Telavancin Hydrochloride

Class: Glycopeptides
ATC Class: J01XA03
VA Class: AM900
Chemical Name: Vancomycin, N3″-[2-(decylamino)ethyl}-29-{[(phosphono-methyl)-amino]-methyl}-hydrochloride
Molecular Formula: C₈₀H₁₀₆C₁₂N₁₁O₂₇P • xHCl (where x=1 to 3)
CAS Number: 380636-75-9
Brands: Vibativ

• Fetal Risk


• 
  

  Women of childbearing potential should have a serum pregnancy test to exclude pregnancy prior to administration of telavancin.¹

  
  


• 
  

  Avoid use of telavancin during pregnancy unless potential benefits to the woman outweigh potential risks to the fetus.¹

  
  


• 
  

  Concerns about potential adverse developmental outcomes in humans based on adverse developmental outcomes observed in 3 animal species given telavancin at clinically relevant doses during the period of organogenesis.¹ (See Pregnancy under Cautions.)

  
  

REMS:

FDA approved a REMS for telavancin to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of telavancin and consists of the following: medication guide and communication plan. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Antibacterial; lipoglycopeptide; synthetic derivative of vancomycin.^{1 2 3 4 5}

Uses for Telavancin Hydrochloride

Skin and Skin Structure Infections

Treatment of complicated skin and skin structure infections caused by susceptible Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA; also known as oxacillin-resistant S. aureus or ORSA]), Streptococcus pyogenes (group A β-hemolytic streptococci), S. agalactiae (group B streptococci), S. anginosus group (includes S. anginosus, S. intermedius, S. constellatus), or Enterococcus faecalis (vancomycin-susceptible strains only).¹

Indicated only for treatment of certain infections caused by certain gram-positive bacteria; if documented or presumed pathogens include gram-negative or anaerobic bacteria, concomitant use of another anti-infective may be clinically indicated.¹

Telavancin Hydrochloride Dosage and Administration

Administration

Administer by IV infusion.¹

IV Infusion

Must be reconstituted and then further diluted prior to administration.¹

Should not be admixed or added to solutions containing other drugs.¹

If the same IV line is used for sequential infusion of other drugs, flush the IV line with 0.9% sodium chloride injection, 5% dextrose injection, or lactated Ringer's injection before and after the telavancin infusion.¹

Reconstitution

Reconstitute vials containing 250 or 750 mg of telavancin with 15 or 45 mL, respectively, of 5% dextrose injection, sterile water for injection, or 0.9% sodium chloride injection to provide a solution containing 15 mg/mL.¹

Discard vial if the vacuum is insufficient to pull diluent into vial.¹

Mix thoroughly and ensure that drug has dissolved completely.¹ Usually reconstitutes in <2 minutes, but reconstitution may take up to 20 minutes.¹

Dilution

For doses of 150–800 mg, withdraw correct dose from the reconstituted vial and add to 100–250 mL of appropriate IV infusion fluid (i.e., 0.9% sodium chloride injection, 5% dextrose injection, lactated Ringer's injection).¹

For doses <150 mg or >800 mg, withdraw correct dose from the reconstituted vial and add to a volume of appropriate IV infusion fluid (i.e., 0.9% sodium chloride injection, 5% dextrose injection, lactated Ringer's injection) that results in a final concentration of 0.6–8 mg/mL.¹

Rate of Administration

Administer by IV infusion over 1 hour.¹ Avoid rapid IV infusion.¹ (See Infusion Reactions under Cautions.)

Dosage

Available as telavancin hydrochloride; dosage is expressed in terms of telavancin.¹

Adults

Skin and Skin Structure Infections

IV

10 mg/kg once every 24 hours for 7–14 days.¹

Duration of therapy based on severity and location of infection and patient's clinical and bacteriologic response.¹

Special Populations

Hepatic Impairment

Dosage adjustment not needed in adults with mild to moderate hepatic impairment.^{1 8}

Renal Impairment

Reduce dosage in adults with Cl_cr 10–50 mL/minute.¹ Data insufficient to make dosage recommendations for adults with end-stage renal disease (Cl_cr <10 mL/minute), including those undergoing hemodialysis.¹

Table 1. Telavancin Dosage for Adults with Renal Impairment1

Clcr Calculated Using Cockcroft-Gault Formula (mL/minute)	Telavancin Dosage
>50	10 mg/kg once every 24 hours
30–50	7.5 mg/kg once every 24 hours
10 to <30	10 mg/kg once every 48 hours

Geriatric Patients

Select dosage with caution because of age-related decreases in renal function.¹ (See Geriatric Use under Cautions.)

Cautions for Telavancin Hydrochloride

Contraindications

• 
  

  Manufacturer states none known.¹

  
  

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity

Adverse developmental outcomes reported in 3 animal species given telavancin at clinically relevant doses during the period of organogenesis.¹

Exclude pregnancy (negative serum pregnancy test) prior to initiation of telavancin in females of childbearing potential (i.e., those who have not had complete absence of menses for ≥24 months, medically confirmed menopause or primary ovarian failure, hysterectomy, bilateral oophorectomy, or tubal ligation).¹

Use effective contraception to prevent pregnancy during treatment.¹

Avoid use of telavancin during pregnancy unless potential benefits to the woman outweigh potential risks to the fetus.¹ (See Pregnancy under Cautions.)

FDA required and approved a Risk Evaluation and Mitigation Strategy (REMS) for telavancin;¹⁷ goal of the telavancin REMS is to avoid unintended telavancin exposure in pregnant women by educating health-care providers and patients about potential risk of fetal developmental toxicity and recommended measures to exclude and prevent pregnancy.¹⁷ The REMS requires that a telavancin medication guide be provided to patient each time the drug is dispensed and outlines a communication plan requiring initial and periodic communications from manufacturer to certain targeted groups of prescribers and pharmacists.¹⁷

Nephrotoxicity

Renal impairment reported in patients receiving telavancin.¹ In patients with normal baseline S_cr concentrations, increased S_cr (1.5 times baseline) reported more frequently in telavancin-treated patients than in vancomycin-treated patients.¹

Adverse renal effects more likely in patients with conditions known to increase the risk of renal impairment (e.g., preexisting renal disease, diabetes mellitus, CHF, hypertension) and in those receiving concomitant therapy with an agent that affects renal function (e.g., NSAIAs, certain diuretics, ACE inhibitors).¹

Monitor renal function (i.e., S_cr, Cl_cr).¹ Perform renal function tests prior to initiation of telavancin, every 48–72 hours during therapy (more frequently if indicated), and at end of therapy.¹

If renal function decreases, weigh benefits of continuing telavancin versus discontinuing the drug and initiating an alternative anti-infective.¹

