rezafungin

Action and Spectrum

Actions and Spectrum: 

• rezafungin is a novel echinocandin antifungal agent currently under investigation for treating invasive fungal infections. It works by inhibiting the synthesis of beta(1,3)-D-glucan, a vital fungal cell wall component. This leads to osmotic instability and eventual death of the fungal cell. 

• rezafungin has a broad spectrum of activity against various clinically relevant fungal pathogens, including Candida spp. (including azole-resistant strains), Aspergillus spp., and certain rare molds. Its activity against these pathogens is similar to other echinocandins, such as caspofungin and micafungin. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Pyrexia (12%) 

Hypokalemia (15%) 

Diarrhea (11%)  

1-10% 

Vomiting (9%) 

Hypomagnesemia (8%) 

Constipation (5%) 

Infusion-related reactions (<5%) 

Dysphagia (<5%) 

Fluid overload (<5%) 

Insomnia (<5%) 

Headache (<5%) 

Dizziness (<5%) 

Acute kidney injury (<5%) 

Anemia (10%) 

Nausea (9%) 

Abdominal pain (7%) 

Hypophosphatemia (5%) 

Disseminated intravascular coagulation (<5%) 

Gastrointestinal bleeding (<5%) 

Erythema (<5%) 

Black Box Warning

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

rezafungin is a type of antifungal medication used to treat various fungal infections. As with any medication, there are potential contraindications or reasons why it may not be safe for specific individuals. 

Some of the contraindications of rezafungin include: 

• Allergy: If an individual is allergic to rezafungin or any ingredients in the medication, they should not take it. 
• Hepatic impairment: rezafungin can cause liver damage, so individuals with severe liver disease or impairment should avoid taking it. 
• Pregnancy and breastfeeding: The effects of rezafungin on pregnant women and their unborn babies are not fully understood, so it should be used during pregnancy only if the potential benefits outweigh the risks. It is also unknown if rezafungin passes into breast milk, so it should not be used during breastfeeding. 
• Interactions with other medications: rezafungin can interact with certain medications, such as statins and immunosuppressants, increasing the risk of side effects. 
• Age: The safety and effectiveness of rezafungin in children have yet to be established, and it should be used with caution in older adults.

Caution: 

• Renal impairment: rezafungin is primarily eliminated through the kidneys, so individuals with severe kidney disease or impairment should use caution when taking it. 
• QT prolongation: rezafungin can prolong the QT interval of the heart’s electrical cycle, leading to a potentially life-threatening irregular heartbeat. It should be used cautiously in individuals with a history of heart problems or those taking medications that can also prolong the QT interval. 
• Liver function monitoring: rezafungin can cause liver damage, so liver function tests should be monitored regularly during treatment. 
• Drug interactions: rezafungin can interact with other medications, such as certain antibiotics and antifungal medications, which can increase the risk of side effects. 
• Allergic reactions: Allergic reactions, such as rash, itching, and difficulty breathing, have been reported using rezafungin, so individuals should be monitored for these symptoms. 
• Use in immunocompromised individuals: rezafungin may not be as effective in individuals with weakened immune systems, such as HIV or cancer. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

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 available 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: 

• rezafungin is a novel, long-acting echinocandin antifungal medication that is administered intravenously. Echinocandins are a class of antifungal agents that inhibit the synthesis of fungal cell walls, ultimately leading to cell death. 

• rezafungin inhibits the enzyme (1,3)-beta-D-glucan synthase, which produces (1,3)-beta-D-glucan, a key component of fungal cell walls. By inhibiting this enzyme, rezafungin prevents the production of (1,3)-beta-D-glucan and disrupts the integrity of the fungal cell wall, ultimately leading to cell death. 

• rezafungin has a unique pharmacokinetic profile with a long half-life that allows for once-weekly dosing. It has a low potential for drug interactions, as non-renal pathways primarily eliminate it. Additionally, rezafungin has broad-spectrum activity against many fungi, including Candida and Aspergillus species. 

• Overall, the pharmacology of rezafungin makes it a promising option for treating various fungal infections, particularly in individuals with compromised immune systems or those at high risk for developing fungal infections. 

Pharmacodynamics: 

The pharmacodynamics of rezafungin is related to its mechanism of action as an echinocandin antifungal agent. Rezafungin specifically inhibits the enzyme (1,3)-beta-D-glucan synthase, which synthesizes fungal cell walls.  

The inhibition of (1,3)-beta-D-glucan synthase by rezafungin prevents the production of (1,3)-beta-D-glucan, a vital component of the fungal cell wall. This leads to a weakening and destabilization of the cell wall, ultimately leading to fungal cell death. Unlike other antifungal agents, echinocandins like rezafungin do not affect human cells as humans do not produce (1,3)-beta-D-glucan in their cell walls.  

rezafungin has broad-spectrum activity against many types of fungi, including Candida and Aspergillus species. It is effective in treating invasive candidiasis, including candidemia and invasive candidiasis in non-neutropenic patients, as well as invasive aspergillosis. 

Pharmacokinetics: 

Absorption 

rezafungin is administered intravenously, meaning it is injected directly into a vein. Because it is not absorbed through the digestive system, it is not subject to first-pass metabolism, which can reduce the amount of a drug that reaches the bloodstream.  

Distribution 

rezafungin is highly protein-bound, binding firmly to proteins in the blood and other tissues. This can limit its distribution to some body regions, such as the central nervous system.  

Metabolism 

rezafungin is metabolized in the liver by cytochrome P450 (CYP) enzymes. However, unlike other antifungal agents, such as azoles, rezafungin is not a significant inhibitor or inducer of CYP enzymes and is not subject to significant drug interactions through this mechanism. 

Elimination and Excretion 

rezafungin is eliminated from the body primarily through non-renal pathways, such as metabolism in the liver and biliary excretion. Only a tiny amount of the drug is eliminated through the kidneys, which can make it a useful option in individuals with renal impairment. 

Adminstartion

Administration: 

rezafungin is administered intravenously (IV) by a healthcare professional in a hospital or clinic setting. The drug is available as a lyophilized powder that must be reconstituted with sterile water for injection before administration. 

The recommended dose of rezafungin is a loading dose of 400 mg on day 1, followed by a maintenance dose of 200 mg once weekly. The drug should be infused over 1-2 hours, and the infusion site should be monitored for signs of phlebitis or other complications. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: rezafungin 

Why do we use rezafungin? 

rezafungin is an antifungal medication used for the treatment of invasive fungal infections, including: 

• Invasive candidiasis includes candidemia (fungal infection of the blood) and other invasive Candida infections. Candida is a type of yeast that can cause infections in patients with weakened immune systems or those who have undergone invasive medical procedures. 
• Invasive aspergillosis: This is a severe fungal infection caused by Aspergillus species, which can affect the lungs and other organs in patients with compromised immune systems.