Drospirenone Ethinyl Estradiol is a combination of two medicines. These drugs are primarily used as oral contraceptives.

Drospirenone Ethinyl estradiol Uses:

• Acne vulgaris (Gianvi, Loryna, Nikki, Vestura, Yaz):

  • Only if the patient is open to using an oral contraceptive for birth control is it utilised for the treatment of moderate acne vulgaris in women 14 years of age and older.

• Contraception:

  • It is very advised for preventing pregnancy.

• Premenstrual dysphoric disorder (Gianvi, Yaz):

  • It is appropriate for women who choose to use an oral contraceptive for contraception in a variety of situations, such as premenstrual dysphoric disorder (PMDD).

• Off Label Use of Ethinyl estradiol and drospirenone in Adults:

  • Abnormal uterine bleeding
  • Dysmenorrhea (pain during menstruation)
  • Hirsutism ( excessive facial hair)
  • Menstrual bleeding (menorrhagia)
  • Pain associated with endometriosis
  • Polycystic ovary syndrome (PCOS) in women with menstrual irregularities and hirsutism/acne

Drospirenone Ethinyl estradiol Dose in Adults

The treatment dose of drospirenone Ethinyl estradiol for Acne vulgaris:

• Oral therapy for females:

  • Refer to dosing for contraception.

Drospirenone Ethinylestradiol Dose in the treatment of Premenstrual Dysphoric Disorder:

• Oral dose for females:

  • Refer to dosing for contraception.

Drospirenone Ethinyl estradiol Dosage for Contraception:

• Female:

  • One oral pill, once every 24 hours.

• Schedule 1 (Sunday starter):

  • The first Sunday following the start of the menstrual cycle is when the dose starts.
  • Take the first tablet the same day, if your period begins on a Sunday.
  • A second method of birth control should be utilised with a Sunday start until the end of the first week of continuous administration.

• Schedule 2 (Day 1 starter):

  • On the first day of the menstrual cycle, the dose is started with 1 tablet every 24 hours.

• Switching from a different contraceptive:

  • Oral contraceptive:

    • Start the new oral contraceptive on the same day as the old one would have been taken.

  • Transdermal patch/vaginal ring/injection:

    • Begin the day before the subsequent dose was to be given.

  • Intra-uterine device or implant:

    • Begin the day after the gadget is removed.

  • Use after childbirth (in women who are not breast-feeding) or after second-trimester abortion:

    • Beginning therapy should happen four weeks after delivery.
    • If menstrual cycles have not yet resumed, pregnancy should be checked out before treatment begins, and a second means of contraception (non-hormonal, such as barrier techniques), should be used until after the first week of continuous administration.

• Missed or late doses:

  • If a dose is skipped or taken recently (within 24 hours of when it should have been taken) (one to two since dose should have been taken):

    • Take the medication as soon as you can. Maintain the same regimen for the remaining dosages (even if that means 2 doses on the same day).

  • If two doses are missed back-to-back (within 48 hours of the due date),:

    • Any other missed doses should be disregarded, and the most recent missing dose should be taken as soon as feasible.
  • Use another method of birth control until hormonal tablets have been taken for 7 days in a row. Subsequent doses should be given at the prescribed time (even if that means taking 2 doses on the same day).
  • When using hormonal (active) tablets, bypass the hormone-free interval by finishing the current pack before beginning a new one if doses were missed during the final seven days of the pack (days 15 to 21 of a 28-day pack, for example).
  • In the event that a new pack cannot be begun right away, a backup method of contraception must be used until hormone tablets from a fresh pack have been taken for 7 days in a row.
  • In such circumstances, take into account using emergency contraception (refer to guidelines for details).

Dose in Children

Refer to adult dosing.

Pregnancy Risk Factor: X

• It is not recommended for pregnant women.
• Combination oral contraceptives can be helpful in preventing pregnancy
• If pregnancy is confirmed, the treatment should be stopped.
• If given early in pregnancy, combined hormonal contraceptives are not associated with any adverse effects on the fetus or mother.
• According to the manufacturer, combined oral contraceptive medications should not be taken until one month after birth if women aren't willing to breastfeed or after a second-trimester miscarriage or abortion.
• Because of the higher incidence of postpartum vein thromboembolism, combination hormonal contraceptives shouldn't be used for at least 21 days after delivery.
• Postpartum day 42 has a lower risk of venous embolism than the baseline.
• Women should not take combination hormonal contraceptives for more than 21 days after delivery. This is dependent on their individual risk factors for Venous embolism.

