natgillin/translations-raw huggingface dataset:
However, there is no information to indicate that ADROVANCE affects a patient’ s ability to drive or operate machines.
Vendar pa ni podatkov, ki bi kazali, da ADROVANCE vpliva na sposobnost vožnje ali upravljanja s stroji.
The following adverse reactions have been reported during clinical studies and/ or post-marketing use with alendronate.
Iz kliničnih raziskav in/ ali s tržišča so poročali o naslednjih neželenih učinkih alendronata.
No additional adverse reactions have been identified for ADROVANCE.
Pri zdravilu ADROVANCE niso ugotovili dodatnih neželenih učinkov.
[Common (≥ 1/ 100, < 1/ 10), uncommon (≥ 1/ 1000, < 1/ 100), rare (≥ 1/ 10,000, < 1/ 1000), very rare (< 1/ 10,000)]
[Pogosti (≥ 1/ 100, < 1/ 10), občasni (≥ 1/ 1. 000, < 1/ 100), redki (≥ 1/ 10. 000, < 1/ 1. 000), zelo redki (< 1/ 10. 000)]
5 Nervous system disorders:
Pogosti: glavobol Bolezni živčevja Redke: uveitis, skleritis, episkleritis Očesne bolezni
Common: headache
Prepoznani dejavniki tveganja so tudi rak, kemoterapija, radioterapija, kortikosteroidi in slaba ustna higiena (glej poglavje 4. 4); otekli sklepi
Gastrointestinal disorders:
astenija, periferni edemi Splošne težave in spremembe na mestu aplikacije
Skin and subcutaneous tissue disorders:
Izvidi laboratorijskih preiskav:
Uncommon: rash, pruritus, erythema Rare: rash with photosensitivity Very rare: severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis
V kliničnih raziskavah so opazili asimptomatska, blaga in prehodna zmanjšanja serumskega kalcija in fosfata: pri bolnikih, ki so jemali alendronat 10 mg na dan, za približno 18% oz.
Musculoskeletal and connective tissue disorders:
10%, pri bolnikih, ki so jemali placebo, pa za približno 12% oz.
Metabolism and nutrition disorders:
3%.
(see section 4.4) Rare: transient symptoms as in an acute-phase response (myalgia, malaise and rarely, fever), typically in association with initiation of treatment.
Pojavnost zmanjšanja serumskega kalcija na < 8, 0 mg/ dl (2, 0 mmol/ l) in serumskega fosfata na ≤ 2, 0 mg/ dl (0, 65 mmol/ l) pa je bila v obeh skupinah podobna.
Nervous system disorders:
4. 9 Preveliko odmerjanje
The majority of the reports refer to cancer patients, but such cases have also been reported in patients treated for osteoporosis.
Alendronat Zaradi prekomernih peroralnih odmerkov lahko pride do hipokalcemije, hipofosfatemije in neželenih učinkov v zgornjem delu prebavil, kot so razdraženost želodca, zgaga, ezofagitis, gastritis ali razjeda.
General disorders and administration site conditions:
Posebnih napotkov o ukrepih pri prekomernem odmerjanju alendronata ni na voljo.
However, the incidences of decreases in serum calcium to < 8.0 mg/ dl (2.0 mmol/ l) and serum phosphate to ≤ 2.0 mg/ dl (0.65 mmol/ l) were similar in both treatment groups.
Če bolnik vzame prekomeren odmerek zdravila ADROVANCE, naj pije mleko ali vzame antacid, ki vežeta alendronat.
6 4.9 Overdose
6 Zaradi nevarnosti draženja požiralnika se bruhanja ne sme izzvati.
No specific information is available on the treatment of overdose with alendronate.
Bolnik mora ostati v popolnoma vzravnanem položaju.
Colecalciferol Vitamin D toxicity has not been documented during chronic therapy in generally healthy adults at a dose less than 10,000 IU/ day.
Holekalciferol Toksičnega učinka vitamina D pri sicer na splošno zdravih odraslih, ki so dlje časa dobivali odmerke manj kot 10. 000 i. e. dnevno, niso ugotovili.