Infusion Reactions

Rapid IV administration of glycopeptide anti-infectives (including telavancin) can result in a reaction referred to as the “red-man syndrome.”¹ Flushing of the upper body, urticaria, pruritus, or rash may occur.¹

To reduce risk of infusion-related reactions, give IV infusion over 1 hour.¹ If an infusion reaction occurs, the reaction may cease if the infusion is discontinued or slowed.¹

Superinfection/Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Possible emergence and overgrowth of nonsusceptible organisms, including fungi.¹ Monitor carefully; institute appropriate therapy if superinfection occurs.¹

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.^{1 12 13 14 15 16} C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported with nearly all anti-infectives and may range in severity from mild diarrhea to fatal colitis.¹ Hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.¹

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.^{1 12 13 14 15 16} Obtain a careful medical history since CDAD may occur as late as ≥2 months after anti-infective therapy is discontinued.¹

If CDAD is suspected or confirmed, anti-infectives not directed against C. difficile may need to be discontinued.¹ Manage moderate to severe cases with fluid, electrolyte, and protein supplementation, anti-infective therapy active against C. difficile (e.g., oral metronidazole or vancomycin), and surgical evaluation when clinically indicated.^{1 12 13 14 15 16}

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of telavancin and other antibacterials, use only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria.¹

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.¹ In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.¹

If documented or presumed pathogens include gram-negative or anaerobic bacteria, concomitant use of an anti-infective active against such bacteria may be clinically indicated.¹ (See Uses.)

Cardiovascular Effects

Prolongation of the QT_c interval reported.¹ Caution advised if used with drugs known to prolong QT interval.¹

Avoid use in individuals with congenital long QT syndrome, known prolongation of the QT_c interval, uncompensated heart failure, or severe left ventricular hypertrophy; such individuals not included in telavancin clinical trials.¹

Hematologic Effects

Does not interfere with coagulation and has no effect on platelet aggregation.¹ Increased risk of bleeding not observed in clinical trials.¹ Evidence of hypercoagulability not observed; healthy adults receiving telavancin have normal levels of D-dimer and fibrin degradation products.¹

Interferes with certain tests used to monitor coagulation (i.e., PT, INR, aPTT, activated clotting time, tests based on factor Xa).¹ (See Specific Drugs and Laboratory Tests under Interactions.)

Specific Populations

Pregnancy

Category C.¹ Pregnancy registry at 888-658-4228.¹

In reproduction studies in rats, rabbits, and minipigs, there was evidence that telavancin has the potential to cause limb and skeletal malformations and reduced fetal weight.¹

Has not been evaluated in pregnant women, but animal data raise concerns about potential adverse developmental outcomes in humans.¹ Avoid use during pregnancy unless potential benefits to the patient outweigh potential risks to the fetus.¹ (See Fetal/Neonatal Morbidity under Cautions.)

Lactation

Not known whether telavancin is distributed into milk in humans.¹ Use with caution.¹

Pediatric Use

Safety and efficacy not established in children or adolescents <18 years of age.¹

Geriatric Use

In clinical studies evaluating telavancin for treatment of complicated skin and skin structure infections, the drug appeared to be less effective in adults ≥65 years of age relative to adults <65 years of age.¹

No overall differences in frequency of treatment-emergent adverse events compared with younger adults; however, incidence of adverse events indicating renal impairment was higher in geriatric adults than in younger adults.¹

Substantially eliminated by kidneys; select dosage with caution since geriatric patients are more likely to have decreased renal function.¹

Hepatic Impairment

Pharmacokinetics not altered in adults with moderate hepatic impairment (Child-Pugh class B);^{1 8} pharmacokinetics not evaluated in those with severe hepatic impairment (Child-Pugh class C).¹ Dosage adjustment not needed in adults with mild to moderate hepatic impairment.^{1 8}

Renal Impairment

In clinical studies evaluating telavancin for treatment of complicated skin and skin structure infections, the drug appeared to be less effective in adults with Cl_cr ≤50 mL/minute relative to those with Cl_cr >50 mL/minute.¹ Consider possible reduced effectiveness when selecting an anti-infective for adults with baseline moderate or severe renal impairment (Cl_cr ≤50 mL/minute).¹

Risk of adverse renal effects may be greater in patients with preexisting renal impairment or risk factors for renal dysfunction.¹ (See Nephrotoxicity under Cautions.)

Reduce dosage in adults with Cl_cr 10–50 mL/minute.¹ (See Renal Impairment under Dosage and Administration.)

Hydroxypropyl-β-cyclodextrin (an inactive ingredient in the formulation) may accumulate in individuals with renal impairment.¹ If renal toxicity is suspected, consider an alternative anti-infective.¹

Common Adverse Effects

GI effects (taste disturbance,^{1 2 3} nausea,^{1 2 3} vomiting,^{1 2 3} constipation² ), headache,^{2 3} insomnia,^{2 3} foamy urine.^{1 2}

Interactions for Telavancin Hydrochloride

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Inhibits CYP 3A4/5.¹

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Aminoglycosides (amikacin, gentamicin)	Gentamicin: In vitro evidence of synergistic antibacterial effects against MRSA6 Amikacin or gentamicin: No in vitro evidence of antagonistic antibacterial effects against telavancin-susceptible staphylococci, streptococci, or enterococci1
Aztreonam	No effect on pharmacokinetics of either drug1 9 No in vitro evidence of antagonistic antibacterial effects against telavancin-susceptible staphylococci, streptococci, or enterococci1	Dosage adjustments not needed1
Carbapenems (imipenem, meropenem)	Meropenem: In vitro evidence of synergistic antibacterial effects against MRSA6 Imipenem or meropenem: No in vitro evidence of antagonistic antibacterial effects against telavancin-susceptible staphylococci, streptococci, or enterococci1
Cephalosporins	Cefepime or ceftriaxone: In vitro evidence of synergistic antibacterial effects against MRSA6 Cefepime or ceftriaxone: No in vitro evidence of antagonistic antibacterial effects against telavancin-susceptible staphylococci, streptococci, or enterococci1
Co-trimoxazole	No in vitro evidence of antagonistic antibacterial effects against telavancin-susceptible staphylococci, streptococci, or enterococci1
Fluoroquinolones	Ciprofloxacin: In vitro evidence of synergistic antibacterial effects against MRSA6 Ciprofloxacin: No in vitro evidence of antagonistic antibacterial effects against telavancin-susceptible staphylococci, streptococci, or enterococci1
Midazolam	No effect on pharmacokinetics of either drug1 7
Penicillins	Piperacillin and tazobactam: No effect on pharmacokinetics of either drug1 9 Oxacillin or piperacillin and tazobactam: No in vitro evidence of antagonistic antibacterial effects against telavancin-susceptible staphylococci, streptococci, or enterococci1	Piperacillin and tazobactam: Dosage adjustments not needed1
Rifampin	In vitro evidence of synergistic antibacterial effects against MRSA6 No in vitro evidence of antagonistic antibacterial effects against telavancin-susceptible staphylococci, streptococci, or enterococci1
Tests, coagulation	Telavancin interferes with PT, INR, aPTT, activated clotting time, and tests based on factor Xa if blood samples are drawn 0–18 hours after a dose of the anti-infective1 Does not affect thrombin time, whole blood (Lee-White) clotting time, ex vivo platelet aggregation, chromogenic factor Xa assay, functional (chromogenic) factor X assay, bleeding time, or tests for D-dimer or fibrin degradation products1	Draw blood samples for PT, INR, aPTT, activated clotting time, and tests based on factor Xa just before a telavancin dose1
Tests, urine protein	Telavancin interferes with urine qualitative dipstick protein assays and quantitative dye methods used to measure urine protein (e.g., pyrogallol red-molybdate);1 does not affect microalbumin assays1	Use microalbumin assays to monitor urinary protein excretion in patients receiving telavancin1

