Prezentace se nahrává, počkejte prosím

Prezentace se nahrává, počkejte prosím

Dagmar Dobrovolná Key Account Manager

Podobné prezentace

Prezentace na téma: "Dagmar Dobrovolná Key Account Manager"— Transkript prezentace:

1 Dagmar Dobrovolná Key Account Manager
„Představujeme nový inovativní produkt v anestézii za poslední dvě desetiletí...“

2 Limitace pro AChEI antagonizační látky
Před objevení BRIDIONu (sugammadex) byly antagonizační látky pouze inhibitory acetylcholinesterázy (AChEIs) jako je Syntostigmin (neostigmini bromidum) Mají mnoho limitací: Nepřímý mechanizmus účinku Signifikantní vedlejší účinky Nemožnost antagonizovat hlubokou blokádu Nemožnost získat rychlou a kompletní antagonizaci Možnost rizika prodloužení blokády BEFORE BRIDION, the only reversal agents were anticholinesterase inhibitors, notably neostigmine Despite being used for many years, these are not perfect, having many limitations: They work indirectly, by increasing neurotransmission at cholinergic receptors through reducing the action of the enzyme that normally breaks down acetylcholine This is not specific for nicotinic receptors on the muscle membrane, leading to many unwanted side effects (e.g. cardiovascular – on heart rate, gastrointestinal – nausea and vomiting) This requires co-administration of other drugs to counter these side effects – which can in themselves cause unwanted CV effects too AChEIs cannot reverse block so deep that there is no response to tetanic stimulation (intense block) They can prolong depolarizing NMB, and in high doses may increase non-depolarizing NMB. Použití Atropinu v závislosti na dávce způsobuje nežádoucí účinky. ChE, cholinesterázy Syntostimin SPC – Zentiva

3 Limitace Succinylcholinjodidu pro RSI
Pro rychlý nástup & krátké působení blokády při intubacích v naléhavých případech, se jeví Succinylcholinjodid jako NMBA volby; (protože na trhu nebyly dostupné jiné alternativy) Succinylcholinjodid má mnoho nedostatků: hodně vedlejších účinků některé opravdu vážné občas prodlouží svalovou blokádu SPC – Succinylcholinjodid - Valeant Succinylcholine is usually seen as NMBA of choice for emergency tracheal intubation, due to its rapid onset of action [30-60 sec] and short duration [wearing off in 2-6 min] But it has serious disadvantages, being the only NMBA with a depolarizing MOA: Many side effects – some of which, like malignant hyperthermia and cardiac arrhythmia, are potentially serious It also causes muscle pain – through fasciculations [simultaneous twitching of many muscle groups] – and increased intraocular pressure Its effects cannot be reversed pharmacologially – it simply wears off after being broken down by pseudocholinesterase [NOT by acetylcholinesterase at the synapse] In some people this enzyme is abnormal and so succinylcholine block can be prolonged in these patients [while rare this can increase block for hours] However, succinylcholine still perceived by many as the only NMBA for rapid block and fast reversal, though clearly not ideal So what would the ideal reversal agent be able to achieve?

4 Ideální reverzní (antagonizační) látka by měla…
Poskytnout rychlou reverzi (antagonizaci) jakékoliv hloubky blokády umožňující požadovanou hloubku NMB během celého výkonu Mít přímý mechanizmus účinku Poskytnout alternativu k Succinylcholinjodidu pro rychlý nástup účinku, krátké trvání svalové blokády Vyloučit potřebu zvládat řešení vedlejších nežádoucích účinků The ideal reversal agent should be able to: Provide rapid reversal of NMB from any depth of block – so allowing clinicians to keep the desired level of block right through to the end of the procedure, rather than letting it lighten towards the end to avoid problems of reversal Work directly to reverse the effects of the NMBA, rather than indirectly on another physiological system [i.e. on cholinergic transmission throughout the body] Offer an alternative to succinylcholine for emergency NMB and rapid reversal [e.g. if the emergency intubation fails] Have no side effects requiring the use of additional drugs to manage them. Let’s look at how BRIDION fits this profile…

