Telavancin

Pronunciation: TEL-a-VAN-sin
Class: Anti-infective agent

Trade Names

Vibativ
- Injection, lyophilized powder for solution 250 mg
- Injection, lyophilized powder for solution 750 mg

Pharmacology

Inhibits bacterial cell wall synthesis by interfering with the polymerization and cross-linking of peptidoglycan.

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Pharmacokinetics

Absorption

C max is 93.6 mcg/mL (single dose) and 108 mcg/mL (multiple dosing). Steady-state is reached by day 3.

Distribution

90% protein bound. Steady-state volume is 145 mL/kg (single dose) and 133 mL/kg (multiple dosing).

Metabolism

3 hydroxylated metabolites identified; THRX-651540 is the predominant metabolite.

Elimination

Half-life is 8 h. 76% is excreted in urine and less than 1% in the feces. Cl is 13 mL/kg/h.

Special Populations

Renal Function Impairment

The mean AUC values were approximately 13%, 29%, and 118% higher for subjects with CrCl greater than 50 to 80 mL/min, CrCl 30 to 50 mL/min, and CrCl 30 mL/min or less, respectively, compared with subjects with healthy renal function. Dosage adjustment required in patients with CrCl 50 mL/min or less.

Hepatic Function Impairment

Pharmacokinetics are not altered in patients with moderate hepatic impairment (Child-Pugh class B); studies have not been conducted in patients with severe hepatic impairment (Child-Pugh class C).

Elderly

Age alone does not have a clinically meaningful impact on the pharmacokinetics of telavancin.

Gender

Pharmacokinetics were similar in men and women.

Indications and Usage

For the treatment of adult patients with complicated skin and skin structure infections caused by susceptible isolates of the following gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and -resistant isolates), Streptococcus pyogenes , Streptococcus agalactiae , Streptococcus anginosus group (includes S. anginosus , Streptococcus intermedius , and Streptococcus constellatus ), or Enterococcus faecalis (vancomycin-susceptible isolates only).

Contraindications

Standard considerations.

Dosage and Administration

Complicated Skin and Skin Structure Infections
Adults

IV 10 mg/kg administered over a 60-min period by IV infusion once every 24 h for 7 to 14 days.

Renal Function Impairment

CrCl 30 to 50 mL/min, give 7.5 mg/kg every 24 h. CrCl 30 to 10 mL/min, give 10 mg/kg every 48 h.

General Advice

  • Reconstitute the 250 mg vial with 15 mL of dextrose 5% injection , sterile water for injection, or sodium chloride 0.9% injection; reconstitute the 750 mg vial with 45 mL of dextrose 5% injection, sterile water for injection, sodium chloride 0.9% injection. The resultant solution has a concentration of 15 mg/mL.
  • Reconstituted powder must be further diluted prior to administration. Refer to the manufacturer's prescribing information for instructions.
  • Administer over a period of no less than 60 min by IV infusion.
  • Parenteral drugs products should be inspected visually for particulate matter prior to administration.
  • Discard the vial if the vacuum did not pull the diluent into the vial.
  • Additives or other medications should not be added to single-use vials or infused simultaneously through the same IV line.
  • If the same IV line is used for sequential infusion of additional medications, the line should be flushed before and after infusion of telavancin with dextrose 5% injection, sodium chloride 0.9% injection, or Ringer's lactate injection.

Storage/Stability

Store original packages at 35° to 46°F. Excursions to ambient temperatures (77°F) are acceptable. Avoid excessive heat. The reconstituted solution in the vial should be used within 4 h when stored at room temperature or within 72 h when stored at 36° to 46°F. The diluted (dosing) solution in the infusion bag should be used within 4 h when stored at room temperature or used within 72 h when stored at 36° to 46°F. However, the total time in the vial plus the time in the infusion bag should not exceed 4 h when stored at room temperature and 72 h when stored at 36° to 46°F.

