Ethinyl estradiol and norethindrone - Dosage, Side effects, Brand Names

A combination oral contraceptive tablet called ethinyl estradiol and norethindrone is primarily used to prevent conception (as an oral hormonal contraceptive drug).

Ethinyl estradiol and norethindrone Uses:

  • Acne vulgaris (Estrostep Fe, Tilia Fe, Tri-Legest Fe):

    • Used to treat mild acne vulgaris in females older than 15 years.
    • Limitations of use:
    • Use only in females 15 years of age or older who have reached menarche, who also want combination hormonal contraceptive therapy, who are unresponsive to topical treatments, have no contraindications to using combination hormonal contraceptives, and who intend to stay on therapy for at least six months.

  • Contraception:

    • Utilised to prevent pregnancy.
    • Use restrictions: The effectiveness of some products has not been shown in women with a BMI more than 35 kg/m2.

  • Osteoporosis prevention (female) (femhrt, Jevantique Lo, Jinteli):

    • Used as a postmenopausal osteoporosis preventive measure.
    • Use is restricted to women who are at high risk for developing postmenopausal osteoporosis; other treatments should be considered.

  • Vasomotor symptoms associated with menopause (femhrt, Jevantique Lo, Jinteli):

    • Used to treat menopausal vasomotor symptoms that range from mild to severe.

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

    • Abnormal uterine bleeding (acute)
    • Polycystic ovary syndrome (PCOS) in women with menstrual irregularities and hirsutism/acne
    • Dysmenorrhea
    • Hirsutism
    • Menstrual bleeding (menorrhagia)

Ethinyl estradiol and norethindrone Dose in Adults

Using a combination of ethinyl estradiol and norethindrone to treat abnormal uterine bleeding, acute (off-label):

  • Oral: For a weak, take ethinyl estradiol 0.035 mg/norethindrone 1 mg three times per day.

Ethinyl estradiol and norethindrone Dose in the treatment of Acne:

  • Adolescents ≥15 years of age and Adults:

    • Females: Oral (Estrostep Fe, Tilia Fe, TriLegest Fe):
      • Refer to dosing for contraception

Ethinyl estradiol and norethindrone Dose in the treatment of Contraception:

  • Females:

    • One tablet once a day.

  • Schedule 1 (Sunday starter):

    • The dose starts on the first Sunday following the start of menstruation;
    • Take the first tablet the same day, if your period begins on a Sunday. (For some products, such as Generess Fe and Lo Loestrin Fe, this schedule is not preferred.)
    • A second method of contraception should be used with a Sunday start till after the first weak of each subsequent administration (all products).

  • Schedule 2 (Day 1 starter):

    • Take 1 pill once daily beginning on the first day of the menstrual cycle.

Additional contraceptive dosing considerations:

  • Switching from a different contraceptive:

    • Oral contraceptive:
      • Start on the day that you would have taken a fresh supply of the prior oral contraceptive.
    • Transdermal patch, vaginal ring, injection:
      • Begin the day after the deadline for the subsequent dose.
    • IUD or implant:
      • Begin on the removal day.
      • If the IUD is not taken out on the first day of the menstrual cycle, a backup form of contraception should be utilised for the first period.
    • Use after first-trimester abortion or miscarriage:
      • Therapy can begin right away.
      • A backup form of contraception should be used for the first weak if it is not started within 5 days.
    • Use after childbirth (in women who are not breastfeeding) or after second-trimester abortion or miscarriage:
      • Four or more weeks after giving birth, therapy may be started.
      • If menstrual cycles have not resumed again, pregnancy should be checked out before starting medication.
      • The first weak of sequential administration should be followed by the use of a second form of contraception (nonhormonal).
      • Additionally, for general advice, see the prescribing label for information unique to the medicine.

  • 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 are missed in a row (within 48 hours of the scheduled dose),:
      • 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).
    • For information relevant to a product, consult the prescribing information as well.

Ethinyl estradiol and norethindrone Dose in the Postmenopausal indications:

  • General dosing guidelines:

    • Hormone therapy should be frequently assessed for each patient to determine the best dose, duration, and method of administration depending on treatment objectives, risk factors, and general health.
    • For postmenopausal women with uteruses, combined estrogen/progestin therapy is recommended to lower the risk of endometrial cancer.
    • In general, people who have had hysterectomies do not require a progestin; however, if endometriosis has a history, one can be required.
    • Based on the patient's response, adjust the dose.

