Mono-Linyah

Taking birth control pills can increase your risk of blood clots, stroke, or heart attack. You are even more at risk if you have high blood pressure, diabetes, high cholesterol, or if you are overweight. Your risk of stroke or blood clot is highest during your first year of taking birth control pills. Your risk is also high when you restart birth control pills after not taking them for 4 weeks or longer.

Smoking can greatly increase your risk of blood clots, stroke, or heart attack. Your risk increases the older you are and the more you smoke. You should not take combination birth control pills if you smoke and are over 35 years old.

Do not use if you are pregnant. Stop taking this medicine and tell your doctor if you become pregnant, or if you miss two menstrual periods in a row. If you have recently had a baby, wait at least 4 weeks before taking birth control pills.

You should not take birth control pills if you have:

• untreated or uncontrolled high blood pressure;

• heart disease (coronary artery disease, uncontrolled heart valve disorder, history of heart attack, stroke, or blood clot);

• chest pain;

• unusual vaginal bleeding that has not been checked by a doctor;

• problems with your eyes, kidneys or circulation caused by diabetes;

• a history of hormone-related cancer such as breast or uterine cancer;

• liver cancer;

• a history of jaundice caused by pregnancy or birth control pills; or

• severe migraine headaches (with aura, numbness, weakness, or vision changes).

To make sure birth control pills are safe for you, tell your doctor if you have:

• heart disease, high blood pressure;

• high cholesterol or triglycerides;

• a history of depression;

• gallbladder disease;

• liver or kidney disease;

• diabetes;

• seizures or epilepsy;

• a history of irregular menstrual cycles; or

• a history of fibrocystic breast disease, lumps, nodules, or an abnormal mammogram.

The hormones in birth control pills can pass into breast milk and may harm a nursing baby. This medication may also slow breast milk production. Do not use if you are breast feeding a baby.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using birth control pills and call your doctor at once if you have:

• signs of a stroke--sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance;

• signs of a blood clot in the lung--chest pain, sudden cough, wheezing, rapid breathing, coughing up blood;

• signs of a blood clot in your leg--pain, swelling, warmth, or redness in one or both legs;

• heart attack symptoms--chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating;

• liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

• a change in the pattern or severity of migraine headaches;

• swelling in your hands, ankles, or feet;

• a breast lump; or

• symptoms of depression--sleep problems, weakness, tired feeling, mood changes.

Common side effects may include:

• nausea, vomiting;

• breast tenderness;

• freckles or darkening of facial skin, loss of scalp hair;

• headache, dizziness, nervousness;

• problems with contact lenses;

• changes in weight or appetite;

• irregular menstrual bleeding or spotting;

• vaginal itching or discharge; or

• rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• Store at room temperature.
• Protect from light.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

How to Start Mono-Linyah

Mono-Linyah is dispensed in 28-tablet blister [see How Supplied/Storage and Handling (16)].   Mono-Linyah may be started using either a Day 1 start or a Sunday start (see Table 1). The plastic compact is pre-set for a Sunday start. Day 1 Start day-label stickers are a vailable. F or the first c ycle of a Sunday Start regimen, an additional method of contraception should be used until after the first 7 consecutive days of administration.

How to Take Mono-Linyah

Starting Mono-Linyah after Abortion or Miscarriage

First-trimester

● After a first-trimester abortion or miscarriage, Mono-Linyah may be started immediately. An additional method of contraception is not needed if Mono-Linyah is started immediately.

●    If Mono-Linyah is not started within 5 days after termination of the pregnancy, the patient should use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of her first cycle pack of Mono-Linyah.

Second-trimester

●   Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start Mono-Linyah, following the instructions in Table 1 for Day 1 or Sunday start, as desired. If using Sunday start, use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of the patient's first cycle pack of Mono-Linyah. [See Contraindications (4), Warnings and Precautions (5.1), and FDA-Approved Patient Labeling.]

Starting Mono-Linyah after Childbirth

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

● Mono-Linyah is not recommended for use in lactating women [see Use in Specific Populations (8.3)].

● If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of Mono-Linyah. [See Contraindications (4), Warnings and Precautions (5.1), Use in Specific Populations(8.1 and 8.3), and FDA-Approved Patient Labeling].

Compact Blister Dispenser

If the patient starts pill-taking on Sunday, the first active pill should be taken on the first Sunday after the patient's menstrual period begins. Remove the first active pill at the top of the dispenser (Sunday) by pressing the pill through the blister foil.

If the pa tient will start pill-taking on "Day 1," place a day-label sticker on the compact which starts with the day of the week the patient will take the first pill. Remove the first active pill a t the top of the dispenser (Day 1) by pressing the pill through the blister foil.

Missed Tablets

Advice in Case of Gastrointestinal Disturbances

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

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

Mono-Linyah is a combination oral contraceptive containing the progestational compound norgestimate and the estrogenic compound ethinyl estradiol. Norgestimate is designated as (18,19-Dinor-17-pregn-4-en-20-yn-3-one,17-(acetyloxy)-13-ethyl-,oxime,(17α)-(+)-) and ethinyl estradiol is designated as (19-nor-17α-pregna,1,3,5(10)-trien-20-yne-3,17-diol).

