qanastek/EMEA-V3 huggingface dataset:
Osteonecrosis of the jaw (ONJ):
Ostejonekrożi tax- xedaq (ONJ):
Osteonecrosis of the jaw has been reported predominantly in patients with cancer receiving treatment regimens including bisphosphonates, including zoledronic acid.
Ostejonekrożi tax- xedaq kienet rapurtata l- aktar f’ pazjenti b’ kanċer li kienu qed jirċievu reġimens ta ’ kura li tinkludi bisphosphonates, inkluż zoledronic acid.
Many of these patients were also receiving chemotherapy and corticosteroids.
Ħafna minn dawn- il pazjenti kienu qed jirċievu kimoterapija u kortikosterojdi.
The majority of reported cases have been associated with dental procedures such as tooth extraction.
Il- maġġoranza mill- każi rrapurtati kienu assoċjati ma ’ proċeduri li għandhom x’ jaqsmu mas- snien bħal qlugħ ta ’ snien.
Many had signs of local infection including osteomyelitis.
Ħafna kellhom sinjali ta ’ infezzjoni lokali inkluża ostejomajlajtis.
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, corticosteroids, poor oral hygiene).
Għandu jkun ikkonsidrat li jkunu eżaminati s- snien u tingħata terapija preventiva xierqa qabel jibda t- trattament b’ bisphosphonates f’ pazjenti li jkollhom fatturi ta ’ riskju konkomitanti (eż.
While on treatment, these patients should avoid invasive dental procedures if possible.
Kanċer, kimoterapija, kortikosterojdi, nuqqas ta ’ iġjene fil- ħalq).
For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition.
Waqt il- kura, dawn- il pazjenti għandhom jevitaw proċeduri dentali invażivi jekk jista ’ jkun.
For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw.
Għall- pazjenti li jkollhom bżonn proċedura dentali, m’ hemmx tagħrif biex jagħti parir dwar jekk it- twaqqif tat- trattament b’ bisphosphonate jnaqqasx ir- riskju ta ’ ostejonekrożi tax- xedaq.
The clinical judgement of the treating physician should guide the management plan of each patient based on individual benefit/ risk assessment.
Il- ġudizzju kliniku tat- tabib li jkun qed jikkura għandu jservi ta ’ gwida għall- pjan ta ’ immaniġġjar ta ’ kull pazjent bażat fuq l- istima tal- benefiċċju/ riskju individwali.
Specific drug-drug interaction studies have not been conducted with zoledronic acid.
Studji speċifiċi fuq in- nuqqas ta ’ qbil bejn mediċina u oħra ma sarux b’ zoledronic acid.
Zoledronic acid is not systemically metabolised and does not affect human cytochrome P450 enzymes in vitro (see section 5.2).
Zoledronic acid ma jkunx metabolizzat b’ mod sistemiku u ma jeffettwax l- enzimi tal- bniedem cytochrome P450 in vitro (ara sezzjoni 5. 2).
Zoledronic acid is not highly bound to plasma proteins (approximately 43-55% bound) and interactions resulting from displacement of highly protein-bound drugs are therefore unlikely.
Zoledronic acid ma jingħaqadx bil- qawwa mal- proteini tal- plażma (madwar 43- 55% jingħaqad) u għaldaqstant nuqqas ta ’ qbil li jirriżulta minn qlugħ ta ’ mediċini li jkunu marbutin mal- proteini m’ huwiex probabbli.
Zoledronic acid is eliminated by renal excretion.
Zoledronic acid jiġi eliminat permezz ta ’ l- eskrezzjoni renali.
Caution is indicated when Aclasta is administered in conjunction with medicinal products that can significantly impact renal function (e. g. aminoglycosides or diuretics that may cause dehydration).
Għandha ssir attenzjoni meta Aclasta tingħata ma ’ prodotti mediċinali li jista ’ jkollhom impatt sinifikanti fuq il- funzjoni renali (eż. aminoglycosides jew dijuretiċi li jikkawżaw deidrazzjoni).
There are no adequate data on the use of zoledronic acid in pregnant women.
M’ hemmx tagħrif biżżejjed dwar l- użu ta ’ zoledronic acid waqt it- tqala.
Studies in animals with zoledronic acid have shown reproductive toxicological effects including malformations (see section 5.3).
Studji fuq bhejjem b’ zoledronic acid urew effetti tossikoloġiċi fis- sistema riproduttiva inklużi malformazzjonijiet (ara sezzjoni 5. 3).
It is not known whether zoledronic acid is excreted into human breast milk.
Mhux magħruf jekk zoledronic acid joħroġx mal- ħalib tal- mara.
Aclasta is contraindicated during pregnancy and in breast-feeding women (see section 4.3).
Aclasta m’ għandux jingħata waqt it- tqala u f’ nisa waqt it- treddigħ (ara sezzjoni 4. 3).
No studies on the effects on the ability to drive and use machines have been performed.
Ma sarux studji dwar l- effetti fuq il- ħila biex issuq u tħaddem magni.
4 4.8 Undesirable effects
4 4. 8 Effetti mhux mixtieqa
The overall percentage of patients who experienced post-dose symptoms were 44.7%, 16.7% and 10.2% after the first, second and third infusion, respectively.
Il- perċentwali globali tal- pazjenti li ħassew sintomi ta ’ wara d- doża kienu 44. 7%, 16. 7% u 10. 2% wara l- ewwel, it- tieni u t- tielet infużjoni rispettivament.
Incidence of individual symptoms following the first infusion was: fever (17.1%), myalgia (7.8%), flu-like symptoms (6.7%), arthralgia (4.8%) and headache (5.1%).
L- inċidenza tas- sintomi individwali wara l- ewwel infużjoni kienu: deni (17. 1%), majalġja (7. 8%), sintomi bħal ta ’ l- influwenza (6. 7%), artralġja (4. 8%) u uġigħ ta ’ ras (5. 1%).
The incidence of these symptoms decreased markedly with subsequent doses of Aclasta.
L- inċidenza ta ’ dawn is- sintomi naqset b’ mod sostanzjali mad- dożi sussegwenti ta ’ Aclasta.
The majority of these symptoms occur within the first three days following Aclasta administration.
Il- maġġoranza ta ’ dawn is- sintomi iseħħu fl- ewwel tlett ijiem wara li tingħata Aclasta.
The majority of these symptoms were mild to moderate and resolved within three days of the event onset.
Il- maġġoranza ta ’ dawn is- sintomi kienu ħfief għal moderati u għaddew fi żmien tlett ijiem minn meta jkun beda l- każ.
The percentage of patients who experienced post-dose symptoms was lower in a smaller study (19.5%, 10.4%, 10.7% after the first, second and third infusion, respectively), where prophylaxis against post-dose symptoms was used as described below.
Il- perċentwali tal- pazjenti li ħassew sintomi ta ’ wara d- doża kien aktar baxx fi studju iżgħar (19. 5%, 10. 4%, 10. 7% wara l- ewwel, it- tieni u t- tielet infużjoni, rispettivament), fejn intużat profilassi kontra s- sintomi ta ’ wara d- doża kif deskritt hawn isfel.
The incidence of post-dose symptoms occurring within the first three days after administration of Aclasta can be reduced with the administration of paracetamol or ibuprofen shortly following Aclasta administration (see section 4.2).
