Stimate

Mechanism of Action

Synthetic analogue of vasopressin with prompt onset and longer, more specific antidiuretic action; desmopressin increases water permeability in renal tubular cells, which in turn decreases urine volume and increases urine osmolality

Also produces dose-related increase in von Willebrand factor VIII and t-PA levels; this shortens activated partial thromboplastin time (aPTT), as well as bleeding time

Absorption

Bioavailability: 3.5% (nasal); 5% (oral; compared to intranasal, 0.16% compared to IV)

Onset: ADH effect (intranasal), 60 min; hemophilia and von Willebrand disease (IV), 30 min

Duration: 6-14 hr (intranasal, IV infusion, oral)

Peak plasma time: 1-5 hr (intranasal); 0.25 hr for 0.83 mcg dose and 0.75 hr for 1.66 mcg dose (preservative-free nasal spray)

Metabolism

Unknown

Elimination

Half-life: 3.5 hr (intranasal); 3 hr (IV); 2-3 hr (PO); 2.8 hr (1.66 mcg dose; preservative-free nasal spray)

Excretion: Urine

Stimate® Nasal Spray
(Pronounced Stim-ate)
(desmopressin acetate)

Read this patient information leaflet before you start taking Stimate® Nasal Spray and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about Stimate® Nasal Spray?

All patients using Stimate® Nasal Spray are at risk for water intoxication, fluid overload and low sodium levels in the blood. You must follow your healthcare provider's instructions on limiting the amount of fluid you can drink when taking Stimate® Nasal Spray.

• Do not drink more than you need to satisfy your thirst.
• You can have serious side effects such as seizures, coma, and death from drinking too much fluid.
• Children and elderly patients are at higher risk for these conditions and must follow their healthcare provider's restrictions on drinking fluids.

Call your healthcare provider right away if you have any of the following symptoms while using Stimate® Nasal Spray. They may mean that your blood sodium level is low:

• Headache
• Loss of appetite
• Nausea
• Irritability
• Vomiting
• Muscle weakness
• Weight gain
• Muscle spasms or cramps
• Restlessness
• Hallucinations
• Tiredness
• Confusion

Using Stimate® Nasal Spray the wrong way may cause it not to work to control bleeding.

Call your healthcare provider right away if you have any uncontrolled bleeding.

What is Stimate® Nasal Spray?

Stimate® Nasal Spray is a prescription medicine used to stop some types of bleeding in people with mild hemophilia A or mild to moderate von Willebrand's disease Type 1. Stimate® Nasal Spray should not be used in children under 11 months of age.

What should I tell my healthcare provider before I use Stimate® Nasal Spray?

Before taking Stimate® Nasal Spray, tell your healthcare provider about all of your medical conditions, including if you:

• Have any nasal problems such as a stuffy nose, have ever had surgery on your nose, or have trouble breathing through your nose. You may need to use another form of this medicine.
• Have or have had any heart, blood circulation, or blood pressure problems.
• Have a condition that causes fluid or water imbalance problems such as:
  • Cystic fibrosis
  • Heart failure
  • Kidney problems
• Have or have had a condition that causes you to be very thirsty.
• Are pregnant or plan to become pregnant. It is not known if Stimate® Nasal Spray will harm your unborn baby.
• Are breast-feeding or plan to breast-feed. It is not known if Stimate® Nasal Spray passes into your breast milk. You and your healthcare provider should decide if you will take Stimate® Nasal Spray.

Tell your healthcare provider and pharmacist about all the medicines you take, including prescription and non-prescription medicines, such as over-the-counter medicines, vitamins, supplements and herbal remedies.

Using Stimate® Nasal Spray with certain other medicines can affect the way Stimate® Nasal Spray works.

Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.

It is especially important to tell your healthcare provider if you take:

• Blood pressure or heart medicines
• Antidepressants
• Anti-anxiety medicines
• Antihistamines
• Pain relievers such as narcotics or non-steroidal anti-inflammatory medicines (NSAIDs)
• Seizure medicines
• Medicines for over-active urinary bladder

Ask your healthcare provider or pharmacist if you are not sure if your medicine is one of these.

How should I use Stimate® Nasal Spray?

