qanastek/EMEA-V3 huggingface dataset:
Coadministration of a thiazide may increase the incidence of hypersensitivity reactions to allopurinol.
L- għoti konġunt ta ’ thiazide jista ’ jgħolli l- inċidenza ta ’ reazzjonijiet ta ’ sensittività eċċessiva għal allopurinol.
Anticholinergic agents (e. g. atropine, biperiden) Increase of the bioavailability to thiazide-type diuretics by decreasing gastrointestinal motility and stomach emptying rate.
Sustanzi antikolinerġiċi (eż. atropine, biperiden) Żieda fil- bijodisponibilità ta ’ dijuretiċi tat- tip thiazide bi tnaqqis ta ’ motilità gastro- intestinali u fir - rata ta ’ l- iżvojtar ta ’ l- istonku.
Cytotoxic agents (eg cyclophosphamide, methotrexate) Thiazides may reduce the renal excretion of cytotoxic medicinal products and potentiate their myelosuppressive effects.
Sustanzi ċitotossiċi (eż cyclophosphamide, methotrexate) Thiazides jistgħu jnaqqsu l- eliminazzjoni mill- kliewi ta ’ prodotti mediċinali ċitotossiċi u jħarrxu l - effetti majelosuppressivi tagħhom.
Salicylates In case of high dosages of salicylates hydrochlorothiazide may enhance the toxic effect of the salicylates on the central nervous system.
Salicylates F’ każ ta ’ dożi għoljin ta ’ salicylates, hydrochlorothiazide jista ’ jħarrax l- effetti tossiċi ta ’ salicylates fuq is- sistema nervuża ċentrali.
Methyldopa There have been isolated reports of haemolytic anaemia occurring with concomitant use of hydrochlorothiazide and methyldopa.
Methyldopa Kien hemm rapporti iżolati ta ’ anemija emolitika li seħħet meta hydrochlorothiazide u methyldopa ngħataw flimkien.
Cyclosporine Concomitant treatment with cyclosporine may increase the risk of hyperuricaemia and gout-type complications.
Cyclosporine Trattament flimkien ma ’ cyclosporine jista ’ jżid ir- riskju għal iperurikemija u kumplikazzjonijiet tat- tip tal- gotta.
Digitalis glycosides Thiazide-induced hypokalaemia or hypomagnesaemia may favour the onset of digitalis-induced cardiac arrhythmias.
24 Glikoċidi ta ’ diġitalis Ipokalemija jew ipomagnesemja sensitizzati b’ thiazide jistgħu jifavorixxu l- bidu ta ’ arritmiji kardijaċi indotti b’ diġitalis
Losartan/ hydrochlorothiazide is administered with medicinal products affected by serum potassium disturbances (e. g. digitalis glycosides and antiarrhythmics) and with the following torsades de pointes
Prodotti mediċinali affettwati b’ disturbi tal- potassju fis- serum Monitoraġġ perijodiku għal potassju fis- serum u ECG huma rakkomandati meta Losartan/ hydrochlorothiazide jiġu mogħtija ma ’ prodotti mediċinali affettwati b’ disturbi ta ’ potassju fis- serum (eż. glikoċidi ta ’ diġitalis u mediċini anti- arritmiċi) u bit- torsades de pointes li ġejjin (takikardja ventrikulari) tal- prodotti mediċinali li jissensitizzaw (li jinkludu xi anti- arritmiċi), l- ipokalemja tkun fattur ta ’ riskju għal torsades de pointes (takikardja ventrikulari):
• Class Ia antiarrythmics (eg quinidine, hydroquinidine, disopyramide). • Class III antiarrythmics (eg amiodarone, sotalol, dofetilide, ibutilide). • Some antipsychotics (eg thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol). • Others (eg bepridil, cisapride, diphemanil, erythromycin IV, halofantrin, mizolastin, pentamidine, terfenadine, vincamine IV).
• Antiarritmiċi ta ’ Klassi Ia (eż. quinidine, hydroquinidine, disopyramide). • Antiarritmiċi ta ’ Klassi III (eż. amiodarone, sotalol, dofetilide, ibutilide). • Xi antipsikotiċi (eż. thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol). • Oħrajn (eż bepridil, cisapride, diphemanil, erythromycin IV, halofantrin, mizolastin, pentamidine, terfenadine, vincamine IV).
Calcium salts Thiazide diuretics may increase serum calcium levels due to decreased excretion.
Mluħa tal- kalċju Id- dijuretiċi ta ’ thiazide jistgħu jgħollu l- livell ta ’ kalċju fis- serum minħabba tnaqqis fl- eliminazzjoni.
If calcium supplements must be prescribed, serum calcium levels should be monitored and calcium dosage should be adjusted accordingly.
Jekk supplimenti tal- kalċju għandhom jiġu preskritti, il- livelli ta ’ kalċju fis- serum għandhom jiġu monitorati u d- doża ta ’ kalċju għandha tiġi aġġustata skond dan.
Laboratory Test Interactions Because of their effects on calcium metabolism, thiazides may interfere with tests for parathyroid function (see section 4.4).
Interazzjonijiet tal- mediċina/ testijiet tal- laboratorju Minħabba l- effetti tagħhom fuq il- metaboliżmu tal- kalċju, thiazides jistgħu jinterferixxu ma ’ testijiet għal funzjoni tal- paratirojde (ara sezzjoni 4. 4).
Carbamazepine Risk of symptomatic hyponatremia.
Carbamazepine Riskju ta ’ iponatremja sintomatika.
Clinical and biological monitoring is required.
Monitoraġġ kliniku u bijoloġiku meħtieġ.
Iodine Contrast Media In case of diuretic-induced dehydration, there is an increased risk of acute renal failure, especially with high doses of the iodine product.
Medja ta ’ Kuntrast bil- Jodju F’ każ ta ’ deidrazzjoni sensitizzata b’ dijuretiku, hemm riskju ogħla ta ’ insuffiċjenza renali akuta, speċjalment b’ dożi għoljin tal- prodott jodiku.
