Aromasin / Pharmacy & UpJohn description, Aromasin / Pharmacy & UpJohn side effects, Aromasin / Pharmacy & UpJohn price, Aromasin / Pharmacy & UpJohn substance

Terms & Conditions | F.A.Q.

  Your Cart:


Your Cart is empty


Home Checkout My Cart My Order Contact us
Buy Steroids Online:
Bulking Steroids:
Anabol 10mg x 100 tablets
Anabol 10mg x 1000 tablets
Anabol 5mg x 1000 tablets BD
Anabol 5mg x 1000 tablets BP
Anabol 50mg Methandienone 100 tabs
Anabol 50mg 100 tabs C&K
Anabol 5mg Methandienone 1000 tabs
Anabol 5mg 100 tabs C&K
Anadrol 50 / oxymetholone
Anapolon 50mg (Oxymetholone)
Anavar (oxandrolone) 5 mg
Anazol (Stanozolol) 2mg
Andriol / Testosterone Undecanoate
Andriol testocaps 40mg
Andriol Testocaps (Testosterone Undecanoate) 40mg caps
Andriol Testocaps 40mg
Androgel / Testosterone Gel 1% 5gms
Androlic (Oxymetholone) 50mg
Androlic 50mg
Androlic 50mg, C&K, China
Andropen 275mg/1ml, 10ml
Andropen 275mg/1ml, 20ml
Androvit Depot 5ml Vial/250mg/1ml
Averbol 25, 10ml (Injectable Dianabol)
Azolol (Stanozolol) 5mg
BONALONE (Oxymetholone)
Clomid 50mg, Global Napi
Cypioject 10 ml Testosterone cypionate
Cypionator 10ml Vial / 300mg/1ml
Cypionax 200 mg (Testosterone cypionate)
Cytopilin-200 (Testosterone Cypionate)
Danabol (Methandrostenolone) 10mg
Deca Durabolin (Nandrolone decanoate) 1 ml
Deca Durabolin (Nandrolone decanoate) 2 ml.Vial/200mg/2ml
Deca-Durabolin (Nandrolone decanoate) 2 ml / 100mg/ml
Deca-Durabolin (Nandrolone decanoate) 2 ml / 100mg/ml
Deca-durabolin 100mg
Deca-durabolin 50mg
Decabol 250 (Nandrolone Decanoate)
Decabole 300 (Nandrolone Decanoate)
Decadubol-100 (Nandrolone Decanoate)
Decaject (nandrolone decanoate)
Dinandrol 100mg (Nandrolone Mix)
Durabol 100, Nandrolone Phenylpropionate
Durabol 200 (Nandrolone Phenylpropionate)
Durabole 200 (Nandrolone Phenylpropionate)
Durabolin 25, nandrolone phenylpropionate
Halotestex 10mg (Fluoxymesterone)
Halotestin 5mg (Fluoxymesterone)
Mastabol Depot 200 BD
Metanabol 5mg / Jelfa
Methanabol (Methandienone) 10mg 100tabs
Methanabol (Methandienone) 10mg
Methanabol (Methandienone) 50mg
Methandriol Dipropionate 75
Methandrostenoloni - 5mg
Nandrolone decanoate 2ml
Naposim (Dianabol/Methandianone) 5mg
Naposim 5mg (Dianabol/Methandianone)
Omnadren 250mg/1ml Jelfa
Oxanabol (Oxandrolone) 10mg 50tabs
Oxanabol, 5mg, C&K
Oxandrolone (Oxandrolone) 5mg
Oxandrolone SPA (Oxandrolone) 2.5mg
Oxydrol 50mg (Oxymetholone) 100 Tabs
Oxydrol 50mg (Oxymetholone)
Oxymetholone (Oxymetholone) 50mg
Primobolan Depot (Methenolone) 1ml
Primoteston Depot 1ml
Propionator 200 (Testosterone Propionate)
Restandol 60 caps (40mg/tab)
Sostenon 250 / Sustanon 250 (4 Testosterones) 250mg/1ml
SustaJect 250
Sustanon 250
Sustanon 250 (4 Testosterones)
Sustanon 250mg/1ml Nile
Sustor 250 (4 Testosterones) 10 ml
Testabol Cypionate
Testabol Depot / testosterone cypionate
Testabol Enanthate 250mg
Testabol Enanthate 250mg/1ml
Testabol Propionate 100 BD
Testex Prolongatum 250mg/2ml Q Pharma, Laboratiries., Spain
TestoJect 10 ml bottle 250 mg/ml
Testole Depot (Testosterone Enanthate)
Testolic (Testosterone Propionate) 100mg/ml, 2ml amps
Testoprop (Testosterone Propionate)
Testosterone (Testosterone Enanthate)
Testosterone Compound (Sustanon)
Testosterone cypionate 10ml
Testosterone Enanthate 250
Testosterone Enanthate 250 Norma
Testosterone Propionate, 50mg/ml , 1ml amp, Farmak
Testosterone suspension / Aqiaviron
Testoviron Depot / Schering
TESTOVIS / testosterone-propionate
Trenabol 75 / Trenbolone Acetate
Tri-Trenabol 150
Turanabol 10mg
Vironate (Testosterone Cypionate)
Virormone 2ml (Testosterone Propionate) 100mg (50mg/1ml)



