natgillin/translations-raw huggingface dataset:
Ibandronsyre hører til bisphosphonatgruppen, som har stor affinitet til knoglemineraler.
Ibandronic acid belongs to the bisphosphonate group of compounds which act specifically on bone.
Den selektive virkning på knogler er baseret på en høj affinitet for bisphosphonater til knoglemineraler.
Their selective action on bone tissue is based on the high affinity of bisphosphonates for bone mineral.
Virkningsmekanismen er endnu ikke klarlagt.
Bisphosphonates act by inhibiting osteoclast activity, although the precise mechanism is still not clear.
In vivo forhindrer ibandronsyre eksperimentelt- induceret knogleødelæggelse forårsaget af ophøret af den gonadale funktion, retinoider, tumorer eller tumorekstrakter.
In vivo, ibandronic acid prevents experimentally-induced bone destruction caused by cessation of gonadal function, retinoids, tumours or tumour extracts.
Kliniske undersøgelser ved behandling af tumorinduceret hypercalcæmi Kliniske studier ved malign hypercalcæmi har vist, at ibandronsyres hæmmende virkning på tumorinduceret osteolyse og specifikt på tumorinduceret hypercalcæmi er karakteriseret ved nedsættelse af serum calcium og urin calcium udskillelsen.
Clinical Studies in the Treatment of Tumour-Induced Hypercalcemia Clinical studies in hypercalcaemia of malignancy demonstrated that the inhibitory effect of ibandronic acid on tumour-induced osteolysis, and specifically on tumour-induced hypercalcaemia, is characterised by a decrease in serum calcium and urinary calcium excretion.
Indenfor det rekommenderede dosisinterval har kliniske studier vist helbredelsesrater som anført i figuren med respektive konfidensintervaller for patienter, som har en udgangsværdi for albuminkorrigeret serum calcium ≥ 3, 0 mmol/ l efter nødvendig rehydrering.
In the dose range recommended for treatment, the following response rates with the respective confidence intervals have been shown in clinical trials for patients with baseline albumin-corrected serum calcium ≥ 3.0 mmol/ l after adequate rehydration.
8 88
8 88
86
78 86 100%
76 64
64
80 62
62
50 44 40 6 mg 30
40
20 10
20
ibandronicsyre dosis
ibandronic ac id dos e
høj 90%
high 90%
konfidens
c onf idenc e int erv al
helbredelses
res pons e rat e
lav 90% konfidens interval
low 90% c onf idenc e int erv al
Mediantiden for opnåelse af normocalcæmi var 4- 7 dage for disse patienter og disse doser.
For these patients and dosages, the median time to achieve normocalcaemia was 4 to 7 days.
Mediantiden for tilbagefald (tilbagevenden af albumin- korrigeret serum- calcium til mere end 3 mmol/ l) var 18- 26 dage.
The median time to relapse (return of albumin-corrected serum calcium above 3.0 mmol/ l) was 18 to 26 days.
Kliniske undersøgelser ved forebyggelse af knoglerelaterede hændelser hos patienter med brystkræft og knoglemetastaser Kliniske undersøgelser hos patienter med brystkræft og knoglemetastaser har vist at der er en dosisafhængig hæmmende effekt på knogleosteolysen, udtrykt ved markører for knogleresorption, og en dosisafhængig effekt på de skeletale hændelser.
Clinical Studies in the Prevention of Skeletal Events in Patients with Breast Cancer and Bone Metastases Clinical studies in patients with breast cancer and bone metastases have shown that there is a dose dependent inhibitory effect on bone osteolysis, expressed by markers of bone resorption, and a dose dependent effect on skeletal events.
Behandlingen med Bondronat 6 mg administreret intravenøst ved forebyggelse af knoglerelaterede hændelser hos patienter med brystkræft og knoglemetastaser blev vurderet i en randomiseret, placebokontrolleret fase III undersøgelse, som varede i 96 uger.
Prevention of skeletal events in patients with breast cancer and bone metastases with Bondronat 6 mg administered intravenously was assessed in one randomized placebo controlled phase III trial with duration of 96 weeks.
