PlaniJens^® drospi (Tablets) Instructions for Use

Marketing Authorization Holder

Pharmasintez-Tyumen, LLC (Russia)

ATC Code

G03AA12 (Drospirenone and Ethinylestradiol)

Active Substances

Ethinylestradiol (Rec.INN registered by WHO)

Drospirenone (Rec.INN registered by WHO)

Dosage Forms

	PlaniJens® drospi	Film-coated tablets 3 mg+0.02 mg: 28 pcs., incl. 24 pcs. tablets from pink to reddish-brown and 4 pcs. white tablets.
		Film-coated tablets 3 mg+0.03 mg: 21 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets from pink to reddish-brown color, round, biconvex, containing active substances and white tablets, not containing active substances (placebo); on the cross-section, the tablet core is white or almost white.

Excipients: corn starch, lactose monohydrate, hypromellose E15, povidone K25, crospovidone, colloidal silicon dioxide, magnesium stearate.

Film coating composition: hypromellose E15, macrogol 6000, talc, magnesium carbonate hydroxide, iron oxide red dye.

28 pcs. – blister packs (PVC/aluminum foil) – cardboard blister books (1 or 3) – polypropylene film.

Film-coated tablets from light yellow to yellow color, round, biconvex; on the cross-section, the tablet core is white or almost white.

Excipients: corn starch, lactose monohydrate, hypromellose E15, povidone K25, crospovidone, colloidal silicon dioxide, magnesium stearate.

Film coating composition: hypromellose E15, macrogol 6000, talc, magnesium carbonate hydroxide, iron oxide yellow dye.

21 pcs. – blister packs (1) – cardboard blister books (1 or 3) – polypropylene film.

Clinical-Pharmacological Group

Combined hormonal contraceptive with antimineralocorticoid and antiandrogenic action

Pharmacotherapeutic Group

Sex hormones and modulators of the genital system; systemic hormonal contraceptives; progestogens and estrogens, fixed combinations

Pharmacological Action

A combined monophasic hormonal contraceptive agent. The contraceptive effect is based on the interaction of various factors, the most important of which are inhibition of ovulation and an increase in the viscosity of cervical secretion, making it impermeable to spermatozoa.

With correct use, the Pearl index (an indicator reflecting the number of pregnancies in 100 women using a contraceptive drug for one year) is less than 1. If a dose is missed or used incorrectly, the Pearl index may increase.

In therapeutic doses, Drospirenone also has antiandrogenic and weak antimineralocorticoid properties. Lacking estrogenic, glucocorticoid, and antiglucocorticoid activity, Drospirenone has a pharmacological profile similar to that of natural progesterone. Possessing antiandrogenic activity, it helps reduce sebum production and improve the clinical course in women with acne (acne vulgaris). This should be considered when choosing a contraceptive, especially for women with hormone-dependent fluid retention, as well as women with acne and seborrhea. In combination with ethinylestradiol, it improves the lipid profile and increases HDL concentration.

The use of this combination regulates menstrual-like bleeding, helping to reduce the severity of pain and the volume of menstrual-like bleeding, reducing one of the risk factors for the development of iron deficiency anemia.

Pharmacokinetics

When taken orally, Drospirenone is rapidly and almost completely absorbed. After a single oral dose, C_max in blood plasma is about 35 ng/ml, T_max in blood plasma is 1-2 hours. Bioavailability is 76-85%. Food intake does not affect the bioavailability of drospirenone. It binds to blood plasma albumin and does not bind to sex hormone-binding globulin (SHBG) or corticosteroid-binding globulin (CBG). The concentration of free drospirenone does not exceed 3-5% of the administered dose. Estradiol-induced increase in SHBG does not affect the binding of drospirenone to plasma proteins. The mean apparent V_d is 3.7±1.2 L/kg. C_ss of drospirenone in blood plasma is reached between days 7 and 14 of treatment and is approximately 60 ng/ml. A further increase in concentration is noted approximately between cycles 1 and 6 of administration, with no subsequent increase in concentration observed. It is metabolized in the liver with practically no involvement of the cytochrome P450 system. Metabolites in blood plasma are mainly represented by acidic forms of drospirenone formed by lactone ring cleavage and 4,5-dihydro-Drospirenone-3-sulfate. It is almost completely metabolized. The metabolic clearance rate is 1.5±0.2 ml/min/kg. Metabolites are excreted via the intestine and kidneys in a ratio of 1.2:1.4. T_1/2 of metabolites is about 40 hours.