5 BRIDION (sugammadex): ideální látka
Idealní látka BRIDION / Sugammadex Rychlá revezre jakékoliv hloubky Rychlá a bezpečná reverze JAKÉKOLIV hloubky NMB Přímý mechanizmus účinku enkapsulace NMBA Poskytovat alternativu Succinylcholinjodidu Okamžitá reverze rychlejší než spontální zotavení po Succinylcholinjodidu Vyloučit potřebu zvládat řešení vedlejších nežádoucích účinků Není potřeba vzvládat nežádoucí účinky žádný účinek na cholinergní nervový systém BRIDION is the first reversal agents that offers: Rapid and safe reversal from ANY depth of NMB, including deep and intense block A DIRECT mode of action – directly surrounding, or encapsulating, the steroidal NMBAs rocuronium and vecuronium An alternative to succinylcholine for emergency intubation, when given in combination with rocuronium, providing rapid block with faster reversal than spontaneous recovery from succinylcholine A novel mode of action that has no unwanted effects on cholinergic transmission, removing the need to manage cholinergic side effects seen with AChEIs We’ll look next at BRIDION and its mode of action more closely.

6 Sugammadex je modifikovaný gama-cyclodextrin
8 prstencových molekul cukru modifikovaných s 8 dlouhými postraními řetězci tyto rozšíří ‘lipofilní’ centrální dutinu BRIDION is a cyclodextrin – a doughnut shaped molecule whose outside surface is water soluble [hydrophilic], and inner cavity repels water [hydrophobic] and attracts lipids such as the steroid NMBAs rocuronium and vecuronium Its structure is an 8 sugar ring molecule, i.e. it’s a GAMMAdextrin. Unlike other cyclodextrins, it has been modified to have 8 long side chains, that extends its steroid-capturing inner cavity, making it large enough to accommodate the rocuronium molecule the generic name sugammadex thus comes from: sug – the sugar molecules gamma – the type of cyclodextrin molecule (8 sugars) dex – from cyclodextrin The next slide shows molecular modeling of BRIDION’s encapsulating mode of action Davis ME, Brewster ME. Cyclodextrin-based pharmaceutics: past, present, and future. Nat Rev Drug Discov. 2004;3:

7 Naguib, Sugammadex: Another Milestone in Clinical NM Pharmacology2007
Sugammadex: mechanizmus účinku Sugammadex encapsuluje rokuronium a vekuronium, a tím je inaktivuje (v poměru 1 : 1) These are 3-D radiographic images of the BRIDION molecule – green – and the rocuronium [Esmeron/Zemuron] molecule – blue. Because of BRIDION’s strongly lipophilic [fat-loving] central cavity, it attracts and encapsulates the steroidal NMBA rocuronium if the NMBA is present in patient’s body The fit is specific, with binding in 1:1 ratio By encapsulating the NMBA, BRIDION: Reduces the amount of available NMBA to bind to Ach receptors in the neuromuscular junction Renders rocuronium or vecuronium inactive Rapidly reverses neuromuscular blockade. This makes BRIDION a first in class drug: a SELECTIVE RELAXANT-BINDING AGENT [SRBA] BRIDION has the strongest affinity for rocuronium, and a less strong affinity for vecuronium – but is indicated for reversal of both these NMBAs. Naguib, Sugammadex: Another Milestone in Clinical NM Pharmacology2007

8 Scene 1 Acetylcholine Cholinesterase
In the following 4 scenes the mechanisms by which neuromuscular function, blockade, and reversal take place will be depicted. The main purpose of these animations is to demonstrate the novelty and superiority of encapsulation using Bridion versus traditional reversal with cholinesterase inhibitors. This first scene shows the manner in which normal neuromuscular function takes place. As you can see, the acetylcholine (shown in blue) is released from the nerve axon into the synaptic cleft. From there, the acetylcholine binds to the nicotinic acetylcholine receptor on the muscle endplate. Once there is a sufficient number acetylcholine receptors are filled, a electrical depolarization of the postjunctional membrane takes place. This process allows for the conduction of the muscle action potential and, subsequently, the contraction of skeletal muscles (shown as a flash). Cholinesterase (depicted as rotating arrows), degrades the acetylcholine into acetate and choline, thus allowing the body to recycle the neurotransmitter for future release. This enzyme is important since it is exploited in traditional reversal as illustrated later in scene 3. Reference 1. Booij LHDJ. Neuromuscular transmission and its pharmacological blockade. Part 1: Neuromuscular transmission and general aspects of its blockade. Pharm World Sci :1-12.

