Fyarro
(Sirolimus)Dosage & Administration
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Fyarro Prescribing Information
FYARRO™ is indicated for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).
- The recommended dosage of FYARRO is 100 mg/m2 administered as an IV infusion over 30 minutes on Days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity. ()
2.1 Recommended DosageThe recommended dosage of FYARRO is 100 mg/m2 administered as an intravenous infusion over 30 minutes on Days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity.
For injectable suspension: white to yellow, sterile lyophilized powder containing 100 mg of sirolimus formulated as albumin-bound particles in single-dose vial for reconstitution.
- Hepatic Impairment: Reduce the dose of FYARRO in patients with mild or moderate hepatic impairment. Avoid use in patients with severe hepatic impairment. (,
2.4 Patients with Hepatic ImpairmentThe recommended dosage modification of FYARRO in patients with mild or moderate hepatic impairment is described in Table 3
[see Use in Specific Populations , Clinical Pharmacology ]. Closely monitor patients with hepatic impairment for increased toxicity. Avoid use in patients with severe hepatic impairment[see Use in Specific Populations ].Table 3. Recommended FYARRO Dosage in Patients with Mild or Moderate Hepatic Impairment Hepatic Impairment (based on NCI criteria) Dosage Mild (total bilirubin ≤ULN, AST >ULN or total bilirubin >1 to 1.5×ULN, any AST) 75 mg/m2 Moderate (total bilirubin >1.5 to 3.0×ULN, any AST) 56 mg/m2 )8.6 Hepatic ImpairmentFYARRO is not recommended for use in patients with severe hepatic impairment. Reduce FYARRO dosage in patients with mild or moderate hepatic impairment
[see Dosage and Administration , Clinical Pharmacology ]. - Lactation: Advise not to breastfeed. ()
8.2 LactationRisk SummaryThere are no data on the presence of FYARRO in human milk or its effects on the breastfed child or on milk production.
It is not known whether sirolimus is present in human milk. There are no data on its effects on the breastfed infant or milk production. The pharmacokinetic and safety profiles of sirolimus in infants are not known. Sirolimus is present in the milk of lactating rats. There is potential for serious adverse effects from sirolimus in breastfed infants based on mechanism of action
[see Clinical Pharmacology ]. Because of the potential for serious adverse reactions in breastfed infants from FYARRO, advise women not to breastfeed during treatment with FYARRO and for 2 weeks after the last dose. - Females and Males of Reproductive Potential: May impair fertility in
females and males. (,5.9 Embryo-Fetal ToxicityBased on animal studies and the mechanism of action
[see Clinical Pharmacology ], FYARRO can cause fetal harm when administered to a pregnant woman. In animal studies, mechanistic target of rapamycin kinase (mTOR) inhibitors caused embryo-fetal toxicity when administered during the period of organogenesis at maternal exposures that were equal to or less than human exposures at the recommended lowest starting dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to avoid becoming pregnant and to use effective contraception while using FYARRO and for 12 weeks after the last dose[see Use in Specific Populations ].,5.10 Male InfertilityAzoospermia or oligospermia may be observed in patients treated with FYARRO
[see Use in Specific Populations , Nonclinical Toxicology ]. FYARRO is an anti-proliferative drug and affects rapidly dividing cells such as germ cells.)8.3 Females and Males of Reproductive PotentialFYARRO can cause fetal harm when administered to a pregnant woman
[see Warnings and Precautions , Use in Specific Populations ].Pregnancy TestingVerify pregnancy status of females of reproductive potential prior to initiating FYARRO.
ContraceptionFemalesAdvise females of reproductive potential to use effective contraception during treatment with FYARRO and for 12 weeks after the last dose.
MalesAdvise males with female partners of reproductive potential to use effective contraception during treatment with FYARRO and for 12 weeks after the last dose.
InfertilityAlthough there are no data on the impact of FYARRO on fertility, based on available clinical findings with oral formulation of sirolimus and findings in animals, male and female fertility may be compromised by the treatment with FYARRO
[see Warnings and Precautions , Nonclinical Toxicology ]. Ovarian cysts and menstrual disorders (including amenorrhea and menorrhagia) have been reported in females with the use of oral formulation of sirolimus. Azoospermia has been reported in males with the use of oral formulation sirolimus and has been reversible upon discontinuation in most cases.
FYARRO is contraindicated in patients with a history of severe hypersensitivity to sirolimus, other rapamycin derivatives, or albumin
FYARRO can cause hypersensitivity reactions
- Hypersensitivity reactions, including anaphylactic, angioedema, exfoliative dermatitis and hypersensitivity vasculitis have been observed with administration of the oral formulation of sirolimus.
- Hypersensitivity reactions including anaphylaxis have been observed with human albumin administration.
Monitor patients closely for signs and symptoms of infusion reactions during and following each FYARRO infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Monitor patients for at least 2 hours after the first infusion and as clinically needed for each subsequent infusion.
Reduce the rate, interrupt infusion, or permanently discontinue FYARRO based on severity and institute appropriate medical management as needed.
