How is MIRENA inserted?

Before MIRENA is inserted, you will have a pelvic examination to determine the position and size of your uterus. Your doctor will insert the thin flexible plastic tube of the insertion device containing MIRENA into your uterus. At this point you may feel a little discomfort.

Once MIRENA is in the correct position, your doctor will withdraw the tube leaving the system in place in the uterus. Finally, your doctor will trim the removal threads to a suitable length.

After insertion you may feel some cramp-like menstrual pain; however, this usually disappears within a few days.

Most women find that the insertion procedure causes minor discomfort; however, for some it may be more uncomfortable. If concerned, you may wish to discuss the need for a painkiller or local anesthetic with your doctor. Some women may feel faint after MIRENA is inserted, but this feeling subsides after a short rest. The insertion procedure may precipitate a seizure in epileptic patients.

It is uncommon, but part or all of MIRENA may penetrate the wall of the uterus during insertion and come to rest outside the uterus. If this happens, MIRENA must be removed.

When Should MIRENA Be Inserted?

MIRENA should be inserted within seven days of starting your period. When replacing an existing system for a new one, it is not necessary to wait for your period.

How Long Does Insertion Take?

The insertion procedure usually takes a few minutes after your doctor has completed the pelvic examination.

How Quickly Does MIRENA Start to Work?

When MIRENA is inserted within seven days of starting your period, you will be protected from pregnancy immediately. However, it is best to wait 24 to 48 hours before having sexual intercourse in the event of general discomfort.

A reduction in menstrual blood loss should be apparent from the first menstrual cycle.

How Often Should I Have MIRENA Checked?

You should have MIRENA checked approximately 4 to 12 weeks after it is inserted, again at 12 months and then once a year until it is removed. MIRENA can stay in place for 5 years before it must be removed.

How Can I Check if MIRENA is in Place?

After each menstrual period or about once a month, you should check by feeling if the two threads are still in place. Your doctor will show you how to do this. Do not pull on the threads as you may accidentally pull MIRENA out.

If you cannot feel the threads, this may indicate that MIRENA has fallen out or uterine perforation has occurred. See your doctor and in the meantime use another method of nonhormonal contraception. You should also see your doctor if you can feel the lower end of MIRENA itself.

Will MIRENA Interfere with Sexual Intercourse?

During sexual intercourse, you or your partner should not be able to feel MIRENA. If you can feel MIRENA, or any pain or discomfort that you suspect may be caused by it, then you should not have sexual intercourse until you see your doctor to verify it is still in the correct position.

The removal threads may be felt by your partner during intercourse.

Can Tampons be Used?

Use of sanitary pads is recommended. If tampons are used, you should change them with care so as not to pull the threads of MIRENA.

Can MIRENA Fall Out?

It is unlikely, but possible that MIRENA can come out either completely or partially. If this happens, you are not protected against pregnancy.

An unusual increase in the amount of bleeding during your period might be a sign that this has happened.

If you think it has come out, use another method of nonhormonal contraception until you see your doctor.

Removal of MIRENA:

MIRENA should not be left in place for more than 5 years. You should see your doctor when you want to have MIRENA taken out. Removal of MIRENA is usually very easy. However, you should be aware that you may become pregnant upon removal of MIRENA if you have had sexual intercourse during the previous week.

Tell your doctor if you have had sexual intercourse during the preceding week.

Missed dose:

If you wish to continue using MIRENA after 5 years, your doctor can insert a new system after removing the old system. If the same MIRENA system has been left in place for longer than 5 years, you may become pregnant. Pregnancy should be ruled out before insertion of a new system.

Side effects with MIRENA are more common during the first months after insertion; they gradually decrease over time.

Menstrual bleeding irregularities are the most common side effects of MIRENA during the first months after the system is inserted, but these effects should decrease over time. Other common side effects might include abdominal pain and absence of menstruation.

The following side effects have also been observed in studies of women taking MIRENA:

Breast pain, IUD complication, pain, painful periods, altered mood, headache, acne, genital discharge, back pain, withdrawal bleeding, ovarian cyst, decreased sex drive, weight increase, menorrhagia, depression, vaginal infection, nervousness, nausea, vaginal hemorrhage, skin disorder. Device breakage has been reported.

Side effects such as irregular menstrual bleeding and nausea should go away as your body adjusts to MIRENA. If these symptoms do not go away or if you think you are reacting poorly to MIRENA or having other problems which are not listed above, please tell your doctor.

