dienogest/estradiol valerate

Action and Spectrum

Actions and Spectrum: 

dienogest/estradiol valerate is a combination medication used as an oral contraceptive, commonly known as a birth control pill. It contains two active ingredients: dienogest, a progestin, and estradiol valerate, an estrogen.  

• dienogest: dienogest is a synthetic progestin, which means it is an artificial hormone that mimics the action of the natural hormone progesterone. Progestins play a crucial role in hormonal contraception. They help prevent pregnancy by suppressing ovulation, thickening cervical mucus, and altering the endometrial lining, making it less receptive to a fertilized egg. 

Actions: 

• Inhibition of ovulation: By suppressing ovulation, dienogest prevents the release of eggs from the ovaries during the menstrual cycle, reducing the chance of fertilization. 
• Thickening of cervical mucus: This makes it harder for sperm to enter uterus and reach the egg, reducing the likelihood of fertilization. 
• Changes in the endometrial lining: dienogest causes changes in the uterine lining, making it less suitable for the implantation of a fertilized egg, which can help prevent pregnancy. 

estradiol Valerate: estradiol valerate is an estrogen, precisely the biologically active form of estrogen known as 17β-estradiol. Estrogens are female sex hormones crucial in regulating the menstrual cycle and maintaining reproductive health. 

Actions: 

• Support of regular menstrual cycle: estradiol helps regulate the menstrual cycle and also preparing the uterine lining for possible pregnancy and ensuring it is shed during the menstruation if pregnancy does not occur. 
• Counteracting side effects of progestin: The addition of estradiol in the combination helps mitigate some potential side effects associated with progestin-only contraceptives, such as irregular bleeding or spotting. 

Spectrum:  

Combining dienogest and estradiol valerate provides a comprehensive and highly effective contraception. When taken correctly, these pills offer reliable protection against pregnancy by inhibiting ovulation, thickening cervical mucus, and changing the endometrial lining. The spectrum of action primarily focuses on preventing pregnancy and does not protect against the sexually transmitted infections. It is essential to take these pills as a healthcare professional prescribes to ensure their effectiveness.

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Headache 

Migraines 

1-10% 

Breast pain, discomfort/tenderness  

Nausea 

Vomiting  

Metrorrhagia  

Irregular menstruation  

Weight gain  

Acne  

<1% 

Depression 

Jaundice or cholestasis 

Venous thromboembolism 

Gallbladder disease 

Black Box Warning

Black Box Warning: 

• Heart Attack and Stroke: Hormonal contraceptives have been associated with an elevated risk of the heart attack and stroke, particularly in women with pre-existing cardiovascular conditions. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Pregnancy: This medication is contraindicated during pregnancy, intended for contraceptive use and not pregnancy maintenance. If pregnancy is suspected while taking this medication, it should be discontinued immediately. 
• Breastfeeding: dienogest/estradiol valerate should generally not be used while breastfeeding. Estrogens and progestins can pass into breast milk and may affect the nursing infant. 
• History of blood clots: Women with a history of blood clots or known clotting disorders should avoid using this medication, as it may increase the risk of blood clots. 
• History of heart attack or stroke: Women who have experienced a heart attack or stroke should not use dienogest/estradiol valerate due to the increased risk of cardiovascular events. 
• Liver disease: Severe liver disease or a history of liver tumors may contraindicate the use of this medication, as it can affect liver function. 
• Hypersensitivity to the active ingredients: Individuals with known hypersensitivity or allergy to dienogest, estradiol valerate, or other medication components should avoid its use. 
• Undiagnosed vaginal bleeding: If a woman experiences unexplained vaginal bleeding, the cause should be determined before starting this medication. 
• Hormone-sensitive cancers: Women with hormone-sensitive cancers, such as certain types of breast or endometrial cancer, should not use this medication, as it contains hormones that could stimulate tumor growth. 
• Severe migraines with aura: Women with a history of severe migraines with visual disturbances (aura) may be at an increased risk of stroke when using hormonal contraceptives and should avoid this medication. 
• Pancreatitis: A history of pancreatitis may contraindicate dienogest/estradiol valerate use. 

