natgillin/translations-raw huggingface dataset:
Valsartan udskilles i mælk hos diegivende rotter.
Valsartan was excreted in the milk of lactating rats.
Ved et sådant valg skal der tages hensyn til denne behandlings vigtighed for moderen.
Because of the potential adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue therapy, taking into account the importance of this therapy for the mother.
Sikkerheden ved brug af Copalia er blevet evalueret i fem kontrollerede kliniske undersøgelser med 5. 175 patienter, hvoraf 2. 613 modtog valsartan i kombination med amlodipin.
The safety of Copalia has been evaluated in five controlled clinical studies with 5,175 patients, 2,613 of whom received valsartan in combination with amlodipine.
Meget almindelig (≥1/ 10); almindelig (≥1/ 100 til, < 1/ 10); usædvanlig (≥1/ 1. 000 til, < 1/ 100); sjælden (≥1/ 10. 000 til, < 1/ 1. 000); meget sjælden (< 1/ 10. 000), inklusive enkeltstående rapporter.
Adverse reactions have been ranked under headings of frequency 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), including isolated reports.
Takykardi, palpitationer Synkope
Tachycardia, palpitations Syncope
Hovedpine Svimmelhed, somnolens, postural svimmelhed, paræsthesia
Headache Dizziness, somnolence, dizziness postural, paraesthesia
Vertigo Tinnitus
Vertigo Tinnitus
Hoste, smerte i næse - og halssvælg
Cough, pharyngolaryngeal pain
Gastrointestinale sygdomme
Gastrointestinal disorders Renal
Usædvanlig:
Uncommon: and urinary disorders Rare:
Diarré, kvalme, mavesmerte, forstoppelse, mundtørhed
Diarrhoea, nausea, abdominal pain, constipation, dry mouth Pollakisuria, polyuria
Udslæt, erytem Øget svedtendens, exanthema, pruritus
Rash, erythema Hyperhidrosis, exanthema, pruritus
6 Sygdomme i bevægeapparatet og bindevæv
Musculoskeletal and connective tissue disorders
Hævet led, rygsmerter, arthralgia Muskelspasme, følelsen af tunghed
Joint swelling, back pain, arthralgia Muscle spasm, sensation of heaviness
Næsesvælgskatar, influenza
Nasopharyngitis, influenza
Ødem, fingertryksødem, ansigtsødem, perifert ødem, træthed, opblussen, asteni, hedeture
Oedema, pitting oedema, facial oedema, oedema peripheral, fatigue, flushing, asthenia, hot flush
Lidelser i forplantningsorganerne og brystsygdomme
Reproductive system and breast disorders
Yderligere information for kombinationen Perifert ødem, en kendt bivirkning ved amlodipin, blev generelt observeret ved en lavere incidens hos patienter, som fik amlodipin/ valsartan kombinationen end hos patienter, som fik amlodipin alene.
Additional information on the combination Peripheral oedema, a recognised side effect of amlodipine, was generally observed at a lower incidence in patients who received the amlodipine/ valsartan combination than in those who received amlodipine alone.
I dobbeltblindede, kontrollerede kliniske undersøgelser var incidensen af perifert ødem fordelt på dosis følgende:
In double-blind, controlled clinical trials, the incidence of peripheral oedema by dose was as follows:
% patienter, som perifert ødem
% of patients who experienced peripheral oedema
Amlodipin (mg)
0 2.5 Amlodipine 5 (mg) 10
3, 1 4, 8 10, 3 NA
3.0 5.5 8.0 2.3 3.1 4.8 10.3 NA
2, 3 NA
2.4 5.4 2.3 NA
2, 1 9, 0
1.6 2.4 2.1 9.0
2, 4 9, 5
0.9 3.9 2.4 9.5
Den gennemsnitlige incidens af perifert ødem fordelt ligeligt over alle doser var 5, 1% med amlodipin/ valsartan kombinationen.
The mean incidence of peripheral oedema evenly weighted across all doses was 5.1% with the amlodipine/ valsartan combination.
Yderligere information om de individuelle komponenter Bivirkninger, som tidligere er indrapporteret for hver enkelt af de individuelle komponenter (amlodipin eller valsartan), kan også være potentielle bivirkninger med Copalia, selv i de tilfælde, hvor de ikke er set i kliniske undersøgelser eller i perioden efter markedsføring.
