natgillin/translations-raw huggingface dataset:
Anvendelse til ældre Strontiumranelats sikkerhed og virkning er fastlagt i et bredt aldersudsnit (op til 100 år ved inklusion) af postmenopausale kvinder med osteoporose.
Use in the elderly The efficacy and safety of strontium ranelate have been established in a broad age range (up to 100 years at inclusion) of postmenopausal women with osteoporosis.
Dosisjustering på grund af alder er ikke nødvendigt.
No dosage adjustment is required in relation to age.
Nedsat nyrefunktion Dosisjustering er ikke nødvendigt hos patienter med let til moderat nyrefunktionsnedsættelse (kreatininclearance 30- 70 ml/ min) (se pkt.
Use in renal impairment No dosage adjustment is required in patients with mild-to-moderate renal impairment (30-70 ml/ min creatinine clearance) (see section 5.2).
4. 4 og 5. 2).
Strontium ranelate is not recommended for patients with severe renal impairment (creatinine clearance below 30 ml/ min) (see sections 4.4 and 5.2).
Nedsat leverfunktion Da strontiumranelat ikke metaboliseres, er dosisjustering ikke nødvendigt hos patienter med nedsat leverfunktion.
2 Use in hepatic impairment As strontium ranelate is not metabolised, no dosage adjustment is required in patients with hepatic impairment.
2 Børn og unge OSSEOR bør ikke anvendes til børn og unge, p. g. a. manglende dokumentation for sikkerhed og virkning.
Use in children and adolescents OSSEOR is not recommended for use in children and adolescents due to a lack of data on safety and efficacy.
5. 2).
In the absence of bone safety data in patients with severe renal impairment treated with strontium ranelate, OSSEOR is not recommended in patients with a creatinine clearance below 30 ml/ min (see section 5.2).
I henhold til god lægelig praksis anbefales regelmæssig vurdering af nyrefunktionen hos patienter med kronisk nedsættelse af nyrefunktionen.
In accordance with good medical practice, periodic assessment of renal function is recommended in patients with chronic renal impairment.
Hos patienter, der udvikler alvorlig nedsættelse af nyrefunktionen, bør det overvejes i det enkelte tilfælde, om behandlingen med OSSEOR kan fortsættes.
Continuation of treatment with OSSEOR in patients developing severe renal impairment should be considered on an individual basis.
4. 8).
In phase III placebo-controlled studies, strontium ranelate treatment was associated with an increase in the annual incidence of venous thromboembolism (VTE), including pulmonary embolism (see section 4.8).
OSSEOR bør anvendes med forsigtighed til patienter med risiko for VTE, herunder patienter med VTE i anamnesen.
OSSEOR should be used with caution in patients at increased risk of VTE, including patients with a past history of VTE.
Ved behandling af patienter med risiko for VTE eller som er ved at komme i risikogruppen, skal man være særlig opmærksom på mulige symptomer på VTE og træffe passende forebyggende foranstaltninger.
When treating patients at risk, or developing risk of VTE, particular attention should be given to possible signs and symptoms of VTE and adequate preventive measures taken.
I lægelig praksis bør der derfor anvendes en metode baseret på atomemissionsspektrometri med induktivt koblet plasma (ICP- AES) eller atomabsorptionsspektrofotometri for at sikre en nøjagtig vurdering af calciumkoncentrationerne i blod og urin.
Therefore, in medical practice, inductively coupled plasma atomic emission spectrometry or atomic absorption spectrometry methods should be used to ensure an accurate assessment of blood and urinary calcium concentrations.
OSSEOR indeholder en kilde til phenylalanin, som kan være skadeligt i tilfælde af phenylketonuri.
OSSEOR contains a source of phenylalanine, which may be harmful for people with phenylketonuria.
I tilfælde af en alvorlig allergisk reaktion skal OSSEOR seponeres.
Treatment with OSSEOR should be discontinued in case of serious allergic reaction.
Det drejer sig især om DRESS- syndromet (Drug Rash with Eosinophilia and Systemic Symptoms), som kan føre til dødsfald.
Cases of severe hypersensitivity syndromes, including, in particular, drug rash with eosinophilia and systemic symptoms (DRESS), sometimes fatal, have been reported with the use of OSSEOR (see section 4.8).
