ABPI COMPENDIUM OF DATA SHEETS
`
`AND
`
`SUMMARIES OF PRODUCT CHARACTERISTICS
`
`1999-2000
`
`With The Code of Practice for the
`
`Pharmaceutical Industry
`
` ».:,~,
`"32 Datapharm Publications Limited
`5
`12 Whitehall, London SWIA 2DY
`
`Astrazeneca Ex. 2091 p. 1
`Mylan Pharms. Inc. V. AstraZeneca AB IPR2016-01326
`
`

`
`I
`Responsibility for Data Sheets and Summaries of Product Characteristics
`The data sheets and summaries of product characteristics in this Compendium are prepared independently DY each
`participating company and each proof is checked and the text confirmed as correct by the participant concerneop
`Neither Datapharm Publications Limited nor The Association of the British Pharmaceutical industry IABPH gives an;
`guarantee whatsoever as to the accuracy of the information contained in the data sheets or summaries of pmduq;
`characteristics and accepts no liability whatsoever in respect of any loss, damage or expense arising from anv Such
`information or for any error or omission in the data sheets or summaries of product characteristics and in particula.
`(but without prejudice to the generality of the foregoing) shall not be liable for any consequential darn8Q95 0:
`expenses or any toss of profit or any liability to third parties incurred by anyone relying on the information container;
`in the data sheets and summaries of product characteristics appearing in this Compendium.
`
`P‘-’b“5"l€-‘G bv Datanharm Publications Limited
`
`‘C°¥7YflQht 1999
`Copyright in the material included in this Compendium
`is reserved by the individual companies and
`Wganrsationswhich have Contributed it,
`
`rssrr 0 901192 is 2
`ISSN r3s.r—5ocs
`
`T‘.-"P‘«‘5E?i. Drinted and bound in Great Britain
`UV William Clowr,-5 Lirnized. Beccles and London
`7:
`
`Astrazeneca Ex. 2091 p. 2
`
`

`
`Special warnings and special precautions for use:
`Belore therapy isinitiatcd. nthoroiugh medical history
`should be taken, A complete gynaccoicsgical exami-
`nation should be porlormed and repeated at least
`once a yoarduring therapy.
`Prolonged use without addition of a progestogen
`may cause endometrial ilyperalasia. Therefore.
`in
`women with an intact uterus. Sandrcno treatment
`should be combined with cyclic orogestcgen admin-
`istration. Withdrawal bleeding resembling normal
`menstruation will usually occur after each course ol
`progestogen. The cause of unexpected or prolonged
`uterine bleeding during therapy should be clarified.
`Pityplcal adonomatous hyperplasia of the endomo-
`triurn must be treated before commencing oestrogen
`lheratny.
`Consider discontinuation prior to surgery or pro-
`longed irnmobilis
`on. Development of do nova
`lroquent severe headaches or migraine should be
`investigated and possible prodromal symntoms ol
`vascular occlusion should be clnrilied.
`The risks and bsnolits or treatment should be
`evaluated and close monitoring performed for pa-
`tients with:
`- cndornetriosis
`- uterineleiumvarnfi
`- endometrial hypcrplasia (simple glandular hyper-
`piasia or hyperala sia glandularis cyclical
`- diseases of the cardiovascular system including
`com brova ocular disorders.
`- a historyo-fthruomboemboticdisease,
`- severe hypertension.
`- history of (or close larnily history of! breast cancer.
`- severe disturbances of lipid metabolism.
`— renaldyslunction
`systemic lupus erythernstosus
`- Dorphyria
`at present there is suggestive evidence of a slight
`increase in the relative risk of carcinoma of the breast
`with long-term hormone replacement therapy, how-
`ever. the results are contradictory. Regular breast
`examinations and mammography. where appropri-
`ate. should be carried out in women on hormone
`reolacementtherapy.
`Some conditions may be aggravated during oestro-
`gen therapy or pregnancy. Women on Sandrcna
`treatment with one of the following condlticne -tor
`~.-aitl'1 8 history thereol during previous pregnancy or
`hormone usel should therefore be closely monitored.
`These conditions include:
`- mild hypertension.
`- migrainoorscvcre headache.
`- benign breast disease.
`liver function disturbs nces.
`- chalestasls.
`- cholelhhlasis.
