbiet kuljum).
The primary endpoint of this prospective study was the all-cause mortality.
Il- punt ta ’ riferiment aħħari prinċipali ta ’ dan l- istudju kienet il- mortalità ta ’ kull kawża.
In this study 3152 patients with heart failure (NYHA Class II-IV) were followed for almost two years (median:
31 F’ dan l- istudju 3, 152 pazjent b’ insuffiċjenza kardijaka (NYHA Klassi II- IV) kienu invistati għal madwar sentejn (medjan:
1.5 years) in order to determine whether Losartan is superior to captopril in reducing all cause mortality.
1. 5 sena) sabiex jiġi stabbilit jekk Losartan hux superjuri għal captopril biex inaqqas il- mortalità ta ’ kull kawża.
The primary endpoint did not show any statistically significant difference between Losartan and captopril in reducing all-cause mortality.
Il- punt ta ’ riferiment aħħari prinċipali ma wriex differenza statistikament differenti bejn Losartan u captopril fi tnaqqis tal- mortalità ta ’ kull kawża.
In both comparator-controlled (not placebo-controlled) clinical studies on patients with heart failure the tolerability of Losartan was superior to that of captopril, measured on the basis of a significantly lower rate of discontinuations of therapy on account of adverse events and a significantly lower frequency of cough.
Fiż- żewġ studji kliniċi komparattivi b’ kontrolli (mhux kontrollati bi plaċebo) fuq pazjenti b’ insuffiċjenza kardijaka, it- tollerabilità ta ’ Losartan kienet superjuri għal dik ta ’ captopril, imkejla fuq bażi ta ’ rata sinifikament mnaqqsa ta waqfiet mit- terapija minħabba każijiet avversi u frekwenza sinifikament mnaqqsa ta ’ sogħla.
An increased mortality was observed in ELITE II in the small subgroup (22% of all HF patients) taking beta-blockers at baseline.
Kienet osservata żieda fil- mortalità f’ ELITE II fis- sottogrupp (22% tal- pazjenti HF) li kien qed jieħu beta- blockers bħala punt ta ’ riferiment.
35 The antihypertensive effect of Cozaar was established in a clinical study involving 177 hypertensive pediatric patients 6 to 16 years of age with a body weight > 20 kg and a glomerular filration rate > 30 ml/ min/ 1.73 m2.
Pressjoni għolja fit- tfal L- effett kontra l- pressjoni għolja ta ’ Cozaar ġie stabbilit fi studju kliniku li kien jinvolvi 177 tifel u tifla bħala pazjenti bil- pressjoni għolja bejn l- etajiet ta ’ 6 snin u 16- il sena, b’ piż korporali ta ’ > 20 kg u b’ rata ta ’ filtrazzjoni glomerulari ta ’ > 30 ml/ min/ 1. 73m2.
Patients who weighted > 20kg to< 50 kg received either 2.5, 25 or 50 mg of losartan daily and patients who weighted > 50 kg received either 5, 50 or 100 mg of losartan daily.
Pazjenti li kienu jiżnu > 20 kg sa < 50 kg irċevew jew 2. 5, 25 jew 50 mg ta ’ losartan kuljum u pazjenti li kienu jiżnu > 50 kg irċevew jew 5, 50 jew 100 mg ta ’ losartan kuljum.
At the end of three weeks, losartan administration once daily lowered trough blood pressure in a dose-dependent manner.
Fl- aħħar ta ’ tliet ġimgħat, l- għoti ta ’ losartan darba kuljum naqqas il- pressjoni l- aktar baxxa tad- demm skond id- doża.
Overall, there was a dose-response.
Globalment, kien hemm rispons għad- doża.
The dose-response relationship became very obvious in the low dose group compared to the middle dose group (period I: -6.2 mmHg vs. -11.65 mmHg), but was attenuated when comparing the middle dose group with the high dose group (period I: -11.65 mmHg vs. -12.21 mmHg).
12. 21 mmHg).
The lowest doses studied, 2.5 mg and 5 mg, corresponding to an average daily dose of 0.07 mg/ kg, did not appear to offer consistent antihypertensive efficacy.
L- aktar dożi baxxi studjati, 2. 5 mg u 5 mg, li jikkorispondu għal doża medja ta ’ kuljum ta ’ 0. 07 mg/ kg, ma dehrux li jistgħu joffru effikaċja konsistenti kontra l- pressjoni għolja.
These results were confirmed during period II of the study where patients were randomized to continue losartan or placebo, after three weeks of treatment.