Serious Warnings and Precautions

MIRENA DOES NOT PROTECT against Sexually Transmitted Infections (STIs), including HIV/AIDS. For protection against STIs, it is advisable to use latex or polyurethane condoms while using MIRENA.

Cigarette smoking increases the risk of serious adverse effects on the heart and blood vessels. Women should be counseled not to smoke.

MIRENA may penetrate or perforate (punch a hole in) the wall of the uterus.

BEFORE you use MIRENA, talk to your doctor or pharmacist if you:

• are breast-feeding
• have given birth in the last 36 weeks
• have ever had an ectopic pregnancy (development of a fertilized egg outside the uterus). Ectopic pregnancy is more likely if you accidentally become pregnant while using MIRENA
• have had surgery on your Fallopian tubes
• have a history of ovarian cysts. There is an increased risk of cysts on the ovary
• have an unusual menstrual bleeding pattern
• have an unusual or unpleasant (e.g. smelly) vaginal discharge or vaginal itching
• have had a stroke, heart attack or any heart problems
• have or have had jaundice (a yellowing of the skin, whites of the eyes and/or nails)
• are diabetic or have a family history of diabetes, have high blood pressure or abnormal blood lipid levels
• have a history of blood clots (thrombosis)
• are taking any other medication
• have a history of migraine, dizziness or blurred vision
• have severe headaches
• have a history of depression
• wear contact lenses
• have an abnormality of your heart or if you have any problem with your heart valves
• smoke

You should also inform your doctor about a family history of blood clots, heart attacks, or strokes.

MIRENA is not the method of first choice for young women who have never been pregnant. MIRENA is intended for use only in women of child-bearing age.

Women who had never given birth to a child or were less than 18 years of age were not included in controlled trials using MIRENA.

If you see a different doctor, inform him or her that you are using MIRENA.

Tell your doctor if you are scheduled for any laboratory tests, since certain tests may be affected by hormonal contraceptives. Also, tell your doctor if you are scheduled for surgery requiring prolonged bed rest.

MIRENA should be used only under the supervision of a doctor, with regular follow-up to identify side effects associated with its use. Your visits may include a blood pressure check, a breast exam, an abdominal exam and a pelvic exam, including a Pap smear. Visit your doctor 4 to 12 weeks after the initial examination. Afterward, visit your doctor at least once a year. Use MIRENA only on the advice of your doctor and carefully follow all directions given to you. Otherwise, you may become pregnant.

If you and your doctor decide that, for you, the benefits of MIRENA outweigh the risks, you should be aware of the following:

The Risks of Using MIRENA:

1. Circulatory Disorder (including blood clot in legs, lungs, heart, eyes, or brain)
2. Some studies have suggested that women who use progestogen-only oral contraceptives might have a slightly higher risk of blood clots; however, the results are not certain. You should discuss risk factors for blood clots with your doctor.
3. Be alert for the following symptoms and signs of serious adverse effects. Call your doctor immediately if they occur:
   • Sharp pain in the chest, coughing blood, or sudden shortness of breath. These symptoms could indicate a possible blood clot in the lung.
   • Pain and/or swelling in the calf. These symptoms could indicate a possible blood clot in the leg.
   • Crushing chest pain or heaviness. These symptoms could indicate a possible heart attack.
   • Sudden severe or worsening headache or vomiting, dizziness or fainting, disturbances of vision or speech, or weakness or numbness in an arm or leg. These symptoms could indicate a possible stroke.
   • Sudden partial or complete loss of vision. This symptom could indicate a blood clot in the eye.
   • Any of these conditions can cause death or disability. Clots also occur rarely in the blood vessels of the eye, resulting in blindness or impaired vision or in a blood vessel leading to an arm or leg, resulting in damage to or loss of a limb.
4. Breast Cancer
5. The most significant risk factors for breast cancer are increasing age and a strong history of breast cancer in the family (mother or sister). Other established risk factors include onset of menstrual periods before age 12 years, never having children, having your first full-term pregnancy after the age of 30 years, never having breast fed a child, and daily alcohol consumption.
6. Some studies have shown that the risk of developing breast cancer does not appear to be increased by using progestogen-only forms of birth control like MIRENA. However, more thorough studies are needed to confirm that there is no increased risk. You should notify your doctor if you notice any breast lumps. You should also discuss breast self-examination with your doctor. A yearly breast examination by a health care professional is recommended for all women.
7. Diabetes
8. In diabetic users of MIRENA, the blood glucose concentration should be closely monitored.
9. Infections
10. There is an increased risk of a serious pelvic infection called pelvic inflammatory disease (PID) in the first three weeks after insertion of an intrauterine system or device. Other known risk factors include multiple sexual partners, frequent intercourse, and young age. PID can cause serious problems such as infertility, ectopic pregnancy, or constant pelvic pain. PID is usually treated with antibiotics; however, more serious cases of PID may require surgery. Tell your doctor right away if you have any of these signs of PID: long-lasting or heavy bleeding, unusual vaginal discharge, low abdominal (stomach area) pain, painful sex, chills or fever.
11. Ectopic Pregnancy
12. Ectopic pregnancy (development of a fertilized egg outside the uterus) is possible when using MIRENA, as it is in women using no contraception. However, if you accidentally become pregnant while using MIRENA, an ectopic pregnancy is more likely. Ectopic pregnancy is a serious condition. Therefore, you should tell your doctor if you have lower abdominal pain, especially if you have missed a period and/or have unexpected bleeding, since these can be signs of an ectopic pregnancy.
13. Cysts on the Ovary
14. Cysts on the ovary commonly occur in women using MIRENA. These cysts usually disappear on their own and within a few months. However, cysts can sometimes cause pain and may need medical attention.
15. Uterine Perforations
16. In rare cases (occurring at a rate of between 1/1000 and 1/10 000), and most often during insertion, MIRENA may penetrate or perforate (punch a hole in) the wall of the uterus. If this happens, MIRENA must be removed.
17. The risk of perforation is higher (occurring at a rate of between 1/100 and 1/1000) in women who are breastfeeding at the time of MIRENA insertion and/or when MIRENA is inserted up to 36 weeks after a delivery. The risk of perforation may be increased in women with an abnormally shaped uterus or with the uterus leaning backwards.
18. Use While Breast-Feeding
19. Hormonal contraceptives are not recommended as a birth control method of first choice in women who are breast-feeding. Small quantities of levonorgestrel, the medicinal ingredient in MIRENA, have been found in the milk of breast-feeding women using MIRENA. However, there does not appear to be a detrimental effect on growth or development of breast-fed infants whose mothers started using the product six weeks after delivery.
20. Use in Pregnancy
21. If you become pregnant with MIRENA in place, you should have it removed as soon as possible. If it is left in place during pregnancy, the chances of having a miscarriage or premature delivery increase. The effect of levonorgestrel on a developing infant is not well known, and therefore, a detrimental effect cannot be completely ruled out. Removal of MIRENA or probing of the uterus may result in spontaneous abortion. You should check with your doctor about risks to your unborn child.
22. Use After Pregnancy and Abortion
23. Following childbirth, MIRENA should be inserted only after the womb has returned to its normal size, and not earlier than 6 weeks after delivery.
24. MIRENA can be inserted immediately after a first trimester abortion.
25. Pregnancy After Stopping MIRENA
26. If you wish to become pregnant, ask your doctor to remove MIRENA. Your usual level of fertility should return soon after the system is removed. Nearly 90% of women wishing to become pregnant conceive within 24 months after removal of the system.

Driving or Using Machines:

The effect of MIRENA on the ability to drive or to use machines has not been studied. Do not drive or use machines until you know how you react to MIRENA.

How Will MIRENA Affect My Periods?

MIRENA will affect your menstrual cycle. You might experience frequent spotting (a small amount of blood loss) or light bleeding in addition to your periods for the first 3 to 6 months. In some cases, you may have heavy or prolonged bleeding during this time.

Overall, you are likely to have a gradual reduction in the number of bleeding days and in the amount of blood loss each month. Some women using MIRENA eventually find that their periods stop altogether.

When MIRENA is removed, periods should return to normal.

What if I Stop Having Periods?

Over time, your menstrual period may gradually disappear when using MIRENA. This is because of the effect of the hormone on the lining of the uterus. The normal monthly thickening of the uterine lining with blood does not happen; therefore there is little or no bleeding, as happens during a usual menstrual period. It does not necessarily mean you have reached menopause or are pregnant.

If, however, you are having regular menstrual periods and then do not have one for 6 weeks or longer, it is possible that you may be pregnant. You should speak to your doctor.

Please inform your doctor or pharmacist if you are taking or have recently taken any other drugs or herbal products, even those without a prescription.

Hormonal contraceptives may become less reliable if you are also taking drugs that affect the liver (such as primidone, barbiturates, phenytoin, carbamazepine, rifampicin and griseofulvin) at the same time. The influence of these drugs on the reliability of MIRENA has not been studied, but is unlikely since MIRENA releases a very small amount of hormone and delivers the hormone inside the uterus.

