Telavancin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution Reconstituted, Intravenous [preservative free]:

Vibativ: 250 mg (1 ea [DSC]); 750 mg (1 ea)

Pharmacology

Mechanism of Action

Exerts concentration-dependent bactericidal activity; inhibits bacterial cell wall synthesis by blocking polymerization and cross-linking of peptidoglycan by binding to D-Ala-D-Ala portion of cell wall. Unlike vancomycin, additional mechanism involves disruption of membrane potential and changes cell permeability due to presence of lipophilic side chain moiety.

Pharmacokinetics/Pharmacodynamics

Distribution

V_ss: 0.13 L/kg

Excretion

Urine (~76%); feces (<1%)

Half-Life Elimination

6.6 to 9.6 hours

Protein Binding

~90%; primarily to albumin

Use in Specific Populations

Special Populations: Renal Function Impairment

The mean AUC values were approximately 13%, 29%, and 118% higher for subjects with CrCl >50 to 80 mL/minute, CrCl 30 to 50 mL/minute, and CrCl ≤30 mL/minute, respectively when compared with subjects with healthy renal function.

Use: Labeled Indications

Complicated skin and skin structure infections: Treatment of complicated skin and skin structure infections caused by susceptible gram-positive organisms including methicillin-susceptible or -resistant Staphylococcus aureus, vancomycin-susceptible Enterococcus faecalis, and Streptococcus pyogenes, Streptococcus agalactiae, or Streptococcus anginosus group

Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP): Treatment of HABP/VABP caused by susceptible isolates of Staphylococcus aureus when alternative treatments are not appropriate

Use: Off Label

Bacteremia due to S. aureuscyes

Based on the Infectious Diseases Society of America (IDSA) guidelines for the Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) Infections in Adults and Children, telavancin, as monotherapy or in combination with other agents, may be considered as an alternative agent for persistent bacteremia due to MRSA that has reduced susceptibility to vancomycin and daptomycin.

Data from a small randomized, double-blind, phase 2 trial demonstrated utility for the treatment of uncomplicated S. aureus bacteremia Stryjewski 2014

Contraindications

Hypersensitivity to telavancin or any component of the formulation; concomitant use of intravenous unfractionated heparin

Dosage and Administration

Dosing: Adult

Bacteremia due to S. aureus (off-label use): IV: 10 mg/kg every 24 hours (IDSA [Liu 2011]; Stryjewski 2014)

Complicated skin and skin structure infection: IV: 10 mg/kg every 24 hours for 1 to 2 weeks

Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) due to S. aureus: IV: 10 mg/kg every 24 hours for 1 to 3 weeks

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

Reconstitute 250 mg vial with 15 mL of D5W, NS, or SWFI to yield 15 mg/mL (total volume of ~17 mL). Reconstitute 750 mg vial with 45 mL of of D5W, NS, or SWFI to yield 15 mg/mL (total volume of ~50 mL). Allow vacuum to pull the diluent into the vial; discard vial if this did not occur. Reconstitution generally takes <2 minutes, although may take up to 20 minutes. Do not shake the vial or final solution for infusion. Prior to administration, dilute dose in 100 to 250 mL D5W, LR, or NS to a final concentration of 0.6 to 8 mg/mL.

Administration

IV: Administer IV over 60 minutes. Other medications should not be infused simultaneously through the same IV line. When the same intravenous line is used for sequential infusion of other medications, flush line with D₅W, LR, or NS before and after infusing telavancin.

Red-man syndrome may occur if the infusion is too rapid. It is not an allergic reaction, but may be characterized by hypotension and/or a maculopapular rash appearing on the face, neck, trunk, and/or upper extremities. If this should occur, discontinuing or slowing the infusion rate may eliminate these reactions.

Storage

Store intact vials at 2°C to 8°C (35°F to 46°F); excursions permitted up to 25°C (77°F); avoid excess heat. Note: Vials contain no bacteriostatic agent. Reconstituted solution in the vial should be used within 12 hours at room temperature or 7 days refrigerated; solutions admixed for infusion in NS, LR, or D5W are stable at room temperature for 12 hours or under refrigeration for 7 days. Total time in vial plus time in infusion bag should not exceed 12 hours at room temperature or 7 days if refrigerated at 2°C to 8°C (35°F to 46°F). Solutions admixed for infusion can also be stored at -30°C to -10°C (-22°F to 14°F) for ≤32 days.

Drug Interactions

Anticoagulants: Telavancin may diminish the therapeutic effect of Anticoagulants. Specifically, telavancin may artificially increase the results of laboratory tests commonly used to monitor anticoagulant effectiveness, which could lead to incorrect decisions to decrease anticoagulant doses. Exceptions: Antithrombin; Bemiparin; Dalteparin; Enoxaparin; Fondaparinux; Nadroparin; Protein C Concentrate (Human); Tinzaparin. Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

Heparin: Telavancin may diminish the therapeutic effect of Heparin. Specifically, telavancin may artificially increase the results of laboratory tests commonly used to monitor IV heparin effectiveness, which could lead to incorrect decisions to decrease heparin doses. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Test Interactions

Interferes with the following coagulation assessments when using samples drawn 18 hours or less after telavancin administration (causes artificially increased clotting times): PT, INR, aPTT, ACT, Xa (coagulation based assay). Collect blood samples for these coagulation tests as close as possible prior to administration of the next dose of telavancin, use a non-phospholipid dependent coagulation test (eg, bleeding time, factor Xa [chromogenic assay], platelet aggregation study, thrombin time), or select an alternative anticoagulant not requiring aPTT monitoring; concomitant use of telavancin and IV unfractionated heparin is contraindicated.

