Torisel

Generic Name: Temsirolimus
Class: Antineoplastic Agents
VA Class: AN900
Chemical Name: Rapamycin, 42-[3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate]
Molecular Formula: C₅₆H₈₇NO₁₆
CAS Number: 162635-04-3

Introduction

Antineoplastic agent; inhibitor of mammalian target of rapamycin (mTOR) kinase.^{1 2 3 4 5 6 7 8 9 10 11 12}

Uses for Torisel

Renal Cell Carcinoma

Treatment of advanced renal cell carcinoma^{1 2 12} (designated an orphan drug by FDA for this use);¹⁷ considered to be a first-line therapy in poor-risk patients.^{2 10 13 14 20}

Also has been studied in combination with interferon alfa to treat advanced renal cell carcinoma†.^{1 2 19} Results from a randomized study indicate overall survival benefit with temsirolimus alone compared with interferon alfa alone.^{1 2} Combination therapy with interferon alfa and temsirolimus also did not result in improved overall survival compared with interferon alfa alone.^{1 2}

Torisel Dosage and Administration

General

• 
  

  To minimize risk of hypersensitivity reactions, premedicate with IV diphenhydramine hydrochloride 25–50 mg (or a similar antihistamine) administered about 30 minutes before beginning temsirolimus infusion.^{1 2 6 12 19}

  
  

Administration

Administer by IV infusion.¹

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Use infusion pump to administer.¹

Use of an inline polyethersulfone filter with a pore size ≤5 μm and polyethylene-lined administration sets is recommended.¹ (See Concentrate for Injection under Stability.)

Protect drug from excessive room light and sunlight during handling and preparation.^{1 6}

Dilution

To avoid precipitation, temsirolimus for injection concentrate must be diluted in a 2-step process prior to administration.¹

First dilution step: Add 1.8 mL of the nonaqueous diluent supplied by the manufacturer to vial containing 25 mg/mL of temsirolimus (total volume of 1.2 mL); the resultant solution contains approximately 10 mg/mL of the drug in a total volume of 3 mL.¹ Mix well by inversion of the vial; allow sufficient time for air bubbles to subside.¹

Second dilution step: Withdraw the appropriate dose of temsirolimus from the vial, then rapidly dilute in 250 mL of 0.9% sodium chloride injection in a suitable container (polypropylene, polyolefin, polyethylene, or glass).¹ (See Concentrate for Injection under Stability.) Mix the final diluted solution by gently inverting the bag or bottle; avoid shaking to prevent excessive foaming of the solution.¹ Precipitation will occur if undiluted temsirolimus for injection concentrate is added directly to an aqueous infusion solution (e.g., 0.9% sodium chloride injection).¹

Rate of Administration

Infuse over 30–60 minutes.¹

Dosage

Adults

Renal Cell Carcinoma

General Dosage

IV

25 mg once weekly.¹

Continue therapy for as long as the patient derives clinical benefit from the drug or until unacceptable toxicity occurs.^{1 2}

Dosage adjustments should be considered when used in conjunction with potent inhibitors or inducers of CYP3A4.¹ (See Interactions.)

Dosage Modification for Toxicity

Temporarily interrupt therapy if hematologic toxicities (e.g., ANC <1000/mm³, platelet count <75,000/mm³) or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or greater occur.¹

Following resolution of toxicity to grade 2 or less, consider resuming temsirolimus at a reduced weekly dosage that is 5 mg less than the previous dosage, but not less than 15 mg weekly.¹

Prescribing Limits

Adults

Renal Cell Carcinoma

IV

Doses >25 mg may increase risk of serious adverse events (e.g., thrombosis, bowel perforation, interstitial lung disease, seizure, psychosis).¹

Special Populations

Hepatic Impairment

Temsirolimus is cleared predominantly by the liver.^{1 20} Dosage reduction or discontinuance may be warranted to reduce potential for toxicity, but no specific dosage recommendations at this time.¹⁵ (See Hepatic Impairment under Cautions.)

Renal Impairment

No specific dosage reduction recommended.¹ (See Renal Impairment under Cautions.) Not studied in patients undergoing hemodialysis.^{1 20}

Geriatric Patients

No specific dosage recommendations at this time.¹ (See Geriatric Use under Cautions.)

Cautions for Torisel

Contraindications

• 
  

  Manufacturer states none known.¹

  
  

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis, dyspnea, flushing, and chest pain reported.¹

Use with caution in patients with known hypersensitivity to temsirolimus or its metabolites (e.g., sirolimus), polysorbate 80, or any other ingredient in the formulation.¹

Pretreatment with an antihistamine prior to each dose of temsirolimus is recommended to prevent hypersensitivity reactions.^{1 2 6} Use temsirolimus with caution in patients with known hypersensitivity to antihistamines or with conditions requiring avoidance of antihistamines.¹

If a hypersensitivity reaction develops, discontinue the infusion, and observe the patient for at least 30–60 minutes.¹ Treatment may be resumed with administration of an H₁-receptor antagonist (e.g., diphenhydramine hydrochloride), if not previously used, and/or with an H₂-receptor antagonist (e.g., famotidine 20 mg, ranitidine 50 mg) administered IV approximately 30 minutes before restarting the temsirolimus infusion.¹ Resume IV infusion at a slower rate (up to 60 minutes).¹

Hyperglycemia/Glucose Intolerance

Hyperglycemia is likely to develop.¹ May require initiation or increased dosage of insulin and/or an oral hypoglycemic agent.¹ Monitor glucose levels prior to and during therapy.¹

Immunosuppression

Immunosuppression may occur.¹ Monitor patients for infections, including opportunistic infections.¹

Instruct patient to avoid use of live vaccines and close contact with those who have received live vaccines.¹

Interstitial Lung Disease

Interstitial lung disease, sometimes fatal, has occurred.¹ Monitor patients for symptoms (e.g., dyspnea, cough, hypoxia, fever) and for radiographic changes.¹ If suspected, discontinue temsirolimus and consider use of corticosteroids and/or antibiotics.¹

