Safyral is a low-dose monophasic oral combined estrogen-gestagen contraceptive, which includes active tablets and supplementary vitamin tablets containing calcium levomefolate.
Indications for use
- contraception, prescribed predominantly for women suffering from the symptoms of hormone-dependent fluid retention in the body;
- contraception and treatment of a moderate form of acne (acne vulgaris);
- contraception in women with folate deficiency;
- contraception and treatment of the severe premenstrual syndrome.
Mechanism of action
Safyral contraceptive effect is mainly carried out by suppressing ovulation and increasing cervical mucus viscosity.
Drospirenone contained in the preparation has anti-aldosterone action and helps prevent hormone-dependent fluid retention, which can manifest itself in reducing body weight and decreasing the likelihood of peripheral edema. Drospirenone also has anti-androgenic activity and helps reduce acne, skin and hair oiliness. This effect of drospirenone is similar to the action of natural progesterone, produced in the female body. This should be considered when choosing a contraceptive, especially for women with hormone-dependent fluid retention, as well as women with acne and seborrhea. When used correctly, Perl’s index is less than 1. When missing tablets or improperly used, the Pearl index may increase.
The acid form of calcium levomefolate is identical in structure to natural L-5-methyltetrahydrofolate (L-5-methyl-THF), the main folate form contained in food. The average concentration in the blood plasma of people not using food enriched with folic acid is about 15 nmol/l.
Levomefolate, in contrast to folic acid, is a biologically active form of folate. Due to this, it is digested better than folic acid. Levomefolate is indicated for meeting the increased need and providing the necessary folate content in the body of a woman during pregnancy and breastfeeding. The introduction of calcium levomolephate into the oral contraceptive reduces the risk of a fetal neural tube defect if the woman becomes pregnant unexpectedly, immediately after the termination of contraception (or in very rare cases, with oral contraception).
Mode of application and dosage
For oral reception in the order indicated on the package. The regimen is an everyday application at about the same time, without chewing, washed down with a little water. Take in 1 pill per day, continuously, for 28 days. Intake of tablets from the next package begins immediately after the reception of the previous one. Menstruation, as a rule, begins on the 2nd-3rd day after the start of taking auxiliary tablets and may not be completed before taking the tablets from the next package.
- Hypersensitivity or intolerance to any of the drug components;
- Thrombosis including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, cerebrovascular disorders;
- Diagnosed acquired or hereditary predisposition to venous or arterial thrombosis, including resistance to activated protein C, deficiency of antithrombin III, deficiency of protein C, deficiency of protein S, hyperhomocysteinemia, antibodies to phospholipids;
- A high risk of venous or arterial thrombosis;
- Migraine with focal neurologic symptoms at present or in the medical history;
- Pancreatitis with severe hypertriglyceridemia at present or in the medical history;
- Diabetes mellitus;
- Hepatic failure and severe hepatic disorders;
- Severe and/or acute kidney failure;
- Hepatic tumors (benign or malignant) at present or in the medical history;
- Diagnosedor suggested hormone-dependent malignant neoplasms;
- Vaginal hemorrhages of unclear etiology;
- Diagnosed or suspected pregnancy;
- Breastfeeding period;
- Presence of a rare hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption.
At the very beginning of the substitution therapy, this drug may provoke bleeding and spotting, the pain of the mammary glands.
When using this drug, such adverse reactions may manifest themselves:
- anemia, anorexia, increased appetite, changes in body weight, constipation;
- irritability, depressive state, emotional instability, tachycardia, phlebitis;
- visual impairment, tinnitus, tremor, vertigo, candidal stomatitis;
- thromboembolism, arterial hypertension, varicose veins, thrombophlebitis, venous thrombosis;
- shortbreathing, abdominal pain, nausea, dyspepsia, vomiting, xerostomia;
- stones in the gallbladder, cholecystitis;
- hirsutism, alopecia, acne;
- urinary tract infection, dysmenorrhea, uterine fibroids, benign tumors in the mammary glands, uterus, cervix;
- edema, chest pain, chills;
- chloasma, purpura, erythema multiforme.
The interaction of oral contraceptives with other drugs can lead to breakthrough uterine bleeding and/or a decrease in the reliability of contraception.
Interactions, leading to a decrease in Safyral effectiveness
Influence on Hepatic Metabolism
The use of drugs that induce hepatic microsomal enzymes can lead to an increase in the sex hormones clearance. These drugs include phenytoin, barbiturates, primidone, carbamazepine, rifampicin, possibly also – oxcarbazepine, topiramate, felbamate, griseofulvin and preparations containing St. John’s Wort. HIV protease inhibitors (eg ritonavir).
Effect on intestinal hepatic recirculation
According to individual trials, some antibiotics (eg, penicillins and tetracycline) can reduce intestinal hepatic recycling of estrogens, thereby reducing the concentration of ethinyl estradiol.
During the administration of drugs affecting the hepatic microsomal enzymes, and within 28 days after their withdrawal, the barrier method of contraception should additionally be used.
During the reception of antibiotics and within 7 days after their withdrawal, the barrier contraceptive methods should additionally be applied. If the period of application of the barrier contraceptive methods ends later than the hormone-containing tablets in the package, you should skip the remaining inert tablets and start taking the drug with a new package without interruption in taking the tablets.
Interactions that reduce the effectiveness of calcium levomefolate
Effect on Folate Metabolism
Some drugs reduce the folate concentration in the blood or reduce the effectiveness of calcium levomefolate by inhibiting the enzyme dihydrofolate reductase (eg methotrexate, trimethoprim, sulfasalazine and triamterene) or by reducing the absorption of folate (eg cholestyramine) or by unknown mechanisms (eg antiepileptic drugs: carbamazepine, phenytoin, phenobarbital, primidone and valproic acid).
Effect of COC or calcium levomefolate on the activity of other drugs
COCs can affect the metabolism of other drugs, leading to an increase (eg, cyclosporine) or a decrease (eg lamotrigine) in their plasma and tissue concentrations.
Based on interaction trials, as well as studies involving female volunteers taking omeprazole, simvastatin and midazolam, it can be concluded that drospirenone at a dose of 3 mg has no influence on the metabolism of other drugs.
Folates can change the pharmacokinetics or pharmacodynamics of some drugs that affect its metabolism, such as antiepileptic drugs (phenytoin), methotrexate, or pyrimethamine, which may be accompanied by a decrease in their therapeutic effect (mainly reversible, if the dose of folate is increased). The folates appointment on the background of treatment with such drugs is recommended mainly to reduce the toxicity of the latter.
What if I miss a dose?
If you skip the contraceptive pill intake you should specify how much time is left from that moment. If no more than 12 hours have passed the contraceptive effect is maintained. The additional contraceptive methods are not required.
If more than 12 hours have passed you should pay attention to the decreased contraceptive effect. It is better to apply the skipped pill immediately. The additional contraceptive methods such as condoms or spermicides should be utilized.
If you have any problems with the digestive system and risk to vomit is high you should predominantly inform the doctor about your organism specificity. All the details about missed pills you should ask of your attending doctor or get acquainted with the instruction for use carefully.
Safyral and pregnancy
Drospirenone/ethinyl estradiol/calcium levomefolate is contraindicated during pregnancy. If pregnancy is detected during the drug, the drug should be immediately discontinued. The drug is contraindicated in the period of breastfeeding.