When taken orally, Ethinylestradiol is rapidly and almost completely absorbed. After a single oral dose, C_max is 88-100 ng/ml, T_max is 1-2 hours. It is metabolized during absorption and during the “first pass” through the liver. The absolute bioavailability after oral administration is 60%. Concomitant food intake reduces bioavailability in approximately 25% of volunteers. Binding to plasma proteins is about 98.5%. Ethinylestradiol induces the synthesis of SHBG in the liver. The apparent V_d of ethinylestradiol is about 5 L/kg. C_ss is achieved during the second half of the administration cycle. Ethinylestradiol penetrates into breast milk in small amounts (0.02% of the administered dose). About 50-60% of ethinylestradiol undergoes presystemic conjugation in the small intestinal mucosa and liver (“first-pass” effect). The main metabolic pathway is aromatic hydroxylation, resulting in hydroxylated and methylated metabolites, both free and as conjugates with glucuronic and/or sulfuric acids. A portion of ethinylestradiol conjugated with glucuronic acid is reabsorbed in the intestine after biliary excretion (enterohepatic recirculation). It is completely metabolized (practically not excreted unchanged). The metabolic clearance rate from blood plasma is 5 ml/min/kg. Ethinylestradiol metabolites are excreted by the kidneys and via the intestine in a ratio of 4:6, T_1/2 is about 24 hours.

Indications

Contraception.

ICD codes

Dosage Regimen

Take one tablet orally at the same time every day.

Follow the blister pack order strictly. For the 28-tablet pack, take 24 active tablets followed by 4 placebo tablets. For the 21-tablet pack, take all active tablets and then have a 7-day tablet-free interval.

Start the first pack on the first day of your menstrual period. If starting after day 1, use an additional barrier method of contraception for the first 7 days of tablet-taking.

Take a missed active tablet as soon as possible, even if it means taking two tablets in one day. If you are more than 24 hours late, contraceptive protection may be reduced.

Use a barrier method of contraception for the next 7 days if you miss a tablet in the first week of the pack and had intercourse in the preceding week. If you miss any of the last 7 active tablets in a 28-tablet pack, omit the placebo tablets and start a new pack immediately.

If no withdrawal bleeding occurs in the placebo week or tablet-free interval and tablets have been taken correctly, continue with the next pack. If this happens for two consecutive cycles, rule out pregnancy.

In cases of severe vomiting or diarrhea, absorption may be impaired. Continue taking the tablets as usual, but consider this day as a missed tablet and follow the respective instructions.

If concomitant therapy with liver enzyme-inducing drugs is required, use a barrier method of contraception during and for 28 days after discontinuation of such therapy.

Adverse Reactions

Immune system disorders rarely – bronchial asthma, hypersensitivity reactions.

Nervous system disorders often – headache.

Psychiatric disorders often – depressive state; infrequently – change in libido.

Ear and labyrinth disorders rarely – hearing loss.

Cardiac disorders often – migraine; infrequently – increased blood pressure, decreased blood pressure; rarely – thromboembolism.

Gastrointestinal disorders often – nausea; infrequently – vomiting, diarrhea.

Skin and subcutaneous tissue disorders infrequently – acne, eczema, pruritus; rarely – erythema nodosum, erythema multiforme.

Reproductive system and breast disorders often – menstrual cycle disorders, acyclic bleeding, breast pain, breast tenderness, leukorrhea, candidal vulvovaginitis; infrequently – breast enlargement, vaginitis; rarely – breast discharge.

Other infrequently – fluid retention, change in body weight.

