natgillin/translations-raw huggingface dataset:
Imidlertid kan en lille øget risiko ikke udelukkes.
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.
Hvis der er givet angiotensin II- receptor- antagonister under graviditetens anden trimester, anbefales ultralydskontrol af nyrefunktionen og kraniet.
6 Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
6 Thiazider passerer placentabarrieren og findes i navlesnorsblod.
Thiazides cross the placental barrier and appear in cord blood.
Der er rapporteret tilfælde af neonatal trombocytopeni eller føtal/ neonatal gulsot ved maternel thiazidbehandling.
Cases of neonatal thrombocytopenia, or foetal or neonatal jaundice have been reported with maternal thiazide therapy.
CoAprovel er kontraindiceret under amning.
CoAprovel is contraindicated during breast-feeding.
Kombination af irbesartan/ hydrochlorthiazid:
Irbesartan/ hydrochlorothiazide combination:
Tabel 1 viser hyppigheden af bivirkninger rapporteret efter markedsføring og bivirkninger observeret i placebokontrollerede studier, hvor 898 hypertensive patienter blev behandlet med forskellige doser (interval:
Table 1 gives the adverse reactions observed from spontaneous reporting and in placebo-controlled trials in which 898 hypertensive patients received various doses (range:
37, 5 mg/ 6, 25 mg til 300 mg/ 25 mg irbesartan/ hydrochlorthiazid).
37.5 mg/ 6.25 mg to 300 mg/ 25 mg irbesartan/ hydrochlorothiazide).
Hyppigheden af uønskede hændelser anført nedenfor defineres i henhold til følgende konventioner:
The frequency of adverse reactions listed below is defined using the following convention: very common (≥ 1/ 10); common (≥ 1/ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000); very rare (< 1/ 10,000).
Meget almindelig (≥ 1/ 10); almindelig (≥ 1/ 100 til < 1/ 10); ikke almindelig (≥ 1/ 1. 000 til < 1/ 100); sjælden (≥ 1/ 10. 000 til < 1/ 1. 000); meget sjælden (< 1/ 10. 000).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Bivirkninger fra placebokontrollerede studier, og bivirkninger rapporteret efter markedsføring * Undersøgelser:
Adverse Reactions in Placebo-Controlled Trials and Spontaneous Reports* Investigations:
Svimmelhed Ortostatisk svimmelhed Hovedpine
dizziness orthostatic dizziness headache
Mave- tarm- kanalen:
Respiratory, thoracic and mediastinal disorders:
Tinnitus Hoste Kvalme/ opkastning Diarré Dyspepsi, smagsforstyrrelse
nausea/ vomiting diarrhoea dyspepsia, dysgeusia
4. 4)
abnormal urination impaired renal function including isolated cases of renal failure in patients at risk (see section 4.4)
Metabolisme og ernæring:
Metabolism and nutrition
Ikke almindelig:
disorders:
Hævelse af ekstremiteter Artralgi, myalgi Hyperkalæmi Rødme Træthed
flushing fatigue
7 Det reproduktive system og mammae:
Reproductive system and breast Uncommon: disorders:
* Hyppigheden af bivirkninger rapporteret efter markedsføring er angivet som “ ikke kendt ”.
* Frequency for adverse reactions detected by spontaneous reports is described as “ not known”
Udover ovenfor nævnte bivirkninger for kombinationspræparatet, kan andre tidligere rapporterede bivirkninger i forbindelse med ét af de individuelle stoffer være potentielle bivirkninger ved CoAprovel.
Additional information on individual components: in addition to the adverse reactions listed above for the combination product, other adverse reactions previously reported with one of the individual components may be potential adverse reactions with CoAprovel.