`diabetes mellitus.
`-asthma.
`A
`- otosclerc-sis.
`- multiplesclerosis.
`- galat:lorrhlaa,elevatetJ prolactin levels,
`- history of herpes gcstatlunis.
`~ eailepsy.
`interaction with other rrIadl'c.ami.-nls and other forms
`or interaction: Nu interactions between Sandrena and
`other medicines have been reported. There are some
`indications that oestrogene may reduce the effects ol
`antihyoertonsive.
`anticoagulant and
`nntitfabeti-c
`drugs. can comita nt treatment with potent inducers ot
`liver enzymes -leg. barbiturates. carbarnazepine. gri-
`seolulvin and rifampicinl may reduce the plasma
`levels of oestradicil. The significance of these interac-
`date:
`.
`lionsbln transoerrnal aplollciltion has not been eluci-
`Pregriencyand isolation: So ndrena is not indicated in
`women at child-bearing capacity. It has no contrcced
`[we efficacy. Sand”.-na should not be used during
`pregnancy or lactation.
`Effects on ability to drive and use machines: Destro-
`genc such as Sandrena do not allcct the ability to
`drive or use machines.
`Undasiroble effects: Adverse drug reactions are usu~
`ally mild and only seldom lead to discontinuation of
`treatment. if they do occur. it will usually be during
`the first months of treatment.
`Occasionally lor oestrogen;
`in general; Breast
`tenderness. headache. oedema, weight Increase. un-
`scheduled vaginal bleeding or spotting.
`narelylor oestregensin generaI:Migraino. changes
`in libido and mood. gastrointestinal discomfort le.g.
`ncusea_ vomiting, stomach crampsl, hypertension,
`alterations in liver function and billarvflow.
`in clinical trials dermat irritation has been very
`infreuuentwith Sandrana.
`Di/erdosagmfienerally. oestrogen: are well tolerated
`even in massive doses. Possible symptoms of over-
`uose include those listed under undesirable effects.
`Treatment is symptomatic.
`
`OHGA NON LABORATORIES LIMITED
`
`Pharmacological properties Therapeutic classifica-
`tion: G03 CA 03. Oeslrogen preparation for h-ormane
`replacement therapy.
`Pharrnacodynamic properties: The pharrnacodynam
`lcs atsandrena are similarto those at oral oestrogen 5.
`but the major diflerence to oral administration lies in
`the phermacoliinetic profile.
`The clinical clficacy at Sandrena in the treatrnentol
`menopausal symptoms is comparable to that of
`peroral oestrogen Combined with medroxyflmlles‘
`terone acetate. peicutsneous oestradiol lowers 1013'
`cholesterol without reducing the HDL cholesterol
`level.
`Pharniacokinaricprops-rtios:Sandiena isnn alcohut
`based ocstradiol gel. when applied to the skin the
`alcohol em purales rapidly and oostradiol is absorb cd
`through the skin into the circulation, To some extent.
`hcrwaver. the oestradial is stored in the subcutaneous
`tissue from where it is released nraduallv FMO WW‘
`latlun. Percutztneous administration circumvents the
`hepatic first-pass metabolism. For these ieasonsithe
`fluctuations in the plasma oestrogen concetttrallcirls
`with Sanclrena are less pronounced than peroral
`oestrogen.
`A 1.5 mg pcrcuinncous dose of oestradi-0| (1-59
`Sandrenal results in a plasma concentration of about
`340 pmolrl. which corresponds to the level of earl?
`follicular stage in premenopausal women. During
`Sandrena treatment the oestradiolrocstronc ratio re-
`mains in 9.7. while {luring peroraloestru gentreatrnent
`it usually drops to less than 0.2.
`The mean oestradi-ol exposure at steady state of
`Sandrena is 32 percent compared with an equnralerlt
`oral dose of ostradiol vale-rate. Otherwise the metab-
`olism and excretion of transdsrmal ocstradiol follow
`the late of natural oestrogens.
`Preclinicalsafely data:Oestradiol is a natural female
`hormone with an established clinical use. lherelore
`no toxicological studies have been perloirned with
`Sanorena. The necessary studies on the irritantellccts
`of the ye! have been studied in rabbits and skin
`senailisaticn in guinea pig. Based on the results from
`these studies it can be concluded that Sanorena could
`very infrequently cause mild skin irritation. The
`lrequcrtcy of the occurrence :1! dermal irritation can
`be reduced by daily change oi the application site.