Patients should be rehydrated before the administration.
Il- pazjenti għandhom jiġu idrati mill- ġdid qabel l- għoti.
Amphotericin B (parenteral), corticosteroids, ACTH or stimulant laxatives Hydrochlorothiazide may intensify electrolyte imbalance, particularly hypokalaemia.
Amphotericin B (parenterali), kortikosterojds, ACTH jew purganti stimulanti Hydrochlorothiazide għandu mnejn jintensifika l- iżbilanċ elettrolitiku, b’ mod partikolari l - ipokalemija
Pregnancy The use of Cozaar Comp is not recommended during the first trimester of pregnancy (see section 4.4).
L- użu ta ’ Cozaar Comp mhux rakkomandat waqt l- ewwel tliet xhur ta ’ tqala (ara sezzjoni 4. 4).
The use of Cozaar Comp is contra-indicated during the 2nd and 3rd trimester of pregnancy (see section 4.3 and 4.4).
L- użu ta ’ Cozaar- Comp 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 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 m’ hemmx dejta epidemjoloġika b’ kontrolli fuq ir- riskju b’ Impedituri għar - Riċettaturi ta ’ Amgiotensin II (AIIRAs), riskji simili 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 tkomplija bit- terapija b’ ARB 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 Cozaar Comp should be stopped immediately and, if appropriate, alternative therapy should be started.
Meta tqala tiġi dijanjonizzata, it- trattament b’ Cozaar Comp għandu jitwaqqaf immedjatament, u jekk jixraq, terapija alternattiva għandha tinbeda.
Cozaar Comp 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’ Cozaar Comp 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 Cozaar Comp have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
25 Jekk l- espożizzjoni għal Cozaar- Comp tkun seħħet mit- tieni xahar ta ’ tqala, verifiċi bl- ultrasawnd għal funzjoni renali u l- kranju huma rakkomandati.
Infants whose mothers have taken Cozaar Comp should be closely observed for hypotension (see also section 4.3 and 4.4).
Trabi li ommhom tkun ħadet Cozaar Comp għandhom jiġu osservati għal pressjoni baxxa (ara wkoll sezzjonijiet 4. 3 u 4. 4).
Hydrochlorothiazide may reduce both plasma volume and uteroplacental blood flow.
Hydrochlorothiazide għandu jnaqqas kemm il- volum ta ’ plażma kif ukoll il- fluss uteroplaċentali tad- demm.
Thiazides pass the placental barrier and are found in cord blood.
Thiazides jgħaddu mis- sekonda u jinsabu wkoll fid- demm tal- kurdun.
26 possibly other reactions that have been observed in adults.
Jistgħu joħolqu disturbi elettrolitiċi fetali u possibilment reazzjonijiet oħra li ġew osservati f’ adulti.
Cases of thrombocytopenia in neonates and fetal or neonatal jaundice were reported after treating the mothers with thiazides.
Każijiet ta ’ tromboċitopenija fi trabi għadhom jitwieldu u suffejra fetali jew fi trabi għadhom jitwieldu ġew rapportati wara li ommijiet ġew ittrattati b’ thiazides.
Lactation It is not known whether losartan is excreted in human milk.
Treddigħ Mhux magħruf jekk losartan jiġix eliminat fil- ħalib ta ’ l- omm.
However, losartan is excreted in the milk of lactating rats.
Madankollu losartan huwa eliminat fil- ħalib ta ’ firien qegħdin ireddgħu.
Thiazides pass into human milk and may inhibit lactation.
Thiazides jgħaddu fil- ħalib tal- bniedem u jistgħu jimpedixxu t- treddigħ.
Because of the potential for adverse effects on the nursing infant, Cozaar Comp is contraindicated during breast-feeding (see section 4.3).
Minħabba l- potenzjal għal effetti avversi fuq it- trabi mredda ’, Cozaar Comp hu kontra- indikat waqt it- treddigħ (ara sezzjoni 4. 3).
However, when driving vehicles or operating machinery it must be borne in mind that dizziness or drowsiness may occasionally occur when taking antihypertensive therapy, in particular during initiation of treatment or when the dose is increased.
Madankollu, meta wieħed issuq vetturi jew iħaddem magni, wieħed għandu jżomm quddiem għajnejh li sturdamenti jew ngħas jistgħu iseħħu ta ’ spiss meta wieħed jieħu terapija kontra l- pressjoni għolja, b’ mod partikolari waqt il- bidu tat- tratatment jew meta tiżdied id- doża.
The adverse events below are classified where appropriate by system organ class and frequency according to the following convention:
Il- każijiet avversi t’ hawn isfel huma klassifikati fejn jixraq skond il- klassi ta ’ l- organi tas- sistema u l- frekwenza skond il- konvenzjoni li ġejja:
Very common: ≥ 1/ 10 Common:
Komuni ħafna: ≥ 1/ 10 Komuni:
Rare:
≥ 1/ 100, < 1/ 10
≥ 1/ 100, < 1/ 10 ≥ 1/ 1,000, ≤ 1/ 100 ≥ 1/ 10,000, ≤ 1/ 1,000 ≤ 1/ 10,000 ≤ 1/ 10,000
Mhux komuni: ≥ 1/ 1, 000, ≤ 1/ 100 Rari: ≥ 1/ 10, 000, ≤ 1/ 1, 000 Rari ħafna:
(cannot be estimated from the available data)
Mhux magħruf: ≤ 1/ 10, 000 (ma jistax jiġi stmat mit- tagħrif disponibbli)
In clinical trials with losartan potassium salt and hydrochlorothiazide, no adverse events peculiar to this combination of substances were observed.
Fi provi kliniċi bil- melħ ta ’ losartan potassium u hydrochlorothiazide, ma ġewx osservati każijiet avversi partikulari għal din il- mediċina kkombinata.
