Rilovir200 mg+50 mg

Rilovir is a fixed-dose combination of an HIV-1 protease inhibitor (lopinavir) with a pharmacokinetic booster (ritonavir), indicated for the treatment of HIV-1 infection in adults and pediatric patients (14 days of age and older).

• Established/approved use: Rilovir is indicated, always in combination with other antiretroviral agents, for the treatment of HIV-1 infection in treatment-naive and treatment-experienced adults and children.
• Guideline-supported use: Recommended by WHO and national HIV treatment guidelines as an alternative boosted-protease-inhibitor-based regimen, including for infants, young children, and pregnant women where integrase-inhibitor-based regimens are not suitable or available.
• Combination therapy requirement: Rilovir must always be prescribed with at least two other active antiretroviral agents as part of a complete regimen; it is never used as monotherapy.

Use of Rilovir must always be directed by a physician experienced in HIV management, with regular monitoring of viral load, CD4 count, hepatic function, lipids, and treatment adherence.

Lopinavir + Ritonavir is available in the following strengths and formulations (exact presentations vary by manufacturer):

• Film-coated tablet: Lopinavir 200 mg + Ritonavir 50 mg (adult strength)
• Film-coated tablet: Lopinavir 100 mg + Ritonavir 25 mg (pediatric strength)
• Oral solution: Lopinavir 400 mg + Ritonavir 100 mg per 5 mL (contains alcohol and propylene glycol as excipients)

Lopinavir + Ritonavir also contains standard pharmaceutical excipients appropriate to the dosage form; patients with known excipient sensitivities, and caregivers of neonates, should review the specific product's package insert.

Rilovir is a co-formulated antiretroviral product combining lopinavir, an HIV-1 protease inhibitor with direct antiviral activity, with a low dose of ritonavir, which itself has minimal independent antiviral effect at this dose but strongly inhibits the hepatic enzyme CYP3A4, thereby slowing the metabolism of lopinavir and boosting (increasing and prolonging) its plasma concentrations.

Rilovir is supplied as film-coated tablets (adult and pediatric strengths) and as an oral solution for patients, including young children, unable to swallow tablets. It is administered orally, generally with food to enhance and stabilize absorption, and is metabolized predominantly by the liver.

Rilovir belongs to the therapeutic class of Antiretroviral agents, specifically the subclass HIV Protease Inhibitors, formulated as a ritonavir-boosted (pharmacokinetically enhanced) protease inhibitor combination.

Mechanism of Action

Lopinavir, the active antiretroviral component of Lopinavir + Ritonavir, inhibits the HIV-1 protease enzyme, preventing cleavage of the viral Gag-Pol polyprotein precursors. This results in the production of immature, non-infectious viral particles unable to initiate new infection cycles. Ritonavir, present at a low dose, has minimal antiviral activity of its own but potently inhibits cytochrome P450 3A4 (CYP3A4)-mediated metabolism of lopinavir, substantially increasing lopinavir's plasma concentrations and half-life, allowing effective dosing.

Pharmacokinetics

• Absorption: Absorption of lopinavir is enhanced when Lopinavir + Ritonavir is taken with food; the oral solution should be taken with food, while tablets may be taken with or without food (with food generally preferred).
• Distribution: Both components are highly bound to plasma proteins.
• Metabolism: Lopinavir is extensively metabolized by hepatic CYP3A4; ritonavir inhibits this pathway, which is the basis of the pharmacokinetic boosting effect. Because of this, Lopinavir + Ritonavir is both a substrate and a strong inhibitor of CYP3A4, giving it extensive drug interaction potential.
• Elimination: Predominantly eliminated via hepatic metabolism and biliary/fecal excretion, with only a small fraction excreted unchanged in urine.

• Rilovir tablets should be swallowed whole, without chewing, crushing, or breaking, generally with food.
• The oral solution must be taken with food and measured accurately using an appropriate oral dosing syringe or device (not a household spoon); it has a bitter taste, which can be reduced by mixing with certain foods if advised by the physician or pharmacist.
• Take Rilovir at the same times each day to maintain consistent drug levels.
• Do not skip, delay, or double doses; if a dose is missed, take it as soon as remembered unless it is close to the time of the next dose.
• Rilovir must always be taken exactly as prescribed and in combination with the other antiretroviral medicines in the regimen; do not stop, interrupt, or take it alone without medical advice, as incomplete adherence promotes HIV drug resistance and treatment failure.