In a clinical study of healthy adults a 4000 IU daily dose of vitamin D3 for up to five months was not associated with hypercalciuria or hypercalcaemia.
V klinični raziskavi pri zdravih odraslih, ki so do 5 mesecev jemali 4. 000 i. e. vitamina D3 dnevno, niso ugotovili povezave s hiperkalciurijo ali hiperkalcemijo.
Pharmacodynamic properties
5. 1 Farmakodinamične lastnosti
Bisphosphonates, combinations, ATC code:
Oznaka ATC:
ADROVANCE is a combination tablet containing the two active substances alendronate sodium trihydrate and colecalciferol (vitamin D3).
ADROVANCE je kombinirana tableta, ki vsebuje dve zdravilni učinkovini natrijev alendronat trihidrat in holekalciferol (vitamin D3).
Alendronate Alendronate sodium is a bisphosphonate that inhibits osteoclastic bone resorption with no direct effect on bone formation.
Alendronat Natrijev alendronat je bisfosfonat, ki zavira osteoklastno kostno resorpcijo brez neposrednega učinka na tvorbo kosti.
Preclinical studies have shown preferential localisation of alendronate to sites of active resorption.
Predklinične raziskave so pokazale, da se alendronat lokalizira predvsem v predelih, kjer poteka aktivna resorpcija.
Activity of osteoclasts is inhibited, but recruitment or attachment of osteoclasts is not affected.
Zavrto je delovanje osteoklastov, ne pa tudi njihovo pridobivanje oziroma privabljanje.
Colecalciferol (vitamin D3) Vitamin D3 is produced in the skin by conversion of 7-dehydrocholesterol to vitamin D3 by ultraviolet light.
Holekalciferol (vitamin D3) Vitamin D3 se tvori v koži s pretvorbo 7- dehidroholesterola v vitamin D3 z ultravijolično svetlobo.
In the absence of adequate sunlight exposure, vitamin D3 is an essential dietary nutrient.
Če oseba ni dovolj izpostavljena soncu, je vitamin D3 treba vnesti s hrano.
Vitamin D3 is converted to 25-hydroxyvitamin D3 in the liver, and stored until needed.
Vitamin D3 se v jetrih presnovi v 25- hidroksivitamin D3, nato pa se uskladišči, dokler ni potreben.
Conversion to the active calcium-mobilizing hormone 1,25-dihydroxyvitamin D3 (calcitriol) in the kidney is tightly regulated.
Presnova v aktivni 1, 25- dihidroksivitamin D3 (kalcitriol), ki mobilizira kalcij, poteka v ledvicah in je strogo nadzorovana.
The principal action of 1,25-dihydroxyvitamin D3 is to increase intestinal absorption of both calcium and phosphate as well as regulate serum calcium, renal calcium and phosphate excretion, bone formation and bone resorption.
Glavni učinek 1, 25- dihidroksivitamina D3 je povečanje absorpcije kalcija in fosfata v črevesu, uravnava pa tudi serumski kalcij, izločanje kalcija in fosfata z ledvicami ter tvorbo in resorpcijo kosti.
Vitamin D3 is required for normal bone formation.
Vitamin D3 je potreben za tvorbo normalne kosti.
Insufficiency is associated with negative calcium balance, bone loss, and increased risk of skeletal fracture.
Pri pomanjkanju pride do negativne bilance kalcija, izgube kostnine in povečanja tveganja zlomov kosti.
In severe cases, deficiency results in secondary hyperparathyroidism, hypophosphataemia, proximal muscle weakness and osteomalacia, further increasing the risk of falls and fractures in osteoporotic individuals.
Pri hudem pomanjkanju se pojavi sekundarni hiperparatiroidizem, hipofosfatemija, oslabelost proksimalnih mišic in osteomalacija, kar še bolj poveča tveganje padcev in zlomov pri bolnikih z osteoporozo.
Osteoporosis is defined as bone mineral density (BMD) of the spine or hip 2.5 standard deviations (SD) below the mean value of a normal young population or as a previous fragility fracture, irrespective of BMD.