• Use Stimate® Nasal Spray exactly as your healthcare provider told you. Do not use more Stimate® Nasal Spray or take it more often than your healthcare provider told you.
• The Stimate® Nasal Spray pump provides the correct dose of your medicine. For detailed instructions on how to use the nasal spray pump, see the Patient Instructions for Use at the end of this leaflet.
• The nasal spray pump delivers 25 doses of Stimate® Nasal Spray and each spray contains a measured amount of medicine. Any medicine left in the spray pump after 25 sprays should be thrown away because, at that time, the amount of medicine in each spray may be a lot less than the correct amount. Do not put any leftover medicine into another bottle.
• If your symptoms do not improve, or if they become worse, contact your healthcare provider. Do not stop taking Stimate® Nasal Spray without talking to your healthcare provider.
• If you use too much Stimate® Nasal Spray, call your healthcare provider or go to the nearest hospital emergency department right away.

What are the possible side effects of Stimate® Nasal Spray?

Stimate® Nasal Spray may cause serious side effects, that come from having too much water in the body. See “What is the most important information I should know about Stimate® Nasal Spray?”.

Common side effects of Stimate Nasal Spray include:

• Occasional facial flushing
• Nasal congestion
• Runny nose
• Nosebleed
• Sore throat
• Cough
• Upper respiratory infections.

Tell your healthcare provider about any side effect that bothers you or does not go away.

These are not all the possible side effects of Stimate® Nasal Spray. If you have questions, talk to your healthcare provider.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Stimate® Nasal Spray?

• Store at room temperature, but not higher than 77°F (25°C).
• Throw away Stimate® Nasal Spray six months after it is opened, or when the expiration date has passed, if this date is before the six months is up.
• Store Stimate® Nasal Spray standing upright.

Keep Stimate® Nasal Spray and all medicines out of the reach of children.

General information about Stimate® Nasal Spray

Medicines are sometimes prescribed for conditions that are not mentioned in the patient leaflet. Do not use Stimate® Nasal Spray for a condition for which it was not prescribed. Do not give Stimate® Nasal Spray to other people, even if they have the same symptoms you have. It may harm them.

This patient information leaflet summarizes the most important information about Stimate® Nasal Spray. If you would like more information about Stimate® Nasal Spray, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about Stimate® Nasal Spray that is written for health professionals. For more information, go to www.stimate.com or call CSL Behring Medical Affairs at 1-800-504-5434.

What are the ingredients in Stimate® Nasal Spray?

Active ingredients: desmopressin acetate

Inactive ingredients: sodium chloride, citric acid monohydrate, disodium phosphate dihydrate, benzalkonium chloride, purified water.

Patient Instructions for Use

Read these instructions carefully before you use your Stimate® Nasal Spray pump. The following instructions tell you how to prepare, or prime, your Stimate® Nasal Spray pump so that it is ready to use.

Using your Stimate® Nasal Spray Pump

1. Remove the protective cap.

2. When using Stimate® Nasal Spray for the first time, the spray pump must be primed by pressing down on the ring at the top of the pump 4 times. Hold the spray tip away from your face and eyes. See Figure A.

Figure A

3. When primed, the Stimate® Nasal Spray pump delivers one dose of medicine each time it is pressed. For the right dose, tilt your Stimate® Nasal Spray pump so that the tube inside the spray pump draws the medicine up from the deepest part of the medicine inside the container. See Figures A and B.

Figure B

4. Put the spray nozzle tip into your nostril and press the spray pump one time for one dose (150-micrograms). If two doses are prescribed, spray each nostril one time (for a dose of 300-micrograms).

5. When you finish using your Stimate® Nasal Spray, put the cap over the tip of the pump.

6. If Stimate® Nasal Spray has not been used for one week, you will need to prime the pump again by pressing one time, or until you see a fine mist.

Use this check-off chart to help you keep track of the number of sprays used. This will help make sure that you receive 25 doses with each bottle of Stimate® Nasal Spray. There is extra medicine in the bottle to allow for priming. When using the chart to check off sprays, do not count the priming sprays.

Stimate® Nasal Spray

25 Spray Check-off Chart

1. Keep this chart with your Stimate® Nasal Spray or put it someplace where you can easily get it.

2. Check off number 1 on the chart with your first dose of Stimate® Nasal Spray. Check off the numbers after each use of Stimate® Nasal Spray. If your healthcare provider prescribed a 2-spray dose (300-micrograms), then two numbers should be checked off.

