Endometriosis: Females: Oral: 2 mg once daily; has been studied for up to 16 months (Petraglia 2012)
No dosage adjustment necessary.
Mild to moderate impairment: No dosage adjustment provided in manufacturer's labeling; dienogest undergoes hepatic metabolism and therefore systemic exposure may be increased.
Severe impairment: Use is contraindicated in patients with a history of or current severe hepatic disease.
Endometriosis: Children ≥12 years and Adolescents: Females (postmenarche): Oral: 2 mg once daily; has been studied for up to 12 months of therapy
No dosage adjustment necessary.
Mild to moderate impairment: There are no dosage adjustments provided in manufacturer's labeling; dienogest undergoes hepatic metabolism and therefore systemic exposure may be increased.
Severe impairment: Use is contraindicated in patients with a history of or current severe hepatic disease.
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Visanne: 2 mg
Generic: 2 mg
Not available in the US
Oral: Administer preferably at the same time each day with liquid and without regard to meals. Tablets should be taken continuously regardless of any vaginal bleeding. If vomiting and/or diarrhea occur within 3 to 4 hours of administration, repeat dose.
Oral: Administer preferably at the same time each day with liquid and without regard to meals. Tablets should be taken continuously regardless of any vaginal bleeding. If vomiting and/or diarrhea occur within 3 to 4 hours of administration, repeat dose.
Note: Not approved in the US
Endometriosis: Management of pelvic pain associated with endometriosis
Visanne may be confused with Vyvanse
ALERT: Canadian Boxed Warning: Health Canada-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Central nervous system: Headache (7%), depression (3%), disturbed sleep (2%), irritability (1%), migraine (1%), nervousness (1%)
Dermatologic: Acne vulgaris (2%), alopecia (1%)
Endocrine & metabolic: Breast changes (discomfort: 5%), weight gain (4%), ovarian cyst (3%), decreased libido (2%)
Gastrointestinal: Nausea (4%), abdominal pain (2%)
Genitourinary: Vaginal hemorrhage (1%)
Neuromuscular & skeletal: Weakness (2%)
<1%, postmarketing, and/or case reports: Abdominal distress, anemia, anxiety, back pain, breast induration, constipation, decreased glucose tolerance, dermatitis, diarrhea, disturbance in attention, dysautonomia, edema, feeling of heaviness (extremities), fibrocystic breast disease, flatulence, genital discharge, GI inflammation, hot flash, increased appetite, limb pain, lump in breast, mood changes, muscle spasm, onychoclasis, ostealgia, palpitations, pelvic pain, pruritus, skin pigmentation, skin photosensitivity, tinnitus, urinary tract infection, vulvovaginal candidiasis, vomiting, vulvar dryness, xeroderma, xerophthalmia
Hypersensitivity to dienogest or any component of the formulation; undiagnosed abnormal vaginal bleeding; active venous thromboembolic disorder; history of or current arterial and cardiovascular disease (eg, MI, ischemic heart disease, cerebrovascular accident); diabetes mellitus with vascular involvement; history of or current severe hepatic disease where liver function tests remain abnormal; history of or current hepatic neoplasia (benign or malignant); known or suspected sex-hormone-dependent malignancy; ocular lesions due to ophthalmic vascular disease, such as partial or complete vision loss or defect in visual fields; current or history of migraine with focal aura; breast-feeding; known or suspected pregnancy
Concerns related to adverse effects:
• Bleeding: Use is associated with irregular menstrual bleeding (eg, amenorrhea, infrequent or frequent bleeding, prolonged bleeding) and may be aggravated in some women (eg, those with fibroids). Bleeding patterns generally show a reduced intensity over time. If bleeding irregularities continue with prolonged use, appropriate diagnostic measures should be taken to rule out endometrial pathology (eg, endometrial sampling, pelvic ultrasound). Consider discontinuation of therapy with prolonged heavy bleeding. Pretreatment menstrual bleeding patterns return within 2 months of therapy discontinuation.