9 Scene 2 Acetylcholine Cholinesterase Rocuronium
Because the contraction of skeletal muscles is ultimately dependent on the ability of acetylcholine to attach to its receptor, the blockade of such receptors would inhibit skeletal muscle contraction. This process of neuromuscular blockade is depicted here in scene 2. Rocuronium (shown in green), a neuromuscular blocking agent, readily fills the nicotinic acetylcholine receptor. In doing so the acetylcholine is unable to attach to its receptor resulting in neuromuscular blockade and paralysis (note that no flash takes place). Reference 1. Booij LHDJ. Neuromuscular transmission and its pharmacological blockade. Part 1: Neuromuscular transmission and general aspects of its blockade. Pharm World Sci 1997 February;19(1):1-12.

10 Cholinesterase Inhibitor
Scene 3 Acetylcholine Cholinesterase Rocuronium Cholinesterase Inhibitor Traditional reversal, as shown here in scene 3, exploits cholinesterase (depicted as rotating arrows). This works based on the simple fact that rocuronium, as well as other neuromuscular blocking agents, are competitive antagonists of the nicotinic acetylcholine (ACh) receptor. For this reason, all one has to do is provide enough competition for the same receptor, namely with ACh, to cause the displacement of rocuronium from the nicotinic ACh receptor. To provide for the necessary amount of ACh to cause this displacement, cholinesterase is blocked using cholinesterase inhibitors (e.g. neostigmine, edrophonium, pyridostigmine). The blockade of this enzyme causes a flood of acetylcholine into the synaptic cleft, displacing the rocuronium, and allowing for acetylcholine to reattach and neuromuscular function to return (shown as a flash). The problem with this method is that too much acetylcholine is often released, resulting in cholinergic adverse events such as bradycardia, bronchospasm, increased bronchial secretions etc. To combat these adverse events, the appropriate amount of antimuscarinics (e.g. glycopyrrolate, atropine) are administered, but they too can cause anticholinergic adverse events such as tachycardia, bronchodilation, dry mouth etc. Reference 1. Fisher DM. Clinical pharmacology of neuromuscular blocking agents. American Journal of Health System Pharmacy 1999 June 1;56(11):S4-S9.

11 Scene 4 Acetylcholine Cholinesterase Rocuronium Bridion
This final scene shows reversal via encapsulation with Bridion (shown in orange). In contrast to traditional reversal which affects the cholinergic system, resulting in related adverse events, Bridion works by directly encapsulating rocuronium or vecuronium (not shown here). This method has no influence on the cholinergic system, giving Bridion a superior adverse events profile that is similar to placebo.1,2 As Bridion is administered, free rocuronium is rapidly encapsulated due to Bridion’s high affinity for the neuromuscular blocking agents rocuronium and vecuronium. This rapid encapsulation creates a concentration gradient, which draws rocuronium away from the nicotinic acetylcholine receptor, allowing for the return of acetylcholine to its receptor and the restoration of neuromuscular function (shown as a flash).1 References 1. Adam JM, Bennett DJ, Bom A et al. Cyclodextrin-derived host molecules as reversal agents for the neuromuscular blocker rocuronium bromide: synthesis and structure-activity relationships. J Med Chem April 25;45: 2. Berner C. Integrated Summary of Safety. September 2007.

12 Srovnání reverzních (antagonizačních) látek
Here you can see a summary of the features of BRIDION at the bottom in orange compared with those of AChEI reversal agents like neostigmine in purple above BRIDION is clearly much closer to the ideal reversal agent than AChEIs

13 Srovnání rychlého nástupu látek
Here you can see the features of relaxation and reversal with the rocuronium-sugammadex [Esmeron-BRIDION] combination compared with those of succinylcholine and no reversal agent While both scenarios allow rapid onset, only BRIDION plus rocuronium also gives no significant side effects and rapid, predictable recovery, allowing the anesthesiologist optimal control of the patient’s level of muscle relaxation The next slide introduces the data supporting these claims in an overview of BRIDION’s features.

