Version May 2024
Endometriosis: Oral: 2 mg once daily. Dosing may begin on any day of the menstrual cycle.
No dosage adjustment necessary.
Mild to moderate impairment: No dosage adjustment provided in manufacturer's labeling (has not been studied); 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.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults and adolescents.
>10%: Endocrine & metabolic: Change in menstrual flow (including amenorrhea, frequent bleeding, infrequent bleeding, irregular bleeding, prolonged bleeding)
1% to 10%:
Dermatologic: Acne vulgaris (2%), alopecia (1%)
Endocrine & metabolic: Loss of libido (2%), spotting (≤1%), weight gain (4%)
Gastrointestinal: Abdominal pain (2%), nausea (4%)
Genitourinary: Breast engorgement (≤5%), mastalgia (≤5%), ovarian cyst (3%), uterine hemorrhage (≤1%), vaginal hemorrhage (≤1%)
Nervous system: Asthenia (2%), depressed mood (3%), headache (7%), irritability (1%), migraine (1%), nervousness (1%), sleep disorder (2%)
<1%:
Cardiovascular: Edema, palpitations
Dermatologic: Dermatitis, onychoclasis, pruritus, skin photosensitivity, skin pigmentation, xeroderma
Endocrine & metabolic: Hot flash
Gastrointestinal: Abdominal distress, constipation, diarrhea, flatulence, gastrointestinal inflammation, increased appetite, vomiting
Genitourinary: Breast induration, fibrocystic breast disease, genital discharge, lump in breast, pelvic pain, urinary tract infection, vaginal dryness, vulvar dryness, vulvovaginal candidiasis
Hematologic & oncologic: Anemia
Nervous system: Anxiety, depression, disturbance in attention, dysautonomia, emotional lability, feeling of heaviness (extremities), mood changes
Neuromuscular & skeletal: Back pain, limb pain, muscle spasm, ostealgia
Ophthalmic: Dry eye syndrome
Otic: Tinnitus
Frequency not defined:
Genitourinary: Anovulation
Neuromuscular & skeletal: Decreased bone mineral density (adolescents: loss or plateauing)
Postmarketing: Nervous system: Insomnia (Lee 2021), major depressive disorder (including suicidal ideation) (Lee 2021)
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, myocardial infarction, 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; breastfeeding; 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 patients (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: 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 of age 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 adolescents as clinically appropriate. In a small study of adult patients, a reduction in mean BMD was not observed 6 months after initiating therapy though long-term data are not available. Risk assessment should also be performed in patients of any age at increased risk of osteoporosis.
• Chloasma: May occur occasionally; patients 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.
• Thromboembolic disorders: Use with caution in patients with risk factors for venous thromboembolism (VTE), including personal or family history of VTE, obesity, prolonged immobilization, major surgery, or major trauma. Discontinue use if an arterial or venous thrombotic event occurs.
Disease-related concerns:
• Breast cancer: In patients at risk for breast cancer due to family history or susceptibility genes (BRCA1, BRCA2), it is unclear if combination hormonal contraceptives increase the risk for breast cancer and there are insufficient data specific to progestin-only contraceptives. However, breast cancer is a hormonal-sensitive tumor and the prognosis for patients with a current or recent history of breast cancer may be worse with hormonal contraceptive use (CDC [Curtis 2016]; SGO/ASRM [Chen 2019]). Although this formulation of dienogest is not used as a contraceptive, warnings associated with progestin-only therapies are applicable.
• Cardiovascular disease: Use with caution in patients with risk factors for cardiovascular disease (eg, hypertension, older age, smoking). The risk of stroke may be increased in patients with hypertension. 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.
• Diabetes: May impair glucose tolerance; use caution in patients with diabetes or a history of gestational diabetes mellitus.
Special populations:
• Smoking: The risk of cardiovascular side effects and the risk of BMD decline is increased in patients who smoke cigarettes. Patients should be advised not to smoke.
• Surgical patients: Whenever possible, use should be discontinued at least 4 weeks prior to and through 2 weeks following major surgery or other surgeries known to have an increased risk of thromboembolism or during periods of prolonged immobilization.
Other warnings/precautions:
• Appropriate use: Not intended for use as a contraceptive. However, warnings associated with progestin-only therapies are applicable
Not available in the US
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Visanne: 2 mg
Generic: 2 mg
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
Limitations of use: Not for use prior to menarche or post menopause.
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.
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Chlorprothixene: Progestins may enhance the adverse/toxic effect of Chlorprothixene. Progestins may enhance the therapeutic effect of Chlorprothixene. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Dienogest. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Dienogest. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Dienogest. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Dienogest. Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
MetyraPONE: Progestins may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking progestins. Risk D: Consider therapy modification
Ulipristal: May diminish the therapeutic effect of Progestins. Progestins may diminish the therapeutic effect of Ulipristal. Risk X: Avoid combination
Pregnancy status should be evaluated prior to use. Nonhormonal contraception (eg, barrier method) 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 patients. The risk of thromboembolism may be increased immediately postpartum.
Ensure adequate calcium and vitamin D intake.
Evaluate pregnancy status prior to initiating therapy; 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 adolescents); BP; depression; endometrial-related pain.
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)
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