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

Ethinyl estradiol and norgestrel (Cryselle 28, Elinest) is a combination of two hormonal formulations containing estrogen and 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 Adults

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

Contraception:

  • Oral: 1 tablet once a day.
    • Schedule 1 (Sunday starter):
      • The dose begins on the first Sunday after the onset of menstruation;
      • Take the first tablet the same day, if your period begins on a Sunday.
      • The second method of birth control should be used with a Sunday start until after the first weak of each subsequent dose.
    • Schedule 2 (Day 1 starter):
      • Take 1 pill once daily beginning on the first day of the menstrual cycle.
  • Missed or late doses:

    • If one dose is missed (more than 48 hours after the dose was supposed to be taken) or is taken late (less than 24 hours after the dose should have been taken):
      • Take the medication as soon as you can. Take the remaining doses as usual (even if that means 2 doses on the same day).
    • If two or more doses in a row are missed (48 hours and more than 48 hours since the dose should have been taken):
      • Discard any more missed pills and take the most recent missed dose as soon as you remember. Use backup contraception until hormonal tablets have been taken for 7 days straight; continue remaining doses at the regular time (even if it means taking 2 doses on the same day).
      • When starting a new pack, finish the previous pack if doses were missed during the final week of hormonal (active) pills (e.g., days 15 to 21 of a 28-day pack).
      • Back-up contraception must be used until hormone tablets from a new pack have been taken for 7 days straight if a new pack cannot be started right away.
      • In such circumstances, take into account using emergency contraception (refer to guidelines for details).

Ethinyl estradiol and norgestrel (Cryselle 28, Elinest) Dose in Children

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, a combination of 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 the 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 haemorrhage.
  • 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:

For 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 
  • Breast cancer or another estrogen- or progestin dependent Neoplasms 
  • Hepatic tumours (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 venous thrombotic disease, such as women with:

  • Cerebrovascular Disease
  • Diabetes mellitus and vascular disease
  • Coronary artery disease
  • DVT or PE (current and/or historical),
  • 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 the heart (eg subacute bacteria endocarditis or atrial fibrillation)
  • Women over 35 who smoke.

Warnings and precautions

  • Breast cancer

    • Breast cancer is a hormone-sensitive tumour. 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 a 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
    • Cholestasis 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 incomplete, women who had to endure difficult organ transplants reported experiencing major medical consequences (eg rejections, graft failures, and cardiac allograft vasculopathy).
    • Women who have undergone numerous organ transplants shouldn't use combination hormonal contraceptives.
  • 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.

Ethinyl estradiol and norgestrel: Drug Interaction

Risk Factor C (Monitor therapy)

Ajmaline

Estrogen derivatives may intensify ajmaline's harmful or hazardous effects. In particular, there may be an elevated risk for cholestasis.

Anthrax Immune Globulin (Human)

Anthrax Immune Globulin's thrombogenic action may be enhanced by oestrogen derivatives (Human).

Antidiabetic Agents

The therapeutic benefit of anti-diabetic agents may be reduced by hyperglycemia-associated agents.

Ascorbic Acid

May raise the level of oestrogen derivatives in the serum.

C1 inhibitors

The thrombogenic impact of C1 inhibitors may be enhanced by oestrogen derivatives.

C1 inhibitors

The thrombogenic action of C1 inhibitors may be enhanced by progestins.

Chenodiol

Estrogen derivatives may lessen Chenodiol's therapeutic efficacy. When administered with any oestrogen derivative, chenodiol's clinical reaction should be continuously monitored.

CloZAPine

CYP1A2 Inhibitors (Weak) may raise the level of CloZAPine in the serum. Management: Separate drug interaction monographs go into further detail about the medications indicated as exceptions to this book.

Corticosteroids (Systemic)

Estrogen derivatives may raise the level of corticosteroids in the blood (Systemic).

CYP3A4 Inducers (Moderate)

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

CYP3A4 Inhibitors (Moderate)

May raise the level of oestrogen derivatives in the serum.

CYP3A4 Inhibitors (Strong)

May increase the serum concentration of Estrogen Derivatives.

Dantrolene

Dantrolene's hepatotoxic action may be enhanced by oestrogen derivatives.