The adverse events were restricted to those which were formerly observed with losartan potassium salt and/ or hydrochlorothiazide.
Il- każijiet avversi kienu ristretti għal dawk rapportati qabel b’ losartan potassium u/ jew hydrochlorothiazide.
In controlled clinical trials for essential hypertension, dizziness was the only adverse experience reported as substance-related that occurred with an incidence greater than placebo in 1% or more of patients treated with losartan and hydrochlorothiazide.
Fi provi kliniċi b’ kontrolli għal pressjoni essenzjali għolja, l- isturdament kien l- uniku każ avvers rapportat bħala relatat mas- sustanza li seħħ b’ inċidenza akbar minn plaċebo f’ 1% jew aktar ta ’ pazjenti trattati b’ losartan u hydrochlorothiazide.
Next to these effects, there are further adverse reactions reported after the introduction of the product to the market as follows:
Barra dawn l- effetti, kien hemm aktar reazzjonijiet avversi relatati rapportati wara l- introduzzjoni tal- prodott fis- suq kid ġej:
Hepato-biliary disorders Rare:
Disturbi fil- fwied u fil- marrara Rari:
Hyperkalaemia, elevation of ALT
Iperkalemija, livell ogħal ta ’ ALT
Additional adverse events that have been seen with one of the individual components and may be potential adverse events with losartan potassium/ hydrochlorothiazide are the following:
Każijiet avversi addizzjonali li seħħew b’ wieħed mill- komponenti individwali u li jista ’ jikkawża effetti avversi potenzjali b’ losartan potassium/ hydrochlorothiazide huma li ġejjin:
Losartan
26 Losartan
Anaemia, Henoch-Schönlein purpura, ecchymosis, haemolysis
Disturbi tad- demm u tas- sistema limfatika Mhux komuni: anemija, purpura Henoch- Schönlein, eċċimosi, emolisi
Anaphylactic reactions, angioedema, urticaria
Reazzjonijiet anafilattiċi, anġjodema, urtikarja
27 Metabolism and nutrition disorders Uncommon:
Disturbi fil- metaboliżmu u n- nutrizzjoni Mhux komuni:
Anorexia, gout
Anoreksja, gotta
Insomnia Uncommon:
Nuqqas ta ’ rqad
Anxiety, anxiety disorder, panic disorder, confusion, depression, abnormal dreams, sleep disorder, somnolence, memory impairment
Ansjetà, Disturb dwar l- ansjetà, Disturb ta ’ paniku, konfużjoni, dipressjoni, ħolm abnormali, disturbi fl- irqad, ħedla, memorja mfixxkla
Headache, dizziness Uncommon:
Uġigħ ta ’ ras, sturdament
Nervousness, paraesthesia, peripheral neuropathy, tremor, migraine, syncope
Nervożità, paraestesja, newropatija periferika, rogħda, emikranja, sinkope
Eye disorders Uncommon:
Disturbi fl- għajnejn Mhux komuni:
Blurred vision, burning/ stinging in the eye, conjunctivitis, decrease in visual acuity
Vista mċajpra, ħruq/ tingiż fl- għajn, konġuntivite, tnaqqis fiċ- ċarezza tal- vista.
Vertigo, tinnitus
Vertġini, tinnite
Hypotension, orthostatic hypotension, sternalgia, angina pectoris, grade II-AV block, cerebrovascular event, myocardial infarction, palpitation, arrhythmias (atrial fibrillations, sinus bradycardia, tachycardia, ventricular tachycardia, ventricular fibrillation)
Pressjoni baxxa, pressjoni baxxa malli tqum minn pożizzjoni ta ’ serħan, sternalġja, anġina pectoris, grad II - blokk AV, każ ċerebrovaskulari, infart mijokardijaku, palpitazzjoni, arritmiji (fibrillazzjonijiet atrijali, bradikardja tas- sinus, takikardja ventrikulari, fibrillazzjoni ventrikulari)
Cough, upper respiratory infection, nasal congestion, sinusitis, sinus disorder Uncommon:
Sogħla, infezzjoni fil- passaġġ ta ’ fuq, konġestjoni nażali, sinusite, disturb fis- sinus
Pharyngeal discomfort, pharyngitis, laryngitis, dyspnoea, bronchitis, epistaxis, rhinitis, respiratory congestion
Skumdità farinġeali, farinġite, larinġite, dispnea, bronkite, epistassi, rinite, konġestjoni respiratorja
Abdominal pain, nausea, diarrhoea, dyspepsia Uncommon:
Uġigħ addominali, nawsea, dijarea, dispepsja
Constipation, dental pain, dry mouth, flatulence, gastritis, vomiting
Stitikezza, uġigħ fis- snien, ħalq xott, gass, gastrite, remettar
Hepato-biliary disorders Not known:
Disturbi fil- fwied u fil- marrara Mhux magħruf:
Liver function abnormalities
Abnormalitajiet fil- funzjoni tal- fwied
Skin and subcutaneous tissue disorders Uncommon:
Disturbi fil- ġilda u tat- tessut ta ’ taħt il- ġilda Mhux komuni:
Alopecia, dermatitis, dry skin, erythema, flushing, photosensitivity, pruritus, rash, urticaria, sweating
Alopeċja, dermatite, ġilda xotta, eritema, ħmura, fotosensittività, ħakk, raxx, urtikarja, togħrieq
Musculoskeletal and connective tissue disorders Common:
Disturbi muskolu- skeletriku u tat- tessut konnettiv Komuni:
Muscle cramp, back pain, leg pain, myalgia Uncommon:
Bugħawwieġ, uġigħ fid- dahar, uġigħ fir- riġlejn, uġigħ fil- muskolu
Arm pain, joint swelling, knee pain, musculoskeletal pain, shoulder pain, stiffness, arthralgia, arthritis, coxalgia, fibromyalgia, muscle weakness
Uġigħ fid- dirgħajn, tinfiħ tal- ġogi, uġigħ fl- irkoppa, uġigħ muskoloskeletriku, uġigħ fl- ispallejn, ebusija, artrite, koxalġja, fibromajlaġja, debolezza muskolari.
