Darunavir

INTRODUCTION

Indications

HIV infection (with other antiretrovirals) in adults who have already received and progressed on other antiretroviral combinations.

Action

Inhibits HIV-1 protease, selectively inhibiting the cleavage of HIV-encoded specific polyproteins in infected cells. This prevents the formation of mature viral particles. Therapeutic Effects: Increased CD4 cell counts and decreased viral load with subsequent slowed progression of HIV infection and its sequelae.

Adverse Reactions/Side Effects

Based on concurrent use with ritonavir GI: HEPATOTOXICITY, constipation, diarrhea, nausea, vomiting. Endo: hyperglycemia. Metab: body fat redistribution. Derm: rash.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Be alert for signs of hepatotoxicity, including anorexia, abdominal pain, severe nausea and vomiting, yellow skin or eyes, fever, sore throat, malaise, weakness, facial edema, lethargy, and unusual bleeding or bruising. Notify physician immediately if these signs occur.

• Monitor and report signs of hyperglycemia, including confusion, drowsiness, fatigue, weakness, rapid breathing, fruity or pungent breath, excessive thirst, frequent urination, nausea, vomiting, and abdominal pain.

Interventions

• Implement resistive exercises and other therapeutic exercises as tolerated 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 darunavir 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 darunavir does not cure HIV or AIDS or prevent associated or opportunistic infections. Darunavir 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.

• Inform patient that redistribution and accumulation of body fat may occur, causing central obesity, thin arms and legs, dorsocervical fat enlargement (buffalo hump), breast enlargement, and other symptoms that resemble Cushing's syndrome (moon face, striations on abdominal skin). Discuss possible effects on body image, and help patient explore coping mechanisms.

• Instruct patient to report other troublesome side effects such as prolonged or severe skin rash or GI problems (diarrhea, nausea, vomiting, constipation).

Pharmacokinetics

Absorption: Without ritonavir—37% absorbed following oral administration; with ritonavir—82%. Food increases absorption by 30%.

Distribution: Unknown.

Protein Binding: 95% bound to plasma proteins.

Metabolism and Excretion: Extensively metabolized by CYP3A enzyme system. 41% eliminated unchanged in feces, 8% in urine.

Half-life: 15 hr.