Cutting Steroids:
Aldactazide 25mg
Anadiol Depot 75mg/ml
Boldabol 10ml 200mg/ml
Boldabol 10ml 200mg/ml
Boldenol 100 10ml Vial/100mg/1ml
Bonavar 2.5mg
BU - Equipoise 200 mg/ml
Cetabon
Danabolan 76mg/1.5ml
Drive (Boldenone undecylenate) 25mg/ml, 10ml vial
Equilon 100mg/1ml
Equipoise 50mg/1ml
ILIUM Stanabolic 50mg/ml 20ml
Lasix 40mg
Mastabol 100 / 100mg/ml
Mastabol Depot 200 / 200 mg/ml
Masteron 100 / 100mg/1ml
Parabolan / trenbolone acetate, 25mg
Primobol 50mg
Primobol-100 10ml
Primobolan Depot (Methenolone) 1ml
Primobol-100 (Methenolone Enanthate) 10ml
Primoject 10ml vial contains 1000mg
Protabol (methandriol dipropionate) 75mg/ml, 10ml vial
Stanabol 10mg (Stanozolol) BD
Stanabol 10mg (Stanozolol) BD
Stanabol 50injectable (Stanozolol) BD
Stanabol 50mg (Stanozolol) BD
Stanabol 50mg (Stanozolol) C&K
Stanabol 5mg (Stanozolol)
Stanazol (Stanozolol) 50mg/ml, 20ml vial
Stanoject (Stanozolol) 10 ml, 50mg/ml
STANOL (stanozolol) 5 mg 200tab
Stanol 50mg/1ml (stanozolol)
STANOZOLOL (Winstrol) 1ml x 50mg/ml
Stanozolol 10mg 100Tabs
STANOZOLOL 50mg/ml (ILIUM)
Testolic (Testosterone Propionate) 100mg/ml, 2ml amps
TESTOPIN-100 2ml (testosterone propinoate)
Trenabol 200 (Trenbolone Enanthate) 10ml
Trenabol 75 (Trenbolone Acetate) 10ml
Trenabol depot 100mg/1ml, 10ml
Trenbola 100 (Trenbolone Acetate) 10ml
Trenbolone Acetate 25 mg
Trenbolone Depot (Trenbolone Enanthate) 10ml
Tri-Trenbola (Testosterone Mix) 10ml
Turanabol (Chlorodehydromethyltestosterone)
Virormone 2ml (Testosterone Propionate)
Voltaren 75 Diclofenac sodium
Winstrol (Stanozolol) 20mg 50tabs
Winstrol Depot (stanozolol) 50mg



Man's Health:
Apcalis (Tadalafil) 20mg
Caverject 10mcg
Caverject 20mcg
Caverject 20mcg
Cialis (Eli Lilly) 20mg Qty. 4
Cialis 25 mg
Kamagra Gold 100mg Sildenafil Citrate
Kamagra Jelly 100mg Sildenafil Citrate Oral Jelly
Propecia 1mg (Finasteride)
Viagra
Viagra 100mg (Sildenafil Citrate) 4 Tabs/100mg



HCG / HGH / Human Hormones:
Choriomon 5000 IU
Chorionic Gonadotropin 10 x 2000 IU
Chorionic Gonadotropin 10 x 5000 IU
EPIAO 10000IU/1ml
EPIAO 2000IU/1ml
Humatrope Somatropin 60IU Package (4 Vials x 15 IU)
Humulin (100iu per 1ml / 3ml Vial)
IGF1 Long R3 100mcg per Vial
Jintropin 10IU(100IU/box)
Jintropin 4IU(40IU/box)
Jintropin™ AQ 30iu (150iu/kit)
Jintropin™ AQ 30iu (300iu/kit)
Norditropin (HGH) 4iu (1.3mg) + Solvent
Pregnyl 5000 IU
Pregnyl 15'000 IU
Riptropin 10iu vial - (100ui kit)
Somatropin 8IU, (80IU per kit), 10 vials
SymbioTropin Pro hgh 40 tabs