Nocturia, urinary frequency, urinary tract infection
Nokturja, frekwenza awrinarja, infezzjoni fil- passaġġ awrinarju
Reproductive system and breast disorders Uncommon:
27 Disturbi fis- sistema riproduttiva u fis- sider Mhux komuni:
Decreased libido, impotence
Tnaqqis fl- aptit sesswali, impotenza
Asthenia, fatigue, chest pain
Astenja, għeja, uġigħ fis- sider
28 Uncommon:
Mhux komui:
Facial oedema, fever
Edema fil- wiċċ, deni
Hyperkalaemia, mild reduction of haematocrit and haemoglobin Uncommon:
Iperkalemja, tnaqqis ħafif fil- ematokrit u l- emoglobina
Mild increase in urea and creatinine serum levels Very rare:
Żieda ħafifa fil- livelli ta ’ urea u kreatinina fis- serum Rari ħafna:
Increase in hepatic enzymes and bilirubin.
Żieda fl- enżimi epatiċi u bilirubin
Agranulocytosis, aplastic anaemia, haemolytic anaemia, leukopenia, purpura, thrombocytopenia
Agranuloċitosi, anemija aplastika, anemija emolitika, lewkopenja, purpura, tromboċitopenija
Anorexia, hyperglycaemia, hyperuricaemia, hypokalaemia, hyponatraemia
Anoreksja, ipergliċemija, iperuriċemija, ipokalemja, iponatremja
Cephalalgia
Ċefalalġja
Transient blurred vision, xanthopsia Vascular disorders Uncommon:
Vista mċajjra għaddiena, ksantopsja
Necrotizing angiitis (vasculitis, cutaneous vasculitis)
Anġijite nekrotizzanti (vaskulite, vaskulite kutanea)
Respiratory, thoracic and mediastinal disorders Uncommon:
Mhux magħruf:
Respiratory distress including pneumonitis and pulmonary oedema
Distress respiratorju (li jinkludi pnewmonite u edema pulmonari)
Gastrointestinal disorders Uncommon:
Mhux magħruf:
Sialoadenitis, spasms, stomach irritation, nausea, vomiting, diarrhoea, constipation
Sijaloadenite, spażmi, irritazzjoni fl- istonku, tqalligħ, remettar, dijarea, stitikezza
Hepato-biliary disorders Uncommon:
Disturbi fil- fwied u fil- marrara:
Icterus (intrahepatic cholestatis), pancreatitis
Ikterus, (suffejra kolestatika intraepatika), pankreatite
Skin and subcutaneous tissue disorders Uncommon:
Disturbi tal- ġilda u fit- tessuti ta ’ taħt il- ġilda Mhux magħruf:
Photosensitivity, urticaria, toxic epidermal necrolysis
Reazzjonijiet ta ’ sensittività għad- dawl, urtikarja, nekrolisi epidermali tossika
Musculoskeletal and connective tissue disorders Uncommon:
Mhux magħruf:
Renal and urinary disorders Uncommon:
Disturbi fil- kliewi u fis- sistema urinarja:
Glycosuria, interstitial nephritis, renal dysfunction, renal failure
Glikosurja, nefrite interstizjali, problemi fil- funjoni renali, insuffiċjenza renali
General disorders and administration site conditions Uncommon:
Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata Mhux komuni:
Fever, dizziness
Deni, stordament
4.9 Overdose
28 4. 9 Doża eċċessiva
No specific information is available on the treatment of overdosage with Cozaar Comp.
L- ebda tagħrif speċifiku mhu disponibbli dwar kura għal doża eċċessiva b’ Cozaar Comp.
Treatment is symptomatic and supportive.
Il- kura hija sintomatika u ta ’ appoġġ.
Therapy with Cozaar Comp should be discontinued and the patient observed closely.
It- terapija b’ Cozaar Comp għandha titwaqqaf u l- pazjent għandu jiġi osservat mill- qrib.
29 correction of dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures.
Miżuri ssuġġeriti jinkludu t- tqanqil ta ’ emesi jekk it- teħid sar riċentement, u korrezzjoni ta ’ deidrazzjoni, żbilanċ elettrolitiku, koma epatika u pressjoni baxxa bi proċeduri stabbiliti.
Losartan Limited data are available in regard to overdosage in humans.
Losartan Hemm tagħrif ristrett dwar każijiet ta ’ doża eċċessiva fil- bniedem.
The most likely manifestation of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation.
L- aktar manifestazzjoni probabbli ta ’ doża eċċessiva tkun presjoni baxxa u takikardja; bradikardja tista ’ sseħħ minn stimulazzjoni parasimpatetika (vegus).
If symptomatic hypotension should occur, supportive treatment should be instituted.
Jekk ikun hemm pressjoni sintomatika baxxa, trattament ta ’ appoġġ għandu jiġi mibdi.
Neither losartan nor the active metabolite can be removed by hemodialysis.
La losartan u lanqas il- metabolit attiv ma jistgħu jiġu eliminati f’ emodijaliżi.
Hydrochlorothiazide The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis.
L- aktar sinjali u sintomi komuni osservati huma dawk ikkawżati bi żvojtar elettrolitiku (ipokalemija, ipokloremja, iponatremja) u diżidrazzjoni li tirrużulta minn dijuresi eċċessiva.
If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.
Jekk digitalis ġie mogħti wkoll, ipokalemja jista ’ jimmodera l- arritmiji kardijaċi.
The degree to which hydrochlorothiazide is removed by hemodialysis has not been established.
Il- grad li bih hydrochlorothiazide jitneħħa f’ emodijaliżi għadu ma ġiex stabbilit.