Hyperlipemia

Hyperlipemia with increased triglycerides and cholesterol is likely to develop.¹ May require initiation or increased dosage of a lipid-lowering agent.¹ Monitor serum cholesterol and triglycerides prior to and during therapy.¹

Bowel Perforation

Bowel perforations, sometimes fatal, reported.¹ Promptly evaluate patients with metabolic acidosis, fever, abdominal pain, bloody stools, diarrhea, and/or acute abdomen.¹

Acute Renal Failure

Acute renal failure that is rapidly progressive and sometimes fatal has occurred; was not clearly related to disease progression.¹ Monitor renal function prior to and during therapy.¹

Wound Healing Complications

Abnormal wound healing reported.¹ Use caution in patients during the perioperative period.¹

Intracerebral Hemorrhage

Increased risk of intracerebral bleeding, sometimes fatal, reported in patients with primary CNS tumors or metastases and/or in those receiving anticoagulation therapy.¹

Drug and Food Interactions

Avoid concomitant use with certain drugs (e.g., potent inhibitors or inducers of CYP3A4) or foods (e.g., grapefruit juice); if alternative treatment cannot be given, adjustment of temsirolimus dosage is recommended.¹ (See Interactions.)

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.¹ Animal studies indicate adverse effects on embryofetal development.¹

Women should avoid becoming pregnant during and for 3 months after discontinuing temsirolimus therapy.¹ If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.¹

Male patients with partners of childbearing potential also should use reliable contraception during temsirolimus treatment and for 3 months after the last dose.¹

Adequate Patient Evaluation and Monitoring

Periodically monitor CBC and chemistry panels in patients receiving temsirolimus.¹ In clinical trials, CBC was assessed prior to and on a weekly basis during therapy; chemistry panels were checked every 2 weeks. ^{1 2} These tests may be monitored more or less frequently during temsirolimus therapy at the discretion of the clinician.¹

Periodically monitor glucose and lipid profiles and renal function tests.¹

Specific Populations

Pregnancy

Category D.¹ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether temsirolimus is distributed into milk; discontinue nursing or the drug, taking into account the importance of the drug to the woman.¹

Pediatric Use

Safety and efficacy not established in pediatric patients.¹

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹

Hepatic Impairment

Safety and efficacy in patients with hepatic impairment not studied specifically to date;^{1 15} studies in this patient population are ongoing.¹⁵ (See Special Populations under Pharmacokinetics.)

Renal Impairment

Safety and efficacy in patients with renal impairment not studied specifically to date.¹ (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Rash,^{1 2 6 19} asthenia,^{1 2 6 19} mucositis/stomatitis,^{1 2 6 19} nausea,^{1 2 6 19} edema,^{1 2} anorexia,^{1 2 19} anemia,^{1 2 19} hyperglycemia,^{1 2} hyperlipemia,^{1 2} hypertriglyceridemia,^{1 19} lymphopenia,¹ increased alkaline phosphatase,¹ increased serum creatinine,^{1 2} hypophosphatemia,^{1 19} thrombocytopenia,^{1 2 19} increased AST levels,^{1 2} leukopenia.^{1 2 19}

Interactions for Torisel

Both temsirolimus and its principal active metabolite, sirolimus, metabolized principally by CYP3A4.^{1 6 16 18 20} .^{1 6 16 18} Temsirolimus inhibits CYP isoenzymes 2D6 and 3A4 in vitro.¹

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inhibitors: Potential pharmacokinetic interaction (increased plasma concentrations of the principal active metabolite sirolimus).¹ Avoid concomitant use with potent CYP3A4 inhibitors; if no alternative is available, consider temsirolimus dosage adjustment.¹ (See Specific Drugs and Foods under Interactions.)

CYP3A4 inducers: Potential pharmacokinetic interaction (decreased plasma concentrations of the principal active metabolite sirolimus).¹ Avoid concomitant use with potent CYP3A4 inducers; if no alternative is available, consider temsirolimus dosage adjustment.¹ (See Specific Drugs and Foods under Interactions.)

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP2D6 and CYP3A4: No evidence of clinically important effects in drug interaction studies with substrates of CYP2D6; no effect anticipated on substrates of CYP3A4.¹

Specific Drugs and Foods

Drug or Food	Interaction	Comments
ACE inhibitors	Angioedema-type reactions observed during concomitant therapy1	Caution is advised
Anticoagulants	Increased risk of intracerebral bleeding1	Caution is advised1
Anticonvulsants (carbamazepine, phenobarbital, phenytoin)	Decreased plasma sirolimus concentrations may occur1 20	Increase temsirolimus dosage from 25 to 50 mg weekly; if potent CYP3A4 inducer is discontinued, resume temsirolimus dosage at previous level1
Antifungals, azoles (itraconazole, ketoconazole, voriconazole)	Increased plasma sirolimus concentrations may occur1 20	Decrease temsirolimus dosage from 25 to 12.5 mg weekly; if potent CYP3A4 inhibitor is discontinued, allow interval of 1 week before resuming previous level of temsirolimus dosage1
Antimycobacterials, rifamycins (rifabutin, rifampin)	Decreased plasma sirolimus concentrations1	Increase temsirolimus dosage from 25 to 50 mg weekly; if potent CYP3A4 inducer is discontinued, resume previous level of temsirolimus dosage1
Dexamethasone	Decreased plasma sirolimus concentrations may occur1 20 21	Increase temsirolimus dosage from 25 to 50 mg weekly; if potent CYP3A4 inducer is discontinued, resume previous level of temsirolimus dosage1
Grapefruit juice	Increased plasma sirolimus concentrations may occur1	Avoid concomitant use1
HIV protease inhibitors (atazanavir, indinavir, nelfinavir, ritonavir, saquinavir)	Increased plasma sirolimus concentrations may occur1 20	Decrease temsirolimus dosage from 25 to 12.5 mg weekly; if potent CYP3A4 inhibitor is discontinued, allow interval of 1 week before resuming previous level of temsirolimus dosage1
Macrolides (clarithromycin, telithromycin)	Increased plasma sirolimus concentrations may occur1 20	Decrease temsirolimus dosage from 25 to 12.5 mg weekly; if potent CYP3A4 inhibitor is discontinued, allow interval of 1 week before resuming previous level of temsirolimus dosage1
Nefazodone	Increased plasma sirolimus concentrations1	Decrease temsirolimus dosage from 25 to 12.5 mg weekly; if potent CYP3A4 inhibitor is discontinued, allow interval of 1 week before resuming previous level of temsirolimus dosage1
St. John's wort (Hypericum perforatum)	Unpredictable decreases in plasma temsirolimus concentrations1	Avoid concomitant use 1
Sunitinib	Increased risk of dose-limiting toxicity requiring hospitalization (e.g., grade 3/4 erythematous maculopapular rash, gout/cellulitis) reported with concurrent use 1

