No information provided.
See WARNINGS and PRECAUTIONS.
The following adverse reactions have been observed in women taking progestins:
AYGESTIN (norethindrone acetate tablets USP) is indicated for the treatment of secondary amenorrhea, endometriosis, and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids or uterine cancer. AYGESTIN (norethindrone acetate tablets USP) is not intended, recommended or approved to be used with concomitant estrogen therapy in postmenopaus al women for endometrial protection.
Norethindrone acetate is completely and rapidly deacetylated to norethindrone (NET) after oral administration, and the disposition of norethindrone acetate is indistinguishable from that of orally administered norethindrone. Norethindrone acetate is rapidly absorbed from AYGESTIN tablets, with maximum plasma concentration of norethindrone generally occurring at about 2 hours post-dose. The pharmacokinetic parameters of norethindrone following single oral administration of AYGESTIN in 29 healthy female volunteers are summarized in Table 1.
Table 1: Pharmacokinetic Parameters after a
Single Dose of AYGESTIN® in Healthy Women
| AYGESTIN® (n = 29) Arithmetic Mean ± SD |
|
| Norethindrone (NET) | |
| AUC (0-inf)(ng/ml*h) | 166.90 ± 56.28 |
| Cmax (ng/ml) | 26.19 ± 6.19 |
| tmax (h) | 1.83 ± 0.58 |
| t½ (h) | 8.51 ± 2.19 |
| AUC = area under the curve, Cmax = maximum plasma concentration, tmax = time at maximum plasma concentration, t½ = half-life, SD = standard deviation |
|
Figure 1: Mean Plasma Concentration Profile after a
Single Dose of 5 mg Administered to 29 Healthy Female Volunteers under Fasting
Conditions
The effect of food administration on the pharmacokinetics of AYGESTIN has not been studied.
DistributionNorethindrone is 36% bound to sex hormone-binding globulin (SHBG) and 61% bound to albumin. Volume of distribution of norethindrone is about 4 L/kg.
MetabolismNorethindrone undergoes extensive biotransformation, primarily via reduction, followed by sulfate and glucuronide conjugation. The majority of metabolites in the circulation are sulfates, with glucuronides accounting for most of the urinary metabolites.
ExcretionPlasma clearance value for norethindrone is approximately 0.4 L/hr/kg. Norethindrone is excreted in both urine and feces, primarily as metabolites. The mean terminal elimination half-life of norethindrone following a single dose administration of AYGESTIN is approximately 9 hours.
Norethindrone acetate is contraindicated during pregnancy as it may cause fetal harm when administered to pregnant women. Several reports suggest an association between intrauterine exposure to progestational drugs in the first trimester of pregnancy and congenital abnormalities in male and female fetuses. Some progestational drugs induce mild virilization of the external genitalia of female fetuses.
AYGESTIN® (norethindrone acetate tablets USP) is available as:
5 mg: White, oval, flat-faced, beveled edge, tablet scored on one side. Debossed with 5 AYGESTIN on the unscored side and stylized b / 424 on the scored side. Available in bottles of 50 tablets (NDC 51285-424-10).
Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
Store at 20° to 25°C (68° to 77°F).
KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.
TEVA WOMEN'S HEALTH, INC. Subsidiary of TEVA PHARMACEUTICALS USA, INC. North Wales, PA 19454. Revised: Oct 2015
Patients with risk factors for arterial vascular disease (e.g., hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (e.g., personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately.
Visual AbnormalitiesDiscontinue medication pending examination if there is a sudden partial or complete loss of vision or if there is sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or retinal vascular lesions, medication should be discontinued.
PRECAUTIONS GeneralHealthcare providers are advised to discuss the PATIENT INFORMATION leaflet with patients for whom they prescribe AYGESTIN.
Carcinogenesis, Mutagenesis, And Impairment Of FertilitySome beagle dogs treated with medroxyprogesterone acetate developed mammary nodules. Although nodules occasionally appeared in control animals, they were intermittent in nature, whereas nodules in treated animals were larger and more numerous, and persisted. There is no general agreement as to whether the nodules are benign or malignant. Their significance with respect to humans has not been established.
Pregnancy Category XNorethindrone acetate is contraindicated during pregnancy as it may cause fetal harm when administered to pregnant women. Several reports suggest an association between intrauterine exposure to progestational drugs in the first trimester of pregnancy and congenital abnormalities in male and female fetuses. Some progestational drugs induce mild virilization of the external genitalia of female fetuses.
Nursing MothersDetectable amounts of progestins have been identified in the milk of mothers receiving them. Caution should be exercised when progestins are administered to a nursing woman.
Pediatric UseAYGESTIN tablets are not indicated in children.
Therapy with AYGESTIN must be adapted to the specific indications and therapeutic response of the individual patient.
Secondary amenorrhea, abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology
2.5 to 10 mg AYGESTIN may be given daily for 5 to 10 days to produce secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen. Progestin withdrawal bleeding usually occurs within three to seven days after discontinuing AYGESTIN therapy. Patients with a past history of recurrent episodes of abnormal uterine bleedingmay benefit from planned menstrual cycling with AYGESTIN.
EndometriosisInitial daily dosage of 5 mg AYGESTIN for two weeks. Dosage should be increased by 2.5 mg per day every two weeks until 15 mg per day of AYGESTIN is reached. Therapy may be held at this level for six to nine months or until annoying breakthrough bleeding demands temporary termination.
See WARNINGS and PRECAUTIONS.
The following adverse reactions have been observed in women taking progestins:
The following laboratory test results may be altered by the use of estrogen/progestin combination drugs:
