Ethinyl Estradiol is an active pharmaceutical ingredient in the Natural and Semisynthetic Estrogens, Plain group (G03CA). The information below is compiled per regulator from the product labels on record, with direct links to the original documents.
GBOfficial regulatory label· revised April 11, 2025[1]
Oral Contraception. 4).
How to take
GBOfficial regulatory label· revised April 11, 2025
CACanada· Health Canada
12 products
Uses
CAOfficial regulatory label· revised March 22, 2025[2]
LOLO® (ethinyl estradiol / norethindrone acetate and ethinyl estradiol) is indicated for: • the prevention of pregnancy. In a one year (thirteen 28-day cycles) multicenter open-label clinical trial 1,582 women were studied to assess the safety and efficacy of LOLO.
In this study 1,270 women 18 to 35 years of age were studied to assess the efficacy of LOLO, completing the equivalent of 12,482 28-day evaluable cycles of exposure. 92 pregnancies per 100 women-years of use. See 14 CLINICAL TRIALS. The efficacy of LOLO in women with a body mass index > 35 kg/m2 has not been evaluated.
Exposure to exogenous estrogen with LOLO is less than with other combined oral contraceptives with similar synthetic estrogens. Any benefits from the lower estrogen exposure provided by LOLO have not been evaluated. 1 Pediatrics Pediatrics (< 18 years): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use.
USUnited States· FDA
1 product
Uses
USOfficial regulatory label· revised January 29, 2026[3]
INDICATIONS AND USAGE
5/30 is indicated for the prevention of pregnancy in women who elect to use oral contraceptives as a method of contraception. Oral contraceptives are highly effective. Table 1 lists the typical accidental pregnancy rates for users of combination oral contraceptives and other methods of contraception.
The efficacy of these contraceptive methods, except sterilization, depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates. 15 Adapted from RA Hatcher et al, Reference 7.
*The authors' best guess of the percentage of women expected to experience an accidental pregnancy among couples who initiate a method (not necessarily for the first time) and who use it consistently and correctly during the first year if they do not stop for any other reason.
**This term represents “typical” couples who initiate use of a method (not necessarily for the first time), who experience an accidental pregnancy during the first year if they do not stop use for any other reason. ***N/A-Data not available.
Drug interactions
Known interactions involving Ethinyl Estradiol. Select one for details. This list is informational and not a complete interaction checker.
Showing 240 of 375. Type above to find a specific drug.
Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
[1]MHRA (UK) · PL204160667 · revised April 11, 2025
[2]Health Canada (DPD) · 02417456 · revised March 22, 2025
[3]FDA DailyMed · 021df70a-0c37-42… · revised January 29, 2026 [PDF]
[4]OpenFDA adverse-event reports (US), 12 months ending June 4, 2026.
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
Route of administration: oral use Posology How to take Ambelina Tablets must be taken at approximately the same time each day, with some liquid if needed. One tablet is to be taken daily for 21 consecutive days. Each subsequent pack is started after a 7-day tablet free interval, during which time a withdrawal bleed usually occurs.
The bleeding usually starts within 2 to 3 days after the last tablet and may not end before the next pack is started. How to start Ambelina • No preceding hormonal contraceptive use [in the past month]: Tablet-taking is started on day 1 of the woman’s natural cycle (the first day of menstrual bleeding).
Starting on day 2-day 5 is allowed, but in that case an additional nonhormonal contraceptive method (barrier method) should be used during the first 7 days of treatment. • Changing from another combined hormonal contraceptive (combined oral contraceptive (COC), vaginal ring, transdermal patch): The use of Ambelina tablets is preferably started on the day after the last active tablet of the previous COC (or after removal of the ring or patch), but at the latest on the day following the usual tablet- free (ring-free, patch-free) break or the last placebo tablet of the previous hormonal contraceptive.
• Changing from a progestogen-only method (oral contraceptive with only progesterone, injection, implant) or progestogen-releasing intrauterine system (IUS) If the oral contraceptive with only progesterone was used previously, the change can take place on any day; the change from an implant or IUS must take place on the day of removal, and from an injectable contraceptive at the time when the next injection would be due.
In each case, the use of an additional nonhormonal contraceptive method (barrier method) is necessary during the first 7 days taking Ambelina. • Following first-trimester abortion Ambelina may be started immediately. In this case, no additional contraceptive method is required.
• Following childbirth or second-trimester abortion The use of the tablets is started 21 to 28 days after delivery or second-trimester abortion. When starting later, an additional non-hormonal contraceptive method (barrier method) should be used during the first 7 days of tablet-taking If intercourse has already taken place, pregnancy must be ruled out before starting the use of Ambelina, or the woman must wait until her first menstrual period.
6 Pregnancy and Lactation. Management of missed tablets If one tablet is missed, but remembered and taken within 12 hours of the usual time, then contraceptive protection is not reduced. The subsequent tablets should be taken at the usual time.
If the usual tablet-taking time is missed by more than 12 hours, full contraceptive protection is no longer assured. The following two basic rules apply when a tablet is missed: 1. Tablet-taking must never be discontinued for longer than 7 days.
2. Tablets must be taken regularly for a minimum of 7 days in order to effectively suppress the hypothalamic-pituitary-ovarian axis. Therefore, the following procedures should be followed in the event that tablets are missed: • Week 1 The last tablet missed should be taken as soon as possible, even if this means taking 2 tablets in one day.
The remaining tablets are then taken at the usual time. In addition, a nonhormonal contraceptive method such as a condom should be used for the next 7 days. If intercourse took place in the 7 days before missing the tablet, the possibility of a pregnancy must be considered.
The more tablets missed and the closer they are to the usual tablet-free interval, the higher the risk of pregnancy. • Week 2 The last tablet missed should be taken as soon as possible, even if this means taking 2 tablets at the same time.