Torisel Pharmacokinetics

Absorption

Bioavailability

100% bioavailable after IV administration.¹⁵ Peak temsirolimus blood concentration occurred at the end of the IV infusion.^{1 15 18} Sirolimus was evident in blood within 15 minutes after the temsirolimus infusion, and peak sirolimus blood concentration occurred at a median of 2 hours.^{6 18}

Distribution

Extent

Extensively distributed into blood cells and peripheral tissues.^{1 15} Following IV administration of a single 25-mg dose, mean volume of distribution in whole blood was 172 L.¹

Not known if temsirolimus or its metabolites cross the blood-brain barrier in humans.¹⁵ However, the drug and its metabolites distribute into brain tissue in rats.¹⁵

Not known whether temsirolimus is distributed into milk.¹

Plasma Protein Binding

Approximately 85 and 87% at in vitro concentrations of 10 and 100 ng/mL, respectively.^{15 18}

Elimination

Metabolism

Temsirolimus metabolized by hydrolysis to sirolimus, the principal active metabolite.^{1 15 16} Temsirolimus and sirolimus both also are metabolized by CYP3A4.^{16 18}

Elimination Route

Excreted in feces (78%) and urine (5%) following IV dosing within 14 days.¹

Half-life

Temsirolimus: 17.3 hours.^{1 15 18} Sirolimus: 54.6 hours.^{1 15 18}

Special Populations

Metabolism in patients with hepatic dysfunction under investigation; no data currently available.^{1 15}

Renal impairment is not expected to markedly influence drug exposure.¹

Stability

Storage

Parenteral

Concentrate for Injection

2–8°C; protect from light.¹ Protect from excessive room light and sunlight during handling and preparation.^{1 6}

Temsirolimus solutions that have been diluted to 10 mg/mL (initial dilution) may be stored for ≤24 hours at room temperature.¹

The final diluted solution of temsirolimus (i.e., after the second dilution) for infusion should be administered ≤6 hours from the time that the diluted temsirolimus mixture is added to the sodium chloride injection.¹

Polysorbate 80 (in the diluent supplied by the manufacturer) can cause leaching of diethylhexyl phthalate (DEHP) from PVC containers or administration sets.¹ Store the final temsirolimus diluted solution (i.e., after the second dilution) in glass or polypropylene bottles or in plastic (polypropylene or polyolefin) bags and administer through polyethylene-lined administration sets.¹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Do not add temsirolimus concentrate for injection to the infusion solution without performing the first dilution step; precipitation will occur.¹ (See Dilution under Dosage and Administration.)

Compatible1
Sodium chloride 0.9% (after first dilution step)

Drug Compatibility

Avoid addition of other drugs or nutritional agents to admixtures of temsirolimus in 0.9% sodium chloride injection; compatibility not evaluated.¹

Temsirolimus concentrate for injection is unstable in the presence of acids or bases; avoid combining with agents capable of modifying pH.¹

ActionsActions

• 
  

  Inhibits mammalian target of rapamycin (mTOR) kinase.^{1 2 3 4 5 6 7 8 9 10 11 12}

  
  


• 
  

  Although the mechanism of action has not been fully elucidated, temsirolimus binds to the intracellular protein FK506 binding protein-12, forming a drug-protein complex that inhibits activation of mTOR signaling (which regulates cell division).^{1 2 3 6 12} Proteins that regulate cell-cycle progression are suppressed, and G₁ phase of the cell cycle is blocked.^{1 2 3 8 11}

  
  


• 
  

  Temsirolimus also reduces expression of hypoxia inducible factor 1α and 2α (HIF-1α and HIF-1β) in vitro, resulting in reduced expression of vascular endothelial growth factor (VEGF) and a potential antiangiogenic effect .^{1 3 6 7 10}

  
  


• 
  

  Although temsirolimus is metabolized to sirolimus, temsirolimus itself exhibits antitumor activity and is not considered a prodrug.¹⁵

  
  


• 
  

  Temsirolimus inhibited T lymphocyte activity in mice, but effects were reversible and T lymphocyte activity returned to normal within 24 hours of discontinuance.⁶ No consistent effect demonstrated on lymphocyte population or activation in humans.⁶ However, infections may result from immunosuppression.¹

  
  

Advice to Patients

• 
  

  Risk of serious allergic reactions, including anaphylaxis; importance of immediately reporting any facial swelling or difficulty breathing.¹

  
  


• 
  

  Risk of increased blood glucose levels; importance of reporting excessive thirst or any increase in volume or frequency of urination.¹

  
  


• 
  

  Risk of increased triglyceride and/or cholesterol levels.¹

  
  


• 
  

  Increased susceptibility to infection or renal failure.¹

  
  


• 
  

  Risk of abnormal wound healing in the event that surgery is performed within a few weeks of therapy initiation or during therapy.¹

  
  


• 
  

  Risk of interstitial lung disease, which may be fatal; importance of reporting any new or worsening respiratory symptoms.¹

  
  


• 
  

  Risk of bowel perforation, which may be fatal; importance of reporting any new or worsening abdominal pain or blood in stools.¹

  
  


• 
  

  Importance of advising patients with CNS tumors and/or receiving anticoagulant therapy of the potential for increased risk of intracerebral bleeding, which may be fatal.¹

  
  


• 
  

  Risk of decreased efficacy of vaccination; importance of avoiding use of live vaccines and close contact with those who have received live vaccines.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women of childbearing potential and men with partners of childbearing potential to avoid pregnancy and to use effective contraceptive methods during therapy and for 3 months following discontinuance of therapy.¹ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Temsirolimus

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection concentrate, for IV infusion only	25 mg/mL (30 mg)	Torisel (with dehydrated alcohol 39.5% w/v and propylene glycol 50.3% w/v and with diluent containing dehydrated alcohol)	Wyeth

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions February 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Wyeth Pharmaceuticals Inc. Torisel (temsirolimus) injection prescribing information. Philadelphia, PA: 2008 Sep.

