Description
Exemestane 250
Strength: 25 mg
Molecular Formula: C20H2402
Molecular Weight: 296.41 g/mol
Active Ingredient: Exemestane
CAS number: 107868-30-4
Dosage Form: Tablet
Route: Oral
Market Status: Prescription
Company: Hilma Biocare
DESCRIPTION
Exemestane is a synthetic androgen analogue. It is a steroidal inhibitor of aromatase which
binds irreversibly to and inhibits the enzyme aromatase, thereby blocking the conversion of
cholesterol to pregnenolone and the peripheral aromatization of androgen precursors into
estrogens. Exemestane has been associated with a low rate of serum enzyme elevations
during therapy and rare instances of clinically apparent liver injury. This medication is used
to treat certain types of breast cancer (such as hormone-receptor-positive breast cancer) in
women after menopause. Exemestane is also used to help prevent the cancer from
returning. Some breast cancers are made to grow faster by a natural hormone called
estrogen. Exemestane decreases the amount of estrogen the body makes and helps to slow
or reverse the growth of these breast cancers. Exemestane is usually not used in women of
childbearing age. Exemestane is usually taken once a day after a meal. Take Exemestane at
around the same time every day. You may need to take Exemestane for several years or
longer. Continue to take Exemestane even if you feel well. Do not stop taking Exemestane
without talking to your doctor.
PHARMACODYNAMICS
Effect On Estrogens Plasma estrogen (estradiol, estrone, and estrone sulfate) suppression
is 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 reduces 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 17dihydrometabolite 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 androstenedione,
dehydroepiandrosterone sulfate, or 17- hydroxyprogesterone, and were associated with
small decreases in circulating levels of testosterone. 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, non dose-dependent increases in serum
luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels have been observed
even at low doses as a consequence of feedback at the pituitary level. Exemestane 25 mg
daily had no significant effect on thyroid function [free triiodothyronine (FT3), free thyroxine
(FT4), and thyroid stimulating hormone (TSH). Absorption 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 a11-acid glycoprotein both
contribute to the binding. The distribution of Exemestane and its metabolites into blood cells
is negligible. Metabolism Exemestane is extensively metabolized. 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]. Studies using human
liver preparations indicate that cytochrome P 450 3A4 (CYP 3A4) is the principal isoenzyme
involved in the oxidation of Exemestane. Exemestane is metabolized also by aldo keto
reductases.
CONTRAINDICATIONS
Exemestane is contraindicated in patients with a known hypersensitivity to the drug or to any
of the excipients.
PRECAUTIONS
Reductions in bone mineral density (BMD) over time are seen with Exemestane use.
Concomitant use of bisphosphonates, vitamin D supplementation, and calcium was not
allowed. It is very important that your doctor check your progress at regular visits to make
sure that this medicine is working properly. Blood tests may be needed to check for
unwanted effects. It is important for women to have regular gynecology check-ups while
taking this medicine. It is unlikely that a postmenopausal woman may become pregnant. But,
you should know that using this medicine while you are pregnant could harm your unborn
baby. If you are a woman who can bear children, your doctor may give you a pregnancy test
7 days before you start using this medicine to make sure you are not pregnant. Use an
effective form of birth control during treatment and for 1 month after the last dose f you think
you have become pregnant while using this medicine, call your doctor right away. This
medicine may decrease bone mineral density when used for a long time. A low bone mineral
density can cause weak bones or osteoporosis. If you have any questions about this, talk to
your doctor. Do not take this medicine if you are also using medicines that contain estrogen,
birth control pills or patches, or other medicines used for hormone replacement therapy. Do
not take other medicines unless they have been discussed with your doctor. This includes
prescription or nonprescription (over-the-counter) medicines and herbal (eg, St. John’s wort)
or vitamin supplements.
ADVERSE REACTIONS
Most people using this medication do not have serious side effects. Typically observed side
effects in some cases are: hot flashes, hair loss, joint/bone/muscle pain, tiredness, unusual
sweating, nausea, diarrhea, dizziness, and trouble sleeping may occur. If any of these
effects persist or worsen, notify your doctor or pharmacist promptly. Remember that your
doctor has prescribed this medication because he or she has judged that the benefit to you
is greater than the risk of side effects. Tell your doctor right away if you have any serious
side effects, including: bone fractures, mental/mood changes (such as depression, anxiety),
vaginal bleeding. persistent nausea/vomiting, unusual tiredness, dark urine, yellowing
eyes/skin.
DRUG INTERACTION
Exemestane does not inhibit any of the major CYP isoenzymes, including CYP 1A2, 2C9,
2D6, 2E1, and 3A4. In a clinical pharmacokinetic study, coadministration of ketoconazole, a
potent inhibitor of CYP 3A4, has no significant effect on Exemestane pharmacokinetics.
Although no other formal drug-drug interaction studies with inhibitors have been conducted,
significant effects on Exemestane clearance by CYP isoenzyme inhibitors appear unlikely.
Using this medicine with any of the following medicines is usually not recommended, but
may be required in some cases. If both medicines are prescribed together, your doctor may
change the dose or how often you use one or both of the medicines. Be careful using
Exemestane together with Carbamazepine, Enzalutamide, Fosphenytoin, Mitotane,
Phenytoin, Primidone, Rifabutin, St John’s Wort.
DOSAGE
The recommended dose of Exemestane in early and advanced breast cancer is one 25 mg
tablet once daily after a meal. If you miss a dose of this medicine, take it as soon as
possible. However, if it is almost time for your next dose, skip the missed dose and go back
to your regular dosing schedule. Do not double doses.
STORAGE
Store in a cool dry place between 15-25°C. Protect from light.
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