`Pharmaceutical paniintlers
`List of excipients: Carbomor 934 81'‘: Sodium l'IVd'0Kr
`ide: Propylene glycol PhEur: Spit. lort.-Ethanol 5&9’:
`Bl”. Aq. puril.-Purified wator PhEur.
`incompatibilities: Nu incompatibilities have been
`icund.
`Shelflife: 3 years.
`Special preca unions for storage: At room to mperature
`ltieiow 2513).
`Nature and contents ofcunlainc-r." Single dD5!!AEl|L.lIT|ifl-
`lurn toil sachets supplied in packages containing 28
`ol either close or 91 sachets of 7 mg dose.
`instructions for use/handling; No he
`Marketing authorisation holder
`Orion Corporation. Orioninite 1, P.O. Box 55. Fill»
`D2101. ESPOQ, FINLAND
`_
`_
`Distributed by Organon Laboratories Limited, Carn-
`0 L.
`béidga Science Park, Milton Road. Cambridge. CH4
`Murltetlna authorisation number
`1:!911.!DtJlN-D005
`Date at tpartlall revision of the text October 1996
`Legal Category POM
`
`SUSTANDN' 100
`Qualitative and quantitative composition
`Testosterone ore nionate Ph Eur 20 ms
`Testosterone phe nylpriopionate SP -40 mt!
`Testosterone lsoeaproate BF -til mt!
`lEciuivaIentto a total ofild mg oltestosteronel
`Pharntncguticaliui-n1 Sustanon1DEi_is
`clear. sterile.
`oily solution for deep intramuscular Injection.
`Clinical particulars
`Therapeutic indications: Testosterone rahlacement
`therapy in male hypogonadal disorders. for elamplct
`alter castration: eunuchoidisrn: hvpopitultaiisn1:e-nv
`docrinc impotence; male climacteric 5‘l’|”FlFilDI'I1s like
`decreased libido: cerisl" W995 07 lfifertility due to
`disorders of sparimllngenesis.
`Testosterone therami may also be indicated tor the
`prevention andtroatmont olestc-opotosis in hy pagan-
`aclal males
`Posalog-yen-:1‘ rnolhod afaclrnlnisrratio n:
`Dosagerln general. dosage should be adj1.|5ted[()[i19
`iridlvidual response ulth-e patient.
`Adults: Usually, one inlectionol ‘I ml per two weeks
`l5 ucleq-uatc-.
`Elderly: it should be noted that smaller and less
`frequent doses may achieve the same response.
`
`1095
`
`Cririu.-on.-it should be noted that smaller and less
`frequent doses may achieve the same response.
`Admin.-'srr::tl'on: Deep intramuscular in; action
`Contra-iiio‘lcar."ons:Known or susoected prostanc fir
`mamrnarycarcinoma. Pregnancy. Breast-leading, Hy.
`persensitivity to one of the exciuiants.
`Special warnings and special precautions for use:
`Patients. especially the elderly. with the following
`conditions should be monitored:
`ischaemic heart
`disease. since androgens may produce hypefchglgs.
`terclaemla: latent or overt cardiac lailure. renal u-,5.
`function, hypertension. epilepsy or migraine (or a
`history of these conditionsl. since androgen; may
`occasionally induce fluid and sodium retention: skel-
`etal metastases. since androgens may induce hyper-
`calcacmio or hypercalciuria in these panama,
`The use of steroids may inlluence the resuflg or
`certain laboratory tests.
`Androgen: should be usedcautiously in p;ep.uben;.i
`boys to avoid premature ttplphyseal closure at pm.
`cocious sexual development.
`ll androgen-associated adverse reactions occur
`Sustanon toe treatment should be interrupted and:
`alter disappearance of the symptoms. be resumed 3,
`a lower dosage.
