Valerate

COCs lower the risk of becoming pregnant primarily by suppressing ovulation.

• • Natazia is a combination of dienogest , a progestin, and estradiol valerate, an estrogen, indicated for use by females of reproductive potential to prevent pregnancy. ( 1 ) • The efficacy of Natazia in females of reproductive potential with a body mass index (BMI) of >30 kg/m 2 has not been evaluated.

• Natazia is contraindicated in females who are known to have or develop the following conditions: • A high risk of arterial or venous thrombotic diseases. Examples include women who are known to: • Smoke, if over age 35 [see Boxed Warning and Warnings and Precautions ( 5.1 )] • Have deep vein thrombosis or pulmonary embolism, now or in the past [see Warnings and Precautions ( 5.1 )] • Have cerebrovascular disease [see Warnings and Precautions ( 5.1 )] • Have coronary artery disease [see Warnings and Precautions ( 5.1 )] • Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see Warnings and Precautions ( 5.1 )] • Have inherited or acquired hypercoagulopathies [see Warnings and Precautions ( 5.1 )] • Have uncontrolled hypertension [see Warnings and Precautions ( 5.4 )] • Have diabetes mellitus with vascular disease [see Warnings and Precautions ( 5.6 )] • Have headaches with focal neurological symptoms or have migraine headaches with or without aura if over age 35 [see Warnings and Precautions ( 5.7 )] • Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (…contraindicated

• Take one tablet daily by mouth at the same time every day. ( 2.1 ) • Tablets must be taken in the order directed on the blister pack. ( 2.1 ) • Do not skip or delay intake by more than 12 hours. ( 2.1 ) 2.1 How to Take Natazia To achieve maximum contraceptive effectiveness, 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. For patient instructions for missed pills, see FDA-Approved Patient Labeling. 2.2 How to Start Natazia Instruct the patient to begin taking Natazia on Day 1 of her menstrual cycle (that is, the first day of her menstrual bleeding). See FDA-Approved Patient Labeling . Instruct the patient to use a non-hormonal contraceptive as back-up during the first 9 days. For postpartum women who do not breastfeed or after a second trimester abortion, start Natazia no earlier than 4 weeks postpartum due to the increased risk of thromboembolism. If the patient starts on Natazia postpartum and has not yet had a period, evaluate for possible pregnancy, and instruct her to use an additional method of contraception until she has taken Natazia for 9 consecutive days. The possibility of ovulation and conception prior to initiation of medication should also be considered. If the patient is switching from a combination hormonal method such as: • Another pill • Vaginal ring • Patch • Instruct her to take the first dark yellow pill on the first day of her withdrawal bleed.

• Vascular risks : Stop Natazia if a thrombotic event occurs. Stop Natazia at least 4 weeks before and through 2 weeks after major surgery. Start Natazia no earlier than 4 weeks after delivery, in women who are not breastfeeding. ( 5.1 ) • Liver disease : Discontinue Natazia if jaundice occurs. ( 5.3 ) • High blood pressure : Do not prescribe Natazia for women with uncontrolled hypertension or hypertension with vascular disease. ( 5.4 ) • Carbohydrate and lipid metabolic effects : Monitor prediabetic and diabetic women taking Natazia. Consider an alternate contraceptive method for women with uncontrolled dyslipidemia. ( 5.6 ) • Headache : Evaluate significant change in headaches and discontinue Natazia if indicated. ( 5.7 ) • Uterine bleeding : Evaluate irregular bleeding or amenorrhea. ( 5.8 ) • CYP3A4 induction : Women taking strong CYP3A4 inducers (for example, carbamazepine, phenytoin, rifampicin, and St. John’s wort) should not choose Natazia as their oral contraceptive due to the possibility of decreased contraceptive efficacy. ( 5.13 , 7.1 ) 5.1 Thromboembolic Disorders and Other Vascular Problems Stop Natazia if an arterial or venous thrombotic event (VTE) occurs. The use of COCs increases the risk of venous thromboembolism. However, pregnancy increases the risk of venous thromboembolism as much or more than the use of COCs. The risk of VTE in women using COCs has been estimated to be 3 to 9 per 10,000 woman-years. The risk of VTE is highest during the first year of use.

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 ( 5.1 )] • Vascular events [see Warnings and Precautions ( 5.1 )] • Liver disease [see Warnings and Precautions ( 5.3 )] Adverse reactions commonly reported by COC users are: • Irregular uterine bleeding • Nausea • Breast tenderness • Headache The most common adverse reactions (≥ 2%) in clinical trials for Natazia are headache (including migraines) 13%, breast pain 7%, menstrual disorders 7%, nausea/vomiting 6%, acne 4%, mood changes (3%) and increased weight 3%. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc. at 1-888-842-2937 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 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.

