Combipatch transdermal

You should not use this medicine if you are allergic to estradiol or norethindrone, or if you have:

• a history of heart attack, stroke, or blood clot (especially in your lung or your lower body);

• liver disease;

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

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

• a bleeding or blood-clotting disorder;

• if you have had a hysterectomy; or

• if you are pregnant or may become pregnant.

Estradiol and norethindrone should not be used to prevent heart disease, stroke, or dementia, because this medicine may actually increase your risk of developing these conditions. Long-term use may also increase your risk of breast cancer or blood clot. Talk with your doctor about your individual risks before using this medicine long-term.

To make sure this medicine is safe for you, tell your doctor if you have:

• unusual vaginal bleeding;

• heart disease;

• risk factors for coronary artery disease (such as diabetes, lupus, smoking, being overweight, having high blood pressure or high cholesterol, having a family history of coronary artery disease);

• liver or kidney disease;

• hereditary angioedema;

• lupus;

• asthma;

• epilepsy or other seizure disorder;

• migraines;

• porphyria;

• gallbladder disease;

• endometriosis or uterine fibroid tumors;

• a thyroid disorder; or

• high levels of calcium levels in your blood (hypercalcemia).

Do not use estradiol and norethindrone if you are pregnant. Tell your doctor right away if you become pregnant during treatment.

Estradiol and norethindrone can pass into breast milk. This medicine may slow breast milk production. Do not use if you are breast-feeding a baby.

Grapefruit and grapefruit juice may interact with this medicine and lead to unwanted side effects. Discuss the use of grapefruit products with your doctor.

This medication contains 2 female hormones: an estrogen (estradiol) and a progestin (norethindrone). It is used by women to help reduce symptoms of menopause (such as hot flashes, vaginal dryness). These symptoms are caused by the body making less estrogen. The progestin in this medication helps to reduce the risk of cancer of the uterus which can be caused by using estrogen. Women who have had their uterus removed do not need the progestin and therefore should not use this combination medication. This medication may also be used by women who are not able to produce enough estrogen (for example, due to hypogonadism, primary ovarian failure).

If you are using this medication to treat symptoms only in and around the vagina, products applied directly inside the vagina should be considered before medications that are taken by mouth, absorbed through the skin, or injected.

How to use Combipatch Patch, Transdermal Semiweekly

Read the Patient Information Leaflet if available from your pharmacist before you start using this medication and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Peel off the backing from the patch and apply the patch to a clean, dry area of the lower stomach. Press the patch firmly in place for about 10 seconds to make sure it stays on. Do not apply the patch on the breast or on oily, broken, or irritated skin. Avoid applying the patch to areas of the skin where it might be easily rubbed off (such as the waistline). When wearing the patch, do not expose it to the sun for long periods of time. Use this medication as directed by your doctor. The patch is usually replaced twice a week (every 3 to 4 days). Follow the dosing schedule carefully.

The dosage is based on your medical condition and response to treatment.

When replacing your patch, make sure to apply the new patch to a different area. Wait at least 1 week before applying a patch to the same area. Fold the old patch in half with the sticky side together and throw away in the trash away from children and pets. Do not flush the patch down the toilet.

If a patch falls off, reapply it to a different area. If the patch does not stick completely, then apply a new patch and wear it for the rest of the scheduled period. Do not wear 2 patches at the same time.

Use this medication regularly to get the most benefit from it. To help you remember, change the patch on the same days each week. It may help to mark your calendar with a reminder.

Tell your doctor if your condition does not improve or if it worsens.

See also Warning section.

Skin redness/irritation at the application site, abdominal pain, nausea/vomiting, bloating, breast tenderness, headache, back pain, or weight changes may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: mental/mood changes (such as depression, memory loss), breast lumps, unusual vaginal bleeding (such as spotting, breakthrough bleeding, prolonged/recurrent bleeding), increased or new vaginal irritation/itching/odor/discharge, severe stomach/abdominal pain, persistent nausea/vomiting, yellowing eyes/skin, dark urine, swelling hands/ankles/feet, increased thirst/urination.

This medication may rarely cause serious problems from blood clots (such as heart attacks, strokes, deep vein thrombosis, pulmonary embolism). Get medical help right away if you have any serious side effects, including: chest/jaw/left arm pain, unusual sweating, sudden/severe headache, weakness on one side of the body, confusion, slurred speech, sudden vision changes (such as partial/complete blindness), pain/redness/swelling of legs, tingling/weakness/numbness in the arms/legs, trouble breathing, coughing up blood, sudden dizziness/fainting.

A very serious allergic reaction to this product is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Common side effects of CombiPatch include: asthenia, dysmenorrhea, menstrual disease, pharyngitis, vaginitis, back pain, and mastalgia. Other side effects include: nervousness. See below for a comprehensive list of adverse effects.

Applies to estradiol / norethindrone: oral tablet, transdermal film extended release

Gastrointestinal

Gastrointestinal side effects have included nausea (8% to 11%), abdominal pain (6% to 7%), diarrhea (4% to 5%), flatulence (4% to 5%), and dyspepsia (1% to 5%).[Ref]

General

General side effects have included headache (18% to 20%), asthenia (8% to 12%), back pain (9% to 11%), flu syndrome (5% to 9%), pain (4% to 6%), and accidental injury (4% to 5%). Postmarketing side effects include increased weight.[Ref]

Genitourinary

Genitourinary side effects have included breast pain (25% to 31%), dysmenorrhea (20% to 21%), vaginitis (6% to 13%), menstrual disorder (6% to 12%), suspicious Papanicolaou smear (4% to 8%), and leukorrhea (5%). Endometrial thickening (10% to 4%) and vaginal hemorrhage (26% to 12%) have also been reported. Postmarketing side effects include endometrial hyperplasia, endocervical polyp, uterine leiomyomata, fallopian tube cyst, uterine spasms, and breast cancer.[Ref]

Local

Local side effects have included reactions at the application site (2% to 6%).[Ref]

Psychiatric

Psychiatric side effects have included nervousness (3% to 6%) and depression (3% to 6%).[Ref]

Respiratory

Respiratory side effects have included rhinitis (7% to 13%), respiratory disorder (7% to 12%), pharyngitis (4% to 10%), and sinusitis (4% to 9%).[Ref]

Cardiovascular

Cardiovascular side effects include postmarketing reports of hypertension and varicose veins.

Dermatologic

Dermatologic side effects include postmarketing reports of skin discoloration.

Hepatic

Hepatic side effects include postmarketing reports of jaundice cholestatic, cholelithiasis, gall bladder disorder, and increased transaminases.

Hypersensitivity

Hypersensitivity side effects include postmarketing reports of angioedema and hypersensitivity.

Nervous system

Nervous system side effects include postmarketing reports of affect lability, libido disorder, migraine, vertigo, and paraesthesia.

Some side effects of CombiPatch may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.