Lopinavir is always co-formulated with ritonavir and is generally referred to as lopinavir/ritonavir. Ritonavir acts as a pharmacokinetic enhancer, increasing the plasma concentrations of lopinavir. Therefore, the information below refers to the combined formulation.
Usage
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Medical Conditions: Lopinavir/ritonavir is prescribed for the treatment of HIV-1 infection, in combination with other antiretroviral agents. It is not indicated as monotherapy. It is no longer recommended as an agent against COVID-19.
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Pharmacological Classification: Antiretroviral, Protease Inhibitor
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Mechanism of Action: Lopinavir is a protease inhibitor that prevents the maturation of HIV-1 virions by inhibiting the viral protease enzyme. This inhibition blocks the cleavage of viral polyproteins, resulting in the production of immature, non-infectious viral particles. Ritonavir inhibits CYP3A4, which metabolizes lopinavir, thereby increasing lopinavir’s plasma concentration and extending its half-life.
Alternate Names
How It Works
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Pharmacodynamics: Lopinavir/ritonavir inhibits HIV-1 protease, preventing the formation of mature, infectious viral particles. It exhibits antiviral activity against both wild-type and resistant strains of HIV-1.
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Pharmacokinetics:
- Absorption: Lopinavir is rapidly absorbed orally, and its bioavailability is enhanced by ritonavir co-administration. Food can also increase absorption of certain formulations.
- Metabolism: Lopinavir is primarily metabolized by CYP3A4 in the liver. Ritonavir, a potent CYP3A4 inhibitor, significantly decreases the metabolism of lopinavir, leading to higher plasma concentrations and a longer half-life.
- Elimination: Primarily fecal excretion, minimal renal excretion.
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Mode of Action: Lopinavir competitively binds to the active site of the HIV-1 protease enzyme, blocking the cleavage of viral polyproteins essential for the formation of mature, infectious virions.
Dosage
Standard Dosage
Adults:
- Standard Dosage: 400 mg lopinavir/100 mg ritonavir twice daily or 800 mg lopinavir/200 mg ritonavir once daily (for protease inhibitor-naive patients with <3 lopinavir resistance-associated substitutions only).
- Administration: Oral route, with or without food (depending on formulation, check individual product labels).
Children (over 6 months of age):
- Dosage: Weight-based or body surface area (BSA)-based. Various guidelines and formulations exist; refer to specific product information or pediatric antiretroviral dosing guides.
- Pediatric Safety Considerations: Careful monitoring of growth, lipid levels, and liver function is crucial in pediatric patients. Use of oral solution containing alcohol and propylene glycol should be avoided in infants and young children.
Special Cases:
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Elderly Patients: No specific dosage adjustments based on age are indicated.
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Patients with Renal Impairment: No dosage adjustment required.
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Patients with Hepatic Dysfunction: Contraindicated in severe hepatic impairment. Use with caution and monitor closely in mild to moderate impairment.
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Patients with Comorbid Conditions: Close monitoring of relevant parameters is recommended for patients with conditions such as diabetes, hyperlipidemia, and cardiovascular disease.
Clinical Use Cases Lopinavir/ritonavir is not indicated for use in these clinical settings outside of HIV treatment.
Dosage Adjustments
Dosage adjustment may be required due to drug interactions (see Drug Interactions section). Increased doses are sometimes recommended during pregnancy.
Side Effects
Common Side Effects:
- Diarrhea
- Nausea
- Vomiting
- Hypertriglyceridemia
- Hypercholesterolemia
- Abdominal pain
Rare but Serious Side Effects:
- Pancreatitis
- Hepatotoxicity (including hepatic failure)
- Allergic reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis)
- Cardiac arrhythmias (including QT prolongation)
- Nephrolithiasis
- Hyperglycemia
- New onset diabetes mellitus or exacerbation of pre-existing diabetes
Long-Term Effects:
- Lipodystrophy
- Insulin resistance
- Cardiovascular disease risk
Adverse Drug Reactions (ADR): Severe skin reactions, pancreatitis, hepatotoxicity, severe allergic reactions, cardiac arrhythmias.
Contraindications
- Hypersensitivity to lopinavir, ritonavir, or any component of the formulation.
- Severe hepatic insufficiency.
- Co-administration with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events.