Deferasirox

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Erdafitinib

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Flibanserin

The serum levels of flibanserin may rise in response to oestrogen derivatives (contraceptive)

Flibanserin

Flibanserin's serum levels may rise in response to progestins (contraceptive).

Guanethidine

Guanethidine's therapeutic impact may be diminished by oestrogen derivatives (contraceptive).

Herbs (Estrogenic Properties)

Estrogen derivatives' harmful or toxic effects might be amplified.

Herbs (Progestogenic Properties) (eg, Bloodroot, Yucca)

Could make progestins' harmful or hazardous effects worse.

Immune Globulin

Estrogen derivatives may intensify Immune Globulin's thrombogenic action.

Lenalidomide

Lenalidomide's ability to induce thrombosis may be enhanced by oestrogen derivatives.

Metreleptin

Might lower the serum level of oestrogen derivatives (Contraceptive). The serum levels of oestrogen derivatives may rise in response to metreleptin (Contraceptive).

Metreleptin

May lower the level of progestins in the serum (Contraceptive). The serum concentration of progestins may rise in response to metreleptin (Contraceptive).

Mivacurium

The serum concentration of mivacurium may rise in response to oestrogen derivatives.

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective)

Could make oestrogen derivatives' thrombogenic impact stronger. The serum concentration of oestrogen derivatives may rise in response to non-steroidal anti-inflammatory drugs (COX-2 selective).

Proguanil

It's possible that ethinyl estradiol will lessen proguanil's therapeutic effects.

ROPINIRole

The serum concentration of ROPINIRole may rise in response to oestrogen derivatives.

Sarilumab

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Selegiline

Selegiline's serum levels may rise in response to oestrogen derivatives (contraceptive).

Selegiline

Selegiline's serum levels may rise in response to progestins (contraceptive).

Siltuximab

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Succinylcholine

The serum content of succinylcholine may rise as a result of oestrogen derivatives.

Thalidomide

Thalidomide's thrombogenic action may be enhanced by oestrogen derivatives (contraceptive).

Thalidomide

The thrombogenic action of thalidomide may be enhanced by progestins (contraceptive).

Thalidomide

The thrombogenic effect of thalidomide may be enhanced by oestrogen derivatives.

Theophylline Derivatives

Theophylline derivatives' serum levels may be raised by oestrogen derivatives. Dyphylline is an exception.

Thyroid Products

Estrogen derivatives may reduce a thyroid product's ability to treat you.

Tocilizumab

May lower the serum level of CYP3A4 substrates (High risk with Inducers).

Ursodiol

Ursodiol's therapeutic effects could be lessened by oestrogen derivatives.

Valproate Products

The serum content of valproate products may be reduced by oestrogen derivatives (contraceptive).

Voriconazole

Estrogen derivatives' metabolism might be slowed (Contraceptive). The serum levels of voriconazole may rise in response to oestrogen derivatives (contraceptive).

Voriconazole

May raise progesterone levels in the blood (Contraceptive). The serum levels of voriconazole may rise in response to progestins (contraceptive).

Risk Factor D (Consider therapy modification)

Acitretin

May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: Progestin-only preparations shouldn't be depended upon because they may not be effective at preventing pregnancy while using acitretin. During acitretin therapy, alternative, nonhormonal methods of contraception must be used.

Anticoagulants

Estrogen derivatives might lessen an anticoagulant's ability to stop bleeding. More particular, some estrogens and progestin-estrogen combos may have prothrombotic actions that work against any anticoagulant effects. Management: Carefully balance the potential advantages of estrogens against the probable elevated risk of thromboembolism and procoagulant effects. Under some conditions, use is deemed contraindicated. For particular advice, consult the relevant policies.

Anticoagulants

Anticoagulants' therapeutic effects may be lessened by progestins. More particular, some progestins and progestin-estrogen combos may have prothrombotic actions that work against any anticoagulant effects. Management: Carefully balance the progestins' possible advantages against their potential increased risk of thromboembolism and procoagulant effects. Under some conditions, use is deemed contraindicated. For particular advice, consult the relevant policies.

Aprepitant

Might lower the serum level of oestrogen derivatives (Contraceptive). Treatment: It is advised to use a contraception that is not hormone-based.