• Bone mineral density loss [Canadian Boxed Warning]: Dienogest has been associated with plateauing and loss of bone mineral density (BMD) which may not be completely reversible; BMD loss may be greater with prolonged use of dienogest and the effects may be of greater concern during adolescence and periods of bone accretion. It is not known if use of dienogest during adolescence will decrease peak bone mass and increase the risk of osteoporosis. A mean decrease in BMD in the lumbar spine of 1.2% has been observed in patients 12 to <18 years after 12 months of therapy; BMD increased towards pretreatment levels within 6 months of therapy discontinuation. Risks/benefits of therapy in adolescents should be evaluated prior to initiating therapy and regularly during therapy. BMD monitoring should be considered in adolescent females as clinically appropriate. In a small study of adult patients, a reduction in mean bone mineral density was not observed 6 months after initiating therapy though long term data are not available. Risk assessment should also be performed in women of any age at increased risk of osteoporosis; adequate calcium and vitamin D intake should be encouraged in females of all ages.
• Breast cancer: 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 (Curtis 2016). Data are insufficient to determine if progestin only preparations also increase this risk. Routine breast examinations are recommended during therapy. Use is contraindicated with known or suspected sex-hormone-dependent malignancy.
• Carbohydrate intolerance: May impair glucose tolerance; use caution in women with diabetes or a history of gestational diabetes mellitus.
• Chloasma: May occur occasionally; women with a history of chloasma should avoid sun or ultraviolet radiation exposure during therapy.
• Cholestatic jaundice: Patients with a prior history of cholestatic jaundice during pregnancy or due to the use of sex steroids should discontinue use of dienogest if cholestatic jaundice reoccurs during therapy.
• Hepatic tumors: Rare cases of benign and malignant hepatic tumors have been reported with use.
• Ovarian cysts: Persistent ovarian cysts which are often asymptomatic may occur during therapy.
• Pruritus: Patients with a prior history of pruritus during pregnancy or due to use of sex steroids should discontinue dienogest therapy if pruritus reoccurs during therapy.
• Venous thromboembolism (VTE): Progestin-only therapy has been associated with a slight but non-significant increase risk of VTE in some studies; discontinue therapy promptly with suspicion or symptoms of a thrombotic event. Discontinue use in patients with prolonged immobilization and at least 4 weeks prior to elective surgery; may resume therapy 2 weeks after complete remobilization. The risk of thromboembolism may be increased immediately postpartum.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with multiple risk factors for cardiovascular disease (eg, older age, hypertension, hypercholesterolemia, morbid obesity, diabetes, women who smoke); use of progestin only preparations may increase the risk of cardiovascular disease (Curtis 2016). Use is contraindicated in women with a history of or current arterial and cardiovascular disease. Discontinue if clinically significant hypertension develops during therapy.
• Depression: Use with caution in patients with depression; discontinue use with onset of clinically relevant depression or with aggravation of pre-existing depression.
• Hepatic disease: Use is contraindicated in patients with a history of or current severe hepatic disease.
Special populations:
• Elderly: Not indicated for use in the geriatric population.
• Pediatric: Not for use prior to menarche.
• Smokers: The risk of cardiovascular side effects and the risk of bone mineral density decline is increased in women who smoke cigarettes. Women should be advised not to smoke.
Other warnings/precautions:
• Appropriate use: Not intended for use as a contraceptive.
