REZZAYO™ Generic Name: rezafungin

Class: Antifungal, 

Approval date of Rezzayo drug from FDA: March 22nd, 2023

Cidara Therapeutics and Melinta Therapeutics have jointly announced that the US Food and Drug Administration (FDA) has approved REZZAYO™ (rezafungin for injection) for treating Candidemia and Invasive Candidiasis. The announcement was made on March 22, 2023, from San Diego and Parsippany, N.J. by Cidara Therapeutics, Inc.

Rezzayo indication:

REZZAYO™ (rezafungin) has been approved by the US Food and Drug Administration (FDA) for treating of Candidemia and Invasive Candidiasis in patients who are 18 years of age or older and who have no alternative treatment options available.

REZZAYO is not recommended in patients with endocarditis, osteomyelitis, and meningitis due to Candida because its safety and efficacy has not been established in these cases.

While REZZAYO may be a viable treatment option for patients with limited or no alternative options, healthcare professionals should carefully consider the individual patient's medical history and potential risks and benefits before prescribing REZZAYO. Additionally, patients who are prescribed REZZAYO should be closely monitored for any potential adverse reactions or complications.

Usage:

It is recommended to obtain specimens for culture and other laboratory data, such as histopathology or non-culture diagnostics, before initiating antifungal therapy.

This is important because it allows for the identification of the specific fungal species causing the infection, as well as the determination of the susceptibility of the fungus to different antifungal agents.

While it may be necessary to initiate antifungal therapy before the results of these tests are known, it is important to adjust the therapy accordingly once the results become available.

This is because the susceptibility of the fungal infection may vary depending on the species involved and different antifungal agents may be more effective against certain species.

Therefore, adjusting the therapy based on the results of these tests can help ensure that the patient is receiving the most appropriate and effective treatment for their specific fungal infection.

Healthcare professionals should carefully consider the individual patient's medical history and potential risks and benefits before initiating any antifungal therapy.

Patients who are prescribed antifungal therapy should be closely monitored for any potential adverse reactions or complications. Additionally, healthcare professionals should stay up-to-date with the latest guidelines and recommendations regarding the use of antifungal therapy to ensure the most effective and safe treatment for their patients.

REZZAYO™ (Rezafungin) Dosage recommendation:

The recommended dosage of REZZAYO™ (rezafungin for injection) is once weekly by intravenous (IV) infusion.

It is given as an initial loading dose of 400 mg, followed by a 200 mg once weekly thereafter.

It is important to note that the safety of REZZAYO has not been established beyond four weekly doses.

It is essential to administer REZZAYO via intravenous infusion only, and it should not be administered by any other route. The duration of treatment is based on the inidividuals response to treatment and the severity of the underlying condition.

Healthcare professionals should follow the recommended dosage and administration guidelines closely to ensure the maximum effectiveness and safety of the treatment. Patients who are prescribed REZZAYO should receive the medication only under the supervision of a healthcare professional in a healthcare facility. They should be closely monitored for any potential adverse reactions or complications and should report any symptoms to their healthcare provider immediately.

Missed dose:

If a scheduled dose of REZZAYO™ (rezafungin for injection) is missed, it should be administered as soon as possible. If the missed dose is administered within three days of the assigned day, the next weekly dose may be given on schedule. However, if the missed dose is administered more than three days after the assigned day, the dosing schedule should be revised to ensure that there are at least four days before the next dose.

If a patient has missed two or more consecutive weekly doses and at least two weeks have passed since the last dose, the dosing should be started again at the 400 mg loading dose. Healthcare professionals should closely monitor the patient for any potential adverse reactions or complications when restarting the treatment.

It is important for healthcare professionals to inform their patients about the importance of adhering to the prescribed dosing schedule and what to do if a dose is missed. In case a dose is missed, doubling the dose is not recommended. It is better to get advice from your physician.

Overall, following the recommended dosing schedule is crucial for the effectiveness of the treatment, and any missed doses should be addressed promptly to ensure the safety and efficacy of the medication.

How to administer REZZAYO through intravenous infusion solution:

REZZAYO™ (rezafungin) should be administered as an intravenous infusion slowly over one hour, (at a rate of about 250 mL/h). However, if the patient experiences any infusion-related reactions, such as fever, chills, headache, or rash, the healthcare professional administering the medication may choose to slow down or pause the infusion.

After the symptoms of reactions have resolved, the infusion can then be restarted at a slower rate.

Healthcare professionals should monitor patients closely during the infusion and be prepared to manage any potential adverse reactions that may occur. They should be familiar with the signs and symptoms of infusion-related reactions and have appropriate medical interventions available if necessary.

