Endometriosis Drug Summary

• Effects due to inhibition of pituitary-ovarian axis (menstrual disturbances, amenorrhea, sweating, hot flushes, libido changes, vaginal dryness and irritation, decreased breast size, nervousness); Androgenic effects (increased hair growth, acne, oily skin, mood changes, deepening of voice, weight gain, effects on serum lipids [ie decreased HDL and TG, increased LDL] and rarely liver damage); Other effects (GI disturbances, headache, dizziness, fatigue, muscle spasm, tachycardia, hypertension)

• Gestrinone: If a dose is missed, take dose as soon as possible and maintain dose sequence; if ≥2 doses are missed, discontinue and restart on the first day of a new menstrual cycle after a negative pregnancy test
• Contraindicated in patients with severe hepatic, renal or cardiac dysfunction, porphyria, thromboembolic disease, undiagnosed genital bleeding and androgen-dependent tumors
• Use with caution in conditions that may worsen fluid retention (eg CV, hepatic and renal disorders) and in patients with migraine, epilepsy, DM or polycythemia
• Liver function should be monitored regularly during therapy

• Hypoestrogenism effects (hot flushes, night sweats, insomnia, headache, arthralgia, bone loss, amenorrhea); CNS effects (anxiety, depression-related adverse reactions, mood changes); Other effects (nausea, hepatic transaminase elevations)

• Take at approximately the same time each day, with or without food, using the lowest effective dose
  • A missed dose can be taken on the same day then continue regular dosing schedule
• Use non-hormonal contraception during treatment and for 1 week after discontinuing Elagolix
• Contraindicated in pregnant patients and those with known osteoporosis, severe hepatic impairment and concomitant use of strong organic anion transporting polypeptide 1B1 inhibitors
• Use with caution in patients with bone loss
• Counsel patient on signs and symptoms of liver injury, advise to perform testing if pregnancy is suspected and to seek medical attention for suicidal ideation and mood disorders

Adverse Reactions

• CNS effects (headache, mood disorders, dizziness); GI effects (nausea, toothache, hepatic transaminase elevations); Other effects (abnormal uterine bleeding, back pain, arthralgia, fatigue, decreased sexual desire and arousal, vasomotor symptoms)

Special Instructions

• Take the missed dose as soon as possible on the same day and then resume regular dosing the next day at the usual time
• Use non-hormonal contraception during treatment and for 1 week after discontinuing treatment
• Contraindicated in women with current or history of thrombotic or thromboembolic disorders and in those at increased risk for these events, including women >35 years of age who smoke or women with uncontrolled hypertension
• Avoid in pregnant patients and those with known osteoporosis, current or history of breast cancer or other hormone-sensitive malignancies, hepatic impairment or disease, undiagnosed abnormal uterine bleeding
• Counsel patient on signs and symptoms of liver injury to seek medical attention for mood changes and not to breastfeed while on treatment
• Exclude pregnancy and discontinue hormonal contraceptives prior to treatment initiation
• Limit use to 24 months due to the risk of continued bone loss which may not be reversible; assess BMD annually

• Hypoestrogenism effects (transient vaginal bleeding, hot flushes, vaginal dryness, decreased libido, breast tenderness, insomnia, depression, irritability and fatigue, decreased elasticity of the skin, headache, after several weeks of treatment: Increased bone pain and osteoporosis); GI effects (nausea, abdominal discomfort); Other effects (reduction in glucose tolerance, changes in serum lipids, hepatic effects and hypersensitivity reactions, skin rashes, hair loss, increased sweating)

• Addback strategy with estrogen/progesterone or Tibolone can eliminate most of the side effects
• Oral contraceptives should be discontinued prior to therapy and other non-hormonal methods of birth control should be used
  • In later stages of treatment, pregnancy is unlikely as long as recommended doses are administered
• Avoid in patients with metabolic bone disease, urinary tract obstruction or metastatic vertebral lesions
• Monitor bone density during long-term treatment

• GI effects (GI disturbances, change in weight/appetite); Breast effects (enlargement, secretion, discomfort); Androgenic effects (acne, mental depression, changes in libido, hair loss, hirsutism, irregular menstrual bleeding); Dermatologic effects (allergic rash, pruritus, erythema multiforme, erythema nodosum, urticaria); Other effects (asthenia, malaise, headache, migraine, change in vaginal secretions, fluid retention, edema, fatigue, alterations in lipid profile)
  • Androgenic effects and lipid changes are more likely with Norethisterone

• Avoid use in patients with unexplained vaginal bleeding, history or current high risk of arterial disease, severe hepatic impairment, breast or genital tract carcinoma unless progestogen is part of the management
• Use with caution in women with hypertension, cardiac or renal impairment, asthma, epilepsy, migraine, history of depression, or other conditions aggravated by fluid retention
  • High doses should be used with caution in patients at risk for thromboembolism