Tri-Lo-Sprintec

In the U.S.

• Estarylla
• MonoNessa
• Ortho-Cyclen
• Ortho Tri-Cyclen
• Ortho Tri-Cyclen Lo
• Previfem
• Sprintec
• Tri-Lo-Sprintec
• TriNessa
• TriNessa 28
• Tri-Previfem
• Tri-Sprintec

Available Dosage Forms:

• Tablet

Therapeutic Class: Triphasic Contraceptive Combination

Pharmacologic Class: Estrogen

Ethinyl estradiol and norgestimate combination is used to prevent pregnancy. It is a birth control pill that contains two types of hormones, ethinyl estradiol and norgestimate, and when taken properly, prevents pregnancy. It works by stopping a woman's egg from fully developing each month. The egg can no longer accept a sperm and fertilization is prevented.

Ethinyl estradiol and norgestimate combination is also used to treat moderate acne in females (at least 15 years of age) who started having menstrual period and also wants to use this medicine for birth control.

No contraceptive method is 100 percent effective. Birth control methods such as having surgery to become sterile or not having sex are more effective than birth control pills. Discuss your options for birth control with your doctor.

This medicine does not prevent HIV infection or other sexually transmitted diseases. It will not help as emergency contraception, such as after unprotected sexual contact.

This medicine is available only with your doctor's prescription.

• Tell all of your health care providers that you take Tri-Lo-Sprintec. This includes your doctors, nurses, pharmacists, and dentists.
• This medicine may raise the chance of blood clots, a stroke, or a heart attack. Talk with the doctor.
• Talk with your doctor if you will need to be still for long periods of time like long trips, bedrest after surgery, or illness. Not moving for long periods may raise your chance of blood clots.
• If you have high blood sugar (diabetes), talk with your doctor. This medicine may raise blood sugar.
• Check your blood sugar as you have been told by your doctor.
• Have your blood pressure checked often. Talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Be sure to have regular breast exams and gynecology check-ups. Your doctor will tell you how often to have these. You will also need to do breast self-exams as your doctor has told you. Talk with your doctor.
• If you drink grapefruit juice or eat grapefruit often, talk with your doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
• Certain drugs, herbal products, or health problems could cause Tri-Lo-Sprintec to not work as well. Be sure your doctor knows about all of your drugs and health problems.
• This medicine does not stop the spread of diseases like HIV or hepatitis that are passed through blood or having sex. Do not have any kind of sex without using a latex or polyurethane condom. Do not share needles or other things like toothbrushes or razors. Talk with your doctor.
• Do not use in children who have not had their first menstrual period.
• If you have any signs of pregnancy or if you have a positive pregnancy test, call your doctor right away.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Follow how to use as you have been told by the doctor or read the package insert.
• Take Tri-Lo-Sprintec at the same time of day.
• Take with or without food. Take with food if it causes an upset stomach.
• If you also take colesevelam, take it at least 4 hours after you take this medicine.
• Do not skip doses, even if you do not have sex very often.
• If you throw up or have diarrhea, Tri-Lo-Sprintec may not work as well to prevent pregnancy. If this happens within 3 to 4 hours after you take an active tablet, take another tablet. If it goes on for more than 1 day, use an extra form of birth control and call your doctor. Call your doctor if you throw up or have diarrhea and are not sure what to do.
• If you miss 2 periods in a row, take a pregnancy test before starting a new cycle.

What do I do if I miss a dose?

• If a dose is missed, check the package insert or call the doctor to find out what to do. If using this medicine to prevent pregnancy, another form of birth control may need to be used for some time to prevent pregnancy.

