qanastek/EMEA-V3 huggingface dataset:
Physicians should be alert to signs or symptoms signalling a possible oesophageal reaction during therapy, and patients should be instructed to discontinue Bondronat and seek medical attention if they develop symptoms of oesophageal irritation such as new or worsening dysphagia, pain on swallowing, retrosternal pain, or heartburn.
It- tobba għandhom ikunu attenti għas- sinjali jew sintomi li jindikaw il- possibilità ta ’ reazzjoni oseofaġali matul it- terapija, u l- pazjenti għandhom ikunu mħarrġa biex iwaqqfu Bondronat u jfittxu l - attenzjoni medika jekk jiżviluppaw sintomi ta ’ irritazzjoni oseofaġali bħal disfaġja ġdida jew li taqleb għall- agħar, uġigħ meta tibla, uġigħ retrosternali, jew ħruq fl- istonku.
Since NSAIDS are associated with gastrointestinal irritation, caution should be taken during concomitant oral medication with Bondronat.
Ladarba - NSAIDS huma assoċjati ma ’ irritazzjoni gastro- intestinali, wieħed irid joqgħod attent meta jieħu dawn il- mediċini flimkien ma ’ Bondronat.
Clinical studies have not shown any evidence of deterioration in renal function with long term Bondronat therapy.
Studji kliniċi ma wrewx evidenza ta ’ taqlib għall- agħar fil- funzjoni renali b’ terapija fit- tul ta ’ Bondronat.
Nevertheless, according to clinical assessment of the individual patient, it is recommended that renal function, serum calcium, phosphate and magnesium should be monitored in patients treated with Bondronat.
Madankollu, skond l- eżami kliniku tal- pazjent individwali, huwa rakkomandat li jsir monitoraġġ tal- funzjoni renali, kalċju, fosfat u manjesju fis- serum f’ pazjenti li jiġu trattati b’ Bondronat.
Bondronat tablets contain lactose and should not be administered to patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
Il- pilloli Bondronat għandhom lactose u m’ għandhomx jingħataw lill- pazjenti bi problemi ereditarji rari ta ’ intolleranza għall- galattosju, nuqqas ta ’ Lapp lactase u malassorbiment ta ’ glukożju - galacttosju.
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.
Ħafna minn dawn il- pazjenti kienu qegħdin jirċievu l -
Many of these patients were also receiving chemotherapy and corticosteroids.
15 kemjoterapija u kortikosterojdi.
Osteonecrosis of the jaw has also been reported in patients with osteoporosis receiving oral bisphosphonates.
L- osteonekrożi tax- xedaq ġie rapportat f’ pazjenti li jsoffru minn osteoporożi waqt li jirċievu bisfosfonati orali.
15 While on treatment, these patients should avoid invasive dental procedures if possible.
Jekk ikun possibbli dawn il- pazjenti għandhom jevitaw proċeduri dentali invażivi waqt it- trattment.
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 jinħteġilhom proċeduri dentali, ma hemm l- ebda tagħrif disponibbli li jissuġerixxi jekk it- twaqqif tat- trattament bil- bisfosfonati tnaqqasx ir- riskju ta ’ l- osteonekrożi tax- xedaq.
Drug-Food Interactions Products containing calcium and other multivalent cations (such as aluminium, magnesium, iron), including milk and food, are likely to interfere with absorption of Bondronat tablets.
Interazzjonijiet bejn Mediċina u Ikel Prodotti li fihom l- kalċju u ketajins mutivalenti (bħal aluminju, manjesju, ħadid), inkluż il- ħalib u l - ikel, x’ aktarx jinterferixxu fl- assorbiment tal- pilloli Bondronat.
Therefore, with such products, including food, intake must be delayed at least 30 minutes following oral administration.
Għalhekk, dawn il- prodotti, inkluż l - ikel, ma jistgħux jittieħdu sa mill- inqas 30 minuta wara l- amministrazzjoni orali.
Bioavailability was reduced by approximately 75% when Bondronat tablets were administered 2 hours after a standard meal.
Il- biodisponibiltà ġiet mnaqqsa b’ bejn wieħed u ieħor b’ 75% meta l- pilloli Bondronat ġew mogħtija sagħtejn wara ikla normali.
Therefore, it is recommended that the tablets should be taken after an overnight fast (at least 6 hours) and fasting should continue for at least 30 minutes after the dose has been taken (see section 4.2).
Għalhekk, huwa rakkomandat li l- pilloli jittieħdu wara s- sawma ta ’ bil- lejl (mill- inqas 6 sigħat) u s- sawma għandha titkompla għal mill- inqas 30 minuta wara li tkun ittieħdet id - doża (ara sezzjoni 4. 2).
Drug-Drug Interactions When co-administered with melphalan/ prednisolone in patients with multiple myeloma, no interaction was observed.
Interazzjoni bejn Mediċina u Mediċina Meta mogħtija flimkien ma ’ melphalan/ prednisolone f’ pazjenti b’ mijeloma multipla, l- ebda interazzjoni ma ġiet osservata.
In healthy male volunteers and postmenopausal women, intravenous ranitidine caused an increase in ibandronic acid bioavailability of about 20% (which is within the normal variability of the bioavailability of ibandronic acid), probably as a result of reduced gastric acidity.
F’ voluntiera rġiel b’ saħħithom u nisa li għaddew mill- menopawża, ranitidina ġol- vina ġab żieda fil - biodisponibiltà ta ’ ibandronic acid ta ’ bejn wieħed u ieħor 20% (li hi fil- varjabbilità normali tal - biodisponibiltà ta ’ ibandronic acid), probabilment bħala riżultat ta ’ aċidità gastrika mnaqqsa.
However, no dosage adjustment is required when Bondronat is administered with H2-antagonists or other drugs that increase gastric pH.
Madankollu, l- ebda aġġustament fid- doża mhux meħtieġ meta Bondronat jiġi amministrat ma ’ antagonisti għall- H2 jew mediċini oħra li jgħollu l- pH gastriku.
In relation to disposition, no drug interactions of clinical significance are likely.
B’ relazzjoni mad- disposizzjoni, x’ aktarx li m’ hemm l- ebda interazzjoni ta ’ sinifikat kliniku.
The secretory pathway does not appear to include known acidic or basic transport systems involved in the excretion of other active substances.
Il- passaġġ li jnixxih ma jidhirx li jinkludi sistemi ta ’ trasport aċidużi jew alkalini li jinvolvu t- tneħħija ta ’ sustanzi attivi oħra.
Plasma protein binding is low at therapeutic concentrations and ibandronic acid is therefore unlikely to displace other active substances.
Twaħħil mal- proteini fil- plażma hija baxxa f’ konċentrazzjonijiet terapewtiċi u ibandronic acid x’ aktarx ma jissostitwix sustanzi attivi oħra.
4.6 Pregnancy and lactation
16 4. 6 Tqala u Treddigħ
16 It is not known whether ibandronic acid is excreted in human milk.
Għadu mhux magħruf jekk ibandronic acid jitneħħix fil- ħalib tal- bnedmin.
