(ETH in il es tra DYE ole & droh SPYE re none)
Acne vulgaris (Gianvi, Loryna, Nikki, Vestura, Yaz): Treatment of moderate acne vulgaris in women 14 years and older only if the patient desires an oral contraceptive for birth control
Contraception: Prevention of pregnancy
Premenstrual dysphoric disorder (Gianvi, Yaz): Treatment of premenstrual dysphoric disorder (PMDD) for women who choose to use an oral contraceptive for contraception
Adrenal insufficiency, breast cancer or other estrogen- or progestin-sensitive cancer (current or a history of), hepatic tumors (benign or malignant) or disease, pregnancy, renal impairment, undiagnosed abnormal uterine bleeding. Use is also contraindicated in women at high risk of arterial or venous thrombotic diseases including: Cerebrovascular disease, coronary artery disease, diabetes mellitus with vascular disease, DVT or PE (current or history of), hypercoagulopathies (inherited or acquired), hypertension (uncontrolled), headaches with focal neurological symptoms or migraine headaches (with or without aura) if >35 years of age, thrombogenic valvular or rhythm diseases of the heart (eg, subacute bacterial endocarditis with valvular disease or atrial fibrillation), women >35 years of age who smoke.
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, combination oral contraceptives should not be used by women who are over 35 years of age and smoke.
Acne (Gianvi, Loryna, Nikki, Vestura, Yaz): Females: Oral: Refer to dosing for contraception.
PMDD (Gianvi, Yaz): Females: Oral: Refer to dosing for contraception.
Contraception: Female: Oral: Dosage is 1 tablet daily for 28 consecutive days. Dosing may be started on the first day of menstrual period (Day 1 starter) or on the first Sunday after the onset of the menstrual period (Sunday starter). With a Sunday start, an additional method of contraception should be used until after the first 7 days of consecutive administration.
Day 1 starter: Dose starts on first day of menstrual cycle taking 1 tablet daily.
Sunday starter: Dose begins on first Sunday after onset of menstruation; if the menstrual period starts on Sunday, take first tablet that very same day.
Switching from a different contraceptive:
Oral contraceptive: Start on the same day that a new pack of the previous oral contraceptive would have been taken
Transdermal patch, vaginal ring, injection: Start on the day the next dose would have been due
IUD or implant: Start on the day of removal
Use after childbirth (in women who are not breast-feeding) or after second trimester abortion: Therapy may be started ≥4 weeks postpartum. Pregnancy should be ruled out prior to treatment if menstrual periods have not restarted and an additional method of contraception (nonhormonal) should be used until after the first 7 days of consecutive administration.
Missed doses:
If all doses have been taken on schedule and one menstrual period is missed, continue dosing cycle. If two consecutive menstrual periods are missed, pregnancy test is required before new dosing cycle is started.
If doses have been missed during the first 3 weeks and the menstrual period is missed, pregnancy should be ruled out prior to continuing treatment.
Missed doses (monophasic formulations) (refer to package insert for complete information):
One dose missed: Take as soon as remembered or take 2 tablets next day
Two consecutive doses missed in the first 2 weeks: Take 2 tablets as soon as remembered or 2 tablets next 2 days. An additional method of contraception should be used for 7 days after missed dose.
Two consecutive doses missed in week 3 or three consecutive doses missed at any time: An additional method of contraception must be used for 7 days after a missed dose.
Day 1 starter: Current pack should be discarded, and a new pack should be started that same day.
Sunday starter: Continue dose of 1 tablet daily until Sunday, then discard the rest of the pack, and a new pack should be started that same day.
Any number of doses missed in week 4: Continue taking one pill each day until pack is empty; no back-up method of contraception is needed
Note: Not to be used prior to menarche.
Acne (Gianvi, Loryna, Nikki, Vestura, Yaz): Females: Adolescents ≥14 years: Oral: Refer to adult dosing.
PMDD (Gianvi,Yaz): Females: Oral: Refer to adult dosing.
Contraception: Females: Oral: Refer to adult dosing.
Contraindicated in patients with renal dysfunction.
Contraindicated in patients with hepatic dysfunction.
Dose should be taken at the same time each day, preferably either after the evening meal or at bedtime. If severe vomiting or diarrhea occurs, additional contraceptive measures (nonhormonal) should be taken. If vomiting occurs within 3 to 4 hours of dosing, consider the dose to be missed.
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 2]).
