Saphris

Asenapine is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions). Asenapine is used alone or in combination with other medications to treat or prevent episodes of mania (frenzied, abnormally excited mood) or mixed mania (frenzied, abnormally excited mood and symptoms of depression) in adults and children 10 years of age and older with bipolar I disorder (manic depressive disorder; a disease that causes episodes of mania, episodes of depression and other abnormal moods). Asenapine is in a class of medications called atypical antipsychotics. It works by changing the activity of certain natural substances in the brain.

Tell your doctor about all prescription, non-prescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking while on Saphris, especially:

• Certain antibiotics including gatifloxacin (Tequin) (not available in the U.S.) and moxifloxacin (Avelox)
• Antidepressants including clomipramine (Anafranil), duloxetine (Cymbalta), fluvoxamine (Luvox), and paroxetine (Paxil, Pexeva)
• Antihistamines
• Dextromethorphan (in Delsym, in Mucinex)
• Ipratropium
• Drugs for anxiety and high blood pressure
• Certain drugs for irregular heartbeat such as amiodarone (Cordarone, Pacerone), procainamide, quinidine, and sotalol (Betapace, Sorine)
• Medications for glaucoma, inflammatory bowel disease, motion sickness, myasthenia gravis, Parkinson's disease, ulcers, or urinary problems
• Drugs for mental illness such as chlorpromazine (Thorazine), thioridazine, and ziprasidone (Geodon)
• Medications for seizures
• Sedatives
• Sleeping pills
• Tranquilizers

Saphris and Alcohol

Alcohol can worsen the side effects of Saphris.

Talk to your doctor about the risks of consuming alcoholic beverages while taking this medicine.

Saphris and Other Interactions

Saphris can make you drowsy.

You should exercise caution when driving or performing any activity that requires alertness.

Sublingual Tablets: 2.5, 5, and 10 mg

Asenapine should be stored at room temperature, between 15 C to 30C (59 F and 86 F).

If you take too much Saphris, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

While you are taking asenapine, you may be more sensitive to temperature extremes such as very hot or cold conditions. Avoid getting too cold, or becoming overheated or dehydrated. Drink plenty of fluids, especially in hot weather and during exercise. It is easier to become dangerously overheated and dehydrated while you are taking asenapine.

Asenapine may impair your thinking or reactions. Avoid driving or operating machinery until you know how this medicine will affect you.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Dizziness or severe drowsiness can cause falls, fractures, or other injuries.

Avoid drinking alcohol. Dangerous side effects could occur.

General

• When switching from other antipsychotic agents to asenapine, immediate discontinuance of previous agent may be acceptable for some patients with schizophrenia, but gradual discontinuance may be most appropriate for others.1 In all cases, minimize period of overlapping antipsychotic administration.1

Administration

Sublingual Administration

Administer tablets sublingually twice daily.1

Do not remove sublingual tablet from blister pack until just prior to administration.1 With dry hands, pull blister pack out of case and peel back colored tab to expose the tablet; do not push tablet through blister pack.1 Gently remove tablet and place under the tongue, then allow to dissolve completely (usually takes about 10 seconds).1 6

Do not eat or drink for 10 minutes following administration.1 74 Do not crush, chew, or swallow the sublingual tablets.1 (See Food and Water under Pharmacokinetics.)

Dosage

Available as asenapine maleate; dosage expressed in terms of asenapine.1 4 81

Adults

For acute treatment, recommended initial and target dosage is 5 mg twice daily.1 A higher dosage (10 mg twice daily) did not provide additional therapeutic benefit in clinical trials, but was clearly associated with increased adverse effects.1 82 Safety of dosages >10 mg twice daily not evaluated.1

For maintenance treatment, recommended initial dosage is 5 mg twice daily for 1 week.1 May increase to recommended target dosage of 10 mg twice daily after 1 week based on tolerability.1

Optimum duration of therapy not known.1 28 If used for an extended time, periodically reassess need for continued therapy.1 28