Additional information on the individual components Adverse drug reactions previously reported with one of the individual components (amlodipine or valsartan) may be potential undesirable effects with Copalia as well, even if not observed in clinical trials or during the post-marketing period.
7 Amlodipin Almindelig Usædvanlig
Amlodipine Common Uncommon
Alopeci, ændrede afføringsvaner, dyspepsi, dyspnø, rhinitis, gastritis, gingival hyperplasi, gynækomasti, hyperglykæmi, impotens, øget vandladningshyppighed, leukopeni, utilpashed, humørsvingninger, myalgia, perifer neuropati, pankreatitis, hepatitis, trombocytopeni, vaskulitis, angioødem og erythema multiforme.
Alopecia, altered bowel habits, dyspepsia, dyspnoea, rhinitis, gastritis, gingival hyperplasia, gynaecomastia, hyperglycaemia, impotence, increased urinary frequency, leucopenia, malaise, mood changes, myalgia, peripheral neuropathy, pancreatitis, hepatitis, thrombocytopenia, vasculitis, angioedema and erythema multiforme.
Arytmi, myokardieinfarkt.
Arrhythmia, myocardial infarction.
I sjældne tilfælde har patienter, især dem med svær obstruktiv koronarsygdom, udviklet en øget hyppighed, varighed eller sværhedsgrad af angina eller akut myokardieinfarkt ved behandlingsstart med calciumantagonister eller ved dosisstigning.
Rarely, patients, particularly those with severe obstructive coronary artery disease, have developed increased frequency, duration or severity of angina or acute myocardial infarction on starting calcium channel blocker therapy or at the time of dosage increase.
Der er også rapporteret om arytmier (inklusive ventrikulær takykardi og atrialfibrillation).
Arrhythmia (including ventricular tachycardia and atrial fibrillation) has also been reported.
Disse bivirkninger adskiller sig sandsynligvis ikke fra den naturlige historie af den underliggende sygdom.
These adverse events may not be distinguishable from the natural history of the underlying disease.
Cholestatisk gulsot, forhøjet AST og ALT, purpura, udslæt and pruritus.
Cholestatic jaundice, AST and ALT increase, purpura, rash and pruritus.
Enestående tilfælde af ekstrapyramidale syndromer er blevet rapporteret.
Exceptional cases of extrapyramidal syndrome have been reported.
Fald i hæmoglobin, fald I hæmatokrit, neutropeni, trombocytopeni, øget serum - kalium, forhøjede leverfunktionstal, inklusive øget serum- bilirubin, nyresvigt og nedsat nyrefunktion, forhøjet serum- kreatinin, angioødem, myalgi, vaskulitis, overfølsomhed inklusive serumsyge.
Decrease in haemoglobin, decrease in haematocrit, neutropenia, thrombocytopenia, increase of serum potassium, elevation of liver function values including increase of serum bilirubin, renal failure and impairment, elevation of serum creatinine, angioedema, myalgia, vasculitis, hypersensitivity including serum sickness.
Symptomer Der er ingen erfaring med overdosering af Copalia.
Symptoms There is no experience of overdose with Copalia.
Overdosering med amlodipin kan resultere i udtalt perifer vasodilation og risiko for refleks- takykardi.
Overdose with amlodipine may result in excessive peripheral vasodilation and, possibly, reflex tachycardia.
Behandling Hvis overdoseringen er sket kort tid forinden, skal det overvejes at fremkalde opkastning eller foretage en maveskylning.
Treatment If ingestion is recent, induction of vomiting or gastric lavage may be considered.
Klinisk signifikant hypotension pga. overdosering med Copalia kræver aktiv kardiovaskulær støttebehandling, inklusive hyppig monitorering af hjerte - og respirationsfunktionen, hævede ekstremiteter og opmærksomhed på cirkulerende blodvolumen eller urinproduktion.
Clinically significant hypotension due to Copalia overdose calls for active cardiovascular support, including frequent monitoring of cardiac and respiratory function, elevation of extremities, and attention to circulating fluid volume and urine output.
Det regnes ikke for muligt at fjerne hverken valsartan eller amlodipin ved hæmodialyse.