Rilovir is both a substrate and a strong inhibitor of hepatic CYP3A4 (via its ritonavir component), giving it an extensive potential for clinically significant drug interactions. Key examples include:

• Drugs highly dependent on CYP3A for clearance (contraindicated combinations): Certain ergot derivatives, oral midazolam, triazolam, pimozide, cisapride, lovastatin, simvastatin, ranolazine, dronedarone, lurasidone, alfuzosin, and sildenafil when used for pulmonary arterial hypertension — co-administration can raise plasma levels of these drugs to dangerous levels, risking serious or life-threatening events (see Contraindications).
• Rifampin and St. John's Wort: Strongly induce CYP3A4, substantially reducing lopinavir concentrations and risking loss of virologic response and resistance; contraindicated with Rilovir.
• Statins (atorvastatin, rosuvastatin): Levels can be significantly increased; use the lowest effective statin dose with monitoring, and avoid simvastatin/lovastatin entirely.
• Other antiretrovirals and hormonal contraceptives: Rilovir can alter levels of certain other antiretroviral agents and reduce the effectiveness of estrogen-containing hormonal contraceptives; alternative or additional contraception is advised.
• QT/PR-prolonging drugs: Additive risk of cardiac conduction effects when combined with other drugs known to prolong the QT or PR interval.

Always inform the prescribing physician and pharmacist of all other medicines, supplements, and herbal products being used before starting Rilovir, as many interactions require dose adjustment, additional monitoring, or avoidance.

Common side effects

• Diarrhea (very common) and other gastrointestinal upset
• Nausea, vomiting, abdominal pain
• Headache
• Asthenia (weakness) and fatigue
• Insomnia and other sleep disturbances
• Rash

Serious side effects

• Pancreatitis, including fatal cases, particularly in patients with markedly elevated triglycerides or a history of pancreatitis; seek immediate care for severe abdominal pain, nausea, or vomiting.
• Hepatotoxicity, including hepatic transaminase elevations and, rarely, hepatic failure, especially in patients with underlying liver disease or hepatitis B/C co-infection.
• QT and PR interval prolongation, which can lead to cardiac arrhythmias in susceptible patients.
• Lipid abnormalities — significant elevations in triglycerides and cholesterol.
• Hyperglycemia and new-onset diabetes mellitus, or worsening of pre-existing diabetes.
• Redistribution/accumulation of body fat (lipodystrophy) with long-term antiretroviral therapy.
• Immune reconstitution inflammatory syndrome (IRIS) after starting therapy.
• Increased bleeding episodes have been reported in patients with hemophilia.

Pregnancy: Rilovir has been used as part of combination antiretroviral therapy during pregnancy under guideline-directed care to treat maternal HIV infection and reduce the risk of mother-to-child transmission. It should be used in pregnancy only under physician direction; the once-daily dosing option is not recommended during pregnancy because of reduced drug exposure. Consult current perinatal HIV treatment guidelines and do not start or stop Rilovir during pregnancy without medical advice.

Lactation: Lopinavir and ritonavir are excreted into breast milk. Infant feeding decisions for mothers living with HIV should be individualized based on maternal viral suppression, local guidelines, and physician advice, since breastfeeding carries a risk of postnatal HIV transmission. Consult the treating physician before breastfeeding while taking Rilovir.