Aprepitant

May lower the level of progestins in the serum (Contraceptive). Treatment: Alternative or additional methods of contraception should be used for at least one month after the final dosage of aprepitant or fosaprepitant, as well as while using aprepitant or fosaprepitant.

Armodafinil

Might lower the serum level of oestrogen derivatives (Contraceptive). Therapy: During and for one month after treatment with armodafinil, the manufacturer advises patients to take nonhormonal contraceptives in addition to or in place of hormonal contraceptives.

Artemether

Might lower the serum level of oestrogen derivatives (Contraceptive). Management: All women of reproductive potential who are taking artemether should think about utilising an alternative method of contraception (i.e., one that is not hormonal).

Artemether

May lower the level of progestins in the serum (Contraceptive). Management: All women of reproductive potential who are taking artemether should think about utilising an alternative method of contraception (i.e., one that is not hormonal).

Asunaprevir

May lower the level of ethinyl estradiol in the serum. Management: Using a high-dose oral contraceptive during asunaprevir treatment that contains at least 30 mcg of ethinyl estradiol coupled with norethindrone acetate/norethindrone is advised for patients who use hormone-based contraception.

Atazanavir

May raise progesterone levels in the blood (Contraceptive). Atazanavir, however, may result in lower ethinyl estradiol levels and reduced efficiency of oral contraceptive medications. Management: When using combination estrogen/progestin medications, take into account an extra means of contraception. It is possible to utilise depot medroxyprogesterone acetate without the use of supplementary contraception.

Barbiturates

Might reduce the therapeutic benefit of oestrogen derivatives (Contraceptive). Failure with contraception is possible. Use of a non-hormonal contraception is advised for management.

Barbiturates

May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: It is advised to use complementary, nonhormonal contraception.

Bexarotene (Systemic)

Might lower the serum level of oestrogen derivatives (Contraceptive). Management: Women who are sexually active and on bexarotene should utilise two trustworthy methods of contraception (including at least one nonhormonal form).

Bexarotene (Systemic)

May lower the level of progestins in the serum (Contraceptive). Management: Women who are sexually active and on bexarotene should utilise two trustworthy methods of contraception (including at least one nonhormonal form).

Bile Acid Sequestrants

Might lower the serum level of oestrogen derivatives (Contraceptive). Treatment: Give bile acid sequestrants at least 1 to 4 hours before or 6 to 8 hours after giving estrogen-based oral contraceptives.

Bile Acid Sequestrants

May lower the level of progestins in the serum (Contraceptive). Treatment: Give oral contraceptives containing progestin at least one to four hours before or six to eight hours after taking a bile acid sequestrant.

Bosentan

Might lower the serum level of oestrogen derivatives (Contraceptive). Management: Do not solely rely on hormonal contraceptives for all women of reproductive potential who are taking bosentan; instead, use an alternative (i.e., non-hormonal) method of contraception.

Bosentan

May lower the level of progestins in the serum (Contraceptive). Management: Do not solely rely on hormonal contraceptives for all women of reproductive potential who are taking bosentan; instead, use an alternative (i.e., non-hormonal) method of contraception.

Brigatinib

Might lower the serum level of oestrogen derivatives (Contraceptive). Management: For at least 4 months following the last dosage of brigatinib, females of reproductive potential should use an alternative, non-hormonal method of contraception.

Brigatinib

May lower the level of progestins in the serum (Contraceptive). Management: For at least 4 months following the last dosage of brigatinib, females of reproductive potential should use an alternative, non-hormonal method of contraception.

CarBAMazepine

Might reduce the therapeutic benefit of oestrogen derivatives (Contraceptive). Failure with contraception is possible. Treatment: It is advised to use a nonhormonal contraception.

CarBAMazepine

May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: It is advised to use complementary, nonhormonal contraception.

Carfilzomib

Could make oestrogen derivatives' thrombogenic impact stronger (Contraceptive). In patients who need carfilzomib medication, alternate, non-hormonal methods of contraception should be taken into account.

Carfilzomib

Could make progestins' thrombogenic impact stronger (Contraceptive). In patients who need carfilzomib medication, alternate, non-hormonal methods of contraception should be taken into account.

Cladribine

May reduce the hormonal contraceptives' therapeutic effect. Management: During cladribine dosage and for at least 4 weeks after the final dose in each treatment period, women who are using systemically acting hormonal contraceptives should add a barrier device.

