Versacloz

Clozapine comes as a tablet, an orally disintegrating tablet (tablet that dissolves quickly in the mouth), and an oral suspension (liquid) to take by mouth. It is usually taken once or twice daily. Take clozapine at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take clozapine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Do not try to push the orally disintegrating tablet through the foil packaging. Instead, use dry hands to peel back the foil. Immediately take out the tablet and place it on your tongue. The tablet will quickly dissolve and can be swallowed with saliva. No water is needed to swallow disintegrating tablets.

To measure clozapine oral suspension, follow these steps:

1. Make sure the cap is tight on the oral suspension container by turning the cap clockwise (to the right). Shake the bottle up and down for 10 seconds before use.
2. Remove the bottle cap by pushing down on the cap, then turn it counterclockwise (to the left). The first time you open a new bottle, push the adaptor into the bottle until the top of the adaptor is lined up with the top of the bottle.
3. If your dose is 1 mL or less, use the smaller (1 mL) oral syringe. If your dose is more than 1 mL, use the larger (9 mL) oral syringe.
4. Fill the oral syringe with by air by drawing back the plunger. Then insert the open tip of the oral syringe into the adaptor. Push all the air from the oral syringe into the bottle by pushing down on the plunger.
5. While holding the oral syringe in place, carefully turn the bottle upside down. Draw some of the medication out of the bottle into the oral syringe by pulling back on the plunger. Be careful not to pull the plunger all the way out.
6. You will see a small amount of air near the end of the plunger in the oral syringe. Push on the plunger so the medication goes back into the bottle and the air disappears. Pull back on the plunger to draw your correct medication dose into the oral syringe.
7. While still holding the oral syringe in the bottle, carefully turn the bottle upwards so the syringe is on top. Remove the oral syringe from the bottle neck adaptor without pushing on the plunger. Take the medication right after you draw it into the oral syringe. Do not prepare a dose and store it in the syringe for later use.
8. Place the open tip of the oral syringe into one side of your mouth. Tightly close your lips around the oral syringe and push on the plunger slowly as the liquid goes into your mouth. Swallow the medication slowly as it goes into your mouth.
9. Leave the adaptor in the bottle. Place the cap back on the bottle and turn it clockwise (to the right) to tighten it.
10. Rinse the oral syringe with warm tap water after each use. Fill a cup with water and place the tip of the oral syringe into the water in the cup. Pull back on the plunger and draw the water into the oral syringe. Push on the plunger to squirt the water into a sink or a separate container until the oral syringe is clean. Allow the oral syringe air dry and dispose of any leftover rinse water.

Clozapine controls schizophrenia but does not cure it. It may take several weeks or longer before you feel the full benefit of clozapine. Continue to take clozapine even if you feel well. Do not stop taking clozapine without talking to your doctor. Your doctor will probably want to decrease your dose gradually.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your body's response to clozapine.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Get emergency medical help if you have signs of an allergic reaction: hives, skin pain, rash that spreads and causes blistering or peeling; difficult breathing; swelling of your face, lips, tongue, or throat.

Serious and sometimes fatal infections may occur during treatment with clozapine. Call your doctor right away if you have signs of infection such as: sudden weakness or ill feeling; fever, swollen glands, sore throat, flu symptoms; or mouth sores, red or swollen gums, and trouble swallowing.

High doses or long-term use of clozapine can cause a serious movement disorder that may not be reversible. Symptoms of this disorder include uncontrollable muscle movements of your lips, tongue, eyes, face, arms, or legs. The longer you take clozapine, the more likely you are to develop a serious movement disorder. The risk of this side effect is higher in women and older adults.

Also call your doctor at once if you have:

• headache with chest pain and severe dizziness, pounding heartbeats or fluttering in your chest;
• a light-headed feeling, like you might pass out;
• sudden cough, rapid breathing, coughing up blood;
• tight feeling in your neck or jaw, twitching or uncontrollable movements of your eyes, lips, tongue, face, arms, or legs;
• a seizure (black-out or convulsions);
• swelling, rapid weight gain, little or no urinating;
• severe nervous system reaction--very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out;
• high blood sugar--increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss; or
• signs of inflammation in your body--easy bruising or bleeding, severe tingling or numbness, muscle weakness, upper stomach pain, jaundice (yellowing of the skin or eyes), chest pain, new or worsening cough, trouble breathing.

