levonorgestrel and ethinyl estradiol
Generic: LEVONORGESTREL AND ETHINYL ESTRADIOL
Basic Information
Manufacturer
Acella Pharmaceuticals
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
FDA Set ID
167b12a0-cdff-4081-a0a4-164482c239fa
Indications & Usage
1 INDICATIONS AND USAGE Levonorgestrel and ethinyl estradiol tablets, USP and ferrous bisglycinate tablets are indicated for use by females of reproductive potential to prevent pregnancy.
Levonorgestrel and ethinyl estradiol tablets, USP and ferrous bisglycinate tablets are progestin/estrogen COC indicated for use by females of reproductive potential to prevent pregnancy.
( 1 )
Levonorgestrel and ethinyl estradiol tablets, USP and ferrous bisglycinate tablets are progestin/estrogen COC indicated for use by females of reproductive potential to prevent pregnancy.
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling: Serious cardiovascular events and stroke [see Boxed Warning and Warnings and Precautions ( 5.1 )] Vascular events [see Warnings and Precautions ( 5.1 )] Liver disease [see Warnings and Precautions ( 5.2 )] Adverse reactions commonly reported by COC users are: Irregular uterine bleeding Nausea Breast tenderness Headache Common adverse reactions (≥2% of women): headache (14%), metrorrhagia (8%), dysmenorrhea and nausea (7% each), abdominal pain and breast pain (4% each), emotional lability and acne (3% each), and depression, amenorrhea, and vaginal moniliasis (2% each) ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Acella Pharmaceuticals, LLC at 1-800-541-4802 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
In a clinical trial with levonorgestrel 0.1 mg and ethinyl estradiol 0.02 mg tablets, a total of 1477 healthy women of child-bearing potential were enrolled and had 7870 cycles of exposure.
Of these, 792 subjects had completed 6 cycles of treatment.
The women ranged in age from 17 to 49 years and 87% were Caucasian.
Common Adverse Reactions (≥ 2% of women): headache (14%) metrorrhagia (8%) dysmenorrhea (7%) nausea (7%) abdominal pain (4%) breast pain (4%) emotional lability (3%) acne (3%) depression (2%) amenorrhea (2%) vaginal moniliasis (2%) At the time of the report, 133 (9%) subjects had withdrawn from the study due to adverse events.
The most frequent were due to headache and metrorrhagia (1% each).
Other adverse events occurring in < 1% of those who discontinued included amenorrhea, depression, emotional lability, hypertension, acne, menorrhagia, nausea, hypercholesterolemia, weight gain, dysmenorrhea, and flatulence.
All other reasons for discontinuation were reported by 3 or fewer subjects.
6.2 Postmarketing Experience Five studies that compared breast cancer risk between ever-users (current or past use) of COCs and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90 - 1.12 (Figure 1).
Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 1).
One of these studies reported no association between breast cancer risk and COC use.
The other two studies found an increased relative risk of 1.19 - 1.33 with current or recent use.
Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8-10 years of COC use.
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.
The following additional adverse drug reactions have been reported from worldwide postmarketing experience with levonorgestrel 0.1 mg and ethinyl estradiol 0.02 mg tablets.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cardiac disorder: chest pain, dyspnea, palpitations Gastrointestinal disorders: abdominal pain, nausea, vomiting, diarrhea General disorders and administration site conditions: chest pain, fatigue, pain, malaise, injection site pain or erythema, feeling abnormal, pyrexia, condition aggravated, asthenia Immune system disorders: hypersensitivity reactions, including pruritus, rash, urticaria,erythema Injury, poisoning, and procedural complications: i njury Investigations: weight decreased Musculoskeletal and connective tissue disorders: pain in extremity, arthralgia, back pain,muscle spasm Nervous system disorders: headache, migraine, dizziness, hypoesthesia, paresthesia Psychiatric disorders: depression, insomnia, anxiety Reproductive system and breast disorders: metrorrhagia, menorrhagia, hot flush, vaginal hemorrhage Respiratory, thoracic, and mediastinal disorders: nasopharyngitis, cough Sleep disorders and disturbances: somnolence Vascular disorders: deep vein thrombosis, pulmonary embolism 1
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
In a clinical trial with levonorgestrel 0.1 mg and ethinyl estradiol 0.02 mg tablets, a total of 1477 healthy women of child-bearing potential were enrolled and had 7870 cycles of exposure.
Of these, 792 subjects had completed 6 cycles of treatment.
The women ranged in age from 17 to 49 years and 87% were Caucasian.
Common Adverse Reactions (≥ 2% of women): headache (14%) metrorrhagia (8%) dysmenorrhea (7%) nausea (7%) abdominal pain (4%) breast pain (4%) emotional lability (3%) acne (3%) depression (2%) amenorrhea (2%) vaginal moniliasis (2%) At the time of the report, 133 (9%) subjects had withdrawn from the study due to adverse events.
The most frequent were due to headache and metrorrhagia (1% each).
Other adverse events occurring in < 1% of those who discontinued included amenorrhea, depression, emotional lability, hypertension, acne, menorrhagia, nausea, hypercholesterolemia, weight gain, dysmenorrhea, and flatulence.
All other reasons for discontinuation were reported by 3 or fewer subjects.
6.2 Postmarketing Experience Five studies that compared breast cancer risk between ever-users (current or past use) of COCs and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90 - 1.12 (Figure 1).
Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 1).
One of these studies reported no association between breast cancer risk and COC use.
The other two studies found an increased relative risk of 1.19 - 1.33 with current or recent use.
Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8-10 years of COC use.
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.
The following additional adverse drug reactions have been reported from worldwide postmarketing experience with levonorgestrel 0.1 mg and ethinyl estradiol 0.02 mg tablets.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cardiac disorder: chest pain, dyspnea, palpitations Gastrointestinal disorders: abdominal pain, nausea, vomiting, diarrhea General disorders and administration site conditions: chest pain, fatigue, pain, malaise, injection site pain or erythema, feeling abnormal, pyrexia, condition aggravated, asthenia Immune system disorders: hypersensitivity reactions, including pruritus, rash, urticaria,erythema Injury, poisoning, and procedural complications: i njury Investigations: weight decreased Musculoskeletal and connective tissue disorders: pain in extremity, arthralgia, back pain,muscle spasm Nervous system disorders: headache, migraine, dizziness, hypoesthesia, paresthesia Psychiatric disorders: depression, insomnia, anxiety Reproductive system and breast disorders: metrorrhagia, menorrhagia, hot flush, vaginal hemorrhage Respiratory, thoracic, and mediastinal disorders: nasopharyngitis, cough Sleep disorders and disturbances: somnolence Vascular disorders: deep vein thrombosis, pulmonary embolism 1