Should be taken at the same time each day; may be taken with or without a meal
Store at 25 � �C (77 � �F); excursions permitted to 15 � �C to 30 � �C (59 � �F to 86 � �F).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral:
Gianvi: Ethinyl estradiol 0.02 mg and drospirenone 3 mg [24 light pink active tablets and 4 white inactive tablets] (28s)
Loryna: Ethinyl estradiol 0.02 mg and drospirenone 3 mg [24 peach active tablets and 4 white inactive tablets] (28s)
Nikki: Ethinyl estradiol 0.02 mg and drospirenone 3 mg [24 pink active tablets and 4 white inactive tablets] (28s)
Ocella: Ethinyl estradiol 0.03 mg and drospirenone 3 mg [21 yellow active tablets and 7 white inactive tablets] (28s)
Syeda: Ethinyl estradiol 0.03 mg and drospirenone 3 mg [21 yellow active tablets and 7 white inactive tablets] (28s)
Vestura: Ethinyl estradiol 0.02 mg and drospirenone 3 mg [24 pink active tablets and 4 peach inactive tablets] (28s)
Yasmin: Ethinyl estradiol 0.03 mg and drospirenone 3 mg [21 yellow active tablets and 7 white inactive tablets] (28s)
Yaz: Ethinyl estradiol 0.02 mg and drospirenone 3 mg [24 light pink active tablets and 4 white inactive tablets] (28s)
Zarah: Ethinyl estradiol 0.03 mg and drospirenone 3 mg [21 blue active tablets and 7 peach inactive tablets] (28s)
Generic: Ethinyl estradiol 0.02 mg and drospirenone 3 mg [21 active tablets and 7 inactive tablets] (28s); Ethinyl estradiol 0.03 mg and drospirenone 3 mg [21 active tablets and 7 inactive tablets] (28s)
ACE Inhibitors: May enhance the hyperkalemic effect of Drospirenone. Monitor therapy
Acitretin: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Given the potential for progestin-only preparations to fail to prevent pregnancy during acitretin therapy, such products should not be relied upon. Alternative, nonhormonal forms of contraception must be employed during acitretin therapy. Consider therapy modification
Agomelatine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Agomelatine. Monitor therapy
Ajmaline: Estrogen Derivatives may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Monitor therapy
Aliskiren: Drospirenone may enhance the hyperkalemic effect of Aliskiren. Monitor therapy
Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination
Anastrozole: Estrogen Derivatives may diminish the therapeutic effect of Anastrozole. Avoid combination
Angiotensin II Receptor Blockers: May enhance the hyperkalemic effect of Drospirenone. Monitor therapy
Anthrax Immune Globulin (Human): Estrogen Derivatives may enhance the thrombogenic effect of Anthrax Immune Globulin (Human). Monitor therapy
Anticoagulants: Estrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of estrogens against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Consider therapy modification
Anticoagulants: Progestins may diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of progestins against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Consider therapy modification
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Antihepaciviral Combination Products: Ethinyl Estradiol may enhance the hepatotoxic effect of Antihepaciviral Combination Products. Avoid combination
Aprepitant: May decrease the serum concentration of Contraceptives (Estrogens). Management: Use of a non-hormone-based contraceptive is recommended. Consider therapy modification
Aprepitant: May decrease the serum concentration of Contraceptives (Progestins). Management: Alternative or additional methods of contraception should be used both during treatment with aprepitant or fosaprepitant and for at least one month following the last aprepitant/fosaprepitant dose. Consider therapy modification
Armodafinil: May decrease the serum concentration of Contraceptives (Estrogens). Management: The manufacturer recommends that patients use nonhormonal contraceptives, in addition to or in place of hormonal contraceptives, during and for one month following treatment with armodafinil. Consider therapy modification
Artemether: May decrease the serum concentration of Contraceptives (Estrogens). Management: Consider the use of an alternative (i.e., non-hormonal) means of contraception in all women of childbearing potential who are using artemether. Consider therapy modification
Artemether: May decrease the serum concentration of Contraceptives (Progestins). Management: Consider the use of an alternative (i.e., non-hormonal) means of contraception in all women of childbearing potential who are using artemether. Consider therapy modification
Ascorbic Acid: May increase the serum concentration of Estrogen Derivatives. Monitor therapy
Asunaprevir: May decrease the serum concentration of Ethinyl Estradiol. Management: For patients using hormone-based contraception, a high-dose oral contraceptive containing at least 30 mcg of ethinyl estradiol combined with norethindrone acetate/norethindrone is recommended during treatment with asunaprevir. Consider therapy modification
Atazanavir: May increase the serum concentration of Contraceptives (Progestins). However, atazanavir may lead to decreased ethinyl estradiol concentrations and decreased effectiveness of oral contraceptive products. Management: Consider an alternative or additional method of contraception, particularly with combined estrogen/progestin products. Depot medroxyprogesterone acetate may be used without a need for additional contraception. Consider therapy modification
Barbiturates: May diminish the therapeutic effect of Contraceptives (Estrogens). Contraceptive failure is possible. Management: Use of a non-hormonal contraceptive is recommended. Consider therapy modification
Barbiturates: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Consider therapy modification
Bexarotene (Systemic): May decrease the serum concentration of Contraceptives (Estrogens). Management: Women of childbearing potential receiving bexarotene should use two reliable forms of contraception (including at least one nonhormonal form). Consider therapy modification
Bexarotene (Systemic): May decrease the serum concentration of Contraceptives (Progestins). Management: Women of childbearing potential receiving bexarotene should use two reliable forms of contraception (including at least one nonhormonal form). Consider therapy modification
Bile Acid Sequestrants: May decrease the serum concentration of Contraceptives (Estrogens). Management: Administer estrogen-based oral contraceptives at least 1-4 hours prior to or 4-6 hours after administration of a bile acid sequestrant. Consider therapy modification
