Cylert

• Abbott Pharmaceutical

In the U.S.

• Cylert

Available Dosage Forms:

• Tablet
• Tablet, Chewable

Therapeutic Class: CNS Stimulant

Chemical Class: Amphetamine Related

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

Slowed growth rate in children who received medicines like pemoline for a long period of time has been reported. Some doctors recommend medicine-free periods during treatment with pemoline to help prevent slowed growth.

Pemoline may make behavior worse in children with serious mental illness.

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. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

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:

• Drug abuse or dependence (or history of)—Dependence on pemoline may develop.

• Gilles de la Tourette's syndrome or other tics or
• Liver disease or
• Mental illness (severe)—Pemoline may make the condition worse.

• Kidney disease—Higher blood levels of pemoline may occur, increasing the chance of side effects.

Cylert (pemoline) is a central nervous system stimulant. Pemoline is structurally dissimilar to the amphetamines and methylphenidate.

It is an oxazolidine compound and is chemically identified as 2-amino-5-phenyl-2-oxazolin-4-one. Pemoline has the following structural formula:

Pemoline is a white, tasteless, odorless powder, relatively insoluble (less than 1 mg/mL) in water, chloroform, ether, acetone, and benzene; its solubility in 95% ethyl alcohol is 2.2 mg/mL.

Cylert (pemoline) is supplied as tablets containing 18.75 mg, 37.5 mg or 75 mg of pemoline for oral administration. Cylert is also available as chewable tablets containing 37.5 mg of pemoline.

Inactive Ingredients

18.75 mg tablet: corn starch, gelatin, lactose, magnesium hydroxide, polyethylene glycol and talc.

37.5 mg tablet: corn starch, FD&C Yellow No. 6, gelatin, lactose, magnesium hydroxide, polyethylene glycol and talc.

37.5 mg chewable tablet: corn starch, FD&C Yellow No. 6, magnesium hydroxide, magnesium stearate, mannitol, polyethylene glycol, povidone, talc and artificial flavor.

75 mg tablet: corn starch, gelatin, iron oxide, lactose, magnesium hydroxide, polyethylene glycol and talc.

Controlled Substance

Cylert is subject to control under DEA schedule IV.

Abuse

Cylert failed to demonstrate a potential for self-administration in primates. However, the pharmacologic similarity of pemoline to other psychostimulants with known dependence liability suggests that psychological and/or physical dependence might also occur with Cylert. There have been isolated reports of transient psychotic symptoms occurring in adults following the long-term misuse of excessive oral doses of pemoline. Cylert should be given with caution to emotionally unstable patients who may increase the dosage on their own initiative.

Cylert (pemoline) is administered as a single oral dose each morning. The recommended starting dose is 37.5 mg/day. This daily dose should be gradually increased by 18.75 mg at one week intervals until the desired clinical response is obtained. The effective daily dose for most patients will range from 56.25 to 75 mg. The maximum recommended daily dose of pemoline is 112.5 mg.

Clinical improvement with Cylert is gradual. Using the recommended schedule of dosage titration, significant benefit may not be evident until the third or fourth week of drug administration. Because Cylert provides an observable symptomatic benefit, patients who fail to show substantial clinical benefit within 3 weeks of completing dose titration, should be withdrawn from Cylert therapy.

Where possible, drug administration should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued therapy.

Cylert (pemoline) is supplied as monogrammed, grooved tablets in three dosage strengths:

18.75 mg white tablets (imprinted with Abbott “A” logo and the Abbo-Code TH),

Bottles of 100 (NDC 0074-6025-13).

37.5 mg orange-colored tablets (imprinted with Abbott“A” logo and the Abbo-Code TI),

Bottles of 100 (NDC 0074-6057-13).

75 mg tan-colored tablets (imprinted with Abbott“A” logo and the Abbo-Code TJ),

Bottles of 100 (NDC 0074-6073-13).