Bivirkninger rapporteret ved anvendelse af irbesartan alene Almene symptomer og reaktioner Ikke almindelig: på administrationsstedet:
Adverse reactions reported with the use of irbesartan alone General disorders and administration site conditions:
Brystsmerter
chest pain
lægemidlet) rapporteret ved anvendelse
Adverse reactions (regardless of relationship to medicinal product) reported with the use of hydrochlorothiazide alone Investigations:
4. 4), hyperurikæmi, glukosuri, hyperglykæmi, stigning i kolesterol og triglycerider
electrolyte imbalance (including hypokalaemia and hyponatraemia, see section 4.4), hyperuricaemia, glycosuria, hyperglycaemia, increases in cholesterol and triglycerides
Hjertearytmi Aplastisk anæmi, knoglemarvsdepression, neutropeni/ agranulocytose, hæmolytisk anæmi, leukopeni, trombocytopeni
cardiac arrhythmias aplastic anaemia, bone marrow depression, neutropenia/ agranulocytosis, haemolytic anaemia, leucopenia, thrombocytopenia
Nervesystem:
Nervous system disorders:
Forbigående sløret syn, xanthopsia Åndenød (inklusive pneumoni og pulmonalt ødem)
transient blurred vision, xanthopsia respiratory distress (including pneumonitis and pulmonary oedema)
pancreatitis, anorexia, diarrhoea, constipation, gastric irritation, sialadenitis, loss of appetite
pancreatitis, anorexia, diarrhoea, constipation, gastric irritation, sialadenitis, loss of appetite
Interstitiel nefritis, nyreinsufficiens Anafylaktiske reaktioner, toksisk epidermal nekrolyse, nekrotiserende angitis (vasculitis, kutan vasculitis), kutan lupus erythematosus- lignende reaktioner, reaktivering af kutan lupus erythematosus, fotosensitivitetsreaktioner, udslæt, urticaria
interstitial nephritis, renal dysfunction anaphylactic reactions, toxic epidermal necrolysis, necrotizing angitis (vasculitis, cutaneous vasculitis), cutaneous lupus erythematosus-like reactions, reactivation of cutaneous lupus erythematosus, photosensitivity reactions, rash, urticaria
Knogler, led, muskler og Ikke kendt: bindevæv:
Musculoskeletal and connective tissue disorders:
Almene symptomer og reaktioner Ikke kendt: på administrationsstedet:
Not known:
Postural hypotension Feber
postural hypotension fever
Gulsot (intrahepatisk kolestatisk gulsot) Depression, søvnforstyrrelser
depression, sleep disturbances
De dosisafhængige bivirkninger med hydrochlorthiazid (specielt elektrolytforstyrrelser) kan øges ved anvendelse af højere dosis af hydrochlorthiazid.
8 The dose dependent adverse events of hydrochlorothiazide (particularly electrolyte disturbances) may increase when titrating the hydrochlorothiazide.
8 4. 9 Overdosering
4.9 Overdose
Serum- elektrolytter og kreatinin monitoreres tæt.
Serum electrolytes and creatinine should be monitored frequently.
Ved hypotension lægges patienten i rygleje og salt - og væsketilskud administreres straks.
If hypotension occurs, the patient should be placed in a supine position, with salt and volume replacements given quickly.
Bradykardi kan dog ligeledes forekomme.
The most likely manifestations of irbesartan overdose are expected to be hypotension and tachycardia; bradycardia might also occur.
På grund af voldsom diurese medfører overdosis af hydrochlorthiazid elektrolyt- depletion (hypokaliæmi, hypochloræmi, hyponatriæmi) og dehydrering.
Overdose with hydrochlorothiazide is associated with electrolyte depletion (hypokalaemia, hypochloremia, hyponatraemia) and dehydration resulting from excessive diuresis.
Hypokaliæmi kan medføre muskelkramper og/ eller medvirke til kardiel arytmi, som er forbundet med samtidig anvendelse af digitalisglykosider eller visse antiarytmiske lægemidler.
Hypokalaemia may result in muscle spasms and/ or accentuate cardiac arrhythmias associated with the concomitant use of digitalis glycosides or certain anti-arrhythmic medicinal products.
ATC- kode:
Pharmacotherapeutic group: angiotensin-II antagonists, combinations ATC code:
CoAprovel er en kombination af en angiotensin- II receptorantagonist, irbesartan, og et thiaziddiuretikum, hydrochlorthiazid.
CoAprovel is a combination of an angiotensin-II receptor antagonist, irbesartan, and a thiazide diuretic, hydrochlorothiazide.