Drug Interactions

Drugs affecting kidney function (eg, ACE inhibitors, loop diuretics, NSAIDs)

Risk of renal adverse events may be increased. Use with caution. Observe the patient for adverse renal events. Monitor renal function.

QT-prolonging drugs (eg, amiodarone, pimozide, ziprasidone)

Possible additive effects with other drugs that prolong the QT interval. Use with caution.

Laboratory Test Interactions

Telavancin does not interfere with coagulation; however, it interferes with certain tests used to monitor coagulation, including activated clotting time, APTT, coagulation-based factor Xa tests, INR, and PT. No evidence of increased risk of bleeding has been observed. Telavancin interferes with urine qualitative dipstick protein assays and quantitative dye methods (eg, pyrogallol red-molybdate). However, microalbumin assay are not affected and can be used to monitor urinary protein excretion during telavancin treatment.

Adverse Reactions

CNS

Dizziness (6%).

Dermatologic

Pruritus (6%); rash (4%); generalized pruritus (3%).

GI

Taste disturbance (33%); nausea (27%); vomiting (14%); diarrhea (7%); abdominal pain (2%).

Local

Infusion-site pain (4%); infusion-site erythema (3%).

Miscellaneous

Foamy urine (13%); rigors (4%); decreased appetite (3%).

Precautions

Warnings

Fetal risk

Women of childbearing potential should have a serum pregnancy test prior to administration. Avoid use during pregnancy unless the potential benefit to the patient outweighs the potential risk to the fetus. Adverse developmental outcomes observed in 3 animal species at clinically relevant doses raise concerns about potential adverse developmental outcomes in humans.


Monitor

Perform monitoring of renal function prior to initiation of treatment, during treatment (at 48- to 72-h intervals or more frequently if indicated), and at the end of therapy. Preform a serum pregnancy test in women of childbearing potential before start of therapy.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and effectiveness have not been studied.

Elderly

Because elderly patients are more likely to have decreased renal function, take care with dose selection.

Renal Function

Dosage adjustment required; use with caution.

Superinfection

May result in bacterial or fungal overgrowth of nonsusceptible organisms.

Clostridium difficile –associated diarrhea

Consider possibility in patients with diarrhea

Infusion reactions

Rapid IV infusion of the glycopeptide class of antimicrobial agents can cause “red man syndrome”–like reactions. Administer over 60 min to reduce this risk.

Nephrotoxicity

Increases in serum creatinine to 1.5 times baseline have occurred. Renal adverse reactions are more likely to occur in patients with baseline comorbidities known to predispose patients to renal dysfunction (eg, preexisting renal disease, diabetes, CHF, hypertension) and in patients who take concomitant medications known to affect kidney function (eg, NSAIDs, ACE inhibitors, loop diuretics).

QTc Prolongation

Avoid use in patients with congenital long QT syndrome, known prolongation of the QTc interval, uncompensated heart failure, or severe left ventricular hypertrophy.

Overdosage

Symptoms

No information available.

Patient Information

  • Advise patients to read the Medication Guide before starting therapy.
  • Advise women of childbearing age they must have a negative serum pregnancy test prior to administration.
  • Instruct women of childbearing potential to use an effective method of birth control during therapy.
  • Instruct patient to notify health care provider immediately if pregnancy is suspected.
  • Explain to patient that medication will be prepared and administered by a health care provider.
  • Instruct patients to contact health care provider as soon as possible if watery or bloody stools occur, even as late as 2 or more months after receiving the last dose of telavancin.
  • Instruct patients not to stop taking this medicine, even if they start to feel better.
  • Common adverse effects are foamy urine, headache, nausea, taste disturbance, and vomiting. Advise patients to notify their health care provider if these symptoms persist or worsen.
  • Advise patient that telavancin has been associated with elevations in serum creatinine and ECG changes (QTc prolongation).
  • Advise patients that telavancin may interfere with some coagulation tests.

Copyright © 2009 Wolters Kluwer Health.

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