Aromasin, 30 pcs., 25 mg, film-coated tablets
INSTRUCTIONS for use
APPROVED by the FC Ministry of Health of the Russian Federation 03/16/2000, pr. No. 1b
Description.
Round, biconvex tablets, white with a slightly grayish tint, sugar-coated, about 6 mm in diameter, inscribed with the number 7663 in black printing ink on one side.
Compound.
Each tablet contains:
active substance:
exemestane 25 mg;
Excipients:
mannitol, hypromellose, polysorbate 80, crospovidone, silicon dioxide, colloidal, hydrated, MCC, sodium starch glycolic acid, magnesium stearate; shell: hypromellose, simethicone, macrogol 6000, sucrose, magnesium carbonate, titanium dioxide, methyl n-hydroxybenzoate, polyvinyl alcohol.
Pharmacological properties.
Aromasin is an irreversible steroidal aromatase inhibitor, similar in structure to the natural substance androstenedione.
Pharmacodynamics.
In postmenopausal women, estrogens are produced primarily by the conversion of androgens to estrogens by the enzyme aromatase in peripheral tissues. Blocking estrogen production by aromatase inhibition is an effective and selective treatment for hormone-dependent breast cancer in postmenopausal women. The mechanism of action of the drug Aromasin is due to the fact that it irreversibly binds to the active fragment of the enzyme, causing its inactivation. In postmenopausal women, Aromasin significantly reduces the concentration of estrogen in the serum, already starting with a dose of 5 mg; maximum reduction (>90%) is achieved at a dose of 10–25 mg. In postmenopausal patients diagnosed with breast cancer who received 25 mg of the drug daily, the total level of the aromatase enzyme in the body decreased by 98%.
Aromasin does not have progestogenic or estrogenic activity. Only minor androgenic activity is detected, mainly when using high doses. In tests with repeated doses throughout the day, Aromasin had no effect on the biosynthesis of cortisol and aldosterone in the adrenal glands, which confirms the selectivity of the action of this drug.
In this regard, there is no need for replacement therapy with glucocorticoids and mineralocorticoids. Slight increases in serum LH and FSH levels are observed even at low doses; this effect, however, is expected for drugs of this pharmacological group; it probably develops according to the feedback principle at the level of the pituitary gland: a decrease in the concentration of estrogen stimulates the secretion of gonadotropins in the pituitary gland also in postmenopausal women.
Pharmacokinetics.
Suction.
After oral administration, Aromasin is rapidly and extensively absorbed. With a single dose of 25 mg after a meal, the average maximum plasma level of 18 ng/ml is achieved within 2 hours. It has been established that food improves absorption, the plasma level achieved is 40% higher than in patients taking drug on an empty stomach.
Distribution.
After reaching a maximum, the plasma level of Aromasin decreases, with a final T1/2 of approximately 24 hours. Aromasin is widely distributed in tissues, as indicated by a large volume of distribution. The binding of the drug Aromasin to plasma proteins is approximately 90%, and the degree of binding does not depend on the total concentration.
Metabolism and excretion.
After repeated doses of 25 mg/day, plasma concentrations of unchanged drug were similar to those measured after a single dose. After oral administration of a single dose of the radiolabeled drug Aromasin, it was found that the elimination of the drug and its metabolites was largely completed within 1 week, with approximately equal parts of the dose being excreted in the urine and feces. The amount of drug excreted unchanged in the urine is less than 1% of the administered dose. Aromasin is characterized by high clearance, mainly due to metabolism. The biotransformation process is carried out by oxidation of the methylene group at position 6 with the participation of the CYP 3A4 isoenzyme and/or by reduction of the 17-keto group with the participation of aldokereductases. As a result, numerous secondary metabolites are formed, but the amount of each of them is very small compared to the administered dose. With respect to aromatase inhibition, these metabolites are either inactive or less active than the parent compound.
Indications for use.
Aromasin is indicated for the treatment of advanced breast cancer in women in natural or induced postmenopause in whom disease progression has been detected during anti-estrogen therapy.
Aromasin is also indicated as third-line hormonal therapy for advanced breast cancer in women in natural or induced postmenopause whose disease has progressed on anti-estrogen therapy, as well as therapy with either non-steroidal aromatase inhibitors or progestins.
Dosage and method of application.
Adults and elderly patients
are recommended to take Aromasin 25 mg daily, 1 time per day, preferably after meals. Treatment should be continued until signs of tumor progression appear.
In patients with hepatic or renal insufficiency, no dose adjustment is required.
Children.
Not recommended for use in children.
Side effect.
During clinical trials of the drug Aromasin, side effects were observed to be minor or moderate. The most common side effects, both drug-related and unspecified, were hot flushes, nausea, fatigue, sweating, and dizziness. Less frequently observed were headache, insomnia, skin rash, abdominal pain, anorexia, depression, alopecia, peripheral edema (swelling of the feet, legs), constipation or dyspepsia.
Episodes of decreased lymphocyte levels were observed in approximately 20% of patients receiving Aromasin, especially in patients with baseline lymphopenia; however, the average level of lymphocytes did not change significantly in these patients over a fairly long period of time, and there was no concomitant increase in the incidence of viral infections.