2. Hudes G, Carducci M, Tomczak P et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007; 356:2271-81. [PubMed 17538086]

3. Cho D, Signoretti S, Regan M et al. The role of mammalian target of rapamycin inhibitors in the treatment of advanced renal cancer. Clin Cancer Res. 2007; 13(Suppl 2):758s-63s. [PubMed 17255306]

4. Atkins MB, Ernstoff MS, Figlin RA et al. Innovations and challenges in renal cell carcinoma: summary statement from the Second Cambridge Conference. Clin Cancer Res. 2007; 13(Suppl 2):667S-70S. [PubMed 17255291]

5. Motzer RJ, Bukowski RM. Targeted therapy for metastatic renal carcinoma. J Clin Oncol. 2006; 24:5601-8. [PubMed 17158546]

6. Hidalgo M, Buckner JC, Erlichman C et al. A phase I and pharmacokinetic study of temsirolimus (CCI-779) administered intravenously daily for 5 days every 2 weeks to patients with advanced cancer. Clin Cancer Res. 2006; 12:5755-63. [PubMed 17020981]

7. Rini BI. Molecularly targeted therapy in renal cell carcinoma: where do we go from here? Expert Rev Anticancer Ther. 2006; 6:1753-60.

8. Pouessel D, Culine S. Targeted therapies in metastatic renal cell carcinoma: the light at the end of the tunnel. Expert Rev Anticancer Ther. 2006; 6:1761-7. [PubMed 17181490]

9. Hutson TE, Sonpavde G, Galsky MD. Targeting growth factor and antiangiogenic pathways in clear-cell renal cell carcinoma: rationale and ongoing trials. Clin Genitourin Cancer. 2006; 5(Suppl 1):31S-9S.

10. Escudier B. Advanced renal cell carcinoma: current and emerging management strategies. Drugs. 2007; 67:1257-64. [PubMed 17547470]

11. Reddy GK, Mughal TI, Rini BI. Current data with mammalian target of rapamycin inhibitors in advanced-stage renal cell carcinoma. Clin Genitourin Cancer. 2006; 5:110-3. [PubMed 17026798]

12. Atkins MB, Hidalgo M, Stadler WM et al. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol. 2004; 22:909-18. [PubMed 14990647]

13. Halbert RJ, Figlin RA, Atkins MB et al. Treatment of patients with metastatic renal cell cancer: a RAND appropriateness panel. Cancer. 2006; 107:2375-83. [PubMed 17048248]

14. Ozols RF, Herbst RS, Colson YL et al. Clinical cancer advances 2006: major research advances in cancer treatment, prevention, and screening–a report from the American Society of Clinical Oncology. J Clin Oncol. 2007; 25:146-62. [PubMed 17158528]

15. Wyeth Pharmaceuticals Inc. Collegeville, PA: Personal communication. 2007 Jul 2.

16. Boni JP, Leister C, Bender G et al. Population pharmacokinetics of CCI-779: correlations to safety and pharmacogenomic responses in patients with advanced renal cancer. Clin Pharmacol Ther. 2005; 77:76-89. [PubMed 15637533]

17. Food and Drug Administration. Orphan designations pursuant to section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97 414). Rockville, MD. From FDA web site (). Accessed 2007 Jul 25.

18. Office of Clincial Pharmacology, Food and Drug Administration. Clinical pharmacology and biopharmaceutics review section of FDA approval package for temsirolimus. From the FDA website

19. Motzer RJ, Hudes GR, Curti BD et al. Phase I/II trial of temsirolimus combined with interferon alfa for advanced renal cell carcinoma. J Clin Oncol. 2007: 25:3958-64.

20. Wyeth Pharmaceuticals Inc. Collegeville, PA: Personal communication.

21. Kato M, Chiba K, Horikawa M et al. The quantitative prediction of in vivo enzyme induction caused by drug exposure from in vitro information on human hepatocytes. Drug Metab Pharmocokinet. 2005; 20: 236-43.

More Torisel resources

• Torisel Side Effects (in more detail)
• Torisel Use in Pregnancy & Breastfeeding
• Torisel Drug Interactions
• Torisel Support Group
• 0 Reviews for Torisel - Add your own review/rating

• Torisel Prescribing Information (FDA)


• Torisel Consumer Overview


• Torisel Advanced Consumer (Micromedex) - Includes Dosage Information


• Torisel MedFacts Consumer Leaflet (Wolters Kluwer)


• Temsirolimus Professional Patient Advice (Wolters Kluwer)

Compare Torisel with other medications

• Renal Cell Carcinoma

Topsyn

Generic Name: fluocinonide (Topical application route)

floo-oh-SIN-oh-nide

Commonly used brand name(s)

In the U.S.

• Lidex


• Lidex-E


• Vanos

In Canada

• Lidemol


• Lidex Mild


• Lidex Regular


• Lyderm


• Tcis


• Tiamol


• Topsyn


• Trisyn

Available Dosage Forms:

• Ointment


• Emollient Cream


• Cream


• Solution


• Gel/Jelly

Therapeutic Class: Corticosteroid, Strong

Pharmacologic Class: Adrenal Glucocorticoid

Uses For Topsyn

Fluocinonide topical is used to help relieve redness, itching, swelling, or other discomfort caused by skin conditions. This medicine is a corticosteroid (cortisone-like medicine or steroid).

This medicine is available only with your doctor's prescription.

