ABPI COMPENDIUM OF DATA SHEETS
`
`AND
`
`SUMMARIES OF PRODUCT CHARACTERISTICS
`
`1999-2000
`
`With The Code of Practice for the
`
`Pharmaceutical Industry
`
`3
`
`3
`
`Datapharm Publications Limited
`T2 Whitehall, London SW1A ZDY
`
`Astrazeneca Ex. 2091 p. 1
`Mylan Pharms. Inc. V. Astrazeneca AB IPR2016-01325
`
`

`
`[
`Responsibility for Data Sheets and Summaries of Product Characteristics
`The data sheets and summaries of product characteristics in this Compendium are prepared independently by Bee}.
`participating company and each proof is checked and the text confirmed as correct by the participant concerned.
`Neither Datapharm Publications Limited not The Association of the British Pharmaceutical Industry lABF‘iJ QN95 an‘,
`guarantee whatsoever as to the accuracy of the information contained in the data sheets or summaries of produq;
`characteristics and accepts no liability whatsoever in respect of any ioss, damage or expense arising from ar1V‘SUcl"
`information or for any error or omission in the data sheets or summaries of product characteristics and in parilcula.
`(but without prejudice to the generality of the foregoing) shall not be liable for any consequential damages 0;
`expenses or any loss of profit or any Iiabiiityto third parties incurred by anyone relying on the information contaihei:
`in the data sheets and summaries of product characteristics appearing in this Compendium.
`
`P‘-’b"5h<-‘d by Dataliharrn Publications Limited
`
`Copyright 1999
`C0Dy|'iQht in the material included in this Compendium
`is reserved by the individual companies and
`Oiganisations which have Contributed it,
`
`ISBN 0 907102 18 2
`Issn 1364—50os
`
`TVp°5e‘- p”"‘T9U and Ufiund in Great Britain
`bi’ William Clowes Limited, Beccles and London
`
`Astrazeneca Ex. 2091 p. 2
`
`

`
`Special warnings and special precautions for use:
`Before therapy is initiated. rt thorough medical history
`should be taken. A complete gynaecological exami-
`natéorl should be performed and repeated at least
`once a year during therapy.
`Prolonged use without addition of a progestogon
`may cause endometrial hyperplasia. Therefore.
`in
`women with an intact uterus. Standrcna treatment
`should be combined with cyclic progcstogcn admin-
`istration. Withdrawal blending resembling normal
`menstruation will usually occur after each course of
`progcstogen. The cause of unexpected or prolongccl
`uterine bleeding during therapy should be clarified.
`Atypical adcnomatous hyperplasia of the endomo-
`trium must be treated before commencing oestrogen
`therapy.
`Consider discontinuation prior to surgery or pro-
`longed immobilisation. Development of do novo
`frequent severe headaches or migraine should be
`investigated and possible prodromal symptoms of
`vascular occlusion should be clarified.
`The risks and benefits of treatment should be
`evaluated and close monitoring performed for pa-
`tients with:
`— endometriosis
`- uterine-leiomyoma
`- endomctrial hyporplasia lsimple glandular hyper-
`plasia or hypcrplasia glandularis cystical
`- diseases of the cardiovascular system including
`cerebrovasculardisorders.
`— a history ofthromboemhciiic disease,
`— severe hypertension.
`- history of for close family history oil breast cancer,
`- scvare disturbances of lipid metabolism.
`- rnnaldysfunction
`systemic lupus erythemtttosus
`- porphyria
`At. present there is suggestive evidence of a slight
`increase in the relative risk of carcinoma of the breast
`with long-tcrm 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
`replaccrnenttherapy.
`some conditions may be aggravated during oestro~
`gen therapy or pregnancy. Women on Santtrcna
`treatment with one of the following conditions tor
`with a history thereof during previous pregnancy or
`hormone uscl should therefore be closely monitored.
`These conditions include:
`- mild hypertension.
`- migrainoor severe headache.
`- benign breast disease.
`-
`liver function disturbances.
`- chdlestasis.
`- cholellthiasis.
`- diabetes mellltus.
`- asthma.