The remaining tablets are then taken at the usual time. Provided that the user has taken the tablets correctly in the 7 days prior to the first missed tablet, it is not necessary to use additional contraceptive measures. However, if this is not the case or she has missed more than one tablet, the user should be advised to take additional contraceptive precautions for the next 7 days.
• Week 3 The risk of reduced reliability is imminent because of the forthcoming tablet-free interval. However, by adjusting the tablet-taking schedule, reduced contraceptive protection can still be prevented. Therefore, by adhering to one of the following two options, there is no need to take additional contraceptive precautions, provided that in the 7 days prior to the first missed tablet the user has taken all the tablets correctly.
If this is not the case, the user should be advised to follow the first of these two options and take additional precautions for the next 7 days: 1. The user should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time.
She then continues to take the tablets at the usual time. e. without a break between packs. The user is unlikely to have withdrawal bleeding until the end of the second pack but she may experience spotting or breakthrough bleeding on tablet-taking days.
2. It is also possible to stop taking tablets from the current pack. The woman must then have a tablet-free break of 7 days, including the days she missed tablets, and then continue with the next pack. If the user misses several tablets and subsequently has no withdrawal bleeding in the first normal tablet-free interval, the possibility of pregnancy should be considered.
Advice in case of gastrointestinal disorders In case of severe gastrointestinal disorders (vomiting or diarrhea), absorption of the active ingredients may not be complete and additional contraceptive measures should be taken. If vomiting or severe diarrhea occurs within 3 to 4 hours after taking a tablet, a new tablet should be taken as soon as possible.
The new tablet should be taken within 12 hours of the usual […]
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
GBOfficial regulatory label· Adverse reactions· revised April 11, 2025[1]
The following undesirable effects have been observed with use of combined oral contraceptives containing ethinylestradiol/levonorgestrel: Adverse events reported in clinical trialsOrgan system Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1,000 to <1/100) Rare (≥1/10,000 to < 1/1,000) Unknown Eye disorders Contact lens intolerance Gastrointestinal disorders Nausea abdominal pain Vomiting Diarrhea Immune system disorders Hypersensitivity Exacerbation of symptoms of hereditary and acquired angioedema.
4. 4: Tumors • The frequency of diagnosis of breast cancer is very slightly increased among OC users. As breast cancer is rare in women under 40 years of age the excess number is small in relation to the overall risk of breast cancer.
Causation with COC use is unknown. 4. • Liver tumors (benign and malignant) Other conditions • Increased risk of pancreatitis in women with hypertriglyceridemia • Hypertension • Occurrence or deterioration of conditions for which association with COC use is not conclusive: jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham’s chorea; herpes gestationis; otosclerosis- related hearing loss • Liver function disturbances • Changes in glucose tolerance or effect on peripheral insulin resistance • Crohn’s disease, ulcerative colitis.
5). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
GBOfficial regulatory label· Warnings and precautions· revised April 11, 2025[1]
Warnings If any of the conditions or risk factors mentioned below is present, the suitability of Ambelina should be discussed with the woman. In the event of aggravation, or first appearance of any of these conditions or risk factors, the woman should be advised to contact her doctor to determine whether the use of Ambelina should be discontinued.
Risk of venous thromboembolism (VTE) The use of any combined hormonal contraceptive (CHC) increases the risk of venous thromboembolism (VTE) compared with no use. Products that contain levonorgestrel, such as Ambelina, norgestimate or norethisterone are associated with the lowest risk of VTE.
The decision to use Ambelina should be taken after a discussion with the woman to ensure she understands the risk of VTE with Ambelina, how her current risk factors influence this risk, and that her VTE risk is highest in the first ever year of use.
There is also some evidence that the risk is increased when a CHC is re-started after a break in use of 4 weeks or more. In women who do not use a CHC and are not pregnant, about 2 out of 10,000 will develop a VTE over the period of one year.
However, in any individual woman the risk may be far higher, depending on her underlying risk factors (see below). It is estimated that out of 10,000 women who use a CHC that contains levonorgestrel, about 61 will develop a VTE in a year.
This number of VTEs per year is fewer than the number expected in women during pregnancy or in the postpartum period. VTE may be fatal in 1-2% of cases. g. hepatic, mesenteric, renal, cerebral or retinal veins and arteries. Risk factors for VTE The risk for venous thromboembolic complications in CHC users may increase substantially in a woman with additional risk factors, particularly if there are multiple risk factors (see table).
3). If a woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the individual factors – in this case her total risk of VTE should be considered. 3).
Table:
Risk factors for VTE Risk factor Comment Obesity (body mass index over 30 kg/m2) Risk increases substantially as BMI rises. Particularly important to consider if other risk factors also present. Prolonged immobilisation, major surgery, any surgery to the legs or pelvis, neurosurgery, or major trauma Note: temporary immobilisation including air travel >4 hours can also be a risk factor for VTE, particularly in women with other risk factors.
In these situations, it is advisable to discontinue use of the pill (in the case of elective surgery at least four weeks in advance) and not resume until two weeks after complete remobilisation. Another method of contraception should be used to avoid unintentional pregnancy.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
GBOfficial regulatory label· Contraindications· revised April 11, 2025[1]
Combined hormonal contraceptives (CHCs) should not be used in the following conditions. If any of the conditions appear for the first time during CHC use, the product should be stopped immediately. g. g. g. g. g. 1. 5).
This is not medical advice. Consult a qualified healthcare professional.
2 Geriatrics Geriatrics: No data are available to Health Canada; therefore, Health Canada has not authorized an indication for geriatric use.
How to take
CAOfficial regulatory label· revised March 22, 2025[2]
1 Dosing Considerations To achieve maximum contraceptive effectiveness, LOLO should be taken exactly as directed and at intervals not exceeding 24 hours. • LOLO tablets may be administered without regard to meals. • LOLO provides a regimen consisting of 24 blue estrogen-progestin tablets, 2 white estrogen-only tablets, and 2 lilac placebo tablets.