The T-frame of MIRENA contains barium sulphate, which makes it visible in X-ray examinations.

Use this medication exactly as directed on the label, or as prescribed by your doctor. Do not use it in larger amounts or for longer than recommended. Follow the directions on your prescription label.

Hydrocortisone and pramoxine topical is usually applied 3 or more times daily, depending on which form of this medication you use. Follow the label directions or your doctor's instructions about how much of this medication to use and how often. Do not use hydrocortisone and pramoxine topical for any condition that has not been checked by a doctor.

Wash your hands before and after applying this medication, unless you are using hydrocortisone and pramoxine topical to treat a hand condition.

When using this medication on the skin, apply just enough of the medication to cover the area to be treated. Rub in gently.

Avoid using this medication on your face, near your eyes or mouth, or on body areas where you have skin folds or thin skin.

Do not cover treated skin areas with a bandage or other covering unless your doctor has told you to. If you are treating the diaper area of a baby, do not use plastic pants or tight-fitting diapers. Covering the skin that is treated with hydrocortisone topical can increase the amount of the drug your skin absorbs, which may lead to unwanted side effects. Follow your doctor's instructions.

Before apply the rectal form of this medication (cream, lotion, or foam), clean the rectal area with mild soap and pat dry.

Use only a small amount of medicine when applying hydrocortisone and pramoxine around the outside of the rectum. You may first place the medicine onto a clean tissue and then wipe it gently onto your rectum.

When using this medication inside the rectum, insert only the applicator tip of the medicine tube or foam can into the anus, no deeper than 1 inch.

Shake the hydrocortisone and pramoxine rectal foam before each use.

Contact your doctor if your condition does not improve or if it gets worse after using this medication for several days, or if your condition clears up and then comes back.

Do not stop using hydrocortisone and pramoxine topical suddenly after long-term use, or you could have unpleasant withdrawal symptoms. Talk to your doctor about how to avoid withdrawal symptoms when you stop using the medication.

Store this medication at room temperature away from moisture and heat. Keep the rectal foam canister away from open flame or high heat. The canister may explode if it gets too hot. Do not puncture or burn an empty canister.

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

Stop using this medication and call your doctor at once if you have any of these serious side effects:

• blurred vision, or seeing halos around lights;

• uneven heartbeats;

• sleep problems (insomnia);

• ongoing headache;

• weight gain, puffiness in your face;

• increased thirst or urination, weight loss, unusual weakness;

• fever, sore throat, tired feeling;

• severe pain, burning, or irritation of treated skin;

• rectal bleeding;

• any new redness or swelling where the medicine was applied; or

• itching, oozing, or other signs of infection.

Less serious side effects may include:

• mild skin redness, burning, itching, dryness, or peeling;

• acne;

• changes in the color of treated skin;

• thinning of your skin;

• blistering skin; or

• stretch marks.

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.

Avoid using this medication on your face, near your eyes, or on body areas where you have skin folds or thin skin. If it does get into any of these areas, wash with water. Do not use hydrocortisone and pramoxine topical on deep skin wounds, blistered skin, severe burns, irritated skin, or large skin areas. Also avoid using this medication in open wounds.

Avoid applying other skin medications on the same treatment area with hydrocortisone and pramoxine topical, unless your doctor has told you to.

Using a steroid can lower the blood cells that help your body fight infections. This can make it easier for you to get sick from being around others who are ill. Call your doctor for preventive treatment if you are exposed to chicken pox or measles. These conditions can be serious or even fatal in people who are using steroid medicines.

It is not likely that other drugs you take orally or inject will have an effect on topically applied hydrocortisone and pramoxine. But many drugs can interact with each other. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

Follow your doctor’s instructions carefully. Do not take more JAKAVI than what your doctor told you.

How long to take JAKAVI:

You should continue taking JAKAVI for as long as your doctor tells you to. This is a long-term treatment. Your doctor will regularly monitor your condition to make sure that the treatment is having the desired effect.

If you have questions about how long to take JAKAVI, talk to your doctor or pharmacist.

Monitoring during your treatment with JAKAVI:

Before you start treatment with JAKAVI, your doctor will perform blood tests and other tests for your heart beat and your blood pressure to determine the starting dose for you.