Dawn ir- riżultati kienu konfermati waqt perijodu II ta ’ l- istudju meta pazjenti kienu randomizzati biex jissoktaw jieħdu losartan jew plaċebo, wara tliet ġimgħat ta ’ terapija.
The difference in blood pressure increase as compared to placebo was largest in the middle dose group (6.70 mm Hg middle dose vs.
Id- differenza fiż- żieda fil- pressjoni tad- demm meta mqabbla mal- plaċebo kienet l- akbar fil- grupp tad- doża tan- nofs, (doża tan- nofs ta ’ 6. 70 mmHg vs.
The rise in trough diastolic blood pressure was the same in patients receiving placebo and in those continuing losartan at the lowest dose in each group, again suggesting that the lowest dose in each group did not have significant antihypertensive effect.
Iż- żieda fl- aktar pressjoni dijastolika baxxa kienet l- istess f’ pazjenti li kienu qed jirċievu u losarten fl- inqas doża f’ kull grupp, li jindika għal darb ’ oħra li l- inqas doża f’ kull grupp ma kelliex effett sinifikanti fuq il- pressjoni għolja.
Long-term effects of losartan on growth, puberty and general development have not been studied.
Effetti fuq tul ta ’ żmien ta ’ losartan fuq tkabbir, pubertà u żvilupp ġenerali ma ġewx studjati.
The long-term efficacy of antihypertensive therapy with losartan in childhood to reduce cardiovascular morbidity and mortality has also not been established.
L - effikaċja ta ’ terapija kontra l- pressjoni għolja b’ losartan fit- tfulija sabiex titnaqqas il- morbidità u l - mortalità kardjovaskulari għada ma ġietx stabbilita.
Following oral administration, losartan is well absorbed and undergoes first-pass metabolism, forming an active carboxylic acid metabolite and other inactive metabolites.
Wara li jingħata mill- ħalq, losartan jiġi assorbit sew u jgħaddi minn proċess ta ’ first- pass metabolism, bil- formazzjoni ta ’ metabolit attiv ta ’ carboxylic acid u metaboliti mhux attivi oħra.
Both losartan and its active metabolite are ≥ 99% bound to plasma proteins, primarily albumin.
Kemm losartan u l- metabolit attiv tiegħu huma ≥99% marbutin ma ’ proteini fil- plażma, prinċipalment l- albumina.
The volume of distribution of losartan is 34 litres.
Il- volum ta ’ distribuzzjoni ta ’ losartan hi ta ’ 34 litru.
About 14% of an intravenously- or orally-administered dose of losartan is converted to its active metabolite.
Madwar 14% ta ’ doża mogħtija ġol- vina - jew mill- ħalq - ta ’ losartan tinbidel fil- metabolit attiv tiegħu.
Following oral and intravenous administration of 14C-labeled losartan potassium, circulating plasma radioactivity primarily is attributed to losartan and its active metabolite.
Wara l- għoti mill- ħalq u ġol- vina ta ’ losartan potassium ittikkettat b’ 14C, ir- radjoattività 32 prinċipali fiċ- ċirkolazzjoni hija attribwita għal losartan u l- metabolit attiv tiegħu.
In addition to the active metabolite, inactive metabolites are formed.
Barra mill- metabolit attiv ifformat, metaboliti mhux attivi huma fformati wkoll.
Plasma clearance of losartan and its active metabolite is about 600 mL/ min and 50 mL/ min, respectively.
It- tneħħija ta ’ losartan mill- plażma u tal- metabolit attiv tiegħu hija ta ’ madwar 600 ml/ min u 50 ml/ min, rispettivament.
When losartan is administered orally, about 4% of the dose is excreted unchanged in the urine, and about 6% of the dose is excreted in the urine as active metabolite.
Meta losartan jiġi mogħti mill- ħalq, madwar 4% tad- doża tiġi eliminata mingħajr ma titbidel fl- urina, u madwar 6% tad- doża tiġi eliminata fl- urina bħala l- metabolit attiv.
36 Following oral administration, plasma concentrations of losartan and its active metabolite decline polyexponentially with a terminal half-life of about 2 hours and 6-9 hours, respectively.
Wara l- għoti mill- ħalq, il- konċentrazzjonijiet fil- plażma ta ’ losartan u l- metabolit attiv tiegħu jonqsu b’ mod poliesponenzjali b’ half- life terminali ta ’ madwar sagħtejn u 6- 9 sigħat, rispettivament.
Both biliary and urinary excretion contribute to the elimination of losartan and its metabolites.
Kemm l- eliminazzjoni biljari u dik urinarja jikkontribwixxu għall- eliminazzjoni ta ’ losartan u l- metabolit tiegħu.