qanastek/EMEA-V3 huggingface dataset:
Adverse reactions, defined as adverse events considered at least possibly attributable to cinacalcet treatment based on best-evidence assessment of causality and reported in excess of placebo in double- blind clinical studies are listed below using the following convention: 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).
Reazzjonijiet avversi, definiti bħala episodi avversi ikkunsidrati bħala ta ’ l- inqas possibilment attribwiti mal- kura b’ cinacalcet ibbażat fuq valutazzjoni ta ’ l- aqwa evidenza ta ’ kawżalità u rrappurtati aktar milli bil- plaċebo fl- istudji kliniċi double- blind huma mniżżla hawn taħt skond il- konvenzjoni li ġejja: 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).
Immune system disorders Uncommon: hypersensitivity reactions
Disturbi fis- sistema immuni Mhux komuni: rezzjonijiet ta ’ sensitività eċċessiva
Nervous system disorders Common: dizziness, paraesthesia Uncommon: seizures
Disturbi fis- sistema nervuża Komuni: sturdament, parasteżija Mhux komuni: aċċessjonijiet
Gastrointestinal disorders Very common:
Disturbi gastro- intestinali Komuni ħafna: tqallih, rimettar Mhux komuni: dispepsja, dijarea
Skin and subcutaneous tissue disorders Common: rash
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Komuni: raxx
Musculoskeletal, connective tissue and bone disorders Common: myalgia
Disturbi muskolu- skeletrali, tal- connective tissue u tal- għadam Komuni: mijalġja
General disorders and administration site conditions Common: asthenia
6 Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata Komuni: astenja
6 Investigations Common: hypocalcaemia (see section 4.4), reduced testosterone levels (see section 4.4)
Investigazzjonijiet Komuni: ipokalċimja (ara sezzjoni 4. 4), tnaqqis fil- livelli ta ’ testosterone (ara sezzjoni 4. 4)
The safety profile of Mimpara in these patient populations is generally consistent with that seen in patients with Chronic Kidney Disease.
Il- profil ta ’ sigurtà ta ’ Mimpara f’ dawn il- popolazzjonijiet ta ’ pazjenti ġeneralment huwa konsistenti ma ’ dak li deher f’ pazjenti b’ Mard Kroniku tal- Kliewi.
The most frequent ADRs in these patient populations were nausea and vomiting.
L- aktar ADRs frekwenti f’ dawn il - popolazzjonijiet ta ’ pazjenti kienu tqalligħ u rimettar.
Post-marketing Experience
Esperjenza ta 'wara t- tqegħid fuq is- suq
There have been reports of isolated, idiosyncratic cases of hypotension and/ or worsening heart failure in cinacalcet-treated patients with impaired cardiac function in post marketing safety surveillance.
Kien hemm rapporti ta 'każijiet iżolati, idjosinkratiċi ta' pressjoni baxxa u/ jew insuffiċjenza tal- qalb li sejra għall- agħar, f 'pazjenti b' indeboliment fil- funzjoni tal- qalb li ngħataw cinacalcet waqt l - immonitorjar tas- sigurtà ta 'wara t- tqegħid fuq is- suq.
Doses titrated up to 300 mg once daily have been safely administered to patients receiving dialysis.
Dożi ttitrati sa 300 mg darba kuljum ingħataw b’ sigurtà lill- pazjenti li kienu fuq dijalisi.
Overdosage of Mimpara may lead to hypocalcaemia.
Doża eċċessiva ta ’ Mimpara tista ’ twassal għal ipokalċimja.
In the event of overdosage, patients should be monitored for signs and symptoms of hypocalcaemia, and treatment should be symptomatic and supportive.
F’ każ ta ’ doża eċċessiva, il- pazjenti għandhom jiġu sorveljati għas- sinjali u s- sintomi ta ’ ipokalċimja, u l- kura għandha tkun sintomatika u ta ’ appoġġ.
Since cinacalcet is highly protein-bound, haemodialysis is not an effective treatment for overdosage.
Minħabba li cinacalcet jintrabat b’ mod qawwi mal- proteini, l- emodijalisi mhix kura effettiva għal doża eċċessiva.
ATC code:
Kategorija farmakoterapewtika: sustanzi anti- paratirojde, Kodiċi ATC:
The calcium sensing receptor on the surface of the chief cell of the parathyroid gland is the principal regulator of PTH secretion.
Ir- riċettur li jħoss il- kalċju fuq il- wiċċ taċ- ċellola maġġuri tal- glandola paratirojde huwa r- regolatur prinċipali tat- tnixxija ta ’ PTH.
Cinacalcet is a calcimimetic agent which directly lowers PTH levels by increasing the sensitivity of the calcium sensing receptor to extracellular calcium.
Cinacalcet huwa sustanza kalċjumimetika li jbaxxi direttament il- livelli ta ’ PTH billi jżid is- sensitività tar- riċettur li jħoss il- kalċju għall- kalċju extraċellolari.
The reduction in PTH is associated with a concomitant decrease in serum calcium levels.
It- tnaqqis ta ’ PTH huwa assoċjat ma’ tnaqqis fl- istess ħin fil- livelli tal- kalċju fis- serum.
Reductions in PTH levels correlate with cinacalcet concentration.
Tnaqqis fil- livelli ta ’ PTH jikkorrela mal- konċetrazzjoni ta ’ cinacalcet.
Soon after dosing, PTH begins to decrease until a nadir at approximately 2 to 6 hours postdose, corresponding with cinacalcet Cmax.
Ftit wara d- dożaġġ, PTH jibda jonqos sa nadir f’ madwar sagħatejn sa 6 sigħat wara d- doża, li jikkorrespondi ma ’ Cmax. ta ’ cinacalcet.
Thereafter, as cinacalcet levels begin to decline, PTH levels increase until 12 hours post-dose, and then PTH suppression remains approximately constant to the end of the once-daily dosing interval.
Minn hemm ’ l quddiem, kif il- livelli ta ’ cinacalcet jibdew jonqsu, il- livelli ta ’ PTH jiżdiedu sa 12- il siegħa wara d- doża, u wara s- soppressjoni ta ’ PTH tibqa bejn wieħed u ieħor kostanti sa l- aħħar tal - intervall ta ’ dożaġġ ta ’ darba kuljum.
PTH levels in Mimpara clinical trials were measured at the end of the dosing interval.
Il- livelli ta ’ PTH fil- provi kliniċi b’ Mimpara tkejjlu fl- aħħar ta ’ l- intervall tad- dożaġġ.
After steady state is reached, serum calcium concentrations remain constant over the dosing interval.
Wara li jintlaħaq stat stabbli, il- konċentrazzjonijiet tal- kalċju fis- serum jibqgħu kostanti tul l- intervall ta ’ dożaġġ.
Three, 6-month, double-blind, placebo-controlled clinical studies were conducted in ESRD patients with uncontrolled secondary HPT receiving dialysis (n=1136).
Twettqu tlett studji kliniċi ta ’ 6- xhur, double- blind u kkontrollati bil- plaċebo f’ pazjenti b’ ESRD b’ HPT sekondarja mhux kontrollata, li kienu qed jirċievu d- dijalisi (n=1136).