Primære effektparametre Det primære endepunkt i undersøgelsen var skeletal morbidity period rate (SMPR).
Primary Efficacy Endpoints The primary endpoint of the trial was the skeletal morbidity period rate (SMPR).
Dette var et sammensat endepunkt som havde følgende skeletrelaterede hændelser (SREs) inkluderet:
This was a composite endpoint which had the following skeletal related events (SREs) as sub-components:
- knoglestrålebehandling for behandling af frakturer/ truende frakturer
- radiotherapy to bone for treatment of fractures/ impending fractures
- knoglekirurgi for behandling af frakturer
- surgery to bone for treatment of fractures
- vertebrale frakturer
- vertebral fractures
- non- vertebrale frakturer
- non-vertebral fractures.
Multiple hændelser blev derfor kun talt én gang for analyseformål.
Multiple events were therefore counted only once for the purposes of the analysis.
Resultaterne fra denne undersøgelse viste en signifikant fordel for intravenøs Bondronat 6 mg frem for placebo, ved reduktion af SREs målt ved den tidsjusterede SMPR (p=0, 004).
Data from this study demonstrated a significant advantage for intravenous Bondronat 6 mg over placebo in the reduction in SREs measured by the time-adjusted SMPR (p=0.004).
Antallet af SREs var desuden signifikant reduceret ved Bondronat 6 mg ligesom der var en 40% reduktion i risiko for en SRE i forhold til placebo (relativ risiko 0, 6, p=0, 003).
The number of SREs was also significantly reduced with Bondronat 6 mg and there was a 40% reduction in the risk of a SRE over placebo (relative risk 0.6, p = 0.003).
Effektresultaterne fremgår af tabel 3.
Efficacy results are summarised in Table 3.
9 Tabel 3
9 Table 3
Effektresultater (Brystkræft patienter med metastaserende knoglesygdom)
Efficacy Results (Breast Cancer Patients with Metastatic Bone Disease)
Alle skeletrelaterede hændelser (SREs) Placebo Bondronat 6 mg p- værdi n=158 n=154
All Skeletal Related Events (SREs) Placebo Bondronat 6 mg p-value n=158 n=154
1, 48 1, 19 p=0, 004
p=0.004
Sekundære effektparametre Intravenøs Bondronat 6 mg viste i sammenligning med placebo en statistisk signifikant forbedring i knoglesmertescore.
Secondary Efficacy Endpoints A statistically significant improvement in bone pain score was shown for intravenous Bondronat 6 mg compared to placebo.
Forringelsen i livskvalitet var signifikant mindre for Bondronat behandlede patienter i forhold til placebo.
The deterioration in Quality of Life was significantly less in Bondronat treated patients compared with placebo.
En oversigt over de sekundære effektresultater fremgår af Tabel 4.
A tabular summary of these secondary efficacy results is presented in Table 4.
Sekundære effektresultater (brystkræft patienter med metastaserende knoglesygdom)
cancer Patients with Metastatic Bone Disease)
Placebo Bondronat 6 mg p- værdi n=158 n=154
Placebo n=158
Knoglesmerte *
Bondronat 6 mg p-value n=154
0, 21
Bone pain *
- 0, 28
0.21
P < 0, 001
-0.28 p < 0.001
Analgetika forbrug *
Analgesic use *
I en klinisk undersøgelse med 130 patienter med metastatisk brystkræft blev sikkerheden af Bondronat sammenlignet ved infusion over 1 time i forhold til infusion over 15 minutter.
In a study in 130 patients with metastatic breast cancer the safety of Bondronat infused over 1 hour or 15 minutes was compared.
Der blev heller ikke identificeret nogen nye sikkerhedsrisici ved anvendelsen af en 15 minutters infusionstid.
The overall adverse event profile of ibandronic acid following the 15 minute infusion was consistent with the known safety profile over longer infusion times and no new safety concerns were identified relating to the use of a 15 minute infusion time.
