Aurovela Fe

Name: Aurovela Fe

Aurovela Fe Dosage and Administration

How to Start Aurovela 24 Fe

Aurovela 24 Fe is available in a blister pack [see How Supplied/Storage and Handling (16)]. Aurovela 24 Fe may be started using either a Day 1 start or a Sunday start (see Table 1). For the first cycle of a Sunday Start regimen, an additional method of contraception must be used until after the first 7 consecutive days of administration.

How to Take Aurovela 24 Fe

Table 1: Instructions for Administration of Aurovela 24 Fe
Starting COCs in women not currently using hormonal contraception (Day 1 Start or Sunday Start)
 
Important:
Consider the possibility of ovulation and conception prior to initiation of this product.
 
 
Tablet Color:
·    Aurovela 24 Fe active tablets are light yellow to yellow (Day 1 to Day 24).
·    Aurovela 24 Fe inactive tablets are brown (Day 25 to Day 28).
Day 1 Start:
·    Take first light yellow to yellow active tablet without regard to meals on the first day of menses.
·    Take subsequent active tablets once daily at the same time each day for a total of 24 days.
·    Take one brown inactive tablet daily for 4 days and at the same time of day that active tablets were taken.
·    Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the day after taking the last inactive tablet).
Sunday Start:
For each 28-day course, take in the following order:
·    Take the light yellow to yellow active tablet without regard to meals on the first Sunday after the onset of menses. Due to the potential risk of becoming pregnant, use additional non-hormonal contraception (such as condoms and spermicide) for the first 7 days of the patient’s first cycle pack of Aurovela 24 Fe.
·    Take subsequent active tablets once daily at the same time each day for a total of 24 days.
·    Take one brown tablet (ferrous fumarate) daily for the following 4 days and at the same time of day that active tablets were taken. A scheduled period should occur during the 4 days that the brown tablets are taken.
·     Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the Sunday after taking the last inactive tablet) and additional non-hormonal contraceptive is not needed.
Switching to Aurovela 24 Fe from another oral contraceptive
Start on the same day that a new pack of the previous oral contraceptive would have started.
Switching from another contraceptive method to Aurovela 24 Fe
Start Aurovela 24 Fe:
·    Transdermal patch
·    On the day when next application would have been scheduled.
·    Vaginal ring
·    On the day when next insertion would have been scheduled.
·    Injection
·    On the day when next injection would have been scheduled.
·    Intrauterine contraceptive
·    On the day of removal
·    If the IUD is not removed on first day of the patient’s menstrual cycle, additional non-hormonal contraceptive (such as condoms and spermicide) is needed for the first seven days of the first cycle pack.
·    Implant
·    On the day of removal
Complete instructions on proper tablet usage are located in the FDA-approved patient labeling.  


Starting Aurovela 24 Fe after Abortion or Miscarriage

First-trimester


  • After a first-trimester abortion or miscarriage, Aurovela 24 Fe may be started immediately. An additional method of contraception is not needed if Aurovela 24 Fe is started immediately.

  • If Aurovela 24 Fe is not started within 5 days after termination of the pregnancy, the patient must use additional non-hormonal contraception (such as condoms and spermicide) for the first 7 days of her first 28-day course of Aurovela 24 Fe.

Second-trimester


  • Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start Aurovela 24 Fe following the instructions in Table 1 for Sunday start. Use additional non-hormonal contraception (such as condoms and spermicide) for the first 7 days of the patient’s first 28-day course of Aurovela 24 Fe [see Contraindications (4), Warnings and Precautions (5.1), and FDA-approved Patient Labeling].

Starting Aurovela 24 Fe after Childbirth


  • Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with Aurovela 24 Fe following the instructions in Table 1 for women not currently using hormonal contraception.

  • If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of Aurovela 24 Fe [see Contraindications (4), Warnings and Precautions (5.1), Use in Specific Populations (8.1 and 8.3)].

