Atazanavir + Lamotrigine = Precautionary

Effect on Concentration

Atazanavir
No change
Applies within class?
No
Lamotrigine
Decrease
Applies within class?
No

Pharmacologic Effects

Atazanavir
Effect
N/A
Applies within class?
No
Lamotrigine
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 01-Aug-2018

Summary

Sources

Atazanavir/Ritonavir versus Lamotrigine ^

Study Design

Twenty‐one healthy volunteers received a single dose of 100 mg of oral lamotrigine on days 1, 13, and 27; on each occasion blood was sampled before the dose was administered and through 120 h after ingestion of the drug. On days 8–17 the subjects received oral ATV 400 mg q.d. On days 18–30 the subjects received oral ATV 300 mg plus oral RTV 100 mg q.d. Seventeen subjects were evaluable for pharmacokinetic analysis.

Study Results

ATV/r can decrease lamotrigene concentrations by up to 32% by induction of UGT1A4 metabolism, this only occurs with ATV/r and not with ATV alone. Geometric mean ratios (+90% confidence intervals (CIs)) of lamotrigine area under the plasma concentration‐time curve (AUC)0–inf and peak plasma concentration (Cmax) for ATV + lamotrigine and for lamotrigine alone were 0.88 (0.86–0.91) and 0.99 (0.95–1.02), respectively; the corresponding ratios for ATV/RTV and for lamotrigine were 0.68 (0.65–0.70) and 0.94 (0.90–0.97), respectively. The mean ratio of lamotrigine‐2N‐glucuronide to lamotrigine AUC0–inf increased from 0.45 for lamotrigine to 0.71 for ATV/RTV + lamotrigine.

Study Conclusions

The co-administration of ritonavir with lamotrigine may cause a decrease in the plasma concentration of lamotrigine. ATV alone does not significantly influence glucuronidation of lamotrigine. In contrast, ATV/RTV results in moderately decreased exposure to lamotrigine.Dose adjustments to lamotrigene are probably needed

References

Burger DM, Huisman A, Van Ewijk N, Neisingh H, Van Uden P, Rongen GA, Bertz RJ. The effect of atazanavir and atazanavir/ritonavir on udp‐glucuronosyltransferase using lamotrigine as a phenotypic probe. Clinical Pharmacology And Therapeutics. 2008; 6: 698-703.