drospirenone/ethinyl estradiol/levomefolate

Action and Spectrum

Actions and Spectrum: 

drospirenone/ethinyl estradiol/levomefolate is a combined oral contraceptive (COC) medication for pregnancy prevention. It combines three active ingredients: drospirenone, ethinyl estradiol, and levomefolate. 

• drospirenone: drospirenone is a progestin (synthetic progesterone) with antiandrogenic and mild antimineralocorticoid properties. It primarily works by inhibiting ovulation (release of an egg from the ovary) and altering the cervical mucus to make it less permeable to sperm, thus preventing fertilization. It also affects the endometrium (lining of the uterus) to reduce the likelihood of implantation. 
• ethinyl estradiol: ethinyl estradiol is a synthetic estrogen. It acts by suppressing the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland, thereby preventing the development and release of eggs from the ovaries. It also helps to stabilize the endometrium, making it less likely for a fertilized egg to implant. 
• levomefolate: levomefolate is the active form of folic acid, a B vitamin essential for cell growth and replication. In the context of this medication, levomefolate is included to provide additional supplementation of folic acid, which is essential for women of reproductive age to help reduce the risk of neural tube defects in case of an unplanned pregnancy. 

The spectrum of activity of drospirenone/ethinyl estradiol/levomefolate is primarily a contraceptive. It is effective in preventing pregnancy when used correctly and consistently. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Migraine/headache (10.7%) 

Premenstrual syndrome (13.2%) 

1-10% 

Menstrual irregularities (4.7%) 

Abdominal pain /tenderness (2.3%) 

Breast pain/tenderness (8.3%) 

Nausea (4.5%)  

Frequency not defined 

Hypersensitivity 

Chloasma 

Toxic skin eruption 

Hypertension 

Hyperkalemia 

Gallbladder disease 

Uterine leiomyoma 

Black Box Warning

Black box warning: 

Cigarette smoking is associated with an increased risk of cardiovascular disease. Smoking is a significant risk factor for cardiovascular conditions, including heart disease, stroke, and blood clots. 

Regarding the use of oral contraceptives (birth control pills) and smoking, it is generally advised that women over 35 who smoke should not use oral contraceptives.

This recommendation is based on the increased risk of serious cardiovascular adverse effects associated with the combination of smoking and oral contraceptive use. 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: It is contraindicated in individuals with known hypersensitivity or allergic reactions to any of the medication’s active ingredients or other components. 
• Thromboembolic disorders: This medication is contraindicated in individuals with a history of or current thromboembolic disorders, such as deep vein thrombosis (DVT), pulmonary embolism (PE), or arterial thromboembolism. These conditions are associated with an increased risk of blood clots, and the estrogen component of the medication can further increase this risk. 
• History of cardiovascular disease: Individuals with a history of certain cardiovascular conditions, such as coronary artery disease, heart attack, stroke, or angina, may have an increased risk of cardiovascular events with this medication. Therefore, it may be contraindicated in these cases. 
• Liver disease: Severe liver disease or liver tumors are contraindications for the use of this medication due to the potential for impaired drug metabolism and increased risk of liver-related complications. 
• Renal impairment: Severe renal impairment or acute renal failure may be a contraindication for this medication, as renal function plays a role in eliminating specific components. 

Caution: 

