tafamidis meglumine

Action and Spectrum

Actions and Spectrum: 

tafamidis meglumine is a medication that belongs to a class of drugs known as transthyretin stabilizers. It is primarily used for the treatment of a rare and progressive genetic disease called transthyretin amyloidosis (ATTR), which can lead to the accumulation of abnormal deposits of proteins in various tissues and organs. 

The action of tafamidis meglumine involves stabilizing the tetrameric structure of transthyretin (TTR), a protein responsible for carrying thyroid hormone and retinol-binding protein in the blood. In ATTR, mutations in the TTR gene can cause the protein to misfold and form amyloid fibrils, which can accumulate in different organs, particularly the heart and peripheral nerves. 

tafamidis meglumine works by binding to the tetrameric form of TTR, preventing it from dissociating into monomers that can misfold and aggregate into amyloid fibrils. By stabilizing the tetrameric structure, tafamidis meglumine helps to inhibit the formation of amyloid deposits and slow down the progression of the disease. 

The spectrum of tafamidis meglumine mainly focuses on treating ATTR in adults with early-stage symptomatic polyneuropathy or cardiomyopathy. It has shown efficacy in reducing the progression of neurological impairment and preserving cardiac function in these patients. tafamidis meglumine is available in oral capsule form and is typically taken once daily. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Fast heartbeat 

Itching 

Hives 

Difficulty swallowing 

Skin rash 

Unusual tiredness or weakness 

Dizziness 

Tightness in chest 

Cough 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

tafamidis meglumine has certain contraindications, meaning there are specific conditions or situations in which its use is not recommended.  

• Hypersensitivity: tafamidis meglumine should not be used in people with known hypersensitivity or allergic reaction to tafamidis or its components. Allergic reactions can range from mild skin reactions to more severe symptoms like difficulty breathing, swelling, or anaphylaxis. 
• Pregnancy: tafamidis meglumine is not recommended for use during pregnancy. Limited data are available on the safety of tafamidis meglumine in pregnant women, and there is a potential risk to the developing fetus. Suppose you are planning to become pregnant or suspect you might be pregnant. In that case, discussing the potential risks and benefits of tafamidis meglumine with your healthcare provider is essential. 
• Lactation: Whether tafamidis meglumine is excreted in human breast milk is unknown. Due to the lack of data on medication safety during breastfeeding, caution should be exercised. Your healthcare provider can help assess tafamidis meglumine’s potential risks and benefits while breastfeeding and provide appropriate guidance. 

Caution 

• Hepatic Impairment: tafamidis meglumine is metabolized primarily in the liver, and caution should be exercised when using the medication in individuals with moderate to severe hepatic impairment. Close monitoring of liver function tests might be necessary for these patients. 
• Renal Impairment: tafamidis meglumine does not undergo significant renal excretion. However, caution should be exercised when using the medication in individuals with severe renal impairment or end-stage renal disease, as limited data are available in this patient population. 
• Co-administration with Strong CYP2B6 Inducers: tafamidis meglumine is a substrate of the enzyme CYP2B6. Co-administration with potent inducers of CYP2B6, such as rifampin, phenytoin, or carbamazepine, may decrease the plasma concentrations of tafamidis meglumine. If co-administration is necessary, close monitoring of the clinical response to tafamidis meglumine is recommended. 
• Co-administration with P-gp and BCRP Inhibitors: tafamidis meglumine is a substrate of P-glycoprotein and breast cancer resistance protein. Co-administration with potent inhibitors of P-gp and BCRP, such as cyclosporine, may increase the plasma concentrations of tafamidis meglumine. Caution should be exercised when using tafamidis meglumine with these inhibitors, and monitoring for potential adverse effects is recommended. 
• Pediatric Use: The safety and efficacy of tafamidis meglumine in pediatric patients have not been established. Its use in children and adolescents is not recommended. 

Pregnancy / Lactation

Pregnancy consideration:  

AU TGA pregnancy category: D
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: 

tafamidis meglumine is a transthyretin (TTR) stabilizer used to treat transthyretin amyloidosis (ATTR). It binds to the tetrameric form of TTR, preventing its dissociation into monomers that can misfold and form amyloid fibrils. By stabilizing the tetrameric structure, tafamidis meglumine inhibits the formation of amyloid deposits, thereby slowing down the progression of the disease.

