qanastek/EMEA-V3 huggingface dataset:
Data support continuous treatment with Preotact for up to 24 months (see section 4.4).
L- informazzjoni ssostni trattament kontinwu bi Preotact sa perjodu ta ’ 24 xahar (ara sezzjoni 4. 4).
Following treatment with Preotact patients can be treated with a bisphosphonate to further increase bone mineral density (see section 5.1).
Wara l- kura bi Preotact il- pazjenti jistgħu jiġu ttrattati b’ bisphosphonate biex iżidu aktar id- densità tal - minerali fl- għadam (ara sezzjoni 5. 1).
2 Specific populations Renal impairment No dose adjustment is necessary in patients with mild to moderate renal impairment (creatinine clearance 30 to 80 ml/ min).
2 Popolazzjonijiet speċifiċi Indeboliment renali M’ hemmx bżonn ta ’ aġġustament fid- doża f’ pazjenti b’ indeboliment renali ħafif għal moderat (tneħħija tal- kreatinina ta ’ 30 sa 80 ml/ min).
There is no data available in patients with severe renal impairment.
M’ hemmx informazzjoni disponibbli dwar pazjenti b’ indeboliment sever renali.
Preotact should therefore not be used in patients with severe renal impairment (see section 4.3).
Preotact għalhekk m’ għandux jintuża f’ pazjenti b’ indeboliment sever renali (ara sezzjoni 4. 3).
Hepatic impairment No dose adjustment is needed for patients with mild or moderate hepatic impairment (total score of 7 to 9 on the Child-Pugh scale).
Indeboliment epatiku M’ hemmx bżonn ta ’ aġġustament fid- doża għal pazjenti b’ indeboliment epatiku ħafif għal moderat (punteġġ totali ta ’ 7 sa 9 fuq l- iskala Child- Pugh).
There is no data available in patients with severe hepatic impairment.
M’ hemmx informazzjoni disponibbli dwar pazjenti b’ indeboliment epatiku sever.
Preotact should therefore not be used in patients with severe hepatic impairment (see section 4.3).
Preotact għalhekk m’ għandux jintuża f’ pazjenti b’ indeboliment epatiku sever (ara sezzjoni 4. 3).
Children and adolescents The safety and efficacy of Preotact in patients under 18 years have not been studied.
Tfal u adoloxxenti Is- sigurtà u l- effikaċja ta ’ Preotact f’ pazjenti ta ’ taħt it- 18- il sena ma ġewx studjati.
Preotact should not be used in paediatric patients or young adults.
Preotact m’ għandux jintuża f’ pazjenti pedjatriċi jew żgħażagħ.
Elderly Dose adjustment based upon age is not required (see section 5.2).
Anzjani M’ hemmx bżonn ta ’ aġġustament fid- doża bbażat fuq l- età.
Preotact is contraindicated in patients • with hypersensitivity to parathyroid hormone or to any of the excipients (see section 6.1) • who have previously received radiation therapy to the skeleton • with pre-existing hypercalcemia and other disturbances in the phosphocalcic metabolism • with metabolic bone diseases other than primary osteoporosis (including hyperparathyroidism and Paget’ s disease of the bone) • with unexplained elevations of bone-specific alkaline phosphatase • with severe renal impairment • with severe hepatic impairment
Preotact huwa kontra- indikat f’ pazjenti • b’ sensittività eċċessiva għall- ormon tal- paratirojde jew għal xi sustanzi mhux attivi (ara sezzjoni 6. 1) • li qabel irċevew terapija bir- radjazzjoni fl- iskeletru • b’ iperkalċimja diġà eżistenti u disturbi oħra fil- metaboliżmu tal- kalċju u l- fosfru • b’ mard metaboliku ta ’ l- għadam differenti minn osteoporożi primarja (fosthom iperparatirojdiżmu u l- marda ta ’ l- għadam ta ’ Paget) • b’ livelli għolja mhux spjegati ta ’ alkaline phosphatase speċifiku għall- għadam • b’ indeboliment sever renali • b’ indeboliment epatiku sever
Patients initiated on Preotact therapy should be monitored at months 1, 3 and 6 for elevated levels of serum and/ or urinary calcium.
Il- pazjenti mibdija fuq terapija bi Preotact għandhom jiġu mmonitorjati fl- 1, it- 3 u s- 6 xahar għal livelli għoljin ta ’ kalċju fis- serum u/ jew fl- awrina.
Monitoring beyond 6 months is not recommended for patients whose total serum calcium is within the normal limits at 6 months.
Mhuwiex rakkomandat monitoraġġ lil hinn minn 6 xhur għal pazjenti li l- kalċju totali fis- serum tagħhom ikun fil- limiti normali wara 6 xhur.
Elevated serum calcium was observed during Preotact treatment.
Kien osservat livell għoli ta ’ kalċju fis- serum matul it- trattament bi Preotact.
Serum calcium concentrations reach a maximum between 6 and 8 hours post dose and normally return to baseline by 20 to 24 hours after each administration of parathyroid hormone.
Il- konċentrazzjonijiet tal - kalċju fis- serum jilħqu l- massimu bejn 6 u 8 sigħat wara doża u normalment jirritornaw għal- linja bażi fi żmien 20 sa 24 siegħa wara kull għoti ta ’ ormon tal- paratirojde.
Therefore if any blood samples are taken from a patient for monitoring of calcium levels, this should be done at least 20 hours after the most recent injection.
Għalhekk, jekk jittieħdu xi kampjuni tad- demm minn pazjent sabiex jiġu mmonitorjati l- livelli tal- kalċju, dan għandu jsir talanqas 20 siegħa wara l- aħħar injezzjoni.
Management of elevated serum calcium Patients with persistent elevated serum calcium (above the upper normal level) should be evaluated for underlying disease (e. g. hyperparathyroidism).
Ġestjoni ta ’ kalċju elevat fis- serum Pazjenti b’ livell ta ’ kalċju kontinwament għoli fis- serum (ogħla mil- livell normali ta ’ fuq) għandhom jiġu evalwati għal mard kawżali (p. e. iperparatirojdiżmu).
If no underlying condition is found, the following management procedures should be followed:
Jekk ma tinstab l- ebda kondizzjoni kawżali, għandhom jiġu segwiti l- proċeduri ta ’ ġestjoni li ġejjin:
Calcium and vitamin D supplementation should be withdrawn The frequency of Preotact dosing should be changed to 100 micrograms every other day If elevated levels continue, Preotact therapy should be stopped and the patient monitored until the abnormal values have reverted to normal
l- għoti supplimentari ta ’ kalċju u vitamina D għandu jiġi mwaqqaf • il- frekwenza tad- dożaġġ ta ’ Preotact għandha tinbidel għal 100 mikrogramm ġurnata iva u • oħra le jekk il- livelli għoljin jissoktaw, it- terapija bi Preotact għandha titwaqqaf u l- pazjent għandu • jiġi mmonitorjat sakemm il- valuri anormali jerġgħu lura għan- normal
Patients with pre-existing hypercalcemia and/or hypercalciuria Preotact has been studied in patients with pre-existing hypercalcemia and/or hypercalciuria.