Both valsartan and amlodipine are unlikely to be removed by haemodialysis.
Angiotensin II- antagonist, almindelig (valsartan), kombination med dihydropyridinderivater (amlodipin), ATC- kode:
Pharmacotherapeutic group: angiotensin II antagonists, plain (valsartan), combinations with dihydropyridine derivatives (amlodipine), ATC code:
Copalia kombinerer to antihypertensive stoffer, som kontrollerer blodtrykket hos patienter med essentiel hypertension ved komplementære virkningsmekanismer: amlodipin tilhører klassen kaldet calciumantagonister og valsartan tilhører klassen kaldet angiotensin II- antagonister.
Copalia combines two antihypertensive compounds with complementary mechanisms to control blood pressure in patients with essential hypertension: amlodipine belongs to the calcium antagonist class and valsartan to the angiotensin II antagonist class of medicines.
8 Amlodipin Amlodipin- delen af Copalia hæmmer den transmembrane indtrængning af calciumioner i hjertets og karvæggens glatte muskulatur.
Amlodipine The amlodipine component of Copalia inhibits the transmembrane entry of calcium ions into cardiac and vascular smooth muscle.
Data fra dyreforsøg tyder på, at amlodipin binder til både dihydropyridin og ikke - dihydropyridin- bindingssteder.
Experimental data suggest that amlodipine binds to both dihydropyridine and non-dihydropyridine binding sites.
Som med andre calciumantagonister har hæmodynamiske undersøgelser af hjertefunktionen i hvile og ved fysisk aktivitet (eller vedvarende aktivitet) hos patienter med normal ventrikelfunktion og i behandling med amlodipin, generelt vist en lille forøgelse i hjerteindekset uden signifikant indflydelse på dP/ dt eller venstre ventrikels slutdiastoliske tryk eller volumen.
As with other calcium channel blockers, haemodynamic measurements of cardiac function at rest and during exercise (or pacing) in patients with normal ventricular function treated with amlodipine have
I hæmodynamiske studier har amlodipin ikke været forbundet med negativ inotropisk effekt, når det blev givet til mennesker eller levende dyr i det terapeutiske dosisinterval.
8 generally demonstrated a small increase in cardiac index without significant influence on dP/ dt or on left ventricular end diastolic pressure or volume.
Det samme gjaldt, når det blev givet til mennesker sammen med betablokkere.
In haemodynamic studies, amlodipine has not been associated with a negative inotropic effect when administered in the therapeutic dose range to intact animals and humans, even when co-administered with beta blockers to humans.
Valsartan Valsartan er en oral, aktiv, potent og specifik angiotensin II- receptorantagonist.
Valsartan Valsartan is an orally active, potent and specific angiotensin II receptor antagonist.
Det virker selektivt på AT1- receptor subtypen, som er ansvarlig for angiotensin II’ s kendte virkninger.
It acts selectively on the receptor subtype AT1, which is responsible for the known actions of angiotensin II.
Dette kan stimulere den ublokerede AT2- receptor subtype, som tilsyneladende modvirker virkningen af AT1- receptoren.
The increased plasma levels of angiotensin II following AT1 receptor blockade with valsartan may stimulate the unblocked receptor subtype AT2, which appears to counterbalance the effect of the AT1 receptor.
20. 000 gange) affinitet for AT1- receptoren end for AT2- receptoren.
Valsartan does not exhibit any partial agonist activity at the AT1 receptor and has much (about 20,000-fold) greater affinity for the AT1 receptor than for the AT2 receptor.
Da der ikke er nogen effekt på ACE og ingen potensering af bradykinin eller substans P, er det usandsynligt, at angiotensin II- antagonister kan forbindes med hoste.
Since there is no effect on ACE and no potentiation of bradykinin or substance P, angiotensin II antagonists are unlikely to be associated with coughing.
I kliniske undersøgelser, hvor valsartan blev sammenlignet med en ACE- hæmmer, var incidensen af tør hoste signifikant (p < 0, 05) mindre hos patienter i behandling med valsartan end hos patienter i behandling med en ACE- hæmmer (2, 6% versus 7, 9%, henholdsvis).
