DescriptionCurator's Comment: description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21040LBL.PDF
Curator's Comment: description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21040LBL.PDF
Norgestimate is a steroidal progestin of the 19-nortestosterone group that is used in combination with ethinylestradiol as an oral contraceptive and for treatment of acne. and in combination with estradiol in menopausal hormone replacement therapy. Norgestimate shows high selectivity for the progesterone receptor and low androgenic activity.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL208 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2335104 |
3.4 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Preventing | ORTHO CYCLEN-21 Approved UseNorgestimate and Ethinyl Estradiol lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation. Launch Date1989 |
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Primary | ORTHO CYCLEN-21 Approved UseAcne is a skin condition with a multifactorial etiology, including androgen stimulation of sebum production. Norgestimate and Ethinyl Estradiol Tablets USP, are indicated for the treatment of moderate acne vulgaris in females at least 15 years of age, who have no known contraindications to oral contraceptive therapy and have achieved menarche. Norgestimate and Ethinyl Estradiol Tablets USP should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control. Launch Date1989 |
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Palliative | ORTHO-PREFEST Approved UseORTHO-PREFEST™ therapy is indicated in women with an intact uterus for the treatment of moderate to severe vasomotor symptoms associated with the menopause, treatment of vulvar and vaginal atrophy, prevention of osteoporosis. Launch Date1999 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
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515 pg/mL |
0.09 mg single, oral dose: 0.09 mg route of administration: Oral experiment type: SINGLE co-administered: ESTRADIOL |
NORGESTIMATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
|
779.2 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10883418 |
180 μg single, oral dose: 180 μg route of administration: Oral experiment type: SINGLE co-administered: ESTRADIOL |
NORGESTIMATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED |
|
643 pg/mL |
0.09 mg 1 times / day multiple, oral dose: 0.09 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
NORGESTIMATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2146 pg × h/mL |
0.09 mg single, oral dose: 0.09 mg route of administration: Oral experiment type: SINGLE co-administered: ESTRADIOL |
NORGESTIMATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
|
9522.7 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10883418 |
180 μg single, oral dose: 180 μg route of administration: Oral experiment type: SINGLE co-administered: ESTRADIOL |
NORGESTIMATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED |
|
5322 pg × h/mL |
0.09 mg 1 times / day multiple, oral dose: 0.09 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
NORGESTIMATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
37 h |
0.09 mg single, oral dose: 0.09 mg route of administration: Oral experiment type: SINGLE co-administered: ESTRADIOL |
NORGESTIMATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
|
30.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10883418 |
180 μg single, oral dose: 180 μg route of administration: Oral experiment type: SINGLE co-administered: ESTRADIOL |
NORGESTIMATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1% |
0.09 mg single, oral dose: 0.09 mg route of administration: Oral experiment type: SINGLE co-administered: ESTRADIOL |
NORGESTIMATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
215 ug 1 times / day multiple, oral (median) Dose: 215 ug, 1 times / day Route: oral Route: multiple Dose: 215 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 48 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 48 Sources: |
Other AEs: Vomiting, Abdominal pain... Other AEs: Vomiting (4 patients) Sources: Abdominal pain (15 patients) Nausea (27 patients) Sinusitis (8 patients) URTI (8 patients) Breast pain (13 patients) Dysmenorrhea (13 patients) Headache (38 patients) |
305 ug 1 times / day multiple, oral (mean) Dose: 305 ug, 1 times / day Route: oral Route: multiple Dose: 305 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 49 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 49 Sources: |
Other AEs: Vomiting, Abdominal pain... Other AEs: Vomiting (4 patients) Sources: Abdominal pain (4 patients) Nausea (20 patients) URTI (16 patients) Breast pain (4 patients) Dysmenorrhea (12 patients) Headache (27 patients) |
305 ug 1 times / day multiple, oral (mean) Dose: 305 ug, 1 times / day Route: oral Route: multiple Dose: 305 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 48 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 48 Sources: |