DRESS- syndromet kendetegnes ved udslæt, feber, eosinofili og systemisk påvirkning (fx adenopati, hepatitis, interstitiel nefropati, interstitiel lungesygdom).
The DRESS syndrome is characterised by rash, fever, eosinophilia and systemic involvement (e. g. adenopathy, hepatitis, interstitial nephropathy, interstitial lung disease).
Symptomerne viste sig sædvanligvis efter 3- 6 uger, og udfaldet var i de fleste tilfælde gunstigt efter seponering af OSSEOR og indledning af behandling med kortikosteroider.
Time to onset was usually around 3-6 weeks and the outcome in most cases favourable upon discontinuation of OSSEOR and after initiation of corticosteroid therapy.
Det kunne tage lang tid at opnå bedring, og i nogle tilfælde er der rapporteret recidiv af syndromet efter seponering af kortikosteroider.
Recovery could be slow and recurrences of the syndrome have been reported in some cases after discontinuation of corticosteroid therapy.
Patienter, der får udslæt, bør rådes til omgående og permanent at stoppe behandlingen med OSSEOR og søge lægehjælp.
Patients should be informed to stop OSSEOR immediately and permanently when a rash occurs and to seek medical advice.
Patienter, som er holdt op med at tage OSSEOR på grund af overfølsomheds - reaktioner, bør ikke genoptage behandlingen.
Patients who have stopped treatment due to hypersensitivity reactions should not re-start therapy with OSSEOR.
60- 70%.
Food, milk and derivative products, and medicinal products containing calcium may reduce the bioavailability of strontium ranelate by approximately 60-70%.
5. 2).
Therefore, administration of OSSEOR and such products should be separated by at least two hours (see section 5.2).
Et klinisk interaktionsforsøg udført in vivo viste, at administration af aluminium og magnesiumhydroxid enten to timer før eller sammen med strontiumranelat gav en mindre nedsættelse i strontiumranelats absorption (AUC faldt med 20- 25%), mens absorptionen var næsten upåvirket, når antacida blev givet to timer efter strontiumranelat.
An in vivo clinical interaction study showed that the administration of aluminium and magnesium hydroxides either two hours before or together with strontium ranelate caused a slight decrease in the absorption of strontium ranelate (20-25% AUC decrease), while absorption was almost unaffected when the antacid was given two hours after strontium ranelate.
Antacida skal derfor fortrinsvis tages mindst to timer efter OSSEOR.
It is therefore preferable to take
3 Divalente kationer kan danne komplekser med peroralt tetracyclin og quinolon i det gastrointestinale system, hvorved absorptionen af disse antibiotika reduceres, og samtidig indgivelse af strontium - ranelat og disse lægemidler anbefales derfor ikke.
As divalent cations can form complexes with oral tetracycline and quinolone antibiotics at the gastro- intestinal level and thereby reduce their absorption, simultaneous administration of strontium ranelate with these medicinal products is not recommended.
Der er ikke konstateret interaktion med perorale D- vitamintilskud.
No interaction was observed with oral supplementation of vitamin D.
De omfattede følgende:
No evidence of clinical interactions or relevant increase of blood strontium levels with medicinal products expected to be commonly prescribed concomitantly with OSSEOR in the target population were found during clinical trials.
Nonsteroide antiinflammatoriske midler (inklusive acetylsalicyl - syre), anilider (såsom paracetamol), H2- receptorantagonister og syrepumpehæmmere, diuretika, digoxin og hjerteglycosider, organiske nitrater og andre vasodilatatorer til hjertesygdom, calcium - antagonister, betablokkere, ACE- hæmmere, angiotensin II- antagonister, selektive beta- 2- adreno - ceptoragonister, peroral antikoagulantia, trombocytfunktionshæmmende midler, statiner, fibrater og benzodiazepinderivater.
These included: nonsteroidal anti-inflammatory agents (including acetylsalicylic acid), anilides (such as paracetamol), H2 blockers and proton pump inhibitors, diuretics, digoxin and cardiac glycosides, organic nitrates and other vasodilators for cardiac diseases, calcium channel blockers, beta blockers, ACE inhibitors, angiotensin II antagonists, selective beta-2 adrenoceptor agonists, oral anticoagulants, platelet aggregation inhibitors, statins, fibrates and benzodiazepine derivatives.
