qanastek/EMEA-V3 huggingface dataset:
In the initial three-year, randomised, double-blind, placebo-controlled, fracture study (MF 4411), a statistically significant and medically relevant decrease in the incidence of new radiographic morphometric and clinical vertebral fractures was demonstrated (table 4).
Fl- istudju tal- bidu, ta ’ tliet snin dwar il- ksur, tat- tip randomised, double- blind u kkontrollat bil - plaċebo (MF 4411), intwera tnaqqis statistikament sinifikanti u ta ’ relevanza medika fl- inċidenza ta ’ ksur vertebrali ġdid radjografiku, morfometriku u kliniku (tabella 4).
In this study, ibandronic acid was evaluated at oral doses of 2.5 mg daily and 20 mg intermittently as an exploratory regimen.
F’ dan l- istudju, ibandronic acid kien evalwat f’ dożi orali ta ’ 2. 5 mg kuljum u 20 mg b’ mod intermittenti bħala kors epsloratorju.
Ibandronic acid was taken 60 minutes before the first food or drink of the day (post-dose fasting period).
Ibandronic acid ttieħed 60 minuta qabel l- ewwel ikel jew xorb tal- ġurnata (perijodu ta ’ sawn ta ’ wara d- doża).
The study enrolled women aged 55 to 80 years, who were at least 5 years postmenopausal, who had a BMD at lumbar spine of 2 to 5 SD below the premenopausal mean (T-score) in at least one vertebra [L1-L4], and who had one to four prevalent vertebral fractures.
L- istudju involva nisa b’ età minn 55 sa 80 sena, li kienu mill- inqas 5 snin wara l- menopawża u li kellhom BMD fis- sinsla lumbari ta ’ 2 sa 5 SD taħt il- medja ta ’ qabel il- menopawża (punteġġ T) f’ mill- inqas vertebra waħda [L1- L4], u li kellhom minn wieħed sa erba ’ ksur vertebrali prevalenti.
All patients received 500 mg calcium and 400 IU vitamin D daily.
Il - pazjenti kollha rċevew 500 mg kalċju u 400 IU vitamina D kuljum.
Efficacy was evaluated in 2,928 patients. ibandronic acid 2.5 mg administered daily, showed a statistically significant and medically relevant reduction in the incidence of new vertebral fractures.
Ibandronic acid 2. 5 mg mogħti kuljum wera tnaqqis statistikament sinifikanti u ta ’ relevanza medika fl- inċidenza ta ’ ksur vertebrali ġdid.
This regimen reduced the occurrence of new radiographic vertebral fractures by 62% (p=0.0001) over the three year duration of the study.
Matul it- tliet snin ta ’ studju, dan il- kors naqqas l - okkorrenza ta ’ ksur vertebrali radjografiku ġdid b’ 62% (p=0. 0001).
A relative risk reduction of 61% was observed after 2 years (p=0.0006).
Wara sentejn kien osservat tnaqqis relattiv fir- riskju ta ’ 61% (p=0. 0006).
No statistically significant difference was attained after 1 year of treatment (p=0.056).
L- ebda differenza statistikament sinifikanti ma ntlaħqet wara sena ta ’ kura (p=0. 056).
The anti-fracture effect was consistent over the duration of the study.
L- effett ta ’ kontra l- ksur kien konsistenti matul il- perjodu ta ’ l- istudju.
There was no indication of a waning of the effect over time.
Ma kien hemm l- ebda indikazzjoni ta ’ tnaqqis fl- effett biż- żmien.
The incidence of clinical vertebral fractures was also significantly reduced by 49% (p=0.011).
L- inċidenza ta ’ ksur vertebrali kliniku kienet ukoll mnaqqsa b’ mod sinifikanti b’ 49% (p=0. 011).
The strong effect on vertebral fractures was furthermore reflected by a statistically significant reduction of height loss compared to placebo (p < 0.0001).
L - effett qawwi fuq il- ksur vertebrali kien rifless ukoll minn tnaqqis statistikament sinifikanti ta ’ telf fit - tul meta mqabbel mal- plaċebo (p < 0. 0001).
Results from 3 years fracture study MF 4411 (%, 95% CI)
Riżultati mill- istudju ta ’ 3 snin dwar ksur, MF 4411 (%, 95%, CI)
Placebo (N=974)
Plaċebo (N=974)
ibandronic acid 2.5 mg daily (N=977) 62% (40.9, 75.1)
ibandronic acid 2. 5 mg kuljum (N=977)
Incidence of new morphometric vertebral fractures
Inċidenza ta ’ ksur vertebrali morfometriku ġdid
9.56% (7.5, 11.7)
9. 56% (7. 5, 11. 7)
4.68% (3.2,6.2)
4. 68% (3. 2, 6. 2)
Relative risk reduction of clinical vertebral fracture
Tnaqqis relattiv tar- riskju ta ’ ksur vertebrali kliniku
49% (14.03, 69.49)
49% (14. 03, 69. 49)
Incidence of clinical vertebral fracture BMD – mean change relative to baseline lumbar spine at year 3
Inċidenza ta ’ ksur vertebrali kliniku
5.33% (3.73, 6.92) 1.26% (0.8, 1.7)
1. 26% (0. 8, 1. 7)
2.75% (1.61, 3.89) 6.54% (6.1, 7.0)
6. 54% (6. 1, 7. 0)
BMD – mean change relative to baseline total hip at year 3
10 BMD – bidla medja relattiva għal - linja bażi tal- ġenbejn totali fit- tielet sena
-0.69% (-1.0, -0.4)
- 0. 69% (- 1. 0, - 0. 4)
3.36% (3.0, 3.7)
3. 36% (3. 0, 3. 7)
The treatment effect of ibandronic acid was further assessed in an analysis of the subpopulation of patients who at baseline had a lumbar spine BMD T-score below – 2.5.
L- effett tal- kura ta ’ ibandronic acid kien evalwat ukoll f’ analiżi tas- sottopopolazzjoni ta ’ pazjenti li fil- linja bażi kellhom il- punteġġ T tal- BMD tas- sinsla lumbari taħt - 2. 5.
The vertebral fracture risk reduction was very consistent with that seen in the overall population.
It- tnaqqis fir- riskju ta ’ ksur vertebrali kien ferm konsistenti ma ’ dak li kien osservat fil- popolazzjoni ġenerali.
Results from 3 years fracture study MF 4411 (%, 95% CI) for patients with lumbar spine BMD T-score below – 2.5 at baseline
Riżultati mill- istudju ta ’ 3 snin dwar ksur, MF 4411 (%, 95% CI), għall- pazjenti b’ punteġġ T tal- BMD tas- sinsla lumbari taħt - 2. 5 fil- linja bażi.