2 Recommended Dose and Dosage Adjustment During the first cycle of use: • The possibility of ovulation and conception prior to initiation of medication should be considered. The patient is instructed to begin taking LOLO on either Day 1 of menstruation (Day 1 Start) or the first Sunday after the onset of menstruation (Sunday Start).
If menstruation begins on a Sunday, the first tablet (blue) is taken that day. One blue tablet should be taken daily for 24 consecutive days followed by one white tablet for 2 consecutive days, followed by one lilac tablet daily for 2 consecutive days.
During the first cycle with a Sunday Start, contraceptive reliance should not be placed on LOLO until a blue tablet has been taken daily for 7 consecutive days and a non-hormonal back-up method of birth control (such as latex or polyurethane condoms or spermicide) should be used during those 7 days.
LOLO is effective from the first day of therapy if the tablets are begun on the first day of the menstrual cycle. • The patient begins her next and all subsequent 28-day courses of tablets on the same day of the week on which she began her first course, following the same schedule: 24 days on blue tablets – 2 days on white tablets - 2 days on lilac tablets.
If in any cycle the patient starts tablets later than the proper day, she should protect herself against pregnancy by using a non-hormonal back-up method of birth control until she has taken a blue tablet daily for 7 consecutive days.
Health Canada has not authorized an indication for pediatric use. See 1 INDICATIONS. 4 Administration Switching from another hormonal method of contraception: When the patient is switching to LOLO after completing a 21-day regimen of oral contraceptive tablets, transdermal patches, or a vaginal ring, she should wait 7 days after her last tablet, patch, or ring before she starts LOLO.
She will probably experience withdrawal bleeding during that week. She should be sure that no more than 7 days pass after her previous 21-day regimen. When the patient is switching to LOLO after completing a 28-day regimen of oral contraceptive tablets, she should start her first pack of LOLO on the day after her last tablet.
She should not wait any days between packs. The patient may switch any day from a progestin-only pill and should begin LOLO the next day. If switching from an implant or injection, the patient should start LOLO on the day of implant removal or, if using an injection, the day the next injection would be due.
If switching from an intrauterine device (IUD), depending on the timing of removal, back-up contraception may be needed.
If spotting or breakthrough bleeding occurs:
Breakthrough bleeding or spotting may occur in women taking combination oral contraceptives (COC), especially during the first 3 months of use. The patient is instructed to continue on the same regimen. This type of bleeding is usually transient and without significance; however, if the bleeding is persistent or prolonged, the patient is advised to consult her healthcare provider.
If withdrawal bleeding does not occur:
Although pregnancy is unlikely if LOLO is taken according to directions, if withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed schedule (missed one or more tablets or started taking them on a day later than she should have), the probability of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken.
If the patient has adhered to the prescribed regimen and misses two LOLO (ethinyl estradiol / norethindrone acetate and ethinyl estradiol) Page 7 of 52 consecutive periods, pregnancy should be ruled out. Hormonal contraceptives should be discontinued if pregnancy is confirmed.
Use after pregnancy, abortion or miscarriage:
LOLO should be initiated no earlier than 28 days postpartum in the nonlactating mother due to the increased risk for thromboembolism. When the tablets are administered in the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered (see 2 CONTRAINDICATIONS, and 7 WARNINGS AND PRECAUTIONS concerning thromboembolic disease).
The patient should be advised to use a non-hormonal back-up method for the first 7 days of tablet taking. However, if intercourse has already occurred, the possibility of ovulation and conception prior to initiation of medication should be considered.
LOLO may be initiated immediately after a first-trimester abortion or miscarriage; if the patient starts LOLO immediately, additional contraceptive measures are not needed. 5 Missed Dose The possibility of follicular growth, ovulation, and risk of pregnancy increases with each successive day that scheduled blue or white tablets are missed.
If the patient misses one or more lilac tablets, she is still protected against pregnancy provided she begins taking the active blue tablets again on the proper day. Delayed restarting of active pills may result in reduction of contraceptive reliability.
Missing pills can cause spotting or light bleeding, even if the missed pills are made up. If breakthrough bleeding occurs following missed blue or white tablets, it will usually be transient and of no consequence. Nausea may also occur on the days two pills are taken to make up for missed pills.
The patient should be instructed to use the following chart if she misses 1 or more of her birth control pills. She should be told to match the number of pills […]
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
CAOfficial regulatory label· Adverse reactions· revised March 22, 2025[2]
, retinal thrombosis) • pulmonary embolism • thrombophlebitis The following adverse reactions also have been reported in patients receiving oral contraceptives: Nausea and vomiting, usually the most common adverse reaction, occurs in approximately 10% or fewer of patients during the first cycle.
The following other reactions, as a general rule, are seen less frequently or only occasionally: Blood and lymphatic system disorders: hemolytic uremic syndrome Ear and labyrinth disorders: auditory disturbances, otosclerosis-related hearing loss1 Eye disorders: cataracts, change in corneal curvature (steepening), intolerance to contact lenses, retinal thrombosis Gastrointestinal disorders: abdominal pain, Crohn’s disease1, diarrhea, gastrointestinal symptoms (such as abdominal cramps and bloating), pancreatitis, ulcerative colitis1 General disorders and administration site conditions: edema LOLO (ethinyl estradiol / norethindrone acetate and ethinyl estradiol) Page 17 of 52 Hepatobiliary disorders: cholestatic jaundice, gallstone formation1, liver function disturbances1 Immune system disorders: hypersensitivity Infections and infestations: rhinitis, vaginal candidiasis, vaginitis Investigations: change in weight (increase or decrease), reduced tolerance to carbohydrates Metabolism and nutrition disorders: changes in appetite, hypertriglyceridemia (increased risk of pancreatitis when using COCs)1, porphyria Musculoskeletal and connective tissue disorders: systemic lupus erythematosus1 Neoplasms benign, malignant and unspecified (including cysts and polyps): increase in size of uterine leiomyomata Nervous system disorders: chorea, dizziness, headache, migraine, optic neuritis, Sydenham’s chorea1 Psychiatric disorders: changes in libido, mental depression, nervousness Renal and urinary disorders: cystitis-like syndrome, impaired renal function Reproductive system and breast disorders: amenorrhea during and after treatment, breakthrough bleeding, breast changes including tenderness, enlargement, and secretion, change in menstrual flow, dysmenorrhea, endocervical hyperplasia, possible diminution in lactation when given immediately post- partum, premenstrual-like syndrome, spotting, temporary infertility after discontinuance of treatment, vaginal discharge Skin and subcutaneous tissue disorders: chloasma or melasma which may persist, loss of scalp hair, hirsutism, erythema multiforme, erythema nodosum, hemorrhagic eruption, herpes gestationis1, pruritis related to cholestasis1, rash (allergic), urticaria Vascular disorders: hypertension1, Raynaud's phenomenon 1.