OSSEOR er kun beregnet til postmenopausale kvinder.
OSSEOR is only intended for use in postmenopausal women.
Der foreligger ikke kliniske data om eksponering for strontiumranelat under graviditet.
No clinical data on exposed pregnancies are available for strontium ranelate.
5. 3).
At high doses, animal studies have shown reversible bone effects in the offspring of rats and rabbits treated during pregnancy (see section 5.3).
Strontium udskilles i modermælk.
Strontium is excreted in milk.
Strontiumranelat bør ikke gives til ammende kvinder.
Strontium ranelate should not be given to nursing women.
Strontiumranelat påvirker ikke eller i ubetydelig grad evnen til at føre motorkøretøj eller betjene maskiner.
Strontium ranelate has no or negligible influence on the ability to drive and use machines.
OSSEOR er undersøgt i kliniske forsøg med næsten 8. 000 deltagere.
OSSEOR has been studied in clinical trials involving nearly 8,000 participants.
Langtidssikkerheden er evalueret hos postmenopausale kvinder med osteoporose, der blev behandlet i op til 60 måneder med 2 g strontiumranelat daglig (n = 3. 352) eller placebo (n = 3. 317) i fase III- forsøg.
Long-term safety has been evaluated in postmenopausal women with osteoporosis treated for up to 60 months with strontium ranelate 2 g/ day (n=3,352) or placebo (n=3,317) in phase III studies.
Gennemsnitsalderen var 75 år ved inklusion, og 23% af de deltagende patienter var 80- 100 år.
Mean age was 75 years at inclusion and 23% of the patients enrolled were 80 to 100 years of age.
Der var ingen forskel mellem den generelle incidens af hændelser med strontiumranelat og placebo, og hændelserne var sædvanligvis milde og forbigående.
Overall incidence rates for adverse events with strontium ranelate did not differ from placebo and adverse events were usually mild and transient.
De mest almindelige hændelser var kvalme og diaré, som især opstod ved behandlingens start og uden nogen bemærkelsesværdig forskel mellem de to grupper bagefter.
The most common adverse events consisted of nausea and diarrhoea, which were generally reported at the beginning of treatment with no noticeable difference between groups afterwards.
Seponering forekom især på grund af kvalme (1, 3% og 2, 2% i henholdsvis placebo - og strontiumranelatgruppen).
Discontinuation of therapy was mainly due to nausea (1.3% and 2.2% in the placebo and strontium ranelate groups respectively).
Uønskede reaktioner, defineret som uønskede hændelser, der i hvert fald muligvis skyldes behandling med strontiumranelat i fase III- forsøg, er angivet nedenfor i henhold til følgende konvention (hyppighed ved sammenligning med placebo): meget almindelige, (> 1/ 10), almindelige (> 1/ 100, < 1/ 10), usædvanlige (> 1/ 1. 000 < 1/ 100), sjældne (> 1/ 10. 000, < 1/ 1. 000) og meget sjældne (< 1/ 10. 000).
Adverse reactions, defined as adverse events considered at least possibly attributable to strontium ranelate treatment in phase III studies are listed below using the following convention (frequencies versus placebo): 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).
Nervesystemet Almindelige: hovedpine (3, 3% versus 2, 7%)
2.7%)
Mave- tarm- kanalen Almindelige: kvalme (7, 1% versus 4, 6%), diaré (7, 0% versus 5, 0%), løs afføring (1, 0% versus 0, 2%)
4.6%), diarrhoea (7.0% vs.
Hud og subkutane væv
5.0%), loose stools (1.0% vs.
4 Almindelige: dermatit (2, 3% versus 2, 0%), eksem (1, 8% versus 1, 4%)
1.4%)
Der var ingen forskel på typen af hændelser behandlingsgrupperne imellem, uanset om patienterne var over eller under 80 år ved inklusion.
4 There were no differences in the nature of adverse events between treatment groups regardless of whether patients were aged below or above 80 at inclusion.
4. 4).
