Triphasil

A synthetic progestational hormone with actions similar to those of progesterone and about twice as potent as its racemic or (+-)-isomer (norgestrel). It is used for contraception, control of menstrual disorders, and treatment of endometriosis.

Triphasil (Levonorgestrel (Triphasil) and Ethinyl estradiol (Triphasil)) is indicated for the prevention of pregnancy in women who elect to use oral contraceptives as a method of contraception.

Oral contraceptives are highly effective. Table II lists the typical accidental pregnancy rates for users of combination oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, the IUD, and Norplant® System, depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates.

Table II: Percentage Of Women Experiencing An Unintended Pregnancy During The First Year Of Typical Use And The First Year Of Perfect Use Of Contraception And The Percentage Continuing Use At The End Of The First Year. United States.

In a clinical trial with Triphasil (Levonorgestrel (Triphasil) and Ethinyl estradiol (Triphasil) tablets), 1,477 subjects had 7,720 cycles of use and a total of 5 pregnancies were reported. This represents an overall pregnancy rate of 0.84 per 100 woman-years. This rate includes patients who did not take the drug correctly. One or more pills were missed during 1,479 (18.8%) of the 7,870 cycles; thus all tablets were taken during 6,391 (81.2%) of the 7,870 cycles. Of the total 7,870 cycles, a total of 150 cycles were excluded from the calculation of the Pearl index due to the use of backup contraception and/or missing 3 or more consecutive pills.

See also: Mirena

Triphasil is a combination birth control pill containing female hormones that prevent ovulation (the release of an egg from an ovary). Triphasil also causes changes in your cervical mucus and uterine lining, making it harder for sperm to reach the uterus and harder for a fertilized egg to attach to the uterus.

Triphasil is used as contraception to prevent pregnancy. There are many brands and forms of this medicine available. Not all brands are listed on this leaflet.

Triphasil may also be used for purposes not listed in this medication guide.

Triphasil® (Levonorgestrel (Triphasil) and Ethinyl estradiol (Triphasil) Tablets USP)

To achieve maximum contraceptive effectiveness, Triphasil must be taken exactly as directed at intervals not exceeding 24-hours.

Triphasil is a monophasic preparation plus 7 inert tablets. The dosage of Triphasil is one tablet daily for 21 consecutive days per menstrual cycle plus 7 peach inert tablets according to the prescribed schedule. It is recommended that Triphasil be taken at the same time each day, preferably after the evening meal or at bedtime. During the first cycle of medication, the patient should be instructed to take one white Triphasil tablet daily and then 7 peach inert tablets for twenty-eight (28) consecutive days, beginning on day one (1) of her menstrual cycle. (The first day of menstruation is day one.) Withdrawal bleeding usually occurs within 3 days following the last white tablet. (If Triphasil is first taken later than the first day of the first menstrual cycle of medication or postpartum, contraceptive reliance should not be placed on Triphasil until after the first 7 consecutive days of administration. The possibility of ovulation and conception prior to initiation of medication should be considered.)

When switching from another oral contraceptive, Triphasil should be started on the first day of bleeding following the last active tablet taken of the previous oral contraceptive. The patient begins her next and all subsequent 28-day courses of Triphasil on the same day of the week that she began her first course, following the same schedule. She begins taking her white tablets on the next day after ingestion of the last peach tablet, regardless of whether or not a menstrual period has occurred or is still in progress.

Anytime a subsequent cycle of Triphasil is started later than the next day, the patient should be protected by another means of contraception until she has taken a tablet daily for seven consecutive days.

If spotting or breakthrough bleeding occurs, the patient is instructed to continue on the same regimen. This type of bleeding is usually transient and without significance, however, if the bleeding is persistent or prolonged, the patient is advised to consult her physician. Although the occurrence of pregnancy is highly unlikely if Triphasil is taken according to directions, if withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed schedule (missed one or more active tablets or started taking them on a day later than she should have), the probability of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken before the medication is resumed. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.

The risk of pregnancy increases with each active (white) tablet missed. For additional patient instructions regarding missed pills, see the "WHAT TO DO IF YOU MISS PILLS" section in the DETAILED PATIENT LABELING below. If breakthrough bleeding occurs following missed tablets, it will usually be transient and of no consequence. If the patient misses one or more peach tablets, she is still protected against pregnancy provided she begins taking white tablets again on the proper day.

