Fixed-Dose Combination: This pediatric formulation contains a fixed-dose combination of two active ingredients: Lopinavir (A), a protease inhibitor, and Ritonavir (B), a pharmacokinetic boosting agent.
Formulation: It is supplied in capsules or sachets that contain small pellets or granules. This form is designed for children (indicated by “P”) who cannot swallow tablets.
Pharmacokinetic Booster: Ritonavir is included at a low dose not for its direct antiviral effect, but to inhibit the metabolism of Lopinavir, thereby increasing its concentration in the bloodstream.
Component of cART: This combination is a core component of combination antiretroviral therapy (cART) and must be used with other antiretroviral agents to provide a complete and effective treatment regimen.
Advantages
Accurate Weight-Based Dosing: The pellet/granule formulation allows for flexible and accurate dosing based on a child’s body weight, which is critical for therapeutic effectiveness and avoiding toxicity.
Ease of Administration: The pellets can be sprinkled on a small amount of soft food, making it easier to administer to infants and young children who may reject the taste of liquid formulations or cannot swallow tablets.
Improved Adherence: This formulation simplifies the treatment regimen for pediatric patients and their caregivers, leading to improved adherence and better treatment outcomes.
Avoids Liquid-Specific Issues: This formulation avoids the taste issues, potential for spillage, and alcohol content that can be associated with the oral liquid formulation of this combination.
Uses
Pediatric HIV-1 Infection: Indicated for the treatment of HIV-1 infection in pediatric patients, including infants as young as 14 days old, as part of a combination regimen.
First-Line Therapy: It is a common component of first-line antiretroviral therapy (ART) regimens for children, particularly in regions with a high prevalence of HIV.
Prevention of Mother-to-Child Transmission: This combination is a key component of regimens used to prevent the transmission of HIV from mother to child.
Patients Unable to Swallow Tablets: This formulation is specifically designed for pediatric patients who are unable to swallow tablets but can tolerate a small amount of food.
Nature
Drug Classes: Lopinavir is a protease inhibitor (PI) and Ritonavir is also a PI, but it is primarily used as a cytochrome P450 (CYP450) inhibitor.
Mechanism of Action (Lopinavir): Lopinavir works by selectively inhibiting the viral enzyme protease, which is essential for the cleavage of viral polyproteins into functional proteins. This results in the production of immature, non-infectious viral particles.
Mechanism of Action (Ritonavir): At a low dose, Ritonavir is a potent inhibitor of the CYP3A4 enzyme in the liver. By blocking this enzyme, it prevents the rapid metabolism of Lopinavir, leading to higher and more sustained therapeutic concentrations.
Side Effects: Common side effects include gastrointestinal issues like diarrhea, nausea, and vomiting. There is also a potential for metabolic abnormalities such as high blood lipids and insulin resistance.
Storage
Temperature: Store the capsules/sachets at a controlled room temperature, typically between 20∘C to 25∘C (68∘F to 77∘F).
Protection: Keep the medication in its original, tightly closed container, protected from light and moisture.
Administration: The pellets should be sprinkled on a small amount of soft food (e.g., applesauce, pudding) and consumed immediately. They should not be chewed.
Patient Compliance: Patients must be educated on the importance of taking every dose as prescribed and on time to prevent the development of viral resistance and to ensure long-term treatment success.
