Divalproex Sodium (Page 7 of 14)

6.3 Migraine

Based on two placebo-controlled clinical trials and their long term extension, valproate was generally well tolerated with most adverse reactions rated as mild to moderate in severity. Of the 202 patients exposed to valproate in the placebo-controlled trials, 17% discontinued for intolerance. This is compared to a rate of 5% for the 81 placebo patients. Including the long term extension study, the adverse reactions reported as the primary reason for discontinuation by ≥ 1% of 248 valproate-treated patients were alopecia (6%), nausea and/or vomiting (5%), weight gain (2%), tremor (2%), somnolence (1%), elevated SGOT and/or SGPT (1%), and depression (1%).

Table 6 includes those adverse reactions reported for patients in the placebo-controlled trial where the incidence rate in the divalproex sodium extended-release tablets-treated group was greater than 5% and was greater than that for placebo patients.

Table 6 Adverse Reactions Reported by > 5% of Divalproex Sodium Extended-Release Tablets-Treated Patients During the Migraine Placebo-Controlled Trial with a Greater Incidence than Patients Taking Placebo *

* The following adverse reactions occurred in greater than 5% of divalproex sodium extended-release tablets-treated patients and at a greater incidence for placebo than for divalproex sodium extended-release tablets: asthenia and flu syndrome.
Body System Event	Divalproex Sodium Extended-Release Tablets	Placebo
	(N=122)	(N=115)
Gastrointestinal System	%	%
Nausea	15	9
Dyspepsia	7	4
Diarrhea	7	3
Vomiting	7	2
Abdominal Pain	7	5
Nervous System
Somnolence	7	2
Other
Infection	15	14

The following additional adverse reactions were reported by greater than 1% but not more than 5% of divalproex sodium extended-release tablets-treated patients and with a greater incidence than placebo in the placebo-controlled clinical trial for migraine prophylaxis:

Body as a Whole

Accidental injury, viral infection.

Digestive System

Increased appetite, tooth disorder.

Metabolic and Nutritional Disorders

Edema, weight gain.

Nervous System

Abnormal gait, dizziness, hypertonia, insomnia, nervousness, tremor, vertigo.

Respiratory System

Pharyngitis, rhinitis.

Skin and Appendages

Rash.

Special Senses

Tinnitus.

Table 7 includes those adverse reactions reported for patients in the placebo-controlled trials where the incidence rate in the valproate-treated group was greater than 5% and was greater than that for placebo patients.

Table 7 Adverse Reactions Reported by > 5% of Valproate-Treated Patients During Migraine Placebo-Controlled Trials with a Greater Incidence than Patients Taking Placebo *

* The following adverse reactions occurred in greater than 5% of divalproex sodium delayed-release tablets-treated patients and at a greater incidence for placebo than for divalproex sodium delayed-release tablets: flu syndrome and pharyngitis.
Body System Reaction	Divalproex Sodium Delayed-Release Tablets	Placebo
	(n=202)	(n=81)
	%	%
Gastrointestinal System
Nausea	31	10
Dyspepsia	13	9
Diarrhea	12	7
Vomiting	11	1
Abdominal Pain	9	4
Increased Appetite	6	4
Nervous System
Asthenia	20	9
Somnolence	17	5
Dizziness	12	6
Tremor	9	0
Other
Weight gain	8	2
Back pain	8	6
Alopecia	7	1

The following additional adverse reactions were reported by greater than 1% but not more than 5% of the 202 valproate-treated patients in the controlled clinical trials:

Body as a Whole

Chest pain.

Cardiovascular System

Vasodilatation.

Digestive System

Constipation, dry mouth, flatulence, and stomatitis.

Hemic and Lymphatic System

Ecchymosis.

Metabolic and Nutritional Disorders

Peripheral edema.

Musculoskeletal System

Leg cramps.

Nervous System

Abnormal dreams, confusion, paresthesia, speech disorder, and thinking abnormalities.

Respiratory System

Dyspnea, and sinusitis.

Skin and Appendages

Pruritus.

Urogenital System

Metrorrhagia.