Contraindications

Thrombosis (venous and arterial) currently or in history (including deep vein thrombosis, pulmonary embolism, myocardial infarction, cerebrovascular disorders); conditions preceding thrombosis (including transient ischemic attacks, atrial fibrillation, angina pectoris) currently or in history; presence of multiple or pronounced risk factors for venous or arterial thrombosis, including complicated lesions of the heart valves, atrial fibrillation, cerebrovascular or coronary artery diseases; uncontrolled arterial hypertension, prolonged immobilization, major surgery, surgical operations on the lower limbs, extensive trauma, smoking at the age over 35 years, obesity with BMI over 30 kg/m²; hereditary or acquired predisposition to venous or arterial thrombosis, such as resistance to activated protein C (APC), antithrombin III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and the presence of antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant); migraine with focal neurological symptoms currently or in history; diabetes mellitus with diabetic angiopathy; hepatic insufficiency and severe liver diseases (until normalization of liver function tests and for 3 months after these indicators return to normal); liver tumors (benign or malignant) currently or in history; severe or acute renal failure; identified hormone-dependent malignant diseases (including of the genital organs or mammary glands) or suspicion of them; vaginal bleeding of unknown origin; pregnancy or suspicion of it; lactation period (breastfeeding); pancreatitis with severe hypertriglyceridemia currently or in history; hypersensitivity to the components of the combination.

If any of the above diseases or conditions develop for the first time while using a drug containing this combination, it should be immediately discontinued.

With caution

Risk factors for the development of thrombosis and thromboembolism: smoking, obesity with BMI less than 30 kg/m², dyslipoproteinemia, controlled arterial hypertension, migraine without focal neurological symptoms, uncomplicated heart valve defects, family history of thrombosis and thromboembolism (thrombosis, myocardial infarction or cerebrovascular accident at a young age in any of the close relatives); age over 35 years in non-smoking women.

Diseases in which peripheral circulatory disorders may be noted: diabetes mellitus without vascular complications, SLE, hemolytic-uremic syndrome, Crohn’s disease, ulcerative colitis, sickle cell anemia, superficial phlebitis.

Hereditary angioedema.

Hypertriglyceridemia;

Mild to moderate liver diseases.

Diseases that first appeared or worsened during pregnancy or against the background of previous use of sex hormones (including jaundice and/or pruritus associated with cholestasis, cholelithiasis, otosclerosis with hearing impairment, porphyria, herpes during pregnancy in history, Sydenham’s chorea, chloasma, postpartum period).

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated in women with severe liver diseases until liver function tests normalize; liver tumors (benign or malignant) currently or in history.

Use in Renal Impairment

Contraindicated in severe or acute renal failure.

Pediatric Use

The drug is indicated only after menarche.

Geriatric Use

The drug is not indicated after menopause.

Special Precautions

Before starting the use of drugs containing this combination, pregnancy should be excluded and a thorough general medical and gynecological examination is recommended, including breast examination and cytological examination of the cervix. In addition, disorders of the blood coagulation system should be excluded. In case of long-term use, preventive control examinations should be carried out at least once every 6 months.

A number of epidemiological studies have revealed an increased incidence of venous and arterial thrombosis and thromboembolism when taking COCs. The greatest risk of developing these complications exists in the first year of taking the drug (especially in the first 3 months) or resuming intake after a 4-week break. The use of any COC may be complicated by the development of venous thromboembolism (VTE), manifested as deep vein thrombosis and pulmonary embolism. The approximate frequency of VTE in women taking oral contraceptives with a low dose of estrogens (less than 50 mcg of ethinylestradiol) is up to 4 per 10,000 women per year compared to 0.5-3 per 10,000 women not using oral contraceptives.

The risk of thrombosis (venous and/or arterial) and thromboembolism increases: with age, in smokers (with an increase in the number of cigarettes smoked or increasing age, the risk further increases, especially in women over 35 years of age), in the presence of a family history (i.e., venous or arterial thromboembolism ever in close relatives or parents at a relatively young age), obesity (BMI more than 30 kg/m²); dyslipoproteinemia, arterial hypertension, heart valve diseases, atrial fibrillation; prolonged immobilization; temporary immobilization, including air travel for more than 4 hours; major surgical intervention; any surgery on the lower limbs or extensive trauma – in these situations, it is necessary to stop taking the drug; in case of planned surgery – 4 weeks before it and not to resume intake for 2 weeks after the end of immobilization.