Before Using Topsyn

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of fluocinonide topical in the pediatric population. However, because of this medicine's toxicity, it should be used with caution. Children may absorb large amounts through the skin, which can cause serious side effects. If your child is using this medicine, follow your doctor's instructions very carefully. For Vanos® cream, safety and efficacy have not been established in children younger than 12 years of age.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of Vanos® cream in the elderly. However, elderly patients are more likely to have age-related medical problems, which may require caution in patients receiving Vanos® cream.

No information is available on the relationship of age to the effects of fluocinonide topical in geriatric patients.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Cushing's syndrome (adrenal gland disorder) or


• Diabetes or


• Hyperglycemia (high blood sugar) or


• Intracranial hypertension (increased pressure in the head)—Use with caution. May make these conditions worse.

• Infection of the skin at or near the place of application or


• Large sores, broken skin, or severe skin injury at the place of application—The chance of side effects may be increased.

• Perioral dermatitis (skin problem) or


• Rosacea (skin problem)—Vanos® cream should not be used in patients with these conditions.

Proper Use of fluocinonide

This section provides information on the proper use of a number of products that contain fluocinonide. It may not be specific to Topsyn. Please read with care.

It is very important that you use this medicine only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. To do so may cause unwanted side effects or skin irritation.

This medicine is for use on the skin only. Do not get it in your eyes, nose, mouth, or vagina. Do not use it on skin areas that have cuts, scrapes, or burns. If it does get on these areas, rinse it off right away with water.

This medicine should only be used for skin conditions that your doctor is treating. Check with your doctor before using it for other conditions, especially if you think that a skin infection may be present. This medicine should not be used to treat certain kinds of skin infections or conditions, such as severe burns.

If you are using the Vanos® cream:

• Do not use it on the face, groin, or underarms unless directed to do so by your doctor.


• Do not use it for more than 2 weeks unless your doctor tells you otherwise.

To use:

• Wash your hands with soap and water before and after using this medicine.


• Apply a thin layer of this medicine to the affected area of the skin. Rub it in gently.


• Do not bandage or otherwise wrap the skin being treated unless directed to do so by your doctor.


• If the medicine is applied to the diaper area of an infant, do not use tight-fitting diapers or plastic pants unless directed to do so by your doctor.


• If your doctor ordered an occlusive dressing or airtight covering to be applied over the medicine, make sure you know how to apply it. Occlusive dressings increase the amount of medicine absorbed through your skin, so use them only as directed. If you have any questions about this, check with your doctor.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For topical dosage forms (cream, gel, ointment, or solution):
  
  • For redness, itching, and swelling of the skin:
    
    • Adults—Apply to the affected area of the skin two to four times per day.
    
    
    • Children—Apply to the affected area of the skin two to four times per day.
    
    
  
  


• For topical dosage form (cream):
  
  • For atopic dermatitis:
    
    • Adults and children 12 years of age and older—Apply to the affected area of the skin once a day.
    
    
    • Children younger than 12 years of age—Use is not recommended.
    
    
  
  
  • For psoriasis:
    
    • Adults and children 12 years of age and older—Apply to the affected area of the skin one to two times per day.
    
    
    • Children younger than 12 years of age—Use is not recommended.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, apply it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using Topsyn

It is very important that your doctor check the progress of you or your child at regular visits for any unwanted effects that may be caused by this medicine.

If your or your child's symptoms do not improve within a few days, or if they become worse, check with your doctor.

Using too much of this medicine or using it for a long time may increase your risk of having adrenal gland problems. The risk is greater for children and patients who use large amounts for a long time. Talk to your doctor right away if you or your child have more than one of these symptoms while you are using this medicine: blurred vision; dizziness or fainting; a fast, irregular, or pounding heartbeat; increased thirst or urination; irritability; or unusual tiredness or weakness.

Stop using this medicine and check with your doctor right away if you or your child have a skin rash, burning, stinging, swelling, or irritation on the skin.

Do not use cosmetics or other skin care products on the treated areas.

Topsyn Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Incidence not known

• Blistering, burning, crusting, dryness, or flaking of the skin


• irritation


• itching, scaling, severe redness, soreness, or swelling of the skin


• redness and scaling around the mouth


• thinning of the skin with easy bruising, especially when used on the face or where the skin folds together (e.g. between the fingers)


• thinning, weakness, or wasting away of the skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

• Fever


• headache


• muscle aches


• sore throat


• stuffy or runny nose


• unusual tiredness or weakness

Incidence not known

• Acne or pimples


• burning and itching of the skin with pinhead-sized red blisters


• burning, itching, and pain in hairy areas, or pus at the root of the hair


• increased hair growth on the forehead, back, arms, and legs


• lightening of normal skin color


• lightening of treated areas of dark skin


• reddish purple lines on the arms, face, legs, trunk, or groin


• softening of the skin

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Topsyn side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Topsyn resources

• Topsyn Side Effects (in more detail)
• Topsyn Use in Pregnancy & Breastfeeding
• Topsyn Drug Interactions
• Topsyn Support Group
• 12 Reviews for Topsyn - Add your own review/rating

Compare Topsyn with other medications

• Atopic Dermatitis
• Dermatitis
• Psoriasis

Torsemide

Class: Loop Diuretics
VA Class: CV702
Chemical Name: N-[[(1-Methylethyl)amino]carbonyl]-4-[(3-methylphenyl) amino]-3-pyridinesulfonamide
Molecular Formula: C₁₆H₂₀N₄O₃S
CAS Number: 56211-40-6
Brands: Demadex

Introduction

A sulfonamide, loop-type diuretic and antihypertensive agent.^{1 a}

Uses for Torsemide

Edema

Management of edema associated with CHF^{1 4} or hepatic¹ or renal¹ disease (including chronic renal failure).^a

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).^{1 2 3}

One of several preferred initial therapies in hypertensive patients with CHF, acute pulmonary edema, or renal disease.^{2 3}

Can be used as monotherapy for initial management of uncomplicated hypertension;^{1 2 3 a} however, thiazide diuretics are preferred by JNC 7.¹¹

Torsemide Dosage and Administration

General

• 
  

  The manufacturer states that since oral and IV doses of torsemide are therapeutically equivalent, torsemide dosage is identical for oral or IV administration.¹

  
  