Other AEs: Vomiting, Abdominal pain... Other AEs: Vomiting (11 patient) Sources: Abdominal pain (13 patients) Nausea (21 patient) Sinusitis (6 patients) URTI (13 patients) Breast pain (9 patients) Dysmenorrhea (15 patients) Headache (26 patients) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Breast pain | 13 patients | 215 ug 1 times / day multiple, oral (median) Dose: 215 ug, 1 times / day Route: oral Route: multiple Dose: 215 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 48 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 48 Sources: |
Dysmenorrhea | 13 patients | 215 ug 1 times / day multiple, oral (median) Dose: 215 ug, 1 times / day Route: oral Route: multiple Dose: 215 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 48 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 48 Sources: |
Abdominal pain | 15 patients | 215 ug 1 times / day multiple, oral (median) Dose: 215 ug, 1 times / day Route: oral Route: multiple Dose: 215 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 48 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 48 Sources: |
Nausea | 27 patients | 215 ug 1 times / day multiple, oral (median) Dose: 215 ug, 1 times / day Route: oral Route: multiple Dose: 215 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 48 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 48 Sources: |
Headache | 38 patients | 215 ug 1 times / day multiple, oral (median) Dose: 215 ug, 1 times / day Route: oral Route: multiple Dose: 215 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 48 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 48 Sources: |
Vomiting | 4 patients | 215 ug 1 times / day multiple, oral (median) Dose: 215 ug, 1 times / day Route: oral Route: multiple Dose: 215 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 48 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 48 Sources: |
Sinusitis | 8 patients | 215 ug 1 times / day multiple, oral (median) Dose: 215 ug, 1 times / day Route: oral Route: multiple Dose: 215 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 48 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 48 Sources: |
URTI | 8 patients | 215 ug 1 times / day multiple, oral (median) Dose: 215 ug, 1 times / day Route: oral Route: multiple Dose: 215 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 48 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 48 Sources: |
Dysmenorrhea | 12 patients | 305 ug 1 times / day multiple, oral (mean) Dose: 305 ug, 1 times / day Route: oral Route: multiple Dose: 305 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 49 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 49 Sources: |
URTI | 16 patients | 305 ug 1 times / day multiple, oral (mean) Dose: 305 ug, 1 times / day Route: oral Route: multiple Dose: 305 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 49 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 49 Sources: |
Nausea | 20 patients | 305 ug 1 times / day multiple, oral (mean) Dose: 305 ug, 1 times / day Route: oral Route: multiple Dose: 305 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 49 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 49 Sources: |
Headache | 27 patients | 305 ug 1 times / day multiple, oral (mean) Dose: 305 ug, 1 times / day Route: oral Route: multiple Dose: 305 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 49 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 49 Sources: |
Abdominal pain | 4 patients | 305 ug 1 times / day multiple, oral (mean) Dose: 305 ug, 1 times / day Route: oral Route: multiple Dose: 305 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 49 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 49 Sources: |
Breast pain | 4 patients | 305 ug 1 times / day multiple, oral (mean) Dose: 305 ug, 1 times / day Route: oral Route: multiple Dose: 305 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 49 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 49 Sources: |
Vomiting | 4 patients | 305 ug 1 times / day multiple, oral (mean) Dose: 305 ug, 1 times / day Route: oral Route: multiple Dose: 305 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 49 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 49 Sources: |
Vomiting | 11 patient | 305 ug 1 times / day multiple, oral (mean) Dose: 305 ug, 1 times / day Route: oral Route: multiple Dose: 305 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 48 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 48 Sources: |
Abdominal pain | 13 patients | 305 ug 1 times / day multiple, oral (mean) Dose: 305 ug, 1 times / day Route: oral Route: multiple Dose: 305 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 48 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 48 Sources: |
URTI | 13 patients | 305 ug 1 times / day multiple, oral (mean) Dose: 305 ug, 1 times / day Route: oral Route: multiple Dose: 305 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 48 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 48 Sources: |
Dysmenorrhea | 15 patients | 305 ug 1 times / day multiple, oral (mean) Dose: 305 ug, 1 times / day Route: oral Route: multiple Dose: 305 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 48 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 48 Sources: |
