qanastek/EMEA-V3 huggingface dataset:
The serum calcium may fall to asymptomatic hypocalcaemic levels in approximately 3% of patients.
Il- livell ta ’ calcium fis- serum jista ’ jinżel għal livelli baxxi mingħajr sintomi f’ madwar3% tal- pazjenti.
Gastrointestinal reactions, such as nausea (5.8%) and vomiting (2.6%) have been reported following intravenous infusion of Zometa.
Effetti gastrointestinali, bħal tqallih (5. 8%) u rimettar (2. 6%) ġew irrapportati wara infużjoni ta ’ Zometa ġol- vini.
Occasionally local reactions at the infusion site such as redness or swelling and/ or pain were also observed in less than 1% of the patients.
Xi kultant, effetti lokali fil- post fejn tingħata l- infużjoni, bħal ħmura jew nefħa u/ jew uġigħ ġew osservati f’ inqas minn 1% tal- pazjenti.
Anorexia was reported in 1.5% of patients treated with Zometa 4 mg.
Anoreksja ġiet rrappurtata f’ 1. 5% ta ’ pazjenti li ngħataw Zometa 4 mg.
Few cases of rash or pruritus have been observed (below 1%).
Ġew osservati ftit każijiet ta ’ raxx u ħakk (taħt 1%).
As with other bisphosphonates, cases of conjunctivitis in approximately 1% have been reported.
Bħal ma jiġri b’ bisphosphonates oħrajn ġew irrappurtati każijiet ta ’ konġunktivite, f’ madwar 1% tal - pazjenti.
There have been some reports of impaired renal function (2.3%), although the aetiology appears to be multifactorial in many cases.
Ġew irrapporati xi ftit każi ta ’ indeboliment tal- funzjoni tal- kliewi (2. 3%), għalkemm l- etjoloġija tidher li ġejja minn diversi fatturi f’ ħafna każijiet.
Based on pooled analysis of placebo controlled studies, severe anaemia (Hb < 8.0 g/ dl) was reported in 5.2% of patients receiving Zometa 4 mg versus 4.2% on placebo.
Analiżi ta ’ ġabra ta ’ studji kkontrollati bil- plaċebo wriet li anemija severa (Hb < 8. 0 g/ dl) ġiet irrapportata f’ 5. 2% tal- pazjenti li qed jirċievu Zometa, meta mqabbla ma ’ 4. 2% li kienu jieħdu plaċebo.
The following adverse drug reactions, listed in Table 1, have been accumulated from clinical studies following predominantly chronic treatment with zoledronic acid:
L- effetti avversi li ġejjin, elenkati f’ Tabella 1 inġabru f’ daqqa mill- istudji kliniċi wara kura li fil- parti l- kbira kienet kronika b’ zoledronic acid:
Very common (≥ 1/ 10), common (≥ 1/ 100, < 1/ 10), uncommon (≥ 1/ 1,000, < 1/ 100), rare (≥ 1/ 10,000, < 1/ 1,000), very rare (< 1/ 10,000), including isolated reports.
Ir- reazzjonijiet avversi qegħdin imqassmin taħt it- titlu tal- frekwenza, l- aktar frekwenti l- ewwel, bil - konvenzjoni: komuni ħafna (≥1/ 10), komuni (≥1/ 100, < 1/ 10), mhux komuni (≥1/ 1, 000, < 1/ 100), rari (≥1/ 10, 000, < 1/ 1, 000), rari ħafna (< 1/ 10, 000), inklużi rapporti iżolati.
6 Blood and lymphatic system disorders
6 Disturbi tad- demm u tas- sistema limfatika
Anaemia Thrombocytopenia, leukopenia Pancytopenia
Anemija Thromboċitopenja, lewkopenja Panċitopenja
Headache Dizziness, paraesthesia, taste disturbance, hypoaesthesia, hyperaesthesia, tremor
Uġigħ ta ’ ras Sturdament, parasteżija, disturbi tat- togħma, ipoesteżija, iperesteżija, tregħid
Psychiatric disorders Eye disorders
Disturbi psikjatriċi
Anxiety, sleep disturbance Confusion
Ansjetà, disturbi ta ’ l- irqad Konfużjoni
Conjunctivitis Blurred vision Uveitis, episcleritis
Konġunktivite Vista mċajpra Uvejite, episklerite
Nausea, vomiting, anorexia Diarrhoea, constipation, abdominal pain, dyspepsia, stomatitis, dry mouth
Tqallih, rimettar, anoreksja Dijarea, stitikezza, uġigħ addominali, dispepsja, stomatite, ħalq xott
Pruritus, rash (including erythematous and macular rash), increased sweating
Ħakk, raxx, (inklużi raxx bi ħmura u dak makulari), żieda fl- għaraq
Bone pain, myalgia, arthralgia, generalised pain
Uġigħ fl- għadam, mijalġja, artralġja, uġigħ mal- ġisem kollu
Muscle cramps
Bugħawwieġ fil- muskoli
Cardiovascular disorders Renal and urinary
Disturbi kardjovaskulari Disturbi fil- kliewi
Rare: disorders Common:
Rari: u fis- sistema urinarja Komuni:
Hypertension, hypotension Bradycardia Renal impairment Acute renal failure, haematuria, proteinuria
Pressjoni għolja, pressjoni baxxa Bradikardja Indeboliment renali Insuffiċjenza renali, ħematurja, proteinurja
Immune system disorders General disorders
Disturbi fis- sistema immuni
Rare: and administration site conditions Common:
Reazzjoni ta ’ sensittività eċċessiva Edima anġonewrotika
Hypersensitivity reaction Angioneurotic oedema Fever, flu-like syndrome (including fatigue, rigors, malaise and flushing)
Deni, sindrome li tixbah l- influwenza (inklużi għejja, tertir, tħossok marid u ssir ruxxan)
Asthenia, peripheral oedema, injection site reactions (including pain, irritation, swelling, induration), chest pain, weight increase
Astenja, edima periferali, reazzjoni fis- sit ta ’ l - injezzjoni (inklużi uġigħ, irritazzjoni, nefħa, ebusija), uġigħ fis- sider, u żieda fil- piż
Laboratory abnormalities
Anormalitajiet tal- laboratorji
Hypophosphataemia Blood creatinine and blood urea increased, hypocalcaemia
Inżul fil- livell tal- phosphate fid- demm Żieda fil- livelli tal- krejatinina u urea fid - demm, u inżul fil- livell tal- calcium
Hypomagnesaemia, hypokalaemia Hyperkalaemia, hypernatraemia
Żieda fil- livelli ta ’ potassium u sodium fid - demm
In one 3-year, randomised, double-blind controlled trial that evaluated the efficacy and safety of zoledronic acid 5 mg once yearly vs. placebo in the treatment of postmenopausal osteoporosis (PMO), 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 zoledronic acid 5 mg and placebo, respectively.
Fi prova ta ’ 3 snin, randomised, double- blind kontrollata li evalwat l- effikaċja u s- sigurtà ta ’ zoledronic acid 5 mg darba fis- sena kontra plaċebo fil- kura ta ’ osteoporosi ta ’ wara l- menopawża (PMO), 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 zoledronic acid 5 mg u plaċebo, rispettivament.