Placebo (N=587)
Plaċebo (N=587)
ibandronic acid 2.5 mg daily (N=575) 59% (34.5, 74.3)
ibandronic acid 2. 5 mg kuljum (N=575)
Incidence of new morphometric vertebral fractures
Tnaqqis relattiv tar- riskju Ksur vertebrali morfometriku ġdid
Relative risk reduction of clinical vertebral fracture
Inċidenza ta ’ ksur vertebrali morfometriku ġdid
50% (9.49, 71.91)
5. 36% (3. 31, 7. 41)
Incidence of clinical vertebral fracture
Tnaqqis relattiv tar- riskju ta ’ ksur vertebrali kliniku
3.57% (1.89, 5.24)
50% (9. 49, 71. 91)
BMD – mean change relative to baseline lumbar spine at year 3
Inċidenza ta ’ ksur vertebrali kliniku BMD - bidla medja relattiva għas - sinsla lumbari fil- linja bażi fit- tielet sena
1.13% (0.6, 1.7)
6. 97% (4. 67, 9. 27) 1. 13% (0. 6, 1. 7)
7.01% (6.5, 7.6)
3. 57% (1. 89, 5. 24) 7. 01% (6. 5, 7. 6)
BMD – mean change relative to baseline total hip at year 3
BMD - bidla medja relattiva għal - linja bażi tal- ġenbejn totali fit- tielet sena
-0.70% (-1.1, -0.2)
- 0. 70% (- 1. 1, - 0. 2)
3.59% (3.1, 4.1)
3. 59% (3. 1, 4. 1)
In the overall patient population of the study MF4411, no reduction was observed for non-vertebral fractures, however daily ibandronate appeared to be effective in a high-risk subpopulation (femoral neck BMD T-score < -3.0), where a non-vertebral fracture risk reduction of 69% was observed.
Fil- popolazzjoni globali tal- pazjenti ta ’ l- istudju MF4411, ma kien osservat l- ebda tnaqqis għall- ksur mhux vertebrali, madankollu ibandronate kuljum deher li huwa effettiv f’ sottopopolazzjoni ta ’ riskju għoli (punteġġ T tal- BMD tal- għonq femorali < - 3. 0), fejn kien osservat tnaqqis ta ’ 69% fir- riskju ta ’ ksur mhux vertebrali.
Daily treatment with 2.5 mg resulted in progressive increases in BMD at vertebral and nonvertebral sites of the skeleton.
Kura ta ’ kuljum b’ 2. 5 mg irriżultat f’ żidiet progressivi fil- BMD f’ postijiet vertebrali u mhux vertebrali ta ’ l- iskeletru.
Three-year lumbar spine BMD increase compared to placebo was 5.3% and 6.5% compared to baseline.
Iż- żjieda fil- BMD tas- sinsla lumbari fuq tliet snin meta mqabbla mal- plaċebo kienet ta ’ 5. 3% u 6. 5% meta mqabbla mal- linja bażi.
Increases at the hip compared to baseline were 2.8% at the femoral neck, 3.4% at the total hip, and 5.5% at the trochanter.
Żidiet fil- ġenbejn meta mqabbla mal- linja bażi kienu ta ’ 2. 8% fl- għonq femorali, 3. 4% fil- ġenbejn totali, u 5. 5% fit- troċantru.
Biochemical markers of bone turnover (such as urinary CTX and serum Osteocalcin) showed the expected pattern of suppression to premenopausal levels and reached maximum suppression within a period of 3-6 months.
Markaturi biokimiċi tal- bidla ta ’ l- għadam (bħal CTX urinarju u Osteocalcin tas- serum) urew id - disinn mistenni tas- soppressjoni għal- livelli ta ’ qabel il- menopawża u laħqu s- soppressjoni massima f’ perijodu ta ’ 3- 6 xhur.
A clinically meaningful reduction of 50% of biochemical markers of bone resorption was observed as early as one month after start of treatment with ibandronic acid 2.5 mg.
Tnaqqis ta ’ sinifikanza klinika ta ’ 50% tal- markaturi biokimiċi ta ’ assorbiment mill- ġdid ta ’ l- għadam kien osservat minn xahar wara l- bidu tal- kura b ’ ibandronic acid 2. 5 mg.
Following treatment discontinuation, there is a reversion to the pathological pre-treatment rates of elevated bone resorption associated with postmenopausal osteoporosis.
Wara li titwaqqaf il- kura, jkun hemm rġigħ lura għar- rati patoloġiċi ta ’ żjieda fl- assorbiment mill- ġdid tal- għadam ta ’ qabel il- kura assoċjata ma ’ osteoporożi wara l- menopawża.
The histological analysis of bone biopsies after two and three years of treatment of postmenopausal women showed bone of normal quality and no indication of a mineralization defect.
L- analiżi istoloġika ta ’ bijopsiji ta ’ l- għadam wara sentejn u tliet snin ta ’ kura ta ’ nisa wara l - menopawża wriet għadam ta ’ kwalità normali u l- ebda indikazzjoni ta ’ difett tal- mineralizzazzjoni.
The primary pharmacological effects of ibandronic acid on bone are not directly related to actual plasma concentrations, as demonstrated by various studies in animals and humans.
L- effetti farmakoloġiċi primarji ta ’ ibandronic acid fuq l- għadam m’ humiex relatati direttament mal - konċentrazzjonijiet attwali fil- plażma, kif muri b’ diversi studji fuq l- annimali u l- bnedmin.
Absorption The absorption of ibandronic acid in the upper gastrointestinal tract is rapid after oral administration and plasma concentrations increase in a dose-proportional manner up to 50 mg oral intake, with greater than dose-proportional increases seen above this dose.
Assorbiment L- assorbiment ta ’ ibandronic acid fil- parti ta ’ fuq tas- sistema gastro- intestinali iseħħ malajr wara għoti mill- ħalq u l- konċentrazzjonijiet fil- plażma jiżdiedu proporzjonalment mad- doża sa 50 mg ta ’ teħid orali, b’ żjiediet akbar milli proporzjonalment mad- doża osservati ’ l fuq minn din id- doża.
Maximum observed plasma concentrations were reached within 0.5 to 2 hours (median 1 hour) in the fasted state and absolute bioavailability was about 0.6%.
Il - konċentrazzjonijiet massimi osservati fil- plażma ntlaħqu fi żmien 0. 5 sa 2 sigħat (medjan ta ’ siegħa) fi
The extent of absorption is impaired when taken together with food or beverages (other than plain water).
L- ammont ta ’ kemm jiġi assorbit jonqos meta jittieħed flimkien ma ’ ikel jew xorb (għajr ilma waħdu).
Bioavailability is reduced by about 90% when ibandronic acid is administered with a standard breakfast in comparison with bioavailability seen in fasted subjects.
Il- biodisponibiltà tonqos b’ madwar 90% meta ibandronic acid jingħata ma ’ kolazzjon stàndard meta mqabbla ma ’ biodisponibiltà osservata f’ individwi sajmin.
There is no meaningful reduction in bioavailability provided ibandronic acid is taken 60 minutes before the first food of the day.
M’ hemmx tnaqqis sinifikanti fil- biodisponibiltà jekk ibandronic acid jittieħed 60 minuta qabel l- ewwel ikel tal- ġurnata.
Both bioavailability and BMD gains are reduced when food or beverage is taken less than 60 minutes after ibandronic acid is ingested.
Kemm il- biodisponibiltà kif ukoll ż- żidiet fil- BMD jonqsu meta ikel jew xorb jittieħed inqas minn 60 minuta wara li jittieħed ibandronic acid.
11 Distribution After initial systemic exposure, ibandronic acid rapidly binds to bone or is excreted into urine.
Distribuzzjoni Wara espożizzjoni sistematika inizjali, ibandronic acid jingħaqad malajr mal- għadam jew jitneħħa fl - urina.