• Lactation: can decrease milk production. ( 8.2 ) • Body Mass Index: The safety and efficacy of Natazia in women with a body mass index (BMI) of >30 kg/m 2 has not been evaluated. ( 8.8 ) 8.1 Pregnancy Risk Summary There is no reason to use COCs in pregnancy Discontinue Natazia if pregnancy occurs. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to COCs prior to conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively. 8.2 Lactation Risk Summary Contraceptive hormones and/or metabolites are present in human milk. CHCs can reduce milk production in breastfeeding females. This reduction can occur at any time but is less likely to occur once breastfeeding is well-established. When possible, advise the nursing female to use other forms of contraception until she discontinues breastfeeding. [See also Dosage and Administration ( 2.2 )]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Natazia and any potential adverse effects on the breast-fed child from Natazia or from the underlying maternal condition.

Metabolism

Absorption After oral administration of estradiol valerate, cleavage to 17β-estradiol and valeric acid takes place during absorption by the intestinal mucosa or in the course of the first liver passage. This gives rise to estradiol and its metabolites, estrone and other metabolites.

There have been no reports of serious ill effects from overdose, including ingestion by children. Overdosage may cause withdrawal bleeding in females and nausea.

• Jul 15, 1954NDANDA009402Ph Health
• Mar 24, 1983NDANDA018642Cosette
• Aug 31, 1983NDANDA018861Fougera Pharms Inc
• Aug 31, 1983NDANDA018865Fougera Pharms Inc
• Aug 31, 1983NDANDA018866Fougera Pharms Inc
• Dec 19, 1985ANDAANDA070069Cosette
• Jan 6, 1988ANDAANDA072041Sun Pharma Canada
• May 6, 2010NDANDA022252Bayer Hlthcare

1. 1Drug Ineffective1,27920%
2. 2Pain72011%
3. 3Macular Degeneration6369.8%
4. 4Off Label Use6279.7%
5. 5Nausea5518.5%
6. 6Headache5428.4%
7. 7Weight Decreased4967.7%
8. 8Malaise4757.3%
9. 9Pyrexia4376.7%
10. 10Pruritus4106.3%
11. 11Fatigue3956.1%
12. 12Rash3956.1%
13. 13Dyspnoea3946.1%
14. 14Diarrhoea3715.7%
15. 15Vomiting3515.4%

Recent PubMed references pinned to Valerate as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Diosgenin ameliorates behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid.
  Metabolic brain disease · 2026 · Dehkhodaei S, Naghdibadi MR, Ahadi R, et al.
  PMID 42262415DOI 10.1007/s11011-026-01851-7
• Comparing the safety and efficacy of sodium valproate, levetiracetam, and phenytoin in attenuating the severity of agitation in patients with post-traumatic brain injury: An observational study.
  PloS one · 2026 · Singh S, Nayak R, Gangachannaiah S, et al.
  PMID 42234767DOI 10.1371/journal.pone.0350585
• Treadmill Exercise Alleviates Motor Deficits of PD Mice via Regulating STING-Mediated Valeric Acid-Th17/Treg-IL-17A Axis.
  Molecular neurobiology · 2026 · Liu X, Lv M, Liu D, et al.
  PMID 42234336DOI 10.1007/s12035-026-05924-7
• Abnormal Enteric Nervous System Organization and Gastrointestinal Motility in Mice With Valproic Acid-Induced Neural Tube Defects.
  Neurogastroenterology and motility · 2026 · Barsh GR, Banducci K, Kaltschmidt JA, et al.
  PMID 42231590DOI 10.1111/nmo.70368
• Combinatorial drug repurposing of Valproic acid and Zebularine regulates Krüppel-like factor 4 and β-catenin expression in colon cancer cells.
  PloS one · 2026 · Kandhavelu J, Subramanian K, Moodley N, et al.
  PMID 42224286DOI 10.1371/journal.pone.0348215
• Impaired Neuregulin 1 Processing is Associated with Synaptic and Behavioral Abnormalities in a Prenatal Valproic Acid Model of Autism.
  International journal of biological sciences · 2026 · Kim YJ, Kim HB, Lim HM, et al.
  PMID 42212327DOI 10.7150/ijbs.133137
• Synergistic Cardiac Protection by Thymoquinone and Valproic Acid in Absence Epilepsy.
  Physiological research · 2026 · Cimen YA, Karakaya-Cimen FB, Demirci H, et al.
  PMID 42187503DOI 10.33549/physiolres.935733
• Quality improvement project improving awareness of family planning risks with valproate in male patients.
  The British journal of general practice : the journal of the Royal College of General Practitioners · 2026 · Shahul SF
  PMID 42134936DOI 10.3399/bjgp26X745605