The rate of atrial fibrillation serious adverse events was 1.3% (51 out of 3,862) and 0.6% (22 out of 3,852) in patients receiving zoledronic acid 5 mg and placebo, respectively.
Ir- rata ta ’ 7 każijiet avversi serji ta ’ fibrillazzjoni atrijali kienet 1. 3% (51 minn 3, 862) u 0. 6% (22 minn 3, 852) f’ pazjenti li kienu qed jirċievu zoledronic acid 5 mg u plaċebo, rispettivament.
The imbalance observed in this trial has not been observed in 7 other trials with zoledronic acid, including those with Zometa (zoledronic acid) 4 mg every 3-4 weeks in oncology patients.
L- iżbilanċ li deher f’ din il- prova ma deherx fi provi oħrajn b’ zoledronic acid, inklużi dawk b’ Zometa (zoledronic acid) 4 mg kull 3- 4 ġimgħat f’ pazjenti b’ mard tat- tumur.
The mechanism behind the increased incidence of atrial fibrillation in this single clinical trial is unknown.
Mhux magħruf il- mekkaniżmu taż- żieda fil- fibrillazzjoni atrijali f’ din il- prova waħda klinika.
Post-marketing experience The following adverse reactions have been reported during post-approval use of Zometa.
Esperjenza wara t- tqegħid fis- suq Ir- reazzjonijiet avversi li ġejjin kienu rrappurtati fiż- żmien wara li ġie approvat l- użu ta ’ Zometa.
Cases of osteonecrosis (primarily of the jaws) have been reported, predominantly in cancer patients treated with bisphosphonates, including Zometa.
Każijiet ta ’ osteonekrożi (l- aktar tax- xedaq) kienu rappurtati, l- aktar f’ pazjenti bil- kanċer kurati b’ bisphosphonates, inkluż Zometa.
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 inkluż ostejomajelitis, u il- parti l- kbira tar- rapporti jirreferu għall- pazjenti wara li kellhom qlugħ ta ’ snien jew operazzjonijiet oħra fis- snien.
Osteonecrosis of the jaws has multiple 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 oral disease).
Ostejonekrożi tax- xedaq għandha fatturi ta ’ riskju multipli dokumentati sew li jinkludu dijanjożi ta ’ kanċer, terapiji li jkunu qed jingħataw fl- istess waqt (eż kimoterapija, radjuterapija, kortikosterojdi) u kundizzjonijiet li jdgħajjfu li jkollhom fl- istess ħin tal - kura (eż anemija, mard tat- tgħaqid tad- demm, infezzjoni, mard tal- ħalq 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 ġewx determinati, ikun prudenti li kirurġiji fil- ħalq jiġu evitati għax l- irkupru jista ’ jieħu aktar żmien (ara sezzjoni 4. 4).
In very rare cases, the following events have been reported: hypotension leading to syncope or circulatory collapse, primarily in patients with underlying risk factors, atrial fibrillation, somnolence, bronchoconstriction, anaphylactic reaction/ shock, and urticaria.
F’ każijiet rari ħafna, dawn il- ġrajjiet kienu rrappurtati: pressjoni baxxa li wasslet għal sinkope jew kollass ċirkolatorju, l- aktar f’ pazjenti b’ fatturi ta ’ riskju oħrajn, fibrillazzjoni atrijali, ngħas, bronkospażmu, reazzjoni anafilattika/ xokk, u urtikarja.
Because these reports are from a population of uncertain size and are subject to confounding factors, it is difficult to assess causality and to estimate event incidence rates.
Minħabba li dawn ir- rapporti ġejjin minn popolazzjoni ta ’ daqs mhux aċċertat u huma suġġetti għal fatturi li jistgħu ixekklu, huwa diffiċli li tkun stmata l- kawża u li jiġu stmati r- rati ta ’ l- inċidenza tal- każijiet.
Clinical experience with acute overdose of Zometa is limited.
L- esperjenza klinika b’ doża eċċessiva akuta ta ’ Zometa hija limitata.
Patients who have received doses higher than those recommended should be carefully monitored, since renal function impairment (including renal failure) and serum electrolyte (including calcium, phosphorus and magnesium) abnormalities have been observed.
Pazjenti li ngħataw dożi ogħla minn dawk rakkommandati għandhom jiġu sorveljati bir- reqqa peress li dehru indeboliment tal - funzjoni renali (inkluża insuffiċjenza renali) u anormalitajiet ta ’ l- elettroliti fis- serum (inklużi calcium, phosphorus u magnesium).
In the event of hypocalcaemia, calcium gluconate infusions should be administered as clinically indicated.
F’ każ li jkun hemm inżul fil- livell ta ’ calcium fid- demm infużjonijiet ta ’ calcium gluconate għandhom jingħataw hekk kif ikun klinikament indikat.
Zoledronic acid belongs to the class of bisphosphonates and acts primarily on bone.
Zoledronic acid jagħmel parti mill- klassi ta ’ bisphosphonates u jaħdem l- aktar fuq l- għadam.
It is an inhibitor of osteoclastic bone resorption.
Huwa impeditur tar- risorbiment ta ’ l- għadam minn osteoklasts.
The selective action of bisphosphonates on bone is based on their high affinity for mineralised bone, but the precise molecular mechanism leading to the inhibition of osteoclastic activity is still unclear.
Il- mod silettiv ta ’ kif jaħdmu l- bisphosphonates fuq l- għadam ġej mill- affinità qawwija li għandhom għall- għadam mineralizzat, iżda l- mekkaniżmu preċiz fuq livell molekulari li jwassal għall - impedizzjoni ta ’ l- attività ta ’ l- osteoklasts għadu mħux magħruf għal kollox.
In long-term animal studies, zoledronic acid inhibits bone resorption without adversely affecting the formation, mineralisation or mechanical properties of bone.
Fi studji fuq annimali li damu għaddejin għal tul ta ’ żmien urew li zoledronic acid jimpedixxi r- risorbiment ta ’ l- għadam mingħajr ma jaffettwa ħażin il- formazzjoni, mineralizzazzjoni jew il- propjetajiet mekkaniċi ta ’ l - għadam.
In addition to being a potent inhibitor of bone resorption, zoledronic acid also possesses several anti- tumour properties that could contribute to its overall efficacy in the treatment of metastatic bone disease.
Barra li hu impeditur tar- risorbiment ta ’ l- għadam, zoledronic acid għandu wkoll diversi effetti kontra t- tumuri li jistgħu jikkontribwixxu lejn l- effikaċja tiegħu fil- kura ta ’ metastasi fl- għadam.
The following properties have been demonstrated in preclinical studies:
Studji ta ’ qabel l- użu kliniku wrew dawn il- kwalitajiet li ġejjin:
Inhibition of osteoclastic bone resorption, which alters the bone marrow
Impediment tar- risorbiment ta ’ l- għadam minn osteoklasts, biex b’ hekk ibiddlu l- mikro -
microenvironment, making it less conducive to tumour cell growth, anti-angiogenic activity and anti-pain activity.
ambjent tal- mudullun u allura titnaqqaslu l- ħila li jkattar iċ- ċelloli tat- tumur, għandu effett kontra t- tkattir mill- ġdid tal- provvista ta ’ demm lit- tumur u effett kontra l- uġigħ.
