What Is Natazia?
Natazia (estradiol valerate and estradiol valerate/dienogest) is an oral contraceptive used to prevent pregnancy.
What Are Side Effects of Natazia?
Common side effects of Natazia include:
- irregular or light menstrual periods,
- nausea (especially when you first start taking Natazia),
- breast pain/tenderness/enlargement,
- stomach cramping or bloating,
- freckles or darkening of facial skin,
- weight gain,
- problems with contact lenses,
- vaginal itching or discharge,
- decreased sex drive, or
Acne may improve or get worse. Tell your doctor if you have serious side effects of Natazia including:
- a lump in your breast,
- unusual changes in vaginal bleeding,
- mental/mood changes (such as new or worsening depression),
- dark urine,
- yellowing eyes or skin,
- severe stomach/abdominal/pelvic pain, or
- unusual tiredness.
Seek medical care or call 911 at once if you have the following serious side effects:
- Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
- Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheartedness, or passing out;
- 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.
This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.
Dosage for Natazia
Natazia must be taken exactly as directed. Take one tablet by mouth at the same time every day. Tablets must be taken in the order directed on the blister pack. Tablets should not be skipped or intake delayed by more than 12 hours.
What Drugs, Substances, or Supplements Interact with Natazia?
Natazia may interact with bosentan, antibiotics, tuberculosis medications, drugs to treat hepatitis C or HIV/AIDS, phenobarbital and other barbiturates, St. John's wort, seizure medications, dantrolene, tizanidine, or tranexamic acid. Tell your doctor all medications and supplements you use.
Do not use Natazia if you are pregnant; it can cause birth defects.
Natazia During Pregnancy or Breastfeeding
Do not use Natazia if you are pregnant; it can cause birth defects.Tell your doctor right away if you become pregnant, or if you miss two menstrual periods in a row. If you have recently had a baby, wait at least 4 weeks before taking Natazia. The hormones in Natazia can pass into breast milk and may harm a nursing baby. Natazia may also slow breast milk production. Breastfeeding while using Natazia is not recommended.
Our Natazia (estradiol valerate and estradiol valerate/dienogest) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Stop taking this medicine and call your doctor at once if you have:
- signs of a stroke--sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance;
- signs of a blood clot--chest pain, sudden cough, wheezing, coughing up blood, swelling or warmth in one or both legs;
- heart attack symptoms--chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating;
- liver problems--severe stomach pain, fever, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
- sudden and severe pelvic pain;
- a change in the pattern or severity of migraine headaches;
- swelling in your hands, ankles, or feet;
- a breast lump; or
- symptoms of depression--sleep problems, weakness, tired feeling, mood changes.
Common side effects may include:
- light vaginal bleeding or spotting;
- nausea (especially during the first few months of taking this medicine), vomiting;
- breast pain or tenderness;
- weight gain; or
- problems with contact lenses.
Read the entire detailed patient monograph for Natazia (Estradiol Valerate and Estradiol Valerate Dienogest Tablets)
The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling:
- Serious cardiovascular events and stroke [see BOXED WARNING and WARNINGS AND PRECAUTIONS]
- Vascular events [see WARNINGS AND PRECAUTIONS]
- Liver disease [see WARNINGS AND PRECAUTIONS]
Adverse reactions commonly reported by COC users are:
- Irregular uterine bleeding
- Breast tenderness
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Contraception And Heavy Menstrual Bleeding Studies
A total of 2,131 women, 18 to 54 years of age, who took at least one dose of Natazia were enrolled in four clinical phase 3 trials. A total of 1,867 subjects were included in two clinical phase 3 studies with a treatment duration up to 28 cycles with Natazia as an oral contraceptive and 264 subjects in the two phase 3 clinical trials with a treatment duration of 7 cycles evaluating Natazia in the treatment of heavy, prolonged, and/or frequent menstrual bleeding in women without organic pathology [see Clinical Studies].
Adverse Reactions Leading to Study Discontinuation: 11.4% of the women discontinued from the clinical trials due to an adverse reaction; the most frequent adverse reactions leading to discontinuation were menstrual disorder (metrorrhagia, menorrhagia, menstruation irregular, genital hemorrhage, vaginal hemorrhage, dysfunctional uterine bleeding) (2.3%); mood changes (depression, mood swings, mood altered, depressed mood, dysthymic disorder, crying) (1.2%); acne (1.1%), headache (including migraines) (1.1%), and weight increased (0.7 %).