Pazjenti b’ iperkalċimja u/ jew iperkalċurja diġà preżenti
3 Preotact has not been studied in patients with active urolithiasis.
3 Preotact ġie studjat f’ pazjenti b’ iperkalċimja u/ jew b’ iperkalċurja diġà eżistenti.
Preotact should be used with caution in patients with active or previous urolithiasis.
Preotact għandu jintuża b’ kawtela f’ pazjenti b’ urolitjasis attiva jew preċedenti.
Caution should be exercised in patients receiving cardiac glucosides (see section 4.5).
Trid tingħata attenzjoni għal dawk il- pazjenti li jkunu qegħdin jirċievu glukosidi kardijaċi (ara sezzjoni 4. 5).
Studies in rats indicate an increased incidence of osteosarcoma with long-term administration of Preotact (see section 5.3).
L- istudji fuq il- firien juru inċidenza akbar ta ’ osteosarkoma bl- għoti fuq perjodu fit- tul ta ’ Preotact (ara sezzjoni 5. 3).
The occurrence of osteosarcoma only occurred at doses that produced systemic exposures > 27-times higher than that observed in humans at the 100 micrograms dose.
L- okkorrenza ta ’ osteosarkoma seħħet biss f’ dożi li pproduċew espożizzjonijiet sistemiċi > 27 darba ogħla minn dawk osservati fil- bniedem bid- doża ta ’ 100 mikrogramma.
Until further clinical data becomes available the recommended treatment time of 24 months should not be exceeded.
Sakemm ikun hemm aktar informazzjoni klinika disponibbli, iż- żmien ta ’ kura rakkomandat ta ’ 24 xahar m’ għandux jinqabeż.
Preotact contains metacresol, which may cause allergic reactions.
Preotact fih metacresol, li jista ’ jikkawża reazzjonijiet allerġiċi.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose.
Dan il- prodott mediċinali fih anqas minn 1 mmol ta ’ sodju (23 mg) għal kull doża.
Parathyroid hormone is a natural peptide that is not metabolised by, and does not inhibit hepatic microsomal drug-metabolising enzymes (e.g. cytochrome P450 isoenzymes).
L- ormon tal- paratirojde huwa peptide naturali li ma jiġix metabolizzat minn, u ma jinibixxix enzimi mikrosomali epatiċi li jimmetabolizzaw il- mediċina (p. e. isoenzimi ta ’ cytochrome P450).
Furthermore, parathyroid hormone is not protein bound and has a low volume of distribution.
Barra minn hekk, l- ormon tal- paratirojde ma jaqbadx mal- proteini u għandu volum ta ’ distribuzzjoni baxx.
Consequently, no interaction with other medicinal products would be anticipated and no specific drug-drug interactions studies were performed.
Għalhekk, ma hija mistennija l- ebda interazzjoni ma ’ prodotti mediċinali oħra u ma saru l- ebda studji speċifiċi dwar l- interazzjonijiet bejn il- mediċini.
No potential for drug interactions was identified in the clinical program.
Ma ġie identifikat l- ebda potenzjal għal interazzjonijiet bejn il- mediċini fil- programm kliniku.
Combining parathyroid hormone with alendronate use has not been shown to provide any advantage over either form of treatment alone, when the end point of bone mineral density was evaluated.
It- taħlit ta ’ l- ormon tal- paratirojde ma ’ alendronate ma wera li jipprovdi l- ebda vantaġġ fuq xi forma ta ’ kura waħedha, meta kien evalwat l- end point tad- densità minerali fl- għadam.
(see section 5.1).
(ara sezzjoni 5. 1).
From the knowledge of the mechanism of action, combined use of Preotact and cardiac glucosides may predispose patients to digitalis toxicity if hypercalcemia develops.
Minn dak li huwa magħruf dwar il- mod ta ’ kif jaħdem, l- użu flimkien ta ’ Preotact u glukosidi kardijaċi jista ’ jippredisponi lill- pazjenti għal tossiċità mid- diġitalis jekk tiżviluppa l- iperkalċimja.
There are no data available from the use of parathyroid hormone during pregnancy and lactation.
M’ hemmx informazzjoni disponibbli mill- użu ta ’ l- ormon tal- paratirojde waqt it- tqala u t- treddigħ.
Animal studies of reproductive toxicity are incomplete (see section 5.3).
L - istudji fuq l- annimali dwar l- effett tossiku fuq is- sistema riproduttiva huma nkompleti (ara sezzjoni 5. 3).
Parathyroid hormone should not be used during pregnancy or breast-feeding.
L- ormon tal- paratirojde m’ għandux jintuża waqt it- tqala jew treddigħ.
As some episodes of dizziness have been described in patients treated with Preotact, patients should refrain from driving or using machines until symptoms have subsided.
Billi kienu deskritti xi episodji ta ’ sturdament f’ pazjenti kkurati bi Preotact, il- pazjenti għandhom jevitaw li jsuqu jew iħaddmu magni sakemm is- sintomi jgħaddu.
The following adverse reaction (ADR) data are based on two placebo-controlled studies involving 2642 postmenopausal osteoporotic women of whom 1341 received parathyroid hormone.
L- informazzjoni segwenti dwar ir- reazzjonijiet avversi (ADR) hija bbażata fuq żewġ studji kkontrollati bil- plaċebo li kienu jinvolvu 2642 mara ta ’ wara l- menopawsa b’ osteoporożi li minnhom 1341 irċevew l- ormon tal- paratirojde.
Approximately 71.4% of the patients on parathyroid hormone reported at least one ADR.
Madwar 71. 4% tal- pazjenti fuq l- ormon tal- paratirojde rrapportaw mill- anqas ADR wieħed.
Hypercalcemia and/or hypercalciuria reflect the known pharmacodynamic actions of parathyroid hormone in the gastrointestinal tract, the kidney, and the bone.
L- iperkalċimja kienet irrapportata
Hypercalcemia was reported in 25.3% of patients and hypercalciuria in 39.3% of patients treated with Preotact.
4 f’ 25. 3% tal- pazjenti u l- iperkalċurja f’ 39. 3% tal- pazjenti kkurati bi Preotact.
Hypercalcemia was transient and was reported most frequently in the first 3 months of treatment.
L- iperkalċimja kienet għaddiena u ġiet irrapportata bl- aktar mod frekwenti fl- ewwel 3 xhur tal- kura.
It was managed during the clinical programme by monitoring laboratory values and the use of a pre-specified management algorithm (see sections 4.3, 4.4, and 5.1).
Matul il- programm kliniku hija kienet ġestita bil- monitoraġġ tal- valuri tal- laboratorju u l- użu ta ’ proċeduri ta ’ ġestjoni stabbiliti minn qabel (ara sezzjoni 4. 3, 4. 4, u 5. 1).
The only other very commonly reported ADR was nausea.
L- uniku ADR ieħor irrapportat b’ mod komuni ħafna kien id- dardir.
4 The table below gives an overview of the ADRs where the incidence is at least 0.5% higher in the parathyroid hormone group compared to placebo.
It- tabella ta ’ hawn isfel tagħti ħarsa ġenerali ta ’ l- ADRs fejn l- inċidenza hija mill- anqas 0. 5% ogħla fil- grupp ta ’ l- ormon tal- paratirojde meta mqabbel mal- plaċebo.