Inhibition of osteoblast proliferation, direct cytostatic and pro-apoptotic activity on
Iwaqqaf it- tkattir ta ’ osteoblasts, għandu effett dirett kontra t- tkattir taċ- ċelluli tat -
tumour cells, synergistic cytostatic effect with other anti-cancer drugs, anti-adhesion/ invasion activity.
tumur u wkoll effett pro- apoptotiku fuq iċ- ċelloli tat- tumur, jaħdem b’ mod sinerġistiku ma ’
8 Clinical trial results in the prevention of skeletal related events in patients with advanced malignancies involving bone The first randomised, double-blind, placebo-controlled study compared Zometa to placebo for the prevention of skeletal related events (SREs) in prostate cancer patients.
8 mediċini oħrajn kontra l- kanċer biex jagħmel effett li jfixkel it- tkattir taċ- ċelloli tat- tumur, kif ukoll għandu attività kontra l- adeżjoni/ l- invażjoni.
Zometa 4 mg significantly reduced the proportion of patients experiencing at least one skeletal related event (SRE), delayed the median time to first SRE by > 5 months, and reduced the annual incidence of events per patient - skeletal morbidity rate.
Zometa 4 mg naqqas b’ mod sinifikanti n- numru ta ’ pazjenti li ħassew mill- inqas effett skeletriku (SRE) wieħed, tawwal iż- żmien medja għall- ewwel SRE b ’ > 5 xhur, u naqqas l- inċidenża annwali ta ’ dawn l- effetti bħala rata għal kull pazjent – rata ta ’ morbożità skeletrika.
Multiple event analysis showed a 36% risk reduction in developing SREs in the Zometa group compared with placebo.
Analiżi ta ’ ħafna avvenimenti f’ daqqa wrew tnaqqis ta ’ 36% fir- riskju li wieħed jiżviluppa SRE fil- grupp fuq Zometa, meta mqabbel ma ’ pazjenti fuq plaċebo.
Patients receiving Zometa reported less increase in pain than those receiving placebo, and the difference reached significance at months 3, 9, 21 and 24.
Pazjenti fuq kura b’ Zometa rrapurtaw inqas żieda fl- uġigħ minn dawk li kienu fuq plaċebo, u d - differenza kienet sinifikanti fit- 3, 9, 21 u 24 xhar.
Fewer Zometa patients suffered pathological fractures.
Pazjenti fuq Zometa sofrew anqas ksur patoloġiku.
The treatment effects were less pronounced in patients with blastic lesions.
L- effetti tal- kura kienu inqas f’ pazjenti li kellhom leżjonijiet blastiċi.
Efficacy results are provided in Table 2.
Riżultati li juru l- effikaċja ta ’ Zometa f’ dawn il- pazjenti jinsabu f’ Tabella 2.
In a second study including solid tumours other than breast or prostate cancer, Zometa 4 mg significantly reduced the proportion of patients with an SRE, delayed the median time to first SRE by > 2 months, and reduced the skeletal morbidity rate.
Fi studju ieħor li nkluda tumuri solidi oħra barra dawk tas- sider jew tal- prostata, urew li Zometa 4 mg naqqas b’ mod sinifikanti l- proporzjon ta ’ pazjenti li kellhom SRE, tawwal iż- żmien medju għall - ewwel SRE b ’ > xahrejn, u naqqas ir- rata ta ’ morbożità skeletrika.
Multiple event analysis showed 30.7% risk reduction in developing SREs in the Zometa group compared with placebo.
Analiżi ta ’ ħafna avvenimenti f’ daqqa wrew tnaqqis ta ’ 30. 7% tar- riskju li wieħed jiżviluppa SRE għal dawk fuq kura b’ Zometa, meta mqabbla ma ’ pazjenti fuq plaċebo.
Efficacy results are provided in Table 3.
Riżultati dwar l- effikaċja jinsabu f’ Tabella 3.
Efficacy results (prostate cancer patients receiving hormonal therapy)
Riżultati li juru l- effikaċja (pazjenti b’ kanċer tal- prostata li qed jieħdu kura b’ ormoni)
Radiation therapy to bone
Kwalunkwe SRE (+TIH) Ksur * Terapija ta ’ l- għadam bir- radjazzjoni Zometa Placebo Zometa Placebo Zometa Placebo 4 mg 4 mg 4 mg
N Proportion of patients with SREs (%)
N Proporzjon ta ’ b’ SREs (%)
208 214 25 26
214 208 214 208 214 208 pazjenti 38 49 17 25 26 33
0.052 0.119
0. 028 0. 052 0. 119
Median time to SRE (days)
Żmien medjan għal SRE (jiem)
NR NR
MM
0.009
0. 020
0.020 0.055
0. 055
Skeletal morbidity rate
Rata ta ’ morbożità skeletrika
0.77
0. 20
1.47 0.20
0. 45
0.45 0.42
0. 42
0.005
0. 023
0.023 0.060
0. 060
Risk reduction of suffering from multiple events** (%)
Tnaqqis ta ’ riskju li wieħed jiżviluppa ħafna avvenimenti f’ daqqa ** (%)
- NA
MA
NA NA
MA
NA
MA
* Includes vertebral and non-vertebral fractures ** Accounts for all skeletal events, the total number as well as time to each event during the trial NR Not Reached NA Not Applicable
* Jinkludi ksur fl- għadam tas- sinsla tad- dahar u wkoll ksur band’ oħra ** Jiġbor l- avvenimenti skeletrali kollha, kemm in- numru totali kif ukoll il- ħin sa ma seħħ kull avveniment tul il- prova MM Mhux Milħuq MA Mhux Applikabbli
Any SRE (+TIH)
Riżultati li juru l- effikaċja (pazjenti b’ tumuri solidi oħra barra dawk tas- sider u tal - prostata)
Radiation therapy to bone
Kwalunkwe SRE (+TIH) Ksur * Terapija ta ’ l- għadam bir- radjazzjoni Zometa Plaċebo Zometa Plaċebo Zometa Plaċebo 4 mg 4 mg 4 mg
Zometa 4 mg
N
Placebo Zometa 4 mg
257 250 257 250 257 250
N Proportion of patients with SREs (%)
Proporzjon ta ’ pazjenti b’ SREs (%)
257 39
39
250 257 48 16
16
250 257 22 29
22
250 34
34
0.039
0. 064
0.064 0.173
0. 173
0.020 0.079
0. 079
1.74
0. 39
2.71 0.39
0. 63
0.63 1.24
1. 24
1.89
1. 89
0.012
0. 012
0.099
0. 099
30.7
30. 7
* Includes vertebral and non-vertebral fractures ** Accounts for all skeletal events, the total number as well as time to each event during the trial NR Not Reached NA Not Applicable
* Jinkludi ksur fl- għadam tas- sinsla tad- dahar u dawk band’ oħra ** Jiġbor l- avvenimenti skeletrali kollha, kemm in- numru totali kif ukoll il- ħin sa ma seħħ kull avveniment tul il- prova MM Mhux Milħuq MA Mhux Applikabbli
In a third phase III randomised, double-blind trial, 4 mg Zometa or 90 mg pamidronate every 3 to 4 weeks were compared in patients with multiple myeloma or breast cancer with at least one bone lesion.