Der er ikke foretaget undersøgelser med en infusionstid på 15 minutter hos cancerpatienter med kreatininclearance på < 50 ml/ min.
A 15 minute infusion time has not been studied in cancer patients with a creatinine clearance of < 50ml/ min.
Hos mennesker er det tilsyneladende terminale fordelingsvolumen mindst 90 liter og det estimeres at 40- 50% af den cirkulerende dosis bindes til knoglerne.
In humans, the apparent terminal volume of distribution is at least 90 l and the amount of dose reaching the bone is estimated to be 40-50% of the circulating dose.
87%
Protein binding in human plasma is
Lægemiddelinteraktioner på grund af displacering er derfor usandsynlig.
10 approximately 87% at therapeutic concentrations, and thus drug-drug interaction due to displacement is unlikely.
Metabolisme Der er ikke tegn på at ibandronsyre metaboliseres i dyr eller mennesker.
Metabolism There is no evidence that ibandronic acid is metabolized in animals or humans.
Elimination Måleområdet for de tilsyneladende halveringstider er bredt og afhænger af dosis og målefølsomhed, men den tilsyneladende terminale halveringstid er generelt i området 10- 60 timer.
Elimination The range of observed apparent half-lives is broad and dependent on dose and assay sensitivity, but the apparent terminal half-life is generally in the range of 10-60 hours.
De tidlige plasma - værdier falder dog hurtigt og når 10% af peakværdien indenfor 3 og 8 timer efter henholdsvis intravenøs og peroral administration.
However, early plasma levels fall quickly, reaching 10% of peak values within 3 and 8 hours after intravenous or oral administration respectively.
60 ml/ min. hos raske postmenopausale kvinder) udgør 50- 60% af den totale clearance og er relateret til kreatininclearance.
Renal clearance (about 60 ml/ min in healthy postmenopausal females) accounts for 50-60% of total clearance and is related to creatinine clearance.
Farmakokinetik hos særlige populationer
Pharmacokinetics in Special Populations
Race Der er ikke noget der tyder på en klinisk relevant inter- etnisk forskel i tilstedeværelsen af ibandronsyre mellem asiater og kaukasere.
Race There is no evidence for clinically relevant interethnic differences between Asians and Caucasians in ibandronic acid disposition.
Patienter med nedsat nyrefunktion Eksponering af ibandronsyre hos patienter med forskellige grader af nedsat nyrefunktion er relateret til kreatininclearance (CLcr).
Patients with renal impairment Exposure to ibandronic acid in patients with various degrees of renal impairment is related to creatinine clearance (CLcr).
Den kliniske farmakoligiske undersøgelse WP18551 viste følgende: efter administration af en enklet intravenøs dosis på 6 mg (15 minutters infusion) steg middel AUC0- 24 med henholdsvis 14% og 86% hos patienter med lettere (middel estimeret CLcr=68, 1 ml/ min) og moderat (middel estimeret CLcr=41, 2 ml/ min) nedsat nyrefunktion, sammenlignet med raske frivillige (middel estimeret CLcr=120 ml/ min).
In clinical pharmacology trial WP18551, after a single dose intravenous administration of 6 mg (15 minutes infusion), mean AUC0-24 increased by 14% and 86%, respectively, in subjects with mild (mean estimated CLcr=68.1 mL/ min) and moderate (mean estimated CLcr=41.2 mL/ min) renal impairment compared to healthy volunteers (mean estimated CLcr=120 mL/ min).
Middel C max var ikke øget hos patienter med lettere nedsat nyrefunktion, og den var øget med 12% hos patienter med moderat nedsat nyrefunktion.
Mean Cmax was not increased in patients with mild renal impairment and increased by 12% in patients with moderate renal impairment.
Der er ingen tegn på, at tolerancen reduceres i forbindelsen med en øgning i eksponeringen.
There is no evidence of a reduction in tolerability associated with an increase in exposure.
4. 2).
However, an adjustment in the dose or infusion time is recommended in patients being treated for the prevention of skeletal events in patients with breast cancer and bone metastases (see section 4.2).
