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The kidneys are a pair of organs on either side of the spine in the lower abdomen. Each kidney is about the size of a fist. Attached to the top of each kidney is an adrenal gland. A mass of fatty tissue and an outer layer of fibrous tissue (Gerota's fascia) enclose the kidneys and adrenal glands.
The kidneys are part of the urinary tract. They make urine by removing wastes and extra water from the blood. Urine collects in a hollow space (renal pelvis) in the middle of each kidney. It passes from the renal pelvis into the bladder through a tube called a ureter. Urine leaves the body through another tube (the urethra).
The kidneys also make substances that help control blood pressure and the production of red blood cells.
Cancer begins in cells, the building blocks that make up ...
The following serious adverse reactions have been associated with TORISEL (temsirolimus injection) in clinical trials and are discussed in greater detail in other sections of the label [see WARNINGS AND PRECAUTIONS].
Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
Hyperglycemia/Glucose Intolerance [see WARNINGS AND PRECAUTIONS]
Interstitial Lung Disease [see WARNINGS AND PRECAUTIONS]
Hyperlipemia [see WARNINGS AND PRECAUTIONS]
Bowel Perforation [see WARNINGS AND PRECAUTIONS]
Renal Failure [see WARNINGS AND PRECAUTIONS]
The most common ( ≥ 30%) adverse reactions observed with TORISEL (temsirolimus injection) are rash, asthenia, mucositis, nausea, edema, and anorexia. The most common ( ≥ 30%) laboratory abnormalities observed with TORISEL (temsirolimus injection) are anemia, hyperglycemia, hyperlipemia, hypertriglyceridemia, lymphopenia, elevated alkaline phosphatase, elevated serum creatinine, hypophosphatemia, thrombocytopenia, elevated AST, and leukopenia.
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, TORISEL (temsirolimus injection) alone, and TORISEL (temsirolimus injection) and IFN-α, a total of 616 patients were treated. Two hundred patients received IFN-α weekly, 208 received TORISEL (temsirolimus injection) 25 mg weekly, and 208 patients received a combination of TORISEL and IFN-α weekly [see Clinical Studies].
Treatment with the combination of TORISEL (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 TORISEL (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 TORISEL (temsirolimus injection) or IFN-α in the Randomized Trial
| Adverse Reaction | TORISEL 25 mg n=208 |
IFN-a n=200 |
||
| All Grades* n (%) |
Grades 3&4* n (%) |
All Grades* n (%) |
Grades 3&4* n (%) |
|
| Any | 208 (100) | 139 (67) | 199 (100) | 155 (78) |
| General disorders | ||||
| Asthenia | 106 (51) | 23 (11) | 127 (64) | 52 (26) |
| Edemaa | 73 (35) | 7 (3) | 21 (11) | 1 (1) |
| Pain | 59 (28) | 10 (5) | 31 (16) | 4 (2) |
| Pyrexia | 50 (24) | 1 (1) | 99 (50) | 7 (4) |
| Weight Loss | 39 (19) | 3 (1) | 50 (25) | 4 (2) |
| Headache | 31 (15) | 1 (1) | 30 (15) | 0 (0) |
| Chest Pain | 34 (16) | 2 (1) | 18 (9) | 2 (1) |
| Chills | 17 (8) | 1 (1) | 59 (30) | 3 (2) |
| Gastrointestinal disorders | ||||
| Mucositisb | 86 (41) | 6 (3) | 19 (10) | 0 (0) |
| Anorexia | 66 (32) | 6 (3) | 87 (44) | 8 (4) |
| Nausea | 77 (37) | 5 (2) | 82 (41) | 9 (5) |
| Diarrhea | 56 (27) | 3 (1) | 40 (20) | 4 (2) |
| Abdominal Pain | 44 (21) | 9 (4) | 34 (17) | 3 (2) |
| Constipation | 42 (20) | 0 (0) | 36 (18) | 1 (1) |
| Vomiting | 40 (19) | 4 (2) | 57 (29) | 5 (3) |
| Infections | ||||
| Infectionsc | 42 (20) | 6 (3) | 19 (10) | 4 (2) |
| Urinary tract infectiond | 31 (15) | 3 (1) | 24 (12) | 3 (2) |
| Pharyngitis | 25 (12) | 0 (0) | 3 (2) | 0 (0) |
| Rhinitis | 20 (10) | 0 (0) | 4 (2) | 0 (0) |
| Musculoskeletal and connective tissue disorders | ||||
| Back Pain | 41 (20) | 6 (3) | 28 (14) | 7 (4) |
| Arthralgia | 37 (18) | 2 (1) | 29 (15) | 2 (1) |
| Myalgia | 16 (8) | 1 (1) | 29 (15) | 2 (1) |
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnea | 58 (28) | 18 (9) | 48 (24) | 11 (6) |
| Cough | 53 (26) | 2 (1) | 29 (15) | 0 (0) |
| Epistaxis | 25 (12) | 0 (0) | 7 (4) | 0 (0) |
| Skin and subcutaneous tissue disorders | ||||
| Rashe | 97 (47) | 10 (5) | 14 (7) | 0 (0) |
| Pruritus | 40 (19) | 1 (1) | 16 (8) | 0 (0) |
| Nail Disorder | 28 (14) | 0 (0) | 1 (1) | 0 (0) |
| Dry Skin | 22 (11) | 1 (1) | 14 (7) | 0 (0) |
| Acne | 21 (10) | 0 (0) | 2 (1) | 0 (0) |
| Nervous system disorders | ||||
| Dysgeusiaf | 41 (20) | 0 (0) | 17 (9) | 0 (0) |
| Insomnia | 24 (12) | 1 (1) | 30 (15) | 0 (0) |
| Depression | 9 (4) | 0 (0) | 27 (14) | 4 (2) |
| * 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 |
||||
The following selected adverse reactions were reported less frequently ( < 10%).