The safety profile of Bondronat is derived from controlled clinical trials in the approved indication and after the oral administration of Bondronat at the recommended dose.
Il- profil tas- sigurtà ta ’ Bondronat ġej mill- istudji kliniċi kontrollati fl- indikazzjoni approvata u wara l - amministrazzjoni orali ta ’ Bondronat fid- doża rakkomandata.
In the pooled database from the 2 pivotal phase III trials (286 patients treated with Bondronat 50 mg), the proportion of patients who experienced an adverse reaction with a possible or probable relationship to Bondronat was 27%.
Fil- bażi tat- tagħrif miġbur flimkien taż- żewġ studji f’ fażi III (286 pazjent trattati b’ Bondronat 50 mg), il- proporzjon ta ’ pazjenti li ġarrab effetti mhux mixtieqa b’ relazzjoni possibli jew probabbli ma’ Bondronat kien ta ’ 27%.
Adverse reactions are ranked under heading of frequency, the most frequent first, using the following convention: very common (≥ 10%), common (≥ 1% and < 10%), uncommon (≥ 0.1% and < 1%), rare (≥ 0.01% and < 0.1%), very rare (≤ 0.01%).
Reazzjonijiet avversi huma kklassifikati taħt it- titlu tal- frekwenza, l- aktar frekwenti l- ewwel, bil - konvenzjoni li ġejja: komuni ħafna (≥ 10%), komuni (≥ 1% u < 10%), mhux komuni (≥0. 1% u < 1%), rari (≥ 0. 01% u < 0. 1%), rari ħafna (≤ 0. 01%).
Table 1 lists common adverse reactions from the pooled phase III trials.
Tabella 1 turi reazzjonijiet avversi miġbura mill- istudji kliniċi f’ fażi III.
Adverse reactions that are equally frequent in both active and placebo or more frequent in placebo-treated patients are excluded.
Reazzjonijiet avversi li huma frekwenti ndaqs kemm fis- sustanza attiva kif ukoll fil- plaċebo jew aktar frekwenti fil- plaċebo ġew esklużi.
Adverse ReactionsReported Commonly and Greater than Placebo
Reazzjonijiet Avversi Rapportati bi Frekwenza Komuni jew Akbar mill- Plaċebo
Adverse Reaction
Reazzjoni Avversa
Placebo
Plaċebo
p. o. daily
p. o. kuljum
Metabolism and Nutrition Disorders
Mard marbut mal- metaboliżmu u n - nutrizzjoni
(%)
(n=277 pazjent) Numru (%)
(%)
(n=286 pazjent) Numru (%)
Hypocalcaemia Gastrointestinal Disorders
Ipokalċemja Mard Gastro- intestinali
14 (5.1)
14 (5. 1)
27 (9.4)
27 (9. 4)
Dyspepsia Nausea Abdominal Pain Oesophagitis General Disorders
Dispepsja Tqallih Uġigħ addominali Esofaġite Mard Ġenerali
13 (4.7) 4 (1.4) 2 (0.7) 2 (0.7)
13 (4. 7) 4 (1. 4) 2 (0. 7) 2 (0. 7)
20 (7.0) 10 (3.5) 6 (2.1) 6 (2.1)
20 (7. 0) 10 (3. 5) 6 (2. 1) 6 (2. 1)
Asthenia
Astenja
2 (0.7)
2 (0. 7)
4 (1.4)
4 (1. 4)
Adverse drug reactions occurring at a frequency < 1%:
Reazzjonijiet avversi li jiġru b’ frekwenza < 1%:
The following list provides information on adverse drug reactions reported in study MF 4414 and MF 4434 occurring more frequently with Bondronat 50 mg than with placebo:
Il- lista li ġejja tipprovdi informazzjoni fuq reazzjonijiet avversi rrappurtati fl- studji MF 4414 u MF 4434 bi frekwenza akbar b’ Bondronat 50 mg milli bil- plaċebo:
Blood and Lymphatic System Disorders Nervous System Disorders Gastrointestinal Disorders
Mard tad- Demm u tas- Sistema Limfatika Mard tas- sistema nervuża Mard Gastro- intestinali
anaemia paraesthesia, dysgeusia (taste perversion) haemorrage, duodenal ulcer, gastritis, dysphagia, abdominal pain, dry mouth
anemija parastesja, disgewsja (togħma ħażina) emorraġija, ulċera duodenali, 17 gastrite, disfaġja, uġigħ abdominali, ħalq xott
Skin and Subcutaneous Tissue Disorders Renal and Urinary Disorders General Disorders:
Mard tal- ġilda u tat- tessuti ta ’ taħt il- ġilda Mard tal- kliewi u tas- sistema urinarja Mard Ġenerali:
Investigations
Investigazzjonijiet
pruritus azotaemia (uraemia) chest pain, influenza-like illness, malaise, pain Blood parathyroid hormone increased
ħakk ażotemja (uremja) uġigħ fis- sider, mard bħall- influwenza, telqa, uġigħ Żieda fl- ormon tal- paratirojde fid- demm
17 Osteonecrosis of the jaw has been reported in patients treated by bisphosphonates.
L- osteonekrożi tax- xedaq kien rapportat f’ pazjenti li rċevew kura bil- bisfosfonati.
No case of overdose has been reported.
L- ebda każ ta ’ doża eċċessiva ma ġie rrapurtat.
No specific information is available on the treatment of overdosage with Bondronat.
M’ hemm l- ebda informazzjoni speċifika dwar it- trattament ta ’ doża eċċessiva b’ Bondronat.
However, oral overdosage may result in upper gastrointestinal events, such as upset stomach, heartburn, oesophagitis, gastritis or ulcer.
Madankollu, doża eċċessiva orali tista ’ twassal għal effetti fil- parti gastrointestinali ta ’ fuq, bħal taqlib fl- istonku, ħruq fl- istonku, esofaġite, gastrite jew ulċera.
Milk or antacids should be given to bind Bondronat.
Għandu jingħata l- ħalib jew l- antaċidi biex jingħaqdu ma ’ Bondronat.
Owing to the risk of oesophageal irritation, vomiting should not be induced and the patient should remain fully upright.
Minħabba r- riskju ta ’ irritazzjoni fl- osofagu, rimettar m’ għandux jiġi ndott u l- pazjent għandu jibqa ’ kompletament f’ qagħda wieqfa.
In vivo, ibandronic acid prevents experimentally-induced bone destruction caused by cessation of gonadal function, retinoids, tumours or tumour extracts.
In vivo, l- ibandronic acid jimpedixxi l- qerda ta ’ l- għadam stimolat b’ mod sperimentali u kkawżat bil - waqfien tal- funzjoni tal- gonadi, retinojdi, tumuri jew estratti tat- tumuri.
The inhibition of endogenous bone resorption has also been documented by 45Ca kinetic studies and by the release of radioactive tetracycline previously incorporated into the skeleton.
