"Jess" for acne: effectiveness, indications for use, side effects

Acne in adolescence is a common occurrence due to hormonal changes in the body. But if acne occurs in an older person, then pimples may indicate an imbalance. They are eliminated in such a situation with the help of specialized drugs.

These include oral contraceptives, which have two important actions for the female body - they protect against unwanted pregnancy and help cope with cosmetic defects such as acne. Will Jess help with acne?

Actions of oral contraceptives

Contraceptive drugs contain a combination of hormones that inhibit the ovulation process, that is, they prevent the release of an egg from the ovaries. In addition, they change the structure of the secretion of the cervical canal, it becomes denser, which prevents sperm from entering the uterus.

Their main task is related to this - preventing unwanted pregnancy. But there are certain contraceptives that have the property of blocking androgen receptors. They reduce the intensity of production of male sex hormones, including testosterone, in women’s bodies. It is these hormones that, as a rule, increase the activity of the sebaceous glands, which leads to the appearance of acne.

This group of oral contraceptives includes:

"Jess."
"Yarina."
"Janine."

With their use, hormonal levels are stabilized, and rashes stop bothering the patient.

Herpes in the intimate area in women: symptoms and routes of transmission

Having entered the body through the skin or mucous membranes, the virus moves to the nerve ganglia - a collection of nerve cells - where it remains for life. Strong immunity prevents the manifestation of GG activity. But as soon as a person is exposed to stress in the form of the appearance of various concomitant diseases (ARVI and others), hypothermia or overheating, overwork, intoxication from alcoholic drinks and smoking, excessive ultraviolet radiation, exhaustion due to poor nutrition, psycho-emotional stress and any other reasons that weaken immune system, the virus immediately makes itself felt.

Among the most common symptoms of herpes in the intimate area in women:

hyperemia and swelling of the skin and mucous membranes in the affected area - the vulva, clitoris, vagina, cervix, pubis, perineum, perianal area; sometimes the inner thighs are involved in the process;
the appearance of small yellowish bubbles with transparent contents located on the genitals;
the development of erosive and ulcerative elements at the site of the vesicles, which leads to the appearance of symptoms such as pain, itching and burning in the area where the rash is localized.

In addition to dermatological manifestations, GG may be accompanied by the appearance and development of symptoms of intoxication caused by viremia: low-grade body temperature, general weakness, and malaise. The inguinal lymph nodes may also become enlarged and painful.

In men, HS manifests itself in the form of rashes in the penis, scrotum, pubis, perineum and perianal area. However, it must be remembered that in both men and women, genital herpes infection can be asymptomatic. Atypical forms of HS can only lead to almost imperceptible redness of the skin and mucous membranes, as well as slight swelling, which can be ignored. But even in the complete absence of complaints, the infected partner spreads the virus, often without knowing it. This once again indicates the need to regularly visit a gynecologist, urologist and get tested. A blood serum test will help detect antibodies to the virus even in the absence of any symptoms.

Barrier contraceptives such as a condom reduce the risk of HG infection, especially during casual sexual contact, but do not reduce it to zero. On mucous membranes and skin not protected by a condom, there may be visually invisible microcracks and tissue damage, through which the virus can still penetrate inside. Treating the skin and mucous membranes with antiseptic solutions somewhat reduces the likelihood of infection.

Does Jess help with acne?

First of all, it should be noted that the drug is prescribed to adolescents and women in situations where they are sexually active, since the main purpose of this medication is contraception. Acne therapy is considered only a side effect of its use.

Therefore, you can use “Jess” only after consulting a gynecologist and having a blood test for hormone levels. The drug is prescribed only in the situation if it turns out that:

The level of male hormones is increased.
A girl or woman is worried about acne.
At the same time, the representative of the fair half of humanity leads an active sex life.
The woman is not planning a pregnancy.

If the patient has one goal - eliminating acne, then taking contraceptive medications is not recommended, since these are very strong drugs that have certain adverse reactions.

Therefore, before purchasing Jess birth control pills for acne, it is necessary to consult several medical specialists, for example, a dermatologist or gynecologist.

Suppositories, gel and ointment for herpes in the intimate area

Correction of IFN deficiency in herpes and the strategy of combining acyclic nucleosides and interferon alpha-2b are recognized by the medical community as reasonable and most effective, which is reflected in clinical recommendations.iii It is necessary to use not only local, but also systemic interferon therapy to restore local and systemic immunity in order to prevent the development of inflammatory diseases of the pelvic organs, because herpes viruses can cause asymptomatic inflammation of the uterus and its appendages, which subsequently increases the risk of infertility.

One of the drugs used to treat herpes is VIFERON, an antiviral and immunomodulatory drug that has a number of unique pharmacological properties.

The drug contains interferon alpha-2b, which helps block the proliferation of viruses, and also helps to correct the body’s own immunity. VIFERON is available in the form of suppositories, ointments and gels. It has been scientifically proven that the release form provides the drug with unique pharmacodynamic characteristics, and the presence of highly active antioxidants, vitamins E and C, makes it possible to enhance the antiviral activity of interferon. To treat herpesvirus infections in adults, suppositories are used in a dosage of 1,000,000 IU, and in pregnant women - 500,000 IU.

Advantages

"Jess" is a contraceptive for oral use that contains estrogen and gestagen, which inhibits the excessive production of testosterone, the male sex hormone. Positive reviews from medical specialists confirm not only its effectiveness, but also many other advantages compared to drugs with similar effects:

The hormone content in the medication is as low as possible compared to generics, which helps to achieve a milder effect on the body and reduce the severity of side effects, while the effect of the oral contraceptive also remains at a high level.
Eliminates acne of the second degree.
Does not provoke weight gain.
Improves the condition of the hair and nail plate.
Stabilizes the regularity of menstruation, helps eliminate pain during periodic bleeding.

In addition, the drug “Jess Plus” is produced, the structure of which includes folic acid. They are intended for representatives of the fair half who plan to become pregnant immediately after stopping the drug, since folic acid is needed for the proper formation of the central nervous system of the unborn baby.