Edema

• 
  

  Most experts state that all patients with symptomatic CHF who have evidence for, or a prior history of, fluid retention generally should receive diuretic therapy in conjunction with moderate sodium restriction (≤3 g of sodium daily), an ACE inhibitor, and usually a β-blocker, with or without a cardiac glycoside.⁴

  
  


• 
  

  Hospitalization of the patient during initiation of therapy is advisable for patients with hepatic cirrhosis and ascites or chronic renal failure.^{1 a b}

  
  


• 
  

  Chronic use of any diuretic in hepatic disease has not been adequately studied.^{1 a}

  
  

Administration

Administer orally, by direct IV injection, or by continuous IV infusion.¹

Oral Administration

Administer orally without regard to meals.¹

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

IV administration may be used when a rapid onset of diuresis is desired or when oral therapy is not practical.¹

If torsemide is administered through an IV line, flush the IV line with 0.9% sodium chloride before and after administration.^a

Dilution

For IV infusion, dilute in 5% dextrose, 0.9% sodium chloride, or 0.45% sodium chloride injection.^a

Rate of Administration

For direct IV injection, administer slowly over a period of 2 minutes.¹

Dosage

Adults

Edema

CHF

Oral

Initially, 10–20 mg, given as a single dose.¹ Increase as necessary by approximately doubling daily dosage until desired diuresis is attained.¹ Single doses exceeding 200 mg not adequately studied.¹

IV

Initially, 10–20 mg, given as a single dose.¹ Increase as necessary by approximately doubling dosage until desired diuresis is attained.¹ Single doses exceeding 200 mg not adequately studied.¹

Hypertension

Oral

Initially, 5 mg once daily.¹ If adequate hypotensive response not attained in 4–6 weeks, may increase dosage to 10 mg once daily.¹ If adequate response not observed with 10 mg once daily, an additional antihypertensive agent should be added to antihypertensive therapy.¹

IV

Initially, 5 mg once daily.¹ If adequate hypotensive response not attained in 4–6 weeks, may increase dosage to 10 mg once daily.¹ If adequate response not observed with 10 mg once daily, an additional antihypertensive agent should be added to antihypertensive therapy.¹

Prescribing Limits

Adults

Edema

CHF

Oral

Maximum of 200 mg as a single dose (daily).¹

IV

Maximum of 200 mg as a single dose (daily).¹

Hypertension

Oral

Maximum of 10 mg once daily.¹

IV

Maximum of 10 mg once daily.¹

Special Populations

Renal Impairment

Edema

Edema Associated with Chronic Renal Failure

Oral or IV

In adults, initially, 20 mg once daily.¹ Increase as necessary by approximately doubling dosage until desired diuresis is attained.¹ Single doses exceeding 200 mg not adequately studied.^{1 a}

Hepatic Impairment

Chronic use in hepatic disease not adequately studied.¹

Edema

Edema Associated with Hepatic Cirrhosis

Oral or IV

In adults, initially, 5–10 mg once daily, given concomitantly with an aldosterone antagonist or a potassium-sparing diuretic.^a Increase as necessary by approximately doubling dosage until desired diuresis is attained.^a Single doses exceeding 40 mg not adequately studied.¹

Cautions for Torsemide

Contraindications

• 
  

  Anuria.¹

  
  


• 
  

  Known hypersensitivity to torsemide or to sulfonylureas.¹

  
  

Warnings/Precautions

Warnings

Hepatic Effects

Sudden alterations of electrolyte balance in patients with cirrhosis may precipitate hepatic coma; use with caution in patients with hepatic cirrhosis and ascites.¹

Therapy in such patients is best initiated in the hospital.¹ Use an aldosterone antagonist or potassium-sparing agent concomitantly with torsemide to prevent hypokalemia and metabolic alkalosis in such patients.¹

Ototoxicity

Tinnitus and hearing loss, usually reversible, have been observed following rapid IV injection of other loop diuretics and following oral torsemide administration.¹ Administer IV slowly (over 2 minutes); do not exceed 200 mg as a single dose.¹

Fluid, Electrolyte, and Cardiovascular Effects

Observe carefully for manifestations of fluid and electrolyte depletion (e.g., dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, nausea, vomiting).^{1 a}

Excessive diuresis may cause dehydration and blood volume reduction with circulatory collapse and possibly vascular thrombosis and embolism, particularly in geriatric patients.^{1 a}

Laboratory changes may include altered serum concentrations of sodium, chloride, and potassium; acid-base abnormalities; and increased BUN.^{1 a} If electrolyte imbalance, hypovolemia, or prerenal azotemia develops, torsemide should be discontinued until the abnormality is corrected; treatment then may be restarted at a reduced dosage.^{1 a}

Risk of hypokalemia, especially with brisk diuresis, with inadequate oral electrolyte intake, in those with cirrhosis, or during concomitant use of corticosteroids or ACTH.^{1 a} Risk of arrhythmias secondary to hypokalemia in patients with cardiovascular disease, especially those receiving concomitant therapy with a cardiac glycoside.^{1 a}

Periodically monitor serum potassium and other electrolyte concentrations.^{1 a}

General Precautions

Endocrine Effects

Possible increased blood glucose concentrations; hyperglycemia occurred rarely. ^{1 a}

Renal and Electrolyte Effects

Small, dose-related, reversible increases in BUN, serum creatinine, and uric acid concentrations reported.^{1 a} Symptomatic gout reported at an incidence similar to placebo.¹

Slight alterations in calcium and magnesium concentrations.^{1 a}

Other Effects

Increases in total plasma cholesterol concentrations may occur; usually subside during chronic therapy.^{1 a}

Increases in plasma triglyceride concentrations reported.^{1 a}

In long-term studies, no clinically important differences in lipid profiles compared to baseline.^{1 a}

No clinically important effects on hemoglobin; hematocrit; WBC, erythrocyte, or platelet counts; or serum alkaline phosphatase concentrations.^{1 a}

Specific Populations

Pregnancy

Category B.¹

Lactation

Not known whether torsemide is distributed into milk.¹ Caution if used in nursing women.¹