L- inibizzjoni ta ’ assorbiment endoġenu mill- ġdid ta ’ l- għadam ġie dokumentat ukoll permezz ta ’ studji kinetiċi ta ’ 45Ca u l - liberazzjoni ta ’ tetraċiklina radjuattiva li kienet qabel inkorporata fl- iskeletru.
At doses that were considerably higher than the pharmacologically effective doses, ibandronic acid did not have any effect on bone mineralisation.
F’ dożi li kienu ogħla mhux ħażin minn dożi effettivi farmakoloġiċi, ibandronic acid ma kellu l- ebda effett fuq il- mineraliżżazzjoni ta ’ l- għadam.
Bone resorption due to malignant disease is characterized by excessive bone resorption that is not balanced with appropriate bone formation.
Assorbiment mill- ġdid ta ’ l- għadam ikkawżat minn mard malinn huwa kkaratteriżżat b’ assorbiment eċċessiv ta ’ l- għadam li mhuwiex ibbilanċjat minn formazzjoni ta ’ l- għadam adegwat.
Clinical studies in patients with breast cancer and bone metastases have shown that there is a dose dependent inhibitory effect on bone osteolysis, expressed by markers of bone resorption, and a dose dependent effect on skeletal events.
Studji kliniċi f’ pazjenti b’ kanċer tas- sider u metastasi fl- għadam urew li hemm effett inibitorju dipendenti mid- doża fuq l- osteoliżi ta ’ l- għadam, espress b’ markaturi ta ’ assorbiment mill- ġdid ta ’ l - għadam, u effett dipendenti mid- doża fuq episodji skeletriċi.
Prevention of skeletal events in patients with breast cancer and bone metastases with Bondronat 50 mg tablets was assessed in two randomized placebo controlled phase III trials with duration of 96 weeks.
Il- prevenzjoni ta ’ episodji skeletriċi f’ pazjenti b’ kanċer tas- sider u metastasi fl- għadam bil- pilloli Bondronat 50 mg ġiet eżaminata f’ żewġ studji ta’ fażi III ikkontrollati bil- plaċebo u magħżula bl - addoċċ b’ tul ta ’ terapija ta ’ 96 ġimgħa.
Female patients with breast cancer and radiologically confirmed bone metastases were randomised to receive placebo (277 patients) or 50 mg Bondronat (287 patients).
Pazjenti femminili b’ kanċer tas- sider u metastasi fl- għadam ikkonfermat radjoloġikalment ġew randomised biex jirċievu plaċebo (277 pazjent) jew 50 mg Bondronat (287 pazjent).
The results from these trials are summarised below.
Ir- riżultati minn dawn l- istudji huma miġbura fil- qosor hawn taħt.
Primary Efficacy Endpoints The primary endpoint of the trials was the skeletal morbidity period rate (SMPR).
18 L- Miri Primarji ta ’ l- Effikaċja L- mira primarja ta ’ l- istudji kienet ir- rata tal- perijodu tal- morbidità skeletrika (SMPR).
This was a composite endpoint which had the following skeletal related events (SREs) as sub-components:
Din kienet mira finali komposta li kellha l- episodji relatati ma ’ l- iskeletru (SREs) li ġejjin bħala l- komponenti tagħha:
- radiotherapy to bone for treatment of fractures/ impending fractures
- radjuterapija fl- għadam għat- trattament ta ’ fratturi/ fratturi imminenti
- surgery to bone for treatment of fractures
- kirurġija fl- għadam għat- trattament ta ’ fratturi
- vertebral fractures
- fratturi vertebrali
- non-vertebral fractures
- fratturi mhux vertebrali
18 The analysis of the SMPR was time-adjusted and considered that one or more events occurring in a single 12 week period could be potentially related.
L- analisi tal- SMPR kienet aġġustata mal- ħin u kkunsidrat li wieħed jew aktar effetti f’ perijodu singolu ta ’ 12- il ġimgħa seta ’ kien potenzjalment relatat.
Multiple events were therefore, counted only once in any given 12 week period for the purposes of the analysis.
Effetti multipli kienu għalhekk, magħduda biss darba fi kwalunkwe perijodu ta ’ 12- il ġimgħa għall- iskopijiet ta ’ din l- analiżi.
Pooled data from these studies demonstrated a significant advantage for Bondronat 50 mg p. o. over placebo in the reduction in SREs measured by the SMPR (p=0.041).
Tagħrif miġbura minn dawn l - istudji uriet vantaġġ sinifikanti għal Bondronat 50 mg p. o. fuq il- plaċebo fit- tnaqqis ta ’ SREs imkejla permezz tal- SMPR (p=0. 041).
There was also a 38% reduction in the risk of developing an SRE for Bondronat treated patients when compared with placebo (relative risk 0.62, p=0.003).
Kien hemm ukoll tnaqqis ta ’ 38% fir- riskju ta ’ l- iżvilupp ta ’ SRE għall- pazjenti trattati b’ Bondronat meta mqabbla mal- plaċebo (riskju relattiv 0. 62, p=0. 003).
Efficacy results are summarised in Table 2.
Tabella 2
Efficacy Results (Breast Cancer Patients with Metastatic Bone Disease)
Riżultati ta ’ l- Effikaċja (Pazjenti b’ Kanċer tas- Sider b’ Mard Metastatiku ta ’ l - Għadam)
All Skeletal Related Events (SREs) Placebo Bondronat 50 mg p-value n=277 n=287
Episodji Kollha Relatati ma ’ l- Iskeletru (SREs) Plaċebo Bondronat 50 mg Valur- p n=277 n=287
p=0.041
p=0. 041
SRE relative risk
SRE riskju relattiv
p=0.003
p=0. 003
Secondary Efficacy Endpoints A statistically significant improvement in bone pain score was shown for Bondronat 50 mg compared to placebo.
L- Miri Sekondarji ta ’ l- Effikaċja Titjib għall- aħjar fil- marka ta ’ l- uġigħ fl- għadam statistikament sinifikanti intwera għal Bondronat 50 mg meta mqabbel mal- plaċebo.
The pain reduction was consistently below baseline throughout the entire study and accompanied by a significantly reduced use of analgesics compared to placebo.
It- tnaqqis fl- uġigħ kien b’ mod konformi taħt il- linja bażika matul l - istudju kollu u kien akkumpanjat b’ użu mnaqqas sinifikattiv ta ’ analġesiċi meta mqabbel mal- plaċebo.
The deterioration in Quality of Life and WHO performance status was significantly less in Bondronat treated patients compared with placebo.
It- taqlib għall- agħar fil- Kwalità tal- Ħajja u l- istat ta’ mġieba tal- WHO kienu anqas b’ mod sinifikanti f’ pazjenti trattati b’ Bondronat meta mqabbla mal- plaċebo.
Urinary concentrations of the bone resorption marker CTx (C-terminal telopeptide released from Type I collagen) were significantly reduced in the Bondronat group compared to placebo.
