DESCRIPTION

DESOXYN® (methamphetamine hydrochloride tablets, USP), chemically known as (S)-N,α-dimethylbenzeneethanamine hydrochloride, is a member of the amphetamine group of sympathomimetic amines. It has the following structural formula:

DESOXYN tablets contain 5 mg of methamphetamine hydrochloride for oral administration.

Inactive Ingredients:

Corn starch, lactose, sodium paraminobenzoate, stearic acid and talc.

CLINICAL PHARMACOLOGY

Methamphetamine is a sympathomimetic amine with CNS stimulant activity. Peripheral actions include elevation of systolic and diastolic blood pressures and weak bronchodilator and respiratory stimulant action. Drugs of this class used in obesity are commonly known as "anorectics" or "anorexigenics". It has not been established, however, that the action of such drugs in treating obesity is primarily one of appetite suppression. Other central nervous system actions, or metabolic effects, may be involved, for example.

Adult obese subjects instructed in dietary management and treated with "anorectic" drugs, lose more weight on the average than those treated with placebo and diet, as determined in relatively short-term clinical trials.

The magnitude of increased weight loss of drug-treated patients over placebo-treated patients is only a fraction of a pound a week. The rate of weight loss is greatest in the first weeks of therapy for both drug and placebo subjects and tends to decrease in succeeding weeks. The origins of the increased weight loss due to the various possible drug effects are not established. The amount of weight loss associated with the use of an "anorectic" drug varies from trial to trial, and the increased weight loss appears to be related in part to variables other than the drug prescribed, such as the physician-investigator, the population treated, and the diet prescribed. Studies do not permit conclusions as to the relative importance of the drug and non-drug factors on weight loss.

The natural history of obesity is measured in years, whereas the studies cited are restricted to a few weeks duration; thus, the total impact of drug-induced weight loss over that of diet alone must be considered clinically limited.

The mechanism of action involved in producing the beneficial behavioral changes seen in hyperkinetic children receiving methamphetamine is unknown.

In humans, methamphetamine is rapidly absorbed from the gastrointestinal tract. The primary site of metabolism is in the liver by aromatic hydroxylation, N-dealkylation and deamination. At least seven metabolites have been identified in the urine. The biological half-life has been reported in the range of 4 to 5 hours. Excretion occurs primarily in the urine and is dependent on urine pH. Alkaline urine will significantly increase the drug half-life. Approximately 62% of an oral dose is eliminated in the urine within the first 24 hours with about one-third as intact drug and the remainder as metabolites.

INDICATIONS AND USAGE

Attention Deficit Disorder with Hyperactivity: DESOXYN tablets are indicated as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children over 6 years of age with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate to severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. The diagnosis of this syndrome should not be made with finality when these symptoms are only of comparatively recent origin. Nonlocalizing (soft) neurological signs, learning disability, and abnormal EEG may or may not be present, and a diagnosis of central nervous system dysfunction may or may not be warranted.

Exogenous Obesity: as a short-term (i.e., a few weeks) adjunct in a regimen of weight reduction based on caloric restriction, for patients in whom obesity is refractory to alternative therapy, e.g., repeated diets, group programs, and other drugs.

The limited usefulness of DESOXYN tablets (see CLINICAL PHARMACOLOGY) should be weighed against possible risks inherent in use of the drug, such as those described below.

CONTRAINDICATIONS

DESOXYN tablets are contraindicated during or within 14 days following the administration of monoamine oxidase inhibitors; hypertensive crisis may result. It is also contraindicated in patients with glaucoma, advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism or known hypersensitivity or idiosyncrasy to sympathomimetic amines. Methamphetamine should not be given to patients who are in an agitated state or who have a history of drug abuse.

WARNINGS

Tolerance to the anorectic effect usually develops within a few weeks. When this occurs, the recommended dose should not be exceeded in an attempt to increase the effect; rather, the drug should be discontinued (see DRUG ABUSE AND DEPENDENCE).

Serious Cardiovascular Events

Sudden Death and Pre-existing Structural Cardiac Abnormalities or Other Serious Heart Problems:

•Children and Adolescents: Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, stimulant products generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug.

•Adults: Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs.

