Ethinyl estradiol and norgestrel (Cryselle 28, Elinest) – Brands, Side effects

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Ethinyl estradiol and norgestrel (Cryselle 28, Elinest) uses dose side effects brands in pakistan

Ethinyl estradiol and norgestrel (Cryselle 28, Elinest) is a combination of two hormonal formulations containing an estrogen and a progestin. It is used primarily to prevent pregnancy.

Ethinyl estradiol and norgestrel Uses:

  • Contraception:

    • Used in the prevention of pregnancy
  • Off Label Use of Ethinyl estradiol and norgestrel in Adults:

    • Used for abnormal uterine bleeding.
    • Used for dysmenorrhea
    • Used for hirsutism
    • Used for menstrual bleeding (menorrhagia)
    • Used for pain associated with endometriosis
    • Used for polycystic ovary syndrome (PCOS) in women with menstrual irregularities and hirsutism/acne

Ethinyl estradiol and norgestrel (Cryselle 28, Elinest) Dose in Adult females:

Contraception:

  • Oral: 1 tablet once in a day.
    • Schedule 1 (Sunday starter):
      • Dose begins on the first Sunday after the onset of menstruation;
      • if the menstrual period starts on Sunday, take the first tablet that very same day.
      • With a Sunday start, an additional method of contraception should be used until after the first weak of consecutive administration.
    • Schedule 2 (Day 1 starter):
      • Dose starts on the first day of the menstrual cycle taking 1 tablet once in a day.
  • Missed or late doses:

    • If one dose is late (less than 24 hours since the dose should have been taken) or if one dose is missed (24 to <48 hours since the dose should have been taken):
      • Take the dose as soon as possible. Continue remaining doses at the usual time (even if that means 2 doses on the same day).
    • If 2 or more than 2  consecutive doses are missed (48 hours and more than 48 hours since dose should have been taken):
      • Take the most recently missed dose as soon as possible, discard any other missed doses. Continue remaining doses at the usual time (even if that means taking 2 doses on the same day);
      • use back-up contraception until hormonal pills have been taken for 7 consecutive days.
      • If doses were missed during the last week of hormonal (active) tablets (eg, days 15 to 21 of a 28-day pack), omit the hormone-free interval by finishing the current pack and starting a new pack.
      • If unable to start a new pack immediately, back up contraception is needed until hormonal pills from a new pack have been taken for 7 consecutive days.
      • Consider the use of emergency contraception in some situations (refer to guidelines for details).

 

Females: Contraception or emergency contraception:

  • Oral: See adult dosing; not to be used prior to menarche.

 

Pregnancy Risk Factor X

      • It is not recommended for pregnant women.
      • To prevent pregnancy, combination hormonal contraceptives can be used. If pregnancy does occur, treatment should be stopped.
      • Combination hormonal contraceptives are generally not associated with any adverse effects on the fetus or mother if used inadvertently early in pregnancy.
      • Manufacturers advise that women who have chosen not to breastfeed should not start combination hormonal contraceptives until 4 to 6 weeks after birth.
      • Combination hormonal contraceptives should be stopped in women 21 days after delivery due to increased risk of venous embolism (VTE).
      • Postpartum day 42 sees a decrease in the risk to baseline.
      • Combination hormonal contraceptives should be used in women 21 to 42 days after birth. Women who use combination hormonal contraceptives must take into account the risk factors for VTE.

Use of norgestrel and ethinyl estradiol during breastfeeding

    • Breast milk may contain contraceptive steroids.
    • Postpartum day 42 sees a decrease in the risk to baseline.
    • Combination hormonal contraceptives should be used in women 21 to 42 days after delivery. Women must consider their individual risk factors for VTE (eg., age 35 and over, immobility and preeclampsia), BMI >=30kg/m2, smoking, and postpartum hemorhage.
    • Exogenous estrogens in breastfeeding women have not been linked to adverse health outcomes, or persistent effects on infant growth and illness (Curtis 2016,b).
    • The manufacturer suggests that contraceptives containing estrogen be used until the child is no longer weaned.
    • Breastfeeding women should not start combination hormonal contraceptives less than 21 days after delivery due to an increased risk of venous embolism (VTE).
    • When starting treatment for breastfeeding women, it is important to consider the risks and benefits of combination hormonal contraception.

 

Ethinyl estradiol and norgestrel (Cryselle 28, Elinest) Dose in Kidney Disease:

Manufacturer’s labeling doesn’t provide any adjustment labeling (has not been studied); use with caution and monitor blood pressure closely.

 

Ethinyl estradiol and norgestrel (Cryselle 28, Elinest) Dose in Liver disease:

Patients with hepatic impairment its use is contradicted.