Telavancin Hydrochloride Pharmacokinetics

Absorption

Plasma Concentrations

In healthy young adults, pharmacokinetics are linear following single IV doses of 5–12.5 mg/kg or multiple IV doses of 7.5–15 mg/kg given once daily for up to 7 days.¹

Steady-state concentrations achieved by day 3 of once-daily dosage.¹

Special Populations

AUC increased in patients with renal impairment.¹

Distribution

Extent

Concentration in skin blister fluid is 40% of plasma concentrations after administration of 7.5 mg/kg once daily for 3 days.¹

Not known whether telavancin is distributed into milk in humans.¹

Plasma Protein Binding

90%, primarily albumin.¹ Protein binding not affected by renal or hepatic impairment.¹

Elimination

Metabolism

Metabolic pathway not elucidated to date.¹ Three hydroxylated metabolites identified; the major metabolite is THRX-651540.¹

Not metabolized by CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 3A4, 3A5, or 4A11.¹

Elimination Route

Approximately 76% of a dose recovered in urine; <1% of dose recovered in feces.¹

In adults with end-stage renal disease, approximately 5.9% of a dose is removed by 4 hours of hemodialysis.¹ In vitro date indicate telavancin may be removed by continuous venovenous hemofiltration (CVVH).¹

Half-life

Approximately 8 hours in adults.¹

Special Populations

Pharmacokinetics not altered in geriatric individuals based solely on age.¹

Pharmacokinetics altered by decreased renal function.¹

No clinically important change in pharmacokinetics in adults with moderate hepatic impairment (Child-Pugh class B).^{1 8} Not evaluated in adults with severe hepatic impairment (Child-Pugh class C).¹

Stability

Storage

Parenteral

Powder for Injection

2–8°C; may be exposed to temperatures up to 25°C.¹ Avoid excessive heat.¹

Following reconstitution and further dilution, administer within 4 hours when stored at room temperature or within 72 hours when stored at 2–8°C.¹

Actions

• 
  

  Lipoglycopeptide antibacterial.^{1 2 3 4 5} Synthetic derivative of vancomycin.^{1 2 3 4 5}

  
  


• 
  

  Usually bactericidal in action.¹ Inhibits bacterial cell wall synthesis by inhibiting peptidoglycan synthesis and blocking the transglycosylation step.^{1 4} Binds to the bacterial membrane and disrupts membrane barrier function.^{1 4}

  
  


• 
  

  Active against some gram-positive bacteria, including Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA; also known as oxacillin-resistant S. aureus or ORSA]),^{1 2 3 5 11} Streptococcus pyogenes (group A β-hemolytic streptococci),¹ S. agalactiae (group B streptococci),¹ S. anginosus group (includes S. anginosus, S. intermedius, S. constellatus),¹ and Enterococcus faecalis (vancomycin-susceptible strains only).^{1 5}

  
  


• 
  

  Some vancomycin-resistant enterococci have reduced susceptibility to telavancin.^{1 5} Cross-resistance between telavancin and other anti-infectives not reported to date.¹

  
  

Advice to Patients

• 
  

  Telavancin medication guide must be provided to patient each time the drug is dispensed;¹⁷ importance of patient reading the medication guide prior to initiating telavancin therapy and each time the prescription is refilled.¹

  
  


• 
  

  Advise patients that antibacterials (including telavancin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).¹

  
  


• 
  

  Importance of completing full course of therapy, even if feeling better after a few days.¹

  
  


• 
  

  Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with telavancin or other antibacterials in the future.¹

  
  


• 
  

  Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.¹ Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.¹

  
  


• 
  

  Advise patients about the common adverse effects reported with telavancin (e.g., taste disturbance, nausea, vomiting, headache, foamy urine) and importance of informing a clinician if any unusual symptom develops or if any known symptom persists or worsens.¹

  
  


• 
  

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

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹ Advise women of childbearing potential about potential risk of fetal harm if telavancin is used during pregnancy.¹ (See Pregnancy under Cautions.)

  
  


• 
  

  Importance of excluding pregnancy with a serum pregnancy test before starting telavancin.¹ Advise women of childbearing potential to use effective contraception to prevent pregnancy during telavancin therapy and to notify a clinician if pregnancy occurs during telavancin therapy.¹ (See Pregnancy 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.

Telavancin Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for IV infusion	250 mg (of telavancin)	Vibativ	Theravance
		750 mg (of telavancin)	Vibativ	Theravance

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 October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Theravance. Vibativ (telavancin) for injection prescribing information. South San Francisco, CA; 2009 Sep.

2. Stryjewski ME, Graham DR, Wilson SE et al. Telavancin versus vancomycin for the treatment of complicated skin and skin-structure infections caused by gram-positive organisms. Clin Infect Dis. 2008; 46:1683-93. [PubMed 18444791]

3. Stryjewski ME, Chu VH, O'Riordan WD et al. Telavancin versus standard therapy for treatment of complicated skin and skin structure infections caused by gram-positive bacteria: FAST 2 study. Antimicrob Agents Chemother. 2006; 50:862-7. [PubMed 16495243]

4. Shaw JP, Seroogy J, Kaniga K et al. Pharmacokinetics, serum inhibitory and bactericidal activity, and safety of telavancin in healthy subjects. Antimicrob Agents Chemother. 2005; 49:195-201. [PubMed 15616296]

5. Dunbar LM, Tang DM, Manausa RM. A review of telavancin in the treatment of complicated skin and skin structure infections (cSSSI). Ther Clin Risk Manag. 2008; 4:235-44. [PubMed 18728713]

6. Lin G, Pankuch GA, Ednie LM et al. Antistaphylococcal activity of telavancin tested alone and in combination by time-kill assay. Antimicrob Agents Chemother. 2010; :.