Nausea | 21 patient | 305 ug 1 times / day multiple, oral (mean) Dose: 305 ug, 1 times / day Route: oral Route: multiple Dose: 305 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 48 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 48 Sources: |
Headache | 26 patients | 305 ug 1 times / day multiple, oral (mean) Dose: 305 ug, 1 times / day Route: oral Route: multiple Dose: 305 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 48 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 48 Sources: |
Sinusitis | 6 patients | 305 ug 1 times / day multiple, oral (mean) Dose: 305 ug, 1 times / day Route: oral Route: multiple Dose: 305 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 48 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 48 Sources: |
Breast pain | 9 patients | 305 ug 1 times / day multiple, oral (mean) Dose: 305 ug, 1 times / day Route: oral Route: multiple Dose: 305 ug, 1 times / day Co-administed with:: ethinyl estradiol(35 ug) Sources: |
healthy, 18 - 40 years n = 48 Health Status: healthy Age Group: 18 - 40 years Sex: F Population Size: 48 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
weak | yes (co-administration study) Comment: Simultaneous and staggered EE/norgestimate and lomitapide administration resulted in an approximately 1.3-fold increase in lomitapide exposure Sources: https://pubmed.ncbi.nlm.nih.gov/26120010/ |
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yes | ||||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | ||||
minor | ||||
minor | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes | ||||
yes |
Sample Use Guides
Norgestimate and Ethinyl Estradiol Tablets are dispensed in a blister pack . Norgestimate and Ethinyl Estradiol Tablets USP may be started using either a Day 1 start or a Sunday start. For the first cycle of a Sunday Start regimen, an additional method of contraception should be used until after the first 7 consecutive days of administration.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2335104
The relative affinities of the steroids for cytosolic progestin receptors were assessed by their ability to displace 3H-R5020, a highly specific synthetic progestin, from rabbit uterine receptors. Immature female rabbits were primed with 17 beta-estradiol (5 mcg sc) daily for five days and then sacrificed on day six. The excised uteri were washed and homogenized in ice cold Tris-EDTA buffer (1:5 w/v; pH 7.4). The homogenate was centrifuged at 105,000 x g at 4°C for one hour and the supernatant was used as the cytosolic progestin receptor preparation. Aliquots of the cytosol preparation were incubated with 0.4 nM 3H-R5020 (86.2 Ci/mmole; New England Nuclear) and unlabelled test steroids in Tris-EDTA buffer for 5 hours at 4°C. After incubation, free 3H-R5020 was extracted with dextran-coated charcoal from the bound ligand, and the amount of 3H-R5020 bound to the receptor was determined by liquid scintillation spectrometry. The concentration of the test progestin corresponding to 50% inhibition of total 3H-R5020 binding (IC50) was used as the measure of binding affinity for the progestin receptor. For norgestimate IC50 was found to be 3.4 nM.
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Classification Tree | Code System | Code | ||
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WHO-VATC |
QG03AA11
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NDF-RT |
N0000011301
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NDF-RT |
N0000175602
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WHO-ATC |
G03FA13
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WHO-VATC |
QG03FA13
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NCI_THESAURUS |
C776
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LIVERTOX |
698
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WHO-ATC |
G03AA11
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C66245
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7091
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NORGESTIMATE
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31994
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35189-28-7
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SUB09369MIG
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DTXSID1046922
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m8062
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50815
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1968
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759159
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C017576
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7898
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C291HFX4DY
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C291HFX4DY
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DB00957
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CHEMBL1200934
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All of the following components must be present:
ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE ACTIVE (PARENT)