Interferes with urine protein via qualitative dipstick and quantitative dye methods.

Adverse Reactions

>10%:

Central nervous system: Metallic taste (33%)

Gastrointestinal: Nausea (5% to 27%), vomiting (5% to 14%)

Renal: Increased serum creatinine (8% to 16%; ≥65 years of age: 11%; <65 years of age: 8%), foamy urine (13%)

1% to 10%:

Central nervous system: Dizziness (6%), infusion site pain (4%), rigors (4%)

Dermatologic: Pruritus (3% to 6%), skin rash (4%), localized erythema (3%)

Gastrointestinal: Diarrhea (7%), decreased appetite (3%), abdominal pain (2%)

Local: Infusion site reaction (3%)

Renal: Renal insufficiency (3%; ≥65 years of age: 9%; <65 years of age: 2%), acute renal failure (5%)

<1%, postmarketing, and/or case reports: Clostridioides (formerly Clostridium) difficile-associated diarrhea, flushing, hypersensitivity reaction (including anaphylaxis), nephrotoxicity, prolonged Q-T interval on ECG, transient flushing of upper body, urticaria

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis/hypersensitivity reactions: Serious hypersensitivity reactions, including anaphylaxis, have been reported after first or subsequent doses; some have been fatal. Discontinue if hypersensitivity or rash occurs. Telavancin is a semisynthetic derivative of vancomycin; cross-reactivity rates are unknown. Use with caution in patients with known vancomycin hypersensitivity.
• Cardiac conduction alteration: May prolong QTc interval; avoid use in patients with congenital long QT syndrome, known QTc prolongation, uncompensated heart failure, or severe left ventricular hypertrophy (were excluded from studies); use with caution in patients with concurrent administration of other medications known to prolong the QT interval. Clinical studies indicate mean maximal QTc prolongation of 12 to 15 msec at the end of 10 mg/kg infusion.
• Infusion reactions: Rapid IV administration may result in flushing, rash, urticaria, and/or pruritus; slowing or stopping the infusion may alleviate these symptoms.
• Nephrotoxicity: [US Boxed Warning]: New onset or worsening renal impairment has occurred. Monitor renal function prior to, during (at least every 48 to 72 hours; more frequently if indicated), and following therapy in all patients. Usual risk factors include concomitant nephrotoxic medications or baseline comorbidities associated with decreased renal function (eg baseline renal dysfunction, diabetes, hypertension, or heart failure). Contains solubilizer cyclodextrin (hydroxypropyl-beta-cyclodextrin) which may accumulate in patients with renal dysfunction, although the clinical significance of this finding is uncertain (Luke 2010).
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Renal impairment: [US Boxed Warning]: In clinical studies, patients with pre-existing moderate-to-severe renal impairment (CrCl ≤50 mL/minute) treated for hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) had increased (all cause) mortality versus vancomycin. Use in HABP/VABP only when benefit outweighs risk. In patients with complicated skin and skin structure infections, efficacy may be reduced in patients with a baseline CrCl ≤50 mL/minute.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Lower doses are often required secondary to age-related decreases in renal function.
• Pregnancy: [US Boxed Warning]: Based on animal data, adverse developmental outcomes have been observed. Prior to use, women of childbearing potential should have a serum pregnancy test. Use of telavancin is not recommended during pregnancy unless the potential benefit outweighs the risk to the fetus.

Other warnings/precautions:

• Coagulation tests: May interfere with tests used to monitor coagulation (eg, prothrombin time, INR, activated partial thromboplastin time, activated clotting time, coagulation based factor Xa tests) when samples drawn ≤18 hours after drug administration. Blood samples should be collected as close to the next dose of telavancin as possible or a non-phospholipid dependent coagulation test (eg, bleeding time, factor Xa [chromogenic assay], platelet aggregation study, thrombin time) should be used. Consider selecting an alternative anticoagulant not requiring aPTT monitoring; concomitant use of telavancin with IV unfractionated heparin is contraindicated.

Monitoring Parameters

Renal function (prior to start, every 48 to 72 hours; more frequently if indicated, and following therapy), pregnancy test

Pregnancy

Pregnancy Risk Factor

C

Pregnancy Considerations

Telavancin crosses the placenta (Nanovskaya 2012). [US Boxed Warning]: Avoid use during pregnancy unless the potential benefit to the patient outweighs the potential risk to the fetus. Adverse developmental outcomes observed in three animal species at clinically relevant doses raise concerns about potential adverse developmental outcomes in humans.

[US Boxed Warning]: Women of childbearing potential should have a serum pregnancy test prior to administration. Women of childbearing potential should use effective contraception during therapy.

Health care providers are encouraged to enroll women exposed to telavancin during pregnancy in the Vibativ Pregnancy Registry (855-633-8479).

Patient Education

What is this drug used for?

• It is used to treat bacterial infections.

Frequently reported side effects of this drug

• Proteinuria
• Change in taste
• Nausea
• Vomiting
• Headache
• Diarrhea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Kidney problems like unable to pass urine, blood in urine, change in amount of urine passed, or weight gain
• Fast heartbeat
• Arrhythmia
• Severe dizziness
• Passing out
• Flushing
• Rash during infusion
• Severe injection site irritation
• Clostridium difficile (C. diff)-associated diarrhea like stomach pain or cramps, very loose or watery stools, or bloody stools
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.