The onset of puberty is associated with activation of the hypothalamic-pituitary system, followed by activation of the ovaries, which are the main source of estrogens - hormones that form the female-type phenotype, or feminization. In addition to influencing the development of sexual characteristics, estrogens play an extremely important role in the functioning of the cardiovascular, nervous, musculoskeletal and immune systems of the body. Due to estrogen, the skin looks smooth and toned, the hair on the head is long and elastic, and the nails are shiny and strong. The role of estrogen in sexual life is invaluable. Thanks to them, libido is formed, the glands of the genitourinary tract function and attractant pheromones are produced that attract the opposite sex. The secretion of the sweat glands is also under the direct control of estrogens [3].

The biochemical precursors of estrogens are androgens, 50% of which are synthesized in the ovaries and adrenal glands, and the second half are formed in adipose tissue. The role of androgens in the physiology of the female body has received less attention compared to estrogens and progesterone, but their influence on the functioning of almost all body systems and participation in the development of many pathological conditions is very significant and diverse. By binding to the receptors of the limbic system of the brain, androgens form libido and influence initiative in actions and aggressiveness in behavior. Under the influence of androgens, linear growth and closure of the epiphyses in tubular bones occurs. In the bone marrow, androgens stimulate the mitotic activity of stem cells, in the kidneys - the production of erythropoietin; in the liver - blood proteins. An increase in muscle mass, hair growth, and the functioning of apocrine and sebaceous glands are androgen-dependent processes [4, 5, 7].

The bulk of testosterone circulating in the blood (about 80%) is bound to sex hormone-binding globulin (SHBG), approximately 17-19% is bound to albumin, and only 1-3% circulates in a free state (biologically active testosterone) [5]. Hyperandrogenism (HA) is one of the most common causes of not only menstrual irregularities, chronic anovulation (35%) and, as a consequence, infertility, but also a wide range of cosmetic problems such as seborrhea, hypertrichosis and acne of varying severity [1, 6— 8].

Acne (acne vulgaris) is a chronic inflammatory skin disease that affects up to 85-90% of adolescents; a severe course of the process is observed in 5-10%. Approximately more than 40% of patients demonstrate nosogenic psychoemotional disorders, predominantly of the depressive spectrum, as a result of persistence of the disease due to inadequate therapy [2, 6].

In the pathogenesis of acne, the initial link is hereditarily determined GA, which can manifest itself in the form of an absolute increase in the amount of hormones (AGA) or in the form of increased sensitivity of receptors to a normal or reduced amount of androgens in the body [6]. Conditions of relative GA are more often observed. In the cells of the sebaceous glands - sebocytes, testosterone, under the influence of the enzyme 5α-reductase type I, transforms into the most active metabolite - dihydrotestosterone, which is a direct stimulator of the growth and maturation of sebocytes, the formation of sebum. The main causes of relative GA are:

1) increased activity of the enzyme 5α-reductase type I;

2) increased density of nuclear dihydrotestosterone receptors;

3) an increase in the free fraction of testosterone in the blood as a result of a decrease in the synthesis of SHSH in the liver.

Up to 80% of women with acne note an increase in the number of non-inflammatory and inflammatory rashes in phase II of the cycle (10-12 days before the onset of bleeding). This is due to microedema of the skin (narrowing of the mouth of the pilosebaceous follicle - SVF), aggravation of the key link in the pathogenesis of acne - follicular hyperkeratosis and, as a consequence, aggravation of the outflow of sebum. Pathogenetically, this condition is explained by stimulation of the renin-aldosterone-angiotensin system by estrogen and progesterone, followed by sodium and water retention [6, 8].

If the initial link in the pathogenesis of acne is an increase in the intensity of sebum formation, then the key is follicular hyperkeratosis as a result of the predominance of keratinization processes over desquamation processes at the mouth of the SVF.

Acne rashes are represented by a pseudopolymorphic rash, which is characterized by a clear stage in the evolution of elements. Initial skin changes in acne are represented by open and closed comedones (according to the level of obstruction of the SVF duct). The addition of an inflammatory reaction around the comedone leads to its destruction and the subsequent formation of papules and then pustules. The development of an inflammatory reaction in the dermis leads to the formation of nodes, and when they suppurate, cysts [6].

Anti-acne agents used today are represented by both systemic and local drugs that act primarily on one factor in the pathogenesis of acne. Any local anti-acne drugs (retinoids and retinoid-like compounds, azelaic acid, benzoyl peroxide, antibiotics, drugs with zinc) do not guarantee the patient a stable and long-term remission of the process after cessation of therapy [3].

Based on the basics of the etiology and pathogenesis of acne, for the treatment of this disease in women, substances that have a suppressive effect on HA conditions are adequate and pathogenetically justified, i.e. antiandrogens, which have taken a strong position in international algorithms for the management of women with mild to moderate acne [2, 12].

Among the drugs that affect the severity of androgenization, the most widely used are combined oral contraceptives (COCs). All COCs consist of ethinyl estradiol and a progestin component. Based on the amount of ethinyl estradiol, COCs are divided into high-dose (50 mcg/day), low-dose (30-35 mcg/day) and micro-dose (15-20 mcg/day) [1, 10].

The desired actions of ethinyl estradiol include: antigonadotropic (potentiation of the action of gestagens), endometrial proliferation and stimulation of protein synthesis in the liver (in particular, SHSG), blood coagulation factors, high-density lipoprotein apoproteins. Side effects include activation of the renin-angiotensin-aldosterone system with subsequent retention of sodium and water in the body.

The main effect of synthetic gestagens is their gestagenic activity, which consists of an antigonadotropic effect, secretory transformation of the endometrium and maintenance of pregnancy [7, 13].

The optimal combination in COCs used for the treatment of acne and seborrhea is the presence of estrogens in the minimum amount required for the normal course of the menstrual cycle (microdosage, or 0.015-0.02 mg of ethinyl estradiol) and a gestagen, which has progestogenic, antiandrogenic and antimineralocorticoid activity.

At the end of the 90s of the twentieth century, a unique progestogen, drospirenone, was synthesized - a fourth-generation progestogen, a spirolactone derivative, without an ethynyl radical, different from all previously existing progestogens. In terms of its biological effects, drospirenone is as close as possible to endogenous progesterone. In addition to the gestagenic effect, drospirenone has antiandrogenic and antimineralocorticoid properties. Due to its antiandrogenic activity, drospirenone effectively reduces the severity of acne, seborrhea and hirsutism [9, 12].

In 2006, an innovative low-dose COC containing 0.02 mg ethinyl estradiol and 3 mg drospirenone in a regimen of 24 active tablets + 4 placebo tablets appeared - the drug Jess (Bayer HealthCare Pharmaceuticals, Germany).