Occurrence or deterioration of conditions for which association with COC use is not conclusive. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and approximate rates of adverse drug reactions in real-world use. A multicenter phase 3 clinical trial evaluated the safety and efficacy of LOLO for pregnancy prevention.
The study was a one year, open-label, single-arm, uncontrolled study. A total of 1,660 women aged 18 to 45 were enrolled and took at least one dose of LOLO. A list of adverse reactions experienced by ≥ 1% of the subjects is listed in Table 2.
8 lb). Serious Adverse Events leading to discontinuation included: deep vein thrombosis, ovarian vein thrombosis and cholecystitis. 7% of the women discontinued from the clinical trial due to an adverse event. Adverse events occurring in ≥ 1% of subjects leading to discontinuation of treatment were, in decreasing order: menstrual irregularities (including metrorrhagia, irregular menstruation, menorrhagia and vaginal hemorrhage) (4%), headache/migraine (1%), mood disorder (including mood swings, depression, anxiety) (1%), and weight fluctuation (1%).
Less than 1% of subjects discontinued because of amenorrhea. 1 Clinical Trial Adverse Reactions – Pediatrics The safety and efficacy of LOLO have not been established in women under the age of 18 years. 3 Less Common Clinical Trial Adverse Reactions Rare adverse reactions (< 1%) which were observed in clinical trials and deemed to be at least possibly related to LOLO are as follows: Eye disorders: vision blurred, contact lens intolerance, dry eye Gastrointestinal disorders: abdominal pain, vomiting, diarrhea, abdominal distension, LOLO (ethinyl estradiol / norethindrone acetate and ethinyl estradiol) Page 19 of 52 gastroesophageal reflux disease, constipation, dyspepsia, stomach discomfort, abdominal discomfort General disorders and administration site conditions: fatigue, irritability, peripheral edema, swelling, edema, drug intolerance […]
CAOfficial regulatory label· Warnings and precautions· revised March 22, 2025[2]
• LOLO is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, COMPOSITION AND PACKAGING.
, due to MTHFR C677T, A1298 mutations), prothrombin mutation G20210A, and antiphospholipid- antibodies (anticardiolipin antibodies, lupus anticoagulant) - severe dyslipoproteinemia - over age 35 and smoke - diabetes mellitus with vascular involvement - major surgery associated with an increased risk of postoperative thromboembolism - prolonged immobilization 3 SERIOUS WARNINGS AND PRECAUTIONS BOX Serious Warnings and Precautions • Cigarette smoking increases the risk of serious cardiovascular events associated with the use of hormonal contraceptives.
This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, LOLO should not be used by women who are over 35 years of age and smoke. See Cardiovascular. • Patients should be counselled that birth control pills DO NOT PROTECT against sexually transmitted infections (STIs) including HIV/AIDS.
For protection against STIs, it is advisable to use latex or polyurethane condoms IN COMBINATION WITH birth control pills. 1 Dosing Considerations To achieve maximum contraceptive effectiveness, LOLO should be taken exactly as directed and at intervals not exceeding 24 hours.
• LOLO tablets may be administered without regard to meals. • LOLO provides a regimen consisting of 24 blue estrogen-progestin tablets, 2 white estrogen-only tablets, and 2 lilac placebo tablets. 2 Recommended Dose and Dosage Adjustment During the first cycle of use: • The possibility of ovulation and conception prior to initiation of medication should be considered.
The patient is instructed to begin taking LOLO on either Day 1 of menstruation (Day 1 Start) or the first Sunday after the onset of menstruation (Sunday Start). If menstruation begins on a Sunday, the first tablet (blue) is taken that day.
One blue tablet should be taken daily for 24 consecutive days followed by one white tablet for 2 consecutive days, followed by one lilac tablet daily for 2 consecutive days. During the first cycle with a Sunday Start, contraceptive reliance should not be placed on LOLO until a blue tablet has been taken daily for 7 consecutive days and a non-hormonal back-up method of birth control (such as latex or polyurethane condoms or spermicide) should be used during those 7 days.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
CAOfficial regulatory label· Contraindications· revised March 22, 2025[2]
• Use with the hepatitis C virus (HCV) combination drug regimen ombitasvir, paritaprevir, ritonavir with or without dasabuvir. See 7 WARNINGS AND PRECAUTIONS. • LOLO is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.
For a complete listing, see 6 DOSAGE FORMS, COMPOSITION AND PACKAGING. , due to MTHFR C677T, A1298 mutations), prothrombin mutation G20210A, and antiphospholipid- antibodies (anticardiolipin antibodies, lupus anticoagulant) - severe dyslipoproteinemia - over age 35 and smoke - diabetes mellitus with vascular involvement - major surgery associated with an increased risk of postoperative thromboembolism - prolonged immobilization
This is not medical advice. Consult a qualified healthcare professional.
