Dienogest-Estradiol Valerate

Dienogest-Estradiol Valerate is an oral contraceptive used to prevent pregnancy. 

• Dienogest-Estradiol Valerate is available under the following different brand names: Natazia.

Common side effects of Dienogest-Estradiol Valerate include:

• Light vaginal bleeding or spotting,
• Nausea,
• Vomiting,
• Breast pain or tenderness,
• Weight gain, and
• Problems with contact lenses

Serious side effects of Dienogest-Estradiol Valerate include:

• Hives,
• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat,
• Sudden numbness or weakness (especially on one side of the body),
• Sudden severe headache,
• Slurred speech,
• Problems with vision or balance,
• Chest pain or pressure,
• Sudden cough,
• Wheezing,
• Coughing up blood,
• Swelling or warmth in one or both legs,
• Pain spreading to the jaw or shoulder,
• Nausea,
• Sweating,
• Severe stomach pain,
• Fever,
• Tiredness,
• Loss of appetite,
• Dark urine,
• Clay-colored stools,
• Yellowing of the skin or eyes (jaundice),
• Sudden and severe pelvic pain,
• Changes in the pattern or severity of migraine headaches,
• Swelling in your hands, ankles, or feet,
• Breast lump,
• Sleep problems,
• Weakness,
• Tired feeling, and
• Mood changes

Rare side effects of Dienogest-Estradiol Valerate include:

• None 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out. 

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Tablet

Contains 4 phases of doses for estrogen or combined estrogen/progestin throughout the 28-day cycle.

• Days 1-2: estradiol valerate 3 mg
• Days 3-7: estradiol valerate 2 mg and dienogest 2 mg
• Days 8-24: estradiol valerate 2 mg and dienogest 3 mg
• Days 25-26: estradiol valerate 1 mg
• Days 27-28: inert tablets

Contraception

Adult dosage

• 1 tab orally once a day; take at the same time each day and in precise order as directed on the blister pack.
• Do not skip tablets or delay intake by more than 12 hours.
• Initiate by the beginning pack on day 1 of the menstrual cycle and use a nonhormonal contraceptive backup method (. g, condoms, and foam) during the first 9 days
• Initiating after pregnancy
  • Increased risk for venous thromboembolism (VTE) following delivery with combined hormonal contraceptives; risk declines rapidly after 21 days but does not return to normal until 42 days after delivery.
  • CDC guidelines recommend waiting 3-6 weeks in postpartum women without additional VTE risks (MMWR July 7, 2011)
  • Initiating after vaginal birth: Wait at least 3 weeks.
  • Initiating after cesarean section birth: Wait at least 6 weeks.
  • Women with other risk factors for VTE in addition to postpartum: Do not use combined hormonal contraceptives.

Pediatric dosage

• Safety and efficacy are established in women of reproductive age; efficacy is expected to be the same for post-pubertal adolescents under the age of 18 as for users 18 years and older.

Adolescents requiring contraception: As adults.

• 1 tablet orally once a day; take at the same time each day and in precise order as directed on the blister pack
• Do not skip tablets or delay intake by more than 12 hours.
• Initiate by the beginning pack on day 1 of the menstrual cycle and use a nonhormonal contraceptive backup method (. g, condoms, and foam) during the first 9 days

Initiating after pregnancy

• Increased risk for venous thromboembolism (VTE) following delivery with combined hormonal contraceptives; risk declines rapidly after 21 days but does not return to normal until 42 days after delivery.
• CDC guidelines recommend waiting 3-6 weeks in postpartum women without additional VTE risks (MMWR July 7, 2011)
• Initiating after vaginal birth: Wait at least 3 weeks.
• Initiating after cesarean section birth: Wait at least 6 weeks.
• Women with other risk factors for VTE in addition to postpartum: Do not use combined hormonal contraceptives.