The drug Jess combines the advantages of a low dose of estrogen (0.02 mg/day compared to the standard dose of 0.03 mg/day) and the innovative progestogen drospirenone. Reducing the dose of estrogen increases the safety of the drug and improves its tolerability.

The anti-acne activity of COC Jess is due to the following mechanisms:

- direct antiandrogenic effect (blockade of androgen receptors);

- indirect antiandrogenic effect;

- antigonadotropic activity;

- stimulation by ethinyl estradiol and drospirenone of the synthesis of SHG by the liver;

- absence of displacement of testosterone from its connection with SHSG (since drospirenone is transported in the blood bound to albumin);

- suppressive effect on the renin-angiotensin-aldosterone system (blockade of aldosterone receptors by drospirenone).

The last property of Jess is very important, especially for women who notice an exacerbation of acne in the second half of the cycle.

In Russia, Jess is a COC registered according to the following indications:

- contraception;

- contraception and treatment of moderate acne;

- contraception and treatment of severe premenstrual syndrome.

Thanks to the antimineralocorticoid effect of drospirenone, Jess prevents sodium and water retention in the body, reducing associated side effects such as breast engorgement and weight gain, thereby improving the tolerability of the drug and the possibility of its long-term use.

In a study assessing the cosmetic aspects of taking an antiandrogenic COC with drospirenone, by the end of 6 months of therapy, a decrease in seborrhea (by 71%), acne (by 75%) and hypertrichosis (Ferryman-Gallwey index - by 43%), increased hydration of the epidermis was demonstrated. by 26% and a decrease in transepidermal fluid loss (by 35%) [12].

The new 24+4 regimen extends the effect of drospirenone by 3 additional days (compared to the standard regimen of other COCs: 21 active tablets and 7 days off), which enhances its antiandrogenic and antimineralkorticoid effects. In addition, the prolonged action of drospirenone provides a more stable hormonal balance and reduces the symptoms observed during breaks in taking standard COCs (during menstruation), such as dysmenorrhea, headache, mood changes.

At the end of 2012, modified forms of drospirenone-containing COCs, Jess Plus and Yarina Plus (Bayer HealthCare Pharmaceuticals, Germany), appeared on the domestic pharmaceutical market. Compared to its predecessors, each tablet (including 4 or 7 placebo tablets, respectively), in addition to ethinyl estradiol (20 or 30 mcg, respectively) and drospirenone (3 mg), contains calcium levomefolate (Metafolin[]) at a dose of 451 mcg - stable and metabolically active calcium salt of folic acid (vitamin B9). Folates are not synthesized in the human body. When supplied with food, they take an active part in DNA synthesis and repair, synoptic transmission and erythropoiesis. There is information about the key role of folic acid in the DNA repair processes of keratinocytes and skin fibroblasts, in particular, after photolysis induced by UV radiation [11]. These data allow us to consider folates as an important component in the prevention of skin photoaging (“endogenous” photoprotector), especially considering the fact that estrogens increase the sensitivity of the skin to UV radiation (Fig. 1).

Figure 1. Folate (B9) in protecting skin components from UV radiation.

The extremely important role of folates during the first month of embryonic development is their effect on the proliferation and differentiation of neural stem cells, i.e. the formation of the neural tube of the embryo - the precursor of the fetal central nervous system. Lack of folic acid in the body of a pregnant woman (when the woman does not yet know that she is pregnant: for 36% of women the first pregnancy is not planned) leads to defects of the neural tube of the embryo - congenital malformations incompatible with life (anencephaly) or leading to disability (spina bifida) . Therefore, for women of childbearing age taking COCs and planning to become pregnant soon, folate intake should be started well before conception to achieve sufficient folate levels during neural tube formation. Considering that 21.1% of women become pregnant after the first cycle of taking COCs, and 45.7% after the third, there was a need to create COCs containing a stable form of folate. Studies have shown that after 24 weeks of daily dosing, Yarina Plus slow release maintains plasma folate concentrations above baseline for 20 weeks in a significant proportion of women [11].

The use of the drugs Yarina Plus and Jess Plus as contraception in women of the childbearing period receiving therapy for severe forms of acne with systemic isotretinoin (Acnecutane) throughout the entire period of treatment (on average 8 months) and 2 months after its completion is especially valuable [3].

The minimum course of acne treatment with both Jess and Jess Plus is 6 months. If contraception is necessary, as well as to maintain skin, hair and nails in optimal condition, in accordance with WHO recommendations (2009), the drug can be used for a long time [2].

Before prescribing Jess Plus to a woman with acne as a basic anti-acne agent, it is necessary to ensure that there are no contraindications both from the gynecological status and from other organs and systems.

A gynecologist-endocrinologist and a dermatocosmetologist can recommend acne therapy with COCs with antiandrogenic effects. The dynamics of skin lesions during treatment are monitored by a dermatocosmetologist, and the absence of contraindications for prescribing a woman a COC with an antiandrogenic effect is assessed by a gynecologist-endocrinologist. Before starting therapy, as well as after its completion, a gynecological examination, examination of the mammary glands and a cytological examination of the epithelium of the vaginal part of the cervix are necessary to exclude morphological signs characterizing dysplastic processes (Papanicolaou smear - PAP smear). If AGA is suspected, an assessment of the blood hormonal profile (LH, FSH, estradiol, progesterone, testosterone, prolactin and DHEA sulfate), ultrasound of the pelvic organs and adrenal glands, and X-ray/tomography of the skull may be required (Fig. 2).

Figure 2. Algorithm for interaction between specialists in the treatment of acne in women. It is necessary to explain to the woman the regimen of taking the drug, the features of contraception during the 1st month of use, possible side effects during the first two cycles, as well as what the patient should do if she misses taking the next pill depending on the day of the cycle [2].

We observed 47 women aged 16–32 years with acne of II–III severity. In 19 women, the pathological process was localized only on the face, in 28 - on the face and torso. COC Jess (43 women) and COC Jess Plus (4) were prescribed on a continuous basis (the first tablet - on the 1st day of menstruation and over the next 23 days - 1 tablet, followed by placebo tablets (Jes) for 4 days. or 4 tablets with Metafolin (Jess Plus) for a period of 6 months. By the end of the 3rd month, in the whole group there was a regression of non-inflammatory elements by 46%, inflammatory elements by 55% compared to the initial indicators. The level of sebum secretion decreased by 31%. By the end of the treatment period, non-inflammatory and inflammatory elements regressed by 85 and 89%, respectively, compared to the initial level; sebum secretion decreased by 56%. A state of clinical cure was achieved in 22 (46.8%) patients (Fig. 3 , 4),

Figure 3. Patient Zh., 20 years old. a - before treatment; b — after 6 months of therapy with COC Jess.