Missed Tablets


Table 2: Instructions for Missed Aurovela 24 Fe Tablets
  • If one active tablet is missed in Weeks 1, 2 or 3
Take the tablet as soon as possible. Take the next pill at the regular time, and continue taking one tablet a day until the pack is finished. Back-up contraception is not needed
 
  • If two consecutive active tablets are missed in Week 1 or Week 2
Take the two missed tablets as soon as possible and the next two active tablets the next day. Continue taking one tablet a day until the pack is finished. Additional non-hormonal contraception (such as condoms and spermicide) must be used as back-up if the patient has sex within 7 days after missing tablets.
  • If two consecutive active tablets are missed in Week 3 or Week 4 or three or more consecutive active tablets are missed at any time
Day 1 Start: Throw out the rest of the pack and start a new pack that same day.
Sunday Start: Continue taking one tablet a day until Sunday, then throw out the rest of the pack and start a new pack that same day. Additional non-hormonal contraception (such as condoms and spermicide) must be used as back-up if the patient has sex within 7 days after missing tablets.


Advice in Case of Gastrointestinal Disturbances

In case of severe vomiting or diarrhea, absorption may not be complete and additional contraceptive measures must be taken. If vomiting or diarrhea occurs within 3 to 4 hours after taking a light yellow to yellow tablet, handle this as a missed tablet [see FDA-Approved Patient Labeling].

Overdosage

There have been no reports of serious ill effects from overdose of oral contraceptives, including ingestion by children. Overdosage may cause withdrawal bleeding in females and nausea.

Aurovela Fe Description

Aurovela 24 Fe is a combination oral contraceptive for oral administration consisting of active tablets containing norethindrone acetate, a progestin, and ethinyl estradiol, an estrogen, and placebo tablets containing ferrous fumarate, which serve no therapeutic purpose.



  • Each active light yellow to yellow tablet contains 1 mg norethindrone acetate USP and  20 mcg ethinyl estradiol USP. Inactive ingredients include compressible sugar, croscarmellose sodium, D & C Yellow No. 10 Aluminum Lake, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone and vitamin E.

  • Each placebo brown tablet contains 75 mg ferrous fumarate, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, Nat spearmint FL SD #11475, povidone and sucralose. The ferrous fumarate tablets do not serve any therapeutic purpose. Ferrous fumarate tablets are not USP for dissolution and assay.

The chemical name of ethinyl estradiol is 19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol. The molecular formula of ethinyl estradiol is C20H24O2 and the structural formula is:


 


The chemical name of norethindrone acetate is 17-hydroxy-19-nor-17α-pregn-4-en-20-yn-3-one acetate. The molecular formula of norethindrone acetate is C22H28O3 and the structural formula is:


 



 

 

USP Dissolution Test Pending.

Aurovela Fe - Clinical Pharmacology

Mechanism of Action

COCs 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.

Pharmacodynamics

No specific pharmacodynamic studies were conducted with Aurovela 24 Fe.

Pharmacokinetics

Absorption


Norethindrone acetate appears to be completely and rapidly deacetylated to norethindrone after oral administration, because the disposition of norethindrone acetate is indistinguishable from that of orally administered norethindrone. Norethindrone acetate and ethinyl estradiol are rapidly absorbed from Aurovela 24 Fe tablets, with maximum plasma concentrations of norethindrone and ethinyl estradiol occurring 1 to 4 hours postdose. Both are subject to first-pass metabolism after oral dosing, resulting in an absolute bioavailability of approximately 64% for norethindrone and 43% for ethinyl estradiol.

The plasma norethindrone and ethinyl estradiol pharmacokinetics following single- and multiple-dose administrations of Aurovela 24 Fe tablets in 17 healthy female volunteers are provided in Figures 1 and 2, and Table 3.

Following multiple-dose administration of Aurovela 24 Fe tablets, mean maximum concentrations of norethindrone and ethinyl estradiol were increased by 95% and 27%, respectively, as compared to single-dose administration. Mean norethindrone and ethinyl estradiol exposures (AUC values) were increased by 164% and 51% respectively, as compared to single-dose administration of Aurovela 24 Fe tablets.

Steady-state with respect to norethindrone was reached by Day 17 and steady-state with respect to ethinyl estradiol was reached by Day 13.

