Vibativ

Telavancin hydrochloride is an off-white to slightly colored amorphous powder with the empirical formula C₈₀H₁₀₆Cl₂N₁₁O₂₇P•xHCl (where x = 1 to 3) and a free-base molecular weight of 1755.6. It is highly lipophilic and slightly soluble in water.

VIBATIV is a sterile, preservative-free, white to slightly colored lyophilized powder containing telavancin hydrochloride (equivalent to either 250 mg or 750 mg of telavancin as the free base) for intravenous use. The inactive ingredients are Hydroxypropylbetadex, Ph. Eur (hydroxypropyl-beta-cyclodextrin) (2500 mg per 250 mg telavancin, 7500 mg per 750 mg telavancin), mannitol (312.5 mg per 250 mg telavancin, 937.5 mg per 750 mg telavancin), and sodium hydroxide and hydrochloric acid used in minimal quantities for pH adjustment. When reconstituted, it forms a clear to slightly colored solution with a pH of 4.5 (4.0 to 5.0).

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Telavancin is an antibacterial drug [see Clinical Pharmacology (12.4)].

12.2 Pharmacodynamics

The antimicrobial activity of telavancin appears to best correlate with the ratio of area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC) for Staphylococcus aureus based on animal models of infection. Exposure-response analyses of the clinical trials support the dose of 10 mg/kg every 24 hours.

Cardiac Electrophysiology

The effect of telavancin on cardiac repolarization was assessed in a randomized, double-blind, multiple-dose, positive-controlled, and placebo-controlled, parallel study (n=160). Healthy subjects received VIBATIV 7.5 mg/kg, VIBATIV 15 mg/kg, positive control, or placebo infused over 60 minutes once daily for 3 days. Based on interpolation of the data from VIBATIV 7.5 mg/kg and 15 mg/kg, the mean maximum baseline-corrected, placebo-corrected QTc prolongation at the end of infusion was estimated to be 12-15 msec for VIBATIV 10 mg/kg and 22 msec for the positive control (Table 7). By 1 hour after infusion the maximum QTc prolongation was 6-9 msec for VIBATIV and 15 msec for the positive control.

ECGs were performed prior to and during the treatment period in patients receiving VIBATIV 10 mg/kg in 3 cSSSI studies to monitor QTc intervals. In these trials, 214 of 1029 (21%) patients allocated to treatment with VIBATIV and 164 of 1033 (16%) allocated to vancomycin received concomitant medications known to prolong the QTc interval and known to be associated with definite or possible risk of torsades de pointes. The incidence of QTc prolongation >60 msec was 1.5% (15 patients) in the VIBATIV group and 0.6% (6 patients) in the vancomycin group. Nine of the 15 VIBATIV patients received concomitant medications known to prolong the QTc interval and definitely or possibly associated with a risk of torsades de pointes, compared with 1 of the 6 patients who received vancomycin. A similar number of patients in each treatment group (<1%) who did not receive a concomitant medication known to prolong the QTc interval experienced a prolongation >60 msec from baseline. In a separate analysis, 1 patient in the VIBATIV group and 2 patients in the vancomycin group experienced QTc >500 msec. No cardiac adverse events were ascribed to prolongation of the QTc interval. In the Phase 3 HABP/VABP studies, the incidence of QTc prolongation >60 msec or mean value >500 msec was 8% (52 patients) in the telavancin group and 7% (48 patients) in the vancomycin group.

12.3 Pharmacokinetics

The mean pharmacokinetic parameters of telavancin (10 mg/kg) after a single and multiple 60-minute intravenous infusions (10 mg/kg every 24 hours) are summarized in Table 8.

In healthy young adults, the pharmacokinetics of telavancin administered intravenously were linear following single doses from 5 to 12.5 mg/kg and multiple doses from 7.5 to 15 mg/kg administered once daily for up to 7 days. Steady-state concentrations were achieved by the third daily dose.

