Medicinal Products

AVADENE 1 mg / 0.025 mg

Generic drug of the therapeutic class: Gynecology
Active Ingredients: Beige Tablet: Estradiol, Blue Tablet: Estradiol, Gestodene
laboratory: Bayer Healthcare

Coated tablet
Box of 28
All forms

Indication

Hormone Replacement Therapy (HRT) symptoms of estrogen deficiency in postmenopausal women whose last menstrual period is at least 6 months old.

Prevention of postmenopausal osteoporosis in women with an increased risk of osteoporotic fracture and intolerance or contraindication to other treatments indicated for the prevention of osteoporosis.

(See also Warnings and Precautions for Use ).

The experience of this treatment in women over 65 is limited.

Dosage AVADENE 1 mg / 0.025 mg Film-coated tablet Box of 28

Oral way.

Continuous sequential processing.

AVADENE 1 mg / 0.025 mg is a continuous, sequential combination of estrogen and progestin. Estrogen is administered throughout the cycle. The progestin is sequentially associated for 12 days of the cycle.

The therapeutic scheme is as follows:

Take one tablet daily for 28 consecutive days in the following order:

· From the 1st to the 16th day, a beige tablet (estradiol);

· From the 17th to the 28th day, a blue tablet (associating estradiol and gestodene).

At the end of the 28 days, continue treatment directly with the next pack of 28 tablets, without interruption of treatment between the platelets.

The tablets should be swallowed whole with a little liquid. They can be taken during or outside meals, preferably always at the same time.

If this is a first-time prescription for women who have never taken HRT or if it is a relay of a continuous combined HRT, treatment can be started any day of the day. cycle.

On the other hand, if it is a relay of a sequential THS, the treatment must be started the day after the end of the previous treatment.

To start or continue treatment for the indication of post-menopausal symptoms, the minimum effective dose should be used for the shortest possible duration (see section 4.4). Special warnings and precautions for use )

Missed one tablet:

If you forget a tablet, it should be taken within 12 to 24 hours after the usual time of taking. If treatment is interrupted for a longer period, irregular bleeding may occur.

Information about special populations

Children and adolescents:

AVADENE is not indicated in children and adolescents.

The elderly :

There is no evidence to suggest that a dosage adjustment is necessary for the elderly.

For women aged 65 and over, see Warnings and Precautions section. Special warnings and precautions for use.

Patients with hepatic insufficiency:

AVADENE is contraindicated in women with severe hepatic disease (see Contraindications Contraindications section).

Patients with renal insufficiency:

AVADENE has not been specifically studied in women with renal impairment. However, estrogens may cause fluid retention, and therefore patients with renal dysfunction should be closely monitored (see also Warnings and Precautions for Use Special Warnings and Precautions for Use).

Against indications

· Known or suspected breast cancer or history of breast cancer

· Known or suspected estrogen-dependent malignancies (eg, endometrial cancer);

· Undiagnosed genital haemorrhage;

· Untreated endometrial hyperplasia;

· History of venous thromboembolic accident or evolving venous thromboembolic event (deep vein thrombosis, pulmonary embolism);

· Known thrombophilic disorders (eg protein C, protein S or antithrombin deficiency, see Warnings and Precautions section );

· Recent or evolving arterial thromboembolic stroke (eg, angina, myocardial infarction);

· Acute liver disease or history of liver disease, until hepatic tests are normalized;

· Known hypersensitivity to any of the active ingredients or to any of the excipients;

· Porphyria.

Avadene side effects

The table below lists the adverse effects by system organ class according to MedDRA (MedDRA CSO). The frequencies are based on data from clinical studies. These adverse effects are from the 10 phase III clinical studies (n = 1542 exposed women) considered to be related to AVADENE. The most commonly reported side effect was breast pain.

System Organ Classification
MedRA version 9.0

Frequent
> 1/100 to <1/10

Rare
> 1/1000 to <1/100

Metabolism and nutrition disorders

Weight gain, increased appetite

Psychiatric disorders

Nervousness, depression

Nervous system disorders

Headache

Migraine, vertigo

Heart conditions

Angina pectoris

Vascular disorders

Stroke, superficial and deep vein thrombosis, thrombophlebitis, high blood pressure

Gastrointestinal disorders

Abdominal pain, abdominal swelling

Vomiting, constipation, diarrhea

Hepatobiliary disorders

Lithiasis of the bile duct, abnormal liver function tests

Skin and subcutaneous tissue disorders

Acne, rash, pruritus, alopecia, seborrhea

Musculoskeletal and connective tissue disorders

Cramp, limb pain

arthralgia

Reproductive and breast disorders

Cystic fibrosis of the breast, breast tenderness, vaginal / uterine bleeding including spotting (irregular bleeding generally decreasing with continued treatment), dysmenorrhea, menorrhagia, leucorrhoea

Benign breast tumor, increased breast volume, endometriosis, uterine polyp, exacerbation of uterine fibroids, vaginal candidiasis

General disorders and administration site conditions

Peripheral edema, asthenia

The most appropriate term MedRA is used to describe an effect, its synonyms and associated conditions.