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.
Fil- bnedmin, il- volum ta ’ distribuzzjoni terminali apparenti huwa mill- inqas 90 1 u l- ammont ta ’ doża li tilħaq l- għadam hija stmata li hija 40- 50% tad- doża li tkun qed tiċċirkola.
Protein binding in human plasma is approximately 85% - 87% (determined in vitro at therapeutic concentrations), and thus there is a low potential for interaction with other medicinal products due to displacement.
It- twaħħil mal - proteini fil- plażma umana hija madwar 85% - 87% (determinata in vitro f’ konċentrazzjonijiet terapewtiċi), u għalhekk hemm potenzjal żgħir għall- interazzjoni ma ’ prodotti mediċinali oħra minħabba spostament.
Metabolism There is no evidence that ibandronic acid is metabolised in animals or humans.
Metaboliżmu M’ hemm l- ebda evidenza li ibandronic acid huwa metabolizzat fl- annimali jew fil- bnedmin.
Elimination The absorbed fraction of ibandronic acid is removed from the circulation via bone absorption (estimated to be 40-50% in postmenopausal women) and the remainder is eliminated unchanged by the kidney.
Eliminazzjoni Il- frazzjoni ta ’ ibandronic acid assorbita titneħħa miċ- ċirkolazzjoni permezz ta ’ assorbiment fl - għadam (stmat li huwa 40- 50% f’ nisa wara l- menopawża) u l- bqija jiġi eliminat mingħajr ma jinbidel mill- kliewi.
The unabsorbed fraction of ibandronic acid is eliminated unchanged in the faeces.
Il- frazzjoni mhux assorbita ta ’ ibandronic acid tiġi eliminata mingħajr ma tinbidel fl - ippurgar.
The range of observed apparent half-lives is broad, the apparent terminal half-life is generally in the range of 10-72 hours.
L- skala tal- half- lifes apparenti osservati hija wiesgħa, l- half- life terminali apparenti ġeneralment hija fl- iskala ta ’ 10- 72 siegħa.
As the values calculated are largely a function of the duration of study, the dose used, and assay sensitivity, the true terminal half-life is likely to be substantially longer, in common with other bisphosphonates.
Minħabba li l- valuri kkalkulati huma fil- biċċa l- kbira funzjoni tat- tul ta ’ l - istudju, id- doża wżata, u s- sensittività ta ’ l- analiżi, il- half- life terminali vera x’ aktarx li hija itwal sew, bħal b’ bisphosphonati oħrajn.
Early plasma levels fall quickly reaching 10% of peak values within 3 and 8 hours after intravenous or oral administration respectively.
Livelli bikrija fil- plażma jinżlu malajr u jilħqu 10% tal- valuri massimi fi 3 u 8 sigħat wara għoti minn ġol- vina jew mill- ħalq rispettivament.
Total clearance of ibandronic acid is low with average values in the range 84-160 ml/ min.
It- tneħħija totali ta ’ ibandronic acid hija baxxa b’ valuri medji fl- iskla ta ’ 84- 160 ml/ min.
Renal clearance (about 60 mL/ min in healthy postmenopausal females) accounts for 50-60% of total clearance and is related to creatinine clearance.
It- tneħħija mill- kliewi (madwar 60 ml/ min f’ nisa b’ saħħithom wara l- menopawża) tkopri 50- 60% tat- tneħħija totali u hija relatata mat- tneħħija tal- krejatinina.
The difference between the apparent total and renal clearances is considered to reflect the uptake by bone.
Id- differenza bejn it- tneħħija totali apparenti u t - tneħħija mill- kliewi hija kkunsidrata li tirrifletti it- teħid mill- għadam.
Pharmacokinetics in special clinical situations
Farmakokinetika f’ sitwazzjonijiet kliniċi speċjali
Gender Bioavailability and pharmacokinetics of ibandronic acid are similar in men and women.
Sess Il- biodisponibiltà u l- farmakokinetika ta ’ ibandronic acid huma simili fl- irġiel u fin- nisa.
Race There is no evidence for any clinically relevant inter-ethnic differences between Asians and Caucasians in ibandronic acid disposition.
Razza Ma hemm l- ebda evidenza ta ’ xi differenza ta ’ relevanza klinika bejn ir- razez bejn l- Ażjatiċi u l - Kawkasi fid- disposizjoni ta ’ ibandronic acid.
There are few data available on patients of African origin.
Ftit hemm tagħrif disponibbli dwar pazjenti ta ’ oriġini Afrikana.
Patients with renal impairment Renal clearance of ibandronic acid in patients with various degrees of renal impairment is linearly related to creatinine clearance.
Pazjenti b’ indeboliment tal- kliewi It- tneħħija ta ’ ibandronic acid mill- kliewi f’ pazjenti bi gradi diversi ta ’ indeboliment tal- kliewi hija relatata b’ mod lineari mat- tneħħija tal- krejatinina.
No dose adjustment is necessary for patients with mild or moderate renal impairment (CLcr equal or greater than 30 ml/ min), as shown in study BM 16549 where the majority of patients had mild to moderate renal impairment.
L- ebda tibdil tad- dożaġġ ma hu meħtieġ għall- pazjenti b’ indeboliment ħafif jew moderat tal- kliewi (CLcr ugwali jew aktar minn 30 ml/ min), kif muri f’ studju BM 16549 fejn il- maġġoranza tal- pazjenti kellhom indeboliment renali ħafif sa moderat.
Subjects with severe renal failure (CLcr less than 30 ml/ min) receiving daily oral administration of 10 mg ibandronic acid for 21 days, had 2-3 fold higher plasma concentrations than subjects with normal renal function and total clearance of ibandronic acid was 44 ml/ min.
Individwi b’ indeboliment sever tal- kliewi (CLcr inqas minn 30 ml/ min) li rċevew għoti orali kuljum ta ’ 10 mg ibandronic acid għal 21 ġurnata, kellhom konċentrazzjonijiet fil- plażma 2- 3 darbiet għola minn individwi b’ funzjoni tal- kliewi normali u t- tneħħija totali ta ’ ibandronic acid kienet ta ’ 44 ml/ min.
After intravenous administration of 0.5 mg, total, renal, and non-renal clearances decreased by 67%, 77% and 50%, respectively, in subjects with severe renal failure but there was no reduction in tolerability associated with the increase in exposure.
Wara għoti minn ġol- vina ta ’ 0. 5 mg, it- tneħħija totali, renali u mhux renali naqsu b’ 67%, 77% u 50% rispettivament, f’ individwi b’ insuffiċjenza severa tal- kliewi iżda ma kien hemm l- ebda tnaqqis fit- tollerabilità assoċjata maż- żjieda fl- espożizzjoni.
Due to the limited clinical experience, Bondenza is not recommended in patients with severe renal impairment (see section 4.2 and section 4.4).
Minħabba li l- esperjenza klinika hija limitata, Bondenza mhux rakkomandat f’ pazjenti b’ indeboliment sever tal- kliewi (ara sezzjoni 4. 2 u sezzjoni 4. 4).
The pharmacokinetics of ibandronic acid was not assessed in patients with end-stage renal disease managed by other than hemodialysis.