Caution 

• Age: The safety and efficacy of this medication have not been established in women over 35 years old who smoke. Smoking enhances the risk of severe cardiovascular side effects when combined with hormonal contraceptives. 
• Smoking: Women who smoke are at an enhanced risk of severe cardiovascular side effects, like blood clots, heart attack, and stroke, when using hormonal contraceptives. It is advisable to quit smoking before starting this medication. 
• Hypertension (high blood pressure): This medication can cause an increase in blood pressure. It should be used cautiously in women with hypertension, and blood pressure should be monitored regularly. 
• Diabetes: Women with diabetes may experience changes in blood glucose levels while using hormonal contraceptives. Regular monitoring of blood glucose is recommended for those with diabetes. 
• Dyslipidemia (abnormal lipid levels): Hormonal contraceptives may affect lipid metabolism. It is essential to monitor lipid levels in women with dyslipidemia. 
• Obesity: Obesity may increase the risk of severe side effects associated with hormonal contraceptives. Healthcare providers should consider alternative contraceptive methods for obese women. 
• Gallbladder disease: Hormonal contraceptives may worsen existing gallbladder disease or increase the risk of developing gallbladder problems. Women with a history of gallbladder disease should be closely monitored. 
• Cholestatic jaundice: This medication may cause cholestatic jaundice, a condition which is characterized by yellowing of the skin and eyes. It should be used cautiously in women with a history of cholestatic jaundice. 
• History of depression: Hormonal contraceptives may affect mood and exacerbate depression in some women. Those with a history of depression should be closely monitored while using this medication. 
• Epilepsy: Women with epilepsy should be closely monitored while using hormonal contraceptives, as they may sometimes affect seizure control. 
• Hepatic (liver) impairment: dienogest/estradiol valerate should be used cautiously in women with mild to moderate liver impairment. It is generally contraindicated in severe liver disease. 
• Interaction with other medications: Some medications, including certain anticonvulsants, antifungals, antibiotics, and herbal supplements, may interact with hormonal contraceptives.

Pregnancy / Lactation

Pregnancy consideration:  

AU TGA pregnancy category: B3
US FDA pregnancy category: Not assigned 

Lactation:   

Excreted into human milk: Yes. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• <b>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: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

dienogest/estradiol valerate is a combination medication used as an oral contraceptive and hormone therapy. dienogest, a synthetic progestin, binds to progesterone receptors, inhibiting ovulation, thickening cervical mucus, and altering the endometrial lining to prevent fertilization and implantation. estradiol valerate, an estrogen, complements the contraceptive effect by supporting a regular menstrual cycle and counteracting some progestin-related side effects.

The combination provides effective contraception, regulates menstrual cycles, and may be used to treat dysmenorrhea, premenstrual syndrome, endometriosis, and polycystic ovary syndrome. Its pharmacology involves modulating hormone receptors and the hormonal balance to prevent pregnancy and manage various gynecological conditions. 

Pharmacodynamics: 

Mechanism of action: The action of dienogest/estradiol valerate is based on the combined effects of its two active ingredients: dienogest, a progestin, and estradiol valerate, an estrogen. Together, they work to prevent pregnancy and regulate the menstrual cycle.  

dienogest (Progestin): dienogest is a synthetic progestin, which means it is an artificial hormone miming the action of natural progesterone. Its primary mechanism of action as a contraceptive includes the following: 

• Inhibition of ovulation: dienogest suppresses the secretion of hormones responsible for stimulating the release of eggs (ovulation) from the ovaries. Preventing ovulation reduces the chance of an egg being available for fertilization. 
• Thickening of cervical mucus: dienogest causes the cervical mucus to become thicker and less hospitable to sperm. This impedes the movement of sperm through the cervix and reduces the likelihood of sperm reaching and fertilizing an egg. 
• Changes in the endometrial lining: dienogest alters the endometrial lining of the uterus, making it lesser receptive to the implantation of the fertilized egg. This further prevents pregnancy by reducing the likelihood of successful embryo implantation. 

estradiol Valerate (Estrogen): estradiol valerate is a synthetic form of estrogen, the biologically active form known as 17β-estradiol. Its primary role in this combination medication is to complement the actions of dienogest and provide additional benefits: 

• Support of regular menstrual cycle: estradiol valerate helps regulate the menstrual cycle, promoting the development and shedding of the uterine lining (endometrium) during each menstrual period. 
• Mitigation of progestin-related side effects: Adding estradiol valerate helps counteract some side effects of progestin-only contraceptives, such as irregular bleeding or spotting. 

Overall, this medication’s combined effects of dienogest and estradiol valerate offer a comprehensive contraceptive effect by inhibiting ovulation, altering the cervical mucus, and modifying the endometrial lining to prevent pregnancy.  