`- otosclnrosis.
`- multiplesclcrosis.
`- galactorrhea. elevated prolactin Ieveis.
`- history of herpes gcstatlonis.
`- epilepsy.
`interaction with other rncdicaments and other forms
`of interaction: No interactions between Sandrena and
`other medicines have been reported. There are some
`indications that oestrogcns may reduce the effects of
`antihypertcnsivo.
`anticoagulant
`and
`anti-diabetic
`drugs. Concomitant treatment with potent inducers of
`liver enzymes log. barbiturates, carbamazepine. gri-
`seofulvin and rifampicinl may reduce the plasma
`levels of oestradiol. The significance of these interac-
`tions in transderrnol application has not been eluci-
`dated.
`Pregnancyand iactstion:Sar1dr-ena is not indicated in
`-.-rnmcn of childbearing capacity. It has no contracep-
`tive efficacy. Sandrana should not be used during
`pregnancy or lactation.
`Effects on ability to drive and use machines: Destro-
`gon: such as Sandrena do not affect the ability to
`drive or use machines.
`Uncfosirable effects:-kdvcrse 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 for ocstrogons in general: Breast
`tenderness. headache. oedema, weight increase. un-
`scheduled vaginal bleeding or spotting.
`Fla rely for oestro-g ens in general: Migraine. changes
`ln libido and mood. gastrointestinal discomfort le.g.
`nausea. vomiting. stomach crampsl. hypertension.
`alterations in liver function and biliary flow.
`In clinical trials dermai irritation has been very
`lnfreuuentwith Sandrena.
`Ovcrdasage: Generally. oestrogcns are well tolerated
`~‘:'.rl'.>l"l in massive doses. Possible symptoms of over-
`dose include those listed under undesirable effects.
`Trcazment is syntptomatic.
`
`ORGA NON l_ABOFlfiiTOFi|E‘5 LINHTED
`
`Pharmacological properties Therapeutic classifica-
`tion: GD3 CA 03. oestrogen preparation for hormone
`replacement therapy.
`Pharmacodyndmic properties: The pharmacodynam
`lcs of 5a ndrena are similarto those of oral oestrogen s.
`but the major difference to oral administration lies in
`the pharmacokinetic profile.
`The clinical efficacy of Sandrena in the trealm cm of
`menopausal symptoms is comparable to that Of
`peroral oestrogen Combined with medraxy}5I'0El95'
`tcrone acetate. percutancous oestradiol lowers total
`cholesterol without reducing the HDL cholesterol
`level.
`Pharniacaltincrlc oroportics:Sa ndrena isan alcohol-
`hased oestradiol gal. When applied to the skin the
`alcohol ova poratos rapidly and ocstradiol is absorb ad
`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 circu-
`lation. Fcrculanr.-ous administration circumvents “'13
`
`hepati
`first-pass metabolism. For these reasons. the
`fluctuations in the plasma oestrogen concentrations
`with Sandrana are less pronounced than FBYDT-'5'
`oestrogen.
`_
`A 1.5 mg pcrcutancous dose of oestrad-ol‘ (3.59
`Sandrenal results in a plasma concentration of about
`340 pmolll. which corresponds to the level of coil!‘
`follicular stage in premenopausal women. During
`Sandrcna treatment the oestradiollocstrone ratio re-
`mains at 0.7. while during pcroral oestro gent-reatmcnt
`it usually drops to less than 0.2.
`The mean oestradiol exposure at steady state of
`Sandrcna is B2 per cent compared with an cttl-I“-'319fll
`oral dose of oestradiol valerate. Otherwise the metab-
`olism oncl excretion of transdarmal ocstradiol follow
`the fate of natural ocstrogc-ns.
`Precflnicalsafery data:Oestr:ldiol is a natural female
`hormone with an established clinical use. therefore
`no toxicological studios have been performed with
`Sanclrena. The necessary studies on the irrita nt effects
`of the gel have been studied in rabbits and Skln
`sensitisatlon in guinea pig, Based on the results lrorn
`these studies it can be concluded that Sandrena could
`very infrequently cause milcl skin Irritation. The
`frequency of the occurrence of dermal irritation can
`be reduced by daily change of the application site.