- Stomatitis: Withhold, resume at reduced dose, or permanently discontinue based on severity. ()
5.1 StomatitisStomatitis, including mouth ulcers and oral mucositis, occurred in 79% of patients treated with FYARRO, including 18% Grade 3. Stomatitis was most often first reported within 8 weeks of treatment. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO
[see Dosage and Administration , Adverse Reactions ] - Myelosuppression: Monitor blood counts prior to and during FYARRO treatment as clinically indicated. Withhold, resume at reduced dose, or permanently discontinue based on severity. ()
5.2 MyelosuppressionFYARRO can cause myelosuppression including anemia, thrombocytopenia and neutropenia. Anemia occurred in 68% of patients; 6% were Grade 3. Thrombocytopenia and neutropenia occurred in 35% of patients each.
Obtain blood counts at baseline and every 2 months for the first year of treatment and every 3 months thereafter, or more frequently if clinically indicated. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO
[see Dosage and Administration , Adverse Reactions ]. - Infections: May result from immunosuppression. Monitor for signs and symptoms of infection. Withhold, resume at reduced dose, or permanently discontinue based on severity. ()
5.3 InfectionsFYARRO can cause infections. Infections such as urinary tract infections (UTI), upper respiratory tract infections and sinusitis occurred in 59% of patients. Grade 3 infections occurred in 12% of patients, including a single case each of a UTI, pneumonia, skin, and abdominal infections. Monitor patients for infections, including opportunistic infections. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO
[see Dosage and Administration , Adverse Reactions ]. - Hypokalemia and hyperglycemia: Monitor serum potassium and glucose prior to starting FYARRO and as clinically indicated. Withhold, resume at reduced dose, or permanently discontinue based on severity. (,
5.4 HypokalemiaFYARRO can cause hypokalemia. Hypokalemia occurred in 44% of patients, including 12% Grade 3 events. Monitor potassium levels prior to starting FYARRO and implement potassium supplementation as medically indicated. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO
[see Dosage and Administration , Adverse Reactions ].)5.5 HyperglycemiaFYARRO can cause hyperglycemia. Hyperglycemia occurred in 12% of patients treated with FYARRO, all of which were Grade 3 events. Monitor fasting serum glucose prior to starting FYARRO. During treatment, monitor serum glucose every 3 months in non-diabetic patients, or as clinically indicated. Monitor serum glucose more frequently in diabetic patients. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO
[see Dosage and Administration , Adverse Reactions ]. - 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. ()
5.6 Interstitial Lung Disease / Non-Infectious PneumonitisFYARRO can cause interstitial lung disease (ILD) / non-infectious pneumonitis. ILD / non-infectious pneumonitis occurred in 18% of patients treated with FYARRO, of which all were Grades 1 or 2. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO
[see Dosage and Administration ]. - Hemorrhage: Monitor for signs and symptoms. Withhold, resume at reduced dose, or permanently discontinue based on severity. ()
5.7 HemorrhageFYARRO can cause serious and sometimes fatal hemorrhage. Hemorrhage occurred in 24% of patients treated with FYARRO, including Grade 3 and Grade 5 events in 2.9% of patients each
[see Adverse Reactions ]. Monitor patients for signs and symptoms of hemorrhage. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO[see Dosage and Administration ]. - 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. ()
5.8 Hypersensitivity ReactionsFYARRO can cause hypersensitivity reactions
[see Contraindications ].- Hypersensitivity reactions, including anaphylactic, angioedema, exfoliative dermatitis and hypersensitivity vasculitis have been observed with administration of the oral formulation of sirolimus.
- Hypersensitivity reactions including anaphylaxis have been observed with human albumin administration.
Monitor patients closely for signs and symptoms of infusion reactions during and following each FYARRO infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Monitor patients for at least 2 hours after the first infusion and as clinically needed for each subsequent infusion.
Reduce the rate, interrupt infusion, or permanently discontinue FYARRO based on severity and institute appropriate medical management as needed.
- Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential hazard to the fetus and to use effective contraception. ()
5.9 Embryo-Fetal ToxicityBased on animal studies and the mechanism of action
[see Clinical Pharmacology ], FYARRO can cause fetal harm when administered to a pregnant woman. In animal studies, mechanistic target of rapamycin kinase (mTOR) inhibitors caused embryo-fetal toxicity when administered during the period of organogenesis at maternal exposures that were equal to or less than human exposures at the recommended lowest starting dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to avoid becoming pregnant and to use effective contraception while using FYARRO and for 12 weeks after the last dose[see Use in Specific Populations ]. - Male Infertility: Azoospermia or oligospermia may occur. ()
5.10 Male InfertilityAzoospermia or oligospermia may be observed in patients treated with FYARRO
[see Use in Specific Populations , Nonclinical Toxicology ]. FYARRO is an anti-proliferative drug and affects rapidly dividing cells such as germ cells. - Immunizations: Avoid live vaccines ()
5.11 Immunizations and Risks Associated with Live VaccinesNo studies in conjunction with immunization have been conducted with FYARRO. Immunization during FYARRO treatment may be ineffective. Update immunizations according to immunization guidelines prior to initiating FYARRO, if possible. Immunization with live vaccines is not recommended during treatment and avoid close contact with those who have received live vaccines while on FYARRO. The interval between live vaccinations and initiation of FYARRO should be in accordance with current vaccination guidelines for patients on immunosuppressive therapies.