Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
WARNINGS AND PRECAUTIONS
QT Interval Prolongation
Patients initiating therapy with INVIRASE/ritonavir:
- An ECG should be performed prior to initiation of treatment. Patients with a QT interval = 450 msec should not initiate treatment with INVIRASE/ritonavir.
- Treatment-naïve patients initiating treatment with INVIRASE/ritonavir should receive a reduced starting dose of INVIRASE 500-mg twice daily with ritonavir 100-mg twice daily for the first 7 days of treatment followed by INVIRASE/ritonavir 1000/100 mg twice daily due to potential for an increased risk of PR and QT interval prolongation with the standard 1000/100-mg twice daily dose [see Clinical Pharmacology (12.2)].
- For patients with a baseline QT interval < 450 msec, an on-treatment ECG is recommended after approximately 10 days of therapy. Patients with a QT interval prolongation over pre-treatment by > 20 msec should discontinue INVIRASE/ritonavir.
WARNINGS AND PRECAUTIONS
- INVIRASE is not recommended for use in combination with cobicistat. Dosing recommendations for this combination have not been established. Cobicistat is also not recommended in combination with regimens containing ritonavir due to similar effects of cobicistat and ritonavir on CYP3A. Please refer to the cobicistat full prescribing information for additional precautionary measures.
- Concomitant use of fusidic acid and saquinavir/ritonaviris not recommended due to potential for increased mutual toxicities.The interaction between INVIRASE/ritonavir and fusidic acid has not been formally evaluated. Co-administration of fusidic acid and INVIRASE/ritonavir can cause increased plasma concentrations of fusidic acid, saquinavir and ritonavir
WARNINGS AND PRECAUTIONS
Immune Reconstitution Syndrome
- Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.
Established and Other Potentially Significant Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interactions with Invirase/ritonavir (TABLE)
- Titrate atorvastatin dose carefully and use the lowest dose necessary; do not exceed atorvastatin 20 mg/day.
PATIENT COUNSELING INFORMATION
- Invirase is not a cure for HIV-1 infection and patients may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. Patients should remain under the care of a physician when using Invirase.
- Patients should be advised to avoid doing things that can spread HIV-1 infection to others…Do not share needles or other injection equipment…Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades…Do not have any kind of sex without protection…Do not breastfeed…
What should I tell my healthcare provider before taking Invirase?
- are breast-feeding or plan to breastfeed…Do not breastfeed…
- Invirase is not a cure for HIV-1 infection and you may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. You should remain under the care of a doctor when using Invirase.
- Avoid doing things that can spread HIV-1 infection.
- Do not share needles or other injection equipment.
- Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades.
- Do not have any kind of sex without protection. Always practice safe sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood.
- Invirase is contraindicated in patients with clinically significant hypersensitivity (e.g. anaphylactic reaction, Stevens-Johnson syndrome) to saquinavir, saquinavir mesylateor to any of its ingredients including ritonavir.
- Table 4: Drugs That Are Contraindicated With Invirase/Ritonavir, content has been updated
Invirase must be used in combination with ritonavir.
- Table 5: Established and Other Potentially Significant Drug Interactions; Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or on Predicted Interaction, content updated
Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Additional Adverse Reactions Reported with Saquinavir
- Infections and Infestations: abscess, angina tonsillaris, candidiasis, cellulitis, herpes simplex, herpes zoster, infection bacterial, infection mycotic, infection staphylococcal, influenza, moniliasis,
PATIENT PACKAGE INSERT
- Medicines/interactions with Invirase/Norvir content updated.