dienogest/estradiol valerate (Rx)

Brand and Other Names:Natazia
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

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

1 tab PO qDay; take at same time each day and in precise order as directed on blister pack

Do not skip tablets or delay intake by more than 12 hr

Initiate by beginning pack on day 1 of menstrual cycle and use nonhormonal contraceptive back-up method (eg, condoms and foam) during 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 caesarean 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 Forms & Strengths

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

Safety and efficacy established in women of reproductive age; efficacy is expected to be the same for postpubertal adolescents under the age of 18 as for users 18 years and older

Adolescents requiring contraception: As adults

1 tab PO qDay; take at same time each day and in precise order as directed on blister pack

Do not skip tablets or delay intake by more than 12 hr

Initiate by beginning pack on day 1 of menstrual cycle and use nonhormonal contraceptive back-up method (eg, condoms and foam) during 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 caesarean section birth: Wait at least 6 weeks
  • Women with other risk factors for VTE in addition to postpartum: Do not use combined hormonal contraceptives
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Interactions

Interaction Checker

and dienogest/estradiol valerate

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            Contraindicated (18)

            • bosentan

              bosentan will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

            • carbamazepine

              carbamazepine will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

            • dexamethasone

              dexamethasone will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

            • efavirenz

              efavirenz will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

            • nafcillin

              nafcillin will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

            • nevirapine

              nevirapine will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

            • ospemifene

              ospemifene, dienogest/estradiol valerate. Either increases effects of the other by pharmacodynamic synergism. Contraindicated.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

            • pentobarbital

              pentobarbital will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

            • phenobarbital

              phenobarbital will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

            • phenytoin

              phenytoin will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

            • primidone

              primidone will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

            • rifabutin

              rifabutin will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

            • rifapentine

              rifapentine will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

            • St John's Wort

              St John's Wort will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Women should not choose estradiol valerate/dienogest as their contraceptive while using strong CYP3A4 inducers due to potential decrease in contraceptive efficacy. Estradiol valerate/dienogest should not be used for at least 28 days after discontinuation of the inducer due to possibility of decreased contraceptive efficacy.

            • tranexamic acid oral

              tranexamic acid oral, dienogest/estradiol valerate. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Coadministration of tranexamic acid oral and combination hormonal contraceptives increases thrombotic risk.

            Serious - Use Alternative (12)

            • belzutifan

              belzutifan will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of belzutifan with hormonal contraceptives may lead to contraceptive failure or increased breakthrough bleeding. Advise females of reproductive potential to use effective nonhormonal contraception. Based on animal studies, belzutifan can cause fetal harm.

            • brigatinib

              brigatinib will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Brigatinib induces CYP3A4 in vitro. Coadministration of hormonal contraceptives with brigatinib can result in decreased concentrations and loss of efficacy. Brigatinib can cause fetal harm. Women should use an effective nonhormonal method of contraception during treatment and for at least 4 months after the last brigatinib dose.

            • calaspargase pegol

              calaspargase pegol, dienogest/estradiol valerate. unknown mechanism. Avoid or Use Alternate Drug. Due to the potential for an indirect interaction between calaspargase pegol and oral contraceptives, concomitant use of these drugs is not recommended. Use another non-oral contraceptive method for females of childbearing potential.

            • elagolix

              dienogest/estradiol valerate decreases effects of elagolix by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Based on the mechanism of action of elagolix, estrogen-containing contraceptives are expected to reduce elagolix efficacy. Effects of progestin-only contraceptives on the efficacy of elagolix is unknown. Advise women to use nonhormonal contraceptives during treatment with elagolix and for 1 week after discontinuing elagolix.

            • encorafenib

              encorafenib will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of encorafenib with hormonal contraceptives (CYP3A4 substrates) can result in decreased concentrations and loss of hormonal contraceptive efficacy. Encorafenib can cause fetal harm. Advise women of childbearing potential to use a highly effective nonhormonal contraceptive during treatment and for 2 weeks after final encorafenib dose.

            • isavuconazonium sulfate

              isavuconazonium sulfate will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lesinurad

              lesinurad decreases effects of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Use additional methods of nonhormonal contraception. Do not rely on hormonal contraception alone when taking lesinurad.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of dienogest/estradiol valerate by unspecified interaction mechanism. Avoid or Use Alternate Drug. Avoid coadministration unless benefit outweighs risk. When coadministered, hormonal contraceptives are not a reliable method of effective birth control. Concomitant use may increase incidence of menstruation associated adverse effects (amenorrhea, dysmenorrhea, menorrhagia).