Common Adverse Reactions (≥ 2%): headache (including migraines) (12.7%), breast pain, discomfort or tenderness (7.0%), menstrual disorders (metrorrhagia, menstruation irregular, menorrhagia, vaginal hemorrhage, dysfunctional uterine bleeding, genital hemorrhage, abnormal withdrawal bleeding, uterine hemorrhage) (6.9%), nausea or vomiting (6.0%), acne (3.9%), mood changes (depression, mood swings, depressed mood, mood altered, affect lability, dysthymic disorder, crying) (3.0%) and increased weight (2.9%).
Serious Adverse Reactions: myocardial infarction (2 cases), ruptured ovarian cyst (2 cases), deep vein thrombosis, focal nodular hyperplasia of the liver, uterine leiomyoma, acute cholecystitis, and chronic acalculous cholecystitis.
Five studies that compared breast cancer risk between ever-users (current or past use) of COCs and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90 - 1.12 (Figure 1).
Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 1). One of these studies reported no association between breast cancer risk and COC use. The other two studies found an increased relative risk of 1.19-1.33 with current or recent use. Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8-10 years of COC use.
Figure 1: Relative Studies of Risk of Breast Cancer with Combined Oral Contraceptives
The following adverse reactions have been identified during post-approval use of Natazia. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Vascular disorders: Venous and arterial thromboembolic events (including pulmonary emboli, deep vein thrombosis, cerebral thrombosis, myocardial infarction and stroke), hypertension
Hepatobiliary disorders: Gallbladder disease, hepatitis
Immune system disorders: Hypersensitivity
Metabolism and nutrition disorders: Fluid retention, hypertriglyceridemia
Nervous system disorders: Dizziness
Skin and subcutaneous tissue disorders: Chloasma, angioedema, erythema nodosum, erythema multiforme
Gastrointestinal disorders: Gastrointestinal symptoms (for example, abdominal pain)
Infections and infestations: Vulvovaginal candidiasis
Consult the labeling of all concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.
Effects Of Other Drugs On Combined Oral Contraceptives
Substances Diminishing The Efficacy Of COCs
Dienogest is a substrate of CYP3A4. Women who take medications that are strong CYP3A4 inducers should not choose Natazia as their oral contraceptive while using these inducers and for at least 28 days after discontinuation of these inducers due to the possibility of increased breakthrough bleeding and/or decreased contraceptive efficacy.
Drugs or herbal products that induce certain enzymes, including CYP3A4, may decrease the effectiveness of COCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampin, topiramate and products containing St. John's wort. Interactions between oral contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative method of contraception or a back-up method when enzyme inducers are used with COCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability.
Multiple dose co-administration of the strong CYP3A4 inducer rifampin with estradiol valerate/dienogest tablets in healthy postmenopausal women led to a decrease in dienogest and estradiol systemic exposure at steady state. [See CLINICAL PHARMACOLOGY]
Substances Increasing The Systemic Exposure Of COCs (enzyme inhibitors)
Concomitant administration of moderate or strong CYP3A4 inhibitors like azole antifungals (for example, ketoconazole, itraconazole, voriconazole, fluconazole), verapamil, macrolides (for example, clarithromycin, erythromycin), diltiazem, and grapefruit increase the serum concentrations of both estradiol and dienogest.
In a multiple dose study investigating the effect of CYP3A4 inhibitors (ketoconazole and erythromycin) on Natazia, steady state estradiol and dienogest exposures were increased when co-administered with ketoconazole or erythromycin [see CLINICAL PHARMACOLOGY].
Human Immunodeficiency Virus (HIV)/Hepatitis C Virus (HCV) Protease Inhibitors And Non-Nucleoside Reverse Transcriptase Inhibitors
Significant changes (increase and decrease) in plasma concentrations of estrogen and progestin have been noted in some cases of co-administration of HIV/HCV protease inhibitors or with non-nucleoside reverse transcriptase inhibitors.
There have been reports of pregnancy while taking hormonal contraceptives and antibiotics, but clinical pharmacokinetic studies have not shown consistent effects of antibiotics on plasma concentrations of synthetic steroids.
Effects Of Combined Oral Contraceptives On Other Drugs
COCs containing ethinyl estradiol may inhibit the metabolism of other compounds. COCs have been shown to significantly decrease plasma concentrations of lamotrigine, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Consult the labeling of the concurrently-used drug to obtain further information about interactions with COCs or the potential for enzyme alterations. [See CLINICAL PHARMACOLOGY]
In vitro studies with human CYP enzymes did not indicate an inhibitory potential of dienogest at clinically relevant concentrations.
Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because serum concentrations of thyroid-binding globulin increase with use of COCs.
Interference With Laboratory Tests
The use of contraceptive steroids may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS].
Read the entire FDA prescribing information for Natazia (Estradiol Valerate and Estradiol Valerate Dienogest Tablets)
© Natazia Patient Information is supplied by Cerner Multum, Inc. and Natazia Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.
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