`Phamtaceutical particulars
`List of excr'pr'enls.' Carbomr.-r 934 BF’: Sodium h'rd'0K'
`ide; 2'-'ropylene glycol Phfiur: Spir. fort.-Ethanol 55%
`BP. Au. purlf.-Purified water PhEur.
`incompatibilities: Nu incompatibilities have been
`found.
`Shelflife: 3 years.
`Specialprc-cautions forstaragz.-:At room temperature
`lbclow 25‘Cl.
`Nature and contents ofcontainr.-r.' Single doscAal_urnin-
`lum foil sachets supplied in packages containing 28
`of either dose or 91 sachets of 1 mg dose.
`instructions for use/handling: None
`Marketing authorisation holder
`Orion Corporation. Urioni
`its 1, PD. Boat 55. FW-
`l321El1. ESPOO, FINLAND
`Distributed by Organon Laboratories Limited. Cam-
`bfidfla Science Park. Milton Road. Camt:lrld§°- 554
`DFL.
`13911.-TIIJEI4-D005
`Marketing truth ptisation number
`Data of lpartlall revision of the text October 1995
`Legal catugory POM
`
`SUSTANDN’ 100
`Qualitative and quantitative composition
`Testosterone propionate PhEur 20 fi'|!l
`Testosterone phenylpriopicnate SP -10 mil
`Testosterone Isocaproate BP 40 mt!
`lfiquivalent to a total of 7-: mg of testostcronel
`Pharmaceutical form Sustanon 1lJD_is ll clear. sterile.
`oily solution for deep intramuscular Injection.
`clinical particulars
`Therapeutic indications: Testosterone replacement
`therapy in male hypogonadal disorders, for example‘.
`after castration: eunuchoidism.‘ hvpflnituitarism: en-
`docrine impotence: male climacteric symptoms like
`decreased libido: certain woes of infertility due to
`disorders of spermalogcnesis.
`Testosterone therapy may also be indicated for the
`prevention and treatment of osteoporosis in hypo gon-
`adal males
`Posdiog-y and method ofadministratio n:
`Dosagczln general. dosage should be adjusted to the
`individual response of the patient.
`Adulrsrusually. one iniection of 1 ml per two weeks
`is adequate.
`Elderly: it should be noted that smaller and less
`frequent doses may achieve the same response.
`
`1095
`
`Children: It should be noted that smaller and less
`frequent doses may achieve the same response.
`A-dmi'nislratl'on: Deep intramuscular injection
`Contra-r'r1di'cat.*‘ons: Known or stlspected prostaur; or
`rnammary carcinoma. Pregnancy. Breast-leading, Hy.
`pcrsensitivity to one of the oxcipients.
`Special warmn99 -‘Md Special precautions for use:
`Patients. especially the elderly. with the following
`conditions should be monitored:
`ischaemic heart
`disease. since androgens may produce hyperchglg5_
`lerolaemia: latent or overt cardiac failure. renal dys-
`function. hvperlc.-ns-on. epilepsy or migraine (or 3
`history of these conditions}. since androgen; may
`occasionally induce fluid and sodium retention: skel-
`etal metastases, since an-dragons may induce hyper-
`calcacmia or hypercalciuria in these pa'[i9n[5_
`The use of steroids may influence the results of
`certarn laboratory tests.
`Andrngens should be uscdcautiously in prep.ut;e.1;.t
`boys to avoid premature cpiphyseal closure or png.
`cocious sexual development.
`” findfflgt-‘Wassuciated adverse reactions occur
`Sustanon 100 troatrnent should be interrupted and-
`aner disappearance of the syntptorns‘ be resumed 5;
`a lower dosage.