In phase III studies, the annual incidence of venous thromboembolism (VTE) observed over5 years was approximately 0.7%, with a relative risk of 1.4 (95% CI = [1.0; 2.0]) in strontium ranelate treated patients as compared to placebo (see section 4.4).
I fase III- forsøg blev der over en 5- årig periode indberettet en højere forekomst af sygdomme i nerve - systemet hos patienter, der fik strontiumranelat, end hos dem, der fik placebo: bevidsthedsforstyrrelser (2, 6% versus 2, 1%), hukommelsestab (2, 5% versus 2, 0%) og krampeanfald (0, 4% versus 0, 1%).
0.1%).
Undersøgelser Forbigående pludseligt opstående stigninger (> 3 gange den øvre grænse for normalværdier) i kreatin - kinaseaktivitet (i skeletmuskulatur) forekom hos 1, 4% og 0, 6% i henholdsvis strontiumranelat - og placebogruppen.
Laboratory test findings Transient emergent increases (> 3 times the upper limit of the normal range) in creatine kinase (CK) activity (musculo-skeletal fraction) were reported in 1.4% and 0.6% of the strontium ranelate and placebo groups respectively.
Følgende hændelser er rapporteret efter markedsføring af produktet:
The following events have been reported in post-marketing experience:
Hud og subkutane væv Hyppighed ikke kendt: overfølsomhedsreaktioner i huden inklusive udslæt, pruritus, urticaria, angioødem, Stevens- Johnsons syndrom.
Gastrointestinal disorders Frequency unknown: vomiting, abdominal pain, oral mucosal irritation including stomatitis and/ or mouth ulceration Skin and subcutaneous tissue disorders Frequency unknown: hypersensitivity skin reactions including rash, pruritus, urticaria, angioedema, Stevens-Johnson syndrome. Cases of severe hypersensitivity syndromes including drug rash with eosinophilia and systemic symptoms (DRESS) (see section 4.4).
4. 4).
Musculoskeletal and connective tissue disorders Frequency unknown: musculoskeletal pain including muscle spasm, myalgia, bone pain, arthralgia and pain in extremity.
Almene symptomer og reaktioner på administrationsstedet Ikke kendt: perifert ødem Psykiske forstyrrelser Ikke kendt: konfusion
General disorders and administration site conditions Frequency unknown: peripheral oedema Psychiatric disorders Frequency unknown: confusional state
I et klinisk forsøg, der undersøgte gentagne doser på 4 g strontiumranelat daglig i 25 dage hos raske postmenopausale kvinder, viste lægemidlet sig at være veltolereret.
Good tolerance was shown in a clinical study investigating the repeated administration of 4 g strontium ranelate per day over 25 days in healthy postmenopausal women.
Efter episoder med overdosering i kliniske forsøg (op til 4 g daglig i maksimalt 147 dage) blev der ikke observeret klinisk relevante hændelser.
Following episodes of overdoses during clinical trials (up to 4 g/ day for a maximal duration of 147 days), no clinically relevant events were observed.
I tilfælde af en større overdosis bør det overvejes at få patienten til at kaste op for at fjerne ikke - absorberet lægemiddel.
In the event of substantial overdose, vomiting may be considered to remove unabsorbed active substance.
Midler til behandling af knoglesygdomme - Andre lægemidler med virkning på knoglestruktur og - mineralisering ATC- kode:
Drugs for the treatment of bone diseases - Other drugs affecting bone structure and mineralisation ATC code:
M05BX03
M05BX03
5
In vitro, strontium ranelate:
- øger knogledannelsen i knoglevævskultur samt replikation af osteoblast- prækursorer og
- increases bone formation in bone tissue culture as well as osteoblast precursor replication and
kollagensyntese i knoglecellekultur
collagen synthesis in bone cell culture;
Herved genetableres balancen i knogleomsætningen, og knogledannelsen fremmes.
5 This results in a rebalance of bone turnover in favour of bone formation.
Strontiumranelats aktivitet er undersøgt i en række ikke- kliniske modeller.
The activity of strontium ranelate was studied in various non-clinical models.
I biopsier fra crista iliaca taget op til 60 måneder efter behandling med 2 g strontiumranelat daglig i fase III- forsøg sås ingen skadelig virkning på knoglekvalitet eller - mineralisering.