Konċentrazzjonijiet urinarji tal- markatur ta ’ l- assorbiment mill- ġdid ta ’ l- għadam CTx (Cterminal- telopeptide rilaxxata mill- collagen Tip I) kienu mnaqqsa b’ mod sinifikattiv fil- grupp ta ’ Bondronat meta mqabbla mal- plaċebo.
This reduction in urinary CTx levels was significantly correlated with the primary efficacy endpoint SMPR (Kendall-tau-b (p < 0.001)).
Dan it- tnaqqis fil - livelli urinarji ta ’ CTx kien ikkorrelat b’ mod sinifikattiv ma ’ l- mira primarja ta ’ l- effikaċja SMPR (Kendall- tau- b (p < 0. 001)).
A tabular summary of the secondary efficacy results is presented in Table 3.
Tabella 3
Cancer Patients with Metastatic Bone
Riżultati Sekondarji ta ’ l- Effikaċja (Pazjenti b’ Kanċer tas- Sider b’ Mard Metastatiku ta ’ l- Għadam)
Bondronat 50 mg p-value n=287
Plaċebo Bondronat 50 mg Valur- p n=277 n=287
Bone pain *
Uġigħ fl- għadam *
-0.10 p=0.001
p=0. 001
p=0.019
p=0. 019
-26.8
- 26. 8
-8.3
- 8. 3
p=0.032
p=0. 032
WHO performance score *
Marka ta ’ l- imġieba skond il- WHO *
0.33
0. 33
p=0.008
p=0. 008
Urinary CTx **
CTx urinarju **
10.95
10. 95
-77.32
- 77. 32
p=0.001
p=0. 001
* Mean change from baseline to last assessment. ** Median change from baseline to last assessment
* Bidla medja mill- linja bażika sa l- aħħar eżami ** Bidla medjana mill- linja bażika sa l- aħħar eżami
Absorption The absorption of ibandronic acid in the upper gastrointestinal tract is rapid after oral administration.
Assorbiment L- assorbiment ta ’ ibandronic acid fil- passaġġ gastro- intestinali ta ’ fuq huwa mgħaġġel wara amministrazzjoni orali.
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%.
L- ogħla konċentrazzjonijiet osservati fil- plażma ġew milħuqa f’ nofs siegħa sa sagħtejn (ħin medjan ta ’ siegħa) fi stat sajjem u l- biodisponibiltà kienet ta ’ 0. 6%.
The extent of absorption is impaired when taken together with food or beverages (other than plain water).
Il- medda ta ’ l - assorbiment hija mfixkla meta jittieħed flimkien ma ’ ikel jew xorb (ħlief għall- ilma naturali).
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 hija mnaqqsa b’ 90% meta ibandronic acid jingħata ma ’ kolazzjon normali meta mqabbla mal- biodisponibiltà f’ pazjenti sajmin.
19 bioavailability is approximately 30%.
Meta jittieħed 30 minuta qabel ikla, it- tnaqqis fil - biodisponibiltà hija ta ’ bejn wieħed u ieħor 30%.
There is no meaningful reduction in bioavailability provided ibandronic acid is taken 60 minutes before a meal.
M’ hemmx tnaqqis sinifikattiv fil- biodisponibiltà sakemm ibandronic acid jittieħed 60 minuta qabel ikla.
Bioavailability was reduced by approximately 75% when Bondronat tablets were administered 2 hours after a standard meal.
Il- biodisponibiltà kienet imnaqqsa b’ bejn wieħed u ieħor 75% meta l- pilloli ta ’ Bondronat ingħataw sagħtejn wara ikla normali.
Therefore, it is recommended that the tablets should be taken after an overnight fast (minimum 6 hours) and fasting should continue for at least 30 minutes after the dose has been taken (see Section 4.2).
Għalhekk, huwa rakkomandat li l- pilloli jittieħdu wara sawma ta ’ bil- lejl (minimu ta ’ 6 sigħat) u s- sawma trid titkompla għal mill- inqas 30 minuta wara li tkun ittieħdet id- doża (ara Sezzjoni 4. 2).
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 apparenti tad- distribuzzjoni terminali huwa mill- inqas 90 l u l- ammont tad- doża li jilħaq l- għadam huwa stmat li huwa 40- 50% tad- doża fiċ- ċirkolazzjoni.
Protein binding in human plasma is approximately 87% at therapeutic concentrations, and thus drug-drug interaction due to displacement is unlikely.
L - għaqda mal- proteini fil- plażma umana hija bejn wieħed u ieħor 87% f’ konċentrazzjonijiet terapewtiċi, u għalhekk interazzjoni bejn mediċini minħabba spostament mhuwiex probabbli.
Elimination The absorbed fraction of ibandronic acid is removed from the circulation via bone absorption (estimated to be 40-50%) and the remainder is eliminated unchanged by the kidney.
Eliminazzjoni Il- frazzjoni ta ’ ibandronic acid assorbit jitneħħa miċ- ċirkolazzjoni permezz ta ’ assorbiment mill - għadam (kalkolat li hu 40- 50%) u l- kumplament jiġi eliminat kif inhu permezz tal- kliewi.
The unabsorbed fraction of ibandronic acid is eliminated unchanged in the faeces.
Il- frazzjoni ta ’ ibandronic acid mhux assorbit jiġi eliminat kif inhu fl- ippurgar.
The range of observed apparent half-lives is broad and dependent on dose and assay sensitivity, but the apparent terminal half-life is generally in the range of 10-60 hours.
Il- firxa osservata ta ’ half- lifes apparenti hija wiesa u tiddependi fuq id- doża u s- sensittività ta ’ l - analiżi, imma l- half- life apparenti terminali ġeneralment taqa ’ fil- firxa ta ’ bejn 10- 60 siegħa.
However, early plasma levels fall quickly, reaching 10% of peak values within 3 and 8 hours after intravenous or oral administration respectively.
Madankollu, livelli bikrin fil- plażma jaqgħu malajr, u jilħqu 10% tal- livelli massimi fi 3 u 8 sigħat wara amministrazzjoni ġol- vina jew orali rispettivament.
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 f’ saħħithom li għaddew mill- menopawża) tagħmel għal 50 - 60% mit- tneħħija totali u hija relatata mat- tneħħija tal- kreatinina.
The difference between the apparent total and renal clearances is considered to reflect the uptake by bone.
Id- differenza bejn it- tneħħija apparenti totali u dik mill- kliewi hija kkunsidrata li tirrifletti l- assorbiment mill- għadam.
Pharmacokinetics in Special Populations
Tagħrif Farmakokinetiku f’ Popolazzjonijiet Speċjali
Race There is no evidence for clinically relevant interethnic differences between Asians and Caucasians in ibandronic acid disposition.
Razza M’ hemmx evidenza għal differenzi interetniċi ta ’ rilevanza klinika bejn l- Ażjatiċi u l- Kawkasi fid - disposizzjoni ta ’ l- ibandronic acid.
Patients with renal impairment Renal clearance of ibandronic acid in patients with various degrees of renal impairment is linearly related to creatinine clearance (CLcr).