Osteoporoza je opredeljena z zmanjšanjem mineralne kostne gostote (MKG) hrbtenice ali kolka za 2, 5 standardni deviaciji (SD) pod povprečje za normalno mlado populacijo ali populacijo s predhodnimi zlomi krhkih kosti ne glede na MKG.
ADROVANCE studies The effect of ADROVANCE (alendronate 70 mg/ vitamin D3 2800 IU) on vitamin D status was demonstrated in a 15-week, multinational study that enrolled 682 osteoporotic post-menopausal women (serum 25-hydroxyvitamin D at baseline: mean, 56 nmol/ l [22.3 ng/ ml]; range, 22.5- 225 nmol/ l [9-90 ng/ ml]).
Raziskave z zdravilom ADROVANCE Vpliv zdravila ADROVANCE (alendronat 70 mg/ vitamin D3 2. 800 i. e.) na status vitamina D so ugotavljali v 15- tedenski, mednarodni raziskavi, v katero je bilo vključenih 682 žensk s pomenopavzalno osteoporozo (serumski 25- hidroksivitamin D ob začetku raziskave: povprečna vrednost 56 nmol/ l [22, 3 ng/ ml]; obseg vrednosti 22, 5– 225 nmol/ l [9– 90 ng/ ml].
Patients received the lower strength (70 mg/ 2800 IU) of ADROVANCE (n=350) or FOSAMAX (alendronate) 70 mg (n=332) once a week; additional vitamin D supplements
Bolnice so enkrat tedensko dobivale manjšo jakost (70 mg/ 2. 800 i. e.) zdravila ADROVANCE (n = 350) ali zdravilo FOSAMAX (alendronat) 70 mg (n = 332) enkrat tedensko; dodatno jemanje vitamina D je bilo prepovedano.
After 15 weeks of treatment, the mean serum 25-hydroxyvitamin D levels were significantly higher (26%) in the ADROVANCE (70 mg/ 2800 IU) group (56 nmol/ l [23 ng/ ml]) than in the alendronate-only group (46 nmol/ l [18.2 ng/ ml]).
Po 15 tednih zdravljenja so bile srednje serumske vrednosti 25- hidroksivitamina D v skupini, ki je dobivala ADROVANCE (70 mg/ 2. 800 i. e.), pomembno večje (26%) (56 nmol/ l [23 ng/ ml]) kot v skupini, ki je jemala samo alendronat (46 nmol/ l [18, 2 ng/ ml]).
The percentage of patients with vitamin D insufficiency (serum 25-hydroxyvitamin D < 37.5 nmol/ l [< 15 ng/ ml]) was significantly reduced by 62.5% with ADROVANCE (70 mg/ 2800 IU) vs. alendronate-only (12% vs.
Delež bolnic s pomanjkanjem vitamina D (serumski 25- hidroksivitamin D < 37, 5 nmol/ l [< 15 ng/ mol]) je bil v skupini, ki je prejemala ADROVANCE (70 mg/ 2. 800 i. e.) pomembno nižji (za 62, 5%) kot v skupini,
32%, respectively), through week 15.
32%) vse do 15. tedna.
The percentage of patients with vitamin D deficiency (serum 25-hydroxyvitamin D < 22.5 nmol/ l [<  9 ng/ ml]) was significantly reduced by 92% with ADROVANCE (70 mg/ 2800 IU) vs. alendronate-only (1% vs 13%, respectively).
Delež bolnic s hudim pomanjkanjem vitamina D (serumski 25- hidroksivitamin D ≤ 22, 5 nmol/ l [≤ 9 ng/ mol]) je bil v skupini, ki je prejemala ADROVANCE (70 mg/ 2. 800 i. e.) pomembno nižji (za 92%) kot v skupini, ki je prejemala le alendronat (1% oz.