7. Wong SL, Goldberg MR, Ballow CH et al. Effect of Telavancin on the pharmacokinetics of the cytochrome P450 3A probe substrate midazolam: a randomized, double-blind, crossover study in healthy subjects. Pharmacotherapy. 2010; 30:136-43. [PubMed 20099988]

8. Goldberg MR, Wong SL, Shaw JP et al. Lack of effect of moderate hepatic impairment on the pharmacokinetics of telavancin. Pharmacotherapy. 2010; 30:35-42. [PubMed 20030471]

9. Wong SL, Sörgel F, Kinzig M et al. Lack of pharmacokinetic drug interactions following concomitant administration of telavancin with aztreonam or piperacillin/tazobactam in healthy participants. J Clin Pharmacol. 2009; 49:816-23. [PubMed 19443680]

11. Kosowska-Shick K, Clark C, Pankuch GA et al. Activity of telavancin against staphylococci and enterococci determined by MIC and resistance selection studies. Antimicrob Agents Chemother. 2009; 53:4217-24. [PubMed 19620338]

12. Johnson S, Gerding DN. Clostridium difficile-associated diarrhea. Clin Infect Dis. 1998; 26:1027-36. [IDIS 407733] [PubMed 9597221]

13. Gerding DN, Johnson S, Peterson LR et al for the Society for Healthcare Epidemiology of America. Position paper on Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol. 1995; 16:459-77. [PubMed 7594392]

14. Fekety R for the American College of Gastroenterology Practice Parameters Committee. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. Am J Gastroenterol. 1997; 92:739-50. [IDIS 386628] [PubMed 9149180]

15. American Society of Health-System Pharmacists Commission on Therapeutics. ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile-associated disease. Am J Health-Syst Pharm. 1998; 55:1407-11. [IDIS 407213] [PubMed 9659970]

16. Wilcox MH. Treatment of Clostridium difficile infection. J Antimicrob Chemother. 1998; 41(Suppl C):41-6. [IDIS 407246] [PubMed 9630373]

17. NDA 22-110 Vibativ (telavancin) risk evaluation and mitigation strategy (REMS). From FDA website.

More Telavancin Hydrochloride resources

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

Compare Telavancin Hydrochloride with other medications

• Skin and Structure Infection

Uroeze

Dosage Form: FOR ANIMAL USE ONLY
Uroeze® 400

Each 0.65 g (1/4 level teaspoonful) contains: Ammonium Chloride 400 mg in a palatable protein base.

INDICATION

For use as a urinary acidifier in cats and dogs.

CAUTION: Federal law (USA) restricts this drug to use by on the order of a licensed veterinarian.

Warning

Do not administer to animals with severe liver or kidney damage or to animals exhibiting acidosis.

CAUTION: May cause gastric mucosal irritation.

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

STORE AT CONTROLLED ROOM TEMPERATURE OF 15°- 30°C (59°- 86°F).

DOSAGE

The suggested dosage of Uroeze for adult cats and dogs is 0.32 - 0.65 g (1/8 - 1/4 level teaspoonful) per 10 lbs. (4.5 kg) body weight twice daily with food. Daily dose may vary with different diets depending on alkalinity of diet. Dosage should be adjusted to maintain urine pH consistently below 6.6. Not intended for use in kittens.

ID# 854004

301599-02

Mfg. by:

Virbac AH, Inc. • P.O. Box 162059

Fort Worth, TX 76161 • (800) 338-3659

PRINCIPAL DISPLAY PANEL - 4 oz Bottle Label

NDC 051311-850-04

Uroeze® 400

Each 0.65 g (1/4 level teaspoonful) contains:

Ammonium Chloride 400 mg

in a palatable protein base.

INDICATION: For use as a urinary

acidifier in cats and dogs.

4 oz

CAUTION: Federal law (USA) restricts this drug to use

by or on the order of a licensed veterinarian.

Virbac

ANIMAL HEALTH

Mfg. by:

Virbac AH, Inc. • P.O. Box 162059

Fort Worth, TX 76161 • (800) 338-3659

Uroeze  ammonium chloride  powder

Product Information Product Type PRESCRIPTION ANIMAL DRUG NDC Product Code (Source) 51311-850 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ammonium chloride (ammonia) ammonium chloride 400 mg  in 0.65 g

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color BROWN Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 51311-850-04 113.3981 g In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
UNAPPROVED DRUG OTHER		01/26/2010

Labeler - Virbac AH, Inc. (131568396)

Establishment
Name	Address	ID/FEI	Operations
Virbac Bridgeton		808558100	MANUFACTURE

Revised: 01/2010Virbac AH, Inc.

Triesence

triamcinolone acetonide

Dosage Form: injection
FULL PRESCRIBING INFORMATION

Indications and Usage for Triesence

Ophthalmic Diseases

Triesence® (triamcinolone acetonide injectable suspension) 40 mg/mL is indicated for:

• sympathetic ophthalmia,

• temporal arteritis,

• uveitis, and

• ocular inflammatory conditions unresponsive to topical corticosteroids.

Visualization during Vitrectomy

Triesence® suspension is indicated for visualization during vitrectomy.

Triesence Dosage and Administration

Dosage for Treatment of Ophthalmic Diseases

The initial recommended dose of Triesence® suspension is 4 mg (100 microliters of 40 mg/mL suspension) with subsequent dosage as needed over the course of treatment.

Dosage for Visualization during Vitrectomy

The recommended dose of Triesence® suspension is 1 to 4 mg (25 to 100 microliters of 40 mg/mL suspension) administered intravitreally.

Preparation for Administration

STRICT ASEPTIC TECHNIQUE IS MANDATORY. The vial should be vigorously shaken for 10 seconds before use to ensure a uniform suspension. Prior to withdrawal, the suspension should be inspected for clumping or granular appearance (agglomeration). An agglomerated product results from exposure to freezing temperatures and should not be used. After withdrawal, Triesence® suspension should be injected without delay to prevent settling in the syringe. Careful technique should be employed to avoid the possibility of entering a blood vessel or introducing organisms that can cause infection.

Administration

The injection procedure should be carried out under controlled aseptic conditions, which include the use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide should be given prior to the injection. Following the injection, patients should be monitored for elevation in intraocular pressure and for endophthalmitis. Monitoring may consist of a check for perfusion of the optic nerve head immediately after the injection, tonometry within 30 minutes following the injection, and biomicroscopy between two and seven days following the injection. Patients should be instructed to report any symptoms suggestive of endophthalmitis without delay.

Each vial should only be used for the treatment of a single eye. If the contralateral eye requires treatment, a new vial should be used and the sterile field, syringe, gloves, drapes, eyelid speculum, and injection needles should be changed before Triesence® suspension is administered to the other eye.

Dosage Forms and Strengths

Single use 1 mL vial containing 40 mg/mL of sterile triamcinolone acetonide suspension.