20 It- tneħħija ta ’ ibandronic acid mill- kliewi f’ pazjenti b’ livelli varji ta ’ indeboliment tal- kliewi hija relatata b’ mod lineari mat- tneħħija tal- kreatinina (CLcr).
No dosage adjustment is necessary for patients with mild or moderate renal impairment (CLcr > 30 ml/ min).
L- ebda aġġustament fid- doża ma huwa neċessarju għall- pazjenti b’ indeboliment tal- kliewi ħafif jew moderat (CLcr ≥ 30 ml/ min).
Subjects with severe renal impairment (CLcr ≤ 30 ml/ min) receiving oral administration of 10 mg ibandronic acid daily for 21 days, had 2-3 fold higher plasma concentrations than subjects with normal renal function.
Pazjenti b’ indeboliment serju tal- kliewi (CLcr ≤ 30 ml/ min) li qed jirċievu doża orali ta ’ 10 mg ibandronic acid kuljum għal 21 ġurnata, kellhom konċentrazzjonijiet ogħla fil- plażma, id- doppju jew it- triplu ta ’ pazjenti bil- kliewi normali.
Total clearance of ibandronic acid was reduced to 44 ml/ min in the subjects with severe renal impairment.
It- tneħħija totali ta ’ ibandronic acid kien imnaqqas għal 44 ml/ min fil - pazjenti b’ indeboliment serju tal- kliewi.
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 impairment.
Wara amministrazzjoni ġol- vina ta ’ 0. 5 mg, it- tneħħija totali, renali u mhux renali naqsu b’ 67%, 77% u 50%, rispettivament, f’ pazjenti b’ indeboliment serju tal - kliewi.
However, there was no reduction in tolerability associated with the increase in exposure.
Madankollu, ma kien hemm l- ebda tnaqqis fit- tollerabbilità assoċjata maż- żieda fl - espożizzjoni.
Reduction of the oral dose to one 50 mg tablet once weekly is recommended in patients with severe renal impairment (CLcr < 30 ml/ min) (see Section 4.2).
Tnaqqis fid- doża orali għal pillola waħda ta ’ 50 mg darba fil- ġimgħa hija rakkomandata f’ pazjenti b’ indeboliment serju tal- kliewi (CLcr < 30 ml/ min) (ara Sezzjoni 4. 2).
The liver has no significant role in the clearance of ibandronic acid since it is not metabolized but is
Pazjenti b’ indeboliment tal- fwied M’ hemm l- ebda tagħrif farmakokinetiku għal ibandronic acid f’ pazjenti li għandhom indeboliment tal - fwied.
20 cleared by renal excretion and by uptake into bone.
Il- fwied m’ għandu l- ebda rwol sinifikanti fit- tneħħija ta ’ ibandronic acid għax ma jiġix metabolizzat imma jitneħħa permezz tal- kliewi u b’ assorbiment fl- għadam.
Elderly In a multivariate analysis, age was not found to be an independent factor of any of the pharmacokinetic parameters studied.
L- anzjani F’ analiżi multivarjata, instab li l- eta ’ mhix fattur indipendenti ta ’ kwalunkwe parametru farmakokinetiku li ġie studjat.
As renal function decreases with age, this is the only factor to take into consideration (see renal impairment section).
Hekk kif il- funzjoni renali tonqos bl- eta ’, dan huwa l- uniku fattur li għandu jiġi kkunsidrat (ara sezzjoni indeboliment tal- kliewi).
Effects in non-clinical studies were observed only at exposures sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.
Fi studji mhux kliniċi ġew osservati effetti biss f’ esposizzjonijiet ħafna aktar eċċessivi mill - esposizzjoni massima umana li tindika ftit rilevanza għall- użu kliniku.
Tests for genotoxicity revealed no evidence of genetic activity for ibandronic acid.
Testijiet għal ġenotossiċità ma urew l- ebda evidenza ta ’ attività ġenetika għalibandronic acid.
No evidence of direct foetal toxicity or teratogenic effects was observed for ibandronic acid in intravenously or orally treated rats and rabbits.
L- ebda evidenza ta ’ tossiċità diretta fuq il- fetu jew effetti teratoġeniċi ma ġew osservati għalibandronic acid fil- firien u fil- fniek trattati ġol- vina jew b’ mod orali.
Adverse effects of ibandronic acid in reproductive toxicity studies in the rat were those expected for this class of drugs (bisphosphonates).
Effetti mhux mixtieqa ta ’ ibandronic acid fi studji ta ’ tossiċità riproduttiva fil- far kienu dawk mistennija għal din il- klassi ta ’ mediċini (bisfosfonati).
Tablet core:
Il- qalba tal- pillola:
Lactose monohydrate Povidone Cellulose, microcrystalline Crospovidone Stearic acid Silica, anhydrous colloidal
Lactose monohydrate Povidone Cellulose, microcrystalline Crospovidone
Tablet coat:
21 Stearic acid Silica, anhydrous colloidal
Hypromellose Titanium dioxide E171 Talc Macrogol 6000
Ir- rita tal- pillola Hypromellose Titanium dioxide E171 Talc Macrogol 6000
Not applicable.
Mhux applikabbli
21 6.4 Special precautions for storage
6. 4 Tagħrif speċjali dwar kif għandu jinħażen
Store in the original package in order to protect from moisture.
Aħżen fil- pakkett oriġinali sabiex tipproteġi mill- umdità.
Bondronat 50 mg film coated tablets are supplied in blisters (aluminium) containing 7 tablets, which are presented as packs containing 28 or 84 tablets.
Il- pilloli miksija b’ rita ta ’ Bondronat 50 mg jiġu fornuti f’ folji( aluminju) ta ’ 7 pilloli, li huma preżentati bħala pakketti li fihom 28 jew 84 pillola.
Roche Registration Limited 6 Falcon Way Shire Park Welwyn Garden City AL7 1TW United Kingdom
Roche Registration Limited 6 Falcon Way 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/.
22 Informazzjoni dettaljata dwar din il- mediċina tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il - mediċini (EMEA) http: // www. emea. europa. eu /.
Bondronat 6 mg Concentrate for solution for infusion
Bondronat 6 mg Konċentrat għal soluzzjoni għall- infużjoni
One vial with 6 ml concentrate for solution for infusion contains 6 mg ibandronic acid, (as 6.75 mg ibandronic acid monosodium salt, monohydrate)
Kunjett wieħed b’ 6 ml konċentrat għal soluzzjoni għall- infużjoni fiha 6 mg ta ’ ibandronic acid, (bħala 6. 75 mg ibandronic acid, monosodium salt, monohydrate)
For infusion, the contents of the vials(s) should only be added to 100 ml isotonic sodium chloride solution or 100 ml 5% glucose solution.
Għall- infużjoni, il- kontenut tal- kunjett( i) għandu jiżdied ma ’ 100 ml soluzzjoni ta ’ isotonic sodium chloride jew 100 ml 5% soluzzjoni ta ’ glucose.
