ixempra kit

Important safety information

Peripheral Neuropathy: Monitor for symptoms of neuropathy (sensory and motor neuropathy).) Withhold, reduce, or discontinue IXEMPRA depending on severity. ( 2.3 , 5.1 ). Myelosuppression: Neutropenia, febrile neutropenia, and infections have occurred. Monitor blood cell counts before and during treatment with IXEMPRA. Withhold, reduce, or discontinue IXEMPRA depending on severity ( 2.3 , 5.2 ). Increased Toxicity in Patients with Hepatic Impairment: Grade 4 neutropenia, febrile neutropenia, and serious adverse reactions may occur in patients with hepatic impairment during treatment with IXEMPRA. Reduce dose depending on severity. ( 2.3 , 5.3 , 6.1 ). Hypersensitivity Reactions: Severe hypersensitivity reactions (including anaphylaxis) have occurred. Premedicate all patients before treatment with IXEMPRA. Withhold, reduce, or discontinue IXEMPRA depending on severity ( 2.1 , 2.3 , 5.4 ). Cardiac Adverse Reactions: Myocardial ischemia and ventricular dysfunction have occurred. Closely monitor patients with a history of cardiac disease during treatment with IXEMPRA. Consider discontinuation of IXEMPRA in patients who develop cardiac ischemia or impaired cardiac function ( 2.3 , 5.5 ). Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception ( 5.6 , 8.1 , 8.3) Alcohol Content: The alcohol content in a dose of IXEMPRA may affect the central nervous system. This may include impairment of a patient's ability to drive or use machines immediately after infusion. ( 5.7 ). 5.2 Myelosuppression Severe, life-threatening, or fatal myelosuppression can occur in patients treated with IXEMPRA. Myelosuppression is dose-dependent and primarily manifests as neutropenia. In clinical studies, grade 4 neutropenia (<500 cells/mm 3 ) occurred in 36% of patients treated with IXEMPRA in combination with capecitabine and 23% of patients treated with single agent IXEMPRA monotherapy. Febrile neutropenia and infection with neutropenia were reported in 5% and 6% of patients treated with IXEMPRA in combination with capecitabine, respectively, and 3% and 5% of patients treated with IXEMPRA as a single agent, respectively. Neutropenia-related death occurred in 1.9% of 414 patients with normal hepatic function or mild hepatic impairment treated with IXEMPRA in combination with capecitabine. The rate of neutropenia-related deaths was higher (29%, 5 out of 17) in patients with AST or ALT >2.5 x ULN or bilirubin >1.5 x ULN [see Boxed Warning, Contraindications ( 4 ), and Warnings and Precautions ( 5.3 )] . Neutropenia-related death occurred in 0.4% of 240 patients treated with IXEMPRA as a single agent. No neutropenia-related deaths were reported in 24 patients with AST or ALT >2.5 x ULN or bilirubin >1.5 x ULN treated with IXEMPRA as a single agent. IXEMPRA is contraindicated for use in patients with a neutrophil count of <1500 cells/mm 3 . [see Contraindications ( 4 )] . Monitor patients receiving IXEMPRA for myelosuppression with frequent peripheral blood cell counts. Withhold, reduce, or discontinue IXEMPRA depending on the severity and persistence of myelosuppression [see Dosage and Administration ( 2.3 )] . 5.1 Peripheral Neuropathy Peripheral neuropathy (sensory and motor neuropathy) occurred in patients treated with IXEMPRA in combination with capecitabine and in patients treated with single agent IXEMPRA as shown in Table (see Table 3 ). Table 3: Peripheral Neuropathy a Sensory and motor neuropathy combined. b 24% and 27% of patients in 046 and 081, respectively, had preexisting neuropathy (grade 1). IXEMPRA IXEMPRA as with capecitabine Single Agent Study 046 Study 081 Peripheral neuropathy (all grades) a,b 67% 63% Peripheral neuropathy (grades 3/4) a,b 23% 14% Discontinuation due to neuropathy 21% 6% Median number of cycles to onset of grade 3/4 neuropathy 4 4 Median time to improvement of grade 3/4 neuropathy to baseline or to grade 1 6.0 weeks 4.6 weeks In Studies 