Mean SHBG concentrations were increased by 150% from baseline (57.5 nmol/L) to    144 nmol/L at steady-state.


Figure 1. Mean Plasma Norethindrone Concentration-Time Profiles Following Single- and Multiple-Dose Oral Administration of Aurovela 24 Fe Tablets to Healthy Female Volunteers Under Fasting Condition (n = 17)



Figure 2. Mean Plasma Ethinyl Estradiol Concentration-Time Profiles Following Single- and Multiple-Dose Oral Administration of Aurovela 24 Fe Tablets to Healthy Female Volunteers Under Fasting Condition (n = 17)


Table 3. Summary of Norethindrone (NE) and Ethinyl Estradiol (EE) Pharmacokinetics Following Single- and Multiple-Dose Oral Administration of Aurovela 24 Fe Tablets to Healthy Female Volunteers Under Fasting Condition (n = 17)

 
Regimen
 
Analyte
 
Arithmetic Meana  (% CV) by Pharmacokinetic Parameter
Cmax (pg/mL)
tmax
(hr)
AUC(0−24) (pg/mL•h)
Cmin (pg/mL)
t½ (hr)
Cavg (pg/mL)
 
 
 
Day 1 (Single Dose)
NE
8420 (31)
1.0
(0.7 to 4.0)
33390 (40)
--
--
--
EE
64.5 (27)
1.3
(0.7 to 4.0)
465.4 (26)
--
--
--
SHBG
--
--
--
57.5
(37)b
--
--
Day 24
(Multiple Dose)
NE
16400 (26)
1.3
(0.7 to 4.0)
88160 (30)
880 (51)
8.4
3670 (30)
EE
81.9 (24)
1.7
(1.0 to 2.0)
701.3
(28)
11.4
(43)
14.5
29.2
(28)
SHBG
--
--
--
144
(24)
--
--

Cmax = Maximum plasma concentration

tmax = Time of Cmax

Cmin = minimum plasma concentration at steady-state

AUC(0−24) = Area under plasma concentration versus time curve from 0 to 24 hours

t½ = Apparent first-order terminal elimination half-life

Cavg = Average plasma concentration = AUC(0–24)/24

% CV = Coefficient of Variation (%)

SHBG = Sex Hormone Binding Globulin (nmol/L)

a The harmonic mean (0.693/mean apparent elimination rate constant) is reported for t½, and the median (range) is reported for tmax.

b The SHBG concentration reported here is the pre-dose concentration.


Food Effect


A single-dose administration of Aurovela 24 Fe tablet with food decreased the maximum concentration of norethindrone by 11% and increased the extent of absorption by 27% and decreased the maximum concentration of ethinyl estradiol by 30% but not the extent of absorption.


Distribution


Volume of distribution of norethindrone and ethinyl estradiol ranges from 2 to 4 L/kg. Plasma protein binding of both steroids is extensive (greater than 95%); norethindrone binds to both albumin and SHBG, whereas ethinyl estradiol binds only to albumin. Although ethinyl estradiol does not bind to SHBG, it induces SHBG synthesis.


Metabolism


Norethindrone 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.


Ethinyl estradiol is also extensively metabolized, both by oxidation and by conjugation with sulfate and glucuronide. Sulfates are the major circulating conjugates of ethinyl estradiol and glucuronides predominate in urine. The primary oxidative metabolite is 2-hydroxy ethinyl estradiol, formed by the CYP3A4 isoform of cytochrome P450. Part of the first-pass metabolism of ethinyl estradiol is believed to occur in gastrointestinal mucosa. Ethinyl estradiol may undergo enterohepatic circulation.


Excretion


Norethindrone and ethinyl estradiol are excreted in both urine and feces, primarily as metabolites. Plasma clearance values for norethindrone and ethinyl estradiol are similar (approximately 0.4 L/hr/kg). Steady-state elimination half-lives of norethindrone and ethinyl estradiol following administration of Aurovela 24 Fe tablets are approximately 8 hours and 14 hours, respectively.