Gastrointestinal Disorders - Fatal bowel perforation occurred in 1 patient (1%).
Eye Disorders - Conjunctivitis (including lacrimation disorder) occurred in 15 patients (7%).
Immune System - Allergic/Hypersensitivity reactions occurred in 18 patients (9%).
Angioneurotic edema-type reactions have been observed in some patients who received TORISEL (temsirolimus injection) and ACE inhibitors concomitantly.
Infections - Pneumonia occurred in 17 patients (8%); upper respiratory tract infection occurred in 14 patients (7%).
General Disorders and Administration Site Conditions - Impaired wound healing occurred in 3 patients (1%).
Respiratory, Thoracic and Mediastinal Disorders – Interstitial lung disease occurred in 5 patients (2%), including rare fatalities.
Vascular - Hypertension occurred in 14 patients (7%); venous thromboembolism (including deep vein thrombosis and pulmonary embolus) occurred in 5 patients (2%); thrombophlebitis occurred in 2 patients (1%).
Table 2 : Incidence of Selected Laboratory Abnormalities
in Patients Who Received 25 mg IV TORISEL (temsirolimus injection) or IFN-α in the Randomized Trial
| Laboratory Abnormality | TORISEL 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 | 195 (94) | 41 (20) | 180 (90) | 43 (22) |
| Lymphocytes Decreased** | 110 (53) | 33 (16) | 106 (53) | 48 (24) |
| Neutrophils Decreased** | 39 (19) | 10 (5) | 58 (29) | 19 (10) |
| Platelets Decreased | 84 (40) | 3 (1) | 51 (26) | 0 (0) |
| Leukocytes Decreased | 67 (32) | 1 (1) | 93 (47) | 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) |
| *NCI CTC version 3.0 **Grade 1 toxicity may be under-reported for lymphocytes and neutrophils |
||||
The following adverse reactions have been identified during postapproval use of TORISEL (temsirolimus injection) . Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to readily estimate their frequency or establish a causal relationship to drug exposure.
There have been reports of rhabdomyolysis in patients who received TORISEL (temsirolimus injection) .
Co-administration of TORISEL (temsirolimus injection) with rifampin, a potent CYP3A4/5 inducer, had no significant effect on temsirolimus Cmax (maximum concentration) and AUC (area under the concentration versus the time curve) after intravenous administration, but decreased sirolimus Cmax by 65% and AUC by 56% compared to TORISEL (temsirolimus injection) treatment alone. If alternative treatment cannot be administered, a dose adjustment should be considered [see DOSAGE AND ADMINISTRATION].
Co-administration of TORISEL (temsirolimus injection) with ketoconazole, a potent CYP3A4 inhibitor, had no significant effect on temsirolimus Cmax or AUC; however, sirolimus AUC increased 3.1-fold, and Cmax increased 2.2-fold compared to TORISEL (temsirolimus injection) alone. If alternative treatment cannot be administered, a dose adjustment should be considered. [see DOSAGE AND ADMINISTRATION].
The concentration of desipramine, a CYP2D6 substrate, was unaffected when 25 mg of TORISEL (temsirolimus injection) was co-administered. No clinically significant effect is anticipated when temsirolimus is co-administered with agents that are metabolized by CYP2D6 or CYP3A4.
Last reviewed on RxList: 8/5/2010
This monograph has been modified to include the generic and brand name in many instances.
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