Common side effects may include:

• weight gain;
• tremor, dizziness, spinning sensation;
• headache, drowsiness;
• fast heart rate;
• nausea, constipation;
• dry mouth, or increased salivation;
• blurred vision; or
• increased sweating.

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.

Versacloz is part of the drug class:

• Diazepines, oxazepines, thiazepines and oxepines

Take Versacloz exactly as prescribed. Do not change your dose or stop taking Versacloz without talking to your healthcare provider.

• If you miss a dose of Versacloz for more than 2 days, do not restart Versacloz at the same dosage. Instead, contact your physician for dosing instructions.
• Do not drink alcohol while taking Versacloz. It can increase your chances of getting serious side effects.
• Do not drive, operate machinery, swim, climb, or do other dangerous activities until you know how Versacloz affects you.

Your blood counts will be reported to a special program called The Clozapine REMS Program. You will receive each refill of Versacloz only if you have a blood test and your blood test result is acceptable to your healthcare provider.

During your first 6 months of Versacloz treatment, you will have weekly blood tests. If you have not taken clozapine before, you will need weekly blood tests when you first start Versacloz. If you have acceptable blood test results during your first 6 months of clozapine treatment, you can have a blood test every other week for the next 6 months. After a year of acceptable blood test results, you can have blood tests every 4 weeks.

• Versacloz oral suspension bottle
• a bottle neck adaptor
• the correct oral syringe to measure your dose
  • If your dose is 1 mL (50 mg) or less, use the smaller 1 mL oral syringe.
  • If your dose is more than 1 mL (50 mg), use the larger 9 mL oral syringe.

How to take Versacloz:

• Make sure the cap is tight on the Versacloz bottle by turning the cap clockwise. Shake the bottle up and down for 10 seconds before use.
• Remove the bottle cap by pushing down on the cap and then turning it counterclockwise.
• The first time you open a new bottle, push the adapter into the bottle until the top of the adaptor is lined up with the top of the bottle. 
• Select the correct oral dose of your Versacloz as your pharmacist showed you.
  • If your dose is 1 mL (50 mg) or less, use the smaller 1 mL oral syringe.
  • If your dose is more than 1 mL (50 mg), use the larger 9 mL oral syringe.
• Fill the oral syringe with air by drawing back the plunger. 
• Insert the open tip of the oral syringe into the bottle neck adaptor. Push all the air from the oral syringe into the bottle by pushing down on the plunger. 
• While holding the oral syringe in place, carefully turn the bottle upside down. Draw some of the medicine out of the bottle into the oral syringe by pulling back on the plunger. Be careful not to pull the plunger all the way out.
• You will see a small amount of air near the end of the plunger in the oral syringe. Push on the plunger so the medicine goes back into the bottle and the air disappears. 
• Pull back on the plunger to draw your correct dose of medicine into the oral syringe.
• While still holding the oral syringe in the bottle, carefully turn the bottle upwards so the syringe is on top. Remove the oral syringe from the bottle neck adaptor without pushing on the plunger. 
• Take your medicine as soon as you draw it into the oral syringe. Do not store the medicine in the oral syringe for later use. 
• Put the open tip of the oral syringe into 1 side of your mouth. Close your lips around the oral syringe as tightly as you can. Push on the plunger slowly so the liquid goes into your mouth. Swallow the medicine slowly as it goes into your mouth.
• Leave the bottle neck adaptor in the bottle. Put the cap back on the bottle and turn it clockwise to tighten it. 
• Rinse the oral syringe with warm tap water after each use. Fill a cup with water. Put the tip of the oral syringe into the water in the cup, pull back on the plunger and draw the water into the oral syringe. Push on the plunger to squirt the water into the sink or a separate container. Repeat until the oral syringe is clean. 
• Let the oral syringe air dry. Throw away any leftover rinse water. 