            • mobocertinib

              mobocertinib will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of mobocertinib with hormonal contraceptives may lead to contraceptive failure or increased breakthrough bleeding. Advise females of reproductive potential to use effective non-hormonal contraception.

            • pexidartinib

              dienogest/estradiol valerate and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

            • pretomanid

              dienogest/estradiol valerate, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

            • sugammadex sodium

              sugammadex sodium decreases effects of dienogest/estradiol valerate by receptor binding competition. Avoid or Use Alternate Drug. In vitro binding studies showed that sugammadex may bind to progestogen, thereby decreasing progestogen exposure. Therefore, a sugammadex bolus dose is considered to be equivalent to missing dose(s) of hormonal contraceptives containing an estrogen or progestogen. If an oral contraceptive is taken on the same day of sugammadex, or the patient has a transdermal or implant hormonal contraceptive, the patient must use an additional, nonhormonal contraceptive method or back-up method of contraception (eg, condoms and spermicides) for the next 7 days.

            Monitor Closely (111)

            • aldesleukin

              aldesleukin will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • amikacin

              amikacin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • amiodarone

              amiodarone will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • amoxicillin

              amoxicillin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • ampicillin

              ampicillin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • aprepitant

              aprepitant will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • armodafinil

              armodafinil will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.

            • atazanavir

              atazanavir, dienogest/estradiol valerate. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of dienogest/estradiol valerate. Use alternatives if available. .

            • azithromycin

              azithromycin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • aztreonam

              aztreonam will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • basiliximab

              basiliximab will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • bexarotene

              bexarotene will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.

            • calcitriol

              calcitriol will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.

            • cefaclor

              cefaclor will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • cefamandole

              cefamandole will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • cefazolin

              cefazolin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • cefdinir

              cefdinir will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • cefditoren

              cefditoren will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • cefepime

              cefepime will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • cefixime

              cefixime will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • cefotaxime

              cefotaxime will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • cefotetan

              cefotetan will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • cefoxitin

              cefoxitin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • cefpodoxime

              cefpodoxime will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • cefprozil

              cefprozil will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • ceftazidime

              ceftazidime will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • ceftibuten

              ceftibuten will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • ceftriaxone

              ceftriaxone will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • cefuroxime

              cefuroxime will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • cenobamate

              cenobamate will decrease the level or effect of dienogest/estradiol valerate by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Advise women to use additional or alternative non-hormonal birth control when concomitantly using cenobamate with oral contraceptives.

            • cephalexin

              cephalexin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • cimetidine

              cimetidine will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • ciprofloxacin

              ciprofloxacin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • clarithromycin

              clarithromycin will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

              clarithromycin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • clindamycin

              clindamycin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • colchicine

              colchicine will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.

            • conivaptan

              conivaptan will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • danazol

              danazol will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • darunavir

              darunavir will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Significant changes (increase or decrease) in plasma levels of estrogen and progestin have been seen when HIV protease inhibitors are administered. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • dasatinib

              dasatinib will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • deferasirox

              deferasirox will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dicloxacillin

              dicloxacillin will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.

              dicloxacillin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • dronedarone

              dronedarone will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • ertapenem

              ertapenem will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • erythromycin base

              erythromycin base will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

              erythromycin base will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

              erythromycin ethylsuccinate will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • erythromycin lactobionate

              erythromycin lactobionate will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

              erythromycin lactobionate will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • erythromycin stearate

              erythromycin stearate will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

              erythromycin stearate will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • estradiol

              estradiol will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.

            • felbamate

              felbamate will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.

            • fluconazole

              fluconazole will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • fosamprenavir

              fosamprenavir will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Significant changes (increase or decrease) in plasma levels of estrogen and progestin have been seen when HIV protease inhibitors are administered. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • gemifloxacin

              gemifloxacin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • gentamicin

              gentamicin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • griseofulvin

              griseofulvin will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.

            • hemin

              dienogest/estradiol valerate decreases effects of hemin by pharmacodynamic antagonism. Use Caution/Monitor. Drugs that increase delta-aminolevulinic acid synthetase may decrease hemin effect.