046 and 081, 80% and 87%, respectively, of patients with peripheral neuropathy who received IXEMPRA had improvement or no worsening of their neuropathy following dose reduction. For patients with grade 3 or 4 neuropathy in Studies 046 and 081, 76% and 79%, respectively, had documented improvement to baseline or grade 1, twelve weeks after onset. A pooled analysis of 1540 cancer patients treated with IXEMPRA indicated that patients with diabetes mellitus or preexisting peripheral neuropathy may be at increased risk of severe neuropathy. Patients with moderate to severe neuropathy (grade 2 or greater) were excluded from studies with IXEMPRA. Monitor patients for symptoms of neuropathy, such as burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, or neuropathic pain. Withhold, reduce, or discontinue IXEMPRA depending on the severity and persistence of peripheral neuropathy [ see Dosage and Administration ( 2.3 ) ]. 5.3 Increased Toxicities in Patients with Hepatic Impairment Patients with baseline AST or ALT >2.5 x ULN or bilirubin >1.5 x ULN experienced greater toxicity than patients with baseline AST or ALT ≤2.5 x ULN or bilirubin ≤1.5 x ULN when treated with IXEMPRA at 40 mg/m 2 in combination with capecitabine or as single agent in breast cancer studies. In combination with capecitabine, the overall frequency of grade 3/4 adverse reactions, febrile neutropenia, serious adverse reactions, and toxicity-related deaths was increased oin patients with hepatic impairment. IXEMPRA in combination with capecitabine is contraindicated in patients with AST or ALT >2.5 x ULN or bilirubin >1 x ULN due to increased risk of toxicity- and neutropenia-related death [see Boxed Warning , Contraindications ( 4 ), and Warnings and Precautions ( 5.2 )]. With IXEMPRA single agent therapy, grade 4 neutropenia, febrile neutropenia, and serious adverse reatcitons were increased in patients with hepatic impairment [see Warnings and Precautions ( 5.2 ) and Adverse Reactions ( 6.1 ). Reduce the dose IXEMPRA based in the degree of hepatic impairment. Avoid use in patients with AST or ALT >10 x ULN or bilirubin >3 x ULN [see Dosage and Administration ( 2.4 )] 5.4 Hypersensitivity Reactions IXEMPRA is contraindicated in patients with a history of a severe hypersensitivity reaction to agents containing Cremophor ® EL or its derivatives (eg, polyoxyethylated castor oil) [ see Contraindications ( 4 )] . Of the 1323 patients treated with IXEMPRA in clinical studies, 9 patients (1 %) had experienced severe hypersensitivity reactions (including anaphylaxis). Three of the 9 patients were able to be retreated. Patients who experience a hypersensitivity reaction in one cycle of IXEMPRA must be premedicated in subsequent cycles with a corticosteroid in addition to the H 1 and H 2 antagonists, and extension of the infusion time should be considered [see Dosage and Administration ( 2.3 ) and Contraindications ( 4 )] Administer an H 1 and H 2 antagonist approximately 1 hour before IXEMPRA infusion and observe patients for hypersensitivity reaction occur, stop the infusion of IXEMPRA provide supportive treatment as clinically indicated (e.g.. epinephrine, corticosteriods). 5.5 Cardiac Adverse Reactions Cardiac adverse reactions (myocardial ischemia and ventricular dysfunction) occurred in patients receiving IXEMPRA in combination with capecitabine (1.9%) and as a single agent (0.3%). Supraventricular arrhythmias were observed in the combination arm (0.5%). Closely monitor patients with a history of cardiac disease during treatment with IXEMPRA. Consider discontinuation of IXEMPRA in patients who develop cardiac ischemia or impaired cardiac function [see Dosage and Administration ( 2.3 )]. 5.6 Embryo-Fetal Toxicity Based on findings in animals and its mechanism of action, IXEMPRA can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, intravenous administration of ixabepilone to pregnant rats and rabbits during the period of…