CloBAZam

Might lower the serum level of oestrogen derivatives (Contraceptive).

CloBAZam

May lower the level of progestins in the serum (Contraceptive

Cobicistat

Might lower the serum level of oestrogen derivatives (Contraceptive). When treating patients who are using cobicistat-containing products, take into account a different, nonhormone-based method of contraception.

Cobicistat

May raise progesterone levels in the blood (Contraceptive). When treating patients who are taking cobicistat-containing medications, take into account an alternative, nonhormone-based method of contraception. Atazanavir and cobicistat are specifically contraindicated with dronabinol.

Colesevelam

May lower the level of ethinyl estradiol in the serum. Treatment: Ethinyl estradiol and norethindrone-containing oral contraceptives should be used at least 4 hours before colestipol.

Cosyntropin

Cosyntropin's diagnostic potential may be diminished by oestrogen derivatives. Treatment: Stop taking any medications that include oestrogen 4 to 6 weeks before cosyntropin (ACTH) testing.

CYP3A4 Inducers (Strong)

May speed up CYP3A4 substrate metabolism (High risk with Inducers). Management: Take into account a substitute for one of the interfering medications. Specific contraindications may apply to some combinations. the relevant manufacturer's label.

Dabrafenib

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: When possible, look for substitutes for the CYP3A4 substrate. If concurrent therapy cannot be avoided, pay special attention to the substrate's clinical consequences (particularly therapeutic effects).

Dabrafenib

Might lower the serum level of oestrogen derivatives (Contraceptive). Treatment: Women who are sexually active or who are planning a pregnancy should take contraception that is highly effective, nonhormonal, and alternative for at least 2 weeks (if taking dabrafenib alone) or 4 months (if taking dabrafenib plus trametinib).

Dabrafenib

May lower the level of progestins in the serum (Contraceptive). Treatment: Women who are sexually active or who are planning a pregnancy should take contraception that is highly effective, non-hormonal, and alternative for at least 2 weeks (if taking dabrafenib alone) or 4 months (if taking dabrafenib plus trametinib).

Darunavir

May lower the level of progestins in the serum (Contraceptive). Management: Take into account utilising a different or additional method of contraception. There is no requirement for supplemental contraception when using injected depot medroxyprogesterone acetate.

Efavirenz

May lower the level of progestins in the serum (Contraceptive). Management: In light of potentially decreased contraceptive effectiveness, use an extra or alternative method of contraception. Depot medroxyprogesterone administered intravenously does not seem to be involved in this interaction.

Elagolix

The therapeutic benefit of Elagolix may be diminished by oestrogen derivatives (contraceptive). Use a different, non-hormonal method of birth control while taking elagolix and for at least a week after stopping the medication.

Elvitegravir

Might lower the serum level of oestrogen derivatives (Contraceptive). Management: If a patient is on elvitegravir-containing medication, they should think about switching to an other, non-hormone-based method of birth control.

Enzalutamide

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: Enzalutamide should not be used concurrently with CYP3A4 substrates that have a limited therapeutic index. Enzalutamide use, like with the use of any other CYP3A4 substrate, should be done cautiously and under close observation.

Eslicarbazepine

Might lower the serum level of oestrogen derivatives (Contraceptive). Management: Women who are capable of having children should think about non-hormonal birth control alternatives.

Eslicarbazepine

May lower the level of progestins in the serum (Contraceptive). Management: For women who are capable of having children, alternative, non-hormonal methods of birth control should be taken into account.

Exenatide

Might lower the serum level of oestrogen derivatives (Contraceptive). Treatment: Oral contraceptives should be taken at least an hour before exenatide.

Exenatide

May lower the level of progestins in the serum (Oral Contraceptive). Treatment: Oral contraceptives should be taken at least an hour before exenatide.

Felbamate

Might lower the serum level of oestrogen derivatives (Contraceptive). Failure with contraception is possible. Treatment: It is advised to use a nonhormonal contraception.

Felbamate

May lower the level of progestins in the serum (Contraceptive). Management: It is possible for contraceptives to fail. It is advised to use an alternative, nonhormonal method of contraception.