Ethinyl estradiol and norethindrone Dose in the prevention  of Osteoporosis:

  • Females:

    • Oral (femhrt, Jevantique Lo, Jinteli):
      • One tablet once in a day.

Ethinyl estradiol and norethindrone Dose in the treatment of Vasomotor symptoms associated with menopause:

  • Females:

    • Oral (femhrt, Jevantique Lo, Jinteli):
      • Initial: One tablet once in a day.

Ethinyl estradiol and norethindrone Dose in Childrens

Ethinyl estradiol and norethindrone Dose in the treatment of Acne:

  • Adolescent females ≥15 years:

    • Oral contraceptives (Estrostep Fe, Tilia Fe, Tri-Legest Fe): Consult the adult dosage; do not use before menarche

Ethinyl estradiol and norethindrone Dose in the treatment of Contraception:

  • Females:

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

Pregnancy Risk Factor X

  • Pregnant women should not use this product.
  • Breastfeeding should be stopped at 4 weeks post-birth for women who have chosen not to breastfeed.
  • 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.
  • 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.
  • According to the manufacturer, combination hormonal contraceptives are sho
  • 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.

Breastfeeding: Ethinyl estradiol, norethindrone

  • The manufacturer suggests that contraceptives containing estrogen be used until the child is weaned. This will reduce milk production.
  • Breastfeeding women should not start combination hormonal contraceptives within 21 days of delivery due to an increased risk for venous embolism (VTE).
  • Breast milk may contain contraceptive steroids.
  • Breastfeeding mothers who use combination hormonal contraceptives have not reported any adverse health effects or persistent effects on infant growth and illness.
  • 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.
  • When starting treatment for breastfeeding women, it is important to consider the risks and benefits of combination hormonal contraception.

Ethinyl estradiol and norethindrone Dose in Kidney Disease:

The manufacturer's labeling doesn't provide any dosage adjustments (has not been studied). Use with caution and monitor blood pressure closely.

Ethinyl estradiol and norethindrone Dose in Liver disease:

Its use is contraindicated in patients with hepatic impairment.

Menopausal vasomotor symptoms and osteoporosis prevention:

Common Side Effects of Ethinyl estradiol and norethindrone:

  • Endocrine & metabolic:

    • Increased sex hormone-binding globulin

Less Common Side Effects of Ethinyl estradiol and norethindrone:

  • Cardiovascular:

    • Edema

  • Central Nervous System:

    • Headache

  • Gastrointestinal:

    • Abdominal Pain

  • Genitourinary:

    • Mastalgia
    • Endometrial Hyperplasia

Contraception And Acne:

Common Side Effects Of Ethinyl Estradiol And Norethindrone:

  • Endocrine & Metabolic:

    • Change In Menstrual Flow
    • Amenorrhea

  • Genitourinary:

    • Breakthrough Bleeding
    • Spotting

Less Common Side Effects Of Ethinyl Estradiol And Norethindrone:

  • Central Nervous System:

    • Headache
    • Migraine
    • Depression
    • Mood Changes
    • Mood Disorder
    • Anxiety

  • Dermatologic:

    • Acne Vulgaris

  • Endocrine & Metabolic:

    • Heavy Menstrual Bleeding
    • Weight Changes
    • Weight Gain

  • Gastrointestinal:

    • Nausea
    • Vomiting
    • Abdominal Pain

  • Genitourinary:

    • Vulvovaginal Candidiasis
    • Abnormal Uterine Bleeding
    • Dysmenorrhea
    • Uterine Cramps
    • Abnormal Cervical Or Vaginal Papanicolaou Smear
    • Bacterial Vaginosis
    • Breast Tenderness
    • Mastalgia
    • Irregular Menses
    • Vaginal Hemorrhage

Frequency of Side effects Not Defined:

  • Cardiovascular:

    • Hypertension

  • Endocrine & Metabolic:

    • Decreased Libido

Contraindications to Ethinyl estradiol and norethindrone:

