Nelfinavir + Rifabutin = Precautionary

Effect on Concentration

Nelfinavir
Decrease
Applies within class?
No
Rifabutin
Increase
Applies within class?
No

Pharmacologic Effects

Nelfinavir
Effect
N/A
Applies within class?
No
Rifabutin
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 02-Jul-2018

Summary

Sources

Clinical Evaluation of the Nelfinavir‐Rifabutin Interaction in Patients with Tuberculosis and Human Immunodeficiency Virus Infection. ^

Study Design

Prospective cohort study in Seven patients with HIV‐related tuberculosis from Three clinical research centers. Rifabutin 300 mg and isoniazid 15 mg/kg (maximum dose 900 mg) twice/week were administered for at least 2 weeks during the continuation phase of tuberculosis treatment. Antiretroviral therapy with nelfinavir 1250 mg twice/day and two nucleoside reverse transcriptase inhibitors was then added. Patients underwent blood sampling for pharmacokinetic analysis during the continuation phase of tuberculosis therapy and after a median of 21 days after the addition of antiretroviral treatment.

Study Results

When rifabutin was coadministered with nelfinavir, its area under the concentration‐time curve from 0–21 hours (AUC0–21) increased 22% (geometric mean 5.01 μg•hr/ml [90% confidence interval (CI) 3.25–7.71] with nelfinavir vs 4.10 μg•hr/ml [90% CI 3.18–5.27] without nelfinavir; geometric mean ratio 1.22 [90% CI 0.78–1.92]). Also, the AUC0–21 for the active metabolite, desacetylrifabutin, increased significantly (geometric mean ratio 3.46, 90% CI 1.84–6.47, p=0.009). In the presence of rifabutin, the pharmacokinetic parameters of nelfinavir and its principal metabolite M8 were similar to those of patients not taking rifabutin. No drug interaction between nelfinavir and isoniazid was detected.

Study Conclusions

With the concomitant use of nelfinavir and rifabutin it is recommended to reduce the dose of rifabutin by half of the standard dosage and to increase the dosage of nelfinavir to 1250mg twice daily due to decreased concentrations of nelfinavir and increased concentrations of rifabutin.

References

Benator DA, Weiner MH, Burman WJ, Vernon AA, Zhao ZA, Khan AE, Hsyu PH. Clinical evaluation of the nelfinavir‐rifabutin interaction in patients with tuberculosis and human immunodeficiency virus infection. Pharmacotherapy: The Journal Of Human Pharmacology And Drug Therapy. 2007; 6: 793-800.