● Each active blue tablet contains 0.25 mg of norgestimate and 0.035 mg of ethinyl estradiol. Inactive ingredients include: FD&C Blue No. 2 Aluminium Lake, FD&C Blue No. 1 Aluminum lake, FD&C Red No. 40 Aluminum Lake, FD&C Yellow No. 10 Aluminum Lake, titanium dioxide, polyvinyl alcohol, talc, macrogol/PEG 3350 NF, lecithin, lactose monohydrate, magnesium stearate and pregelatinized corn starch.

● Each white placebo tablet containing only inert ingredients, as follows: titanium dioxide, polydextrose, hypromellose, triacetin, macrogol/polyethylene glycol, lactose monohydrate, magnesium stearate and pregelatinized corn starch.

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 Mono-Linyah.

Pharmacokinetics

Absorption

Norgestimate (NGM) and EE are rapidly absorbed following oral administration. NGM  is rapidly and completely metabolized by first pass (intestinal and/or hepatic) mechanisms to norelgestromin (NGMN) and norgestrel (NG), which are the major active metabolites of norgestimate.

Peak serum concentrations of NGMN and EE are generally reached by 2 hours after administration of Mono-Linyah. Accumulation following multiple dosing of the 250 mcg NGM / 35 mcg EE dose is approximately 2-fold for NGMN and EE compared with single dose administration. The pharmacokinetics of NGMN is dose-proportional following NGM doses of 180 mcg to 250 mcg. Steady-state concentration of EE is achieved by Day 7 of each dosing cycle. Steady-state concentrations of NGMN and NG are achieved by Day 21. Non-linear accumulation (approximately 8 fold) of NG is observed as a result of high-affinity binding to SHBG, which limits its biological activity (Table 3).

Food Effect

The effect of food on the pharmacokinetics of Mono-Linyah has not been studied.

Distribution

Norelgestromin and norgestrel are highly bound (>97%) to serum proteins. Norelgestromin is bound to albumin and not to SHBG, while norgestrel is bound primarily to SHBG. Ethinyl estradiol is extensively bound (>97%) to serum albumin and induces an increase in the serum concentrations of SHBG.

Metabolism

NGM is extensively metabolized by first-pass mechanisms in the gastrointestinal tract and/or liver. NGM's primary active metabolite is NGMN. Subsequent hepatic metabolism of NGMN occurs and metabolites include NG, which is also active, and various hydroxylated and conjugated metabolites. Although NGMN and its metabolites inhibit a variety of P450 enzymes in human liver microsomes, under the recommended dosing regimen, the in vivo concentrations of NGMN and its metabolites, even at the peak serum levels, are relatively low compared to the inhibitory constant (Ki). EE is also metabolized to various hydroxylated products and their glucuronide and sulfate conjugates.

Excretion

The metabolites of NGMN and EE are eliminated by renal and fecal pathways. Following administration of 14C-norgestimate, 47% (45-49%) and 37% (16-49%) of the administered radioactivity was eliminated in the urine and feces, respectively. Unchanged NGM was not detected in the urine. In addition to 17-deacetyl norgestimate, a number of metabolites of NGM have been identified in human urine following administration of radiolabeled NGM. These include 18, 19-Dinor-17-pregn-4-en-20-yn-3-one,17-hydroxy-13-ethyl,(17α)-(-);18,19-Dinor-5β-17-pregnan-20-yn,3α,17β-dihydroxy-13-ethyl,(17α), various hydroxylated metabolites and conjugates of these metabolites.

See FDA-approved patient labeling (Patient Information and Instructions for Use). Counsel patients about the following information:

● 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].

● Increased risk of VTE compared to non-users of COCs is greatest after initially starting a COC or restarting (following a 4-week or greater pill-free interval) the same or a different COC [see Warnings and Precautions (5.1)].

● Mono-Linyah does not protect against HIV infection (AIDS) and other sexually transmitted infections.

●Mono-Linyah is not to be used during pregnancy; if pregnancy occurs during use of Mono-Linyah instruct the patient to stop further use [see Warnings and Precautions (5.8)].

● Take one tablet daily by mouth at the same time every day. Instruct patients what to do in the event tablets are missed [see Dosage and Administration (2.2)].

● Use a back-up or alternative method of contraception when enzyme inducers are used with Mono-Linyah [see Drug Interactions (7.1)].

● COCs may reduce breast milk production; this is less likely to occur if breastfeeding is well established [see Use in Specific Populations (8.3)].

● Women who start COCs postpartum, and who have not yet had a period, should use an additional method of contraception until they have taken an active tablet for 7 consecutive days [see Dosage and Administration (2.2)].

● Amenorrhea may occur. Consider pregnancy in the event of amenorrhea at the time of the first missed period. Rule out pregnancy in the event of amenorrhea in two or more consecutive cycles [see Warnings and Precautions (5.7)].

Manufactured for:                    Northstar Rx LLC

                                               Memphis, TN 38141

                                               Toll Free 1-800-206-7821

Manufactured by:                    Novast Laboratories Ltd.

                                               Nantong, China 226009

Revised : Oct 2015                                                                              I0020  Rev.C