lopinavir and ritonavir

Action and Spectrum

Actions and spectrum: 

Actions: 

• lopinavir: It inhibits the protease enzyme of the human immunodeficiency virus (HIV), preventing the virus from replicating and producing new viral particles. 
• ritonavir: It works as a booster for lopinavir, increasing its levels in the blood and prolonging its effectiveness. Ritonavir also has some antiviral activity of its own. 

Spectrum: 

• lopinavir and ritonavir combination is specifically used for the treatment of HIV-1 infection in adults & children above a certain age and weight. 
• It is used as a part of highly active antiretroviral therapy (HAART) to control viral replication, improve immune function, and reduce the progression of HIV-related illnesses. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% (selected) 

Elevated LFTs (2-10%) 

Hyperuricemia (< 5%) 

Neutropenia (1-5%) 

Headache (2-6%) 

Weakness (< 9%) 

Flatulence (1-4%)  

>10% 

Hyperlipidemia (3-39%) 

Rash (12%) 

Nausea (5-16%) 

Diarrhea (7-9%) 

Abdominal pain (1-11%) 

ALT increased (1-11%)  

<1% 

Erythema multiforme 

Stevens Johnson Syndrome 

Toxic epidermal necrolysis  

Post marketing Reports 

Urinary and renal disorders: Nephrolithiasis 

Black Box Warning

Black Box Warning: 

There were no specific black box warnings for lopinavir and ritonavir. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: Contraindicated in individuals who have a known hypersensitivity or allergy to lopinavir, ritonavir, or any of the ingredients in the formulation. 
• Co-administration with certain medications: lopinavir and ritonavir can interact with other medications, leading to potential adverse effects. It is contraindicated to use them with certain medications, especially those that may increase their levels in the blood to unsafe levels or reduce their effectiveness. 
• Severe liver disease: Contraindicated in patients with severe liver impairment, as these medications are primarily metabolized by the liver. 
• Severe kidney disease: Contraindicated in patients with severe kidney impairment, as dosage adjustment may be necessary for individuals with renal dysfunction. 
• Cardiovascular disease: lopinavir and ritonavir may have effects on the cardiovascular system, and their use should be approached with caution in patients with a history of certain heart conditions or risk factors. 
• Pancreatitis: Contraindicated in individuals with a history of pancreatitis, as there have been reports of pancreatitis associated with the use of these medications.

Caution: 

• Drug Interactions: lopinavir and ritonavir can interact with many other medications, including over-the-counter drugs, herbal supplements, and prescription medications.  
• Pancreatitis: Both drugs have been associated with cases of pancreatitis, a potentially serious inflammation of the pancreas. Patients should be monitored for symptoms such as severe abdominal pain and promptly report any signs to their healthcare provider. 
• Immune Reconstitution Inflammatory Syndrome (IRIS): In some patients with advanced HIV infection, the immune system may become overactive once antiretroviral therapy is initiated, leading to IRIS. It is crucial to monitor for signs of this condition during the initial phase of treatment. 
• Pregnancy and Breastfeeding: lopinavir and ritonavir should be used with caution during pregnancy and breastfeeding, and the potential risks & benefits should be discussed. 
• Resistance: Over time, HIV can develop resistance to lopinavir and ritonavir if not taken as prescribed. Adherence to the prescribed dosing schedule is essential to maintain the effectiveness of these medications. 
• Allergic Reactions: Like all medications, lopinavir and ritonavir can cause allergic reactions in some individuals.

Comorbidities: 

• Cardiovascular Disease: HIV infection may have an increased risk of heart disease, stroke, and hypertension. 
• Metabolic Disorders: Some antiretroviral drugs, including lopinavir and ritonavir, have been associated with metabolic disorders such as lipid abnormalities and insulin resistance. 
• Bone Health: Long-term use of certain antiretroviral drugs can be associated with decreased bone density and an increased risk of fractures. 
• Neurological Disorders: HIV infection can affect the central nervous system, leading to neurological complications like cognitive impairment and peripheral neuropathy. 
• Opportunistic Infections: HIV weakens immune system, making individuals more susceptible to the opportunistic infections, such as tuberculosis, pneumonia, and certain types of cancer. 
• Mental Health Issues: HIV infection can be associated with mental health challenges, including depression, anxiety, and stress. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned 

Lactation: Excreted into human milk: Yes  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

lopinavir and ritonavir are antiretroviral drugs used in combination therapy to treat HIV (human immunodeficiency virus) infection. They belong to a class of medications known as protease inhibitors. The combination of lopinavir and ritonavir is commonly referred to as “lopinavir/ritonavir” or “LPV/r.” 

lopinavir and ritonavir inhibit the activity of the HIV protease enzyme. HIV protease is essential for the replication of the virus, as it cleaves viral polyproteins into functional and structural proteins. Inhibition of the protease enzyme prevents the formation of mature and infectious viral particles, thereby reducing the viral load in the body.  

