(ETH in il es tra DYE ole & nor el JES troe min)
Contraception: For the prevention of pregnancy
Limitations of use: The topical patch may be less effective in patients weighing ≥90 kg (198 lb).
Breast cancer or other estrogen- or progestin-dependent neoplasms (current or a history of), hepatic tumors (benign or malignant) or hepatic disease, pregnancy, undiagnosed abnormal uterine bleeding.
Use is also contraindicated in women at high risk of arterial or venous thrombotic diseases for example, women with: 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, migraine headaches with aura or migraine headaches 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.
Canadian-labeling: Additional contraindications (not in US labeling): Hypersensitivity to any component of the formulation; actual or history of thrombophlebitis or thromboembolic disorders; thrombophilia; myocardial infarction; carcinoma of the endometrium; steroid dependent jaundice, cholestatic jaundice, or history of jaundice of pregnancy; ocular lesions due to ophthalmic vascular disease including partial or complete loss of vision or defect in visual fields; persistent blood pressure ≥160 mm Hg systolic or ≥100 mm Hg diastolic; severe dyslipoproteinemia; hereditary or acquired predisposition for venous or arterial thrombosis; major surgery associated with an increased risk of post-operative thromboembolism; prolonged immobilization.
Documentation of allergenic cross-reactivity for estrogens and progestins is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Cigarette smoking increases the risk of serious cardiovascular events from hormonal contraceptive use. This risk increases with age, particularly in women older than 35 years, and with the number of cigarettes smoked. For this reason, hormonal contraceptives, including norelgestromin/ethinyl estradiol, should not be used by women who are older than 35 years and smoke.
Risk of venous thromboembolism:The risk of venous thromboembolism among women 15 to 44 years of age who used the contraceptive patch, compared with women who used several different oral contraceptives, was assessed in 5 US epidemiologic studies using electronic health care claims data. The relative risk estimates ranged from 1.2 to 2.2; one of the studies found a statistically significant increased risk of venous thromboembolism for current users of the contraceptive patch.
Hormone exposure:The pharmacokinetic profile for the contraceptive patch is different from the pharmacokinetic profile for oral contraceptives in that it has higher steady-state concentrations and lower peak concentrations. Area under the concentration-time curve (AUC) and average concentration at steady state for ethinyl estradiol are approximately 60% higher in women using the contraceptive patch compared with women using an oral contraceptive containing ethinyl estradiol 35 mcg. In contrast, peak concentrations for ethinyl estradiol are approximately 25% lower in women using the contraceptive patch. It is not known whether there are changes in the risk of serious adverse events based on the differences in pharmacokinetic profiles of ethinyl estradiol in women using the contraceptive patch compared with women using oral contraceptives containing ethinyl estradiol 30 to 35 mcg. Increased estrogen exposure may increase the risk of adverse events, including venous thromboembolism.
Females: Contraception: Topical:
Apply one patch each week for 3 weeks (21 total days); followed by one week that is patch-free. Each patch should be applied on the same day each week ( "patch change day " �) and only one patch should be worn at a time. No more than 7 days should pass during the patch-free interval.
Schedule 1 (Sunday starter): Dose begins on first Sunday after onset of menstruation; if the menstrual period starts on Sunday, apply one patch that very same day. With a Sunday start, an additional method of contraception (nonhormonal) must be used until after the first 7 days of consecutive administration unless the menstrual period starts on Sunday. Each patch change will then occur on Sunday.
Schedule 2 (Day 1 starter): Dose starts on first day of menstrual cycle, applying one patch during the first 24 hours of menstrual cycle. Each patch change will then occur on that same day of the week. The US labeling does not indicate that a back-up method of contraception is needed as long as the patch is applied on the first day of cycle. The Canadian labeling recommends a back-up method of non-hormonal contraception be used concurrently for the first 7 consecutive days of the first treatment cycle.
Additional dosing considerations:
No bleeding during patch-free week/missed menstrual period: If patch has been applied as directed, continue treatment on usual "patch change day " �. If used correctly, no bleeding during patch-free week does not necessarily indicate pregnancy. However, if no withdrawal bleeding occurs for 2 consecutive cycles, pregnancy should be ruled out. If patch has not been applied as directed, and one menstrual period is missed, pregnancy should be ruled out prior to continuing treatment.