Bile Acid Sequestrants: May decrease the serum concentration of Contraceptives (Progestins). Management: Administer oral progestin-containing contraceptives at least 1-4 hours prior to or 4-6 hours after administration of a bile acid sequestrant. Consider therapy modification
Boceprevir: May increase the serum concentration of Drospirenone. Avoid combination
Bosentan: May decrease the serum concentration of Contraceptives (Estrogens). Management: Use an alternative (i.e., non-hormonal) means of contraception for all women of childbearing potential who are using bosentan, and do not rely on hormonal contraceptives alone. Consider therapy modification
Bosentan: May decrease the serum concentration of Contraceptives (Progestins). Management: Use an alternative (i.e., non-hormonal) means of contraception for all women of childbearing potential who are using bosentan, and do not rely on hormonal contraceptives alone. Consider therapy modification
C1 inhibitors: Estrogen Derivatives may enhance the thrombogenic effect of C1 inhibitors. Monitor therapy
C1 inhibitors: Progestins may enhance the thrombogenic effect of C1 inhibitors. Monitor therapy
CarBAMazepine: May diminish the therapeutic effect of Contraceptives (Estrogens). Contraceptive failure is possible. Management: Use of a nonhormonal contraceptive is recommended. Consider therapy modification
CarBAMazepine: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Consider therapy modification
Carfilzomib: May enhance the thrombogenic effect of Contraceptives (Estrogens). Management: Consider alternative, non-hormonal methods of contraception in patients requiring therapy with carfilzomib. Consider therapy modification
Carfilzomib: May enhance the thrombogenic effect of Contraceptives (Progestins). Management: Consider alternative, non-hormonal methods of contraception in patients requiring therapy with carfilzomib. Consider therapy modification
Chenodiol: Estrogen Derivatives may diminish the therapeutic effect of Chenodiol. Management: Monitor clinical response to chenodiol closely when used together with any estrogen derivative. Monitor therapy
CloBAZam: May decrease the serum concentration of Contraceptives (Estrogens). Consider therapy modification
CloBAZam: May decrease the serum concentration of Contraceptives (Progestins). Consider therapy modification
Cobicistat: May decrease the serum concentration of Contraceptives (Estrogens). Management: Consider an alternative, non-hormone-based contraceptive in patients receiving cobicistat-containing products. Consider therapy modification
Cobicistat: May increase the serum concentration of Contraceptives (Progestins). Management: Consider an alternative, non-hormone-based contraceptive in patients receiving cobicistat-containing products. Consider therapy modification
Colesevelam: May decrease the serum concentration of Ethinyl Estradiol. Consider therapy modification
Corticosteroids (Systemic): Estrogen Derivatives may increase the serum concentration of Corticosteroids (Systemic). Monitor therapy
CYP1A2 Substrates: CYP1A2 Inhibitors (Moderate) may decrease the metabolism of CYP1A2 Substrates. Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Drospirenone. Monitor therapy
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dabrafenib: May decrease the serum concentration of Contraceptives (Estrogens). Management: Females of reproductive potential should use an alternative, highly effective, non-hormonal means of contraception during and at least 2 weeks (dabrafenib alone) or 4 months (dabrafenib + trametinib) after discontinuation of dabrafenib treatment. Consider therapy modification
Dabrafenib: May decrease the serum concentration of Contraceptives (Progestins). Management: Females of reproductive potential should use an alternative, highly effective, non-hormonal means of contraception during and at least 2 weeks (dabrafenib alone) or 4 months (dabrafenib + trametinib) after discontinuation of dabrafenib treatment. Consider therapy modification
Darunavir: May decrease the serum concentration of Contraceptives (Progestins). Management: Consider using an alternative or additional means of contraception. Injected depot medroxyprogesterone acetate may be used without a need for additional contraception. Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Dehydroepiandrosterone: May enhance the adverse/toxic effect of Estrogen Derivatives. Avoid combination
Efavirenz: May decrease the serum concentration of Contraceptives (Progestins). Management: Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Consider therapy modification
Elvitegravir: May decrease the serum concentration of Contraceptives (Estrogens). Management: Consider the use of an alternative, non-hormone-based contraceptive, in patients who are being treated with elvitegaravir-containing products. Consider therapy modification
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Eslicarbazepine: May decrease the serum concentration of Contraceptives (Estrogens). Management: Alternative non-hormonal means of birth control should be considered for women of child-bearing potential. Consider therapy modification
Eslicarbazepine: May decrease the serum concentration of Contraceptives (Progestins). Management: Alternative, non-hormonal means of birth control should be considered for women of child-bearing potential. Consider therapy modification
Exemestane: Estrogen Derivatives may diminish the therapeutic effect of Exemestane. Avoid combination
Exenatide: May decrease the serum concentration of Contraceptives (Estrogens). Management: Administer oral contraceptives at least one hour prior to exenatide. Consider therapy modification
Exenatide: May decrease the serum concentration of Oral Contraceptive (Progestins). Management: Administer oral contraceptives at least one hour prior to exenatide. Consider therapy modification
Felbamate: May decrease the serum concentration of Contraceptives (Estrogens). Contraceptive failure is possible. Management: Use of a nonhormonal contraceptive is recommended. Consider therapy modification
Felbamate: May decrease the serum concentration of Contraceptives (Progestins). Management: Contraceptive failure is possible. Use of an alternative, nonhormonal method of contraception is recommended. Consider therapy modification
Flibanserin: Contraceptives (Estrogens) may increase the serum concentration of Flibanserin. Monitor therapy