USOfficial regulatory label· revised January 29, 2026[3]
DOSAGE AND ADMINISTRATION
The tablet dispenser has been designed to make oral contraceptive dosing as easy and as convenient as possible. The tablets are arranged in three rows of seven tablets each, with the days of the week appearing on the tablet dispenser above the first row of tablets.
Note:
Each tablet dispenser has been preprinted with the days of the week, starting with Sunday, to facilitate a Sunday-Start regimen. Six different day label strips have been provided with the Detailed Patient & Brief Summary Patient Package Insert in order to accommodate a Day-1 Start regimen.
If the patient is using the Day-1 Start regimen, she should place the self-adhesive day label strip that corresponds to her starting day over the preprinted days.
Important:
The patient should be instructed to use an additional method of protection until after the first week of administration in the initial cycle when utilizing the Sunday-Start regimen. The possibility of ovulation and conception prior to initiation of use should be considered.
5/30 must be taken exactly as directed and at intervals not exceeding 24 hours. 5/30 provides the patient with a convenient tablet schedule of “3 weeks on-1 week off”. Two dosage regimens are described, one of which may be more convenient or suitable than the other for an individual patient.
For the initial cycle of therapy, the patient begins her tablets according to the Day-1 Start or Sunday-Start regimen. With either regimen, the patient takes one tablet daily for 21 consecutive days followed by one week of no tablets.
A.
Sunday-Start Regimen:
The patient begins taking tablets from the top row on the first Sunday after menstrual flow begins. When menstrual flow begins on Sunday, the first tablet is taken on the same day. The last tablet in the dispenser will then be taken on a Saturday, followed by no tablets for a week (7 days).
For all subsequent cycles, the patient then begins a new 21-tablet regimen on the eighth day, Sunday, after taking her last tablet. Following this regimen, of 21 days on-7 days off, the patient will start all subsequent cycles on a Sunday.
B.
Day-1 Regimen:
The first day of menstrual flow is Day 1. The patient places the self-adhesive day label strip that corresponds to her starting day over the preprinted days on the tablet dispenser. She starts taking one tablet daily, beginning with the first tablet in the top row.
The patient completes her 21-tablet regimen when she has taken the last tablet in the tablet dispenser. She will then take no tablets for a week (7 days). For all subsequent cycles, the patient begins a new 21-tablet regimen on the eighth day after taking her last tablet, again starting with the first tablet in the top row after placing the appropriate day label strip over the preprinted days on the tablet dispenser.
Following this regimen of 21 days on-7 days off, the patient will start all subsequent cycles on the same day of the week as the first course. Likewise, the interval of no tablets will always start on the same day of the week. Tablets should be taken regularly with a meal or at bedtime.
It should be stressed that efficacy of medication depends on strict adherence to the dosage schedule. Special Notes on Administration Menstruation usually begins two or three days, but may begin as late as the fourth or fifth day, after discontinuing medication.
If spotting occurs while on the usual regimen of one tablet daily, the patient should continue medication without interruption.
If the patient forgets to take one or more tablets, the following is suggested:
One tablet is missed • take tablet as soon as remembered • take next tablet at the regular time Two consecutive tablets are missed (week 1 or week 2) • take two tablets as soon as remembered • take two tablets the next day • use another birth control method for seven days following the missed tablets Two consecutive tablets are missed (week 3) Sunday-Start Regimen: • take one tablet daily until Sunday • discard remaining tablets • start new pack of tablets immediately (Sunday) • use another birth control method for seven days following the missed tablets Day-1 Start Regimen: • discard remaining tablets • start new pack of tablets that same day • use another birth control method for seven days following the missed tablets Three (or more) consecutive tablets are missed Sunday-Start Regimen: • take one tablet daily until Sunday • discard remaining tablets • start new pack of tablets immediately (Sunday) • use another birth control method for seven days following the missed tablets Day-1 Start Regimen: • discard remaining tablets • start new pack of tablets that same day • use another birth control method for seven days following the missed tablets The possibility of ovulation occurring increases with each successive day that scheduled tablets are missed.
While there is little likelihood of ovulation occurring if only one tablet is missed, the possibility of spotting or bleeding is increased. This is particularly likely to occur if two or more consecutive tablets are missed. In the rare case of bleeding which resembles menstruation, the patient should be advised to discontinue medication and then begin taking tablets from a new tablet dispenser on the next Sunday or the first day (Day 1), depending on her regimen.
Persistent bleeding which is not controlled by this method indicates the need for reexamination of the patient, at which time nonfunctional causes should be considered. Use of Oral Contraceptives in the Event of a Missed Menstrual Period 1.
If the patient has not adhered to the prescribed dosage regimen, the possibility of pregnancy should be considered after the first missed period and oral contraceptives should be withheld until pregnancy has been ruled out. 2. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.
After several months on treatment, bleeding may be reduced to a point of virtual absence. This reduced flow may occur as a result of medication, in which event it is not indicative of pregnancy.
This is not medical advice. Consult a qualified healthcare professional.
Most-reported reactions to the US regulator (12 mo to June 4, 2026): 1,635 reports total. [4]
Off Label Use 157
Nausea 133
Drug Ineffective 132
Fatigue 104
Product Use In Unapproved Indication 100
Dyspnoea 87
Headache 85
Condition Aggravated 84
Dizziness 80
Product Dose Omission Issue 80
Rash 80
Pruritus 78
Side effects & warnings
USOfficial regulatory label· Adverse reactions· revised January 29, 2026[3]
ADVERSE REACTIONS
12 (Figure 1) (70-74). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 1) (70, 73, 75). One of these studies reported no association between breast cancer risk and COC use.
33 with current or recent use. 4 with more than 8 to 10 years of COC use.
FIGURE 1:
RELEVANT STUDIES OF RISK OF BREAST CANCER WITH COMBINED ORAL CONTRACEPTIVES RR = relative risk; OR = odds ratio; HR = hazard ratio. “ever COC” are females with current or past COC use; “never COC use” are females that never used COCs.