The following categories are used to rank the undesirable effects by frequency of occurrence: very common (> 1/10); common (> 1/100 and < 1/10); uncommon (> 1/1000 and < 1/100); rare (> 1/10,000 and < 1/1000); and very rare (< 1/10,000), including isolated reports.
Il- kategoriji li ġejjin huma użati biex jikklassifikaw l- effetti mhux mixtieqa skond il- frekwenza ta ’ l- okkorrenza: komuni ħafna (> 1/ 10); komuni (> 1/ 100 u < 1/ 10); mhux komuni (> 1/ 1000 u < 1/ 100); rari (> 1/ 10, 000 u < 1/ 1000); u rari ħafna (< 1/ 10, 000), fosthom rapporti iżolati.
N=1341 (%) Infections and Infestations Uncommon Influenza
N=1341 (%) Infezzjonijiet u infestazzjonijiet Mhux komuni Influwenza
Metabolism and nutrition disorders Very common
Disturbi fil- metaboliżmu u n- nutrizzjoni Komuni ħafna
Hypercalcemia Common
Iperkalċimja Komuni
Blood calcium increased Uncommon
Żieda ta ’ kalċju fid- demm Mhux komuni Żieda ta ’ alkaline phosphatase fid -
Blood alkaline phosphatase increased Anorexia Blood uric acid increased
demm Anoreksja Żieda ta ’ l- aċidu uriku fid- demm
0.8 0.6 0.6
0. 8 0. 6 0. 6
Nervous system disorders Common Headache Dizziness Uncommon
Disturbi fis- sistema nervuża Komuni
9.3 3.9
9. 3 3. 9
Dysgeusia Parosmia
Togħma ħażina Parosmja
0.8 0.7
0. 8 0. 7
Cardiac disorders Common
Disturbi fil- qalb Komuni Palpitazzjonijiet
Palpitations
1. 0
1.0
Disturbi gastro- intestinali Komuni ħafna
Gastrointestinal disorders Very common Nausea Common
Dardir Komuni
13.5
13. 5
Vomiting Constipation Dyspepsia Diarrhoea Uncommon
Rimettar Stitikezza Dispepsja Dijarea Mhux komuni
2.5 1.8 1.3 1.0
2. 5 1. 8 1. 3 1. 0
Abdominal pain
Uġigħ addominali
Musculoskeletal, connective tissue and bone disorders Common Muscle cramp Pain in extremity Back pain
5 Disturbi muskolu- skeltrali, tal- connective tissue u ta ’ l- għadam Komuni Bugħawwieġ fil- muskoli Uġigħ fl- estremità Uġigħ fid- dahar
1.1 1.1 1.0
1. 1 1. 1 1. 0
Renal and urinary disorders
Disturbi fil- kliewi u fis- sistema urinarja Komuni ħafna
5 Very common Hypercalciuria Common
Iperkalċurja Komuni Żieda fil- proporzjon ta ’
39.3
39. 3
Urine calcium/creatinine ratio increased Urine calcium increased
kalċju/ kreatinina fl- awrina Żieda ta ’ kalċju fl- awrina
2.9 2.2
2. 9 2. 2
General disorders and administration site conditions Common Injection site erythema 2.6 Fatigue 1.8 Asthenia 1.2 Uncommon Injection site irritation 0.9
Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata Komuni Eritema fil- post ta ’ l- injezzjoni Għeja Astenja Mhux komuni
Preotact increases serum uric acid concentrations.
Preotact iżid il- konċentrazzjonijiet ta ’ aċidu uriku
For all subjects who received parathyroid hormone 100 micrograms blood uric acid increase was reported for 8 subjects (0.6%) and hyperuricemia was reported for 5 subjects (0.4%).
tal- paratirojde 100 mikrogramma, żieda ta ’ l- aċidu uriku fid- demm ġiet irrapportata għal 8 pazjenti (0. 6%) u iperuriċemja kienet irrapportata għal 5 pazjenti (0. 4%).
Although gout, arthralgia and nephrolithiasis were reported as ADRs, the relationship to elevations in uric acid due to Preotact administration has not been fully established.
Għalkemm il- gotta, l- artralġja u n - nefrolitjasi ġew irrapportati bħala ADRs, ir- relazzjoni maż- żieda fl- aċidu uriku minħabba l- għoti ta ’ Preotact ma ġietx stabbilita kompletament.
Antibodies to parathyroid hormone In a large phase III clinical study, antibodies to parathyroid hormone were detected in 3% of women receiving Preotact compared to 0.2% of women receiving placebo.
Antikorpi għall- ormon tal- paratirojde Fi studju kliniku kbir ta ’ Fażi III, antikorpi għall- ormon tal- paratirojde ġew rilevati fi 3% tan- nisa li rċevew Preotact meta mqabbel ma ’ 0. 2% tan- nisa li rċevew plaċebo.
In these women with a positive titer, there was no evidence of hypersensitivity reactions, allergic reactions, effects on bone mineral density response, or effects on serum calcium.
F’ dawn in- nisa b’ titer pożittiv, ma kien hemm ebda evidenza ta ’ reazzjonijiet ta ’ sensittività eċċessiva, reazzjonijiet allerġiċi, effetti fuq ir- rispons tad- densità minerali fl- għadam, jew effetti fuq il- kalċju fis- serum.
Signs and symptoms In the Preotact clinical program, accidental overdose was reported for 17 subjects.
Sinjali u sintomi Fil- programm kliniku bi Preotact, doża eċċessiva aċċidentali ġiet irrapportata fi 17- il pazjent.
Preotact has been administered in single doses up to 5 micrograms/kg and in repeated doses of up to 3 micrograms/kg/day for 3 days and up to 2.5 micrograms/kg/day for 7 days.
Preotact ingħata f’ dożi uniċi sa 5 mikrogrammi/ kg u f’ dożi ripetuti sa 3 mikrogrammi/ kg/ kuljum għal 3 ijiem u sa 2. 5 mikrogrammi/ kg/ kuljum għal 7 ijiem.
The effects of overdose that might be expected include delayed hypercalcemia, nausea, vomiting, dizziness and headache.
L- effetti ta ’ doża eċċessiva li wieħed jista ’ jistenna jinkludu iperkalċimja ttardjata, dardir, rimettar, sturdament u wġigħ ta ’ ras.
Overdose management There is no specific antidote for Preotact.
Ġestjoni ta ’ doża eċċessiva M’ hemmx antidotu speċifiku għal Preotact.
Treatment of suspected overdose should include temporary discontinuation of Preotact, monitoring of serum calcium, and implementation of appropriate, supportive measures, such as hydration.
Il- kura ta ’ doża eċċessiva suspettata għandha tinkludi t - twaqqif temporanju ta ’ Preotact, monitoraġġ tal- kalċju fis- serum, u implimentazzjoni ta ’ miżuri xierqa ta ’ sostenn, bħal idratazzjoni.
Due to the relatively short duration of the pharmacological activity of Preotact further measures should not be necessary.
Minħabba t- tul relattivament qasir ta ’ l- attività farmakoloġika ta ’ Preotact m’ għandhomx ikunu meħtieġa aktar miżuri.