Combination hormonal contraceptives

  • Hypersensitivity to any ingredient in the formulation, including ethinyl estradiol, norethindrone, or others
  • Breast cancer or another estrogen- or progestin sensitive cancer (currently or in the past);
  • Hepatic tumors (benign and malignant) or hepatic diseases;
  • pregnancy;
  • Undiagnosed abnormal uterine bleeding
  • concomitant 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
  • Coronary artery disease
  • Diabetes mellitus and vascular disease
  • DVT or PE (current and/or historical of);
  • hypertension (uncontrolled);
  • Headaches with focal neurological symptoms
  • Migraine headaches with aura, migraine headaches, if you are >35 years old
  • Women over 35 years old who smoke;
  • Hypercoagulopathies (inherited and acquired);
  • Thrombogenic valvular and thrombogenic rhythm disorders of the heart 

Canadian labeling: Additional contraindications not in US labeling

  • Angina pectoris 
  • steroid-dependent jaundice, cholestatic jaundice
  • Any ocular lession that results from ophthalmic vessels disease (partial or complete loss of sight, or visual field defect)
  • Migraine with focal aura (currently or in the past);
  • Pancreatitis in association with severe hypertriglyceridemia (current and/or history of);
  • severe dyslipoproteinemia;
  • Persistent blood pressure >=160mm Hg systolic, or >=100mm Hg diastolic
  • Women with an acquired or hereditary predisposition to arterial or vein thrombosis may be:
    • factor V Leiden mutation,
    • activated protein C (APC-) resistance,
    • antithrombin-III-deficiency,
    • protein C deficiency,
    • protein S deficiency,
    • Hyperhomocysteinemia (eg due to MTHFR C677T and A1298 mutations)
    • Prothrombin mutation G20210A
    • antiphospholipid-antibodies (anticardiolipin antibodies, lupus anticoagulant);
    • coadministration with paritaprevir, ritonavir, ombitasvir (with or without dasabuvir)

Products for postmenopausal indications

  • Hypersensitivity to any ingredient of the formulation, anaphylactic reaction or angioedema.
  • Undiagnosed abnormal Genital Bleeding;
  • DVT or PE (current and/or historical of);
  • Active or past history of arterial embombolic disease (eg stroke, MI);
  • Breast cancer (known, suspected, or history of);
  • An estrogen-dependent tumor (known, suspected)
  • Hepatic impairment or disease
  • known antithrombin deficiencies, known protein C and protein S;
  • pregnancy

Canadian labeling: Additional contraindications not in US labeling

  • Endometrial hyperplasia
  • Classic migraine
  • lactation

Warnings and precautions

  • Breast cancer: [US Boxed Warn]

    • According to data from the Women's Health Initiative (WHI), invasive breast cancer is more likely to occur in postmenopausal women who use conjugated estrogens (CE) and medroxyprogesterone (MPA).
    • Hormone therapy may be linked to increased breast density. It has been observed that using oestrogen alone or in combination increases the likelihood of abnormal mammography findings that call for additional assessment.
    • Patients with breast cancer or bone metastases may experience severe hypercalcemia from estrogen use. If this happens, discontinue estrogen.
    • This risk decreases when therapy is stopped, according to observational studies.
    • The WHI study found no evidence of an increase in breast cancer risk for women who had a hysterectomy with CE.
    • Postmenopausal women receiving hormone therapy could be at greater risk for breast cancer due to their estrogen or progestin doses, timing of therapy initiation, length of therapy, route of administration and patient characteristics.
    • 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)
    • 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.
    • Patients with breast cancer history or symptoms are advised to avoid this medication.

  • Cervical cancer:

    • 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.
    • Theoretically, it may influence the prognosis for existing diseases.

  • Chloasma

    • Treatment should be avoided for women who are susceptible to chloasma and other risk factors.
    • Hormone replacement therapy, hormonal combination contraceptives, and sun exposure are all triggers for chloasma.

  • Cholestasis:

    • Cholesteasis risk may increase if there has been a history of cholestasis in pregnancy, or with prior oral contraceptive use.