Fit- tielet prova randomised u double- blind tal- fażi III, 4 mg ta ’ Zometa jew 90 mg ta ’ pamidronate, mogħtija kull 3 sa 4 gimgħat ġew imqabbla f’ pazjenti b’ majeloma multipla jew kanċer tas- sider li kellhom mill- inqas leżjoni waħda fl- għadam.
The results demonstrated that Zometa 4 mg showed comparable efficacy to 90 mg pamidronate in the prevention of SREs.
Ir- riżultati wrew li 4 mg Zometa kellu effikaċja komparabbli ma ’ 90 mg pamidronate fil- prevenżjoni ta ’ SREs.
The multiple event analysis revealed a significant risk reduction of 16% in patients treated with Zometa 4 mg in comparison with patients receiving pamidronate.
Analiżi ta ’ ħafna avvenimenti f’ daqqa wrew tnaqqis sinifikanti ta ’ 16% tar- riskju f’ pazjenti fuq kura b’ Zometa, meta mqabbla ma ’ pazjenti fuq pamidronate.
Efficacy results are provided in Table 4.
Riżultati li juru l- effikaċja ta ’ Zometa f’ dawn il- pazjenti jinsabu f’ Tabella 4.
Efficacy results (breast cancer and multiple myeloma patients)
Riżultati li juru l- effikaċja (pazjenti b’ kanċer fis- sider jew b’ majeloma multipla)
Any SRE (+TIH)
Kwalunkwe SRE (+TIH)
Fractures*
Ksur *
Radiation therapy to bone
Terapija ta ’ l- għadam bir- radjazzjoni
Pam 90 mg Zometa Pam Zome
Pam Zometa
Zometa
Pam
Pam 90 mg Zometa Pam Zome
Zometa Pam
Zometa Pam 90 mg Zometa Pam Zometa
90 mg
N Proportion of patients with SREs (%)
N Proporzjon ta ’ pazjenti b’ SREs (%)
555 561 52 37
561 37
0.198
0. 198
0.653
0. 653
0.037
0. 037
NR
MM
0.151
0. 151
0.672
0. 672
0.026
0. 026
1.04
1. 39
1.39 0.53
0. 53
0.47
0. 47
0.084
0. 084
0.614
0. 614
0.015
0. 015
0.030
0. 030
* Includes vertebral and non-vertebral fractures ** Accounts for all skeletal events, the total number as well as time to each event during the trial NR Not Reached NA Not Applicable
* Jinkludi ksur fl- għadam tas- sinsla tad- dahar kif ukoll band’ oħra ** Jagħti kont għall- avvenimenti skeletrali kollha, kemm in- numru totali kif ukoll il- ħin sa ma seħħ kull avveniment tul il- prova MM Mhux Milħuq MA Mhux Applikabbli
Zometa was also studied in a double-blind, randomised, placebo-controlled trial in 228 patients with documented bone metastases from breast cancer to evaluate the effect of Zometa on the skeletal related event (SRE) rate ratio, calculated as the total number of SRE events (excluding hypercalcaemia and adjusted for prior fracture), divided by the total risk period.
Zometa kien studjat ukoll fi prova double- blind, randomised, kontrollata bi plaċebo f’ 228 pazjent b’ metastasi ta ’ l- għadam dokumentata minn kanċer tas- sider sabiex ikun evalwat l- effett ta ’ Zometa fuq ir- rata tal- proporzjon tal- każijiet relatati ma ’ l- għadam (SRE), kalkulat bħala n- numru totali ta ’ każijiet ta ’ SRE (bl- esklużjoni ta ’ iperkalċimja u rranġata għall- qabel il- ksur), diviż mat- totali tal - perijodu ta ’ riskju.
Patients received either 4 mg Zometa or placebo every four weeks for one year.
Il- pazjenti jirċievu jew 4 mg Zometa jew plaċebo kull erba ’ ġimgħat għal sena.
Patients were evenly distributed between Zometa-treated and placebo groups.
Il - pazjenti kienu mqassmin l- istess fil- grupp ikkurat b’ Zometa u dak bi plaċebo.
The SRE rate (events/ person year) was 0.628 for Zometa and 1.096 for placebo.
Ir- rata ta ’ SRE (każijiet/ sena persuna) kienet 0. 628 għal Zometa u 1. 096 għall- plaċebo.
The proportion of patients with at least one SRE (excluding hypercalcaemia) was 29.8% in the Zometa-treated group versus 49.6% in the placebo group (p=0.003).
Il- proporzjon ta ’ pazjenti b’ għalmenu SRE wieħed (bl- esklużjoni ta ’ iperkalċimja) kienet 29. 8% fil- grupp ikkurat b’ Zometa kontra 49. 6% fil- grupp tal- plaċebo (p=0. 003).
Median time to onset of the first SRE was not reached in the Zometa-treated arm at the end of the study and was significantly prolonged compared to placebo (p=0.007).
Iż- żmien medjan sabiex beda l- ewwel SRE ma ntlaħaqx fil- fergħa kkurata b’ Zometa meta ntemm l- istudju u kien imtawwal b’ mod sinifikanti meta mqabbel mal- plaċebo (p=0. 007).
Zometa reduced the risk of SREs by 41% in a multiple event analysis (risk ratio=0.59, p=0.019) compared with placebo.
Zometa naqqas ir- riskju ta SRE’ s b’ 41% f’ analiżi ta ’ ħafna avveniment (proporzjon tar- riskju=0. 59, p=0. 019) meta mqabbel mal- plaċebo.
In the Zometa-treated group, statistically significant improvement in pain scores (using the Brief Pain Inventory, BPI) was seen at 4 weeks and at every subsequent time point during the study, when compared to placebo (Figure 1).
Fil- grupp ikkurat b’ Zometa, titjib statistikament sinifikanti fil- punteġġi ta ’ l- uġigħ (permezz tal- Brief Pain Inventory, BPI) deher mar- 4 ġimgħat u ma ’ kull punt sussegwenti waqt l- istudju, meta mqabbel mal- plaċebo (Figura 1).
The pain score for Zometa was consistently below baseline and pain reduction was accompanied by a trend in reduced analgesics score.
Il- punteġġ ta ’ l- uġigħ għal Zometa kien taħt il- linja bażi b’ mod konsistenti u tnaqqis fl- uġigħ kellu tendenza li jġib miegħu tnaqqis fil- punteġġ ta ’ anaġelżiċi.
Mean changes from baseline in BPI scores.
Medja tal- bidliet mill- linja bażi fil- punteġġi BPI.
Statistically significant differences are marked (*p < 0.05) for between treatment comparisons (Zometa vs.
Differenzi statistikament sinifikanti huma mmarkati (* p < 0. 05) għat- tqabbil bejn kura u oħra.
Placebo)
(Zometa vs Plaċebo)
Placebo ∆ Zometa BPI mean change from baseline
Plaċebo ∆ Tibdil fil- medja tal- BPI mill- linja bażi
Time on study (weeks)
Zometa
Clinical trial results in the treatment of TIH Clinical studies in tumour-induced hypercalcaemia (TIH) demonstrated that the effect of zoledronic acid is characterised by decreases in serum calcium and urinary calcium excretion.