87% ved terapeutiske koncentrationer, er det ikke sandsynligt at hypoproteinæmi ved svær leversygdom medfører væsentlig øgning af frie plasmakoncentrationer.
Further, as protein binding of ibandronic acid is approximately 87% at therapeutic concentrations, hypoproteinaemia in severe liver disease is unlikely to lead to clinically significant increases in free plasma concentration.
Ældre I en multivariat analyse kunne alder ikke påvises som en uafhængig faktor for nogen af de undersøgte farmakokinetiske parametre.
Elderly In a multivariate analysis, age was not found to be an independent factor of any of the pharmacokinetic parameters studied.
Børn og unge Der findes ikke data vedrørende brugen af Bondronat til patienter under 18 år.
Children and adolescents There are no data on the use of Bondronat in patients less than 18 years old.
Disse virkninger vurderes derfor til at være af ringe relevans ved klinisk brug.
11 Effects in non-clinical studies were observed only at exposures sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.
Undersøgelser for genotoksicitet viste ingen tegn på genetisk aktivitet af ibandronsyre.
Tests for genotoxicity revealed no evidence of effects on genetic activity for ibandronic acid.
Bivirkningerne af ibandronsyre hos rotter i reproduktionstoksicitets - undersøgelserne var de samme som forventet for bisphosphonatklassen.
Adverse effects of ibandronic acid in reproductive toxicity studies in the rat were those expected for this class of drug (bisphosphonates).
De omfatter en nedsættelse af antallet af implanta- tionssteder, forstyrrelser af den normale fødsel (dystocia), en øgning af viscerale variationer (nyre pelvis ureter syndrom) og tandabnormaliteter på F1 afkommet hos rotter.
They include a decreased number of implantation sites, interference with natural delivery (dystocia), an increase in visceral variations (renal pelvis ureter syndrome) and teeth abnormalities in F1 offspring in rats.
Natriumchlorid Eddikesyre( 99%) Natriumacetat Vand til injektionsvæsker
Sodium chloride Acetic acid (99%) Sodium acetate Water for injections
For at undgå potentielle uforligeligheder bør Bondronat koncentrat til infusionsvæske, opløsning kun fortyndes med isotonisk natriumklorid- infusionsvæske eller 5% glucose- infusionsvæske.
To avoid potential incompatibilities Bondronat concentrate for solution for infusion should only be diluted with isotonic sodium chloride solution or 5% glucose solution.
5 år Efter rekonstituering:
5 years After reconstitution:
24 timer
24 hours.
Ingen særlige opbevaringsbetingelser inden rekonstitution.
No special precautions for storage prior to reconstitution.
Opbevares ved 2 °C - 8 °C (i køleskab)
Store at 2 °C – 8 °C (in a refrigerator).
Udfra et mikrobiologisk synspunkt skal præparatet anvendes med det samme.
From a microbiological point of view, the product should be used immediately.
Hvis det ikke anvendes straks er opbevaringstiden og betingelserne for opbevaring før anvendelsen brugerens ansvar, og opbevaringstiden må normalt ikke være længere end 24 timer ved 2 °C - 8 °C, medmindre rekonstitueringen har fundet sted under kontrollerede og validerede aseptiske betingelser.
If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8 °C, unless reconstitution has taken place in controlled and validated aseptic conditions.
Bondronat leveres i pakninger med 1 hætteglas (2 ml hætteglas af type I glas).
Bondronat is supplied as packs containing 1 vial (2 ml type I glass vial).
Dato for første tilladelse:
Date of first Authorisation:
25, juni, 1996
25 June 1996
Dato for sidste genregistrering:
Date of last renewal:
25, juni, 2006
25 June 2006
Bondronat 50 mg filmovertrukne tabletter.
Bondronat 50 mg Film Coated Tablets
Hver filmovertrukket tablet indeholder 50 mg ibandronsyre, (som natriumibandronat monohydrat).
Each film-coated tablet contains 50 mg of ibandronic acid (as ibandronic sodium monohydrate).
