MECHANISM OF ACTION
Carbamazepine may induce the metabolism of the
protease inhibitors at CYP P-450-3A4.(1-7) Ritonavir may inhibit the
metabolism of carbamazepine by CYP P-450-3A4.(8,9)
DISCUSSION
In a case report, an HIV-positive male restarted antiretroviral
therapy with indinavir (800 mg every 8 hours), lamivudine (150 mg twice
daily), and zidovudine (200 mg three times daily) in November of 1997. In
January of 1998, carbamazepine (200 mg daily) was started for post-herpetic
neuralgia. Despite the low dose of carbamazepine, carbamazepine levels were
6.7 mg/L and 8.9 mg/L in February, 1998 and March, 1998, respectively. At
the end of March, 1998, carbamazepine was discontinued. In January and
February of 1998, the patient's viral load was undetectable and his CD4+
count was 340x106/L and 400x106/L, respectively. By April of 1998, his
HIV-RNA level had risen to 6x103 copies/ml and his CD4+ count decreased to
200x106/L. His HIV-RNA level increased to 300x103 copies/ml three months
later. Prior to carbamazepine therapy, the patient's indinavir levels had
been 61% of the reference population. During carbamazepine therapy, his
indinavir levels decreased to a value of 4% of the reference population. Two
weeks after carbamazepine was discontinued, his indinavir levels increased
to a value of 173% of the reference population.(2)
CLINICAL EFFECTS
The concurrent use of indinavir and carbamazepine may
result in higher than anticipated carbamazepine levels, decreased indinavir
plasma levels, and antiretroviral therapy failure.(1,2)
SEVERITY LEVEL
2-Severe Interaction: Action is required to reduce the risk
of severe adverse interaction.
PATIENT MANAGEMENT
Consider avoiding the concurrent use of carbamazepine
and amprenavir, fosamprenavir, indinavir, lopinavir nelfinavir, or
saquinavir. If concurrent therapy is warranted, carbamazepine and protease
inhibitor levels, as well as antiretroviral response, should be closely
monitored.
PREDISPOSING FACTORS
None determined.
REFERENCES