Lenzetto®

Transdermalni sprej 17β estradiola namijenjen hormonskom liječenju simptoma nedostatka estrogena u menopauzi

Andrea J. & Ivan F.

Modified biopolymer-dextrin based crosslinked hydrogels: application in controlled drug delivery Dipankar D, Sagar P. RSC Adv., 2015,5, 25014-25050

http://www.google.hr/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjOpKvhl73SAhUE3iwKHQ9yCtoQjRwIBw&url=http://pubs.rsc.org/en/content/articlehtml/2015/ra/c4ra16103c&bvm=bv.148747831,d.bGs&psig=AFQjCNEgHH-al8JOJ1ErLFgBQD5EhCA88g&ust=1488728258571495 http://www.google.hr/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjOpKvhl73SAhUE3iwKHQ9yCtoQjRwIBw&url=http://pubs.rsc.org/en/content/articlehtml/2015/ra/c4ra16103c&bvm=bv.148747831,d.bGs&psig=AFQjCNEgHH-al8JOJ1ErLFgBQD5EhCA88g&ust=1488728258571495

http://transascity.org/sublingual-versus-oral-estrogen/

Transas City

Serving the Kansas and Missouri Transgender Community

http://transascity.org/

AERODIOL 150 Micrograms/g Nasal Spray Solution

Aerodiol nasal spray (discontinued in the UK - December 2006)

17-β estradiol implant -25mg - 6 mo

17-β estradiol implant -25mg - 6 mo

del Carmen Cravioto, et al. Menopause 2001;8(5):353-60.

Average E2 plasma concentrations

Stevenson JC. Optimising delivery systems for HRT, Maturitas, 1999;33(suppl 1): S 31-S38

0 20 40 60 80

pg/mL

Postmenopausal women - patch

Healthy premenopausal

women, early follicular

phase

45-50

40-60

https://hiddenjewels.wordpress.com/tag/fertility-medications/ https://hiddenjewels.wordpress.com/tag/fertility-medications/

A unit dose of 1.25g contains 0.75 mg estradiol

http://www.google.hr/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwi0_vD1nrrSAhXKXSwKHftFBgYQjRwIBw&url=http://www.mystore.easyshopping24hours.com/Oestrogel-80g&psig=AFQjCNHnegYz2mtmXptV4RS_SE7j5Ow84A&ust=1488627279837653 http://www.google.hr/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwi0_vD1nrrSAhXKXSwKHftFBgYQjRwIBw&url=http://www.mystore.easyshopping24hours.com/Oestrogel-80g&psig=AFQjCNHnegYz2mtmXptV4RS_SE7j5Ow84A&ust=1488627279837653

Participants who received two and three 90-μL sprays daily

had average trough serum estradiol concentrations of 18.1 and

19.6 pg/mL, respectively; these concentrations are both above

the minimum effective serum level.

Stabilna koncentracija Buster JE et al. 2008, Obstetrics &Gynecology

1 potisak 2 potiska 3 potiska

0,021 mg/dan 0,029 mg/dan 0,04 mg dan

Lenzetto® - farmakokinetika

Lenzetto®

INDIKACIJA Hormonsko nadomjesno liječenje (HNL) simptoma nedostatka estrogena u žena u postmenopauzi.

Prvi transdermalni estrogenski sprej koji omogućava individualno doziranje i odgovara zahtjevu primjene „minimalne učinkovite doze”, jednostavan za primjenu, diskretan.

U žena bez uterusa – kao jedina terapija U žena s uterusom – uz dodatak gestagena

Poboljšanje simptoma (% žena)

77

86

87

88

94

Učinkovito smanjenje učestalosti simptoma

Buster JE et al. 2008. Obstet Gynecol

Učinkovito smanjenje intenziteta vazomotorne simptomatologije

Buster JE et al. 2008. Obstet Gynecol

3 mogućnosti doziranja omogućavaju postepeno podizanje doze do one najmanje potrebne za regulaciju simptoma. Povećanjem broja potisaka povećava se izloženost estradiolu.

Princip primjene

1. Nanošenje Lenzetta iz dozirnog

spremnika na površinu kože od 20 cm2

u točnoj dozi od 1,53 mg estradiola (17β

estradiol)

2. Brzo isparavanje alkohola i prodiranje

estradiola s nosačem (octisalat) kroz

kožu

3. Stvaranje depoa estradiola u stratum

corneumu iz kojeg se kroz 24 sata

estradiol kontinuirano ispušta u

mikrocirkulaciju.