Pediatric Use

Safety and efficacy not established.¹

Renal calcifications reported in severely premature infants with edema secondary to patent ductus arteriosus and hyaline membrane disease receiving another loop diuretic.^{1 a} Increased risk of persistent patent ductus arteriosus in premature neonates with hyaline membrane disease receiving another loop diuretic also has been reported.^{1 a}

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.^{1 a}

Renal Impairment

Seizures reported in patients with acute renal failure receiving higher than recommended dosages of torsemide.^{1 a}

Common Adverse Effects

Headache, excessive urination, dizziness, rhinitis, asthenia, diarrhea, ECG abnormality, increased cough.^{1 a}

Interactions for Torsemide

Specific Drugs

Drug	Interaction	Comments
Cholestyramine	Decreased absorption of torsemide in animals1 a	Avoid simultaneous administration when used concomitantly1 a
Digoxin	Increased torsemide AUC1 a	Torsemide dosage adjustment not necessary1 a
Lithium	Reduced renal clearance of lithium and increased risk of lithium toxicity reported with other diuretics 1 a	Avoid concomitant use or use great caution1 a
Ototoxic drugs (e.g., aminoglycoside antibiotics, ethacrynic acid)	Possible additive ototoxic effect when ototoxic drugs used concomitantly with other diuretics, especially in those with impaired renal function1 a
Probenecid	Reduced secretion of torsemide into proximal tubule and decreased diuretic activity1 a
Salicylates (e.g., aspirin, NSAIAs)	Concomitant use of NSAIAs with another loop diuretic (furosemide) occasionally associated with renal dysfunction.1 a Indomethacin may partially inhibit natriuretic effect of torsemide in those with dietary sodium restriction (50 mEq daily) 1 a Concomitant use with high dosages of salicylates may result in salicylate toxicity1 a
Spironolactone	Reduced renal clearance of spironolactone1 a	Adjustment of spironolactone or torsemide dosage not necessary1 a

Torsemide Pharmacokinetics

Absorption

Bioavailability

Bioavailability is approximately 80%.¹

Onset

Following oral administration, onset of diuresis occurs within 1 hour; maximal effect during the first or second hour.^{1 a}

Following IV administration, onset of diuresis occurs within 10 minutes; maximal effect within 1 hour.^{1 a}

Duration

Diuretic effect persists 6–8 hours following oral or IV administration.^{1 a}

Food

Food delays the time to peak plasma concentration following oral dosing but does not affect extent of absorption or diuretic activity.^{1 a}

Plasma Concentrations

Following oral administration, peak plasma concentrations achieved within 1 hour.¹

Distribution

Extent

Not known whether torsemide is distributed into milk.^{1 a}

Plasma Protein Binding

>99%.^{1 a}

Elimination

Metabolism

Hepatic metabolism accounts for approximately 80% of total clearance.^{1 a} Carboxylic acid derivative, the major metabolite, is inactive.^{1 a}

Elimination Route

Urinary excretion accounts for approximately 20% of total clearance in patients with normal renal function.^{1 a} Most renal clearance occurs via active secretion of the drug by the proximal tubules into tubular urine.^{1 a}

Half-life

Approximately 3.5 hours.^{1 a}

Special Populations

In patients with decompensated CHF, hepatic and renal clearance are reduced, resulting in delivery of less drug to the intraluminal site of action and decreased natriuretic effect.^{1 a} Total clearance is about half of that of healthy individuals; half-life and AUC increased.^{1 a}

In patients with renal failure, renal clearance (but not total clearance) is reduced, resulting in delivery of less drug to the intraluminal site of action and decreased natriuretic effect.^{1 a}

In patients with hepatic cirrhosis, renal clearance (but not total clearance) and half-life are increased.¹

In geriatric patients, decreased renal clearance.^{1 a}

Stability

Storage

Oral

Tablets

15–30°C.¹ Do not freeze.^{1 a}

Parenteral

Injection

15–30°C.^{1 a} Do not freeze.^{1 a}

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^HID

Compatible
Dextrose 5% in water
Sodium chloride 0.45 or 0.9%

Y-Site CompatibilityHID

Compatible
Milrinone lactate

ActionsActions

• 
  

  Acts from within the lumen of the thick ascending portion of the loop of Henle, where it inhibits the sodium/potassium/chloride carrier system.¹

  
  


• 
  

  Increases urinary excretion of sodium, chloride, and water without having an important effect on glomerular filtration rate, renal plasma flow, or acid-base balance.¹

  
  

Advice to Patients

• 
  

  Risks associated with excessive fluid loss or electrolyte imbalance.^{1 a}

  
  


• 
  

  Potential for postural hypotension; importance of rising slowly from a seated position.¹

  
  


• 
  

  Importance of informing patients with diabetes mellitus that blood glucose concentrations may increase.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Torsemide

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	5 mg*	Demadex (with povidone; scored)	Roche
			Torsemide Tablets	Apotex, Par, Pliva, Roxane, Teva
		10 mg*	Demadex (with povidone; scored)	Roche
			Torsemide Tablets	Apotex, Par, Pliva, Roxane, Teva, UDL,
		20 mg*	Demadex (with povidone; scored)	Roche
			Torsemide Tablets	Apotex, Par, Pliva, Roxane, Teva, UDL
		100 mg*	Demadex (with povidone; scored)	Roche
			Torsemide Tablets	Apotex, Par, Pliva, Teva
Parenteral	Injection, for IV use	10 mg/mL	Demadex	Roche

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Demadex 10MG Tablets (MEDA PHARMACEUTICALS): 30/$43.69 or 90/$110.37

Demadex 100MG Tablets (MEDA PHARMACEUTICALS): 30/$160.99 or 90/$455.97

Demadex 20MG Tablets (MEDA PHARMACEUTICALS): 30/$55.99 or 90/$139.97

Torsemide 10MG Tablets (TEVA PHARMACEUTICALS USA): 30/$29.99 or 90/$79.97

Torsemide 100MG Tablets (TEVA PHARMACEUTICALS USA): 30/$89.99 or 90/$249.96

Torsemide 20MG Tablets (TEVA PHARMACEUTICALS USA): 30/$22.99 or 90/$59.98

Torsemide 5MG Tablets (CAMBER PHARMACEUTICALS): 30/$18.99 or 90/$56.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions August 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Boehringer Mannheim. Demadex (torsemide) tablets and injection prescribing information. Rockville, MD: 1993 Oct.

2. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Bethesda, MD: National Institutes of Health. (NIH publication No. 98-4080.)

3. Kaplan NM. Choice of initial therapy for hypertension. JAMA. 1996; 275:1577-80. [IDIS 365188] [PubMed 8622249]

4. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure: approaches to the prevention of heart failure. Am J Cardiol. 1999; 83:9-38A.

5. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4. [PubMed 10818056]

6. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20. [PubMed 10818055]

7. Bakris GL, Williams M, Dworkin L et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000; 36:646-61. [IDIS 452007] [PubMed 10977801]

8. Associated Press (American Diabetes Association). Diabetics urged: drop blood pressure. Chicago, IL; 2000 Aug 29. Press Release from web site.

9. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-42. [IDIS 490723] [PubMed 12479770]

10. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288:2981-97. [IDIS 490721] [PubMed 12479763]

11. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) Express. Bethesda, MD: May 14 2003. From NIH website. (http://www.nhlbi.nih.gov/guidelines/hypertension/jncintro.htm). (Also published in JAMA. 2003; 289:2560-72.

a. Roche Pharmaceuticals. Demadex (torsemide) tablets and injection prescribing information. Nutley, NJ: 2003 Apr.

b. AHFS Drug Information 2007. McEvoy GK, ed. Furosemide. American Society of Health-System Pharmacists; 2007: 2690-4.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1581.

More Torsemide resources

• Torsemide Side Effects (in more detail)
• Torsemide Use in Pregnancy & Breastfeeding
• Drug Images
• Torsemide Drug Interactions
• Torsemide Support Group
• 0 Reviews for Torsemide - Add your own review/rating

• Torsemide MedFacts Consumer Leaflet (Wolters Kluwer)


• Torsemide Prescribing Information (FDA)


• Torsemide Professional Patient Advice (Wolters Kluwer)


• torsemide Concise Consumer Information (Cerner Multum)


• torsemide Advanced Consumer (Micromedex) - Includes Dosage Information


• Demadex Prescribing Information (FDA)

Compare Torsemide with other medications

• Ascites
• Edema
• Heart Failure
• High Blood Pressure
• Nonobstructive Oliguria
• Renal Failure

Topcare Tioconazole 1

Dosage Form: ointment
Topco Tioconazole 1 Drug Facts

Active ingredient (in each applicator)

Tioconazole 300 mg (6.5%)

Purpose

Vaginal antifungal

Uses

• treats vaginal yeast infections

Warnings

For vaginal use only

Do not use

if you have never had a vaginal yeast infection diagnosed by a doctor

Ask a doctor before use if you have

• vaginal itching and discomfort for the first time


• lower abdominal, back or shoulder pain, fever, chills, nausea, vomiting, or foul-smelling vaginal discharge. You may have a more serious condition.


• vaginal yeast infections often (such as once a month or 3 in 6 months). You could be pregnant or have a serious underlying medical cause for your symptoms, including diabetes or a weakened immune system.


• been exposed to human immunodeficiency virus (HIV) that causes AIDS

When using this product

• do not use tampons, douches, spermicides, or other vaginal products. Condoms and diaphragms may be damaged and fail to prevent pregnancy or sexually transmitted disease (STDs).


• do not have vaginal intercourse


• mild increase in vaginal burning, itching or irritation may occur

Stop use and ask a doctor if

• symptoms do not get better after 3 days


• symptoms last more than 7 days


• you get a rash or hives, abdominal pain, fever, chills, nausea, vomiting, or foul-smelling vaginal discharge

If pregnant or breast-feeding,

ask a health professional before use.

Keep out of reach of children.

If swallowed, get medical help or contact a Poison Control Center right away.

Directions

• before using this product read the enclosed brochure and instructions on foil packet for complete directions and information


• adults and children 12 years and over:


• open the foil packet just before use and remove purple cap


• insert entire contents of applicator into the vagina at bedtime. Throw applicator away after use.


• children under 12 years of age: ask a doctor

Other information

• this product is a 1-dose treatment, most women do not experience complete relief of their symptoms in just one day. Most women experience some relief within one day and complete relief of symptoms within 7 days.


• if you have questions about vaginal yeast infections, consult your doctor


• store at 20° - 25°C (68° - 77°F)


• see end flap of carton for lot number and expiration date

Inactive ingredients

butylated hydroxyanisole, magnesium aluminum silicate, white petrolatum

Questions or comments?

1-888-423-0139

Principal Display Panel

1-Dose Vaginal Treatment

Tioconazole 1

Tioconazole Ointment 6.5%

Vaginal Antifungal

Cures Most Vaginal Yeast Infections

1 Ready-to-Use Convenient Prefilled Applicator

Compare to 1-Day™ active ingredient

Tioconazole 1 Carton

Topcare Tioconazole 1  tioconazole  ointment

Product Information Product Type HUMAN OTC DRUG NDC Product Code (Source) 36800-426 Route of Administration VAGINAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength TIOCONAZOLE (TIOCONAZOLE) TIOCONAZOLE 6.5 g  in 100 g

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color BROWN (light to dark tan) Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 36800-426-54 1 APPLICATOR In 1 CARTON contains a APPLICATOR 1 4.6 g In 1 APPLICATOR This package is contained within the CARTON (36800-426-54)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA075915	03/03/2008

Labeler - Topco Associates LLC (006935977)

Revised: 11/2009Topco Associates LLC

More Topcare Tioconazole 1 resources

• Topcare Tioconazole 1 Side Effects (in more detail)
• Topcare Tioconazole 1 Use in Pregnancy & Breastfeeding
• Topcare Tioconazole 1 Support Group
• 7 Reviews for Topcare Tioconazole - Add your own review/rating

Compare Topcare Tioconazole 1 with other medications

• Vaginal Yeast Infection