Sirolimus Albumin-bound Nanoparticles

What is Sirolimus Albumin-bound Nanoparticles?

• Sirolimus Albumin-bound Nanoparticles (Fyarro) is an mTOR inhibitor used to treat adults with Perivascular epithelioid cell tumors.

• Sirolimus protein-bound particles are a form of sirolimus contained in nanoparticles (very tiny particles of protein).
• The drug is also called nanoparticle albumin-bound rapamycin.
• This form may work better than other forms of sirolimus and have fewer side effects.

Sirolimus structure

Sirolimus3d

Sirolimus binding sites

What are the uses of this medicine?

• Sirolimus Albumin-bound Nanoparticles (Fyarro) used for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).

How does this medicine work?

• The macrolide antibiotic rapamycin bound to nanoparticle albumin with immunosuppressant (see sirolimus) and potential antiangiogenic and antineoplastic activities.
• Rapamycin binds to the immunophilin FK Binding Protein-12 (FKBP-12) to generate a complex that binds to and inhibits the activation of the mammalian Target Of Rapamycin (mTOR), a key regulatory kinase.
• In turn, inhibition of mTOR may result in the inhibition of the phosphatidylinositol 3 (PI-3) kinase/Akt pathway and vascular endothelial cell growth factor (VEGF) secretion, which may result in decreased tumor cell proliferation and tumor angiogenesis.
• The binding of water-insoluble rapamycin to nanoparticle albumin permits the albumin-mediated endocytosis of rapamycin by tumor cells and endothelial cells.

Who Should Not Use this medicine ?

This medicine cannot be used in patients:

• who hypersensitivity to sirolimus, other rapamycin derivatives, or albumin.

What drug interactions can this medicine cause?

• Avoid concomitant use of Fyarro with grapefruit or grapefruit juice.
• Avoid concomitant use of Fyarro with strong CYP3A4 and/or P-gp inhibitors or strong CYP3A4 and/or P-gp inducers.
• Reduce the dosage of Fyarro when used concomitantly with a moderate or weak CYP3A4 inhibitor.
• Use of Fyarro may result in decreased effectiveness of moderate or weak CYP3A4 Inducers.

Be sure to mention any of the following:

• boceprevir, bromocriptine, carbamazepine, cimetidine, cisapride, clarithromycin, clotrimazole, cyclosporine, danazol, diltiazem, erythromycin, indinavir, itraconazole, ketoconazole, metoclopramide, nicardipine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, ritonavir, telaprevir, telithromycin, troleandomycin, verapamil, or voriconazole.

Is this medicine FDA approved?

• Initial U.S. Approval: 2021

How should this medicine be used?

Recommended dosage:

• The recommended dosage of Fyarro is 100 mg/m 2 administered as an IV infusion over 30 minutes on Days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity.

Administration:

• Administer the reconstituted Fyarro suspension intravenously over 30 minutes.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As injectable suspension: lyophilized powder containing 100 mg of sirolimus formulated as albumin-bound particles in single-dose vial for reconstitution.

This medicine is available in fallowing brand namesː

• Fyarro

What side effects can this medication cause?

The most common side effects of this medicine include:

• stomatitis
• fatigue
• rash
• infection
• nausea
• edema
• diarrhea
• musculoskeletal pain
• decreased weight
• decreased appetite
• cough
• vomiting
• dysgeusia

The most common laboratory abnormalities were:

• decreased lymphocytes
• increased glucose
• decreased potassium
• decreased phosphate
• decreased hemoglobin
• increased lipase

What special precautions should I follow?

• Stomatitis, including mouth ulcers and oral mucositis, occurred in patients treated with Fyarro. Withhold, resume at reduced dose, or permanently discontinue based on severity.
• Fyarro can cause myelosuppression including anemia, thrombocytopenia and neutropenia. Monitor blood counts prior to and during Fyarro treatment as clinically indicated. Withhold, resume at reduced dose, or permanently discontinue based on severity.
• Fyarro can cause infections. Monitor for signs and symptoms of infection. Withhold, resume at reduced dose, or permanently discontinue based on severity.
• Fyarro can cause hypokalemia. Monitor serum potassium and glucose prior to starting Fyarro and as clinically indicated. Withhold, resume at reduced dose, or permanently discontinue based on severity.
• Fyarro can cause interstitial lung disease (ILD) / non-infectious pneumonitis. ILD / non-infectious pneumonitis. Monitor for new or worsening respiratory symptoms or radiological changes. Withhold, resume at reduced dose, or permanently discontinue based on severity.
• Fyarro can cause serious and sometimes fatal hemorrhage. Monitor for signs and symptoms. Withhold, resume at reduced dose, or permanently discontinue based on severity.
• Fyarro can cause hypersensitivity reactions. Monitor for hypersensitivity during and following each Fyarro infusion. Monitor for at least 2 hours following completion of the first infusion and as clinically indicated for each subsequent infusion. Reduce the rate, interrupt infusion, or permanently discontinue based on severity.
• Fyarro Can cause fetal harm. Advise patients of the potential hazard to the fetus and to use effective contraception.
• Azoospermia or oligospermia may occur. Fyarro is an anti-proliferative drug and affects rapidly dividing cells such as germ cells.
• Immunization during Fyarro treatment may be ineffective. Avoid live vaccines.
• Fyarro contains human albumin, a derivative of human blood. Human albumin carries only a remote risk of transmission of viral diseases because of effective donor screening and product manufacturing processes.

What to do in case of emergency/overdose?

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

• Based on animal studies and the mechanism of action, Fyarro can cause fetal harm when administered to a pregnant woman.
• Advise pregnant women of the potential risk to a fetus.

Can this medicine be used in children?

• The safety and efficacy of Fyarro in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• SIROLIMUS

Inactive ingredients:

• ALBUMIN HUMAN

Who manufactures and distributes this medicine?

• Manufactured for Aadi Bioscience, Inc., Pacific Palisades, CA
• Fyarro is a trademark of Aadi Bioscience, Inc.

What should I know about storage and disposal of this medication?

• Store the vials in the original cartons at 2° to 8°C(36° to 46°F).
• Retain in the original package to protect from light.
• Fyarro is a hazardous drug.
• Follow applicable special handling and disposal procedures.

• Dailymed label info on Sirolimus Albumin-bound Nanoparticles
• FDA Sirolimus Albumin-bound Nanoparticles