 

Side effects of Ethinyl estradiol and norgestrel (Cryselle 28, Elinest):

  • Cardiovascular:

    • Edema
    • Pulmonary Thromboembolism
    • Retinal Thrombosis
    • Arterial Thromboembolism
    • Budd-Chiari Syndrome
    • Cerebral Thrombosis
    • Cerebrovascular Accident
    • Hypertension
    • Local Thrombophlebitis
    • Mesenteric Thrombosis
    • Myocardial Infarction
  • Central Nervous System:

    • Cerebral Hemorrhage
    • Nervousness
    • Depression
    • Dizziness
    • Headache
    • Migraine
  • Dermatologic:

    • Acne Vulgaris
    • Loss Of Scalp Hair
    • Allergic Skin Rash
    • Chloasma (May Persist)
    • Erythema Multiforme
    • Erythema Nodosum
  • Endocrine & Metabolic:

    • Amenorrhea
    • Change In Libido
    • Decreased Glucose Tolerance
    • Decreased Serum Folate Level
    • Hirsutism
    • Premenstrual Syndrome
    • Weight Gain
    • Weight Loss
    • Increased Serum Triglycerides
    • Increased Sex Hormone Binding Globulin
    • Increased Thyroxine Binding Globulin
    • Menstrual Disease (Flow Changes)
    • Porphyria
  • Gastrointestinal:

    • Abdominal Cramps
    • Gallbladder Disease
    • Nausea
    • Vomiting
    • Bloating
    • Carbohydrate Intolerance
    • Change In Appetite
    • Cholestasis
    • Colitis
  • Genitourinary:

    • Breakthrough Bleeding
    • Transient Infertility (Following Discontinuation)
    • Vaginitis
    • Breast Hypertrophy
    • Breast Secretion
    • Breast Tenderness
    • Change In Cervical Erosion
    • Change In Cervical Secretions
    • Cystitis-Like Syndrome
    • Decreased Lactation (Postpartum)
    • Spotting
    • Vulvovaginal Candidiasis
  • Hematologic & Oncologic:

    • Hemorrhagic Eruption
    • Increased Clotting Factor VII
    • Increased Clotting Factor VIII
    • Increased Clotting Factor IX
    • Decreased Antithrombin III Plasma Level
    • Hemolytic-Uremic Syndrome
    • Increased Clotting Factor X
    • Increased Norepinephrine-Induced Platelet Aggregation
    • Prolonged Prothrombin Time
  • Hepatic:

    • Hepatic Adenoma
    • Hepatic Neoplasm (Benign)
    • Jaundice
    • Cholestatic Jaundice
  • Ophthalmic:

    • Change In Corneal Curvature (Steepening)
    • Contact Lens Intolerance
    • Optic Neuritis
    • Cataract
  • Renal:

    • Renal Insufficiency

 

Contraindications to Ethinyl estradiol and norgestrel (Cryselle 28, Elinest):

      • Hypersensitivity to Ethinylestradiol or norgestrel or any other component of the formulation
      • Breast cancer or other estrogen- or progestin dependent Neoplasms (current or past), including endometrial and undiagnosed abnormal bleeding.
      • Hepatic tumors (benign and malignant) or hepatic diseases.
      • pregnancy,
      • Cholestatic jaundice during pregnancy
      • jaundice due to prior hormonal contraceptive combination use
      • concurrent use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir (with or without dasabuvir).

Women at high risk for arterial or vein thrombotic disease, such as women with:

      • Cerebrovascular Disease
      • Diabetes mellitus and vascular disease
      • Coronary artery disease
      • DVT or PE (current and/or historical of),
      • Hypercoagulopathies (inherited and acquired)
      • Headaches with focal neurological symptoms
      • hypertension (uncontrolled)
      • Migraine headaches with aura and migraine headaches in people over 35 years old
      • Thrombogenic valvular and rhythm diseases of heart (eg subacute bacteria endocarditis or atrial fibrillation)
      • Women over 35 who smoke.