Demographic and baseline characteristics were representative of the dialysis patient population with secondary HPT.
Karatteristiċi demografiċi u tal- linja bażi kienu rappreżentattivi tal- popolazzjoni ta ’ pazjenti fuq dijalisi b’ HPT sekondarja.
Mean baseline iPTH concentrations across the 3 studies were 733 and 683 pg/ ml (77.8 and 72.4 pmol/ l) for the cinacalcet and placebo groups, respectively.
7 (77. 8 u 72. 4 pmol/ l) għall- gruppi ta ’ cinacalcet u plaċebo, rispettivament.
66% of patients were receiving vitamin D sterols at study entry, and > 90% were receiving phosphate binders.
66% tal- pazjenti kienu qed jirċievu sterols ta ’ vitamina D fil- bidu ta ’ l- istudju, u > 90% kienu qed jirċievu binders tal- fosfat.
Significant reductions in iPTH, serum calcium-phosphorus product (Ca x P), calcium, and phosphorus were observed in the cinacalcet treated patients compared with placebo-treated patients receiving standard of care, and the results were
Tnaqqis sinifikanti f’ iPTH, fil- prodott ta ’ kalċju- fosforu fis- serum (Ca x P), fil- kalċju, u fil- fosforu kien osservat fil- pazjenti kkurati b’ cinacalcet meta mqabbla mal- pazjenti kkurati bil- plaċebo li kienu qed jirċievu kura stàndard, u r- riżultati kienu konsistenti tul it- tlett studji.
In each of the studies, the primary endpoint (proportion of patients with an iPTH ≤ 250 pg/ ml (≤ 26.5 pmol/ l)) was achieved by 41%, 46%, and 35% of patients receiving cinacalcet, compared with 4%, 7%, and 6% of patients receiving placebo.
F’ kull wieħed mill- istudji, il - mira primarja (proporżjon ta ’ pazjenti b’ iPTH ≤ 250 pg/ ml (≤ 26. 5 pmol/ l)) intlaħqet minn 41%, 46%, u 35% tal- pazjenti li rċevew cinacalcet, meta mqabbla ma ’ 4%, 7%, u 6% tal- pazjenti li rċevew il - plaċebo.
Approximately 60% of cinacalcet-treated patients achieved a ≥ 30% reduction in iPTH levels, and this effect was consistent across the spectrum of baseline iPTH levels.
Madwar 60% tal- pazjenti kkurati b’ cinacalcet laħqu tnaqqis ta ’ ≥ 30% fil- livlli ta ’ iPTH, u dan l- effett kien konsistenti tul il- firxa tal- livelli ta ’ linja bażi ta ’ iPTH.
The mean reductions in serum Ca x P, calcium, and phosphorus were 14%, 7% and 8%, respectively.
It- tnaqqis medju ta ’ Ca x P, kalċju, u fosforu fis- serum kienu 14%, 7% u 8%, rispettivament.
Reductions in iPTH and Ca x P were maintained for up to 12 months of treatment.
Tnaqqis f’ iPTH u f’ Ca x P inżammu sa 12- il xahar ta ’ l- kura.
Cinacalcet decreased iPTH and Ca x P, calcium and phosphorus levels regardless of baseline iPTH or Ca x P level, dialysis modality (PD versus HD), duration of dialysis, and whether or not vitamin D sterols were administered.
Cinacalcet naqqas il- livelli ta ’ iPTH u ta ’ Ca x P, ta ’ kalċju u ta ’ fosforu indipendentament mill- livelli ta ’ linja bażi ta ’ iPTH jew livelli ta ’ Ca x P, modalità ta ’ dijalisi (PD kontra HD), tul tad- dijalisi, u jekk ingħatawx sterols ta ’ vitamina D.
Reductions in PTH were associated with non-significant reductions of bone metabolism markers (bone specific alkaline phosphatase, N-telopeptide, bone turnover and bone fibrosis).
(alkaline phosphatase speċifiku għall- għadam, N- telopeptide, tibdil tal- għadam u fibrożi tal- għadam).
In post-hoc analyses of pooled data from 6 and 12 months clinical studies, Kaplan-Meier estimates of bone fracture and parathyroidectomy were lower in the cinacalcet group compared with the control group.
F’ analiżi post- hoc ta ’ tagħrif miġbur minn studji kliniċi ta ’ 6 xhur u 12- il xahar, l- istimi Kaplan- Meier ta ’ ksur tal- għadam u l- paratirojdektomija kienu inqas fil- ġrupp ta ’ cinacalcet meta mqabbla mal - grupp ta ’ kontroll.
Investigational studies in patients with CKD and secondary HPT not undergoing dialysis indicated that cinacalcet reduced PTH levels to a similar extent as in patients with ESRD and secondary HPT receiving dialysis.
Studji investigattivi fuq pazjenti b 'CKD u HPT sekondarja li mhux qed jirċievu dijalisi indikaw li cinacalcet naqqas il- livelli ta ’ PTH b’ ammont simili għal dak f’ pazjenti b’ ESRD u HPT sekondarja li qed jirċievu d- dijalisi.
However, efficacy, safety, optimal doses and treatment targets have not been established in treatment of predialytic renal failure patients.
Iżda, l- effikaċja, s- sigurtà, d- dożi ottimali u l- miri tal- kura ma ġewx stabbiliti fil- kura ta ’ pazjenti b’ indeboliment renali qabel id- dijalisi.
These studies show that CKD patients not undergoing dialysis treated with cinacalcet have an increased risk for hypocalcaemia compared with cinacalcet-treated ESRD patients receiving dialysis, which may be due to lower baseline calcium levels and/ or the presence of residual kidney function.
Dawn l- istudji juru li pazjenti b’ CKD li mhux qegħdin fuq id- dijalisi li jingħataw cinacalcet għandhom riskju akbar ta ’ ipokalċimja meta mqabbla ma ’ pazjenti b’ ESRD li qed jirċievu d- dijalisi li jingħataw cinacalcet, li jista ’ jkun minħabba livelli ta ’ kalċju fil- linja bażi aktar baxxi u/ jew il- preżenza ta 'fdal ta' funzjoni tal- kliewi.
Parathyroid carcinoma and Primary Hyperparathyroidism
Karċinoma tal- paratirojde u Iperparatirojdiżmu Primarju
In a key study,46 patients (29 with parathyroid carcinoma and 17 with primary HPT (who had failed or had contraindications to parathyroidectomy) received cinacalcet for up to 3 years (mean of 328 days for patients with parathyroid carcinoma and mean of 347 days for patients with primary HPT).
Fi studju kruċjali, 46 pazjent (29 b’ karċinoma tal- paratirojde u 17 b’ HPT primarja (li kienu fallew jew li kellhom kontra- indikazzjonijiet għall- paratirojdektomija) irċevew cinacalcet sa 3 snin (medja ta ’ 328 ġurnata għall- pazjenti b’ karċinoma tal- paratirojde u medja ta ’ 347 ġurnata għall- pazjenti b’ HPT primarja).
Cinacalcet was administered at doses ranging from 30 mg twice daily to 90 mg four times daily.
Cinacalcet ingħata f’ firxa ta ’ dożi minn 30 mg darbtejn kuljum sa 90 mg erba ’ darbiet kuljum.
