From the Guidelines
Rifampin significantly decreases lamotrigine blood levels, potentially reducing its effectiveness in treating epilepsy or bipolar disorder, and the lamotrigine dose may need to be increased to maintain therapeutic effects, as indicated in the study by 1. The interaction between lamotrigine and rifampin is a significant concern due to the potential for reduced efficacy of lamotrigine.
- The study by 1 highlights that rifampin substantially decreases the concentrations of various drugs, including lamotrigine, by inducing UDP-glucuronosyltransferase enzymes.
- This enzyme induction accelerates lamotrigine metabolism and clearance from the body, necessitating a potential dose increase to maintain therapeutic effects.
- The exact dose adjustment required may vary, but therapeutic drug monitoring is recommended to ensure that lamotrigine levels remain within the therapeutic range.
- It is crucial to monitor patients closely for signs of reduced efficacy, such as seizure breakthrough or mood symptoms, during concurrent therapy with rifampin and lamotrigine.
- Additionally, patients should be monitored for signs of lamotrigine toxicity, such as dizziness, headache, vision changes, or rash, when rifampin is discontinued, as the lamotrigine dose may need to be gradually reduced over 1-2 weeks to avoid toxicity as enzyme induction wears off.
From the Research
Drug Interaction Between Lamotrigine and Rifampin
- The interaction between lamotrigine and rifampin has been studied in healthy subjects, where rifampicin significantly increased the clearance of lamotrigine and decreased its half-life and area under the serum concentration-time curve 2.
- Rifampicin, a potent inducer of the microsomal P450 enzyme system and specific isoforms of the uridine 5'-diphosphate(UDP)-glucuronyl-transferase enzyme system, altered the pharmacokinetics of lamotrigine due to induction of the hepatic enzymes responsible for glucuronidation 2.
- The study found that rifampicin increased the amount of lamotrigine excreted as glucuronide, indicating that rifampicin induces the glucuronidation of lamotrigine 2.
- Another study evaluated the impact of therapeutic drug monitoring on patients on lamotrigine therapy and the evaluation of possible drug interactions, but it did not specifically examine the interaction between lamotrigine and rifampin 3.
- However, the study found that hepatic enzyme inducers, such as carbamazepine and phenytoin, can increase the clearance of lamotrigine, which is similar to the effect of rifampicin 3.
- A review of the clinical pharmacokinetics of newer antiepileptic drugs, including lamotrigine, found that lamotrigine has linear kinetics and reliable absorption, and is not metabolized through the cytochrome P450 system 4.
- The review also noted that valproic acid inhibits the glucuronidation of lamotrigine and increases its half-life, which is the opposite effect of rifampicin 4.
- Other studies have evaluated the impact of therapeutic drug monitoring on pediatric patients on lamotrigine therapy and the evaluation of possible drug interactions, but they did not specifically examine the interaction between lamotrigine and rifampin 5.