Anti Estrogens:
Anastrozole 1mg
Anastrozole / Altraz 1mg
Arimidex / Anastrozole 1mg
Aromasin 20mg / Exemestane Tablets
Aromasin 25 mg / Pfizer
Aromasin 25 mg / Pharmacy & UpJohn
Capoten / Captopril 60 tabs 25mg
Cialis, 20mg, Tadalafil
Cialis, 20mg, Tadalafil, (bottle type)
Cialis, 25mg C&K
Clenbuterol 40mcg 100 Tabs
Clenbuterol / Hubei Huangshi
Clenbuterol / Hydrochloride 20mcg
Clenbuterol / Hydrochloride 0,02 mg
Clomid (Clomiphene Citrate) 50mg
Clomid 50mg Clomiphene citrate
Clomid 50mg, Aventis
Clomid 50mg, Brunno Farmaceutici
Clomifen 25 mg
Clomiphene (Clomiphene Citrate) 50mg
Clomiphene 50mg Clomifene citrate
Clomiphene Citrate 12 Tabs/50mg
Clomiphene citrate 50mg
Clostilbegyt (Clomiphene) 50mg
Eltroxin (T4) (Thyroxin Sodium) 100mcg 1000tabs
Euthyrox 100 (Levothyroxine Sodium/T4)100mg
Euthyrox 50 (Levothyroxine Sodium / T4) 100 tabs/50mg
GP Letrozole (20 tabs 2.5 mg/tab)
Legalon 70 (70mg Thistle Milk Fruit Extract)
Liv-52 (100 Tabs per bottle)
Mesterolone BD (Proviron)
Nolvadex (Tamoxifene) 10mg
Nolvadex 10mg
Nolvadex, 20mg, AstraZeneca
Nolvadex, 40mg, AstraZeneca
Nolvadex, 50mg
Omifin 50 mg
Ovinum (Clomiphene Citrate) 50mg
Proviron (Mesterolone) 25mg
Proviron (Mesterolone) 50mg
Proviron 25mg Mesterolone
Provironum (Mesterolone) 25mg / 150 Tabs
Provironum 25 mg / (Mesterolone)
Spiropent (Clenbuterol) 100 Tabs/20mcg (Clenbuteroli Hydrochloridum)
Tamoxifen (Tamoxifeni Dihydrogenocitras) 10mg/100 Tabs
Teslac (Testolactone) 50mg / 100 tabs
Tiratricol (T3) 50 x 1mg tablets
Xenical (Orlistat) 84 x 120mg capsules



Anti Depressants:
Rivotril (CLONAZEPAM) 2 mg
Rivotril (Clonazepam) 2mg 60tabs
Rohypnol (Flunitrazepam) 1mg
Valium (Diazepam) 10mg 50tabs
Valium (DIAZEPAM) 5mg 60tabs



Head Ache:
Maxalt (Rizatripan) 10 mg
Relpax 40mg
Zomigon (Zolmitriptane) 2.5mg



Herpes:
Famvir (Famciclovir) 125 mg
Viranet / Valtrex (Valacyclovir) 500mg
Zovirax, 5%, 15 gm Tube (Acyclovir)



Muscle Relaxers:
Baclofen 25mg
Muscoril Caps 20 x 4 mg
Norgesic generic (Nuberol) (Orphenadrine)



Pain Releaf:
Advil (Ibuprofen) 200mg
Celebrex 200mg 120caps
Celebrex 200mg 20caps
Mesulid (Nimesulide) 100mg
Movatec (Meloxicam) 15mg
Naprosyn 500mg
Oruvail (Ketoprofen) 200mg
Vioxx 25mg



Quit Smoking:
Zyban (bupropion) 150 mg



Skin Care:



Weight Loss:
Cytomel / T3 (liothyronine sodium) 50mcg / 100 Tabs
Cytomel / T3 / Cynomel / Liothyronine Sodium
Cytomel / T4 50 mg (levothyroxine sodium)
DNP (2,4-Dinitrophenol) 100 mg Capsules
Helios - Clenbuterol & Yohimbine HCL blend
Phentermine (blue/clear) 30mg. 100 Caps
Reductil 15mg Sibutramine Hydrochloride
T3 Cytomel (Liothyronine Sodium) 100mcg / 100 Tabs
Thiomucase cream (mucopolisacaridasa) 100 mg/Tube
TRIACANA 0.35 mcg (3,5,3´-triiodothyroacetic acid - Tiratricol)
Xenical 120mg



Genital Warts:
Aldara cream 5% (Imiquimod)
Wartek (Podophyllotoxin) cream 5 gr x 0,15%



Anti-hair loss:
Harifin 5 (Finasteride) 5mg
Propecia (Finasteride) 1mg
Proscar (Finasteride) 5mg / 15 Tabs



Stimulants:
Efedrina Level 25mg (Efedrina Clorhidrato)
Nucofed (Ephedrine)



 
Menu



Aromasin / Pharmacy & UpJohn

Aromasin / Pharmacy & UpJohn

Name Manufacturer Volume Price $ Price Quantity
Aromasin 25 mg / PfizerPfizer30 tabs $80.00  €71.00 

 

AROMASIN®(exemestane) Tablets

Aromasin / Pharmacy & UpJohn

DESCRIPTION:

AROMASIN® Tablets for oral administration contain 25 mg of exemestane, an irreversible, steroidal aromatase inactivator. Exemestane is chemically described as 6-methylenandrosta-1,4-diene-3,17 -dione. Its molecular formula is C20H2402and its structural formula is as follows:


the active ingredient is a white to slightly yellow crystalline powder with a molecular weight of 296.41. Exemestane is freely soluble in N, N-dimethylformamide, soluble in methanol, and practically insoluble in water.

Each AROMASIN Tablet contains the following inactive ingredients: mannitol, crospovidone, polysorbate 80, hydroxypropyl methylcellulose, colloidal silicon dioxide, microcrystalline cellulose, sodium starch glycolate, magnesium stearate, simethicone, polyethylene glycol 6000, sucrose, magnesium carbonate, titanium dioxide, methylparaben, and polyvinyl alcohol.