How to Start Tri-Lo-Sprintec

Tri-Lo-Sprintec is dispensed in a blister pack tablet dispenser [see How Supplied/Storage and Handling (Table 1). For the first cycle 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 Tri-Lo-Sprintec

Table 1: Instructions for Administration of Tri-Lo-Sprintec
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: • Tri-Lo-Sprintec active tablets are gray (Day 1 to Day 7), light blue (Day 8 to Day 15) and blue (Day 16 to Day 21)	Day 1 Start: • Take first 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 21 days. • Take one white inactive tablet daily for 7 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: • Take first 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 seven days of the patient’s first cycle pack of Tri-Lo-Sprintec. • Take subsequent active tablets once daily at the same time each day for a total of 21 days. • Take one white inactive tablet daily for the following 7 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 Sunday after taking the last inactive tablet) and additional non-hormonal contraceptive is not needed.
Switching to Tri-Lo-Sprintec 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 Tri-Lo-Sprintec	Start Tri-Lo-Sprintec:
• 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 to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling.

Starting Tri-Lo-Sprintec after Abortion or Miscarriage

First-trimester

• After a first-trimester abortion or miscarriage, Tri-Lo-Sprintec may be started immediately. An additional method of contraception is not needed if Tri-Lo-Sprintec is started immediately. • If Tri-Lo-Sprintec 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 Tri-Lo-Sprintec.

Second-trimester

• Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start Tri-Lo-Sprintec, 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 Tri-Lo-Sprintec. [See Contraindications (4), Warnings and Precautions (5.1), and FDA-Approved Patient Labeling.]

Starting Tri-Lo-Sprintec after Childbirth

• Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with Tri-Lo-Sprintec following the instructions in Table 1 for women not currently using hormonal contraception. • Tri-Lo-Sprintec 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 Tri-Lo-Sprintec. [See Contraindications (4), Warnings and Precautions (5.1), Use in Specific Populations (8.1 and 8.3), and FDA-Approved Patient Labeling].

How to Use the Blister Cards

There are two ways to start taking birth control pills, Sunday Start or Day 1 Start. Your healthcare professional will tell you which to use.

1. Pick the Days of the Week Sticker that starts the first day of your period. (This is the day you begin bleeding or spotting, even if it is midnight when bleeding begins.) When you have picked the right sticker, throw away the others and place the sticker on the blister card over the pre-printed days of the week and make sure it lines up with the pills. 2. Your blister package consists of three parts, the foil pouch, wallet, and a blister pack containing 28 individually sealed pills. Note that the pills are arranged in four numbered rows of 7 pills, with the pre-printed days of the week printed above them. There are 7 gray “active” pills, 7 light blue “active” pills, 7 blue “active” pills, and 7 white “reminder” pills. Refer to the sample of the blister card below: 3. After taking the last white pill, start a new blister card the very next day no matter when your period started. You will be taking a pill every day without interruption. Anytime you start the pills later than directed, protect yourself by using another method of birth control until you have taken a pill a day for seven consecutive days. After taking the last white pill, start taking the first gray pill from the blister card the very next day. 4. Take the pills in each new package as before. Start with the gray pill on row #1 and take one pill each day, left to right, until the last white pill has been taken.

Three Ways to Remember in What Order to Take the Pills

1. Follow the sticker with the days of the week (placed above the pills). 2. Always go from left to right. 3. Always finish all your pills.

Missed Tablets

Table 2: Instructions for Missed Tri-Lo-Sprintec Tablets
• If one active tablet is missed in Weeks 1, 2, or 3	Take the tablet as soon as possible. Continue taking one tablet a day until the pack is finished.
• If two 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) should be used as back‑up if the patient has sex within 7 days after missing tablets.
• If two active tablets are missed in the third week or three or more active tablets are missed in a row in Weeks 1, 2, or 3	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) should 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 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].

Do not prescribe Tri-Lo-Sprintec to women who are known to have the following conditions:

• A high risk of arterial or venous thrombotic diseases. Examples include women who are known to: ∘ Smoke, if over age 35 [see Boxed Warning and Warnings and Precautions (5.1)] ∘ Have deep vein thrombosis or pulmonary embolism, now or in the past [see Warnings and Precautions (5.1)] ∘ Have inherited or acquired hypercoagulopathies [see Warnings and Precautions (5.1)] ∘ Have cerebrovascular disease [see Warnings and Precautions (5.1)] ∘ Have coronary artery disease [see Warnings and Precautions (5.1)] ∘ Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see Warnings and Precautions (5.1)] ∘ Have uncontrolled hypertension [see Warnings and Precautions (5.3)] ∘ Have diabetes mellitus with vascular disease [see Warnings and Precautions (5.5)] ∘ Have headaches with focal neurological symptoms or migraine headaches with aura [see Warnings and Precautions (5.6)] ▪ Women age 35 with any migraine headaches [see Warnings and Precautions (5.6)] • Liver tumors, benign or malignant, or liver disease [see Warnings and Precautions (5.2)] • Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (5.7)] • Pregnancy, because there is no reason to use COCs during pregnancy [see Warnings and Precautions (5.8) and Use in Specific Populations (8.1)] • Breast cancer or other estrogen- or progestin-sensitive cancer, now or in the past [see Warnings and Precautions (5.10)]

Pregnancy

There is little or no increased risk of birth defects in women who inadvertently use COCs during early pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb reduction defects) following exposure to low dose COCs prior to conception or during early pregnancy.

Do not administer COCs to induce withdrawal bleeding as a test for pregnancy. Do not use COCs during pregnancy to treat threatened or habitual abortion.

Nursing Mothers

Advise the nursing mother to use other forms of contraception, when possible, until she has weaned her child. COCs can reduce milk production in breastfeeding mothers. This is less likely to occur once breastfeeding is well-established; however, it can occur at any time in some women. Small amounts of oral contraceptive steroids and/or metabolites are present in breast milk.

Pediatric Use

Safety and efficacy of Tri-Lo-Sprintec tablets have been established in women of reproductive age. Efficacy is expected to be the same for post-pubertal adolescents under the age of 18 and for users 18 years and older. Use of this product before menarche is not indicated.

Geriatric Use

Tri-Lo-Sprintec has not been studied in postmenopausal women and is not indicated in this population.

Hepatic Impairment

The pharmacokinetics of Tri-Lo-Sprintec has not been studied in subjects with hepatic impairment. However, steroid hormones may be poorly metabolized in patients with hepatic impairment. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded. [See Contraindications (4) and Warnings and Precautions (5.2).]

Renal Impairment

The pharmacokinetics of Tri-Lo-Sprintec has not been studied in women with renal impairment.

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.

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 Tri-Lo-Sprintec.

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 NGM.

Mean pharmacokinetic parameters for NGMN, NG and EE during three cycles of administration of Tri-Lo-Sprintec are summarized in Table 3.

Peak serum concentrations of NGMN and EE were generally reached by 2 hours after administration of Tri-Lo-Sprintec. Accumulation following multiple dosing of the 0.180 mg NGM / 0.025 mg EE dose is approximately 1.5 to 2 fold for NGMN and approximately 1.5 fold for EE compared with single dose administration, in agreement with that predicted based on linear kinetics of NGMN and EE. The pharmacokinetics of NGMN is dose proportional following NGM doses of 0.180 to 0.250 mg. Steady-state conditions for NGMN following each NGM dose and for EE were achieved during the three cycle study. Non-linear accumulation (4.5 to 14.5 fold) of NG was observed as a result of high affinity binding to SHBG, which limits its biological activity.

Table 3 Summary of NGMN, NG and EE pharmacokinetic parameters.

Table 3: Mean (SD) Pharmacokinetic Parameters of Tri-Lo-Sprintec During a Three Cycle Study