The primary endpoint of the study was a reduction of serum calcium of ≥ 1 mg/ dl (≥ 0.25 mmol/ l).
Il- mira pimarja ta ’ l- istudju kienet tnaqqis tal- kalċju fis- serum ta ’ ≥ 1 mg/ dL (≥ 0. 25 mmol/ l).
In patients with parathyroid carcinoma, mean serum calcium declined from 14.1 mg/ dl to 12.4 mg/ dl (3.5 mmol/ l to 3.1 mmol/ l), while in patients with primary HPT, serum calcium levels declined from 12.7 mg/ dl to 10.4 mg/ dl (3.2 mmol/ l to 2.6 mmol/ l).
F’ pazjenti b’ karċinoma tal- paratirojde, il- medja tal- kalċju fis- serum naqset minn 14. 1 mg/ dl għal 12. 4 mg/ dl (3. 5 mmol/ l għal 3. 1 mmol/ l), filwaqt li f’ pazjenti b’ HPT primarja, l- livelli ta ’ kalċju fis - serum naqsu minn 12. 7 mg/ dl għal 10. 4 mg/ dl (3. 2 mmol/ l għal 2. 6 mmol/ l).
Eighteen of 29 patients (62%) with parathyroid carcinoma and 15 of 17 subjects (88%) with primary HPT achieved a reduction in serum calcium of ≥ 1 mg/ dl (≥ 0.25 mmol/ l).
Tmintax minn 29 pazjent (62%) b’ karċinoma tal- paratirojde u 15 minn 17 - il individwu (88%) b’ HPT primarja laħqu tnaqqis tal- kalċju fis- serum ta ’ ≥ 1 mg/ dl (≥ 0. 25 mmol/ l).
After oral administration of Mimpara, maximum plasma cinacalcet concentration is achieved in approximately 2 to 6 hours.
Wara għotja orali ta ’ Mimpara, konċentrazzjoni massima fil- plażma ta ’ cinacalcet tintlaħaq f’ madwar sagħtejn sa 6 sigħat.
Based on between-study comparisons, the absolute bioavailability of cinacalcet in fasted subjects has been estimated to be about 20-25%.
Ibbażat fuq paragun ta ’ bejn l- istudji, il- biodisponibilità assoluta ta ’ cinacalcet f’ pazjenti sajma kienet stmata li hi madwar 20- 25%.
Administration of Mimpara with food results in an approximate 50 – 80% increase in cinacalcet bioavailability.
Għotja ta ’ Mimpara ma ’ l- ikel wasslet għal żieda ta ’ madwar 50 – 80% fil- biodisponibilità ta ’ cinacalcet.
Increases in plasma cinacalcet concentration are similar, regardless of the fat content of the meal.
Iż- żiediet fil- konċentrazzjoni ta ’ cinacalcet fil- plażma huma simili, ikun kemm ikun il- kontenut ta ’ xaħam fl- ikel.
After absorption, cinacalcet concentrations decline in a biphasic fashion with an initial half-life of approximately 6 hours and a terminal half-life of 30 to 40 hours.
Wara l- assorbiment, il- konċentrazzjonijiet ta ’ cinacalcet jonqsu b’ mod bifażiku b’ half- life tal- bidu ta ’ madwar 6 sigħat u half- life terminali ta ’ 30 sa 40 siegħa.
Steady state drug levels are achieved within 7 days with minimal accumulation.
Livelli tal- mediċina fi stat stabbli jintlaħqu f’ 7 ijiem b’ akkumulazzjoni minima.
The AUC and Cmax of cinacalcet increase approximately linearly over the dose range of 30 to 180 mg once daily.
L- AUC u Cmax ta ’ cinacalcet jiżdiedu, bejn wieħed u ieħor b’ mod linejari fuq il- firxa ta ’ dożi ta ’ 30 sa 180 mg darba kuljum.
At doses above 200 mg, the absorption was saturated probably due to poor solubility.
F’ dożi ogħla minn 200 mg, l- assorbiment kien saturat probabbilment minħabba li ma tantx huma solubili.
The pharmacokinetics of cinacalcet does not change over time.
Il- farmakokinetika ta ’ cinacalcet ma
The volume of distribution is high (approximately 1000 litres), indicating extensive distribution.
Il- volum ta ’ distribuzzjoni huwa għoli (madwar 1000 litru), b’ hekk jindika distribuzzjoni estensiva.
Cinacalcet is approximately 97% bound to plasma proteins and distributes minimally into red blood cells.
Madwar 97% ta ’ cinacalcet jintrabat mal- proteini tal- plażma u ftit li xejn jiġi distribwit fiċ- ċelloli l- ħomor tad- demm.
8 Cinacalcet is metabolised by multiple enzymes, predominantly CYP3A4 and CYP1A2 (the contribution of CYP1A2 has not been characterised clinically).
Cinacalcet jiġi metabolizzat minn bosta enżimi, primarjament CYP3A4 u CYP1A2 (il- kontribuzzjoni ta ’ CYP1A2 għadha ma ġietx ikkaratterizzata klinikament).
The major circulating metabolites are inactive.
Il- metaboliti prinċipali fiċ- ċirkulazzjoni huma inattivi.
Based on in vitro data, cinacalcet is a strong inhibitor of CYP2D6, but is neither an inhibitor of other CYP enzymes at concentrations achieved clinically, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP3A4 nor an inducer of CYP1A2, CYP2C19 and CYP3A4.
Ibbażat fuq tagħrif in vitro, cinacalcet huwa inibitur qawwi ta ’ CYP2D6, iżda f’ konċentrazzjonijiet milħuqa klinikament, la huwa inibitur ta ’ enżimi ta ’ CYP oħra, inkluż CYP1A2, CYP2C8, CYP2C9, CYP2C19, u CYP3A4, u lanqas induttur ta ’ CYP1A2, CYP2C19 u CYP3A4.
After administration of a 75 mg radiolabelled dose to healthy volunteers, cinacalcet was rapidly and extensively metabolised by oxidation followed by conjugation.
Wara għotja ta ’ doża radjutikketjata ta ’ 75 mg lill- voluntiera b’ saħħithom, cinacalcet kien metabolizzat malajr u estensivament permezz ta ’ ossidazzjoni segwit minn konjugazzjoni.
Renal excretion of metabolites was the prevalent route of elimination of radioactivity.
Tneħħija renali tal- metaboliti kienet ir- rotta primarja għall- eliminazzjoni tar- radjuattività.
Approximately 80% of the dose was recovered in the urine and 15% in the faeces.
Madwar 80% tad - doża kienet irkuprata fl- awrina u 15% fl- ippurgar.
There are no clinically relevant differences due to age in the pharmacokinetics of cinacalcet.
M’ hemmx differenzi klinikament rilevanti fil- farmakokinetika ta ’ cinacalcet minħabba l- età.
Renal Insufficiency:
Insuffiċjenza Renali:
The pharmacokinetic profile of cinacalcet in patients with mild, moderate, and severe renal insufficiency, and those on haemodialysis or peritoneal dialysis is comparable to that in healthy volunteers.