• Cardiovascular risk: Although the medication is generally considered safe, there is a slightly increased risk of cardiovascular events (such as heart attack, stroke, and blood clots) associated with combined oral contraceptives. This risk may be higher in women who smoke, are over 35, or have other risk factors for cardiovascular disease. Close monitoring and consideration of alternative contraceptive options may be necessary for individuals with existing cardiovascular risk factors. 
• Venous and arterial thromboembolism: A small increased risk of venous and arterial thromboembolic events is associated with combined oral contraceptives. Individuals with a personal or family history of blood clotting disorders, obesity, prolonged immobilization, or a history of thromboembolism should be closely monitored. 
• Hypertension: The use of combined oral contraceptives has been associated with an increase in blood pressure. Women with uncontrolled or poorly controlled hypertension should be carefully monitored while taking this medication. 
• Liver function: Combined oral contraceptives may affect liver function. Individuals with a history of liver disease, jaundice, cholestasis, or hepatic adenoma should be closely monitored, and the use of this medication should be carefully evaluated. 
• Migraines: Women with a history of migraines, especially with aura, may have an increased risk of stroke while using combined oral contraceptives. The benefits and risks should be carefully assessed in these cases. 
• Hyperlipidemia: Combined oral contraceptives have been associated with changes in lipid profiles. Regular monitoring of lipid levels is recommended, particularly in individuals with existing hyperlipidemia or a family history of lipid disorders. 
• Depression: Some studies have suggested a potential association between combined oral contraceptive use and an increased risk of depression. Individuals with a history of depression should be monitored for mood changes or depressive symptoms. 

Pregnancy / Lactation

Pregnancy consideration: It is primarily used as a combined oral contraceptive to prevent pregnancy; therefore, it is not intended for use during pregnancy 

Lactation: Excretion of the drug in human breast milk is known 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

drospirenone/ethinyl estradiol/levomefolate is a combined oral contraceptive medication that contains three active ingredients: drospirenone, ethinyl estradiol, and levomefolate. Each of these components contributes to the pharmacological effects of the medication. 

• drospirenone: drospirenone is a synthetic progestin with antiandrogenic and mild antimineralocorticoid properties. It acts primarily by binding to the progesterone and mineralocorticoid receptors. drospirenone inhibits ovulation (release of an egg from the ovary) through suppression of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) release from the pituitary gland. It also alters the cervical mucus, making it less permeable to sperm, reducing the likelihood of fertilization. Additionally, drospirenone affects the endometrium by inhibiting its growth, resulting in a thinner lining that is less suitable for implantation. 
• ethinyl estradiol: ethinyl estradiol is a synthetic estrogen that binds to estrogen receptors in target tissues. It primarily works by inhibiting FSH and LH’s release, thereby preventing eggs’ development and release from the ovaries. ethinyl estradiol also helps stabilize the endometrium, reducing the chances of implantation. 
• levomefolate: levomefolate is the active form of folic acid, a B vitamin necessary for various cellular processes. In the context of this medication, levomefolate is included to provide additional supplementation of folic acid, which is essential for women of reproductive age to help reduce the risk of neural tube defects in case of an unplanned pregnancy. 

By combining these three components, drospirenone/ethinyl estradiol/levomefolate provides contraceptive effects by inhibiting ovulation, altering the cervical mucus, and modifying the endometrium. levomefolate supplements folic acid to support overall reproductive health. 

Pharmacodynamics: 

The pharmacodynamics of drospirenone/ethinyl estradiol/levomefolate involves the actions and effects of its active ingredients on the body. Here is a breakdown of the pharmacodynamics of each component: 

• drospirenone: drospirenone is a progestin with antiandrogenic and mild antimineralocorticoid properties. It acts on progesterone receptors and exhibits similar effects to natural progesterone. Its primary pharmacodynamic actions include: 
• Inhibition of ovulation: drospirenone suppresses the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland, thereby preventing the development and release of eggs from the ovaries. 
• Modification of cervical mucus: drospirenone alters the cervical mucus, making it thicker and less permeable to sperm, reducing the likelihood of fertilization. 
• Endometrial effects: drospirenone affects the endometrium, leading to a thinner and less receptive lining that is less suitable for implantation. 

1. ethinyl estradiol: ethinyl estradiol is a synthetic estrogen that acts on estrogen receptors in target tissues. Its pharmacodynamic effects include: 

• Inhibition of FSH and LH release: ethinyl estradiol suppresses the release of FSH and LH from the pituitary gland, preventing the development and release of eggs from the ovaries. 
• Stabilization of the endometrium: ethinyl estradiol helps maintain a stable endometrium, reducing the chances of implantation. 