CLINICAL PHARMACOLOGY


Mechanism of Action

Breast cancer cell growth may be estrogen-dependent. Aromatase(exemestane) is the principal enzyme that converts androgens to estrogens both in pre- and postmenopausal women. While the main source of estrogen (primarily estradiol) is the ovary in premenopausal women, the principal source of circulating estrogens in postmenopausal women is from conversion of adrenal and ovarian androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) by the aromatase enzyme in peripheral tissues. Estrogen deprivation through aromatase inhibition is an effective and selective treatment for some postmenopausal patients with hormone-dependent breast cancer.

Exemestane is an irreversible, steroidal aromatase inactivator, structurally related to the natural substrate androstenedione. It acts as a false substrate for the aromatase enzyme, and is processed to an intermediate that binds irreversibly to the active site of the enzyme causing its inactivation, an effect also known as “suicide inhibition.” Exemestane significantly lowers circulating estrogen concentrations in postmenopausal women, but has no detectable effect on adrenal biosynthesis of corticosteroids or aldosterone. Exemestane has no effect on other enzymes involved in the steroidogenic pathway up to a concentration at least 600 times higher than that inhibiting the aromatase enzyme.

Aromasin / Pharmacy & UpJohn

Pharmacokinetics

Following oral administration to healthy postmenopausal women, exemestane is rapidly absorbed. After maximum plasma concentration is reached, levels decline polyexponentially with a mean terminal half-life of about 24 hours. Exemestane is extensively distributed and is cleared from the systemic circulation primarily by metabolism. the pharmacokinetics of exemestane are dose proportional after single (10 to 200 mg) or repeated oral doses (0.5 to 50 mg). Following repeated daily doses of exemestane 25 mg, plasma concentrations of unchanged drug are similar to levels measured after a single dose.

Pharmacokinetic parameters in postmenopausal women with advanced breast cancer following single or repeated doses have been compared with those in healthy, postmenopausal women. Exemestane appeared to be more rapidly absorbed in the women with breast cancer than in the healthy women, with a mean tmaxof 1.2 hours in the women with breast cancer and 2.9 hours in the healthy women. After repeated dosing, the average oral clearance in women with advanced breast cancer was 45% lower than the oral clearance in healthy postmenopausal women, with corresponding higher systemic exposure. Mean AUC values following repeated doses in women with breast cancer (75.4 ng®h/mL) were about twice those in healthy women

(41.4 ng®h/mL).

Absorption: Following oral administration of radiolabeled exemestane, at least 42% of radioactivity was absorbed from the gastrointestinal tract. Exemestane plasma levels increased by approximately 40% after a high-fat breakfast. Distribution:Exemestane is distributed extensively into tissues. Exemestane is 90% bound to plasma proteins and the fraction bound is independent of the total concentration. Albumin and a1-acid glycoprotein both contribute to the binding. the distribution of exemestane and its metabolites into blood cells is negligible.

Metabolism and Excretion:Following administration of radiolabeled exemestane to healthy postmenopausal women, the cumulative amounts of radioactivity excreted in urine and feces were similar (42 – 3% in urine and 42 – 6% in feces over a 1-week collection period). the amount of drug excreted unchanged in urine was less than 1% of the dose.

Exemestane is extensively metabolized, with levels of the unchanged drug in plasma accounting for less than 10% of the total radioactivity. the initial steps in the metabolism of exemestane are oxidation of the methylene group in position 6 and reduction of the 17-keto group with subsequent formation of many secondary metabolites. Each metabolite accounts only for a limited amount of drug-related material. the metabolites are inactive or inhibit aromatase with decreased potency compared with the parent drug. One metabolite may have androgenic activity (see Pharmacodynamics, Other Endocrine Effects). Studies using human liver preparations indicate that cytochrome P-450 3A4 (CYP 3A4) is the principal isoenzyme involved in the oxidation of exemestane.


Special Populations

Geriatric: Healthy postmenopausal women aged 43 to 68 years were studied in the pharmacokinetic trials. Age-related alterations in exemestane pharmacokinetics were not seen over this age range. Gender:the pharmacokinetics of exemestane following administration of a single, 25-mg tablet to fasted healthy males (mean age 32 years) were similar to the pharmacokinetics of exemestane in fasted healthy postmenopausal women (mean age 55 years). Race:the influence of race on exemestane pharmacokinetics has not been evaluated. Hepatic Insufficiency: the pharmacokinetics of exemestane have been investigated in subjects with moderate or severe hepatic insufficiency (Childs-Pugh strong or C). Following a single 25-mg oral dose, the AUC of exemestane was approximately 3 times higher than that observed in healthy volunteers. (See Precautions) Renal Insufficiency:the AUC of exemestane after a single 25-mg dose was approximately 3 times higher in subjects with moderate or severe renal insufficiency (creatinine clearance <35 mL/min/1.73 m2) compared with the AUC in healthy volunteers (see Precautions). Pediatric:the pharmacokinetics of exemestane have not been studied in pediatric patients.