Risultati ta ’ provi kliniċi fil- kura ta ’ TIH Studji kliniċi ta ’ żieda fil- livell ta ’ calcium fid- demm minħabba tumuri (TIH) wrew li l- effett ta ’ zoledronic acid huwa karatterizzat minn tnaqqis ta ’ calcium fis- serum u tnaqqis fl- eskrezzjoni urinarja ta ’ calcium.
In Phase I dose finding studies in patients with mild to moderate tumour-induced hypercalcaemia (TIH), effective doses tested were in the range of approximately 1.2– 2.5 mg.
Fi studji ta ’ Fazi I għat- tfittxija tad- doża li għandha tingħata f’ pazjenti b’ TIH ta ’ grad ħafif sa moderat, id- dożi effettivi li ġew ittestjati kienu fil- medda ta ’ madwar 1. 2– 2. 5 mg.
To assess the effects of Zometa versus pamidronate 90 mg, the results of two pivotal multicentre studies in patients with TIH were combined in a pre-planned analysis.
Biex jiġu evalwati l- effetti ta ’ Zometa mqabbla ma ’ dawk ta ’ pamidronate 90 mg, ir- riżultati ta ’ żewġ studji pivitali multiċentriċi f’ pazjenti b’ TIH ġew ikkombinati f’ analiżi ippjanata minn qabel.
There was faster normalisation of corrected serum calcium at day 4 for Zometa 8 mg and at day 7 for Zometa 4 mg and 8 mg.
Il- livelli ta ’ calcium fis- serum ikkoreġut, marru lura għan- normal b’ pass aktar mgħaġġel fir- raba ’ jum b’ Zometa 8 mg u fis- seba ’ jum b’ Zometa 4 mg u 8 mg.
The following response rates were observed:
Ir- rati ta ’ rispons li ġejjin ġew osservati:
Proportion of complete responders by day in the combined TIH studies
Proporzjon ta ’ pazjenti li rrispondew kompletament għall- kura skond il- ġurnata fl- istudji kkombinati ta ’ TIH
Day 4
4 Ġurnata
Day 7
7 Ġurnata
Day 10
10 Ġurnata
Zometa 4 mg (N=86) Zometa 8 mg (N=90) Pamidronate 90 mg (N=99)
Zometa 4 mg (N=86) Zometa 8 mg (N=90) Pamidronate 90 mg (N=99)
45.3% (p=0.104) 55.6% (p=0.021)* 33.3%
45. 3% (p=0. 104) 55. 6% (p=0. 021) * 33. 3%
82.6% (p=0.005)* 83.3% (p=0.010)* 63.6%
82. 6% (p=0. 005) * 83. 3% (p=0. 010) * 63. 6%
88.4% (p=0.002)* 86.7% (p=0.015)* 69.7%
88. 4% (p=0. 002) * 86. 7% (p=0. 015) * 69. 7%
*p-values compared to pamidronate.
* Valur- p imqabbla ma ’ pamidronate
Median time to normocalcaemia was 4 days.
Iż- żmien medjan li ħa l- livell ta ’ calcium fid- demm biex mar lura għan- normal kien 4 ijiem.
Median time to relapse (re-increase of albumin-corrected serum calcium ≥ 2.9 mmol/ l) was 30 to 40 days for patients treated with Zometa versus 17 days for those treated with pamidronate 90 mg (p-values:
Iż- żmien medjan biex jerġa ’ jogħla (livell ta ’ kaljċu fis- serum ikkoreġut għall- albumina reġa ’ tela ’ għal - ≥ 2. 9 mmol/ l) kien ta ’ 30 sa 40 ġurnata għall- pazjenti fuq kura b’ Zometa kontra 17- il ġurnata f’ pazjenti li kienu fuq pamidronate 90 mg (valuri- p:
0.001 for 4 mg and 0.007 for 8 mg).
0. 001 għal 4 mg u 0. 007 għal 8 mg).
There were no statistically significant differences between the two Zometa doses.
Ma kienx hemm differenzi statistikament rilevanti bejn iż- żewġ dożi ta ’ Zometa.
In clinical trials 69 patients who relapsed or were refractory to initial treatment (Zometa 4 mg, 8 mg or pamidronate 90 mg) were retreated with Zometa 8 mg.
F’ provi kliniċi, 69 pazjent li rkadew jew ma kellhomx effett bl- ewwel kura (b’ Zometa 4 mg, 8 mg jew pamidronate 90 mg), reġgħu ngħataw Zometa 8 mg.
The response rate in these patients was about 52%.
Ir- rata ta ’ rispons f’ dawn il- pazjenti kienet ta ’
Since those patients were retreated with the 8 mg dose only, there are no data available allowing comparison with the 4 mg dose.
Billi dawk il- pazjenti reġgħu ngħataw kura b’ doża ta ’ 8 mg biss, m’ hemmx tagħrif biex ikun jista ’ jitqabbel ma ’ rispons għal doża ta ’ 4 mg.
12 In clinical trials performed in patients with tumour-induced hypercalcaemia (TIH), the overall safety profile amongst all three treatment groups (zoledronic acid 4 and 8 mg and pamidronate 90 mg) was similar in types and severity.
Fi provi kliniċi fuq pazjenti b’ żieda fil- livell tal- calcium fid- demm minħabba tumuri (TIH), il- profil ta ’ sigurtà fost it- tliet gruppi ttrattati (zoledronic acid 4 mg u zoledronic acid 8 mg u pamidronate) kien ta ’ l- istess mill- lat ta ’ tipi u severità.
Single and multiple 5- and 15-minute infusions of 2, 4, 8 and 16 mg zoledronic acid in 64 patients with bone metastases yielded the following pharmacokinetic data, which were found to be dose independent.
Infużjonijiet ta ’ darba jew multipli fuq medda ta ’ 5- minuti u 15- il minuta, u f’ dożi ta ’ 2, 4, 8, u 16 mg ta ’ zoledronic acid f’ 64 pazjent b’ metastasi fl- għadam, taw tagħrif farmakokinetiku hekk kif ġej, u li nstab li ma kienux jiddependu fuq id- doża.
After initiating the infusion of zoledronic acid, the plasma concentrations of drug rapidly increased, 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 prior to the second infusion of drug on day 28.
Wara li nbdiet l- infużjoni ta ’ zoledronic acid, il- konċentrazzjoni tal- mediċina fil- plażma telgħet malajr ħafna u laħqet l- ogħla livelli ma ’ tmiem l- infużjoni u minn hemm ’ l quddiem naqset malajr għal < 10% ta ’ l- ogħla livelli wara 4 sigħat u < 1% ta ’ l- għola livell wara 24 siegħa, u wara dan kien hemm perijodu twil fejn il- konċentrazzjoni kienet baxxa ħafna, mhux aktar minn 0. 1% ta ’ l- ogħla livell sa ma kienet tmiss it- tieni infużjoni fit- 28 jum.
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 mill- ġisem bi proċess li fih tliet fażijiet: proċess mgħaġġel b’ żewġ fażijiet li jneħħi l- mediċina miċ- ċirkolazzjoni sistemika, b’ half- lives ta ’ t1/ 2α0. 24 u t/ 2β 1. 87 sigħat, segwit minn fażi ta ’ eliminazzjoni twila b’ half- life ta ’ eliminazzjoni terminali ta ’ t/ 2γ 146 sigħat.