In clinical trials where valsartan was compared with an ACE inhibitor, the incidence of dry cough was significantly (p < 0.05) lower in patients treated with valsartan than in those treated with an ACE inhibitor (2.6% versus 7.9%, respectively).
Til sammenligning oplevede 68, 5% af patienterne, som blev behandlet med en ACE- hæmmer, hoste (p < 0, 05).
In a clinical trial of patients with a history of dry cough during ACE inhibitor therapy, 19.5% of trial subjects receiving valsartan and 19.0% of those receiving a thiazide diuretic experienced coughing, compared to 68.5% of those treated with an ACE inhibitor (p < 0.05).
Den maksimale reduktion af blodtrykket opnås inden for 4- 6 timer.
In most patients, after administration of a single oral dose, onset of antihypertensive activity occurs within 2 hours, and the peak drop in blood pressure is achieved within 4– 6 hours.
Ved gentagen dosering opnås den maksimale reduktion af blodtrykket inden for 2- 4 uger, og den opretholdes ved vedvarende behandling.
During repeated administration, the maximum reduction in blood pressure with any dose is generally attained within 2– 4 weeks and is sustained during long-term therapy.
Pludselig seponering af valsartan har ikke været forbundet med rebound- hypertension eller andre uønskede kliniske hændelser.
Abrupt withdrawal of valsartan has not been associated with rebound hypertension or other adverse clinical events.
Amlodipin/ valsartan Mere end 1. 400 hypertensive patienter har fået Copalia en gang daglig i to placebokontrollerede undersøgelser.
Amlodipine/ Valsartan Over 1,400 hypertensive patients received Copalia once daily in two placebo-controlled trials.
Voksne med mildt til moderat ukompliceret essentiel hypertension (middel siddende diastolisk blodtryk ≥95 og < 110 mmHg) blev inkluderet.
Adults with mild to moderate uncomplicated essential hypertension (mean sitting diastolic blood pressure ≥ 95 and < 110 mmHg) were enrolled.
Patienter med høje kardiovaskulære risici – hjertesvigt, type I - og dårligt kontrolleret type II- diabetes og en historie med myokardieinfarkt eller slagtilfælde inden for det sidste år – blev ekskluderet.
Patients with high cardiovascular risks – heart failure, type I and poorly controlled type II diabetes and history of myocardial infarction or stroke within one year – were excluded.
Kombinationen af amlodipin og valsartan giver et dosisrelateret, additivt blodtryksfald på tværs af det terapeutiske dosisinterval.
The combination of amlodipine and valsartan produces dose-related additive reduction in blood pressure across its therapeutic dose range.
Til sammenligning blev der set en normalisering af blodtrykket hos 53% af patienterne, som forblev på valsartan 160 mg.
A multicentre, randomised, double-blind, active-controlled, parallel-group trial showed normalisation of blood pressure (trough sitting diastolic blood pressure < 90 mmHg at the end of the trial) in patients not adequately controlled on valsartan 160 mg in 75% of patients treated with amlodipine/ valsartan 10 mg/ 160 mg and 62% of patients treated with amlodipine/ valsartan 5 mg/ 160 mg, compared to 53% of patients remaining on valsartan 160 mg.
Tillæg af amlodipin 10 mg og 5 mg gav et yderligere nedsat systolisk/ diastolisk blodtryk på henholdsvis 6, 0/ 4, 8 mmHg og 3, 9/ 2, 9 mmHg sammenlignet med patienter, som forblev på valsartan 160 mg alene.
The addition of amlodipine 10 mg and 5 mg produced an additional reduction in systolic/ diastolic blood pressure of 6.0/ 4.8 mmHg and 3.9/ 2.9 mmHg, respectively, compared to patients who remained on valsartan 160 mg only.
Til sammenligning blev der set en normalisering af blodtrykket hos 67% af patienterne, som forblev på amlodipin 10 mg.
9 A multicentre, randomised, double-blind, active-controlled, parallel-group trial showed normalisation of blood pressure (trough sitting diastolic blood pressure < 90 mmHg at the end of the trial) in patients not adequately controlled on amlodipine 10 mg in 78% of patients treated with amlodipine/ valsartan 10 mg/ 160 mg, compared to 67% of patients remaining on amlodipine 10 mg.