In iliac crest bone biopsies obtained after up to 60 months of treatment with strontium ranelate 2 g/ day in phase III trials, no deleterious effects on bone quality or mineralisation were observed.
5. 2) og øget absorption af strontium sammenlignet med calcium påvist ved røntgen førte til en udvidet måling af knoglernes mineraltæthed (BMD = bone mineral density) ved DXA- skanning (DXA = dual- energy x- ray absorptiometry).
The combined effects of strontium distribution in bone (see section 5.2) and increased X-ray absorption of strontium as compared to calcium, leads to an amplification of bone mineral density (BMD) measurement by dual-photon X-ray absorptiometry (DXA).
50% af den målte ændring i mineraltætheden i løbet af de 3 års behandling med 2 g OSSEOR daglig.
Available data indicate that these factors account for approximately 50% of the measured change in BMD over 3 years of treatment with OSSEOR 2 g/ day.
4% om året ved columna lumbalis og 2% om året ved collum femoris og nåede efter 3 år op på henholdsvis 13- 15% og 5- 6% afhængigt af forsøget.
In phase III studies, which demonstrated the anti-fracture efficacy of OSSEOR treatment, measured mean BMD increased from baseline with OSSEOR by approximately 4% per year at the lumbar spine and 2% per year at the femoral neck, reaching 13% to 15% and 5% to 6% respectively after 3 years, depending on the study.
I fase III- forsøg ved sammenligning med placebo steg de biokemiske markører for knogleformation (knoglespecifikt alkalisk fosfatase og C- terminalt propeptid af type I- prokollagen), og markørerne for knogleresorption (serum- C- telopeptid - og urin- N- telopeptid- tværbindinger) faldt efter 3 måneders behandling og op til 3 år.
In phase III studies, as compared to placebo, biochemical markers of bone formation (bone-specific alkaline phosphatase and C-terminal propeptide of type I procollagen) increased and those of bone resorption (serum C-telopeptide and urinary N-telopeptide cross links) decreased from the third month of treatment up to 3 years.
Klinisk virkning Osteoporose defineres som BMD i columna eller hofter med en standardiseret afvigelse (SD), der er mindst 2, 5 under middelværdien hos yngre voksne.
Clinical efficacy Osteoporosis is defined as BMD of the spine or hip 2.5 SD or more below the mean value of a normal young population.
OSSEOR- forsøgsprogrammet til undersøgelse af virkningen mod frakturer omfattede to placebo - kontrollerede fase III- forsøg:
The anti-fracture studies program of OSSEOR was made up of two placebo-controlled phase III studies:
SOTI og TROPOS.
SOTI study and TROPOS study.
SOTI omfattede 1. 649 postmenopausale kvinder med påvist osteoporose (lavt BMD i columna lumbalis og udbredt forekomst af vertebralfrakturer) og en gennemsnitsalder på 70 år.
SOTI involved 1,649 postmenopausal women with established osteoporosis (low lumbar BMD and prevalent vertebral fracture) and a mean age of 70 years.
TROPOS omfattede 5. 091 postmenopausale kvinder med osteoporose (lavt BMD i collum femoris og udbredt forekomst af frakturer hos over halvdelen) og en gennemsnitsalder på 77 år.
TROPOS involved 5,091 postmenopausal women with osteoporosis (low femoral neck BMD and prevalent fracture in more than half of them) and a mean age of 77 years.
Tilsammen rekrutterede SOTI og TROPOS 1. 556 patienter, der var over 80 år ved inklusion (23, 1% af forsøgspopulationen).
Together, SOTI and TROPOS enrolled 1,556 patients over 80 years at inclusion (23.1% of the study population).
Ud over forsøgsbehandling (strontiumranelat 2 g daglig eller placebo) fik patienterne i begge forsøg tilpassede calcium - og D- vitamintilskud.
In addition to their treatment (2 g/ day strontium ranelate or placebo), the patients received adapted calcium and vitamin D supplements throughout both studies.
OSSEOR nedsatte den relative risiko for nye vertebralfrakturer med 41% i løbet af 3 år i SOTI (Tabel 1).
OSSEOR reduced the relative risk of new vertebral fracture by 41% over 3 years in the SOTI study (table 1).