Irbesartan er en potent, oral aktiv, selektiv angiotensin- II receptor (AT1 undergruppe) antagonist.
Irbesartan is a potent, orally active, selective angiotensin-II receptor (AT1 subtype) antagonist.
Den selektive antagonisme mod angiotensin- II (AT1) receptorerne resulterer i enforhøjelse af plasma- renin - og angiotensin- II - niveauerne og i nedsat aldosteron i plasma.
The selective antagonism of the angiotensin-II (AT1) receptors results in increases in plasma renin levels and angiotensin-II levels, and a decrease in plasma aldosterone concentration.
Serum- kalium påvirkes ikke nævneværdigt, når irbesartan administreres alene ved de anbefalede doser til patienter, udenudvikling af elektrolytforstyrrelser (se pkt.
Serum potassium levels are not significantly affected by irbesartan alone at the recommended doses in patients without risk of electrolyte imbalance (see sections 4.4 and 4.5).
Irbesartan hæmmer ikke ACE (kininase- II), et enzym, som producerer angiotensin- II og også nedbryder bradykinin til inaktive metabolitter.
Irbesartan does not inhibit ACE (kininase-II), an enzyme which generates angiotensin-II and also degrades bradykinin into inactive metabolites.
Thiazider påvirker den renale tubulære mekanisme for elektrolyt- reabsorption og øger udskillelsen af natrium og chlorid i omtrent ækvivalente mængder.
Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts.
Den diuretiske virkning af hydrochlorthiazid reducerer plasmavolumen, øger plasma- reninaktiviteten, øger aldosteron - udskillelsen med heraf følgende øget urinært kalium - og bikarbonat- tab og nedsat serum- kalium.
The diuretic action of hydrochlorothiazide reduces plasma volume, increases plasma renin activity, increases aldosterone secretion, with consequent increases in urinary potassium and bicarbonate loss, and decreases in serum potassium.
Samtidig administration af irbesartan ændrer det kalium- tab, der er forbundet med disse diuretika, formodentligt ved at blokere renin- angiotensin- aldosteronsystemet.
Presumably through blockade of the renin-angiotensin-aldosterone system, co-administration of irbesartan tends to reverse the potassium loss associated with these diuretics.
6- 12 timer.
With hydrochlorothiazide, onset of diuresis occurs in 2 hours, and peak effect occurs at about 4 hours, while the action persists for approximately 6-12 hours.
Kombinationen af hydrochlorthiazid og irbesartan giver en dosisrelateret additiv reduktion af blodtrykket over hele det terapeutiske dosisinterval for de enkelte lægemidler.
9 The combination of hydrochlorothiazide and irbesartan produces dose-related additive reductions in blood pressure across their therapeutic dose ranges.
Tillæg af 12, 5 mg hydrochlorthiazid til 300 mg irbesartan, 1 gang dagligt hos patienter, der ikke er adækvat behandlede med 300 mg irbesartan alene, medførte yderligere placebo- korrigeret diastolisk blodtryksreduktion ved
The addition of 12.5 mg hydrochlorothiazide to 300 mg irbesartan once daily in patients not adequately controlled on 300 mg irbesartan alone resulted in further placebo-corrected diastolic blood pressure reductions at trough (24 hours post-dosing) of 6.1 mm Hg.
Kombinationen af 300 mg irbesartan og 12, 5 mg hydrochlorthiazid medførte en total placebo- korrigeret systolisk/ diastolisk reduktion på op til 13, 6/ 11, 5 mmHg.
The combination of 300 mg irbesartan and 12.5 mg hydrochlorothiazide resulted in an overall placebo-subtracted systolic/ diastolic reductions of up to 13.6/ 11.5 mm Hg.
Begrænsede kliniske data (7 patienter ud af 22) tyder på, at patienter, som ikke er tilstrækkelig regulerede med 300 mg/ 12, 5 mg- kombinationen, kan respondere ved dosisøgning til 300/ 25 mg.
Limited clinical data (7 out of 22 patients) suggest that patients not controlled with the 300 mg/ 12.5 mg combination may respond when uptitrated to 300 mg/ 25 mg.