            • hydrocortisone

              hydrocortisone will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.

            • imatinib

              imatinib will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • indinavir

              indinavir will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Significant changes (increase or decrease) in plasma levels of estrogen and progestin have been seen when HIV protease inhibitors are administered. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • insulin degludec

              dienogest/estradiol valerate decreases effects of insulin degludec by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens and progesterones may impair glucose tolerance.

            • insulin degludec/insulin aspart

              dienogest/estradiol valerate decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens and progesterones may impair glucose tolerance.

            • insulin inhaled

              dienogest/estradiol valerate decreases effects of insulin inhaled by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens and progesterones may impair glucose tolerance.

            • isoniazid

              isoniazid will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • itraconazole

              itraconazole will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • ivosidenib

              ivosidenib will decrease the level or effect of dienogest/estradiol valerate by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ivosidenib may decrease the concentrations of hormonal contraceptives, consider alternative methods of contraception in patients receiving ivosidenib.

            • ketoconazole

              ketoconazole will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • lamotrigine

              dienogest/estradiol valerate decreases levels of lamotrigine by Other (see comment). Use Caution/Monitor. Comment: Mechanism: likely due to induction of lamotrigine glucuronidation; dosage adjustments may be necessary for proper seizure control.

              dienogest/estradiol valerate will decrease the level or effect of lamotrigine by increasing hepatic clearance. Use Caution/Monitor. Combination oral contraceptives have been shown to significantly decrease plasma concentrations of lamotrigine, likely due to induction of lamotrigine glucuronidation.

            • lanreotide

              lanreotide will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • lapatinib

              lapatinib will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • levofloxacin

              levofloxacin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • lixisenatide

              lixisenatide will decrease the level or effect of dienogest/estradiol valerate by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. GLP1 agonists delay gastric emptying, which may affect absorption of concomitantly administered oral medications. Oral contraceptives should be taken at least 1 hr before lixisenatide administration or 11 hr after lixisenatide.

            • lopinavir

              lopinavir will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Significant changes (increase or decrease) in plasma levels of estrogen and progestin have been seen when HIV protease inhibitors are administered. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • maraviroc

              dienogest/estradiol valerate increases levels of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity.

            • medroxyprogesterone

              medroxyprogesterone will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.

            • meropenem

              meropenem will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • meropenem/vaborbactam

              meropenem/vaborbactam will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • metformin

              dienogest/estradiol valerate decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor.

            • metyrapone

              metyrapone will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.

            • mifepristone

              mifepristone will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

              mifepristone decreases effects of dienogest/estradiol valerate by pharmacodynamic antagonism. Use Caution/Monitor. Backup contraceptive method recommended.

            • modafinil

              modafinil will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.

            • moxifloxacin

              moxifloxacin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • nefazodone

              nefazodone will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache

            • nelfinavir

              nelfinavir will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Significant changes (increase or decrease) in plasma levels of estrogen and progestin have been seen when HIV protease inhibitors are administered. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • nicardipine

              nicardipine will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • nilotinib

              nilotinib will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • octreotide

              octreotide will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • ofloxacin

              ofloxacin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • paclitaxel

              paclitaxel will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.

            • paclitaxel protein bound

              paclitaxel protein bound will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.

            • penicillin G aqueous

              penicillin G aqueous will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • penicillin G benzathine

              penicillin G benzathine will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • penicillin G procaine

              penicillin G procaine will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • penicillin VK

              penicillin VK will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • pioglitazone

              pioglitazone will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.

            • pitolisant

              pitolisant will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pitolisant is a borderline/weak inducer of CYP3A4. Monitor sensitive CYP3A4 substrates for reduced effectiveness if coadministered.

            • posaconazole

              posaconazole will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • prednisone

              prednisone will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.

            • quinidine

              quinidine will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • ranolazine

              ranolazine will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • ritonavir

              ritonavir will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Significant changes (increase or decrease) in plasma levels of estrogen and progestin have been seen when HIV protease inhibitors are administered. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • saquinavir

              saquinavir will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Significant changes (increase or decrease) in plasma levels of estrogen and progestin have been seen when HIV protease inhibitors are administered. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • siltuximab

              siltuximab, dienogest/estradiol valerate. Other (see comment). Use Caution/Monitor. Comment: CYP450 activity in the liver is down regulated by infection and inflammation stimuli including cytokines (eg, IL-6); inhibition of IL-6 by siltuximab may restore CYP450 enzymatic activity; caution if coadministered with CYP substrates that have a narrow therapeutic index.