Figure 4. Patient Sh., 22 years old. a - before treatment; b — after 5 months of therapy with COC Jess Plus. significant improvement - in 18 (38.3%), improvement - in 7 (14.9%). Excellent tolerability of therapy was noted; no side effects were recorded. An examination by a gynecologist after 6 months did not reveal any pathology in any woman. PAP smear after 6 months of therapy was negative in all patients. Of particular note is the decrease in the patients’ body weight by 1.7±0.3 kg by the end of the 6th month of therapy, which is explained by the antimineralocorticoid effect of the drugs. During the course of treatment, most women noted an improvement in the condition of the hair on their heads, a decrease in the growth of vellus hair in areas “inherent” to men, as well as the disappearance of emotional lability.

Based on our own many years of experience in treating acne with anti-androgenic drugs, it should be concluded that the clinically significant anti-acne effect of COCs appears no earlier than 3-4 months of therapy, which dictates the advisability of prescribing external anti-acne agents to some patients, in particular, the anti-acne line of medicinal cosmetics [2], on during the first half of the course of therapy (first 2-3 months).

Thus, joint observation of patients with acne by a gynecologist-endocrinologist and a dermatocosmetologist made it possible to develop a new direction for taking COCs Jess and Jess Plus:

1. Elimination of acne and seborrhea.

2. Improved hair condition.

3. Improving skin quality indicators (increasing hydration and skin turgor due to estrogen stimulation of hyaluronic acid synthesis; reducing the level of moisture evaporation from the surface of the epidermis).

4. Suspension of hypertrichosis (decrease in the Ferriman-Gallwey index).

5. Normalization of eating behavior.

6. Prevents fluid retention in the body (unlike other COCs).

7. Stabilization or reduction of body weight.

8. Improvement in general well-being (more than 85%).

9. Relief of psycho-emotional lability.

10. Photoprotection of epidermal structures due to metafolin.

[]Calcium levomefolate (Metafolin) is registered and supplied by Merck & Cie, Switzerland. Metafolin is a registered trademark of Merck KGaA, Germany.

How quickly does the drug work?

If acne appears while using Jess, this can happen in the first or third months of use, while the body is still adjusting to new hormones. Positive dynamics can be noted no earlier than the beginning of the second menstrual cycle, then the situation may improve until the rashes are completely eliminated.

The result of “Jesa” for acne occurs with the start of using the medicine (contraceptive effect), but positive changes in a woman’s appearance will be noticeable a little later, after the second or third menstruation.

After stopping taking Jess, acne may return as the previous hormonal levels are restored. That is, the drug helps against acne only with constant use.

Minuses

Like any other hormonal contraceptive, Jess acne pills have certain disadvantages that cannot be avoided. These are negative effects after taking a medicine that may not occur to everyone. They usually appear in the first months of using the drug, while the body gets used to the new regime:

Dizziness.
Headache.
Change of mood.
Irritability.
Decreased sexual desire.

When do side effects go away? This happens differently for all people, but, as a rule, after the second or third menstruation, the woman’s well-being completely returns to normal and no unpleasant symptoms appear in the future.

In any situation, hormonal contraceptives should be used under the supervision of the medical specialist who prescribed them. And if you have any questions or doubts, you should contact him for advice.

Herpes in women during pregnancy: how to avoid complications

For a pregnant woman, HS poses the greatest danger if it is primary, i.e. had not been detected in the body before. The virus can be transmitted through the placenta and mainly affects the nervous tissue of the fetus. The degree of harm to the fetus from this virus depends on the duration of infection and the dose. With primary HS, infection of up to 80% of fetuses is observed. If the viral disease is recurrent, approximately 7-10% of the fetuses become infected. HH at its primary manifestation increases the incidence of miscarriage in the first trimester in more than 50% of cases, in the second – by 30%, and in the third – by 10-15%.i

In approximately 50% of cases, infection of the expectant mother with the herpes virus leads to the birth of a premature baby. Unfortunately, in some cases, severe damage to newborns by this virus is observed, which manifests itself in the form of herpetic meningoencephalitis and sepsis, as well as organic and dysfunctional disorders such as cerebral palsy, epilepsy, heart defects, deafness and retinal pathologies.

Given the high prevalence of HH and the high risks for newborns, early and accurate diagnosis of the disease is necessary for all pregnant women. For these purposes, PCR (polymerase chain reaction), enzyme-linked immunosorbent assay (ELISA) and DIF (direct immunofluorescence method) are used.

Starting and skipping pills

If a woman has not used any other contraceptive drugs in the past month, then the use of “Jess” begins on the first day of menstruation. It is allowed to take the medication on the second day of the menstrual cycle, but in this situation it is already necessary to additionally use condoms during the first seven days of taking the medicine from the first package.

If an inactive pill was missed, this point can be ignored. However, they must be thrown away to avoid accidentally prolonging their use.

If the delay in taking the active tablet is less than twelve hours, then the protection is not reduced. A woman should take the missed tablet as quickly as possible and take the next one as usual.

If the delay is more than twelve hours, then contraceptive protection may be slightly reduced. The more pills a woman has missed and the closer the skip is to the inactive phase, the greater the likelihood of pregnancy. In this case, you must be guided by the following rules:

the use of the medication should never be interrupted for more than four days;
To achieve a stable contraceptive effect, approximately seven days of continuous use of the drug are required.

Jess

Use during pregnancy and breastfeeding

Jess® is not prescribed during pregnancy and breastfeeding.
If pregnancy is detected while taking Jess®, the drug should be discontinued immediately. However, extensive epidemiological studies have not shown any increased risk of developmental defects in children born to women who received sex steroids (including combined oral contraceptives) before pregnancy, or teratogenic effects when sex steroids were taken inadvertently in early pregnancy.

Existing data on the results of taking the drug Jess® during pregnancy are limited, which does not allow us to draw any conclusions about the effect of the drug on the course of pregnancy, the health of the newborn and the fetus. There are currently no significant epidemiological data on the drug Jess®.

