Safety

Safety Tolerability

*	Total bound and unbound valproate.
†	Concurrent use of TRILEPTAL with the oral contraceptive components ethinyl estradiol and levonorgestrel may render these contraceptives less effective; studies with other oral or implant contraceptives have not been conducted.
‡	Causes a decrease in lamotrigine efficacy.
§	The possibility of decreased contraceptive efficacy should be considered at dosages between 200 and 800 mg/day.

	Low rates of discontinuation due to behavioral, psychiatric, or cognitive side effects in clinical trials with monotherapy
	Linear pharmacokinetics with no autoinduction
	No routine hematologic or hepatic monitoring required
	Minimal interaction with the CYP450 enzyme system||
	Pregnancy category C See TRILEPTAL Prescribing Information

^||A decrease in the dose of phenytoin may be required when TRILEPTAL is added on at doses >1200 mg/day. TRILEPTAL may also reduce the effectiveness of certain oral contraceptives.

Considerations regarding hyponatremia

	In 14 controlled epilepsy trials, 2.5% (38/1524) of patients treated with TRILEPTAL developed clinically significant hyponatremia (sodium <125 mEq/L)1 — Most cases were asymptomatic
	Experience from clinical trials indicates that sodium levels returned toward normal when the TRILEPTAL dosage was reduced or discontinued, or when the patient was treated conservatively (eg, fluid restriction)1
	Most cases of hyponatremia (78%) were associated with the use of concomitant medications, including carbamazepine, steroids, antidepressants, vasodilators, diuretics, female hormones, and cathartics9
	Measurement of serum sodium levels should be considered for patients at risk of hyponatremia.1 (Please see WARNINGS section of complete prescribing information)

Clinically significant hyponatremia* per week after initial dose of TRILEPTAL⁹


*Sodium <125 mEq/L.

References:

1.		TRILEPTAL® [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; January 2006.
2.		Tegretol® (carbamazepine USP) tablets [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; September 2003.
3.		Dilantin® (phenytoin) [prescribing information]. New York, NY: Pfizer Inc; February 2003.
4.		Depakote® (divalproex sodium delayed-release tablets) [prescribing information]. North Chicago, Ill: Abbott Laboratories; September 2004.
5.		Lamictal® (lamotrigine) tablets [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; August 2004.
6.		Topamax® (topiramate) [prescribing information]. Titusville, NJ: Ortho-McNeil Neurologics, Inc; June 2005.
7.		Keppra® (levetiracetam) tablets [prescribing information]. Smyrna, Ga:UCB Pharma Inc; June 2005.
8.		Drug Facts and Comparisons. Facts and Comparisons. Wolters Kluwer Company, St. Louis, Mo; 2003.
9.		Data on file. Novartis Pharmaceuticals Corporation, East Hanover, NJ.