L- inċidenza tas- sintomi ta ’ wara d- doża li jseħħu fi żmien tlett ijiem wara li tingħata Aclasta tista ’ titnaqqas bl- għotja ta ’ paracetamol jew ibuprofen ftit wara li tingħata Aclasta (ara sezzjoni 4. 2).
In the HORIZON – Pivotal Fracture Trial [PFT] (see section 5.1), the overall incidence of atrial fibrillation was 2.5% (96 out of 3,862) and 1.9% (75 out of 3,852) in patients receiving Aclasta and placebo, respectively.
Fl- istudju HORIZON – Prova Pivitali tal- Ksur [PFT] (ara sezzjoni 5. 1), l- inċidenza globali tal - fibrillazzjoni atrijali kienet 2. 5% (96 minn 3, 862) u 1. 9% (75 minn 3, 852) f’ pazjenti li kienu qed jirċievu Aclasta u plaċebo, rispettivament.
The rate of atrial fibrillation serious adverse events was increased in patients receiving Aclasta (1.3%) (51 out of 3,862) compared with patients receiving placebo (0.6%) (22 out of 3,852).
Ir- rata ta ’ każijiet avversi serji ta ’ fibrillazzjoni atrijali żdiedet f’ pazjenti li kienu qed jirċievu Aclasta (1. 3%) (51 minn 3, 862) meta mqabbla ma ’ pazjenti li kienu qed jirċievu plaċebo (0. 6%) (22 minn 3, 852).
The mechanism behind the increased incidence of atrial fibrillation is unknown.
Mhux magħruf il- mekkaniżmu taż- żieda fil - fibrillazzjoni atrijali.
In the osteoporosis trials (PFT, HORIZON - Recurrent Fracture Trial [RFT]) the pooled atrial fibrillation incidences were comparable between Aclasta (2.6%) and placebo (2.1%).
Fil- provi fuq l- osteoporożi (PFT, HORIZON – Prova dwar il- ksur Rikurrenti [RFT]) l- inċidenza tal- każijiet ta ’ fibrillazzjoni fl- atrija miġbura flimkien kienu jaqblu bejn Aclasta (2. 6%) u l- plaċebo (2. 1%).
For atrial fibrillation serious adverse events the pooled incidences were 1.3% for Aclasta and 0.8% for placebo.
Għal- każijiet serji ta ’ fibrillazzjoni fl- atrija miġbura flimkien il- każijiet kienu 1. 3% għal Aclasta u 0. 8% għal plaċebo.
Very common (≥ 1/ 10), common (≥ 1/ 100, < 1/ 10), uncommon (≥ 1/ 1,000, < 1/ 100), rare (≥ 1/ 10,000, < 1/ 1,000) adverse drug reactions are shown in Table 1.
Reazzjonijiet avversi għall- mediċina komuni ħafna (≥1/ 10), komuni (≥1/ 100, < 1/ 10), mhux komuni (≥1/ 1, 000, < 1/ 100), rari (≥1/ 10, 000, < 1/ 1, 000) qed jidhru f’ Tabella 1.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
F’ kull sezzjoni ta ’ frekwenza, l - effetti mhux mixtieqa għandhom jitniżżlu skond is- serjetà ta ’ tagħhom.
Table 1*
Tabella 1 *
Investigations Cardiac disorders Nervous system disorders
Investigazzjonijiet
Uncommon Common Common Uncommon
Mhux komuni
Blood pressure increased Atrial fibrillation Headache, dizziness Lethargy, paraesthesia, somnolence, tremor, syncope
Disturbi fis- sistema nervuża
Eye disorders
Uġigħ ta ’ ras, sturdament
Uncommon Rare
Mhux komuni
Conjunctivitis, eye pain Uveitis, episcleritis, iritis
Tħeddil, parasteżija, ngħas, tregħid, sinkope
Ear and labyrinth disorders Respiratory, thoracic and mediastinal disorders
Konġunktivite, uġigħ fl- għajnejn
Uncommon Uncommon
Rari Mhux komuni
Vertigo Dyspnoea
Uveite, episklerite, irite Vertigo
Gastrointestinal disorders
Disturbi respiratorji, toraċiċi u medjastinali
Common Uncommon
Mhux komuni
Nausea, vomiting Diarrhoea, dyspepsia, abdominal pain, dry mouth
Disturbi gastro- intestinali
Renal and urinary disorders Skin and subcutaneous tissue disorders
Dardir, rimettar
Uncommon Uncommon
Mhux komuni
Blood creatinine increased, pollakiuria Rash, night sweats, hyperhydrosis, pruritus, erythema
Dijarea, dispepsja, uġigħ fl- addome, ħalq xott
Musculoskeletal and connective tissue disorders
Disturbi fil- kliewi u fis- sistema urinarja
Myalgia, arthralgia, bone pain, back pain, pain in extremity Neck pain, musculoskeletal stiffness, joint swelling, shoulder pain, muscle spasms, musculoskeletal pain, non-cardiac chest pain, arthritis, muscular weakness, joint stiffness
Żieda fil- krejatinina tad- demm, pollakurja
Metabolism and nutrition disorders
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il - ġilda
Hypocalcaemia† Anorexia, decreased appetite
Raxx, għaraq bil- lejl, iperidrosi, ħakk, eritema
5
5 Disturbi muskolu- skeletrali u tal - connective tissue
Infections and infestations Vascular disorders General disorders and administration site conditions
Majalġja, artralġja, uġigħ fl- għadam, uġigħ fid- dahar, uġigħ fit- truf
Uncommon Uncommon Very common Common
Mhux komuni
Influenza Hypertension, flushing Fever Flu-like symptoms, chills, fatigue, asthenia, pain, malaise, rigors†
Disturbi fil- metaboliżmu u n- nutrizzjoni
Uncommon
Mhux komuni Mhux komuni
Peripheral oedema, thirst
Mhux komuni Komuni ħafna Deni
Immune system disorders
Pressjoni għolja, fwawar
Not known**
magħruf **
Hypersensitivity reactions including rare cases of bronchoconstriction, urticaria and angioedema, and very rare cases of anaphylactic reaction/ shock
jinkludu każijiet rari ta ’ tidjiq tal- bronki, urtikarja u anġjoedema, u każijiet rari ħafna ta ’ reazzjoni/ xokk anafilattiku
Psychiatric disorders
Disturbi psikjatriċi
Uncommon
Mhux komuni
Insomnia
Nuqqas ta ’ rqad
* Additional adverse events which were reported in the individual studies but were not included due to the pooled presentation are:
* Episodji avversi oħra li ġew irrappurtati fl- istudji individwali iżda li ma ġewx inklużi minħabba l - preżentazzjoni kollettiva huma:
Uncommon: dysgeusia, oesophagitis, toothache. † Common in Paget’ s disease only.
Mhux komuni: togħma ħażina, esofaġite, uġigħ fis- snien. † Komuni fil- marda ta ’ Paget biss.
For hypocalcaemia, see also text below. ** Based on post-marketing reports.
Għal ipokalċimja, ara wkoll il- kitba hawn taħt. ** Ibbażati fuq rapporti ta ’ wara t- tqegħid fis- suq tal- prodott.