In this study, mean 25-hydroxyvitamin D levels in patients with vitamin D insufficiency at baseline (25- hydroxyvitamin D, 22.5 to 37.5 nmol/ l [9 to < 15 ng/ ml]) increased from 30 nmol/ l (12.1 ng/ ml) to 40 nmol/ l (15.9 ng/ ml) at week 15 in the ADROVANCE (70 mg/ 2800 IU) group (n=75) and decreased from 30 nmol/ l (12.0 ng/ ml) at baseline to 26 nmol/ l (10.4 ng/ ml) at week 15 in the alendronate-only group (n=70).
V tej raziskavi so se srednje vrednosti 25- hidroksivitamina D pri bolnicah s pomanjkanjem vitamina D (25- hidroksivitamin D, 22, 5 do 37, 5 nmol/ l [9 do < 15 ng/ ml]) dvignili z začetnih 30 nmol/ l (12, 1 ng/ ml) na 40 nmol/ l (15, 9 ng/ ml) v 15. tednu v skupini, ki je prejemala ADROVANCE (70 mg/ 2. 800 i. e.) (n=75) in znižali z začetnih 30 nmol/ l (12, 0 ng/ ml) na 26 nmol/ l (10, 4 ng/ ml) v 15. tednu v skupini, ki je prejemala le alendronat (n=70).
There were no differences in mean serum calcium, phosphate, or 24-hour urine calcium between treatment groups.
Med skupinama ni bilo razlik v povprečni vrednosti serumskega kalcija, serumskega fosfata ali kalcija v 24- urnem urinu.
Alendronate studies The therapeutic equivalence of alendronate once weekly 70 mg (n=519) and alendronate 10 mg daily (n=370) was demonstrated in a one-year multicentre study of post-menopausal women with osteoporosis.
Raziskave z alendronatom Terapevtsko ekvivalenco alendronata 70 mg enkrat tedensko (n = 519) in alendronata 10 mg enkrat dnevno (n = 370) so dokazali v enoletni multicentrični raziskavi pri ženskah s pomenopavzalno osteoporozo.
The mean increases from baseline in lumbar spine BMD at one year were 5.1% (95% CI:
Po enem letu se je pri skupini, ki je jemala 70 mg odmerek enkrat tedensko, MKG ledvene hrbtenice glede na izhodiščno vrednost povišala povprečno za 5, 1% (95% interval zaupanja:
4.8, 5.4%) in the 70 mg once-weekly group and 5.4% (95% CI:
4, 8%, 5, 4%), pri skupini, ki je jemala 10 mg odmerek enkrat dnevno pa povprečno za 5, 4% (95% interval zaupanja:
The mean BMD increases were 2.3% and 2.9% at the femoral neck and 2.9% and 3.1% at the total hip in the 70 mg once weekly and 10 mg daily groups, respectively.
Povprečno zvečanje MKG na vratu stegnenice je bilo pri skupini, ki je jemala 70 mg odmerek enkrat tedensko 2, 3%, pri skupini, ki je jemala 10 mg odmerek enkrat dnevno pa 2, 9%.
The two treatment groups were also similar with regard to BMD increases at other skeletal sites.
MKG celotnega kolka se je v prvi skupini povprečno zvišala za 2, 9%, v drugi skupini pa za 3, 1%.
The effects of alendronate on bone mass and fracture incidence in post-menopausal women were examined in two initial efficacy studies of identical design (n=994) as well as in the Fracture Intervention Trial (FIT: n=6,459).
Učinek alendronata na kostno maso in pojavnost zlomov pri ženskah po menopavzi so raziskovali v dveh začetnih enako zasnovanih raziskavah učinkovitosti (n = 994), kot tudi v raziskavi FIT (Fracture Intervention Trial, n = 6. 459).
In the initial efficacy studies, the mean BMD increases with alendronate 10 mg/ day relative to placebo at three years were 8.8%, 5.9% and 7.8% at the spine, femoral neck and trochanter, respectively.
7, 8%.
There was a 48% reduction (alendronate 3.2% vs placebo 6.2%) in the proportion of patients treated with alendronate experiencing one or more vertebral fractures relative to those treated with placebo.
