What it's for (Indications)
- Lopinavir, co-formulated with ritonavir (e.
- g.
- , Kaletra), is indicated for the treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection in adult and pediatric patients aged 14 days and older.
- It must be used in combination with other antiretroviral agents.
- Lopinavir is a protease inhibitor, and ritonavir serves as a pharmacokinetic enhancer, increasing lopinavir plasma concentrations and prolonging its half-life by inhibiting its metabolism.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | For adults, the typical oral dosage is lopinavir 400 mg/ritonavir 100 mg (two 200/50 mg tablets or 5 mL of oral solution) administered twice daily. In some situations, depending on treatment history and concomitant medications, a once-daily regimen of lopinavir 800 mg/ritonavir 200 mg (four 200/50 mg tablets or 10 mL of oral solution) may be prescribed. Pediatric dosing is weight-based and generally administered twice daily. Dosage adjustments may be necessary for patients with certain degrees of hepatic impairment or when co-administered with specific medications due to significant drug interactions. |
Safety & Warnings
Common Side Effects
- Common adverse reactions associated with lopinavir/ritonavir include gastrointestinal disturbances such as diarrhea, nausea, vomiting, and abdominal pain.
- Other frequently reported side effects include asthenia, headache, and rash.
- More serious and potentially severe adverse events include hepatotoxicity (ranging from asymptomatic transaminase elevations to hepatic failure), pancreatitis, hyperglycemia and new onset or exacerbation of diabetes mellitus, hyperlipidemia (elevations in triglycerides and cholesterol), and cardiac conduction abnormalities (e.
- g.
- , PR interval prolongation).
- Immune Reconstitution Inflammatory Syndrome (IRIS) and increased bleeding events in hemophiliac patients have also been reported.
Serious Warnings
- Black Box Warning: Lopinavir/ritonavir (Kaletra) does not carry a formal FDA Black Box Warning. However, due to its significant potential for severe adverse events and numerous clinically important drug interactions, several serious warnings warrant prominent attention. Lopinavir/ritonavir is associated with a risk of severe and potentially fatal hepatotoxicity, particularly in individuals with pre-existing liver disease or co-infection with hepatitis B or C. Vigilant monitoring of liver function tests is imperative, especially for vulnerable populations. Furthermore, this medication is a potent inhibitor of cytochrome P450 3A (CYP3A) and can induce other enzymes, leading to a high potential for numerous clinically significant and potentially life-threatening drug interactions. Co-administration with certain medications can result in severe adverse events or a loss of therapeutic effect due to altered plasma concentrations; therefore, a comprehensive review of all concomitant medications is essential to mitigate these risks. Patients should also be informed about the potential for metabolic abnormalities including hyperglycemia, new onset or exacerbation of diabetes mellitus, and significant lipid elevations (hypertriglyceridemia, hypercholesterolemia). Additionally, cardiac conduction abnormalities, specifically PR interval prolongation, have been observed, necessitating caution in patients with pre-existing cardiac conditions or those receiving other drugs known to prolong the PR interval.
- Lopinavir/ritonavir is associated with several important warnings.
- Severe, and occasionally fatal, hepatotoxicity has been reported, particularly in patients with pre-existing hepatic impairment or co-infection with hepatitis B or C; liver function tests should be monitored regularly.
- Pancreatitis has occurred, and patients should be evaluated for symptoms.
- New onset or worsening of diabetes mellitus and hyperglycemia have been observed.
- Significant elevations in plasma lipids, including triglycerides and cholesterol, can occur.
- Immune Reconstitution Inflammatory Syndrome (IRIS) may develop in HIV-infected patients initiating antiretroviral therapy, manifesting as an inflammatory response to opportunistic pathogens.
- Cardiac conduction abnormalities, specifically PR interval prolongation, have been noted, requiring caution in patients with underlying heart conditions or those on medications known to prolong the PR interval.
- Increased bleeding, including spontaneous hematomas and hemarthrosis, has been reported in patients with hemophilia A and B.
- Lopinavir/ritonavir is a potent inhibitor of CYP3A and an inducer of other enzymes, leading to a high potential for clinically significant drug interactions that can result in serious adverse effects or loss of therapeutic efficacy.
- Adherence to the prescribed regimen is crucial to prevent the development of viral resistance.
- Fat redistribution (lipodystrophy) has also been reported with antiretroviral therapy.
How it Works (Mechanism of Action)
Lopinavir is an antiviral agent belonging to the protease inhibitor class. It selectively binds to and inhibits HIV-1 protease, an enzyme critical for the proteolytic cleavage of viral Gag-Pol polyprotein precursors. This cleavage is necessary for the formation of functional proteins required for assembly of mature, infectious HIV virions. By inhibiting HIV-1 protease, lopinavir prevents the production of infectious viral particles, thereby reducing viral load. Ritonavir is co-formulated with lopinavir primarily as a pharmacokinetic boosting agent. Ritonavir is a potent inhibitor of the cytochrome P450 3A (CYP3A) isoenzyme, which is responsible for the metabolism of lopinavir. By inhibiting CYP3A, ritonavir significantly increases the systemic exposure to lopinavir, leading to higher plasma concentrations and a prolonged half-life, which allows for more convenient dosing schedules and sustained antiviral activity.
Commercial Brands (Alternatives)
No other brands found for this formula.