Taking combined oral contraceptives may reduce the amount of breast milk and change its composition, so their use is not recommended until you stop breastfeeding. Small amounts of sex steroids and/or their metabolites may be excreted in breast milk.

Use for liver dysfunction

The drug is contraindicated in:

liver failure and severe liver disease (until liver tests return to normal);
liver tumors (benign or malignant) currently or in history.

Use for renal impairment

The drug is contraindicated in severe renal failure, acute renal failure.

special instructions

If any of the conditions/risk factors listed below currently exist, the potential risks and expected benefits of combined oral contraceptives should be carefully weighed on an individual basis and discussed with the woman before she decides to start taking the drug. If any of these conditions or risk factors worsen, intensify, or appear for the first time, a woman should consult her doctor, who may decide whether to discontinue the drug.

Diseases of the cardiovascular system

The results of epidemiological studies indicate a relationship between the use of combined oral contraceptives and an increased incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disease) when taking combined oral contraceptives. These diseases are rare.

The risk of developing venous thromboembolism (VTE) is greatest in the first year of taking such drugs. An increased risk is present after initial use of oral contraceptives or resumption of use of the same or different combined oral contraceptives (after a dosing interval of 4 weeks or more). Data from a large prospective study involving 3 groups of patients suggest that this increased risk is predominantly present during the first 3 months.

The overall risk of VTE in patients taking low-dose combined oral contraceptives (<50 mcg ethinyl estradiol) is 2-3 times higher than in non-pregnant patients not taking combined oral contraceptives, however, this risk remains lower than the risk VTE during pregnancy and childbirth. VTE can be life-threatening or fatal (in 1-2% of cases).

VTE, manifested as deep vein thrombosis or pulmonary embolism, can occur with the use of any combined oral contraceptives.

It is extremely rare that when using combined oral contraceptives, thrombosis of other blood vessels occurs, for example, hepatic, mesenteric, renal, cerebral veins and arteries or retinal vessels. There is no consensus regarding the relationship between the occurrence of these events and the use of combined oral contraceptives. Symptoms of deep vein thrombosis (DVT) include: unilateral swelling of the lower extremity or along a vein in the leg, pain or discomfort in the leg only when standing or walking, localized warmth in the affected leg, redness or discoloration of the skin on the leg.

Symptoms of pulmonary embolism (PE) include: difficulty or rapid breathing; sudden cough, incl. with hemoptysis; sharp pain in the chest, which may intensify with deep inspiration; sense of anxiety; severe dizziness; fast or irregular heartbeat. Some of these symptoms (eg, shortness of breath, cough) are nonspecific and may be misinterpreted as symptoms of other more or less severe events (eg, respiratory tract infection).

Arterial thromboembolism can lead to stroke, vascular occlusion, or myocardial infarction. Symptoms of a stroke: sudden weakness or loss of sensation in the face, arm or leg, especially on one side of the body, sudden confusion, problems with speech and comprehension; sudden unilateral or bilateral vision loss; sudden disturbance in gait, dizziness, loss of balance or coordination; sudden, severe or prolonged headache for no apparent reason; loss of consciousness or fainting with or without an epileptic seizure. Other signs of vascular occlusion: sudden pain, swelling and slight blue discoloration of the extremities, acute abdomen.

Symptoms of myocardial infarction include: pain, discomfort, pressure, heaviness, a feeling of squeezing or fullness in the chest, arm, or behind the breastbone; discomfort radiating to the back, cheekbone, larynx, arm, stomach; cold sweat, nausea, vomiting or dizziness, severe weakness, anxiety or shortness of breath; fast or irregular heartbeat.

Arterial thromboembolism can be life-threatening or fatal.

The risk of developing thrombosis (venous and/or arterial) and thromboembolism increases:

with age;
in smokers (with increasing number of cigarettes or increasing age, the risk increases, especially in women over 35 years of age);
for obesity (BMI more than 30 kg/m2);
if there is a family history (for example, venous or arterial thromboembolism ever occurred in close relatives or parents at a relatively young age). In the case of a hereditary or acquired predisposition, the woman should be examined by an appropriate specialist to decide on the possibility of taking combined oral contraceptives;
with prolonged immobilization, major surgery, any leg surgery or major trauma. In these situations, it is advisable to stop using combined oral contraceptives (in the case of planned surgery, at least four weeks before it) and not resume use for two weeks after the end of immobilization;
with dyslipoproteinemia;
with arterial hypertension;
for migraines;
for diseases of the heart valves;
with atrial fibrillation.

The possible role of varicose veins and superficial thrombophlebitis in the development of venous thromboembolism remains controversial. The increased risk of thromboembolism in the postpartum period should be taken into account.

Peripheral circulatory disorders may also occur in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell anemia.

An increase in the frequency and severity of migraine during use of combined oral contraceptives (which may precede cerebrovascular events) may be grounds for immediate discontinuation of these drugs.

Biochemical indicators indicating a hereditary or acquired predisposition to venous or arterial thrombosis include: resistance to activated protein C, hyperhomocysteinemia, antithrombin III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).

When assessing the risk-benefit ratio, it should be taken into account that adequate treatment of the relevant condition may reduce the associated risk of thrombosis. It should also be taken into account that the risk of thrombosis and thromboembolism during pregnancy is higher than when taking low-dose oral contraceptives (<50 mcg ethinyl estradiol).

Tumors

The most significant risk factor for developing cervical cancer is persistent human papillomavirus infection. There are reports of a slight increase in the risk of developing cervical cancer with long-term use of combined oral contraceptives. The connection with the use of combined oral contraceptives has not been proven. Controversy remains regarding the extent to which these findings are related to screening for cervical pathology or to sexual behavior (lower use of barrier methods of contraception).

A meta-analysis of 54 epidemiological studies found that there is a slightly increased relative risk of developing breast cancer diagnosed in women currently taking combined oral contraceptives (relative risk 1.24). The increased risk gradually disappears within 10 years of stopping these drugs. Because breast cancer is rare in women under 40 years of age, the increase in breast cancer diagnoses in women currently or recently taking combined oral contraceptives is small relative to the overall risk of breast cancer. The observed increased risk may be due to earlier diagnosis of breast cancer in women using combined oral contraceptives, the biological effects of oral contraceptives, or a combination of both factors. Women who have used combined oral contraceptives have clinically less severe breast cancer than women who have never used them.