In patients with remitted first or multiple episodes, APA recommends either indefinite maintenance therapy or gradual discontinuance of the antipsychotic with close follow-up and a plan to reinstitute treatment upon symptom recurrence.28 Consider antipsychotic therapy discontinuance only after ≥1 year of symptom remission or optimal response while receiving the drug.28 Indefinite maintenance treatment recommended if patient has experienced multiple previous psychotic episodes or 2 episodes within 5 years.28

Monotherapy: Initially, 10 mg twice daily.1 3 83 May decrease dosage to 5 mg twice daily if adverse effects occur or based on individual tolerability.1 Safety of dosages >10 mg twice daily not evaluated.1

Adjunctive therapy with lithium or valproate: Initially, 5 mg twice daily.1 May increase dosage to 10 mg twice daily based on clinical response and tolerability.1 Safety of dosages >10 mg twice daily not evaluated.1

Optimum duration of therapy not known.1 In responsive patients, continue drug therapy beyond the acute response; periodically reassess long-term risks and benefits.1

Prescribing Limits

Adults

Safety of dosages >10 mg twice daily not evaluated.1

Safety of dosages >10 mg twice daily not evaluated.1

Special Populations

Hepatic Impairment

Severe hepatic impairment (Child-Pugh class C): Use not recommended.1 7 95

Mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment: Dosage adjustment not necessary.1 7 95 (See Absorption: Special Populations, under Pharmacokinetics.)

Renal Impairment

Routine dosage adjustment not required.1 7 95 (See Absorption: Special Populations, under Pharmacokinetics, and also see Elimination: Special Populations, under Pharmacokinetics.)

Geriatric Patients

Routine dosage adjustment not required.1 (See Geriatric Use under Cautions, Absorption: Special Populations, under Pharmacokinetics, and also see Elimination: Special Populations, under Pharmacokinetics.)

Gender or Race

Dosage adjustment not routinely required based on gender or race.1

• Importance of advising patients and caregivers that elderly patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death.1 28 39 73 Patients and caregivers also should be informed that asenapine is not approved for treating elderly patients with dementia-related psychosis.1 73

• Risk of serious allergic reactions.1 96 Importance of informing patients of signs and symptoms of such reactions (e.g., difficulty breathing; swelling of the face, tongue, or throat; lightheadedness; itching) and to immediately seek emergency medical attention if they develop.1 96

• Importance of informing patients that application site reactions (e.g., oral ulcers, blisters, peeling/sloughing, inflammation), primarily in the sublingual area, have been reported.1 Instruct patients to monitor for such reactions during therapy.1

• Risk of somnolence (i.e., sleepiness, drowsiness).1 Importance of advising patients to exercise caution when performing activities requiring mental alertness (e.g., driving, operating hazardous machinery) until they gain experience with the drug’s effects.1

• Importance of avoiding alcohol during asenapine therapy.1

• Importance of informing patients and caregivers about the risk of NMS, which can cause high fever, stiff muscles, sweating, fast or irregular heart beat, change in BP, and confusion.1

• Importance of patients being aware of the symptoms of hyperglycemia and diabetes mellitus (e.g., increased thirst, increased urination, increased appetite, weakness).1 Importance of informing patients with diabetes, those with risk factors for diabetes, and those who develop hyperglycemia symptoms during treatment that they should have their blood glucose monitored at the beginning of and periodically during asenapine treatment.1

• Risk of weight gain.1 Importance of patients being aware of need to monitor their weight during therapy.1

• Risk of orthostatic hypotension and syncope (fainting), especially when initiating or reinitiating treatment or increasing the dosage.1 Importance of informing patients about interventions that may help (e.g., sitting on the edge of the bed for several minutes before standing in the morning, slowly rising from a seated position).1

• Risk of leukopenia/neutropenia.1 Importance of advising patients with a preexisting low WBC count or history of drug-induced leukopenia/neutropenia that their CBC count should be monitored during asenapine therapy.1

• Importance of informing patients in whom chronic asenapine use is contemplated of risk of tardive dyskinesia.1 67 Importance of advising patients to report any muscle movements that cannot be stopped to a healthcare professional.67