Pharmacotherapeutic group: parathyroid hormone, ATC code:
Kategorija farmakoterapewtika: ormon tal- paratirojde, Kodiċi ATC:
Mechanism of action Preotact contains recombinant human parathyroid hormone which is identical to the full-length native 84-amino acid polypeptide.
6 Mod ta ’ kif jaħdem Preotact fih ormon tal- paratirojde uman rikombinanti li huwa identiku għall- polipeptide nattiv ta ’ tul sħiħ ta ’ 84 aċidu amminiku.
Physiological actions of parathyroid hormone include stimulation of bone formation by direct effects on bone forming cells (osteoblasts) indirectly increasing the intestinal absorption of calcium and increasing the tubular reabsorption of calcium and excretion of phosphate by the kidney.
L- effetti fiżjoloġiċi ta ’ l- ormon tal- paratirojde jinkludu stimulazzjoni tal- formazzjoni ta ’ l- għadam b’ effetti diretti fuq iċ- ċelloli li jiffurmaw l- għadam (osteoblasts) li indirettament iżidu l- assorbiment intestinali tal- kalċju u jżidu r- riassorbiment tubulari tal- kalċju u l- eskrezzjoni tal- fosfat mill- kliewi.
6 The skeletal effects of parathyroid hormone depend upon the pattern of systemic exposure.
Effetti farmakodinamiċi L- effetti skeletali ta ’ l- ormon tal- paratirojde jiddependu fuq il- mudell ta ’ l- espożizzjoni sistemiku.
Transient elevations in parathyroid hormone levels after subcutaneous injection of Preotact stimulates new bone formation on trabecular and cortical (periosteal and/or endosteal) bone surfaces by preferential stimulation of osteoblastic activity over osteoclastic activity.
Iż - żidiet għaddiena fil- livelli ta ’ l- ormon tal- paratirojde wara injezzjoni taħt il- ġilda ta ’ Preotact jistimulaw il- formazzjoni ġdida ta ’ l- għadam fuq is- superfiċje ta ’ l- għadam trabekulari u kortikali (perjosteali u/ jew endosteali) bi stimulazzjoni preferenzjali ta ’ l- attività osteoblastika fuq l- attività osteoklastika.
Effects on serum calcium concentrations Parathyroid hormone is the principal regulator of serum calcium homeostasis.
Effetti fuq il- konċentrazzjonijiet ta ’ kalċju fis- serum L- ormon tal- paratirojde huwa r- regolatur prinċipali ta ’ l- omeostasi tal- kalċju fis- serum.
In response to subcutaneous doses of Preotact (100 micrograms parathyroid hormone), serum total calcium levels increase gradually and reach peak concentration (mean increase in 129 patients, 0.15 mmol/l) at approximately 6 to 8 hours after dosing.
B’ rispons għad- dożi taħt il- ġilda ta ’ Preotact (100 mikrogramma ta ’ ormon tal- paratirojde), il- livelli totali ta ’ kalċju fis- serum jiżdiedu b’ mod gradwali u jilħqu l- konċentrazzjoni massima (żieda medja f’ 129 pazjenta, 0. 15 mmol/ l) madwar 6 sa 8 sigħat wara d- doża.
In general, serum calcium levels return to baseline levels 24 hours after dosing.
Ġeneralment, il- livelli tal- kalċju fis- serum jerġgħu jura fil- livelli tal- linja bażi 24 siegħa wara d- doża.
Based on two placebo-controlled studies involving 2642 postmenopausal osteoporotic women, hypercalcemia was reported in 25.3% of patients treated with Preotact compared to 4.3% of placebo- treated patients.
Ibbażat fuq żewġ studji kliniċi kkontrollati bil- plaċebo li kienu jinvolvu 2642 mara b’ osteoporożi ta ’ wara l- menopawsa, l- iperkalċimja ġiet irrapportata f’ 25. 3% tal- pazjenti kkurati bi Preotact meta mqabbel ma ’ 4. 3% tal- pazjenti kkurati bi plaċebo.
The hypercalcemia was transient and was reported most frequently in the first 3 months of treatment.
L- iperkalċimja kienet għaddiena u ġiet irrapportata l- aktar ta ’ sikwit fl- ewwel 3 xhur tal- kura.
It was managed during the clinical programme by monitoring laboratory values and the use of a pre-specified management algorithm.(see sections 4.3 and 4.4).
Matul il- programm kliniku hija kienet ġestita bil - monitoraġġ tal- valuri tal- laboratorju u l- użu ta ’ proċeduri ta ’ ġestjoni stabbiliti minn qabel (ara sezzjoni 4. 3 u 4. 4).
Clinical efficacy Effect on fracture incidence The pivotal study was an 18-month double-blind, placebo-controlled, phase III study (TOP) of the effect of Preotact on fracture incidence in women with postmenopausal osteoporosis.
Effikaċja klinika Effett fuq l- inċidenza tal- ksur L- istudju pivitali kien studju kliniku ta ’ Fażi III, tat- tip double- blind ikkontrollat bil- plaċebo, mifrux fuq 18- il xahar (TOP) dwar l- effett ta ’ Preotact fuq l- inċidenza tal- ksur f’ nisa b’ osteoporożi ta ’ wara l - menopawsa.
A total of 2532 patients (1286 Preotact and 1246 placebo), aged 45-94 years (8.1% 45-54 years and 11.4% > 75 years), were randomised to receive 100 micrograms/day or placebo with daily calcium (700 mg) and vitamin D (400 IU) supplementation.
Total ta ’ 2532 pazjent (1286 Preotact u 1246 plaċebo), ta ’ 45- 94 sena (8. 1% ta ’ 45- 54 sena u 11. 4% > 75 sena), ġew magħżula b’ mod każwali biex jirċievu 100 mikrogramma/ kuljum jew plaċebo b’ suppliment kuljum ta ’ kalċju (700 mg) u vitamina D (400 IU).
Overall, approximately 19% of the subjects in each treatment group had at least 1 prevalent vertebral fracture at baseline.
B’ mod globali, madwar 19% tal- pazjenti f’ kull grupp ta ’ kura kellhom mill- anqas ksur vertebrali prevalenti wieħed fil- linja bażi.
The mean baseline lumbar T score was approximately -3.0 in each treatment group.
Il- medja tal- lumbar T score fil- linja bażi kienet madwar - 3. 0 f’ kull grupp ta ’ kura.
Of the 2532 randomised intention-to-treat (ITT) patients, a total of 59 patients experienced at least one new vertebral fracture, placebo:
Mill- 2532 pazjent magħżula b’ mod każwali bl- intenzjoni ta ’ kura (ITT), total ta ’ 59 pazjent esperjenzaw mill- anqas ksur vertebrali ġdid, plaċebo:
42 (3.37%) – Preotact:
42 (3. 37%) – Preotact:
17 (1.32%), p=0.001.
17 (1. 32%), p = 0. 001.
Patients in the Preotact treatment group had a 61% relative risk reduction of a new vertebral fracture at month 18 compared to the patients in the placebo group.