Since these reports are from a population of uncertain size and are subject to confounding factors, it is not possible to reliably estimate their frequency or establish a causal relationship to exposure to the medicinal product.
Peress li dawn ir- raporti huma minn popolazzjoni ta ’ daqs mhux magħruf u effettwati minn fatturi li jistgħu jifxlu, mhux possibli li ssir stima tal- frekwenza tagħhom b’ mod li wieħed jista ’ joqod fuqha jew li tiġi stabbilita relazzjoni bejn il- kawża u l- esponiment għall- mediċina.
Class effects:
Effetti skond il- klassi:
Renal dysfunction Zoledronic acid has been associated with renal dysfunction manifested as deterioration in renal function (i. e. increased serum creatinine) and in rare cases acute renal failure.
Disfunzjoni renali Zoledronic acid kien assoċjat ma ’ disfunzjoni renali li kienet manifestata bħala tħażżin fil- funzjoni renali (jiġifieri żieda tal- krejatinina fis- serum) u f’ każijiet rari insuffiċjenza renali akuta.
Renal dysfunction has been observed following the administration of zoledronic acid, especially in patients with pre-existing renal compromise or additional risk factors (e. g oncology patients with chemotherapy, concomitant nephrotoxic medications, severe dehydration), the majority of whom received a 4 mg dose every 3– 4 weeks, but it has been observed in patients after a single administration.
Funzjoni renali ħażina kienet osservata wara li ngħata zoledronic acid, l- aktar f’ pazjenti li kellhom il- kliewi kompromessi minn qabel jew li kellhom xi fatturi ta ’ riskji oħrajn (eż. pazjenti ta ’ l- onkoloġija fuq kimoterapija, l- użu konkomitanti ta ’ mediċini nefrotossiċi fl- istess waqt, deidrazzjoni severa), li l- parti l- kbira tagħhom irċevew doża ta ’ 4 mg kull 3- 4 ġimgħat, iżda dehret f’ pazjenti wara doża waħda.
In clinical trials in osteoporosis, the change in creatinine clearance (measured annually prior to dosing) and the incidence of renal failure and impairment was comparable for both the Aclasta and placebo treatment groups over three years.
Fi provi kliniċi dwar l- osteoporożi, il- bidla fit- tneħħija tal- krejatinina (imkejla kull sena qabel ma tingħata d- doża) u l- inċidenza ta ’ insuffiċjenza u indeboliment renali setgħu jitqabblu kemm fil- gruppi ta ’ kura fuq Aclasta kif ukoll dawk fuq plaċebo matul it- tlett snin.
There was a transient increase in serum creatinine observed within 10 days in 1.8% of Aclasta-treated patients versus 0.8% of placebo-treated patients.
Kien hemm żieda momentanja tal - krejatinina fis- serum fi żmien 10 ijiem f’ 1. 8% tal- pazjenti kkurati b’ Aclasta kontra 0. 8% tal- pazjenti kkurati bi plaċebo.
Hypocalcaemia In clinical trials in osteoporosis, approximately 0.2% of patients had notable declines of serum calcium levels (less than 1.87 mmol/ l) following Aclasta administration.
Ipokalċimja Fi provi kliniċi dwar l- osteoporożi, madwar 0. 2% tal- pazjenti kellhom tnaqqis notevoli fil- livelli tal - calcium fis- serum (anqas minn 1. 87 mmol/ l) wara li ngħataw Aclasta.
No symptomatic cases of hypocalcaemia were observed.
Ma kien dehru l- ebda każijiet ta ’ sintomi ta ’ ipokalċimja.
In the Paget’ s disease trials, symptomatic hypocalcaemia was observed in approximately 1% of patients, in all of whom it resolved.
Fil- provi dwar il- marda ta ’ Paget, ipokalċimja b’ sintomi dehret f’ madwar 1% tal- pazjenti, u għaddiet f’ kollha kemm huma.
Based on laboratory assessment, transient asymptomatic calcium levels below the normal reference range (less than 2.10 mmol/ l) occurred in 2.3% of Aclasta-treated patients in a large clinical trial compared to 21% of Aclasta-treated patients in the Paget’ s disease trials.
Minn stima tal- laboratorju, livelli ta ’ calcium taħt il- livelli tal- medda ta ’ referenza normali mingħajr sintomi għal mument (anqas minn 2. 10 mmol/ l) seħħew f’ 2. 3% tal- pazjenti kkurati b’ Aclasta fi prova
The frequency of hypocalcaemia was much lower following subsequent infusions.
Il - frekwenza ta ’ ipokalċimja kienet aktar baxxa wara l- infużjonijiet ta ’ wara.
All patients received adequate supplementation with vitamin D and calcium in the post-menopausal osteoporosis trial, the prevention of clinical fractures after hip fracture trial, and the Paget’ s disease trials (see also section 4.2).
Il- pazjenti kollha rċevew supplimenti xierqa ta ’ vitamina D u calcium fil- prova dwar l- osteoporożi wara l- menopawsa, fil- prevenzjoni tal- ksur kliniku wara prova dwar il- ksur fil- ġenbejn, kif ukoll fil - provi dwar il- marda ta ’ Paget (ara wkoll sezzjoni 4. 2).
In the trial for the prevention of clinical fractures following a recent hip fracture, vitamin D levels were not routinely measured but the majority of patients received a loading dose of vitamin D prior to Aclasta administration (see section 4.2).
Fil- prova għall- prevenzjoni tal- ksur kliniku wara ksur riċenti fil- ġenbejn, il- livelli tal- vitamina D ma ġewx ikejla b’ mod regolari iżda l - maġġoranza tal- pazjenti rċevew loading dose ta ’ vitamina D qabel ma ngħataw Aclasta (ara sezzjoni 4. 2).
Local reactions In a large clinical trial, local reactions at the infusion site, such as redness, swelling and/ or pain, were reported (0.7%) following the administration of zoledronic acid.
Reazzjonijiet lokali Fi prova klinika kbira, reazzjonijiet lokali fis- sit mnejn ingħatat l- infużjoni, bħal ħmura, nefħa u/ jew uġigħ, kienu rrappurtati (0. 7%) wara l- għotja ta ’ zoledronic acid.
6 Osteonecrosis of the jaw Uncommonly, cases of osteonecrosis (primarily of the jaw) have been reported, predominantly in cancer patients treated with bisphosphonates, including zoledronic acid.
Ostejonekrożi tax- xedaq Każijiet mhux komuni ta ’ osteonekrożi (l- aktar tax- xedaq) kienu rapurtati, l- aktar f’ pazjenti li jsofru minn kanċer kurati b’ bisphosphonates, inkluż zoledronic acid.
Many of these patients had signs of local infection including osteomyelitis, and the majority of the reports refer to cancer patients following tooth extractions or other dental surgeries.
Ħafna minn dawn il- pazjenti kellhom sinjali ta ’ infezzjoni lokali inkluża ostejomajlajtis, u l- parti l- kbira tar- rapporti jirreferu għall- pazjenti b’ kanċer wara li qalgħu sinna jew għamlu xi kirurġiji dentali.
Osteonecrosis of the jaw has multiple well documented risk factors including a diagnosis of cancer, concomitant therapies (e. g. chemotherapy, radiotherapy, corticosteroids) and co-morbid conditions (e. g. anaemia, coagulopathies, infection, pre- existing dental disease).