23 the humoral type of hypercalcaemia.
24 ġenerali pazjenti b’ metastażi ostejolitiku fl- għadam jirrikjedu dożi aktar baxxi minn pazjenti b’ iperkalċemja tat- tip umorali.
In most patients with severe hypercalcaemia (albumin-corrected serum calcium* ≥ 3 mmol/ l or ≥ 12 mg/ dl) 4 mg is an adequate single dosage.
Fil- parti l- kbira tal- pazjenti b’ iperkalċemja severa (kalċju fis- serum ikkoreġut bl- albumina * ≥3 mmol/ l jew ≥12 mg/ dl) doża waħda ta '4 mg hija adegwata.
Albumin-corrected Serum calcium (mmol/ l)
Kalċju fis- serum ikkoreġut bl- albumina (mmol/ l)
Or Albumin-corrected Serum calcium (mg/ dl)
Kalċju fis- serum ikkoreġut bl- albumina (mg/ dl)
Patients with renal impairment There is no evidence of a reduction in tolerability associated with an increase in exposure to ibandronate in patients with various degrees of renal impairment.
Pazjenti b’ indeboliment tal -- kliewi Ma hemm l- ebda evidenza ta ’ tnaqqis fit- tollerabilità assoċjata ma ’ żjieda fl- espożizzjoni għal ibandronate f’ pazjenti b’ diversi gradi ta ’ indeboliment renali.
Infusion Volume 2
Dożaġġ / Ħin ta ’ I- infużjoni1
6 mg / 15 minutes
Volum ta ’ l- Infużjoni 2
30 < CLcr < 50 < 30
≥ 50 30 < CLcr < 50 < 30
6 mg / 1 hour 2 mg / 1 hour
6mg / 15 minuta 6mg / 1 siegħa 2mg / 1 siegħa
500 ml 500 ml
100ml 500ml 500ml
Administration every 3 to 4 week 2 0.9% sodium chloride solution or 5% glucose solution
Amministrazzjoni kull 3 sa 4 ġimgħat 2 soluzzjoni ta ’ 0. 9% sodium chloride jew soluzzjoni ta ’ 5% glucose
A 15 minute infusion time has not been studied in cancer patients with CLCr < 50 mL/ min.
Ħin ta ’ l- infużjoni ta ’ 15- il minuta ma ġiex studjat f’ pazjenti tal- kanċer bi CLCr < 50 mL/ min.
Elderly No dose adjustment is required.
25 L- anzjani L- ebda aġġustament fid- doża ma huwa meħtieġ.
24 Children and adolescents Bondronat is not recommended for patients below age 18 years due to insufficient data on safety and efficacy.
Tfal u adoloxxenti Bondronat mhux irrakkomandat għall- użu fit- tfal ta ’ taħt it- 18- il sena peress li m’ hemmx biżżejjed informazzjoni dwar is- sigurtà u l- effikaċja.
Caution is to be taken in patients with known hypersensitivity to other bisphosphonates.
Għandha tingħata l- attenzjoni f’ pazjenti b’ sensittività eċċessiva għal bisfosfonati oħrajn.
Nevertheless, according to clinical assessment of the individual patient, it is recommended that renal function, serum calcium, phosphate and magnesium should be monitored in patients treated with Bondronat.
Madankollu, skond l- eżami kliniku tal- pazjent individwali, huwa rrikkmandat li jsir monitoraġġ tal - funzjoni renali, tal- kalċju fis- serum, tal- fosfat u tal- manjesju f’ pazjenti li jiġu trattati b’ Bondronat.
Hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting Bondronat therapy for metastatic bone disease.
Ipokalċimja u mard ieħor ta ’ l- għadam u tal- metaboliżmu minterali għandhom jingħataw kura effettiva qabel ma tinbeda kura b ’ Bondronat għal mard ta ’ l- għadam metastatiku.
Clinical judgement of the treating physician should guide the management plan of each patient based on individual benefit/ risk assessment.
Id- deċiżjoni klinika tat- tabib responsabbli għandha tagħti direzzjoni għall- pjan ta ’ immaniġġjar għal kull pazjent bbażat fuq stima tal- benefiċju/ riskju individwali.
Bondronat should not be mixed with calcium containing solutions.
Bondronat ma għandux jitħallat ma ’ soluzzjonijiet li fihom il- kalċju
No interaction was observed when co-administered with melphalan/ prednisolone in patients with multiple myeloma.
26 Ma ġiet osservata ebda interazzjoni meta mogħtija flimkien ma ’ melphalan/ prednisolone f’ pazjenti b’ mijeloma multipla.
25 In relation to disposition, no drug interactions of clinical significance are likely.
B’ relazzjoni mad- disposizzjoni, x’ aktarx li m’ hemm l- ebda interazzjoni ta ’ sinifikat kliniku.
Plasma protein binding is low at therapeutic concentrations and ibandronic acid is therefore unlikely to displace other active substances.
Twaħħil ma 'proteini fil- plażma hija baxxa f’ konċentrazzjonijiet terapewtiċi u ibandronic acid x’ aktarx ma jissostitwix sustanzi attivi oħra.
In clinical studies, Bondronat has been administered concomitantly with commonly used anticancer agents, diuretics, antibiotics and analgesics without clinically apparent interactions occurring.
Fi studji kliniċi, Bondronat ġie amministrat flimkien ma ’ aġenti użat b’ modkomuni kontra l- kanċer, dijuretiċi, antibijotiċi u analġesjiċi mingħajr ma ġraw interazzjonijiet kliniċi evidenti.
Studies in lactating rats have demonstrated the presence of low levels of ibandronic acid in the milk following intravenous administration.
Studji fuq firien li qed ireddgħu urew il- presenza ta ’ livelli baxxi ta ’ ibandronic acid fil- ħalib wara amministrazzjoni ġol- vina.
Adverse reactions are ranked under heading of frequency, the most frequent first, using the following convention: very common (≥ 10%), common (≥ 1% and < 10%), uncommon (≥ 0.1% and < 1%), rare (≥ 0.01% and < 0.1%), and very rare (≤ 0.01%).
Reazzjonijiet avversi huma kklassifikati taħt it- titlu tal- frekwenza, l- aktar frekwenti l- ewwel, bil - konvenzjoni li ġejja: komuni ħafna (≥ 10%), komuni (≥ 1% u < 10%), mhux komuni (≥0. 1% u < 1%), rari (≥ 0. 01% u < 0. 1%), rari ħafna (≤ 0. 01%).
Table 1
27 Tabella 1
System Organ
Sistema tal- klassifika tal- organi / Reazzjoni Avversa Mard marbut mal- metaboliżmu u n- nutrizzjoni:
Hypocalcaemia
Komuni: ipokalċemja
10 (2.8)
10 (2. 8)
26 System Organ Class / Adverse reaction
Mard muskolu- skeltrali u tal- connective tissue
Uncommon:
Uġigħ fl- Għadam Mhux Komuni:
Bone Pain Myalgia
Mijalgja
Data for both the 2 mg and 4 mg doses of ibandronic acid are pooled.
