Body as a Whole
Dehydration, usually associated with gastrointestinal symptoms, and sometimes resulting in hypotension, syncope, or renal insufficiency has been reported. Syncope, orthostatic hypotension, and renal insufficiency have also been reported without known dehydration.

Co-administration of ritonavir with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system.

Redistribution/accumulation of body fat has been reported (see PRECAUTIONS - Fat Redistribution).

Cardiovascular System
First –degree AV block, second-degree AV block, third-degree AV block, right bundle branch block have been reported (See PRECAUTIONS – PR Interval Prolongation).
Cardiac and neurologic events have been reported when ritonavir has been co-administered with disopyramide, mexiletine, nefazodone, fluoxetine, and beta blockers. The possibility of drug interaction cannot be excluded.

Endocrine System
Cushing's syndrome and adrenal suppression have been reported when ritonavir has been co-administered with fluticasone propionate.

Hemic and Lymphatic System
There have been reports of increased bleeding in patients with hemophilia A or B (see PRECAUTIONS - Hemophilia).

Nervous System
There have been postmarketing reports of seizure. Also, see Cardiovascular System.

Laboratory Abnormalities
Table 8 shows the percentage of adult patients who developed marked laboratory abnormalities.

Table 8. Percentage of Adult Patients, by Study and Treatment Group, with Chemistry and Hematology Abnormalities Occurring in > 3% of Patients Receiving NORVIR   Study 245
Naive Patients Study 247
Advanced Patients Study 462PI-Naive Patients
Variable  Limit  NORVIR + ZDV NORVIR  ZDV  NORVIR  Placebo  NORVIR + Saquinavir 
- Indicates no events reported.
 
Chemistry  High       
Cholesterol > 240 mg/dL 30.7 44.8 9.3 36.5 8.0 65.2
CPK > 1000 IU/L 9.6 12.1 11.0 9.1 6.3 9.9
GGT > 300 IU/L 1.8 5.2 1.7 19.6 11.3 9.2
SGOT (AST) > 180 IU/L 5.3 9.5 2.5 6.4 7.0 7.8
SGPT (ALT) > 215 IU/L 5.3 7.8 3.4 8.5 4.4 9.2
Triglycerides > 800 mg/dL 9.6 17.2 3.4 33.6 9.4 23.4
Triglycerides > 1500 mg/dL 1.8 2.6 - 12.6 0.4 11.3
Triglycerides Fasting > 1500 mg/dL 1.5 1.3 - 9.9 0.3 -
Uric Acid > 12 mg/dL - - - 3.8 0.2 1.4
Hematology  Low       
Hematocrit < 30% 2.6 - 0.8 17.3 22.0 0.7
Hemoglobin < 8.0 g/dL 0.9 - - 3.8 3.9 -
Neutrophils ≤0.5 x 109/L - - - 6.0 8.3 -
RBC < 3.0 x 1012/L 1.8 - 5.9 18.6 24.4 -
WBC < 2.5 x 109/L - 0.9 6.8 36.9 59.4 3.5

Pediatrics

Treatment-Emergent Adverse Events
NORVIR has been studied in 265 pediatric patients > 1 month to 21 years of age. The adverse event profile observed during pediatric clinical trials was similar to that for adult patients.

Vomiting, diarrhea, and skin rash/allergy were the only drug-related clinical adverse events of moderate to severe intensity observed in ≥ 2% of pediatric patients enrolled in NORVIR clinical trials.

Laboratory Abnormalities
The following Grade 3-4 laboratory abnormal