Der er hos disse patienter observeret en øgning i blodtryksreduktionen for såvel systolisk blodtryk (SBP) som diastolisk blodtryk (DBP) (henholdsvis 13, 3 mmHg og 8, 3 mmHg).
In these patients, an incremental blood pressure lowering effect was observed for both systolic blood pressure (SBP) and diastolic blood pressure (DBP) (13.3 and 8.3 mm Hg, respectively).
Dosering 1 gang dagligt med 150 mg irbesartan og 12, 5 mg hydrochlorthiazid gav en systolisk/ diastolisk gennemsnitlig placebojusteret blodtryksreduktion ved laveste måling (24 timer efter dosis) på 12, 9/ 6, 9 mmHg hos patienter med let til moderat hypertension.
Once daily dosing with 150 mg irbesartan and 12.5 mg hydrochlorothiazide gave systolic/ diastolic mean placebo-adjusted blood pressure reductions at trough (24 hours post-dosing) of 12.9/ 6.9 mm Hg in patients with mild-to-moderate hypertension.
Den maksimale effekt blev opnået efter 3- 6 timer.
Peak effects occurred at 3-6 hours.
Ved ambulant blodtrykskontrol medførte kombinationen af 150 mg irbesartan og 12, 5 mg hydrochlorthiazid, 1 gang dagligt, en vedvarende reduktion af blodtrykket over en 24 timers periode med en gennemsnitlig 24 timers placebo- korrigeret systolisk/ diastolisk reduktion på 15, 8/ 10, 0 mmHg.
When assessed by ambulatory blood pressure monitoring, the combination 150 mg irbesartan and 12.5 mg hydrochlorothiazide once daily produced consistent reduction in blood pressure over the 24 hours period with mean 24-hour placebo-subtracted systolic/ diastolic reductions of 15.8/ 10.0 mm Hg.
Forholdet mellem den laveste og den maksimale effekt af CoAprovel 150 mg/ 12, 5 mg var 100%, når blodtrykket blev monitoreret ambulant.
When measured by ambulatory blood pressure monitoring, the trough to peak effects of CoAprovel 150 mg/ 12.5 mg were 100%.
Forholdet mellem den laveste og den maksimale effekt var henholdsvis 68% og 76% for CoAprovel 150 mg / 12, 5 mg og CoAprovel 300 mg / 12, 5 mg, når effekten blev målt med blodtryksmanchet ved kontrolbesøg.
The trough to peak effects measured by cuff during office visits were 68% and 76% for CoAprovel 150 mg/ 12.5 mg and CoAprovel 300 mg/ 12.5 mg, respectively.
De er sammenlignelige med den sikre og effektive reduktion af blodtrykket, som opnås med dosering 1 gang dagligt.
These 24-hour effects were observed without excessive blood pressure lowering at peak and are consistent with safe and effective blood-pressure lowering over the once-daily dosing interval.
Hos patienter, der ikke var tilstrækkeligt kontrolleret med 25 mg hydrochlorthiazid alene, gav et tillæg af irbesartan en yderligere placebo- korrigeret systolisk/ diastolisk gennemsnitlig reduktion på 11, 1/ 7, 2 mmHg.
In patients not adequately controlled on 25 mg hydrochlorothiazide alone, the addition of irbesartan gave an added placebo-subtracted systolic/ diastolic mean reduction of 11.1/ 7.2 mm Hg.
Den blodtryksnedsættende effekt af irbesartan i kombination med hydrochlorthiazid viser sig efter første dosis og varer ved i 1- 2 uger, med maksimal effekt efter 6- 8 uger.
The blood pressure lowering effect of irbesartan in combination with hydrochlorothiazide is apparent after the first dose and substantially present within 1-2 weeks, with the maximal effect occurring by 6-8 weeks.
I langsigtede opfølgningsstudier blev virkningen af irbesartan/ hydrochlorthiazid opretholdt i mere end 1 år.
In long-term follow-up studies, the effect of irbesartan/ hydrochlorothiazide was maintained for over one year.
Dette er dog ikke undersøgt specifikt for CoAprovel.
Although not specifically studied with the CoAprovel, rebound hypertension has not been seen with either irbesartan or hydrochlorothiazide.
