lumasiran

Action and Spectrum

Actions and Spectrum: 

lumasiran is a therapeutic agent for treating primary hyperoxaluria type 1 (PH1) in pediatric and adult patients. 

Action: 

lumasiran is a small interfering RNA (siRNA) therapeutic. It specifically targets and inhibits the expression of the hydroxyacid oxidase 1 (HAO1) enzyme, which is responsible for the overproduction of oxalate in patients with PH1. By reducing the levels of HAO1, lumasiran helps to decrease the excessive synthesis of oxalate, thereby preventing the buildup of oxalate crystals in the kidneys and other organs. This action helps to manage the disease and prevent its serious complications, such as kidney damage and renal failure. 

Spectrum:  

lumasiran’s spectrum refers to the range of diseases or conditions that the drug is designed to treat. As mentioned earlier, lumasiran is specifically indicated for treating primary hyperoxaluria type 1 (PH1). It is not known to be effective for treating other medical conditions aside from PH1. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Abdominal pain (15%) 

Injection site reaction (38%) 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Hypersensitivity: A contraindication exists if a patient has a known allergy or hypersensitivity to lumasiran or its components. If a patient has experienced a severe allergic reaction to the drug or its ingredients, its use would be contraindicated. 
• Concomitant use with specific medications: Some medications can interact with lumasiran and may lead to adverse effects or reduced efficacy. Contraindications might exist when lumasiran is used concurrently with certain drugs, depending on their potential interactions. 
• Pre-existing medical conditions: There could be specific medical conditions or diseases where lumasiran use is contraindicated due to safety concerns or possible exacerbation. 
• Pregnancy and breast-feeding: If lumasiran poses risks to the fetus during pregnancy or can be excreted in breast milk, it may be contraindicated during these situations. 

Caution 

• Hypersensitivity reactions: Like any medication, lumasiran may cause allergic or hypersensitivity reactions in some individuals. Patients and healthcare providers should be vigilant for signs of an allergic reaction, like itching, rash, swelling, severe dizziness, or difficulty breathing. If any of these symptoms occur, instant medical attention should be sought. 
• Injection site reactions: lumasiran is administered via subcutaneous injection, and some patients may experience injection site reactions, such as redness, swelling, pain, or itching. Proper injection procedures and rotation of injection sites can help minimize these reactions. 
• Coagulation disorders: lumasiran contains a lipid nanoparticle component, and in rare cases, it could potentially interfere with coagulation (blood clotting) in susceptible individuals. Patients with a history of bleeding disorders or those taking medications that affect blood clotting should be closely monitored during lumasiran treatment. 
• Potential drug interactions: lumasiran is a relatively new therapeutic, and its potential drug interactions may not be fully elucidated. Healthcare providers should review the patient’s medication regimen to identify possible interactions with lumasiran. 
• Use during pregnancy and breastfeeding: The safety of lumasiran during pregnancy or breastfeeding has not been extensively studied. Therefore, its use during these periods should be carefully considered, and the potential risks and benefits should be evaluated case-by-case. 
• Monitoring and follow-up: Regular monitoring of kidney function and urinary oxalate levels is essential to assess the efficacy and safety of lumasiran treatment and to make any necessary adjustments in the management plan. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: Not assigned. 

Lactation:   

Excreted into human milk: Not known. 

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: 

lumasiran is a small interfering RNA (siRNA) therapeutic designed to treat primary hyperoxaluria type 1 (PH1). It specifically targets and inhibits the expression of hydroxy acid oxidase 1 (HAO1) enzyme, which is responsible for the overproduction of oxalate in patients with PH1.

Once administered via subcutaneous injection, lumasiran enters the cells and utilizes the RNA interference pathway to bind to and degrade the HAO1 messenger RNA, leading to reduced levels of the HAO1 enzyme.

By disrupting the excessive production of oxalate, lumasiran helps to lower the oxalate levels in the body, preventing the formation of oxalate crystals in the kidneys and other organs. This targeted mechanism of action aims to manage PH1 and potentially prevent its serious complications, such as kidney damage and renal failure. 

Pharmacodynamics: 

Mechanism of action: lumasiran is a small interfering RNA (siRNA) therapeutic designed to target and inhibit the production of the hydroxy acid oxidase 1 (HAO1) enzyme. The drug’s mechanism of action involves RNA interference, a natural cellular process that generally regulates gene expression. 