En liste over alle hjælpestoffer er anført under pkt 6. 1.
For a full list of excipients, see section 6.1.
Bondronat tabletter indeholder lactose og bør ikke administreres til patienter med arvelig galactoseintolerans, en særlig form af hereditær lactasemangel (Lapp Lactase deficiency) eller glucose/ galactosemalabsorption.
Bondronat tablets contain lactose and should not be administered to patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
Hvide til råhvide filmovertrukne, aflange tabletter mærket ” L2 ” på den ene side og ” IT ” på den anden side.
White to off-white film-coated tablets, of oblong shape engraved “ L2” on one side and “ IT” on the other side.
Bondronat er indiceret til forebyggelse af knoglerelaterede hændelser (patologiske frakturer, knoglekomplikationer, som kræver strålebehandling eller operation) hos patienter med brystkræft og knoglemetastaser.
Bondronat is indicated for the prevention of skeletal events (pathological fractures, bone complications requiring radiotherapy or surgery) in patients with breast cancer and bone metastases.
Behandling med Bondronat bør kun initieres af læger med erfaring med behandling af cancer.
Bondronat therapy should only be initiated by physicians experienced in the treatment of cancer.
Bondronat skal indtages efter natlig faste (mindst 6 timer) og før indtagelse af mad - eller drikkevarer.
Bondronat tablets should be taken after an overnight fast (at least 6 hours) and before the first food or drink of the day.
Medicin og kosttilskud (herunder calcium) skal ligeledes undgås inden indtagelse af Bondronat tabletter.
Medicinal products and supplements (including calcium) should similarly be avoided prior to taking Bondronat tablets.
Almindeligt postevand kan indtages på ethvert tidspunkt under Bondronat behandlingen.
Plain water may be taken at any time during the course of Bondronat treatment.
• Tabletterne skal synkes hele med et glas postevand (180 til 240 ml), med patienten i siddende eller oprejst stilling.
- The tablets should be swallowed whole with a full glass of plain water (180 to 240 ml) while the
• Patienter må ikke ligge ned i op til 60 minutter efter indtagelse af Bondronat
- Patients should not lie down for 60 minutes after taking Bondronat.
• Patienterne må ikke tygge eller sutte på tabletterne på grund af risiko for oropharyngeal ulceration
- Patients should not chew or suck the tablet because of a potential for oropharyngeal ulceration.
• Bondronat må kun indtages sammen med postevand.
- Plain water is the only drink that should be taken with Bondronat.
Visse typer mineralvand kan indeholde en højere koncentration af calcium og bør derfor ikke benyttes.
waters may have a higher concentration of calcium and therefore should not be used.
Patienter med nedsat leverfunktion
Patients with hepatic impairment No dosage adjustment is required (see section 5.2).
5. 2).
Patients with renal impairment
Patienter med nedsat nyrefunktion Dosisreduktion er ikke nødvendig hos patienter med lettere eller moderat nyreinsufficiens hvor kreatinin - clearance er lig med eller større end 30 ml/ min.
14 No dosage adjustment is necessary for patients with mild or moderate renal impairment where creatinine clearance is equal to or greater than 30 ml/ min.
Ved kreatininclearance under 30 ml/ min., er den anbefalede dosis 50 mg én gang ugentligt.
Below 30 ml/ min creatinine clearance, the recommended dose is 50 mg once weekly.
Ældre Dosisjustering er ikke nødvendig.
Elderly No dose adjustment is necessary.
Børn og unge Bondronat bør ikke anvendes til børn under 18 år p. g. a. utilstrækkelig dokumentation for sikkerhed og virkning.
Children and adolescents Bondronat is not recommended for patients below age 18 years due to insufficient data on safety and efficacy.
Overfølsomhed over for det aktive stof eller over for et eller flere af hjælpestofferne.
Hypersensitivity to ibandronic acid or to any of the excipients.
Forsigtighed skal udvises hos patienter med kendt overfølsomhed overfor bisphosphonater.
Caution is indicated in patients with known hypersensitivity to other bisphosphonates.
