Profile of darunavir in the management of treatment-experienced HIV patients

Figures & data

Figure 1 The structural similarity of darunavir (left) and amprenavir (right).

Figure 2 Percentage of patients in whom pretreatment isolates that were susceptible to protease inhibitors remained so after failure of darunavir/ritanovir (DRV/RTV) or lopinavir/ritanovir (LPV/RTV) in the TITAN trial. Drawn from data of de Meyer.³⁵

Table 1 Recommended dose for pediatric patients (6 to <18 years of age) for Prezista^® tablets with ritonavir body weight dose³⁶

Body weight		Dose
(kg)	(lbs)
≥20 kg to <30 kg	≥44 lbs to <66 lbs	375 mg darunavir/50 mg ritonavir twice daily
≥30 kg to <40 kg	≥66 lbs to <88 lbs	450 mg darunavir/60 mg ritonavir twice daily
≥40 kg	≥88 lbs	600 mg darunavir/100 mg ritonavir twice daily

Appendix 1 Interactions with darunavir/ritonavir^36,43

Drug class	Drug of concern	Interaction
Anti-infectives	rifampicin	Reduced DRV levels, avoid
	rifabutin	Increased rifabutin levels and toxicity; recommended rifabutin dose reduction to 150 mg every other day
	voriconazole	Significant decrease in voriconazole level expected with DRV/r – must use with caution and possible use therapeutic drug monitoring of voriconazole; individually, 39% reduction and 24% reduction in voriconazole dose with DRV and RTV respectively
	fluconazole	No significant interaction
	itraconazole/ketaconazole	Increased azole and DRV levels
	halofantrine/lumafantrine	Avoid – increased risk of prolonged QTc via reduced P450-3A4 metabolism
Cardiovascular medication	amiodarone	Increased levels of amiodarone expected, watch for cardiac arrhythmia
	lidocaine (lignocaine)	Increased levels of lidocaine expected, watch for cardiac arrhythmia
	warfarin	Reduced warfarin exposure (21% following a single dose), should check INR levels more frequently
	CCB, BBs	Potential increase in most CCB and BBs
Lipid-lowering agents	statin class	Increased levels of most statins (reduced metabolism via 3A4); avoid simvastatin, caution and possible dose reduction with pravastatin/atorvastatin
Immunosuppressants	cyclosporin/tacrolimus/sirolimus	Expected increased levels of immunosuppressant – recommend therapeutic drug monitoring
Psychotropics	SSRI	Generally reduced SSRI levels, watch therapeutic response
	respiridone/clozapine/haloperidol	Increased psychotropic levels, watch therapeutic response
Erectile dysfunction	sildenafil/vardenafil	Increased levels, suggest lower doses
Illicit drugs	amphetamines, gamma-hydroxybutyrate	Increased levels and possibly toxicity from illict agents
Herbals	St John’s wort	Decreased DRV levels. Avoid. Prolonged effect even after discontinuation
Antiretrovirals	maraviroc	Complex interaction – expected 4 × increase in AUC and 2.3 × increase in Cmax of maraviroc, but recommend careful review of all medications
Contraceptives	ethinylestradiol/norethindrone	Significant decreased levels – recommend seek alternative contraceptive methods
Anticonvulsants	phenytoin, phenobarbital	Decreased concentrations of anticonvulsants and DRV; avoid if possible

Abbreviations: AUC, area under the curve; BB, beta-blockers; C_max, maximum concentration; CCB, calcium-channel blockers; DRV, darunavir; INR, international normalized ratio; RTV, ritanovir; SSRI, selective serotonin reuptake inhibitors.

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Prezista^® [package insert]2009TibotecTherapeuticsEast Bridgewater, NJ, USA

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