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Included as part of the PRECAUTIONS section.

Women of Childbearing Potential

Women of childbearing potential should have a serum pregnancy test prior to administration of VIBATIV (telavancin for injection) . If not already pregnant, women of childbearing potential should use effective contraception during VIBATIV (telavancin for injection) treatment.

Pregnancy

Avoid use of VIBATIV (telavancin for injection) during pregnancy unless the potential benefit to the patient outweighs the potential risk to the fetus. VIBATIV (telavancin for injection) caused adverse developmental outcomes in 3 animal species at clinically relevant doses. This raises concern about potential adverse developmental outcomes in humans [see Use in Specific Populations].

Nephrotoxicity

Increases in serum creatinine to 1.5 times baseline occurred more frequently among VIBATIV (telavancin for injection) -treated patients with normal baseline serum creatinine (15%) compared with vancomycin-treated patients with normal baseline serum creatinine (7%).

In 30/929 (3.1%) of VIBATIV (telavancin for injection) -treated patients compared to 10/938 (1.1%) of vancomycin-treated patients, renal adverse events indicative of renal impairment occurred, as defined by the following terms: increased serum creatinine, renal impairment, renal insufficiency, and/or renal failure. In 17 of the 30 VIBATIV (telavancin for injection) -treated patients, these adverse events had not completely resolved by the end of the trials, compared with 6 of the 10 vancomycin-treated patients. Serious adverse events indicative of renal impairment occurred in 11/929 (1.2%) of VIBATIV (telavancin for injection) -treated patients compared to 3/938 (0.3%) of vancomycin-treated patients. Twelve patients treated with VIBATIV (telavancin for injection) discontinued treatment due to adverse events indicative of renal impairment compared to 2 patients treated with vancomycin. Adverse events were more likely to occur in patients with baseline comorbidities known to predispose patients to kidney dysfunction (pre-existing renal disease, diabetes mellitus, congestive heart failure, or hypertension). The renal adverse event rate was also higher in patients who received concomitant medications known to affect kidney function (eg, non-steroidal antiinflammatory drugs, ACE inhibitors, and loop diuretics). Fifteen of 174 patients (8.6%) ≥ 65 years of age had adverse events indicative of renal impairment compared to 16 of 755 patients (1.9%) < 65 years of age [see Use in Specific Populations].

Monitor renal function (i.e., serum creatinine, creatinine clearance) in all patients receiving VIBATIV (telavancin for injection) . Values should be obtained prior to initiation of treatment, during treatment (at 48- to 72-hour intervals or more frequently, if clinically indicated), and at the end of therapy. If renal function decreases, the benefit of continuing VIBATIV (telavancin for injection) versus discontinuing and initiating therapy with an alternative agent should be assessed [see DOSAGE AND ADMINISTRATION, CLINICAL PHARMACOLOGY].

In patients with renal dysfunction, accumulation of the solubilizer hydroxypropyl-beta-cyclodextrin can occur [see Patients with Renal Impairment and CLINICAL PHARMACOLOGY].

Decreased Efficacy with Moderate/Severe Baseline Renal Impairment

In a subgroup analysis of the pooled cSSSI studies, clinical cure rates in the telavancin-treated patients were lower in patients with baseline CrCl 50 mL/min compared to those with CrCl > 50 mL/min (Table 2). A decrease of this magnitude was not observed in vancomycin-treated patients. Consider these data when selecting antibacterial therapy for use in patients with baseline moderate/severe renal impairment.

Table 2: Clinical Cure by Baseline Renal Function

Infusion-Related Reactions

VIBATIV (telavancin for injection) is a lipoglycopeptide antibacterial agent and should be administered over a period of 60 minutes to reduce the risk of infusion-related reactions. Rapid intravenous infusions of the glycopeptide class of antimicrobial agents can cause “Red-man Syndrome”-like reactions including: flushing of the upper body, urticaria, pruritus, or rash. Stopping or slowing the infusion may result in cessation of these reactions.

Clostridium difficile-Associated Diarrhea

Clostridium difficile-associated diarrhea (CDAD) has been reported with nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the flora of the colon and may permit overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hyper-toxin-producing strains of C. difficile cause increased morbidity and mortality, since these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary because CDAD has been reported to occur over 2 months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Development of Drug-Resistant Bacteria

Prescribing VIBATIV (telavancin for injection) in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

As with other antibacterial drugs, use of VIBATIV (telavancin for injection) may result in overgrowth of nonsusceptible organisms, including fungi. Patients should be carefully monitored during therapy. If superinfection occurs, appropriate measures should be taken.