  • Dementia: [US Boxed Warning]

    • To prevent dementia, it is not a good idea to use estrogens without or with progestin.
    • According to the Women's Health Initiative Memory Study (WHIMS), women over 65 who took CE alone or in combination had a higher risk of developing dementia.
    • For the treatment or prevention of cognitive decline or dementia at any age, hormone therapy is not advised.
    • The WHI memory studies were performed on women over 65 years old. It is not known if the findings can be applied to younger postmenopausal women.

  • Endometrial Cancer: [US Boxed Warn]

    • Endometrial cancer is more likely to occur in women who have an intact uterus.
    • A progestin may be added to estrogen therapy to reduce the risk of endometrial Hyperplasia, which is a precursor of endometrial carcinoma.
    • It is crucial to carry out the proper diagnostic procedures, including endometrial sampling, if required, in order to rule out cancer in women who have undetected irregular vaginal blood flow.
    • A progestin should not be used if low doses are being administered locally to treat vaginal atrophy. However, there are insufficient long-term data (>1 years) supporting this recommendation.
    • Endometrial cancer is less common in women who use combined hormonal contraception.
    • Combination hormonal contraceptives may be used by women who are awaiting treatment for endometrial carcinoma.
    • In comparison to synthetic estrogens with identical oestrogen dosages, there is no evidence to imply that natural estrogens have a different risk profile.
    • Endometrial cancer risk appears to be dependent on the duration and dose of treatment. It is highest for patients who have been using therapy for more than 5 years. This may continue even after discontinuation.

  • Endometriosis:

    • Post-hysterectomy with estrogen therapy unopposed has led to malignant transformation of the remaining endometrial implants.
    • Women with endometriosis after hysterectomy should consider adding a progestin.
    • Estrogens may exacerbate endometriosis.

  • 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.
    • 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.

  • Ovarian cancer:

    • The information available regarding the risk of ovarian carcinoma and the use of estrogen/progestin therapy or menopausal estrogen is not consistent.
    • An association may exist, but the risk of developing a serious condition is unlikely. The duration of therapy can also influence the likelihood of an association.
    • Women who use combination hormonal contraceptives have a lower risk of developing ovarian cancer.
    • 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 carcinoma.

  • Retinal vascular embolism:

    • Stop using immediately and get tested for a retinal vein embolism if you develop an undetected loss of vision, proptosis, diplopia, or lesions of the retinal vessels.

  • Thromboembolic disorders

    • If you experience an arterial or vein thrombotic event, discontinue using combination hormonal contraceptives.
    • Women who use combined hormonal contraceptives have a higher risk of developing thrombotic events if they are older than 35 years.
    • 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.
    • The risk of venous thromboembolism increased by oral contraceptives is less than the risk associated with pregnancy and is greatest during the first year of use. Some studies indicate that the risk may be higher in preparations containing high doses of ethinylestradiol and/or third- or fourth-generation progestins.
    • The risk of venous thromboembolism may be higher in women who have genetic thrombophilias, such as protein C or S deficiency, factor V Leiden mutation, antithrombin deficiencies, or prothrombin mutation.
    • Combination hormonal contraceptives are not recommended for women at high risk of venous or arterial thrombotic diseases.

  • Vaginal bleeding

    • There may be occasional missed periods.
    • 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.

  • Abnormal uterine bleeding:

    • For abnormal uterine bleeding (AUB) caused by ovulatory dysfunction (not caused by structural factors), whether chronic or acute, a specific treatment should be taken into account.
    • Likewise, take medical restrictions on the treatments that are offered into account. Think about if pregnancy or contraception are needed concurrently.

  • Cardiovascular disease: [US-Boxed Warning]

