Telavancin (Monograph)

Brand name: Vibativ
Drug 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

Medically reviewed by Drugs.com on Sep 16, 2024. Written by ASHP.

Introduction

Antibacterial; lipoglycopeptide; semisynthetic derivative of vancomycin.

Uses for Telavancin

Nosocomial Pneumonia

Treatment of nosocomial pneumonia, including hospital-acquired and ventilator-associated pneumonia, caused by susceptible Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA; also known as oxacillin-resistant S. aureus or ORSA]).

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

Manufacturer states reserve telavancin for use when alternative treatments for hospital-acquired or ventilator-associated bacterial pneumonia not suitable.

Skin and Skin Structure Infections

Treatment of complicated skin and skin structure infections caused by susceptible S. aureus (including MRSA), Streptococcus pyogenes (group A β-hemolytic streptococci, GAS), S. agalactiae (group B streptococci, GBS), S. anginosus group (includes S. anginosus, S. intermedius, S. constellatus), or Enterococcus faecalis (vancomycin-susceptible strains only).

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

For information on diagnosis and management of skin and skin structure infections, consult current clinical practice guidelines from the Infectious Diseases Society of America (IDSA) available at [Web].

Telavancin Dosage and Administration

Administration

Administer by IV infusion.

IV Infusion

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

Must be reconstituted and then further diluted prior to administration.

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

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.

Reconstitution

Reconstitute single-dose 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.

To minimize foaming during reconstitution, allow vial vacuum to pull diluent from the syringe into vial; do not forcefully inject diluent into vial. Discard vial if the vacuum is insufficient to pull diluent into vial.

Mix thoroughly without forcefully shaking the vial and ensure that drug has dissolved completely. Usually reconstitutes in <2 minutes, but reconstitution may take up to 20 minutes.

Dilution

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

For doses <150 mg or >800 mg, withdraw correct dose from the reconstituted vial and add to a volume of appropriate IV infusion solution (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.

Do not shake final infusion solution.

Rate of Administration

Administer by IV infusion over 1 hour.

Avoid rapid IV infusion. (See Infusion Reactions under Cautions.)

Dosage

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

Adults

Nosocomial Pneumonia

IV

10 mg/kg once every 24 hours for 7–21 days.

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

Skin and Skin Structure Infections

IV

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

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

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment: Dosage adjustments not needed.

Severe hepatic impairment: Pharmacokinetics not evaluated.

Renal Impairment

Reduce dosage in adults with Cl_cr 10–50 mL/minute. (See Table 1.)

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

Consider use in patients with preexisting moderate or severe renal impairment (Cl_cr ≤50 mL/minute) only when anticipated benefits outweigh potential risks. (See Increased Mortality in Patients with Renal Impairment under Cautions.)

Calculate using Cockcroft-Gault formula and ideal body weight; use actual body weight if it is less than ideal body weight.

Geriatric Patients

Dosage adjustments not needed based solely on age. Select dosage with caution because of age-related decreases in renal function. (See Geriatric Use under Cautions.)

Cautions for Telavancin

Contraindications

• Patients with known hypersensitivity to telavancin.

• Concomitant use with IV unfractionated heparin; aPTT expected to be artificially prolonged for up to 18 hours after telavancin administration. (See Tests Used to Monitor Coagulation under Cautions.)

Warnings/Precautions

Warnings

Increased Mortality in Patients with Renal Impairment

Increased mortality observed in patients with preexisting moderate or severe renal impairment (Cl_cr ≤50 mL/minute) receiving telavancin for hospital-acquired or ventilator-associated bacterial pneumonia compared with those receiving vancomycin.

Consider use of telavancin in patients with preexisting moderate or severe renal impairment (Cl_cr ≤50 mL/minute) only when anticipated benefits outweigh potential risks.

Nephrotoxicity

New-onset or worsening renal impairment reported in patients receiving telavancin. 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.

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).

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

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

Fetal/Neonatal Morbidity

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

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).

Use effective contraception to prevent pregnancy during treatment.