Hypertension and other Cardiovascular Conditions: Stimulant medications cause a modest increase in average blood pressure (about 2-4 mmHg) and average heart rate (about 3-6 bpm), and individuals may have larger increases. While the mean changes alone would not be expected to have short-term consequences, all patients should be monitored for larger changes in heart rate and blood pressure. Caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, e.g., those with pre-existing hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia.

Assessing Cardiovascular Status in Patients being Treated with Stimulant Medications: Children, adolescents, or adults who are being considered for treatment with stimulant medications should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further cardiac evaluation if findings suggest such disease (e.g., electrocardiogram and echocardiogram). Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation.

Psychiatric Adverse Events

Pre-existing Psychosis: Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder.

Bipolar Illness: Particular care should be taken in using stimulants to treat ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in such patients. Prior to initiating treatment with a stimulant, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.

Emergence of New Psychotic or Manic Symptoms: Treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by stimulants at usual doses. If such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate. In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% (4 patients with events out of 3482 exposed to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated patients compared to 0 in placebo-treated patients.

Aggression: Aggressive behavior or hostility is often observed in children and adolescents with ADHD, and has been reported in clinical trials and the postmarketing experience of some medications indicated for the treatment of ADHD. Although there is no systematic evidence that stimulants cause aggressive behavior or hostility, patients beginning treatment for ADHD should be monitored for the appearance of or worsening of aggressive behavior or hostility.

Long-Term Suppression of Growth: Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated children over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated children (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development. Published data are inadequate to determine whether chronic use of amphetamines may cause a similar suppression of growth, however, it is anticipated that they likely have this effect as well. Therefore, growth should be monitored during treatment with stimulants, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.

Seizures; There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued.

Visual Disturbance: Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

PRECAUTIONS

ADVERSE REACTIONS

The following are adverse reactions in decreasing order of severity within each category that have been reported:

Cardiovascular: Elevation of blood pressure, tachycardia and palpitation. Fatal cardiorespiratory arrest has been reported, mostly in the context of abuse/misuse.

Central Nervous System: Psychotic episodes have been rarely reported at recommended doses. Dizziness, dysphoria, overstimulation, euphoria, insomnia, tremor, restlessness and headache. Exacerbation of motor and phonic tics and Tourette's syndrome.

Gastrointestinal: Diarrhea, constipation, dryness of mouth, unpleasant taste and other gastrointestinal disturbances.

Hypersensitivity: Urticaria.

Endocrine: Impotence and changes in libido.

Miscellaneous: Suppression of growth has been reported with the long-term use of stimulants in children (see WARNINGS).

To report SUSPECTED ADVERSE REACTIONS, contact Lundbeck Inc. at 1-800-455-1141 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG ABUSE AND DEPENDENCE

Controlled Substance: DESOXYN tablets are subject to control under DEA schedule II.

Abuse: Methamphetamine has been extensively abused. Tolerance, extreme psychological dependence, and severe social disability have occurred. There are reports of patients who have increased the dosage to many times that recommended. Abrupt cessation following prolonged high dosage administration results in extreme fatigue and mental depression; changes are also noted on the sleep EEG. Manifestations of chronic intoxication with methamphetamine include severe dermatoses, marked insomnia, irritability, hyperactivity, and personality changes. The most severe manifestation of chronic intoxication is psychosis often clinically indistinguishable from schizophrenia. Abuse and/or misuse of methamphetamine have resulted in death. Fatal cardiorespiratory arrest has been reported in the context of abuse and/or misuse of methamphetamine.

OVERDOSAGE

Manifestations of acute overdosage with methamphetamine include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia, and rhabdomyolysis. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmias, hypertension or hypotension, and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning usually terminates in convulsions and coma.

Consult with a Certified Poison Control Center regarding treatment for up to date guidance and advice. Management of acute methamphetamine intoxication is largely symptomatic and includes gastric evacuation, administration of activated charcoal, and sedation. Experience with hemodialysis or peritoneal dialysis is inadequate to permit recommendations in this regard.

Acidification of urine increases methamphetamine excretion, but is believed to increase risk of acute renal failure if myoglobinuria is present. Intravenous phentolamine (Regitine*) has been suggested for possible acute, severe hypertension, if this complicates methamphetamine overdosage. Usually a gradual drop in blood pressure will result when sufficient sedation has been achieved. Chlorpromazine has been reported to be useful in decreasing CNS stimulation and sympathomimetic effects.