14 Farmakokinetika BRIDIONu
BRIDION je vylučován, nezměněný, ledvinami – netvoří žádné metabolity Vykazuje v dávkování v rozmezí 1 – 16mg/kg při podávání ve formě i.v. bolusu lineární kinetiku Eliminační (t1/2)poločas u dospělých je 1.8 hod Plazmatická clearance je přibližně 88 ml/min > 90% dávky se vyloučí za 24 hod 96% dávky se vyloučí močí, z čehož 95% může být přisuzováno nezměněnému sugammadexu After IV administration, BRIDION shows following pharmacokinetic parameters: Like all cyclodextrins, it is not metabolized by the body but excreted unchanged by the kidneys A plasma half life of around 1.8 hours [note: US manuals cite 2.2 but this is not in line with SmPC] which is very short – i.e. it is quickly removed from the body It is cleared from the plasma at a rate of around 88 ml/min More than 90% of the BRIDION dose has been excreted by the body within 24 hours, with 96% of the dose excreted in the urine Shows linear kinetics in the dosage range of 1 to 16 mg/kg when administered as an IV bolus dose. The next part of the presentation covers key data from the Phase II and III clinical trials on BRIDION. Bridion® [SPC]. Organon; 2008.

15 Dokazování klinické účinnosti a bezpečnosti
Klinické studie This slide summarizes the clinical trials carried out on almost 2000 subjects A total of 30 trials: 12 Phase II trials, including those which aimed at establishing the optimum doses for BRIDION – dose-finding studies 11 Phase III trials, looking at the safety and efficacy of BRIDION in both general and special patient populations The next section of the presentation looks at first the Phase II studies, and then the Phase III studies, and summarizes the data that came out of these trials.

16 Závěry studií fáze II - stanovení optimální dávky
Doporučené dávky: 2 mg/kg při obnovení T2 ( mírná blokáda) 4 mg/kg při 1-2 PTC ( hluboká blokáda) 16 mg/kg pro okamžitou reverzi (pouze po podání 1.2 mg/kg rokuronia) This summary slide explains itself: the same BRIDION doses of 2 and 4 mg/kg are recommended for reversing moderate and deep rocuronium AND vecuronium induced NMB; and a dose of 16 mg/kg is recommended for immediate reversal of rocuronium block only Bridion® [SPC]. Organon; 2008.

17 Studie fáze III – (všeobecná populace)
Trial porovnání AURORA (301) sugammadex vs. neostigmine STŘEDNÍ roc/vec blokáda SIGNAL (302) HLUBOKÁ roc/vec blokáda SPECTRUM (303) sugammadex vs. succinylcholinjodid Reverze sugammadexem hluboké roc. blokády vs. zotavení po succinylcholinjodidu CRYSTAL (310) sugammadex vs. neostigmin Reverze sugammadexem roc blokády vs. Antagonizace neostigmin cisatrakurium blokády VISTA (311) sugammadex 15 min po roc-indukované NMB Here we see the 5 key Phase III trials of BRIDION carried out in the general population they were given names* as well as numbers; we’ll look at each of these next, before going on to the 5 trials on special populations * If you think these are helpful names in understanding the trials, they could be mentioned in turn, but I don’t find them particularly useful… Všichni ležící pacienti v celkové anestézi za použití NMBA

18 Fáze III studií (spec. populace) - závěry
BRIDION 2 mg/kg Bezpečnost reverze rokuroniem-indukované NMB pacienti se sníženou renální funkcí BRIDION není doporučen pro pacienty s těžkým poškozením ledvin (včetně dialyzovaných) Starší pacienti Žádné signifikantní zvýšení času do zotavení u pacientů > 65 let BRIDION 2 mg/kg a 4 mg/kg bezpečná reverze rokuroniem-indukované NMB Pacienti s plicní chorobou bronchospasmus hlášen jako možná souvislost s nepříznivými údálostmi u 2 pacientů s asthma Pacienti s CV onemocněním postupující ne-kardiochirurgické operace BRIDION rychleji a efektivněji ruší mírnou rokuroniem-indukovanou NMB u dětských pacientů Použití u pacientů < 2 let není doporučeno, dokud nebude dostatek dat k dispozici This summary slide is self-explanatory – summarizing the key data from the Phase III clinical trials on special population patients. Data from Libra trial. Plaud B et al. Anesthesiology. 2009;110:

19 Bezpečnost a snášenlivost
Bezpečnost a snášenlivost BRIDIONu byla testována v klinických studiích u více jak 2000 pacientů The safety and tolerability of BRIDION has been tested in clinical trials involving more than 2000 subjects [NOTE: discrepancy here between US and EU numbers; UK asked for change to over 1800] These included subjects of different ASA classes – around 85% falling in Classes I and II, the least severe health impairment (normal and mild systemic disease only) Next slide shows ‘common’ adverse events, i.e. occurring in more than 2% of patients treated with BRIDION

