Signifor LAR

>10%

Diarrhea (58%)

Nausea (52%)

Hyperglycemia (40%)

Cholelithiasis (30%)

Headache (28%)

Abdominal pain (24%)

Fatigue (19%)

Diabetes mellitus (18%)

Injection site reactions (17%)

Nasopharyngitis (13%)

Alopecia (12%)

Asthenia (11%)

Increased A1c (11%)

1-10%

Increased ALT (10%)

Increased GGT (10%)

Edema, peripheral (10%)

Upper abdominal pain (10%)

Decreased appetite (10%)

Hypercholesterolemia (10%)

Hypertension (10%)

Dizziness (9%)

Hypoglycemia (9%)

Type 2 diabetes mellitus (9%)

Anxiety (9%)

Influenza (9%)

Insomnia (9%)

Myalgia (9%)

Arthralgia (8%)

Pruritus (8%)

Increased lipase (7%)

Constipation (7%)

Hypotension (7%)

Vomiting (7%)

Back pain (6%)

Dry skin (6%)

Prolonged QT interval (6%)

Hypokalemia (6%)

Pain in extremity (6%)

Sinus bradycardia (6%)

Vertigo (6%)

Abdominal distension (6%)

Adrenal insufficiency (6%)

Increased AST (6%)

Increased blood glucose (6%)

Anemia (4%)

Increased amylase (2%)

Prolonged PTT (2%)

Pregnancy Category: C

Lactation: Unknown whether distributed in human breast milk; excreted in rat milk at levels 30% of the plasma level; cannot exclude risk to breastfeeding children

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

SIGNIFOR LAR (pasireotide) for injectable suspension is a long-acting release form of pasireotide pamoate, as powder to be suspended in the provided diluent immediately prior to intramuscular injection. SIGNIFOR LAR is a somatostatin analog. Pasireotide pamoate, chemically known as (2-Aminoethyl) carbamic acid (2R,5S,8S,11S,14R,17S,19aS)-11-(4-aminobutyl)-5-benzyl-8-(4-benzyloxybenzyl)-14-(1H-indol-3-ylmethyl)4,7,10,13,16,19-hexaoxo-17-phenyloctadecahydro-3a,6,9,12,15,18-hexaazacyclopentacyclooctadecen-2-yl ester pamoic acid salt, is a cyclohexapeptide with pharmacologic properties mimicking those of the natural hormone somatostatin.

The molecular formula of pasireotide pamoate is C58H66N10O9•C23H16O6 and the molecular weight is 1435.58. The structural formula is:

The drug product consists of pasireotide pamoate uniformly distributed within microspheres which are made of biodegradable copolymers of poly (D,L-lactide-co-glycolide) acids (PLGA).

SIGNIFOR LAR is available in a vial containing the sterile pasireotide pamoate, PLGA microspheres powder, 20 mg, 40 mg and 60 mg to be reconstituted with the provided 2 mL sterile diluent. The product should be prepared immediately prior to use for intramuscular injection given once every 4 weeks.

Each vial contains:

Each diluent prefilled syringe contains:

• Parlodel
• Sandostatin
• Sandostatin LAR

• Somatuline Depot
• Somavert

© Signifor-LAR Patient Information is supplied by Cerner Multum, Inc. and Signifor-LAR Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

Signifor LAR is a prescription medication used to treat acromegaly, a condition caused by high growth hormone levels, when surgery has failed or is otherwise not an option for treatment. Signifor LAR belongs to a group of drugs called somatostatin analogues. These work to treat acromegaly by reducing growth hormone levels in the body.

The medication is available in an injectable form to be given directly into a muscle by a healthcare professional, typically once monthly.

Common side effects of Signifor LAR include diarrhea, nausea, and high blood sugar.

Signifor LAR can also cause dizziness and/or drowsiness. Do not drive or operate heavy machinery until you know how Signifor LAR affects you.

If Signifor LAR is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of the pasireotide injection in the pediatric population. Safety and efficacy have not been demonstrated.