If a patch becomes partially or completely detached for <24 hours: Try to reapply to same place, or replace with a new patch immediately. Do not reapply if patch is no longer sticky, if it is sticking to itself or another surface, or if it has material sticking to it.
If a patch becomes partially or completely detached for >24 hours (or time period is unknown): Apply a new patch and use this day of the week as the new "patch change day " � from this point on. An additional method of contraception (nonhormonal) must be used until after the first 7 days of consecutive administration.
Switching from oral contraceptives or vaginal ring:
US labeling: Complete current cycle and apply the first patch on the day the next pill cycle would be started or ring would be inserted. If there is no menstrual bleeding within 7 days of taking the last active tablet, the patient can initiate the first patch application; however, pregnancy must be ruled out. If patch is applied later than 7 days after the last active pill or removal of the vaginal ring, an additional method of contraception (nonhormonal) should be used until after the first 7 days of consecutive administration
Canadian labeling: Apply the first patch on the first day of withdrawal bleeding. If there is no withdrawal bleeding within 5 days of taking the last active tablet, rule out pregnancy prior to applying first patch. If the patch is applied after the first day of withdrawal bleeding, a non-hormonal contraceptive should be used concurrently for 7 days. If more than 7 days have elapsed after the last active tablet was taken, evaluate patient prior to starting patch to rule out ovulation or pregnancy.
Use after childbirth: Therapy should not be started <4 weeks after childbirth. Pregnancy should be ruled out prior to treatment if menstrual periods have not restarted. An additional method of contraception (nonhormonal) should be used until after the first 7 days of consecutive administration.
Use after abortion or miscarriage:
US labeling: Therapy may be started immediately if abortion/miscarriage occurs within the first trimester. If therapy is not started within 5 days, follow instructions for first time use. An additional method of contraception (nonhormonal) should be used until after the first 7 days of consecutive administration. If abortion/miscarriage occurs during the second trimester, therapy should not be started for at least 4 weeks. Follow directions for use after childbirth.
Canadian labeling: Therapy may be started immediately if abortion/miscarriage occurs prior to 20 weeks gestation. An additional method of contraception is not necessary if therapy is started immediately. If abortion/miscarriage occurs at or beyond 20 weeks gestation, therapy may be started on day-21 post-abortion or on the first day of the first spontaneous menstrual cycle, whichever comes first.
Females: Contraception: Topical: Refer to adult dosing; not to be used prior to menarche.
There are no dosage adjustments provided in manufacturers labeling (has not been studied); use with caution and monitor blood pressure closely.
Contraindicated in patients with hepatic impairment.
New patches should be applied on the same day each week. Apply to clean, dry, intact, healthy skin on the buttock, abdomen, upper outer arm, or back. Avoid areas that will be rubbed by tight clothing. Do not apply to the breasts or to skin that is red, irritated, or cut. Alternate application sites; do not apply to the same place as the previous patch. Do not apply make-up, creams, lotions, powders, or other topical products to the skin where the patch will be placed. Remove the patch and the plastic liner from the foil pouch, being careful not to remove the clear liner when removing the patch. Apply patch by first peeling back half of the clear protective liner. Avoid touching surface of patch. Apply patch to skin and remove the rest of the liner. Press patch down firmly onto skin using palm of the hand; apply pressure for 10 seconds. Run fingers over entire surface area to smooth out any wrinkles in the patch. The patch should be checked daily to ensure all edges are sticking. When changing the patch each week, the new patch may be applied in the same anatomic area but should be applied to a new spot in that area. Do not use supplemental adhesives or wraps to hold patch into place. Do not cut, damage or alter the size of the patch; contraceptive efficacy may be impaired.
Forgetting to apply the patch at the start of cycle (week 1/day 1): Apply first patch as soon as remembering, using this day of the week as the new "patch change day " � from this point on. An additional method of contraception (nonhormonal) must be used until after the first 7 days of consecutive administration.