Kemm għad- doża ta ’ 2 mg kif ukoll ta ’ 4 mg ta ’ ibandronic acid huma miġbura flimkien.
Respiratory, thoracic and mediastinal disorders:
Mard respiratorju, toraċiki u medjastinali:
Administration
Bronkospażmu
acetylsalicylic acid-sensitive asthmatic patients.
L- amministrazzjoni ta ’ bisfosfonati oħrajn kienet assoċjata ma ’ branko- kostrizzjoni f’ pazjenti li jbatu bl- ażma b’ sensittività għal acetylsalicylic acid.
Table 2 lists adverse reactions from the pivotal phase III study (152 patients treated with Bondronat 6 mg), i. e. adverse events with a remote, possible, or probable relationship to study medication, occurring commonly and more frequently in the active treatment group than in placebo.
Tabella 2 telenka reazzjonijiet avversi mill- fażi pivotali III (152 pazjent trattati b’ Bondronat 6 mg), jiġifieri effetti avversi b’ relazzjoni remota, possibbli, jew probabbli mal- medikazzjoni taħt studju, li jseħħu ta ’ spiss u iktar frekwentement fil- grupp attiv tat- trattament milli fil- plaċebo.
Adverse Reactions Occurring Commonly and Greater than Placebo in Patients with Metastatic Bone Disease due to Breast Cancer Treated with Bondronat 6 mg administered intravenously
Reazzjonijiet Avversi li Jseħħu ta ’ Spiss u iktar mill- Plaċebo f’ Pazjenti b’ Metastażi fl- għadam minnħabba kanċer tas- Sider Trattat b’ Bondronat 6 mg mogħtija ġol- vina
Placebo (n = 157) No.
Plaċebo
Infections and Infestations:
Reazzjoni Avversa
Infection
Plaċebo
1 (0.6)
Bondronat 6 mg
2 (1.3)
(n = 157) No.
Endocrine disorders:
(n = 152) No.
Nervous
(%)
Parathyroid disorder System disorders:
Infezzjoni
Headache Dizziness Dysgeusia (taste perversion)
Mard fis- sistema endokrinarja:
4 (2.5) 2 (1.3) 0 (0.0)
Mard tal- paratirojd
9 (5.9) 4 (2.6) 2 (1.3)
2 (1. 3)
27 Adverse Reaction
Mard tas- Sistema Nervuża:
Bondronat 6 mg
4 (2. 5) 2 (1. 3) 0 (0. 0)
(%)
Mard ta’ l -- Għajnejn:
Pharyngitis Gastrointestinal disorders:
Disturbi respiratorji, toraċiċi u medjastinali:
Skin disorder Ecchymosis Musculoskeletal and connective tissue disorders:
Mard tal- ġilda
Myalgia Arthralgia Joint disorder Osteoarthritis General disorders:
Disturbi Muskoluskeletriċi u ta ’ tessut ta ’ tgħaqqid ta 'tessut:
Infection and infestation: cystitis, vaginitis, oral candidiasis Neoplasms benign and malignant (including cysts and polyps): benign skin neoplasm Blood and lymphatic system: anaemia, blood dyscrasia Metabolism and nutrition disorders: hypophosphataemia Psychiatric disorders: sleep disorder, anxiety, affection lability Nervous system disorders: cerbrovascular disorder, nerve root lesion, amnesia, migraine, neuralgia, hypertonia, hyperaestesia, paraesthesia circumoral, parosmia.
Infezzjonijiet u infestazzjonijiet: ċistite, vaġinite, kandidjażi orali Neoplażmi beninni, malinni u dawk mhux speċifikati (inklużi ċesti u polipi): neoplażmi tal- ġilda beninji Mard tad- demm u tas- sistema limfatika: anemja, diskrajażi tad- demm Mard marbut mal- metabolismu u nutrizzjoni: ipofosfatemja Mard psikjatriku: mard ta ’ l -- irqad, ansjetà, lijabilità affettiva Mard tas- sistema nervuża: mard ċerbovaskulari, ferita ta ’ l- għerq tan- nerv, amneżja, migranja, newroloġija, ipertonja, parasteżija ċirkumorali, parosmja.
Ear and labyrinth disorders: deafness Cardiac disorders: myocardial ischaemia, cardiovascular disorder, palpitations Vascular disorders: hypertension, lymphoedema, varicose veins Respiratory, thoracic and mediastinal disorders: lung oedema, stridor Gastrointestinal disorders: gastroenteritis, dysphagia, gastritis, mouth ulceration, cheilitis Hepato-biliary disorders: cholelithiasis Skin and subcutaneous tissue disorders: rash, alopecia Renal and urinary disorders: urinary retention, renal cyst Reproductive system and breast disorders: pelvic pain General disorders and administration site conditions: hypothermia Investigations: blood alkaline phosphatase increase, weight decrease Injury, poisoning and procedural complications: injury, injection site pain
Mard tal- kliewi u tas- sistema urinarja: retenzjoni ta ’ l- urina, ċista tal- kliewi Mard tas- sistema riproduttiva u tas- sider: uġigħ pelviku Mard ġenerali u kundizzjonijiet ta 'mnejn jingħata: ipotermja Investigazzjonijiet: żjieda ta ’ alkaline phosphatase fid- demm, tnaqqis fil- piż Korriment, avvelenament u komplikazzjonijiet ta ’ xi proċedura: korriment, uġigħ fil- lok ta ’ l - injezzjoni
28 Osteonecrosis of the jaw has been reported in patients treated by bisphosphonates.
L- osteonekrożi tax- xedaq kien rapportat f’ pazjenti li rċevew kura bil- bisfosfonati.
Since both the kidney and the liver were found to be target organs for toxicity in preclinical studies with high doses, kidney and liver function should be monitored.
Minħabba li fi studji pre- kliniċi b’ doża għolja, kemm il- kliewi kif ukoll il- fwied instabu li kienu organi li setgħu kienu milquta minn tossiċita, il- funzjoni tal- kliewi u tal- fwied għandhom jiġu mmonitorjati.
Clinically relevant hypocalcaemia should be corrected by intravenous administration of calcium gluconate.
Ipokalċemja li tkun klinikament relevanti għandha tkun ikkurata permezz ta ’ amministrazzjoni ġol - vina ta ’ calcium gluconate.
Ibandronic acid belongs to the bisphosphonate group of compounds which act specifically on bone.
Ibandronic acid jappartjeni għas- sustanzi ta ’ grupp ta ’ bisfosfonati li jaħdmu speċifikament fuq l - għadam.
Clinical Studies in the Treatment of Tumour-Induced Hypercalcemia Clinical studies in hypercalcaemia of malignancy demonstrated that the inhibitory effect of ibandronic acid on tumour-induced osteolysis, and specifically on tumour-induced hypercalcaemia, is characterised by a decrease in serum calcium and urinary calcium excretion.
