TEVA-MODAFINIL

1 Dosing Considerations • A cardiac evaluation, including an electrocardiogram (ECG), should be obtained for all patients before treatment with Teva-Modafinil is initiated. This is particularly recommended for patients with coronary artery disease, a recent history or myocardial infarction, or unstable angina.

Patients with abnormal findings should receive further evaluation before Teva-Modafinil treatment is considered. See 7 WARNINGS AND PRECAUTIONS, Cardiovascular. 1 TEVA-MODAFINIL (modafinil tablets) Page 6 of 49 Pregnant Women). Women of reproductive potential should have a negative pregnancy test within a week prior to starting treatment with modafinil.

4 Drug-Drug Interactions). Alternative or concomitant methods of contraception other than steroidal are recommended for patients treated with Teva-Modafinil, and for two months after discontinuation of Teva- Modafinil. 2 Recommended Dose and Dosage Adjustment Recommended Dose Narcolepsy: The adult daily dosage of Teva-Modafinil for patients with narcolepsy is between 200 to 400mg, divided between morning and noon doses.

The initial daily dose should be 200mg in divided doses, increasing in increments of 100mg as needed and tolerated. The total daily dose can be divided according to the needs and response of the patient. The timing should be aimed to coincide with the periods of greatest excessive daytime sleepiness.

The second dose should generally be taken no later than the early afternoon to minimize the risk of insomnia. d. Single doses of 300mg or more, or total daily doses of more than 400mg are therefore not recommended.

Obstructive Sleep Apnea:

In OSA, Teva-Modafinil is indicated as an adjunct to successful standard treatment(s) for the underlying obstruction (see 1 INDICATIONS). For patients with OSA, the adult daily dosage of Teva-Modafinil is 200mg taken as a single dose in the morning.

Circadian Rhythm Sleep Disorder, Shift Work Type (Shift Work Disorder):

For patients with SWD, the adult daily dosage of Teva-Modafinil is 200mg taken approximately 1 hour prior to the start of their work shift. Dosage Adjustment Pediatric (<18 years of age) The safety and efficacy of modafinil in children under the age of 18 years has not been established.

1 Adverse Reaction Overview The most commonly observed adverse events (≥5%) associated with the use of modafinil and observed more frequently than placebo treated patients in the placebo controlled clinical studies in primary disorders of sleep and wakefulness were headache, nausea, rhinitis, nervousness, diarrhea, back pain, anxiety, dizziness, dyspepsia, and insomnia.

The adverse event profile was similar across these studies. In the placebo controlled clinical trials, 74 of the 934 patients (8%) who received modafinil discontinued due to an adverse experience compared to 3% of patients that received placebo.

The most frequent reasons for discontinuation that occurred at a higher rate for modafinil than placebo patients were headache (2%), anxiety (1%), nervousness (1%), agitation, chest pain, confusion, depression, dizziness, insomnia, and nausea (each <1%).

2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. The following table presents the adverse experiences that occurred at a rate of 1% or more and TEVA-MODAFINIL (modafinil tablets) Page 17 of 49 were more frequent in adult patients treated with modafinil than in placebo-treated patients in the principal, placebo-controlled clinical trials.

Table 2:

Incidence of Treatment-Emergent Adverse Experiences in Parallel-Group, Placebo-controlled Clinical Trials1 with modafinil in Adults with Narcolepsy and Obstructive Sleep Apnea and Circadian Rhythm Sleep Disorder, Shift Work Type (Shift Work Disorder) (200mg, 300mg and 400mg)* Modafinil n=934 (%) Placebo n=567 (%) Body as Whole Headache 34% 23% Back Pain 6% 5% Flu Syndrome 4% 3% Chest Pain 3% 1% Chills 1% 0% Neck Rigidity 1% 0% Cardiovascular Hypertension 3% 1% Tachycardia 2% 1% Palpitation 2% 1% Vasodilatation 2% 0% Digestive Nausea 11% 3% Diarrhea 6% 5% Dyspepsia 5% 4% Dry Mouth 4% 2% Anorexia 4% 1% Constipation 2% 1% Abnormal Liver Function2 2% 1% Flatulence 1% 0% Mouth Ulceration 1% 0% Thirst 1% 0% Hemic/Lymphatic Eosiniphilia 1% 0% Metabolic/Nutritional Edema 1% 0% Nervous Nervousness 7% 3% Insomnia 5% 1% Anxiety 5% 1% TEVA-MODAFINIL (modafinil tablets) Page 18 of 49 Modafinil n=934 (%) Placebo n=567 (%) Dizziness 5% 4% Depression 2% 1% Paresthesia 2% 0% Somnolence 2% 1% Hypertonia 1% 0% Dyskinesia3 1% 0% Hyperkinesia 1% 0% Agitation 1% 0% Confusion 1% 0% Tremor 1% 0% Emotional Lability 1% 0% Vertigo 1% 0% Respiratory Rhinitis 7% 6% Pharyngitis 4% 2% Lung Disorder 2% 1% Epistaxis 1% 0% Asthma 1% 0% Skin/Appendages Sweating 1% 0% Herpes Simplex 1% 0% Special Senses Amblyopia 1% 0% Abnormal Vision 1% 0% Taste Perversion 1% 0% Eye Pain 1% 0% Urogenital Urine Abnormality 1% 0% Hematuria 1% 0% Pyuria 1% 0% * Six double-blind, placebo controlled clinical studies in narcolepsy (200 and 400 mg), OSA (200 and 400 mg) and SWD (200 mg and 300 mg).

, General). There is no evidence that normal levels of alertness can be heightened by Teva-Modafinil. 1 Clinical Trial Adverse Reactions – Pediatric). Therefore, Teva-Modafinil is not approved for use in pediatric patients for any indication including Attention Deficit Hyperactivity Disorder (ADHD).

Serious cutaneous adverse reactions have been reported with modafinil use in pediatric patients (see 7 WARNINGS AND PRECAUTIONS, Skin). 4 Geriatrics). 2 CONTRAINDICATIONS Teva-Modafinil is contraindicated: • In patients who are hypersensitive to modafinil, armodafinil (the R-enantiomer of modafinil; not marketed in Canada) or to any ingredient in the formulation, including any nonmedicinal ingredient, or component of the container.

For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. • In patients in agitated states and in patients with severe anxiety. • In women who are pregnant or may become pregnant. 1 Pregnant Women). 1 Dosing Considerations • A cardiac evaluation, including an electrocardiogram (ECG), should be obtained for all patients before treatment with Teva-Modafinil is initiated.

This is particularly recommended for patients with coronary artery disease, a recent history or myocardial infarction, or unstable angina. Patients with abnormal findings should receive further evaluation before Teva-Modafinil treatment is considered.

See 7 WARNINGS AND PRECAUTIONS, Cardiovascular. 1 TEVA-MODAFINIL (modafinil tablets) Page 6 of 49 Pregnant Women). Women of reproductive potential should have a negative pregnancy test within a week prior to starting treatment with modafinil.

4 Drug-Drug Interactions). Alternative or concomitant methods of contraception other than steroidal are recommended for patients treated with Teva-Modafinil, and for two months after discontinuation of Teva- Modafinil. 2 Recommended Dose and Dosage Adjustment Recommended Dose Narcolepsy: The adult daily dosage of Teva-Modafinil for patients with narcolepsy is between 200 to 400mg, divided between morning and noon doses.

Teva-Modafinil is contraindicated: • In patients who are hypersensitive to modafinil, armodafinil (the R-enantiomer of modafinil; not marketed in Canada) or to any ingredient in the formulation, including any nonmedicinal ingredient, or component of the container.

For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. • In patients in agitated states and in patients with severe anxiety. • In women who are pregnant or may become pregnant. 1 Pregnant Women).