Active ingredients: Megestrol (Megestrol acetate)
MEGACE 160 mg tablets
Indications Why is Megace used? What is it for?
The medicine is indicated in the palliative treatment of advanced breast or endometrial cancer.
MEGACE is indicated for the treatment of anorexia and weight loss secondary to cancer or AIDS, in patients of both sexes.
Contraindications When Megace should not be used
Hypersensitivity to the active substance or to any of the excipients Megestrol acetate is contraindicated as a diagnostic pregnancy test.
MEGACE is contraindicated:
- in pregnancy and lactation (see Pregnancy and lactation);
- in the prevention of recurrent abortion and in the treatment of the threatened abortion (see Special Warnings).
Precautions for use What you need to know before taking Megace
No specific precautions have been identified for the use of MEGACE when used as directed.
Careful and constant monitoring of all patients treated with recurrent or metastatic cancer is advised.
Use with caution in patients with a history of thrombophlebitis.
Interactions Which drugs or foods can modify the effect of Megace
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
There are no known interactions with other medicines.
Warnings It is important to know that:
As elderly patients are more likely to have impaired renal function, care should be taken in dosage selection, and monitoring of renal function may be useful.
Megestrol acetate is known to be substantially excreted by the kidneys, and the risk of toxic drug reactions may be greater in patients with impaired renal function (see Dose, method and time of administration).
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Pregnancy: A correlation has been shown between the administration of progestogens in the first months of pregnancy and congenital anomalies, including congenital heart abnormalities, changes in the female and male genital organs and the appearance of phocomelic limbs.
The use of MEGACE is contraindicated during pregnancy. Therefore, women of childbearing potential should be informed of the potential risks to the fetus associated with the use of the medicinal product and of the need to adopt an effective method of contraception during treatment with the medicinal product. need, in case of pregnancy, to consult your doctor quickly.
Breastfeeding: Due to the potential adverse effects on the newborn, the use of MEGACE is contraindicated during breastfeeding.
Effects on ability to drive and use machines
There is no known interference with the ability to drive and use machines
Important information about some of the ingredients: MEGACE contains lactose. If your doctor has diagnosed an intolerance to some sugars, contact your doctor before taking this medicinal product.
Dosage and method of use How to use Megace: Dosage
Breast cancer: 160 mg / day.
Endometrial cancer: 160-320 mg / day.
Anorexia / cachexia: 400-800 mg / day, given as a single dose.
MEGACE should generally be administered for at least two months to evaluate its effects for efficacy.
Pediatric patients
Safety and efficacy in pediatric patients have not been established.
Elderly patients
Dosage selection in elderly patients should be made with caution, usually from the low end of the dosage range, due to the increased frequency of hepatic, renal or cardiac dysfunction and concomitant disease or other drug therapies.
Overdose What to do if you have taken too much Megace
Doses of up to 1600 mg / day of MEGACE for over six months produced no acute toxic effects.
Cases of overdose have been reported in the post-marketing period. Observed signs and symptoms included diarrhea, nausea, abdominal pain, shortness of breath, cough, unsteady gait, listlessness and chest pain.
As there are no specific antidotes, treatment should be symptomatic and supportive in the event of an overdose.
In case of accidental ingestion / intake of an excessive dose of MEGACE, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of MEGACE, ask your doctor or pharmacist.
Side Effects What are the side effects of Megace
Like all medicines, MEGACE can cause side effects, although not everybody gets them.
- Weight gain: represents a frequent undesirable effect of megestrol acetate, particularly at high doses, when used in patients treated for cancer. This increase has been associated with increased appetite, fat and cell mass, and is not usually associated with water retention. This very effect is at the basis of the use of megestrol acetate in patients with anorexia and weight loss.
- Thromboembolic phenomena: Thromboembolic phenomena including thrombophlebitis and pulmonary embolisms (in some cases fatal) have been observed.
- Other undesirable effects: nausea, vomiting, edema, uterine blood loss, are observed in 1-2% of patients. Dyspnoea, pain, heart failure, hypertension, flushing, mood changes, cushingoid facies, tumor growth (with or without hypercalcemia), hyperglycemia, alopecia, carpal tunnel syndrome, diarrhea, lethargy and rash. In clinical trials with megestrol acetate in patients with acquired immunodeficiency syndrome, overall there was no statistically significant difference between treatment with the drug and placebo in patients who reported at least one adverse event. Adverse events reported in one greater than or equal to 5% of patients included in the study included diarrhea, impotence, rash, flatulence, asthenia and pain.
Constipation and increased urination frequency have also been reported in patients treated in high dose clinical trials.Cases of hypothalamic-adrenal axis abnormalities including glucose intolerance, non-pre-existing diabetes or exacerbation of a previous diabetic state with lower glucose tolerance and Cushing's syndrome have been reported.
Clinically manifest adrenal insufficiency has been reported rarely immediately after megestrol acetate discontinuation. Adrenal suppression syndrome should be considered in patients on megestrol acetate therapy or soon after its discontinuation. Replacement glucocorticoids may be indicated. Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.