Il- profil farmakokinetiku ta ’ cinacalcet f’ pazjenti b’ insuffiċjenza renali ħafifa, moderata u severa, u dawk fuq emodijalisi jew dijalisi tal- peritonew huwa komparabbli ma ’ dak f’ voluntiera b’ saħħithom.
Mild hepatic impairment did not notably affect the pharmacokinetics of cinacalcet.
Indeboliment epatiku ħafif ma affettwax il- farmakokinetika ta ’ cinacalcet b’ mod notevoli.
Compared to subjects with normal liver function, average AUC of cinacalcet was approximately 2-fold higher in subjects with moderate impairment and approximately 4-fold higher in subjects with severe impairment.
Meta mqabbla ma ’ individwi b’ funzjoni normali tal- fwied, l- AUC medja ta ’ cinacalcet kienet madwar darbtejn ogħla f’ individwi b’ indeboliment moderat u madwar 4- darbiet ogħla f’ individwi b’ indeboliment sever.
The mean half-life of cinacalcet is prolonged by 33% and 70% in patients with moderate and severe hepatic impairment, respectively.
F’ pazjenti b’ indeboliment epatiku moderat u sever, il- half- life medja ta ’ cinacalcet hija mtawwla bi 33% u 70% rispettivament.
Protein binding of cinacalcet is not affected by impaired hepatic function.
Ir- rabta ta ’ cinacalet mal- proteini mhix affettwata minn funzjoni epatika indebolita.
(see sections 4.2 and 4.4).
Minħabba li d- dożi huma ttitrati għal kull individwu ibbażat fuq parametri ta ’ siġurtà u effikaċja, mhux neċessarju aktar aġġustament fid- doża għal - individwi b’ indeboliment epatiku (are sezzjonijiet 4. 2 u 4. 4).
Clearance of cinacalcet may be lower in women than in men.
Tneħħija ta ’ cinacalcet tista ’ tkun inqas fin- nisa milli fl- irġiel.
Because doses are titrated for each subject, no additional dose adjustment is necessary based on gender.
Minħabba li d- dożi huma ttitrati għal kull indiviwu, mhux neċessarju aktar aġġustament fid- doża bbażat fuq is- sess.
The pharmacokinetics of cinacalcet have not been studied in patients < 18 years of age.
Il- farmakokinetika ta ’ cinacalcet ma ġietx studjata f’ pazjenti ta ’ età ta ’ < 18- il sena.
Smoking:
Tipjip:
Clearance of cinacalcet is higher in smokers than in non-smokers, likely due to induction of CYP1A2- mediated metabolism.
It- tneħħija ta ’ cinacalcet hija ogħla f’ min ipejjep milli f’ min ma jpejjipx, probabbilment minħabba induzzjoni ta ’ metaboliżmu medjat minn CYP1A2.
If a patient stops or starts smoking, cinacalcet plasma levels may change and dose adjustment may be necessary.
Jekk pazjent jieqaf jew jibda jpejjep, il - livelli ta ’ cinacalcet fil- plażma jistgħu jinbidlu u jista ’ jkun neċessarju aġġustament fid- doża.
Cinacalcet was not teratogenic in rabbits when given at a dose of 0.4 times, on an AUC basis, the maximum human dose for secondary HPT (180 mg daily).
Cinacalcet ma kienx teratoġeniku fil- fniek meta ngħata f’ doża li fuq bażi ta ’ l- AUC kienet 0. 4 drabi id- doża massima tal- kura ta ’ HPT sekondarja fil- bniedem (180 mg kuljum).
The non-teratogenic dose in rats was 4.4 times, on an AUC basis, the maximum dose for secondary HPT.
Fuq bażi ta ’ l- AUC, id - doża mhux teratoġenika fil- firien kienet 4. 4 darbiet, id- doża massima għal HPT sekondarja.
There were no effects on fertility in males or females at exposures up to 4 times a human dose of 180 mg/ day (safety margins in the small population of patients administered a maximum clinical dose of 360 mg daily would be approximately half those given above).
Ma kienx hemm effetti fuq il- fertilità fl- irġiel jew n- nisa f’ espożizzjonijiet sa 4 darbiet id- doża umana ta ’ 180 mg/ kuljum (marġini ta ’ siġurtà fil- popolazzjoni żgħira ta ’ pazjenti mogħtija id- doża klinika massima ta ’ 360 mg kuljum tkun madwar nofs dawk mogħtija hawn fuq).
In pregnant rats, there were slight decreases in body weight and food consumption at the highest dose.
F’ firien tqal, fl- ogħla doża kien hemm tnaqqis żgħar fil- piż tal- ġisem u fl- ammont ta ’ ikel meħud.
Decreased foetal weights were seen in rats at doses where dams had severe hypocalcaemia.
Tnaqqis fil- piż tal- feti deher fil- firien f’ dożi fejn l- ommijiet kellhom ipokalċimja severa.
Cinacalcet has been shown to cross the placental barrier in rabbits.
Cinacalcet intwera li jaqsam il- barriera tal- plaċenta fil- fniek.
Cinacalcet did not show any genotoxic or carcinogenic potential.
Cinacalcet ma wera l- ebda potenzjal ġenotossiku jew karċinoġeniku.
Cataracts and lens opacities were observed in the repeat dose rodent toxicology and carcinogenicity studies, but were
Il- marġini ta ’ siġurtà minn studji tossikoloġiċi huma żgħar minħabba ipokalċimja li tillimita d- doża osservata f’ mudelli ta ’ annimali.
9 not observed in dogs or monkeys or in clinical studies where cataract formation was monitored.
9 Katarretti u opaċitajiet fil- lenti kienu osservati fl- istudji ta ’ tossikoloġija u karċenoġeniċità fil- firien b’ doża ripetuta, iżda ma kienux osservati fil- klieb jew xadini jew fi studji kliniċi fejn il- formazzjoni tal- katarretti kienet issorveljata.
Cataracts are known to occur in rodents as a result of hypocalcaemia.
Katarretti huma magħrufa li jseħħu fil- firien minħabba ipokalċimja.
In in vitro studies, IC50 values for the serotonin transporter and KATP channels were found to be 7 and 12 fold greater, respectively, than the EC50 for the calcium-sensing receptor obtained under the same experimental conditions.
Fi studji in vitro, valuri ta ’ IC50 għat- trasportatur ta ’ serotonin u tal- kanali KATP instabu li kienu 7 u 12 - il darba ikbar, rispettivament, mill- EC50 tar- riċettur li jħoss il- kalċju, miġbura taħt l- istess kundizzjonijiet sperimentali.
The clinical relevance is unknown, however, the potential for cinacalcet to act on these secondary targets cannot be fully excluded.
Ir- rilevanza klinika mhux magħrufa, iżda, il- potenzjal għal cinacalcet biex jaħdem fuq dawn il- miri sekondarji ma jistax jiġi eskluż kompletament.