Drug-Drug Interactions

Exemestane is metabolized by cytochrome P-450 3A4 (CYP 3A4) and aldoketoreductases. It does not inhibit any of the major CYP isoenzymes, including CYP 1A2, 2C9, 2D6, 2E1, and 3A4. In a clinical pharmacokinetic study, ketoconazole showed no significant influence on the pharmacokinetics of exemestane. Although no other formal drug-drug interaction studies have been conducted, significant effects on exemestane clearance by CYP isoenzymes inhibitors appear unlikely. However, a possible decrease of exemestane plasma levels by known inducers of CYP 3A4 cannot be excluded.


Pharmacodynamics

Effect on Estrogens:Multiple doses of exemestane ranging from 0.5 to 600 mg/day were administered to postmenopausal women with advanced breast cancer. Plasma estrogen (estradiol, estrone, and estrone sulfate) suppression was seen starting at a 5-mg daily dose of exemestane, with a maximum suppression of at least 85% to 95% achieved at a 25-mg dose. Exemestane 25 mg daily reduced whole body aromatization (as measured by injecting radiolabeled androstenedione) by 98% in postmenopausal women with breast cancer. After a single dose of exemestane 25 mg, the maximal suppression of circulating estrogens occurred 2 to 3 days after dosing and persisted for 4 to 5 days. Effect on Corticosteroids:In multiple-dose trials of doses up to 200 mg daily, exemestane selectivity was assessed by examining its effect on adrenal steroids. Exemestane did not affect cortisol or aldosterone secretion at baseline or in response to ACth at any dose. thus, no glucocorticoid or mineralocorticoid replacement therapy is necessary with exemestane treatment. Other Endocrine Effects:Exemestane does not bind significantly to steroidal receptors, except for a slight affinity for the androgen receptor (0.28% relative to dihydrotestosterone). the binding affinity of its 17-dihydrometabolite for the androgen receptor, however, is 100-times that of the parent compound. Daily doses of exemestane up to 25 mg had no significant effect on circulating levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, or 17-hydroxy-progesterone. Increases in testosterone and androstenedione levels have been observed at daily doses of 200 mg or more. A dose-dependent decrease in sex hormone binding globulin (SHBG) has been observed with daily exemestane doses of 2.5 mg or higher. Slight, nondose-dependent increases in serum lutenizing hormone (LH) and follicle-stimulating hormone (FSH) levels have been observed even at low doses as a consequence of feedback at the pituitary level.


CLINICAL STUDIES

Exemestane 25 mg administered once daily was evaluated in a randomized double-blind, multicenter, multinational comparative study and in two multicenter single-arm studies of postmenopausal women with advanced breast cancer who had disease progression after treatment with tamoxifen for metastatic disease or as adjuvant therapy. Some patients also have received prior cytotoxic therapy, either as adjuvant treatment or for metastatic disease.

the primary purpose of the three studies was evaluation of objective response rate (complete response [CR] and partial response [PR]). Time to tumor progression and overall survival were also assessed in the comparative trial. Response rates were assessed based on World Health Organization (WHO) criteria, and in the comparative study, were submitted to an external review committee that was blinded to patient treatment. In the comparative study, 769 patients were randomized to receive AROMASIN (exemestane) 25 mg once daily (N=366) or megestrol acetate 40 mg four times daily (N=403). Demographics and baseline characteristics are presented in Table1.

Table 1. Demographics and Baseline Characteristics from the Comparative Study of Postmenopausal Women with Advanced Breast Cancer Whose Disease Had Progressed after Tamoxifen therapy

Parameter AROMASIN Megestrol Acetate
(N=366) (N=403)
Median Age (range) 65 (35-89) 65 (30-91)
ECOG Performance Status
0 167 (46%) 187 (46%)
1 162 (44%) 172 (43%)
2 34 (9%) 42 (10%)
Receptor Status
ER and/or PgR + 246 (67%) 274 (68%)
ER and PgR unknown 116 (32%) 128 (32%)
Responders to prior tamoxifen 68 (19%) 85 (21%)
NE for response to prior tamoxifen 46 (13%) 41 (10%)
Site of Metastasis
Visceral – other sites 207 (57%) 239 (59%)
Bone only 61 (17%) 73 (18%)
Soft tissue only 54 (15%) 51 (13%)
Bone & soft tissue 43 (12%) 38 (9%)
Measurable Disease 287 (78%) 314 (78%)
Prior Tamoxifen therapy
Adjuvant or Neoadjuvant 145 (40%) 152 (38%)
Advanced Disease, Outcome
CR, PR or SD> 6 months SD<6 months, PD or NE 179 (49%) 42 (12%) 210 (52%) 41 (10%)
Prior Chemotherapy
For advanced disease – adjuvant 58 (16%) 67 (17%)
Adjuvant only 104 (28%) 108 (27%)
No chemotherapy 203 (56%) 226 (56%)

the efficacy results from the comparative study are shown in Table 2. the objective response rates observed in the two treatment arms showed that AROMASIN(exemestane) was not different from megestrol acetate. Response rates for exemestane from the two single-arm trials were 23.4% and 28.1%.