In the nonlactating mother, Triphasil may be initiated postpartum, for contraception. When the tablets are administered in the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. It is to be noted that early resumption of ovulation may occur if bromocriptine mesylate has been used for the prevention of lactation.

See also:
What is the most important information I should know about Triphasil?

Do not prescribe Triphasil to women who are known to have the following conditions:

Use Triphasil as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Triphasil. Talk to your pharmacist if you have questions about this information.
• Take Triphasil by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation.
• Do not remove the tablet from the blister packaging until you are ready to take Triphasil.
• Begin taking Triphasil on the first Sunday following the start of your period, unless otherwise directed by your doctor. If your period begins on a Sunday, begin taking Triphasil on that day.
• If you are switching from another form of hormonal birth control to Triphasil, be sure you know when you should start taking Triphasil. Talk with your doctor if you have any questions about how to switch from another form of hormonal birth control to Triphasil.
• Try to take Triphasil at the same time every day, not more than 24 hours apart. After taking the last pill in the pack, start taking the first pill from a new pack the very next day.
• For Triphasil to be effective it must be taken every day. Do not skip doses, even if you are spotting, bleeding, or nauseous. Do not skip pills even if you do not have sex very often.
• If you miss 1 dose of Triphasil, take it as soon as you remember. Take your next dose at the regular time. This means you may take 2 doses on the same day. You do not need to use a backup method of birth control if you only miss 1 pill. If you miss more than 1 dose of Triphasil, read the extra patient information leaflet that comes with Triphasil or contact your doctor for instructions. You must use a backup method of birth control if you miss more than 1 dose of Triphasil. If you are not sure about how to handle missed doses, use an extra form of birth control (eg, condoms) until you talk with your doctor.

Ask your health care provider any questions you may have about how to use Triphasil.

This combination hormone medication is used to prevent pregnancy. It contains 2 hormones: a progestin (Levonorgestrel (Triphasil)) and an estrogen (Ethinyl estradiol (Triphasil)). It works mainly by preventing the release of an egg (ovulation) during your menstrual cycle. It also makes vaginal fluid thicker to help prevent sperm from reaching an egg (fertilization) and changes the lining of the uterus (womb) to prevent attachment of a fertilized egg. If a fertilized egg does not attach to the uterus, it passes out of the body.

Besides preventing pregnancy, birth control pills may make your periods more regular, decrease blood loss and painful periods, decrease your risk of ovarian cysts, and also treat acne.

Using this medication does not protect you or your partner against sexually transmitted diseases (such as HIV, gonorrhea, chlamydia).

How to use Triphasil

Read the Patient Information Leaflet provided by your pharmacist before you start using this product and each time you get a refill. The leaflet contains very important information on when to take your pills and what to do if you miss a dose. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth as directed by your doctor, usually once daily. Pick a time of day that is easy for you to remember, and take your pill at the same time each day.

It is very important to continue taking this medication exactly as prescribed by your doctor. Follow the package instructions to find the first tablet, start with the first tablet in the pack, and take them in the correct order. Do not skip any doses. Pregnancy is more likely if you miss pills, start a new pack late, or take your pill at a different time of the day than usual.

Taking this medication after your evening meal or at bedtime may help if you have stomach upset or nausea with the medication. You may choose to take this medication at another time of day that is easier for you to remember. No matter what dosing schedule you use, it is very important that you take this medication at the same time each day, 24 hours apart. Ask your doctor or pharmacist if you have any questions.

Begin taking this medication on the first Sunday following the beginning of your menstrual period. If your period begins on a Sunday, begin taking this medication on that day. Your pill pack contains 84 estrogen/progestin pills and 7 estrogen-only pills. Take one estrogen/progestin pill daily for 84 days in a row. The day after you finish all the combination pills, start taking one estrogen-only pill daily for 7 days in a row. You should have your period during the week you are taking the estrogen-only pills. The day after you take the last estrogen-only pill, start a new pack whether or not you have your period. If you do not get your period, consult your doctor.