Ostejonekrożi tax- xedaq għandha għadd ta ’ fatturi ta ’ riskji inklużi d- dijanjożi ta ’ kanċer, terapiji konkomitanti (eż. kimoterapija, radjuterapija, kortikosterojdi) u kundizzjonijiet oħra li fl- istess waqt idgħajjfu l- pazjent (eż anemija, mard tal - koagulazzjoni, infezzjonijiet, mard tas- snien li jkun hemm minn qabel).
Although causality has not been determined, it is prudent to avoid dental surgery as recovery may be prolonged (see section 4.4).
Għalkemm il- kawżi ma kienux determinati, ikun għaqli li kirurġiji dentali jiġu evitati minħabba li l- konvalexxenza tista ’ tittawwal (ara sezzjoni 4. 4).
In a large clinical trial in 7,736 patients, osteonecrosis of the jaw has been reported in one patient treated with Aclasta and one patient treated with placebo.
Fi prova klinika kbira, minn 7, 736 pazjent, l- osteonekrożi tax- xedaq kienet irrappurtata f’ pazjent wieħed ikkurat b’ Aclasta u f’ pazjent wieħed ikkurat bi plaċebo.
Both cases resolved.
Iż- żewġ każijiet fiequ.
There is no experience of acute intoxication with Aclasta.
M’ hemmx esperjenza ta ’ intossikazzjoni akuta b’ Aclasta.
Patients who have received doses higher than those recommended should be carefully monitored.
Pazjenti li jkunu ħadu dożi ogħla minn dawk rakkomandati għandhom ikunu monitorati bir- reqqa.
In the event of overdose leading to clinically significant hypocalcaemia, reversal may be achieved with supplemental oral calcium and/ or an intravenous infusion of calcium gluconate.
F’ każ ta ’ doża eċċessiva li twassal għal ipokalċimja li tkun klinikament sinifikanti, din tista ’ titreġġa lura b’ suppliment ta ’ calcium orali u/ jew infużjoni fil- vini ta ’ calcium gluconate.
Bisphosphonate, ATC code:
Bisphosphonate, Kodiċi ATC:
Mechanism of action Zoledronic acid belongs to the class of nitrogen-containing bisphosphonates and acts primarily on bone.
Mod kif jaħdem Zoledronic acid jaqa ’ fil- klassi ta ’ bisphosphonates li fihom nitrogen u jaħdem l- aktar fuq l- għadam.
It is an inhibitor of osteoclast-mediated bone resorption.
Huwa inibitur tar- risorbiment ta ’ l- għadam medjat bl- ostejoklasts.
Pharmacodynamic effects Aclasta treatment rapidly reduced the rate of bone turnover from elevated post-menopausal levels with the nadir for resorption markers observed at 7 days, and for formation markers at 12 weeks.
Effetti farmakodinamiċi Il- kura b’ Aclasta tnaqqas b’ mod mgħaġġel ir- rata ta ’ tibdil ta ’ l- għadam minn livelli għoljin ta ’ wara l - menopawsa għall- inqas livell ta ’ markaturi ta ’ risorbiment li dehru fis- 7 jum, u għal markaturi tal - formazzjoni li dehru fit- 12- il ġimgħa.
Thereafter bone markers stabilised within the pre-menopausal range.
Minn hemm ‘ l quddiem il- markaturi ta ’ l- għadam stabilizzaw rwieħhom fil- medda ta’ qabel il- menopawsa.
There was no progressive reduction of bone turnover markers with repeated annual dosing.
Ma kienx hemm tnaqqis progressiv fil- markaturi tat- tibdil ta ’ l- għadam b’ dożi li ngħataw sena wara l- oħra.
Clinical efficacy in the treatment of post-menopausal osteoporosis (PFT) The efficacy and safety of Aclasta 5 mg once a year for 3 consecutive years were demonstrated in post-menopausal women (7,736 women aged 65– 89 years) with either: a femoral neck bone mineral density (BMD) with a T-score ≤ – 1.5 and at least two mild or one moderate existing vertebral fracture(s); or a femoral neck BMD T-score ≤ – 2.5 with or without evidence of existing vertebral fracture(s).
L- effikaċja klinika tal- kura ta ’ l- osteoporożi ta ’ wara l- menopawsa (PFT) L- effikaċja u s- sigurtà ta ’ Aclasta 5 mg darba fis- sena għal tliet snin konsekuttivi ntwerew f’ nisa ta ’ wara l- menopawsa (7, 736 mara ta ’ etajiet bejn 65- 89 sena) b’ densità minerali ta ’ l- għadam ta ’ l- għonq femorali (BMD) bil- punteġġ- T ≤ – 1. 5 u għalmenu żewġ fratturi fl- irkiekel ħfief jew jekk ikun hemm frattura( i) ta ’ l- irkiekel waħda moderata; jew inkella BMD ta ’ l- għonq femorali bil- punteġġ- T ≤ – 2. 5
85% of patients were bisphosphonate-naïve.
85% tal- pazjenti qatt ma kienu ħadu kura b’ bisphosphonate.
Women who were evaluated for the incidence of vertebral fractures did not receive concomitant osteoporosis therapy, which was allowed for women contributing to the hip and all clinical fracture evaluations.
In- nisa li kienu evalwati għall- inċidenza tal- fratturi ta ’ l- irkiekel ma rċevewx terapija għall- osteoprożi fl- istess ħin, li kienet permessa għal nisa li kienu qed jikkontribwixxu għall evalwar tal- ġenbejn u l- fratturi kliniċi kollha.
Concomitant osteoporosis therapy included: calcitonin, raloxifene, tamoxifen, hormone replacement therapy, tibolone; but excluded other bisphosphonates.
Terapija għall- osteoporożi fl- istess ħin kienet tinkludi: calcitonin, raloxifene, tamoxifen, terapija tal- hormone replacement, tibolone; iżda kienet teskludi bisphosphonates oħrajn.
All women received 1,000 to 1,500 mg elemental calcium and 400 to 1,200 IU of vitamin D supplements daily.
In- nisa kollha irċevew 1, 000 sa 1, 500 mg calcium bħala element u 400 sa 1, 200 IU ta ’ vitamina D bħala suppliment kuljum.
Effect on morphometric vertebral fractures Aclasta significantly decreased the incidence of one or more new vertebral fractures over three years and as early as the one year timepoint (see Table 2).
L- effett fuq fratturi morfometriċi ta ’ l- irkiekel Aclasta naqqas b’ mod sinifikanti l- inċidenza ta ’ wieħed jew aktar fratturi ġodda fl- irkiekel fuq perijodu ta ’ tlett snin u dan sa mill- ewwel sena li ttieħdet bħala timepoint (ara Tabella 2).
