Signifor is a man-made protein that is similar to a hormone in the body called somatostatin. Pasireotide lowers certain hormone substances produced in the body.

Signifor is used to treat Cushing's disease or acromegaly (endocrine disorders).

Signifor is usually given after surgery or other treatments have been tried without success.

Signifor may lower your cortisol levels. Tell your doctor if you have symptoms such as nausea, vomiting, appetite changes, headache, irritability, confusion, slurred speech, or feeling weak, tired, unsteady, anxious, shaky, or light-headed.

Signifor can raise your blood sugar and may cause diabetes. Your blood sugar may need to be tested before and during treatment with this medicine. Call your doctor if you have increased thirst or urination, tiredness, and weight loss even if you are more hungry than usual.

Before taking this medicine

You should not use Signifor if you are allergic to pasireotide.

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

• diabetes, or high blood sugar;

• liver disease;

• heart problems;

• gallstones; or

• an electrolyte imbalance (such as low levels of potassium or magnesium in your blood).

It is not known whether pasireotide will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Pasireotide may alter hormone levels in a premenopausal woman and may increase the risk of unintended pregnancy. Talk to your doctor about your risk.

You should not breast-feed while using Signifor.

Use Signifor exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

Your doctor will perform blood tests to make sure you do not have conditions that would prevent you from safely using pasireotide.

Signifor is injected under the skin, usually twice per day. A healthcare provider can teach you how to properly use the medication by yourself.

Signifor LAR is injected into a muscle once every 4 weeks. A healthcare provider will give you this type of long acting injection.

Read and carefully follow any Instructions for Use provided with your medicine. Do not use this medicine if you don't understand all instructions for proper use. Ask your doctor or pharmacist if you don't understand all instructions.

Your care provider will show you where on your body to inject Signifor. Use a different place each time you give an injection. Do not inject into the same place two times in a row. Avoid skin that is red or irritated.

Signifor can raise your blood sugar, and you may develop diabetes or pre-diabetes. Your blood sugar will need to be tested before and during your treatment with pasireotide. You may need to start using diabetes medication, or adjust the dose of medication you already use. Follow your doctor's instructions very carefully.

Your heart function may need to be checked using an electrocardiograph or ECG (sometimes called an EKG).

Store at room temperature, away from moisture, heat, and light. Throw away an ampule after one use, even if there is still medicine left inside.

If you store Signifor LAR at home, keep it in the original carton in the refrigerator. Do not freeze. Take the medicine out of the refrigerator and let it reach room temperature for 30 minutes before injecting your dose. Do not leave the medicine out for longer than 24 hours.

Use a needle and syringe only once and then place them in a puncture-proof "sharps" container. Follow state or local laws about how to dispose of this container. Keep it out of the reach of children and pets.

Usual Adult Dose for Cushing's Syndrome:

Intramuscular formulation:
Initial dose: 10 mg intramuscularly every 4 weeks (28 days)
Maximum dose: 40 mg intramuscularly every 4 weeks (28 days), after 4 months of treatment with 10 mg for patients without normalized 24-hour urinary free cortisol (UFC) levels after 4 months treatment who tolerated the 10 mg dose


Subcutaneous formulation:
Initial dose: 0.6 mg or 0.9 mg subcutaneously twice daily.
Maintenance dose: 0.3 to 0.9 mg subcutaneously twice daily.
Maximum dose: 0.9 mg subcutaneously twice daily
Duration of therapy: Treatment should be continued as long as benefit is derived.

Comments:
-Titrate dose based on response and tolerability.
-Perform baseline evaluations of fasting plasma glucose, hemoglobin A1c, liver tests, electrocardiogram, serum potassium, and serum magnesium prior to initiating therapy.
-Optimize glucose control in poorly controlled diabetics prior to initiating therapy.

Use: The treatment of adult patients with Cushing's disease for whom pituitary surgery is not an option or has not been curative.

Usual Adult Dose for Acromegaly:

Intramuscular formulation:
Initial dose: 40 mg, IM, every 28 days
Maximum dose: 60 mg, IM, every 28 days for patients without normalized growth hormone (GH) and/or age and sex adjusted insulin-like growth factor (IGF-1) levels after 3 months treatment who tolerated the 40 mg dose

Comments:
-Titrate dose based on response and tolerability.
-Evaluate fasting plasma glucose, HbA1c, liver enzymes, electrocardiogram, and serum magnesium and potassium prior to therapy.
-Optimize glucose control in poorly controlled diabetes prior to therapy.

Use: Treatment of patients with acromegaly with an inadequate response to surgery and/or for whom surgery is not an option.

You should not use Signifor if you are allergic to pasireotide.

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

• diabetes, or high blood sugar;

• liver disease;

• heart problems;

• gallstones; or

• an electrolyte imbalance (such as low levels of potassium or magnesium in your blood).

It is not known whether pasireotide will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Pasireotide may alter hormone levels in a premenopausal woman and may increase the risk of unintended pregnancy. Talk to your doctor about your risk.

You should not breast-feed while using Signifor.

Use the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not use two doses at one time.

If you miss a dose of Signifor LAR, you can receive your missed dose up to 14 days before your next dose.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

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

Call your doctor at once if you have:

• fast or slow heartbeats;

• sudden dizziness (like you might pass out);

• high blood sugar - increased thirst, increased urination, fruity breath odor, tiredness, and weight loss even if you are more hungry than usual;

• ketoacidosis (too much acid in the blood) - nausea, vomiting, stomach pain, confusion, unusual drowsiness, or trouble breathing;

• low cortisol levels - nausea, vomiting, appetite changes, headache, irritability, confusion, slurred speech, or feeling weak, tired, unsteady, anxious, shaky, or light-headed; or

• gallbladder problems - chalky-colored stools, stomach pain just after eating a meal, heartburn, bloating, and upper stomach pain that may spread to your back.

Common Signifor side effects may include:

• high blood pressure;

• abnormal blood test results;

• feeling weak or tired;

• loss of appetite, nausea, stomach pain or bloating, diarrhea;

• headache;

• swelling, rapid weight gain;

• back pain;

• cold symptoms such as stuffy nose and sneezing;

• hair loss; or

• pain, redness, itching, bruising or bleeding where the medicine was injected.

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.

Signifor can cause a serious heart problem. Your risk may be higher if you also use certain other medicines for infections, asthma, heart problems, high blood pressure, depression, mental illness, cancer, malaria, or HIV.

Tell your doctor about all your current medicines. Many drugs can interact with Signifor, especially:

• bromocriptine;

• cyclosporine;

• heart or blood pressure medication; or

• medicines to control blood levels of magnesium or potassium.

This list is not complete and many other drugs may interact with Signifor. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.