Forgetting to change patch in the middle of the cycle (week 2/day 8 or week 3/day 15): If <48 hours from normal "patch change day, " � apply new patch immediately. No back-up contraception is needed. If >48 hours from normal "patch change day, " � apply a new patch and use this day of the week as the new "patch change day " � from this point on. An additional method of contraception (nonhormonal) must be used until after the first 7 days of consecutive administration.
Forgetting to remove patch at end of cycle (week 4/day 22): Take off as soon as remembering, start new cycle on usual "patch change day. " �
Changing the "patch change day " �: The "patch change day " � can be changed to an earlier day in the week by first completing the current cycle. Then, during the "patch-free interval " �, select an earlier day to start the new cycle. Shortening the patch free interval may increase the incidence of spotting or breakthrough bleeding. Do not allow >7 consecutive patch-free days.
Skin irritation: If patch is in an uncomfortable location, it can be removed and a new patch applied to a different location until the next "patch change day. " �
To dispose of patch, fold the sticky sides together and dispose in the trash within a child-resistant container. Do not flush down the toilet.
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 2]).
Store at controlled room temperature of 20 � �C to 25 � �C (68 � �F to 77 � �F); do not refrigerate or freeze.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Patch, transdermal:
Ortho Evra: Ethinyl estradiol 0.75 mg and norelgestromin 6 mg [releases ethinyl estradiol 35 mcg and norelgestromin 150 mcg per day] (1s DSC], 3s [DSC])
Xulane: Ethinyl estradiol 0.53 mg and norelgestromin 4.86 mg [releases ethinyl estradiol 35 mcg and norelgestromin 150 mcg per day] (3s)
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
Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination
Anastrozole: Estrogen Derivatives may diminish the therapeutic effect of Anastrozole. Avoid combination
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
Asunaprevir: May decrease the serum concentration of Norelgestromin. 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 decrease the serum concentration of Contraceptives (Estrogens). Management: Patients receiving boceprevir, ribavirin, and peginterferon alfa should use two reliable forms of contraception. Norethindrone/ethinyl estradiol may be used for one of these when norethindrone dose is at least 1 mg/day. Consider therapy modification
Boceprevir: May increase the serum concentration of Contraceptives (Progestins). This has been seen specifically with norethindrone. Boceprevir may increase the serum concentration of Contraceptives (Progestins). This has been seen specifically with drospirenone. Management: Patients receiving boceprevir, ribavirin, and peginterferon alfa should use two reliable forms of contraception. Norethindrone/ethinyl estradiol may be used for one of these when norethindrone dose is at least 1 mg/day. Avoid drospirenone. Consider therapy modification
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
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
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
NSAID (COX-2 Inhibitor): May enhance the thrombogenic effect of Estrogen Derivatives. NSAID (COX-2 Inhibitor) may increase the serum concentration of Estrogen Derivatives. 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
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).
If all patches have not been applied on schedule and one menstrual period is missed, the possibility of pregnancy should be considered. If two consecutive menstrual periods are missed, a pregnancy test is recommended before a new dosing cycle is started.
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 should be performed to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding.
The following reactions have been reported with the contraceptive patch. Adverse reactions associated with oral combination hormonal contraceptive agents are also likely to appear with the topical contraceptive patch (frequency difficult to anticipate). See individual oral contraceptive monographs for additional information.