Contraindications

Corticosteroids are contraindicated in patients with systemic fungal infections.

Triamcinolone is contraindicated in patients who are hypersensitive to corticosteroids or any components of this product. Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroid therapy. [See Adverse Reactions (6)].

Warnings and Precautions

Ophthalmic Effects

Triesence® suspension should not be administered intravenously. Strict aseptic technique is mandatory.

Risk of infection

Corticosteroids may mask some signs of infection, and new infections may appear during their use. There may be decreased resistance and inability to localize infection when corticosteroids are used. Corticosteroids may enhance the establishment of secondary ocular infections due to fungi or viruses. If an infection occurs during corticosteroid therapy, it should be promptly controlled by suitable antimicrobial therapy.

See also Increased Risks Related to Infection (5.3).

Elevated Intraocular Pressure

Increases in intraocular pressure associated with triamcinolone acetonide injection have been observed in 20-60% of patients. This may lead to glaucoma with possible damage to the optic nerve. Effects on intraocular pressure may last up to 6 months following injection and are usually managed by topical glaucoma therapy. A small percentage of patients may require aggressive non-topical treatment. Intraocular pressure as well as perfusion of the optic nerve head should be monitored and managed appropriately.

Endophthalmitis

The rate of infectious culture positive endophthalmitis is 0.5%. Proper aseptic techniques should always be used when administering triamcinolone acetonide. In addition, patients should be monitored following the injection to permit early treatment should an infection occur.

Cataracts

Use of corticosteroids may produce cataracts, particularly posterior subcapsular cataracts.

Patients with Ocular Herpes Simplex

Corticosteroids should be used cautiously in patients with ocular herpes simplex because of possible corneal perforation. Corticosteroids should not be used in active ocular herpes simplex.

Alterations in Endocrine Function

Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome, and hyperglycemia. Monitor patients for these conditions with chronic use.

Corticosteroids can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Drug induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted.

Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient may necessitate adjustment in dosage.

Increased Risks Related to Infections

Corticosteroids may increase the risks related to infections with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic infections. The degree to which the dose, route and duration of corticosteroid administration correlates with the specific risks of infection is not well characterized; however, with increasing doses of corticosteroids, the rate of occurrence of infectious complications increases.

Corticosteroids may mask some signs of infection and may reduce resistance to new infections.

Corticosteroids may exacerbate infections and increase risk of disseminated infection. The use of corticosteroids in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with an appropriate antituberculous regimen.

Chickenpox and measles can have a more serious or even fatal course in non-immune children or adults on corticosteroids. In children or adults who have not had these diseases, particular care should be taken to avoid exposure. If a patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If patient is exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.

Corticosteroids should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.

Corticosteroids may increase risk of reactivation or exacerbation of latent infection. If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis.

Corticosteroids may activate latent amebiasis. Therefore, it is recommended that latent or active amebiasis be ruled out before initiating corticosteroid therapy in any patient who has spent time in the tropics or in any patient with unexplained diarrhea.

Corticosteroids should not be used in cerebral malaria.

Alterations in Cardiovascular/Renal Function

Corticosteroids can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium and calcium. These effects are less likely to occur with the synthetic derivatives except when used in large doses. Dietary salt restriction and potassium supplementation may be necessary. These agents should be used with caution in patients with hypertension, congestive heart failure, or renal insufficiency.

Literature reports suggest an association between use of corticosteroids and left ventricular free wall rupture after a recent myocardial infarction; therefore, therapy with corticosteroids should be used with caution in these patients.

Use in Patients with Gastrointestinal Disorders

There is an increased risk of gastrointestinal perforation in patients with certain GI disorders. Signs of GI perforation, such as peritoneal irritation, may be masked in patients receiving corticosteroids.

Corticosteroids should be used with caution if there is a probability of impending perforation, abscess or other pyogenic infections; diverticulitis; fresh intestinal anastomoses; and active or latent peptic ulcer.

Behavioral and Mood Disturbances

Corticosteroid use may be associated with central nervous system effects ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids.

Decrease in Bone Density

Corticosteroids decrease bone formation and increase bone resorption both through their effect on calcium regulation (i.e., decreasing absorption and increasing excretion) and inhibition of osteoblast function. This, together with a decrease in the protein matrix of the bone secondary to an increase in protein catabolism, and reduced sex hormone production, may lead to inhibition of bone growth in children and adolescents and the development of osteoporosis at any age. Special consideration should be given to patients at increased risk of osteoporosis (i.e., postmenopausal women) before initiating corticosteroid therapy and bone density should be monitored in patients on long term corticosteroid therapy.

Vaccination

Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered; however, the response to such vaccines cannot be predicted. Immunization procedures may be undertaken in patients who are receiving corticosteroids as replacement therapy, e.g., for Addison's disease.

While on corticosteroid therapy, patients should not be vaccinated against smallpox. Other immunization procedures should not be undertaken in patients who are on corticosteroids, especially on high dose, because of possible hazards of neurological complications and a lack of antibody response.

Effect on Growth and Development

Long-term use of corticosteroids can have negative effects on growth and development in children. Growth and development of pediatric patients on prolonged corticosteroid therapy should be carefully monitored.

Use in Pregnancy

Triamcinolone acetonide can cause fetal harm when administered to a pregnant woman. Human and animal studies suggest that use of corticosteroids during the first trimester of pregnancy is associated with an increased risk of orofacial clefts, intrauterine growth restriction and decreased birth weight. If this drug is used during pregnancy, or if the patient becomes pregnant while using this drug, the patient should be apprised of the potential hazard to the fetus. [See Use inSpecific Populations (8.1)].

Weight Gain

Systemically administered corticosteroids may increase appetite and cause weight gain.

Neuromuscular Effects

Although controlled clinical trials have shown corticosteroids to be effective in speeding the resolution of acute exacerbations of multiple sclerosis, they do not show that they affect the ultimate outcome or natural history of the disease. The studies do show that relatively high doses of corticosteroids are necessary to demonstrate a significant effect.

An acute myopathy has been observed with the use of high doses of corticosteroids, most often occurring in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium). This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.

Kaposi's Sarcoma

Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement.

Adverse Reactions

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse event data were collected from 300 published articles containing data from controlled and uncontrolled clinical trials which evaluated over 14,000 eyes treated with different concentrations of triamcinolone acetonide. The most common dose administered within these trials was triamcinolone acetonide 4 mg administered as primary or adjunctive therapy primarily as a single injection.

The most common reported adverse events following administration of triamcinolone acetonide were elevated intraocular pressure and cataract progression. These events have been reported to occur in 20-60% of patients.