In rare cases, during the use of combined oral contraceptives, the development of benign, and in extremely rare cases, malignant liver tumors, which in some cases led to life-threatening intra-abdominal bleeding, was observed. If severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding occur, this should be taken into account when making a differential diagnosis.

Tumors can be life-threatening or fatal.

Other states

Clinical studies have shown no effect of drospirenone on serum potassium concentrations in patients with mild to moderate renal failure. There is a theoretical risk of developing hyperkalemia in patients with impaired renal function with an initial potassium concentration at ULN who are simultaneously taking medications that lead to potassium retention in the body. However, in women at increased risk of developing hyperkalemia, it is recommended that plasma potassium concentrations be determined during the first cycle of taking Jess®.

Women with hypertriglyceridemia (or a family history of this condition) may have an increased risk of developing pancreatitis while taking combined oral contraceptives.

Although slight increases in blood pressure have been described in many women taking combined oral contraceptives, clinically significant increases have rarely been reported. However, if a persistent, clinically significant increase in blood pressure develops while taking combined oral contraceptives, these drugs should be discontinued and treatment of arterial hypertension should be initiated. Taking combined oral contraceptives can be continued if normal blood pressure values are achieved with antihypertensive therapy.

The following conditions have been reported to develop or worsen both during pregnancy and while taking combined oral contraceptives, but their relationship with taking combined oral contraceptives has not been proven: jaundice and/or pruritus associated with cholestasis; formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham's chorea; herpes during pregnancy; hearing loss associated with otosclerosis. Cases of Crohn's disease and ulcerative colitis have also been described during the use of combined oral contraceptives.

In women with hereditary forms of angioedema, exogenous estrogens may cause or worsen symptoms of angioedema.

Acute or chronic liver dysfunction may require discontinuation of combined oral contraceptives until liver function tests return to normal. Recurrent cholestatic jaundice, which develops for the first time during pregnancy or previous use of sex hormones, requires discontinuation of combined oral contraceptives.

Although combined oral contraceptives may have an effect on insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using low-dose combined oral contraceptives (<50 mcg ethinyl estradiol). However, women with diabetes should be closely monitored while taking combined oral contraceptives.

Chloasma can sometimes develop, especially in women with a history of pregnancy chloasma. Women prone to chloasma should avoid prolonged exposure to the sun and ultraviolet radiation while taking combined oral contraceptives.

Laboratory tests

Taking combined oral contraceptives may affect the results of some laboratory tests, including liver, kidney, thyroid, adrenal function, plasma transport protein levels, carbohydrate metabolism, coagulation and fibrinolysis parameters. Changes usually do not go beyond normal values.

Drospirenone increases plasma renin and aldosterone activity, which is associated with its antimineralocorticoid effect.

Medical examinations

Before starting or resuming the use of the drug Jess®, it is necessary to familiarize yourself with the woman’s life history, family history, conduct a thorough general medical examination (including measuring blood pressure, heart rate, determining BMI) and gynecological examination (including examination of the mammary glands and cytological examination of cervical mucus), and exclude pregnancy. The scope of additional studies and the frequency of follow-up examinations are determined individually. Typically, follow-up examinations should be carried out at least once a year.

The woman should be warned that combined oral contraceptives do not protect against HIV infection (AIDS) and other sexually transmitted diseases.

Reduced efficiency

The effectiveness of combined oral contraceptives may be reduced if active tablets (light pink) are missed, vomiting and diarrhea occur, or due to drug interactions.

Poor control of the menstrual cycle

While taking combined oral contraceptives, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use. Therefore, any irregular bleeding should be assessed only after an adaptation period of approximately three cycles.

If irregular bleeding recurs or develops after previous regular cycles, careful evaluation should be performed to rule out malignancy or pregnancy.

Some women may not develop withdrawal bleeding during a break from taking the active tablets (light pink). If combined oral contraceptives are taken as directed, the woman is unlikely to be pregnant. However, if combined oral contraceptives have not been taken regularly before or if there are no consecutive withdrawal bleeds, pregnancy should be ruled out before continuing to take the drug.

Impact on the ability to drive vehicles and operate machinery

Not found.

How to use "Jess"

There are twenty-eight tablets in total in the package. The blister contains graphic marks that indicate the order in which they should be taken. It is necessary to take 1 tablet per day at the same time with water.

Doctors advise using oral contraceptives in the morning. Of all the tablets, twenty-four are considered active, and four are considered inactive, that is, a placebo (a substance without obvious medicinal properties). They are necessary so as not to get lost in the order of using this drug.

Each subsequent package should be started only after the previous one has been completed, without allowing breaks. Bleeding similar to menstruation may occur while using inactive tablets. How long does it take for Jess Plus to have an effect on acne? Positive dynamics can be noted seven days after the start of therapy, after which time the contraceptive effect appears.

Restrictions

The use of the drug "Jess" is contraindicated in the following situations:

Myocardial infarction (ischemic heart disease, which occurs with the appearance of ischemic necrosis).
Angina pectoris (a disease characterized by an unpleasant sensation in the chest).
Thrombosis (formation of clots inside blood vessels).
Damage to cerebral vessels.
Diabetes mellitus (an endocrine disease characterized by improper absorption of glucose).
High blood pressure.
Pancreatitis (inflammation of the pancreas).
Migraine (a neurological disease characterized by pain in the head).
Damage to the liver and kidneys.
Lactation.
Smoking over the age of thirty-five.
Malignant tumors of the genital organs or mammary glands.

Before using the medication, it is necessary to exclude conditions in the body that limit its use. To do this, it is enough to donate blood for analysis.

Is it possible to smoke while using the drug?

Smoking while taking the medication increases the risk of arterial thromboembolism. This is a condition characterized by loss or confusion of consciousness, as well as severe weakness or fainting. It can cause death. The occurrence of thromboembolism is higher the more cigarettes a representative of the fair half smokes per day.

The risk group includes women over thirty-five years of age who smoke more than one pack of cigarettes per day. For women under this age or who smoke a small amount of cigarettes, there is no direct contraindication in this regard. If acne appears from “Jess”, what should you do?

Alcohol and Jess

When taking the drug and alcoholic drinks, women are afraid that the effect of the pills may be reduced. Medical experts note that alcohol in small dosages does not reduce the contraceptive effect of the drug.