Fosamprenavir

The serum concentrations of the active metabolite(s) of fosamprenavir may drop when using progestins (contraceptives). Fosamprenavir may lower the level of progestins in the serum (Contraceptive). Management: Take into account utilising a different or additional method of contraception. There is no requirement for supplemental contraception when using injected depot medroxyprogesterone acetate.

Fosaprepitant

Might lower the serum level of oestrogen derivatives (Contraceptive). Probably the active metabolite aprepitant is the cause of this effect. Therapy: Alternative or additional methods of contraception should be used for at least a month after the last dosage of fosaprepitant or aprepitant, as well as while receiving treatment with these drugs.

Fosaprepitant

May lower the level of progestins in the serum (Contraceptive). Probably the active metabolite aprepitant is the cause of this effect. Treatment: Alternative or additional methods of contraception should be used for at least one month after the final dosage of aprepitant or fosaprepitant, as well as while using aprepitant or fosaprepitant.

Fosphenytoin:

Might reduce the therapeutic benefit of oestrogen derivatives (Contraceptive). Failure with contraception is possible. Management: It is advised to use an alternative, nonhormonal method of contraception.

Fosphenytoin

May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: It is possible for contraceptives to fail. It is advised to use an alternative, nonhormonal method of birth control.

Hyaluronidase

Estrogen derivatives may lessen Hyaluronidase's therapeutic impact. Treatment: Standard doses of hyaluronidase may not produce the desired clinical response in patients receiving estrogens (especially at higher doses). Hyaluronidase may be needed at higher doses.

Ivosidenib

Might lower the serum level of oestrogen derivatives (Contraceptive). Treatment: If a patient is taking ivosidenib, consider non-hormonal contraception alternatives.

Ivosidenib

May lower the level of progestins in the serum (Contraceptive). Treatment: If a patient is taking ivosidenib, consider non-hormonal contraception alternatives.

LamoTRIgine

The serum content of LamoTRIgine may be decreased by oestrogen derivatives (contraceptive). After discontinuing or reducing the dosage of a hormonal contraceptive, patients should be watched for any changes in lamotrigine's serum concentrations and potential side effects (this includes during a pill-free week). Lamotrigine dosage may need to be decreased.

Lesinurad

Might lower the serum level of oestrogen derivatives (Contraceptive). Treatment: Patients on lesinurad who want reliable contraception are advised to use an additional nonhormonal method of contraception.

Lesinurad

May lower the level of progestins in the serum (Contraceptive). Treatment: Patients on lesinurad who want reliable contraception are advised to use an additional nonhormonal method of contraception.

Lixisenatide

Might lower the serum level of oestrogen derivatives (Contraceptive). Treatment: Give oral contraceptives 11 hours or more after giving lixisenatide, whichever comes first.

Lixisenatide

May lower the level of progestins in the serum (Contraceptive). Treatment: Give oral contraceptives 11 hours or more after giving lixisenatide, whichever comes first.

Lomitapide

The serum concentration of lomitapide may rise in response to ethinyl estradiol. Treatment: Patients taking 5 mg/day of lomitapide may continue doing so. Patients taking 10 mg or more of lomitapide per day should cut their dosage in half. The dosage of lomitapide may thereafter be increased up to a maximum daily adult dose of 40 mg.

Lopinavir

May lower the level of progestins in the serum (Contraceptive). Lopinavir may raise the level of progestins in the serum (Contraceptive). Management: Take into account utilising a different or additional method of contraception. Without the need for supplementary contraception, injectable depot medroxyprogesterone acetate and etonogestrel implants may be utilised.

Lorlatinib

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Avoid taking lorlatinib at the same time as any CYP3A4 substrates for which even a small drop in serum levels of the substrate could result in therapeutic failure and negative clinical outcomes.

Lumacaftor

Might lower the serum level of oestrogen derivatives (Contraceptive).  Management: If lumacaftor and ivacaftor are taken together, avoid using  hormone-based contraceptives; instead, choose an other, non-hormonal type of contraception.

Lumacaftor

May lower the level of progestins in the serum (Contraceptive). Management: If lumacaftor and ivacaftor are taken together, avoid using hormone-based contraceptives; instead, choose an other, non-hormonal type of contraception.

MiFEPRIStone

May reduce the progestins' therapeutic impact (Contraceptive). MiFEPRIStone may raise the level of progestins in the serum (Contraceptive). Management: During and for four weeks after mifepristone treatment, women of reproductive potential should use an efficient, nonhormonal method of contraception.