            • streptomycin

              streptomycin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • tamoxifen

              tamoxifen will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • ticarcillin

              ticarcillin will decrease the level or effect of dienogest/estradiol valerate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. An alternate or additional form of birth control may be advisable during concomitant use.

            • tipranavir

              tipranavir will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Significant changes (increase or decrease) in plasma levels of estrogen and progestin have been seen when HIV protease inhibitors are administered. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • topiramate

              topiramate will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Advise women to use alternative method of contraception or back-up method when moderate or weak enzyme inducer is used with combination contraceptives. Back-up contraception should be continued for 28 days after discontinuing medication to ensure contraceptive reliability.

            • verapamil

              verapamil will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • voriconazole

              voriconazole will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • zafirlukast

              zafirlukast will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            Minor (1)

            • enasidenib

              enasidenib, dienogest/estradiol valerate. unknown mechanism. Minor/Significance Unknown. Coadministration of enasidenib may increase or decrease the concentrations of combined hormonal contraceptives. Clinical significance of this interaction is unknown.

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            Adverse Effects

            >10%

            Headache, including migraines (13.2%)

            1-10%

            Metrorrhagia and irregular menstruation (8%)

            Breast pain, discomfort, or tenderness (6.6%)

            Nausea or vomiting (6.5%)

            Acne (3.9%)

            Weight gain (2.85)

            <1%

            Venous thromboembolism

            Jaundice or cholestasis

            Gallbladder disease

            Depression

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            Warnings

            Black Box Warnings

            Cigarette smoking

            • Cigarette smoking increases risk of serious cardiovascular adverse effects from combination hormonal contraceptive use
            • This risk increases with age (>35 yr) and heavy smoking (15 or more cigarettes/day)
            • Advise women who use hormonal oral contraceptives not to smoke

            Contraindications

            Pregnancy

            Hypersensitivity

            Breast Cancer, or other estrogen- or progestin-sensitive cancer

            A high risk of arterial or venous thromboembolic disorders

            Undiagnosed uterine bleeding

            Cautions

            Poorly metabolized with hepatic impairment

            Use caution in patients with history of migraine, seizure disorder,

            Not recommended for women smokers >35 years

            Oral contraceptives can reduce 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 >30 kg/m²

            CDC guidelines recommend waiting at least 3 weeks following vaginal birth or 6 weeks after cesarean section to decrease 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)

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            Pregnancy & Lactation

            Pregnancy considerations: There is little or no increased risk of birth defects in women who inadvertently use combined oral contraceptives (COCs) during early pregnancy; epidemiologic studies and meta-analyses have not found increased risk of genital or non-genital birth defects following exposure to low dose COCs prior to conception or during early pregnancy; the administration of COCs to induce withdrawal bleeding should not be used as a test for pregnancy; COCs should not be used during pregnancy to treat threatened or habitual abortion; women who do not breastfeed may start COCs no earlier than four weeks postpartum.

            Lactation: May decrease breast milk production; enters milk; not recommended

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Estrogen/progestin combined oral contraceptive; decreases risk of becoming pregnant primarily by suppressing ovulation May also cause cervical mucus changes that inhibit sperm penetration and endometrial changes that decrease ability for implantation

            Pharmaockinetics

            Bioavailability: 91% (dienogest)

            Vd: 1.2 L/kg (estradiol IV)

            Peak Plasma Time: 6 hr (17-beta estradiol); 11 hr (dienogest)

            Peak Plasma Concentration: 73.3 pg/mL (17-beta estradiol); 91.7 ng/mL (dienogest)

            Protein Bound: 60% (estradiol); 90% (dienogest)

            Half-life elimination

            • estradiol: 14 hr
            • dienogest: 1 hr

            Excretion

            • estradiol and its metabolites: feces (10%), urine (90%)
            • dienogest: predominantly via urine as metabolites and unchanged dienogest
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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Natazia oral
            -
            3 mg/2 mg-2 mg/ 2 mg-3 mg/1 mg tablet
            Natazia oral
            -
            3 mg/2 mg-2 mg/ 2 mg-3 mg/1 mg tablet