Table 2. Efficacy Results from the Comparative Study of Postmenopausal Women with Advanced Breast Cancer Whose Disease Had Progressed after Tamoxifentherapy

AROMASIN Megestrol
Response Characteristics (N=366) acetate (N=403)
Objective Response Rate=CR + PR (%) 15.0 12.4
Difference in Response Rate (AR-MA) 2.6
95% C. I. 7.5, -2.3
CR (%) 2.2 1.2
PR (%) 12.8 11.2
SD ‡ 24 Weeks (%) 21.3 21.1
Median Duration of Response (weeks) 76.1 71.0
Median TTP (weeks) 20.3 16.6
Hazard Ratio (AR-MA) 0.84

Abbreviations: CR=complete response, PR=partial response, SD=stable disease (no change), TTP=time to tumor progression, , C.I.=confidence interval. MA=megestrol acetate, AR=AROMASIN

there were too few deaths occurring across treatment groups to draw conclusions on overall survival differences. the Kaplan-Meier curve for time to tumor progression in the comparative study is shown in Figure 1.

CONTRAINDICATIONS

AROMASIN(exemestane) Tablets are contraindicated in patients with a known hypersensitivity to the drug or to any of the excipients.


WARNINGS

AROMASIN(exemestane) Tablets may cause fetal harm when administered to a pregnant woman. Radioactivity related to 14C-exemestane crossed the placenta of rats following oral administration of 1 mg/kg exemestane. the concentration of exemestane and its metabolites was approximately equivalent in maternal and fetal blood. When rats were administered exemestane from 14 days prior to mating until either days 15 or 20 of gestation, and resuming for the 21 days of lactation, an increase in placental weight was seen at 4 mg/kg/d (approximately 1.5 times the recommended human daily dose on a mg/m2basis). Prolonged gestation and abnormal or difficult labor was observed at doses equal to or greater than 20 mg/kg/d. Increased resorption, reduced number of live fetuses, decreased fetal weight, and retarded ossification were also observed at these doses. No malformations were noted when exemestane was administered to pregnant rats during the organogenesis period at doses up to 810 mg/kg/day (approximately 320 times the recommended human dose on a mg/m2basis). Daily doses of exemestane, given to rabbits during organogenesis caused a decrease in placental weight at 90 mg/kg/day (approximately 70 times the recommended human daily dose on a mg/m2basis). Abortions, an increase in resorptions, and a reduction in fetal body weight were seen at 270 mg/kg/day. there was no increase in the incidence of malformations in rabbits at doses up to 270 mg/kg/day (approximately 210 times the recommended human dose on a mg/m2basis).

there are no studies in pregnant women using AROMASIN. AROMASIN is indicated for postmenopausal women. If there is exposure to AROMASIN during pregnancy, the patient should be apprised of the potential hazard to the fetus and potential risk for loss of the pregnancy.


PRECAUTIONS

General.AROMASIN(exemestane) Tablets should not be administered to premenopausal women. AROMASIN should not be coadministered with estrogen-containing agents as these could interfere with its pharmacologic action.

Hepatic Insufficiency. the pharmacokinetics of exemestane have been investigated in subjects with moderate or severe hepatic insufficiency (Childs-Pugh strong or C). Following a single 25-mg oral dose, the AUC of exemestane was approximately 3 times higher than that observed in healthy volunteers. the safety of chronic dosing in patients with moderate or severe hepatic impairment has not been studied. Based on experience with exemestane at repeated doses up to 200 mg daily that demonstrated a moderate increase in non-life threatening adverse events, dosage adjustment does not appear to be necessary.

Renal Insufficiency.the AUC of exemestane after a single 25-mg dose was approximately 3 times higher in subjects with moderate or severe renal insufficiency (creatinine clearance <35 mL/min/1.73 m2) compared with the AUC in healthy volunteers. the safety of chronic dosing in patients with moderate or severe renal impairment has not been studied. Based on experience with exemestane at repeated doses up to 200 mg daily that demonstrated a moderate increase in non-life threatening adverse events, dosage adjustment does not appear to be necessary.

Laboratory Tests.Approximately 20% of patients receiving exemestane in clinical studies,experienced Common Toxicity Criteria (CTC) grade 3 or 4 lymphocytopenia. Of these patients, 89% had a pre-exisiting lower grade lymphopenia. Forty percent of patients either recovered or improved to a lesser severity while on treatment. Patients did not have a significant increase in viral infections, and no opportunistic infections were observed. Elevations of serum levels of AST, ALT, alkaline phosphatase and gamma glutamyl transferase> 5 times the upper value of the normal range (i.e., ‡ CTC grade 3) have been rarely reported but appear mostly attributable to the underlying presence of liver and/or bone metastases. In the comparative study, CTC grade 3 or 4 elevation of gamma glutamyl transferase without documented evidence of liver metastasis was reported in 2.7% of patients treated with AROMASIN(exemestane) and in 1.8% of patients treated with megestrol acetate.