    • Estrogens shouldn't be used with progestin or without it to prevent heart disease.
    • According to data from the Women's Health Initiative research, CE increases the risk of deep vein thrombosis and stroke.
    • In postmenopausal females aged 50 to 79, there has also been a reported rise in DVT, stroke, and pulmonary emboli (PE).
    • Diabetes mellitus, hypercholesterolemia, hypertension, SLE, obesity, cigarette use, and/or a history of venous thromboembolism are additional risk factors (VTE).
    • You should manage your risk factors well. If you suspect that adverse cardiovascular events may occur, stop using the medication immediately.
    • Consider the age, cardiovascular, metabolic, and other risk factors of patients with diabetes before beginning treatment for menopausal symptoms.
    • Women at high risk for arterial or vein thrombotic disease may find it contraindicated to use combination hormonal contraceptives.
    • When treating vasomotor symptoms of menopause in patients at high risk of thrombotic events, transdermal administration is preferable.
    • It is not advised for women who have an active DVT, PE, or arterial thromboembolic disorders (stroke and MI).
    • Use of combination hormonal contraceptives should be avoided in patients with cardiovascular risk factors, such as hypertension, low HDL and high LDL cholesterol, advanced age, diabetes, or women who smoke.

  • Depression

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

  • Diabetes:

    • Contraceptive use should not be used in women who have concomitant neuropathy, nephropathy, retinopathy or other vascular conditions.
    • Consider the age, cardiovascular, metabolic, and other risk factors of patients with diabetes before beginning treatment for menopausal symptoms.
    • Women with diabetes mellitus or vascular disease should not use combination hormonal contraceptives.
    • This may impair glucose tolerance. Women with diabetes and prediabetes should be cautious.
    • Combination oral contraceptives have a limited effect on insulin requirements and are not effective for long-term diabetes control in women who do not have nonvascular diseases.

  • Fluid retention can lead to more severe diseases

    • Patients with fluid retention-related diseases, such as cardiac or renal dysfunction, should be cautious.

  • Epilepsy:

    • Epilepsy can be aggravated if you are careful.

  • Gallbladder disease

    • Postmenopausal estrogen use may increase the risk of gallbladder diseases that require surgery.
    • Combination hormonal contraceptives have the potential to aggravate or raise the risk of gallbladder problems.

  • Hepatic adenomas and carcinomas

    • Hepatic tumours may develop as a result of combined hormonal contraceptives (rare). An abdominal rupture could cause catastrophic internal haemorrhage.
    • A higher risk of developing hepatocellular carcinoma in the long term (rare).
    • Preexisting hepatic cancers are not recommended.

  • Hepatic impairment

    • Women with hepatic impairment may not be able to process estrogens properly.
    • If jaundice occurs during treatment or if the liver function is abnormal, discontinue use.
    • Preexisting hepatic diseases are contraindicated.
    • Combination hormonal contraceptives can be used for women with mild (compensated), but not severe (decompensated), cirrhosis.

  • 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.

  • Hepatic hemomangiomas

    • Patients with hepatic hemomangiomas should be cautious; it may worsen the condition.

  • Hereditary angioedema:

    • Exogenous estrogens may cause angioedema symptoms in women with hereditary angioedema.

  • Hypertension:

    • Hypertension risk may increase with age, dosage, and length of use.
    • 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.
    • The manufacturer warns against use in women with uncontrolled hypertension. They recommend monitoring women with well-controlled hypertension. Stop taking the medication if your blood pressure increases significantly.
    • Women with hypertension or vascular disease or persistent blood pressure levels >=160mm Hg Systolic or >=100mm Hg Diastolic should not use combination hormonal contraceptives.

  • Hypoparathyroidism:

    • Patients with hypoparathyroidism should exercise caution because estrogen-induced hypocalcemia is a possibility.

  • Migraine

    • Examine headaches that are recent, ongoing, severe, or recurrent.

  • Otosclerosis

    • Women with migraines without aura, including menstrual migraines, may consider using combination hormonal contraceptives.
    • If >35 years old, it is not recommended to be used in women suffering from headaches that have focal neurological symptoms or migraine headaches without or with aura.
    • Patients with otosclerosis should exercise caution.

  • Porphyria

    • Patients with porphyria should be cautious as it can worsen the condition.

  • Transplantation of solid-organs:

    • Despite a lack of data, women who had to endure difficult organ transplants reported severe medical consequences (eg rejection, graft failure and cardiac allograft vasculopathy).
      Women who have undergone numerous organ transplants shouldn't use combination hormonal contraceptives.

  • Systemic lupus, erythematosus

    • SLE women are more at risk for heart disease, stroke and VTE.
    • Patients with systemic Lupus Erythematosus (SLE) should be cautious. This could worsen the condition.
    • 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.