Tillæg af valsartan 160 mg gav et yderligere nedsat systolisk/ diastolisk blodtryk på henholdsvis 2, 9/ 2, 1 mmHg sammenlignet med patienter, som forblev på amlodipin 10 mg alene.
The addition of valsartan 160 mg produced an additional reduction in systolic/ diastolic blood pressure of 2.9/ 2.1 mmHg compared to patients who remained on amlodipine 10 mg only.
Copalia er også undersøgt i et aktivt kontrolleret studie med 130 hypertensive patienter med diastolisk blodtryk ≥110 mmHg og < 120 mmHg.
Copalia was also studied in an active-controlled study of 130 hypertensive patients with diastolic blood pressure ≥ 110 mmHg and < 120 mmHg.
Til sammenligning nedsatte et behandlingsregime bestående af lisinopril/ hydrochlorthiazid 10/ 12, 5 mg titreret op til 20/ 12, 5 mg blodtrykket i siddende stilling med 32/ 28 mmHg.
In this study (baseline blood pressure 171/ 113 mmHg), an Copalia regimen of 5 mg/ 160 mg titrated to 10 mg/ 160 mg reduced sitting blood pressure by 36/ 29 mmHg as compared to 32/ 28 mmHg with a regimen of lisinopril/ hydrochlorothiazide 10 mg/ 12.5 mg titrated to 20 mg/ 12.5 mg.
I to langtids- og opfølgningsstudier blev effekten af Copalia opretholdt i over et år.
In two long-term follow-up studies the effect of Copalia was maintained for over one year.
Patienter, der ikke er tilstrækkelig kontrolleret på amlodipin 5 mg, kan opnå blodtrykskontrol med amlodipin/ valsartan 5 mg/ 80 mg på lige fod med amlodipin 10 mg men med mindre forekomst af ødem.
In patients not adequately controlled on amlodipine 5 mg, amlodipine/ valsartan 5 mg/ 80 mg may achieve blood pressure control similar to amlodipine 10 mg with less oedema.
Hos patienter, som er tilstrækkeligt kontrolleret på amlodipin 10 mg, men som oplever uacceptable ødemer, kan amlodipin/ valsartan 5 mg/ 80 mg opnå samme blodtrykskontrol med mindre forekomst af ødem.
In patients adequately controlled on amlodipine 10 mg but who experience unacceptable oedema, amlodipine/ valsartan 5 mg/ 80 mg may achieve similar blood pressure control with less oedema.
Alder, køn og race havde ingen indflydelse på Copalias virkning.
Age, gender and race did not influence the response to Copalia.
10 Copalia er ikke undersøgt i andre patientgrupper end hypertension.
Copalia has not been studied in any patient population other than hypertension.
Valsartan er undersøgt til patienter med post- myokardieinfarkt og hjertesvigt.
Valsartan has been studied in patients with post myocardial infarction and heart failure.
Linaritet Amlodipin og valsartan udviser linær farmakokinetik.
Linearity Amlodipine and valsartan exhibit linear pharmacokinetics.
Amlodipin Absorption:
Amlodipine Absorption:
Efter oral administration af amlodipin alene i terapeutiske doser opnås maksimal plasmakoncentration af amlodipin efter 6- 12 timer.
After oral administration of therapeutic doses of amlodipine alone, peak plasma concentrations of amlodipine are reached in 6– 12 hours.
Fordelingsvolumen er omkring 21 l/ kg.
Volume of distribution is approximately 21 l/ kg.
97, 5% af det cirkulerende stof er bundet til plasmaproteiner i hypertensive patienter.
In vitro studies with amlodipine have shown that approximately 97.5% of circulating drug is bound to plasma proteins in hypertensive patients.
90%) metaboliseret i leveren til inaktive metabolitter.
Amlodipine is extensively (approximately 90%) metabolised in the liver to inactive metabolites.
30 til 50 timer.
Amlodipine elimination from plasma is biphasic, with a terminal elimination half-life of approximately 30 to 50 hours.
Steady- state- plasmaniveauerne opnås efter vedvarende administration i 7- 8 dage.
Steady-state plasma levels are reached after continuous administration for 7– 8 days.
Ti procent uomdannet amlodipin og 60% af amlodipin- metabolitterne udskilles i urinen.