Less common reactions occurring in up to 2% include endophthalmitis (infectious and non-infectious), hypopyon, injection site reactions (described as blurring and transient discomfort), glaucoma, vitreous floaters, and detachment of retinal pigment epithelium, optic disc vascular disorder, eye inflammation, conjunctival hemorrhage and visual acuity reduced. Cases of exophthalmos have also been reported.

Common adverse reactions for systemically administered corticosteroids include fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain.

Other reactions reported to have occurred with the administration of corticosteroids include:

Allergic Reactions: Anaphylactoid reaction, anaphylaxis, angioedema

Cardiovascular: Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, fat embolism, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction, pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis

Dermatologic: Acne, allergic dermatitis, cutaneous and subcutaneous atrophy, dry scalp, edema, facial erythema, hyper or hypopigmentation, impaired wound healing, increased sweating, petechiae and ecchymoses, rash, sterile abscess, striae, suppressed reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria

Endocrine: Abnormal fat deposits, decreased carbohydrate tolerance, development of Cushingoid state, hirsutism, manifestations of latent diabetes mellitus and increased requirements for insulin or oral hypoglycemic agents in diabetics, menstrual irregularities, moon facies, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery or illness), suppression of growth in children

Fluid and Electrolyte Disturbances: Potassium loss, hypokalemic alkalosis, sodium retention

Gastrointestinal: Abdominal distention, elevation in serum liver enzymes levels (usually reversible upon discontinuation), hepatomegaly, hiccups, malaise, nausea, pancreatitis, peptic ulcer with possible perforation and hemorrhage, ulcerative esophagitis

Metabolic: Negative nitrogen balance due to protein catabolism

Musculoskeletal: Aseptic necrosis of femoral and humeral heads, charcot-like arthropathy, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, steroid myopathy, tendon rupture, vertebral compression fractures

Neurological: Arachnoiditis, convulsions, depression, emotional instability, euphoria, headache, increased intracranial pressure with papilledema (pseudo-tumor cerebri) usually following discontinuation of treatment, insomnia, meningitis, neuritis, neuropathy, paraparesis/paraplegia, paresthesia, sensory disturbances, vertigo

Reproductive: Alteration in motility and number of spermatozoa.

Drug Interactions

• Amphotericin B: There have been cases reported in which concomitant use of Amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure. See Potassium depleting agents.

• Anticholinesterase agents: Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy.

• Anticoagulant agents: Co-administration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Therefore, coagulation indices should be monitored frequently to maintain the desired anticoagulant effect.

• Antidiabetic agents: Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents may be required.

• Antitubercular drugs: Serum concentrations of isoniazid may be decreased.

• CYP 3A4 inducers (e.g., barbiturates, phenytoin, carbamazepine, and rifampin): Drugs such as barbiturates, phenytoin, ephedrine, and rifampin, which induce hepatic microsomal drug metabolizing enzyme activity may enhance metabolism of corticosteroid and require that the dosage of corticosteroid be increased.

• CYP 3A4 inhibitors (e.g., ketoconazole, macrolide antibiotics): Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60% leading to an increased risk of corticosteroid side effects.

• Cholestyramine: Cholestyramine may increase the clearance of corticosteroids.

• Cyclosporine: Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with concurrent use.

• Digitalis: Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia.

• Estrogens, including oral contraceptives: Estrogens may decrease the hepatic metabolism of certain corticosteroids thereby increasing their effect.

• NSAIDS including aspirin and salicylates: Concomitant use of aspirin or other non-steroidal antiinflammatory agents and corticosteroids increases the risk of gastrointestinal side effects. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance of salicylates may be increased with concurrent use of corticosteroids.

• Potassium depleting agents (e.g., diuretics, Amphotericin B): When corticosteroids are administered concomitantly with potassium-depleting agents, patients should be observed closely for development of hypokalemia.

• Skin tests: Corticosteroids may suppress reactions to skin tests.

• Toxoids and live or inactivated vaccines: Due to inhibition of antibody response, patients on prolonged corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines.

USE IN SPECIFIC POPULATIONS

Pregnancy

Teratogenic Effects: Pregnancy Category D

[See Warnings and Precautions (5.10)]

Multiple cohort and case controlled studies in humans suggest that maternal corticosteroid use during the first trimester increases the rate of cleft lip with or without cleft palate from about 1/1000 infants to 3- 5/1000 infants. Two prospective case control studies showed decreased birth weight in infants exposed to maternal corticosteroids in utero.

Triamcinolone acetonide was teratogenic in rats, rabbits, and monkeys. In rats and rabbits, triamcinolone acetonide was teratogenic at inhalation doses of 0.02 mg/kg and above and in monkeys, triamcinolone acetonide was teratogenic at an inhalation dose of 0.5 mg/kg (1/4 and 7 times the recommended human dose). Dose-related teratogenic effects in rats and rabbits included cleft palate and/or internal hydrocephaly and axial skeletal defects, whereas the effects observed in monkeys were cranial malformations. These effects are similar to those noted with other corticosteroids.

Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Infants born to mothers who received corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.

Nursing Mothers

Corticosteroids are secreted in human milk. Reports suggest that steroid concentrations in human milk are 5 to 25% of maternal serum levels, and that total infant daily doses are small, less than 0.2% of the maternal daily dose. The risk of infant exposure to steroids through breast milk should be weighed against the known benefits of breastfeeding for both the mother and baby.

Pediatric Use

The efficacy and safety of corticosteroids in the pediatric population are based on the well established course of effect of corticosteroids which is similar in pediatric and adult populations.

The adverse effects of corticosteroids in pediatric patients are similar to those in adults. [See Adverse Reactions (6)].

Like adults, pediatric patients should be carefully observed with frequent measurements of blood pressure, weight, height, intraocular pressure, and clinical evaluation for the presence of infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis. Children, who are treated with corticosteroids by any route, including systemically administered corticosteroids, may experience a decrease in their growth velocity. This negative impact of corticosteroids on growth has been observed at low systemic doses and in the absence of laboratory evidence of HPA axis suppression (i.e., cosyntropin stimulation and basal cortisol plasma levels). Growth velocity may therefore be a more sensitive indicator of systemic corticosteroid exposure in children than some commonly used tests of HPA axis function. The linear growth of children treated with corticosteroids by any route should be monitored, and the potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the availability of other treatment alternatives. In order to minimize the potential growth effects of corticosteroids, children should be titrated to the lowest effective dose.

Geriatric Use

No overall differences in safety or effectiveness were observed between elderly subjects and younger subjects, and other reported clinical experience with triamcinolone has not identified differences in responses between the elderly and younger patients. However, the incidence of corticosteroid-induced side effects may be increased in geriatric patients and are dose-related. Osteoporosis is the most frequently encountered complication, which occurs at a higher incidence rate in corticosteroid-treated geriatric patients as compared to younger populations and in age-matched controls. Losses of bone mineral density appear to be greatest early on in the course of treatment and may recover over time after steroid withdrawal or use of lower doses.