Flibanserin: Contraceptives (Progestins) may increase the serum concentration of Flibanserin. Monitor therapy
Fosamprenavir: Contraceptives (Progestins) may decrease serum concentrations of the active metabolite(s) of Fosamprenavir. Fosamprenavir may decrease the serum concentration of Contraceptives (Progestins). Management: Consider using an alternative or additional means of contraception. Injected depot medroxyprogesterone acetate may be used without a need for additional contraception. Consider therapy modification
Fosaprepitant: May decrease the serum concentration of Contraceptives (Estrogens). The active metabolite aprepitant is likely responsible for this effect. Management: Alternative or additional methods of contraception should be used both during treatment with fosaprepitant or aprepitant and for at least one month following the last fosaprepitant/aprepitant dose. Consider therapy modification
Fosaprepitant: May decrease the serum concentration of Contraceptives (Progestins). The active metabolite aprepitant is likely responsible for this effect. Management: Alternative or additional methods of contraception should be used both during treatment with aprepitant or fosaprepitant and for at least one month following the last aprepitant/fosaprepitant dose. Consider therapy modification
Fosphenytoin: May diminish the therapeutic effect of Contraceptives (Estrogens). Contraceptive failure is possible. Management: Use of an alternative, nonhormonal means of contraception is recommended. Consider therapy modification
Fosphenytoin: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification
Griseofulvin: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Avoid combination
Hemin: Estrogen Derivatives may diminish the therapeutic effect of Hemin. Avoid combination
Herbs (Estrogenic Properties): May enhance the adverse/toxic effect of Estrogen Derivatives. Monitor therapy
Herbs (Progestogenic Properties) (eg, Bloodroot, Yucca): May enhance the adverse/toxic effect of Progestins. Monitor therapy
Hyaluronidase: Estrogen Derivatives may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving estrogens (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification
Immune Globulin: Estrogen Derivatives may enhance the thrombogenic effect of Immune Globulin. Monitor therapy
Indium 111 Capromab Pendetide: Estrogen Derivatives may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Avoid combination
LamoTRIgine: Contraceptives (Estrogens) may decrease the serum concentration of LamoTRIgine. Management: Monitor for increased serum concentrations/effects of lamotrigine in patients in whom a hormonal contraceptive is discontinued/dose decreased (this includes during a pill-free week). A reduced dosage of lamotrigine may be needed. Consider therapy modification
LamoTRIgine: May decrease the serum concentration of Contraceptives (Progestins). Management: Women using progestin-only "minipill " � products may be at risk for contraceptive failure; it is unclear if other progestin-containing products would be significantly impacted. Alternative, non-hormonal, means of contraception are recommended. Consider therapy modification
Lenalidomide: Estrogen Derivatives may enhance the thrombogenic effect of Lenalidomide. Monitor therapy
Lesinurad: May decrease the serum concentration of Contraceptives (Estrogens). Management: Use of an additional, nonhormonal contraceptive is recommended in patients being treated with lesinurad who desire effective contraception. Consider therapy modification
Lesinurad: May decrease the serum concentration of Contraceptives (Progestins). Management: Use of an additional, nonhormonal contraceptive is recommended in patients being treated with lesinurad who desire effective contraception. Consider therapy modification
Lixisenatide: May decrease the serum concentration of Contraceptives (Estrogens). Management: Administer oral contraceptives 1 hour before or at least 11 hours after administration of lixisenatide. Consider therapy modification
Lixisenatide: May decrease the serum concentration of Contraceptives (Progestins). Management: Administer oral contraceptives 1 hour before or at least 11 hours after administration of lixisenatide. Consider therapy modification
Lomitapide: Ethinyl Estradiol may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 40 mg/day. Consider therapy modification
Lopinavir: May decrease the serum concentration of Contraceptives (Progestins). Lopinavir may increase the serum concentration of Contraceptives (Progestins). Management: Consider using an alternative or additional means of contraception. Injected depot medroxyprogesterone acetate and etonogestrel implants may be used without a need for additional contraception. Consider therapy modification
Lumacaftor: May decrease the serum concentration of Contraceptives (Estrogens). Management: Do not rely on hormone-based contraceptives with concurrent use of lumacaftor/ivacaftor; an alternative, non-hormonal, method of contraception should be used if this combination is required. Consider therapy modification
Lumacaftor: May decrease the serum concentration of Contraceptives (Progestins). Management: Do not rely on hormone-based contraceptives with concurrent use of lumacaftor/ivacaftor; an alternative, non-hormonal, method of contraception should be used if this combination is required. Consider therapy modification
Metreleptin: May decrease the serum concentration of Contraceptives (Estrogens). Metreleptin may increase the serum concentration of Contraceptives (Estrogens). Monitor therapy
Metreleptin: May decrease the serum concentration of Contraceptives (Progestins). Metreleptin may increase the serum concentration of Contraceptives (Progestins). Monitor therapy
MiFEPRIStone: May diminish the therapeutic effect of Contraceptives (Progestins). MiFEPRIStone may increase the serum concentration of Contraceptives (Progestins). Management: Women of childbearing potential should use an effective, nonhormonal means of contraception during and 4 weeks following mifepristone treatment. Consider therapy modification
MiFEPRIStone: May diminish the therapeutic effect of Contraceptives (Estrogens). MiFEPRIStone may increase the serum concentration of Contraceptives (Estrogens). Management: Women of childbearing potential should use an effective, nonhormonal means of contraception during and 4 weeks following mifepristone treatment. Consider therapy modification
Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Modafinil: May decrease the serum concentration of Contraceptives (Estrogens). Management: The manufacturer recommends that patients use nonhormonal contraceptives, in addition to or in place of hormonal contraceptives, during and for one month following treatment with modafinil. Consider therapy modification
Mycophenolate: May decrease the serum concentration of Contraceptives (Estrogens). Average AUC values were unchanged, but there was evidence of substantial patient-to-patient variability in response to this combination. Management: Women of childbearing potential who are receiving mycophenolate mofetil should consider using an alternative and/or additional form of contraception. Consider therapy modification
Mycophenolate: May decrease the serum concentration of Contraceptives (Progestins). Management: Use of an additional or alternative (nonhormonal) method of contraception should be considered. Consider therapy modification
Nafcillin: May increase the metabolism of Contraceptives (Estrogens). Management: Use of an alternative, nonhormonal form of contraception during nafcillin therapy is recommended. Consider therapy modification
Nelfinavir: May decrease the serum concentration of Contraceptives (Progestins). Management: Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Consider therapy modification
Nevirapine: May decrease the serum concentration of Contraceptives (Estrogens). Consider therapy modification
Nevirapine: May decrease the serum concentration of Contraceptives (Progestins). Management: Instruct patients receiving nevirapine to use an alternative or additional nonhormonal contraceptive. Nevirapine product labeling however suggests that depo-medroxyprogesterone acetate may be used as a sole method of contraception. Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May enhance the hyperkalemic effect of Drospirenone. Monitor therapy
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Ospemifene: Estrogen Derivatives may enhance the adverse/toxic effect of Ospemifene. Estrogen Derivatives may diminish the therapeutic effect of Ospemifene. Avoid combination
OXcarbazepine: May decrease the serum concentration of Contraceptives (Estrogens). Contraceptive failure is possible. Management: Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification
OXcarbazepine: May decrease the serum concentration of Contraceptives (Progestins). Management: Contraceptive failure is possible. Use of an additional or alternative, nonhormonal method of contraception is recommended. Consider therapy modification
Perampanel: May decrease the serum concentration of Contraceptives (Progestins). Management: Patients should use an alternative, non-hormonal based form of contraception for the duration of concurrent perampanel. Both oral and non-oral progestin-based contraceptives are likely to be impacted by this interaction. Consider therapy modification
Phenytoin: May diminish the therapeutic effect of Contraceptives (Estrogens). Contraceptive failure is possible. Management: Use of an alternative, nonhormonal means of contraception is recommended. Consider therapy modification
Phenytoin: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification
Pirfenidone: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pirfenidone. Management: Use any such combination with caution and close monitoring for pirfenidone toxicity. Avoid the use of pirfenidone with moderate CYP1A2 inhibitors whenever CYP2C9, 2C19, 2C6, or 2E1 is also inhibited (either by the CYP1A2 inhibitor or by a third drug). Consider therapy modification
Pomalidomide: May enhance the thrombogenic effect of Estrogen Derivatives. Management: Canadian pomalidomide labeling recommends caution with use of hormone replacement therapy and states that hormonal contraceptives are not recommended. US pomalidomide labeling does not contain these specific recommendations. Consider therapy modification
Pomalidomide: Progestins may enhance the thrombogenic effect of Pomalidomide. Management: Canadian pomalidomide labeling recommends caution with use of hormone replacement therapy and states that hormonal contraceptives are not recommended. US pomalidomide labeling does not contain these specific recommendations. Consider therapy modification
Potassium-Sparing Diuretics: Drospirenone may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy
Primidone: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Consider therapy modification
Protease Inhibitors: May decrease the serum concentration of Contraceptives (Estrogens). Management: Use oral contraceptives containing at least 35mcg ethinyl estradiol with atazanavir/ritonavir, or no more than 30mcg in patients receiving atazanavir alone. Use of an alternative, non-hormonal contraceptive is recommended with other protease inhibitors. Exceptions: Indinavir. Consider therapy modification
Prucalopride: May decrease the serum concentration of Contraceptives (Estrogens). Consider therapy modification
Prucalopride: May decrease the serum concentration of Contraceptives (Progestins). Consider therapy modification
Retinoic Acid Derivatives: May diminish the therapeutic effect of Contraceptives (Progestins). Retinoic Acid Derivatives may decrease the serum concentration of Contraceptives (Progestins). Management: Two forms of effective contraception should be used in patients receiving retinoic acid derivatives. Particularly, microdosed progesterone-only preparations may be inadequately effective. Exceptions: Adapalene; Bexarotene (Topical); Tretinoin (Topical). Consider therapy modification
Rifamycin Derivatives: May decrease the serum concentration of Contraceptives (Estrogens). Contraceptive failure is possible. Management: Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification
Rifamycin Derivatives: May decrease the serum concentration of Contraceptives (Progestins). Contraceptive failure is possible. Management: Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification
ROPINIRole: Estrogen Derivatives may increase the serum concentration of ROPINIRole. Monitor therapy
Rufinamide: May decrease the serum concentration of Ethinyl Estradiol. Consider therapy modification
Saquinavir: May decrease the serum concentration of Contraceptives (Progestins). Management: Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Consider therapy modification
Selegiline: Contraceptives (Estrogens) may increase the serum concentration of Selegiline. Monitor therapy