• Pancreatitis: Discontinue promptly if clinical signs, symptoms, or laboratory findings suggestive of pancreatitis develop; use with caution in patients with elevated triglycerides or a history of pancreatitis.
• Hepatotoxicity: Monitor liver function, particularly in patients with pre-existing liver disease or hepatitis B/C co-infection; use with caution and closer monitoring in hepatic impairment.
• QT and PR interval prolongation: Use with caution in patients with structural heart disease, conduction abnormalities, or those taking other drugs that prolong the QT/PR interval.
• Lipid and glucose abnormalities: Monitor triglycerides, cholesterol, and blood glucose periodically during treatment.
• Extensive drug interaction potential: Due to strong CYP3A4 inhibition by the ritonavir component, review all concomitant medicines, supplements, and herbal products before and during use of Rilovir (see Interaction).
• Adherence and resistance: Rilovir must be taken exactly as prescribed, as part of the complete combination regimen, without stopping, skipping doses, altering the dose, or sharing this medicine with others without medical advice — incomplete adherence promotes selection of drug-resistant HIV strains and treatment failure.
• Oral solution in neonates: The oral solution contains alcohol and propylene glycol and is not recommended for premature neonates before 14 days of postnatal age due to the risk of serious toxicity (see Pediatric Uses).

Limited data exist on acute overdose with Rilovir. No specific antidote is known. In the event of a suspected overdose, seek immediate medical attention or contact a poison control center or emergency services right away. Management is supportive and symptomatic, including monitoring of vital signs, cardiac rhythm (given the potential for QT/PR prolongation), and organ function. Because both components are highly protein-bound, hemodialysis is unlikely to significantly remove the drug. Do not attempt to manage a suspected overdose at home without medical guidance.

Tablets: store at room temperature (below 30°C), away from light and moisture. Oral solution: preferably store in a refrigerator (2–8°C) until dispensed; if refrigeration is not available, it may be stored below 25°C for a limited period as specified on the product label, protected from excessive heat. Keep out of reach of children.

• Renal impairment: No dose adjustment of Rilovir is generally required, as renal elimination is minimal.
• Hepatic impairment: Use with caution and close monitoring in mild-to-moderate hepatic impairment; not recommended in severe hepatic impairment due to limited safety data and higher risk of drug accumulation.
• Elderly: Limited specific data are available; no specific dose adjustment is established, but age-related organ function decline should be considered.
• Pediatric patients: Approved for use from 14 days of age using weight- or body-surface-area-based dosing (see Pediatric Uses); the oral solution's alcohol and propylene glycol content requires caution in young infants.
• Pregnancy and lactation: See Pregnancy and Lactation section.

Rilovir is intended for long-term, typically lifelong, use as part of a continuous combination antiretroviral regimen for the management of chronic HIV-1 infection. Duration and regimen composition should be determined and periodically reviewed by the treating physician based on virologic response, immune status, tolerability, and resistance considerations. Rilovir should not be discontinued or interrupted without medical supervision, as this risks viral rebound and the development of HIV drug resistance.

Antiretroviral agents; HIV Protease Inhibitors (ritonavir-boosted/pharmacokinetically enhanced)

Lopinavir + Ritonavir combines lopinavir, which binds directly to the active site of HIV-1 protease and inhibits cleavage of the Gag-Pol polyprotein precursors, resulting in the formation of immature, non-infectious viral particles, with low-dose ritonavir, which strongly inhibits hepatic cytochrome P450 3A4 (CYP3A4). By blocking the CYP3A4-mediated metabolism of lopinavir, ritonavir substantially increases lopinavir's plasma concentration and half-life (a "pharmacokinetic boosting" effect), allowing lopinavir to achieve and sustain antiviral concentrations with practical twice-daily (or, in select patients, once-daily) dosing.

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Rilovir is approved for the treatment of HIV-1 infection in pediatric patients from 14 days of age, always as part of a combination antiretroviral regimen appropriate for the child's age and weight.

• Dosing is weight- or body-surface-area-based, typically using the oral solution (400 mg/100 mg per 5 mL) in infants and young children unable to swallow tablets, transitioning to the pediatric or adult tablet strength as the child grows.
• Rilovir oral solution is not recommended for premature neonates before 14 days of postnatal age (or in full-term neonates before 14 days of age) because of its alcohol and propylene glycol content, which can cause serious toxicity (including cardiac and renal effects) in this age group due to immature drug-clearing capacity.
• Safety and efficacy in neonates younger than 14 days have not been established.
• Pediatric patients should be monitored regularly for growth, adherence, virologic and immunologic response, lipid and glucose abnormalities, and hepatic function by a pediatric HIV specialist.