Comparison of Currently Available Protease Inhibitors
	Invirase™ Roche saquinavir	Norvir™ Abbott ritonavir	Crixivan® Merck indinavir
Dosage	600mg tid	600mg bid	800mg q8h
Dosage Strength/ Dosage Form	200mg capsule	100mg capsule 600mg/7.5ml oral solution	200mg capsule 400mg capsule
Number of Capsules per Full Dose	3 capsules (9/day full dose)	6 capsules (12/day full dose)	2 (400mg) capsules (6/day full dose)
Volume per Full Dose	n/a	7.5ml (15ml/day full dose)	n/a
Relation to Food	Take on a full stomach, within 2 hours of a high calorie, high fat meal if possible. (e.g., 48 g protein, 60 g carbohydrate, 57g fat; 1006 kcal) (Administration of saquinavir on an empty stomach dramatically reduces the drug's absorption.)	Take with food if possible. The taste of the oral solution may be improved by mixing with chocolate milk, Ensure or Advera. If the solution is mixed to improve the taste, it must be taken within 1 hour of mixing.	Take on an empty stomach with water 1 hour before or 2 hours after a meal. May be administered with other liquids such as skim milk, juice, coffee, or tea or with a light meal. (Ingestion of Crixivan with a meal high in calories, fat, and protein reduces the drug's absorption.) At least 1.5 liters of liquids should be taken during the course of 24 hours to ensure adequate hydration and minimize potential side effect of nephrolithiasis.
Dosage Initiation/ Adjustments (Also see drug interactions)	In combination therapy, dose adjustment of the nucleoside analogue should be based on the drug's toxicity profile. Lower doses of saquinavir are not recommended due to poor bioavailability.	Dose escalation may provide relief of nausea when initiating therapy.(1) 300mg bid x 1 day 400mg bid x 2 days 500mg bid x 1 day, then 600mg bid	Reduce the dose to 600mg q 8 h in mild-to-moderate hepatic insufficiency due to cirrhosis. Patients who experience nephrolithiasis may interrupt or discontinue therapy (e.g., 1-3 days) during the acute episode.
Storage Requirements	Room Temperature Tightly Closed Bottle	Store capsules in the refrigerator at all times and protect from light. Store oral solution in the refrigerator until dispensed. Refrigeration by the patient of the oral solution is recommended but not required if used within 30 days. Store in original container. Avoid exposure to excessive heat.	Room Temperature Tightly Closed Bottle. Capsules are sensitive to moisture and should be dispensed and stored in the original container. The desiccant should remain in the original bottle.
Combination or Monotherapy	Combination Use Only	Combination and Monotherapy Use	Combination and Monotherapy Use
Route of Metabolism	Cytochrome P450, specifically CYP3A4 isoenzyme. Undergoes extensive first-pass metabolism.	Cytochrome P450 3A (CYP3A)	Cytochrome P-450 3A4 (CYP344)
Adverse Effects (Most frequently reported- check with your physician for complete information)	diarrhea, abdominal discomfort and nausea	asthenia, diarrhea, nausea, vomiting, circumoral paresthesia, taste perversion, peripheral paresthesia	nephrolithiasis, asymptomatic hyperbilirubinemia, nausea, abdominal pain
FDA Status (as of 6/96)	Accelerated Approval	Accelerated and Traditional Approval(2)	Accelerated Approval

*bid-twice a day, tid-three times a day, q8h-every eight hours

1) Patients initiating combination regimens with Norvir™ and nucleoside analogues may improve GI tolerance by initiating Norvir alone and subsequently adding nucleosides before completing two weeks of Norvir™ monotherapy.

2) Traditional approval for treatment of patients with advanced HIV disease.