Triesence Description

Triesence® (triamcinolone acetonide injectable suspension) 40 mg/mL is a synthetic corticosteroid with anti-inflammatory action. Each mL of the sterile, aqueous suspension provides 40 mg of triamcinolone acetonide, with sodium chloride for isotonicity, 0.5% (w/v) carboxymethylcellulose sodium and 0.015% polysorbate 80. It also contains potassium chloride, calcium chloride (dihydrate), magnesium chloride (hexahydrate), sodium acetate (trihydrate), sodium citrate (dihydrate) and water for injection. Sodium hydroxide and hydrochloric acid may be present to adjust pH to a target value 6 - 7.5.

The chemical name for triamcinolone acetonide is 9-Fluro- 11β, 16α, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17- acetal with acetone. Its structural formula of C24H31FO6 is:

434.50 MW

Triamcinolone acetonide occurs as a white to cream-colored, crystalline powder having not more than a slight odor and is practically insoluble in water and very soluble in alcohol.

Triesence - Clinical Pharmacology

Mechanism of Action

Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs such as prednisolone and triamcinolone are primarily used for their anti-inflammatory effects in disorders of many organ systems.

Triamcinolone acetonide possesses glucocorticoid activity typical of this class of drug, but with little or no mineralocorticoid activity. For the purposes of comparison, the following is the equivalent milligram dosage of the various glucocorticoids:

Cortisone, 25	Prednisone, 5	Paramethasone, 2
Hydrocortisone, 20	Methylprednisolone, 4	Betamethasone, 0.75
Prednisolone, 5	Triamcinolone, 4	Dexamethasone, 0.75

Corticosteroids have been demonstrated to depress the production of eosinophils and lymphocytes, but erythropoiesis and production of polymorphonuclear leukocytes are stimulated. Inflammatory processes (edema, fibrin deposition, capillary dilatation, migration of leukocytes and phagocytosis) and the later stages of wound healing (capillary proliferation, deposition of collagen, cicatrization) are inhibited.

Pharmacokinetics

Aqueous humor pharmacokinetics of triamcinolone have been assessed in 5 patients following a single intravitreal administration (4 mg) of triamcinolone acetonide. Aqueous humor samples were obtained from 5 patients (5 eyes) via an anterior chamber paracentesis on Days 1, 3, 10, 17 and 31 post injection. Peak aqueous humor concentrations of triamcinolone ranged from 2151 to 7202 ng/mL, half-life 76 to 635 hours, and the area under the concentration-time curve (AUC0-t) from 231 to 1911 ng.h/mL following the single intravitreal administration. The mean elimination half-life was 18.7 ± 5.7 days in 4 nonvitrectomized eyes (4 patients). In a patient who had undergone vitrectomy (1 eye), the elimination half-life of triamcinolone from the vitreous was much faster (3.2 days) relative to patients that had not undergone vitrectomy.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of mutagenicity was detected from in-vitro tests conducted with triamcinolone acetonide including a reverse mutation test in Salmonella bacteria and a forward mutation test in Chinese hamster ovary cells. With regard to carcinogenicity, in a two-year study in rats, triamcinolone acetonide caused no treatment-related carcinogenicity at oral doses up to 0.001mg/kg and in a two-year study in mice, triamcinolone acetonide caused no treatment-related carcinogenicity at oral doses up to 0.003 mg/kg (less than 1/25th of the recommended human dose). In male and female rats, triamcinolone acetonide caused no change in pregnancy rate at oral doses up to 0.015 mg/kg, but caused increased fetal resorptions and stillbirths and decreases in pup weight and survival at doses of 0.005 mg/kg (less than 1/10th of the recommended human dose).

Animal Toxicology and/or Pharmacology

Studies were conducted with triamcinolone acetonide, including those employing the proposed dosage form, i.e., 4.0% triamcinolone acetonide injectable suspension formulation containing 0.5% carboxymethylcellulose and 0.015% polysorbate-80 in a balanced salt solution.

Triamcinolone acetonide was demonstrated to be non-inflammatory when injected intravitreally in NZW rabbits, non-cytotoxic to mouse L-929 cells in an in-vitro assay and non-sensitizing in a guinea-pig maximization assay. Furthermore, the results of single-dose intravitreal injection studies with triamcinolone acetonide in both rabbits and monkeys demonstrate that the drug is well tolerated for up to one month with only minor findings of slight decrease in body weight gain and slight corneal thinning.

How Supplied/Storage and Handling

Triesence® (triamcinolone acetonide injectable suspension) 40 mg/mL is supplied as 1 mL of a 40 mg/mL sterile triamcinolone acetonide suspension in a flint Type 1 single use glass vial with a gray rubber stopper and an open target aluminum seal. Each labeled vial is sealed in a polycarbonate blister with a backing material which provides tamper evidence and is stored in a carton.

• 1 mL single use vial (NDC 0065-0543-01)

Storage

Store at 4° - 25° C (39° - 77° F); Do Not Freeze. Protect from light by storing in carton.

Patient Counseling Information

Patients should discuss with their physician if they have had recent or ongoing infections or if they have recently received a vaccine.

There are a number of medicines that can interact with corticosteroids such as triamcinolone. Patients should inform their health-care provider of all the medicines they are taking, including over-thecounter and prescription medicines (such as phenytoin, diuretics, digitalis or digoxin, rifampin, amphotericin B, cyclosporine, insulin or diabetes medicines, ketoconazole, estrogens including birth control pills and hormone replacement therapy, blood thinners such as warfarin, aspirin or other NSAIDS, barbiturates), dietary supplements, and herbal products. If patients are taking any of these drugs, alternate therapy, dosage adjustment, and/or special test may be needed during the treatment.

Patients should be advised of common adverse reactions that could occur with corticosteroid use to include elevated intraocular pressure, cataracts, fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain.

     

U.S. Patent No. 6,395,294

    

© 2007, 2008 Alcon, Inc.

    

ALCON LABORATORIES, INC.

Fort Worth, Texas 76134 USA

9003982-0908

PRINCIPAL DISPLAY PANEL

NDC 0065 - 09543 - 01                Sterile

Triesence

(triamcinolone acetonide

Injectable suspension)

40 mg/mL

                                               1 mL

Preservative Free                Alcon®

         

Triesence  triamcinolone acetonide  injection

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0065-0543 Route of Administration OPHTHALMIC DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength TRIAMCINOLONE ACETONIDE (TRIAMCINOLONE ACETONIDE) TRIAMCINOLONE ACETONIDE 40 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength SODIUM CHLORIDE   CARBOXYMETHYLCELLULOSE SODIUM   POLYSORBATE 80   POTASSIUM CHLORIDE   CALCIUM CHLORIDE   MAGNESIUM CHLORIDE   SODIUM ACETATE   SODIUM CITRATE   WATER   SODIUM HYDROXIDE   HYDROCHLORIC ACID

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0065-0543-01 1 mL In 1 VIAL, GLASS None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA022048	10/01/2010

Labeler - Alcon Laboratories, Inc. (008018525)

Registrant - Alcon Laboratories, Inc. (008018525)

Establishment
Name	Address	ID/FEI	Operations
Alcon Laboratories, Inc.		008018525	MANUFACTURE

Revised: 06/2011Alcon Laboratories, Inc.