`interaction with other mcdicamenrs and Qfhgy fa.“-,-,5
`of interaction: Enzyme-mducing agents may “en
`increasing or decreasing effects on testosterone
`levels. Therefore adjustment of
`the dose. andfor
`intervals between iniections may be l'equfred_ '
`Frcgnancy and lactation: On the basis of its pharma-
`cological effect, Sustanon too is suspected to cause
`birth defects andlor other irreversible adverse err._-:15
`0" l3"-’_!l"'-‘_i|"-Cir outcome. Therefore, Sustanon 100 is
`contraindicated during pregnancy and Ia|:|_a1iQn_
`Effects on ability to drive and use ofmachines: A; far
`as is known Sustanon lfifl has no influence n
`alertness and concentration
`Undesirable effects: The following adverse reactions
`have been associated with androgen therapy in
`Qenfitfili "1 Pfepubertal boys, precocious sexual (in.
`veloornent. an Increased frequency of arecfigl-_5_
`phallic enlargement and premature cpiphyseal cto.
`sure: l‘-"|_€DIsm and other signs of excessive sexual
`stimulation; water and sodium retention; Dfignspgr.
`rrlia and a decreased ejaculatory volume.
`Treatment should be interrupted until these symp-
`toms have disappeared, after which it should be
`continued at a lower dosage.
`I-loarseness of the voice may be the first symptom
`of vocal change which may lead to irreversible
`lowering of the voice. If signs of virilisation, particu~
`larly lowering of the voice. develop. treatment ghould
`oediscontinued.
`'
`
`Overdosag-e:The acute intramuscular toxicity or 5.45.
`tanon too is very low. Therefore toxic s rn t
`not expected to occur.
`V p mm are
`Pharmacological properties
`Pharmacodynamir: 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 me
`testosterone is essential [or the functioning of the
`testes and accessory structures, and for the mainte-
`nance of libido. sense oi’ well-being. erectile pnlency
`prostate and seminal vesi{;|3 tunmio,.,_
`‘
`’
`Treatment of hypogonadal males with Sustangn
`‘I00 results in a clinically significant ,1“ 9, mas,‘_na
`concentrations of testosterone. dihydtoteslostcrone
`and andrastenl:c|ionc.as well as a decrease of SHBG
`[sex hormone binding globulin}.
`in the males with
`lJ"“”n3|'V fh‘rDe'9DnadotropicI hypo-gonadism treat-
`ment with Sustanon results in
`'
`‘
`pituitaryfunction.
`‘1 normalmahun "f
`Phafmafiflkfflfillc Properties.‘ Susta
`1
`-
`number of esters of testosterone
`d‘i]f'lJeE1:-ggfadns a
`tions of action. The esters are hydrolysed int
`uttha‘
`natural hormone tEsltJStel'ol'Ie,as man as me‘ : IE
`the general circulation.
`5' " E’
`A single (1059 Of Sustanon 103:9 d
`-
`‘
`
`.«
`avbroinmatclv 24-4-Bhrs (rm) aflgr ..d,..,..,i,,,,
`the normal ran e i
`.
`-
`Plasma testosterone levels rclurn to the lower |i.:-gr-$102.‘
`day;
`9
`" males’ 3'19’ aflllroximatcly 2'1
`we the
`-
`_
`.
`Testosterone is metabolisod '
`ways. Excretion mainly takes place viar11$i‘bmt.:!rI‘r?:hh
`Cflnluttales of etiocholanolone and androsterorfe
`as
`Preclinical safety data: Not applim; b|g
`?harmnceutica1 particulars
`List of exciplents
`Bemvl Alcohol PhEur 0.1 ml
`Arachis Oil PhEur 15 1_(; mi
`
`1-;l'rvlcoo£;I1pati‘olliries: No relevant incompatibilities are
`Shelf-life: 5 years.
`
`AstraZeneca Ex. 2091 p. 3
`
`

`
`1056
`
`OHGANON LABORATORIES LIMITED
`
`tanon 250 is very low. Therefore toxic symptoms are
`not expected to occur.
`Pharmacological properties
`Pharmacodlrnamic propanies: ‘Testosterone is the
`principal endogenous hormone essential for normal
`growth and development of the male sex organs and
`male secondary sex characteristics. During adult life
`testosterone is essential for the functioning of the
`testes and accessory structures. and for the mainte-
`nance of libido. sense of well-being, erectile potency.
`prostate and seminal vesicle function.