Delež bolnic, ki so se zdravile z alendronatom in so doživele enega ali več zlomov vretenc, se je v primerjavi s tistimi, ki so dobivale placebo, znižal za 48% (alendronat 3, 2% v primerjavi s placebom 6, 2%).
In the two-year extension of these studies BMD at the spine and trochanter continued to increase and BMD at the femoral neck and total body were maintained.
V dvoletnem podaljšku teh raziskav se je MKG hrbtenice in trohantra še naprej zviševala, MKG vratu stegnenice in celotnega telesa pa sta se vzdrževali.
FIT consisted of two placebo-controlled studies using alendronate daily (5 mg daily for two years and 10 mg daily for either one or two additional years):
Raziskava FIT sestoji iz dveh s placebom primerjanih raziskav, v katerih so bolnice jemale alendronat vsak dan (2 leti po 5 mg dnevno in 10 mg dnevno nadaljnje leto ali dve leti):
• FIT 1:
FIT 1:
A three-year study of 2,027 patients who had at least one baseline vertebral (compression) fracture.
Triletna raziskava pri 2. 027 bolnicah, ki so imele ob začetku raziskave vsaj en • (kompresijski) zlom vretenca.
In this study alendronate daily reduced the incidence of ≥ 1 new vertebral fracture by 47% (alendronate 7.9% vs. placebo 15.0%).
V tej raziskavi je dnevno zdravljenje z alendronatom zmanjšalo pojavnost enega ali več novih zlomov vretenc za 47% (alendronat 7, 9% v primerjavi s placebom 15, 0%).
2.2%, a reduction of 51%).
Statistično značilno zmanjšanje je bilo ugotovljeno tudi pri pojavnosti zlomov kolka (1, 1% v primerjavi z 2, 2%, 51% zmanjšanje).
• FIT 2:
FIT 2:
A four-year study of 4,432 patients with low bone mass but without a baseline vertebral fracture.
Štiriletna raziskava pri 4. 432 bolnicah z nizko kostno maso, vendar na začetku brez zloma • vretenca.
5.8%, a reduction of 50%).
V tej raziskavi so pri analizi podskupine žensk z osteoporozo (37% svetovne populacije, ki ustreza že omenjeni definiciji osteoporoze) opazili pomembno razliko v pojavnosti zlomov kolka (alendronat 1, 0% v primerjavi s placebom 2, 2%, 56% zmanjšanje) in v pojavnosti ≥ 1 zlomov vretenc (2, 9% v primerjavi s 5, 8%, 50% zmanjšanje).
Pharmacokinetic properties
5. 2 Farmakokinetične lastnosti
Absorption Relative to an intravenous reference dose, the oral mean bioavailability of alendronate in women was 0.64% for doses ranging from 5 to 70 mg when administered after an overnight fast and two hours before a standardised breakfast.
Absorpcija Po peroralni uporabi (zjutraj na tešče in dve uri pred standardiziranim zajtrkom) je bila pri ženskah povprečna biološka uporabnost alendronata za odmerke od 5 do 70 mg v primerjavi z intravenskim referenčnim odmerkom 0, 64%.
Bioavailability was decreased similarly to an estimated 0.46% and 0.39% when alendronate was administered one hour or half an hour before a standardised breakfast.
8 pred standardiziranim zajtrkom podobno zmanjšala na ocenjenih 0, 46% in 0, 39%.
In osteoporosis studies, alendronate was effective when administered at least 30 minutes before the first food or beverage of the day.
V raziskavah osteoporoze je bil alendronat učinkovit pri jemanju vsaj 30 minut pred prvim dnevnim obrokom hrane ali pijače.
The alendronate component in the ADROVANCE (70 mg/ 2800 IU) combination tablet is bioequivalent to the alendronate 70 mg tablet.
Alendronat v kombinirani tableti ADROVANCE (70 mg/ 2. 800 i. e.) je bioekvivalenten alendronatu v 70 mg tableti.
Concomitant administration of alendronate with coffee or orange juice reduced bioavailability by approximately 60%.
Zaradi sočasnega zaužitja alendronata in kave ali pomarančnega soka se je biološka uporabnost zmanjšala za približno 60%.
