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Divigel® (Estradiol Gel sachets) 0.1%




Other brand names: Sandrena® (UK, Italy), Ercostrol (Denmark), Délidose (France), Sisare® Gel Mono




1 g of the Divigel contains:

  • Active ingredient – Estradiol Hemihydrate (equivalent to estradiol) 1 mg,
  • Excipients: carbomer (carbopol 974 R), trolamine, propylene glycol, ethyl alcohol 96%, purified water.


Indications for use

Symptoms associated with estrogen deficiency in natural or artificial menopause and other estrogen-deficient conditions
Prevention of postmenopausal osteoporosis


Method of administration and dosage

Divigel is a transdermal gel for long-term or cyclic treatment. The usual starting dose is 1 g of gel per day, which corresponds to 1 mg of estradiol. The duration of use and dose is selected by the doctor, taking into account the individual characteristics of patients (depending on the clinical condition, after 2-3 cycles, the dose can be adjusted: from 0.5 g to 1.5 g of gel per day, which corresponds to 0.5 up to 1.5 mg of estradiol per day).

In patients with an intact uterus, it is necessary to combine Divigel with an adequate dose of progesterone according to the duration of admission, for example, 12-14 days in a row for a month or constantly, to prevent the development of estrogen-stimulated endometrial hyperplasia. The Divigel dose is applied once a day to the skin of the lower part of the anterior abdominal wall, or alternately to the right or left buttocks. The area of ​​application is equal in size to 1-2 palms. Divigel should not be applied to breasts, face, genitals, or irritated skin. After applying the drug, you need to let the gel dry. Avoid accidental contact with the Divigel in the eyes, wash your hands immediately after applying the gel. If the patient forgot to apply the gel on time, it is necessary to do it as soon as possible, but no later than within 12 hours from the moment of applying the drug according to the established schedule. If more than 12 hours have passed, then the application of Divigel should be postponed until the next time. With irregular use of the drug, menstrual uterine bleeding may occur.


Possible side effects


– edema, weight gain

– nausea, vomiting, stomach cramps

– vaginal bleeding or discharge

– headache

– skin irritation


– mood swings and impaired libido

– mammary cancer

– migraine


– increased blood pressure, venous thromboembolism

– changes in liver function and bile secretion

– skin rash



– a history of hypersensitivity to the components of the drug, to estrogen-containing drugs

– breast cancer (diagnosed, suspected, or history)

– diagnosed or suspected estrogen-dependent malignant tumors (eg, endometrial cancer)

– vaginal bleeding of unknown etiology

– early untreated endometrial hyperplasia

– current or history of thromboembolic diseases (deep vein thrombosis (DVT), pulmonary embolism)

– current or history of acute thromboembolism of the arteries (eg, stroke, myocardial infarction)

– liver disease at present or in history (before the normalization of laboratory parameters of liver function)

– porphyria

– pregnancy and lactation


Drug interactions

There is evidence in the literature that estrogens can reduce the effect of antihypertensive and antidiabetic drugs and anticoagulants. Concomitant use of drugs that induce liver enzymes (barbiturates, carbamazepine, griseofulvin and rifampicin) can reduce the level of estradiol in the blood plasma. Ritonavir and nelfinavir, although they are strong inhibitors, when used simultaneously with estrogens, on the contrary, have an inducing effect. Herbal preparations that contain the herb St. John’s wort can increase the metabolism of estrogens and progestogens. With transdermal use, the drug bypasses the effect of “first pass” through the liver, respectively, transdermally applied estrogens and progestogens are less exposed to enzyme inducers than hormones taken orally.

Clinically increased metabolism of estrogens and progestogens can lead to a decrease in the effect and a change in the nature of vaginal bleeding.


Special instructions

Divigel should only be used as directed by a physician.

Before starting or re-prescribing hormone replacement therapy (HRT), the doctor needs to collect a complete personal and family history of the patient, a medical (including pelvic organs and mammary glands) examination should be performed in order to identify possible contraindications and observe the necessary precautions when prescribing the drug.

In the course of treatment, it is recommended to carry out periodic examinations. The frequency and type of methods included in it are determined for each patient individually. Women need to be informed about what changes in their mammary glands should be reported to the attending physician. Research, including mammography, must be carried out in accordance with accepted standards and adapted to individual clinical needs each patient.

Therapy should be discontinued if contraindications were found and if the following conditions occur: jaundice or deterioration of liver function, marked increase in blood pressure, new attacks of migraine-like headache. Long-term use of estradiol without the addition of gestagenic drugs can cause endometrial hyperplasia, which increases the risk of developing endometrial cancer. Thus, in patients with an intact uterus, the use of the Divigel must be combined with the cyclic administration of gestagens.

While taking Divigel in combination with a progestogen, 80-90% of women experience regular menstrual bleeding with an average duration of 5-6 days. Estrogens can cause fluid retention in the body, so patients with impaired heart and kidney function should be closely monitored. Patients with renal insufficiency require especially careful observation, since an increase in the level of the active substances of Divigel in the blood should be expected.

In patients with diabetes mellitus, blood glucose levels should be closely monitored in the first months of hormone replacement therapy.

It is known to increase the risk of surgically confirmed cholelithiasis in postmenopausal women using estrogens.

The use of estrogens can change the results of some endocrinological tests, indicators of liver function.

Patients with hypertriglyceridemia using HRT should be closely monitored. Estrogens increase the level of thyroid-binding globulin (TSH), which leads to an increase in the level of circulating thyroid hormones, as measured by the protein-bound iodine concentration of T4 (columnar or radioimmunoassay) or TK concentration (radioimmunoassay). An increase in the level of TK decreases, which reflects an increased TSH, the concentrations of free T4 and TK change. Serum concentrations of other binding proteins, for example, corticoid-binding globulin (CBG), sex hormone binding globulin (SHBG), may increase, which leads to an increase in the concentration of circulating corticosteroids and sex steroid hormones, respectively. Concentrations of free or biologically active hormone remain unchanged. The concentration of other plasma proteins may increase (angiotensin / renin substrate, alpha-1 -trypsin, ceruloplasmin).

Features of the influence of the drug on the ability to drive vehicles and potentially dangerous mechanisms

The drug does not affect the ability to drive vehicles or other potentially dangerous machinery.



Symptoms: breast pain, bloating, anxiety, irritability.
Treatment: drug withdrawal or dose reduction.


Storage conditions

Store at a temperature not exceeding 25 ° C.
Keep out of the reach of children!

Shelf life – 3 years
Do not use after the expiration date printed on the package



Some analogues of Divigel based on the active substance estradiol include:

  1. Estrace (oral tablet or vaginal cream)
  2. Estraderm (transdermal patch)
  3. Estrasorb (topical emulsion)
  4. Estrogel (topical gel)
  5. Climara (transdermal patch)
  6. Vivelle-Dot (transdermal patch)
  7. Alora (transdermal patch)
  8. Femring (vaginal ring)
  9. Vagifem (vaginal tablet)
  10. Estradiol (oral tablet, topical cream or gel, vaginal cream or tablet)

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