How to dispose of Versacloz bottle and supplies:

• Place the cap back on the empty Versacloz bottle before you throw it away. The oral syringe, empty bottle and bottle neck adaptor should be placed in your household trash when you finish your bottle of Versacloz. The oral syringe should not be shared with other people or used for medicines other than Versacloz.

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

• Store Versacloz at room temperature between 68°F to 77°F (20°C to 25°C).
• Do not refrigerate or freeze Versacloz.
• Protect Versacloz from light.
• Shake your Versacloz bottle well for 10 seconds before each use.
• Keep this and all other medications out of the reach of children

Clozapine can cause severe dizziness, slow heartbeats, fainting, or seizures. Do not take more of this medicine than recommended. Be careful if you drive or do anything that requires you to be alert. 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.

• If you have an allergy to clozapine or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have a low white blood cell count.
• If you have bone marrow disease.
• If you have any of these health problems: Low potassium or magnesium levels.
• If you have ever had a low white blood cell count when taking a drug before.
• If you are taking any drugs that can stop your bone marrow from making some of the cells that your body needs. There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure.
• If you are not able to get blood tests as you have been told by your doctor.
• If you are breast-feeding. Do not breast-feed while you take Versacloz.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Versacloz with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how Versacloz affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• High blood sugar or diabetes, high cholesterol, and weight gain have happened with drugs like this one. These changes may raise the chance of heart and brain blood vessel disease. Talk with the doctor.
• If you have high blood sugar (diabetes), you will need to watch your blood sugar closely. Tell your doctor if you get signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• An unsafe heartbeat that is not normal (long QT on ECG) has happened with this medicine. Chest pain, heart attack, and sudden deaths have also rarely happened in people taking Versacloz. Talk with the doctor.
• You will need to have heart function tests while taking this medicine. Talk with the doctor.
• Blood clots have happened with Versacloz (clozapine oral suspension). Tell your doctor if you have ever had a blood clot. Talk with your doctor.
• Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
• Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
• Dizziness, sleepiness, and feeling less stable may happen with this medicine. These may lead to falling. Broken bones or other health problems can happen from falling. Talk with the doctor.
• Very bad and sometimes deadly liver problems have happened with Versacloz. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Older adults with dementia taking drugs like this one have had a higher number of strokes. Sometimes these strokes have been deadly. This drug is not approved to treat mental problems caused by dementia. Talk with your doctor.
• If you are 60 or older, use this medicine with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Versacloz while you are pregnant.
• Taking this medicine in the third trimester of pregnancy may lead to muscle movements that cannot be controlled and withdrawal in the newborn. Talk with the doctor.

Treatment-Resistant Schizophrenia

Versacloz is indicated for the treatment of severely ill patients with schizophrenia who fail to respond adequately to standard antipsychotic treatment. Because of the risks of severe neutropenia and of seizure associated with its use, Versacloz should be used only in patients who have failed to respond adequately to standard antipsychotic treatment [see Warnings and Precautions (5.1, 5.5)].

The effectiveness of clozapine in treatment-resistant schizophrenia was demonstrated in a 6-week, randomized, double-blind, active-controlled study comparing clozapine and chlorpromazine in patients who had failed other antipsychotics [see Clinical Studies (14.1)].

Reduction in the Risk of Recurrent Suicidal Behavior in Schizophrenia or Schizoaffective Disorders

Versacloz is indicated for reducing the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are judged to be at chronic risk for re-experiencing suicidal behavior, based on history and recent clinical state. Suicidal behavior refers to actions by a patient that put him/herself at risk for death.

The effectiveness of clozapine in reducing the risk of recurrent suicidal behavior was demonstrated over a two-year treatment period in the InterSePT™ trial [see Clinical Studies (14.2)].

Pregnancy

Pregnancy Category B

Risk Summary

There are no adequate or well-controlled studies of clozapine in pregnant women.

Reproduction studies have been performed in rats and rabbits at doses up to 0.4 and 0.9 times, respectively, the maximum recommended human dose (MRHD) of 900 mg/day on a mg/m2 body surface area basis. The studies revealed no evidence of impaired fertility or harm to the fetus due to clozapine. Because animal reproduction studies are not always predictive of human response, Versacloz should be used during pregnancy only if clearly needed.