Geriatric

Although appropriate studies on the relationship of age to the effects of pasireotide have not been performed in the geriatric population, geriatric-specific problems are not expected to limit the usefulness of pasireotide injection in the elderly. However, elderly patients are more likely to have age-related kidney, liver, or heart problems, which may require caution and an adjustment in the dose for patients receiving pasireotide injection.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Amisulpride
• Bepridil
• Cisapride
• Dronedarone
• Mesoridazine
• Pimozide
• Piperaquine
• Saquinavir
• Sparfloxacin
• Terfenadine
• Thioridazine
• Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acarbose
• Albiglutide
• Alfuzosin
• Alogliptin
• Amiodarone
• Amitriptyline
• Anagrelide
• Apomorphine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Asenapine
• Astemizole
• Atazanavir
• Azithromycin
• Bedaquiline
• Buserelin
• Canagliflozin
• Chloroquine
• Chlorpromazine
• Chlorpropamide
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clomipramine
• Clozapine
• Crizotinib
• Cyclobenzaprine
• Dabrafenib
• Dapagliflozin
• Dasatinib
• Degarelix
• Delamanid
• Desipramine
• Deslorelin
• Deutetrabenazine
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxepin
• Droperidol
• Dulaglutide
• Ebastine
• Efavirenz
• Empagliflozin
• Eribulin
• Erythromycin
• Escitalopram
• Exenatide
• Famotidine
• Felbamate
• Fingolimod
• Flecainide
• Fluconazole
• Fluoxetine
• Formoterol
• Foscarnet
• Fosphenytoin
• Galantamine
• Gatifloxacin
• Gemifloxacin
• Glimepiride
• Glipizide
• Glyburide
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Histrelin
• Hydroquinidine
• Hydroxychloroquine
• Hydroxyzine
• Ibutilide
• Iloperidone
• Imipramine
• Insulin
• Insulin Aspart, Recombinant
• Insulin Bovine
• Insulin Degludec
• Insulin Detemir
• Insulin Glargine, Recombinant
• Insulin Glulisine
• Insulin Lispro, Recombinant
• Itraconazole
• Ivabradine
• Ketoconazole
• Lapatinib
• Leuprolide
• Levofloxacin
• Linagliptin
• Liraglutide
• Lixisenatide
• Lumefantrine
• Mefloquine
• Metformin
• Methadone
• Metronidazole
• Mifepristone
• Miglitol
• Mizolastine
• Moxifloxacin
• Nafarelin
• Nateglinide
• Nelfinavir
• Nilotinib
• Norfloxacin
• Octreotide
• Ofloxacin
• Olanzapine
• Ondansetron
• Paliperidone
• Panobinostat
• Paroxetine
• Pazopanib
• Pentamidine
• Perphenazine
• Pimavanserin
• Pioglitazone
• Pipamperone
• Pitolisant
• Posaconazole
• Pramlintide
• Probucol
• Procainamide
• Prochlorperazine
• Promethazine
• Propafenone
• Protriptyline
• Quetiapine
• Quinidine
• Quinine
• Ranolazine
• Repaglinide
• Ribociclib
• Rilpivirine
• Risperidone
• Ritonavir
• Rosiglitazone
• Saxagliptin
• Sertindole
• Sevoflurane
• Sitagliptin
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sorafenib
• Sotalol
• Sulpiride
• Sunitinib
• Tacrolimus
• Tamoxifen
• Telaprevir
• Telavancin
• Telithromycin
• Tetrabenazine
• Tizanidine
• Tolazamide
• Tolbutamide
• Tolterodine
• Toremifene
• Trazodone
• Trimipramine
• Triptorelin
• Vandetanib
• Vardenafil
• Vemurafenib
• Venlafaxine
• Vilanterol
• Vildagliptin
• Vinflunine
• Voriconazole
• Vorinostat
• Zuclopenthixol

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Adrenal problems or
• Gallstones, or history of or
• Heart disease or
• Heart rhythm problem (eg, QT prolongation)—Use with caution. May make these conditions worse.

• Angina (severe chest pain), unstable or
• Bradycardia (slow heartbeat), history of or
• Congestive heart failure, not properly controlled or
• Heart attack, recent or
• Heart block, history of or
• Heart rhythm problem (eg, congenital long QT prolongation) or
• Hypokalemia (low potassium in the blood) or
• Hypomagnesemia (low magnesium in the blood)—May increase risk for more serious side effects.

• Diabetes, poorly controlled or
• Hyperglycemia (high blood sugar)—Should be treated first before using this medicine.

• Liver disease, moderate—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

This section provides information on the proper use of a number of products that contain pasireotide. It may not be specific to Signifor LAR. Please read with care.

Signifor® is given as a shot under your skin, usually on the thigh or the abdomen (stomach). Signifor® LAR is given as a shot into a muscle, usually on the buttocks.

A nurse or other trained health professional may give you this medicine or this medicine may be given at home by patients who do not need to be in the hospital or clinic. If you are using this medicine at home, your doctor or nurse will teach you how to prepare and inject the medicine. Be sure that you understand how to use the medicine.

This medicine should come with a Medication Guide and patient instructions. Read and follow the instructions carefully. Ask your doctor or pharmacist if you have any questions.

You will be shown the body areas where this shot can be given. Use a different body area each time you give yourself a shot. Keep track of where you give each shot to make sure you rotate body areas.

Use a new needle and syringe each time you inject your medicine.

You might not use all of the medicine in each ampul (glass container). Do not save an opened ampul. If the medicine in the ampul has changed color, or if you see particles in it, do not use it.

Put used needles and syringes in a puncture-resistant disposable container or dispose of them as directed by your doctor. Do not reuse needles and syringes.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For injection dosage form:
  • For treatment of Cushing's disease:
    • Adults—At first, 0.6 or 0.9 milligram (mg) injected under the skin two times a day. Your doctor will adjust your dose as needed and tolerated.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Common side effects of Signifor LAR include: asthenia, cholelithiasis, fatigue, hypoglycemia, increased serum alanine aminotransferase, nausea, and vomiting. Other side effects include: adrenocortical insufficiency, hypotension, and increased serum glucose. See below for a comprehensive list of adverse effects.