Distribution

Telavancin binds to human plasma proteins, primarily to serum albumin, in a concentration-independent manner. The mean binding is approximately 90% and is not affected by renal or hepatic impairment.

Concentrations of telavancin in pulmonary epithelial lining fluid (ELF) and alveolar macrophages (AM) were measured through collection of bronchoalveolar lavage fluid at various times following administration of VIBATIV 10 mg/kg once daily for 3 days to healthy adults. Telavancin concentrations in ELF and AM exceeded the MIC₉₀ for S. aureus (0.5 mcg/mL) for at least 24 hours following dosing.

Concentrations of telavancin in skin blister fluid were 40% of those in plasma (AUC_0-24hr ratio) after 3 daily doses of 7.5 mg/kg VIBATIV in healthy young adults.

Metabolism

No metabolites of telavancin were detected in in vitro studies using human liver microsomes, liver slices, hepatocytes, and kidney S9 fraction. None of the following recombinant CYP 450 isoforms were shown to metabolize telavancin in human liver microsomes: CYP 1A2, 2C9, 2C19, 2D6, 3A4, 3A5, 4A11. The clearance of telavancin is not expected to be altered by inhibitors of any of these enzymes.

In a mass balance study in male subjects using radiolabeled telavancin, 3 hydroxylated metabolites were identified with the predominant metabolite (THRX-651540) accounting for <10% of the radioactivity in urine and <2% of the radioactivity in plasma. The metabolic pathway for telavancin has not been identified.

Excretion

Telavancin is primarily eliminated by the kidney. In a mass balance study, approximately 76% of the administered dose was recovered from urine and <1% of the dose was recovered from feces (collected up to 216 hours) based on total radioactivity.

Specific Populations

Geriatric Patients

The impact of age on the pharmacokinetics of telavancin was evaluated in healthy young (range 21-42 years) and elderly (range 65-83 years) subjects. The mean CrCl of elderly subjects was 66 mL/min. Age alone did not have a clinically meaningful impact on the pharmacokinetics of telavancin [see Use in Specific Populations (8.5)].

Pediatric Patients

The pharmacokinetics of telavancin in patients less than 18 years of age have not been studied.

Gender

The impact of gender on the pharmacokinetics of telavancin was evaluated in healthy male (n=8) and female (n=8) subjects. The pharmacokinetics of telavancin were similar in males and females. No dosage adjustment is recommended based on gender.

Renal Impairment

The pharmacokinetics of telavancin were evaluated in subjects with normal renal function and subjects with varying degrees of renal impairment following administration of a single dose of telavancin 7.5 mg/kg (n=28). The mean AUC_0-∞ values were approximately 13%, 29%, and 118% higher for subjects with CrCl >50 to 80 mL/min, CrCl 30 to 50 mL/min, and CrCl <30 mL/min, respectively, compared with subjects with normal renal function. Dosage adjustment is required in patients with CrCl ≤50 mL/min [see Dosage and Administration (2)].

Creatinine clearance was estimated from serum creatinine based on the Cockcroft-Gault formula:

•   CrCl = [140 – age (years)] x ideal body weight (kg)* {x 0.85 for female patients}
                  [72 x serum creatinine (mg/dL)]
•  
  *Use actual body weight if < ideal body weight (IBW)
  IBW (male) = 50 kg + 0.9 kg/cm over 152 cm height
  IBW (female) = 45.5 kg + 0.9 kg/cm over 152 cm height

Following administration of a single dose of VIBATIV 7.5 mg/kg to subjects with end-stage renal disease, approximately 5.9% of the administered dose of telavancin was recovered in the dialysate following 4 hours of hemodialysis. The effects of peritoneal dialysis have not been studied.

Following a single intravenous dose of VIBATIV 7.5 mg/kg, the clearance of hydroxypropyl-beta-cyclodextrin was reduced in subjects with renal impairment, resulting in a higher exposure to hydroxypropyl-beta-cyclodextrin. In subjects with mild, moderate, and severe renal impairment, the mean clearance values were 38%, 59%, and 82% lower, respectively, compared with subjects with normal renal function. Multiple infusions of VIBATIV may result in accumulation of hydroxypropyl-beta-cyclodextrin.

