Temsirolimus
Generic: TEMSIROLIMUS
Basic Information
Manufacturer
Fresenius Kabi USA, LLC
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
1c207bed-10e3-46f0-ad2c-69d5e5c97736
Indications & Usage
1 INDICATIONS AND USAGE Temsirolimus injection is indicated for the treatment of advanced renal cell carcinoma.
Temsirolimus injection is a kinase inhibitor indicated for the treatment of advanced renal cell carcinoma.
( 1 )
Temsirolimus injection is a kinase inhibitor indicated for the treatment of advanced renal cell carcinoma.
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following serious adverse reactions have been associated with Temsirolimus injection in clinical trials and are discussed in greater detail in other sections of the label [see Warnings and Precautions ( 5 )] .
Hypersensitivity/Infusion Reactions [see Warnings and Precautions ( 5.1 )] Hepatic Impairment [see Warnings and Precautions ( 5.2 )] Hyperglycemia/Glucose Intolerance [see Warnings and Precautions ( 5.3 )] Infections [see Warnings and Precautions ( 5.4 )] Interstitial Lung Disease [see Warnings and Precautions ( 5.5 )] Hyperlipidemia [see Warnings and Precautions ( 5.6 )] Bowel Perforation [see Warnings and Precautions ( 5.7 )] Renal Failure [see Warnings and Precautions ( 5.8 )] Wound Healing Complications [see Warnings and Precautions ( 5.9 )] Intracerebral Hemorrhage [see Warnings and Precautions ( 5.10 )] The most common (≥ 30%) adverse reactions observed with Temsirolimus injection are rash, asthenia, mucositis, nausea, edema, and anorexia.
The most common (≥30%) laboratory abnormalities observed with Temsirolimus injection are anemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia, lymphopenia, elevated alkaline phosphatase, elevated serum creatinine, hypophosphatemia, thrombocytopenia, elevated AST, and leukopenia.
The most common adverse reactions (incidence ≥ 30%) are rash, asthenia, mucositis, nausea, edema, and anorexia.
The most common laboratory abnormalities (incidence ≥30%) are anemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia, elevated alkaline phosphatase, elevated serum creatinine, lymphopenia, hypophosphatemia, thrombocytopenia, elevated AST, and leukopenia.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 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, the adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice.
In the phase 3 randomized, open-label study of interferon alfa (IFN-α) alone, Temsirolimus injection alone, and Temsirolimus injection and IFN-α, a total of 616 patients were treated.
Two hundred patients received IFN-α weekly, 208 received Temsirolimus injection 25 mg weekly, and 208 patients received a combination of Temsirolimus injection and IFN-α weekly [see Clinical Studies ( 14 )].
Treatment with the combination of Temsirolimus injection 15 mg and IFN-α was associated with an increased incidence of multiple adverse reactions and did not result in a significant increase in overall survival when compared with IFN-α alone.
Table 1 shows the percentage of patients experiencing treatment emergent adverse reactions.
Reactions reported in at least 10% of patients who received Temsirolimus injection 25 mg alone or IFN-α alone are listed.
Table 2 shows the percentage of patients experiencing selected laboratory abnormalities.
Data for the same adverse reactions and laboratory abnormalities in the IFN-α alone arm are shown for comparison: Table 1 – Adverse Reactions Reported in at Least 10% of Patients Who Received 25 mg IV Temsirolimus injection or IFN- in the Randomized Trial * Common Toxicity Criteria for Adverse Events (CTCAE), Version 3.0.