Tablet Core
Qalba tal- Pillola
Pre-gelatinised starch (maize) Microcrystalline cellulose Povidone Crospovidone Magnesium stearate Colloidal anhydrous silica
Pre- gelatinised starch (maize) Microcrystalline cellulose Povidone Crospovidone Magnesium stearate Colloidal anhydrous silica
Tablet Coat
Rita tal- Pillola
Carnauba Wax Opadry II green:
Carnauba Wax Opadry II aħdar:
(Lactose monohydrate, hypromellose, titanium dioxide (E171), glycerol triacetate, FD & C Blue (E132), iron oxide yellow (E172)
(Lactose monohydrate, hypromellose, titanium dioxide (E171), glycerol triacetate, FD & C Blu (E132), iron oxide isfar (E172)
Opadry clear:
Opadry ċar:
Opacode Black, printing ink:
Opacode iswed, linka għall- istampar:
(Hypromellose, macrogol) (Shellac glaze (shellac), iron oxide black (E172)
(Hypromellose, macrogol) (Shellac glaze (shellac), iron oxide iswed (E172)
Blister:
Folja:
4 years.
Flixkun:
Bottle:
Erba ’ snin.
4 years.
6. 4 Prekawzjonijiet speċjali għall- ħażna
This medicinal product does not require any special storage conditions.
Dan il- prodott ma jinħtieġx kundizzjonijiet speċjali għall- ħażna.
Aclar/ PVC/ PVAc/ Aluminium blister containing 14 tablets.
Folja ta ’ Aclar/ PVC/ PVAc/ Aluminju li fiha 14- il pillola.
Pack sizes of 1 blister (14 tablets), 2 blisters (28 tablets), 6 blisters (84 tablets) per carton.
Daqsijiet tal- pakketti ta ’ folja waħda (14- il pillola), żewġ folji (28 pillola), 6 folji (84 pillola) f’ kull kartuna.
High Density Polyethylene (HDPE) bottle with a desiccant canister and polyester coil, and a child- resistant polypropylene cap with an induction seal, packed into a carton.
Flixkun ta ’ High Density Polyethylene (HDPE) b’ ċilindru ta ’ dessicant u kolja tal- polyester, u tapp tal- polypropylene li ma jinfetaħx faċilment mit- tfal b’ siġill ta ’ induzzjoni, ippakkjat ġo kartuna.
Each bottle contains 30 tablets.
Kull flixkun fih 30 pillola.
6.6 Special precautions for disposal
10 6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema
22 October 2004
22 ta ’ Ottubru 2004
Detailed information on this product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il- mediċini (EMEA) http: // www. emea. europa. eu /
Mimpara 60 mg film-coated tablets.
Mimpara 60 mg pilloli miksija b’ rita.
Each tablet contains 60 mg cinacalcet (as hydrochloride).
Kull pillola fiha 60 mg cinacalcet (bħala hydrochloride).
Light green, oval, film-coated tablets marked “ AMGEN” on one side and “ 60” on the other.
Pilloli miksija b’ rita, ħodor ċari, ovali mmarkati b ’ “ AMGEN ” fuq naħa u “ 60 ” fuq in- naħa l - oħra.
Mimpara should be titrated every 2 to 4 weeks to a maximum dose of 180 mg once daily to achieve a target parathyroid hormone (PTH) in dialysis patients of between 150-300 pg/ ml (15.9-31.8 pmol/ l) in the intact PTH (iPTH) assay.
Mimpara għandu jiġi ttitrat kull ġimgħatejn sa 4 ġimgħat sa doża massima ta ’ 180 mg darba kuljum biex tintlaħaq il- mira tal - ormon tal- paratirojde (PTH) f’ pazjenti bid- dijalisi li hija bejn 150- 300 pg/ ml (15. 9- 31. 8 pmol/ l)
Reference should be made to current treatment guidelines.
Għandha ssir referenza għall- linji gwida ta ’ kura kurrenti.
12 PTH should be measured 1 to 4 weeks after initiation or dose adjustment of Mimpara.
PTH għandu jitkejjel minn ġimgħa sa 4 ġimgħat wara l- bidu tal- kura jew aġġustament fid- doża ta ’ Mimpara.
If serum calcium levels decrease below the normal range, appropriate steps should be taken (see section 4.4).
Jekk il- livelli ta ’ kalċju fis- serum jonqsu taħt il- firxa normali, għandhom jittieħdu passi xierqa (ara sezzjoni 4. 4).
The dosage of Mimpara should be titrated every 2 to 4 weeks through sequential doses of 30 mg twice daily, 60 mg twice daily, 90 mg twice daily, and 90 mg three or four times daily as necessary to reduce serum calcium concentration to or below the upper limit of normal.
Id- dożaġġ ta ’ Mimpara għandu jiġi ttitrat kull ġimgħatejn sa 4 ġimgħat permeżż ta ’ dożi sekwenzjali ta ’ 30 mg darbtejn kuljum, 60 mg darbtejn kuljum, 90 mg darbtejn kuljum, u 90 mg tlieta jew erba ’ darbiet kuljum, kif neċessarju biex jitnaqqas il- konċetrazzjoni ta ’ kalċju fis- serum sa jew inqas mil- limitu ta ’ fuq tan- normal.
13 Hypotension and/ or worsening heart failure
13 Pressjoni baxxa u/ jew insuffiċjenza tal- qalb li sejra għall- agħar
Investigational studies have shown that CKD patients not on dialysis treated with cinacalcet have an increased risk for hypocalcaemia (serum calcium levels < 8.4 mg/ dl [2.1 mmol/ l]) compared with cinacalcet-treated CKD patients on dialysis, which may be due to lower baseline calcium levels and/ or the presence of residual kidney function.
Dan jista 'jkun minħabba livelli ta ’ kalċju fil - linja bażi aktar baxxi u/ jew il- preżenza ta' fdal ta 'funzjoni fil- kliewi.
Caution should be exercised when Mimpara is administered with individually titrated, narrow therapeutic index medications that are predominantly metabolised by CYP2D6.
14 Għandha tintuża kawtela meta Mimpara tingħata ma ’ mediċini, ttitrati individwalment li għandhom indiċi terapewtiku dejjaq u li huma metabolizzati pimarjament minn CYP2D6.
14 Plasma levels of cinacalcet may be lower in smokers due to induction of CYP1A2-mediated metabolism.
Il- livelli ta ’ cinacalcet fil- plażma jistgħu jkunu inqas f’ min ipejjep minħabba l- induzzjoni ta ’ metaboliżmu medjat minn CYP1A2.
Dose adjustments of concomitant medicinal products may be required when Mimpara is administered with individually titrated, narrow therapeutic index substances that are predominantly metabolised by CYP2D6 (e. g., flecainide, propafenone, metoprolol given in heart failure, desimipramine, nortriptyline, clomipramine) (see section 4.4).
Jista ’ jkun hemm bżonn ta ’ aġġustament fid- doża ta ’ mediċini ttitrati individwalment, li għandhom indiċi terapewtiku dejjaq u li huma metabolizzati pimarjament minn CYP2D6 (e. ż., flecainide, propafenone, metoprolol mogħti f’ każijiet ta ’ insuffiċjenza tal- qalb, desipramine, nortriptyline, clomipramine) meta dawn jingħataw flimkien ma ’ Mimpara (ara sezzjoni 4. 4).
15 4.6 Pregnancy and lactation
15 mmetabolizzati minn CYP3A4 u CYP3A5, bħal ċertu immunosopressanti, inkluż cyclosporine u tacrolimus.