Lenzetto transdermalni sprej - karakteristike

Inovativno

 Novi transdermalni spray system s

preciznim dozama estradiola.

 Indikacija: vazomotorni simptomi

Precizno

doziranje

 Individualno doziranje ovisno o

terapijskom odgovoru

Nevidljiv  Proziran sprej brzog resorpcijskog

potencijala

Mjesta za

aplikaciju  Palmarna strana podlaktice ili medijalna

strana natkoljenica

Estradiol 1.53 mg/ transdermal spray 17-β-

estradiol (1.7%)

octisalate (8.5%)

ethanol (to 100%)

Princip primjene Točnost doziranja – 90 µL po potisku – 1,53 mg 17β estradiola

Ograničena površina – 20 cm2 kože

Stvara se depo E2 subkutano – direktno u mikrocirkulaciju

PRANJE MJESTA APLIKACIJE

 The pharmacokinetic parameters in control period and in after washing period were similar and/or comparable.

 Washing the application site 1 hour after application has no significant effect on the systemic absorption on estradiol.

pg/mL hours

Schumacher RJ et al. 2009, Menopause; baseline-adjusted values ; arithmetic mean;

SLOBODNO PRANJE MJESTA APLIKACIJE SAT

VREMENA NAKON PRIMJENE LIJEKA

PRIJENOS KONTAKTOM KOŽA-KOŽA NA MUŠKARCE

 Cmax values before and after contact were similar.  The results suggest that significant transfer of estradiol to men who

came into contact with women who had applied estradiol MDTS did not occur.

pg/mL

Study EST-06; Schumacher RJ et al. 2009, Menopause; *data from Morton TL et al. 2009, Pharmacokintics; untransformed values; arithmetic mean

NEMA TRANSFERA S KOŽE NA KOŽU!

PREPORUKA: PRIČEKATI SAT

VREMENA NAKON APLIKACIJE LIJEKA (octisalat, etanol)

ISTOVREMENA UPOTREBA KREME ZA SUNČANJE

pg/mL

 The baseline-adjusted mean AUC0-24 when sunscreen was applied 1 hour before estradiol MDTS was slightly higher than that when sunscreen was applied 1 hour after study drug.

 Application of sunscreen 1 hour after estradiol MDTS resulted in a small but significant reduction in estradiol exposure.

Schumacher RJ et al. 2009, Menopause; baseline-adjusted values ; arithmetic mean;

TREBA PROĆI VIŠE OD SAT VREMENA

UKOLIKO SE KREMA ZA

SUNČANJE NANOSI NAKON APLIKACIJE

LIJEKA

Lenzetto® sigurnosni profil Adverse events that were reported with a frequency of 5% or higher in any

treatment group

 Estradiol 1.53 mg/spray transdermalni sprej je dobro podnošljiv

 Reakcija na mjestu primjene primjećene su u 1.3% ispitanica

Buster JE et al. 2008. Obstet Gynecol

Lenzetto®

I oralni i transdermalni put primjene pokazali su jednaku učinkovitost u kontroliranju svih simptoma povezanih s nedostatkom estrogena, međutim imaju različiti metabolički put i zbog toga različite metaboličke učinke.

Transdermalni

estrogen

Aktivni metabolit ulazi direktno u subkutanu mikrocirkulaciju, bez prvog prolaska kroz

jetru (mogu se davati manje doze i odmah je manje metabolita)

Omjer metabolita E1 i E2 je sličniji prirodnom omjeru nego kod oralnog uzimanja.

Minimalan ili bez efekta na faktore zgrušavanja, lipoproteine, SHBG, enzime jetre, C

reaktivni protein (prediktor infarkta*) – metabolički neutralnije!

Ne povisuje se rizik za VTE i CVI (po literaturi!)

Transdermalni put primjene najbolje odgovara principu liječenja „minimalnom učinkovitom dozom”

Drug Interactions Estradiol vs. CYP3A4

CYP3A4is an important enzyme in the body, mainly found in the liver and in the intestine. It owydizes small foreign organic molecules, such as toxins or drugs, so that they can be removed from the body.

• In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4 such as St. John's Wort preparations (Hypericum perforatum), phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects.

• Estrogen drug products administered by non oral routes are not subject to first-pass metabolism, but also undergo significant hepatic uptake, metabolism, and enterohepatic recycling.

Inducers

Inhibitors

Lenzetto®

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