MiFEPRIStone

Might reduce the therapeutic benefit of oestrogen derivatives (Contraceptive). The blood concentration of oestrogen derivatives may rise when using MiFEPRIStone (Contraceptive). Management: During and for four weeks after mifepristone treatment, women of reproductive potential should use an efficient, nonhormonal method of contraception.

Mitotane

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: When administered in individuals receiving mitotane, doses of CYP3A4 substrates may need to be significantly modified.

Modafinil

Might lower the serum level of oestrogen derivatives (Contraceptive). Treatment: During and for one month after modafinil treatment, the manufacturer advises patients to use nonhormonal contraceptives in addition to or in place of hormonal contraceptives.

Mycophenolate

Might lower the serum level of oestrogen derivatives (Contraceptive). However, there was evidence of significant patient-to-patient variability in response to this combination, even if average AUC values remained unchanged. Management: Women who are sexually active and on mycophenolate mofetil should think about using an extra type of birth control.

Mycophenolate

May lower the level of progestins in the serum (Contraceptive). Management: Employing a different (nonhormonal) type of contraception should be taken into consideration.

Nafcillin

Could speed up how quickly oestrogen derivatives are metabolised (Contraceptive). Treatment: It is advised to use an alternative, nonhormonal method of contraception while using nafcillin.

Nelfinavir

May lower the level of progestins in the serum (Contraceptive). Management: In light of potentially decreased contraceptive effectiveness, use an extra or alternative method of contraception. Depot medroxyprogesterone administered intravenously does not seem to be involved in this interaction.

Nevirapine:

Might lower the serum level of oestrogen derivatives (Contraceptive).

Nevirapine

May lower the level of progestins in the serum (Contraceptive). Management: Advise nevirapine-treated individuals to utilise a different or supplemental nonhormonal method of birth control. However, depo-medroxyprogesterone acetate may be used as the exclusive means of contraception, according to the labelling on nevirapine products.

OXcarbazepine

Might lower the serum level of oestrogen derivatives (Contraceptive). Failure with contraception is possible. Management: It is advised to use a complementary, nonhormonal method of birth control.

OXcarbazepine

May lower the level of progestins in the serum (Contraceptive). Management: It is possible for contraceptives to fail. It is advised to use a second or additional nonhormonal method of contraception.

Perampanel

May lower the level of progestins in the serum (Contraceptive). Treatment: Patients should utilise an alternative method of contraception that is not hormonally based both while taking perampanel and for one month after stopping it.

Phenytoin

Might reduce the therapeutic benefit of oestrogen derivatives (Contraceptive). Failure with contraception is possible. Management: It is advised to use an alternative, nonhormonal method of contraception.

Phenytoin

May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: It is possible for contraceptives to fail. It is advised to use an alternative, nonhormonal method of birth control.

Pitolisant

Might reduce the therapeutic benefit of oestrogen derivatives (Contraceptive). Management: An alternative method of contraception should be utilised instead of combining hormonal contraceptives with pitolisant.

Pitolisant

May reduce the progestins' therapeutic impact (Contraceptive). Management: An alternative method of contraception should be utilised instead of combining hormonal contraceptives with pitolisant.

Pitolisant

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Pitolisant should not be used in conjunction with a CYP3A4 substrate that has a limited therapeutic index. When administered with pitolisant, other CYP3A4 substrates need to be checked more carefully.

Pomalidomide

Could make oestrogen derivatives' thrombogenic impact stronger. Care should be taken while using hormone replacement treatment, and hormonal contraceptives are not advised, according to Canadian pomalidomide labelling. These precise guidelines are not included on the pomalidomide labelling in the US.

Pomalidomide

Pomalidomide's thrombogenic action may be strengthened by progestins. Care should be taken while using hormone replacement treatment, and hormonal contraceptives are not advised, according to Canadian pomalidomide labelling.

Primidone

May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: It is advised to use complementary, nonhormonal contraception.

Protease Inhibitors

Might lower the serum level of oestrogen derivatives (Contraceptive). Treatment: For individuals using atazanavir/ritonavir, use oral contraceptives containing no more than 30mcg of ethinyl estradiol or at least 35mcg of ethinyl estradiol. It is advised to use an alternative, non-hormonal method of birth control when using other protease inhibitors. Examples include Indinavir.

