Ritonavir

Protease inhibitors have been associated with a variety of hypersensitivity events (some severe), including rash, anaphylaxis (rare), angioedema, bronchospasm, erythema multiforme, toxic epidermal necrolysis, and/or Stevens-Johnson syndrome (rare). It is generally recommended to discontinue treatment if severe rash or moderate symptoms accompanied by other systemic symptoms occur.

May cause redistribution/accumulation of fat (eg, central obesity, buffalo hump, peripheral wasting, facial wasting, breast enlargement, cushingoid appearance).

May cause hepatitis, jaundice, and/or exacerbation of preexisting hepatic dysfunction (including fatalities); use with caution in patients with underlying hepatic disease, such as hepatitis B or C, cirrhosis, or those with high baseline transaminases; consider increased monitoring of transaminases in these patients.

Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.

Increases in total cholesterol and triglycerides have been reported; screening should be done prior to therapy and periodically throughout treatment.

Ritonavir has been associated with AV block (including second- and third-degree block) due to prolongation of PR interval; use caution with drugs that prolong the PR interval. Disease-related concerns:

Use with caution in patients with cardiomyopathy, ischemic heart disease, preexisting conduction abnormalities, or structural heart disease; may be at increased risk of conduction abnormalities (eg, second- or third-degree AV block).

Hyperglycemia, exacerbation of diabetes, diabetic ketoacidosis, and new-onset diabetes mellitus have been reported in patients receiving protease inhibitors. Consider monitoring for these conditions. In some patients who discontinued protease inhibitors, hyperglycemia persisted.

Use with caution in patients with hemophilia A or B; increased bleeding events, including spontaneous skin hematoma and hemarthrosis, during protease inhibitor therapy have been reported. Additional factor VIII may be needed.

Use is not recommended in patients with severe hepatic impairment (Child-Pugh class C).

Use with caution in patients with increased triglycerides; pancreatitis has been observed (including fatalities). Monitor serum lipase and amylase, and for symptoms of nausea, vomiting, and/or abdominal pain. Temporary or permanent discontinuation may be clinically indicated. Concurrent drug therapy issues:

Coadministration of ritonavir with several classes of drugs, including antiarrhythmics, ergot alkaloids, and sedatives/hypnotics, may result in potentially serious and/or life-threatening adverse reactions due to possible effects of ritonavir on the hepatic metabolism of certain drugs. Review medications taken by patients prior to prescribing ritonavir or when prescribing other medications to patients already taking ritonavir. Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Oral solution contains ethanol and propylene glycol; ethanol competitively inhibits propylene glycol metabolism; preterm infants may be at increased risk of toxicity due to decreased ability to metabolize propylene glycol. Postmarketing adverse reactions (cardiac toxicity, lactic acidosis, renal failure, CNS depression, respiratory complications, acute renal failure including fatalities) have been reported in preterm neonates receiving ritonavir-containing solutions. Do not use in neonates with a postmenstrual age (first day of mother's last menstrual period to birth plus elapsed time after birth) Dosage form specific issues:

Norvir tablets are not bioequivalent to Norvir capsules. Gastrointestinal side effects (eg, nausea, vomiting, abdominal pain, diarrhea) or paresthesias may be more common when patients are switching from the capsule to the tablet formulation due to a higher Cmax (26% increase) observed with the tablet formulation compared to the capsule. These side effects may decrease as therapy is continued.

The oral solution contains large amounts of ethanol (43.2%) and propylene glycol (26.57%). Healthcare providers should pay special attention to accurate calculation, measurement, and administration of dose. Overdose (or cumulative ethanol or propylene glycol content in medications) in a child may lead to lethal ethanol or propylene glycol toxicity.