Il - pazjenti fil- grupp ta ’ kura bi Preotact kellhom tnaqqis relattiv ta ’ 61% fir- riskju ta ’ ksur vertebrali ġdid wara 18- il xahar meta mqabbel mal- pazjenti fil- grupp tal- plaċebo.
To prevent one or more new vertebral fractures, 48 women had to be treated for a median of 18 months for the total population.
Biex ikun evitat ksur vertebrali ġdid, 48 mara kellhom jiġu kkurati medja ta ’ 18- il xahar għall - popolazzjoni kollha.
For patients with pre-existing fractures, number needed to treat (NNT) is 21 patients.
Fil- każ ta ’ pazjenti li diġà kellhom ksur, l- ammont li kellhom bżonn ta ’ kura (NNT) kien 21 pazjent.
There was no significant difference between the treatment groups in the incidence of any non-vertebral clinical fracture:
Ma kienx hemm differenza sinifikanti bejn il- gruppi ta ’ kura fl- inċidenza ta ’ xi ksur kliniku mhux vertebrali:
5.52% for Preotact vs.
5. 52% għal Preotact vs.
5.86% for placebo.
5. 86% għall- plaċebo.
The most relevant fracture reduction was observed among patients at high risk of fractures such as patients with previous fractures and in patients with a lumbar spine T-score of < - 3.
7 L- aktar tnaqqis fil- ksur rilevanti kien osservat fost pazjenti f’ riskju għoli ta ’ ksur bħal pazjenti bi ksur preċedenti u f’ pazjenti b’ T- score għall- parti lombari tas- sinsla ta ’ < - 3.
Relatively few patients less than 5 years postmenopausal and 45-54 years of age were enrolled in the phase III study (2-3%).
Relattivament ftit pazjenti li qabżu l- menopawsa b’ anqas minn 5 snin u ta ’ 45- 54 sena kienu rreġistrati fl- istudju ta ’ fażi III (2- 3%).
The results for these subjects were not different from the results in the study as a whole.
Ir- riżultati għal dawn il- pazjenti ma kinux differenti mir- riżultati fl - istudju komplessiv.
Effect on bone mineral density (BMD) In the pivotal study, Preotact increased BMD in the lumbar spine after 18 months treatment by 6.5% compared with -0.3% for placebo (p < 0.001).
Effett fuq id- densità minerali ta ’ l- għadam (BMD) Fl- istudju pivitali, Preotact żied il- BMD fil- parti lombari tas- sinsla wara 18- il xahar ta ’ kura b’ 6. 5% meta mqabbel ma ’ - 0. 3% għall- plaċebo (p < 0. 001).
Significant increases in hip BMD (total, femoral neck, trochanter) were observed at study endpoint; 1.0, 1.8 and 1.0%, respectively, for Preotact versus -1.1, -0. 7 and -0.6% for placebo (p < 0.001).
1. 0, 1. 8 u 1. 0% rispettivament, għal Preotact kontra - 1. 1, - 0. 7 u - 0. 6% għall- plaċebo (p < 0. 001).
7 Continued treatment for up to 24 months in an open-label extension of this study resulted in a continued increase in BMD.
It- trattament kontinwu sa 24 xahar f’ estensjoni open- label ta ’ dan l- istudju rriżultat f’ żieda kontinwa fil- BMD.
The increase from baseline in lumbar spine and femoral neck BMD was 6.8% and 2.2%, respectively in patients treated with Preotact.
Iż- żieda mil- linja bażi fil- BMD tal- parti lombari tas- sinsla u l- għonq femorali kienet ta ’ 6. 8% u 2. 2%, rispettivament għall- pazjenti kkurati bi Preotact.
The effects of Preotact on bone architecture were evaluated using quantitative computed tomography (QCT) and peripheral QCT.
L- effetti ta ’ Preotact fuq l- arkitettura ta ’ l- għadam ġew evalwati bl- użu ta ’ tomografija kwantitattiva komputata (QCT) u QCT periferali.
Volumetric trabecular BMD at the lumbar spine increased by 38% over baseline at 18 months.
Il- BMD volumetrika trabekulari fil- parti lombari tas- sinsla żdiedet bi 38% fuq il- linja bażi wara 18- il xahar.
Similarly, volumetric trabecular BMD at the total hip increased by 4.7%.
Bl- istess mod, il- BMD volumetrika trabekulari fil- ġenb sħiħ żdiedet b’ 4. 7%.
Similar increases occurred at the femoral neck, trochanter, and intertrochanter.
Żidiet simili seħħew fl- għonq femorali, it- trokanter, u l- intertrokanter.
Treatment with Preotact reduced volumetric cortical bone BMD (measured at the distal radius and mid-shaft tibia), while periosteal circumference or indices of cortical bone strength were maintained.
It- trattament bi Preotact naqqas il- BMD volumetriku ta ’ l- għadma kortikali (imkejla fid- distal radjus u l- mid- xaft tibia), filwaqt li ċ- ċirkonferenza perjosteali jew l- indiċi tas- saħħa ta ’ l- għadma kortikali kienu miżmuma.
In the 24-month alendronate combination therapy study (PaTH), the effects of Preotact on bone architecture were also evaluated using QCT.
Fl- istudju ta ’ 24 xahar dwar it- terapija kombinata b’ alendronate (PaTH), l- effetti ta ’ Preotact fuq l - arkitettura ta ’ l- għadam ġew evalwati wkoll bl- użu ta ’ QCT.
Volumetric trabecular BMD at the lumbar spine increased by 26, 13, and 11% (Preotact, Preotact and alendronate and alendronate, respectively) over baseline at 12 months.
Il- BMD volumetrika trabekulari fil- parti lombari tas- sinsla żdiedet b’ 26, 13 u 11% (Preotact, Preotact u alendronate u alendronate, rispettivament) fuq il- linja bażi wara 12- il xahar.
Similarly, volumetric trabecular BMD at the total hip increased by 9, 6, and 2%, respectively, in the 3 groups.
Bl- istess mod, il- BMD volumetrika trabekulari fil - ġenb sħiħ żdiedet b’ 9, 6 u 2%, rispettivament, fit- 3 gruppi.
Treatment of osteoporosis with combination and sequential therapy The PaTH study was a NIH sponsored randomised, placebo-controlled, 2 year, multicenter, double- blind trial of Preotact and alendronate as monotherapy and in combination for the treatment of postmenopausal osteoporosis.
Trattament ta ’ osteoporożi b’ terapija ta ’ kombinazzjoni u sekwenzjali L- istudju PaTH kien studju multiċentri, randomised, tat- tip double- blind ikkontrollat bil- plaċebo, fuq perjodu ta ’ sentejn, sponsorjat min- NIH, ta ’ Preotact u alendronate bħala monoterapija u flimkien għat- trattament ta ’ l- osteoporożi ta ’ wara l- menopawsa.
Inclusion criterias were; women between 55 and 85 years of age with BMD T-scores below -2.5 or below -2 and at least one additional risk factor for fracture.
Il- kriterji ta ’ l- inklużjoni kienu; nisa ta ’ bejn 55 u 85 sena b’ T- scores tal- BMD taħt - 2. 5 jew taħt - 2 u mill- anqas fattur ta ’ riskju wieħed addizzjonali għal ksur.
A ll women were given calcium (400-500 mg) and vitamin D (400 IU) supplements.