Nausea and vomiting were mild to moderate in severity and transient in nature in the majority of patients.
Fil - maġġoranza tal- pazjenti t - tqalligħ u r- rimettar kienu ħfief sa moderati fis- severità u temporanji fin - natura.
Adverse reactions, defined as adverse events considered at least possibly attributable to cinacalcet treatment based on best-evidence assessment of causality and reported in excess of placebo in double- blind clinical studies are listed below using the following convention: 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).
Reazzjonijiet avversi, definiti bħala episodi avversi ikkunsidrati bħala ta ’ l- inqas possibilment attribwiti mal -- kura b’ cinacalcet ibbażat fuq valutazzjoni ta ’ l- aqwa evidenza ta ’ kawżalità u rrappurtati aktar milli bil- plaċebo fl- istudji kliniċi double- blind huma mniżżla hawn taħt skond il - konvenzjoni li ġejja: 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).
Immune system disorders Uncommon: hypersensitivity reactions
- sistema immuni Mhux komuni: rezzjonijiet ta ’ sensitività eċċessiva
General disorders and administration site conditions Common: asthenia
16 Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata Komuni: astenja
16 Investigations Common: hypocalcaemia (see section 4.4), reduced testosterone levels (see section 4.4)
Investigazzjonijiet Komuni: ipokalċimja (ara sezzjoni 4. 4), tnaqqis fil- livelli ta ’ testosterone (ara sezzjoni 4. 4)
Doses titrated up to 300 mg once daily have been safely administered to patients receiving dialysis.
Dożi ttitrati sa 300 mg darba kuljum ingħataw b’ sigurtà lill- pazjenti li kienu fuq id- dijalisi.
Since cinacalcet is highly protein-bound, haemodialysis is not an effective treatment for overdosage.
Minħabba li cinacalcet jintrabat b ’ mod qawwi mal- proteini, emodijalisi mhix kura effettiva għal doża eċċessiva.
Demographic and baseline characteristics were representative of the dialysis patient population with secondary HPT.
Karatteristiċi demografiċi u tal- linja bażika kienu rappreżentattivi tal- popolazzjoni ta ’ pazjenti fuq id- dijalisi b’ HPT sekondarja.
Mean baseline iPTH concentrations across the 3 studies were 733 and 683 pg/ ml (77.8 and 72.4 pmol/ l) for the cinacalcet and placebo groups, respectively.
17 (77. 8 u 72. 4 pmol/ l) għall- gruppi ta ’ cinacalcet u plaċebo, rispettivament.
Cinacalcet decreased iPTH and Ca x P, calcium and phosphorus levels regardless of baseline iPTH or Ca x P level, dialysis modality (PD versus HD), duration of dialysis, and whether or not vitamin D sterols were administered.
Cinacalcet naqqas il- livelli ta ’ iPTH u ta ’ Ca x P, ta ’ kalċju u ta ’ fosforu indipendentament mill- livelli ta ’ linja bażika ta ’ iPTH jew livelli ta ’ Ca x P, modalità ta ’ dijalisi (PD kontra HD), tul tad- dijalisi, u jekk ingħatawx sterols ta ’ vitamina D.
However, efficacy, safety, optimal doses and treatment targets have not been established in treatment of predialytic renal failure patients.
Iżda, l- effikaċja, s- sigurtà, d- dożi ottimali u miri tal- kura ma ġewx stabbiliti fil - kura ta ’ pazjenti b’ indeboliment renali qabel id- dijalisi.
These studies show that CKD patients not undergoing dialysis treated with cinacalcet have an increased risk for hypocalcaemia compared with cinacalcet-treated ESRD patients receiving dialysis, which may be due to lower baseline calcium levels and/ or the presence of residual kidney function.
Dawn l- istudji juru li pazjenti b’ CKD li mhux qegħdin fuq id- dijalisi, li jingħataw cinacalcet, għandhom riskju miżjud ta ’ ipokalċimja meta mqabbla ma ’ pazjenti b’ ESRD li qed jirċievu d- dijalisi li jingħataw cinacalcet, li jista ’ jkun minħabba livelli ta ’ kalċju fil- linja bażi aktar baxxi u/ jew il- preżenza ta 'fdal ta' funzjoni tal- kliewi.
Cinacalcet was administered at doses ranging from 30 mg twice daily to 90 mg four times daily.
Cinacalcet ingħata f’ firxa ta ’ dożi minn 30 mg darbtejn kuljum sa 90 mg erba dariet kuljum.
Eighteen of 29 patients (62%) with parathyroid carcinoma and 15 of 17 subjects (88%) with primary HPT achieved a reduction in serum calcium of ≥ 1 mg/ dl (≥ 0.25 mmol/ l).
Tmintax minn 29 pazjent (62%) b’ karċinoma tal- paratirojde u 15 minn 17- il individwu (88%) b’ HPT primarja laħqu tnaqqis tal- kalċju fis- serum ta ’ ≥ 1 mg/ dl (≥ 0. 25 mmol/ l).
After absorption, cinacalcet concentrations decline in a biphasic fashion with an initial half-life of approximately 6 hours and a terminal half-life of 30 to 40 hours.
Wara l- assorbiment, konċentrazzjonijiet ta ’ cinacalcet jonqsu b’ mod bifażiku b’ half- life tal- bidu ta ’ madwar 6 sigħat u half- life terminali ta ’ 30 sa 40 siegħa.
The AUC and Cmax of cinacalcet increase approximately linearly over the dose range of 30 to 180 mg once daily.
L- AUC u Cmax ta ’ cinacalcet jiżdiedu bejn wieħed u ieħor b’ mod linejari fuq il- firxa ta ’ dożi ta ’ 30 sa 180 mg darba kuljum.
18 Cinacalcet is metabolised by multiple enzymes, predominantly CYP3A4 and CYP1A2 (the contribution of CYP1A2 has not been characterised clinically).
Cinacalcet jiġi metabolizzat minn bosta enżimi, primarjament CYP3A4 u CYP1A2 (il- kontribuzzjoni ta ’ CYP1A2 għadha ma ġietx ikkaratterizzata klinikament).
After administration of a 75 mg radiolabelled dose to healthy volunteers, cinacalcet was rapidly and extensively metabolised by oxidation followed by conjugation.
Wara għotja ta ’ doża radjutikketjata ta ’ 75 mg lill- voluntiera b’ saħħithom, cinacalcet kien metabolizzat malajr u estensivament permezz ta ’ ossidazzjoni u segwit minn konjugazzjoni.
Compared to subjects with normal liver function, average AUC of cinacalcet was approximately 2-fold higher in subjects with moderate impairment and approximately 4-fold higher in subjects with severe impairment.
Meta mqabbla ma ’ individwi b’ funzjoni normali tal- fwied, l- AUC medja ta ’ cinacalcet kienet madwar darbtejn ogħla f’ individwi b’ indeboliment moderat u madwar 4- darbiet ogħla f ’ individwi b’ indeboliment sever.
The mean half-life of cinacalcet is prolonged by 33% and 70% in patients with moderate and severe hepatic impairment, respectively.
F’ pazjenti b’ indeboliment epatiku moderat u sever, il- half - life medja ta ’ cinacalcet hija mtawwla bi 33% u 70% rispettivament.
