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Adverse Events

LYBREL® was well tolerated and was associated with a low incidence of serious adverse events (AEs) in clinical trials.9 Studies evaluating the safety of LYBREL enrolled healthy, sexually active women (aged 18 to 49 years) who had 3 normal menstrual cycles before enrollment and normal cervical cytology at screening, and excluded those with the standard combination oral contraceptive (COC) contraindications.12 Common AEs reported by women in the North American study (N=2,134) of LYBREL are listed in Table 1.

TABLE 1. Adverse Events Reported by ≥5% of Women Who Received at Least One Dose of LYBREL9

Body System Adverse Event (COSTART* Term) Percentage of Women
LYBREL (N=2,134) n (%)
Any adverse event 1,857 (87.0)
Body as a whole  
Abdominal pain 204 (9.6)
Accidental injury 131 (6.1)
Back pain 213 (10.0)
Flu syndrome 172 (8.1)
Headache 640 (30.0)
Infection 196 (9.2)
Pain 192 (9.0)
Digestive  
Diarrhea 128 (6.0)
Nausea 276 (12.9)
Respiratory  
Pharyngitis 224 (10.5)
Rhinitis 142 (6.7)
Sinusitis 140 (6.6)
Upper respiratory infection 351 (16.4)
Skin and appendages  
Acne 135 (6.3)
Urogenital  
Breast pain 146 (6.8)
Dysmenorrhea 419 (19.6)
Metrorrhagia 132 (6.2)
Vaginal hemorrhage 152 (7.1)
Vaginal moniliasis 149 (7.0)
Vaginitis 124 (5.8)

* COSTART = Coding Symbols for a Thesaurus of Adverse Reaction Terms.

An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives1:

Thromboembolic and thrombotic disorders and other vascular problems (including thrombophlebitis and venous thrombosis with or without pulmonary embolism, mesenteric thrombosis, arterial thromboembolism, myocardial infarction, cerebral hemorrhage, cerebral thrombosis, transient ischemic attack), carcinoma of the reproductive organs and breasts, hepatic neoplasia/liver disease (including hepatic adenomas or benign liver tumors), ocular lesions (including retinal vascular thrombosis), gallbladder disease, carbohydrate and lipid effects, elevated blood pressure, and headache including migraine.1

The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug related (alphabetically listed)1:

  • Acne
  • Amenorrhea
  • Anaphylactic/anaphylactoid reactions, including urticaria, angioedema, and severe reactions with respiratory and circulatory symptoms
  • Breast changes: tenderness, pain, enlargement, secretion
  • Budd-Chiari syndrome
  • Cervical erosion and secretion, change in
  • Cholestatic jaundice
  • Chorea, exacerbation of
  • Colitis
  • Contact lenses, intolerance to
  • Corneal curvature (steepening), change in
  • Dizziness
  • Edema/fluid retention
  • Erythema multiforme
  • Erythema nodosum
  • Gastrointestinal symptoms (such as abdominal pain, cramps, and bloating)
  • Hirsutism
  • Infertility after discontinuation of treatment, temporary
  • Lactation, diminution in, when given immediately postpartum
  • Libido, change in
  • Melasma/chloasma which may persist
  • Menstrual flow, change in
  • Mood changes, including depression
  • Nausea
  • Nervousness
  • Pancreatitis
  • Porphyria, exacerbation of
  • Rash (allergic)
  • Scalp hair, loss of
  • Serum folate levels, decrease in
  • Spotting
  • Systemic lupus erythematosus, exacerbation of
  • Unscheduled bleeding
  • Vaginitis, including candidiasis
  • Varicose veins, aggravation of
  • Vomiting
  • Weight or appetite (increase or decrease), change in

The following adverse reactions have been reported in users of oral contraceptives1:

  • Cataracts
  • Cystitis-like syndrome
  • Dysmenorrhea
  • Hemolytic uremic syndrome
  • Hemorrhagic eruption
  • Optic neuritis, which may lead to partial or complete loss of vision
  • Premenstrual syndrome
  • Renal function, impaired

Important Safety Information

  • Oral contraceptives (OCs) do not protect against HIV infection or other sexually transmitted diseases.
  • When prescribing LYBREL, the convenience of having no scheduled menstrual bleeding should be weighed against the inconvenience of unscheduled breakthrough bleeding and spotting.
  • OCs are contraindicated in women who have blood clots; breast, uterine, or liver cancers; a history of heart attack, stroke, or breast cancer; as well as those who are or may be pregnant.
The risks of serious cardiovascular side effects are substantially increased in women who smoke and use OCs, especially in women over age 35. Women who use oral contraceptives should be strongly advised not to smoke.
  • Serious risks associated with OCs include blood clots, heart attack, and stroke.
  • LYBREL provides women with more hormonal exposure on a yearly basis (13 additional weeks of hormone intake per year) than conventional cyclic oral contraceptives containing the same strength of synthetic estrogens and similar strength of progestins.
  • Scheduled withdrawal bleeding does not occur with the use of LYBREL, therefore, the absence of withdrawal bleeding cannot be used as a sign of an unexpected pregnancy and as such, unexpected pregnancy may be difficult to recognize. Although pregnancy is unlikely if LYBREL is taken as directed, if for any reason, pregnancy is suspected in a woman using LYBREL, a pregnancy test should be performed.
  • The most commonly reported treatment emergent adverse events reported with LYBREL in a clinical trial were headache, dysmenorrhea, upper respiratory infection, vaginal bleeding (defined as metrorrhagia and vaginal hemorrhage), and nausea.

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