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Protease Inhibitors:
Ritonavir
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back to topIntroduction

The information represented on this drug does not necessarily correspond with the information that can be found in the Belgian scientific leaflet.
Ritonavir may be the most potent of HIV-1 PIs in vivo. (100) It was approved for use in the treatment of HIV infection when therapy is warranted.(106)

Abbreviation(s): 
Generic name:
Brand name:		 RTV
ritonavir
Norvir®
USA (FDA)
Adult approval date:
Pediatric approval date:		 March 1, 1996
March 14, 1997
 		 Abbot Laboratories
Pharmaceutical co.: Abbott Laboratories Belgium:
Capsules reimbursable since April 1997
Solution reimbursable since September 1998
  Active
Ingredient		 Dosage form;
Route		  Strength
Solution 80mg/ml Ritonavir Capsule; Oral 100MG
Ritonavir Solution; Oral 80MG/ML

back to topPharmacokinetics

Therapeutic plasma levels are consistently obtained at the current dose recommendations. Although bioavailability is sufficient in the fasting and nonfasting states, absorption increases by 15% when given with meals. Ritonavir induces its own metabolism over time. Because of this the incidence of adverse events is the greatest during the first two weeks of dosing. (106)

back to topDosing

The standard dosage of ritonavir is 600 mg every 12 hours, administered with food. To decrease side effects and improve compliance, the manufacturer recommends starting with 300 mg every 12 hours and escalating the dose in 100-mg increments every several days to achieve full dosing (600 mg twice daily) over a 2-week period. (100,106)

back to topSide effects

Side effects with ritonavir are common. (100) In clinical studies involving an oral suspension, ritonavir was associated with mild to moderate diarrhea, nausea, vomiting, anorexia, headaches, asthenia, fatigue, circumoral parasthesia and taste disturbances. Hyperglycemia and new-onset diabetes mellitus has been reported with ritonavir. (115) The strategy of using ritonavir in combination with saquinavir appears to increase the tolerability of ritonavir. (106)

back to topRemarks

back to topDrug interactions

Ritonavir has potent inhibitory effects on several cytochrome P450 CYP isoforms, including CYP3A, leading to decreased clearance and increased plasma concentrations of several widely used drugs. Ritonavir should not be administered with astemizole, terfenadine, or cisapride, because increased concentrations of these drugs may result in cardiac arrhythmias.
Because of potential toxicities, ritonavir should not be used concurrently with various antiarrhythmics (amiodarone, encainide, flecainide, quinidine) and highly metabolized sedative/hypnotics (i.e., alprazolam, diazepam, flurazepam, midazolam, and triazolam). The co-admistration of clarithromycin and ritonavir resulted in an increase in the AUC of clarithromycin by 77%. Dosage adjustment may be required, espcially in patients with renal dysfunctions. Ritonavir can also decrease the AUC of theophylline by 45%. Ritonavir increases rifabutin significantly (approximately 350%), leading to potential rifabutin toxicity. Ritonavir tends to decrease ethinyl estradiol levels and may increase ergotamine toxicity. Drugs such as rifampin and, to a lesser extent, rifabutin induce P450 CYP3A cytochrome activity. Because ritonavir, are metabolized via this pathway, coadministration with rifampin may lead to subtherapeutic levels of ritonavir. An alternative antimycobacterial prophylactic or therapeutic agent is recommended for patients taking ritonavir.(117) Ritonavir is formulated in alcohol; therefore, patients receiving disulfiram or metronidazole may experience a severe reaction to ritonavir. (106,114)
 

Interactions with other antiretroviral agents 
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