`interaction with other mcdicaments and other {om-is
`of interaction: Enzytrieqnducing agents may exert
`increasing or decreasing ellects on tenostgmne
`levels. ‘lherelom adjustment of the dose. andim
`intervals between injections may be requ[rerj_
`'
`Pregnancy and lactatrori.-On the basis of its pharma-
`cological effect, Suslanun 100 is suspected to cause
`birth defects andfor other irreversible adverse aliens
`on pregnancy outcome. Therefore, susianm-. 100 is
`contraindicated during pregnancy and |a.,m;,._m_
`Effects an ability to drive and use ofmachines: As lar
`as is known Sustttnon ‘IOU has no influence on
`alertness and concentration
`undesirable effects: The following adveygg reamigns
`have been associated with androgen therapy in
`General: ln Wet:-{banal bars. Dfecocious sexual de-
`velopment, an increased lyequgnw of E,3wDns_
`phallic enlargement and premature epiphyseal clo-
`sure: D"_aPl5I'7l and other signs of Excessive sexual
`stimulation; water and sodium retention: oligospm.
`mic and a decreased ejaculatory-mlume.
`Treatment should be interrupted until these symp.
`toms have disappeared, after which it should be
`continued at a lower dosage.
`Hoarseness of the voice may be the first symptom
`09 Vocal change which may lead to iireveysima
`towering of the voice. It signs of \riri|lsation_ parficu.
`larly lowering of the voice. develop, near
`I‘
`be discontinued.
`mam‘ “"5
`Overdosagerflic acute lnllamuscular ruxiciw or 5u5_
`tanori ‘IUD is very low. Therefore toxic sympmms am.
`not expected‘ to eccu r.
`Pharmacological properties
`Pnarrnacodynemic properties: Testosterone is the
`principal endogenous hormone essential for normal
`growth and development ol the male sex organs and
`male secondary cox characteristics. During adult me
`testosterone is essential for the lunctioning of thc
`testes and accessory structures. and for the mainte-
`nance cl libido. sense oi’ well-being. erectile potency
`nrostate and seminal vesicle function.
`'
`Treatment of hypogohadal males with Sustai-ton
`100 results in a clinically signmga;-i[ ,1“ of plasma
`concentrations of testosterone. cliltyoroteslosterong
`and andmstencdione. as well as a decrease oi St-lac-1.
`(sex hormone binding gIobulini_ in me maies with
`PFImar'r_lliypergnnadetroeicl hynct-gongujgm Um,
`3fu'::a‘-rzllgltnigglranofi results In a normalisation of
`Pharrnaoaltirtotic proper1i95_-s
`,
`.
`-»«
`o-
`::::;:::::::::
`tlons of action. The esters re hydrolysed into mu
`natural hormone testosterone, as 5.30,, as the
`the general circulation.
`V Em"
`A single dose all Susm.-.0" mm
`-
`°’ '°‘°' l-""5""3 ‘ems’-*-‘lone. V‘-li1heDa::kll;::lTecar§l:::
`approximately 2-t-dahrs (
`1
`-
`4
`Plasma testosterone levelstrdiurhflgtthiclg-itlgfilfiiir
`the normal ran e ‘n
`i
`-
`davsl
`it
`I males alter appm.x.mma1V 21
`.
`the n
`-
`.
`Testosterone is metabolized via
`ways. Excretion mainly takes place via l?IfEm:l'I'::«h
`coniugates of etlocholancilnne and a‘l"ldl'O$tEfOFl|E
`as
`Preclinical safety data: Not appiicablg
`Phan11nccul.lcaIp.mic._.|,.s
`last or! excipients:
`Benzyl Alcohol Phfiur o_1 mi
`Aracltis 0i|PhEurlc1.(l ml
`
`flitmaaribiliiies: No reievant incompatibilities are
`Shelf-life: 5 years.
`
`Astrazeneca Ex. 2091 p. 3
`
`

`
`1098
`
`URGAHON LABORATORIES LlMl'l'ED
`
`lanon 250 is very low. Therelore toxic symptoms are
`not expected to occur.
`Pharmacological properties
`Pharmacodynamic properties: Testosterone is the
`principal endogenous hormone essential for normal
`growth and development of the male sex organs and
`male secondary sex characteristics. During adult lilo
`testosterone is essential for the functioning of the
`testes and HCCDSSEITV structures. and for the mainte-
`nance of libido. sense of wellrbcing. erectile potency.
`prostate and seminal vesicle lunction.
`Treatment of hypogonadal males with Suslanon
`250 results in a clinically significant rise or plasma
`conccntralions of testosterone, dihydrotestosleronn
`and androslnnediinnmos well as ll decrease of SHSG
`[sex hormone binding globulin).