• Importance of informing patients that oral hypoesthesia, oral paresthesia, and/or dysgeusia (abnormal or altered taste) may occur and that these effects are not serious and are typically transient (i.e., resolving within 1 hour) following sublingual administration.1 74 81 88

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., cardiovascular disease, diabetes mellitus, seizures).1

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 92 Importance of clinicians informing patients about the benefits and risks of taking antipsychotics during pregnancy (see Pregnancy under Cautions).1 92 Importance of advising patients not to stop taking asenapine if they become pregnant without consulting their clinician; abruptly discontinuing antipsychotic agents may cause complications.92 Importance of advising patients not to breast-feed during asenapine therapy.1

• Importance of avoiding overheating or dehydration.1

• Importance of correctly taking sublingual tablets.1 Do not remove sublingual tablet from the blister pack until just before administration.1 With dry hands, pull blister pack out of case, peel back the colored tab on the pack, and gently remove the tablet.1 Place the sublingual tablet under the tongue and allow to dissolve completely.1 Importance of sliding the blister pack back into the case until it clicks after use.1 Importance of not eating or drinking for 10 minutes following administration.1 74 (See Food and Water under Pharmacokinetics.)

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Abnormal or decreased touch sensation
• inability to move the eyes
• inability to sit still
• increase in body movements
• increased blinking or spasms of the eyelid
• lip smacking or puckering
• need to keep moving
• puffing of the cheeks
• rapid or worm-like movements of the tongue
• restlessness
• shakiness in the legs, arms, hands, or feet
• sticking out of tongue
• trembling or shaking of the hands or feet
• trouble with breathing, speaking, or swallowing
• twitching, twisting, uncontrolled repetitive movements of the tongue, lips, face, arms, or legs
• uncontrolled chewing movements
• uncontrolled twisting movements of the neck, trunk, arms, or legs
• unusual facial expressions
• weakness of the arms and legs

• Blurred vision
• dizziness
• headache
• nervousness
• pounding in the ears
• slow or fast heartbeat

• Black, tarry stools
• bleeding gums
• blood in the urine or stools
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• changes in patterns and rhythms of speech
• coma
• confusion
• convulsions
• decreased urine output
• fast, pounding, or irregular heartbeat or pulse
• increased thirst
• muscle pain or cramps
• nausea or vomiting
• pale skin
• pinpoint red spots on the skin
• slurred speech
• swelling of the face, ankles, or hands
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual tiredness or weakness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Constipation
• sleepiness or unusual drowsiness
• trouble sleeping
• unusually deep sleep
• unusually long duration of sleep

• Acid or sour stomach
• belching
• depression
• difficulty with moving
• dry mouth
• fear or nervousness
• heartburn
• increased appetite
• increased watering of the mouth
• increased weight
• indigestion
• irritability
• muscle pain or stiffness
• pain in the arms or legs
• pain in the joints
• stomach discomfort, upset, or pain
• toothache

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Review Date: October 4, 2017

You should not use Saphris if you are allergic to asenapine, or if you have severe liver disease.

Saphris can cause serious neurologic problems. Stop taking this medicine and call your doctor at once if you have: very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, feeling light-headed, tremors, twitching, or uncontrollable movements of your eyes, lips, tongue, face, arms, or legs.

Saphris is not approved for use in psychotic conditions related to dementia. Asenapine may increase the risk of death in older adults with dementia-related conditions.

Saphris is usually taken 2 times per day. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

To take Saphris sublingual (under the tongue) tablets:

• Keep the tablet in its blister pack until you are ready to take the medicine. Open the package and peel back the colored tab from the tablet blister. Do not push a tablet through the blister or you may damage the tablet.

• Using dry hands, gently remove the tablet and place it under your tongue. Do not crush or break the tablet. It will begin to dissolve right away.

• Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing.

• Swallow several times as the tablet dissolves. Do not eat or drink anything for 10 minutes after the tablet has dissolved.

Saphris may cause you to have high blood sugar (hyperglycemia). Symptoms include increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, and blurred vision. If you are diabetic, check your blood sugar levels on a regular basis while you are taking Saphris.

Your doctor will need to check your progress while you are using Saphris.

Store at room temperature away from moisture and heat.

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