Ethinyl estradiol and norethindrone: 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.

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 raise the level of oestrogen derivatives in the serum.

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 individuals who are taking cobicistat-containing medicines, one option for contraception to consider is one that is not hormone-based. 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.

Colesevelam

May lower the level of Norethindrone 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 should utilise a very effective, nonhormonal method of contraception for at least 2 weeks (dabrafenib alone) or 4 weeks.

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 Norethindrone in the serum.

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). 

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. These precise guidelines are not included on the pomalidomide labelling in the US.

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.

Rufinamide

May lower the level of Norethindrone 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. 

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 lower the level of progestins in the serum (Contraceptive).

Exemestane

Estrogen derivatives may reduce Exemestane's therapeutic efficacy.

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.Ospemifene's therapeutic efficacy may be lessened by oestrogen derivatives.

Tranexamic Acid

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. Management: 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:

Hormonal contraceptives:

  • Assessment of weight (optional BMI at baseline may be helpful to track changes throughout therapy), blood pressure (annually), and pregnancy status (prior to therapy). During routine checkups, check for any changes in health status.

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 if 2 consecutive menstrual cycles are missing, determine whether a woman is pregnant. observe the patient for:

  • vision changes;
  • blood pressure;
  • signs and symptoms of thromboembolic disorders;
  • signs or symptoms of depression;
  • glycemic control in patients with diabetes;
  • lipid profiles in patients being treated for hyperlipidemias.
  • In every instance of undetected abnormal vaginal bleeding, adequate diagnostic procedures should be carried out to rule out cancer.

Postmenopausal indications:

  • Prior to therapy, baseline risk for breast cancer and CVD.
  • During therapy, age-appropriate breast, and pelvic exams;
  • blood pressure;
  • abnormal bleeding for endometrial pathology lasting longer than six months (earlier in women who are obese, diabetic, or have a history of endometrial malignancy);
  • serum triglycerides (2 weeks after starting therapy in patients with baseline level >200 mg/dL);
  • TSH (6 to 12 weeks after starting oral therapy in patients taking thyroid replacement).

Menopausal symptoms:

  • Efficacy beginning 1 to 3 months after starting therapy, then every 6 to 12 months as appropriate.
  • The duration of treatment should be evaluated at least annually.

Note: When treating vasomotor symptoms of menopause, monitoring of FSH and serum estradiol is not helpful. Prevention of osteoporosis:

  • Bone density measurement

How to administer Ethinyl estradiol and norethindrone?

Combination hormonal contraceptives:

  • Without regard to meals, administer at the same time every day at intervals of no longer than 24 hours.
  • Whether chewed or consumed whole, the Femcon Fe tablet should be followed by a full glass (240 mL) of liquid.
  • If vomiting or diarrhoea occurs 3 to 4 hours after a dose of some medications (such as Femcon Fe, Generess Fe, or Lo Loestrin Fe), the dose should be missed.
  • For the 21-tablet package, one dose is taken every day for 21 days straight, then there is a 7-day break from the drug before starting a fresh course on the eighth day after the final tablet is taken.
  • One dose every day, uninterrupted, is taken for the 28-tablet supply.

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. After a first or second trimester abortion, combined hormonal contraceptives may be begun right away or within a short period of time; backup contraception is required for 7 days if contraception is not started at the time of the surgical abortion.

Postmenopausal indications:

  • Administer at the same time each day.

Mechanism of action of Ethinyl estradiol and norethindrone:

  • Combination oral 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.
  • Endometrium changes can also happen, which could lead to unfavorable conditions for nidation. 
  • Combination hormonal contraceptives may affect the tubal transport and function of the ova through fallopian tubes. 
  • The fertility of sperm may also be affected by progestational drugs.
  • In postmenopausal females, exogenous oestrogen can be used to make up for the loss of endogenous oestrogen.
  • By taking progestin, women with an intact uterus can lower their risk of developing endometrial hyperplasia and cancer.

Norethindrone: See individual monograph.