In healthy subjects, oral prednisone (20 mg three times daily for five days) did not produce a clinically meaningful change in oral bioavailability of alendronate (a mean increase ranging from 20% to 44%).
Pri zdravih preiskovancih peroralni prednizon (20 mg trikrat dnevno, pet dni) ni povzročil klinično pomembne spremembe v peroralni biološki uporabnosti alendronata (povprečni porast od 20% do 44%).
Distribution Studies in rats show that alendronate transiently distributes to soft tissues following 1 mg/ kg intravenous administration but is then rapidly redistributed to bone or excreted in the urine.
Porazdelitev Raziskave pri podganah kažejo, da se alendronat po intravenski aplikaciji 1 mg/ kg prehodno porazdeljuje v mehka tkiva, nato pa se hitro prerazporedi v kosti ali se izloči z urinom.
Concentrations of alendronate in plasma following therapeutic oral doses are too low for analytical detection (< 5 ng/ ml).
Plazemske koncentracije alendronata po peroralnih terapevtskih odmerkih so za analitsko določitev prenizke (< 5 ng/ ml).
Protein binding in human plasma is approximately 78%.
Vezava na plazemske proteine je pri ljudeh približno 78%.
Biotransformation There is no evidence that alendronate is metabolised in animals or humans.
Presnova Ni dokazov, da se alendronat presnavlja v človeškem ali živalskem organizmu.
Elimination Following a single intravenous dose of [14C]alendronate, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no radioactivity was recovered in the faeces.
Izločanje Po enkratnem intravenskem odmerku [14C] alendronata se je približno 50% radioaktivnosti izločilo z urinom v 72 urah; v blatu so našli le malo ali nič radioaktivnosti.
Following a single 10 mg intravenous dose, the renal clearance of alendronate was 71 ml/ min, and systemic clearance did not exceed 200 ml/ min.
Po enkratnem 10 mg intravenskem odmerku je bil renalni očistek alendronata 71 ml/ min, sistemski očistek pa ni presegel 200 ml/ min.
Plasma concentrations fell by more than 95% within six hours following intravenous administration.
Za več kot 95% so plazemske koncentracije padle v 6 urah po intravenski aplikaciji.
Absorption In healthy adult subjects (males and females), following administration of ADROVANCE after an overnight fast and two hours before a meal, the mean area under the serum-concentration-time curve (AUC0-120 hrs) for vitamin D3 (unadjusted for endogenous vitamin D3 levels) was 296.4 ng• hr/ ml.
Absorpcija Pri zdravih odraslih preiskovancih (moški in ženske) je po zaužitju zdravila ADROVANCE na tešče (po postu celo noč) in dve uri pred obrokom povprečna površina pod krivuljo serumska koncentracija - čas (AUC0- 120 ur) za vitamin D3 (neprilagojen endogenim vrednostim vitamina D3) znašala 296, 4 ng h/ ml.
The mean maximal serum concentration (Cmax) of vitamin D3 was 5.9 ng/ ml, and the median time to maximal serum concentration (Tmax) was 12 hours.
Povprečna maksimalna serumska koncentracija (Cmax) vitamina D3 je znašala 5, 9 ng/ ml, mediana časa do maksimalne serumske koncentracije (Tmax) pa je bila 12 ur.
The bioavailability of the 2800 IU vitamin D3 in ADROVANCE is similar to 2800 IU vitamin D3 administered alone.
Biološka uporabnost 2. 800 i. e. vitamina D3 v zdravilu ADROVANCE je podobna kot pri zaužitju samo 2. 800 i. e. vitamina D3.
Distribution Following absorption, vitamin D3 enters the blood as part of chylomicrons.
Porazdelitev Po absorpciji vitamin D3 vstopi v kri kot del hilomikronov.
Vitamin D3 is rapidly distributed mostly to the liver where it undergoes metabolism to 25-hydroxyvitamin D3, the major storage form.
Vitamin D3 se hitro porazdeli večinoma v jetra, kjer se presnovi v 25- hidroksivitamin D3, glavno skladiščno obliko.