Cylert (pemoline) Chewable is supplied as 37.5 mg monogrammed, grooved orange-colored tablets (imprinted with Abbott“A” logo and the Abbo-Code TK),
Bottles of 100 (NDC 0074-6088-13).

Recommended Storage

Store below 86°F (30°C).

PATIENT INFORMATION/CONSENT FORM

Cylert® (pemoline) should not be used by patients until there has been a complete discussion of the risks and benefits of Cylert therapy and written informed consent has been obtained.

IMPORTANT INFORMATION

Cylert therapy has been associated with liver abnormalities ranging from reversible liver function test increases that do not cause any symptoms to liver failure, which may result in death. Therefore, you should have a full discussion of the risks and benefits of Cylert before beginning therapy.

PATIENT CONSENT

My (son, daughter, ward)___________________________'s treatment with Cylert has been explained to me by Dr.______________.

The following points of information, among others, have been specifically discussed and explained and I have had the opportunity to ask any questions concerning this information.

1. I, ________(Patient/Parent/Guardian's name), understand that Cylert is used to treat certain types of patients with the behavioral syndrome called attention deficit hyperactivity disorder (ADHD) and that I (my son/daughter/ward) am that type of patient.
   Initials:_________
2. I understand that there is a risk that I (my son/daughter/ward) might develop liver failure, which may result in death, while taking Cylert. I understand that this could occur even after long-term therapy.
   Initials:_________
3. I understand that I (my son/daughter/ward) should have blood taken to test liver function before Cylert is begun, and every two weeks from then on while taking Cylert. I understand that although the liver function tests may help detect if I (my son/daughter/ward) develop liver damage, it may do so only after significant, irreversible and potentially fatal damage has already occurred.
   Initials:_________
4. I understand that if I (my son/daughter/ward) stop taking Cylert and then restart it at a later time (e.g., after summer vacation), I (my son/daughter/ward) should again have blood taken to test liver function before Cylert is restarted, and every two weeks from then on while taking Cylert.
   Initials:_________
5. I understand that I should immediately report any unusual symptoms to the doctor and should be especially aware of persistent nausea, vomiting, fatigue, lethargy, loss of appetite, abdominal pain, dark urine, or yellowing of the skin or eyes.
   Initials:_________

I now authorize Dr._____________________ to begin my (son/daughter/ward's) treatment with Cylert, or if treatment with Cylert has already begun, to continue this treatment.

_______________________________________

Signature    Date

_______________________________________

     Address

_______________________________________

     Telephone

PHYSICIAN STATEMENT

I have fully explained to the patient (parent/guardian), _______________________ the nature and purpose of treatment with Cylert and the potential risks associated with that treatment. I have asked if he/she has any questions regarding this treatment or the associated risks and have answered these questions to the best of my ability.

_______________________________________

Physician Signature

_______________________________________

Date

NOTE TO PHYSICIAN: It is strongly recommended that you retain a completed copy of this informed consent form in your patient's records.

SUPPLY OF PATIENT INFORMATION/CONSENT FORMS: A supply of Patient Information/Consent Forms as printed above is available, free of charge, by calling (847) 937-7302. Permission to use the above Patient Information/Consent Form by photocopy reproduction is hereby granted by Abbott Laboratories.

Revised: December, 2004

Manufactured by: Abbott Pharmaceuticals PR Ltd.

Barceloneta, PR 00617

For: Abbott Laboratories

North Chicago, IL  60064  USA

Applies to pemoline: oral tablet, oral tablet chewable

Along with its needed effects, pemoline (the active ingredient contained in Cylert) may cause some unwanted effects. Some side effects will have signs or symptoms that you can see or feel. Your doctor may watch for others by doing certain tests.

Pemoline may cause some serious side effects, including liver problems. Also, medicines like pemoline, when used for a long time, have been reported to slow the growth rate of children. Some doctors recommend medicine-free periods during treatment with pemoline. Pemoline may also cause unwanted effects on behavior in children with severe mental illness.