In- nisa kollha ngħataw supplimenti ta ’ kalċju (400- 500 mg) u vitamina D (400 IU).
A total of 238 postmenopausal women, were randomly assigned to one of the following treatment groups; Preotact (100 micrograms parathyroid hormone), alendronate (10 mg), or the combination of both, and followed for 12 months.
Total ta ’ 238 mara ta ’ wara l- menopawsa ġew assenjati b’ mod każwali għal wieħed mill- gruppi ta ’ kura segwenti; Preotact (100 mikrogramma ta ’ ormon tal- paratirojde), alendronate (10 mg), jew taħlita tat- tnejn, u kienu segwiti għal 12- il xahar.
In the second year of the study women in the original Preotact group were randomly assigned to receive either alendronate or matching placebo, and women in the other two groups received alendronate.
Fit- tieni sena ta ’ l- istudju n- nisa fil- grupp oriġinali ta ’ Preotact ġew magħżula b’ mod każwali biex jirċievu jew alendronate jew plaċebo simili, u n- nisa fiż - żewġ gruppi l- oħra rċevew alendronate.
At baseline a total of 165 women (69%) had a T-score below –2.5, and 112 (47%) reported at least one fracture after menopause.
Fil- linja bażi, total ta ’ 165 mara (69%) kellhom T- score taħt - 2. 5, u 112 (47%) irrapportaw mill- anqas ksur wieħed wara l- menopawsa.
One year of therapy, showed the following results:
Sena waħda ta ’ terapija wriet ir- riżultati li ġejjin:
The increases in lumbar spine BMD above baseline were similar in the Preotact and combination-therapy groups (6.3 and 6.1%, respectively), but were somewhat smaller in the alendronate group (4.6%).
Iż- żidiet fil- BMD tal- parti lombari tas- sinsla fuq il - linja bażi kienu simili fil- gruppi ta ’ Preotact u tat- terapija kombinata (6. 3 u 6. 1%, rispettivament), iżda kienu kemxejn anqas fil- grupp ta ’ alendronate (4. 6%).
Increases in BMD at the total hip were 0.3, 1.9, and 3.0% for the 3 groups, respectively.
Iż- żidiet fil- BMD tal- ġenb sħiħ kienu 0. 3, 1. 9, u 3. 0% għat- tliet gruppi, rispettivament.
At the end of year 2 (12 months after Preotact was discontinued), there was a 12.1% mean increase in dual energy X-ray absorptiometry (DXA) spine BMD for patients who received alendronate for the second year.
Fit- tmiem tat- tieni sena (12- il xahar wara t- twaqqif ta ’ Preotact), kien hemm żieda medja ta ’ 12. 1% fid- dual energy X- ray absorptiometry (DXA) spine BMD għall- pazjenti li rċevew alendronate għat - tieni sena.
For the patients who received placebo during the second year, the mean percent increase was 4.1% compared to baseline, but had decreased slightly compared to the end of 12 months of Preotact treatment.
Għall- pazjenti li rċevew plaċebo matul it- tieni sena, iż- żieda perċentwali medja kienet ta ’ 4. 1% meta mqabbla mal- linja bażi, iżda naqset daqsxejn meta mqabbla mat- tmiem ta ’ 12- il xahar ta ’
For the mean change in hip BMD, there was a 4.5% increase from baseline with one year of alendronate compared to a 0.1% decrease after one year of placebo.
Fil- każ tal- bidla medja fil- BMD tal- ġenb, kien hemm żieda ta ’ 4. 5% mil- linja bażi b’ sena alendronate meta mqabbel ma ’ tnaqqis ta ’ 0. 1% wara sena ta ’ plaċebo.
Preotact in combination with hormone replacement therapy (HRT) in 180 postmenopausal women has been shown to significantly increase lumbar spine BMD at 12 months compared with HRT alone (7.1% vs.
Preotact flimkien ma ’ terapija ta ’ sostituzzjoni ta ’ l- ormoni (HRT) f’ 180 mara ta ’ wara l- menopawsa ġie muri li jżid b’ mod sinifikanti l- BMD fil- parti lombari tas- sinsla wara 12- il xahar meta pparagunat ma ’ HRT waħedha (7. 1% vs.
1.1%, p < 0.001).
1. 1%, p < 0. 001).
The combination was effective regardless of age, baseline rate of bone turnover, or baseline BMD.
It- taħlita kienet effettiva irrispettivament mill- età, ir - rata tal- linja bażi ta ’ l- immudellar mill- ġdid ta ’ l- għadam, jew BMD tal- linja bażi.
Absorption Subcutaneous administration of 100 micrograms of parathyroid hormone into the abdomen produces a rapid increase in plasma parathyroid hormone levels and achieves a peak at 1 to 2 hours after dosing.
Assorbiment L- għoti taħt il- ġilda ta ’ 100 mikrogramma ta ’ ormon tal- paratirojde fl- addome jipproduċi żieda veloċi fil- livelli ta ’ ormon tal- paratirojde fil- plażma u jilħaq il- massimu minn siegħa sa sagħtejn wara d- doża.
8 The average half-life is of about 1.5 hours.
Il- half- life medja hija madwar siegħa u nofs.
The absolute bioavailability of 100 micrograms of parathyroid hormone after subcutaneous administration in the abdomen is 55%.
Il- bijodisponibiltà assoluta ta ’ 100 mikrogramma ta ’ ormon tal- paratirojde wara għoti taħt il- ġilda fl- addome hija 55%.
Distribution The volume of distribution at steady-state following intravenous administration is approximately 5.4 l.
Distribuzzjoni Il- volum tad- distribuzzjoni fiss wara għoti għal ġol- vini huwa madwar 5. 4 1.
Intersubject variability in the volume of distribution of parathyroid hormone is about 40%.
Il- varjabilità bejn persuna u oħra fil- volum tad- distribuzzjoni ta ’ l- ormon tal- paratirojde hija madwar 40%.
Biotransformation Parathyroid hormone is efficiently removed from the blood by a receptor-mediated process in the liver and is broken down into smaller peptide fragments.
Bijotrasformazzjoni L- ormon tal- paratirojde jitneħħa b’ mod effiċjenti mid- demm bi proċess medjat mir- riċetturi fil- fwied u jiġi mkisser fi frammenti iżgħar tal- peptide.
The fragments derived from the amino-terminus are further degraded within the cell while the fragments derived from the carboxy-terminius are released back into the blood and cleared by the kidney.
Il- frammenti derivati mill- amino- terminus ikomplu jiġu degradati fiċ- ċellola filwaqt li l- frammenti derivati mill- carboxy- terminius jerġgħu jiġu rilaxxati fid - demm u jitneħħew mill- kliewi.
These carboxy-terminal fragments are thought to play a role in the regulation of parathyroid hormone activity.
Dawn il- frammenti carboxy- terminali huma maħsuba li għandhom rwol fir- regolazzjoni ta ’ l- attività ta ’ l- ormon tal- paratirojde.
Under normal physiologic conditions, full-length parathyroid hormone (1-84) constitutes only 5-30% of the circulating forms of the molecule, while 70-95% is present as carboxy-terminal fragments.