QTc Prolongation

In a study involving healthy volunteers, doses of 7.5 and 15 mg/kg of VIBATIV prolonged the QTc interval [see CLINICAL PHARMACOLOGY]. Caution is warranted when prescribing VIBATIV (telavancin for injection) to patients taking drugs known to prolong the QT interval. Patients with congenital long QT syndrome, known prolongation of the QTc interval, uncompensated heart failure, or severe left ventricular hypertrophy were not included in clinical trials of VIBATIV (telavancin for injection) . Use of VIBATIV (telavancin for injection) should be avoided in patients with these conditions.

Coagulation Test Interference

Although telavancin does not interfere with coagulation, it interfered with certain tests used to monitor coagulation (Table 3), when conducted using samples drawn 0 to 18 hours after VIBATIV (telavancin for injection) administration for patients being treated once every 24 hours. Blood samples for these coagulation tests should be collected as close as possible prior to a patient's next dose of VIBATIV (telavancin for injection) . Blood samples for coagulation tests unaffected by VIBATIV may be collected at any time [see DRUG INTERACTIONS].

Table 3 : Coagulation Tests Affected and Unaffected by Telavancin

No evidence of increased bleeding risk has been observed in clinical trials with VIBATIV. Telavancin has no effect on platelet aggregation. Furthermore, no evidence of hypercoagulability has been seen, as healthy subjects receiving VIBATIV (telavancin for injection) have normal levels of D-dimer and fibrin degradation products.

Patient Counselling Information

See Medication Guide.

Use during Pregnancy and by Women of Childbearing Potential

Women of childbearing potential (those who have not had: complete absence of menses for at least 24 months or medically confirmed menopause, medically confirmed primary ovarian failure, a history of hysterectomy, bilateral oophorectomy, or tubal ligation) should:

• Be informed about the potential risk of fetal harm if VIBATIV (telavancin for injection) is used during pregnancy
• Have a pregnancy test prior to administration of VIBATIV (telavancin for injection)
• If not pregnant, use effective contraceptive methods to prevent pregnancy during VIBATIV (telavancin for injection) treatment
• Notify their prescribing physician/ healthcare provider if they become pregnant during VIBATIV (telavancin for injection) treatment

Pregnancy Registry

There is a pregnancy registry that monitors pregnancy outcomes in women exposed to VIBATIV (telavancin for injection) during pregnancy. Physicians are encouraged to register pregnant patients, or pregnant women may enroll themselves in the pregnancy registry by calling 1-888-658-4228.

Diarrhea

Diarrhea is a common problem caused by antibiotics that usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having received the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Correct Use of Antibacterial Drugs

Patients should be counseled that antibacterial drugs including VIBATIV (telavancin for injection) should only be used to treat bacterial infections. They do not treat viral infections (eg, the common cold). When VIBATIV (telavancin for injection) is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of immediate treatment, and (2) increase the likelihood that the bacteria will develop resistance and will not be treatable by VIBATIV (telavancin for injection) or other antibacterial drugs in the future.

Common Adverse Effects

Patients should be informed about the common adverse effects of VIBATIV (telavancin for injection) including taste disturbance, nausea, vomiting, headache, and foamy urine. Patients should be instructed to inform their healthcare provider if they develop any unusual symptom, or if any known symptom persists or worsens. Patients should be instructed to inform their healthcare provider of any other medications they are currently taking with VIBATIV (telavancin for injection) , including over-the-counter medications.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals to determine the carcinogenic potential of telavancin have not been performed.

Neither mutagenic nor clastogenic potential of telavancin was found in a battery of tests including: assays for mutagenicity (Ames bacterial reversion), an in vitro chromosome aberration assay in human lymphocytes, and an in vivo mouse micronucleus assay.

Telavancin did not affect the fertility or reproductive performance of adult male rats (exposed to telavancin for at least 4 weeks prior to mating) or female rats (exposed to telavancin for at least 2 weeks prior to mating).

Male rats given telavancin for 6 weeks, at exposures similar to those measured in clinical studies, displayed altered sperm parameters that were reversible following an 8-week recovery period.

Use In Specific Populations

Pregnancy

Teratogenic effects: Pregnancy Category C

Pregnancy Exposure Registry

There is a pregnancy registry that monitors pregnancy outcomes in women exposed to VIBATIV (telavancin for injection) during pregnancy. Physicians are encouraged to register pregnant patients, or pregnant women may enroll themselves in the VIBATIV (telavancin for injection) pregnancy registry by calling 1-888-658-4228.