Lesser amounts are distributed to adipose and muscle tissue and stored as vitamin D3 at
Manjše količine se porazdelijo v maščevje in mišičje, kjer se kot vitamin D3 uskladiščijo za poznejše sproščanje v obtok.
Circulating vitamin D3 is bound to vitamin D-binding protein.
Vitamin D3 v obtoku je vezan na D- vezavno beljakovino.
Biotransformation Vitamin D3 is rapidly metabolized by hydroxylation in the liver to 25-hydroxyvitamin D3, and subsequently metabolized in the kidney to 1,25-dihydroxyvitamin D3, which represents the biologically active form.
Presnova Vitamin D3 se v jetrih s hidroksilacijo hitro presnovi v 25- hidroksivitamin D3, nato pa se v ledvicah presnovi v 1, 25- dihidroksivitamin D3, ki je biološko aktivna oblika.
Elimination When radioactive vitamin D3 was administered to healthy subjects, the mean urinary excretion of radioactivity after 48 hours was 2.4%, and the mean faecal excretion of radioactivity after 4 days was 4.9%.
9 Pri zdravih preiskovancih, ki so dobili radioaktivni vitamin D3, se je z urinom po 48 urah izločilo povprečno 2, 4% radioaktivnosti, povprečno izločanje radioaktivnosti z blatom po 4 dneh pa je bilo 4, 9%.
In both cases, the excreted radioactivity was almost exclusively as metabolites of the parent.
V obeh primerih je bila izločena radioaktivnost skoraj v celoti v obliki bolnikovih presnovkov.
The mean half-life of vitamin D3 in the serum following an oral dose of ADROVANCE (70 mg/ 2800 IU) is approximately 24 hours.
Povprečni razpolovni čas vitamina D3 v serumu po peroralnem odmerku zdravila ADROVANCE (70 mg/ 2. 800 i. e.) je približno 24 ur.
Characteristics in patients Preclinical studies show that alendronate that is not deposited in bone is rapidly excreted in the urine.
Značilnosti pri bolnikih Predklinične raziskave kažejo, da se alendronat, ki se ne odlaga v kosti, hitro izloči z urinom.
No evidence of saturation of bone uptake was found after chronic dosing with cumulative intravenous doses up to 35 mg/ kg in animals.
Po kroničnem odmerjanju kumulativnih intravenskih odmerkov do 35 mg/ kg pri živalih niso našli nobenih dokazov o nasičenju privzema v kosti.
Although no clinical information is available, it is likely that, as in animals, elimination of alendronate via the kidney will be reduced in patients with impaired renal function.
Čeprav kliničnih informacij ni na voljo, je možno, da se, kot pri živalih, izločanje alendronata preko ledvic pri bolnikih z okvaro ledvične funkcije zmanjša.
Therefore, somewhat greater accumulation of alendronate in bone might be expected in patients with impaired renal function (see section 4.2).
Zato se pri bolnikih z okvaro ledvične funkcije pričakuje nekoliko večje kopičenje alendronata v kosteh (glejte poglavje 4. 2).
Non-clinical studies with the combination of alendronate and colecalciferol have not been conducted.
Predkliničnih raziskav kombinacije alendronata in holekalciferola ni bilo.
Alendronate Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.
Alendronat Predklinični podatki, dobljeni s konvencionalnimi raziskavami farmakološke varnosti, toksičnosti pri večkratnih odmerkih, genotoksičnosti in potencialne kancerogenosti niso pokazali posebne nevarnosti za ljudi.
Studies in rats have shown that treatment with alendronate during pregnancy was associated with dystocia in dams during parturition which was related to hypocalcaemia.
Raziskave pri podganah so pokazale, da je bila distocija med porodom zaradi hipokalcemije, povezana z zdravljenjem z alendronatom.
In studies, rats given high doses showed an increased incidence of incomplete foetal ossification.
V raziskavah se je pri podganah, ki so prejemale visoke odmerke, pokazala povišana pojavnost nepopolne fetalne osifikacije.