F’ kondizzjonijiet fiżjoloġiċi normali, ormon tal- paratirojde ta ’ tul sħiħ (1- 84) jikkostitwixxi biss 5- 30% tal- forom fiċ- ċirkolazzjoni tal - molekula, filwaqt li 70- 95% huwa preżenti bħala frammenti carboxy- terminali.
Following a subcutaneous dose of Preotact, C-terminal fragments make up about 60-90% of the circulating forms of the molecule.
Wara doża taħt il- ġilda ta ’ Preotact, il- frammenti C- terminali jikkostitwixxu madwar 60- 90% tal- forom fiċ- ċirkolazzjoni tal - molekula.
Systemic clearance of parathyroid hormone (45.3 l/hour) following an intravenous dose is close to normal liver plasma flow and is consistent with extensive hepatic metabolism of the active substance.
It- tneħħija sistemika ta ’ l- ormon tal- paratirojde (45. 3 l/ siegħa) wara doża ġol- vini hija qrib tal- fluss normali tal- plażma fil- fwied u konsistenti ma ’ metaboliżmu epatiku estensiv tas- sustanza attiva.
Intersubject variability in systemic clearance is about 15%.
Il - varjabilità fit- tneħħija sistemika bejn persuna u oħra hija madwar 15%.
Elimination Parathyroid hormone is metabolised in the liver and to a lesser degree in the kidney.
Eliminazzjoni L- ormon tal- paratirojde jiġi metabolizzat fil- fwied u f’ miżura anqas fil- kliewi.
Parathyroid hormone is not excreted from the body in its intact form.
L- ormon tal- paratirojde ma jitneħħiex mill- ġisem fil- forma intatta tiegħu.
Circulating carboxy-terminal fragments are filtered by the kidney, but are subsequently broken to even smaller fragments during tubular reuptake.
Il- frammenti carboxy- terminali jiġu ffiltrati mill - kliewi, iżda suċċessivament jiġu mkissra fi frammenti saħansitra iżgħar matul ir- riassorbiment tubulari.
Hepatic impairment There was a modest increase of about 20% in the mean baseline corrected exposure (AUC) to parathyroid hormone in a study conducted in 6 men and 6 women with moderate hepatic impairment as compared with a matched group of 12 subjects with normal hepatic function.
Indeboliment epatiku Kien hemm żieda moderata ta ’ madwar 20% fl- espożizzjoni medja korretta mal- linja bażi (AUC) għall- ormon tal- paratirojde fi studju li twettaq fuq 6 irġiel u 6 nisa b’ indeboliment epatiku moderat meta mqabbel ma ’ grupp korrispondenti ta ’ 12- il pazjent b’ funzjoni epatiku normali.
No studies have been conducted in patients with severe hepatic impairment.
Ma sarux studji fuq pazjenti b’ indeboliment epatiku sever.
Renal impairment The overall exposure and Cmax of parathyroid hormone were slightly increased (22% and 56%, respectively) in a group of 8 male and 8 female subjects with mild-to-moderate renal impairment (creatinine clearances of 30 to 80 ml/min) compared with a matched group of 16 subjects with normal renal function.
Indeboliment renali L- espożizzjoni globali u l- Cmax ta ’ l- ormon tal- paratirojde kienu daqsxejn ogħla (22% u 56%, rispettivament) fi grupp ta ’ 8 pazjenti rġiel u 8 pazjenti nisa b’ indeboliment renali ħafif għal moderat (tneħħija tal- kreatinina ta ’ 30 sa 80 ml/ min) meta mqabbel ma ’ grupp korrispondenti ta ’ 16- il pazjent b’ funzjoni renali normali.
The pharmacokinetics of parathyroid hormone in patients with severe renal impairment (creatinine clearance of less than 30 ml/min) has not been investigated.
Il- farmakokinetika ta ’ l- ormon tal- paratirojde f’ pazjenti b’ indeboliment akut renali (tneħħija tal - kreatinina ta ’ anqas minn 30 ml/ min) ma ġietx investigata.
Elderly No differences in Preotact pharmacokinetics were detected with regard to age (range 47-88 years).
9 Ma kienu rilevati l- ebda differenzi fil- farmakokinetiċi ta ’ Preotact fir- rigward ta ’ l- età (medda 44- 88 sena).
Dosage adjustment based on age is not required.
M’ hemmx bżonn ta ’ aġġustament fid- doża bbażat fuq l- età.
Gender The medicinal product has only been studied in postmenopausal women.
Sess tal- persuna Dan il- prodott mediċinali ġie studjat biss f’ nisa li qabżu l- menopawsa.
Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, mutagenicity, toxicity to fertility and general reproduction, and local tolerance.
L- informazzjoni ta ’ qabel l- użu kliniku, magħmula fuq studji konvenzjonali ta ’ sigurtà farmakoloġika, effett tossiku fuq il- ġeni, effett tossiku fuq il- fertilità u r- riproduzzjoni ġenerali, u tolleranza lokali, ma turi l- ebda periklu speċjali għall- bnedmin.
In monkeys receiving daily subcutaneous doses for 6 months, there was an increased occurrence of renal tubular mineralization at exposure levels below clinical exposure levels.
Fix- xadini li rċevew dożi taħt il- ġilda kuljum għal 6 xhur, kien hemm okkorrenza akbar ta ’ mineralizzazzjoni tubulari renali f’ livelli ta ’ espożizzjoni taħt il- livelli ta ’ l- espożizzjoni kliniku.
9 Rats treated with near life-time daily injections had dose-dependent exaggerated bone formation and an increased incidence of bone tumours, including osteosarcoma, most probably due to an epigenetic mechanism.
Il- firien ittrattati b’ injezzjonijiet kuljum kważi tul ħajjithom kollha kellhom formazzjoni esaġerata ta ’ l- għadam dipendenti fuq id- doża u inċidenza akbar ta ’ tumuri ta ’ l- għadam, fosthom osteosarkoma, wisq probabbli minħabba mekkaniżmu epiġenetiku.
Due to the differences in bone physiology in rats and humans, the clinical relevance of these findings is probably minor.
Minħabba d- differenzi fil- fiżjoloġija ta ’ l- għadam fil- firien u l- bnedmin, ir- rilevanza klinika ta ’ dawn is- sejbiet probabbli hija żgħira.
No osteosarcomas have been observed in clinical trials.
Ma kinux osservati osteosarkomi fil- provi kliniċi.
There are no studies of foetal, developmental, perinatal or postnatal toxicity.
M’ hemmx studji dwar l- effett tossiku fuq l- iżvilupp tal- fetu qabel u wara t- twelid.
It is unknown whether recombinant human parathyroid hormone is excreted in the milk of lactating animals.
Mhux magħruf jekk l- ormon tal- paratirojde uman rikombinanti jitneħħiex fil- ħalib ta ’ annimali li jreddgħu.
Powder Mannitol Citric acid monohydrate Sodium chloride Hydrochloric acid, dilute (for pH adjustment) Sodium hydroxide 1N (for pH adjustment)
Trab Mannitol Citric acid monohydrate Sodium chloride Hydrochloric acid, dilwit (għal aġġustament tal- pH) Sodium hydroxide 1N (għal aġġustament tal- pH)
Solvent Metacresol Water for injections
Solvent Metacresol Ilma għall- injezzjonijiet
Mixed solution: chemical and physical in-use stability has been demonstrated for 28 days at 2-8°C.