Pharmacodynamics: 

• Protease Inhibition: Both lopinavir and ritonavir are potent inhibitors of the HIV protease enzyme. HIV protease is responsible for cleaving viral polyproteins into individual functional proteins, a crucial step in the replication of the virus. By inhibiting this enzyme, lopinavir/ritonavir prevents the formation of mature and infectious viral particles. 
• Antiviral Effect: The primary pharmacodynamic effect of lopinavir/ritonavir is its potent antiviral activity against HIV-1. By reducing viral replication, the medication helps lower the viral load in the body, slowing down the progression of HIV infection and delaying the development of AIDS. 
• Synergistic Action: The combination of lopinavir and ritonavir has a synergistic effect. ritonavir functions as a “booster” or “pharmacokinetic enhancer” by inhibiting an enzyme called cytochrome P450 3A4 (CYP3A4). CYP3A4 is involved in the metabolism of lopinavir, and ritonavir’s inhibition of CYP3A4 increases the plasma concentration and half-life of lopinavir. This allows for lower doses of lopinavir to be used, reducing the risk of side effects while maintaining therapeutic efficacy. 
• Resistance Prevention: Protease inhibitors are essential components of highly active antiretroviral therapy (HAART) regimens. By inhibiting the HIV protease, lopinavir/ritonavir helps prevent the development of drug resistance, which is a significant concern in HIV treatment. 
• Immunological Benefits: By reducing viral replication, lopinavir/ritonavir also helps preserve the function of CD4+ T cells, which are crucial for maintaining the immune system’s integrity. This can lead to an increase in CD4+ T-cell count, indicating improved immune function. 
• Adverse Effects: Like all medications, lopinavir/ritonavir may have side effects. Common adverse effects like gastrointestinal symptoms such as nausea, diarrhoea, and abdominal discomfort. Some patients may also experience lipid abnormalities, including elevated triglycerides and cholesterol levels.

Pharmacokinetics: 

Absorption 

lopinavir and ritonavir are available in tablet and liquid formulations. After oral administration, they are absorbed from the gastrointestinal tract. 

Distribution 

Both drugs are extensively distributed throughout the body, including the blood, tissues, and organs. 

Metabolism 

ritonavir is primarily metabolized by the liver through the cytochrome P450 (CYP) 3A4 enzyme. However, it is also known as a potent inhibitor of CYP3A4. When combined with lopinavir, ritonavir functions as a “booster” to increase the concentration and half-life of lopinavir by inhibiting its metabolism. This allows for lower doses of lopinavir to be used, reducing the risk of side effects while maintaining therapeutic efficacy. 

Elimination and excretion 

lopinavir and ritonavir are eliminated through hepatic metabolism, and the metabolites are excreted primarily in the feces. 

Adminstartion

Administration: 

• Dosage: The dosage of lopinavir/ritonavir is determined by the healthcare provider based on the patient’s weight, medical history, and other individual factors. The medication is available in different strengths, so the prescribed dosage may vary. 
• Frequency: lopinavir/ritonavir is usually taken orally and should be taken exactly as prescribed by the healthcare provider. The standard dosing regimen for adults is twice daily (every 12 hours). 
• With or Without Food: lopinavir/ritonavir can be taken with or without food. However, taking it with food, especially a meal containing some fat, can enhance its absorption and effectiveness. 
• Swallow Whole: The tablets or capsules should be swallowed whole with water and should not be crushed, chewed, or broken. 
• Timing: It is important to take lopinavir/ritonavir at the same time(s) each day to maintain consistent drug levels in the bloodstream. 
• Adherence: To achieve the best results in controlling HIV and preventing drug resistance, it is crucial to adhere to the prescribed dosing schedule. Missing doses or not taking the medication regularly may reduce its effectiveness. 
• Avoid Alcohol: While taking lopinavir/ritonavir, it is advisable to avoid excessive alcohol consumption as it may increase the risk of certain side effects and negatively affect liver function. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: lopinavir and ritonavir 

Pronounced: (loh-PIN-uh-veer-and- ri-TOH-na-veer)  

Why do we use lopinavir and ritonavir? 

• HIV Treatment: lopinavir/ritonavir is a component of antiretroviral therapy (ART) used to suppress the replication of HIV and lower the viral load in the blood. By reducing viral replication, the medication helps slow down the progression of the disease and protects the immune system. 
• Prevention of HIV Transmission: In cases where one partner is HIV-positive and other partner is HIV-negative, lopinavir/ritonavir can be prescribed as a pre-exposure prophylaxis to reduced risk of HIV transmission to the uninfected partner.