7 Table 2
Tabella 2
Summary of vertebral fracture efficacy at 12, 24 and 36 months
Sommarju ta ’ l- effikaċja fuq il- fratturi ta ’ l- irkiekel mat- 12, 24 u 36 xahar
Outcome
Riżultat
Aclasta Placebo Absolute reduction in (%) (%) fracture incidence% (CI)
Aclasta Plaċebo Tnaqqis assolut fl -
Relative fracture
Tnaqqis relattiv fl -
reduction in incidence% (CI)
inċidenza tal- fratturi% (CI)
At least one new vertebral fracture (0– 1 year)
Mill- anqas frattura waħda ġdida fl- irkiekel (0- 1 sena)
2.2 (1.4, 3.1)
2. 2 (1. 4, 3. 1)
At least one new vertebral fracture (0– 2 year)
Mill- anqas frattura waħda ġdida fl- irkiekel (0- 2 sentejn)
5.5 (4.4, 6.6)
5. 5 (4. 4, 6. 6)
At least one new vertebral fracture (0– 3 year) ** p < 0.0001
Mill- anqas frattura waħda ġdida fl- irkiekel (0- 3 snin) ** p < 0. 0001
10.9
10. 9
7.6 (6.3, 9.0)
7. 6 (6. 3, 9. 0)
Aclasta-treated patients aged 75 years and older exhibited a 60% reduction in the risk of vertebral fractures compared to placebo patients (p < 0.0001).
Pazjenti ikkurati b’ Aclasta li għandhom ‘ l fuq minn 75 sena urew tnaqqis ta ’ 60% fir- riskju għal fratturi fl- irkiekel meta mqabbla ma ’ pazjenti fuq plaċebo (p < 0. 0001).
Effect on hip fractures Aclasta demonstrated a consistent effect over 3 years, resulting in a 41% reduction in the risk of hip fractures (95% CI, 17% to 58%).
Effett fuq il- fratturi fil- ġenbejn Aclasta wera effett b’ mod konsistenti fuq 3 snin, li wassal ghal tnaqqis ta ’ 41% fir- riskju ta ’ fratturi fil- ġenbejn (95% CI, 17% sa 58%).
The hip fracture event rate was 1.44% for Aclasta-treated patients compared to 2.49% for placebo-treated patients.
Ir- rata tal- każijiet tal- frattura tal- ġenbejn kienet 1. 44% għall - pazjenti kkurati b’ Aclasta meta mqabbla ma ’ 2. 49% għall- pazjenti kkurati bi plaċebo.
The risk reduction was 51% in bisphosphonate-naïve patients and 42% in patients allowed to take concomitant osteoporosis therapy.
It- tnaqqis fir - riskju kien 51% fil- pazjenti li ma ħadux bisphosphone u 42% fil- pazjenti li tħallew jieħu terapija konkomitanti għall- osteoporożi.
A summary of results is presented in Table 3.
L- effett fuq il- fratturi kliniċi kollha Il- fratturi kliniċi kollha kienu verifikati fuq bażi ta ’ radjugrafiji u/ jew evidenza klinika.
Between treatment comparisons of the incidence over 3 years
Sommarju tar - riżultati qed tintwera f’ Tabella 3.
of key clinical fracture variables
Tabella 3 Tqabbil bejn il- kuri ta ’ l- inċidenza ta ’ varjanti kliniċi ewlenin fuq 3 snin
Placebo Absolute reduction (N=3,861) in fracture event
rata tal- każ ta ’
Relative risk reduction in
riskju fl- inċidenza
event rate (%)
rata tal- każ
event rate (%)
rata tal- każ (%)
rate% (CI)
frattura%
fracture incidence% (CI)
tal - frattura%
Any clinical fracture (1) Clinical vertebral fracture (2) Non-vertebral fracture (1) *p-value < 0.001, **p-value < 0.0001
(CI)
8.4 0.5 8.0
(CI)
12.8 2.6 10.7
8. 4 0. 5 8. 0
4.4 2.1 2.7
12. 8 2. 6 10. 7
(3.0, 5.8) (1.5, 2.7) (1.4, 4.0)
4. 4 (3. 0, 5. 8) 2. 1 (1. 5, 2. 7) 2. 7 (1. 4, 4. 0)
(1) Excluding finger, toe and facial fractures (2) Including clinical thoracic and clinical lumbar vertebral fractures
(1) Esklużi fratturi tas- swaba ta ’ l- idejn, tas- saqajn jew fratturi tal- wiċċ (2) Inklużi fratturi kliniċi toraċiċi u l- irkiekel tal- lumbar
Effect on bone mineral density (BMD) Aclasta significantly increased BMD at the lumbar spine, hip, and distal radius relative to treatment with placebo at all timepoints (6, 12, 24 and 36 months).
8 Effett fuq id- densità minerali ta ’ l- għadam (BMD) Aclasta żiedet b’ mod sinifikanti l- BMD fis- sinsla lumbar, ġenbejn u distal radius meta mqabbel mal - kura bil- plaċebo fit- timepoints kollha (6, 12, 24 u 36 xhur).
Treatment with Aclasta resulted in a 6.7% increase in BMD at the lumbar spine, 6.0% at the total hip, 5.1% at the femoral neck, and 3.2% at the distal radius over 3 years as compared to placebo.
Il- kura b’ Aclasta wasslet għal żieda ta ’ 6. 7% fil- BMD fis- sinsla lumbar, 6. 0% tal- ġenbejn totali, 5. 1% fl- għonq femorali, u 3. 2% fid- distal radius fuq 3 snin meta mqabbla mal- plaċebo.
Bone histology Bone biopsies were obtained from the iliac crest 1 year after the third annual dose in 152 post- menopausal patients with osteoporosis treated with Aclasta (N=82) or placebo (N=70).
Istoloġija ta ’ l- għadam Bijopsiji ta ’ l- għadam inkisbu mill- iliac crest sena 1 wara t- tielet doża ta ’ kull sena f’ 152 pazjenta wara l- menopawsa b’ osteoporożi kkurati b’ Aclasta (N=82) jew plaċebo (N=70).
Histomorphometric analysis showed a 63% reduction in bone turnover.
Analiżi istomorfometrika wriet tnaqqis ta ’ 63% fit- tibdil ta ’ l- għadam.
In patients treated with Aclasta, no osteomalacia, marrow fibrosis or woven bone formation was detected.
F’ pazjenti kkurati b’ Aclasta, ma nstabx li kien hemm osteomalaċja, fibrożi fil- mudullun jew formazzjoni ta ’ għadam mhux lamellat.
Microcomputed
Tikketta tat- tetracycline setgħet titkejjel fit- 82 bijopsiji ħlief f’ wieħed li nkisbu minn pazjenti fuq Aclasta.
8 tomography (μ CT) analysis demonstrated increased trabecular bone volume and preservation of trabecular bone architecture in patients treated with Aclasta compared to placebo.
Analiżi tat- tomografija mikrokomputata (μCT) wriet żieda fil- volum trabekulari ta ’ l- għadam u priservazzjoni ta ’ l- arkitettura trabekulari ta ’ l- għadam f’ pazjenti kkurati b’ Aclasta meta mqabbla ma ’ plaċebo.
Bone turnover markers Bone specific alkaline phosphatase (BSAP), serum N-terminal propeptide of type I collagen (P1NP) and serum beta-C-telopeptides (b-CTx) were evaluated in subsets ranging from 517 to 1,246 patients at periodic intervals throughout the study.
Markaturi tat- tibdil ta ’ l- għadam Alkaline phosphatase speċifiku għall- għadam (BSAP), propeptajd N- terminali fis- serum tal- kollaġen tat- tip I (P1NP) u beta- Ċ- telopeptajds (b- CTx) fis- serum kienu evalwati fis- sottosetijiet li kienu jvarjaw minn 517 sa 1, 246 pazjent f’ intervalli perjodiċi matul l- istudju.