Combination containing an angiotensin II-receptor(type AT1)-antagonist and a thiazide diuretic, Antihypertensive, ATC code:
Mediċina kkombinata li fiha antagonist tar- riċettatur ta ’ angiotensin II (tip AT1) u dijuretiku ta ’ thiazide, Mediċina ta ’ kontra l- pressjoni għolja Kodiċi ATC:
Losartan-Hydrochlorothiazide
Losartan- Hydrochlorothiazide
The components of Cozaar Comp have been shown to have an additive effect on blood pressure reduction, reducing blood pressure to a greater degree than either component alone.
Il- komponenti ta ’ Cozaar Comp intwerew li għandhom effett addittiv fit- tnaqqis tal- pressjoni tad- demm, billi jnaqqsu l- pressjoni tad- demm fi grad ogħla minn dawk ta ’ xi komponent waħdu biss.
This effect is thought to be a result of the complimentary actions of both components.
Dan l- effett hu maħsub li huwa r- riżultat ta ’ azzjonijiet kumplimentari taż- żewġ komponenti.
Further, as a result of its diuretic effect, hydrochlorothiazide increases plasma renin activity, increases aldosterone secretion, decreases serum potassium, and increases the levels of angiotensin II.
Barraminhekk, bħala riżultat ta ’ l- effett dijuretiku, hydrochlorothiazide iżid l- attività ta ’ renin fil- plażma, iżid it- tnixxija ta ’ aldosterone, inaqqas il- potassju fis- serum, u jżid l- effetti ta ’ angiotensin II.
Administration of losartan blocks all the physiologically relevant actions of angiotensin II and through inhibition of aldosterone could tend to attenuate the potassium loss associated with the diuretic.
L- għoti ta ’ losartan jimpedixxi l- effetti fiżjoloġiċi rilevanti kollha ta ’ angiotensin II u permezz ta ’ l- impediment ta ’ aldosterone għandu mnejn jimmodera t- telf ta ’ potassju assoċjat mad- dijuretiku.
Losartan has been shown to have a mild and transient uricosuric effect.
Losartan intwera li għandu effett urikosuriku ħafif u għaddien.
Hydrochlorothiazide has been shown to cause modest increases in uric acid; the combination of losartan and hydrochlorothiazide tends to attenuate the diuretic-induced hyperuricemia.
Hydrochlorothiazide intwera li jikkaġuna żidied apprezzabbli fl- aċidu uriku; il- kombinazzjoni ta ’ losartan u hydrochlorothiazide għandu mnejn jimmodera l- iperurikemja sensitizzata bid- dijuretiku.
The antihypertensive effect of Cozaar Comp is sustained for a 24-hour period.
L- effett kontra l- pressjoni għolja ta ’ Cozaar Comp huwa sostnut għal perijodu ta ’ 24 siegħa.
In clinical studies of at least one year's duration, the antihypertensive effect was maintained with continued therapy.
Fi studji kliniċi li damu ta ’ lanqas sena, l- effett kontra l- pressjoni għolja inżamm għal ta ’ lanqas sena b’ terapija kontinwa.
Despite the significant decrease in blood pressure, administration of Cozaar Comp had no clinically significant effect on heart rate.
Minkejja t- tnaqqis sinifikanti fil- pressjoni tad- demm, l- għoti ta ’ Cozaar Comp ma kellux effett sinifikanti fuq ir- rata ta ’ taħbit tal- qalb.
In clinical trials, after 12 weeks of therapy with losartan 50 mg/ hydrochlorothiazide 12.5 mg, trough sitting diastolic blood pressure was reduced by an average of up to 13.2 mmHg.
Fi provi kliniċi, wara 12- il sena ta ’ terapija b’ 50 mg losartan / 12. 5 mg hydrochlorothiazide, il- pressjoni dijastoka l- aktar baxxa meta bilqiegħda tnaqqset għal medja ta ’ 13. 2 mmHg.
Cozaar Comp is effective in reducing blood pressure in males and females, blacks and non-blacks and in younger (< 65 years) and older (≥ 65 years) patients and is effective in all degrees of hypertension.
29 Cozaar Comp huwa effettiv biex inaqqas il- pressjoni tad- demm f’ irġiel u nisa, persuni suwed u dawk mhux suwed u f’ pazjenti iżgħar (< 65 years) u akbar (≥65 years) u hu effettiv f’ kull grad tal- pressjoni għolja.
Losartan is a synthetically produced oral angiotensin-II receptor (type AT1) antagonist.
Losartan huwa riċettatur antagonista sintetiku u orali ta ’ angiotensin- II (tip AT1).
Angiotensin II, a potent vasoconstrictor, is the primary active hormon 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)
Angiotensin II jintrabat mar- riċettatur AT1 li jinstab f’ ħafna tessuti (eż.
30 and elicits several important biological actions, including vasoconstriction and the release of aldosterone. Angiotensin II also stimulates smooth-muscle cell proliferation.
Angiotensin II jissensitizza wkoll il- proliferazzjoni taċ- ċelloli lixxi tal- muskoli.
Losartan selectively blocks the AT1 receptor.
Losartan jimblokka b’ mod silettiv ir- riċettatur AT1.
In vitro and in vivo losartan and its pharmacologically active carboxylic acid metabolite E-3174 block all physiologically relevant actions of angiotensin II, regardless of the source or route of its synthesis.
Losartan in vitro u in vivo u l- metabolit farmakoloġikament attiv tiegħu ta ’ carboxylic acid, E- 3174 jimblokka l- azzjonijiet fiżjoloġiċi rilevanti kollha ta ’ angiotensin II, irrispettivament tas- sors jew il- passaġġ fis- sintesi tiegħu.
Losartan does not have an agonist effect nor does it block other hormone receptors or ion channels important in cardiovascular regulation.
Losartan m’ għandux effett agonista u lanqas ma jimblokka riċettaturi ormonali oħra jew kanali ijoniċi importanti fil- kontroll kardjovaskulari.
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 thus no increase in bradykinin-mediated undesirable effects.
Konsegwentement, m’ hemmx effetti potenzjali mhux mixtieqa li jistgħu jsiru b’ bradykinin.
During the administration of losartan the 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).
Increase in the PRA leads to an increase in angiotensin II in plasma.
Żieda fil- PRA twassal għal żieda f’ angiotensin II fil- plażma.
Despite these increases, antihypertensive activity and suppression of the plasma aldosterone concentration are maintained, indicating effective angiotensin II receptor blockade.
Minkejja dawn iż- żidiet, 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 the discontinuation of losartan, PRA and angiotensin II values fell within 3 days to the baseline values.
Wara l- waqfien ta ’ losartan, 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.
In a study specifically designed to assess the incidence of cough in patients treated with losartan as compared to patients treated with ACE inhibitors, the incidence of cough reported by patients receiving losartan or hydrochlorothiazide was similar and was significantly less than in patients treated with an ACE inhibitor.
Fi studju speċifikament ippjanat biex janalizza l- inċidenza ta ’ sogħla f’ pazjenti trattati b’ losartan meta mqabbla ma ’ pazjenti trattati b’ impedituri ACE, l- inċidenza ta ’ sogħla rapportata minn pazjenti li qed jirċievu losartan jew hydrochlorothiazide kienet simili u kienet sinifikament inqas milli f’ pazjenti trattati b’ impeditur ACE.
In addition, in an overall analysis of 16 double-blind clinical trials in 4131 patients, the incidence of spontaneously reported cough in patients treated with losartan was similar (3.1%) to that of patients treated with placebo (2.6%) or hydrochlorothiazide (4.1%), whereas the incidence with ACE inhibitors was 8.8%.
Barraminhekk, f’ analiżi globali ta ’ 16- il prova klinika double- blind f’ 4131 pazjent, l- inċidenza ta ’ sogħla rapportata spontanjament f’ pazjenti trattati b’ losartan kienet simili (3. 1%) għal dik trattata bi plaċebo (2. 6%) jew hydrochlorothiazide (4. 1%), filwaqt li l- inċidenza ta ’ impedituri ACE kienet ta ’ 8. 8%.
In nondiabetic hypertensive patients with proteinuria, the administration of losartan potassium significantly reduces proteinuria, fractional excretion of albumin and IgG.
F’ pazjenti bi pressjoni għolja li m’ humiex dijabetiċi u bi protejnurja, l- għoti ta ’ losartan potassium inaqqas b’ mod sinifikanti l- protejnurja, l- eliminazzjoni parzjali ta ’ albumina u IgG.
Losartan maintains glomerular filtration rate and reduces filtration fraction.
Losartan iżomm ir- rata ta ’ filtrazzjoni glomerulari u jnaqqas il- porzjon ta ’ filtrazzjoni.
Generally losartan causes a decrease in serum uric acid (usually < 0.4 mg/ dL) which was persistent in chronic therapy.
Ġeneralment losartan jikkaġuna tnaqqis fl- aċidu uriku fis- serum (ġeneralment < 0. 4 mg/ dl) persistenti f’ terapija kronika.
Losartan has no effect on autonomic reflexes and no sustained effect on plasma norepinephrine.
Losartan m’ għandux effett fuq riflessi awtoawtonomiċi u l- ebda effett sostnut fuq norepinephrine fil - plażma.
In patients with left ventricular failure, 25 mg and 50 mg doses of losartan produced positive hemodynamic and neurohormonal effects characterized by an increase in cardiac index and decreases in pulmonary capillary wedge pressure, systemic vascular resistance, mean systemic arterial pressure and heart rate and a reduction in circulating levels of aldosterone and norepinephrine, respectively.
F’ pazjenti li għandhom insuffiċjenza ventrikulari tan- naħa tax- xellug, dożi ta ’ 25 mg u 50 mg ta ’ losartan ipproduċa effetti emodinamiċi u newro- ormonali pożittivi ikkaraterizzati b’ żieda fl- indiċi kardijaku u tnaqqis fil- pulmonary capillary wedge pressure, reżistenza vaskulari sistematika, pressjoni arterjali sistematika medja u r- rata tal- qalb u tnaqqis fil- livelli ċirkolatorji ta aldosterone u norepinephrine, rispettivament.
The occurrence of hypotension was dose related in these heart failure patients.
Il- każijiet ta ’ pressjoni baxxa kienu relatati mad- doża f’ dawn il- pazjenti b’ insuffiċjenza kardijaka
Hypertension Studies
30 Studji ta ’ 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 ikkaġuna 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.
Discontinuation of Losartan in hypertensive patients did not result in an abrupt rise in blood pressure (rebound).
It- twaqqif ta ’ Losartan f’ pazjenti bil- pressjoni għolja ma rriżultatx f’ żieda f’ daqqa fil- pressjoni tad- demm (rebound).
Despite the marked decrease in blood pressure, Losartan had no clinically significant effects on heart rate.
Minkejja t- tnaqqis notevoli fil- pressjoni tad- demm, Losartan ma kellux effetti sinifikanti kliniċi fuq ir- rata ta ’ taħbit tal- qalb.
31 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 50 mg losartan jew 50 mg atenolol 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, l- ewwel ingħatat doża ta ’ hydrochlorothiazide (12. 5 mg) 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.
Jekk meħtieġ, mediċini ta ’ kontra l- pressjoni oħra, bl- eċċezzjoni ta ’ impedituri ACE, antagonisti ta ’ angiotensin II jew beta- blockers ġew magħduda sabiex tintlaħaq 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 mkejla bi tnaqqis fl- inċidenza kkombinata ta ’ mewt kardjovaskulari, puplesija u infart mijokardijaku.
Blood pressure was significantly lowered to similar levels in the two groups.
Il- pressjoni tad- demm kienet sinifikament mnaqqsa għal- livelli simili fiż- żewġ gruppi.
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.