a Includes edema, facial edema, and peripheral edema b Includes aphthous stomatitis, glossitis, mouth ulceration, mucositis, and stomatitis c Includes infections not otherwise specified (NOS) and the following infections that occurred infrequently as distinct entities: abscess, bronchitis, cellulitis, herpes simplex, and herpes zoster d Includes cystitis, dysuria, hematuria, urinary frequency, and urinary tract infection e Includes eczema, exfoliative dermatitis, maculopapular rash, pruritic rash, pustular rash, rash (NOS), and vesiculobullous rash f Includes taste loss and taste perversion Adverse Reaction Temsirolimus injection 25 mg n=208 IFN-α n=200 All Grades* n (%) Grades 3&4* n (%) All Grades* n (%) Grades 3&4* n (%) General disorders Asthenia Edema a Pain Pyrexia Weight Loss Headache Chest Pain Chills 106 (51) 73 (35) 59 (28) 50 (24) 39 (19) 31 (15) 34 (16) 17 (8) 23 (11) 7 (3) 10 (5) 1 (1) 3 (1) 1 (1) 2 (1) 1 (1) 127 (64) 21 (11) 31 (16) 99 (50) 50 (25) 30 (15) 18 (9) 59 (30) 52 (26) 1 (1) 4 (2) 7 (4) 4 (2) 0 (0) 2 (1) 3 (2) Gastrointestinal disorders Mucositis b Anorexia Nausea Diarrhea Abdominal Pain Constipation Vomiting 86 (41) 66 (32) 77 (37) 56 (27) 44 (21) 42 (20) 40 (19) 6 (3) 6 (3) 5 (2) 3 (1) 9 (4) 0 (0) 4 (2) 19 (10) 87 (44) 82 (41) 40 (20) 34 (17) 36 (18) 57 (29) 0 (0) 8 (4) 9 (5) 4 (2) 3 (2) 1 (1) 5 (3) Infections Infections c Urinary tract infection d Pharyngitis Rhinitis 42 (20) 31 (15) 25 (12) 20 (10) 6 (3) 3 (1) 0 (0) 0 (0) 19(10) 24(12) 3(2) 4(2) 4 (2) 3 (2) 0 (0) 0 (0) Musculoskeletal and connective tissue disorders Back Pain Arthralgia Myalgia 41 (20) 37 (18) 16 (8) 6(3) 2( 1) 1 (1) 28(14) 29 (15) 29 (15) 7 (4) 2 (1) 2 (1) Respiratory, thoracic and mediastinal disorders Dyspnea Cough Epistaxis 58 (28) 53 (26) 25 (12) 18 (9) 2 (1) 0 (0) 48 (24) 29 (15) 7 (4) 11 (6) 0 (0) 0 (0) Skin and subcutaneous tissue disorders Rash e Pruritus Nail Disorder Dry Skin Acne 97 (47) 40 (19) 28 (14) 22 (11) 21 (10) 10 (5) 1 (1) 0 (0) 1 (1) 0 (0) 14 (7) 16 (8) 1 (1) 14 (7) 2 (1) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Nervous system disorders Dysgeusia f Insomnia Depression 41 (20) 24 (12) 9 (4) 0 (0) 1 (1) 0 (0) 17 (9) 30 (15) 27 (14) 0 (0) 0 (0) 4 (2) The following selected adverse reactions were reported less frequently (<10%).
Gastrointestinal Disorders – Gastrointestinal hemorrhage (1%), rectal hemorrhage (1%).
Eye Disorders – Conjunctivitis (including lacrimation disorder) (8%).
Immune System – Angioneurotic edema-type reactions (including delayed reactions occurring two months following initiation of therapy) have been observed in some patients who received Temsirolimus injection and ACE inhibitors concomitantly.
Infections – Pneumonia (8%), upper respiratory tract infection (7%), wound infection/post-operative wound infection (1%), sepsis (1%).
General Disorders and Administration Site Conditions -Diabetes mellitus (5%).
Respiratory, Thoracic and Mediastinal Disorders – Pleural effusion (4%).
Vascular – Hypertension (7%), venous thromboembolism (including deep vein thrombosis and pulmonary embolus [including fatal outcomes]) (2%), thrombophlebitis (1%), pericardial effusion (1%).
Nervous System Disorders – Convulsion (1%).
