Blisovi Fe 1/20: Package Insert and Label Information (Page 3 of 7)

Lupin Pharmaceuticals, Inc. 31 March 2023

8. Interactions with Laboratory Tests

Certain endocrine and liver function tests and blood components may be affected by oral contraceptives:

Increased prothrombin and factors VII, VIII, IX, and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregability.
Increased thyroid binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T₄ by column or by radioimmunoassay. Free T₃ resin uptake is decreased, reflecting the elevated TBG; free T₄ concentration is unaltered.
Other binding proteins may be elevated in serum.
Sex-binding globulins are increased and result in elevated levels of total circulating sex steroids and corticoids; however, free or biologically active levels remain unchanged.
Triglycerides may be increased.
Glucose tolerance may be decreased.
Serum folate levels may be depressed by oral contraceptive therapy. This may be of clinical significance if a woman becomes pregnant shortly after discontinuing oral contraceptives.

9. Carcinogenesis

See WARNINGS section.

10. Pregnancy

Discontinue Blisovi Fe 1/20 if pregnancy occurs because there is no reason to use COCs in pregnancy. See WARNINGS sections.

11. Lactation

Small amounts of oral contraceptive steroids have been identified in human milk, and a few adverse effects on the child have been reported, including jaundice and breast enlargement. In addition, oral contraceptives given in the postpartum period may interfere with lactation by decreasing the quantity and quality of breast milk. If possible, the nursing mother should be advised not to use oral contraceptives but to use other forms of contraception until she has completely weaned her child.

12. Pediatric Use

Safety and efficacy of Blisovi Fe 1/20 have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of this product before menarche is not indicated.

PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (PATIENT PACKAGE INSERT BRIEF SUMMARY and DETAILED PATIENT PACKAGE INSERT).

Counsel patients that cigarette smoking increases the risk of serious cardiovascular events from COC use, and that women who are over 35 years old and smoke should not use COCs (see BOXED WARNING and CONTRAINDICATIONS).
Counsel patients that the increased risk of venous thromboembolism compared to non-users of CHCs is greatest after initially starting a CHC or restarting (following a 4-week or greater interruption in intake) the same or a different CHC (see WARNINGS).
Counsel patients that this product does not protect against HIV-infection (AIDS) and other sexually transmitted infections.
Counsel patients to take one tablet daily by mouth at the same time every day. Instruct patients what to do in the event pills are missed (see DOSAGE AND ADMINISTRATION).
Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with COCs (see PRECAUTIONS).
Counsel patients who are breastfeeding or who desire to breastfeed that COCs may reduce breast milk production. This is less likely to occur if breastfeeding is well established (see PRECAUTIONS).
Counsel any patient who starts Blisovi Fe 1/20 postpartum, and who has not yet had a period, to use an additional method of contraception until she has taken a light-orange tablet for 7 consecutive days (see DOSAGE AND ADMINISTRATION).
Counsel patients that amenorrhea may occur. Pregnancy should be considered in the event of amenorrhea, and should be ruled out if amenorrhea is associated with symptoms of pregnancy, such as morning sickness or unusual breast tenderness (see WARNINGS).
Counsel patients with a history of depression that depression may reoccur. Women should contact their healthcare provider if depression occurs (see WARNINGS).

ADVERSE REACTIONS

An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see WARNINGS section):

Thrombophlebitis
Arterial thromboembolism
Pulmonary embolism
Myocardial infarction
Cerebral hemorrhage
Cerebral thrombosis
Hypertension
Gallbladder disease
Hepatic adenomas or benign liver tumors

Post Marketing 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) (70-74).

Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 1) (70,73,75). 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.

FIGURE 1: RELEVANT STUDIES OF RISK OF BREAST CANCER WITH COMBINED ORAL CONTRACEPTIVES

(click image for full-size original)

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.

There is evidence of an association between the following conditions and the use of oral contraceptives, although additional confirmatory studies are needed:

Mesenteric thrombosis
Retinal thrombosis

The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug-related:

Nausea
Vomiting
Gastrointestinal symptoms (such as abdominal cramps and bloating)
Breakthrough bleeding
Spotting
Change in menstrual flow
Amenorrhea
Temporary infertility after discontinuation of treatment
Edema
Melasma which may persist
Breast changes: tenderness, enlargement, secretion
Change in weight (increase or decrease)
Change in cervical erosion and secretion
Diminution in lactation when given immediately postpartum
Cholestatic jaundice
Migraine
Rash (allergic)
Depression
Reduced tolerance to carbohydrates
Vaginal candidiasis
Change in corneal curvature (steepening)
Intolerance to contact lenses

The following adverse reactions have been reported in users of oral contraceptives and the association has been neither confirmed nor refuted:

Pre-menstrual syndrome
Cataracts
Changes in appetite
Cystitis-like syndrome
Headache
Nervousness
Dizziness
Hirsutism
Loss of scalp hair
Erythema multiforme
Erythema nodosum
Hemorrhagic eruption
Vaginitis
Porphyria
Impaired renal function
Hemolytic uremic syndrome
Budd-Chiari syndrome
Acne
Changes in libido
Colitis

OVERDOSAGE

Serious ill effects have not been reported following acute ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea, and withdrawal bleeding may occur in females.