It- trattament b ’ losartan irriżulta fi tnaqqis ta ’ 13. 0% fir- riskju (p=0. 021, 95% intervall ta ’ kunfidenza 0. 77- 0. 98) imqabbel ma ’ atenolol għal pazjenti li jilħqu l- ewwel punt ta ’ riferiment kompost prinċipali.
This was mainly attributable to a reduction of the incidence of stroke.
Dan kien prinċipalment attribwit għall- inċidenza ta ’ puplesija.
Treatment with losartan reduced the risk of stroke by 25% relative to atenolol (p=0.001 95% confidence interval 0.63-0.89).
It- trattament b’ losartan naqqas ir- riskju ta ’ puplesija b’ 25% meta mqabbel ma ’ atenolol (p=0. 001 95% intervall ta ’ kunfidenza 0. 63- 0. 89).
The rates of cardiovascular death and myocardial infarction were not significantly different between the treatment groups.
Ir- rati ta ’ mwiet kardjovaskulari u infarti mijokardjali ma kienux sinifikament differenti bejn il- gruppi ta ’ trattament.
Hydrochlorothiazide is a thiazide diuretic.
Hydrochlorothiazide huwa dijuretiku ta ’ thiazide.
The mechanism of the antihypertensive effect of thiazide diuretics is not fully known.
Il- mekkaniżmu ta ’ l- effett ta ’ kontra l- pressjoni għolja f’ thiazides mhux magħruf sa barra.
Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts.
Thiazides jaffettwaw il- mekkaniżmi tubulari renali ta ’ l- assorbiment mill- ġdid ta ’ l- elettrolitiċi, li direttament jgħollu l- eliminazzjoni ta ’ sodju u chloride f’ madwar ammonti ekwivalenti.
The diuretic action of hydrochlorothiazide reduces plasma volume, increases plasma renin activity and increases aldosterone secretion, with consequent increases in urinary potassium and bicarbonate loss, and decreases in serum potassium.
L- azzjoni dijuretika ta ’ hydrochlorothiazide tnaqqas il- volum ta ’ plażma, tgħolli l- attività ta ’ renin fil- plażma u żżid it- tnixxija ta ’ aldosterone, b’ żidied sussegwenti fit- tnaqqis ta ’ potassju u bikarbonat fl- awrina, u tnaqqis tal- potassju fis- serum.
The renin-aldosterone link is mediated by angiotensin II and therefore coadministration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with thiazide diuretics.
Ir- rabta ta ’ renin- aldosterone ssir permezz ta ’ anġjotensin II u għalhekk amministrazzjoni konġunta ta ’ antagonist riċettatur ta ’ anġjotensin II x’ aktarx tirriversja t- telf ta ’ potassju assoċjat ma ’ dijuretiċi ta ’ thiazide.
After oral use, diuresis begins within 2 hours, peaks in about 4 hours and lasts about 6 to 12 hours the antihypertensive effect persists for up to 24 hours.
Wara l- użu orali, id- dijuresi tibda fi żmien sagħtejn, tilħaq il- qofol tagħha f’ madwar 4 sigħat u ddum sejra għal madwar 6 sa12- il siegħa bl- effett kontra l- pressjoni għolja ddum tippersisti għal 24 siegħa.
5.2 Pharmacokinetic properties
31 5. 2 Tagħrif Farmakokinetiku
Losartan Following oral administration, losartan is well absorbed and undergoes first-pass metabolism, forming an active carboxylic acid metabolite and other inactive metabolites.
Losartan 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.
The systemic bioavailability of losartan tablets is approximately 33%.
Il- bijodisponibilità sistemika tal- pilloli losartan hi ta ’ madwar 33%.
Mean peak concentrations of losartan and its active metabolite are reached in 1 hour and in 3-4 hours, respectively.
L- ogħla konċentrazzjonijiet medji ta ’ losartan u l- metabolit attiv tiegħu jintlaħqu f’ siegħa u fi 3- 4 sigħat, rispettivament.
There was no clinically significant effect on the plasma concentration profile of losartan when the drug was administered with a standardized meal.
Ma kienx hemm effett klinikament sinifikanti fuq il- profil tal- konċentrazzjoni tal- plażma ta ’ losartan meta l- pillola tingħata ma ’ ikla standard.
Losartan Both losartan and its active metabolite are ≥ 99% bound to plasma proteins, primarily albumin.
Losartan 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 liters.
Il- volum ta ’ distribuzzjoni ta ’ losartan hi ta ’ 34 litru.
Studies in rats indicate that losartan crosses the blood- brain barrier poorly, if at all.
Studji fuq il- firien indikaw li losartan jaqsam il- barriera tad- demm- moħħ b’ mod fqir, jekk jaqsam.
32 Hydrochlorothiazide Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.
Hydrochlorothiazide Hydrochlorothiazide jaqsam is- sekonda imma mhux il- barriera tad- demm- moħħ u jiġi eliminat fil- ħalib ta ’ l- omm.
Losartan About 14% of an intravenously- or orally-administered dose of losartan is converted to its active metabolite.
Losartan 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 prinċipali fiċ- ċirkolazzjoni hija attribwita għal losartan u l- metabolit attiv tiegħu.
Minimal conversion of losartan to its active metabolite was seen in about one percent of individuals studied.
Tibdil minimu ta ’ losartan fil- metabolit attiv tiegħu deher f’ madwar perċentwal wieħed ta ’ individwi studjati.
In addition to the active metabolite, inactive metabolites are formed, including two major metabolites formed by hydroxylation of the butyl side chain and a minor metabolite, an N-2 tetrazole glucuronide.
Barra mill- metabolit attiv ifformat, metaboliti mhux attivi huma fformati wkoll, li jinkludu żewġ metaboliti iffurmati mill- idrosilazzjoni tan- naħa tal- katina butyl u metabolit ieħor żgħir, tip ta ’ N- 2 tetrazole glucuronide.
