1. 1 Medication Abortion Dr. Sasan Zaeri (PharmD, PhD) Department of Pharmacology

2. 2 What is medication abortion? Medication abortion, also known as non-aspiration or non-surgical abortion, refers to a family of safe and effective methods for terminating an early unwanted pregnancy. Through the use of a drug or combination of drugs that are administered orally, vaginally, and/or intramuscularly, medication abortion first causes the pregnancy to terminate and then causes the uterus to expel the products of conception

3. 3 Why “medication abortion”? Non-aspiration or non-surgical abortion is commonly referred to as “medical abortion”. However, this phrase has led to confusion among both providers and the public, as the term “medical” is often associated with physician-based practices and/or medical necessity. “Medication abortion” more accurately represents the family of safe and effective drug-based methods that can terminate an unwanted pregnancy and will be used throughout this presentation.

4. 4 Methods of medication abortion  Mifepristone and misoprostol  Methotrexate (MTX) and misoprostol  Misoprostol alone Medication abortion methods can be used throughout early pregnancy (≤63 days’ gestation)

5. 5 Medication abortion Mechanisms of action of the medications  Mifepristone Anti-progestin that blocks the action of progesterone Alters the uteral lining  Methotrexate Anti-metabolite Interferes with DNA synthesis and cell growth  Misoprostol Prostaglandin E 1 analog Stimulates uterine contractions and induces cervical softening

6. 6 Medication abortion Additional uses of the medications  Mifepristone Labor induction (under investigation) Infertility treatment (under investigation)  Methotrexate Treatment of neoplastic diseases Treatment of rheumatoid arthritis  Misoprostol Prevention of NSAID-induced gastric ulcers

7. 7 Medication abortion Dosage forms of the medications  Mifepristone Tablet 200 mg (Mifeprex) and 300 mg (Korlym)  Methotrexate Tablet 2.5, 5, 7.5, 10, 15 mg Injection solution 5 mg/mL Powder for injection 1 g/vial  Misoprostol Tablet 100 and 200 µg (Cytotec)

8. 8 Mifepristone/misoprostol regimen

9. 9 Mifepristone/misoprostol regimen General protocol  Day 1 (Clinic) Mifepristone (100-600 mg) is orally administered  Day 1-4 (Home or clinic) Misoprostol is administered 200-600 µg (oral) or 400-800 µg (vaginal, buccal or sublingual)  Day 7-14 (Clinic) Patient returns to the clinic for follow-up Clinician assesses for the completion of the abortion

10. 10 Mifepristone/misoprostol regimen Efficacy and safety  Approximately 95% of women will have a successful abortion when using mifepristone/misoprostol within 49 days’ gestation  Completion rates appear to decline slightly with increasing durations of pregnancy after 56 days’ gestation

11. 11 Mifepristone/misoprostol regimen Efficacy and safety  Approximately 67% of women will have a complete abortion within four hours of using misoprostol.  Approximately 90% of women will have a complete abortion within 24 hours of using misoprostol.

12. 12 Mifepristone/misoprostol regimen Eligibility for use  Non-ectopic pregnancy of ≤63 days’ gestation  Absence of contraindications  Willingness to undergo vacuum aspiration or dilation and curettage (D&C), if indicated

13. 13 Mifepristone/misoprostol regimen Contraindications to use  Confirmed or suspected ectopic (extra-uterine) pregnancy  Allergy to either mifepristone or misoprostol  Presence of an intrauterine device (IUD)  Chronic systemic use of corticosteroids  Chronic adrenal failure  Coagulopathy or current therapy with anticoagulants

14. 14 Mifepristone/misoprostol regimen Side effects Effects of abortion process  Cramping Often described as similar to menstrual cramps  Vaginal bleeding Median bleeding time 9-13 days Often described as similar to a heavy period or spontaneous miscarriage Common side effects  Nausea  Vomiting  Diarrhea  Headache  Dizziness  Fever, chills, hot flashes, warmth

15. 15 Mifepristone/misoprostol regimen Complications Type of complicationPercentage of women Continued pregnancy1%-5% Incomplete abortion requiring aspiration 1% Hemorrhage requiring aspiration 1%-2% Hemorrhage requiring transfusion 0.1%

16. 16 Mifepristone/misoprostol regimen Summary  Millions of women worldwide have safely used mifepristone/misoprostol  Mifepristone/misoprostol is more than 95% effective in terminating early pregnancies  Mifepristone/misoprostol is widely acceptable to both patients and providers

17. 17 Methotrexate/misoprostol regimen

18. 18 Methotrexate/misoprostol regimen Evidence-based protocol  Day 1 (Clinic) Methotrexate is administered either orally (50 mg) or intramuscularly (50 mg/m2)  Day 3-7 (Home) Misoprostol is self-administered vaginally (800 µg) at home.  Day 8 (Clinic) Clinician performs a vaginal ultrasound to determine if the abortion is complete. If abortion is complete (75% of women) no further visits are required. If the abortion is incomplete additional misoprostol is given and patient returns  On Day 15 if cardiac activity is detected  On Day 28-45 if no cardiac activity is detected on ultrasound

19. 19 Methotrexate/misoprostol regimen Evidence-based protocol continued  Day 15 (Clinic, if necessary) Patient is assessed for continued pregnancy. If cardiac activity is detected, a aspiration termination is performed. If no cardiac activity is detected, patient returns in three weeks.  Day 28-45 (Clinic, if necessary) The patient is assessed for continued pregnancy. If the abortion is incomplete (5% of cases), a aspiration termination is performed.