Soluzzjoni mħallta: stabbilità kimika u fiżika waqt l- użu dehret għal 28 ġurnata f’ temperatura ta ’ 2 - 8°C.
During the 28-day period the mixed solution can be stored for up to 7 days at temperatures below 25°C.
Matul il- perjodu ta ’ 28 ġurnata, is- soluzzjoni mħallta tista ’ tinħażen sa 7 ijiem f’ temperaturi taħt 25°C.
Mixed solution:
10 Soluzzjoni mħallta:
Store in a refrigerator (2-8°C).
Aħżen fi friġġ (2- 8°C).
Once the cartridge is mixed it can be stored outside the refrigerator at temperatures below 25°C for up to 7 days during the 28 day use period.(see section 6.3).
(ara sezzjoni 6. 3).
The container closure system is comprised of a dual-chamber cartridge, a center stopper, a crimp cap (containing a rubber seal) sealing the first chamber containing lyophilised powder and an end stopper sealing the second chamber containing the solvent for mixing.
Is- sistema ta ’ l- għeluq tal- kontenitur hija magħmula minn skartoċċ ta ’ żewġ kompartimenti, tapp fin - nofs, crimp cap (b’ siġill tal- lastku) li jissiġilla l- ewwel kompartiment li fih trab lajofilizzat u tapp fit - tarf li jissiġilla t- tieni kompartiment li fih is- solvent għat- taħlit.
Cartridge:
Skartoċċ:
The glass of the dual-chamber cartridge is made of glass Type I.
Il- ħġieġ ta ’ l- iskartoċċ ta ’ żewġ kompartimenti huwa magħmul minn ħġieġ ta ’ Tip I.
Stopper (center and end):
Tapp (tan- nofs u tat- tarf):
The stopper is made of bromobutyl rubber, grey.
It- tapp huwa magħmul minn lastku tal- bromobutyl, griż.
Crimp cap (containing a rubber seal):
Crimp cap (li fih siġill tal- lastku):
The crimp cap is made of aluminium and the rubber seal is made of bromobutyl rubber.
Il- crimp cap huwa magħmul mill- aluminju u s- siġill tal- lastku huwa magħmul minn lastku tal- bromobutyl.
10 Each dual-chamber cartridge contains 1.61 mg parathyroid hormone and 1.13 ml solvent (14 doses).
Kull skartoċċ ta ’ żewġ kompartimenti fih 1. 61 mg ta ’ ormon tal- paratirojde u 1. 13 ml ta ’ solvent (14- il doża).
Preotact is available in packs of 2 and 6 cartridges.
Preotact huwa disponibbli f’ pakketti ta ’ 2 u 6 skrataċ.
The Preotact pen and needles are not included.
Il- pinna u l- labar Preotact mhumiex inklużi.
Preotact is injected using the re-usable pen, Preotact pen.
Preotact jiġi injettat bl- użu ta ’ pinna li tista ’ terġa ’ tintuża, il- pinna Preotact.
The contents of the dual-chamber cartridge is mixed in the Preotact pen.
Il- kontenut ta ’ l- iskartoċċ ta ’ żewġ kompartimenti jiġi mħallat fil- pinna Preotact.
After mixing the liquid should be clear and colourless.
Wara t- taħlit, il- likwidu għandu jkun ċar u bla kulur.
DO NOT SHAKE; shaking may cause denaturation of the active substance.
TĦAWDUX; it- taħwid jista ’ jikkawża tibdil fin- natura tas- sustanza attiva.
If the mixed solution is cloudy, coloured or contains particles the cartridge should be removed from the Preotact pen and a new cartridge inserted.
Jekk is- soluzzjoni mħallta tkun imdardra, fiha l- kulur jew il- frak, l- iskartoċċ għandu jitneħħa mill - pinna Preotact u jiddaħħal skartoċċ ġdid.
Nycomed Danmark ApS Langebjerg 1 DK-4000 Roskilde Denmark
Nycomed Danmark ApS Langebjerg 1 DK- 4000 Roskilde Id- Danimarka
Boehringer Gasse 5-11 1211 Vienna Austria
Boehringer Gasse 5- 11 1211 Vienna L- Awstrija
Nycomed Danmark ApS Langebjerg 1, 4000 Roskilde Denmark
Nycomed Danmark ApS Langebjerg 1, 4000 Roskilde Id- Danimarka
The Marketing Authorisation Holder commits to performing the study and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan.
Id- Detentur ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq jimpenja ruħu li jwettaq l - istudju u l- attivitajiet addizzjonali ta ’ farmakoviġilanza dettaljati fil- Pjan ta ’ Farmakoviġilanza.
15 PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE PACKAGING
TIKKETTA
Outer Carton (2 and 6 dual-chamber cartridges)
Kartuna ta ’ barra (2 u 6 skrataċ ta ’ żewġ kompartimenti)
Preotact 100 micrograms powder and solvent for solution for injection Parathyroid hormone
Preotact 100 mikrogramm trab u solvent għal soluzzjoni għall- injezzjoni Ormon tal- paratirojde
Each dual-chamber cartridge contains 1.61 mg of parathyroid hormone..
Kull skartoċċ ta ’ żewġ kompartimenti fih 1. 61 mg ta ’ ormon tal- paratirojde.
When the powder and the solvent have been mixed, each dose of 71.4 microliter contains 100 micrograms parathyroid hormone.
Meta t- trab u s- solvent jitħalltu, kull doża ta ’ 71. 4 mikrolitru jkun fiha 100 mikrogramm ta ’ ormon tal - paratirojde.
Sodium chloride 0.4%, mannitol, citric acid monohydrate, hydrochloric acid, metacresol, sodium hydroxide, water for injections.
Sodium chloride 0. 4%, mannitol, citric acid monohydrate, hydrochloric acid, metacresol, sodium hydroxide, ilma għall- injezzjonijiet.
Each dual-chamber cartridge contains 1.61 mg of parathyroid hormone as powder and 1.13 ml of solvent.
Kull skartoċċ ta ’ żewġ kompartimenti fih 1. 61 mg ta ’ ormon tal- paratirojde bħala trab u 1. 13 ml ta ’ solvent.
2 dual-chamber cartridges per pack.
2 skrataċ ta ’ żewġ kompartimenti għal kull pakkett.
6 dual-chamber cartridges per pack.
6 skrataċ ta ’ żewġ kompartimenti għal kull pakkett.
Subcutaneous use Do not shake the reconstituted solution Read the package leaflet before use
Użu għal taħt il- ġilda Tħawwadx is- soluzzjoni rikostitwita Aqra l- fuljett ta ’ tagħrif qabel l- użu
16 EXP MM/YYYY Reconstituted solution:
17 JIS XX/ SSSS Soluzzjoni rikostitwita:
28 days
28 ġurnata
Keep the cartridge in the outer carton in order to protect from light.
Żomm l- iskartoċċ fil - kartuna ta ’ barra sabiex tilqa ’ mid- dawl.
Do not shake.
Tħawwadhiex.