Il- farmakokinetika ta ’ ibandronic acid ma kinietx stmata f’ pazjenti b’ mard tal- kliewi ta ’
The pharmacokinetics of ibandronic acid in these patients is unknown, and ibandronic acid should not be used under these circumstances.
Il- farmakokinetika ta ’ ibandronic acid f’ dawn il - pazjenti mhux magħrufa, u ibandronic acid m’ għandux jintuża taħt dawn iċ- ċirkostanzi.
Patients with hepatic impairment There are no pharmacokinetic data for ibandronic acid in patients who have hepatic impairment.
Pazjenti b’ indeboliment tal- fwied M’ hemm l- ebda informazzjoni farmakokinetika għal ibandronic acid f’ pazjenti b’ indeboliment epatiku.
The liver has no significant role in the clearance of ibandronic acid which is not metabolised but is cleared by renal excretion and by uptake into bone.
Il- fwied m’ għandux rwol sinifikanti fit- tneħħija ta ’ ibandronic acid li m’ huwiex metabolizzat iżda jitneħħa permezz ta ’ eskrezzjoni mill- kliewi u minn teħid fl- għadam.
Therefore dose adjustment is not necessary in patients with hepatic impairment.
Għalhekk tibdil tad- dożaġġ m’ huwiex meħtieġ f’ pazjenti b’ indeboliment tal- fwied.
12 Elderly Population In a multivariate analysis, age was not found to be an independent factor of any of the pharmacokinetic parameters studied.
F’ analiżi multivarjata, l- età ma nstabitx li hija fattur indipendenti fl- ebda wieħed mill- parametri farmakokinetiċi studjati.
As renal function decreases with age this is the only factor to take into consideration (see renal impairment section).
Billi l- funzjoni tal- kliewi tonqos bl- età dan huwa l- uniku fattur li għandu jittieħed f’ konsiderazzjoni (ara s- sezzjoni dwar l- indeboliment tal- kliewi).
Paediatric population There are no data on the use of Bondenza in these age groups.
Popolazzjoni Pedjatrika M’ hemm l- ebda tagħrif dwar l- użu ta ’ Bondenza f’ dawn il- gruppi ta ’ etajiet.
5.3 Preclinical safety data
5. 3 Tagħrif ta ’ qabel l- użu kliniku dwar is- sigurtà tal- medicina
Toxic effects, e. g signs of renal damage, were observed in dogs only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.
Effetti tossiċi, e. ż. sinjali ta ’ ħsara fil- kliewi, ġew osservati fil- klieb biss f’ espożizzjonijiet ikkunsidrati suffiċjentement akbar mill- espożizzjoni massima fil- bniedem u jindikaw relevanza żgħira għall- użu kliniku.
No indication of carcinogenic potential was observed.
Mutaġeniċità/ Karċinoġeniċità Ma ġiet osservata l- ebda indikazzjoni ta ’ potenzjal karċinoġeniku.
Tests for genotoxicity revealed no evidence of genetic activity for ibandronic acid.
Testijiet għall- ġenotossiċità ma żvelaw l- ebda evidenza ta ’ attività ġenetika għal ibandronic acid.
There was no evidence for a direct foetal toxic or teratogenic effect of ibandronic acid in orally treated rats and rabbits and there were no adverse effects on the development in F1 offspring in rats at an extrapolated exposure of at least 35 times above human exposure.
Tossiċità riproduttiva Ma kien hemm l- ebda evidenza ta ’ effett tossiku dirett fuq il- fetu jew effett teratoġeniku ta ’ ibandronic acid f’ firien u fniek ikkurati mill- ħalq u ma kien hemm l- ebda effetti avversi fuq l- iżvilupp tal- ulied F1 fil- firien f’ espożizzjoni estrapolata ta ’ mill- inqas 35 darba għola mill- espożizzjoni fil- bnedmin.
Adverse effects of ibandronic acid in reproductive toxicity studies in the rat were those observed with bisphosphonates as a class.
Effetti avversi ta ’ ibandronic acid fi studji tat- tossiċità riproduttiva fil- far kienu dawk osservati bil - bisphosphonates bħala klassi.
They include a decreased number of implantation sites, interference with natural delivery (dystocia), and an increase in visceral variations (renal pelvis ureter syndrome).
Dawn jinkludu numru mnaqqas ta ’ siti ta ’ impjantazzjoni, interferenza fil- ħlas naturali (distoċija), u żjieda fil- varjazzjonijiet vixxerali (sindrome renali tal- pelvi tal- ureteru).
Tablet core Lactose monohydrate Povidone Cellulose, microcrystalline Crospovidone Stearic acid Silica, colloidal anhydrous
Qalba tal- pillola Lactose monohydrate Povidone Cellulose, microcrystalline Crospovidone Stearic acid Silica, colloidal anhydrous
Tablet coat Hypromellose Titanium dioxide E171 Talc Macrogol 6,000
Kisja tal- pillola Hypromellose Titanium dioxide E171 Talc Macrogol 6, 000
Not applicable.
Ma jgħoddx f’ dan il- każ.
6.3 Shelf life
13 6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
This medicinal product does not require any special storage conditions.
Din il- mediċina m’ għandhiex bżonn ħażna speċjali.
13 6.5 Nature and contents of container
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fiħ
Bondenza 150 mg film-coated tablets are supplied in blisters (PVC/ PVDC) containing 1 or 3 tablets.
Bondenza 150 mg pilloli miksija b’ rita huma disponibbli f’ folji (PVC/ PVDC) li fihom 1 jew 3 pilloli.
6.6 Special precautions for disposal
6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema
No special requirements.
L- ebda ħtiġijiet speċjali.
Roche Registration Limited 6 Falcon Way Shire Park Welwyn Garden City AL7 1TW United Kingdom
Roche Registration Limited 6 Falcon Way Shire Park Welwyn Garden City AL7 1TW Ir- Renju Unit
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il- Mediċini (EMEA) http: // www. emea. europa. eu /.
Bondenza 3 mg solution for injection
Bondenza 3 mg soluzzjoni għall- injezzjoni
One pre-filled syringe of 3 ml solution contains 3 mg ibandronic acid (as 3.375 mg ibandronic acid, monosodium salt, monohydrate).
Siringa mimlija għal lest b’ 3 ml ta ’ soluzzjoni fiha 3 mg ibandronic acid (bħala 3. 375 mg ibandronic acid, monosodium salt, monohydrate).
The concentration of ibandronic acid in the solution for injection is 1mg per ml.
Il- konċentrazzjoni ta ’ ibandronic acid fis- soluzzjoni għall- injezzjoni hija ta ’ 1mg kull ml.
Clear, colourless solution.
Soluzzjoni għall- injezzjoni Soluzzjoni ċara u bla kulur.
The recommended dose of ibandronic acid is 3 mg, administered as an intravenous injection over 15 - 30 seconds, every three months.
Id- doża rakkomandata ta ’ ibandronic acid hija ta ’ 3 mg, mogħtija bħala injezzjoni ġol- vini fuq medda ta ’ 15 – 30 sekonda, kull tliet xhur.
Patients must receive supplemental calcium and vitamin D (see section 4.4 and section 4.5)
Il- pazjenti għandhom jirċievu kalċju u/ jew vitamina D supplimentari (ara sezzjoni 4. 4 u sezzjoni 4. 5).