Breastfeeding: Ethinyl estradiol or drospirenone

• Breast milk contains Drospirenone.
• Less than 0.02% of the maternal dose is present in the concentration. As a result, babies only receive a maximum of 3 mg of drospirenone per day.
• The newborn has not been shown to experience side effects from hormonal contraceptives combined with breastfeeding mothers.
• Contraceptives in estrogen can cause a decrease in milk production. The manufacturer recommends that contraception be used until the child is weaned.
• Breastfeeding women should not take combination hormonal contraceptives within 21 days of delivery. This is because there is a higher risk of venous embolism (VTE), postpartum.
• Postpartum day 42 reduces the risk to baseline.
• Depending on their individual risk factors (such as age >=35, prior VTEs, thrombophilia, or immobility), peripartum cardiomyopathy (BMI >=30kg/m2, postpartum haemorrhage, smoking, and peripartum cardiomyopathy), and other factors, women can use combination hormonal contraceptives between 21 and 42 days after giving birth.
• When starting treatment for breastfeeding women, it is important to consider the risks and benefits of combined hormonal oral contraceptives (Curtis 2016,b).

Renal disease dose adjustment of drospirenone Ethinyl estradiol:

Contraindicated in patients with renal dysfunction.

Liver disease dose adjustment of drospirenone ethinyl estradiol:

Contraindicated in patients with renal dysfunction.

Adverse effects of drospirenone ethinyl estradiol:

The complications described may not specifically be related to drospirenone/ethinyl estradiol and are based on reports for other oral contraceptives in the same pharmacologic class.

Adverse reactions of drospirenone Ethinyl estradiol:

• Cardiovascular:

  • Arterial Thromboembolism
  • Cerebral Thrombosis
  • Hypertension
  • Local Thrombophlebitis
  • Mesenteric Thrombosis
  • Myocardial Infarction
  • Pulmonary Embolism
  • Retinal Thrombosis

• Central Nervous System:

  • Cerebral Hemorrhage

• Gastrointestinal:

  • Gallbladder Disease

• Hepatic:

  • Hepatic Adenoma
  • Hepatic Neoplasm (Benign)

Side effects of drospirenone Ethinyl estradiol (Less common):

• Cardiovascular:

  • Edema
  • Worsening Of Varicose Veins

• Central Nervous System:

  • Depression
  • Exacerbation Of Tics
  • Migraine

• Dermatologic:

  • Allergic Skin Rash
  • Chloasma

• Endocrine & Metabolic:

  • Amenorrhea
  • Breast Changes (Breast Hypertrophy, Breast Secretion, Breast Tenderness, Mastalgia)
  • Decreased Serum Folate Level
  • Exacerbation Of Porphyria
  • Menstrual Disease (Menstrual Flow Changes), Weight Changes

• Gastrointestinal:

  • Abdominal Cramps
  • Bloating
  • Carbohydrate Intolerance
  • Nausea
  • Vomiting

• Genitourinary:

  • Breakthrough Bleeding
  • Cervical Ectropion
  • Cervical Erosion
  • Change In Cervical Secretions
  • Decreased Lactation (With Use Immediately Postpartum)
  • Infertility (Temporary)
  • Spotting
  • Vulvovaginal Candidiasis

• Hepatic:

  • Cholestatic Jaundice

• Hypersensitivity:

  • Anaphylaxis/ Anaphylactoid Reaction (Including Angioedema, Circulatory Shock, Respiratory Collapse, and Urticaria)

• Neuromuscular & Skeletal:

  • Exacerbation Of Systemic Lupus Erythematosus

• Ophthalmic:

  • Change In Corneal Curvature (Steepening)
  • Contact Lens Intolerance

Side effects of Drospirenone Ethinyl estradiol in which the association is not confirmed:

• Cardiovascular:

  • Budd-Chiari Syndrome

• Central Nervous System:

  • Dizziness
  • Headache
  • Nervousness

• Dermatologic:

  • Acne Vulgaris
  • Erythema Multiforme
  • Erythema Nodosum
  • Loss Of Scalp Hair

• Endocrine & Metabolic:

  • Change In Libido
  • Hirsutism
  • Porphyria
  • Premenstrual Syndrome

• Gastrointestinal:

  • Change In Appetite
  • Colitis
  • Pancreatitis

• Genitourinary:

  • Cystitis-Like Syndrome
  • Dysmenorrhea
  • Vaginitis

• Hematologic & Oncologic:

  • Hemolytic-Uremic Syndrome
  • Hemorrhagic Eruption

• Ophthalmic:

  • Cataract
  • Optic Neuritis (With Or Without Partial Or Complete Loss Of Vision)

• Renal:

  • Renal Insufficiency

Contraindication to Drospirenone Ethinyl estradiol:

These include:

• Insufficiency of the adrenals
• Breast cancer and other estrogen- or progestin-sensitive forms of cancer
• Liver disease or tumors (benign and malignant)
• pregnancy
• Renal impairment
• Undiagnosed abnormal uterine bleeding
• concurrent use of hepatitis C drug combinations containing ombitasvir/ paritaprevir/ ritonavir with or without dasabuvir

It is also not recommended for women who are at high risk of venous or arterial thrombotic disease such as:

• Cerebrovascular Disease
• Coronary artery disease
• Diabetes mellitus and vascular disease
• Deep vein thrombosis, or pulmonary embolism.
• Hypercoagulopathies (familial and acquired)
• Hypertension uncontrolled
• Headaches with focused neurological symptoms (also known as migraine headaches) can happen if you are older than 35.
• Thrombogenic valvular diseases and arrhythmias (eg subacute bacteria endocarditis or atrial fibrillation).
• Women and smokers >35 years

It is contraindicated according to the Canadian Guidelines.

• Patients who are hypersensitive to ethinyl estradiol, drospirenone, or any other ingredient in this formulation. Women who have a hereditary or acquired propensity for venous or arterial thrombosis, such as those with hyperhomocysteinemia, activated protein C (APC) resistance, Factor V Leiden mutation, protein C deficiency, protein S deficiency, protein S deficiency, protein S deficiency
• Myocardial Infarction (current and/or history of);
• Persistent hypertension >=160mm Hg Systolic or >=100mm Hg Diastolic
• Prodromal of an thrombotic event, such as transient Ischemic Attack, Angina Pectoris (current or historical)
• Major surgery is associated with a higher incidence of postoperative hemoglobinemia
• Long-term immobilization
• severe dyslipoproteinemia
• Pancreatitis is associated with higher triglyceride levels
• Steroid-induced jaundice/cholestatic jaundice/antenatal transaminitis
• Ocular lesions caused by ophthalmic vessels disease (partial or complete vision loss, visual field defects)
• combination therapy with ombitasvir, paritaprevir, ritonavir (with or without dasabuvir)

Warnings and precautions

• Breast cancer
  • In women with significant family histories of the disease or susceptibility genes, combination hormonal contraceptives have not been found to lower the incidence of breast cancer (BRCA1, BRCA2).
  • Women with a history or breast cancer are at risk for poor prognosis if they use combined oral contraceptives, as breast cancer can be hormone-sensitive.
  • Women with a history or breast cancer are not advised to use oral contraception.

• Cervical cancer:

  • Combination hormonal contraceptives have been shown to slightly increase the risk of developing cervical cancer. However, there is limited evidence and it could be associated with other risk factors.
  • Oral contraception can adversely affect the prognosis for cervical cancer.
  • Women who have not started treatment for cervical carcinoma can receive combination hormonal contraceptives.

• Chloasma

  • The triggers for chloasma are pregnancy, sun exposure and combination hormonal contraceptives.
  • Treatment should be avoided for women who are susceptible to chloasma, or have additional risk factors.

• Cholestasis:

  • Cholestasis is more likely to occur if a woman has cholestasis while pregnant or has previously used an oral contraceptive.

• Hyperkalemia:

  • Drospirenone can result in hyperkalemia due to anti-mineralocorticoid activity
  • Patients with hyperkalemia-predisposing conditions (such as liver dysfunction, renal insufficiency, or adrenal insufficiency) are advised not to use it.
  • When taking drugs that can raise serum potassium levels, exercise caution.

• The Lipid Effects

  • Combination hormonal contraceptives can cause hypertriglyceridemia.
  • Patients with hypertriglyceridemia and a family history are at greater risk for pancreatitis when they use combination hormonal contraceptives.
  • Women with uncontrolled dyslipidemia should consider alternative contraception options.

• Retinal vascular embolism:

  • It should be stopped right away if there is an unexplained loss of vision, proptosis, papilledema, or retinal vascular lesion. As soon as feasible, a retinal vein thrombosis assessment should be carried out.