`Treatment of hypogonadal males with Sustanon
`250 results in a clinically significant rise of plasma
`concentrations of testosterono. ciihydrotestosterone
`and androstenediona, as well as it decrease of SHBG
`[sex hormone binding globulin).
`In the mates with
`primary lhypergonadotrbpicl hypogonadisrn treat-
`ment with Sustanon results in a normalisation of
`pituitary function.
`Pharntacokineticpropenies: Sustanon 2510 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 of Sustanon 250 leads to an increase
`of
`total plasma testosterone with peak-levets of
`approximately 70 nmollt lC.,.,.l. which are reached
`approximately 2-tA4Bh
`ll,...l after administration.
`Plasma testosterone levels roturn to the lower limit of
`the normal range in males in epproximateiyzi days.
`Testosterone is metabolised via the normal path»
`ways. Excretion mainiy takes place via the urine as
`conjugates of etiocholanolone and androsterono.
`Preclinical safety data: Not applicable.
`Pharmaceutical particulars
`List of oxcipienrs:
`Banxyl Alcohol PhEur 0.1 ml
`Arachls UilPl'lEurto1.l1I rnl
`incompatibilities: No relevant incompatibilities are
`known,
`Sheri’-fife-:5 years
`Special precautions for storage: Store between 15-
`25'C. protect from light
`Nature and contents ofccntairlersrl ml ampoules in
`boxes of 3
`instructions for use/handling: not alwlica tile.
`Marketing authorisation number 00655085
`Date of first authorisation 23 Fobruary19‘l’3
`Data of preparation o! the text March 1995
`Legal category POM
`
`Special precautions for storage: Store between 15-
`25‘C, protect from light.
`Nature and contents of containers: ‘l rrtl ompoul-:5 in
`boxes of 3.
`instructions for use/handringrnot applicable.
`Marketing authorisation number 03555019
`Date of tirst authorisation 23 February ‘I973
`Date of preparation of the text hlarch ‘I995
`Legal category POM
`
`SU5TAl'\l0N' 250
`Qualitative and quantitative composition
`Testosterone propionate Pl-iEur 30 mg
`Testosterone ptienylpriopionate BF’ BD mg
`Testosterone isocaproate BP an mg
`Testosterone oecanoate BP 100 mg
`lcauivolentto a total of 1'15 mg of Testosterone:
`Pharmaceutical form Sustanon 250 is a clear, sterile.
`oily solution for deep intramuscular injection.
`Clinical particulars
`Theraperrric indications: Testosterone replacement
`therapy in male hypogonadaldisorders, (or example:
`after castration; eunuchoi-dism; hypopituilarism; en-
`docrine irnpotence: male climacteric symptoms like
`decreased libido: certain types of intimility due to
`disorders of spermatogen esis,
`Testosterone therapy may also be indicated for the
`prevention and trcatment of osteo porpsis in nypagcn-
`a d an m al es
`Posotogy and method of administration:
`Dosage: In general, dosage should be adjusted to the
`individual response of the patient.
`Adults: Usually. one injection of ‘i ml per three
`weeks is adequate.
`Efdefllr-' ll Should be noted that smaller and fess
`frequent doses may achieve the same response.
`Chitdren: It should be noted that smaller and less
`llfittuefil I‘-IOSES may achieve the same response.
`Administration: Deep intramuscular iniection
`Contra-indications: Known or suspected prostatic or
`mammary carcinoma. Pregnancy. Breast-feeding. Hy-
`persensitivity to one of the excipionts.
`5095591 Warnings and special precautions for use:
`Patients. especially the elderly. with the following
`conditions shouid be monitored:
`ischaemic heart
`disease. since anclrogcns may produce hypercholes
`terolaernia. Latent or oven cardiac lailure,
`renal
`dysfunction. hypertension. epilepsy or migraine (or 3
`history of these conditionsl. since androgens may
`°C‘~'-355‘0|”|fill!r induce fluid and sodium retention. Skel-
`etal metastases. since androgen: may induce hyper-
`catcaemia or hypcrcalcluria in these patients.