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Aprepitant: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration with aprepitant, and to continue back-up contraception for 28 days after discontinuing aprepitant to ensure contraceptive reliability. Risk D: Consider therapy modification
Asunaprevir: May decrease the serum concentration of Hormonal Contraceptives. Management: Use of a high-dose oral contraceptive (at least 30 mcg of ethinyl estradiol combined with norethindrone) is recommended when combined with asunaprevir. Consider an additional barrier method when other forms of contraception are used with asunaprevir. Risk D: Consider therapy modification
Atazanavir: May decrease the serum concentration of Hormonal Contraceptives. Specifically, atazanavir/ritonavir may decrease concentrations of estrogens. Atazanavir may increase the serum concentration of Hormonal Contraceptives. Specifically, atazanavir alone may increase concentrations of estrogens and atazanavir alone or boosted may increase concentrations of progestins. Management: Dose adjustment of hormonal contraceptives or use of alternative or additional nonhormonal contraceptive may be needed when combined with atazanavir. See full interact monograph for details. Atazanavir/cobicistat with drospirenone is contraindicated. Risk D: Consider therapy modification
Brigatinib: May decrease the serum concentration of Hormonal Contraceptives. Management: Use a non-hormonal contraceptive during brigatinib use and for at least 4 months after the last brigatinib dose. Males with partners of reproductive potential should use contraception during treatment with brigatinib and for 3 months after brigatinib use. Risk D: Consider therapy modification
Carfilzomib: Hormonal Contraceptives may enhance the thrombogenic effect of Carfilzomib. Management: Consider alternative, non-hormonal methods of contraception in patients requiring therapy with carfilzomib, especially patients using carfilzomib in combination with dexamethasone, lenalidomide plus dexamethasone, or daratumumab plus dexamethasone. Risk D: Consider therapy modification
Cladribine: May diminish the therapeutic effect of Hormonal Contraceptives. Management: In females of reproductive potential using systemically acting hormonal contraceptives, add a barrier method during cladribine dosing and for at least 4 weeks after the last dose in each treatment course Risk D: Consider therapy modification
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Cobicistat: May decrease the serum concentration of Hormonal Contraceptives. Specifically, cobicistat may decrease serum concentrations of estrogens. Cobicistat may increase the serum concentration of Hormonal Contraceptives. Specifically, cobicistat may increase serum concentrations of progestins. Management: Use alternative or additional nonhormonal forms of contraception when estrogen-containing hormonal contraceptives are combined with cobicistat. Progestin-only contraceptives can be used without back up, but monitor for progestin toxicities. Risk D: Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a moderate CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a strong CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification
CYP3A4 Inducers (Weak): May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a weak CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Hormonal Contraceptives. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy
Efavirenz: May decrease the serum concentration of Hormonal Contraceptives. Management: Use a back-up method during coadministration, and to continue back-up contraception for 12 weeks after stopping efavirenz to ensure contraceptive reliability. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Risk D: Consider therapy modification
Elagolix: Hormonal Contraceptives may diminish the therapeutic effect of Elagolix. Specifically, estrogen-containing hormonal contraceptives may diminish the therapeutic effects of elagolix. Elagolix may increase the serum concentration of Hormonal Contraceptives. Specifically, concentrations of ethinyl estradiol may be increased with elagolix therapy. Elagolix may decrease the serum concentration of Hormonal Contraceptives. Specifically, concentrations of progestins may be decreased with elagolix therapy. Management: Use an alternative, nonhormonal contraceptive during treatment with elagolix and for at least 28 days following discontinuation of elagolix treatment. Use of elagolix 200 mg twice daily with an estrogen-containing hormonal contraceptive is not recommended Risk D: Consider therapy modification
Elexacaftor, Tezacaftor, and Ivacaftor: Hormonal Contraceptives may enhance the adverse/toxic effect of Elexacaftor, Tezacaftor, and Ivacaftor. Specifically, the risk for rash may be increased. Risk C: Monitor therapy