Hypocalcæmi og andre forstyrrelser i knogle – mineralstofskiftet bør behandles effektivt før behandling med Bondronat initieres.
Hypocalcaemia and other disturbances of bone and mineral metabolism should be effectively treated before starting Bondronat therapy.
Det er vigtigt at alle patienter har et tilstrækkeligt indtag af calcium og D- vitamin.
Adequate intake of calcium and vitamin D is important in all patients.
Patienterne bør have et calcium - og/ eller vitamin D- tilskud, hvis der ikke indtages tilstrækkeligt gennem føden.
Patients should receive supplemental calcium and/ or vitamin D if dietary intake is inadequate.
Perorale bisfosfonater har været forbundet med dysfagi, oesophagitis og oesophageale eller gastriske ulcerationer.
Oral bisphosphonates have been associated with dysphagia, oesophagitis and oesophageal or gastric ulcers.
4. 2).
Therefore, patients should pay particular attention to the dosing instructions (see section 4.2).
Lægen skal være opmærksom på ethvert tegn eller symptom på oesophagus reaktion under behandlingen, og patienterne skal instrueres i at standse behandlingen med Bondronat og søge læge, hvis de udvikler symptomer på spiserørsirritation som f. eks. nyopstået eller forværret dysfagi, synke - smerter, retrosternal smerte eller halsbrand.
Physicians should be alert to signs or symptoms signalling a possible oesophageal reaction during therapy, and patients should be instructed to discontinue Bondronat and seek medical attention if they develop symptoms of oesophageal irritation such as new or worsening dysphagia, pain on swallowing, retrosternal pain, or heartburn.
Da NSAIDs er forbundet med gastrointestinal irritation, bør der udvises forsigtighed ved samtidig peroral behandling med Bondronat.
Since NSAIDS are associated with gastrointestinal irritation, caution should be taken during concomitant oral medication with Bondronat.
I overensstemmelse med god klinisk praksis anbefales det dog alligevel at kontrollere nyrefunktionen, serum calcium, fosfat og magnesium på den enkelte patient i Bondronat behandling.
Nevertheless, according to clinical assessment of the individual patient, it is recommended that renal function, serum calcium, phosphate and magnesium should be monitored in patients treated with Bondronat.
Bondronat tabletter indeholder laktose og må ikke gives til patienter med sjældne, arvelige problemer med galaktoseintolerans, LAPP laktoseunderskud eller glucose- galaktose malabsorption.
Bondronat tablets contain lactose and should not be administered to patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
15 En tandundersøgelse med passende forebyggende odontologi bør overvejes hos patienter med samtidige risikofaktorer (som f. eks. cancer, kemoterapi, strålebehandling, kortikosteroider, dårlig oral hygiejne) før behandling med bisphosphonater.
A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e. g. cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene).
Hvis det er muligt bør disse patienter under behandlingen undgå invasive dentale indgreb.
15 While on treatment, these patients should avoid invasive dental procedures if possible.
Føde interaktioner Produkter indeholdende calcium og andre multivalente kationer (som f. eks. aluminium, magnesium, jern), herunder mælk og føde, vil sandsynligvis påvirke absorptionen af Bondronat tabletter.
Drug-Food Interactions Products containing calcium and other multivalent cations (such as aluminium, magnesium, iron), including milk and food, are likely to interfere with absorption of Bondronat tablets.
75% når Bondronat tabletter blev indtaget 2 timer efter et standardmåltid.
Bioavailability was reduced by approximately 75% when Bondronat tablets were administered 2 hours after a standard meal.
4. 2).
Therefore, it is recommended that the tablets should be taken after an overnight fast (at least 6 hours) and fasting should continue for at least 30 minutes after the dose has been taken (see section 4.2).
Lægemiddel interaktioner Der blev ikke set interaktion ved samtidig administration af melphalan/ prednisolon hos patienter med myelomatose.
Drug-Drug Interactions When co-administered with melphalan/ prednisolone in patients with multiple myeloma, no interaction was observed.