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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 practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
Adverse events reported in controlled clinical studies of norethindrone acetate and ethinyl estradiol are shown in Table 6 below.
Table 6: All Treatment-Emergent Adverse Events
Reported at a Frequency of ≥ 5% of Patients with Norethindrone Acetate and
|BODY SYSTEM/ Adverse Event||Percent of Patients (%)|
N = 247
|Norethindrone Acetate and Ethinyl Estradiol, 0.5/2.5
N = 244
|Norethindrone Acetate and Ethinyl Estradiol, 1/5
N = 258
|BODY AS A WHOLE||40.1||38.5||39.5|
|Nausea and/or Vomiting||5.3||5.3||7.4|
|Urinary Tract Infection||3.2||3.7||6.2|
Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting; increase in size of uterine leiomyomata, vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; ovarian cancer; endometrial hyperplasia; endometrial cancer.
Retinal vascular thrombosis, intolerance to contact lenses.
Central Nervous Sys tem
Increase or decrease in weight; reduced carbohydrate tolerance; aggravation of porphyria; edema; arthalgias; leg cramps; changes in libido; urticaria, angioedema, anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of asthma; increased triglycerides.
Read the Jinteli (norethindrone acetate and ethinyl estradiol tablets, usp) Side Effects Center for a complete guide to possible side effects
Drug/Laboratory Test Interactions
The following drug/laboratory interactions have been observed with estrogen therapy, and/or norethindrone acetate and ethinyl estradiol:
- In a 12-week study, norethindrone acetate and ethinyl estradiol 0.5/2.5 and norethindrone acetate and ethinyl estradiol 1/5 decreased Factor VII, and norethindrone acetate and ethinyl estradiol 1/5 decreased plasminogen activator inhibitor-1 from baseline in a dose-related manner but remained within the laboratory reference range for postmenopausal women. Mean levels of fibrinogen and partial thromboplastin time changed minimally from baseline for norethindrone acetate and ethinyl estradiol 0.5/2.5 and norethindrone acetate and ethinyl estradiol 1/5.
- Estrogen therapy may increase thyroxine-binding globulin (TBG), leading to increased circulating total thyroid hormone (T4) as measured by protein-bound iodine (PBI), T4 levels (by column or radioimmunoassay), or T3 levels by radioimmunoassay. T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Patients on thyroid replacement therapy may require higher doses of thyroid hormone.
- Estrogen therapy may elevate other binding proteins in serum, i.e., corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG), leading to increased circulating corticosteroids and sex steroids, respectively. Free hormone concentrations may be decreased. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin). Norethindrone acetate and ethinyl estradiol 0.5/2.5 and norethindrone acetate and ethinyl estradiol 1/5 were associated with an SHBG increase of 15% and 22%, respectively.
- Estrogen therapy increases plasma HDL and HDL subfraction concentrations, reduces LDL cholesterol concentration and increases triglyceride levels.
- Estrogen therapy is associated with impaired glucose tolerance.
- Estrogen therapy reduces response to metyrapone test.
No drug-drug interaction studies have been conducted with norethindrone acetate and ethinyl estradiol.
In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4 such as St. John's Wort preparations (Hypericum perforatum), Phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, intraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects.
The following section contains information on drug interactions with ethinyl estradiol-containing products (specifically, oral contraceptives) that have been reported in the public literature. It is unknown whether such interactions occur with norethindrone acetate and ethinyl estradiol or drug products containing other types of estrogens.
The Effect of Ethinyl Estradiol on Other Drugs
Drug products containing ethinyl estradiol may inhibit the metabolism of other compounds. Increased plasma concentrations of cyclosporin, prednisolone, and theophylline have been reported with concomitant administration of certain drugs containing ethinyl estradiol (e.g., oral contraceptives containing ethinyl estradiol). In addition, drugs containing ethinyl estradiol may induce the conjugation of other compounds.
Decreased plasma concentrations of acetaminophen and increased clearance of temazapam, salicylic acid, morphine, and clofibric acid have been noted when these drugs were administered with certain ethinyl-estradiol containing drug products (e.g., oral contraceptives containing ethinyl estradiol).This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 3/31/2014
Additional Jinteli Information
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