Warnings and precautions

    • Breast cancer

      • Breast cancer is a hormone sensitive tumor. Women with a history of breast cancer or a recent diagnosis may have a worse prognosis if they use combination hormonal contraceptives.
      • Combination hormonal contraceptives have not been proven to reduce breast cancer risk in women who are at high risk due to their family history or susceptibility genes (BRCA1, BRCA2)
      • Women with breast cancer history or who have had it are advised to not use this product.
    • Cervical cancer:

      • Theoretically, it may influence the prognosis for an existing disease.
      • Combination hormonal contraceptives may be used by women who are awaiting treatment for cervical carcinoma.
      • Combination hormonal contraceptives have been linked to a slight increase in cervical cancer risk. However, the evidence is inconsistent and could be due to other risk factors.
    • Chloasma

      • Treatment should be avoided for women who are susceptible to chloasma and other risk factors.
      • Combination hormonal contraceptives as well as sun exposure, pregnancy and sun exposure are all triggers for chloasma.
    • Cholestasis:

      • Contraindicated use of cholestatic jaundice and jaundice during pregnancy
      • Cholesteasis risk may increase if there has been a history of cholestasis in pregnancy, or with previous oral contraceptive use.
    • The Lipid Effects

      • Combination hormonal contraceptives can increase the risk of pancreatitis in women with hypertriglyceridemia and a family history.
      • Women with uncontrolled dyslipidemia should consider alternative contraception.
      • Combination hormonal contraceptives can adversely affect lipid levels, especially serum triglycerides.
    • Retinal vascular embolism:

      • If you experience an undiagnosed loss of vision, papilledema or proptosis, discontinue use immediately and have your retinal veins examined for thrombosis.
    • Thromboembolic disorders

      • The risk of venous embolism may be increased by oral contraceptives (risk is highest in the first year and lowest during pregnancy); some studies have suggested that the risk may be greater for preparations containing third- or fourth-generation progestins, and/or high dose Ethinylestradiol.
      • Women who have inherited thrombophilias, such as protein C or S deficiency and factor V Leiden mutation, antithrombin deficiencies, and prothrombin mutations, may be at greater risk for venous thromboembolism.
      • If you experience an arterial or vein thrombotic event, discontinue using combination hormonal contraceptives.
      • Women who use combined hormonal contraceptives for longer periods of time, such as 35 and older, are more likely to experience thrombotic events.
      • Combination hormonal contraceptives are not recommended for women at high risk of venous or arterial thrombotic diseases.
      • Combination hormonal contraceptives can also increase the risk for arterial thrombosis (eg MI, stroke). Women with a history or ischemic heart disease should not use them.
    • Vaginal bleeding

      • Unresolved vaginal bleeding is a sign of malignancy and pregnancy.
      • Combination hormonal contraceptives may cause amenorrhea and oligomenorrhea, particularly if the condition was not present previously.
      • In the initial 3 months of therapy, it is possible to experience intra-cyclic bleeding or breakthrough.
      • There may be occasional missed periods.
    • Cardiovascular disease

      • Patients with high risk factors for cardiovascular disease such as hypertension, high blood pressure, high cholesterol, diabetes, and women who smoke should be cautious. Combination hormonal contraceptives can increase your risk of developing the disease.
      • Women at high risk for arterial or vein thrombotic disease are not advised to use this medication.
    • Depression

      • Patients with a history of depression should be cautious; discontinue use if severe depression recurs.
    • Diabetes:

      • Combination oral contraceptives have a limited effect on insulin requirements and are not long-term effective in controlling diabetes in women who do not have vascular disease.
      • This may impair glucose tolerance. Women with diabetes and prediabetes should be cautious.
      • Contraceptive use should not be used in women who have concomitant retinopathy, neuropathy or nephropathy.
      • Women with diabetes mellitus or vascular disease should not use this medication.
    • Fluid retention can lead to more severe diseases

      • Patients with fluid retention-related diseases should be cautious.
    • Endometrial and ovarian cancers:

      • Women with BRCA1 or BRCA2 mutations may have to use oral contraceptives to lower their risk of developing ovarian cancer.
      • Combination hormonal contraceptives may be used by women awaiting treatment for ovarian or endometrial cancer.
      • Combination hormonal contraceptives reduce the risk of ovarian or endometrial cancer.
    • Gallbladder disease

      • Combining hormonal contraceptives can increase the risk of gallbladder diseases or worsen existing gallbladder diseases (Curtis 2016,b).
    • Hepatic adenomas and carcinomas

      • A rare form of hepatocellular carcinoma is the risk associated with long-term, prolonged use.
      • Preexisting hepatic cancers in women are contraindicated.
      • Combination hormonal contraceptives can cause hepatic tumors (rare); rupture could lead to fatal intra-abdominal bleeding.
    • Hepatic impairment

      • Women with hepatic diseases should not use this product.
      • Combination hormonal contraceptives can be used for women with mild (compensated), but not severe (decompensated), cirrhosis.
      • Women with impaired liver function may not be able to process hormonal contraceptives in combination.
      • If jaundice occurs during treatment or if the liver function is abnormal, discontinue use.
    • Hepatitis