Encorafenib: May decrease the serum concentration of Hormonal Contraceptives. Risk X: Avoid combination
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Etravirine: May decrease the serum concentration of Hormonal Contraceptives. Specifically, progestin concentrations may decrease. Etravirine may increase the serum concentration of Hormonal Contraceptives. Specifically, estrogen concentrations may increase. Risk C: Monitor therapy
Exenatide: Hormonal Contraceptives may diminish the therapeutic effect of Exenatide. Exenatide may decrease the serum concentration of Hormonal Contraceptives. Management: Administer oral hormonal contraceptives at least one hour prior to exenatide. Monitor blood glucose more frequently when patients treated with exenatide initiate therapy with a hormonal contraceptive. Increases in exenatide doses may be needed. Risk D: Consider therapy modification
Felbamate: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing felbamate to ensure contraceptive reliability. Risk D: Consider therapy modification
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Flibanserin: Hormonal Contraceptives may increase the serum concentration of Flibanserin. Risk C: Monitor therapy
Fosaprepitant: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration with fosaprepitant, and to continue back-up contraception for 28 days after discontinuing fosaprepitant to ensure contraceptive reliability. Risk D: Consider therapy modification
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Griseofulvin: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing griseofulvin to ensure contraceptive reliability. Risk D: Consider therapy modification
Interleukin-6 (IL-6) Inhibiting Therapies: May decrease the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy
Ivosidenib: May decrease the serum concentration of Hormonal Contraceptives. Management: Consider alternative methods of contraception (ie, non-hormonal) in patients receiving ivosidenib. Risk D: Consider therapy modification
Ixazomib: May decrease the serum concentration of Hormonal Contraceptives. More specifically, use of ixazomib with dexamethasone may decrease the serum concentrations of hormonal contraceptives. Management: Patients of reproductive potential should use a non-hormonal contraceptive method during treatment with ixazomib and for at least 90 days after the last ixazomib dose. Risk D: Consider therapy modification
LamoTRIgine: May decrease the serum concentration of Progestins (Contraceptive). Risk C: Monitor therapy
Lixisenatide: Hormonal Contraceptives may diminish the therapeutic effect of Lixisenatide. Lixisenatide may decrease the serum concentration of Hormonal Contraceptives. Management: Administer oral hormonal contraceptives 1 hour before or at least 11 hours after administration of lixisenatide. Additionally, monitor blood glucose more frequently when patients treated with lixisenatide initiate therapy with a hormonal contraceptive. Risk D: Consider therapy modification
MiFEPRIStone: May diminish the therapeutic effect of Hormonal Contraceptives. Management: Nonhormonal contraception should be used during, and for 4 weeks following, mifepristone treatment for hyperglycemia due to Cushing syndrome. If used for pregnancy termination, hormonal contraceptives can be used after pregnancy expulsion is confirmed. Risk D: Consider therapy modification
Mobocertinib: May decrease the serum concentration of Hormonal Contraceptives. Risk X: Avoid combination
Mycophenolate: May decrease the serum concentration of Hormonal Contraceptives. Management: Patients of childbearing potential who are taking hormonal contraceptives should use an additional form of barrier contraception during treatment with mycophenolate and for 6 weeks after mycophenolate discontinuation. Risk D: Consider therapy modification
Octreotide: May decrease the serum concentration of Hormonal Contraceptives. Management: Women should use an alternative non-hormonal method of contraception or a back-up method when octreotide is combined with hormonal contraceptives. Risk D: Consider therapy modification
OXcarbazepine: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing oxcarbazepine to ensure contraceptive reliability. Risk D: Consider therapy modification
Perampanel: May decrease the serum concentration of Hormonal Contraceptives. Management: Patients should use an alternative, nonhormonal-based form of contraception during the concurrent use of perampanel and for 1 month after discontinuing perampanel. Risk D: Consider therapy modification
Pexidartinib: May decrease the serum concentration of Hormonal Contraceptives. Risk X: Avoid combination