Expiry and Retention
Warning: do not use the medicine after the expiry date shown on the package. See the expiry date printed on the package.
The expiry date refers to the product in intact packaging, correctly stored. The expiry date refers to the last day of the month.
Do not store above 25 ° C.
Medicines should not be disposed of via wastewater or household waste.
Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Keep this medicine out of the sight and reach of children.
Other Information
Composition MEGACE 160 mg tablets contains
Active ingredient: megestrol acetate 160 mg.
Excipients: lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl starch, povidone, colloidal silica, magnesium stearate.
Pharmaceutical form and content
Tablets Blister packs of 30 tablets
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
MEGACE 160 MG TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 160 mg megestrol acetate (active ingredient).
Excipients with known effects:
Each tablet contains 224.50 mg of lactose monohydrate.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Tablet.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
The medicine is indicated in the palliative treatment of advanced breast or endometrial cancer.
MEGACE is indicated for the treatment of anorexia and weight loss secondary to cancer or AIDS, in patients of both sexes.
04.2 Posology and method of administration
Breast cancer: 160 mg / day.
Endometrial cancer: 160-320 mg / day.
Anorexia / cachexia: 400-800 mg / day, given as a single dose.
MEGACE should generally be administered for at least two months to evaluate its effects for efficacy.
Megestrol acetate can be combined with other antiblastic chemotherapeutic agents.
Pediatric patients
Safety and efficacy in pediatric patients have not been established.
Elderly patients
Dosage selection in elderly patients should be made with caution, usually from the low end of the dosage range, due to the increased frequency of hepatic, renal or cardiac dysfunction and concomitant disease or other drug therapies (see section 4.4).
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients, listed in section 6.1.
Megestrol acetate is contraindicated as a diagnostic pregnancy test.
MEGACE is contraindicated:
• in pregnancy and lactation (see section 4.6);
• in the prevention of recurrent abortion and in the treatment of the threatened abortion (see section 4.4).
04.4 Special warnings and appropriate precautions for use
It is recommended to use the medicine with caution in patients with a history of thrombophlebitis.
Careful and constant monitoring of patients treated with recurrent or metastatic endometrial or breast cancer is recommended.
There are insufficient data to quantify the risk to female fetuses; however some of these medicines cause slight virilization of the female external genital organs.
Elderly patients
There are insufficient data from clinical trials in patients over 65 years treated with megestrol acetate to determine whether they respond differently to therapy than younger patients. Further described clinical experience did not identify response differences between elderly and young patients.
In general, the choice of dosage for an elderly patient should be made with caution, usually starting at the low end of the dosage range, in consideration of the increased frequency of hepatic, renal or cardiac dysfunction and of concomitant diseases or other drug therapies (see paragraph 4.2).
Megestrol acetate is known to be substantially excreted by the kidneys, and the risk of toxic drug reactions may be greater in patients with impaired renal function. As elderly patients are more likely to have impaired renal function, care should be taken in choosing the dosage, and monitoring of renal function may be useful.
Important information about some of the excipients
MEGACE contains lactose. Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
There are no known interactions with other medicines.
04.6 Pregnancy and breastfeeding
Pregnancy
There was a correlation between the administration of progestogens in the first months of pregnancy and congenital anomalies, including congenital cardiac anomalies and the appearance of phocomelic limbs.
In one study it was estimated that intrauterine fetal exposure to sex hormones (oral contraceptives, or treatment attempts for abortion threats) increases the risk of limb phocomelia by 4.7 times. In some cases, hormone exposure was very short and only for a few days of treatment. These data indicate that the risk of limb phocomelia after intrauterine hormone exposure is just under 1 in 1000.
Alteration of the fetal female and male genital organs has been reported following the administration of progestin drugs during the first three months of pregnancy. The risk of hypospadias, in the ratio of 5 to 8 per 1000 male births in the general population, following the administration of these drugs, has almost doubled.
The use of MEGACE is contraindicated in pregnancy.
Therefore, women of childbearing potential must be informed of the potential risks to the fetus associated with the use of the medicinal product and of the need to adopt an effective method of contraception during treatment with the medicinal product and of the need, in the event of pregnancy, to consult the doctor quickly. doctor.
Feeding time
Due to the potential adverse effects on the newborn, the use of MEGACE is contraindicated during breastfeeding.
04.7 Effects on ability to drive and use machines
There is no known interference with the ability to drive and use machines.
04.8 Undesirable effects
The following side effects have been observed:
Weight gain: represents a frequent undesirable effect of megestrol acetate, particularly at high doses, when used in patients treated for cancer. This increase has been associated with increased appetite, fat and cell mass, and is not usually associated with water retention. This very effect is at the basis of the use of megestrol acetate in patients with anorexia and weight loss.
Thromboembolic phenomena: thromboembolic phenomena including thrombophlebitis and pulmonary embolisms (in some cases fatal) have been observed.