Table 2 – Incidence of Selected Laboratory Abnormalities in Patients Who Received 25 mg IV Temsirolimus injection or IFN-α in the Randomized Trial *NCI CTC version 3.0 **Grade 1 toxicity may be under-reported for lymphocytes and neutrophils Laboratory Abnormality Temsirolimus injection 25 mg n=208 IFN-α n=200 All Grades* n (%) Grades 3&4* n (%) All Grades* n (%) Grades 3&4* n (%) Any 208 (100) 162 (78) 195 (98) 144 (72) Hematology Hemoglobin Decreased Lymphocytes Decreased** Neutrophils Decreased** Platelets Decreased Leukocytes Decreased 195 (94) 110 (53) 39 (19) 84 (40) 67 (32) 41 (20) 33 (16) 10 (5) 3 (1) 1 (1) 180 (90) 106 (53) 58 (29) 51 (26) 93 (47) 43 (22) 48 (24) 19 (10) 0 (0) 11 (6) Chemistry Alkaline Phosphatase Increased 141 (68) 7 (3) 111 (56) 13 (7) AST Increased 79 (38) 5 (2) 103 (52) 14 (7) Creatinine Increased 119 (57) 7 (3) 97 ( 49) 2 ( 1) Glucose Increased 186 (89) 33 (16) 128 (64) 6 (3) Phosphorus Decreased 102 (49) 38 (18) 61 ( 31) 17 (9) Total Bilirubin Increased 16 (8) 2 (1) 25 ( 13) 4 (2) Total Cholesterol Increased 181 (87) 5 (2) 95 ( 48) 2 (1) Triglycerides Increased 173 (83) 92 (44) 144 (72) 69 (35) Potassium Decreased 43 (21) 11 (5) 15 (8) 0 (0) 6.2 Post-marketing and Other Clinical Experience The following adverse reactions have been identified during post approval use of Temsirolimus injection.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to readily estimate their frequency or establish a causal relationship to drug exposure.
The following adverse reactions have been observed in patients receiving temsirolimus: angioedema, rhabdomyolysis, Stevens-Johnson Syndrome, complex regional pain syndrome (reflex sympathetic dystrophy), pancreatitis, cholecystitis, and cholelithiasis.
There are also post-marketing reports of temsirolimus extravasations resulting in swelling, pain, warmth, and erythema.
Hypersensitivity/Infusion Reactions [see Warnings and Precautions ( 5.1 )] Hepatic Impairment [see Warnings and Precautions ( 5.2 )] Hyperglycemia/Glucose Intolerance [see Warnings and Precautions ( 5.3 )] Infections [see Warnings and Precautions ( 5.4 )] Interstitial Lung Disease [see Warnings and Precautions ( 5.5 )] Hyperlipidemia [see Warnings and Precautions ( 5.6 )] Bowel Perforation [see Warnings and Precautions ( 5.7 )] Renal Failure [see Warnings and Precautions ( 5.8 )] Wound Healing Complications [see Warnings and Precautions ( 5.9 )] Intracerebral Hemorrhage [see Warnings and Precautions ( 5.10 )] The most common (≥ 30%) adverse reactions observed with Temsirolimus injection are rash, asthenia, mucositis, nausea, edema, and anorexia.
The most common (≥30%) laboratory abnormalities observed with Temsirolimus injection are anemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia, lymphopenia, elevated alkaline phosphatase, elevated serum creatinine, hypophosphatemia, thrombocytopenia, elevated AST, and leukopenia.
The most common adverse reactions (incidence ≥ 30%) are rash, asthenia, mucositis, nausea, edema, and anorexia.
The most common laboratory abnormalities (incidence ≥30%) are anemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia, elevated alkaline phosphatase, elevated serum creatinine, lymphopenia, hypophosphatemia, thrombocytopenia, elevated AST, and leukopenia.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 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, the adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice.