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

Sensitivity Reactions

Serious and potentially fatal hypersensitivity reactions, including anaphylactic reactions, reported after first dose or subsequent doses of telavancin.

Discontinue telavancin at first sign of rash or any other sign of hypersensitivity.

Telavancin is a semisynthetic derivative of vancomycin; not known if patients with hypersensitivity reactions to vancomycin will experience cross-reactivity to telavancin. Use telavancin with caution in patients with known hypersensitivity to vancomycin.

Although data not available regarding cross-reactivity with other glycopeptides (e.g., dalbavancin, oritavancin), consider possibility of cross-sensitivity among the glycopeptides.

General Precautions

Infusion Reactions

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

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

Cardiovascular Effects

Prolongation of corrected QT (QT_c) interval reported.

Caution advised if used with drugs known to prolong QT interval.

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

Hematologic Effects

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

Reduced Efficacy in Patients with Moderate or Severe Renal Impairment

In a subgroup analysis of patients with skin and skin structure infections, clinical cure rate in telavancin-treated patients with baseline moderate or severe renal impairment (Cl_cr ≤50 mL/minute) was 67% compared with clinical cure rate of 87% in those with baseline Cl_cr >50 mL/minute. Reductions in clinical cure rates of this magnitude not observed in patients receiving the comparator anti-infective (vancomycin).

Consider such data regarding reduced efficacy when selecting anti-infectives for treatment of complicated skin and skin structure infections in patients with baseline moderate or severe renal impairment (Cl_cr ≤50 mL/minute).

Tests Used to Monitor Coagulation

Interferes with certain tests used to monitor coagulation, including PT, INR, aPTT, activated clotting time, and tests based on factor X activity assay, if blood for these tests is drawn 0–18 hours after a telavancin dose. (See Specific Drugs and Laboratory Tests under Interactions.)

In patients requiring aPTT monitoring while receiving telavancin, use a non-phospholipid-dependent coagulation test (e.g., factor Xa chromogenic assay) or consider using an alternative anticoagulant not requiring aPTT monitoring.

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

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

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile. C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) have been reported with nearly all anti-infectives and may range in severity from mild diarrhea to fatal colitis. C. difficile produces toxins A and B which contribute to development of CDAD; 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.

Consider CDAD if diarrhea develops during or after therapy and manage accordingly. Obtain careful medical history since CDAD may occur as late as ≥2 months after anti-infective therapy is discontinued.

If CDAD is suspected or confirmed, discontinue anti-infectives not directed against C. difficile whenever feasible. Initiate appropriate supportive therapy (fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.

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.

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

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. (See Uses.)

Specific Populations

Pregnancy

Category C. Pregnancy registry at 855-633-8479.

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.

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

Lactation

Not known whether telavancin is distributed into milk in humans.

Use with caution in nursing women.

Pediatric Use

Safety and efficacy not established in patients <18 years of age.

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. Although there were no overall differences in frequency of treatment-emergent adverse events compared with younger adults, incidence of adverse events indicating renal impairment was higher in geriatric adults than in younger adults.

In clinical studies evaluating telavancin for treatment of hospital-acquired or ventilator-associated bacterial pneumonia, treatment-emergent adverse events as well as deaths and other serious adverse events occurred more often in patients ≥65 years of age than in those <65 years of age in both the telavancin treatment group and comparator treatment group.

Substantially eliminated by kidneys; risk of adverse effects may be greater in patients with impaired renal function. Select dosage with caution since geriatric patients are more likely to have decreased renal function.

Hepatic Impairment

Moderate hepatic impairment (Child-Pugh class B): Pharmacokinetics not altered.

Severe hepatic impairment (Child-Pugh class C): Pharmacokinetics not evaluated.

Renal Impairment

In clinical studies evaluating telavancin for treatment of hospital-acquired or ventilator-associated bacterial pneumonia, mortality rates in adults with Cl_cr ≤50 mL/minute were higher in telavancin-treated patients compared with those receiving the comparator anti-infective (vancomycin).

