Medicinal Products

ANGELIQ 1 mg / 2 mg

Generic drug of the therapeutic class: Gynecology
active ingredients: Estradiol, Drospirenone
laboratory: Bayer Healthcare

Coated tablet
Box of 28
All forms

Indication

Hormone Replacement Therapy (HRT) symptoms of estrogen deficiency in postmenopausal women for more than a year.

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 ANGELIQ 1 mg / 2 mg Film-coated tablet Box of 28

If this is a first prescription in women who have never received hormone replacement therapy (HRT) or if it is a relay of continuous combined HRT, treatment may be started any time. On the other hand, if it is a relay of a sequential or cyclic combined HRT, the treatment must be started the day after the end of the previous treatment.

Dosage

One tablet a day. Each wafer contains the necessary treatment for 28 days.

Administration

The tablets should be swallowed whole with a little liquid, during or outside meals. The treatment is continuous, which means that the following plate must be started at the end of the previous one. The tablets should be taken, preferably, at the same time each day. If you forget a tablet, it should be taken as soon as possible. Beyond 24 hours, do not take extra tablets. If multiple tablets are missed, vaginal bleeding may occur.

For the treatment of menopausal symptoms, the minimum effective dose should be used.

To start or continue treatment for the indication of postmenopausal symptoms, the minimum effective dose should be used for the shortest possible duration (see Warnings and Precautions ).

Additional information on particular populations

Children and adolescents

ANGELIQ 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 section Warnings and precautions for use .

Patients with hepatic insufficiency

In women with mild-to-moderate hepatic impairment, drospirenone is well tolerated (see section 5.2. Pharmacokinetic Properties). ANGELIQ is contraindicated in women with severe hepatic disease (see section 4.3 ).

Patients with renal insufficiency

In women with mild to moderate renal impairment, a slight increase in exposure to drospirenone has been observed, however, without clinical relevance (see section 5.2 ). ANGELIQ is contraindicated in women with severe renal impairment (see section 4.3 ).

Against indications

Undiagnosed genital haemorrhage;

· Known or suspected breast cancer or history of breast cancer;

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

· Untreated endometrial hyperplasia;

· History of venous thromboembolic events or venous thromboembolic events (deep vein thrombosis, pulmonary embolism);

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

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

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

· Severe renal failure or acute renal impairment;

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

· Porphyria.

Angeliq side effects

The table below reports the adverse effects classified according to the MedDRA organ system classification (MedDRA SOCs). The frequencies are based on the results of clinical trials. Adverse events were recorded in 7 phase III clinical studies (n = 2424 women) and were considered to be related to ANGELIQ (1 mg estradiol plus 0.5; 1; 2 or 3 mg drospirenone). ).

The most commonly reported adverse effects were mastodynia (> 10%), and during the first few months of treatment bleeding and spotting (> 10%). Irregular bleeding usually decreases and their frequency decreases with continued treatment (see section 5.1. Pharmacodynamic properties of drospirenone).

System organ classification

Frequent
( 1/100, <1/10)

Rare
( 1/1000, <1/100)

Rare

(<1/1000)

Blood and lymphatic system disorders

Anemia

Metabolism and nutrition disorders

Weight gain or weight loss, anorexia, increased appetite, hyperlipemia

Psychiatric disorders

Depression, emotional lability, nervousness

Sleep disorders, anxiety, decreased libido.

Nervous system disorders

headaches

Paraesthesia, impaired concentration, dizziness

Dizziness

Eye disorders

Eye disorders, visual disturbances

Affections of the ear and labyrinth

tinnitus

Heart conditions

palpitations

Vascular disorders

Embolism, venous thrombosis, high blood pressure, migraine, thrombophlebitis, varicose veins.

Respiratory, thoracic and mediastinal disorders

Dyspnea

Gastrointestinal disorders

Abdominal pain, nausea, abdominal swelling.

Gastrointestinal disorders, diarrhea, constipation, vomiting, dry mouth, flatulence, dysgeusia.

Hepatobiliary disorders

Liver function tests abnormal.

Biliary lithiasis

Affections of the skin and subcutaneous tissue.

Skin disorders, acne, alopecia, pruritus, rash, hirsutism, hair system disorders

Musculoskeletal and systemic disorders

Pains of the extremities, back pains, arthralgia, muscular cramps.

myalgia

Renal and urinary disorders

Urinary disorders, urinary tract infections.

Disorders of reproductive organs and breast

Benign mammary tumors, increased breast volume, increased uterine fibroids, benign tumors of the cervix, menstrual disorders, leucorrhea.

Mammary carcinoma, endometrial hyperplasia, benign tumor of the uterus, fibrocystic breast, uterine affections, ovarian affections, cervical affections, pelvic pain, vulvovaginal conditions, vaginal candidiasis, vaginitis, vaginal dryness.

Salpingitis, galactorrhea

General disorders and administration site conditions

Asthenia, localized edema.

Generalized edema, pain in the chest, malaise, hypersudation.

Chills.

The most appropriate term MedDRA is used to describe a certain type of reaction as well as its related synonyms and pathologies.

Additional information on certain populations:

The following adverse events considered by the investigator to be related to ANGELIQ treatment were recorded in two clinical studies in hypertensive women.

Metabolism and nutrition disorders:

Hyperkalemia.

Heart conditions:

Heart failure, atrial flutter, QT prolongation, cardiomegaly.

Investigations:

Increased aldosteronemia.

The following side effects have been reported in association with HRT:

Erythema nodosum, erythema multiforme, chloasma, hemorrhagic dermatitis.

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 users of estrogen alone compared to users of combined hormonal supplementation.

· 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 1, 000 women not using HRT over 5 years * 2

Relative risk #

Number of additional cases per 1, 000 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)

# 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 Breast Cancer Risk Over 5 Years of Treatment

Age (years)

Incidence per 1, 000 women in the placebo arm over 5 years

Relative risk (95% CI)

Number of additional cases per 1, 000 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) * 3

Estrogen and Progestin EEC + MPA

50-79

17

1.2 (1.0 - 1.5)

+4 (0 - 9)

‡ 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.

2 * Based on basic incidence rates in developed countries

3 * WHI study in hysterectomized women, not showing increased risk of breast cancer

Risk of endometrial cancer

Menopausal women not hysterectomized

The risk of endometrial cancer is approximately 5 per 1, 000 women with intact uteri who do not use 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 was dependent on the duration of treatment with estrogen alone and the dose of estrogen and ranged between 5 and 55 additional cases diagnosed per 1, 000 elderly women. 50 to 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 thromboembolism over 5 years of treatment

Age (years)

Incidence per 1, 000 women in the placebo arm over 5 years

Relative risk (95% CI)

Number of additional cases per 1, 000 HRT users

Estrogen alone orally * 4

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)

4 * 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 * 5 ischemic over 5 years of treatment

Age (years)

Incidence per 1, 000 women in the placebo arm over 5 years

Relative risk (95% CI)

Number of additional cases per 1, 000 HRT users over 5 years

50-59

8

1.3 (1.1-1.6)

3 (1-5)

5 * There is no distinction between ischemic and haemorrhagic stroke.

Other undesirable effects have been reported during the administration of estrogen-progestin therapy:

· 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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