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            estradiol-dienogest oral

            ESTRADIOL VALERATE/DIENOGEST - ESTRADIOL VALERATE - ORAL

            (ES-tra-DYE-ol VAL-er-ate/ dye-EN-oh-jest- ES-tra-DYE-ol VAL-er-ate)

            COMMON BRAND NAME(S): Natazia

            WARNING: Do not use this medication if you smoke cigarettes/use tobacco and are over 35 years old. Smoking raises your risk of stroke, heart attack, blood clots, and high blood pressure from hormonal birth control (such as the pill, patch, ring). The risk of these serious problems increases with age and with the number of cigarettes you smoke. Do not smoke or use tobacco.

            USES: This combination hormone medication is used to prevent pregnancy. It contains 2 hormones: dienogest (a progestin) and estradiol valerate (an estrogen). It works mainly by preventing the release of an egg (ovulation) during your menstrual cycle. It also makes vaginal fluid thicker to help prevent sperm from reaching an egg (fertilization) and changes the lining of the uterus (womb) to prevent attachment of a fertilized egg.Besides preventing pregnancy, birth control pills may make your periods more regular, decrease blood loss and painful periods, decrease your risk of ovarian cysts, and also treat acne.Using this medication does not protect you or your partner against sexually transmitted diseases (such as HIV, gonorrhea, chlamydia).

            HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start taking this medication and each time you get a refill. The leaflet contains very important information on when to take your pills and what to do if you miss a dose. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth as directed by your doctor, usually once daily. Pick a time of day that is easy for you to remember, and take your pill at the same time each day.It is very important to continue taking this medication exactly as prescribed by your doctor. With certain brands of birth control pills, the amount of estrogen and progestin in each active tablet will vary at different times in the cycle. Follow the package instructions to find the first tablet, start with the first tablet in the pack, and take them in the correct order. Do not skip any doses. Pregnancy is more likely if you miss pills, start a new pack late, or take your pill 12 hours later than the usual time.If you have vomiting or diarrhea within 3 to 4 hours after taking your tablet, read the Patient Information Leaflet section titled "What to Do if You Miss Tablets." Follow the instructions as if you had missed your dose because vomiting/diarrhea can stop the tablet from working.Taking this medication after your evening meal or at bedtime may help if you have stomach upset or nausea with the medication. You may choose to take this medication at another time of day that is easier for you to remember. No matter what dosing schedule you use, it is very important that you take this medication at the same time each day, 24 hours apart.Your pill pack contains 26 pills with active medication. It also contains 2 reminder pills with no medication. Take one active pill (with hormones) once daily for 26 days in a row. After you have taken the last active pill, take one reminder pill once daily for 2 days in a row unless otherwise directed by your doctor. You should have your period during the fourth week of the cycle. After you have taken the last reminder tablet in the pack, start a new pack the next day even if your period is continuing or if you do not have your period. If you do not get your period, consult your doctor.If this is the first time you are using this medication and you are not switching from another form of hormonal birth control (such as patch, other birth control pills), take the first tablet in the pack on the first day of your period. For the first cycle of use only, use an additional form of non-hormonal birth control (such as condoms, spermicide) for the first 9 days to prevent pregnancy until the medication has enough time to work.Ask your doctor or pharmacist for information about how to switch from other forms of hormonal birth control (such as patch, other birth control pills) to this product. If any information is unclear, consult the Patient Information Leaflet or your doctor or pharmacist.