*Regitine is a registered trademark of Novartis.

DOSAGE AND ADMINISTRATION

DESOXYN tablets are given orally.

Methamphetamine should be administered at the lowest effective dosage, and dosage should be individually adjusted. Late evening medication should be avoided because of the resulting insomnia.

Attention Deficit Disorder with Hyperactivity: For treatment of children 6 years or older with a behavioral syndrome characterized by moderate to severe distractibility, short attention span, hyperactivity, emotional lability and impulsivity: an initial dose of 5 mg DESOXYN once or twice a day is recommended. Daily dosage may be raised in increments of 5 mg at weekly intervals until an optimum clinical response is achieved. The usual effective dose is 20 to 25 mg daily. The total daily dose may be given in two divided doses daily.

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

For Obesity: One 5 mg tablet should be taken one-half hour before each meal. Treatment should not exceed a few weeks in duration. Methamphetamine is not recommended for use as an anorectic agent in children under 12 years of age.

HOW SUPPLIED

DESOXYN (methamphetamine hydrochloride tablets, USP) is supplied as white tablets imprinted with the letters OV on one side and the number 12 on the opposite side, containing 5 mg methamphetamine hydrochloride in bottles of 100

(NDC 67386-102-01).

Recommended Storage: Store below 86°F (30°C).

Dispense in a USP tight, light resistant container.

Manufactured by:

Abbott Pharmaceuticals PR Ltd.

Barceloneta, PR 00617

For: Lundbeck Inc., Deerfield, IL 60015, U.S.A.

® Trademark of Lundbeck Inc.

Revised: May 2009

MEDICATION GUIDE
CII
Desoxyn®
(Pronounced Dĕ-sŏks-ĭn)
(methamphetamine hydrochloride tablets, USP)

Read the Medication Guide that comes with DESOXYN® before you or your child starts taking it and each time you get a refill.

There may be new information. This Medication Guide does not take the place of talking to your or your child's doctor about your or your child's treatment with DESOXYN.

What is the most important information I should know about DESOXYN?

The following have been reported with use of methamphetamine

hydrochloride and other stimulant medicines.

1. Heart-related problems:

• sudden death in patients who have heart problems or heart defects
• stroke and heart attack in adults
• increased blood pressure and heart rate

Tell your or your child's doctor if you or your child have any heart problems, heart defects, high blood pressure, or a family history of these problems.

Your or your child's doctor should check you or your child carefully for heart problems before starting DESOXYN.

Your or your child's doctor should check you or your child's blood pressure and heart rate regularly during treatment with DESOXYN.

Call your or your child's doctor right away if you or your child has any signs of heart problems such as chest pain, shortness of breath, or fainting while taking DESOXYN.

2. Mental (Psychiatric) problems:

All Patients

• new or worse behavior and thought problems
• new or worse bipolar illness
• new or worse aggressive behavior or hostility

Children and Teenagers

• new psychotic symptoms (such as hearing voices, believing things that are not true, are suspicious) or new manic symptoms

Tell your or your child's doctor about any mental problems you or your child have, or about a family history of suicide, bipolar illness, or depression.

Call your or your child's doctor right away if you or your child have any new or worsening mental symptoms or problems while taking DESOXYN, especially seeing or hearing things that are not real, believing things that are not real, or are suspicious.

What is DESOXYN?

DESOXYN is a central nervous system stimulant prescription medicine. It is used for the treatment of Attention-Deficit Hyperactivity Disorder; (ADHD).

DESOXYN may help increase attention and decrease impulsiveness and hyperactivity in patients with ADHD.

DESOXYN should be used as a part of a total treatment program for ADHD that may include counseling or other therapies.

DESOXYN is also used short-term, along with a low calorie diet, for weight loss in obese patients who have not been able to lose weight on other therapies.

DESOXYN is a federally controlled substance (CII) because it can be abused or lead to dependence. Keep DESOXYN in a safe place to prevent misuse and abuse. Selling or giving away DESOXYN may harm others, and is against the law.

Tell your or your child's doctor if you or your child have (or have a family history of) ever abused or been dependent on alcohol, prescription medicines or street drugs.