Treatment with a 5 mg annual dose of Aclasta significantly reduced BSAP by 30% relative to baseline at 12 months which was sustained at 28% below baseline levels at 36 months.
Kura b’ 5 mg fis- sena ta ’ Aclasta naqqset b’ mod sinifikanti il- BSAP bi 30% meta mqabbel mal- linja bażi fit- 12- il xahar li nżamm bi 28% taħt il- livelli tal- linja bażi mas- 36 xahar.
P1NP was significantly reduced by 61% below baseline levels at 12 months and was sustained at 52% below baseline levels at 36 months.
PINP tnaqqas b’ mod sinfikanti b’ 61% taħt il - livelli tal- linja bażi mat- 12- il xahar u nżamm b’ 52% taħt il- livelli tal- linja bażi mas- 36 xahar.
B-CTx was significantly reduced by 61% below baseline levels at 12 months and was sustained at 55% below baseline levels at 36 months.
B- CTx tnaqqas b’ mod sinfikanti b’ 61% taħt il- livelli tal- linja bażi mat- 12- il xahar u nżamm b’ 55% taħt il - livelli tal- linja bażi mas- 36 xahar.
During this entire time period bone turnover markers were within the pre-menopausal range at the end of each year.
Tul dan il- perijodu kollu l- markaturi tat- tibdil ta ’ l- għadam kienu fil- medda ta ’ qabel il- menopawsa fl- aħħar ta ’ kull sena.
Repeat dosing did not lead to further reduction of bone turnover markers.
Dożi ripetuti ma wasslux għal aktar tnaqqis tal- markaturi tat- tibdil ta ’ l- għadam.
Effect on height In the three-year osteoporosis study standing height was measured annually using a stadiometer.
L- effett fuq it- tul Fl- istudju dwar l- osteoporiżi li dam tlett snin it- tul tal- pożizzjoni wieqfa kien imkejjel kull sena bi stadjometru.
The Aclasta group revealed approximately 2.5 mm less height loss compared to placebo (95% CI:
Il- grupp fuq Aclasta wera madwar 2. 5 mm anqas telf fit- tul meta mqabbla mal- plaċebo (95% CI:
1.6 mm, 3.5 mm) [p < 0.0001].
1. 6 mm, 3. 5 mm) [p < 0. 0001].
Days of disability Aclasta significantly reduced the mean days of limited activity and the days of bed rest due to back pain by 17.9 days and 11.3 days respectively compared to placebo and significantly reduced the mean days of limited activity and the days of bed rest due to fractures by 2.9 days and 0.5 days respectively compared to placebo (all p < 0.01).
Jiem ta ’ diżabilità Aclasta naqqas b’ mod sinifikanti l- medja tal- jiem ta ’ attività limitata u l- jiem ta ’ serħan ġos- sodda minħabba uġigħ tad- dahar b’ 17. 9 jiem u 11. 3 jiem rispettivament meta mqabbla mal- plaċebo u naqqas b’ mod sinifikanti l- medja ta ’ ġranet ta ’ attività limitata u l- ġranet ta ’ serħan ġos- sodda minħabba fratturi b’ 2. 9 jiem u 0. 5 jiem rispettivament meta mqabbla mal- plaċebo (kollha p < 0. 01).
Clinical efficacy in the treatment of osteoporosis in patients at increased risk of fracture after a recent hip fracture (RFT) The incidence of clinical fractures, including vertebral, non-vertebral and hip fractures, was evaluated in 2,127 men and women aged 50-95 years (mean age 74.5 years) with a recent (within 90 days) low- trauma hip fracture who were followed for an average of 2 years on study medication.
L- effikaċja klinika fil- kura ta ’ l- osteoporożi f’ pazjenti li għandhom riskju akbar ta ’ ksur wara ksur riċenti fil- ġenbejn (RFT) L- inċidenza tal- ksur kliniku, inkluż ksur ta ’ l- irkiekel, ksur mhux ta ’ l- irkiekel u ksur tal- ġenbejn, ġiet evalwata f’ 2, 127 raġel u mara b’ etajiet ta ’ bejn 50 u 95 sena (età medja ta ’ 74. 5 sena) bi ksur riċenti (fi żmien 90 ġurnata) fil- ġenbejn bi trawma żgħira li kienu segwiti għal perjodu medju ta ’ sentejn fuq il - medikazzjoni ta ’ l- istudju.
Approximately 42% of patients had a femoral neck BMD T-score below -2.5 and approximately 45% of the patients had a femoral neck BMD T-score above -2.5.
Madwar 42% tal- pazjenti kellhom punteġġ- T BMD għall- għonq tal- femori taħt - 2. 5 u madwar 45% tal- pazjenti kellhom punteġġ- T BMD għall- għonq tal- femori ’ l fuq minn - 2. 5.
Aclasta was administered once a year, until at least 211 patients in the study population had confirmed clinical fractures.
Aclasta ngħatat darba fis- sena, sakemm mill- anqas 211- il pazjent fl- istudju kellhom fratturi kliniċi kkonfermati.
Vitamin D levels were not routinely measured but a loading dose of vitamin D (50,000 to 125,000 IU orally or via the intramuscular route) was given to the majority of patients 2 weeks prior to infusion.
Il- livelli tal- vitamina D ma ġewx imkejla b’ mod regolari iżda ngħatat loading dose ta ’ vitamina D (50, 000 sa 125, 000 IU mill- ħalq jew minn ġol- muskoli) lill- biċċa l- kbira tal- pazjenti ġimagħtejn qabel ma ngħataw l- infużjoni.
All participants received 1,000 to 1,500 mg of elemental calcium plus 800 to 1,200 IU of vitamin D supplementation per day.
Il- parteċipanti kollha rċevew 1, 000 sa 1, 500 mg ta ’ kalċju bħala element flimkien ma ’ 800 sa 1, 200 IU ta ’ supplement ta ’ vitamina D kuljum.
Ninety-five percent of the patients received their infusion two or more weeks after the hip fracture repair and the median timing of infusion was approximately six weeks after the hip fracture repair.
Ħamsa u disgħin fil- mija tal- pazjenti rċievew l- infużjoni ġimgħatejn jew aktar wara li fieqet il- frattura u ż- żmien medju ta ’ meta ingħatat l- infużjoni kien madwar sitt ġimgħat wara li fieqet il- frattura.
The primary efficacy variable was the incidence of clinical fractures over the duration of the study.
Il- varjabbli prinċipali ta ’ l- effikaċja kienet l- inċidenza ta ’ fratturi kliniċi tul il- perjodu ta ’ l- istudju.
Effect on all clinical fractures The incidence rates of key clinical fracture variables are presented in Table 4.
9 Effetti fuq kull ksur kliniku Ir- rati ta ’ l- inċidenzi tal- varjabbli kliniċi tal- fratturi ewlenin qed jintwerew f’ Tabella 4.
