Lopinavir / ritonavir

Atorvastatin

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

Lopinavir / ritonavir may possibly inhibit the metabolism (CYP 3A4) and consequently increase the plasma concentration of Atorvastatin.

Lopinavir / ritonavir

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Atorvastatin

Pharmacodynamic effects

Possible increased risk of HMG CoA inhibitor toxicity.

Recommendations

Start therapy with a 10 mg dose once daily, and increase with caution depending on patient clinical response and tolerance.

In patients already under treatment, a reduction in dosage may be necessary.

We do not recommend more than 20 mg per day (U.S. guidelines) and 40 mg per day (European guidelines).

Or choose an alternative.

Alternative solution(s)

Pravastatin or ezetimibe.

Monitor

Symptoms of toxicity associated with hypolipidemic agents : gastrointestinal effects, fatigue and muscular weaknesses, myalgias, muscular cramps, myopathies, rhabdomyolysis and myoglobinuria leading to renal insufficiency.

Tests

AST

ALT

CK

Lipidic profile

Pharmacokinetic parameters
Parameters
Reference number
Dose
Frequency
# patients
AUC
Cmax
Cmin
Duration (days)
HIV
Lopinavir / ritonavir
1162
400/100 mg
BID
12
- 10%
- 10%
- 8%
14
-
Atorvastatin
1162
20 mg
QD
12
+ 488%
+ 367%
+ 128%
4
-
Comment

Lopinavir/ritonavir substantially reduced o-OH-atorvastatin Cmax and AUC, substantially increased p-OH-atorvastatin AUC and Cmax, and increased HMG-CoA reductase inhibitory activity Cmax and AUC by 4.5 and 2.5 fold, respectively.

We also observe an increase in AUC of atorvastatin with saquinavir/ritonavir, darunavir/ritonavir, tipranavir/ritonavir, fosamprenavir/ritonavir and nelfinavir.

Ref #1695: Case report of drug-induced rhabdomyolysis in a 34-year-old HIV-infected male with a history of liver disease and concomitant use of clarithromycin, atorvastatin, and lopinavir/ritonavir.


Reference
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