Selegiline: Contraceptives (Progestins) may increase the serum concentration of Selegiline. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
St Johns Wort: May diminish the therapeutic effect of Contraceptives (Estrogens). Contraceptive failure is possible. Management: Consider an alternative to St John's wort if possible. If this combination is used, an alternative, nonhormonal contraceptive is recommended. Consider therapy modification
St John's Wort: May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Consider using a product other than St John's wort. Contraceptive failure is possible. Use of an alternative, nonhormonal contraceptive is recommended. Consider therapy modification
St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Sugammadex: May decrease the serum concentration of Contraceptives (Progestins). Management: Patients receiving any hormonal contraceptive (oral or non-oral) should use an additional, nonhormonal contraceptive method during and for 7 days following sugammadex treatment. Consider therapy modification
Sugammadex: May decrease the serum concentration of Contraceptives (Estrogens). Management: Patients receiving any hormonal contraceptive (oral or non-oral) should use an additional, nonhormonal contraceptive method during and for 7 days following sugammadex treatment. Consider therapy modification
Telaprevir: May decrease the serum concentration of Contraceptives (Estrogens). Management: Two different nonhormonal forms of contraception are required for women of childbearing potential taking telaprevir. Hormonal contraceptives may be less effective during concurrent telaprevir and for up to 2 weeks after telaprevir discontinuation. Consider therapy modification
Telaprevir: May decrease the serum concentration of Contraceptives (Progestins). Management: Two different nonhormonal forms of contraception are required for women of childbearing potential taking telaprevir. Hormonal contraceptives may be less effective during concurrent telaprevir and for up to 2 weeks after telaprevir discontinuation. Consider therapy modification
Thalidomide: Contraceptives (Estrogens) may enhance the thrombogenic effect of Thalidomide. Monitor therapy
Thalidomide: Contraceptives (Progestins) may enhance the thrombogenic effect of Thalidomide. Monitor therapy
Thalidomide: Estrogen Derivatives may enhance the thrombogenic effect of Thalidomide. Monitor therapy
Theophylline Derivatives: Estrogen Derivatives may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy
Thyroid Products: Estrogen Derivatives may diminish the therapeutic effect of Thyroid Products. Monitor therapy
Tipranavir: Estrogen Derivatives may enhance the dermatologic adverse effect of Tipranavir. The combination of tipranavir/ritonavir and ethinyl estradiol/norethindrone was associated with a high incidence of skin rash. Tipranavir may decrease the serum concentration of Estrogen Derivatives. Management: Women using hormonal contraceptives should consider alternative, non-hormonal forms of contraception. Consider therapy modification
Tipranavir: May increase the serum concentration of Contraceptives (Progestins). Management: Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Consider therapy modification
TiZANidine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of TiZANidine. Management: If combined use cannot be avoided, initiate tizanidine in adults at 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Topiramate: May decrease the serum concentration of Contraceptives (Estrogens). Contraceptive failure is possible. Management: Risk appears greatest for higher topiramate doses (200 mg/day or greater). Some have recommended using at least 50 mcg/day of ethinyl estradiol, but the effectiveness of this is unclear. Consider a nonhormonal form of contraception. Consider therapy modification
Topiramate: May decrease the serum concentration of Contraceptives (Progestins). Management: Caution patients that this combination may be associated with reduced contraceptive effectiveness. Consider adding an additional (non-hormonal) contraceptive method. Consider therapy modification
Tranexamic Acid: Contraceptives (Progestins) may enhance the thrombogenic effect of Tranexamic Acid. Avoid combination
Tranexamic Acid: Contraceptives (Estrogens) may enhance the thrombogenic effect of Tranexamic Acid. Avoid combination
Ulipristal: May diminish the therapeutic effect of Progestins. Progestins may diminish the therapeutic effect of Ulipristal. Management: Ulipristal for uterine fibroids (Canadian indication): avoid progestins within 12 days of stopping ulipristal; as emergency contraceptive (U.S. indication): avoid progestins within 5 days of stopping ulipristal. Avoid combination
Ursodiol: Estrogen Derivatives may diminish the therapeutic effect of Ursodiol. Monitor therapy
Vitamin K Antagonists (eg, warfarin): Contraceptives (Estrogens) may diminish the anticoagulant effect of Vitamin K Antagonists. In contrast, enhanced anticoagulant effects have also been noted with some products. Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Contraceptives (Progestins) may diminish the anticoagulant effect of Vitamin K Antagonists. In contrast, enhanced anticoagulant effects have also been noted with some products. Management: When possible, concomitant hormonal contraceptives and coumarin derivatives should be avoided in order to eliminate the risk of thromboembolic disorders. Consider using an alternative, nonhormonal contraceptive. Consider therapy modification
Voriconazole: May decrease the metabolism of Contraceptives (Estrogens). Contraceptives (Estrogens) may increase the serum concentration of Voriconazole. Monitor therapy
Voriconazole: May increase the serum concentration of Contraceptives (Progestins). Contraceptives (Progestins) may increase the serum concentration of Voriconazole. Monitor therapy
Assessment of pregnancy status (prior to therapy); blood pressure (prior to therapy and yearly); weight (optional; BMI at baseline may be helpful to monitor changes during therapy); assess potential health status changes at routine visits (CDC, 2013).
Monitor patient for vision changes; blood pressure; signs and symptoms of thromboembolic disorders; signs or symptoms of depression; glycemic control in patients with diabetes; lipid profiles in patients being treated for hyperlipidemias. Adequate diagnostic measures, including endometrial sampling, if indicated, should be performed to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding.