Drug Interactions.Exemestane is extensively metabolized by CYP3A4, but coadministration of ketoconazole, a potent inhibitor of CYP 3A4, has no significant effect on exemestane pharmacokinetics. Significant pharmacokinetic interactions mediated by inhibition of CYP isoenzymes therefore appear unlikely; however, a possible decrease of exemestane plasma levels by known inducers of CYP 3A4 cannot be excluded (see CLINICAL PHARMACOLOGY, Pharmacokinetics).

Drug/ Laboratory Tests Interactions.No clinically relevant changes in the results of clinical laboratory tests have been observed.

Carcinogenesis, Mutagenesis, Impairment of Fertility.Carcinogenicity studies have not been conducted with exemestane. Exemestane was not mutagenic in bacteria (Ames test) or mammalian cells (V79 Chinese hamster lung cells). Exemestane was clastogenic in human lymphocytes in vitro without metabolic activation but was not clastogenic in vivo (micronucleus assay in mouse bone marrow). Exemestane did not increase unscheduled DNA synthesis in rat hepatocytes.

Untreated female rats showed reduced fertility when mated to males treated with 500 mg/kg/day exemestane (approximately 200 times the recommended human dose on a mg/m2basis) for 63 days prior to and during cohabitation. Exemestane given to female rats 14 days prior to mating and through day 15 or 20 of gestation increased the placental weights at 4 mg/kg/day (approximately 1.5 times the human dose on a mg/m2basis). Exemestane showed no effects on female fertility parameters (e.g., ovarian function, mating behavior, conception rate) in rats given doses up to 20 mg/kg/day (approximately 8 times the human dose on a mg/m2basis), but mean litter size was decreased at this dose. In general toxicology studies, changes in the ovary, including hyperplasia, an increase in ovarian cysts and a decrease in corpora lutea were observed with variable frequency in mice, rats and dogs at doses that ranged from 3-20 times the human dose on a mg/m2basis.

Pregnancy.Pregnancy Category D. See WARNINGS.

Nursing Mothers.AROMASIN(exemestane) is only indicated in postmenopausal women. However, radioactivity related to exemestane appeared in rat milk within 15 minutes of oral administration of radiolabeled exemestane. Concentrations of exemestane and its metabolites were approximately equivalent in the milk and plasma of rats for 24 hours after a single oral dose of 1 mg/kg 14C-exemestane. It is not known whether exemestane is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if a nursing woman is inadvertently exposed to AROMASIN (see WARNINGS).

Pediatric Use. the safety and effectiveness of AROMASIN(exemestane) in pediatric patients have not been established.

Geriatric Use.the use of AROMASIN(exemestane) in geriatric patients does not require special precautions.


ADVERSE REACTIONS

A total of 1058 patients were treated with exemestane 25 mg once daily in the clinical trials program. Exemestane was generally well tolerated, and adverse events were usually mild to moderate. Only one death was considered possibly related to treatment with exemestane; an 80-year-old women with known coronary artery disease had a myocardial infarction with multiple organ failure after 9 weeks on study treatment. In the clinical trials program, only 3% of the patients discontinued treatment with exemestane because of adverse events, mainly within the first 10 weeks of treatment; late discontinuations because of adverse events were uncommon (0.3%).

In the comparative study, adverse reactions were assessed for 358 patients treated with AROMASIN(exemestane) and 400 patients treated with megestrol acetate. Fewer patients receiving AROMASIN discontinued treatment because of adverse events than those treated with megestrol acetate (2% versus 5%). Adverse events that were considered drug related or of indeterminate cause included hot flashes (13% vs. 5%), nausea (9% vs. 5%), fatigue (8% vs. 10%), increased sweating (4% vs. 8%), and increased appetite (3% vs. 6%). the proportion of patients experiencing an excessive weight gain (>10% of their baseline weight) was significantly higher with megestrol acetate than with AROMASIN (17% versus 8%). Table 3 shows the adverse events of all CTC grades, regardless of causality, reported in 5% or greater of patients in the study treated either with AROMASIN or megestrol acetate.

Table 3. Incidence (%) of Adverse Events of all Grades * and Causes Occurring in 5% of Patients In Each Treatment Arm in the Comparative Study

AROMASIN Megestrol 25 mg Acetate Event once daily 40 mg QID (N=358) (N=400)


Autonomic Nervous

Increased sweating 6 9

Body as a Whole

Fatigue 22 29 Hot flashes 13 6 Pain 13 13 Influenza-like symptoms 6 5 Edema (includes edema, peripheral edema, leg edema) 7 6


Cardiovascular

Hypertension 5 6


Nervous

Depression 13 9 Insomnia 11 9 Anxiety 10 11 Dizziness 8 6 Headache 8 7

Gastrointestinal

Nausea Vomiting Abdominal pain Anorexia Constipation Diarrhea Increased appetite

18

7

6

6

5

4

3 12 4 11 5 8 5 6


Respiratory

Dyspnea 10 15 Coughing 6 7

• Graded according to Common Toxicity Criteria

Less frequent adverse events of any cause (from 2% to 5%) reported in the comparative study for patients receiving AROMASIN(exemestane) 25 mg once daily were fever, generalized weakness, paresthesia, pathological fracture; bronchitis, sinusitis, rash, itching, urinary tract infection, and lymphedema.