Retinoic Acid Derivatives

May reduce the progestins' therapeutic impact (Contraceptive). Progesterone serum levels may be reduced by retinoic acid derivatives (Contraceptive). Treatment: Patients using retinoic acid derivatives should utilise two kinds of reliable contraception. Particularly, formulations that contain merely microdoses of progesterone may not be sufficient. Adapalene, Bexarotene (Topical), and Tretinoin are exceptions (Topical).

Rifamycin Derivatives

Might lower the serum level of oestrogen derivatives (Contraceptive). Failure with contraception is possible. Management: It is advised to use a complementary, nonhormonal method of birth control.

Rifamycin Derivatives

May lower the level of progestins in the serum (Contraceptive). Failure with contraception is possible. Management: It is possible for contraceptives to fail. It is advised to use an alternative, nonhormonal method of birth control.

Rufinamide

May lower the level of ethinyl estradiol in the serum.

Saquinavir

May lower the level of progestins in the serum (Contraceptive). Management: In light of potentially decreased contraceptive effectiveness, use an extra or alternative method of contraception. Depot medroxyprogesterone administered intravenously does not seem to be involved in this interaction.

St John's Wort

Might reduce the therapeutic benefit of oestrogen derivatives (Contraceptive). Failure with contraception is possible. Management: If possible, look into alternatives to St. John's wort. If this combination is taken, a different, nonhormonal form of birth control is advised.

St John's Wort

May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible. Management: Take into account using something other than St. John's wort. Failure with contraception is possible. It is advised to use an alternative, nonhormonal method of birth control.

St John's Wort

May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Take into account a substitute for one of the interfering medications. Specific contraindications may apply to some combinations. the relevant manufacturer's label.

Sugammadex

May lower the level of progestins in the serum (Contraceptive). Treatment: During and for 7 days after having sugammadex, patients receiving any hormonal contraceptive (oral or non-oral) should utilise an additional, non-hormonal method of contraception.

Sugammadex

Might lower the serum level of oestrogen derivatives (Contraceptive). Treatment: During and for 7 days after having sugammadex, patients receiving any hormonal contraceptive (oral or non-oral) should utilise an additional, non-hormonal method of contraception.

Tipranavir

Estrogen derivatives may intensify Tipranavir's unfavourable effect on the skin. A high incidence of skin rash was linked to the use of tipranavir/ritonavir and ethinyl estradiol/norethindrone together. The serum levels of oestrogen derivatives may drop when taking tipranavir. Management: Women who use hormonal contraceptives should think about non-hormonal alternatives.

Tipranavir

May raise progesterone levels in the blood (Contraceptive). Management: In light of potentially decreased contraceptive effectiveness, use an extra or alternative method of contraception. Depot medroxyprogesterone administered intravenously does not seem to be involved in this interaction.

TiZANidine

The concentration of TiZANidine in the serum may rise in response to CYP1A2 Inhibitors (Weak). Management: Whenever you can, stay away from these pairings. Tizanidine should be started at an adult dose of 2 mg and increased in 2 to 4 mg increments depending on the patient's reaction if combination use is required. Watch out for tizanidine side effects, such as increased effects.

Tobacco (Smoked)

Could intensify the negative or harmful effects of oestrogen derivatives (Contraceptive). In particular, there may be an elevated risk of major cardiovascular events such myocardial infarction, stroke, and venous thromboembolism. Management: Whenever feasible, refrain from smoking if a patient uses an estrogen-containing birth control method. Check for warning signs and symptoms of severe cardiovascular events if they coexist (eg, stroke, venous thromboembolism, myocardial infarction).

Topiramate

Might lower the serum level of oestrogen derivatives (Contraceptive). Failure with contraception is possible. Management: Risk seems to be greatest at dosages of 200 mg or more of topiramate per day. The usefulness of utilising at least 50 mcg/day of ethinyl estradiol has been suggested, but this is debatable. Think about a nonhormonal method of birth control.

Topiramate

May lower the level of progestins in the serum (Contraceptive). Treatment: Inform patients that this combination may result in decreased contraceptive efficacy. Think about including an additional (non-hormonal) type of birth control.

