Lopinavir / ritonavir

Valproic acid (valproate, divalproex)

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

Lopinavir / ritonavir may increase 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.

Reference
  • 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.