      • Women with chronic hepatitis have not been shown to experience an increase in the severity or rate of cirrhotic fibrisis.
      • It has been proven that continued use of a drug by women who are carriers does not cause liver disease or severe hepatic dysfunction.
      • Combination hormonal contraceptives are not recommended for women suffering from acute viral hepatitis, flares, or other severe conditions.
    • Hereditary angioedema:

      • Women with hereditary angioedema may be affected by estrogens (Geng, 2013; Zuraw 2013, 2013).
    • Hypertension:

      • Hypertension can be caused by increased doses, prolonged use, and age.
      • Women with hypertension or vascular disease or persistent blood pressure levels >=160mm Hg Systolic or >=100mm Hg Diastolic should not use combination hormonal contraceptives.
      • 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 older age, smoking, and diabetes.
    • Migraine

      • Women with migraines without aura, including menstrual migraines, may consider using combination hormonal contraceptives.
      • Assess new, persistent, severe or recurring headaches.
      • If you are over 35 years old, it is not recommended to be used in women suffering from migraine headaches or focal neurological symptoms.
    • Transplantation of solid-organs:

      • Although the data is not complete, serious medical complications were reported by women who have had to undergo complicated organ transplants (eg rejections, graft failures, and cardiac allograft vasculopathy).
      • Combination hormonal contraceptives are not recommended for women who have had multiple organ transplants.
    • Systemic lupus, erythematosus

      • Women with SLE should not use combination hormonal contraceptives if they have antiphospholipid antibodies. This is because there is a greater risk of arterial or venous embolism.
      • Systemic lupus is a condition in which women with SLE are more at risk of heart disease, stroke, or VTE.

 

Monitoring parameters:

  • Assessment of pregnancy status (prior to therapy);
  • blood pressure (prior to therapy and yearly);
  • weight (optional;
  • BMI at baseline may be helpful to monitor changes during therapy);
  • assess potential health status changes at routine visits.

If all doses have not been taken on schedule and one menstrual period is missed, the possibility of pregnancy should be considered.

If two consecutive menstrual periods are missed, assess pregnancy status before a new dosing cycle is started.

  • Monitor patient for vision changes;
  • blood pressure;
  • glycemic control in patients with diabetes;
  • signs and symptoms of thromboembolic disorders;
  • signs or symptoms of depression;
  • lipid profiles in patients being treated for hyperlipidemias.
  • Adequate diagnostic measures should be performed to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding.

 

How to administer Ethinyl estradiol and norgestrel (Cryselle 28, Elinest)?

Administer at the same time every day.

Combined hormonal contraceptives may be initiated at any time during the menstrual cycle if it is reasonably sure the woman is not pregnant.

Back-up contraception should be used for 7 days a weak unless contraception is initiated within the first 5 days of menstrual bleeding or the woman abstains from sexual intercourse.

Combined hormonal contraceptives may be started immediately following or within the weak of a first or second-trimester abortion; backup contraception is needed for a weak unless contraception is started at the time of the surgical abortion.

According to the manufacturer, if severe diarrhea or vomiting occurs within 3 to 4 hours after taking an active tablet, it should be considered a missed dose; additional contraceptive measures are recommended. Additional guidelines are also available.

 

Mechanism of action of Ethinyl estradiol and norgestrel (Cryselle 28, Elinest):

Combination hormonal contraceptives can inhibit ovulation through a negative feedback mechanism on hypothalamus. This alters the normal pattern gonadotropin production of a follicle stimulating hormone (FSH), and luteinizing hormone from the anterior pituitary.

FSH in the follicular phase and a midcycle surge with gonadotropins is inhibited. Combination hormonal contraceptives can also cause alterations in the genital system, including cervical mucus changes, which makes it difficult for sperm penetration, even if there is ovulation.

Alterations in the endometrium can also cause unfavorable conditions for nidation.

Combinations of hormonal contraceptives drugs could alter tubal transport of the eggs through the fallopian tubes. The fertility of sperm may also be affected by progestational drugs.

 

International Brands of Ethinyl estradiol and norgestrel:

  • Eugynon 28
  • Eugynon 30
  • Lusia-F
  • Manodiol
  • Microdiol
  • Norfem
  • Cryselle-28
  • Elinest
  • Low-Ogestrel
  • Ogestrel
  • Anfertil
  • Control Pill
  • Duoluton
  • Duoluton-L
  • Ovral
  • Planovar
  • Stediril

 

Ethinyl estradiol and norgestrel Brand Names in Pakistan:

Ethinyl estradiol and norgestrel Tablets 0.5 mg

Estranor Saffron Pharmaceutical Company
Norestra British Pharmaceuticals Ltd
Orgyluton Hansel Pharmacueutical Pvt (Ltd)
Progyluton Bayer Health Care