If a dose is missed, the injection should be administered as soon as convenient.
Jekk tintnesa doża, l- injezzjoni għandha tingħata hekk kif ikun konvenjenti.
Thereafter, injections should be scheduled every 3 months from the date of the last injection.
Minn hemm ’ l quddiem, l- injezzjonijiet għandhom jiġu pprogrammati kull 3 xhur mid- data ta ’ l- aħħar injezzjoni.
Special Populations Patients with renal impairment No dose adjustment is necessary for patients with mild or moderate renal impairment where serum creatinine is equal or below 200 μ mol/ l (2.3 mg/ dl) or where creatinine clearance (measured or estimated) is equal or greater than 30 ml/ min.
Popolazzjonijiet speċjali Pazjenti b’ indeboliment tal- kliewi Ma hu meħtieġ l- ebda tibdil fid- doża għal pazjenti b’ indeboliment ħafif jew moderat tal- kliewi fejn l - krejatinina fis- serum hija daqs jew inqas minn 200 μmol/ l (2. 3 mg/ dl) jew fejn t- tneħħija tal - krejatinina (mkejla jew stmata) hija 30 ml/ min jew aktar.
Bondenza injection is not recommended for use in patients who have a serum creatinine above 200 μ mol/ l (2.3 mg/ dl) or who have a creatinine clearance (measured or estimated) below 30 ml/ min, because of limited clinical data available from studies including such patients (see section 4.4 and section 5.2)
Injezzjoni ta ’ Bondenza mhix irrakkomandata għall- użu f’ pazjenti li għandhom krejatinina fis- serum ’ l fuq minn 200 μmol/ l (2. 3 mg/ dl) jew li għandhom tneħħija tal- krejatinina (mkejla jew stmata) taħt 30 ml/ min minħabba tagħrif kliniku limitat disponibbli minn studji li jinkludu pazjenti bħal dawn (ara sezzjoni 4. 4 u sezzjoni 5. 2)
Patients with hepatic impairment No dose adjustment is required (see section 5.2).
Pazjenti b’ indeboliment tal- fwied L- ebda tibdil fid- doża ma huwa meħtieġ (ara sezzjoni 5. 2).
Elderly Population No dose adjustment is required (see section 5.2).
L- ebda tibdil fid- doża ma huwa meħtieġ (ara sezzjoni 5. 2)
15 Paediatric Population There is no relevant use of Bondenza in children, and Bondenza was not studied in the paediatric population.
15 Tfal u adoloxxenti M’ hemm l- ebda użu rilevanti fit- tfal u Bondenza ma kienx studjat fil- popolazzjoni pedjatrika.
For intravenous use.
Użu għal ġol- vini.
Strict adherence to the intravenous administration route is required (see section 4.4).
Huwa meħtieġ li r- rotta ta ’ għotja minn ġol- vini tiġi segwita b’ mod strett (ara sezzjoni 4. 4).
Administration failures Strict adherence to the intravenous route of administration is required.
Falliment ta ’ l- għotja Huwa meħtieġ li r- rotta ta ’ għotja minn ġol- vini tiġi segwita b’ mod strett.
Care must be taken not to administer Bondenza injection via intra-arterial or paravenous administration as this could lead to tissue damage.
Għandha tingħata attenzjoni biex injezzjoni ta ’ Bonviva ma tingħatax permezz ta ’ għotja minn ġol- arterji jew paravenuża peress li dan jista ’ jwassal għall- ħsara lit- tessut.
Hypocalcaemia Bondenza, like other bisphosphonates administered intravenously, may cause a transient decrease in serum calcium values.
Ipokalċimja Bondenza, bħal bisphosphonates oħra mogħtija minn ġol- vini, jista ’ jikkawża tnaqqis temporanju fil - valuri tal- kalċju fis- serum.
Existing hypocalcaemia must be corrected before starting Bondenza injection therapy.
Ipokalċimja eżistenti għandha tiġi kkorreġuta qabel tinbeda terapija ta ’ Bondenza b’ injezzjoni.
Other disturbances of bone and mineral metabolism should also be effectively treated before starting Bondenza injection therapy.
Disturbi oħra tal- metaboliżmu ta ’ l- għadam u l- minerali ukoll għandhom jiġu kkurati b’ mod effettiv qabel tinbeda terapija ta ’ Bondenza b’ injezzjoni.
All patients must receive adequate supplemental calcium and vitamin D.
L- pazjenti kollha għandhom jirċievu kalċju u vitamina D supplimentari adegwati.
Renal impairment Patients with concomitant diseases, or who use medicinal products which have potential for undesirable effects on the kidney, should be reviewed regularly in line with good medical practice during treatment.
Indeboliment renali Skond prattika medika tajba, pazjenti b’ mard fl- istess waqt, jew li jużaw prodotti mediċinali li għandhom il- potenzjal għall- effetti mhux mixtieqa fuq il- kilwa, għandhom jiġu nvistati regolarment waqt il- kura.
Due to limited clinical experience, Bondenza injection is not recommended for patients with a serum creatinine above 200 μ mol/ l (2.3 mg/ dl) or with a creatinine clearance below 30 ml/ min (see section 4.2 and section 5.2).
Minħabba esperjenza klinika limitata, injezzjoni ta ’ Bondenza mhix irrakkomandata għal pazjenti bi krejatinina fis- serum ’ l fuq minn 200 μmol/ l (2. 3 mg/ dl) jew bi tneħħija tal- krejatinina taħt 30ml/ min (ara sezzjoni 4. 2 u sezzjoni 5. 2).
Osteonecrosis of the jaw Osteonecrosis of the jaw, generally associated with tooth extraction and/ or local infection (including osteomyelitis) has been reported in patients with cancer receiving treatment regimens including primarily intravenously administered bisphosphonates.
Osteonekrosi tax- xedaq Osteonekrosi tax- xedaq, ġeneralment assoċjata mal- qlugħ ta ’ sinna u/ jew infezzjoni lokali (inkluż osteomijelite) kienet irrappurtata f’ pazjenti bil- kanċer li qed jirċievu korsijiet ta ’ kura inkluż primarjament bisphosphonates mogħtija minn ġol- vini.
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).
Eżami dentali b’ dentistrija ta ’ prevenzjoni xierqa għandha tiġi kkunsidrata qabel il- kura b’ bisphosphonates f’ pazjenti b’ fatturi ta ’ riskju fl- istess ħin (e. ż. kanċer, kimoterapija, radjuterapija, kortikosterojdi, iġene tal- ħalq ħażina).
While on treatment, these patients should avoid invasive dental procedures if possible.
Waqt il- kura, dawn il- pazjenti, jekk possibli, għandhom jevitaw proċeduri dentali invasivi.
16 4.5 Interaction with other medicinal products and other forms of interaction
16 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
Metabolic interactions are not considered likely, since ibandronic acid does not inhibit the major human hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats.
Interazzjonijiet metaboliċi mhux ikkunsidrati bħala probabbli peress li ibandronic acid ma jinibixxix l - isoenzimi P450 maġġuri umani tal- fwied u ntwera li ma jinduċix is- sistema taċ- ċitokromju P450 tal - fwied fil- firien.