Frequency not defined. Reactions listed are based on reports for other agents in this same pharmacologic class (oral contraceptives) and may not be specifically reported for drospirenone/ethinyl estradiol.
Increased risk or evidence of association with use:
Cardiovascular: Arterial thromboembolism, cerebral thrombosis, hypertension, local thrombophlebitis, mesenteric thrombosis, myocardial infarction, pulmonary embolism, retinal thrombosis
Central nervous system: Cerebral hemorrhage
Gastrointestinal: Gallbladder disease
Hepatic: Hepatic adenoma, hepatic neoplasm (benign)
Adverse reactions considered drug related:
Cardiovascular: Edema, worsening of varicose veins
Central nervous system: Depression, exacerbation of tics, migraine
Dermatologic: Allergic skin rash, chloasma
Endocrine & metabolic: Amenorrhea, breast changes (breast hypertrophy, breast secretion, breast tenderness, mastalgia), decreased serum folate level, exacerbation of porphyria, menstrual disease (menstrual flow changes), weight changes
Gastrointestinal: Abdominal cramps, bloating, carbohydrate intolerance, nausea, vomiting
Genitourinary: Breakthrough bleeding, cervical ectropion, cervical erosion, change in cervical secretions, decreased lactation (with use immediately postpartum), infertility (temporary), spotting, vulvovaginal candidiasis
Hepatic: Cholestatic jaundice
Hypersensitivity: Anaphylaxis/anaphylactoid reaction (including angioedema, circulatory shock, respiratory collapse, urticaria)
Neuromuscular & skeletal: Exacerbation of systemic lupus erythematosus
Ophthalmic: Change in corneal curvature (steepening), contact lens intolerance
Adverse reactions in which association is not confirmed or denied:
Cardiovascular: Budd-Chiari syndrome
Central nervous system: Dizziness, headache, nervousness
Dermatologic: Acne vulgaris, erythema multiforme, erythema nodosum, loss of scalp hair
Endocrine & metabolic: Change in libido, hirsutism, porphyria, premenstrual syndrome
Gastrointestinal: Change in appetite, colitis, pancreatitis
Genitourinary: Cystitis-like syndrome, dysmenorrhea, vaginitis
Hematologic & oncologic: Hemolytic-uremic syndrome, hemorrhagic eruption
Ophthalmic: Cataract, optic neuritis (with or without partial or complete loss of vision)
Renal: Renal insufficiency
Concerns related to adverse effects:
- Breast cancer: The use of combination hormonal contraceptives has been associated with a slight increase in frequency of breast cancer; however, studies are not consistent. Use is contraindicated in women with (or history of) breast cancer.
- Carbohydrate intolerance: May have adverse effects on glucose tolerance in a dose-related fashion; use caution in women with diabetes (including prediabetic women).
- Chloasma: Use caution with a history of chloasma gravidarum; women with a tendency to chloasma should avoid sun and ultraviolet radiation exposure during therapy.
- Cholestasis: Risk of cholestasis may be increased with previous cholestatic jaundice of pregnancy or jaundice with prior oral contraceptive use.
- Hereditary angioedema: Estrogens may induce or exacerbate symptoms in women with hereditary angioedema.
- Hyperkalemia: Drospirenone has antimineralocorticoid activity that may lead to hyperkalemia in patients with renal insufficiency, hepatic dysfunction, or adrenal insufficiency; use caution with medications that may increase serum potassium.
- Lipid effects: Combination hormonal contraceptives may affect lipid levels. The type of lipid disorder, the severity, and the presence of other cardiovascular risk factors should be considered when prescribing combination hormonal contraceptives to women with lipid disorders (CDC, 2010). Serum triglycerides may also be increased.
- Retinal vascular thrombosis: Discontinue if unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions occur and immediately evaluate for retinal vein thrombosis.
- Thromboembolism: Contraceptives may increase the risk of thromboembolism. Discontinue if an arterial or venous thrombotic event (VTE) occurs. Risk may be greater with contraceptives containing drospirenone. Women with inherited thrombophilias (eg, protein C or S deficiency) may have increased risk of venous thromboembolism (DeSancho, 2010; van Vlijmen, 2011). Use is contraindicated in women with hypercoagulopathies (inherited or acquired).
- Vaginal bleeding: Unscheduled bleeding (breakthrough or intracyclic) and spotting may occur, especially during the first 3 months of therapy. In addition, occasional missed periods may occur. Presentation of irregular, unresolving vaginal bleeding warrants further evaluation including endometrial sampling, if indicated, to rule out malignancy or pregnancy. Amenorrhea or oligomenorrhea may occur after discontinuing combination hormonal contraceptives, especially when such a condition was preexistent.
Disease-related concerns:
- Cardiovascular disease: Use with caution in patients with risk factors for cardiovascular disease (eg, hypertension, hypercholesterolemia, morbid obesity, diabetes, or women who smoke); may lead to increased risk of stroke or myocardial infarction. May have a dose-related risk of vascular disease and hypertension; women with hypertension should be encouraged to use another form of contraception; use is contraindicated with uncontrolled hypertension. Monitor blood pressure and stop therapy if blood pressure rises significantly.
- Depression: Use with caution in patients with depression; discontinue if severe depression occurs.
- Gallbladder disease: May have a dose-related risk of gallbladder disease.