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Dienogest-Estradiol Valerate has severe interactions with the following drugs:
  • bosentan
  • carbamazepine
  • dexamethasone
  • efavirenz
  • eslicarbazepine acetate
  • fosphenytoin
  • nafcillin
  • nevirapine
  • ospemifene
  • oxcarbazepine
  • pentobarbital
  • phenobarbital
  • phenytoin
  • primidone
  • rifabutin
  • rifapentine
  • St John's Wort
  • tranexamic acid oral
• Dienogest-Estradiol Valerate has serious interactions with the following drugs:
  • belzutifan
  • brigatinib
  • calaspargase pegol
  • elagolix
  • encorafenib
  • isavuconazonium sulfate
  • lesinurad
  • lumacaftor/ivacaftor
  • mavacamten
  • mobocertinib
  • pexidartinib
  • pretomanid
  • sugammadex sodium
• Dienogest-Estradiol Valerate has moderate interactions with at least 109 other drugs.
• Dienogest-Estradiol Valerate has minor interactions with the following drug:
  • enasidenib

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Pregnancy
• Hypersensitivity
• Breast Cancer, or another estrogen- or progestin-sensitive cancer
• A high risk of arterial or venous thromboembolic disorders
• Undiagnosed uterine bleeding

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Dienogest-Estradiol Valerate?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Dienogest-Estradiol Valerate?”

Cautions

• Poorly metabolized with hepatic impairment
• Use caution in patients with a history of migraine, seizure disorders,
• Not recommended for women smokers above 35 years
• Oral contraceptives can reduce the production of milk in breastfeeding mothers.
• Evaluate significant change in headaches and discontinue therapy if indicated.
• Women taking strong CYP3A4 inducers (for example, carbamazepine, phenytoin, rifampicin, and St. John’s wort) should choose an alternate oral contraceptive due to the possibility of decreased contraceptive efficacy.
• Discontinue therapy if jaundice occurs.
• Not for administration for women with uncontrolled hypertension or hypertension with vascular disease
• Monitor prediabetic and diabetic women receiving therapy.
• Consider an alternate contraceptive method for women with uncontrolled dyslipidemia.
• Evaluate uterine bleeding or amenorrhea.
• Thromboembolic disease may occur; stop therapy for at least 4 weeks before and through 2 weeks after major surgery; initiate therapy no sooner than 4 weeks after delivery, in women who are not breastfeeding.
• Safety and efficacy not established for BMI above30 kg/m²
• CDC guidelines recommend waiting at least 3 weeks following vaginal birth or 6 weeks after cesarean section to decrease the risk for venous thromboembolism before initiating combined hormonal contraceptives; women with additional risk factors for VTE (besides postpartum) should not use combined hormonal contraceptives (MMWR July 7, 2011)
• Breast cancer
  • Epidemiology studies have not found a consistent association between the use of combined oral contraceptives (COCs) and breast cancer risk; studies do not show an association between every (current or past) use of COCs and the risk of breast cancer.
  • Some studies report a small increase in the risk of breast cancer among current or recent users (below 6 months since last use) and current users with a longer duration of COC use.
  • A woman's risk depends on conditions where naturally high hormone levels persist for long periods including early-onset menstruation before age 12, late-onset menopause, after age 55, first child after age 30, and nulliparity.

Pregnancy and Lactation

• Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives before pregnancy; studies also do not suggest a teratogenic effect, particularly insofar as cardiac anomalies and limb reduction defects are concerned, when taken inadvertently during early pregnancy
• Administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy; oral contraceptives should not be used during pregnancy to treat threatened or habitual abortion.
• It is recommended that for any patient who has missed two consecutive periods, pregnancy should be ruled out before continuing oral contraceptive use; if the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of first missed period; oral contraceptive use should be discontinued if pregnancy is confirmed.
• Lactation
  • Small amounts of oral contraceptive steroids were identified in the milk of nursing mothers, and a few adverse effects on child reported, including jaundice and breast enlargement; in addition, oral contraceptives given in the postpartum period may interfere with lactation by decreasing the quantity and quality of breast milk.
  • If possible, the nursing mother should be advised not to use oral contraceptives but to use other forms of contraception until she has completely weaned her child.