Lamotrigine Ritonavir

Clinically important, potentially hazardous interactions with aminophylline, anticonvulsants, aprepitant, bedomethasone, bosentan, budesonide, cigarette smoking, danazol, efavirenz, exenatide, flucloxacillin, flunisolide, fluticasone, hydrocortisone, insulin detemir, lamotrigine, licorice, lymecycline, methylprednisolone, modafinil, nelfinavir, prednisolone, prednisone, rifabutin, rifampin, ritonavir, saw palmetto, selegiline, St John s wort, triamcinolone, troleandomycin, tuberculostatics, ursodeoxycholic acid, zolmitriptan... 

Lopinavir/ritonavir halved lamotrigine plasma levels, whereas the protease inhibitor levels did not appear to be altered. Saquinavir/ritonavir had similar effects in another patient and therefore reduced lamotrigine levels should be anticipated with any ritonavir-boosted regimen. 

Lopinavir/ritonavir probably decreases lamotrigine levels by induction of glucuronidation (suggested by the increase in the AUC ratio of lamotrigine 2N-glucuronide to lamotrigine). 

The pharmacokinetic interaction would appear to be established however, since the relationship between lamotrigine levels and efficacy is not clear, the clinical relevance of the decrease is uncertain. Lamotrigine efficacy should be monitored in patients taking lopinavir/ritonavir, and probably any ritonavir-boosted regimen. Anticipate the need to increase the lamotrigine dose. 

A 30-year-old woman taking nevirapine, saquinavir 1.2 g daily and ritonavir 600 mg daily with undeteetable viral load had her epilepsy med-ieation ehanged from gabapentin and lorazepam to lamotrigine and phenytoin beeause of inereased frequeney and severity of seizures. She required phenytoin 8 mg/kg daily to maintain therapeutie serum levels. The ritonavir dose was doubled and the saquinavir dose inereased to 2 g daily to eompensate for the enzyme-indueing efifeets of phenytoin. The patient s viral load remained undeteetable, and her seizures deereased over the next 6 months but she died suddenly of unexplained causes following a tonic-elonie seizure (autopsy not performed). ... 

Figure 11 H-bonding functional groups in (a) ritonavir and (b) lamotrigine and methylparaben.

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