There was no accumulation of drug in plasma after multiple doses of the drug given every 28 days.
Ma kien hemm l- ebda akkumulazzjoni tal- mediċina fil- plażma wara dożi multipli tal - mediċina mogħtija kull 28 ġurnata.
Zoledronic acid is not metabolised and is excreted unchanged via the kidney.
Zoledronic acid ma jiġix metabolizzat u jiġi eliminat fi stat mhux mibdul 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 mogħtija tiġi rkuprata fl- awrina, filwaqt li l- bqijja tkun fil- parti l- kbira marbuta mat- tessut ta ’ l- għadam.
From the bone tissue it is released very slowly back into the systemic circulation and eliminated via the kidney.
Mit- tessut ta ’ l- għadam jitħalla jmur lura bil- mod ħafna għal ġoċ- ċirkolazzjoni sistemika u minn hemm jiġi eliminat mill- kliewi.
The total body clearance is 5.04 ± 2.5 l/ h, independent of dose, and unaffected by gender, age, race, and body weight.
It- tneħħija totali mill- ġisem hija ta ’ 5. 04 ± 2. 5 l/ h, indipendenti mid- doża, u mhix affettwata minn sess, età, razza u piż tal- ġisem.
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.
Żieda fil- ħin ta ’ l- infużjoni minn 5 għal 15- il minuta, ikkawżat tnaqqis ta ’ 30% fil - konċentrazzjoni ta ’ zoledronic acid fi tmiem l- infużjoni, iżda ma kellha l- ebda effett fuq l- erja taħt il - kurva ta ’ konċentrazzjoni fil- plażma kontra l- ħin.
The interpatient variability in pharmacokinetic parameters for zoledronic acid was high, as seen with other bisphosphonates.
Bħal ma jiġri fil- każ ta ’ bisphosphonates oħrajn, il- varjabbiltà minn pazjent għal ieħor f’ parametri farmakokinetiċi għal zoledronic acid kienet għolja.
No pharmacokinetic data for zoledronic acid are available in patients with hypercalcaemia or in patients with hepatic insufficiency.
M’ hemm l- ebda tagħrif farmakokinetiku għal pazjenti li għandhom żieda fil- livell ta ’ calcium fid - demm jew li għandhom insuffiċjenza tal- fwied.
Zoledronic acid does not inhibit human P450 enzymes in vitro, shows no biotransformation and in animal studies < 3% of the administered dose was recovered in the faeces, suggesting no relevant role of liver function in the pharmacokinetics of zoledronic acid.
Zoledronic acid ma jimpedixxix l- enzimi tal- bniedem P450 in vitro, ma jurix biotrasformazzjoni, u fi studji li saru fuq annimali, < 3% tad- doża mogħtija nstabet fl- ippurgar li jissuġġerixxi li l- funzjoni tal- fwied ftit li xejn għandha rwol rilevanti fil - farmakokinetiċi ta ’ zoledronic acid.
The renal clearance of zoledronic acid was correlated with creatinine clearance, renal clearance representing 75 ± 33% of the creatinine clearance, which showed a mean of 84 ± 29 ml/ min (range 22 to 143 ml/ min) in the 64 cancer patients studied.
It- tneħħijarenali ta ’ zoledronic acid ġiet korrelatata mat- tneħħija ta ’ krejatinina bi tneħħija renali li tirrappreżenta 75 ± 33% tat- tneħħija tal- krejatinina, li wriet medja ta ’ 84 ± 29 ml/ min (minn 22 sa 143 ml/ min) fl- 64 pazjent bil- kanċer li kienu studjati.
Population analysis showed that for a patient with creatinine clearance of 20 ml/ min (severe renal impairment), or 50 ml/ min (moderate impairment), the corresponding predicted clearance of zoledronic acid would be 37% or 72%, respectively, of that of a patient showing creatinine clearance of 84 ml/ min.
Analiżi tal- popolazzjoni wriet li għal pazjenti bi tneħħija tal- krejatinina ta ’ 20 ml/ min (indeboliment sever tal- kliewi), jew 50 ml/ min (indeboliment moderat), it- tneħħija ta ’ zoledronic acid li jikkorrispondi kien imbassar li jkun 37% jew 72%, rispettivament meta mqabbla ma ’ pazjenti bi tneħħija tal- krejatinina ta ’ 84 ml/ min.
Only limited pharmacokinetic data are available in patients with severe renal insufficiency (creatinine clearance < 30 ml/ min).
Hemm biss tagħrif farmakokinetiku limitat f’ pazjenti b’ insuffiċjenza severa tal- kliewi (tneħħija tal- krejatinina < 30 ml/ min).
Zoledronic acid shows no affinity for the cellular components of blood and plasma protein binding is low (approximately 56%) and independent of the concentration of zoledronic acid.
Zoledronic acid ma juri l- ebda affinità għall- komponenti ċellulari tad- demm, u ftit li xejn jeħel mal - proteini tal- plażma (madwar 56%), tkun xi tkun il- konċentrazzjoni ta ’ zoledronic acid.
Acute toxicity The highest non-lethal single intravenous dose was 10 mg/ kg bodyweight in mice and 0.6 mg/ kg in rats.
Tossiċità akuta L- ogħla doża waħidha ġol- vini li ma wasslitx għall- mewt kienet ta ’ 10 mg/ kg piż tal- ġisem fil- ġrieden, u ta ’ 0. 6 mg/ kg fil- firien.
Subchronic and chronic toxicity Zoledronic acid was well tolerated when administered subcutaneously to rats and intravenously to dogs at doses up to 0.02 mg/ kg daily for 4 weeks.
Tossiċità sottokronika u kronika Zoledronic acid kien tollerat tajjeb meta ġie mogħti permezz ta ’ injezzjoni taħt il- ġilda fil- firien u ġol - vini fil- klieb f’ dożi mhux aktar minn 0. 02 mg/ kg kuljum għal erba ’ ġimgħat.
Administration of 0.001 mg/ kg/ day subcutaneously in rats and 0.005 mg/ kg intravenously once every 2– 3 days in dogs for up to 52 weeks was also well tolerated.
Kienu tollerati tajjeb ukoll dożi ta ’ 0. 001 mg/ kg/ jum mogħtija taħt il- ġilda fil- firien u ta ’ 0. 005 mg/ kg ġol- vini fil- klieb darba kull 2– 3 jiem sa 52 ġimgħa.
13 The most frequent finding in repeat-dose studies consisted of increased primary spongiosa in the metaphyses of long bones in growing animals at nearly all doses, a finding that reflected the compound’ s pharmacological antiresorptive activity.
Studji b’ dożi ripetuti wrew ta ’ spiss li kien hemm żieda fl- ammont ta ’ sponġoża primarja fil- metafiżi ta ’ l- għadam twil f’ annimali li jkunu għadhom qed jiżviluppaw u għal kważi d- dożi kollha, sejba li tirrifletti li din is- sustanza għandha effett farmakoloġiku li timpedixxi r- risorbiment.
The safety margins relative to renal effects were narrow in the long-term repeat-dose parenteral animal studies but the cumulative no adverse event levels (NOAELs) in the single dose (1.6 mg/ kg) and multiple dose studies of up to one month (0.06– 0.6 mg/ kg/ day) did not indicate renal effects at doses equivalent to or exceeding the highest intended human therapeutic dose.