Vitamin K Antagonists (eg, warfarin)

Vitamin K antagonists' ability to prevent clotting may be lessened by oestrogen derivatives (contraceptive). On the other hand, several products have also been observed to have heightened anticoagulant effects.

Vitamin K Antagonists (eg, warfarin)

Vitamin K antagonists' ability to prevent clotting may be lessened by progestins (contraceptives). On the other hand, several products have also been observed to have heightened anticoagulant effects. Management: To reduce the risk of thromboembolic diseases, concurrent hormonal contraceptives and coumarin derivatives should be avoided wherever possible. Think about switching to a hormonal-free method of birth control.

Risk Factor X (Avoid combination)

Anastrozole

Estrogen derivatives may lessen anastrozole's therapeutic efficacy.

Antihepaciviral Combination Products

Antihepaciviral Combination Products' hepatotoxic effects may be increased by ethinyl estradiol. Treatment: Ethinyl estradiol use must be stopped before using this combination; it can be begun again two weeks after stopping the antihepaciviral combo product.

Dasabuvir

Dasabuvir's hepatotoxic effects may be exacerbated by ethinyl estradiol.

Dehydroepiandrosterone

Estrogen derivatives' harmful or toxic effects might be amplified.

Encorafenib

Might lower the serum level of oestrogen derivatives (Contraceptive).

Encorafenib

May decrease the serum concentration of Progestins (Contraceptive).

Exemestane

Estrogen Derivatives may diminish the therapeutic effect of Exemestane.

Glecaprevir and Pibrentasvir

The harmful or hazardous effects of glecaprevir and pibrentasvir may be intensified by ethinyl estradiol. In particular, this combination may raise the risk for ALT elevation.

Griseofulvin

May reduce the progestins' therapeutic impact (Contraceptive). Failure with contraception is possible.

Hemin

Estrogen derivatives may lessen Hemin's therapeutic impact.

Indium 111 Capromab Pendetide

Indium 111 Capromab Pendetide's diagnostic effectiveness may be reduced by oestrogen derivatives.

Ixazomib

May lower the level of progestins in the serum (Contraceptive). More precisely, the serum concentrations of contraceptive progestins may be lowered when ixazomib and dexamethasone are combined. Treatment: Women of reproductive potential should use a nonhormonal barrier contraceptive for the duration of their ixazomib treatment and for 90 days after.

Ospemifene

Estrogen derivatives may intensify Ospemifene's harmful or hazardous effects.

Tranexamic Acid

Ospemifene's therapeutic efficacy may be lessened by oestrogen derivatives.
Tranexamic Acid's thrombogenic impact may be enhanced by progestins (contraceptives).

Tranexamic Acid

The thrombogenic effect of tranexamic acid may be enhanced by oestrogen derivatives (contraceptive).

Ulipristal

May lessen progestins' therapeutic impact. Ulipristal's therapeutic effects may be lessened by progestins. Avoid progestins within 12 days of quitting ulipristal for uterine fibroids (Canadian indication); avoid progestins within 5 days of stopping ulipristal for emergency contraception (U.S. indication).

Monitoring parameters:

  • pregnancy status
  • blood pressure 
  • weight 
  • BMI 
  • health changes 

The potential of pregnancy should be taken into account if all medicines have not been taken as directed and one menstrual period has been missed. Before beginning a new dosage cycle, determine whether pregnancy is present if two consecutive menstrual cycles are missed.

  • vision changes
  • blood pressure
  • glycemic control in patients with diabetes
  • thromboembolic disorders;
  • depression
  • lipid profiles 

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

  • Administer every day at the same time.
  • If it is generally certain the woman is not pregnant, combined hormonal contraceptives may be started at any point throughout the menstrual cycle.
  • Unless contraception is started within the first five days of menstrual bleeding or the woman abstains from sexual activity, backup contraception should be taken for seven days.
  • If contraception is not started at the time of the surgical abortion, backup contraception is required for a weak. Combined hormonal contraceptives may be started right away after or within the weak of a first or second trimester abortion.
  • If severe diarrhoea or vomiting develops within 3 to 4 hours of taking an active pill, the manufacturer advises that it should be regarded as a missed dosage; further contraceptive measures should be taken.

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