NON-CONTRACEPTIVE HEALTH BENEFITS

The following non-contraceptive health benefits related to the use of oral contraceptives are supported by epidemiological studies which largely utilized oral contraceptive formulations containing estrogen doses exceeding 0.035 mg of ethinyl estradiol or 0.05 mg of mestranol (76-81). Effects on menses:

Increased menstrual cycle regularity
Decreased blood loss and decreased incidence of iron deficiency anemia
Decreased incidence of dysmenorrhea

Effects related to inhibition of ovulation:

Decreased incidence of functional ovarian cysts
Decreased incidence of ectopic pregnancies

Effects from long-term use:

Decreased incidence of fibroadenomas and fibrocystic disease of the breast
Decreased incidence of acute pelvic inflammatory disease
Decreased incidence of endometrial cancer
Decreased incidence of ovarian cancer

DOSAGE AND ADMINISTRATION

The blister has been designed to make oral contraceptive dosing as easy and as convenient as possible. The tablets are arranged in four rows of seven tablets each, with the days of the week appearing on the blister above the first row of tablets.

Note: Each blister has been preprinted with the days of the week, starting with Sunday, to facilitate a Sunday-Start regimen. Six different day label strips have been provided with the Detailed Patient & Brief Summary Patient Package Insert in order to accommodate a Day-1 Start regimen. If the patient is using the Day-1 Start regimen, she should place the self-adhesive day label strip that corresponds to her starting day over the preprinted days.

Important: The patient should be instructed to use an additional method of protection until after the first week of administration in the initial cycle when utilizing the Sunday-Start regimen.

The possibility of ovulation and conception prior to initiation of use should be considered.

Dosage and Administration for 28-Day Dosage Regimen

To achieve maximum contraceptive effectiveness, Blisovi Fe 1/20 should be taken exactly as directed and at intervals not exceeding 24 hours.

Blisovi Fe 1/20 provides a continuous administration regimen consisting of 21 yellow tablets of norethindrone acetate and ethinyl estradiol, 1 mg/0.02 mg and 7 brown non-hormone containing tablets of ferrous fumarate. The ferrous fumarate tablets are present to facilitate ease of drug administration via a 28-day regimen and do not serve any therapeutic purpose. There is no need for the patient to count days between cycles because there are no “off-tablet days.”

1. Sunday-Start Regimen: The patient begins taking the first yellow tablet from the top row of the blister (labeled Sunday) on the first Sunday after menstrual flow begins. When the menstrual flow begins on Sunday, the first yellow tablet is taken on the same day. The patient takes one yellow tablet daily for 21 days. The last yellow tablet in the blister will be taken on a Saturday. Upon completion of all 21 yellow tablets, and without interruption, the patient takes one brown tablet daily for 7 days. Upon completion of this first course of tablets, the patient begins a second course of 28-day tablets, without interruption, the next day (Sunday), starting with the Sunday yellow tablet in the top row. Adhering to this regimen of one yellow tablet daily for 21 days, followed without interruption by one brown tablet daily for seven days, the patient will start all subsequent cycles on a Sunday.

2 Day-1 Start Regimen: The first day of menstrual flow is Day 1. The patient places the self-adhesive day label strip that corresponds to her starting day over the preprinted days on the blister. She starts taking one yellow tablet daily, beginning with the first yellow tablet in the top row. After the last yellow tablet (at the end of the third row) has been taken, the patient will then take the brown tablets for a week (7 days). For all subsequent cycles, the patient begins a new 28 tablet regimen on the eighth day after taking her last yellow tablet, again starting with the first tablet in the top row after placing the appropriate day label strip over the preprinted days on the blister. Following this regimen of 21 yellow tablets and 7 brown tablets, the patient will start all subsequent cycles on the same day of the week as the first course.

Tablets should be taken regularly with a meal or at bedtime. It should be stressed that efficacy of medication depends on strict adherence to the dosage schedule.

Special Notes on Administration

Menstruation usually begins two or three days, but may begin as late as the fourth or fifth day, after the brown tablets have been started. In any event, the next course of tablets should be started without interruption. If spotting occurs while the patient is taking yellow tablets, continue medication without interruption.

If the patient forgets to take one or more yellow tablets, the following is suggested:

One tablet is missed

• take tablet as soon as remembered

• take next tablet at the regular time

Two consecutive tablets are missed (week 1 or week 2)

• take two tablets as soon as remembered

• take two tablets the next day