Additional adverse events of any cause observed in the overall clinical trials program (N=1058) in 5% or greater of patients treated with exemestane 25 mg once daily but not in the comparative study included pain at tumor sites (8%), asthenia (6%) and fever (5%). Adverse events of any cause reported in 2% to 5% of all patients treated with exemestane 25 mg in the overall clinical trials program but not in the comparative study included chest pain, hypoesthesia, confusion, dyspepsia, arthralgia, back pain, skeletal pain, infection, upper respiratory tract infection, pharyngitis, rhinitis, and alopecia.


OVERDOSAGE

Clinical trials have been conducted with exemestane given as a single dose to healthy female volunteers at doses as high as 800 mg and daily for 12 weeks to postmenopausal women with advanced breast cancer at doses as high as 600 mg. these dosages were well tolerated. there is no specific antidote to overdosage and treatment must be symptomatic. General supportive care, including frequent monitoring of vital signs and close observation of the patient, is indicated.

A male child (age unknown) accidentally ingested a 25-mg tablet of exemestane. the initial physical examination was normal, but blood tests performed 1 hour after ingestion indicated leucocytosis (WBC 25000/mm3with 90% neutrophils). Blood tests were repeated 4 days after the incident and were normal. No treatment was given.

In mice, mortality was observed after a single oral dose of exemestane of 3200 mg/kg, the lowest dose tested (about 640 times the recommended human dose on a mg/m2basis). In rats and dogs, mortality was observed after single oral doses of exemestane of 5000 mg/kg (about 2000 times the recommended human dose on a mg/m2basis) and of 3000 mg/kg (about 4000 times the recomme nded human dose on a mg/m2basis), respectively.

Convulsions were observed after single doses of exemestane of 400 mg/kg and 3000 mg/kg in mice and dogs (approximately 80 and 4000 times the recommended human dose on a mg/m2basis), respectively.


DOSAGE AND ADMINISTRATION

the recommended dose of AROMASIN(exemestane) Tablets is 25 mg once daily after a meal. Treatment with AROMASIN should continue until tumor progression is evident.

the safety of chronic dosing in patients with moderate or severe hepatic or renal impairment has not been studied. Based on experience with exemestane at repeated doses up to 200 mg daily that demonstrated a moderate increase in non-life threatening adverse events, dosage adjustment does not appear to be necessary (see CLINICAL PHARMACOLOGY, Special Populations and PRECAUTIONS).


HOW SUPPLIED

AROMASIN(exemestane) Tablets are round, biconvex, and off-white to slightly gray. Each tablet contains 25 mg of exemestane. the tablets are printed on one side with the number “7663” in black. AROMASIN is packaged in either HDPE bottles with a child-resistant screw cap, supplied in packs of 30 tablets, or in Aluminium-PVDC/PVC-PVDC opaque white blisters, supplied in packs of 30 tablets.








Popular Steroids:
Jintropin 10IU(100IU/box)
Jintropin 4IU(40IU/box)
Jintropin™ AQ 30iu (150iu/kit)
Jintropin™ AQ 30iu (300iu/kit)

Anadrol (oxymetholone)
Durabol 100, Nandrolone Phenylpropionate
Anavar (oxandrolone)
Andriol (testosterone undecanoate)
Androgel (testosterone)
Arimidex(anastrozole)
Aromasin (exemestane)
Clenbuterol
Clomid (clomiphene citrate)
Cytomel (liothyronine sodium)
Deca Durabolin (nandrolone decanoate)
Deca
Anabol/Dianabol(Methandrostenolone)
Anabol 50mg (Methandrostenolone)
Averbol 25 (Injectable Dianabol)
Ephedrine Level 25mg
Nucofed (Ephedrine)
Equipoise (Boldenone Undecylenate)
GP Letrozole (Letrozole)
Trenabol 75 (Trenbolone Acetate)
Halotestin (fluoxymesterone)
Human Chorionic Gonadotropin 5000IU
Somatropin 8IU
Humulin (Insulin Lispro)
Masteron 100 (Drostanolon Propionate)
Nolvadex 40mg (tamoxifen citrate)
Omnadren 250
Primobol (Methenolone Acetate) 50mg
Primoteston Depot
Cypioject (Testosterone cypionate)
Sustanon 250
Teslac (testolactone)
Testosterone Enanthate 250
Testosterone Cypionate
Testosterone Propionate
Testosterone Suspension
Trenbolone Depot (Trenbolone Enanthate)
Testolic (Testosterone Propionate) 100mg/ml, 2ml amps
Winstrol (Stanozolol)
Winstrol Depot (stanozolol) 50mg
Viagra
Cialis
IGF 1
Propecia













Home | F.A.Q. | Terms & Conditions | Contact us
 
© 2005-2017 pharmaeurope.net
 

www.pharmaeu.net    PharmaEurope.org    PharmaEurope.net    www.BulkPharmaEurope.com    BulkPharmaEurope.net    BulkPharma.net