In the phase 3 randomized, open-label study of interferon alfa (IFN-α) alone, Temsirolimus injection alone, and Temsirolimus injection and IFN-α, a total of 616 patients were treated.
Two hundred patients received IFN-α weekly, 208 received Temsirolimus injection 25 mg weekly, and 208 patients received a combination of Temsirolimus injection and IFN-α weekly [see Clinical Studies ( 14 )].
Treatment with the combination of Temsirolimus injection 15 mg and IFN-α was associated with an increased incidence of multiple adverse reactions and did not result in a significant increase in overall survival when compared with IFN-α alone.
Table 1 shows the percentage of patients experiencing treatment emergent adverse reactions.
Reactions reported in at least 10% of patients who received Temsirolimus injection 25 mg alone or IFN-α alone are listed.
Table 2 shows the percentage of patients experiencing selected laboratory abnormalities.
Data for the same adverse reactions and laboratory abnormalities in the IFN-α alone arm are shown for comparison: Table 1 – Adverse Reactions Reported in at Least 10% of Patients Who Received 25 mg IV Temsirolimus injection or IFN- in the Randomized Trial * Common Toxicity Criteria for Adverse Events (CTCAE), Version 3.0.
a Includes edema, facial edema, and peripheral edema b Includes aphthous stomatitis, glossitis, mouth ulceration, mucositis, and stomatitis c Includes infections not otherwise specified (NOS) and the following infections that occurred infrequently as distinct entities: abscess, bronchitis, cellulitis, herpes simplex, and herpes zoster d Includes cystitis, dysuria, hematuria, urinary frequency, and urinary tract infection e Includes eczema, exfoliative dermatitis, maculopapular rash, pruritic rash, pustular rash, rash (NOS), and vesiculobullous rash f Includes taste loss and taste perversion Adverse Reaction Temsirolimus injection 25 mg n=208 IFN-α n=200 All Grades* n (%) Grades 3&4* n (%) All Grades* n (%) Grades 3&4* n (%) General disorders Asthenia Edema a Pain Pyrexia Weight Loss Headache Chest Pain Chills 106 (51) 73 (35) 59 (28) 50 (24) 39 (19) 31 (15) 34 (16) 17 (8) 23 (11) 7 (3) 10 (5) 1 (1) 3 (1) 1 (1) 2 (1) 1 (1) 127 (64) 21 (11) 31 (16) 99 (50) 50 (25) 30 (15) 18 (9) 59 (30) 52 (26) 1 (1) 4 (2) 7 (4) 4 (2) 0 (0) 2 (1) 3 (2) Gastrointestinal disorders Mucositis b Anorexia Nausea Diarrhea Abdominal Pain Constipation Vomiting 86 (41) 66 (32) 77 (37) 56 (27) 44 (21) 42 (20) 40 (19) 6 (3) 6 (3) 5 (2) 3 (1) 9 (4) 0 (0) 4 (2) 19 (10) 87 (44) 82 (41) 40 (20) 34 (17) 36 (18) 57 (29) 0 (0) 8 (4) 9 (5) 4 (2) 3 (2) 1 (1) 5 (3) Infections Infections c Urinary tract infection d Pharyngitis Rhinitis 42 (20) 31 (15) 25 (12) 20 (10) 6 (3) 3 (1) 0 (0) 0 (0) 19(10) 24(12) 3(2) 4(2) 4 (2) 3 (2) 0 (0) 0 (0) Musculoskeletal and connective tissue disorders Back Pain Arthralgia Myalgia 41 (20) 37 (18) 16 (8) 6(3) 2( 1) 1 (1) 28(14) 29 (15) 29 (15) 7 (4) 2 (1) 2 (1) Respiratory, thoracic and mediastinal disorders Dyspnea Cough Epistaxis 58 (28) 53 (26) 25 (12) 18 (9) 2 (1) 0 (0) 48 (24) 29 (15) 7 (4) 11 (6) 0 (0) 0 (0) Skin and subcutaneous tissue disorders Rash e Pruritus Nail Disorder Dry Skin Acne 97 (47) 40 (19) 28 (14) 22 (11) 21 (10) 10 (5) 1 (1) 0 (0) 1 (1) 0 (0) 14 (7) 16 (8) 1 (1) 14 (7) 2 (1) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Nervous system disorders Dysgeusia f Insomnia Depression 41 (20) 24 (12) 9 (4) 0 (0) 1 (1) 0 (0) 17 (9) 30 (15) 27 (14) 0 (0) 0 (0) 4 (2) The following selected adverse reactions were reported less frequently (<10%).
