FDA label 73ced17e-8a58-44b6-b901-347f1561f238

WARNING: SEVERE MYELOSUPPRESSION AVOPEF can cause severe myelosuppression resulting in infection or bleeding [see Warnings and Precautions (5.1) ] . Do not administer AVOPEF to patients with absolute neutrophil counts of less than 500 cells/mm 3 or platelets less than 50,000 cells/mm 3 [see Warnings and Precautions (5.1) ] . Monitor complete blood cell counts, prior to the administration of AVOPEF and before each subsequent cycle, and at appropriate intervals during and after therapy [see Warnings and Precautions (5.1) ] . WARNING: SEVERE MYELOSUPPRESSION See full prescribing information for complete boxed warning . AVOPEF can cause severe myelosuppression resulting in infection or bleeding. ( 5.1 ) Do not administer AVOPEF to patients with absolute neutrophil counts of less than 500 cells/mm 3 or platelets less than 50,000 cells/mm 3 . ( 5.1 ) Monitor complete blood cell counts, prior to the administration of AVOPEF and before each subsequent cycle, and at appropriate intervals during and after therapy. ( 5.1 )

5 WARNINGS AND PRECAUTIONS Severe Myelosuppression : Monitor complete blood counts before each AVOPEF administration and at appropriate intervals during and after therapy. Interrupt AVOPEF for absolute neutrophil counts below 500 cells/mm 3 or platelet counts below 50,000 cells/mm 3 . ( 5.1 ) Hypersensitivity and Infusion-Related Reactions : At the first sign of hypersensitivity, stop the infusion and administer volume expanders, corticosteroids, antihistamines, and pressor agents as appropriate. Permanently discontinue AVOPEF in patients who experience a severe hypersensitivity reaction. Hypotension has occurred after rapid intravenous injection. ( 5.2 ) Extravasation Resulting in Tissue Necrosis : Extravasation of etoposide can result in swelling, pain, cellulitis, and tissue necrosis. ( 5.3 ) Secondary Leukemia : Secondary leukemia has occurred with use of etoposide. ( 5.4 ) Risk of Increased AVOPEF Toxicity with Low Serum Albumin : Monitor serum albumin during treatment with AVOPEF. Patients with low serum albumin may have increased concentrations of unbound etoposide and may be at an increased risk for etoposide associated adverse reactions. ( 5.5 ) Alcohol Content : The alcohol content in a dose of AVOPEF may affect the central nervous system. This may include impairment of a patient's ability to drive or use machines immediately after infusion. ( 5.6 ) Embryo-Fetal Toxicity : AVOPEF can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.7 ) 5.1 Severe Myelosuppression AVOPEF can cause severe and fatal myelosuppression, including neutropenia, febrile neutropenia, anemia, and thrombocytopenia. Monitor complete blood counts with differential before each AVOPEF administration and at appropriate intervals during and after treatment with AVOPEF. Do not administer AVOPEF to patients with absolute neutrophil counts of less than 500 cells/mm 3 or platelets less than 50,000 cells/mm 3 . 5.2 Hypersensitivity and Infusion-Related Reactions AVOPEF can cause severe and fatal infusion-related reactions including anaphylactic reactions characterized by chills, fever, tachycardia, bronchospasm, dyspnea and hypotension [see Adverse Reactions (6.1) ] . Hypertension and flushing have occurred. At the first sign of hypersensitivity, stop the infusion and administer volume expanders, corticosteroids, antihistamines, and pressor agents as appropriate. Permanently discontinue AVOPEF in patients who experience a severe hypersensitivity reaction. Hypotension due to rapid intravenous injection has also occurred. To reduce the risk of hypotension due to an infusion-related reaction, administer AVOPEF by intravenous infusion over 30 to 60 minutes [see Dosage and Administration (2.5) ]. 5.3 Extravasation Resulting in Tissue Necrosis Extravasation of etoposide can result in swelling, pain, cellulitis, and tissue necrosis. 5.4 Secondary Leukemia Secondary leukemia has occurred with use of etoposide. 5.5 Risk of Increased AVOPEF Toxicity with Low Serum Albumin Etoposide is highly protein-bound. Patients with low serum albumin may have increased concentrations of unbound etoposide and may be at an increased risk for etoposide associated adverse reactions. Monitor for increased adverse reactions during treatment with AVOPEF in patients with low serum albumin. 5.6 Alcohol Content The alcohol content in a dose of AVOPEF may affect the central nervous system and should be taken into account for patients in whom alcohol intake should be avoided or minimized. Consideration should be given to the alcohol content in AVOPEF on the ability to drive or use machines immediately after the infusion. Each administration of AVOPEF at 100 mg/m 2 delivers 1.5 g/m 2 of ethanol. For a patient with a BSA of 2.0 m 2 this would deliver 3.0 grams of ethanol [see Description (11) ]. Other etoposide products may have a different amount of alcohol or no alcohol. 5.7 Embryo-Fetal Toxicity Based on findings from animal studies and its mechanism of action, AVOPEF can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, intravenous or intraperitoneal administration of etoposide to pregnant animals during the period of organogenesis caused embryo-fetal mortality and structural abnormalities at doses below the recommended human dose of 50 mg/m 2 based on body surface area (BSA). Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise female patients of reproductive potential to use effective contraception during treatment with AVOPEF and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with AVOPEF and for 4 months after the last dose [see Use in Specific Populations (8.1, 8.3) ].

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in more detail in other sections of the labeling. Severe Myelosuppression [see Warnings and Precautions (5.1) ] Hypersensitivity and Infusion-Related Reactions [see Warnings and Precautions (5.2) ] Extravasation Resulting in Tissue Necrosis [see Warnings and Precautions (5.3) ] Secondary Leukemia [see Warnings and Precautions (5.4) ] Risk of Increased AVOPEF Toxicity with Low Serum Albumin [see Warnings and Precautions (5.5) ] Alcohol Content [see Warnings and Precautions (5.6) ] The most common adverse reactions are myelosuppression, hypersensitivity, nausea/vomiting, and alopecia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Avyxa Pharma, LLC at 1-888-520-0954 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Blood and lymphatic system disorders : acute leukemia, myelosuppression Eye disorders : transient cortical blindness Gastrointestinal disorders : abdominal pain, anorexia, constipation, diarrhea, dysgeusia, dysphagia, esophagitis, mucositis, nausea, stomatitis and vomiting General disorders and administration site conditions : fatigue, fever, and infusion site extravasation with necrosis Hepatobiliary disorders : hepatotoxicity, metabolic acidosis Immune system disorders : allergic reaction, anaphylactic reaction (including chills, fever, tachycardia, bronchospasm, dyspnea, hypotension, hypertension, flushing, facial swelling, tongue swelling, coughing, diaphoresis, cyanosis, tightness in throat, laryngospasm, back pain, loss of consciousness, hypersensitivity-associated apnea), hypersensitivity, infusion-related reaction. Infections : febrile neutropenia Nervous system disorders : optic neuritis, peripheral neuropathy and seizure Respiratory, thoracic and mediastinal disorders : interstitial pneumonitis and pulmonary fibrosis Skin and subcutaneous tissue disorders : alopecia, pigmentation changes (including pigmented bands in nails, skin darkening and discoloration of tongue and teeth), pruritic erythematous maculopapular rash, pruritus, radiation recall dermatitis, rash, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and urticaria Vascular disorders : hypotension following rapid intravenous administration [see Dosage and Administration (2.5) ] , perivasculitis