Furthermore, plasma protein binding is approximately 85% - 87% (determined in vitro at therapeutic ibandronic acid concentrations), and thus there is a low potential for interaction with other medicinal products due to displacement.
Barra minn hekk, it- twaħħil mal- proteini fil- plażma huwa madwar 85% - 87% (determinat in vitro f’ konċentrazzjonijiet terapewtiċi ta ’ ibandronic acid), u għalhekk hemm potenzjal baxx li jkun hemm interazzjonijiet ma ’ prodotti mediċinali oħra minħabba spostament.
Pharmacokinetic interaction studies in postmenopausal women have demonstrated the absence of any interaction potential with tamoxifen or hormone replacement therapy (oestrogen).
Studji tal- interazzjonijiet farmakokinetiċi f’ nisa wara l- menopawża wrew li m’ hemm l- ebda potenzjal ta ’ interazzjoni ma ’ tamoxifen jew ma ’ terapija ta ’ sostituzzjoni ta ’ l- ormoni (oestrogen).
No interaction was observed when co-administered with melphalan/ prednisolone in patients with multiple myeloma.
L- ebda interazzjoni ma ġiet osservata meta ingħata flimkien ma ’ melphalan/ prednisolone f’ pazjenti b’ majeloma multipla.
The safety of oral treatment with ibandronic acid 2.5 mg once daily was evaluated in 1251 patients treated in 4 placebo-controlled clinical studies; 73% of these patients came from the pivotal three-year treatment study (MF 4411).
Is- sigurtà ta ’ kura orali b’ ibandronic acid 2. 5 mg darba kuljum kienet stmata f’ 1251 pazjent ikkurati f’ 4 studji kliniċi kontrollati bil- plaċebo; 73% minn dawn il- pazjenti ġew mill- istudju pivotali ta ’ tliet snin ta ’ kura (MF 4411).
The overall proportion of patients who experienced an adverse reaction, i. e. adverse event with a possible or probable relationship to trial medicinal product, in the pivotal treatment study (MF 4411) was 19.8% for ibandronic acid and 17.9% for placebo.
Il- proporzjoni globali ta ’ pazjenti li kellhom esperjenza ta ’ reazzjoni avversa, i. e. reazzjoni avversa b’ possibbiltà jew probabbiltà ta ’ relazzjoni mal- prodott mediċinali taħt prova, fl- istudju pivitali tal- kura (MF 4411) kien ta ’ 19. 8% għal ibandronic acid u 17. 9% għal plaċebo.
In the pivotal two-year study in postmenopausal women with osteoporosis (BM16550), the overall safety of intravenous injection of Bondenza 3 mg every 3 months and oral ibandronic acid 2.5 mg daily were shown to be similar.
Fl- istudju pivitali ta ’ sentejn f’ nisa wara l- menopawża b’ osteoprożi (BM16550), is- sigurtà globali ta ’ injezzjoni ġol- vini ta ’ Bondenza 3 mg kull 3 xhur u ibandronic acid 2. 5 mg orali kuljum intweriet li kienet simili.
The overall proportion of patients who experienced an adverse reaction was 26.0% and 28.6% for Bondenza 3 mg injection every 3 months and 20.4% and 22.6% for oral ibandronic acid 2.5 mg daily after one year and two years, respectively.
Il- proporzjon globali ta ’ pazjenti li kellhom esperjenza ta ’ reazzjoni avversa, kien 26. 0% u 28. 6% għall- injezzjoni ta ’ Bondenza 3 mg kull 3 xhur u 20. 4% u 22. 6% għal ibandronic acid 2. 5 mg orali kuljum wara sena u sentejn, rispettivament.
Most cases of adverse reactions did not lead to cessation of therapy.
Il- biċċa l- kbira tal- każijiet ta ’ reazzjonijiet avversi ma wasslux għall- waqfien tat- terapija.
Table 1 and table 2 list adverse events after one year and two years of treatment, respectively, from the pivotal phase III trial BM16550, reported as possibly or probably related to trial medicinal product, in more than 1% of the patients treated with either intravenous injection of Bondenza 3 mg every 3 months or intravenous injection of placebo plus oral ibandronic acid 2.5 mg daily.
Tabella 1 u tabella 2 iniżżlu l- avvenimenti avversi wara sena u sentejn ta ’ kura, rispettivament, mill - prova pivotali ta ’ fażi III BM16550, irrappurtati bħala possibilment jew probabbilment relatati mal - prodott mediċinali taħt prova, f’ iżjed minn 1% tal- pazjenti kkurati b’ injezzjoni ta ’ Bondenza 3 mg kull 3 xhur jew b’ injezzjoni ġol- vini ta ’ plaċebo flimkien ma ’ ibandronic acid 2. 5 mg orali kuljum.
Adverse reactions reported in patients treated with Bondenza 3 mg injection at a frequency equal to or less than that in orally treated patients, are not included.
Tabelli 1 u 2 juru wkoll
Tables 1 and 2 also show adverse reactions in patients treated for 3 years with oral ibandronic acid 2.5 mg daily in the anti-fracture study (MF4411).
17 reazzjonijiet avversi f’ pazjenti kkurati għal 3 snin b’ ibandronic acid 2. 5 mg orali kuljum fl- istudju kontra l- fratturi (MF 4411).
For both studies, adverse reactions are listed which occurred with a higher incidence in ibandronic acid -treated
Għaż- żewġ studji, huma mniżżla reazzjonijiet avversi li seħħew b’ inċidenza ogħla f’ pazjenti kkurati b’ ibandronic acid meta mqabbel mal- pazjenti kkurati bil- plaċebo tal- istudju MF 4411.
17 patients compared with the placebo-treated patients of study MF4411.
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa għandhom jitniżżlu skond is- serjetà tagħhom.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
L- effetti li huma l- aktar serji għandhom jitniżżlu l- ewwel, segwiti minn dawk anqas serji.
Common adverse reactions (> 1/ 100, ≤ 1/ 10) in the phase III osteoporosis study BM16550 after one year of treatment and in the phase III anti-fracture study MF 4411 (three-year study), that were considered by the investigator to be possibly or probably related to study medicinal product.
Reazzjonijiet avversi komuni (> 1/ 100, ≤ 1/ 10) fl- istudju ta ’ fażi III dwar l- osteoporożi MB 16550, wara sena ta ’ kura, u fl- istudju ta ’ fażi III kontra l- ksur MF 4411, (studju ta ’ tliet snin), li kienu kkunsidrati mill- investigatur bħala possibilment jew probabbilment relatati mal- prodott mediċinali taħt studju
One year data in study BM
Tagħrif ta ’ sena fl- istudju
16550
BM 16550
Three year data in 4411
Tagħrif ta ’ tliet snin fl- istudju MF 4411
System Organ Class/ Adverse reaction Gastrointestinal disorders
Sistema tal- klassifika tal- Organi/ Reazzjoni avversa Disturbi gastro - intestinali
Bondenza injection 3 mg every 3 months (N=469) ADR No.
Injezzjoni ta ’ Bondenza 3 mg kull 3 xhur (N=469) ADR No.
Placebo injection + oral ibandronic acid 2.5 mg daily (N=465) ADR No.
Injezzjoni ta ’ plaċebo + ibandronic acid 2. 5 mg orali kuljum (N=465) ADR No.
