Raltegravir with Rifampin Interaction Details

Brand Names Associated with Raltegravir

Brand Names Associated with Rifampin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Jan 04, 2024

Interaction Effect

Decreased plasma concentrations of raltegravir

Interaction Summary

The Cmax, AUC, and Cmin of raltegravir 400 mg were reduced when coadministered with rifampin. However, when the raltegravir dose was doubled to 800 mg, rifampin decreased the trough concentration of raltegravir but increased the AUC and Cmax. Coadministration of raltegravir granules for oral suspension and rifampin in an infant with HIV receiving rifampin for tuberculosis (TB) prophylaxis resulted in subtherapeutic raltegravir trough levels and increased viral load despite using double-dosed raltegravir . Caution is recommended when raltegravir and rifampin are coadministered because rifampin induces the metabolism of raltegravir resulting in reduced raltegravir plasma concentrations. During coadministration with rifampin, close monitoring for virologic response and a dose increase to raltegravir 800 mg twice daily with or without food is recommended for adults; no data is available regarding potential dose adjustments in patients less than 18 years of age .

Severity

Moderate

Onset

Rapid

Evidence

Established

How To Manage Interaction

Caution is recommended when raltegravir and rifampin are coadministered because rifampin induces the metabolism of raltegravir resulting in reduced raltegravir plasma concentrations. During coadministration with rifampin, close monitoring for virologic response and a dose increase to raltegravir 800 mg twice daily with or without food is recommended for adults; no data are available regarding potential dose adjustments in patients less than 18 years of age.

Mechanism Of Interaction

Induction of uridine diphosphate glucuronosyltransferases (UGT1A1) glucuronidation of raltegravir by rifampin

Literature Reports

A) Coadministration of single-dose raltegravir 400 mg with rifampin 600 mg once daily resulted in lower raltegravir AUC and plasma concentrations in an open-label, 2-period, fixed-sequence pharmacokinetic study in healthy volunteers (n=9). Comparing raltegravir plus rifampin to raltegravir alone, the geometric mean trough concentrations (C(12)) were 36.3 and 92.1 nanomoles (nM), AUC values were 16.51 and 27.57 micromole x hour, Cmax values were 5.34 and 8.61 micromoles, and Tmax values were 3 and 1.5 hours, respectively. The geometric mean ratios (raltegravir plus rifampin/raltegravir) for the C(12), AUC, and Cmax were 0.39 (90% CI, 0.3 to 0.51, p=0.0002), 0.6 (90% CI, 0.39 to 0.91, p=0.0514), and 0.62 (90% CI, 0.37 to 1.04, p=0.1234), respectively .

B) Coadministration of raltegravir 400 milligrams (mg) twice daily (double-dose) with rifampin 600 mg once daily resulted in lower raltegravir plasma trough concentration (C(12)), but increased the AUC and Cmax of raltegravir compared to administration of raltegravir 400 mg alone in an open-label, 2-period, fixed-sequence pharmacokinetic study in healthy volunteers (n=17). Comparing raltegravir 800 mg plus rifampin to raltegravir 400 mg alone, the geometric mean trough concentrations (C(12)) were 43.51 and 92.47 nanomoles, AUC values were 5.85 and 4.61 micromole x hr, Cmax values were 1.95 and 1.21 micromoles, and Tmax values were 1.75 and 3 hr, respectively. The geometric mean ratios (raltegravir 800 mg plus rifampin/raltegravir 400 mg) for the C(12), AUC, and Cmax were 0.47 (90% CI, 0.36 to 0.61, p less than 0.0001), 1.27 (90% CI, 0.94 to 1.71, p=0.1862), and 1.62 (90% CI, 1.12 to 2.33, p=0.0329), respectively .

C) Coadministration of raltegravir granules for oral suspension and rifampin in an infant with HIV receiving rifampin for tuberculosis (TB) prophylaxis resulted in subtherapeutic raltegravir trough levels and increased viral load despite using double-dosed raltegravir. At age 5.5 months, the infant's mother was diagnosed with TB and rifampin (10 mg/kg/day) and isoniazid for primary TB prophylaxis was started and continued for 2 and 3 months, respectively. Beginning at 2 months of age, the infant had received combination HIV treatment containing raltegravir granules (6 mg/kg/day). Raltegravir dosing during and after rifampin therapy was guided by therapeutic drug monitoring to maintain trough levels greater than 0.022 mg/L. Raltegravir trough levels dropped to undetectable concentrations within 2 weeks after rifampin initiation and remained subtherapeutic after increasing the raltegravir dose from 11 mg/kg/day to 25 mg/kg/day. Subsequently, a detectable viral load was measured and raltegravir was increased further to 50 mg/kg/day. Two weeks after rifampin was discontinued, the raltegravir dose was lowered to 17 mg/kg/day as enzyme induction was suspected to be negligible; however, raltegravir trough levels remained subtherapeutic. Raltegravir was increased again to 50 mg/kg/day and therapeutic levels were achieved. No subtherapeutic raltegravir levels or detectable viral loads were measured thereafter. No other drugs or supplements known to potentially interfere with raltegravir pharmacokinetics were used .

Raltegravir Overview

• Raltegravir is used along with other medications to treat human immunodeficiency virus (HIV) infection in adults and children who weigh at least 4.5 lbs (2 kg). Raltegravir is in a class of medications called HIV integrase inhibitors. It works by decreasing the amount of HIV in the blood. Although raltegravir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other life-style changes may decrease the risk of transmitting (spreading) the HIV virus to other people.

Rifampin Overview

• Rifampin is used with other medications to treat tuberculosis (TB; a serious infection that affects the lungs and sometimes other parts of the body). Rifampin is also used to treat some people who have Neisseria meningitidis (a type of bacteria that can cause a serious infection called meningitis) infections in their noses or throats. These people have not developed symptoms of the disease, and this treatment is used to prevent them from infecting other people. Rifampin should not be used to treat people who have developed symptoms of meningitis. Rifampin is in a class of medications called antimycobacterials. It works by killing the bacteria that cause infection.

• Antibiotics such as rifampin will not work for colds, flu, or other viral infections. Using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.