`In the males with
`primary ihypergonnclotropicl hyp-ononadism treat-
`ment with Sustanon results in a normalisation oi
`pituitary function.
`Pharmacokinelic propeniesr Suslanon 250 contains a
`number of esters oi testosterone with different dura~
`tions of action. The esters are hydrolysed into the
`natural hormone testosterone as soon as they enter
`the general circulation.
`A single dose ol Suslanon 250 leadstn an increase
`all
`total plasma testosterone with peak-levels of
`approximately 70 nmolll lC.....l. which are reached
`approximately 24-Ash lt.,,..l alter administrarion.
`Plasma testosterone levels return to the lower limit ol
`the normal range in males in arpprclxirnatelyzl days.
`Testosterone is metabclllsed via the normal path-
`ways. Excretion mainly takes place via the urine as
`coniugates ol ctiecholan alone and androslerone.
`Preclinicalsafety data : N 0! soul has hle.
`Pharmacuuticalparticutars
`List of oxcipicnts:
`Bantyl Alcohol Pl1EurD.‘l ml
`Arachis 0iIPl'lEur|o1.lJ ml
`incompatibilities: No relevant incompatibilities are
`ltnovvn.
`Shelf-lll‘e: 5 years
`Special precautions for storage: Store between 15-
`25'C. protect lrom light
`Nature and contents of containers: 1 ml ampcules in
`boxes oi‘ 3
`lnsrrucrlclns for use/l‘ranr.1llng:nol anplir.-a lrle.
`Marhting authorisation number 00655086
`Date of first authorisation 28 February 1973
`Date of proparution til the lurrt March 1995
`Logo! category POM
`
`Special precautiorm for Smragc: Store between 15-
`25‘C. protect from light.
`Nature and contents of containers: ‘l
`r1".| ampoul-:5 in
`boxes ol 3.
`In slrucrion s for usr.=/handling: n (at :3 ppl ital: le.
`Marketing authorisation numbnr 036-35¢! 19
`Date of first authorisation 23 February 1973
`Clare of preparation of the ten March 1995
`Legal ca lltglnrv POM
`
`SUSTANON' 250
`cu alitative and qua nti tative composition
`lestosterone prooionate Pl-l Eur 30 mg
`Testosterone phenylpriopionateBP BEI mg
`Testo slemne isocapro ate BF’ on my
`Testczstcrune or: can care BP 100 mg
`lequivalentto a1o‘.alnl‘I‘l'6 mg 0! ‘Feslosteronel
`Pharmaceutical form _ Sustanon 250 is :1 clear. sterile.
`oily solution lor deep intramuscular irlir,-ction.
`Clinical particulars
`Therapeutic indications: Testosterone replacement
`therapy in male hypogonaclal disorders, for example:
`alter castration: eunuchuicism; hypapituilarlsm; en.
`domino impotence: male climacteric symptoms like
`decreased libido; certain types of inlanilily due to
`disorders ol spermatogeneais.
`Testosterone therapy may also be indicated for the
`orevenllon and treatment Ola-stem porosls in hypogon-
`adal males
`Posology and method afadministration:
`Dosage: In general. dosage should be adjusted to the
`Individual response of the patient.
`Adults: Usually. one injection or 1 ml per lhrrze
`weeks is adequate.
`Elderly: lt should be noted that smaller and less
`frequent doses may achieve lhg gm; rgspqnga
`Children: ll. slrould be noted that smaller and less.
`lrecruent doses may achieve the same response.
`Adrninislrtr lion: Deep intramuscular injection
`Contra-indications: Known or suspected prostatic or
`mammary carcinoma. Pregnancy. Breastfeeding. Hy‘
`persensrtivity to one of the excipiants,
`Special warnings and special precautions for use:
`Patients. Especially the elderly. with the following
`conditions should be monitored:
`ischaemie heart
`disease. since androgen: Tray DlOdlJCt':I'1l'y'[i9lL‘.l‘lCIlt?S
`terolaernia. Latent or overt cardiac lailure.
`renal
`dyslurrction. hypertension, epilepsy or migraine {or a
`history of these condltionsl, since androgens may
`occasionally induce lluid and sodium retention. Skel-
`elal metastases. since androgen: may induce hyper-
`calcaernia or hypcrcalciuria in lhese patients,
`The use of steroids may influence the results of
`certain laboratory tests.