Pitolisant: May decrease the serum concentration of Hormonal Contraceptives. Management: Patients using hormonal contraception should be advised to use an alternative non-hormonal contraceptive method during treatment with pitolisant and for at least 21 days after discontinuation of pitolisant treatment. Risk D: Consider therapy modification
Protease Inhibitors: May decrease the serum concentration of Hormonal Contraceptives. Specifically, protease inhibitors may decrease concentrations of estrogens. Protease Inhibitors may increase the serum concentration of Hormonal Contraceptives. Specifically, protease inhibitors may increase concentrations of progestins. Management: Use alternative or additional nonhormonal forms of contraception when estrogen-containing hormonal contraceptives are combined with protease inhibitors. Progestin-only contraceptives can be used without back up, but monitor for progestin toxicities. Risk D: Consider therapy modification
Sugammadex: May diminish the therapeutic effect of Hormonal Contraceptives. 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. Risk D: Consider therapy modification
Tazemetostat: May decrease the serum concentration of Hormonal Contraceptives. Management: Individuals of childbearing potential should use a non-hormonal contraceptive method during treatment with tazemetostat and for 6 months after. Males with partners of childbearing potential should use contraception during treatment and for 3 months after. Risk D: Consider therapy modification
Tetrahydrocannabinol and Cannabidiol: May decrease the serum concentration of Hormonal Contraceptives. Management: Patients taking hormonal contraceptives should use an additional, non-hormonal contraceptive or reliable barrier method during treatment with tetrahydrocannabinol and cannabidiol buccal spray. Risk D: Consider therapy modification
Thalidomide: Hormonal Contraceptives may enhance the thrombogenic effect of Thalidomide. Risk C: Monitor therapy
Topiramate: May decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing topiramate to ensure contraceptive reliability. Risk D: Consider therapy modification
Tranexamic Acid: Hormonal Contraceptives may enhance the thrombogenic effect of Tranexamic Acid. Risk X: Avoid combination
Ulipristal: May diminish the therapeutic effect of Progestins. Progestins may diminish the therapeutic effect of Ulipristal. Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Hormonal Contraceptives may increase the serum concentration of Vitamin K Antagonists. Hormonal Contraceptives may decrease the serum concentration of Vitamin K Antagonists. Risk C: Monitor therapy
Voriconazole: Hormonal Contraceptives may increase the serum concentration of Voriconazole. Voriconazole may increase the serum concentration of Hormonal Contraceptives. Risk C: Monitor therapy
Pregnancy status should be evaluated prior to use. Nonhormonal contraception should be used if contraception is needed; use of hormonal contraceptives is not recommended during dienogest therapy. Ovulation is often inhibited during therapy; however, this product is not intended for use as a contraceptive. Normal menstruation usually returns within 2 months of therapy discontinuation.
Use is contraindicated during pregnancy. Based on limited data, inadvertent exposure in pregnancy has not shown adverse effects to the fetus.
It is not known if dienogest is present in breast milk.
Use is contraindicated in breastfeeding women. The risk of thromboembolism may be increased immediately postpartum.
Pregnancy test prior to initiating therapy; routine physical examination that includes blood pressure and Papanicolaou smear, breast exam, mammogram; adequate diagnostic measures, including endometrial sampling, if indicated, should be performed to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding; bone mineral density (prior to therapy in patients at risk for osteoporosis and as clinically indicated in adolescent females); signs and symptoms of thromboembolic disorders, vision changes
Dienogest is a steroid with antiandrogen properties that lacks androgen, mineralocorticoid or glucocorticoid activity. Exhibits strong progestogenic effects although it binds uterine progesterone receptors with an affinity much lower (about one-tenth) than that of progesterone. Decreases estradiol production and thus suppresses estradiol's trophic effects on eutopic and ectopic endometrium. Inhibits cellular proliferation via direct antiproliferative, immunologic, and antiangiogenic effects.
Absorption: Rapid and almost complete
Distribution: Vd: 40 L
Protein binding: ~90% nonspecifically to albumin
Metabolism: Hepatic via CYP3A4 to inactive metabolites
Bioavailability: ~91%
Half-life elimination: ~9 to 10 hours
Time to peak: ~1.5 hours
Excretion: Urine (primarily as inactive metabolites)