But when using oral tablets, it is forbidden to take excessive amounts of strong drinks. In case of alcohol poisoning, it is necessary to additionally use other contraceptives.

Responses

On the Internet you can find many reviews about “Jess” for acne. As a rule, representatives of the fair half evaluate this oral contraceptive positively. But there are also reviews of birth control pills from people for whom this medication was not suitable.

As a result, the oral contraceptive caused adverse reactions, including nausea, malaise, and migraines. In such a situation, doctors tried to find another, more suitable medication for women.

According to doctors' reviews of Jess for acne, it is known that the drug has a beneficial effect on the body. Opinions about the drug on various sites also say that the drug helps get rid of acne and improves skin condition.

After stopping taking the oral contraceptive, the body’s condition does not worsen, so many women respond well to this drug.

Reviews of “Jess” for acne are usually positive; adverse reactions when using it occur very rarely. Representatives of the fair half also have a positive opinion about the contraceptive. The ease of use of Jess Plus and its effectiveness are noted. But in rare situations, nausea, headaches, and mood swings still appear.

Jess® Plus (Yaz® Plus)

If any of the conditions, diseases and risk factors listed below currently exist, the potential risks and expected benefits of using Jess® Plus should be carefully weighed in each individual case and discussed with the woman before she decides to start taking of this drug.

For disorders of the cardiovascular system

The results of epidemiological studies indicate a relationship between the use of COCs and an increased incidence of venous and arterial thrombosis and thromboembolism (such as deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders) when taking COCs. These diseases are rare.

The risk of developing VTE is greatest in the first year of taking COCs. An increased risk is present after initial use of a COC or resumption of use of the same or a different COC (after a dosing interval of 4 weeks or more). Data from a large prospective study involving 3 groups of patients indicate that this increased risk is predominantly present during the first 3 months.

The overall risk of VTE in women taking low-dose COCs (<0.05 mg ethinyl estradiol) is two to three times higher than in non-pregnant patients not taking COCs, although this risk remains lower than the risk of VTE during pregnancy and childbirth.

VTE can be life-threatening or lead to death (in 1-2% of cases).

VTE, manifested as deep vein thrombosis or pulmonary embolism, can occur with the use of any COC.

It is extremely rare when using COCs that thrombosis of other blood vessels occurs, for example, hepatic, mesenteric, renal, cerebral veins and arteries or retinal vessels.

Symptoms of deep vein thrombosis: unilateral swelling of the lower extremity or along a vein in the lower extremity, pain or discomfort in the lower extremity only in an upright position or when walking, local increase in temperature in the affected lower extremity, redness or discoloration of the skin on the lower extremity.

Symptoms of pulmonary embolism: difficulty or rapid breathing; sudden cough, including with hemoptysis; sharp pain in the chest, which may intensify with deep inspiration; sense of anxiety; severe dizziness; fast or irregular heartbeat. Some of these symptoms (eg, shortness of breath, cough) are nonspecific and may be misinterpreted as signs of other more common and less severe conditions (eg, respiratory tract infection).

Arterial thromboembolism can lead to stroke, vascular occlusion, or myocardial infarction. Symptoms of a stroke include: sudden weakness or loss of sensation in the face or limbs, especially on one side of the body, sudden confusion, problems with speech and comprehension; sudden unilateral or bilateral vision loss; sudden disturbance in gait, dizziness, loss of balance or coordination; sudden, severe or prolonged headache for no apparent reason; loss of consciousness or fainting with or without convulsions. Other signs of vascular occlusion: sudden pain, swelling and slight cyanosis of the extremities, “acute” abdomen.

Symptoms of myocardial infarction: pain, discomfort, pressure, heaviness, a feeling of compression or fullness in the chest or behind the sternum, radiating to the back, jaw, left upper limb, epigastric region; cold sweat, nausea, vomiting or dizziness, severe weakness, anxiety or shortness of breath; fast or irregular heartbeat. Arterial thromboembolism can be life-threatening or fatal.

In women with a combination of several risk factors or high severity of one of them (for example, complicated heart valve diseases, uncontrolled arterial hypertension, extensive surgical interventions with prolonged immobilization, etc.), the possibility of their mutual reinforcement should be considered. In such cases, the total value of the existing risk factors increases. In this case, taking Jess® Plus is contraindicated (see section “Contraindications”),

The risk of developing thrombosis (venous and/or arterial), thromboembolism or cerebrovascular disorders increases:

- with age;

- in smokers (with an increase in the number of cigarettes or an increase in age, the risk increases, especially in women over 35 years old);

in the presence of:

— obesity (body mass index more than 30 kg/m2);

- family history (for example, venous or arterial thromboembolism ever in close relatives or parents under the age of 50 years). In the case of a hereditary or acquired predisposition, the woman should be examined by an appropriate specialist to decide on the possibility of taking the drug Jess® Plus;

- prolonged immobilization, extensive surgery, any operation on the lower extremities or major trauma. In these situations, it is necessary to stop taking Jess® Plus (in the case of a planned operation at least four weeks before it) and not to resume taking it for two weeks after the end of immobilization. Temporary immobilization (eg, air travel lasting more than 4 hours) may also be a risk factor for the development of venous thromboembolism, especially in the presence of other risk factors;

- dislipoproteinemia;

- arterial hypertension;

- migraine;

— diseases of the heart valves;

- atrial fibrillation.

The use of any combined hormonal contraceptives increases the risk of developing VTE.

The use of drugs containing levonorgestrel, norgestimate or norethisterone carries the lowest risk of developing VTE. The use of other drugs, such as Jess® Plus, can lead to a twofold increase in risk. The choice to use a COC with a higher risk of developing VTE can only be made after consultation with the patient to ensure that she fully understands the risk of VTE associated with the use of Jess® Plus, the effect of the drug on her existing risk factors and that The risk of developing VTE is greatest during the first year of using the drug. According to some data, an increased risk is observed when COC use is resumed after a break of 4 weeks or more.

About 9-12 out of 10,000 women taking COCs containing drospirenone may develop VTE within a year, compared with about 6 in 10,000 women for COCs containing levonorgestrel.

The possible role of varicose veins and superficial thrombophlebitis in the development of VTE remains controversial.