Clinical Considerations

Consider the risk of exacerbation of psychosis when discontinuing or changing treatment with antipsychotic medications during pregnancy and postpartum. Consider early screening for gestational diabetes for patients treated with antipsychotic medications [see Warnings and Precautions (5.10)]. Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Monitor neonates for symptoms of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding difficulties. The severity of complications can vary from self-limited symptoms to some neonates requiring intensive care unit support and prolonged hospitalization.

Animal Data

In embryofetal developmental studies, clozapine had no effects on maternal parameters, litter sizes, or fetal parameters when administered orally to pregnant rats and rabbits during the period of organogenesis at doses up to 0.4 and 0.9 times, respectively, the MRHD of 900 mg/day on a mg/m2 body surface area basis.

In peri/postnatal developmental studies, pregnant female rats were administered clozapine over the last third of pregnancy and until day 21 postpartum. Observations were made on fetuses at birth and during the postnatal period; the offspring were allowed to reach sexual maturity and mated. Clozapine caused a decrease in maternal body weight but had no effects on litter size or body weights of either F1 or F2 generations at doses up to 0.4 times the MRHD of 900 mg/day on a mg/m2 body surface area basis.

Nursing Mothers

Versacloz is present in human milk. Because of the potential for serious adverse reactions in nursing infants from Versacloz, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

There have not been sufficient numbers of geriatric patients in clinical studies utilizing Versacloz to determine whether those over 65 years of age differ from younger subjects in their response to Versacloz.

Orthostatic hypotension and tachycardia can occur with clozapine treatment [see Boxed Warning and Warnings and Precautions (5.3)]. Elderly patients, particularly those with compromised cardiovascular functioning, may be more susceptible to these effects.

Elderly patients may be particularly susceptible to the anticholinergic effects of clozapine, such as urinary retention and constipation [see Warnings and Precautions (5.15)].

Carefully select Versacloz doses in elderly patients, taking into consideration their greater frequency of decreased hepatic, renal, or cardiac function, as well as other concomitant disease and other drug therapy. Clinical experience suggests that the prevalence of tardive dyskinesia appears to be highest among the elderly; especially elderly women [see Warnings and Precautions (5.17)].

Patients with Renal or Hepatic Impairment

Dose reduction may be necessary in patients with significant impairment of renal or hepatic function. Clozapine concentrations may be increased in these patients, because clozapine is almost completely metabolized and then excreted [see Dosage and Administration (2.8), Clinical Pharmacology (12.3)].

CYP2D6 Poor Metabolizers

Dose reduction may be necessary in patients who are CYP2D6 poor metabolizers. Clozapine concentrations may be increased in these patients, because clozapine is almost completely metabolized and then excreted [see Dosage and Administration (2.8), Clinical Pharmacology (12.3)].

Hospice Patients

For hospice patients (i.e., terminally ill patients with an estimated life expectancy of 6 months or less), the prescriber may reduce the ANC monitoring frequency to once every 6 months, after a discussion with the patient and his/her caregiver. Individual treatment decisions should weigh the importance of monitoring ANC in the context of the need to control psychiatric symptoms and the patient's terminal illness.

Overdosage Experience

The most commonly reported signs and symptoms associated with clozapine overdose are: sedation, delirium, coma, tachycardia, hypotension, respiratory depression or failure, and hypersalivation. There are reports of aspiration pneumonia, cardiac arrhythmias, and seizure. Fatal overdoses have been reported with clozapine, generally at doses above 2500 mg. There have also been reports of patients recovering from overdoses well in excess of 4 g.

Management of Overdosage

For the most up-to-date information on the management of Versacloz overdosage, contact a certified Regional Poison Control Center (1-800-222-1222). Telephone numbers of certified Regional Poison Control Centers are listed in the Physicians’ Desk Reference®, a registered trademark of PDR Network. Establish and maintain an airway; ensure adequate oxygenation and ventilation. Monitor cardiac status and vital signs. Use general symptomatic and supportive measures. There are no specific antidotes for Versacloz.

In managing overdosage, consider the possibility of multiple-drug involvement.