Hepatic Impairment

The pharmacokinetics of telavancin were not altered in subjects with moderate hepatic impairment (n= 8, Child-Pugh B) compared with healthy subjects with normal hepatic function matched for gender, age, and weight. The pharmacokinetics of telavancin have not been evaluated in patients with severe hepatic impairment (Child-Pugh C).

Drug Interactions

In Vitro

The inhibitory activity of telavancin against the following CYP 450 enzymes was evaluated in human liver microsomes: CYP 1A2, 2C9, 2C19, 2D6, and 3A4/5. Telavancin inhibited CYP 3A4/5 at potentially clinically relevant concentrations. Upon further evaluation in a Phase 1 clinical trial, telavancin was found not to inhibit the metabolism of midazolam, a sensitive CYP3A substrate (see below).

Midazolam

The impact of telavancin on the pharmacokinetics of midazolam (CYP 3A4/5 substrate) was evaluated in 16 healthy adult subjects following administration of a single dose of VIBATIV 10 mg/kg, intravenous midazolam 1 mg, and both. The results showed that telavancin had no impact on the pharmacokinetics of midazolam and midazolam had no effect on the pharmacokinetics of telavancin.

Aztreonam

The impact of telavancin on the pharmacokinetics of aztreonam was evaluated in 11 healthy adult subjects following administration of a single dose of VIBATIV 10 mg/kg, aztreonam 2 g, and both. Telavancin had no impact on the pharmacokinetics of aztreonam and aztreonam had no effect on the pharmacokinetics of telavancin. No dosage adjustment of telavancin or aztreonam is recommended when both drugs are coadministered.

Piperacillin-tazobactam

The impact of telavancin on the pharmacokinetics of piperacillin-tazobactam was evaluated in 12 healthy adult subjects following administration of a single dose of VIBATIV 10 mg/kg, piperacillin-tazobactam 4.5 g, and both. Telavancin had no impact on the pharmacokinetics of piperacillin-tazobactam and piperacillin-tazobactam had no effect on the pharmacokinetics of telavancin. No dosage adjustment of telavancin or piperacillin-tazobactam is recommended when both drugs are coadministered.

12.4 Microbiology

Telavancin is a semisynthetic, lipoglycopeptide antibiotic. Telavancin exerts concentration-dependent, bactericidal activity against Gram-positive organisms in vitro, as demonstrated by time-kill assays and MBC/MIC (minimum bactericidal concentration/minimum inhibitory concentration) ratios using broth dilution methodology. In vitro studies demonstrated a telavancin post-antibiotic effect ranging from 1 to 6 hours against S. aureus and other Gram-positive pathogens.

Mechanism of Action

Telavancin inhibits cell wall biosynthesis by binding to late-stage peptidoglycan precursors, including lipid II. Telavancin also binds to the bacterial membrane and disrupts membrane barrier function.

Interactions with Other Antibacterial Drugs

In vitro investigations demonstrated no antagonism between telavancin and amikacin, aztreonam, cefepime, ceftriaxone, ciprofloxacin, gentamicin, imipenem, meropenem, oxacillin, piperacillin/tazobactam, rifampin, and trimethoprim/sulfamethoxazole when tested in various combinations against telavancin-susceptible staphylococci, streptococci, and enterococci. This information is not available for other bacteria.

Cross-Resistance

Some vancomycin-resistant enterococci have a reduced susceptibility to telavancin. There is no known cross-resistance between telavancin and other classes of antibacterial drugs.