(%)
ibandronic acid Plaċebo 2. 5 mg orali (N=975) kuljum ADR No.
Gastritis Diarrhoea Abdominal pain Dyspepsia Nausea Constipation Musculoskeletal disorders
Gastrite Dijarea Uġigħ addominali Dispepsja Tqalligħ
5 (1.1) 5 (1.1) 13 (2.8) 12 (2.6) 8 (1.7) 5 (1.1)
5 (1. 1) 5 (1. 1) 13 (2. 8) 12 (2. 6) 8 (1. 7)
4 (0.9) 2 (0.4) 15 (3.2) 18 (3.9) 12 (2.6) 7 (1.5)
4 (0. 9) 2 (0. 4) 15 (3. 2) 18 (3. 9) 12 (2. 6)
7 (0.7) 14 (1.4) 21 (2.1) 40 (4.1) 18 (1.8) 3 (0.3)
7 (0. 7) 5 (0. 5) 14 (1. 4) 10 (1. 0) 21 (2. 1) 28 (2. 9) 40 (4. 1) 26 (2. 7) 18 (1. 8) 22 (2. 3)
5 (0.5) 10 (1.0) 28 (2.9) 26 (2.7) 22 (2.3) 9 (0.9)
Stitikezza Disturbi muskolu - skeltrali
Musculo-skeletal pain
Uġigħ Muskolu - skeltrali
5 (1.1)
5 (1. 1)
2 (0.4)
2 (0. 4)
Arthralgia Myalgia General System disorders
Atralġja Mijalġja Disturbi ġenerali
11 (2.3) 8 (1.7)
11 (2. 3) 8 (1. 7)
4 (0.9) 4 (0.9)
4 (0. 9) 4 (0. 9)
4 (0.4) 18 (1.8)
4 (0. 4) 4 (0. 4) 18 (1. 8) 8 (0. 8)
Influenza-like illness*
Marda li tixbaħ lill - influwenza *
22 (4.7)
22 (4. 7)
4 (0.9)
4 (0. 9)
3 (0.3)
3 (0. 3) 2 (0. 2)
Fatigue Nervous System disorders
Għeja Disturbi fis- sistema nervuża
3 (0.3)
2 (0. 4)
4 (0.4)
3 (0. 3) 4 (0. 4)
Headache Skin disorders
Uġigħ ta ’ ras Disturbi fil- ġilda
3 (0.6)
3 (0. 6)
8 (0.8)
8 (0. 8) 6 (0. 6)
6 (0.6)
Raxx
12 (1.2)
12 (1. 2) 7 (0. 7)
7 (0.7)
MedDRA versjoni 7. 0
* Transient, influenza-like symptoms have been reported in patients receiving intravenous injection of Bondenza 3 mg every 3 months, typically in association with the first dose.
* Sintomi temporanji, li jixbħu lill- influwenza ġew irrappurtati f’ pazjenti li kienu qed jirċievu injezzjoni minn ġol- vini ta ’ Bondenza 3 mg kull 3 xhur, tipikament f’ assoċjazzjoni ma ’ l- ewwel doża.
Influenza-like illness includes events reported as acute phase reaction or symptoms, including myalgia, arthralgia, fever, chills, fatigue, nausea, loss of appetite, and bone pain.
Marda li tixbaħ lill- influwenza tinkludi avvenimenti rrappurtati bħala reazzjoni ta ’ fażi akuta jew sintomi inkluż mijalġja, artralġja, deni, rogħda, għeja, tqalligħ, telf ta ’ aptit, u uġigħ fl- għadam.
Such symptoms were generally of short duration, mild or moderate in intensity, and resolved during continuing treatment without requiring remedial measures.
Sintomi bħal dawn kienu ġeneralment ta ’ tul qasir, ta ’ intensità ħafifa jew moderata, u fiequ waqt li tkompliet il - kura mingħajr il- ħtieġa ta ’ miżuri ta ’ fejqan.
18 Table 2:
18 Tabella 2:
Common adverse reactions (> 1/ 100, ≤ 1/ 10) in the phase III osteoporosis study BM16550 after two years of treatment (cumulative data) and in the phase III anti-fracture study MF 4411 (three- year study), that were considered by the investigator to be possibly or probably related to study medicinal product.
Reazzjonijiet avversi tal- mediċina komuni (> 1/ 100, ≤ 1/ 10) fl- istudji ta ’ Fażi III dwar l - osteoporożi BM16550, wara sentejn ta ’ kura (tagħrif akkumulat) u fl- istudju ta ’ fażi III kontra l - fratturi MF 4411 (studju ta ’ tliet snin), li kienu kkunsidrati mill- investigatur bħala possibilment jew probabbilment relatati mal- prodott mediċinali taħt studju
Two year data in study BM 16550
Tagħrif ta ’ sentejn fl- istudju BM 16550
Bondenza injection Placebo injection 3 mg every 3 + oral ibandronic months acid 2.5 mg daily (N=469) (N=465) ADR No.
Injezzjoni ta ’ Injezzjoni ta ’ Bondenza 3 mg kull plaċebo + 3 xhur (N=469) ibandronic acid 2. 5 ADR No.
(%) ADR No.
(%) mg orali kuljum (N=465) ADR No.
6 (1.3) 4 (0.9) 5 (1.1) 3 (0.6) 17 (3.6) 21 (4.5) 14 (3.0) 19 (4.1) 8 (1.7) 13 (2.8) 5 (1.1) 7 (1.5)
6 (1. 3) 4 (0. 9) 5 (1. 1) 3 (0. 6) 17 (3. 6) 21 (4. 5) 14 (3. 0) 19 (4. 1) 8 (1. 7) 13 (2. 8)
Musculo-skeletal pain
5 (1. 1) 7 (1. 5)
5 (1.1) 2 (0.4)
3 (0. 3) 9 (0. 9)
-
5 (1. 1) 2 (0. 4)
Arthralgia Myalgia Back pain General System disorders
Atralġja Mijalġja Uġigħ ta ’ dahar Disturbi ġenerali
13 (2.8) 4 (0.9) 8 (1.7) 4 (0.9) 5 (1.1) 1 (0.2)
13 (2. 8) 4 (0. 9) 8 (1. 7) 4 (0. 9) 5 (1. 1) 1 (0. 2)
4 (0.4) 18 (1.8) 3 (0.3)
4 (0. 4) 4 (0. 4) 18 (1. 8) 8 (0. 8) 3 (0. 3) 2 (0. 2)
21 (4.5) 4 (0.9)
21 (4. 5) 4 (0. 9)
5 (1.1) 2 (0.4)
5 (1. 1) 2 (0. 4)
6 (1.3) 3 (0.6)
6 (1. 3) 3 (0. 6)
7 (0.7)
MedDRA versjoni 8. 0
Adverse reactions occurring at a frequency of ≤ 1% in study BM16650:
Reazzjonijiet avversi li seħħew bi frekwenza ta ’ ≤ 1% fl- istudju BM16650:
Uncommon (> 1/ 1,000 and < 1/ 100) Musculoskeletal disorders
Mhux komuni (1/ 100 – 1/ 1000) Disturbi muskolu- skeltrali
Bone pain
Uġigħ fl- għadam
General disorders and administration site conditions
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata
Asthenia Injection site reactions
Astenja Reazzjonijiet fis- sit ta ’ l- għotja
19 Vascular Disorders
Disturbi vaskulari
Phlebitis/ thrombophlebitis
Flebite/ tromboflebite
Rare (> 1/ 10,000 and < 1/ 1,000)
19 Rari (> 1/ 10, 000 u < 1/ 1, 000) Disturbi fis- sistema immuni:
Immune system disorders:
Reazzjonijiet ta ’ sensittività eċċessiva
Skin and subcutaneous tissue disorders:
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda:
Hypersensitivity reactions Angioedema Facial swelling/ oedema Urticaria
Anġjoedima Nefħa fil- wiċċ / edima Urtikarja
Laboratory test findings In the pivotal three-year study with oral ibandronic acid 2.5 mg daily (MF 4411) there was no difference compared with placebo for laboratory abnormalities indicative of hepatic or renal dysfunction, impaired haematologic system, hypocalcaemia or hypophosphataemia.