3. Throw away the Stimate® Nasal Spray after 25 doses.

You should not use this medication if you are allergic to desmopressin, or if you have:

• severe kidney disease; or
• if you have ever had hyponatremia (low sodium levels in your body).

Before using desmopressin nasal, tell your doctor if you are allergic to any medications, or if you have:

• heart disease, coronary artery disease;
• congestive heart failure;
• kidney disease;
• cystic fibrosis;
• high or low blood pressure;
• an electrolyte imbalance; or
• a psychologic disorder that causes extreme or unusual thirst.

If you have any of these conditions, you may need a dose adjustment or special tests to safely use desmopressin.

Desmopressin nasal may be less effective if you have any swelling or scarring inside your nose, or any nasal or sinus problems (such as deviated septum).

FDA pregnancy category B. This medication is not expected to harm an unborn baby. Do not use desmopressin nasal without telling your doctor if you are pregnant.

It is not known whether desmopressin nasal passes into breast milk, or if it could harm a nursing baby. Do not use desmopressin nasal without telling your doctor if you are breast-feeding a baby.

Infrequently, DDAVP® Injection has produced transient headache, nausea, mild abdominal cramps and vulval pain. These symptoms disappeared with reduction in dosage. Occasional facial flushing has been reported with the administration of DDAVP® Injection. Infrequently, high doses of intranasal DDAVP® have produced transient headache and nausea. Nasal congestion, rhinitis and flushing have also been reported occasionally along with mild abdominal cramps. These symptoms disappeared with reduction in dosage. Nosebleed, sore throat, cough and upper respiratory infections have also been reported.

In addition to those listed above, the following have also been reported in clinical trials with Stimate® Nasal Spray: Somnolence, dizziness, itchy or light-sensitive eyes, insomnia, chills, warm feeling, pain, chest pain, palpitations, tachycardia, dyspepsia, edema, vomiting, agitation and balanitis.

DDAVP® Injection (desmopressin acetate) has infrequently produced changes in blood pressure causing either a slight elevation or a transient fall with a compensatory increase in heart rate. Severe allergic reactions including anaphylaxis have been reported rarely with DDAVP® Injection.

Post Marketing

There have been rare reports of convulsions from hyponatremia associated with concomitant use of desmopressin and the following medications: oxybutynin and imipramine. See WARNINGS for the possibility of water intoxication, hyponatremia and coma.

To report SUSPECTED ADVERSE REACTIONS, contact CSL Behring Pharmacovigilance at 1-866-915-6958 or FDA at 1-800-FDA-1088 or www. fda.gov/medwatch.

Read the entire FDA prescribing information for Stimate (Desmopressin Acetate Nasal Spray)

Stimate is part of the drug class:

• Vasopressin and analogues

In the U.S.

• DDAVP
• DDAVP Rhinal Tube
• Minirin
• Noctiva
• Stimate

Available Dosage Forms:

• Solution
• Spray

Therapeutic Class: Endocrine-Metabolic Agent

Pharmacologic Class: Vasopressin (class)

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 performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of desmopressin nasal spray for diabetes insipidus in children 3 months of age and older.

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of Stimate® to treat hemophilia A and von Willebrand disease in children 11 months of age and older. However, use is not recommended in children younger than 11 months of age.

Appropriate studies have not been performed on the relationship of age to the effects of Noctiva™ in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of desmopressin nasal spray in the elderly. However, elderly patients are more likely to have age-related kidney problems, which may require caution and an adjustment in the dose for patients receiving desmopressin.

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of Noctiva™ in the elderly. However, elderly patients are more likely to have hyponatremia (low sodium in the blood), which may require caution and an adjustment in the dose for patients receiving Noctiva™.

Pregnancy

Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during 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.

• Alclometasone
• Aldosterone
• Amcinonide
• Beclomethasone
• Betamethasone
• Budesonide
• Bumetanide
• Ciclesonide
• Clobetasol
• Clobetasone
• Clocortolone
• Cortisone
• Deflazacort
• Desonide
• Desoximetasone
• Dexamethasone
• Diflorasone
• Diflucortolone
• Difluprednate
• Ethacrynic Acid
• Flucloronide
• Fludrocortisone
• Flumethasone
• Flunisolide
• Fluocinolone
• Fluocinonide
• Fluocortin
• Fluocortolone
• Fluorometholone
• Flurandrenolide
• Fluticasone
• Furosemide
• Halcinonide
• Halobetasol
• Hydrocortisone
• Loteprednol
• Medrysone
• Methylprednisolone
• Mometasone
• Paramethasone
• Prednicarbate
• Prednisolone
• Prednisone
• Rimexolone
• Torsemide
• Triamcinolone

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.