Protein binding of cinacalcet is not affected by impaired hepatic function.
Ir- rabta ta ’ cinacalcet mal - proteini mhix affettwata minn funzjoni epatika indebolita.
(see sections 4.2 and 4.4).
Minħabba li d- dożi huma ttitrati għal kull individwu ibbażat fuq parametri ta ’ siġurtà u effikaċja, mhux neċessarju aktar aġġustament fid- doża għall- individwi b’ indeboliment epatiku (are sezzjonijiet 4. 2 u 4. 4).
Because doses are titrated for each subject, no additional dose adjustment is necessary based on gender.
Minħabba li d- dożi huma ttitrati għal kull individwu, mhux neċessarju aktar aġġustament fid- doża bbażat fuq is- sess.
The pharmacokinetics of cinacalcet have not been studied in patients < 18 years of age.
Il- farmakokinetika ta ’ cinacalcet ma ġietx studjata f’ pazjenti ta’ età ta ’ < 18- il sena.
Cinacalcet has been shown to cross the placental barrier in rabbits.
Cinacalcet intwera li jaqsam il- barriera plaċentari fil- fniek.
19 not observed in dogs or monkeys or in clinical studies where cataract formation was monitored.
19 Katarretti u opaċitajiet fil- lenti kienu osservati fl- istudji ta ’ tossikoloġija u karċenoġeniċità fil- firien b’ doża ripetuta, iżda ma kienux osservati fil- klieb jew xadini jew fi studji kliniċi fejn il- formazzjoni tal- katarretti kienet issorveljata.
In in vitro studies, IC50 values for the serotonin transporter and KATP channels were found to be 7 and 12 fold greater, respectively, than the EC50 for the calcium-sensing receptor obtained under the same experimental conditions.
Fi studji in vitro, valuri ta ’ IC50 għat- trasportatur ta ’ serotonin u tal- kanali KATP instabu li kienu 7 u 12 - il darba ikbar, rispettivament, mill- EC50 tar- riċettur li jħoss il- kalċju miġbura taħt l- istess kundizzjonijiet sperimentali.
6.6 Special precautions for disposal
20 6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema
Mimpara 90 mg film-coated tablets.
Mimpara 90 mg pilloli miksija b’ rita.
Each tablet contains 90 mg cinacalcet (as hydrochloride).
Kull pillola fiha 90 mg cinacalcet (bħala hydrochloride).
Light green, oval, film-coated tablets marked “ AMGEN” on one side and “ 90” on the other.
Pilloli miksija b’ rita, ħodor ċari, ovali mmarkati b ’ “ AMGEN ” fuq naħa u “ 90 ” fuq in- naħa l - oħra.
PTH levels should be assessed at least 12 hours after dosing with Mimpara.
Il- livelli ta ’ PTH jitkejjlu jiġu mkejla ta ’ l- inqas 12- il siegħa wara li ngħatat ta ’ Mimpara.
22 PTH should be measured 1 to 4 weeks after initiation or dose adjustment of Mimpara.
PTH għandu jitkejjel minn ġimgħa sa 4 ġimgħat wara l- bidu tal- kura jew aġġustament fid- doża ta ’ Mimpara.
Serum calcium should be measured within 1 week after initiation or dose adjustment of Mimpara.
Il- kalċju fis- serum għandu jitkejjel wara sa ġimgħa mill- bidu jew minn mindu jkun sar aġġustament fid- doża ta ’ Mimpara.
After titration to the maximum dose of Mimpara, serum calcium should be periodically monitored; if clinically relevant reductions in serum calcium are not maintained, discontinuation of Mimpara therapy should be considered (see section 5.1).
Wara titrazzjoni sad- doża massima ta ’ Mimpara, il- kalċju fis - serum għandu jiġi sorveljat perjodikament; jekk ma jinżamx tnaqqis klinikment rilevanti tal- kalċju fis - serum, għandu jiġi kkunsidrat twaqqif għal kollox tat- terapija b’ Mimpara (ara sezzjoni 5. 1).
23 Hypotension and/ or worsening heart failure
23 Pressjoni baxxa u/ jew insuffiċjenza tal- qalb li sejra għall- agħar
Clinical trial data showed hypotension occurred in 7% of cinacalcet-treated patients, 12% of placebo-treated patients, and heart failure occurred in 2% of patients receiving cinacalcet or placebo.
Tagħrif minn studji kliniċi wrew li kien hemm pressjoni baxxa f '7% ta' pazjenti li ngħataw cinacalcet, f' i 12% ta 'pazjenti li ngħataw plaċebo, u insuffiċjenza tal- qalb seħħet fi 2% ta' pazjenti li ngħataw cinacalcet jew plaċebo.
Potential manifestations of hypocalcaemia may include paraesthesias, myalgias, cramping, tetany and convulsions.
Manifestazzjonijiet potenzjali ta ’ ipokalċimja jistgħu jinkldu paresteżiji, mijalġiji, bugħawwiġ, tetanu u konvulżjonijiet.
Caution should be exercised when Mimpara is administered with individually titrated, narrow therapeutic index medications that are predominantly metabolised by CYP2D6.
24 Għandha tintuża kawtela meta Mimpara tingħata ma ’ mediċini, ttitrati individwalment li għandhom indiċi terapewtiku dejjaq u li huma metabolizzati pimarjament minn CYP2D6.
24 Plasma levels of cinacalcet may be lower in smokers due to induction of CYP1A2-mediated metabolism.
Il- livelli ta ’ cinacalcet fil- plażma jistgħu jkunu inqas f’ min ipejjep minħabba l- induzzjoni ta ’ metaboliżmu medjat minn CYP1A2.
Dose adjustment of Mimpara may be required if a patient receiving Mimpara initiates or discontinues therapy with a strong inhibitor (e. g. ketoconazole, itraconazole, telithromycin, voriconazole, ritonavir) or inducer (eg rifampicin) of this enzyme (see Section 4.4).
Jista ’ jkun hemm bżonn ta ’ aġġustament fid- doża ta ’ Mimpara jekk pazjent li qed jieħu Mimpara jibda jew iwaqqaf terapija b’ inibitur qawwi( e. ż. ketoconazole, itraconazole, telithromycin, voriconazole, ritonavir) jew induttur qawwi (eg rifampicin) ta ’ din l- enżima (ara sezzjoni 4. 4).
Concurrent administration of 90 mg cinacalcet once daily with 50 mg desipramine, a tricyclic antidepressant metabolised primarily by CYP2D6, significantly increased desipramine exposure 3.6-fold (90% CI 3.0, 4.4) in CYP2D6 extensive metabolizers.
L- għotja ta ’ 90 mg cinacalcet darba kuljum flimkien ma ’ 50 mg desipramine, antidepressanti triċikliċi metabolizzat primarjament minn CYP2D6, żiedet b’ mod sinifikanti l - espożizzjoni ta ’ desipramine bi 3. 6 darbiet (90% CI 3. 0, 4. 4) f’ metabolizzaturi estensivi ta ’ CYP2D6.
25 4.6 Pregnancy and lactation
25 mmetabolizzati minn CYP3A4 u CYP3A5, bħal ċertu immunosopressanti, inkluż cyclosporine u tacrolimus.
