https://interactions.guidetherapeutiquevih.com/en/interaction-details?id=7593

Lopinavir / ritonavir

Valproic acid (valproate, divalproex)

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

Lopinavir / ritonavir may induce the metabolism (UGT) and decrease the plasma concentration of Valproic acid (valproate, divalproex).

Lopinavir / ritonavir

Pharmacodynamic effects

–

Recommendations

–

Alternative solution(s)

–

Valproic acid (valproate, divalproex)

Pharmacodynamic effects

Possible decrease of clinical efficacy.

Recommendations

Monitor for treatment response.

Adjust dosage if necessary.

Alternative solution(s)

–

Monitor

–

Tests

Valproic acid

Pharmacokinetic parameters
Parameters
Reference number
# patients
HIV
Dose
Frequency
AUC
Duration (days)
Lopinavir / ritonavir
1623
8
+
400/100 mg
BID
+ 38% *
 
Valproic acid (valproate, divalproex)
1623
11
+
250 mg
BID
 
7
Comment

Ref #1623 : * Refers to lopinavir.
There were no significant differences in lopinavir Cmin (6.81 vs 10.7 ng/ml) or Cmax (12.4 vs 16.5 ng/ml) when given with valproic acid. Valproic acid trough not significantly
changed.

Ref #1940 : A case report of a 30 year old man with valproic acid concentrations decreased (- 48%) 21 days after starting lopinavir/ritonavir; valproic acid dosage was doubled and levels re-stabilized.

Comment
Reference
  • 2573
    Ritonavir (Norvir), Corporation AbbVie, Quebec, Canada, 5 juillet 2021.
  • 1623
    DiCenzo R, Peterson D, Cruttenden K, et al. Effects of Valproic Acid Coadministration on Plasma Efavirenz and Lopinavir Concentrations in Human Immunodeficiency Virus-Infected Adults. Antimicrob Agents Chemother. 2004 November;48(11):4328–4331.
  • 1940
    Sheehan NL, Brouillette MJ, Delisle MS, and Allan J. Possible interaction between lopinavir/ritonavir and valproic acid exacerbates bipolar disorder. Ann Pharmacother 2006; 40(1):147-150.
  • 2968
    Ritonavir (Norvir), European public assessment report (EPAR) Product Information, London, United Kingdom, 18 fév 2014.