You will have some blood tests during your treatment with JAKAVI to monitor the amount of blood cells in your body (white and red blood cells, platelets), and your kidney and liver functions. These tests are performed to see how you respond to the treatment, or to see if JAKAVI is having an unwanted effect. Your doctor may need to adjust the dose of JAKAVI or interrupt your treatment with JAKAVI. You will also have other tests during your treatment with JAKAVI to monitor the condition of your heart beat and blood pressure.

Overdose:

If you take more JAKAVI than you should or in case of drug overdose, contact a health care practitioner, hospital emergency department or regional Poison Control Centre immediately, even if there are no symptoms.

Missed dose:

Do not use a double dose of JAKAVI to make up for a forgotten dose. If you forgot to take JAKAVI simply take your next dose at the scheduled time.

If you stop taking JAKAVI:

If you are taking JAKAVI to treat myelofibrosis and you interrupt your treatment, your myelofibrosis related symptoms may come back. Therefore, you should not stop taking JAKAVI while being treated for myelofibrosis without checking first with your doctor.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Side effects may include:

• High level of cholesterol (hypercholesterolemia) or fat (hypertriglyceridemia) in the blood
• Dizziness
• Headache
• Abnormal liver function test results
• Weight gain
• Frequently passing gas (flatulence), diarrhea, nausea
• Muscle spasms
• Ringing in the ears
• Back pain
• Numbness
• Anxiety
• Cough, pain in the mouth and/or throat
• Nose bleeds
• Constipation
• High blood pressure (hypertension) may also be the cause of dizziness and headache

If any of these affects you severely, tell your doctor or pharmacist.

BEFORE you use JAKAVI talk to your doctor or pharmacist if you:

• have any infections. It may be necessary to treat your infection before starting JAKAVI. It is important that you tell your doctor if you have ever had tuberculosis or if you have been in close contact with someone who has had or has tuberculosis. Your doctor may test you to see if you have tuberculosis.
• have any kidney problems.
• have or have ever had liver problems.
• have any heart problems, including low heart rate, or if you ever have fainting spells.
• have intolerance to lactose (milk sugar). JAKAVI contains lactose.
• are pregnant or plan to become pregnant. JAKAVI is not recommended during pregnancy. You must use an effective method of birth control to avoid becoming pregnant while taking JAKAVI.
• are breast-feeding. JAKAVI may harm your baby.
• are a male patient. You must take appropriate precautions to avoid fathering a child during JAKAVI treatment.
• have ever had skin cancer.
• have ever had viral hepatitis B (a liver disease).

Children and adolescents (under 18 years old):

The safety of JAKAVI in patients younger than 18 years old have not been established.

During your treatment with JAKAVI:

Tell your doctor straight away:

• If you experience unexpected bruising and/or bleeding, unusual tiredness, shortness of breath with exercise or at rest, looking pale, or frequent infections (signs of blood disorders).
• If you experience fever, chills or other symptoms of infections or develop painful skin rash with blisters (signs of shingles).
• If you experience chronic cough with blood-tinged sputum, fever, night sweats, and weight loss (these are signs of tuberculosis).
• If you have any of the following symptoms or if anyone close to you notices that you have any of these symptoms: confusion or difficulty thinking, loss of balance or difficulty walking, clumsiness, difficulty speaking, decreased strength or weakness on one side of your body, blurred and/or loss of vision (these are signs of progressive multifocal leukoencephalopathy).
• If you notice any skin changes. This may require further observation, as certain types of skin cancer (non-melanoma) have been reported with the use of JAKAVI. You should minimize your exposure to sunlight and other sources of UV light, such as tanning beds, while taking JAKAVI.

As with most medicines, interactions with other drugs are possible. Tell your doctor or pharmacist about all the medicines you take, including drugs prescribed by other doctors, vitamins, minerals, natural supplements, or alternative medicines.

It is particularly important that you mention any of the following medicines:

• some medicines used to treat infections. These include medicines which treat fungal diseases (antifungals like fluconazole, ketoconazole, itraconazole, posaconazole and voriconazole, or medicines to treat types of bacterial infections (antibiotics like clarithromycin, or telithromycin), or medicines to treat viral infections, including HIV/AIDS (atazanavir, indinavir, nelfinavir, ritonavir, saquinavir).
• Any medications that you are taking that affect the heart or blood pressure, such as antiarrhythmics, digitalis glycosides, antihypertensives and cimetidine (a medicine to treat heartburn).

While you are taking JAKAVI you should never start a new medicine without checking first with the doctor who has prescribed you JAKAVI. This includes prescribed medicines, over the counter medicines and herbal or alternative medicines.