Summary of Changes to Contraindications and Warnings

CONTRAINDICATIONS

• Table 1 (new)

WARNINGS AND PRECAUTIONS

• General
• Skin Rash
• Sulfa Allergy
• Drug Interactions

ADVERSE REACTIONS

• Initial Section
• Antiretroviral Treatment-Naïve Adult Subjects
  • Study TMC114-C211
  • • Table 2
  • Laboratory Abnormalities
    • Table 3
• Antiretroviral Treatment-Experienced Adult Subjects
  • Study TMC114-C214
    • Table 4
  • Laboratory Abnormalities
    • Table 5
• Postmarketing Experience (new subsection)
  • ...Rarely, events of hypersensitivity (including facial edema), and rhabdomyolysis (associated with co-administration with HMG-CoA reductase inhibitors and Prezista) have been reported.

DRUG INTERACTIONS

• Potential for Prezista/rtv to Affect Other Drugs (new)
• Potential for Other Drugs to Affect Darunavir (new)
• Table 6 (updated)
• The following language was added after Table 6: "In addition to the drugs included in Table 6, the interaction between Prezista/rtv and the following drugs were evaluated in clinical studies and no dose adjustments are needed for either drug [see Clinical Pharmacology (12.3)]: atazanavir, efavirenz, etravirine, nevirapine, omeprazole, ranitidine, and tenofovir disoproxil fumarate."

USE IN SPECIFIC POPULATIONS

• Pregnancy
  • Pregnancy Category C (new)
  • Prezista should be used during pregnancy only if the potential benefit justifies the potential risk.
  • In the juvenile toxicity study where rats were directly dosed with darunavir, deaths occurred from post-natal day 5 through 11...
• Pediatric Use
  • Prezista/rtv should not be used in pediatric patients below 3 years of age in view of toxicity and mortality observed in juvenile rats dosed with darunavir (from 20 mg/kg to 1000 mg/kg) up to days 23 to 26 of age [see Use in Specific Populations (8.1), Clinical Pharmacology (12.3) and Nonclinical Toxicology (13.2)].

NONCLINICAL TOXICOLOGY

• Carcinogenesis, Mutagenesis, and Impairment of Fertility
  • Carcinogenesis and Mutagenesis

PATIENT COUNSELING INFORMATION

• Instructions for Use
  • Patients Taking 800 mg of Prezista Once Daily (new)

PATIENT PACKAGE INSERT

• What is the most important information I should know about Prezista?
• How should I take Prezista?
• What are the possible side effects of Prezista?

CONTRAINDICATIONS

Table 1: Drugs That Are Contraindicated With Prezista/rtv

WARNINGS AND PRECAUTIONS

General:

Prezista must be co-administered with ritonavir and food to achieve the desired antiviral effect. Failure to administer Prezista with ritonavir and food may result in a loss of efficacy of darunavir.

Skin Rash:

In clinical trials (n=3063), rash (all grades, regardless of causality) occurred in 10.3% of subjects treated with Prezista [also see Adverse Reactions (6)]. Rash was mostly mild-to-moderate, often occurring within the first four weeks of treatment and resolving with continued dosing. The discontinuation rate due to rash in subjects using Prezista/rtv was 0.5%.

Severe skin rash, accompanied by fever and/or elevations of transaminases in some cases, has been reported in 0.4% of subjects. Stevens-Johnson Syndrome has been rarely (<0.1%) reported. Treatment with Prezista should be discontinued if severe rash develops.

Sulfa Allergy:

The following sentence was added:

"In clinical studies with Prezista/rtv, the incidence and severity of rash was similar in subjects with or without a history of sulfonamide allergy."

Drug Interactions:

See Table 1 for a listing of drugs that are contraindicated for use with Prezista/rtv due to potentially lifethreatening adverse events, significant drug-drug interactions, or loss of therapeutic effect to Prezista [see Contraindications (4)]. Please refer to Table 6 for established and other potentially significant drug-drug interactions [see Drug Interactions (7.3)].