Fi studji fl- annimali fuq tul ta’ żmien b’ dożi parenterali ripetuti, il- marġini tas- sigurtà relattivi ma ’ l - effetti fil- kliewi kienu żgħar imma l- livelli kumulattivi ta ’ mingħajr avvenimenti avversi (NOAELs) fi studji b’ doża waħda (1. 6 mg/ kg) u studji b’ dożi multipli meħudin sa xahar (0. 06– 0. 6 mg/ kg/ jum) ma ndikawx effetti fil- kliewi f’ dożi ekwivalenti għal jew għola mill- ogħla dożi terapewtiċi intenzjonati għall- bniedem.
Longer-term repeat administration at doses bracketing the highest intended human therapeutic dose of zoledronic acid produced toxicological effects in other organs, including the gastrointestinal tract, liver, spleen and lungs, and at intravenous injection sites.
L- għotja ripetuta tal- mediċina fuq żmien itwal b’ dożi li laħqu l- ogħla doża terapewtika ta ’ zoledronic acid intenzjonata għall- bniedem ikkawżat effetti tossikoloġiċi f’ organi oħrajn, inkluż fis- sistema gastro- intestinali, fil- fwied, fil- milsa u fil- pulmun, u fil- postijiet minn fejn ikunu ngħataw l- injezzjoniet ġol- vini.
Reproduction toxicity Zoledronic acid was teratogenic in the rat at subcutaneous doses ≥ 0.2 mg/ kg.
Tossiċità fis- sistema riproduttiva Zoledronic acid kellu effetti teratoġeniċi meta ġie mogħti taħt il- ġilda fil- far b’ dożi ta ’ ≥ 0. 2 mg/ kg.
Although no teratogenicity or foetotoxicity was observed in the rabbit, maternal toxicity was found.
Għalkemm ma kienx hemm teratoġeniċità u tossiċità tal- fetu fil- fniek, ġew osservati effetti tossiċi fl - omm.
Dystocia was observed at the lowest dose (0.01 mg/ kg bodyweight) tested in the rat.
Uġigħ tal- ħlas deher bl- aktar doża baxxa (0. 01 mg/ kg piż tal- ġisem) ittestjat fil- far.
Mutagenicity and carcinogenic potential Zoledronic acid was not mutagenic in the mutagenicity tests performed and carcinogenicity testing did not provide any evidence of carcinogenic potential.
Potenzjal mutaġenetiku u karċinoġeniku Zoledronic acid ma kienx mutaġenetiku f’ testijiet għall- mutaġeniċità, filwaqt li testijiet għall - karċinoġeniċità ma ndikawx li għandu potenzjal karċinoġeniku.
Powder vial:
Kunjett bit- trab:
Mannitol Sodium citrate
Mannitol Sodium citrate
Solvent ampoule:
Ampulla bis- solvent:
To avoid potential incompatibilities, Zometa reconstituted solution is to be diluted with 0.9% w/ v sodium chloride solution or 5% w/ v glucose solution.
Biex wieħed jevita inkompatibilitajiet potenzjali, is- soluzzjoni rikostitwita ta ’ Zometa għandha tiġi ddilwita b’ 0. 9% w/ v soluzzjoni ta ’ sodium chloride jew b’ 5% w/ v soluzzjoni ta ’ glucose.
Zometa reconstituted solution must not be mixed with calcium or other divalent cation-containing infusion solutions such as lactated Ringer’ s solution, and should be administered as a single intravenous solution in a separate infusion line.
Is- soluzzjoni rikostitwita ta ’ Zometa m’ għandhiex tiġi mħallta ma ’ soluzzjonijiet oħra li jkun fihom calcium jew ma ’ soluzzjonijiet oħra li jingħataw minn ġol- vina bħal soluzzjoni lactated Ringer, u għandha tingħata bħala soluzzjoni waħda minn ġol- vina f’ linja ta ’ infużjoni separata.
Studies with glass bottles, as well as several types of infusion bags and infusion lines made from polyvinylchloride, polyethylene and polypropylene (prefilled with 0.9% w/ v sodium chloride solution or 5% w/ v glucose solution), showed no incompatibility with Zometa.
Studji bi fliexken tal- ħġieg, u b’ tipi differenti ta ’ boroż u pajpijiet ta ’ l- infużjonijiet magħmulin minn polyvinylchloride, polyethylene u polypropylene (mimlijin minn qabel b’ 0. 9% w/ v soluzzjoni ta ’ sodium chloride jew b’ 5% w/ v soluzzjoni ta ’ glucose), ma wrew l- ebda inkompatibilità ma ’ Zometa.
6.3 Shelf life
14 6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
The reconstituted solution is chemically and physically stable for 24 hours at 2°C – 8°C.
Wara r- rikostituzzjoni s- soluzzjoni tibqa stabbli kimikament u fiżikament għal 24 siegħa f’ temperatura ta ’ 2°C – 8°C.
No special precautions for storage.
L- ebda prekawzjonijiet speċjali għall- ħażna.
After aseptic reconstitution and dilution, it is preferable to use the reconstituted and diluted product immediately.
Wara li jiġi rikostitwit u ddilwit taħt kundizzjonijiet asettiċi, l- prodott rikostitwit u ddilwit għandu preferibbilment jintuża minnufih.
If not used immediately, the duration and conditions of storage prior to use are the user’ s responsibility.
Jekk ma jintużax mill- ewwel, iż- żmien li jdum maħżun u l - kundizzjonijiet li fihom jinħażen qabel ma jintuża huma r- risponsabbiltà ta ’ min ser jużah.
The total time between reconstitution, dilution, storage in a refrigerator at 2°C – 8°C and end of administration must not exceed 24 hours.
Il- ħin totali minn mindu jitħallat, jiġi ddilwit u jkun maħżun fil- friġġ f’ temperatura ta ’ bejn 2°C – 8°C, sa ma tintemm l- għotja tad- doża m’ għandux ikun aktar minn 24 siegħa.
Zometa 4 mg powder for solution for infusion is supplied as packs containing 1, 4 or 10 vials and 1, 4 or 10 ampoules of water for injections, respectively.
Zometa 4 mg trab għal soluzzjoni għall- infużjoni jiġi f’ paketti ta ’ 1, 4 jew 10 kunjetti flimkien ma 1, 4, jew 10 ampulli ta ’ ilma għall- injezzjonijiet, rispettivament.
Powder vial:
Kunjett tat- trab:
6-ml colourless glass vial, hydrolytic glass type I (Ph.
6- ml kunjett tal- ħġieġ bla- kulur, magħmula minn ħġieġ idrolitiku tat- tip I (Ph.
Solvent ampoule:
Ampulla tas- solvent:
5-ml colourless glass ampoule.
5- ml ampulla magħmula minn ħġieġ bla kulur.
The powder must first be reconstituted in the vial using 5 ml water for injections from the ampoule supplied.
It- trab għandu l- ewwel jiġi rikostitwit fil- kunjett b’ 5 ml ilma għall- injezzjonijiet mill- ampulla pprovduta.
Dissolution must be complete before the solution is withdrawn.
It- trab irid ikun inħall għall- kollox qabel ma tinħareġ is- soluzzjoni minn ġol- kunjett.