Som med andre lægemidler, der påvirker renin- angiotensinsystemer, har sorte, hypertensive patienter betydelig mindre respons på enkeltstofbehandling med irbesartan.
As is the case with other medicinal products that affect the renin-angiotensin system, black hypertensive patients have notably less response to irbesartan monotherapy.
Når irbesartan administreres samtidig med en lille dosis hydrochlorthiazid (fx 12, 5 mg dagligt), nærmer det antihypertensive respons hos sorte patienter sig det, der ses hos hvide.
12.5 mg daily), the antihypertensive response in black patients approaches that of non-black patients.
Et randomiseret, dobbeltblindt, aktivt kontrolleret, parallelt multicenterforsøg af 8 ugers varighed har evalueret effekten og sikkerheden af CoAprovel som inital behandling ved svær hypertension (defineret som SeDBT ≥ 110 mmHg).
Efficacy and safety of CoAprovel as initial therapy for severe hypertension (defined as SeDBP ≥ 110 mmHg) was evaluated in a multicenter, randomized, double-blind, active-controlled, 8-week, parallel-arm study.
Ialt 697 patienter randomiseredes i forholdet 2: 1 til irbesartan/ hydrochlorothiazid 150 mg/ 12, 5 mg eller irbesartan 150 mg, og med systematisk titrering (inden evaluering af respons på den lavere dosis) efter 1 uge til henholdsvis irbesartan/ hydrochlorothiazid 300 mg/ 25 mg eller irbesartan 300 mg.
A total of 697 patients were randomized in a 2:1 ratio to either irbesartan/ hydrochlorothiazide 150 mg/ 12.5 mg or to irbesartan 150 mg and systematically force- titrated (before assessing the response to the lower dose) after one week to irbesartan/ hydrochlorothiazide 300 mg/ 25 mg or irbesartan 300 mg, respectively.
Gennemsnitsalderen var 52, 5 år; 13% var ≥ 65 år, og kun 2% var ≥ 75 år.
The mean age of patients was 52.5 years, 13% were ≥ 65 years of age, and just 2% were ≥ 75 years of age.
12% af patienterne var diabetikere, 34% var hyperlipidæmiske, og den hyppigste kardiovaskulære tilstand var stabil angina pectoris hos 3, 5% af patienterne.
Twelve percent (12%) of patients were diabetic, 34% were hyperlipidemic and the most frequent cardiovascular condition was stable angina pectoris in 3.5% of the participants.
47, 2% af patienterne i kombinationsbehandling nåede et dal- SeDBT < 90 mmHg sammenlignet med 33, 2% af patienterne behandlet med irbesartan
Forty-seven percent (47.2%) of patients on
Det gennemsnitlige blodtryk ved baseline var ca.
10 the combination achieved trough SeDBP < 90 mmHg compared to 33.2% of patients on irbesartan (p = 0.0005).
Faldet i SeSBT/ SeDBT ved 5 uger var henholdsvis 30, 8/ 24, 0 mmHg og 21, 1/ 19, 3 mmHg for irbesartan/ hydrochlorothiazid og irbesartan (p < 0, 0001).
The mean baseline blood pressure was approximately 172/ 113 mmHg in each treatment group and decreases of SeSBP/ SeDBP at five weeks were 30.8/ 24.0 mmHg and 21.1/ 19.3 mmHg for irbesartan/ hydrochlorothiazide and irbesartan, respectively (p < 0.0001).
Der blev under den 8- uger lange behandlingsperiode ikke indberettet tilfælde af syncope i nogen af behandlingsgrupperne.
During the 8-week treatment period, there were no reported cases of syncope in either treatment group.
Henholdsvis 0, 6% og 0% af patienterne oplevede hypotension og henholdsvis 2, 8% og 3, 1% oplevede svimmelhed i ved kombinationsbehandling og enkeltstofbehandling.
There were 0.6% and 0% of patients with hypotension and 2.8% and 3.1% of patients with dizziness as adverse reactions reported in the combination and monotherapy groups, respectively.
Ved oral administration af CoAprovel er den absolutte orale biotilgængelighed 60- 80% for irbesartan og 50- 80% for hydrochlorthiazid.