Breast cancer risk

A 2-fold increase in the risk of breast cancer has been reported in women who have taken a combined oral contraceptive regimen for more than 5 years.

The increase in risk is significantly lower among estrogen-only users compared to users of combined-hormonal combination therapy.

The level of risk depends on the duration of treatment (see Warnings and Precautions section ).

The results of the largest randomized placebo-controlled trial (WHI study) and the largest epidemiological study (MWS) are presented below:

Study "Million Women Study" - Estimation of the additional risk of breast cancer over 5 years of treatment

Age (years)

Number of additional cases per 1000 women not using HRT over 5 years *

Relative risk #

Number of additional cases per 1000 users of HRT over 5 years (95% CI)

Estrogen alone

50-65

9-12

1.2

1-2 (0-3)

Estroprogestative Association

50-65

9-12

1.7

6 (5-7)

* Derived from basic incidence rates in developed countries.

# Overall relative risk. The relative risk is not constant but increases with the duration of use.

Note: Since the baseline incidence of breast cancer varies from country to country within the EU, the number of additional breast cancer cases will vary proportionally.

WHI studies in the United States: additional risk of breast cancer over 5 years of treatment

Age (years)

Incidence for 1000 women in the placebo arm over 5 years

Relative risk (95% CI)

Number of additional cases per 1000 users of HRT over 5 years (95% CI)

Estrogen alone (equine conjugated estrogens)

50-79

21

0.8 (0.7-1.0)

-4 (-6 - 0) *

Estrogen and Progestin EEC + MPA ‡

50-79

17

1.2 (1.0-1.5)

+4 (0 - 9)

* WHI study in hysterectomized women who did not show an increased risk of breast cancer.

‡ When the analysis was limited to women who did not use HRT before the study, no increase in risk was observed during the first 5 years of treatment: after 5 years, the risk was higher than among non-users.

Risk of endometrial cancer

Menopausal women not hysterectomized

The risk of endometrial cancer is about 5 per 1000 women with intact uterus and not using HRT.

In women with an intact uterus, the use of estrogen-only HRT is not recommended as it increases the risk of endometrial cancer (see Warnings and Precautions section ).

In epidemiological studies, the increased risk of endometrial cancer depended on the duration of estrogen-only therapy and estrogen dose and ranged from 10 to 60 additional cases diagnosed per 1000 women aged 50 years. at 65 years old.

Adding a progestin to estrogen alone for at least 12 days per cycle helps prevent this increased risk. In the Million Women Study, 5-year use of combined HRT (sequential or continuous) did not increase the risk of endometrial cancer (RR 1.0 (0.8- 1.2)).

Ovarian cancer

Long-term use of estrogen-only HRT and estrogen / progestin combination therapy has been associated with a small increase in ovarian cancer risk. In the Million Women Study, 1 additional case for 2, 500 users appeared after 5 years.

Risk of venous thromboembolism (VTE)

HRT is associated with a 1.3 to 3-fold increase in the relative risk of a venous thromboembolic event, ie, deep vein thrombosis or pulmonary embolism. The probability of occurrence of such an event is higher during the first year of use of HRT (see Warnings and Precautions section ). The results of the WHI studies are presented:

WHI studies - additional risk of venous thromboembolic events over 5 years of treatment

Age (years)

Incidence for 1000 women in the placebo arm over 5 years

Relative risk (95% CI)

Number of additional cases per 1000 users of HRT

Estrogen alone orally *

50-59

7

1.2 (0.6-2.4)

1 (-3 - 10)

Oral Estroprogestative Association

50-59

4

2, 3 (1, 2-4, 3)

5 (1 - 13)

* Study in hysterectomized women.

Risk of coronary heart disease

The risk of coronary heart disease is slightly increased in users of hormone replacement therapy over the age of 60 (see Warnings and precautions for use section ).

Risk of ischemic stroke

The use of estrogen alone or estrogen / progestin-only HRT is associated with up to 1.5-fold increase in the relative risk of ischemic stroke. The risk of haemorrhagic stroke is not increased when using HRT.

This relative risk does not depend on age or duration of treatment, but because the baseline risk is highly age-dependent, the overall risk of stroke in women using HRT increases with age (see section on caution and precautions for use ).

Combined WHI studies: additional risk of stroke * ischemic over 5 years of treatment

Age (years)

Incidence for 1000 women in the placebo arm over 5 years

Relative risk (95% CI)

Number of additional cases per 1000 users of HRT

50-59

8

1.3 (1.1-1.6)

3 (1-5)

* There is no distinction between ischemic and haemorrhagic stroke.

The following side effects have been reported with estrogen-progestin therapy (class effects):

· Biliary diseases;

· Cutaneous and subcutaneous disorders: chloasma, erythema multiforme, erythema nodosum, vascular purpura;

· Likely dementia after age 65 (see Warnings and Precautions section ).

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