There is evidence of an association between the following conditions and the use of oral contraceptives, although additional confirmatory studies are needed: • Mesenteric thrombosis • Retinal thrombosis The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug-related: • Nausea • Vomiting • Gastrointestinal symptoms (such as abdominal cramps and bloating) • Breakthrough bleeding • Spotting • Change in menstrual flow • Amenorrhea • Temporary infertility after discontinuation of treatment • Edema • Melasma which may persist • Breast changes: tenderness, enlargement, secretion • Change in weight (increase or decrease) • Change in cervical erosion and secretion • Diminution in lactation when given immediately postpartum • Cholestatic jaundice • Migraine • Rash (allergic) • Depression • Reduced tolerance to carbohydrates • Vaginal candidiasis • Change in corneal curvature (steepening) • Intolerance to contact lenses The following adverse reactions have been reported in users of oral contraceptives and the association has been neither confirmed nor refuted: • Pre-menstrual syndrome • Cataracts • Changes in appetite • Cystitis-like syndrome • Headache • Nervousness • Dizziness • Hirsutism • Loss of scalp hair • Erythema multiforme • Erythema nodosum • Hemorrhagic eruption • Vaginitis • Porphyria • Impaired renal function • Hemolytic uremic syndrome • Budd-Chiari syndrome • Acne • Changes in libido • Colitis figure1
USOfficial regulatory label· Warnings and precautions· revised January 29, 2026[3]
WARNINGS
The use of oral contraceptives is associated with increased risks of several serious conditions including myocardial infarction, thromboembolism, stroke, hepatic neoplasia, and gallbladder disease, although the risk of serious morbidity or mortality is very small in healthy women without underlying risk factors.
The risk of morbidity and mortality increases significantly in the presence of other underlying risk factors such as hypertension, hyperlipidemias, obesity, and diabetes. Practitioners prescribing oral contraceptives should be familiar with the following information relating to these risks.
The information contained in this package insert is principally based on studies carried out in patients who used oral contraceptives with higher formulations of estrogens and progestogens than those in common use today. The effect of long-term use of the oral contraceptives with lower formulations of both estrogens and progestogens remains to be determined.
Throughout this labeling, epidemiological studies reported are of two types: retrospective or case control studies and prospective or cohort studies. Case control studies provide a measure of the relative risk of a disease, namely, a ratio of the incidence of a disease among oral contraceptive users to that among nonusers.
The relative risk does not provide information on the actual clinical occurrence of a disease. Cohort studies provide a measure of attributable risk, which is the difference in the incidence of disease between oral contraceptive users and nonusers.
The attributable risk does provide information about the actual occurrence of a disease in the population (adapted from References 8 and 9 with the author’s permission). For further information, the reader is referred to a text on epidemiological methods.
1. Thromboembolic Disorders and Other Vascular Problems a. Myocardial infarction An increased risk of myocardial infarction has been attributed to oral contraceptive use. This risk is primarily in smokers or women with other underlying risk factors for coronary artery disease such as hypertension, hypercholesterolemia, morbid obesity, and diabetes.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised January 29, 2026[3]
CONTRAINDICATIONS
Oral contraceptives are contraindicated in women who currently have the following conditions: • Thrombophlebitis or thromboembolic disorders • A past history of deep vein thrombophlebitis or thromboembolic disorders • Cerebral vascular or coronary artery disease • Current diagnosis of, or history of, breast cancer, which may be hormone sensitive • Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia • Undiagnosed abnormal genital bleeding • Cholestatic jaundice of pregnancy or jaundice with prior pill use • Hepatic adenomas or carcinomas • Are receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations (see WARNINGS , RISK OF LIVER ENZYME ELEVATIONS WITH CONCOMITANT HEPATITIS C TREATMENT ).
This is not medical advice. Consult a qualified healthcare professional.
Antithrombotic treatment should be considered if Ambelina has not been discontinued in advance. g. before 50). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any CHC use.
Other medical conditions associated with VTE Cancer, systemic lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell disease. Increasing age Particularly above 35 years.
There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in the onset or progression of venous thrombosis. 6). Symptoms of VTE (deep vein thrombosis and pulmonary embolism) In the event of symptoms women should be advised to seek urgent medical attention and to inform the healthcare professional that she is taking a CHC.
Symptoms of deep vein thrombosis (DVT) can include: - unilateral swelling of the leg and/or foot or along a vein in the leg; - pain or tenderness in the leg which may be felt only when standing or walking, - increased warmth in the affected leg; red or discoloured skin on the leg.
g. g. respiratory tract infections). Other signs of vascular occlusion can include: sudden pain, swelling and slight blue discoloration of an extremity. If the occlusion occurs in the eye symptoms can range from painless blurring of vision which can progress to loss of vision.
Sometimes loss of vision can occur almost immediately. g. transient ischaemic attack, stroke). Arterial thromboembolic events may be fatal. Risk factors for ATE The risk of arterial thromboembolic complications or of a cerebrovascular accident in CHC users increases in women with risk factors (see table).
Ambelina is contraindicated if a woman has one serious or […]
LOLO is effective from the first day of therapy if the tablets are begun on the first day of the menstrual cycle. • The patient begins her next and all subsequent 28-day courses of tablets on the same day of the week on which she began her first course, following the same schedule: 24 days on blue tablets – 2 days on white tablets - 2 days on lilac tablets.
If in any cycle the patient starts tablets later than the proper day, she should protect herself against pregnancy by using a non-hormonal back-up method of birth control until she has taken a blue tablet daily for 7 consecutive days.
Health Canada has not authorized an indication for pediatric use. See 1 INDICATIONS. 4 Administration Switching from another hormonal method of contraception: When the patient is switching to LOLO after completing a 21-day regimen of oral contraceptive tablets, transdermal patches, or a vaginal ring, she should wait 7 days after her last tablet, patch, or ring before she starts LOLO.