- Hepatic adenomas: Use of combination hormonal contraceptives is associated with hepatic adenomas (rare); fatal intra-abdominal hemorrhage may result. Risk is increased with long-term (>8 years) use. Use of this product is contraindicated in women with hepatic tumors.
- Hepatic impairment: Combination hormonal contraceptives may be poorly metabolized in women with hepatic impairment. Discontinue if jaundice develops during therapy or if liver function becomes abnormal. Use is contraindicated with preexisting hepatic disease.
- Migraine: Use with caution in patients with a history of migraine (may increase severity or frequency). Evaluate new, recurrent, severe, or persistent headaches. Use with headaches with focal neurological symptoms or migraine headaches with or without aura if >35 years of age is contraindicated.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
- Thyroid replacement therapy: Estrogens may increase thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels. Women on thyroid replacement therapy may require higher doses of thyroid hormone while receiving estrogens.
Special populations:
- Pediatric: Not for use prior to menarche.
- Postmenopausal women: Use is not indicated in postmenopausal women.
- Smokers: [U.S. Boxed Warning]: The risk of cardiovascular side effects is increased in women who smoke cigarettes; risk increases with age (especially women >35 years of age) and the number of cigarettes smoked; women who use combination hormonal contraceptives should be strongly advised not to smoke. Use is contraindicated in patients >35 years of age who smoke.
- Surgical patients: Whenever possible, should be discontinued at least 4 weeks prior to and for 2 weeks following elective surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization.
Special handling:
- Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 2]).
Other warnings/precautions:
- Acne use: For use only in females ≥14 years of age who have reached menarche, who also desire combination hormonal contraceptive therapy, are unresponsive to topical acne treatments, and have no contraindications to combination hormonal contraceptive use.
- Laboratory changes: The use of estrogens and/or progestins may change the results of some laboratory tests (eg, coagulation factors, lipids, glucose tolerance, binding proteins). Drospirenone can also cause an increase in plasma renin activity and plasma aldosterone. The dose, route, and the specific estrogen/progestin influences these changes. In addition, personal risk factors (eg, cardiovascular disease, smoking, diabetes, age) also contribute to adverse events; use of specific products may be contraindicated in women with certain risk factors.
- Minimum effective dosage: The minimum dosage combination of estrogen/progestin that will effectively treat the individual patient should be used (CDC, 2010).
- Premenstrual dysphoric disorder (PMDD) use: For use only in females who desire combination hormonal contraceptive therapy; use for more than 3 menstrual cycles has not been evaluated. Has not been evaluated for the treatment of premenstrual syndrome.
Pregnancy status should be evaluated prior to prescribing (CDC, 2013); treatment should be discontinued if pregnancy occurs. In general, the use of combination hormonal contraceptives, when inadvertently used early in pregnancy, have not been associated with teratogenic effects. Available evidence is inconsistent if BMI alters the efficacy of combination oral contraceptives (CDC, 2010).
Due to increased risk of venous thromboembolism (VTE) postpartum, combination hormonal contraceptives should not be started in any woman <21 days following delivery. Women without risk factors for VTE and who are not breast-feeding may start combination hormonal contraceptives during 21-42 days postpartum. After 42 days postpartum, restrictions for use are not related to postpartum status and should be based on other medical conditions (CDC, 2011). The manufacturer states that combination hormonal contraceptives should not be started until ≥4 weeks after delivery in women who choose not to breast-feed, or ≥4 weeks after a second trimester abortion or miscarriage.
Combination oral contraceptives inhibit ovulation via a negative feedback mechanism on the hypothalamus, which alters the normal pattern of gonadotropin secretion of a follicle-stimulating hormone (FSH) and luteinizing hormone by the anterior pituitary. The follicular phase FSH and midcycle surge of gonadotropins are inhibited. In addition, oral contraceptives produce alterations in the genital tract, including changes in the cervical mucus, rendering it unfavorable for sperm penetration even if ovulation occurs. Changes in the endometrium may also occur, producing an unfavorable environment for nidation. Oral contraceptive drugs may alter the tubal transport of the ova through the fallopian tubes. Progestational agents may also alter sperm fertility. Drospirenone is a spironolactone analogue with antimineralocorticoid and antiandrogenic activity.
Drospirenone: ~4 L/kg; Ethinyl estradiol: ~4 to 5 L/kg
Drospirenone: To inactive metabolites, minor metabolism hepatically via CYP3A4
Ethinyl estradiol: Hepatic via CYP3A4; forms metabolites; undergoes first-pass metabolism and enterohepatic circulation
Drospirenone, ethinyl estradiol: Urine and feces
1 to 2 hours
Terminal: Drospirenone: ~30 hours; Ethinyl estradiol: ~24 hours
Drospirenone: Serum proteins (excluding sex hormone-binding globulin and corticosteroid-binding globulin): ~97%
Ethinyl estradiol: ~98% to serum albumin
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience lack of appetite, more hungry, weight gain, cramps, bloating, menstrual irregularities, enlarged breasts, decreased libido, or dark patches on face. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), angina, arrhythmia, shortness of breath, coughing up blood, severe dizziness, passing out, severe nausea, vomiting, severe headache, depression, loss of strength and energy, urinary retention, change in amount of urine passed, lump in breast, breast soreness or pain, nipple discharge, vaginal bleeding, vaginitis, vision changes, contact lens discomfort, or bulging eyes (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.