• Target Identification: lumasiran is specifically designed to target and bind to the messenger RNA (mRNA) of the HAO1 gene. 
• RNA-Induced Silencing Complex (RISC) Formation: Once administered via subcutaneous injection, lumasiran enters the cells and is incorporated into the RNA-induced silencing complex (RISC), which is a part of the cellular machinery responsible for RNAi. 
• mRNA Degradation: The RISC complex loaded with lumasiran then recognizes and binds to the complementary HAO1 mRNA. This binding leads to the degradation of the HAO1 mRNA, preventing its translation into the HAO1 enzyme. 
• Reduced HAO1 Enzyme Expression: As a result of lumasiran-induced degradation of the HAO1 mRNA, the expression of the HAO1 enzyme is significantly reduced in the cells. 
• Oxalate Production Inhibition: HAO1 enzyme plays a critical role in the synthesis of glyoxylate, a precursor of oxalate. By inhibiting the HAO1 enzyme, lumasiran decreases the conversion of glyoxylate to oxalate, leading to reduced oxalate production in the body. 
• Lowering Oxalate Levels: With reduced HAO1 activity, lumasiran helps lower oxalate levels in the body. This is especially important in patients with primary hyperoxaluria type 1, an infrequent genetic disorder characterized by the excessive production and accumulation of oxalate, which can lead to kidney stones and kidney damage. 

By specifically targeting and reducing HAO1 enzyme expression, lumasiran aims to manage PH1 and potentially prevent its serious complications, such as kidney stones and renal failure. 

Pharmacokinetics: 

Absorption 

lumasiran is administered via subcutaneous injection, which allows the drug to be directly absorbed into the bloodstream through the subcutaneous tissue. 

Distribution 

Once in the bloodstream, lumasiran can distribute throughout the body, reaching target tissues such as the liver, where it can exert its pharmacological effect by inhibiting the hydroxyacid oxidase 1 (HAO1) enzyme. 

Metabolism 

As a synthetic RNA-based therapeutic, lumasiran is not expected to undergo significant metabolic processes within the body. Instead, it is designed to target the messenger RNA (mRNA) of the HAO1 enzyme and trigger its degradation through the RNA interference pathway. 

Elimination and Excretion 

Since lumasiran is a relatively new therapeutic, specific data on its excretion are not widely available. However, as with most small molecules, the body may eventually eliminate lumasiran and its breakdown products through various pathways, including renal excretion (via the urine) and hepatic/biliary elimination (via the bile). 

Adminstartion

Administration: 

Subcutaneous administration 

lumasiran is administered via subcutaneous injection.  

• Preparation: Wash your hands with soap and water. Gather all the necessary supplies, including the lumasiran vial(s), syringe(s), alcohol swabs, and adhesive bandages. 
• Inspect the vial: Check the lumasiran vial for any signs of damage or contamination. Do not use the vial if it is damaged, if the liquid appears discolored, or contains particles. lumasiran may be supplied as a single-dose vial or a multi-dose vial. Follow the specific instructions the healthcare professional provides or on the product packaging. 
• Preparing the injection: Clean the vial’s rubber stopper with an alcohol swab and let it dry. Draw the appropriate amount of lumasiran into the syringe. The prescribing healthcare professional will determine the dosage based on the patient’s weight and condition. 
• Choosing the injection site: lumasiran is typically injected into the fatty tissue beneath the skin. Common injection sites include the abdomen and thighs. Rotate injection sites to avoid excessive irritation at any one site. 
• Injection technique: Pinch a skin fold between your thumb and forefinger at the chosen injection site. Insert the needle into the skin at a 45 to 90-degree angle, depending on the needle length and patient’s body habitus. Inject the lumasiran solution slowly and steadily. Remove the needle from the skin. 
• Post-injection care: Apply gentle pressure to the injection site with a clean cotton ball/gauze pad if needed. You can use an adhesive bandage if there is minor bleeding or if it helps with patient comfort. 
• Proper disposal: Dispose of the used syringe and needle in a sharps container per local regulations. Do not recap the needle after use. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: lumasiran 

Pronounced: [ LOO-ma-SIR-an ] 

Why do we use lumasiran? 

lumasiran has been approved for treating primary hyperoxaluria type 1 (PH1). PH1 is an infrequent genetic disorder characterized by the overproduction of oxalate, which can lead to the formation of kidney stones, kidney damage, and other serious complications. 

lumasiran is a small interfering RNA (siRNA) therapeutic that targets and inhibits the enzyme hydroxy acid oxidase 1 (HAO1), which is responsible for the excessive production of oxalate in patients with PH1. By reducing HAO1 expression, lumasiran helps to lower the levels of oxalate in the body, thereby preventing the accumulation of oxalate crystals in the kidneys and other organs.