Hvad angår kliniske vertebralfrakturer (defineret som frakturer forbundet med rygsmerter og/ eller legemshøjde nedsat med mindst 1 cm), blev den relative risiko reduceret med 38%.
With respect to clinical vertebral fractures (defined as fractures associated with back pain and/ or a body height loss of at least 1 cm), the relative risk was reduced by 38%.
Vurdering af livskvalitet ifølge QUALIOST- skalaen samt
Quality of life assessment on the QUALIOST specific scale as well as the General Health perception score of the SF-36 general scale indicated benefit of OSSEOR, compared with placebo.
Effekten af OSSEOR til nedsættelse af risikoen for nye vertebralfrakturer blev bekræftet i TROPOS - forsøget, også for osteoporosepatienter uden frakturer på grund af knogleskørhed ved baseline.
6 Efficacy of OSSEOR to reduce the risk of new vertebral fracture was confirmed in the TROPOS study, including for osteoporotic patients without fragility fracture at baseline.
Incidens af patienter med vertebralfrakturer og relativ risikoreduktion
Incidence of patients with vertebral fracture and relative risk reduction
Relativ risikoreduktion versus placebo (95% CI), p- værdi
Relative Risk Reduction vs. placebo (95%CI), p value
(N = 723)
N=723
(N = 719)
N=719
Nye vertebralfrakturer i løbet af 3 år
vertebral fracture over 3 years
41% (27- 52), p < 0, 001)
41% (27-52), p < 0.001
Nye vertebralfrakturer i løbet det første år
vertebral fracture
49% (26- 64), p < 0, 001)
49% (26-64), p < 0.001
Nye
over the 1st year
kliniske vertebralfrakturer i løbet af 3 år
New clinical vertebral fracture over 3 years
38% (17- 53), p < 0, 001)
38% (17-53), p < 0.001
39% (27- 49), p < 0, 001)
39% (27-49), p < 0.001
Hos patienter, der var over 80 år ved inklusion, viste en analyse af de samlede resultater fra SOTI og TROPOS, at OSSEOR nedsatte den relative risiko for at få nye vertebralfrakturer med 32% i løbet af 3 år (incidensen var 19, 1% med strontiumranelat versus 26, 5% med placebo).
26.5% with placebo).
I en à posteriori- analyse af patienter ud fra de samlede resultater af SOTI og TROPOS med BMD - værdier for columna lumbalis og/ eller collum femoris ved baseline, der svarede til osteopeni, og uden udbredte frakturer, men med mindst én yderligere risikofaktor (N = 176) reducerede OSSEOR risikoen for første vertebralfraktur med 72% i løbet af 3 år (incidens af vertebralfraktur 3, 6% med strontiumranelat versus 12, 0% med placebo).
12.0% with placebo).
Der blev udført en à posteriori- analyse af en undergruppe i TROPOS med patienter af særlig medicinsk interesse og med høj risiko for frakturer [defineret som knoglemineraltæthed med T- score i collum femoris ≤- 3 SD (fremstillers interval svarede til - 2, 4 SD med NHANES III) og ≥ 74 år (n = 1. 977, dvs.
An a-posteriori analysis was performed on a subgroup of patients from the TROPOS study of particular medical interest and at high-risk of fracture [defined by a femoral neck BMD T-score ≤ - 3 SD (manufacturer’ s range corresponding to -2.4 SD using NHANES III) and an age ≥ 74 years (n=1,977, i. e.
40% af forsøgspopulationen i TROPOS)].
40% of the TROPOS study population)].
Hos denne gruppe reducerede 3 års behandling med OSSEOR risikoen for hoftefraktur med 36% set i forhold til placebogruppen (Tabel 2).
In this group, over 3 years of treatment, OSSEOR reduced the risk of hip fracture by 36% relative to the placebo group (table 2).
Incidens af patienter med hoftefraktur og relativ risikoreduktion hos patienter med BMD ≤- 2, 4 SD (NHANES III) og ≥ 74 år
Incidence of patients with hip fracture and relative risk reduction in patients with BMD ≤ -2.4 SD (NHANES III) and age ≥ 74 years
36% (0- 59), p < 0, 046)
36% (0-59), p=0.046