Thrombocytopenia and leukopenia have also been detected in rare cases.
Increases in serum liver function tests as well as increases in alkaline phosphatase levels have been reported occasionally. Such an increase in enzyme levels was observed mainly in patients with metastases to the liver and bones, as well as in the presence of other liver lesions. These changes may or may not be related to the drug Aromasin.
Contraindications.
Aromasin is contraindicated in patients with hypersensitivity to the drug or any of the excipients, as well as during pregnancy and while breastfeeding a child.
Interactions with other drugs and other forms of interactions.
Preparations containing estrogens, when used simultaneously with Aromasin, completely neutralize the pharmacological effect of the latter.
To date, there have been no studies of interactions with other drugs. In vitro results
showed that this drug is metabolized by cytochrome P450 (CYP) 3A4 and aldokereductases, and does not inhibit any of the major CYP isoenzymes. During a clinical pharmacokinetic study, it was found that specific inhibition of CYP 3A4 by ketoconazole does not have a significant effect on the pharmacokinetics of Aromasin. However, a possible decrease in the concentration of the drug Aromasin in plasma cannot be excluded under the influence of substances known as inducers of CYP 3A4.
Overdose.
Data on the use of Aromasin in single doses of 600–800 mg indicate good tolerability of these doses. A single dose of Aromasin that can cause life-threatening symptoms has not been established. There are no specific antidotes for overdose; symptomatic treatment should be carried out. General supportive therapy is indicated, as well as regular monitoring of vital functions and careful monitoring.
Special warnings and precautions for use.
Aromasin should not be prescribed to women with premenopausal endocrine status, since the effectiveness and safety of the drug in this group of patients have not been assessed. Therefore, in cases where it is clinically justified, postmenopausal status should be confirmed by determining the levels of LH, FSH and estradiol.
It is unlikely that Aromasin impairs the ability of patients to drive a car or operate moving or precision machinery. However, when using this drug, symptoms such as drowsiness, asthenia and dizziness were observed. Patients should be warned that when these phenomena occur, their physical and/or mental capabilities necessary for work requiring special attention and quick reactions may be impaired.
Release form.
Tablets of 25 mg, sugar-coated, in blister packs of 15 pcs., in a cardboard box 1, 2 or 6 packs.
Storage conditions.
Store at a temperature not exceeding 30 °C, out of the reach of children.
Best before date.
3 years.
Conditions for dispensing from pharmacies.
Dispensed with a doctor's prescription.
Manufacturer.
Pharmacia & Upjohn, Italy.
Aromasin®
In general, Aromasin® is well tolerated; Undesirable effects when using the drug at a dose of 25 mg/day are mostly minor or moderate.
The following are the undesirable reactions, distributed by system-organ classes and frequency: very often (≥1/10), often (≥1/100, but <1/10), infrequently (≥1/1000, but <1/100) , rare (≥ 1/10,000, but < 1/1000).
Metabolic and eating disorders
: often - anorexia.
Gastrointestinal disorders
: very often - abdominal pain, nausea; often - vomiting, diarrhea, constipation, dyspepsia, increased appetite; infrequently - stomach ulcer*.
Mental disorders
: very often - depression, insomnia.
Nervous system disorders
: very often - headache, dizziness; often - anxiety, confusion, carpal tunnel syndrome, paresthesia, hypoesthesia, asthenia; infrequently - neuropathy.
Heart disorders
: often - heart failure; infrequently - myocardial infarction.
Skin and subcutaneous tissue disorders
: very often - increased sweating; often alopecia, rash, itching, dermatitis.
Musculoskeletal and bone disorders
: very often - joint and musculoskeletal pain (including arthralgia, pain in the extremities, back pain, arthritis, myalgia); often - fracture, osteoporosis.
Visual disorders
: often - visual impairment.
Vascular disorders
: very often - increased blood pressure, hot flashes.
Liver and biliary tract disorders
: very often - increased activity of liver enzymes, increased concentration of bilirubin in the blood, increased activity of alkaline phosphatase in the blood.
Respiratory, thoracic and mediastinal disorders
: often - shortness of breath, cough, bronchitis, sinusitis, pharyngitis, rhinitis, chest pain, upper respiratory tract infections.
Renal and urinary tract disorders
: often - urinary tract infections.
Blood and lymphatic system disorders
: often lymphedema.
General and administration site disorders
: very often - pain, increased fatigue; often - peripheral edema, flu-like syndrome, fever, general weakness, infections.
In approximately 20% of patients (especially in patients with initial lymphopenia), a periodic decrease in the number of lymphocytes was observed. However, the mean lymphocyte count in these patients did not change significantly over time, and there was no concomitant increase in the incidence of viral infections.
* most patients had a history of gastric ulcer or were treated with non-steroidal anti-inflammatory drugs.
Post-marketing studies
:
Immune system disorders
: uncommon - hypersensitivity reactions.
Disorders of the liver and biliary tract
: rarely - hepatitis, cholestatic hepatitis.