It is important to follow the recommended infusion rate closely to ensure that the medication is administered safely and effectively. Any changes to the infusion rate should only be made under the guidance and supervision of a healthcare professional.

Contraindications to REZZAYO™ (Rezafungin):

REZZAYO™ (rezafungin for injection) is contraindicated in patients who have a known hypersensitivity or allergic reaction to rezafungin or any other echinocandins. A hypersensitivity reaction is an allergic reaction that can occur when a person's immune system overreacts to a substance that is usually harmless. This can lead to a range of symptoms, from mild itching and rash to severe anaphylaxis, a life-threatening allergic reaction.

Patients who have previously experienced an allergic reaction to any echinocandins, including REZZAYO, may be at increased risk of experiencing a severe hypersensitivity reaction if they are administered the medication. Therefore, healthcare professionals should evaluate the patient's medical records for previous hypersensitivity reactions.

If a patient has a known hypersensitivity to rezafungin or any other echinocandins, alternative treatment options should be considered. If REZZAYO is the only available treatment option, the patient should be closely monitored for any signs or symptoms of an allergic reaction during treatment.

Healthcare professionals should inform their patients of the risk of hypersensitivity reactions associated with REZZAYO and encourage them to report any symptoms such as itching, rash, swelling, or difficulty breathing to their healthcare provider immediately. If an allergic reaction occurs, appropriate medical intervention should be taken promptly to manage the reaction and ensure the safety of the patient.

Warning & Precautions:

• Infusion-related reactions:

Clinical trials have reported reactions such as flushing, warmth sensation, urticaria, nausea, and chest tightness. In such cases, the infusion should be slowed down or paused and restarted at a lower rate, as mentioned in the dosage and administration instructions.

• Photosensitivity:

Patients must be advised to use protective measures against sun exposure and other sources of UV radiation during the treatment period.

• Effects on Liver:

Liver-related side effects, manifesting as raised liver enzymes to full blown liver injury have been documented in clinical trials.

Patients should be monitored for liver injury and continuation of the treatment should be decided by the physicians based on the risk vs benefit of the treatment.

Side Effects caused by Rezzayo:

Rezzayo use in Pregnancy

There are no controlled studies of using REZZAYO™ in pregnant women. It may be used only in severe cases where the benefits of treating the mother far outweigh the risk to the fetus.

In animals, the drug has been shown to have adverse effects on fetal development at higher doses, however, animal studies may not always predict human response.

Women who are on treatment using Rezzayo should immediately inform their doctor if she becomes pregnant.

Lactation:

It is not known if the drug is excreted in breastmilk or not but generally, intravenously administered drugs have little effect on the nursing baby. However, still the baby should be monitored for adverse GI side effects

Rezzayo effects on reproductive system:

The effect of REZZAYO (rezafungin for injection) on the reproductive system in males and females is not fully understood, as there is limited information available on this topic.

Animal studies have shown that echinocandin antifungals, the class of drugs to which REZZAYO belongs, can cause adverse effects on reproductive organs and fertility in both males and females. In male rats, echinocandins caused a reduction in sperm count and testicular weight, while in female rats, these drugs caused a decrease in the number of corpora lutea and implantation sites, indicating a potential effect on fertility.

However, the clinical significance of these findings in humans is not clear. It is recommended that patients, particularly those of reproductive age, discuss the potential risks and benefits of REZZAYO therapy with their healthcare provider before starting treatment.

REZZAYO™ (Rezafungin) MOA:

Rezafungin belongs to the class of drugs known as echinocandins, It inhibits the enzyme 1,3-beta-D-glucan synthase that is responsible for the formation of cell walls of fungi, Beta-glucan in specific. Beta-glucan is a key component of the cell wall in many pathogenic fungi, including Candida and Aspergillus species. By inhibiting beta-glucan synthesis, REZZAYO weakens the fungal cell wall, leading to osmotic instability, cell death, and ultimately, fungal clearance.

The enzyme 1,3-beta-D-glucan synthase is unique to fungi and is absent in human cells, making it an ideal target for antifungal therapy with minimal off-target effects. By inhibiting 1,3-beta-D-glucan synthase, REZZAYO prevents the synthesis of beta-glucan in the fungal cell wall, leading to cell death.

REZZAYO has broad-spectrum activity against a variety of Candida and Aspergillus species, including those that are resistant to other antifungal agents. Its mechanism of action is fungicidal, meaning that it directly kills the fungus, rather than just inhibiting its growth.