Posted by Sunnely on June 18, 2001, at 21:55:27
In reply to Tegretol/depakote start-up issues??? Feel strange, posted by katrina on June 18, 2001, at 16:43:47
Hi Katrina,
The combined use of carbamazepine (Tegretol) and divalproex sodium (Depakote) increases the risk of more pronounced central nervous system (CNS) side effects (neurotoxicity) than if either drug used alone. CNS side effects may include drowsiness, dizziness, vertigo, and unsteadiness. Feelings of derealization or depersonalization (what you probably experienced) may also occur.
Aside from "pharmacodynamic" drug interaction (site of action), "pharmacokinetic" drug interaction (usually involves metabolism) can also occur between Tegretol and Depakote. The addition of Depakote to Tegretol may lead to an increased ratio of 10,11-carbamazepine epoxide (CBZE) via inhibition of the enzyme called epoxide hydroxylase. This could lead to neurotoxicity in some patients. Also, Depakote may cause displacement of Tegretol from protein-binding proteins, producing a transient increase in Tegretol effects. Conversely, Tegretol reduces Depakote levels but increases levels of Depakote's metabolite (daughter compound) called 2-propyl-4-pentanoic acid, which is hepatotoxic (can cause damage to the liver) and teratogenic (can cause birth defects).
Although the Tegretol-Depakote combination is usually well tolerated, avoid this combination if possible. However, if the combination is used, the following measures should be followed to avoid potential toxicity:
1. Monitor blood levels of both Tegretol and Depakote closely.
2. Obtain blood level of CBZE (10,11 carbamazepine epoxide) if possible. (Note: Checking for the blood level of this Tegretol daughter compound is rarely obtained in clinical practice.)
3. Closely monitor the patient for signs of neurotoxicity and adjust the dose accordingly.
4. Liver function tests (LFTs) should be checked more frequently than with either drug alone.
5. This combination seems more useful in patients with bipolar disorder who are partially or treatment-resistant to either drug alone. Patients with schizoaffective disorder and brain-injury seem more prone to occurrence of neurotoxicity with this combinatioin.
6. Keep in mind that in some patients maintained on this combination, discontinuing Tegretol may lead to subsequent increased in Depakote blood level.
7. Last but not least, for women of child-bearing age, supplemental dosage of folic acid (400 mcg) is advisable when taking either or both drugs.
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> Did anyone else feel funny getting on this stuff? I just started 100 mg of tegretol with only 350 mgs. of depakote, but when I added the tegretol I got this weird feeling like I was totally disconected or just really off... Can anyone relate? Does this wear off or just pass etc.? Any help would be great...I am upping the dose in another week so I am not looking forward to it again or more intensely.
poster:Sunnely
thread:66992
URL: http://www.dr-bob.org/babble/20010618/msgs/67016.html