If this is the first time you are using this medication, use an additional form of non-hormonal birth control (such as condoms, spermicide) for the first 7 days to prevent pregnancy until the medication has enough time to work. If you start on the first day of your period, you do not need to use back-up birth control the first week.

Ask your doctor or pharmacist about how to switch from other forms of hormonal birth control (such as patch, other birth control pills) to this product. If any information is unclear, consult the Patient Information Leaflet or your doctor or pharmacist.

See also:
What other drugs will affect Triphasil?

No drug-drug interaction studies were conducted with Triphasil (Levonorgestrel (Triphasil), Ethinyl estradiol (Triphasil)).

Changes in Contraceptive Effectiveness Associated with Co-Administration of Other Products

If a woman on hormonal contraceptives takes a drug or herbal product that induces enzymes, including CYP3A4, that metabolize contraceptive hormones, counsel her to use additional contraception or a different method of contraception. Drugs or herbal products that induce such enzymes may decrease the plasma concentrations of contraceptive hormones, and may decrease the effectiveness of hormonal contraceptives or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include:

• barbiturates
• bosentan
• carbamazepine
• felbamate
• griseofulvin
• oxcarbazepine
• phenytoin
• rifampin
• St. John's wort
• topiramate

HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Significant changes (increase or decrease) in the plasma levels of the estrogen and progestin have been noted in some cases of co-administration of HIV protease inhibitors or with non-nucleoside reverse transcriptase inhibitors.

Antibiotics: There have been reports of pregnancy while taking hormonal contraceptives and antibiotics, but clinical pharmacokinetic studies have not shown consistent effects of antibiotics on plasma concentrations of synthetic steroids.

Consult the labeling of all concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.

Increase in Plasma Levels of Estradiol Associated with Co-Administered Drugs

Co-administration of atorvastatin and certain COCs containing Ethinyl estradiol (Triphasil) increase AUC values for Ethinyl estradiol (Triphasil) by approximately 20%. Ascorbic acid and acetaminophen may increase plasma Ethinyl estradiol (Triphasil) levels, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole or ketoconazole may increase plasma hormone levels.

Changes in Plasma Levels of Co-Administered Drugs

COCs containing some synthetic estrogens (e.g., Ethinyl estradiol (Triphasil)) may inhibit the metabolism of other compounds. COCs have been shown to significantly decrease plasma concentrations of lamotrigine likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Consult the labeling of the concurrently-used drug to obtain further information about interactions with COCs or the potential for enzyme alterations.

See also:
What are the possible side effects of Triphasil?

The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling:

• Serious cardiovascular events and smoking
• Vascular events
• Liver disease

Adverse reactions commonly reported by COC users are:

• Irregular uterine bleeding
• Nausea
• Breast tenderness
• Headache

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The clinical trial that evaluated the safety and efficacy of Triphasil was a 12-month, randomized, multicenter, open-label study, which enrolled women aged 18-40, of whom 1,006 took at least one dose of Triphasil.

Adverse Reactions Leading to Study Discontinuation: 16.3% of the women discontinued from the clinical trial due to an adverse reaction; the most common adverse reactions (≥ 1% of women) leading to discontinuation were irregular and/or heavy uterine bleeding (5.9%), weight gain (2.4%), mood changes (1.5%), and acne (1.0%).

Common Treatment-Emergent Adverse Reactions (≥ 5% of women): irregular and/or heavy uterine bleeding (17%), weight gain (5%), acne (5%).

Serious Adverse Reactions: migraine, cholecystitis, cholelithiasis, pancreatitis, abdominal pain, and major depressive disorder.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Triphasil. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency of establish a causal relationship to drug exposure.

Gastrointestinal disorders: abdominal distension, vomiting

General disorders and administration site conditions: chest pain, fatigue, malaise, edema peripheral, pain

Immune system disorders: hypersensitivity reaction

Investigations: blood pressure increased

Musculoskeletal and connective tissue disorders: muscle spasms, pain in extremity

Nervous system disorders: dizziness, loss of consciousness

Psychiatric disorders: insomnia

Reproductive and breast disorders: dysmenorrhea

Respiratory, thoracic and mediastinal disorders: pulmonary embolism, pulmonary thrombosis

Skin and subcutaneous tissue disorders: alopecia

Vascular disorders: thrombosis