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 while taking pemoline:

• Dark urine
• yellow eyes or skin

Check with your doctor as soon as possible if any of the following side effects occur while taking pemoline:

• Convulsions (seizures)
• hallucinations (seeing, hearing, or feeling things that are not there)
• nausea and vomiting
• shortness of breath, troubled breathing, wheezing, or tightness in chest
• skin rash
• sores, ulcers, or white spots on lips or in mouth
• swollen or painful glands
• uncontrolled movements of eyes, tongue, lips, face, arms, or legs
• unusual bleeding or bruising
• unusual tiredness
• vocal sounds you cannot control

• Agitation
• confusion
• convulsions (seizures)may be followed by coma
• false sense of well-being
• fast heartbeat
• hallucinations (seeing, hearing, or feeling things that are not there)
• headache (severe)
• high blood pressure
• high fever
• large pupils
• muscle trembling or twitching
• restlessness
• sweating
• vomiting

This medicine may also cause the following side effects that your doctor will watch for:

• Liver problems
• slow growth in children

Some side effects of pemoline 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:

• Loss of appetite
• trouble in sleeping
• weight loss

• Dizziness
• drowsiness
• headache
• increased irritability
• mental depression
• stomachache

After you stop using this medicine, it may still produce some side effects that need attention. During this period of time, check with your doctor immediately if you notice the following side effects:

• Abdominal pain
• convulsions (seizures)
• headache
• mental depression
• nausea
• unusual behavior
• unusual tiredness or weakness
• vomiting

Applies to pemoline: oral tablet, oral tablet chewable

Hepatic

Hepatic side effects have included asymptomatic reversible increases in liver enzymes, hepatitis, jaundice, and life threatening hepatic failure.[Ref]

As of October 2005, hepatic failure resulting in liver transplant or death, usually within 4 weeks of onset of signs and symptoms of hepatic failure, has been reported in at least 13 patients receiving pemoline. The reporting rate for hepatic failure with pemoline is 10 to 25 times greater than the background rate of hepatic failure in the general population.[Ref]

General

Insomnia tends to occur early in therapy. Most cases are transient and respond to a reduction in dosage.[Ref]

General side effects have included insomnia which has been reported to be the most frequent side effect with the use of pemoline. Growth suppression has been associated with the long term use of stimulants in children.[Ref]

Hematologic

Hematologic side effects including aplastic anemia have been reported.[Ref]

Nervous system

Nervous system side effects including seizures, hallucinations, dyskinetic movements of the tongue, lips, face, and extremities, mild depression, dizziness, increased irritability, headache, and drowsiness have been reported.[Ref]

Ocular

Ocular side effects have included nystagmus and oculogyric crisis.[Ref]

Gastrointestinal

Anorexia and weight loss tend to occur during the first weeks of therapy. Most cases are transient. Weight gain usually resumes within 3 to 6 months.[Ref]

Gastrointestinal side effects including anorexia, weight loss, nausea, and stomach ache have been reported.[Ref]

Dermatologic

Dermatologic side effects have included skin rash.[Ref]

Cardiovascular

The case of severe hypotension was reported in a patient receiving pemoline (the active ingredient contained in Cylert) during general anesthesia.[Ref]

Cardiovascular side effects including a case of severe hypotension have been reported.[Ref]

Other

Other side effects including ototoxicity have been reported.[Ref]

Genitourinary

Genitourinary side effects have included an isolated case of elevated serum acid phosphatase in one man with prostatic enlargement. (The serum acid phosphatase normalized upon discontinuation of pemoline (the active ingredient contained in Cylert) and elevated again on rechallenge.)[Ref]

Some side effects of Cylert may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Pemoline has been assigned to pregnancy category B by the FDA. Animal studies have revealed evidence of increased incidence of stillbirths, and a decreased rate of postnatal survival of offspring. There are no controlled data in human pregnancy. Pemoline should be given during pregnancy when need has been clearly established.