The increased risk of thromboembolism in the postpartum period should be taken into account. Peripheral circulatory disorders may also occur in diabetes mellitus, systemic lupus erythematosus, hemolytic uremic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell anemia.

An increase in the frequency and severity of migraine during use of the drug Jess® Plus (which may precede cerebrovascular disorders) is grounds for immediate discontinuation of the drug.

When assessing the risk-benefit ratio, it should be taken into account that adequate treatment of the relevant condition can reduce the associated risk of thrombosis. It should also be taken into account that the risk of thrombosis and thromboembolism during pregnancy is higher than when taking low-dose oral contraceptives (<0.05 mg ethinyl estradiol).

Tumors

The most significant risk factor for developing cervical cancer is persistent human papillomavirus infection. There are reports of a slight increase in the risk of developing cervical cancer with long-term use of COCs. However, the connection with taking COCs has not been proven. The possibility of the relationship of these data with screening for cervical diseases and with characteristics of sexual behavior (less frequent use of barrier methods of contraception) is discussed.

A meta-analysis of 54 epidemiological studies showed that there is a slightly increased relative risk of developing breast cancer diagnosed in women currently taking COCs (relative risk 1.24). The increased risk gradually disappears within 10 years of stopping these drugs. Because breast cancer is rare in women under 40 years of age, the increase in breast cancer diagnoses in current or recent COC users is small relative to the overall risk of breast cancer. Its connection with COC use has not been proven. The observed increased risk may be a consequence of careful monitoring and earlier diagnosis of breast cancer in women using COCs, the biological effects of sex hormones, or a combination of both factors. Women who have ever used COCs are diagnosed with earlier stages of breast cancer than women who have never used them.

In rare cases, during the use of COCs, the development of benign, and in extremely rare cases, malignant liver tumors, which in some patients led to life-threatening intra-abdominal bleeding, was observed. If severe abdominal pain, liver enlargement, or signs of intra-abdominal bleeding occur, this should be taken into account when making a differential diagnosis.

Other states

Clinical studies have shown no effect of drospirenone on the concentration of potassium in the blood plasma of patients with mild to moderate renal failure. However, in patients with impaired renal function and an initial potassium concentration at the upper limit of normal, the risk of developing hyperkalemia cannot be excluded while taking medications that lead to potassium retention in the body.

Women with hypertriglyceridemia (or a family history of this condition) may have an increased risk of developing pancreatitis while taking COCs. Although slight increases in blood pressure (BP) have been described in many women taking COCs, clinically significant increases have rarely been reported. However, if a persistent clinically significant increase in blood pressure develops while taking Jess® Plus, this drug should be discontinued and treatment of arterial hypertension should be started. The drug can be continued if normal blood pressure values are achieved with the help of antihypertensive therapy.

The following conditions have been reported to develop or worsen both during pregnancy and while taking COCs, but their relationship with COC use has not been proven: jaundice and/or pruritus associated with cholestasis; formation of gallstones; porphyria; systemic lupus erythematosus; hemolytic-uremic syndrome; chorea; herpes during pregnancy; hearing loss associated with otosclerosis. Cases of worsening the course of endogenous depression, epilepsy, Crohn's disease and ulcerative colitis during the use of COCs have also been described.

In women with hereditary forms of angioedema, exogenous estrogens may cause or worsen symptoms of angioedema.

Acute or chronic liver dysfunction may require discontinuation of Jess® Plus until liver function tests return to normal. Recurrence of cholestatic jaundice, which developed for the first time during a previous pregnancy or previous use of sex hormones, requires discontinuation of the drug Jess® Plus.

Although COCs may have an effect on insulin resistance and glucose tolerance, there is usually no need to adjust the dose of hypoglycemic drugs in patients with diabetes mellitus using low-dose oral contraceptives (<0.05 mg ethinyl estradiol). However, women with diabetes mellitus should be carefully monitored while taking COCs.

Chloasma can sometimes develop, especially in women with a history of chloasma during pregnancy. Women with a tendency to chloasma while taking Jess® Plus should avoid prolonged exposure to the sun and exposure to ultraviolet radiation.

Folates may mask vitamin B12 deficiency.

Laboratory tests

Taking Jess® Plus may affect the results of some laboratory tests, including indicators of liver, kidney, thyroid, adrenal function, the concentration of transport proteins in plasma, indicators of carbohydrate metabolism, parameters of blood coagulation and fibrinolysis. Changes usually do not go beyond normal values. Drospirenone increases plasma renin activity and aldosterone concentrations, which is associated with its antimineralocorticoid effect.

Reduced efficiency

The contraceptive effectiveness of Jess® Plus may be reduced in the following cases: when pink pills are missed, gastrointestinal disorders while taking pink pills, or as a result of drug interactions.

Frequency and severity of menstrual-like bleeding

While taking Jess® Plus during the first few months, irregular (acyclic) bleeding from the vagina may be observed (“spotting” spotting and/or “breakthrough” uterine bleeding). You should use hygiene products and continue taking your pills as usual. Any irregular bleeding should be assessed after an adaptation period of approximately 3 cycles of dosing.

If irregular bleeding recurs or develops after previous regular cycles, careful evaluation should be performed to rule out malignancy or pregnancy.

No regular menstrual bleeding

Some women may not develop bleeding while taking the supplementary light orange tablets; “ooContraindications” and “Use with caution”;

— Local compaction in the mammary gland;

- Concomitant use of other medications (see also section “Interaction with other medications and other types of interactions”);

- If prolonged immobility is expected (for example, a cast is applied to the lower limb), hospitalization or surgery is planned (at least 4 weeks before the proposed operation);

- Unusually heavy bleeding from the vagina;

- Missed a pill in the first week of taking the package and had sexual intercourse seven days or less before;

— Absence of regular menstrual-like bleeding two times in a row or suspicion of pregnancy (you should not start taking pills from the next package before consulting your doctor).

You should stop taking the tablets and consult your doctor immediately if there are possible signs of thrombosis, myocardial infarction or stroke: unusual cough; unusually severe pain behind the sternum, radiating to the left arm; unexpected shortness of breath, unusual, severe and prolonged headache or migraine attack; partial or complete loss of vision or double vision; slurred speech; sudden changes in hearing, smell, or taste; dizziness or fainting; weakness or loss of sensation in any part of the body; severe abdominal pain; severe pain in the lower limb or sudden swelling of any of the lower limbs.