20 Možné nežádoucí příhody, které by mohly souviset s podáním Bridionu
Anesteziologické komplikace Svědčí o obnovení neuromuskulární funkce Dysgeusia (kovová nebo hořká pachuť v ústech) Většina případů nastala po podání dávky ≥ 32 mg/kg Reziduální NMB Výskyt u 0.4%pacientů, většinou poddávkováni (< 2 mg/kg) Alergická reakce Případy byly spontálně mizející The most common adverse events (AEs) considered related to BRIDION treatment were: Anesthetic complications – i.e. restoration of neuromuscular function, which is exactly what BRIDION is designed to achieve; however if occurring to early – e.g. sucking on intubation tube, or moving during surgery – this is undesirable and an AE; frequency around 8% Dysgeusia [pronunciation: dis-gū′sē-ă] – metallic or bitter taste – was seen in over 12% of subjects; however, they were all awake, unanesthetized healthy volunteers taking high doses of BRIDION (mainly above 32 mg/kg) Residual NMB was very rare, at 0.4%, and typically seen in sub-optimal doses during dose-finding studies (i.e. below 2 mg/kg, the lowest recommended dose for BRIDION) Allergic-like reactions occurred In a few individuals (i.e. flushing, erythematous rash), one of which was confirmed as mild allergic, but was self-limiting (i.e. resolved without treatment); all drugs have the possibility of causing an allergic reaction. Bridion® [SPC]. Organon; 2008.

21 V klinických studiích - ŽÁDNÉ klinicky signifikantní interakce
Lékové interakce V klinických studiích - ŽÁDNÉ klinicky signifikantní interakce ‘Vychytávání’ interakce BRIDION může teoreticky vychytávat jiné léky, možnost snížení jejich učinnosti. Po podání BRIDIONu, ženy užívající hormonální antikoncepci by se měly chovat jako při vynechání 1 denní dávky ‘Vytěsnění’ interakce Určité léky mohou teoreticky vytěsnit rokuronium/vekuronium z komplexu BRIDIONu, např. antibiotika toremifene, flucloxacillin a fusidic acid. Před-operační užití těchto látek, může vést k prodloužení zotavení, nebo k reziduální NMB Žádný z těchto není komerčně dostupný na našem trhu Because BRIDION works by specifically encapsulating rocuronium or vecuronium, rather than acting indirectly by e.g. altering liver enzyme function, it does NOT potentially interfere with the action of other drugs the only type of drug–drug interactions are if : BRIDION binds another steroidal drug – capturing interaction Another drug displaces the captured NMBA – displacement interaction Capturing interactions could theoretically interfere with efficacy of hormonal contraceptives, so women taking BRIDION with these should act as if they have missed 1 daily contraceptive dose (should consult package information of their contraceptive) Displacement interactions could theoretically arise if also taking antibiotics toremifene, flucloxacillin and fusidic acid, so clinicians must be aware that recovery from NMB might take longer in these cases (as less NMBA may remain captured by BRIDION) Bridion® [SPC]. Organon; 2008.

22 Speciální skupiny pacientů
Těhotné Data nejsou k dispozici, měla by být zachována opatrnost Kojící BRIDION může být podán Děti BRIDION je doporučován pouze pro běžnou reverzi rokuroniem-indukované blokády u dětí a dospívajících Použití BRIDIONu u novorozenců a malých dětí (3 měcíce – 2 roky) není doporučeno, díky nedostatku dat BRIDION can be given to breastfeeding mothers, but lack of data means it should be used only with caution in pregnant women Because of limited data on the effects of BRIDION in neonates and infants, BRIDION should not be used in children under 2 years In older children – 2 and above – BRIDION is only indicated for routine reversal of rocuronium-induced NMB Pamatuj: BRIDION není doporučen u pacientů s těžkým renálním poškozením Bridion® [SPC]. Organon; 2008.

23 Bridion® [SPC]. Organon; 2008.
BRIDION - Indikace BRIDION je indikován pro reverzi neuromuskulární blokády indukované rokuroniem nebo vekuroniem Poznámka: Děti a dospívající - BRIDION je doporučován pouze pro rutinní reverzi rokuroniem-indukované blokády BRIDION is indicated for reversal of NMB induced by either rocuronium or vecuronium This includes routine reversal of both moderate and deep NMB at reappearance of T2 Also includes immediate reversal (emergency reversal, typically after RSI followed by the inability to secure an airway) For patients aged 2 years to 17 years, BRIDION is recommended for routine (not immediate) reversal only. We’ll look at doses again next. Bridion® [SPC]. Organon; 2008.

