Risks and Side Effects

CONTRAINDICATIONS

  • Do not use JULUCA in patients with previous hypersensitivity reaction to dolutegravir or rilpivirine
  • Do not use JULUCA in patients receiving dofetilide, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, systemic dexamethasone (>1 dose), St John's wort, and proton pump inhibitors (eg, esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole)

Skin and Hypersensitivity Reactions:

  • Hypersensitivity reactions have been reported with dolutegravir and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury
  • Severe skin and hypersensitivity reactions have been reported during postmarketing experience, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), with rilpivirine-containing regimens and have been accompanied by fever and/or organ dysfunctions, including elevations in hepatic serum biochemistries
  • Discontinue JULUCA immediately if signs or symptoms of severe skin or hypersensitivity reactions develop, as a delay in stopping treatment may result in a life-threatening reaction. Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated

Hepatotoxicity:

  • Hepatic adverse events have been reported, including cases of hepatic toxicity (elevated serum liver biochemistries, hepatitis, and acute liver failure), in patients receiving a dolutegravir-containing regimen without pre-existing hepatic disease or other identifiable risk factors
  • Patients with underlying hepatitis B or C or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations with the use of JULUCA. In some cases, the elevations in transaminases were consistent with immune reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn
  • Monitoring for hepatotoxicity is recommended

Embryofetal Toxicity:

  • Avoid use of dolutegravir, a component of JULUCA, at the time of conception through the first trimester due to the risk of neural tube defects
  • Perform pregnancy testing before use of dolutegravir and advise that consistent use of effective contraception is recommended while using dolutegravir in adolescents and adults of childbearing potential

Depressive Disorders:

  • Depressive disorders (including depressed mood, depression, dysphoria, major depression, mood altered, negative thoughts, suicide attempt, and suicidal ideation) have been reported with rilpivirine
  • Promptly evaluate patients with severe depressive symptoms

Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions:

  • The concomitant use of JULUCA and other drugs may result in known or potentially significant drug interactions (see Contraindications and Drug Interactions)
  • Rilpivirine doses 3 and 12 times higher than the recommended dose can prolong the QTc interval. Consider alternatives to JULUCA when coadministered with a drug with a known risk of Torsade de Pointes. Consider the potential for drug interactions prior to and during therapy with JULUCA and monitor for adverse reactions

Adverse Reactions and Rates of Discontinuation Due to Adverse Events Through Week 1001*

 

The most common adverse reactions Grades 1 to 4 with ≥2% frequency in the JULUCA arm through 48 weeks were diarrhea (2%) and headache (2%). Withdrawals due to adverse events through 48 weeks occurred in 4% (21/513) of patients in the JULUCA arm compared to <1% (3/511) with continuing ART.

 

 

*SWORD 1 & 2 (pooled data).
Most common AEs leading to discontinuation were psychiatric disorders: 2% of patients who continued on JULUCA through Week 100 and 1% of patients who switched to JULUCA at Week 52.
AEs=adverse events.

Reference:

  1. Aboud M, Orkin C, Podzamczer D, et al. Durable suppression 2 years after switch to the DTG+RPV 2-drug regimen: SWORD-1 and SWORD-2 studies. Presented at the 22nd International AIDS Conference (IAC); July 23-27, 2018; Amsterdam, the Netherlands. Poster THPEB047.

Risks and Side Effects of Juluca