Peripheral circulatory disorders may also be noted in diabetes mellitus, SLE, hemolytic-uremic syndrome, chronic inflammatory bowel diseases (Crohn’s disease or ulcerative colitis) and sickle cell anemia.

An increase in the frequency and severity of migraine during the use of COCs (which may precede cerebrovascular disorders) may be a reason for immediate discontinuation of these drugs.

In rare cases, the development of liver tumors has been observed against the background of COC use. In case of severe abdominal pain, liver enlargement or signs of intra-abdominal bleeding, this should be considered during differential diagnosis.

Recurrent cholestatic jaundice, which developed for the first time during pregnancy or during previous use of sex hormones, requires discontinuation of COCs.

In women with hypertriglyceridemia or a family history, the risk of developing pancreatitis increases during COC use.

Although a slight increase in blood pressure has been described in many women taking COCs, clinically significant increases have been rare. The relationship between COC use and clinically significant increases in blood pressure has not been established. However, if during COC use a persistent, clinically significant increase in blood pressure develops, it is necessary to discontinue the drug and treat arterial hypertension. COC use may be continued after consultation with a doctor if blood pressure has normalized with antihypertensive therapy.

Although COCs may affect insulin resistance and glucose tolerance, there is no need to change the therapeutic regimen in diabetic patients using COCs. Nevertheless, women with diabetes should be carefully monitored during COC use.

Women prone to chloasma during COC use should avoid prolonged sun exposure and UV radiation.

Due to the antimineralocorticoid activity of Drospirenone, it increases the concentration of renin and aldosterone in blood plasma.

During COC use, the course of endogenous depression and epilepsy may worsen.

During COC use, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use. Therefore, the assessment of any irregular bleeding is significant only after 3-4 months of contraception.

If irregular bleeding recurs or develops after previous regular cycles, a thorough examination should be carried out to exclude malignant neoplasms or pregnancy.

In some women, withdrawal bleeding may not occur during the break in taking the pills. If the COC was taken in accordance with the instructions, pregnancy is unlikely. However, if the COC was taken irregularly before, or if two consecutive withdrawal bleedings are absent, then pregnancy must be excluded before continuing the drug.

Drug Interactions

Long-term treatment with drugs that induce liver microsomal enzymes, which increases the clearance of sex hormones, can lead to a decrease in contraceptive effectiveness. Such drugs include: phenytoin, barbiturates, primidone, carbamazepine, oxcarbazepine, rifampicin, rifabutin, topiramate, felbamate, griseofulvin and preparations containing St. John’s wort.

HIV protease inhibitors (ritonavir), non-nucleoside reverse transcriptase inhibitors (nevirapine) and their combinations may also potentially affect hepatic metabolism. Maximum enzyme induction is usually achieved approximately 10 days after starting these medications but may persist for at least 4 weeks after their discontinuation. When taking drugs that affect the induction of liver microsomal enzymes concomitantly and for 28 days after their discontinuation, it is necessary to temporarily use a barrier method of contraception.

Contraceptive protection is reduced while taking antibiotics of the penicillin and tetracycline series due to their reduction of intrahepatic estrogen circulation and, as a consequence, a decrease in the concentration of ethinylestradiol. During the intake of these antibiotics and for 7 days after their discontinuation, it is necessary to additionally use a barrier method of contraception.

Since the main metabolites of drospirenone in human plasma are formed without the involvement of the cytochrome P450 system, inhibitors of this enzyme system do not affect the metabolism of drospirenone.

Oral combined estrogen-progestogen contraceptives can affect the metabolism of other drugs, leading to an increase (cyclosporine) or decrease (lamotrigine) in their plasma and tissue concentrations.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.