>10%:
Central nervous system: Headache (21%)
Endocrine & metabolic: Breast changes (22%; including breast engorgement, discomfort, mastalgia)
Gastrointestinal: Nausea (17%)
Local: Application site reaction (17%)
1% to 10%:
Cardiovascular: Increased blood pressure (<3%), pulmonary embolism (<3%)
Central nervous system: Anxiety ( ≤6%), mood disorder ( ≤6%), dizziness (3%), fatigue (3%), migraine (3%), insomnia (<3%), malaise (<3%)
Dermatologic: Acne vulgaris (3%), pruritus (3%), chloasma (<3%), contact dermatitis (<3%), erythema (<3%), skin irritation (<3%)
Endocrine & metabolic: Menstrual disease (6%), weight gain (3%), change in libido (<3%), dyslipidemia (<3%), fluid retention (<3%), galactorrhea (<3%), premenstrual syndrome (<3%)
Gastrointestinal: Abdominal pain (8%), vomiting (5%), diarrhea (4%), abdominal distention (<3%), cholecystitis (<3%)
Genitourinary: Dysmenorrhea (8%), vaginal hemorrhage (6%), vulvovaginal candidiasis (4%), genital discharge (<3%), uterine spasm (<3%), vaginal dryness (<3%), vulvar dryness (<3%)
Neuromuscular & skeletal: Muscle spasm (<3%)
<1% (Limited to important or life-threatening): Alopecia, altered serum glucose, arterial thrombosis, benign mammary fibroadenoma, blood cholesterol abnormal, cerebrovascular accident, cervical dysplasia, cholelithiasis, cholestasis, cholestatic jaundice, colitis, contact lens intolerance (or complication), deep vein thrombosis, dysgeusia, eczema, edema, emotional disturbance, erythema multiforme, erythema nodosum, hepatic adenoma, hepatic neoplasm, hyperglycemia, hypersensitivity reaction, hypertension, hypertensive crisis, increased appetite, insulin resistance, intracranial hemorrhage, lesion (hepatic), malignant neoplasm of breast, malignant neoplasm of cervix, mass (breast), migraine with aura, myocardial infarction, skin photosensitivity, skin rash, thrombosis, urticaria, uterine fibroids
Concerns related to adverse effects:
- Breast cancer: The use of combination hormonal contraceptives has not been shown to increase the risk for breast cancer. However, breast cancer is a hormonal sensitive tumor and the prognosis for women with a current or recent history of breast cancer may be worse with combination hormonal contraceptive use (CDC 2010). Use is contraindicated in women with (or history of) breast cancer.
- Carbohydrate intolerance: May impair glucose tolerance; use caution in women with diabetes or prediabetes.
- Cervical cancer: The use of combination hormonal contraceptives has been associated with a slight increased risk of cervical cancer; however, studies are not consistent and may be related to additional risk factors (Gierisch 2013). Women awaiting treatment for cervical cancer may use combination hormonal contraceptives (CDC 2013).
- Chloasma: Combination hormonal contraceptives, as well as sun exposure and pregnancy, are triggers for chloasma. Women with a susceptibility to chloasma or additional risk factors should avoid exposure to sun or ultraviolet radiation during therapy (Handel 2014).
- Cholestasis: Risk of cholestasis may be increased with previous cholestasis of pregnancy or cholestasis with prior oral contraceptive use. Canadian labeling contraindicates use in women with steroid dependent jaundice, cholestatic jaundice, or history of jaundice of pregnancy.
- Lipid effects: Combination hormonal contraceptives may adversely affect lipid levels, including serum triglycerides. 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). Women with hypertriglyceridemia or a family history of hypertriglyceridemia may be at increased risk of pancreatitis when using combination hormonal contraceptives. Consider alternative contraception for women with uncontrolled dyslipidemia.
- 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: Combination hormonal contraceptives may increase the risk of venous thromboembolism. [US Boxed Warning]: The pharmacokinetic profile of the patch is different from oral contraceptives; steady state concentrations of ethinyl estradiol are ~60% higher following use of the patch than with oral tablets containing ethinyl estradiol 35 mcg. Peak concentrations are lower with the patch. The risk of venous thromboembolism (VTE) may be further increased with use of the contraceptive patch due to increased estrogen exposure in comparison to oral contraceptives. The increased estrogen exposure may increase the risk of adverse events, including venous thromboembolism. Discontinue use of combination hormonal contraceptives if an arterial or venous thrombotic event occurs. 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: Breakthrough or intracyclic bleeding 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 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); use of combination hormonal contraceptives may increase the risk of arterial or venous thrombotic events (CDC 2010). Use is contraindicated in women at high risk of arterial or venous thrombotic diseases.
- Depression: Use with caution in patients with a history of depression; discontinue if serious depression recurs.
- Gallbladder disease: May have a risk of gallbladder disease; may worsen existing gallbladder disease.
- Hepatic adenomas: Use of combination hormonal contraceptives is associated with hepatic adenomas (rare); rupture may cause fatal intra-abdominal hemorrhage. Long term use may be associated with an increased risk of hepatocellular carcinoma (rare). Use is contraindicated with preexisting 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.