She will probably experience withdrawal bleeding during that week. She should be sure that no more than 7 days pass after her previous 21-day regimen. When the patient is switching to LOLO after completing a 28-day regimen of oral contraceptive tablets, she should start her first pack of LOLO on the day after her last tablet.
She should not wait any days between packs. The patient may switch any day from a progestin-only pill and should begin LOLO the next day. If switching from an implant or injection, the patient should start LOLO on the day of implant removal or, if using an injection, the day the next injection would be due.
If switching from an intrauterine device (IUD), depending on the timing of removal, back-up contraception may be needed. If […]
The relative risk of heart attack for current oral contraceptive users has been estimated to be two to six (10 - 16). The risk is very low under the age of 30. Smoking in combination with oral contraceptive use has been shown to contribute substantially to the incidence of myocardial infarctions in women in their mid-thirties or older with smoking accounting for the majority of excess cases (17).
Mortality rates associated with circulatory disease have been shown to increase substantially in smokers over the age of 35 and non-smokers over the age of 40 (Table II) among women who use oral contraceptives. Oral contraceptives may compound the effects of well-known risk factors, such as hypertension, diabetes, hyperlipidemias, age and obesity (19).
In particular, some progestogens are known to decrease HDL cholesterol and cause glucose intolerance, while estrogens may create a state of hyperinsulinism (20 - 24). Oral contraceptives have been shown to increase blood pressure among users (see section 9 in WARNINGS ).
Similar effects on risk factors have been associated with an increased risk of heart disease. Oral contraceptives must be used with caution in women with cardiovascular disease risk factors. table2 b. Thromboembolism An increased risk of thromboembolic and thrombotic disease associated with the use of oral contraceptives is well established.
5 to 6 for women with predisposing conditions for venous thromboembolic disease (9, 10, 25 - 30). 5 for new cases requiring hospitalization (31). The risk of thromboembolic disease due to oral contraceptives is not related to length of use and disappears after pill use is stopped (8).
A two- to four-fold increase in relative risk of postoperative thromboembolic complications has been reported with the use of oral contraceptives (15,32). The relative risk of venous thrombosis in women who have predisposing conditions is twice that of women without such medical conditions (15,32).
If feasible, oral contraceptives should be discontinued at least four weeks prior to and for two weeks after elective surgery of a type associated with an increase in risk of thromboembolism and during and following prolonged immobilization.
Since the immediate postpartum period is also associated with an increased risk of thromboembolism, oral contraceptives should be started no earlier than four to six weeks after delivery in women who elect not to breastfeed. c. Cerebrovascular disease Oral contraceptives have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes), although, in general, the risk is greatest among older (greater than 35 years), hypertensive women who also smoke.
Hypertension was found to be a risk factor for both users and nonusers, for both types of strokes, while smoking interacted to increase the risk for hemorrhagic strokes (33 - 35). In a large study, the relative risk of thrombotic strokes has been shown to range from 3 for normotensive users to 14 for users with severe hypertension (36).
7 for users with severe hypertension (36). The attributable risk is also greater in older women (9). d. Dose-related risk of vascular disease from oral contraceptives A positive association has been observed between the amount of estrogen and progestogen in oral contraceptives and the risk of vascular disease (37 - 39).
A decline in serum high-density lipoproteins (HDL) has been reported with many progestational agents (20 - 22). A decline in serum high-density lipoproteins has been associated with an increased incidence of ischemic heart disease. Because estrogens increase HDL cholesterol, the net effect of an oral contraceptive depends on a balance achieved between doses of estrogen and progestin and the nature of the progestin used in the contraceptives.
The amount and activity of both hormones should be considered in the choice of an oral contraceptive. Minimizing exposure to estrogen and progestogen is in keeping with good principles of therapeutics. For any particular oral contraceptive, the dosage regimen prescribed should be one which contains the least amount of estrogen and progestogen that is compatible with the needs of the individual patient.
New acceptors of oral contraceptive agents should be started on preparations containing the lowest dose of estrogen which produces satisfactory results for the patient. e. Persistence of risk of vascular disease There are two studies which have shown persistence of risk of vascular disease for ever-users of oral contraceptives.
In a study in the United States, the risk of developing myocardial infarction after discontinuing oral contraceptives persists for at least 9 years for women 40 to 49 years who had used oral contraceptives for 5 or more years, but this increased risk was not demonstrated in other age groups (14).
In another study in Great Britain, the risk of developing cerebrovascular disease persisted for at least 6 years after discontinuation of oral contraceptives, although excess risk was very small (40). However, both studies were performed with oral contraceptive formulations containing 50 mcg or higher of estrogens.
2. Estimates of Mortality from Contraceptive Use One study gathered data from a variety of sources which have estimated the mortality rate associated with different methods of contraception at different ages (Table III). These estimates include the combined risk of death associated with contraceptive methods plus the risk attributable to pregnancy in the event of method failure.
Each method of contraception has its specific benefits and risks. The study concluded that with the exception of oral contraceptive users 35 and older who smoke and 40 and older who do not smoke, mortality associated with all methods of birth control is low and below that associated with childbirth.
The observation of a possible increase in risk of mortality with age for oral contraceptive users is based on data gathered in the 1970’s but not reported until 1983 (41). However, current clinical practice involves the use of lower estrogen dose formulations combined with careful restriction of oral contraceptive use to women who do not have the various risk factors listed in this labeling.
Because of these changes in practice and, also, because of some limited new data which suggest that the risk of cardiovascular disease with the use of oral contraceptives may now be less than previously observed (Porter JB, Hunter J, Jick H, et al.
Oral contraceptives and nonfatal vascular disease. Obstet Gynecol 1985;66:1-4; and Porter JB, Hershel J, Walker AM. Mortality among oral contraceptive users. Obstet Gynecol 1987;70:29-32), the Fertility and Maternal Health Drugs Advisory Committee was asked to review the topic in 1989.