The medication primarily targets ATTR-CM (cardiomyopathy) and ATTR-PN (polyneuropathy), aiming to improve heart function and delay neurological impairment. tafamidis meglumine is administered orally and is generally well-tolerated, with common side effects including headache, diarrhea, and abnormal liver function tests. 

Pharmacodynamics: 

Mechanism of action: tafamidis meglumine, the prodrug of tafamidis, is a medication used to treat transthyretin amyloidosis (ATTR). Its action mechanism involves stabilizing the tetrameric structure of transthyretin (TTR), a protein responsible for transporting thyroid hormone and retinol-binding protein in the blood. 

In ATTR, genetic mutations in the TTR gene can cause the TTR protein to misfold and aggregate into amyloid fibrils. These fibrils can accumulate in various organs, particularly the heart and peripheral nerves, leading to organ dysfunction and disease progression. 

tafamidis meglumine binds to the tetrameric form of TTR, preventing its dissociation into monomers. The stability of the tetrameric TTR structure inhibits the misfolding and aggregation of the protein into amyloid fibrils. By doing so, tafamidis meglumine helps to reduce the formation and deposition of amyloid fibrils, slowing down the progression of the disease. 

The stabilization of TTR by tafamidis meglumine primarily targets ATTR-CM (cardiomyopathy) and ATTR-PN (polyneuropathy), aiming to preserve cardiac function and delay neurological impairment, respectively. 

Pharmacokinetics: 

Absorption 

tafamidis meglumine is well absorbed after oral administration. It is rapidly converted to its active form, tafamidis, in the body. The absolute bioavailability of tafamidis meglumine is approximately 85%. 

Distribution 

Regarding distribution, tafamidis is highly protein-bound (greater than 99%) to albumin in the bloodstream. It has a large volume of distribution, indicating extensive distribution throughout the body. 

Metabolism 

Metabolism of tafamidis meglumine primarily occurs in the liver via oxidation and glucuronidation processes. The primary metabolite formed is tafamidis glucuronide. The cytochrome P450 (CYP) enzyme system is not significantly involved in the metabolism of tafamidis meglumine. 

Elimination and Excretion 

The excretion of tafamidis and its metabolites occurs mainly through the biliary system. Renal excretion plays a minor role in the elimination of the drug.  

Adminstartion

Administration: 

Oral administration 

tafamidis meglumine is typically administered orally in the form of capsules. A healthcare professional should determine the specific dosage and administration instructions and follow their recommendations.  

• Dosage: The recommended dosage of tafamidis meglumine for treating transthyretin amyloidosis (ATTR) is usually 61 mg (equivalent to 80 mg tafamidis) taken orally once daily. 
• Timing: tafamidis meglumine can be taken with or without food. Taking the medication simultaneously each day is generally recommended to help establish a routine and ensure consistent dosing. 
• Swallowing the Capsule: tafamidis meglumine capsules should be swallowed whole with water. They should not be chewed, crushed, or opened, which may affect the drug’s stability and absorption. 
• Missed Dose: If a dose is missed, taking it as soon as possible is generally recommended. However, if the next scheduled dose is missed, it should be skipped and the following dose should be taken at the appropriate time. It is important to avoid taking a double dose of the medication to compensate for the missed dose.
• Duration of Treatment: The duration of tafamidis meglumine treatment will based on the individual’s condition and the healthcare professional’s recommendation. It is typically a long-term treatment approach aimed at slowing down the progression of ATTR. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: tafamidis meglumine 

Pronounced: [ ta-FAM-id-is ] 

Why do we use tafamidis meglumine? 

tafamidis meglumine is primarily used to treat transthyretin amyloidosis (ATTR), a rare and progressive genetic disease. ATTR is characterized by the accumulation of abnormal deposits of proteins, known as amyloid fibrils, in various tissues and organs of the body. 

• Transthyretin Amyloid Cardiomyopathy (ATTR-CM): tafamidis meglumine is approved for treating ATTR-CM in adults with symptomatic heart disease. It is used to slow the progression of cardiomyopathy, improve functional capacity, and reduce the risk of cardiovascular-related hospitalizations. 
• Transthyretin Amyloid Polyneuropathy (ATTR-PN): tafamidis meglumine is also approved for treating ATTR-PN in adults with symptomatic polyneuropathy. It is used to slow the progression of neurological impairment and delay the loss of motor and sensory function associated with the disease.