No embryonal/ foetal toxicities were seen in studies in pregnant rats and rabbits with the exception of decreased foetal body weights in rats at doses associated with maternal toxicities (see section 5.3).
Ma dehru l- ebda tossiċitajiet fl - embriju/ fetu fi studji li saru b’ firien u fniek tqal bl- eċċeżżjoni ta ’ tnaqqis fil- piż tal- fetu f’ dożi assoċjati ma ’ tossiċitajiet fl- omm (ara sezzjoni 5. 3).
The most commonly reported undesirable effects were nausea and vomiting, occurring in 31% Mimpara and 19% placebo treated patients, and 27% Mimpara and 15% placebo treated patients, respectively.
L- aktar effetti mhux mixtieqa irrappurtati b’ mod komuni kienu tqalligħ u rimettar, li dehru f’ 31% tal- pazjenti kkurati b’ Mimpara u f’ 19% tal- pazjent kkurati bil- plaċebo, u f’ 27% tal - pazjenti kkurati b’ Mimpara u fi 15% tal- pazjenti kkurati bil- plaċebo, rispettivament.
Nausea and vomiting were mild to moderate in severity and transient in nature in the majority of patients.
Fil - maġġoranza tal- pazjenti t- tqallih u r- rimettar kienu ħfief sa moderati fis- severità u temporanji fin - natura.
Musculoskeletal, connective tissue and bone disorders Common: myalgia
Disturbimuskolu- skeletrali, tal- connective tissue u tal- għadam Komuni: mijalġja
General disorders and administration site conditions Common: asthenia
26 Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata Komuni: astenja
26 Investigations Common: hypocalcaemia (see section 4.4), reduced testosterone levels (see section 4.4)
Investigazzjonijiet Komuni: ipokalċimja (ara sezzjoni 4. 4), tnaqqis fil- livelli ta ’ testosterone (ara sezzjoni 4. 4)
Since cinacalcet is highly protein-bound, haemodialysis is not an effective treatment for overdosage.
Minħabba li cinacalcet jintrabat b’ mod qawwi mal- proteini, emodijalisi mhix kura effettiva għal doża eċċessiva.
Mean baseline iPTH concentrations across the 3 studies were 733 and 683 pg/ ml (77.8 and 72.4 pmol/ l) for the cinacalcet and placebo groups, respectively.
27 (77. 8 u 72. 4 pmol/ l) għall- gruppi ta ’ cinacalcet u plaċebo, rispettivament.
In each of the studies, the primary endpoint (proportion of patients with an iPTH ≤ 250 pg/ ml (≤ 26.5 pmol/ l)) was achieved by 41%, 46%, and 35% of patients receiving cinacalcet, compared with 4%, 7%, and 6% of patients receiving placebo.
F’ kull wieħed mill- istudji, il - mira primarja (proporżjon ta ’ pazjenti b’ iPTH ≤ 250 pg/ ml (≤ 26. 5 pmol/ l)) intlaħqet minn 41%, 46%, u 35% tal- pazjenti li rċevew cinacalcet, meta mqabbla ma ’ 4%, 7%, u 6% tal- pazjenti li rċevew plaċebo.
Cinacalcet decreased iPTH and Ca x P, calcium and phosphorus levels regardless of baseline iPTH or Ca x P level, dialysis modality (PD versus HD), duration of dialysis, and whether or not vitamin D sterols were administered.
Cinacalcet naqqas il- livelli ta ’ iPTH u ta ’ Ca x P, kalċju u ta ’ fosforu indipendentament mill- livelli ta ’ linja bażika ta ’ iPTH jew livelli ta ’ Ca x P, modalità ta ’ dijalisi (PD kontra HD), tul tad- dijalisi, u jekk ingħatawx sterols ta ’ vitamina D.
These studies show that CKD patients not undergoing dialysis treated with cinacalcet have an increased risk for hypocalcaemia compared with cinacalcet-treated ESRD patients receiving dialysis, which may be due to lower baseline calcium levels and/ or the presence of residual kidney function.
Dawn l- istudji juru li pazjenti b’ CKD li mhux qegħdin fuq id- dijalisi, li jingħataw cinacalcet għandhom riskju miżjud ta ’ ipokalċimja meta mqabbla ma ’ pazjenti b’ ESRD li qed jirċievu d- dijalisi li jingħataw cinacalcet, li jista ’ jkun minħabba livelli ta ’ kalċju fil- linja bażi aktar baxxi u/ jew il- preżenza ta 'fdal ta' funzjoni tal- kliewi.
Cinacalcet is approximately 97% bound to plasma proteins and distributes minimally into red blood cells.
Madwar 97% ta ’ cinacalcet jintrabat tal- proteini fil- plażma u ftit li xejn jiġi distribwit fiċ- ċelloli l- ħomor tad- demm.
28 Cinacalcet is metabolised by multiple enzymes, predominantly CYP3A4 and CYP1A2 (the contribution of CYP1A2 has not been characterised clinically).
Cinacalcet jiġi metabolizzat minn bosta enżimi, primarjament CYP3A4 u CYP1A2 (il- kontribuzzjoni ta ’ CYP1A2 għadha ma ġietx ikkaratterizzata klinikament).
(see sections 4.2 and 4.4).
Minħabba li d- dożi huma ttitrati għal kull individwu ibbażat fuq parametri ta ’ siġurtà u effikaċja, mhux neċessarju aktar aġġustament fid- doża għall - individwi b’ indeboliment epatiku (are sezzjonijiet 4. 2 u 4. 4).
Because doses are titrated for each subject, no additional dose adjustment is necessary based on gender.
Minħabba li d- dożi huma ttitrati għal kull individw, mhux neċessarju aktar aġġustament fid- doża bbażat fuq is- sess.
There were no effects on fertility in males or females at exposures up to 4 times a human dose of 180 mg/ day (safety margins in the small population of patients administered a maximum clinical dose of 360 mg daily would be approximately half those given above).
Ma kienx hemm effetti fuq il- fertilità fl- irġiel jew n- nisa f’ espożizzjonijiet sa 4 darbiet id- doża umana ta ’ 180 mg/ kuljum (marġini ta ’ siġurtà fil- popolazzjoni żgħira ta ’ pazjenti mogħtija id- doża klinikali massima ta ’ 360 mg kuljum tkun madwar nofs dawk mogħtija hawn fuq).
29 not observed in dogs or monkeys or in clinical studies where cataract formation was monitored.
29 Katarretti u opaċitajiet fil- lenti kienu osservati fl- istudji ta ’ tossikoloġija u karċenoġeniċità fil- firien b’ doża ripetuta, iżda ma kienux osservati fil- klieb jew xadini jew fi studji kliniċi fejn il- formazzjoni tal- katarretti kienet issorveljata.
6.6 Special precautions for disposal
30 6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
DETENTURTA ’ L- AWTORIZZAZZJONI TAL - MANIFATTURA RESPONSABBLI GĦALL- HRUĠ TAL - LOTT
32 A MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
DETENTUR TA ’ L- AWTORIZZAZZJONI TAL- MANIFATTURA RESPONSABBLI GĦALL- HRUĠ TAL- LOTT