Dienogest

Pharmacologic Category

Antiandrogen

Dosing: Adult

Endometriosis: Females: Oral: 2 mg once daily; has been studied for up to 16 months (Petraglia 2012)

Dosing: Renal Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

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.

Dosing: Pediatric

Endometriosis: Children ≥12 years and Adolescents: Females (postmenarche): Oral: 2 mg once daily; has been studied for up to 12 months of therapy

Dosing: Renal Impairment: Pediatric

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Pediatric

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.

Use: Labeled Indications

Note: Not approved in the US

Endometriosis: Management of pelvic pain associated with endometriosis

Administration: 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.

Administration: Pediatric

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.

Storage/Stability

Store in original packaging at 15°C to 30°C (59°F to 86°F).

Medication Safety Issues

​Sound-alike/look-alike issues:

​Other safety concerns:

Contraindications

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

Warnings/Precautions

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.

Reproductive Considerations

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.

Pregnancy Considerations

Use is contraindicated during pregnancy. Based on limited data, inadvertent exposure in pregnancy has not shown adverse effects to the fetus.

Breast-Feeding Considerations

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.

Adverse Reactions

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

Metabolism/Transport Effects

Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

Acitretin: May diminish the therapeutic effect of Progestins (Contraceptive). 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. Risk D: 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. Risk D: Consider therapy modification

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Aprepitant: May decrease the serum concentration of Progestins (Contraceptive). 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. Risk D: Consider therapy modification

Artemether: May decrease the serum concentration of Progestins (Contraceptive). Management: Consider the use of an alternative (i.e., non-hormonal) means of contraception in all women of childbearing potential who are using artemether. Risk D: Consider therapy modification

Atazanavir: May increase the serum concentration of Progestins (Contraceptive). 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. Risk D: Consider therapy modification

Barbiturates: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Risk D: Consider therapy modification

Bexarotene (Systemic): May decrease the serum concentration of Progestins (Contraceptive). Management: Women of childbearing potential receiving bexarotene should use two reliable forms of contraception (including at least one nonhormonal form). Risk D: Consider therapy modification

Bile Acid Sequestrants: May decrease the serum concentration of Progestins (Contraceptive). Management: Administer oral progestin-containing contraceptives at least 1 to 4 hours prior to or 4 to 6 hours after administration of a bile acid sequestrant. Risk D: Consider therapy modification

Bosentan: May decrease the serum concentration of Progestins (Contraceptive). 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. Risk D: Consider therapy modification

Brigatinib: May decrease the serum concentration of Progestins (Contraceptive). Management: Females of childbearing potential should use an alternative, non-hormonal contraceptive during brigatinib therapy and for at least 4 months after the final brigatinib dose. Risk D: Consider therapy modification

C1 inhibitors: Progestins may enhance the thrombogenic effect of C1 inhibitors. Risk C: Monitor therapy

Carfilzomib: May enhance the thrombogenic effect of Progestins (Contraceptive). Management: Consider alternative, non-hormonal methods of contraception in patients requiring therapy with carfilzomib. Risk D: Consider therapy modification

Cenobamate: May decrease the serum concentration of Hormonal Contraceptives. Management: Women should use additional or alternative non-hormonal birth control while taking cenobamate. Risk D: Consider therapy modification

Cladribine: May diminish the therapeutic effect of Hormonal Contraceptives. Management: Women using systemically acting hormonal contraceptives should 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

CloBAZam: May decrease the serum concentration of Progestins (Contraceptive). Management: Use additional non-hormonal forms of contraception in patients treated with clobazam due to the potential for reduced contraceptive efficacy. Risk D: Consider therapy modification

Cobicistat: May increase the serum concentration of Progestins (Contraceptive). Management: Consider an alternative, nonhormone-based contraceptive in patients receiving cobicistat-containing products. Drospirenone is specifically contraindicated with atazanavir and cobicistat. Risk D: Consider therapy modification

Corticosteroids (Systemic): Progestins may increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Dienogest. Risk X: Avoid combination

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Dienogest. Risk C: Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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). Risk D: Consider therapy modification

Dabrafenib: May decrease the serum concentration of Progestins (Contraceptive). 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. Risk D: Consider therapy modification

Darunavir: May decrease the serum concentration of Progestins (Contraceptive). Management: Consider using an alternative or additional means of contraception. Injected depot medroxyprogesterone acetate may be used without a need for additional contraception. Risk D: Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Efavirenz: May decrease the serum concentration of Progestins (Contraceptive). 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. 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 Progestins (Contraceptive). Risk X: Avoid combination

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Eslicarbazepine: May decrease the serum concentration of Progestins (Contraceptive). Management: Alternative, non-hormonal means of birth control should be considered for women of child-bearing potential. Risk D: Consider therapy modification