Between treatment comparisons of the incidence of key clinical fracture variables
Tqabbil bejn kura u oħra tal- varjabbli kliniċi tal- fratturi ewlenin
Aclasta Placebo Absolute reduction (N=1,065) (N=1,062) in fracture event
Aclasta Plaċebo Tnaqqis assolut fir - (N=1, 062) rata tal- każijiet ta ’ (N=1, 065)
Relative risk reduction in
Tnaqqis relattiv fir - riskju ta ’ l -
event rate event rate (%) (%)
rata tal- każ frattura% rata tal- każ
rate% (CI)
(%) (%) (CI)
fracture incidence% (CI)
frattura% (CI)
Any clinical fracture (1) Clinical vertebral fracture (2) Non-vertebral fracture (1) *p-value < 0.05, **p-value < 0.01
Kwalunkwe frattura klinika (1) Frattura klinika fl- irkiekel (2) Frattura mhux fl- irkiekel (1) * valur- p < 0. 05, ** valur- p < 0. 01
8.6 13.9 1.7 3.8 7.6 10.7
8. 6 1. 7 7. 6
5.3 2.1 3.1
13. 9 3. 8 10. 7
(2.3, 8.3) (0.5, 3.7) (0.3, 5.9)
5. 3 (2. 3, 8. 3) 2. 1 (0. 5, 3. 7) 3. 1 (0. 3, 5. 9)
(1) Excluding finger, toe and facial fractures (2) Including clinical thoracic and clinical lumbar vertebral fractures
(1) Minbarra fratturi fis- swaba ta ’ l- idejn, saqajn u fratturi fil- wiċċ (2) Inklużi fratturi kliniċi fl- irkiekel fit- toraċi u dawk kliniċi fil- lumbari
The study was not designed to measure significant differences in hip fracture, but a trend was seen towards reduction in new hip fractures.
L- istudju ma kienx imfassal sabiex jitkejjlu d- differenzi sinifikanti bejn il- fratturi fil- ġenbejn, iżda kien hemm tendenza ta ’ tnaqqis fi fratturi ġodda tal- ġenbejn.
All cause mortality was 10% (101 patients) in the Aclasta-treated group compared to 13% (141 patients) in the placebo group.
Il- mortalità mill- kawżi kollha kienet 10% (101 pazjent) fil- grupp li ngħata kura b’ Aclasta meta mqabbel ma ’ 13% (141 pazjent) fil- grupp li ħa l- plaċebo.
This corresponds to a 28% reduction in the risk of all cause mortality (p=0.01).
Dan jikkorrispondi għal tnaqqis ta ’ 28% fir - riskju ta ’ mortalità mill- kawżi kollha (p=0. 01).
The incidence of delayed hip fracture healing was comparable between Aclasta (34 [3.2%]) and placebo (29 [2.7%]).
L- inċidenza ta ’ dewmien fil- fejqan ta ’ fratturi fil- ġenbejn kienet komparabbli bejn Aclasta (34 [3. 2%]) u l- plaċebo (29 [2. 7%]).
Effect on bone mineral density (BMD) In the HORIZON-RFT study Aclasta treatment significantly increased BMD at the total hip and femoral neck relative to treatment with placebo at all timepoints.
L- effett fuq id- densità minerali ta ’ l- għadam (BMD) Fl- istudju HORIZON- RFT, il- kura b’ Aclasta żiedet b’ mod sinifikanti l- BMD fit- toal tal- ġenbejn u fl - għonq femorali meta mqabbel mal- kura bi plaċebo fil- punti kollha taż- żmien.
Treatment with Aclasta resulted in an increase in BMD of 5.4% at the total hip and 4.3% at the femoral neck over 24 months as compared to placebo.
Il- kura b’ Aclasta rriżultat f’ żieda fil- BMD ta ’ 5. 4% fil- ġenb totali u ta ’ 4. 3% fl- għonq femorali fuq perjodu ta ’ 24 xahar meta mqabbel mal- plaċebo.
Clinical efficacy in men In the HORIZON-RFT study 508 men were randomised into the study and 185 patients had BMD assessed at 24 months.
L- effikaċja klinika fl- irġiel Fl- istudju HORIZON- RFT, 508 irġiel ġew randomised fl- istudju u 185 pazjent kellhom il- BMD tagħhom imkejjel wara 24 xahar.
At 24 months a similar significant increase of 3.6% in total hip BMD was observed for patients treated with Aclasta as compared to the effects observed in post-menopausal women in the HORIZON-PFT study.
Wara 24 xahar kienet osservata żieda sinifikanti simili ta ’ 3. 6% fil - BMD tal- ġenb kollu għall- pazjenti kkurati b’ Aclasta, meta mqabbel ma ’ l- effetti osservati f’ nisa ta ’ wara l- menopawsa fl- istudju HORIZON- PFT.
The study was not powered to show a reduction in clinical fractures in men; the incidence of clinical fractures was 7.5% in men treated with Aclasta versus 8.7% for placebo.
L- istudju ma kienx potenzjat biex juri tnaqqis fil - fratturi kliniċi fl- irġiel; l- inċidenza ta ’ fratturi kliniċi f’ irġiel ikkurati b’ Aclasta kienet 7. 5% kontra 8. 7% għall- plaċebo.
In another study in men (study CZOL446M2308) an annual infusion of Aclasta was non-inferior to weekly alendronate for the percentage change in lumbar spine BMD at month 24 relative to baseline.
Fi studju ieħor fuq l- irġiel (studju CZOL446M2308), infużjoni darba f’ sena ta ’ Aclasta ma kinetx inferjuri għal alendronate kull ġimgħa għall- bidla medja fil- BMD tal- lumbar spine wara 24 xahar meta mqabbel mal- linja bażi.
Clinical efficacy in the treatment of Paget’ s disease of the bone Aclasta was studied in male and female patients aged above 30 years with primarily mild to moderate Paget’ s disease of the bone (median serum alkaline phosphatase level 2.6– 3.0 times the upper limit of the age-specific normal reference range at the time of study entry) confirmed by radiographic evidence.
Effikaċja klinika fil- kura tal- Marda ta ’ Paget ta ’ l- għadam Aclasta kienet studjata f’ pazjenti rġiel u nisa ta ’ etajiet ‘ l fuq minn 30 sena li kellhom primarjament marda ta ’ Paget ta ’ l- għadam minn ħafifa sa moderata (il- medja tal- livell ta ’ alkaline phosphatase fis - serum kienet 2. 6- 3. 0 darbiet l- ogħla limitu tal- medda tar- referenza normali skond l- età fil- ħin li ddaħħlu għall- istudju) konfermata b’ evidenza radjugrafika.
The efficacy of one infusion of 5 mg zoledronic acid versus daily doses of 30 mg risedronate for 2 months was demonstrated in two 6-month comparative trials.
L- effikaċja ta ’ infużjoni waħda ta ’ 5 mg zoledronic acid kontra d- dożi kuljum ta ’ 30 mg risedronate għal xahrejn intweriet f’ żewġ provi kumparattivi li damu 6 xhur.
In the pooled results, a similar decrease in pain severity and pain interference scores relative to baseline were observed over 6 months for Aclasta and risedronate.
Aclasta wriet rati ta ’ respons u ta ’ treġġih lura għan- normal tas- serum alkaline phosphatase (SAP) ta ’ 96% (169/ 176) u 89% (156/ 176) mqabbla ma ’ 74% (127/ 171) u 58% (99/ 171) għal risedronate (kollha kellhom p < 0. 001).