Ethinyl estradiol:

Absorption:

  • Rapid

Bioavailability:

  • 43% to 55%

Protein binding:

  • more than 95 percent to albumin

Metabolism:

  • First-pass action, enterohepatic recirculation, oxidation and conjugation in the GI tract, hydroxylation to metabolites via CYP3A4, and reversible conversion to estrone and estriol

Half-life elimination:

  • 19 to 24 hours

Excretion:

  • Urine (as estriol,estradiol and estrone);
  • feces

International Brand Names of Ethinyl estradiol and norethindrone:

  • Alyacen 1/35
  • Blisovi 24 Fe
  • Blisovi Fe 1.5/30
  • Blisovi FE 1/20
  • Brevicon (28)
  • Briellyn
  • Cyclafem 1/35
  • Cyclafem 7/7/7
  • Dasetta 1/35
  • Dasetta 7/7/7
  • Estrostep Fe
  • Alyacen 7/7/7
  • Aranelle
  • Aurovela 1.5/30
  • Aurovela 1/20
  • Aurovela 24 FE
  • Aurovela FE 1/20
  • Balziva
  • Femcon Fe
  • Femhrt Low Dose
  • Fyavolv
  • Generess FE
  • Gildagia
  • Gildess 1.5/30
  • Gildess 1/20
  • Gildess 24 FE
  • Gildess FE 1.5/30
  • Gildess FE 1/20
  • Hailey 24 Fe
  • Kaitlib Fe
  • Larin 1.5/30
  • Larin 1/20
  • Larin 24 FE
  • Larin Fe 1.5/30
  • Larin Fe 1/20
  • Layolis FE
  • Leena
  • Lo Loestrin Fe
  • Loestrin 1.5/30 (21)
  • Loestrin 1/20 (21)
  • Loestrin Fe 1.5/30
  • Loestrin Fe 1/20
  • Lomedia 24 FE
  • Melodetta 24 Fe
  • Mibelas 24 Fe
  • Microgestin 1.5/30
  • Jevantique Lo
  • Jinteli
  • Junel 1.5/30
  • Junel 1/20
  • Junel FE 1.5/30
  • Junel FE 1/20
  • Junel Fe 24
  • Microgestin 1/20
  • Microgestin 24 Fe
  • Microgestin FE 1.5/30
  • Microgestin FE 1/20
  • Minastrin 24 Fe
  • Modicon (28)
  • Necon 0.5/35 (28)
  • Necon 1/35 (28)
  • Necon 10/11 (28)
  • Necon 7/7/7
  • Norinyl 1+35 (28)
  • Nortrel 0.5/35 (28)
  • Nortrel 1/35 (21)
  • Nortrel 1/35 (28)
  • Nortrel 7/7/7
  • Ortho-Novum 1/35 (28)
  • Ortho-Novum 7/7/7 (28)
  • Ovcon-35 (28)
  • Philith
  • Pirmella 1/35
  • Pirmella 7/7/7
  • Tarina 24 Fe
  • Tarina FE 1/20
  • Tarina FE 1/20 EQ
  • Taytulla
  • Tilia Fe
  • Brevicon 1/35
  • FemHRT
  • Loestrin 1.5/30
  • Lolo
  • Minestrin 1/20
  • Ortho 0.5/35
  • Ortho 1/35
  • Ortho 7/7/7
  • Select 1/35
  • Synphasic
  • Brevinor
  • Covina
  • Estracomb
  • Estragest TTS
  • Eveclin Half
  • Eveprem
  • Eviclin
  • Evorel Cont
  • Evorel Conti
  • Evorel Sequi
  • Evorelconti
  • Lunabell
  • Micropil
  • Tri-Legest Fe
  • Tri-Norinyl (28)
  • Vyfemla
  • Wera
  • Wymzya Fe
  • Zenchent FE
  • Zenchent
  • Brevicon 0.5/35
  • Norimin
  • Ortho 7 7 7
  • Ortho-Novum 1 35
  • Ortho-Novum 1/35
  • Ovysmen
  • Ovysmen 0.5 35
  • Trisequens;
  • Trisequens Forte
  • Ovysmen 1 35
  • Synphase-2
  • Synphasic 28
  • Tri-Sequens
  • Triella
  • Trinovum
  • Trisekvens

Ethinyl estradiol and norethindrone Brand Names in Pakistan:

There is no brand available in Pakistan.

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