20. 20 Methotrexate/misoprostol regimen Efficacy and safety  Approximately 95% of women will have a complete abortion when using methotrexate/misoprostol up to 49 days’ gestation.  Medication abortion completion rates decline with increasing gestational age

21. 21 Methotrexate/misoprostol regimen Eligibility for use  Pregnancy of ≤49 days’ gestation Methotrexate/misoprostol is preferable for women with ectopic pregnancies  Absence of contraindications  Willingness to undergo vacuum aspiration or dilation and curettage (D&C), if indicated

22. 22 Methotrexate/misoprostol regimen Contraindications to use  Allergy to either methotrexate or misoprostol  Presence of an intrauterine device (IUD)  Coagulopathy or current severe anemia  Acute or chronic renal or hepatic disease  Acute inflammatory bowel disease  Uncontrolled seizure disorders.

23. 23 Methotrexate/misoprostol regimen Side Effects Effects of abortion process  Cramping Often described as similar to menstrual cramps  Vaginal bleeding Median bleeding time 2-3 weeks Often described as similar to a heavy period or spontaneous miscarriage Common side effects  Nausea  Vomiting  Diarrhea  Headache  Dizziness  Fever, chills, hot flashes, warmth  Oral ulcers  Fetal malformations

24. 24 Methotrexate/misoprostol regimen Complications (≤49 days’ gestation) Type of complicationPercentage of women Continued pregnancy3-5% Incomplete abortion requiring aspiration 3-5% Hemorrhage requiring aspiration 1%-2% Hemorrhage requiring transfusion 0.1%-0.5%

25. 25 Methotrexate/misoprostol regimen Summary  Methotrexate/misoprostol is approximately 95% effective in terminating pregnancies ≤49 days’ gestation  Methotrexate/misoprostol is the preferred medication abortion method for confirmed or suspected ectopic pregnancies

26. 26 Misoprostol-only regimen

27. 27 Misoprostol-only regimen Evidence-based protocols  No consensus exists on optimal protocol  Various regimens, dosing schedules and routes of administration are currently under investigation  Most commonly used protocol Vaginal administration of 800 µg of misoprostol If abortion fails, misoprostol dose is repeated every 24 hours, up to three doses

28. 28 Misoprostol-only regimen Efficacy and Safety  Efficacy varies widely (65%-93%)  Efficacy varies by route of administration, dose, dosing schedule, and gestational age  Misoprostol-only regimens are not as effective as either mifepristone/misoprostol or methotrexate/misoprostol regimens

29. 29 Misoprostol-only regimen Eligibility for use  Non-ectopic pregnancy of ≤63 days’ gestation  Absence of contraindications  Willingness to undergo vacuum aspiration or dilation and curettage (D&C), if indicated  Lack of access to either mifepristone or methotrexate

30. 30 Misoprostol-only regimen Contraindications for use  Confirmed or suspected ectopic pregnancy  Allergy to misoprostol  Presence of an intrauterine device (IUD)  Uncontrolled seizure disorder  Inflammatory bowel disease

31. 31 Misoprostol-only regimen Side effects Effects of abortion process  Cramping Often described as similar to menstrual cramps Often described as more severe than the cramping of either mifepristone/misoprostol or methotrexate/misoprostol regimens  Vaginal bleeding Median bleeding time 2 weeks Often described as similar to a heavy period or spontaneous miscarriage Common side effects  Nausea  Vomiting  Diarrhea  Headache  Dizziness  Fever and chills  Rashes  Pelvic pain

32. 32 Misoprostol-only regimen Complications  Approximately 10%-35% of women will require an aspiration intervention  Misoprostol-only regimen is less effective in terminating early pregnancy than when used in combination with either mifepristone or methotrexate

33. 33 Misoprostol-only regimen Summary  Misoprostol used in conjunction with either mifepristone or methotrexate is more effective at terminating early pregnancy than misoprostol alone  Efficacy varies widely  Optimal regimen has yet to be determined  Misoprostol-only regimen is an important alternative for women who do not have access to other medical or aspiration abortion methods

34. 34 Medication abortion Comparing the three regimens RegimenAdvantagesDisadvantages Mifepristone/ misoprostol High efficacy (≈95%) Can be used through 63 days’ gestation Abortion typically occurs within hours of misoprostol administration Mifepristone is often expensive Mifepristone is not available in many countries Can not be used to treat ectopic pregnancies Methotrexate/ misoprostol High efficacy (90%-95%) Can be used through 56 days’ gestation Often less expensive than mifepristone Treats ectopic pregnancies Abortion can occur over a four week period May cause fetal abnormalities in continued pregnancies Efficacy decreases after 49 days’ gestation Misoprostol-onlyCan be used through 63 days’ gestation Widely available worldwide Often very inexpensive Stable at room temperature Efficacy is variable (65%-90%) Regimen is currently under investigation May cause fetal anomalies in continued pregnancies Can not be used to treat ectopic pregnancies

35. 35 Medication Abortion in the 2 th trimester  Medication abortion vs. aspiration abortion: similar advantages and disadvantages as in early gestational age  Main medication regimen: High-dose IV oxytocin 50-300 unit oxytocin in 500 mL NS in 3h followed by 1 h diuresis without oxytocin Success rate: 80-90%

36. 36 Medication Abortion in the 2 th trimester- Other medications used  Dinoprostone (Prostin E2 ) (PG E 2 ) One vaginal suppository (20 mg) (high in vagina) More adverse effects than oxytocin  Nausea, vomiting, fever, diarrhea