Clinical Studies

In an active-controlled clinical trial, 743 women 18 to 45 years of age were studied to assess the efficacy of Aurovela 24 Fe, for up to six 28-day cycles. The racial demographic of women randomized to Aurovela 24 Fe was: 69.5% Caucasian, 15.5% African-American, 10.4% Hispanic, 2.3% Asian and 2.3% Native American/Other. Women with body mass index (BMI) greater than 35 mg/m2 were excluded from the study. The weight range for those women treated was 90 to 260 pounds, with a mean weight of 147 pounds. Among the women in the study randomized to Aurovela 24 Fe, 38.9% had not used hormonal contraception immediately prior to enrolling in this study.


A total of 583 women completed 6 cycles of treatment. There were a total of 5 on-treatment pregnancies among women aged 18 to 45 years in 3,565 treatment cycles during which no back-up contraception was used. The Pearl Index for Aurovela 24 Fe was 1.82 (95% confidence interval 0.59 to 4.25).

For the Consumer

Applies to ethinyl estradiol / norethindrone: oral capsule liquid filled, oral tablet, oral tablet chewable

Other dosage forms:

  • oral tablet, oral tablet chewable

Along with its needed effects, ethinyl estradiol / norethindrone may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking ethinyl estradiol / norethindrone:

Incidence not known
  • Abdominal or stomach pain
  • absent, missed, or irregular menstrual periods
  • anxiety
  • change in vision
  • changes in skin color
  • chest pain or discomfort
  • chills
  • clay-colored stools
  • constipation
  • cough
  • dark urine
  • diarrhea
  • dizziness or lightheadedness
  • fainting
  • fast heartbeat
  • fever
  • headache
  • hives or welts
  • itching skin
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • loss of appetite
  • medium to heavy, irregular vaginal bleeding between regular monthly periods, which may require the use of a pad or a tampon
  • nausea and vomiting
  • pain or discomfort in the arms, jaw, back, or neck
  • pain, tenderness, or swelling of the foot or leg
  • pains in the chest, groin, or legs, especially in the calves of the legs
  • pounding in the ears
  • rash
  • redness of the skin
  • severe headaches of sudden onset
  • slow or fast heartbeat
  • sudden loss of coordination or slurred speech
  • sudden onset of shortness of breath for no apparent reason
  • sudden shortness of breath or troubled breathing
  • sweating
  • unusual tiredness or weakness
  • vomiting of blood

Some side effects of ethinyl estradiol / norethindrone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Incidence not known
  • Abdominal or stomach cramps
  • bloating
  • blotchy spots on the exposed skin
  • breast enlargement or tenderness
  • discouragement
  • feeling sad or empty
  • irritability
  • itching of the vagina or outside genitals
  • loss of interest or pleasure
  • pain during sexual intercourse
  • thick, white curd-like vaginal discharge without odor or with mild odor
  • tiredness
  • trouble concentrating
  • trouble sleeping
  • trouble wearing contact lenses

Usual Adult Dose for Prevention of Osteoporosis

ethinyl estradiol-norethindrone 5 mcg/1 mg and 2.5 mcg-0.5 mg (Femhrt):

The initial dosage of ethinyl estradiol-norethindrone recommended in patients with an intact uterus for the prevention of osteoporosis is one tablet (5 mcg/1 mg) orally daily.
Comments: When used solely for the prevention of postmenopausal osteoporosis, approved non-estrogen treatments should be carefully considered, and estrogens and combined estrogen-progestin products should only be considered for women with significant risk of osteoporosis that outweighs the risk of the drug. When used solely for the treatment of vulvar and vaginal atrophy, topical vaginal products should be considered. The U.S. Preventive Services Task Force (USPSTF) recommends against the routine use of estrogen and progestin for the prevention of chronic conditions in postmenopausal women

The initial dosage of ethinyl estradiol-norethindrone recommended in patients with an intact uterus for moderate to severe vasomotor symptoms associated with menopause is one tablet (2.5 mcg/ 0.5 mg or 5 mcg/1 mg) orally daily.
Comment: Patients should be reevaluated at 3 to 6 month intervals to determine if treatment is necessary.

Dialysis

Data not available

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