• Thromboembolic disorders

  • In the event of arterial or venous embolism, discontinue using combination hormonal contraceptives.
  • Because oral contraceptives are more likely to be used in the first year, they have a higher risk of venous embolism.
  • According to certain research, this risk rises when third- or fourth-generation progestins, large doses of ethinylestradiol, or both are used.
  • The risk of venous embolism increases when there are inherited thrombophilias, such as protein C or S deficiencies, factor V Leiden mutations, prothrombin mutations, and antithrombin deficiencies.
  • Women who smoke, are more likely to have thrombotic events than those who are older than 35, or have hypertension.
  • Women with a history or stroke should avoid using hormonal contraceptives in combination.
  • Oral hormonal contraception is not recommended for women at high risk for venous or arterial thrombotic diseases.

• Vaginal bleeding

  • Spotting or unexpected bleeding (breakthrough, intra-cyclic) might happen, particularly during the first three months of treatment.
  • It can lead to amenorrhoea.
  • To rule out pregnancy or cancer, further testing and endometrial sampling are necessary if there is any persistent or irregular vaginal bleeding.
  • After stopping combination hormonal contraceptives, amenorrhea or oligomenorrhea may develop, especially if the patient has a history of irregular periods.

• Cardiovascular disease

  • Use with caution in patients who have cardiovascular disease risk factors, such as hypertension, low levels of high-density lipoproteins, high levels of low-density lipoproteins, hypertriglyceridemia, elderly people with diabetes, smokers, and those who are diabetic or who have low levels of HDL cholesterol. Combination hormonal contraceptives may also increase the risk of cardiovascular disease.
  • Women at high risk for arterial or vein thrombosis should not use combination hormonal contraceptives.

• Depression

  • Patients with depression should be cautious. You should stop using it if you are suffering from severe depression.

• Diabetes:

  • It can lead to impaired glucose tolerance. Be cautious with DM and prediabetes.
  • If there is no history of vascular disease, there have been minimal effects on daily insulin doses and no long-term effects on diabetes control.
  • Patients with concomitant neuropathy, retinopathy or nephropathy may need to use contraceptives depending on their severity.
  • Patients with vascular disease or diabetes mellitus are not advised to take it.

• Endometrial and ovarian cancers:

  • Combination hormonal contraceptives reduce the chance of ovarian or endometrial cancer in women.
  • In women with BRCA1 or BRCA2 mutations, oral contraceptives have been found to reduce the risk of ovarian cancer.
  • Combination hormonal contraceptives are an option for women receiving treatment for ovarian or endometrial cancer.

• Gallbladder disease

  • Combining hormonal contraceptives may raise the chance of developing gallbladder illnesses or make pre-existing gallbladder issues worse.

• Hepatic adenomas

  • Hepatic tumours that can burst and cause intra-abdominal haemorrhage can develop as a result of using combination hormonal contraceptives.
  • If it is used for a prolonged period (rare), it can also be associated with hepatocellular cancer.
  • Patients with hepatic cancers should not take it.

• Hepatic impairment

  • Poor metabolism can occur in the liver.
  • The drug should be discontinued if there is jaundice or other abnormalities in the liver.
  • Preexisting liver disease is not recommended.
  • Combination hormonal contraceptives may be used in mild (compensated), but not severe (decompensated), cirrhosis.

• Hepatitis

  • They should not be used by anyone who have severe viral hepatitis, flares, or who are pregnant while using combination hormonal contraceptives.
  • Women with chronic hepatitis have not experienced an increase in the severity of cirrhotic fibris or hepatocellular malignancy if they continue to use it.
  • It has not been proven that the drug can be continued in carriers without causing liver damage or severe hepatic dysfunction.

• Hereditary angioedema:

  • Hereditary angioedema can be exacerbated by estrogens.

• Hypertension:

  • Hypertension can be caused by factors such as age, dosage, and length of use.
  • In hypertension, vascular disease, persistent blood pressure >=160 mmHg systolic and >=100mmHg diastolic, hormonal contraceptives in combination with other hormones are best avoided.
  • Women with mild hypertension (140-159 mmHg systolic, 90-99 mmHg diastolic) and women with moderate hypertension (140-159 mmHg systolic; or hypertension controlled to an acceptable level) may not be at risk.
  • When prescribing contraceptives, it is important to consider other risk factors such as smoking, age, and diabetes.
  • The manufacturer warns against the use of this drug in women who have uncontrolled hypertension.

• Migraine

  • Combination hormonal contraceptives may be used in migraines that do not have aura (including menstrual migraines).
  • It is not advised for women over 35 who get migraine headaches without or with aura or headaches with specific neurological signs.

• Transplantation of solid-organs

  • Combinations of hormonal contraceptives are not recommended for women who have had complicated organ transplants. This is because of potential complications like graft rejection/ graft failure/ cardiac allograft vasculopathy.

• Systemic lupus erythematosus (SLE):

  • Women with SLE are more likely to experience heart disease, strokes, and vein thrombosis.
  • Hormonal contraceptives shouldn't be used by SLE patients who have antiphospholipid antibodies, whether they are positive or unidentified. The higher risk of arterial and venous embolism is the reason behind this.

Monitoring parameters:

• Pregnancy status 
• Blood pressure 
• Weight (Body mass index)
• Health status changes 
• Serum potassium levels should be measured during the first treatment cycle in patients with illnesses requiring long-term therapy with drugs that can cause hyperkalemia.
• When taking potent CYP3A4 inhibitors, high-risk patients should have their serum potassium levels checked.
  Continue the dosing cycle if all doses have been taken on time and just one period was missed.

Administration of drospirenone ethinyl estradiol:

• Every day, the dose should be given at the same time, ideally right before bed or right after dinner.
• After a pregnancy has been ruled out, combined hormonal contraceptives may be started at any point in the menstrual cycle.
• Unless contraception is initiated within the first five days of monthly bleeding or the woman abstains from coitus, backup contraception should be taken for one week.
• Following a first or second trimester abortion, or within one week of it, combined hormonal contraceptives may be started.
• Unless backup contraception is initiated at the time of the surgical abortion, backup contraception is required for seven days.
• According to the manufacturer, if severe diarrhoea or vomiting develops within 3 to 4 hours of taking a pill, backup contraceptive methods may be necessary.

Mechanism of action of Drospirenone Ethinyl estradiol:

• When oral drospirenone Ethinyl esteradiol and oral drospirenone Ethinyl are combined, the hypothalamus experiences a negative feedback process that inhibits ovulation.
• This alters the normal pattern gonadotropin production of a follicle stimulating hormone (FSH), and luteinizinghormone by the anterior pituitary.
• FSH in the follicular phase and midcycle surge gonadotropins can both be inhibited.
• Oral contraceptives may also alter the vaginal tract, including the cervical mucus.
• This makes it difficult for sperm penetration, even if ovulation happens. Endometrium changes can lead to unfavorable conditions for nidation. 
• Oral contraceptives may alter how ova are transported through the fallopian tubes. Progesterone-releasing hormones can also affect sperm fertility.
• A spironolactone analogue having anti-androgenic and anti-mineralocorticoid properties is drospirenone.

Protein binding:

• Drospirenone: Serum proteins (excluding sex hormone-binding globulin and corticosteroid-binding globulin): ~97%;
• Ethinyl estradiol: ~98% to serum albumin

Metabolism:

• Drospirenone; To inactive metabolites minor metabolism hepatically via CYP3A4:
• Ethinyl estradiol; Hepatic via CYP3A4: Forms metabolites; goes through first-pass metabolism, enterohepatic circulation

Bioavailability:

• Drospirenone: ~76%;
• Ethinyl estradiol: ~40%

Half-life elimination: Terminal:

• Drospirenone: ~30 hours;
• Ethinyl estradiol: ~24 hours

Time to peak:

• 1 to 2 hours

Excretion:

• Drospirenone, Ethinyl estradiol: Urine and feces

International Brands of Ethinyl estradiol and drospirenone:

• Gianvi
• Jasmiel
• Loryna
• Nikki
• Ocella
• Syeda
• Vestura
• Yasmin 28
• YAZ
• Zarah
• MYA
• Yasmin 21
• Yasmin 28
• YAZ
• Zamine 21
• Zamine 28
• Zarah 21
• Zarah 28
• Acondro
• Cleosensa
• Convuline
• Dalyne
• Damsel
• Dileva
• Dretine
• Drosiane
• Drospera
• Drosperin
• Drospifem
• Eloine
• Elvina
• Elvinette
• Femelle
• Gveza
• Isabelle
• Jasmine
• Jasminelle
• Jastinda
• Jazz
• Jazz Plus
• Justima
• Ladonna
• Liara
• Liz
• Liza
• Lizelle
• Lucette
• Melodia
• Midiana
• Mozanglic
• Novelon
• Novelon Lite
• Palandra
• Radiance
• Rosen 28
• Rosen Gold
• Synfonia
• Taz
• Yacella
• Yadine
• Yana
• Yarina
• Yaryna
• Yasmin
• Yasmin IQ
• Yasminelle
• Yax
• Yax Femicare
• Yaz
• YAZ
• YazFlex
• Zahra

Drospirenone ethinyl estradiol Brand Names in Pakistan:

No Brands Available in Pakistan.