Other side effects: nausea, vomiting, edema, uterine blood loss are observed in 1-2% of patients. Dyspnoea, pain, heart failure, hypertension, flushing, mood changes, cushingoid facies, tumor growth with or without hypercalcemia, hyperglycemia , alopecia, carpal tunnel syndrome, diarrhea, lethargy and skin rash. In clinical trials with megestrol acetate in patients with acquired immunodeficiency syndrome, overall there was no statistically significant difference between treatment with the drug and placebo in patients who reported at least one adverse event. Adverse events reported in one greater than or equal to 5% of patients included in the study included diarrhea, impotence, rash, flatulence, asthenia and pain.
Constipation and increased urination frequency have also been reported in patients treated in high dose clinical trials.
Cases of hypothalamic-adrenal axis abnormalities including glucose intolerance, non-pre-existing diabetes or exacerbation of a previous diabetic state with lower glucose tolerance and Cushing's syndrome have been reported.
Clinically manifest adrenal insufficiency has been reported rarely immediately after megestrol acetate discontinuation. Adrenal suppression syndrome should be considered in patients on megestrol acetate therapy or soon after its discontinuation. Replacement glucocorticoids may be indicated.
04.9 Overdose
Doses of up to 1600 mg / day of MEGACE for over six months produced no acute toxic effects.
Cases of overdose have been reported in the post-marketing period. Observed signs and symptoms included diarrhea, nausea, abdominal pain, shortness of breath, cough, unsteady gait, listlessness and chest pain.
As there are no specific antidotes, treatment should be symptomatic and supportive in the event of an overdose.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: hormones and related substances. Progestogens.
ATC code: L02AB01.
Megestrol acetate is endowed with progestin and anti-estrogenic activity. It is also able to compete with the receptor for progesterone, androgens and glucocorticoids.
Therefore the mechanisms of action underlying the pharmacological action are two: a direct cytotoxic effect on tumor cells (through the antagonist effect on the progestin receptor in terms of cell proliferation) and an antiluteinizing effect at the pituitary level.
The mechanism by which MEGACE determines its effect on anorexia and weight loss is not yet fully understood. The weight gain associated with treatment with megestrol acetate is related to an increase in appetite and an increase in weight. fat and body cell mass.
05.2 Pharmacokinetic properties
After oral administration in man, the plasma peaks of the drug are reached after 2-3 hours from the intake. The plasma concentration curve is biphasic with a second phase half-life of 15-20 hours, which allows the drug to be administered once a day. The drug is eliminated in humans mainly in the urine (66%) and 20% in the faeces. The remainder is eliminated by the respiratory route or by accumulation in fat.
Estimates of plasma megestrol acetate levels depend on the measurement method used. Plasma levels are related to the inactivation of the drug by the intestine and liver, which can be influenced by intestinal motility, bacterial flora, concomitant administration of antibiotics, body weight, diet and liver function.
05.3 Preclinical safety data
In mice, LD 50 was not achieved using doses up to 500 mg / kg for both oral and subcutaneous administration and can, therefore, be considered significantly higher than the maximum daily doses provided by therapy in humans. Oral administration in rats of doses ranging from 0.01 mg / kg / day to 20 mg / kg / day for a period of 3 months did not give rise to significant alterations from the biochemical-haematological point of view.
A reduction in the weight of the testis, ovary, adrenal gland and prostate was observed in treated rats due to the progestogenic activity of megestrol acetate.
At higher doses there was no weight gain of the animals. Administration of higher doses to dogs has occasionally resulted in a rise in GPT in some animals.
In monkeys, increased alkaline phosphatase, total bilirubin and total cholesterolemia were observed. Megestrol acetate at a dose of more than 1 mg / kg / day in rats and 9 mg / kg / day in rabbits was not teratogenic.
Administration of megestrol acetate to female dogs for up to seven years has shown an increased incidence of both benign and malignant mammary tumors. In contrast, in comparable studies in rats and in studies in monkeys, the tumor incidence did not increase. Although the correlation between megestrol acetate-induced canine tumors and human ones is not well known, it will have to be considered for both evaluation. risk / benefit in prescribing MEGACE and for patient monitoring Reproduction and fertility studies conducted at high doses of megestrol in rats showed reversible increases in female hormones in male fetuses.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Lactose monohydrate, microcrystalline cellulose, sodium starch carboxymethyl, povidone, colloidal silica, magnesium stearate.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Do not store above 25 ° C
06.5 Nature of the immediate packaging and contents of the package
3 blisters each containing 10 tablets of 160 mg.
06.6 Instructions for use and handling
No special instructions.
Unused medicine and wastes derived from that medicine should be disposed of in
compliance with local legislation in force.
07.0 MARKETING AUTHORIZATION HOLDER
PharmaSwiss? Eská republika s.r.o., Jankovcova 1569 / 2c - 170 00, Prague 7, Czech Republic
Representative for Italy: Swedish Orphan Biovitrum S.r.l. - Via Quarta 6 / 1d - 43123 Parma, Italy
08.0 MARKETING AUTHORIZATION NUMBER
160 mg tablets 30 tablets A.I.C .: 027597020
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 5 May 1992
Last renewal date: 5 May 2007.
10.0 DATE OF REVISION OF THE TEXT
July 2014