In clinical studies evaluating telavancin for treatment of complicated skin and skin structure infections, lower clinical cure rates with telavancin observed in adults with Cl_cr ≤50 mL/minute compared with those with Cl_cr >50 mL/minute.

Consider possible reduced effectiveness when selecting an anti-infective for adults with baseline moderate or severe renal impairment (Cl_cr ≤50 mL/minute); consider use of telavancin in such patients only when anticipated benefits outweigh potential risks.

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

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

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

Common Adverse Effects

Hospital-acquired or ventilator-associated bacterial pneumonia: GI effects (nausea, vomiting, diarrhea, constipation ), anemia, hypokalemia, hypotension, decubitus ulcer, insomnia, peripheral edema, renal effects (renal impairment or insufficiency, acute renal failure, chronic renal failure, increased S_cr).

Complicated skin and skin structure infections: GI effects (taste disturbance, nausea, vomiting, diarrhea, constipation ), headache, insomnia, foamy urine.

Drug Interactions

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Inhibits CYP 3A4/5.

Specific Drugs and Laboratory Tests

Telavancin 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.

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

Special Populations

AUC increased in patients with renal impairment; mean AUC is increased approximately 29% in those with Cl_cr 30–50 mL/minute and 118% in those with Cl_cr <30 mL/minute.

Distribution

Extent

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

Concentrations in pulmonary epithelial lining fluid and alveolar macrophages exceed MIC₉₀ of S. aureus for at least 24 hours after a dose in healthy individuals receiving telavancin 10 mg/kg once daily for 3 days.

Not known whether telavancin is distributed into milk in humans.

Plasma Protein Binding

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

Elimination

Metabolism

Metabolic pathway not elucidated to date. Three hydroxylated metabolites identified; the major metabolite is THRX-651540.

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

Elimination Route

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

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

Half-life

Approximately 8 hours in adults.

Special Populations

Pharmacokinetics not altered in geriatric individuals based solely on age.

Pharmacokinetics altered by decreased renal function.

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

Stability

Storage

Parenteral

Powder for Injection

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

Following reconstitution, may be stored in original vial for up to 12 hours at room temperature or 7 days at 2–8°C. After further dilution, may be stored in infusion bag for 12 hours at room temperature or 7 days at 2–8°C. Combined storage time (vial and infusion bag) should be ≤12 hours at room temperature or ≤7 days when refrigerated.

Diluted telavancin solutions may be stored for up to 32 days at -30 to -10°C.

Compatibility

Parenteral

Solution Compatibility1 HID

Drug CompatibilityHID

Actions

• Lipoglycopeptide antibacterial. Semisynthetic derivative of vancomycin.

• Bactericidal in vitro against susceptible gram-positive bacteria. Inhibits bacterial cell wall synthesis by inhibiting peptidoglycan synthesis and blocking the transglycosylation step. Binds to the bacterial membrane and disrupts membrane barrier function.

• Active in vitro and in clinical infections against S. aureus (including methicillin-resistant S. aureus [MRSA; also known as oxacillin-resistant S. aureus or ORSA]), S. pyogenes (group A β-hemolytic streptococci, GAS), S. agalactiae (group B streptococci, GBS), S. anginosus group (includes S. anginosus, S. intermedius, S. constellatus), and E. faecalis (vancomycin-susceptible strains only).

• Active in vitro against E. faecium (vancomycin-susceptible strains only), S. haemolyticus, S. dysgalactiae subsp. equisimilis, and S. epidermidis. However, safety and efficacy in treating clinical infections caused by these bacteria not established.

• Some vancomycin-resistant enterococci have reduced susceptibility to telavancin. Cross-resistance between telavancin and other anti-infectives not reported to date.

Advice to Patients

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

• 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).

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

• 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.

• Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued. 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.

• 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.

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

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

• Importance of excluding pregnancy with a serum pregnancy test before starting telavancin. 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. (See Pregnancy under Cautions.)

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

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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