The 10 most recently updated of 541 ClinicalTrials.gov registrations naming Valerate as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Using a Contact Dermatitis Model With Biologic Medications to Study Skin Inflammation
  Active not recruiting · Phase 2 · Phase 3 · Interventional · 45 enrolled · Wei-Che Ko
  NCT05535738updated 2026-06-09
• A Study to Assess the Long-term Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-3)
  Recruiting · Phase 3 · Interventional · 450 enrolled · Bristol-Myers Squibb
  NCT06929273updated 2026-06-02
• Bevacizumab and Temsirolimus Alone or in Combination With Valproic Acid or Cetuximab in Treating Patients With Advanced or Metastatic Malignancy or Other Benign Disease
  Terminated · Phase 1 · Interventional · 154 enrolled · M.D. Anderson Cancer Center
  NCT01552434updated 2026-05-15
• Rubinstein-Taybi Syndrome: Functional Imaging and Therapeutic Trial
  Completed · Phase 2 · Interventional · 41 enrolled · University Hospital, Bordeaux
  NCT01619644updated 2026-05-14
• Combining Sodium Valproate With Standard-of-care EGFR (Epidermal Growth Factor Receptor) Monoclonal Antibody Treatment in Patients With Metastatic Colorectal Cancer
  Active not recruiting · Phase 2 · Interventional · 38 enrolled · Australasian Gastro-Intestinal Trials Group
  NCT05694936updated 2026-05-08
• Safety, Tolerability, and Efficacy of PLX-200 in Patients With CLN3
  Not yet recruiting · Phase 3 · Interventional · 39 enrolled · Polaryx Therapeutics, Inc.
  NCT04637282updated 2026-05-08
• Ketogenic Diet for New-Onset Absence Epilepsy
  Recruiting · Phase 3 · Interventional · 40 enrolled · Johns Hopkins University
  NCT04274179updated 2026-05-07
• Efficacy and Safety Trial of Sodium Valproate, in Paediatric and Adult Patients With Wolfram Syndrome
  Completed · Phase 2 · Interventional · 63 enrolled · University of Birmingham
  NCT03717909updated 2026-05-05
• Τhe Combination of Pharmacotherapy With RECOVERYTRSGR and RECOVERYTRSBDGR.
  Active not recruiting · Phase 4 · Interventional · 84 enrolled · Dr. Stavroula Rakitzi
  NCT07047651updated 2026-05-01
• Progesterone-modified Natural Cycle for FET
  Recruiting · Phase 3 · Interventional · 336 enrolled · Shandong University of Traditional Chinese Medicine
  NCT06644794updated 2026-04-29

Frequently asked questions

How does Valerate work?

COCs lower the risk of becoming pregnant primarily by suppressing ovulation.

What is Valerate used for?

According to FDA labeling, Valerate carries indications including: • Natazia is a combination of dienogest , a progestin, and estradiol valerate, an estrogen, indicated for use by females of reproductive potential to prevent pregnancy. ( 1 ) • The efficacy of Natazia in females of reproductive potential with a body mass index (BMI) of >30 kg/m 2 has not been evaluated.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What are the contraindications for Valerate?

Valerate labeling lists contraindications including: Natazia is contraindicated in females who are known to have or develop the following conditions: • A high risk of arterial or venous thrombotic diseases. Examples include women who are known to: • Smoke, if over age 35 [see Boxed Warning and Warnings and Precautions ( 5.1 )] • Have deep vein thrombosis or pulmonary embolism, now or in the past [see Warnings and Precautions ( 5.1 )] • Have cerebrovascular disease [see Warnings and Precautions ( 5.1 )] • Have coronary artery disease [see Warnings and Precautions ( 5.1 )] • Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see Warnings and Precautions ( 5.1 )] • Have inherited or acquired hypercoagulopathies [see Warnings and Precautions ( 5.1 )] • Have uncontrolled hypertension [see Warnings and Precautions ( 5.4 )] • Have diabetes mellitus with vascular disease [see Warnings and Precautions ( 5.6 )] • Have headaches with focal neurological symptoms or have migraine headaches with or without aura if over age 35 [see Warnings and Precautions ( 5.7 )] • Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (…. Always consult the full prescribing information and a clinician.