Antibacterial Activity

Telavancin has been shown to be active against most isolates of the following microorganisms both in vitro and in clinical infections as described in the Indications and Usage section [see Indications and Usage (1)]:

Facultative Gram-Positive Microorganisms

•   Staphylococcus aureus (including methicillin-resistant isolates)
•   Enterococcus faecalis (vancomycin-susceptible isolates only)
•   Streptococcus agalactiae
•   Streptococcus anginosus group (includes S. anginosus, S. intermedius, and S. constellatus)
•   Streptococcus pyogenes

Greater than 90% of the following microorganisms exhibit an in vitro MIC less than or equal to the telavancin-susceptible breakpoint for organisms of similar genus shown in Table 9. The safety and effectiveness of telavancin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

Facultative Gram-Positive Microorganisms

•   Enterococcus faecium (vancomycin-susceptible isolates only)
•   Staphylococcus haemolyticus
•   Streptococcus dysgalactiae subsp. equisimilis
•   Staphylococcus epidermidis

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide cumulative results of the in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antimicrobial drug.

Dilution technique

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure [see References (15)]. Standardized procedures are based on a broth dilution method or equivalent with standardized inoculum concentrations and standardized concentrations of telavancin powder. The test method treats telavancin as a water-insoluble agent. Dimethyl sulfoxide is used as solvent and diluent, and the cation-adjusted Mueller Hinton Broth test medium is supplemented with polysorbate 80 to a final concentration of 0.002%. Telavancin should not be tested by the agar dilution method. The MIC values should be interpreted according to the criteria provided in Table 9.

Diffusion technique

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure requires the use of standardized inoculum concentrations [see References (15)]. This procedure uses paper disks impregnated with 30 mcg of telavancin to test the susceptibility of microorganisms to telavancin. The disk diffusion interpretive criteria are provided in Table 9.

A report of “susceptible" indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound in the blood reaches the concentrations usually achievable.

Quality Control

Standardized susceptibility test procedures require the use of laboratory control microorganisms to monitor the performance of the supplies and reagents used in the assay, and the techniques of the individuals performing the test [see References (15)]. Standard telavancin powder should provide the range of values noted in Table 10.

Quality control microorganisms are specific strains of organisms with intrinsic biological properties relating to resistance mechanisms and their genetic expression within bacteria; the specific strains used for microbiological quality control are not clinically significant.

13 NONCLINICAL TOXICOLOGY

13.1 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.

13.2 Animal Toxicology and/or Pharmacology

Two-week administration of telavancin in rats produced minimal renal tubular vacuolization with no changes in BUN or creatinine. These effects were not seen in studies conducted in dogs for similar duration. Four weeks of treatment resulted in reversible elevations in BUN and/or creatinine in association with renal tubular degeneration that further progressed following 13 weeks of treatment.

These effects occurred at exposures (based on AUCs) that were similar to those measured in clinical trials.

The potential effects of continuous venovenous hemofiltration (CVVH) on the clearance of telavancin were examined in an in vitro model using bovine blood. Telavancin was cleared by CVVH and the clearance of telavancin increased with increasing ultrafiltration rate [see Overdosage (10)].

14 CLINICAL TRIALS

14.1 Complicated Skin and Skin Structure Infections

Adult patients with clinically documented complicated skin and skin structure infections (cSSSI) were enrolled in two randomized, multinational, multicenter, double-blinded trials (Trial 1 and Trial 2) comparing VIBATIV (10 mg/kg IV every 24 hours) with vancomycin (1 g IV every 12 hours) for 7 to 14 days. Vancomycin dosages could be adjusted per site-specific practice. Patients could receive concomitant aztreonam or metronidazole for suspected Gram-negative and anaerobic infection, respectively. These trials were identical in design, enrolling approximately 69% of their patients from the United States.

The trials enrolled adult patients with cSSSI with suspected or confirmed MRSA as the primary cause of infection. The all-treated efficacy (ATe) population included all patients who received any amount of study medication according to their randomized treatment group and were evaluated for efficacy. The clinically evaluable population (CE) included patients in the ATe population with sufficient adherence to the protocol.