Ten per cent of original amlodipine and 60% of amlodipine metabolites are excreted in urine.
Valsartan Absorption:
Valsartan Absorption:
Efter oral administration af valsartan alene opnås valsartans maksimale plasmakoncentration efter 2- 4 timer.
Following oral administration of valsartan alone, peak plasma concentrations of valsartan are reached in 2– 4 hours.
Valsartan udviser tokompartment halveringskinetik (t½α < 1 time og t½ß omkring 9 timer).
Valsartan shows multiexponential decay kinetics (t½α < 1 h and t½ß about 9 h).
8 timer efter dosering er plasmakoncentrationen af valsartan den samme for den bespiste og fastende gruppe.
Food decreases exposure (as measured by AUC) to valsartan by about 40% and peak plasma concentration (Cmax) by about 50%, although from about 8 h post dosing plasma valsartan concentrations are similar for the fed and fasted groups.
Distribution:
10 Distribution:
Steady- state fordelingsvolumen af valsartan efter intravenøs administration er omkring 17 liter, hvilket tyder på, at valsartan ikke fordeles i udtalt grad i væv.
The steady-state volume of distribution of valsartan after intravenous administration is about 17 litres, indicating that valsartan does not distribute into tissues extensively.
Valsartan er i høj grad bundet til serumproteiner (94- 97%), hovedsageligt serumalbumin.
Valsartan is highly bound to serum proteins (94– 97%), mainly serum albumin.
Valsartan omdannes ikke i stor grad, da kun omkring 20% af dosis genfindes som metabolitter.
Valsartan is not transformed to a high extent as only about 20% of dose is recovered as metabolites.
30% af den totale clearence).
Following intravenous administration, plasma clearance of valsartan is about 2 l/ h and its renal clearance is 0.62 l/ h (about 30% of total clearance).
Amlodipin/ valsartan Efter oral administration af Copalia opnås maksimal plasmakoncentration for valsartan og amlodipin efter henholdsvis 3 timer og 6- 8 timer.
Amlodipine/ Valsartan Following oral administration of Copalia, peak plasma concentrations of valsartan and amlodipine are reached in 3 and 6– 8 hours, respectively.
Hastigheden og graden af Copalia- absorptionen er ækvivalent med valsartans og amlodipins biotilgængelighed, når de gives som individuelle tabletter.
The rate and extent of absorption of Copalia are equivalent to the bioavailability of valsartan and amlodipine when administered as individual tablets.
Særlige populationer Pædiatriske patienter (under 18 år) Der er ingen farmakokinetiske data tilgængelige for den pædiatriske population.
Special populations Paediatric patients (age below 18 years) No pharmacokinetic data are available in the paediatric population.
11 Ældre (65 år og derover) Tiden til maksimal plasmakoncentration af amlodipin er den samme for yngre og ældre patienter.
Elderly (age 65 years or over) Time to peak plasma amlodipine concentrations is similar in young and elderly patients.
Derfor kræves forsigtighed, når dosis øges.
Mean systemic AUC of valsartan is higher by 70% in the elderly than in the young therefore caution is required when increasing the dosage.
Nedsat nyrefunktion Nedsat nyrefunktion har ikke en signifikant indflydelse på amlodipins farmakokinetik.
Renal impairment The pharmacokinetics of amlodipine are not significantly influenced by renal impairment.
40- 60%.
Hepatic impairment Patients with hepatic insufficiency have decreased clearance of amlodipine with resulting increase of approximately 40– 60% in AUC.
Hos patienter med mildt til moderat nedsat leverfunktion er den gennemsnitlige eksponering af valsartan (målt ved AUC- værdier) to gange højere end den, der er set hos raske frivillige (passet sammen efter alder, køn og vægt).
On average, in patients with mild to moderate chronic liver disease exposure (measured by AUC values) to valsartan is twice that found in healthy volunteers (matched by age, sex and weight).
Der skal udvises forsigtighed over for patienter med leverlidelser (se pkt. 4. 2).
Caution should be exercised in patients with liver disease (see section 4.2).
Histopatologiske tegn på inflammation i maveslimhinden blev set hos hanrotter ved en eksponering ca.
Adverse reactions observed in animal studies with possible clinical relevance were as follows: