ABPI COMPENDIUM OF DATA SHEETS
`
`AND
`
`SUMMARIES OF PRODUCT CHARACTERISTICS
`
`1 999-2000
`
`With The Code of Practice for the
`
`Pharmaceutical Industry
`
` 4:,
`
`_, Datapharm Publications Limited
`12 Whitehali, London swm 20v
`
`AstraZeneca Exhibit 2091 p. 1
`InnoPharma Licensing LLC V. AstraZeneca AB IPR2017-00904
`Fresenius—Kabi USA LLC V. AstraZeneca AB IPR2017-01910
`
`

`

`1'
`Responsibility for Data Sheets and Summaries of Product Characteristics
`The data sheets and summaries of product characteristics in this Compendium are prepared independently by each
`participating company and each proof is checked and the text confirmed as correct by the participant concerned-
`Neither Datapharm Publications Limited nor The Association of the British Pharmaceutical Industry iABPll givGS anI.
`guarantee whatsoever as to the accuracy of the information contained in the data sheets or summaries of produc;
`characteristics and accepts no liabIIity whatsoeverIn respect of any loss damage or expense arising from anv SUcl
`information or for any error or omission in the data sheets or summaries of product characteristics and in pafiJCUlal
`(but without prejudice to the generality of the foregoing} shall not be liable for any consequential damages 0.
`expenses or any lees of profit or any liability to third parties incurred by anyone relying on the information containec
`in the data sheets and summaries of product characteristics appearing in this Compendium.
`
`Published by Datapharm Publications Limited
`
`Copyright 2 1999
`Copyright in the material included in this Compendium
`IS reserved by the individual companies and
`organisations which have contributed it
`
`iSBN 0 907102 18 2
`ISSN' 1364—5005
`
`Typeset. printed and hound in Great Britain
`by William Clowes Limited. Beccles and London
`
`AstraZeneca Exhibit 2091 p. 2
`
`

`

`DRGANON LABORATORIES LIMlTED
`
`1095
`
`Children: it should be noted that smaller and less
`frequent doses may achieve the same response,
`AdministrallonrDeap intramuscular injection
`Contraindications: Known or suspected prostallc or
`mammary carcrnoma. Pregnancy. Breastfeeding. Hy»
`parsensttivity to one of the excipiems.
`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 hypercholes-
`terolaemia; latent or over-r cardiac failure. renal dys-
`function. hypertension. epilepsy or migraine ior a
`history of these conditions). since androgens may
`occasionally induce fluid and sodium retention:skel-
`etal metastases, since androgens may induce hyper-
`:alcacmia or hypercalciuria in those patients.
`The use of steroids may influence the results of
`certain laboratory tests.
`Androgans should be used cautiously in prepubenal
`boys to avoid premature coiphyseal closure or pre-
`cocious sexual development.
`If androgen-associated adverse reactions occur,
`Sustanon 100 treatment should be interrupted and.
`alter disappearance of the symptoms. be resumed at
`a lower dosage.
`interaction withorher modicaments and other forms
`of interaction: Enzyme-Inducing agents may exert
`increasing or decreasing eflects on testosterone
`levels. Therefore adjustment of the dose. andior
`intervals between iniections may be required.
`Pregnancy and lactation: On the basis of its pharma—
`cological effect. Sustanon 100 is suspected to cause
`birth defects andlor other irreversible adverse effects
`on pregnancy outcome. Therefore. Sustanon 100 is
`contraindicated during pregnancy and lactation.
`Effects on ability to drive and use ofmachines:As far
`as is known Sustanon 100 has no influenCe on
`alertness and concentration
`undesirable effects: The following adverse reactions
`havo been associated with androgen therapy in
`general: In pteoubertal boys. precocious sexual de-
`velopment. an increased frenuency of arectldns.
`phallic enlargement and premature epiphyseat clo-
`sure; prtapism and other signs of excessive sexual
`stimulation; water and sodium retention; oligosper-
`min and a decreased ejaculatory volume.
`7
`Treatment should be interrupted until these sympA
`toms have disappeared. altar which it should be
`continued at a lower dosage.
`Hoarseness of the voice may be the first symptom
`g! vocal change which may lead to irreversible
`lowering of the voice. If signs or yirilisation. particu-
`larly lowarring of the voice. develop. treatment should
`be discontinued.
`
`Pharmacological properties Therapeutic classifica-
`tion: (303 CA 03. Ocstrogen preparation for hormone
`replacement therapy.
`Pharmacodynamir: Properties: The oharmacodynam
`lcs of Sandrena are similar to those of oral oestrogen s.
`but the meter dilterence to oral administration lies in
`the pharmacolcinetic profile.
`The clinical efficacy of Sandrenc in the treatment of
`menopausal symptoms is comparable to that of
`peroral oestrogen Combined with medruxvproges-
`lfltOHe ace:ate. Dercutaneous ocstradiol lowers total
`cholesterol without reducing the HDL cholesterol
`level.
`Pharrtlacolrinorr'cprapeflies:$a ndrena is an alcohol-
`based oestradiol gel. When applied to the: skin the
`alcohol evaporates rapidly and oostradiol is absorbed
`through the skin into the circulation. To some extent.
`however, the oestradiol is stored in the subcutaneous
`tissue from where it is released gradually into cucu-
`Iation. Pcrcutanoous administration circumvents the
`hepatic first-pass metabolism. For these reasons. the
`fluctuations in the plasma oestrogen concentrations
`with Sandrena are less pronounced than normal
`oestrogen.
`_
`A 1.5 mg pctcutoncous dose of oostradlol ”.59
`Snndrenal results in a plasma concentration of about
`340 pmolfl. which corresponds to the level of early
`lolliculat stage in prentenobausal women. During
`Sandrona treatment the oestradiolloestronc ratio re-
`mains at 0.7. while during pcroral oestrogen treatment
`it usually drops to less than 0.2.
`The mean oestradiol exposure at steady state of
`Sandrena is 82 per cent compared with an equivalent
`oral dose of o‘estradiol valorate. Otherwise the metab-
`olism and excretion of transdsrmal ocstradtol follow
`the fate of natural oestrogons.
`Preclinicalsaferydata:Oestmdiol is a natural female
`hormone with an BSIablish‘ed clinical use. therefore
`no toxicological studies have been performed wrth
`Sondrana. The necessary studies on the irritantellocts
`of the gel have been studied in rabbits and skin
`sansitisation in guinea pig. Based on the results from
`tires studies it can be concluded that Sanidrena could
`very infrequently cause mild skin Irritation. The
`Frequency of the occurrence of dermal irritation can
`be reduced by daily change oi the application site.
`Pharmaceutical particulars
`List of excipients: Carbon-nor 934 BP.‘ Sodium hydrox-
`ide: Propylene glycol PhEur: Spit. tom-Ethanol 56%
`3F. Aq. punt-Purified water PhEur.
`incompatibilities: No incompatibilities have been
`iound.
`Shelf life: 3 years.
`Special pmm ulions for storage: At room temperature
`lbelow 251:).
`Nature and contents ofconlar‘ner: Single doscclu rrun~
`lum toil sachets supplied in packages containth 28
`of either (lose or 91 sachets of 1 mg dose.
`instructions for usefl’tandling: None
`Marketing authorisation holder
`Orion Corporation. Orioninite 1. RD. Box ‘65. FIN-
`02101.E5POO,FINLAND
`_
`Distributed by Organon Laboratories Limited. Cam-
`0 L.
`béidge Science Park. Milton Road, Cambridge. CB4
`“filming authorisation number
`1391 110004-0005
`Date 0! Epanlall revision of the text October 1996
`legal Category POM
`
`Special warnings and special precautions for last:
`Before therapy is initiated. tr thorough medical history
`should be taken. A complete gynaecological exami-
`nation should be performed and repeated at least
`once a year during therapy.
`Prolonged use without addition of a progestogen
`may cause endometrlal hyperplasia. Therefore.
`in
`women with an intact uterus. Sandrena treatment
`should be combined with cyclic progeston‘cn admin-
`istration, Withdrawal bleeding resembling normal
`menstruation will usually occur after each course of
`progestogen. The cause of unexpectoo or prolonged
`uterine bleeding during therapy should be clarified.
`Atypical adcnamatous hyperplasia ol the endomo-
`trium must be treated bolero commencing oestrogen
`therapy.
`Consider discontinuation prior to surgery or pro-
`longed immobilisation. Development of do have
`frequent severe headaches or migraine should be
`investigated and possible prodromal symptoms at
`vascular occlusion should be clarified.
`The risks and benolits of treatment should b-
`cvaluatod and close monitoring performed for pa-
`Iionls with:
`. endometriosis
`- uterinoleiomyoma
`- endometrial hypotplasia {simple glandular hyper-
`plasia or hyperplasia niandularis cyclical
`- diseases of tho cardiovascular system including
`corebrovascular disorders.
`- a history of thromboombolic disease.
`- severe hypertension.
`- history of tar closo family history all breast cancer.
`— severe disturbances ol lipid metabolism
`renal dysfunction
`systemic lupus erythematosus
`- potphyrln
`At present there is suggestive evidence of a slight
`increase in the relative risk of carcinoma of the breast
`with Iongtcrm hormone replacement therapy. how-
`ever. the results are contradictory. Rogular breast
`examinations and mammography. where appropri-
`ate. should be carried out in women on hormone
`replacement therapy.
`Some conditions may he aggravated during oestro-
`gen therapy or pregnancy. Women on Sandrcna
`treatment with one of the following conditions for
`with a history thereof during previous pregnancy or
`hormone usel should therefore be closely monitored.
`These conditions include:
`. mild hypertension.
`- migrainoorsevere headache.
`. benign breast disease.
`-
`liver function disturbances.
`- cholestasis.
`. cholelithlasis.
`- diabetes mellirus.
`- asthma,
`- olosclorosis,
`. multiple sclerosis.
`- galactorrhea. elevated prolactin levels.
`- history of herpes gestationis.
`- epilepsy,
`interaction with othcr madicamonts and other forms
`of interaction: No interactions between Sandi-ens and
`other medicines have been reported. There are some
`indications that oestrogons may reduce the effects of
`entihypenensive.
`anticoagulant
`and
`onlidiabatic
`drugs. Concomitant treatment with potent inducers of
`liver enzymes log. barbiturates, carbamazepine. gri-
`seofulvin and rifampicin) may reduce the plasma
`levels of oestradiol. The significance of those interac-
`tions in lransdermol application has not been eluci-
`dated,
`Prognoncyand lactation: Sandrcna is not indicated in
`women of child-bearing capacity. n has no contracep-
`live c‘licacy. Sandrena should not be used during
`pregnancy or lactation.
`Eflocts an ability to drive and use machines: Destro-
`gons such as Sandrena do not aflect 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 oftroatmcnt,
`Occasionally for oestrooans in general: Breast
`tenderness. headache. oedema. weight increase. un-
`5:heduled vaginal bleeding or spotting.
`Rarely for oestrogons in general: Migraine. changes
`in libido and mood. gastrointestinal discomfort (e.g.
`nausea. vomiting. stomach crampsl. hypertension.
`alterations in liver function and biliary flow.
`ln clinical trials dermal irritation has been vury
`infrequent with Sandrena.
`Oucrdosage: Generally. oestrogcns are well tolerated
`even in massive doses. Possible symptoms of over-
`dose include those listed under undesirablo effects.
`Treatment is symptomatic.
`
`Overdosage:'fite acute intramuscular toxicity of Suss
`tanon too is very low. Therefore toxic sym toms are
`not Expected to occur.
`p
`Pharmacological properties
`Pharmacodynamic properties: Testosterone is the
`principal endogenous hormone essential for normal
`growth and development of the male sex organs and
`male secondary sour characteristics. During adult Iile
`testosterone is essential for the functioning of the
`testes and accessory structures, and for the mainte-
`nancc of libido. sense of well-being. erectile potency
`prostate and seminal vesicle function.
`‘
`Treatment of hypogonadal males with Sustanon
`100 results to a clinically significant rise of plasma
`concentrations of testosterone. dihydrotcstmtcrona
`and androstenedione. as well as a decrease of SHBG
`[sex hormone bmding globulinl. in the males with
`SUSTANDN' 100‘
`primary lhyoergonadotrooicl hypogonadism treat-
`'
`.
`_
`ormal
`rnenl with Sustanon results in a n
`'
`‘
`malltatlva and quantitative composition
`pitultaryfunctlon.
`women at
`Testosterone propionate PhEur 20 mg
`Pharmacokinsric properties Sustan.
`
`'on 100 contains a
`
`”testosterone phenylpriopionate BF 40 "19
`‘estostorone lsocaproate BP #0 mg
`number of esters of testosterone with different dura-
`Equivalent to a total of 75 mg of testosteronel
`tions of action. The esters are hydrolysed into the
`the general circulation.
`natural hormone testosterone. as soon as they enter
`Pharmaceutical form Sustanen 100$ a clear. sterile,
`oily solution for deep intramuscular Injection.
`A single dose ol Sustanon 100 leads to an increase
`Clinical particulars
`of total‘plasma testosterona, with peak level reached
`Therapeutic indications: Testosterone replacement
`approximately 24-48hrs llml after administration.
`therapy in male hypogonadal disorders. for example:
`Plasma testosterone levels return to the lower limit of
`the normal ran 9 in
`-
`after castration: eunuchoidism; hypopltuitarism; en—
`docrine impotence: male climacteric symptoms like
`days.
`9
`males alter approximately 21
`decreased libido; certain types of infertility due to
`Testosterone is metabolised ‘
`we the normal
`at
`-
`_
`.
`disorders of spannalogonesis.
`ways. Excretion‘malnly takes place vla the wigs as
`Testosterone therapy may also be indicated for the
`contugatcs oi etiooholanolone and androsterone
`prevention and treatment of osteoporosis in by po gDnA
`adal males
`Preclinical safety data: Not applicable.
`Pharmaceutical particulars
`Posalogry and method of administration:
`list of excfpienls:
`Dosagczln general. dosage should be adjusted to the
`Benzyl Alcohol PhEur 0.1 ml
`individual response ofthe patient.
`Arachis Oil PhEur to 1.0 ml
`Adults: Usually, one injection of 1 ml per lwo weeks
`is adoquato.
`IllCOIY‘lpflTl/bhlthflst N0 relevant ll'lcUl'l"
`Elderly: it should be noted that smaller and less
`frequent doses may achieve the same response.
`Shell-life: 5 years.
`
`
`pa
`
`e
`“hill?! 5 bro
`
`AstraZeneca Exhibit 2091 p. 3
`
`

`

`1096
`
`ORGANON LABURATOHIES LIMITED
`
`tanon 250 is very low. Therelore toxic symptoms are
`not expected to occur.
`Pharmacological properties
`Pharmacad‘ynamic properties: Testosterone is the
`principal endogenous hormone essential for normal
`growth and development at the male sex Organs and
`male secondary sex characteristics. During adult l‘ile
`testesterone is essential for the functioning of the
`testes and accessory structures. and for the mainlel
`nance of libido. sense at welllbeing. erectile potency.
`prostate and seminal vesicle lunction.
`Treatment oi hypogonadal males with Sustanon
`250 results in a clinically significant rise of plasma
`concentrations of testosterone. dihydrotestosterone
`and androstenedionu, as well as it decrease of SHSG
`(sex hormone binding globulin}.
`In the males wrth
`primary lltypergonadotropicl hypogonadiSm treat-
`ment with Sustanon results in a normalisation of
`pituitary lunction.
`Pharmacokineri‘c properties: Sustanon 250 contains a
`number of esters of testosterone with different dura-
`tions ol action. The esters are hydrolysed into the
`natural hormone testosterone as soon as they enter
`the general circulation.
`A single dose 0! Sustanon 250 leads to an increase
`at
`total plasma testosterone with peak-levels at
`approximately 70 nmol‘il
`lC....l. which are reached
`approximately 24~48h it.....i alter administration.
`Plasma testosterone levels return to the lower limit at
`the normal range in males in approximately 21 days.
`Testosterone is metabolised via the normal path-
`ways. Excretion mainly takes place via the urine as
`coniugates of ctiocholanolono and androsterone.
`Proclini'caisafely date: Not applicable.
`Pharmaceutical particular-s
`List of tpxcipicnrs:
`Honzyl Alcohol PhEur 0.1 ml
`Arachis Oil PhEur to 1.0 ml
`incompatibilities: No relevant incompatibilities are
`known.
`Shelf~life:5 years
`Special precautions for storage: Store between 15-
`25'6', protect lrom light
`Nature and contents ot'comainers: 1 ml ampoules in
`boxes of 3
`instructions ior use/handling: not applicable.
`Marketing authorisation number 0065/5086
`Data at first authorisation 28 February 1973
`Date of preparation ol the text March l995
`Legal category POM
`
`Special precautions Ior storage: Store between 15-
`BS'C. protect from light.
`Nature and contents of containers: l ml ampoulcs in
`boxes of 3.
`instructions for use/handling not applicable.
`Marketing authorisation number 0065;5019
`Date of that authorisation 28 February 1973
`Dale of preparation of the text March 1995
`Legal category POM
`
`SUSTANQN' 250
`Qualitative and quantitative composition
`Testosterone propionote PhEur 30 mg
`Testosterone pheny‘lpriopionate EF 60 mg
`Testosterone isocttprodte BP so mg
`Tnstosterone decanoate BP 100 mg
`tequiyalentto a total at 118 mg pl Testosteroncl
`Pharmaceutical form Sustnnon 250 is a clear. sterile.
`oily solution for deep intramuscular injection.
`Clinical particulars
`Therapeutic indications: Testosterone replacement
`therapy in male hypogonadal disorders. for example:
`after castration; eunuchuidism; hypopituitan’sm; en-
`docrine impotence: male climacteric symptoms like
`decreased libido: certain types of iniertilily due to
`disorders of Spermatoganesis.
`Testosterone therapy may also be indicated for the
`preventionand treatment ofosteoporosls in Monaco-
`adal males
`Posolagy and math ad of administration:
`Dosage: In general. dosage should be adjusted to the
`individual response of the patient.
`Adults: Usually. one injection of ‘lml per three
`weeks is adequate.
`Elderly: it should be noted that smaller and less
`{renuent doses may achieve the some resistance.
`Children: It should be noted that smaller and less
`frequent doses may achieve the same response,
`Administration: Deep intramuscular injection
`Contra-indications: Known or suspected prostatic or
`mammary carcinoma. Pregnancy. Breast-feeding. H‘f'
`persensitivity to one or the excipiBntS.
`Special warnings and special precautions for use:
`Patients. especially the elderly. with the following
`conditions should be monitored:
`ischaemic heart
`disease. since androgen; may produce hyperchoics-
`terolaemia. Latent pr overt cardiac failure. renal
`dyslunmion. hypertension. epilepsy or migraine (or a
`history of these conditionsl. since androgens mail
`occasionally induce lluid and sodium retention. Skel-
`etal metastases. since androgens may induce hyper-
`calcaemia or hypercdlciuria in these patients
`The use of steroids may influence the results pl
`certain laboratory tests.
`Androgensshould be used cautiouslyrn prepuhonal
`boys to avoid premature opiphyseal closure or we
`cocious sexual development.
`it androgen-assocrated adverse reactions occur.
`Sustanon 250 treatment should be interrupted and.
`alter disappearance of the symptoms, be resumed at
`a lower dosage.
`interaction with other medicamenls and other forms
`of interaction: Enzyme-inducing agents may exert
`increasing or decreasing effects on testosterone
`levels. Therefore adjustment ol
`the close. and/or
`intervals between injections may be required.
`Pregnancy and lactatiom 0n the basis of its pharma-
`cological cilect. Sustanon 250 is suspected to cause
`hinh defects andior other irreversible adverse effects
`on pregnancy outcome. Therefore. Suslanon 250 is
`contraindicated during pregnancy and lactation.
`Effects an ability to drive and use of machines: As far
`as is known Sustanon 250 has no influence on
`alertness and concentration.
`Undesirable efiectsl' The (allowing adverse reactions
`have been associated with androgen therapy in
`general:
`In prepubcrtal boys. precocious sexual develop-
`ment. an increased frequency of erections, phallic
`enlargement and premature epiphyseal closure: pria-
`prsm and other signs of excessive sexual stimulation:
`water and sodium retention: oligospermia and a
`decreased eiaculatory volume.
`Treatment should be interrupted until these symp-
`toms have disappeared. after which it should be
`continued at a looser dosage.
`Hoarseness of the voice may be the first symptom
`ol vocal change which may lead to irreversible
`iOWEl’ll’lQ ofthe veice. Ii signs of virilisation. particu-
`larly lowering of the voice. develop. treatment should
`be discontinued.
`
`Ov‘ertlasa‘gE.‘ The acute intro muscular toxicity pl Sus-
`
`carcinoma or breast carcinoma in the male. Prog-
`nancy. Breast-reciting.
`Use in prvgflarlcyand lactatioanestosteronc implants
`are contra-indicated during pregnancy and lactation.
`Warnings and precourio n5:
`- Androgens should be used with caution in women
`to avoid unacceptable and irreversible virilization.
`Female patients should therefore be counselled to
`report any deepening or honrsening of the voice
`without delay.
`_
`.
`‘
`. Androgens should be used With caution in prepubw
`onal boys to avoid premature epiphyseal closure or
`precocious sexual development. Skeletal maturzi
`tion should be monitored regularly.
`. Due 10 the long-lasting action and the difficulty of
`removal. Testosterone implants should hr,- used
`with extra caution. Therefore, it may be advisable to
`establish the beneficial client and tolerance [or
`androgen therapy by prior treatment vyith a shorter.
`anting testosterone preparatlon. This flpDileS In
`particular to lprelpuhenal boys. women and elderly
`men.
`- Patiems wrth latent or overt cardiac failure, renal or
`hepatic dysfunction. hypertension. epilepsy or ml-
`amine [or a history of these conditions} should be
`kept under close medical supervision. sir-ice aggra-
`vation of recurrence may occasionally be induced.
`tr androgen-associated adverse reactions occur the
`.
`implant should be removed it possible.
`. The use of steroids may influence the results of
`certain laboratory tests.
`Effects an ability to drive and to use machines: As for
`as is known Testosterone implants have no ellects on
`alertness and concentration.
`interacrians: Enzyme-inducing drugs may influence
`plasma testostm‘onelcvels.
`Other undesirable effects (frequency and serious
`pass): The following adverse reactions have been
`associated with androgen therapy:
`-
`in general: water and sodium retention. hypotcall
`caernia}
`-
`in women: symptoms of virilizntion, such as voice
`changes ldeepening. hoarsoningl and hirsutism;
`in propuberlal‘ boys: precocious sexual develop.
`ment.
`increased frequency of erections. phallic
`enlargement and premature epiphysepl closure;
`in memoriapism and othersipns ofexceseiye sexual
`stimulation, oligospormia and decreased ejacula
`tory volume
`Overdosago:‘lhe acute toxicity of testosterone is lo~.~._
`Priapism in men and undesired deepening of
`tr.»-
`voicelnwomenarosymptomsolchronicoverdosngo.
`In this case the implantlsl should be removed.
`Pharmaceutical precautions Store below 25'C and
`protect [torn light
`incompatibilities: None.
`Legal category POM.
`Package quantities Each sterile implant is supplier:
`singly. in a sealed glass tube.
`Further information Testosterone is a naturally-
`occurring hormone lorr‘ned in the interstitial cells of
`the testes under the control oltho anteriorlobe of the
`pituitary gland which controls the development and.
`maintenance of the male sex organs and male
`secondary sex characteristics. Testosterone also pro‘
`duces systemic clients, such as increasing the rotary
`tion of nitrogen. calcium. sodium, potassium. chloride
`and phosphate leading to an increase in skeletal
`.wgighl, water retention and an increase in the growth.
`at bone.
`.
`,
`Testosterone implants. when inserted subcutane
`Dusly release testosterone into the bloodstream at .1
`relatively even rate supplying near physnoiofjicjl
`plasma testosterone levels.
`.
`Surlace area of the implants is the most Impof‘ta n:
`lactor influencing the rate of absorptIOn. In gen-2m:
`the absorption rate estimated by removal of implants
`at intervals and weighing appears to be appreciabli
`more rapid than when the rate is assessed upon the:
`clinical requirement. in addition to clinical cwdcnct»
`individual variation in the rate of absorption or
`implants must be taken into account.
`The average daily absorption oi testosterone has
`been estimated at 0.5 mg [or e 100 mg impla nt \x-rth
`an approximate duration of 3p weeks.
`Product lie-a nca numbers
`50 mg
`ODBSISOBZR
`103 mu
`Doss/sums
`200 mp
`0065/5034Fl
`
`.
`
`.
`
`ZISPIN Y
`Qualitative and quantitative composition Each to b
`lot contains 30 mg of minazapine.
`Pharmaceuticallorm Tablet
`
`AstraZencca Exhibit 2091 p. 4
`
`TESTOSTERONE IMPLANT
`S'resentation Testosterone implants are pelletscon-
`taining 50, 100 or 200 mg testosterone in glass
`ampoulhs.
`Uses
`in the male: testosterone replacement therapy
`in primary or secondary hypogonadal disorders. for
`example:
`- after castration.
`eunuch oidism,
`hypopltuitarism,
`endocrine impotence.
`.
`>
`iniEl'lilllV due to spermatogenic disorders.
`maleclimacteric sympto ms such as decreased libido
`and decreased mental and physical actrvtly.
`Moreover. testosterone therapy may be indicated
`ill asleomlclsis in the male due to androgen deli-
`clency.
`In the female as an adjunct to oestrogen replace-
`ment therapy in postmenopausalwomcn to alleviate
`Symptoms. such as decreased libido andior loss of
`Energy;
`_
`,
`_
`”03598 and administration
`in malt-5100.500 mg depending on indivrdualrequrro-
`ments. A dosage of 600 mg is x l00_m_gl usually
`maintains plasma testosterone levels Within the nor-
`mal Dthiolopical range tor 4-5 months.
`in females: 50-100 mg as an adjunct to ocstradrol
`implants.
`‘
`Method at
`implantation: Testosterone implants
`should be inserted subcutaneously into an area where
`there is relatively little movement or blood supply.
`SUCh as the lower abdominal wall or the outlook.
`Insertion is made under local anaesthcsm. USll'lq El
`trocar and a cannula. The wound is closed enthsrwlh
`an adhesive dressing or a line suture. The Implants
`must be placed subcutaneously to laminate removal
`if necessary. Full aseptic ’no touch' technique should
`be adopted.
`.
`Contra-indications. warnings, ate.
`Contra-indications: Known or suspected prostatic
`
`