Fetal Risk Summary

All pregnancies have a background risk of birth defects (about 3%), pregnancy loss (about 15%), or other adverse outcomes regardless of drug exposure.

There are no data on VIBATIV (telavancin for injection) use in pregnant women. In 3 animal species, VIBATIV (telavancin for injection) exposure during pregnancy at clinically relevant doses caused reduced fetal weights and increased rates of digit and limb malformations in offspring. These data raise concern about potential adverse developmental outcomes in humans (see Data).

Clinical Considerations

Given the lack of human data and the risks suggested by animal data, avoid using VIBATIV (telavancin for injection) in pregnant women unless the benefits to the patient outweigh the potential risks to the fetus.

Data

Human Data

There are no data on human pregnancies exposed to VIBATIV (telavancin for injection) .

Animal Data

In embryo-fetal development studies in rats, rabbits, and minipigs, telavancin demonstrated the potential to cause limb and skeletal malformations when given intravenously during the period of organogenesis at doses up to 150, 45 or 75 mg/kg/day, respectively. These doses resulted in exposure levels approximately 1- to 2-fold the human exposure (AUC) at the maximum clinical recommended dose. Malformations observed at < 1% (but absent or at lower rates in historical or concurrent controls), included brachymelia (rats and rabbits), syndactyly (rats, minipigs), adactyly (rabbits), and polydactyly (minipigs). Additional findings in rabbits included flexed front paw and absent ulna, and in the minipigs included misshapen digits and deformed front leg. Fetal body weights were decreased in rats.

In a prenatal/perinatal development study, pregnant rats received intravenous telavancin at up to 150 mg/kg/day (approximately the same AUC as observed at the maximum clinical dose) from the start of organogenesis through lactation. Offspring showed decreases in fetal body weight and an increase in the number of stillborn pups. Brachymelia was also observed. Developmental milestones and fertility of the pups were unaffected.

Nursing Mothers

It is not known whether telavancin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when VIBATIV (telavancin for injection) is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of VIBATIV (telavancin for injection) in pediatric patients has not been studied.

Geriatric Use

Of the 929 patients treated with VIBATIV (telavancin for injection) at a dose of 10 mg/kg once daily in clinical trials of cSSSI, 174 (18.7%) were ≥ 65 years of age and 87 (9.4%) were ≥ 75 years of age. In the cSSSI trials, lower clinical cure rates were observed in patients ≥ 65 years of age compared with those < 65 years of age. Overall, treatment-emergent adverse events occurred with similar frequencies in patients ≥ 65 (75% of patients) and < 65 years of age (83% of patients). Fifteen of 174 (8.6%) patients ≥ 65 years of age treated with telavancin had adverse events indicative of renal impairment compared to 16 of 755 (1.9%) patients < 65 years of age [see WARNINGS AND PRECAUTIONS, Clinical Trials].

Telavancin is substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in this age group.

The mean plasma AUC values of telavancin were similar in healthy young and elderly subjects. Dosage adjustment for elderly patients should be based on renal function [see DOSAGE AND ADMINISTRATION, CLINICAL PHARMACOLOGY].

Patients with Renal Impairment

The cSSSI trials included patients with normal renal function and patients with varying degrees of renal impairment. Patients with underlying renal dysfunction or risk factors for renal dysfunction had a higher incidence of renal adverse events [see WARNINGS AND PRECAUTIONS]. Patients with creatinine clearance ≤ 50 mL/min also had lower clinical cure rates. Consider these data when selecting antibacterial therapy in patients with baseline moderate/ severe renal impairment (CrCl 50 mL/min).

Dosage adjustment is required in patients with ≤ 50 mL/min renal impairment [see DOSAGE AND ADMINISTRATION]. There is insufficient information to make specific dosage adjustment recommendations for patients with end-stage renal disease (CrCl < 10 mL/min), including patients receiving hemodialysis [see OVERDOSAGE, CLINICAL PHARMACOLOGY].

Hydroxypropyl-beta-cyclodextrin is excreted in urine and may accumulate in patients with renal impairment. Serum creatinine should be closely monitored and, if renal toxicity is suspected, an alternative agent should be considered [see WARNINGS AND PRECAUTIONS, CLINICAL PHARMACOLOGY].

Patients with Hepatic Impairment

The cSSSI trials included patients with normal hepatic function and with hepatic impairment. No dosage adjustment is recommended in patients with mild or moderate hepatic impairment [see CLINICAL PHARMACOLOGY].

Last reviewed on RxList: 9/17/2009
This monograph has been modified to include the generic and brand name in many instances.