`Androgensshcruld be used cautlouslyiriprepuhanal
`EIOYS to avoid premature epiphyseal closure or pre-
`cotious sexual development.
`if androgen-associated adverse reactions occur.
`Sustancln 250 treatment should be interrupted and.
`after disappearance ol the symptoms, be resumed at
`a lower dosage.
`interaction with other medicament: and other forms
`of Interaction: Enzymeinducing agents may exert
`Increasing or decreasing clients on testosterone
`levels. Therefore adjustment of
`the dose. andlor
`intervals betweeniniections may be required.
`Pregnancy and lactation: On the basis of its pharma-
`cological oflect. Sustanon 250 is suspected to cause
`hill“ delefils and/or other irreversible adverse effects
`on pregnancy outcome. Therelore, Sustanon 250 is
`contraindicated during pregnancy and lactation.
`El'fe_cl'S DH‘ abilllv ll-1 W596’ and use of mer4:lrr'nos:As far
`as I5 known Suslanon 250 has no influence on
`alartness and concentration.
`Ufldesirable effects: The following adverse reactions
`have been associated with androgen therapy in
`general:
`I” P'e9"-‘_b°"W NYE. F"0'3°ClDU5 sexual develop-
`l'l'l9|'llr an increased frequency oi erections. phallic
`enlargement and premature epiphyseal closure; aria.
`warn and other signs ofcxcessive sexual stimulation;
`water and sodium retentign; gllguspgrfnia and a
`decreased e|a:ulatury volume.
`Treatment should be interrupted until mesa symp.
`toms have disappeared. after which it should he
`continued at a Iowerclosagg_
`Hoarseness of the voice may be the Frsl symptom
`pl vocal change which may lead to irreversible
`lowering of the voice. ll signs of virilisalion. particu-
`larly lowering of the voice. develop. treatmentshoulrl
`be dis continued.
`Overcmsage‘,' The acute rnlrarnuscular toxicity cl Sus-
`
`carcinoma or breast carcinoma in the male. Preg-
`nancy. Elreast«l‘eedinl]-
`use in pragnancyand lacrarion:Testoslerr:rneimplants
`are contra-Indicated during pregnancy and la nation.
`Wan-u'rlgs and precautions:
`- Androgens should be used with caution in women
`to avoid unacceptable and irreversible virilization.
`Female patients should therefore be counselled to
`report nrly deepening or hoarsenlng of the voice
`without delay.
`_
`. Androgen: should 1119 used with caution in prepara-
`gnal bays to avoid premature npiphyseal closure or
`precocious sexual development. Skeletal matura-
`tion should be monitored regularlv.
`- Due to the lung-lusting action and the diiliculw or
`removal. Testosterone implants should be used
`with extra caution. Therefore. it may be advisable to
`establish the benelicilal eflect and tolerance lo.-
`androgcn therapy by prior treatment with a shorter-
`acting testosterone preparation. This applies in
`paflicular ta lpreloulzlenal bays. women and elderly
`men.
`~ Pmientswlth intent or over! cardiac lailuro. renal or
`hepafig dysfunction. hypertension, epilepsy or mi.
`gwing (or 3 hisww oi‘ these cundltiortsl should be
`kept under close medical supervision. since aggra-
`vation of recurrence may occasionally be induced.
`ll androgen-associated adverse reactions occur the
`-
`implant should be removed if possible.
`. The use ol steroids may influence the results or
`certain laboratory tests.
`Effects an ability to drive and to use machines: As far
`as is known Testosterone Implants have no ellecls on
`alertness and concamratinn.
`interactions.’ Enzyme-inducing drugs may influence
`plasma testosterone levels.
`Other undesirable effects’ rlrequoncy and serious
`nessl: The following adverse reactions have been
`associated with androgen therapy:
`.
`,',, 9-eneral.'waler and sodium retention, hyparc;-:1.
`caon-rial
`. 1.1 women: symptoms of virllitation, such as voice
`changer: ldeepeninp. hoarsoningl and hirsutisrn;
`.
`,‘,, p;Ep,ube[!al boys: precocious sexual develop.