            SIDE EFFECTS: Nausea, vomiting, headache, abdominal cramps/bloating, breast tenderness, swelling of the ankles/feet (retaining fluid), or weight change may occur. Vaginal bleeding between periods (spotting) or missed/irregular periods may occur, especially during the first few months of use. If any of these effects persist or worsen, tell your doctor or pharmacist promptly. If you miss 2 periods in a row (or 1 period if the pill has not been used properly), contact your doctor for a pregnancy test.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high.Tell your doctor right away if you have any serious side effects, including: a lump in your breast, unusual changes in vaginal bleeding (such as continuous spotting, sudden heavy bleeding), mental/mood changes (such as new/worsening depression), dark urine, yellowing eyes/skin, severe stomach/abdominal/pelvic pain, unusual tiredness.This medication may rarely cause serious (sometimes fatal) problems from blood clots (such as deep vein thrombosis, heart attack, pulmonary embolism, stroke). Get medical help right away if you have: shortness of breath/rapid breathing, chest/jaw/left arm pain, unusual sweating, confusion, sudden dizziness/fainting, pain/swelling/warmth in the groin/calf, sudden/severe headaches, trouble speaking, weakness on one side of the body, sudden vision changes.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: See also Warning section.Before using this medication, tell your doctor or pharmacist if you are allergic to estradiol or dienogest; or to any estrogens (such as mestranol) or any progestins (such as norethindrone, desogestrel); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this product, tell your doctor or pharmacist your medical history, especially of: blood clots (for example, in the legs, eyes, lungs), blood clotting disorders (such as protein C or protein S deficiency), high blood pressure, abnormal breast exam, cancer (especially endometrial or breast cancer), high cholesterol or triglyceride (blood fat) levels, depression, diabetes, family or personal history of a certain swelling disorder (angioedema), gallbladder problems, severe headaches/migraine, heart problems (such as heart valve disease, irregular heartbeat, previous heart attack), history of yellowing eyes/skin (jaundice) during pregnancy or while using hormonal birth control (such as pills, patch), kidney disease, liver disease (including tumors), stroke, swelling (edema), thyroid problems, unexplained vaginal bleeding.If you have diabetes, this medication may affect your blood sugar. Check your blood sugar regularly as directed and share the results with your doctor. Tell your doctor right away if you have symptoms of high blood sugar such as increased thirst/urination. Your doctor may need to adjust your diabetes medication, exercise program, or diet.Tell your doctor if you just had or will be having surgery or if you will be confined to a bed or chair for a long time (such as on a long plane flight). These conditions increase your risk of getting blood clots, especially if you are using hormonal birth control. You may need to stop this medication for a time or take special precautions.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).This medication may cause blotchy, dark areas on your face and skin (melasma). Sunlight may worsen this effect. Limit your time in the sun. Avoid tanning booths and sunlamps. Use sunscreen and wear protective clothing when outdoors.If you are nearsighted or wear contact lenses, you may develop vision problems or trouble wearing your contact lenses. Contact your eye doctor if these problems occur.It may take longer for you to become pregnant after you stop taking birth control pills. Consult your doctor.This medication should not be used during pregnancy. If you become pregnant or think you may be pregnant, tell your doctor right away. If you have just given birth or had a pregnancy loss/abortion after the first 3 months, talk with your doctor about reliable forms of birth control, and find out when it is safe to start using birth control that contains a form of estrogen, such as this medication.This medication may decrease breast milk production. A small amount passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: aromatase inhibitors (such as anastrozole, exemestane, letrozole), ospemifene, tamoxifen, tranexamic acid.Some drugs may cause hormonal birth control to work less well by decreasing the amount of birth control hormones in your body. This effect can result in pregnancy. Examples include griseofulvin, modafinil, rifamycins (such as rifampin, rifabutin), St. John's wort, drugs used to treat seizures (such as barbiturates, carbamazepine, felbamate, phenytoin, primidone, topiramate), HIV drugs (such as nelfinavir, nevirapine, ritonavir), among others.Tell your doctor when you start any new drug, and discuss if you should use additional reliable birth control. Also tell your doctor if you have any new spotting or breakthrough bleeding, because these may be signs that your birth control is not working well.This medication may interfere with certain laboratory tests (such as blood tests for clotting factors, thyroid), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this medication.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe nausea and vomiting, sudden/unusual vaginal bleeding.

            NOTES: Do not share this medication with others.Keep all regular medical and laboratory appointments. You should have regular complete physical exams including blood pressure, breast exam, pelvic exam, and screening for cervical cancer (Pap smear). Follow your doctor's instructions for examining your breasts, and report any lumps right away. Consult your doctor for more details.

            MISSED DOSE: Missed dose advice is different depending on the brand used and the number of doses missed. Refer to the product package information for advice on missed doses. You may need to use back-up birth control (such as condoms, spermicide) to prevent pregnancy. Ask your doctor or pharmacist if you have any questions.If you often forget to take your pills as directed, contact your doctor to discuss switching to another form of birth control.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.