* NGMN = Norelgestromin, NG = norgestrel, EE = ethinyl estradiol † Cmax = peak serum concentration, tmax = time to reach peak serum concentration, AUC0-24h = area under serum concentration vs. time curve from 0 to 24 hours, t1/2 = elimination half-life. ‡ units for NGMN and NG – Cmax = ng/mL, AUC0-24h = h•ng/mL § units for all analytes; h = hours ¶ units for EE only – Cmax = pg/mL, AUC0-24h = h•pg/mL
Analyte*	Cycle	Day	Cmax	tmax (h)	AUC0-24h	t1/2 (h)
NGMN(†-‡)	1	1	0.91 (0.27)	1.8 (1)	5.86 (1.54)	NC
	3	7	1.42 (0.43)	1.8 (0.7)	11.3 (3.2)	NC
		14	1.57 (0.39)	1.8 (0.7)	13.9 (3.7)	NC
		21	1.82 (0.54)	1.5 (0.7)	16.1 (4.8)	28.1 (10.6)
NG(†-‡)	1	1	0.32 (0.14)	2 (1.1)	2.44 (2.04)	NC
	3	7	1.64 (0.89)	1.9 (0.9)	27.9 (18.1)	NC
		14	2.11 (1.13)	4 (6.3)	40.7 (24.8)	NC
		21	2.79 (1.42)	1.7 (1.2)	49.9 (27.6)	36.4 (10.2)
EE(†,§,¶)	1	1	55.6 (18.1)	1.7 (0.5)	421 (118)	NC
	3	7	91.1 (36.7)	1.3 (0.3)	782 (329)	NC
		14	96.9 (38.5)	1.3 (0.3)	796 (273)	NC
		21	95.9 (38.9)	1.3 (0.6)	771 (303)	17.7 (4.4)

NC = not calculated

Food Effect

The effect of food on the pharmacokinetics of Tri-Lo-Sprintec has not been studied.

Distribution

NGMN and NG are highly bound (>97%) to serum proteins. NGMN is bound to albumin and not to SHBG, while NG is bound primarily to SHBG. EE 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

Following 3 cycles of administration of Tri-Lo-Sprintec, the mean (± SD) elimination half-life values, at steady-state, for NGMN, NG and EE were 28.1 (± 10.6) hours, 36.4 (± 10.2) hours and 17.7 (± 4.4) hours, respectively (Table 2). The metabolites of NGMN and EE are eliminated by renal and fecal pathways.

Use in Specific Populations

Effects of Body Weight, Body Surface Area, and Age

The effects of body weight, body surface area, age and race on the pharmacokinetics of NGMN, NG and EE were evaluated in 79 healthy women using pooled data following single dose administration of NGM 0.180 or 0.250 mg / EE 0.025 mg tablets in four pharmacokinetic studies. Increasing body weight and body surface area were each associated with decreases in Cmax and AUC0-24h values for NGMN and EE and increases in CL/F (oral clearance) for EE. Increasing body weight by 10 kg is predicted to reduce the following parameters: NGMN Cmax by 9% and AUC0-24h by 19%, NG Cmax by 12% and AUC0-24h by 46%, EE Cmax by 13% and AUC0-24h by 12%. These changes were statistically significant. Increasing age was associated with slight decreases (6% with increasing age by 5 years) in Cmax and AUC0-24h for NGMN and were statistically significant, but there was no significant effect for NG or EE. Only a small to moderate fraction (5 to 40%) of the overall variability in the pharmacokinetics of NGMN and EE following Tri-Lo-Sprintec tablets may be explained by any or all of the above demographic parameters.

How Supplied

Tri-Lo-Sprintec® 28 (norgestimate and ethinyl estradiol tablets USP) is packaged in cartons of three blister cards (NDC: 0093-2140-62). Each of the 7 gray tablets contains 0.18 mg of the progestational compound, norgestimate, USP together with 0.025 mg of the estrogenic compound, ethinyl estradiol, USP and available as round, film-coated, biconvex, unscored tablets, debossed with stylized b on one side and 451 on the other side; Each of the 7 light blue tablets contains 0.215 mg of the progestational compound, norgestimate, USP together with 0.025 mg of the estrogenic compound, ethinyl estradiol, USP and available as round, film-coated, biconvex, unscored tablets, debossed with stylized b on one side and 452 on the other side; Each of the 7 blue tablets contains 0.25 mg of the progestational compound, norgestimate, USP together with 0.025 mg of the estrogenic compound, ethinyl estradiol, USP and available as round, film-coated, biconvex, unscored tablets, debossed with stylized b on one side and 453 on the other side. The 7 placebo tablets are white, round, biconvex, unscored, placebo tablets, debossed with stylized b on one side and 208 on the other side.

Storage Conditions

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

PROTECT FROM LIGHT.

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.