- Co-administration with potent CYP3A inducers that significantly reduce lopinavir plasma concentrations, leading to potential loss of virologic response and development of resistance.
Drug Interactions
Lopinavir/ritonavir is a substrate and inhibitor of CYP3A4, P-glycoprotein, and other drug transporters. It interacts with numerous medications, including:
- CYP3A4 substrates: Statins (lovastatin, simvastatin), certain sedatives (midazolam, triazolam), ergot derivatives, certain alpha blockers (alfuzosin, tamsulosin), some antiarrhythmics (amiodarone, flecainide, quinidine).
- CYP3A4 inducers: Rifampin, St. John’s wort, anticonvulsants (carbamazepine, phenytoin, phenobarbital).
- Other: Cobicistat, certain HIV medications (fosamprenavir, tipranavir), orlistat.
- Food and lifestyle factors: Alcohol (oral solution contains alcohol), grapefruit juice.
Pregnancy and Breastfeeding
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Pregnancy: Lopinavir/ritonavir concentrations are reduced during pregnancy. Dose increases may be considered, especially in the second and third trimesters. Once-daily dosing and the oral solution (due to alcohol content) should be avoided during pregnancy. Lopinavir/ritonavir can be used during pregnancy when clinically indicated.
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Breastfeeding: Lopinavir is excreted in breast milk in low amounts. Limited data suggest that infant exposure through breastfeeding is negligible. The decision to breastfeed should be made considering the benefits of breastfeeding, the risk of HIV transmission, and the potential for adverse effects on the infant.
Drug Profile Summary
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Mechanism of Action: HIV-1 protease inhibitor
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Side Effects: Diarrhea, nausea, vomiting, hyperlipidemia, hepatotoxicity, pancreatitis, allergic reactions.
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Contraindications: Severe hepatic insufficiency, co-administration with certain medications.
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Drug Interactions: Numerous drug interactions, primarily through CYP3A4.
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Pregnancy & Breastfeeding: Can be used in pregnancy with dose adjustments; excretion in breast milk is low.
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Dosage: Adults: 400/100 mg twice daily or 800/200 mg once daily (for specific populations); Children: Weight-based or BSA-based.
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Monitoring Parameters: Viral load, CD4 cell count, lipid profile, liver function tests, blood glucose.
Popular Combinations
Lopinavir/ritonavir is commonly used in combination with other antiretroviral drugs, such as nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), as part of a comprehensive HIV treatment regimen. Examples: lopinavir/ritonavir + tenofovir disoproxil fumarate/emtricitabine + efavirenz.
Precautions
- Monitor for hepatic dysfunction, hyperlipidemia, pancreatitis, and new-onset or worsening diabetes.
- Screen for potential drug interactions before initiating therapy.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Lopinavir/ritonavir?
A: Adults: 400/100 mg twice daily or 800/200 mg once daily (for specific populations only); Children: Weight-based or BSA-based, refer to pediatric guidelines.
Q2: Can Lopinavir/ritonavir be used during pregnancy?
A: Yes, but concentrations are decreased. Dose increases may be recommended. Once-daily dosing and the oral solution should be avoided.
Q3: What are the most common side effects?
A: Diarrhea, nausea, vomiting, hypertriglyceridemia, and hypercholesterolemia.
Q4: What are the serious side effects I should watch out for?
A: Pancreatitis, hepatotoxicity, allergic reactions, cardiac arrhythmias.
Q5: Does Lopinavir/ritonavir interact with other medications?
A: Yes, numerous drug interactions exist, primarily through CYP3A4. A thorough medication review is essential.
Q6: Can Lopinavir/ritonavir be used in patients with renal impairment?
A: Yes, no dose adjustment is needed.
Q7: Can Lopinavir/ritonavir be used in patients with liver disease?
A: Contraindicated in severe hepatic impairment. Use with caution and monitor in mild to moderate impairment.
Q8: Should Lopinavir/ritonavir be taken with food?
A: Depends on the specific formulation. Consult the product labeling for instructions.
Q9: Is Lopinavir/ritonavir effective against all strains of HIV?
A: While it has activity against a broad range of HIV-1 strains, resistance can develop. Genotypic testing is recommended to guide treatment decisions.
Q10: What monitoring parameters are important for patients on Lopinavir/ritonavir?
A: Viral load, CD4 cell count, lipid profile, liver function tests, and blood glucose.
