Lopinavir/Ritonavir

INTRODUCTION

Indications

HIV infection (with other antiretrovirals).

Action

Lopinavir: Inhibits HIV viral protease. Ritonavir: Although ritonavir has antiretroviral activity of its own (inhibits the action of HIV protease and prevents the cleavage of viral polyproteins), it is combined with lopinavir to inhibit the metabolism of lopinavir, thus increasing its plasma levels. Therapeutic Effects: Increased CD4 cell counts and decreased viral load with subsequent slowed progression of HIV infection and its sequelae.

Adverse Reactions/Side Effects

CNS: headache, insomnia, weakness. GI: diarrhea (↑ in children), abdominal pain, nausea, pancreatitis, taste aversion (in children), vomiting (↑ in children). Derm: rash.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Monitor fatigue and weakness. Some degree of weakness is expected, but excessive or unusual weakness should be reported.

Interventions

• Implement resistive exercises and other therapeutic exercises as needed to maintain muscle strength and function, and prevent muscle wasting associated with HIV infection and AIDS.

Patient/Client-Related Instruction

• Emphasize the importance of taking lopinavir as directed even if the patient is asymptomatic and that this drug must always be used in combination with other antiretroviral drugs. Do not take more than prescribed amount, and do not stop taking without consulting health care professional.

• Inform patient that lopinavir does not cure HIV or AIDS or prevent associated or opportunistic infections. Lopinavir does not reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom, and to avoid sharing needles or donating blood to prevent spreading the AIDS virus to others.

• Advise patient about the likelihood of GI reactions (nausea, diarrhea, vomiting, taste changes). Instruct patient to report severe or prolonged GI problems or signs of pancreatitis such as upper abdominal pain (especially after eating), indigestion, weight loss, and oily stools.

• Instruct patient to report other troublesome side effects such as prolonged or severe headache, skin rash, or sleep loss.

Pharmacokinetics

Absorption: Well absorbed following oral administration; food enhances absorption.

Distribution: Ritonavir—poor CNS penetration.

Protein Binding: Lopinavir—98–99% bound to plasma proteins.

Metabolism and Excretion: Lopinavir—completely metabolized in the liver by cytochrome P450P3A (CYP450P3A); ritonavir is a potent inhibitor of this enzyme. Ritonavir—highly metabolized by the liver (by CYP450P3A and CYP2D6 enzymes); one metabolite has antiretroviral activity; 3.5% excreted unchanged in urine.

Half-life: Lopinavir—5–6 hr; Ritonavir—3–5 hr.