The Committee concluded that although cardiovascular disease risks may be increased with oral contraceptive use after age 40 in healthy non-smoking women (even with the newer low-dose formulations), there are greater potential health risks associated with pregnancy in older women and with the alternative surgical and medical procedures which may be necessary if such women do not have access to effective and acceptable means of contraception.
Therefore, the Committee recommended that the benefits of oral contraceptive use by healthy non-smoking women over 40 may outweigh the possible risks. Of course, older women, as all women who take oral contraceptives, should take the lowest possible dose formulation that is effective.
6 *Deaths are birth related. W. Ory, Reference 41. 3. Malignant Neoplasms Breast Cancer Norethindrone acetate and ethinyl estradiol tablets are contraindicated in females who currently have or have had breast cancer because breast cancer may be hormonally sensitive (see CONTRAINDICATIONS ).
Epidemiology studies have not found a consistent association between use of combined oral contraceptives (COCs) and breast cancer risk. Studies do not show an association between ever (current or past) use of COCs and risk of breast cancer.
However, some studies report a small increase in the risk of breast cancer among current or recent users (<6 months since last use) and current users with longer duration of COC use (see ADVERSE REACTIONS , Postmarketing Experience).
Cervical Cancer Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women (42-45). However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors.
4. Hepatic Neoplasia Benign hepatic adenomas are associated with oral contraceptive use, although the incidence of benign tumors is rare in the United States. 3 cases/100,000 for users, a risk that increases after four or more years of use (46).
Rupture of rare, benign, hepatic adenomas may cause death through intra-abdominal hemorrhage (47,48). Studies from Britain have shown an increased risk of developing hepatocellular carcinoma (49 - 51) in long-term (greater than 8 years) oral contraceptive users.
, and the attributable risk (the excess incidence) of liver cancers in oral contraceptive users approaches less than one per million users. 5. Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment During clinical trials with the Hepatitis C combination drug regimen that contains ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, ALT elevations greater than 5 times the upper limit of normal (ULN), including some cases greater than 20 times the ULN, were significantly more frequent in women using ethinyl estradiol-containing medications such as COCs.
Discontinue norethindrone acetate and ethinyl estradiol tablets prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir (see CONTRAINDICATIONS ). Norethindrone acetate and ethinyl estradiol tablets can be restarted approximately 2 weeks following completion of treatment with the combination drug regimen.
6. Ocular Lesions There have been clinical case reports of retinal thrombosis associated with the use of oral contraceptives. Oral contraceptives should be discontinued if there is unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions.
Appropriate diagnostic and therapeutic measures should be undertaken immediately. 7. Oral Contraceptive Use Before and During Early Pregnancy Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy (52 to 54).
Studies also do not suggest a teratogenic effect, particularly insofar as cardiac anomalies and limb reduction defects are concerned (52,53,55,56), when taken inadvertently during early pregnancy. The administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy.
Oral contraceptives should not be used during pregnancy to treat threatened or habitual abortion. It is recommended that for any patient who has missed two consecutive periods, pregnancy should be ruled out before continuing oral contraceptive use.
If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period. Oral contraceptive use should be discontinued if pregnancy is confirmed. 8. Gallbladder Disease Earlier studies have reported an increased lifetime relative risk of gallbladder surgery in users of oral contraceptives and estrogens (57,58).
More recent studies, however, have shown that the relative risk of developing gallbladder disease among oral contraceptive users may be minimal (59 to 61). The recent findings of minimal risk may be related to the use of oral contraceptive formulations containing lower hormonal doses of estrogens and progestogens.
9. Carbohydrate and Lipid Metabolic Effects Oral contraceptives have been shown to cause glucose intolerance in a significant percentage of users (23). Oral contraceptives containing greater than 75 mcg of estrogens cause hyperinsulinism, while lower doses of estrogen cause less glucose intolerance (62).
Progestogens increase insulin secretion and create insulin resistance, this effect varying with different progestational agents (23,63). However, in the non-diabetic woman, oral contraceptives appear to have no effect on fasting blood glucose (64).
Because of these demonstrated effects, prediabetic and diabetic women should be carefully observed while taking oral contraceptives. A small proportion of women will have persistent hypertriglyceridemia while on the pill. As discussed earlier (see WARNINGS 1a.
and 1d . ), changes in serum triglycerides and lipoprotein levels have been reported in oral contraceptive users. 10. Elevated Blood Pressure An increase in blood pressure has been reported in women taking oral contraceptives (65) and this increase is more likely in older oral contraceptive users (66) and with continued use (65).
Data from the Royal College of General Practitioners (18) and subsequent randomized trials have shown that the incidence of hypertension increases with increasing concentrations of progestogens. Women with a history of hypertension or hypertension-related diseases or renal disease (67) should be encouraged to use another method of contraception.
If women elect to use oral contraceptives, they should be monitored closely, and if significant elevation of blood pressure occurs, oral contraceptives should be discontinued. For most women, elevated blood pressure will return to normal after stopping oral contraceptives (66), and there is no difference in the occurrence of hypertension among ever and never users (65,67,68).
11. Headache The onset or exacerbation of migraine or development of headache with a new pattern which is recurrent, persistent, or severe requires discontinuation of oral contraceptives and evaluation of the cause. 12. Bleeding Irregularities Breakthrough bleeding and spotting are sometimes encountered in patients on oral contraceptives, especially during the first three months of use.
Non-hormonal causes should be considered, and adequate diagnostic measures taken to rule out malignancy or pregnancy in the event of breakthrough bleeding, as in the case of any abnormal vaginal bleeding. If pathology has been excluded, time or a change to another formulation may solve the problem.
In the event of amenorrhea, pregnancy should be ruled out. Some women may encounter post-pill amenorrhea or oligomenorrhea, especially when such a condition was preexistent. 13. Hereditary Angioedema In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema.
14. 5/30 if depression recurs to a serious degree.