- Hereditary angioedema: Estrogens may induce or exacerbate symptoms in women with hereditary angioedema (Geng 2013; Zuraw 2013).
- Hypertension: The risk of hypertension may be increased with age, dose, and duration of use. Combination hormonal contraceptives should not be used in women with persistent blood pressure values ≥160 mm Hg systolic or ≥100 mm Hg diastolic. Women with less severe hypertension (140 to 159 mm Hg systolic or 90 to 99 mm Hg diastolic) or those with hypertension that is adequately controlled should generally not use combination hormonal contraceptives (CDC 2013). Other risk factors for cardiovascular disease (eg, older age, smoking, diabetes) should be considered when prescribing contraceptives (CDC 2010). The manufacturer contraindicates use in women with uncontrolled hypertension and recommends monitoring women with well-controlled hypertension; discontinue therapy if blood pressure rises significantly.
- Migraine: Evaluate new, recurrent, severe or persistent headaches. Use in patients with migraine headaches with aura, or migraine headaches of any type 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.
- Smokers: [US 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. The Canadian labeling contraindicates use in patients who have undergone major surgery associated with an increased risk of post-operative thromboembolism and in patients with prolonged immobilization.
Special handling:
- Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 2]).
Other warnings/precautions:
- Appropriate use: When initiating a combination oral contraceptive, consideration should be given to safety, effectiveness, availability and acceptance to the patient (CDC 2013). Consider initiating with a monthly bleeding monophasic formulation containing ethinyl estradiol 30 to 35 mcg plus a progestin, and adjusting based on adverse events and patient preference (Ott 2014).
- HIV infection protection: Combination hormonal contraceptives do not protect against HIV infection or other sexually-transmitted diseases (CDC 2010; CDC 2013).
- 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). 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.
- Ovarian cancer: The risk of ovarian cancer is decreased in women using combination hormonal contraceptives (CDC 2013; Walker 2015). Oral contraceptives may be used to reduce the risk of ovarian cancer including those women with BRACA1 and BRACA2 mutations (Walker 2015).
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 taken early in pregnancy have not been associated with teratogenic effects. The topical patch may be less effective in patients weighing ≥90 kg (198 lb).
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 breastfeed, or ≥4 weeks after a second trimester abortion or miscarriage.
Combination hormonal 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, combination hormonal 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. Combination hormonal contraceptive drugs may alter the tubal transport of the ova through the fallopian tubes. Progestational agents may also alter sperm fertility.
Topical: Equivalent when applied to abdomen, buttock, upper outer arm, and upper torso
Ethinyl estradiol and norelgestromin: Rapid; reaches plateau by ~48 hours. Absorption of ethinyl estradiol may be increased with heat exposure due to sauna, whirlpool, or treadmill.
The AUC plasma concentration of ethinyl estradiol at steady state are ~60% higher following use of the patch than with those observed following an oral 35 mcg tablet. Peak plasma concentrations of ethinyl estradiol are 25% lower with the patch than with the tablet.
Topical: First-pass effect avoided
Ethinyl estradiol: Forms metabolites
Norelgestromin: Hepatic to norgestrel and others
Metabolites of ethinyl estradiol and norelgestromin: Urine and feces
Topical: Ethinyl estradiol: ~17 hours; Norelgestromin: ~28 hours
Ethinyl estradiol: Albumin
Norelgestromin and norgestrel: >97%; norelgestromin to albumin and norgestrel to sex-hormone-binding globulin
- 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 weight gain, cramps, bloating, macromastia, menstrual irregularities, decreased libido, skin irritation, or facial skin discoloration. Have patient report immediately to prescriber signs of hepatic impairment, angina, dyspnea, hemoptysis, severe dizziness, syncope, considerable nausea, strength differences from one side to another, difficulty speaking or thinking, change in balance, blurred vision, edema of extremities, extremity discoloration, painful extremities, severe headache, depression, intolerable asthenia, considerable dyspepsia, urinary retention, oliguria, lump in breast, mastalgia, nipple discharge, vaginal hemorrhaging, vaginitis, vision changes, exophthalmos, or contact lens discomfort (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.