Felbamate: May decrease the serum concentration of Progestins (Contraceptive). Management: Contraceptive failure is possible. Use of an alternative, nonhormonal method of contraception is recommended. Risk D: Consider therapy modification

Flibanserin: Progestins (Contraceptive) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy

Fosamprenavir: Progestins (Contraceptive) may decrease serum concentrations of the active metabolite(s) of Fosamprenavir. Fosamprenavir may decrease the serum concentration of Progestins (Contraceptive). Management: Consider using an alternative or additional means of contraception. Injected depot medroxyprogesterone acetate may be used without a need for additional contraception. Risk D: Consider therapy modification

Fosaprepitant: May decrease the serum concentration of Progestins (Contraceptive). 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. Risk D: Consider therapy modification

Griseofulvin: May diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Risk X: Avoid combination

Herbs (Progestogenic Properties) (eg, Bloodroot, Yucca): May enhance the adverse/toxic effect of Progestins. Risk C: Monitor therapy

Ivosidenib: May decrease the serum concentration of Progestins (Contraceptive). 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 Progestins (Contraceptive). More specifically, use of ixazomib with dexamethasone may decrease the serum concentrations of contraceptive progestins. Management: Patients of childbearing potential should use a nonhormonal barrier contraceptive during and 90 days following ixazomib treatment. Risk X: Avoid combination

LamoTRIgine: May decrease the serum concentration of Progestins (Contraceptive). Risk C: Monitor therapy

Lesinurad: May decrease the serum concentration of Progestins (Contraceptive). Management: Use of an additional, nonhormonal contraceptive is recommended in patients being treated with lesinurad who desire effective contraception. Risk D: Consider therapy modification

Lixisenatide: May decrease the serum concentration of Progestins (Contraceptive). Management: Administer oral contraceptives 1 hour before or at least 11 hours after administration of lixisenatide. Risk D: Consider therapy modification

Lopinavir: May decrease the serum concentration of Progestins (Contraceptive). Lopinavir may increase the serum concentration of Progestins (Contraceptive). 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. Risk D: Consider therapy modification

Metreleptin: May decrease the serum concentration of Progestins (Contraceptive). Metreleptin may increase the serum concentration of Progestins (Contraceptive). Risk C: Monitor therapy

MiFEPRIStone: May diminish the therapeutic effect of Progestins (Contraceptive). MiFEPRIStone may increase the serum concentration of Progestins (Contraceptive). Management: Women of childbearing potential should use an effective, nonhormonal means of contraception during and 4 weeks following mifepristone treatment. Risk D: Consider therapy modification

Mycophenolate: May decrease the serum concentration of Progestins (Contraceptive). Management: Use of an additional or alternative (nonhormonal) method of contraception should be considered. Risk D: Consider therapy modification

Nelfinavir: May decrease the serum concentration of Progestins (Contraceptive). 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. Risk D: Consider therapy modification

Nintedanib: May diminish the therapeutic effect of Hormonal Contraceptives. Management: Women of reproductive potential taking nintedanib and hormonal contraceptives concomitantly should add a barrier method of contraception during nintedanib treatment for at least 3 months after the last dose. 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 Progestins (Contraceptive). Management: Contraceptive failure is possible. Use of an additional or alternative, nonhormonal method of contraception is recommended. Risk D: Consider therapy modification

Perampanel: May decrease the serum concentration of Progestins (Contraceptive). Management: Patients should use an alternative, nonhormonal-based form of contraception both during the concurrent use of perampanel and for 1 month after discontinuing perampanel. Oral and non-oral contraceptives likely participate in this interaction. Risk D: Consider therapy modification

Pexidartinib: May decrease the serum concentration of Hormonal Contraceptives. Management: Use an effective non-hormonal form of contraception. 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

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. Risk D: Consider therapy modification

Retinoic Acid Derivatives: May diminish the therapeutic effect of Progestins (Contraceptive). Retinoic Acid Derivatives may decrease the serum concentration of Progestins (Contraceptive). Management: Two forms of effective contraception should be used in patients receiving retinoic acid derivatives. Microdosed progesterone-only preparations (ie, minipills that do not contain estrogen) are considered an inadequate method of contraception. Exceptions: Adapalene; Alitretinoin (Topical); Bexarotene (Topical); Tretinoin (Topical). Risk D: Consider therapy modification

Rufinamide: May decrease the serum concentration of Hormonal Contraceptives. Management: Use of rufinamide may reduce the effectiveness of hormonal contraceptives. Advise patients who are using a hormonal contraceptive with rufinamide to use an additional non-hormonal form of contraception during concomitant therapy. Risk D: Consider therapy modification