Who should not take DESOXYN?

DESOXYN should not be taken if you or your child:

• have heart disease or hardening of the arteries
• have moderate to severe high blood pressure
• have hyperthyroidism
• have an eye problem called glaucoma
• are agitated
• have a history of drug abuse
• are taking or have taken within the past 14 days an antidepression medicine called a monoamine oxidase inhibitor or MAOI.
• are sensitive to, allergic to, or had a reaction to other stimulant medicines

DESOXYN is not recommended for use in children less than 6 years old in the treatment of ADHD.

DESOXYN may not be right for you or your child. Before starting DESOXYN tell your or your child's doctor about all health conditions (or a family history of) including:

• heart problems, heart defects, high blood pressure
• mental problems including psychosis, mania, bipolar illness or depression
• tics or Tourette's syndrome
• thyroid problems
• diabetes
• seizures or have had an abnormal brain wave test (EEG)

Tell your or your child's doctor if you or your child is pregnant, planning to become pregnant, or breastfeeding.

Can DESOXYN be taken with other medicines?

Tell your or your child's doctor about all of the medicines that you or your child take including prescription and nonprescription medicines, vitamins, and herbal supplements.

DESOXYN and some medicines may interact with each other and cause serious side effects. Sometimes the doses of other medicines will need to be adjusted while taking DESOXYN.

Your or your child's doctor will decide whether DESOXYN can be taken with other medicines.

Especially tell your or your child's doctor if you or your child takes:

• anti-depression medicines including MAOIs
• anti-psychotic medicines
• blood pressure medicines
• insulin
• seizure medicines

Know the medicines that you or your child takes. Keep a list of your medicines with you to show your doctor and pharmacist.

Do not start any new medicine while taking DESOXYN without talking to your or your child's doctor first.

How should DESOXYN be taken?

• Take DESOXYN exactly as prescribed. Your or your child's doctor may adjust the dose until it is right for you or your child.
• DESOXYN is usually taken 1 or 2 times each day.
• From time to time, your or your child's doctor may stop DESOXYN treatment for a while to check ADHD symptoms.
• Your or your child's doctor may do regular checks of the blood, heart, and blood pressure while taking DESOXYN. Children should have their height and weight checked often while taking DESOXYN. DESOXYN treatment may be stopped if a problem is found during these check-ups.
• If you or your child takes too much DESOXYN or overdoses, call your or your child's doctor or poison control center right away, or get emergency treatment.

What are possible side effects of DESOXYN?

See "What is the most important information I should know about DESOXYN?" for information on reported heart and mental problems.

Other serious side effects include:

• slowing of growth (height and weight) in children
• seizures, mainly in patients with a history of seizures
• eyesight changes or blurred vision

Common side effects include:

     • fast heart beat           • decreased appetite

     • tremors                      • headache

     • trouble sleeping        • dizziness

     • stomach upset          • weight loss

     • dry mouth

DESOXYN may affect your or your child's ability to drive or do other dangerous activities.

Talk to your or your child's doctor if you or your child has side effects that are bothersome or do not go away.

This is not a complete list of possible side effects. Ask your or your child's doctor or pharmacist for more information.

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

How should I store DESOXYN?

• Store DESOXYN in a safe place below 86°F (30°C). Protect from light.
• Keep DESOXYN and all medicines out of the reach of children.

General information about DESOXYN

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use DESOXYN for a condition for which it was not prescribed. Do not give DESOXYN to other people, even if they have the same condition. It may harm them and it is against the law.

This Medication Guide summarizes the most important information about DESOXYN. If you would like more information, talk with your or your child's doctor. You can ask your or your child's doctor or pharmacist for information about DESOXYN that was written for healthcare professionals.

For more information about DESOXYN, contact Lundbeck Inc. at 1-800-455-1141 or visit www.Lundbeckinc.com.

What are the ingredients in DESOXYN?

Active Ingredient: methamphetamine hydrochloride

Inactive Ingredients: Corn starch, lactose, sodium paraminobenzoate, stearic acid and talc

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Lundbeck Inc.

Deerfield, IL 60015, U.S.A.

® Trademark of Lundbeck Inc.

Revised: May 2009

PRINCIPAL DISPLAY PANEL

NDC 67386-102-01