`The use of steroids may influence the results of
`certain laboratory tests.
`Androoensshould be used cautiousl-yin prepubartal
`boys to avoid premature epipltlyseal closure or pre-
`cocious sexual development.
`If androgen-associated adverse reactions occur.
`Sustanon 250 treatment should be interrupted and.
`after disappearance of the symptoms, be resumed at
`a lower dosage.
`interaction with other n-ledicaments and other forms
`of interaction: Enzyme-indur.-inr;l agents may exert
`|"'="=35"'=l3 Or decreasing effects on testosterone
`levels. Therefore adjustment of
`the dose, endior
`Intervals between injections may be required.
`Pregnancy and lactation: On the basis of its pharma-
`cological eflect. Sustanon 250 is suspcctcd to cause
`l'Iil"fl1 defects andror other irreversible adverse effects
`on pregnancy outcome. Therefore, S-ustanon 250 is
`contraindicated during pregnancy and lactation.
`Effects on ability to drive and use of machines: As far
`as IS known Suslanon 250 has no influence on
`alertness and concentration.
`Urldesirable effects: The lotlowirlg adverse reactions
`have been associated with androgen therapy in
`general:
`"1 Preflllbertol boys. precocious sexual develop.
`ment. an Increased frequency of erections. phallic
`enlargement and premature epiphyseal closure; pria.
`D15"! and other signs of excessive sexual stimulation;
`Walter and sodium retention: oligospermia and a
`decreased ejaculatory volume.
`Treatment should be interrupted until these symp.
`toms have disappeared, after which it should be
`continued at a Iowerdosage.
`Hclarseness of the voice may be the first symptom
`of vocal change which may lead to irreversible
`lowering oftite voice. It signs of virilisation. particu-
`larly lowering of the voice. develop. treatment should
`be discontinued.
`0.-5-.'dosage.' The acute mlra muscular toxicity of Sus-
`
`TESTOSTERONE IMPLANT
`Presentation Testosterone implants are pellets con-
`taining 50. 100 or 200 mg testosterone in glass
`ampoules.
`Uses
`in the male: testosterone replacement therapy
`in primary or secondary hypogonadal disorders. for
`example:
`— after castration,
`- aunuchoidism.
`~ hypopitultarisrn,
`- endocrineirnpotence.
`_
`-
`infertility due to spsrmatogenic disorders.
`- rnaleclimactericsyrnptorrlssuchasdecreasecllibtdo
`and decreased mental and physical activity.
`Moreover. testosterone therapy may be indicated
`in osteoporosis in the male due to androgen defi-
`cioncy.
`In the female as an adjunct to oestrogen replace-
`ment therapy in postmenppausalworncn to altavi.-are
`symptoms. such as decreased libido andlor loss of
`energy.
`j
`_
`Dosage and administration
`in mafos1tlu.5no mg depending on individual real ulte-
`rnents. A dosage of 600 mu l5 1:
`ill-0_m‘gl usually
`maintains plasma testosterone levels W'IT.l'lll'l the nor-
`mai Dhtfsiological range for 4-5 rnDnll'|5-
`to ocstradipl
`in females: 50-100 mg as an adjunct
`_
`implants.
`Method of
`implantation: Testosterone implants
`should be insened suocutaneouslll W0 3" 3'93 WW’?
`there is relatively little movement I'll hlflfid Si-lPDl‘l'«
`such as the lower abdominal wall or the huttodt.
`Insertion is made under local anaesthesia using a
`trocar and a cannula, The wound is closed either with
`an adhesive dressing or a fine suture. The lrrIl3lD"l5
`must be placed subcutaneously to facilitate removal
`if necessary. Full aseptic ‘no touch’ technique should
`be adopted.
`Contra-indications. warnings. ate.
`V
`Corltraindications; Known or suspected D'D5i¢"l*C
`
`carcinoma or breast carcinoma in the male. Preg-
`nancy. Breast-feeding.
`U39inprggnancyflndr'J£l'£l'TlOl1TTO$TDS!8f0|'Il!lll1;‘.li{Ih!$
`are contraanrlicated during pregnancy and lactation.