1. levomefolate: levomefolate is the active form of folic acid, a B vitamin essential for cell growth and replication. Its pharmacodynamic action involves providing supplemental folic acid, essential for overall reproductive health, including preventing neural tube defects during pregnancy. 

Combined, these pharmacodynamic effects of drospirenone, ethinyl estradiol, and levomefolate contribute to the contraceptive actions of the medication, preventing pregnancy by inhibiting ovulation, altering the cervical mucus, and modifying the endometrium. 

Pharmacokinetics: 

Absorption 

• drospirenone and ethinyl estradiol: After oral administration, drospirenone and ethinyl estradiol are rapidly and well absorbed from the gastrointestinal tract. 
• levomefolate: levomefolate is also absorbed from the gastrointestinal tract after oral administration. 

Distribution 

• drospirenone and ethinyl estradiol: Both drospirenone and ethinyl estradiol are highly protein-bound in the bloodstream. They bind primarily to serum albumin and sex hormone-binding globulin (SHBG). 
• levomefolate: levomefolate is not extensively bound to plasma proteins and is distributed throughout the body. 

Metabolism 

• drospirenone: drospirenone is extensively metabolized in the liver via oxidative metabolism and reduction. The significant drospirenone metabolites include 4,5-dihydrodrospirenone-3-sulfate, 4,5-dihydrodrospirenone-3-glucuronide, and their acetylated derivatives. 
• ethinyl estradiol: ethinyl estradiol undergoes extensive metabolism in the liver. It is primarily metabolized by hydroxylation at various positions on the aromatic ring. The primary metabolites include 2-hydroxyethinyl estradiol and 2-methoxyethinyl estradiol. 
• levomefolate: levomefolate is converted to active forms of folate in the body through the folate metabolic pathway. 

Elimination and Excretion 

• drospirenone and ethinyl estradiol: Both drospirenone and ethinyl estradiol and their metabolites are excreted primarily in the urine and feces. The elimination half-lives of drospirenone and ethinyl estradiol are approximately 30-40 and 20-30, respectively. 
• levomefolate: levomefolate and its metabolites are primarily excreted in the urine. 

Adminstartion

Administration: 

• Timing: The medication is usually taken once daily. It is important to take the tablet simultaneously every day to maintain consistent hormone levels in the body. 
• Duration: drospirenone/ethinyl estradiol/levomefolate is typically taken in 28-day cycles. The pack contains 28 active hormonal tablets and, in some formulations, placebo or iron-containing tablets. It is important to take the tablets in the prescribed order, following the arrows or instructions on the blister pack. 
• Swallowing: The tablet should be swallowed whole with water. Do not crush, chew, or break the tablet unless specifically instructed by your healthcare professional or the medication instructions. 
• Follow-up: It is important to attend regular follow-up visits with your healthcare professional to monitor your response to the medication, discuss any concerns or side effects, and ensure its continued effectiveness. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: drospirenone/ethinyl estradiol/levomefolate 

Why do we use drospirenone/ethinyl estradiol/levomefolate? 

drospirenone/ethinyl estradiol/levomefolate is a combination medication primarily used as an oral contraceptive to prevent pregnancy. Combining these active ingredients provides contraceptive effects by inhibiting ovulation, altering the cervical mucus, and modifying the endometrium. 

In addition to contraception, drospirenone/ethinyl estradiol/levomefolate may also have the following uses: 

• Iron supplementation: Some drospirenone/ethinyl estradiol/levomefolate formulations may contain iron tablets. These iron tablets are a supplement to help prevent iron deficiency anemia, which can be a concern for menstruating individuals. 
• Folate supplementation: levomefolate, the active form of folic acid, is included in drospirenone/ethinyl estradiol/levomefolate to supplement folic acid. This helps support overall reproductive health and reduce the risk of neural tube defects in case of an unplanned pregnancy.