Studji Kliniċi fit- Trattament ta ’ l- Iperkalċemja Kkawżata minn Tumur Studji kliniċi fl- iperkalċemja malinna wriet li l- effett inibitorju ta ’ Ibandronic acid fuq osteolisi kkawżata mit- tumur, u speċifikament fuq l- iperkalċemja kkawżata minn tumur, hija kkarratterrizzata bi tnaqqis fil- kalċju fis- serum u eliminazzjoni tal- kalċju fl- urina.
In the dose range recommended for treatment, the following response rates with the respective confidence intervals have been shown in clinical trials for patients with baseline albumin-corrected serum calcium ≥ 3.0 mmol/ l after adequate rehydration.
30 Fl- iskala tad- doża rrakkomandata għat- trattament, ir- rati ta ’ rispons li ġejjin, bl- intervalli tal - konfidenza rispettivi, ntwerew fi provi kliniċi għall- pazjenti b’ linja bażika ta’ kalċju fis- serum ikkoreġut bl- albumina ≥3. 0 mmol/ l wara rijidrattazzjoni adegwata.
high 90%
Error!
For these patients and dosages, the median time to achieve normocalcaemia was 4 to 7 days.
Għal dawn il- pazjenti u d- dożaġġi, iż- żmien medjan sa biex tintlaħaq in- normokalċemija kien ta ’ bejn 4 u 7 ijiem.
Prevention of skeletal events in patients with breast cancer and bone metastases with Bondronat 6 mg administered intravenously was assessed in one randomized placebo controlled phase III trial with duration of 96 weeks.
Il- prevenzjoni ta ’ reazzjonijiet skeletriċi f’ pazjenti b’ kanċer tas- sider u metastażi fl- għadam Doża ta ’ ibandronic acid
Female patients with breast cancer and radiologically confirmed bone metastases were randomised to receive placebo (158 patients) or 6 mg Bondronat (154 patients).
Pazjenti femminili b’ kanċer tas- sider u metastażi fl - għadam ikkonfermat radjologikament tħalltu sa biex jirċievu l- plaċebo (158 pazjent) jew 6 mg Interval ta ’ Bondronat90% għolja pazjent).
Primary Efficacy Endpoints The primary endpoint of the trial was the skeletal morbidity period rate (SMPR).
(154 Rata tar- rispons konfidenza Interval ta ’ konfidenza baxxa 90% L- Miri Primarji ta ’ l- Effikaċja L- mira primarja ta ’ l- istudji kienet ir- rata tal- perijodu tal- morbidità skeletrika (SMPR).
- non-vertebral fractures.
Eventi multipli kienu għalhekk, magħduda biss darba
Efficacy Results (Breast Cancer Patients with Metastatic Bone Disease)
Riżultati ta ’ l- Effikaċja (Pazjenti b’ Kanċer tas- Sider b’ Mard Metastatiku fl - għadam)
All Skeletal Related Events (SREs) Placebo Bondronat 6 mg p-value n=158 n=154
Episodji Kollha Relatati ma ’ l- Iskeletru Plaċebo Bondronat 6 mg n=158 n=154
p=0.025
p=0. 025
Secondary Efficacy Endpoints A statistically significant improvement in bone pain score was shown for intravenous Bondronat 6 mg compared to placebo.
31 L- Miri Sekondarji ta ’ l- Effikaċja Titjib għall- aħjar fil- marka ta ’ l- uġigħ fl- għadam statistikament sinifikanti intwera għal Bondronat 6 mg ġol- vina meta mqabbel mal- plaċebo.
The pain reduction was consistently below baseline throughout the entire study and accompanied by a significantly reduced use of analgesics.
It- tnaqqis fl- uġigħ kien b’ mod konformi taħt il - linja bażika matul l- istudju kollu u kien akkumpanjat b’ użu mnaqqas sinifikattiv ta ’ analġesiċi meta mqabbel mal- plaċebo.
cancer Patients with Metastatic Bone Disease)
Riżultati ta ’ l- Effikaċja Sekondarja (Pazjenti b’ Kanċer tas- Sider bil- Mard Metastatiku fl- Għadam)
31 approximately 87% at therapeutic concentrations, and thus drug-drug interaction due to displacement is unlikely.
L - għaqda mal- proteini fil- plażma umana hija bejn wieħed u ieħor 87% f’ konċentrazzjonijiet terapewtiċi, u għalhekk interazzjoni bejn mediċini minħabba spostament mhuwiex probabbli.
Elimination The range of observed apparent half-lives is broad and dependent on dose and assay sensitivity, but the apparent terminal half-life is generally in the range of 10-60 hours.
Eliminazzjoni Il- firxa osservata ta ’ half- lifes apparentihija wiesgħa u tiddependi fuq id- doża u s- sensittività ta ’ l - analażi, iżda jidher li l- half- life terminali apparenti huwa fl- iskala ta ’ bejn 10- 60 siegħa.
No systemic accumulation was observed when ibandronic acid was administered intravenously once every 4 weeks for 48 weeks to patients with metastatic bone disease.
L- ebda akkumulazzjoni sistematika ma ġiet osservata meta bandronic acid ġie amministrat ġol- vina darba kull 4 ġimgħat għal 48 ġimgħa lill - pazjenti b ’ mard metastatiku ta ’ l- għadam.
Total clearance of ibandronic acid is low with average values in the range 84-160 ml/ min.
32 It- tneħħija totali ta ’ ibandronic acid hija baxxa b’ livelli medji b’ firxa ta ’ 84- 160 ml/ min.
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 tagħrif farmakokinetika għal ibandronic acid f’ pazjenti li għandhom indeboliment tal - fwied.
Children and adolescents There are no data on the use of Bondronat in patients less than 18 years old
Tfal u adoloxxenti M’ hemm l- ebda tagħrif fuq l- użu ta ’ Bondronat f’ pazjenti ta ’ eta ’ inqas minn 18- il sena.
32 Effects in non-clinical studies were observed only at exposures sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.
Fi studji mhux kliniċi ġew osservati effetti biss f’ esposizzjonijiet ħafna aktar eċċessivi mill - esposizzjoni massima umana li tindika ftit rilevanza għall- użu kliniku.
Tests for genotoxicity revealed no evidence of effects on genetic activity for ibandronic acid.
Testijiet għal ġenotossiċità ma urew l- ebda evidenza ta ’ attività ġenetika għalibandronic acid.
No evidence of direct foetal toxicity or teratogenic effects were observed for ibandronic acid in intravenously treated rats and rabbits.
L- ebda evidenza ta ’ tossiċità diretta fuq il- fetu jew effetti teratoġeniċi ma ġew osservati għalibandronic acid fil- firien u fil- fniek trattati ġol- vina.
Adverse effects of ibandronic acid in reproductive toxicity studies in the rat were those expected for this class of drug (bisphosphonates).
33 studji ta ’ tossiċità riproduttiva fil- far kienu dawk mistennija għal din il- klassi ta ’ mediċini (bisfosfonati).