• Aceclofenac
• Acemetacin
• Alfentanil
• Amineptine
• Amitriptyline
• Amitriptylinoxide
• Amoxapine
• Amtolmetin Guacil
• Anileridine
• Aspirin
• Bromfenac
• Bufexamac
• Buprenorphine
• Butorphanol
• Carbamazepine
• Celecoxib
• Chlorpromazine
• Choline Salicylate
• Citalopram
• Clomipramine
• Clonixin
• Codeine
• Desipramine
• Dexibuprofen
• Dexketoprofen
• Dezocine
• Diacetylmorphine
• Dibenzepin
• Diclofenac
• Difenoxin
• Diflunisal
• Dihydrocodeine
• Diphenoxylate
• Dipyrone
• Doxepin
• Droxicam
• Escitalopram
• Ethylmorphine
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fentanyl
• Fepradinol
• Feprazone
• Floctafenine
• Flufenamic Acid
• Fluoxetine
• Flurbiprofen
• Fluvoxamine
• Hydrocodone
• Hydromorphone
• Ibuprofen
• Imipramine
• Indomethacin
• Ketobemidone
• Ketoprofen
• Ketorolac
• Lamotrigine
• Levorphanol
• Lofepramine
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Melitracen
• Meloxicam
• Meperidine
• Meptazinol
• Methadone
• Morniflumate
• Morphine
• Morphine Sulfate Liposome
• Nabumetone
• Nalbuphine
• Naproxen
• Nepafenac
• Nicomorphine
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Nortriptyline
• Opipramol
• Opium
• Opium Alkaloids
• Oxaprozin
• Oxycodone
• Oxymorphone
• Oxyphenbutazone
• Papaveretum
• Parecoxib
• Paregoric
• Paroxetine
• Pentazocine
• Phenylbutazone
• Piketoprofen
• Piritramide
• Piroxicam
• Pranoprofen
• Proglumetacin
• Propyphenazone
• Proquazone
• Protriptyline
• Remifentanil
• Rofecoxib
• Salicylic Acid
• Salsalate
• Sertraline
• Sodium Salicylate
• Sufentanil
• Sulindac
• Tapentadol
• Tenoxicam
• Tianeptine
• Tiaprofenic Acid
• Tilidine
• Tolfenamic Acid
• Tolmetin
• Tramadol
• Trimipramine
• Valdecoxib
• Vilazodone
• Vortioxetine

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:

• Blood clotting problems or
• Hypertension (high blood pressure) or
• Hypotension (low blood pressure) or
• Tachycardia (increased heart rate)—Use with caution. May make these conditions worse.

• Coronary artery disease or
• Cystic fibrosis or
• Heart failure or
• Kidney problems or
• Polydipsia (excessive thirst), habitual or psychogenic—Use with caution. May cause side effects to become worse.

• Congestive heart failure or
• Head injury or
• Hypertension (high blood pressure), uncontrolled or
• Urinary retention, or history of—Noctiva™ can cause fluid retention, and should not be used in patients with these conditions.

• Gastroenteritis or
• Infection (systemic) or
• Polydipsia (excessive thirst) or
• Primary nocturnal enuresis (bed-wetting at night) or
• Salt-wasting nephropathies or
• Syndrome of inappropriate antidiuretic hormone (SIADH), known or suspected—Noctiva™ should not be used in patients with these conditions.

• Hyponatremia (low sodium in the blood), or history of or
• Kidney disease, moderate to severe—Should not be used in patients with these conditions.

• Nose problems (eg, nasal mucosa atrophy, rhinitis)—Use with caution. May increase risk for more serious side effects.

• Type IIB von Willebrand disease—Stimate® should not be used in patients with this condition.

• It is used to treat hemophilia.
• It is used to treat von Willebrand disease.
• It may be given to you for other reasons. Talk with the doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Very bad allergic reactions have rarely happened. Sometimes, allergic reactions have been deadly with the shot form of Stimate. Talk with the doctor.
• Use with care in children. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Flushing.
• Runny nose.
• Stuffy nose.
• Cough.
• Nosebleed.
• Sore throat.
• Nose irritation.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.