Saquinavir: May decrease the serum concentration of Progestins (Contraceptive). 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. Risk D: Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Selegiline: Progestins (Contraceptive) may increase the serum concentration of Selegiline. Risk C: Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

St John's Wort: May decrease the serum concentration of Dienogest. Risk X: Avoid combination

Sugammadex: May decrease the serum concentration of Progestins (Contraceptive). 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: Women of reproductive potential should use a non-hormonal contraceptive method during treatment with tazemetostat and for 6 months after. Men with female partners 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: Women using hormonal contraceptives should consider adding a barrier contraceptive due to the potential for tetrahydrocannabinol and cannabidiol to decrease concentrations and effectiveness of hormonal contraceptives. Risk D: Consider therapy modification

Thalidomide: Progestins (Contraceptive) may enhance the thrombogenic effect of Thalidomide. Risk C: Monitor therapy

Tipranavir: May increase the serum concentration of Progestins (Contraceptive). 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. Risk D: Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Topiramate: May decrease the serum concentration of Progestins (Contraceptive). Management: Caution patients that this combination may be associated with reduced contraceptive effectiveness. Consider adding an additional (non-hormonal) contraceptive method. Risk D: Consider therapy modification

Tranexamic Acid: Progestins (Contraceptive) may enhance the thrombogenic effect of Tranexamic Acid. Risk X: Avoid combination

Triazolam: Hormonal Contraceptives may increase the serum concentration of Triazolam. Risk C: Monitor therapy

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. Risk X: Avoid combination

Vitamin K Antagonists (eg, warfarin): Progestins (Contraceptive) 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. Risk D: Consider therapy modification

Voriconazole: May increase the serum concentration of Progestins (Contraceptive). Progestins (Contraceptive) may increase the serum concentration of Voriconazole. Risk C: Monitor therapy

Test Interactions

May interfere with endocrine function tests; may affect test results for glucose tolerance, serum folate, and lipoprotein levels (results may be unreliable for 2-4 weeks after therapy discontinuation)

Genes of Interest

• Cytochrome P450 3A4

Monitoring Parameters

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

Product Availability

Not available in the US

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Visanne: 2 mg

Generic: 2 mg

Anatomic Therapeutic Chemical (ATC) Classification

• G03DB08

Generic Available (US)

Yes

Mechanism of Action

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.

Pharmacodynamics/Kinetics

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)

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

References

Curtis KM, Tepper NK, Jatlaoui TC, et al. US medical eligibility criteria for contraceptive use, 2016. MMWR Recomm Rep. 2016;65(3):1‐103. doi: 10.15585/mmwr.rr6503a1.[PubMed 27467196]

Dunselman GA, Vermeulen N, Becker C, et al; European Society of Human Reproduction and Embryology. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014;29(3):400-412. doi:10.1093/humrep/det457.[PubMed 24435778]

Leyland N, Casper R, Laberge P, Singh SS; SOGC. Endometriosis: diagnosis and management. J Obstet Gynaecol Can. 2010;32(7)(suppl 2):S1-S32.[PubMed 21545757]

Petraglia F, Hornung D, Seitz C, et al. Reduced pelvic pain in women with endometriosis: efficacy of long-term dienogest treatment. Arch Gynecol Obstet. 2012;285(1):167-173. doi: 10.1007/s00404-011-1941-7.[PubMed 21681516]

Strowitzki T, Faustmann T, Gerlinger C, et al, “Dienogest in the Treatment of Endometriosis-Associated Pelvic Pain: A 12-week, Randomized, Double-Blind, Placebo-Controlled Study," Eur J Obstet Gynecol Reprod Biol. 2010;151(2):193-8.[PubMed 20444534]

Strowitzki T, Marr J, Gerlinger C, et al, “Dienogest is as Effective as Leuprolide Acetate in Treating the Painful Symptoms of Endometriosis: A 24-Week, Randomized, Multicentre, Open-Label Trial," Eur J Obstet Gynecol Reprod Biol, 2010, 151(2):193-8.[PubMed 20444534]

Visanne (dienogest) [product monograph]. Mississauga, Ontario, Canada: Bayer Inc; February 2016.

Brand Names: International

Dinagest (JP); Valette (AT); Visabelle (GB); VisaBelle (IL); Visanette (CY); Visanne (AE, AR, AT, AU, BH, CH, CO, CZ, DE, DK, EC, EG, FI, FR, HK, HR, ID, IS, JO, KR, KW, LB, MT, MY, NL, NO, PH, PL, PT, QA, RO, SA, SE, SG, SI, SK, TH, ZW); Visannette (BE, CR, DO, EE, ES, GT, HN, LT, LU, LV, MX, NI, PA, SV, TR)

Last Updated 10/14/20