24 BRIDION – Dávkování a použití
Běžná reverze (rokuronium nebo vekuronium) Mírná blokáda : 2 mg/kg – jestliže nastalo spontální zotavení nejméně na obnovení výskytu T2 Hluboká blokáda : 4 mg/kg – jestliže nastalo zotavení nejméně na 1-2 PTC Okamžitá reverze (rokuronium) 16 mg/kg This slide is self-explanatory Remember that immediate reversal is not indicated in children, or for reversal of vecuronium-induced NMB Bridion® [SPC]. Organon; 2008.

25 Bridion® [SPC]. Organon; 2008.
Kontraindikace Kontraindikací pro BRIDION je pouze hypersenzitiva na látku samou, nebo na některou z jejich složek The ONLY contraindication for BRIDION is hypersensitivity to sugammadex, or to any of its components (hydrochloric acid 3.7 % and sodium hydroxide for adjustment of pH) Bridion® [SPC]. Organon; 2008.

26 Bridion® [SPC]. Organon; 2008.
Speciální upozornění Podpora dýchání je nutná u pacienta až do doby obnovení adekvátního spontálního dýchání Doporučená doba před opětovným podáním rokuronia nebo vekuronia (pokud je nutné pacientovi opět podat NMBA – reoperace...) je 24 hodin, pokud byl k reverzi NMB podán Bridion The first of these special warnings applies to the use of ALL muscle relaxants and reversal agents: until the patient has been shown to be able to breathe spontaneously – i.e. when full muscle strength is restored, ideally to a TOF ratio of 0.9 or above – ventilatory support MUST be maintained The second relates to BRIDION use only: if there is a clinical need to re-induce NMB after a patient has received BRIDION, a waiting time of 24 hours is recommended before giving rocuronium or vecuronium again If the patient needs NMB before this recommended waiting time has passed, a nonsteroidal NMBA should be used. Bridion® [SPC]. Organon; 2008.

27 Data from AURORA Trial (301)
BRIDION: základní vlastnosti Unikátní mechanizmus účinku Enkapsulace steroidních NMBAs Rychlá reverze JAKÉKOLIV hloubky NMB (indukované rokuroniem nebo vekuroniem) ≤4 min z hluboké NMB ≤3 min ze střední NMB Signifikantně rychlejší než neostigmin 18x rychleší (rokuronium) 15x rychlejší (vekuronium) Prokázaná bezpečnost a snášenlivost Studie na > 2000 pacientech Rozmanitost pacientů: obojí (všeobecná + spec. populace) Nízké riziko reziduální blokády The key features of BRIDION are: Its unique first-in-class of mode of action Its ability to reverse ANY depth of NMB induced by rocuronium or vecuronium [we’ll see the data supporting these times of less than 4 or 3 minutes shortly] Significantly faster reversal time than neostigmine [again, we’ll see the data supporting the 18 times faster reversal of rocuronium and up to 15 times faster reversal of vecuronium shortly] Proven safety and tolerability, shown through studies on over 2000 subjects in the general population as well as special populations with particular health issues A very low risk of residual post-operative block. We’ll also see how BRIDION offers immediate reversal faster than recovery from succinylcholine, and has no side effects needing management. Data from AURORA Trial (301)

28 Balení a skladování - BRIDION
Dodává se jako injekční roztok pro intravenózní injekce; každý ml obsahuje sugammadexum natrium, což odpovídá 100mg sugammmadexu BRIDION je dodáván v 2 ml nebo 5 ml lahvičkách (10 lahv. v balení) (na trhu nemusí být dostupné všechny velikosti balení) Lahvičky mohou být skladovány do 30 ºC BRIDION by měl být uchovávaný v původním balení a tím chráněn před světlem. Po prvním otevření a naředění okamžitě použit This slide is self-explanatory Bridion® [SPC]. Organon; 2008.

29 Děkuji za pozornost ...

Stáhnout ppt "Dagmar Dobrovolná Key Account Manager"

Podobné prezentace

Reklamy Google