`Warnings and preco utions:
`— Androgens should be used with caution in women
`to avoid unacceptabio and irreversible virilizotipn.
`Female patients should therefore be counselled to
`report any deepening or l-roan-sening of the voice
`without delay.
`_
`_
`_
`. Anprogens should be used with caution in D!‘-*?P'-'33"
`anal boys to avoid premature epiphyseal closure or
`precocious scxuai devciopment. Skeletal rnatura
`tion should be monitored regulariy.
`. flue m the long-lasting action and the difficulty oi
`removal. Testosterone implants should be used
`with extra caution. Therefore. it may be advisable to
`establish the beneficial effect and tolerance lo.-
`androgen therapy by prior treatment with a shorter-
`acting testosterone preparation. This applies in
`pafliculafifl lprelpulaertal boys. women and eidorly
`men.
`~ Patients with latent or overt cardiac failure. renal or
`hepatic dysfunction. hypertension. epilepsy or mi-
`grgine [or it history of those conditionsl should be
`ltept under close medical supervision. since aggra-
`vation of recurrence may occasionally be induced.
`If androgemassociated adverse reactions occur the
`-
`‘lmpiant should be removed if possible.
`. The use of steroids may influence the results at
`certain laboratory tests.
`Effects on nbility to drive and to use machines: As far
`as is known Testosterone implants have no effects on
`alertness and concentration.
`l'nteracri'ons.' Enzyme-inducing drugs may influence
`plasma testosterone levels.
`Other undesirable effects {frequency and serious
`tress}: The following adverse reactions have been
`associated with androgen therapy:
`-
`in general: water and sodium retention. hyperact-
`cacmia:
`
`~
`in women: symptoms of vii zation, such as voice
`changes ldeepeninp. hoarsonnnpl and hirsutism;
`in pr:-pubertal boys: precocious sexual develop.
`n-rent.
`increased frequency of erections. phallic
`enlargement and premature epiphyseol closure;
`in mempriapism and other signs cfexcossive sexual
`stimulation, oligosparmia and decreased eiacula
`tory volume
`Dverdosapc: The acute to xicity of testosterone is lo-.~..
`Priapism in men and undesired deepening rg.‘
`ti".-."
`ycicelnwomenaresymptomsofcitronicovordosog-:-.
`In this case the implantlsl should be removed.
`Pharmaceutical precautions Store below 2512 and
`protect from light
`incompatibilities: Non a.
`Legal category POM.
`Package quantities Each sterile implant is suppliec
`gingly, in a sealed plass tuba.
`Further information Testosterone is a naturally-
`gccurring hormone formed in the interstitial cells of
`the testes under the control of tho flntorlorlobe of the
`pituitary gland which controls the development and
`maintenance of
`the mate sex organs and male
`secondary sex characteristics. Testosterone also pro-
`duces systemic effects. such as increasing the reten
`tion of nitrogen. calcium. sodium. potassium. chloride
`and phosphate leading to an Increase in sltelem!
`wgigh[_ water retention and an increase in the growth
`of bone.
`Tgsmsterone implants, when inserted subcutanrr
`ously release testosterone into the bloodstream at .1
`relatively even rate supplying near physiological
`ptasma testosterone levels.
`Surface area of the implants is the most important
`factor influencing the rate of absorption. In general
`the absorption rate estimated by removal of implants
`at intervls and weighing appears to be spprociablt
`more rapid than when the rate is assessed upon the
`clinical requirement. in addition to clinical evidence
`individual variation in the rate of absorption o:
`implants must be taken into account.
`The average daily absorption of testosterone ha::
`been estimated at 0.5 mg for 3105 mg implant \-.-urn
`an approximate duration of 30 weeks.
`Product lice nca numbers
`so my
`oossrsoazn
`too my
`tllJ65J5083Fl
`zoo mg
`oussrsoa-an
`
`-
`
`-
`
`ZISPIN V
`Qualitative and quantitative composition Each to 1*’
`lot contains 30 mg of rrlirtazapine.
`Pharma nautical form To blel
`
`Astrazeneca Ex. 2091 p. 4