More Triesence resources

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

• Triesence Suspension MedFacts Consumer Leaflet (Wolters Kluwer)


• Triesence Consumer Overview

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Persantin 25mg tablets

1. Name Of The Medicinal Product

PERSANTIN Tablets 25 mg

2. Qualitative And Quantitative Composition

Dipyridamole 25 mg.

For excipients, see 6.1

3. Pharmaceutical Form

Coated tablets

Orange sugar-coated tablets.

4. Clinical Particulars

4.1 Therapeutic Indications

An adjunct to oral anti-coagulation for prophylaxis of thrombo-embolism associated with prosthetic heart valves.

4.2 Posology And Method Of Administration

Adults:300-600 mg daily in three or four doses.

Children:PERSANTIN is not recommended for children.

PERSANTIN should usually be taken before meals.

4.3 Contraindications

Hypersensitivity to any of the components of the product.

4.4 Special Warnings And Precautions For Use

Among other properties, dipyridamole acts as a vasodilator. It should be used with caution in patients with severe coronary artery disease, including unstable angina and/or recent myocardial infarction, left ventricular outflow obstruction or haemodynamic instability (e.g. decompensated heart failure).

Patients being treated with regular oral doses of PERSANTIN should not receive additional intravenous dipyridamole. Clinical experience suggests that patients being treated with oral dipyridamole who also require pharmacological stress testing with intravenous dipyridamole, should discontinue drugs containing oral dipyridamole for twenty-four hours prior to stress testing.

In patients with myasthenia gravis, readjustment of therapy may be necessary after changes in dipyridamole dosage (see Drug Interactions).

PERSANTIN should be used with caution in patients with coagulation disorders.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Dipyridamole increases plasma levels and cardiovascular effects of adenosine. Adjustment of adenosine dosage should be considered if use with dipyridamole is unavoidable.

There is evidence that the effects of aspirin and dipyridamole on platelet behaviour are additive.

The administration of antacids may reduce the efficacy of PERSANTIN.

It is possible that PERSANTIN may enhance the effects of oral anti-coagulants. When dipyridamole is used in combination with anticoagulants and acetylsalicylic acid, the statements on intolerance and risks for these preparations must be observed. Addition of dipyridamole to acetylsalicylic acid does not increase the incidence of bleeding events. When dipyridamole was administered concomitantly with warfarin, bleeding was no greater in frequency or severity than that observed when warfarin was administered alone.

Dipyridamole may increase the hypotensive effect of drugs which reduce blood pressure and may counteract the anticholinesterase effect of cholinesterase inhibitors thereby potentially aggravating myasthenia gravis.

4.6 Pregnancy And Lactation

There is inadequate evidence of safety in human pregnancy, but PERSANTIN has been used for many years without apparent ill-consequence. Animal studies have shown no hazard. Medicines should not be used in pregnancy, especially the first trimester unless the expected benefit is thought to outweigh the possible risk to the foetus.

Dipyridamole is excreted in breast milk at levels approximately 6% of the plasma concentration. Therefore PERSANTIN should only be used during lactation if considered essential by the physician.

4.7 Effects On Ability To Drive And Use Machines

None stated.

4.8 Undesirable Effects

If these occur, it is usually during the early part of treatment. The vasodilating properties of PERSANTIN may occasionally produce a vascular headache which normally disappears with long-term use. Vomiting, diarrhoea and symptoms such as dizziness, faintness, nausea, dyspepsia and myalgia have been observed.

As a result of its vasodilator properties, PERSANTIN may cause hypotension, hot flushes and tachycardia. Worsening of symptoms of coronary heart disease such as angina and arrhythmias.

Hypersensitivity reactions such as rash, urticaria, severe bronchospasm and angio-oedema have been reported.

In very rare cases, increased bleeding during or after surgery has been observed. Isolated cases of thrombocytopenia have been reported in conjunction with treatment with PERSANTIN.

Dipyridamole has been shown to be incorporated into gallstones.

4.9 Overdose

Symptoms

Due to the low number of observations, experience with dipyridamole overdose is limited. Symptoms such as a warm feeling, flushes, sweating, restlessness, feeling of weakness, dizziness and anginal complaints can be expected. A drop in blood pressure and tachycardia might be observed.

Therapy

Symptomatic therapy is recommended. Administration of xanthine derivatives (e.g. aminophylline) may reverse the haemodynamic effects of dipyridamole overdose. Due to its wide distribution to tissues and its predominantly hepatic elimination, dipyridamole is not likely to be accessible to enhanced removal procedures.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Dipyridamole has an antithrombotic action based on its ability to modify various aspects of platelet function, such as platelet aggregation, adhesion and survival, which have been shown to be factors associated with the initiation of thrombus formation. Dipyridamole also has coronary vasodilator properties.

5.2 Pharmacokinetic Properties

Oral administration of dipyridamole gives a peak plasma level 1-2 hours after dosing. The drug has an apparent bioavailability of 37-66%.

In man the volume of distribution is 2.43±1.1 l/kg. When given orally the elimination half life is 30-50 minutes. In man the major route of excretion of dipyridamole is in the bile.

5.3 Preclinical Safety Data

None

6. Pharmaceutical Particulars

6.1 List Of Excipients

Core:

Lactose monohydrate

Maize starch, dried

Soluble maize starch

Colloidal silica, anhydrous

Magnesium stearate

Sunset yellow, E110

Coating:

Sucrose

Talc

Acacia

Titanium dioxide, E171

Macrogol 6000

Wax, bleached

Carnauba wax

Sunset yellow, E110

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

5 years.

6.4 Special Precautions For Storage

Do not store above 30°C. Protect from light.

6.5 Nature And Contents Of Container

Marketed packs: Blister pack containing 84 orange sugar coated tablets

Non-marketed packs: Blister packs of 100, 112 and 840 orange sugar coated tablets.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Boehringer Ingelheim Limited

Ellesfield Avenue

Bracknell

Berkshire

RG12 8YS

United Kingdom

8. Marketing Authorisation Number(S)

PL 00015/0052R

9. Date Of First Authorisation/Renewal Of The Authorisation

28 July 1988 /01 May 2007

10. Date Of Revision Of The Text

01/05/2007

11. Legal category

POM

P2c/25mg/UK/SPC/7