`rnant,
`increased frequency of erections. phallic
`enlargement ond premature opiphyseal closure;
`in mempliapism and other signs ofexcossiue sexual
`stimulation, eliuospermia and decreased eia:'.ula~
`torv volume
`Dverdosagfll The acute toxicity of testosterone is ID‘ ~'
`
`Prinpism in men and undesired deepening of
`voice in wom an arc symptoms of chronic: overdosn-go.
`In this case the implanllsl should he removed.
`Pharmaceutical precautions Stare below 25‘C and
`proteclfrorn light
`lncomparibilitiosr Non tr.
`Legal category POM.
`Package quantities Each sterile implant is supplied
`singly, in a sealed glass tube.
`Further information Testosterone is a naturally-
`occurring hormone formed in the interstitial cells cl
`the testes under the control oi the anterior lobe cf the
`pituitary gland ‘which controls the development an‘.
`maintenance of
`the mate sex organs and male
`secondary sex characteristics. Testosterone also pro-
`duces systemic effects, such as increasing the rotten»
`tion of nitrogen. calcium. sodium,potassiunmchluricla
`and phosphate leading to an increase in skeletal
`wgight,Wfl1UfFEiCmiOfl and an increase Il'I the growth
`of bone»
`_
`Testosterone implants, when lI'lSEf'iEd suhcutanp
`ously release testuslnmnc into the bloodstream at .1
`relatively even rate supplying near physiological
`plasma testosterone levels.
`Surface area of the implants is the most important
`lacror inlluenclng the rate 0! absorption. In ger=i:r:.:
`the absorption rate estimated by removal of imzillnnls
`at intervals. and weighing appears to be apprecinbli
`more rapid than when lhe rate is assessed upon the
`clinical requirement. in addition to clinical evidence
`individual variation in the rate of absorption or
`implants must be taken into account.
`The average daily absorption of testosterone has
`been estimated at 0.5 mg for a 100 mg implant mtr»
`an approximate duration of Ell weeks.
`Product licence numbers
`so rng
`oosslsoazn
`100 mu
`lJflS5l5{'.|83Fl
`200 mg
`0065/‘5DB4R
`
`.
`
`ZISPIN V
`Qualitative and quantitative composition Each In t‘
`let contains 30 mg ol rnlrtarapin.
`Fharrnacanticailorm Table!
`
`Astrazeneca Ex. 2091 p. 4
`
`TESTOSTERONE IMPLANT
`Presentation Testosterone implanls are pallets con-
`taining 50. 100 or 200 mg testosterone in glass
`ampmrles.
`Uses
`in the male: testosterone replacement therapy
`in primary or secondary hypogonadal disorders. for
`example:
`— afturcastration,
`- eunuchoidism.
`- hypouituilarisrn,
`- endocrine impotence.
`_
`-
`infertility due to spermalogenic disorders.
`- malecllmactoricsymptornssuchasclecreasedlibido
`and decreased mental and physical activity.
`Moreover. testosterone therapy may be indicated
`in osteoporosis in ma male due to androgen deli-
`cisncy.
`In the lcmale as an adjunct to oestrogen rpIa:e-
`ntenl therapy in post:-nenopausalwurnen to alleviate
`symptoms. such as decreased libido andlor loss of
`energy.
`‘
`_
`D9-'-IE0 and administration
`ln males 100-600 mg on pending Dr‘! individual "NI We-
`rnen{5_ A 395;,“ of spa mg :5 x lD0_m_gl usually
`maintains plasma iesmsterone levels within the nor-
`mal physiological range for 3-5 months.
`in females: 50-loo mg as an adjunct to oestradlol
`implants.
`Method of
`Implantation: Testosterone implants
`should be inserted subcutaneously into an area where
`there is rolarlvaly limo movement or blood MP9‘?-
`such as the lower abdominal wall or UN!
`lflullfllik.
`Insertion is made under local anaesthesia using -fl
`trocar and a cannul.a,The wound ls closed either will
`an adhesive dressing or B line su:uro.‘l'l1e Imlfilanfl
`must be placed subcutaneously to laeil-lute retrieval
`if ntrcess aw. Full aseptic 'no touch’ tech nlque should
`be adopted.
`Contra-indications.warnings.etc.
`_
`Corlrra~.-'ndica:lon3: Known or suipeclsd Dlfiiiilllli