10 Patients who were classified as responders at the end of the 6 month core study were eligible to enter an extended follow-up period.
10 Fir- riżultati magħqudin flimkien, tnaqqis simili fis- severità ta ’ l- uġigħ u fil- punteġġi ta ’ interferenza ta ’ l- uġigħ meta mqabbel mal- linja bażi kienu osservati fuq 6 xhur għal Aclasta u risedronate.
Of the 143 Aclasta-treated patients and 107 risedronate-treated patients who entered an extended observation study, after a median duration of follow-up of 18 months from time of dosing, 141 Aclasta-treated patients maintained their therapeutic response compared to 71 risedronate-treated patients.
Mill- 143 pazjent kurati b’ Aclasta u 107 pazjenti kurati b’ risedronate li ddaħħlu fl- istudju estiż ta ’ osservazzjoni, wara perijodu medjan ta ’ follow- up ta ’ 18- il xhar minn meta ngħataw id- dużaggi, 141 pazjenti kurati b’ Aclasta żammew ir - respons terapewtiku tagħhom imqabbla ma ’ 71 pazjent kurati b’ risedronate.
This corresponds to a 96% reduction of risk of relapse in Aclasta versus risedronate-treated patients.
Dan jikkorrispondi għal tnaqqis ta ’ 96% fir- riskju li tirkadi b’ Aclasta mqabbel ma ’ pazjenti kkurati b’ residronate.
Bone histology was evaluated in 7 patients with Paget’ s disease 6 months after treatment with 5 mg zoledronic acid.
L- istoloġija ta ’ l- għadam kienet eżaminata f’ 7 pazjenti bil- marda ta ’ Paget 6 xhur wara kura b’ 5 mg zoledronic acid.
Bone biopsy results showed bone of normal quality with no evidence of impaired bone remodelling and no evidence of mineralisation defects.
Riżultati ta ’ bijopsiji ta ’ l- għadam urew għadam ta ’ kwalità normali mingħajr ebda ħjiel ta ’ indeboliment fir- rimudellar ta ’ l- għadam u ebda ħjiel ta ’ difetti tal- mineralizzazzjoni.
These results were consistent with biochemical marker evidence of normalisation of bone turnover.
Dawn ir- riżultati kienu konsistenti ma ’ evidenza b’ marker biokimiku ta ’ tibdil ta ’ l- għadam b’ rata normali.
Single and multiple 5 and 15-minute infusions of 2, 4, 8 and 16 mg zoledronic acid in 64 patients yielded the following pharmacokinetic data, which were found to be dose independent.
Infużjoni waħda jew multipla ta ’ 5 u 15- il minuta ta ’ 2, 4, 8 u 16 mg zoledronic acid f’ 64 pazjent taw it- tagħrif farmakokinetiku li ġej, li nstabu li kienu marbutin mad- doża.
After initiation of the zoledronic acid infusion, plasma concentrations of the active substance increased rapidly, achieving their peak at the end of the infusion period, followed by a rapid decline to < 10% of peak after 4 hours and < 1% of peak after 24 hours, with a subsequent prolonged period of very low concentrations not exceeding 0.1% of peak levels.
Wara li tinbeda l- infużjoni b’ Zoledronic acid, il- konċentrazzjonijiet fil- plażma tas- sustanza attiva jiżdiedu malajr, u jilħqu l- quċċata fl- aħħar tal- perijodu ta ’ l- infużjoni, segwit b’ waqa ’ mgħaġġla għal < 10% tal- quċċata wara 4 sigħat u < 1% tal- quċċata wara 24 siegħa, u wara jkun hemm perijodu twil ta ’ konċentrazzjonijiet baxxi ħafna li ma jaqbżux 0. 1% tal- livelli tal- quċċata.
Intravenously administered zoledronic acid is eliminated by a triphasic process: rapid biphasic disappearance from the systemic circulation, with half-lives of t½α 0.24 and t½β 1.87 hours, followed by a long elimination phase with a terminal elimination half-life of t½γ 146 hours.
Zoledronic acid mogħti ġol- vina jiġi eliminat minn proċess ta ’ tlett fażijiet: l- għejbien mgħaġġel miċ - ċirkolazzjoni sistemika f’ żewġ fażijiet, b’ half- lives ta ’ t½α 0. 24 u t½β 1. 87 sigħat, segwit b’ fażi twila ta ’ eliminazzjoni b’ half- life terminali ta ’ eliminazzjoni ta ’ t½γ 146 siegħa.
There was no accumulation of the active substance in plasma after multiple doses given every 28 days.
Ma kienx hemm akkumulazzjoni tas- sustanza attiva fil- plażma wara dożi multipli li ngħataw kull 28 ġurnata.
The early disposition phases (α and β, with t½ values above) presumably represent rapid uptake into bone and excretion via the kidneys.
Il- fażijiet ta ’ dispożizzjoni bikrin (α and β, bil- valuri t½ t’ hawn fuq) jistgħu jitqiesu li jirrappreżentaw it- teħid mgħaġġel fl- għadam u t- tneħħija permezz tal- kliewi.
Zoledronic acid is not metabolised and is excreted unchanged via the kidney.
Zoledronic acid ma jiġix metabolizzat u jiġi eskretat mingħajr ma jinbidel mill- kliewi.
Over the first 24 hours, 39 ± 16% of the administered dose is recovered in the urine, while the remainder is principally bound to bone tissue.
Fl- ewwel 24 siegħa, 39 ± 16% tad- doża li tingħata tiġi rkuprata fl- awrina, filwaqt li jibqa jkun fil- parti l- kbira mwaħħal mat- tessuti ta ’ l- għadam.
From the bone tissue it is released very slowly back into the systemic circulation and eliminated via the kidney.
Mit- tessuti ta ’ l- għadam, bil- mod ħafna jintreħa lura fiċ - ċirkolazzjoni sistemika u jiġi eliminat minn ġol- kliewi.
The total body clearance is 5.04 ± 2.5 l/ h, independent of dose, and unaffected by gender, age, race or body weight.
It- tneħħija totali mill- ġisem hija 5. 04 ± 2. 5 l/ h, indipendenti mid- doża, u mhux effettwat mis- sess, età, razza jew piż tal- ġisem.
The inter- and intra-subject variation for plasma clearance of zoledronic acid was shown to be 36% and 34%, respectively.
Il- varjazzjoni bejn l - individwi u fl- individwu u għat- tneħħija ta ’ zoledronic acid mill- plażma ntwera li kienet 36% u 34% rispettivament.
Increasing the infusion time from 5 to 15 minutes caused a 30% decrease in zoledronic acid concentration at the end of the infusion, but had no effect on the area under the plasma concentration versus time curve.
Meta l- ħin ta ’ l- infużjoni kien imtawwal minn 5 għall- 15- il minuta, il- konċentrazzjoni ta ’ Zoledronic acid naqset b’ 30% fl- aħħar ta ’ l- infużjoni, iżda ma kellha l- ebda effett fuq il- kurva ta ’ l - erja taħt il- konċentrazzjoni tal- plażma kontra l- ħin.
No specific drug-drug interaction studies have been conducted with zoledronic acid.
Ma sarux studji speċifiċi dwar nuqqas ta ’ qbil bejn il- mediċini b’ zoledronic acid.