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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 practice.

Most common adverse reactions (≥2%) of moderate or severe intensity in adults and adolescents (13 years and older) are diarrhea, nausea, rash, and flatulence

Most common adverse reactions in pediatric patients (2 to less than 13 years) are diarrhea, leukopenia/neutropenia, rash, anorexia, and abdominal pain. To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials Experience: Adults and Adolescents (13 years and older) The safety of VIRACEPT was studied in over 5000 patients who received drug either alone or in combination with nucleoside analogues. The majority of adverse events were of mild intensity. The most frequently reported adverse event among patients receiving VIRACEPT was diarrhea, which was generally of mild to moderate intensity. Drug-related clinical adverse experiences of moderate or severe intensity in ≥2% of patients treated with VIRACEPT coadministered with d4T and 3TC (Study 542) for up to 48 weeks, or with ZDV plus 3TC (Study 511) for up to 24 weeks are presented in Table 4.

Table 4: Percentage of Patients with Treatment-Emergent Includes those adverse events at least possibly, probably or definitely related to study drug or of unknown relationship and excludes concurrent HIV conditions Adverse Events of Moderate or Severe Intensity Reported in ≥ 2% of Adult and Adolescent Patients Study 511 Study 542 24 weeks 48 weeks Adverse Events Placebo + ZDV/3TC (n=101) 500 mg TID VIRACEPT + ZDV/3TC (n=97) 750 mg TID VIRACEPT + ZDV/3TC (n=100) 1250 mg BID VIRACEPT + d4T/3TC (n=344) 750 mg TID VIRACEPT + d4T/3TC (n=210) Digestive System Diarrhea 3% 14% 20% 20% 15% Nausea 4% 3% 7% 3% 3% Flatulence 0 5% 2% 1% 1% Skin/Appendages Rash 1% 1% 3% 2% 1% Adverse events occurring in less than 2% of patients receiving VIRACEPT in all phase 2 and 3 clinical trials and considered at least possibly related or of unknown relationship to treatment and of at least moderate severity are listed below.

Body as a Whole: abdominal pain, accidental injury, allergic reaction, asthenia, back pain, fever, headache, malaise, pain, and redistribution/accumulation of body fat.

Digestive System: anorexia, dyspepsia, epigastric pain, gastrointestinal bleeding, hepatitis, mouth ulceration, pancreatitis, and vomiting.

Hemic/Lymphatic System: anemia, leukopenia, and thrombocytopenia.

Metabolic/Nutritional System: increases in alkaline phosphatase, amylase, creatine phosphokinase, lactic dehydrogenase, SGOT, SGPT, and gamma-glutamyl transpeptidase; hyperlipemia, hyperuricemia, hyperglycemia, hypoglycemia, dehydration, and liver function tests abnormal.

Musculoskeletal System: arthralgia, arthritis, cramps, myalgia, myasthenia, and myopathy.

Nervous System: anxiety, depression, dizziness, emotional lability, hyperkinesia, insomnia, migraine, paresthesia, seizures, sleep disorder, somnolence, and suicide ideation.

Respiratory System: dyspnea, pharyngitis, rhinitis, and sinusitis.

Skin/Appendages: dermatitis, folliculitis, fungal dermatitis, maculopapular rash, pruritus, sweating, and urticaria.

Special Senses: acute iritis and eye disorder.

Urogenital System: kidney calculus, sexual dysfunction, and urine abnormality. Laboratory Abnormalities The percentage of patients with marked laboratory abnormalities in Studies 542 and 511 are presented in Table 5. Marked laboratory abnormalities are defined as a Grade 3 or 4 abnormality in a patient with a normal baseline value, or a Grade 4 abnormality in a patient with a Grade 1 abnormality at baseline.

Table 5: Percentage of Patients by Treatment Group with Marked Laboratory Abnormalities Marked laboratory abnormalities are defined as a shift from Grade 0 at baseline to at least Grade 3 or from Grade 1 to Grade 4 in >2% of Patients Study 511 Study 542 Placebo + ZDV/3TC (n=101) 500 mg TID VIRACEPT + ZDV/3TC (n=97) 750 mg TID VIRACEPT + ZDV/3TC (n=100) 1250 mg BID VIRACEPT + d4T/3TC (n=344) 750 mg TID VIRACEPT + d4T/3TC (n=210) Hematology Hemoglobin 6% 3% 2% 0 0 Neutrophils 4% 3% 5% 2% 1% Lymphocytes 1% 6% 1% 1% 0 Chemistry ALT (SGPT) 6% 1% 1% 2% 1% AST (SGOT) 4% 1% 0 2% 1% Creatine Kinase 7% 2% 2% NA NA

6.2 Clinical

Trials Experience: Pediatrics (2 to less than 13 years of age) VIRACEPT has been studied in approximately 400 pediatric patients in clinical trials from birth to 13 years of age. The adverse event profile seen during pediatric clinical trials was similar to that for adults. The most commonly reported drug-related, treatment-emergent adverse events reported in the pediatric studies included: diarrhea, leukopenia/neutropenia, rash, anorexia, and abdominal pain. Diarrhea, regardless of assigned relationship to study drug, was reported in 39% to 47% of pediatric patients receiving VIRACEPT in 2 of the larger treatment trials. Leukopenia/neutropenia was the laboratory abnormality most commonly reported as a significant event across the pediatric studies.

6.3 Postmarketing

Experience The following adverse reactions have been identified during post-approval use of VIRACEPT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a Whole: hypersensitivity reactions (including bronchospasm, moderate to severe rash, fever, and edema).

Cardiovascular System: QTc prolongation, torsades de pointes.

Digestive System: jaundice.

Metabolic/Nutritional System: bilirubinemia, metabolic acidosis.