Pharmacokinetics: 

Absorption 

dienogest/estradiol valerate is administered orally as a tablet. After ingestion, the active ingredients are absorbed from the gastrointestinal tract into the bloodstream. estradiol valerate is hydrolyzed (converted) into its biologically active form, estradiol, during absorption. The absorption process varies between individuals and may be influenced by food intake and gastrointestinal motility. 

Distribution 

Once absorbed, dienogest and estradiol are transported via the bloodstream to various tissues and organs throughout the body. Both hormones bind to specific proteins in the blood, such as sex hormone-binding globulin (SHBG) and albumin. Their respective binding affinities influence the distribution of these hormones to these proteins. 

Metabolism 

dienogest and estradiol undergo extensive metabolism in the liver, primarily through hepatic (liver) enzymatic processes. dienogest is metabolized into several active and inactive metabolites. estradiol is metabolized through hydroxylation and conjugation reactions to form various metabolites, including estrone and estriol. These metabolites are then excreted in the urine and feces. 

Elimination and Excretion 

The metabolites of dienogest, estradiol, and the parent compounds, are eliminated primarily through the kidneys via urine and, to a lesser extent, through the feces. The excretion of these hormones and their metabolites occurs over time, with each drug having its specific elimination half-life, which is the time it takes for half of the drug to be removed from the body. 

Adminstartion

Administration: 

dienogest/estradiol valerate combination medication is typically available as an oral contraceptive through tablets. The tablets are taken by mouth, and following the prescribed dosing schedule provided by your healthcare professional is essential.  

• Start the medication: Follow your healthcare provider’s instructions on when to take the pills. It is common to start on the first day of your menstrual cycle (Day 1 Start), but other options like Sunday Start or Quick Start are also available, depending on your healthcare provider’s recommendations. 
• Daily administration: Take one tablet of dienogest/estradiol valerate daily, at around the same time each day. Maintaining a regular dosing schedule is crucial to ensure the contraceptive’s effectiveness. 
• Duration of use: Continue taking the pills for the prescribed duration, typically 21 or 28 days, depending on the product. Some packages include seven “reminder” pills that do not contain active ingredients. These reminder pills help maintain a regular dosing schedule and should be taken even during menstruation. 
• Menstrual cycle and withdrawal bleeding: During the 21-day pill pack, you will usually experience withdrawal bleeding (similar to a menstrual period) during the week of taking the reminder pills. If you use a 28-day pack with active pills throughout, you may experience lighter and more regular bleeding during the reminder pill week. 
• Missed pills: If you got to miss a pill, follow the instructions provided with the drug or consult your healthcare provider. The effectiveness of the contraceptive may be compromised if pills are missed or taken incorrectly. 
• Storage: Store the medication at RT (room temperature), away from direct sunlight and moisture.  
• Additional contraceptive protection: It’s important to note that dienogest/estradiol valerate is not effective in preventing sexually transmitted infections. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: dienogest/estradiol valerate 

Pronounced: [ dye-EN-oh-jest-and-ESS-tra-DYE-ole ] 

Why do we use dienogest/estradiol valerate? 

dienogest/estradiol valerate is a combination medication used primarily for the following purposes: 

• Contraception: dienogest/estradiol valerate is an oral contraceptive, often called a birth control pill.  
• Menstrual cycle regulation: This medication can help regulate menstrual cycles and make them more predictable. It is often prescribed for women with irregular or heavy periods. 
• Treatment of dysmenorrhea: Dysmenorrhea is a medical term for painful menstrual periods. dienogest/estradiol valerate has been shown to reduce menstrual pain and discomfort in some women. 
• Treatment of premenstrual syndrome (PMS): Some women experience physical and emotional symptoms before their periods, collectively known as premenstrual syndrome. This medication may help alleviate these symptoms in some instances. 
• Hormone replacement therapy (HRT): In some postmenopausal women, hormone replacement therapy may alleviate menopausal symptoms like hot flashes, night sweats, and vaginal dryness.  
• Endometriosis: It is when the tissue lining the uterus grows outside uterus, leading to pain and other symptoms. dienogest/estradiol valerate may be used to manage the symptoms of endometriosis. 
• Polycystic ovary syndrome (PCOS): PCOS is a hormonal disorder that can lead to irregular periods, excessive hair growth, and other symptoms. This medication may regulate periods and manage certain aspects of PCOS.