Losartan Plasma clearance of losartan and its active metabolite is about 600 mL/ min and 50 mL/ min, respectively.
Losartan It- tneħħija ta ’ losartan mill- plażma u tal- metabolit attiv tiegħu hija ta ’ madwar 600 ml/ min u 50 ml/ min, rispettivament.
Renal clearance of losartan and its active metabolite is about 74 mL/ min and 26 mL/ min, respectively.
It- tneħħija mill- kliewi ta ’ losartan u l- metabolit attiv tiegħu hi ta ’ madwar 74 ml/ min u 26 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 amministrat 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.
The pharmacokinetics of losartan and its active metabolite are linear with oral losartan potassium doses up to 200 mg.
Il- farmakokinetiċi ta ’ losartan u l- metabolit attiv tiegħu huma linejari b’ dożi sa 200 mg losartan potassium meħuda mill- ħalq.
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.
During once- daily dosing with 100 mg, neither losartan nor its active metabolite accumulates significantly in plasma.
F’ doża ta ’ 100 mg li tittieħed darba biss, la losartan u lanqas il- metabolit attiv tiegħu ma jakkumulaw b’ mod sinifikanti fil- plażma.
Both biliary and urinary excretion contribute to the elimination of losartan and its metabolites.
Kemm l- eliminazzjoni mill- marrara u dik urinarja jikkontribwixxu għall- eliminazzjoni ta ’ losartan u l- metabolit tiegħu.
Following an oral dose of 14C-labeled losartan in man, about 35% of radioactivity is recovered in the urine and 58% in the feces.
Wara doża meħuda mill- ħalq ta ’ losartan ittikkettat b’ 14C fil- bniedem, madwar 35% ta ’ radjoattività ġiet irkuprata fl- urina u 58% fl- ippurgar.
Hydrochlorothiazide Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney.
Hydrochlorothiazide Hydrochlorothiazide mhux metabolizzat imma jiġi eliminat malajr minn ġol- kliewi.
When plasma levels have been followed for at least 24 hours, the plasma half-life has been observed to vary between 5.6 and 14.8 hours.
Wara li l- livelli ta ’ plażma jkunu ġew segwiti għal ta ’ lanqas 24 siegħa, il- half- life fil- plażma instabet li tvarja bejn 5. 6 32 u 14. 8 sigħat.
At least 61 percent of the oral dose is eliminated unchanged within 24 hours.
Ta ’ lanqas 61 fil- mija tad- doża orali hija eliminata mingħajr ma tinbidel fi żmien 24 siegħa.
Characteristics in Patients
Karatteristiċi fil- Pazjenti
Losartan-Hydrochlorothiazide The plasma concentrations of losartan and its active metabolite and the absorption of hydrochlorothiazide in elderly hypertensives are not significantly different from those in young hypertensives.
Losartan- Hydrochlorothiazide Il- konċentrazzjonijiet ta ’ losartan fil- plażma u tal- metabolit attiv u l- assorbiment ta ’ hydrochlorothiazide f’ pazjenti anzjani bil- pressjoni għolja m’ humiex sinifikament differenti minn dawk ta ’ żgħażagħ li għandhom pressjoni għolja.
Losartan Following oral administration in patients with mild to moderate alcoholic cirrhosis of the liver, plasma concentrations of losartan and its active metabolite were, respectively, 5-fold and 1.7-fold greater than those seen in young male volunteers.
Losartan Wara l- għoti mill- ħalq f’ pazjenti b’ ċirrosi alkoħolika fil- fwied minn ħafifa sa moderata, il- konċentrazzjonijiet fil- plażma ta ’ losartan u l- metabolit attiv tiegħu kienu 5 darbiet u 1. 7 darbiet ogħla minn dawk li dehru f’ voluntieri rġiel żgħażagħ.
Neither losartan nor the active metabolite can be removed by hemodialysis.
La Losartan u lanqas il- metabolit attiv ma jistgħu jiġu eliminati f’ emodijaliżi.
The toxic potential of the combination of
Minn tagħrif ta ’ qabel l- użu kliniku ma ġie rivelat ebda periklu speċjali għal bniedem skond studji konvenzjonali ta ’ farmakoloġija, effett tossiku fuq il- ġeni u riskju ta ’ kanċer.
33 losartan/ hydrochlorothiazide was evaluated in chronic toxicity studies for up to six months duration in rats and dogs after oral administration, and the changes observed in these studies with the combination were mainly produced by the losartan component.
Il- potenzjal tossiku ta ’ losartan/ hydrochlorothiazide ġie evalwat fi studji ta ’ tossiċità kronika għal perijodu sa sitt xhur fil - firien u l- klieb wara l- għoti mill- ħalq, u l- bidliet osservati f’ dawn l- istudji bil- kombinazzjoni kineu prodotti prinċipalment mill- komponent ta ’ losartan.
The administration of the losartan/ hydrochlorothiazide combination induced a decrease in the red blood cell parameters (erythrocytes, haemoglobin, haematocrit), a rise in urea-N in the serum, a decrease in heart weight (without a histological correlate) and gastrointestinal changes (mucous membrane lesions, ulcers, erosions, haemorrhages).
L- għoti tal- kombinazzjoni losartan/ hydrochlorothiazide ġabet tnaqqis fil- parametri taċ- ċelluli l- ħomor tad- demm (eritroċiti, emaglobina, ematokrit), żieda fil- urea- N fis- serum, piż imnaqqas tal- qalb (mingħajr spjegazzjoni ħistoloġika), u bidliet gastro- intestinali (feriti mukużi tar- rita, ulċeri, tgħawwir, emorraġiji).
There was no evidence of teratogenicity in rats or rabbits treated with the losartan/ hydrochlorothiazide combination.
Ma kien hemm ebda evidenza ta ’ teratoġeniċità fil- firien jew fniek ittrattati bil- kombinazzjoni ta ’ losartan/ hydrochlorothiazide.