Skin and subcutaneous tissue disorders
: often - urticaria; rarely - acute generalized exanthematous pustulosis.
Aromasin
Release form, composition and packaging Tablets, sugar-coated, white or white with a grayish tint, round, biconvex, marked “7663” on one side, painted in black. 1 tab. exemestane 25 mg
Excipients: mannitol, hypromellose, polysorbate 80, crospovidone, hydrated colloidal silicon dioxide, microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate.
Sugar shell composition: hypromellose, simethicone emulsion, macrogol 6000, magnesium carbonate, titanium dioxide, methyl p-hydroxybenzoate, polyvinyl alcohol, sucrose.
15 pcs. - blisters (1) - cardboard packs. 15 pcs. - blisters (2) - cardboard packs. 15 pcs. - blisters (6) - cardboard packs.
Clinical and pharmacological group: Antitumor drug. Aromatase inhibitor Pharmacotherapeutic group: Antitumor agent, estrogen synthesis inhibitor Indications - advanced breast cancer in women in natural or induced postmenopause with progression of the disease against the background of anti-estrogen therapy, as well as with progression of the disease after repeated use of various types of hormonal therapy,
- adjuvant therapy for early breast cancer in postmenopausal women with estrogen receptor-positive or unknown receptor status, after completion of 2-3 years of initial adjuvant therapy with tamoxifen, in order to reduce the risk of relapses (distant or regional), as well as contralateral breast cancer glands.
ICD-10 codes ICD-10 code Indication C50 Malignant neoplasm of the breast
Dosage regimen: Prescribed orally. For adults and elderly patients, the recommended dose is 25 mg 1 time / day, preferably after meals.
For early breast cancer, treatment with the drug is recommended to be continued until the total duration of sequential adjuvant hormonal therapy reaches 5 years. Treatment for patients with advanced breast cancer is long-term. If signs of progression of the tumor disease appear or if contralateral breast cancer appears, treatment with Aromasin should be discontinued.
In case of hepatic or renal failure, no dose adjustment is required.
It is not recommended to use the drug in children.
Side effects Undesirable effects when using the drug at a dose of 25 mg/day are minor or moderate.
The following are undesirable reactions, distributed by body system and frequency: very often (>10%), often (>1%, 0.1%, 0.01%, From the digestive system: very often - nausea, often - anorexia, abdominal pain , vomiting, constipation, dyspepsia, diarrhea.
From the central and peripheral nervous system: very often - insomnia, headache, often - depression, dizziness, carpal tunnel syndrome.
From the cardiovascular system: very often - hot flashes.
Dermatological reactions: very often - sweating, often - rash, alopecia.
From the musculoskeletal system: very often - joint and musculoskeletal pain.
Other: very often - increased fatigue, often - pain of unspecified localization, peripheral edema or swelling of the legs.
In approximately 20% of patients (especially in patients with initial lymphopenia), a periodic decrease in the number of lymphocytes was observed. However, the mean lymphocyte count in these patients did not change significantly over time, and there was no concomitant increase in the incidence of viral infections.
Sometimes an increase in the activity of liver enzymes and alkaline phosphatase was observed, mainly in patients with metastases to the liver and bones, as well as in the presence of other liver lesions (it has not been established whether these changes are related to taking the drug or not).
Contraindications for use: premenopausal endocrine status,
- pregnancy,
- lactation period (breastfeeding),
- hypersensitivity to exemestane or to any other component of the drug.
The drug should be used with caution if liver or kidney function is impaired.
Use during pregnancy and lactation Aromasin® is contraindicated for use during pregnancy and lactation.
Use for liver dysfunction In case of liver failure, no dose adjustment is required.
The drug should be used with caution if liver function is impaired.
Use for impaired renal function In case of renal failure, no dose adjustment is required.
The drug should be used with caution if renal function is impaired.
Use in children It is not recommended to use the drug in children. Use in elderly patients For elderly patients, the recommended dose is 25 mg 1 time / day, preferably after meals. Special instructions Aromasin® should not be prescribed to women with premenopausal endocrine status; therefore, in cases where clinically justified, postmenopausal status should be confirmed by determining the levels of LH, FSH and estradiol.
Aromasin® should not be prescribed concomitantly with drugs containing estrogens.
Impact on the ability to drive vehicles and operate machinery
Patients should be warned about the possibility of drowsiness, asthenia and dizziness during treatment with Aromasin. If these symptoms occur, patients are advised to refrain from driving and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Overdose A single dose of the drug that could cause life-threatening symptoms has not been established. The use of exemestane in a single dose of up to 800 mg in healthy women and in a daily dose of up to 600 mg in postmenopausal women with advanced breast cancer was well tolerated.
Treatment: There are no specific antidotes. If necessary, symptomatic therapy should be carried out, as well as regular monitoring of vital functions and careful monitoring.
Conditions for dispensing from pharmacies The drug is dispensed with a prescription. Conditions and periods of storage List B. The drug should be stored at a temperature not exceeding 30°C out of the reach of children. Shelf life: 3 years. The drug should not be used after the expiration date indicated on the packaging.