The amount of reconstituted solution as required is then further diluted with 100 ml of calcium-free infusion solution (0.9% w/ v sodium chloride solution or 5% w/ v glucose solution).
Is - soluzzjoni rikostitwita terġa mbagħad tiġi ddilwita b’ 100 ml soluzzjoni għall- infużjoni li ma jkunx fiha calcium (0. 9% w/ v soluzzjoni ta ’ sodium chloride jew 5% w/ v soluzzjoni ta ’ glucose).
If refrigerated, the solution must be allowed to reach room temperature before administration.
Jekk it - taħlita tinżamm fil- friġġ, din għandha titħalla tilħaq it- temperatura ambjentali qabel ma tingħata.
20.03.2001 Date of first renewal:
20. 03. 2001 Data ta ’ l- ewwel tiġdid:
Zometa 4 mg/ 5 ml concentrate for solution for infusion
Zometa 4 mg/ 5 ml konċentrat għal soluzzjoni għall- infużjoni
One vial with 5 ml concentrate contains 4 mg zoledronic acid (anhydrous).
Kunjett wieħed fih 5 ml konċentrat li fih 4 mg zoledronic acid (anhydrous).
One ml concentrate contains zoledronic acid (as monohydrate) corresponding to 0.8 mg zoledronic acid (anhydrous).
Millilitru 1 tal- konċentrat ta ’ zoledronic acid huwa ekwivalenti għal 0. 8 mg zoledronic acid (anhydrous).
Zometa concentrate must not be mixed with calcium or other divalent cation-containing infusion solutions such as lactated Ringer’ s solution, and should be administered as a single intravenous solution in a separate infusion line.
Il- konċentrat ta ’ Zometa m’ għandhiex tiġi mħallta ma ’ soluzzjonijiet oħra li jkun fihom calcium jew ma ’ soluzzjonijiet oħra li jingħataw minn ġol- vina bħal soluzzjoni lactated Ringer, u għandha tingħata bħala soluzzjoni waħda minn ġol- vina f’ linja ta ’ infużjoni separata.
Prevention of skeletal related events in patients with advanced malignancies involving bone Adults and elderly The recommended dose in the prevention of skeletal related events in patients with advanced malignancies involving bone is 4 mg zoledronic acid.
Prevenzjoni ta ’ problemi skeletrali f’ pazjenti b’ kanċer avvanzat li qed jinvolvi l- għadam Adulti u anzjani Id- doża rakkomandata għall- prevenzjoni ta ’ problemi skeletrali f’ pazjenti b’ kanċer avvanzat li jinvolvi l- għadam hija ta ’ 4 mg zoledronic acid.
The concentrate must be further diluted with 100 ml sterile 0.9% w/ v sodium chloride or 5% w/ v glucose solution and given in no less than a 15- minute intravenous infusion every 3 to 4 weeks.
Il- konċentrat jerġa ’ mbagħad jiġi ddilwit b’ 100 ml ta ’ 0. 9% w/ v sodium chloride sterili jew 5% w/ v soluzzjoni ta ’ glucose u mogħtija bħala infużjoni ġol- vini fuq medda ta ’ mhux inqas minn 15- il minuta kull 3 jew 4 gimgħat.
Treatment of TIH Adults and elderly The recommended dose in hypercalcaemia (albumin-corrected serum calcium ≥ 12.0 mg/ dl or 3.0 mmol/ l) is 4 mg zoledronic acid.
Kura ta ’ TIH Adulti u anzjani Id- doża rakkomandata għal kura ta ’ calcium għoli fid- demm (livell ta ’ calcium fis- serum ikkoregut għall- albumina ≥12. 0 mg/ dl jew 3. 0 mmol/ l) hija ta ’ 4 mg zoledronic acid.
The concentrate must be further diluted with 100 ml sterile 0.9% w/ v sodium chloride or 5% w/ v glucose solution and given as a single intravenous infusion in no less than 15 minutes.
Il- konċentrat jerġa mbagħad jiġi ddilwit b’ 100 ml ta ’ 0. 9% w/ v sodium chloride sterili jew 5% w/ v soluzzjoni ta ’ glucose u mogħtija bħala infużjoni ġol- vini ta ’ darba fuq medda ta ’ 15- il minuta.
16 Renal impairment TIH:
16 Indeboliment tal- kliewi TIH:
Instructions for preparing reduced doses of Zometa Withdraw an appropriate volume of the concentrate needed, as follows:
Istruzzjonijiet biex tipprepara dożi imnaqqsa ta ’ Zometa Iġbed volum xieraq tal- konċentrat meħtieġ (4 mg/ 5 ml) kif imiss:
The withdrawn amount of concentrate must be further diluted in 100 ml of sterile 0.9% w/ v sodium chloride solution or 5% w/ v glucose solution.
L- ammont miġbud tal- konċentrat għandu jiġi dilwit f’ 100 ml ta ’ soluzzjoni sterili ta ’ 0. 9% w/ v sodium chloride jew 5% w/ v soluzzjoni ta ’ glucose.
17 4.3 Contraindications
17 4. 3 Kontra- indikazzjonijiet
Zometa concentrate is contraindicated in breast-feeding women and in patients with clinically significant hypersensitivity to zoledronic acid, other bisphosphonates or any of the excipients in the formulation of Zometa.
Il- konċentrat ta ’ Zometa għall- infużjoni m’ għandux jintuża f’ nisa li qed ireddgħu u f’ pazjenti b’ sensitività eċċessiva klinikament sinifikanti għal zoledronic acid, bisphosphonates oħrajn jew sustanżi oħrajn mhux attivi fil- formulazzjoni ta’ Zometa.
Hepatic insufficiency As only limited clinical data are available in patients with severe hepatic insufficiency, no specific recommendations can be given for this patient population.
18 Insuffiċjenza epatika Billi hemm tagħrif kliniku limitat dwar pazjenti b’ insuffiċjenza severa tal- fwied, ma jistgħux jingħataw rakkomandazzjonijiet speċifiċi f’ dan il- grupp ta ’ pazjenti.
18 Osteonecrosis of the jaw Osteonecrosis of the jaw has been reported in patients, predominantly those with cancer, receiving treatment with bisphosphonates, including Zometa.
Osteonekrożi tax- xedaq Osteonekrożi tax- xedaq kienet rappurtat f’ pazjenti, l- aktar dawk b’ kanċer li jkunu qed jirċievu kuri bi bisphosphonates, inkluż Zometa.
Zometa is contraindicated in breast-feeding women (see section 4.3).
Zometa huwa kontraindikat f’ nisa li qed ireddgħu (ara sezzjoni 4. 3).
4.7 Effects on ability to drive and use machines
19 4. 7 Effetti fuq il- ħila biex issuq jew tħaddem magni
19 commonly associated with a flu-like syndrome in about 9% of patients, including bone pain (9.1%), fever (7.2%), fatigue (4.1%) and rigors (2.9%).
L- għoti ġol - vini ġie assoċjat l- aktar ma ’ sintomi bħal ta ’ l- influwenza f’ 9% tal- pazjenti, u jinkludu uġigħ fl - għadam (9. 1%), deni (7. 2%), għejja (4. 1%) u tertir (2. 9%).