Following oral administration of CoAprovel, the absolute oral bioavailability is 60-80% and 50-80% for irbesartan and hydrochlorothiazide, respectively.
Den maksimale plasmakoncentration optræder i løbet af 1, 5- 2 timer efter oral administration af irbesartan og 1- 2, 5 timer efter administration af hydrochlorthiazid.
Peak plasma concentration occurs at 1.5-2 hours after oral administration for irbesartan and 1-2.5 hours for hydrochlorothiazide.
96%, med en ubetydelig binding til cellulære blodkomponenter.
Plasma protein binding of irbesartan is approximately 96%, with negligible binding to cellular blood components.
Fordelingsvolumen er 53- 93 liter for irbesartan.
The volume of distribution for irbesartan is 53-93 litres.
Hydrochlorthiazid er 68% proteinbundet i plasma, og dets tilsyneladende fordelingsvolumen er 0, 83- 1, 14 l/ kg.
Hydrochlorothiazide is 68% protein-bound in the plasma, and its apparent volume of distribution is 0.83-1.14 l/ kg.
Irbesartan udviser lineær og dosisproportionel farmakokinetik i et dosisinterval på 10- 600 mg.
Irbesartan exhibits linear and dose proportional pharmacokinetics over the dose range of 10 to 600 mg.
Der blev observeret en mindre end proportional øgning af peroral absorption ved doser over 600 mg (2 gange den maksimale anbefalede dosis).
A less than proportional increase in oral absorption at doses beyond 600 mg was observed; the mechanism for this is unknown.
Total body - og nyreclearance er henholdsvis 157- 176 og 3- 3, 5 ml/ min.
The total body and renal clearance are 157-176 and 3.0-3.5 ml/ min, respectively.
Steady- state plasmakoncentration nås i løbet af 3 dage efter påbegyndelse af behandling 1 gang dagligt.
Steady-state plasma concentrations are attained within 3 days after initiation of a once-daily dosing regimen.
Den gennemsnitlige plasmahalveringstid for hydrochlorthiazid angives at være på 5- 15 timer.
The mean plasma half-life of hydrochlorothiazide reportedly ranges from 5-15 hours.
Efter oral eller intravenøs administration af 14C irbesartan, kan 80- 85% af den cirkulerende radioaktivitet i plasma tilskrives uomdannet irbesartan.
Following oral or intravenous administration of 14C irbesartan, 80-85% of the circulating plasma radioactivity is attributable to unchanged irbesartan.
20% radioaktivitet i urinen og resten i afføringen.
After either oral or intravenous administration of 14C irbesartan, about 20% of the radioactivity is recovered in the urine, and the remainder in the faeces.
Hydrochlorthiazid passerer placentabarrieren, men ikke blod/ hjernebarrieren, og det udskilles i modermælk.
Hydrochlorothiazide crosses the placental but not the blood-brain barrier, and is excreted in breast milk.
Irbesartans farmakokinetiske parametre ændres ikke væsentligt hos patienter med nedsat nyrefunktion eller i hæmodialyse.
Renal impairment: in patients with renal impairment or those undergoing haemodialysis, the pharmacokinetic parameters of irbesartan are not significantly altered.
Halveringstiden for hydrochlorthiazid forlænges til 21 timer hos patienter med kreatininclearance < 20 ml/ min.
In patients with creatinine clearance < 20 ml/ min, the elimination half-life of hydrochlorothiazide was reported to increase to 21 hours.
Irbesartans farmakokinetiske parametre ændres ikke væsentligt hos patienter med mild/ moderat cirrhose.
11 Hepatic impairment: in patients with mild to moderate cirrhosis, the pharmacokinetic parameters of irbesartan are not significantly altered.
11 5. 3 Prækliniske sikkerhedsdata
5.3 Preclinical safety data
Potentiel toksicitet for irbesartan/ hydrochlorthiazid- kombinationen efter oral administration blev undersøgt hos rotter og makakaber i studier af op til 6 måneders varighed.
Irbesartan/ hydrochlorothiazide: the potential toxicity of the irbesartan/ hydrochlorothiazide combination after oral administration was evaluated in rats and macaques in studies lasting up to 6 months.