Fl- istudju pivotali ta ’ tliet snin b’ ibandronic acid 2. 5 mg orali kuljum (MF 4411), ma kien hemm l - ebda differenza fl- anormalitajiet tal- laboratorju indikattivi għal funzjoni epatika jew tal- kliewi ħażina, sistema ematoloġika indebolita, ipokalċimja jew ipofosfatimja, meta mqabbel mal- plaċebo.
Similarly, no differences were noted between the groups in the pivotal study with Bondenza 3 mg injection every 3 months (BM 16550).
Bl- istess mod, ma kienet osservata l- ebda differenza bejn il- gruppi fl- istudju pivotali b’ injezzjoni ta ’ Bondenza 3 mg kull 3 xhur (BM 16550).
The majority of the reports refer to cancer patients, but such cases have also been reported in patients treated for osteoporosis.
Il- maġġoranza tar - rapporti jirreferu għall- pazjenti bil- kanċer, iżda każijiet bħal dawn kienu rrappurtati wkoll f’ pazjenti kkurati għal osteoporożi.
No specific information is available on the treatment of overdosage with Bondenza.
L- ebda informazzjoni speċifika ma hija disponibbli dwar il- kura ta ’ doża eċċessiva ta ’ Bondenza.
Based on knowledge of this class of compounds, intravenous overdosage may result in hypocalcaemia, hypophosphataemia, and hypomagnesaemia.
Ibbażat fuq tagħrif dwar din il- klassi ta ’ sustanzi, doża eċċessiva meħuda minn ġol- vini tista ’ tirriżulta f’ ipokalċimja, ipofosfatimja u ipomanjesimja.
Clinically relevant reductions in serum levels of calcium, phosphorus, and magnesium should be corrected by intravenous administration of calcium gluconate, potassium or sodium phosphate, and magnesium sulfate, respectively.
Tnaqqis ta ’ relevanza klinika fil- livelli ta ’ kalċju, fosfru u manjesju fis- serum għandu jiġi kkoreġut b’ għotja minn ġol- vini ta ’ calcium gluconate, potassju jew sodium phosphate, u magnesium sulfate, rispettivament.
In vivo, ibandronic acid prevents bone destruction experimentally induced by cessation of gonadal function, retinoids, tumours or tumour extracts.
In vivo, ibandronic acid jipprevjeni id- distruzzjoni ta ’ l- għadam indotta bl- esperimenti permezz ta ’ waqfien tal- funzjoni gonadali, retinojdi, tumuri jew estratti tat- tumur.
In growing rats, there was no evidence of impaired mineralisation even at doses greater than 5,000 times the dose required for osteoporosis treatment.
F’ firien li kienu qed jikbru, ma kien hemm l- ebda evidenza ta ’ tnaqqis fil - mineralizzazjoni anki f’ dożi ta ’ aktar minn 5, 000 darba akbar mid- doża meħtieġa għall- kura ta ’ l - osteoporożi.
20 increased mechanical strength even at doses in the toxic range.
20 L- għoti għall- perijodu twil, kemm kuljum kif ukoll b’ mod intermittenti (b’ intervalli mtawwla bla doża) lill- firien, klieb u xadini kien assoċjat mal- formazzjoni ta ’ għadam ġdid ta ’ kwalità normali u saħħa mekkanika miżmuma jew miżjuda anki b’ dożi fi skala tossika.
In humans, the efficacy of both daily and intermittent administration with a dose-free interval of 9 - 10 weeks of ibandronic acid was confirmed in a clinical trial (MF 4411), in which ibandronic acid demonstrated anti-fracture efficacy.
Fil- bnedmin, kemm l- effikaċja ta ’ għotja kuljum kif ukoll dik ta ’ għotja intermittenti b’ intervall bla doża ta ’ 9- 10 ġimgħat ta ’ ibandronic acid, kienet ikkonfermata fi prova klinika (MF 4411), fejn ibandronic acid wera effikaċja kontra l- ksur.
Both daily, intermittent (with a dose-free interval of 9 - 10 weeks per quarter) oral doses as well as intravenous doses of ibandronic acid in postmenopausal women produced biochemical changes indicative of dose-dependent inhibition of bone resorption.
Kemm dożi orali, intermittenti ta ’ kuljum, (b’ intervall mingħajr doża ta ’ 9 – 10 ġimgħat kull kwart) kif ukoll dożi ġol- vini ta ’ ibandronic acid f’ nisa wara l- menopawża ipproduċew bidliet biokimiċi li jindikaw inibizzjoni dipendenti mid- doża ta ’ assorbmient mill- ġdid ta ’ l- għadam.
Bondenza intravenous injection decreased levels of serum C-telopeptide of the alpha chain of Type I collagen (CTX) within 3 - 7 days of starting treatment and decreased levels of osteocalcin within 3 months.
Injezzjoni ġol- vini ta ’ Bondenza naqqset il- livelli ta ’ C- telopeptide tal- katina alpha tal- collagen tat- Tip 1 (CTX) fis- serum fi żmiet 3 - 7 ijiem mill- bidu tal- kura u naqqset il- livelli ta ’ osteocalcin fi żmien 3 xhur.
Following treatment discontinuation, there is a reversion to the pathological pre-treatment rates of elevated bone resorption associated with postmenopausal osteoporosis.
Wara waqfien tal- kura, hemm ritorn għar- rati patoloġiċi ta ’ qabel il- kura ta ’ assorbiment mill- ġdid ta ’ l- għadam elevat assoċjat ma ’ osteoporożi ta ’ wara l- menopawża.
The histological analysis of bone biopsies after two and three years of treatment of postmenopausal women with doses of oral ibandronic acid 2.5 mg daily and intermittent intravenous doses of up to 1 mg every 3 months showed bone of normal quality and no indication of a mineralisation defect.
L- analiżi istoloġika ta ’ bijopsiji ta ’ l- għadam wara sentejn u tliet snin ta ’ kura ta ’ nisa wara l - menopawża b’ dożi ta ’ ibandronic acid 2. 5 mg orali kuljum u dożi intermittenti ġol- vini sa 1 mg kull 3 xhur wriet għadam ta ’ kwalità normali u l- ebda indikazzjoni ta ’ difett fil- mineralizzazjoni.