Gastrointestinal Disorders – Gastrointestinal hemorrhage (1%), rectal hemorrhage (1%).
Eye Disorders – Conjunctivitis (including lacrimation disorder) (8%).
Immune System – Angioneurotic edema-type reactions (including delayed reactions occurring two months following initiation of therapy) have been observed in some patients who received Temsirolimus injection and ACE inhibitors concomitantly.
Infections – Pneumonia (8%), upper respiratory tract infection (7%), wound infection/post-operative wound infection (1%), sepsis (1%).
General Disorders and Administration Site Conditions -Diabetes mellitus (5%).
Respiratory, Thoracic and Mediastinal Disorders – Pleural effusion (4%).
Vascular – Hypertension (7%), venous thromboembolism (including deep vein thrombosis and pulmonary embolus [including fatal outcomes]) (2%), thrombophlebitis (1%), pericardial effusion (1%).
Nervous System Disorders – Convulsion (1%).
Table 2 – Incidence of Selected Laboratory Abnormalities in Patients Who Received 25 mg IV Temsirolimus injection or IFN-α in the Randomized Trial *NCI CTC version 3.0 **Grade 1 toxicity may be under-reported for lymphocytes and neutrophils Laboratory Abnormality Temsirolimus injection 25 mg n=208 IFN-α n=200 All Grades* n (%) Grades 3&4* n (%) All Grades* n (%) Grades 3&4* n (%) Any 208 (100) 162 (78) 195 (98) 144 (72) Hematology Hemoglobin Decreased Lymphocytes Decreased** Neutrophils Decreased** Platelets Decreased Leukocytes Decreased 195 (94) 110 (53) 39 (19) 84 (40) 67 (32) 41 (20) 33 (16) 10 (5) 3 (1) 1 (1) 180 (90) 106 (53) 58 (29) 51 (26) 93 (47) 43 (22) 48 (24) 19 (10) 0 (0) 11 (6) Chemistry Alkaline Phosphatase Increased 141 (68) 7 (3) 111 (56) 13 (7) AST Increased 79 (38) 5 (2) 103 (52) 14 (7) Creatinine Increased 119 (57) 7 (3) 97 ( 49) 2 ( 1) Glucose Increased 186 (89) 33 (16) 128 (64) 6 (3) Phosphorus Decreased 102 (49) 38 (18) 61 ( 31) 17 (9) Total Bilirubin Increased 16 (8) 2 (1) 25 ( 13) 4 (2) Total Cholesterol Increased 181 (87) 5 (2) 95 ( 48) 2 (1) Triglycerides Increased 173 (83) 92 (44) 144 (72) 69 (35) Potassium Decreased 43 (21) 11 (5) 15 (8) 0 (0) 6.2 Post-marketing and Other Clinical Experience The following adverse reactions have been identified during post approval use of Temsirolimus injection.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to readily estimate their frequency or establish a causal relationship to drug exposure.
The following adverse reactions have been observed in patients receiving temsirolimus: angioedema, rhabdomyolysis, Stevens-Johnson Syndrome, complex regional pain syndrome (reflex sympathetic dystrophy), pancreatitis, cholecystitis, and cholelithiasis.
There are also post-marketing reports of temsirolimus extravasations resulting in swelling, pain, warmth, and erythema.