The ATe population consisted of 1,794 patients. Of these, 1,410 (79%) patients were clinically evaluable (CE). Patient baseline infection types were well-balanced between treatment groups and are presented in Table 11.

The primary efficacy endpoints in both trials were the clinical cure rates at a follow-up (Test of Cure) visit in the ATe and CE populations. Clinical cure rates in Trials 1 and 2 are displayed for the ATe and CE population in Table 12.

The cure rates by pathogen for the microbiologically evaluable (ME) population are presented in Table 13.

In the two cSSSI trials, clinical cure rates were similar across gender and race. Clinical cure rates in the VIBATIV clinically evaluable (CE) population were lower in patients ≥65 years of age compared with those <65 years of age. A decrease of this magnitude was not observed in the vancomycin CE population. Clinical cure rates in the VIBATIV CE population <65 years of age were 503/581 (87%) and in those ≥65 years were 88/122 (72%). In the vancomycin CE population clinical cure rates in patients <65 years of age were 492/570 (86%) and in those ≥65 years was 111/137 (82%). Clinical cure rates in the VIBATIV-treated patients were lower in patients with baseline CrCl ≤50 mL/min compared with those with CrCl >50 mL/min. A decrease of this magnitude was not observed in the vancomycin-treated patients [see Warnings and Precautions (5.2)].

14.2 HABP/VABP

Adult patients with hospital-acquired and ventilator-associated pneumonia were enrolled in two randomized, parallel-group, multinational, multicenter, double-blinded trials of identical design comparing VIBATIV (10 mg/kg IV every 24 hours) with vancomycin (1 g IV every 12 hours) for 7 to 21 days. Vancomycin dosages could be adjusted for body weight and/or renal function per local guidelines. Patients could receive concomitant aztreonam or metronidazole for suspected Gram-negative and anaerobic infection, respectively. The addition of piperacillin/tazobactam was also permitted for coverage of Gram-negative organisms if resistance to aztreonam was known or suspected. Patients with known or suspected infections due to methicillin-resistant Staphylococcus aureus were enrolled in the studies.

Of the patients enrolled across both trials, 64% were male and 70% were white.The mean age was 63 years. At baseline, more than 50% were admitted to an intensive care unit, about 23% had chronic obstructive pulmonary disease, about 29% had ventilator-associated pneumonia and about 6% had bacteremia. Demographic and baseline characteristics were generally well-balanced between treatment groups; however, there were differences between HABP/VABP Trial 1 and HABP/VABP Trial 2 with respect to a baseline history of diabetes mellitus (31% in Trial 1, 21% in Trial 2) and baseline renal insufficiency (CrCl ≤ 50 mL/min) (36% in Trial 1, 27% in Trial 2).

All-cause mortality was evaluated because there is historical evidence of treatment effect for this endpoint. This was a protocol pre-specified secondary endpoint. The 28-day all-cause mortality outcomes(overall and by baseline creatinine clearance categorization) in the group of patients who had at least one baseline Gram-positive respiratory pathogen are shown in Table 14. This group of patients included those who had mixed Gram-positive/Gram-negative infections.

The protocol-specified analysis included clinical cure rates at the TOC (7 to 14 days after the last dose of study drug) in the co-primary All-Treated (AT) and Clinically Evaluable (CE) populations (Table 15). Clinical cure was determined by resolution of signs and symptoms, no further antibacterial therapy for HABP/VABP after end-of-treatment, and improvement or no progression of baseline radiographic findings. However, the quantitative estimate of treatment effect for this endpoint has not been established.

15 REFERENCES

• Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard - Ninth Edition. CLSI document M07-A9, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012.
• Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard – Eleventh Edition. CLSI document M02-A11, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012.
• Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-fourth Informational Supplement, CLSI document M100-S24, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2014.

16 HOW SUPPLIED/STORAGE AND HANDLING

• Cartons of 10 individually packaged 250 mg single-dose vials (NDC 52118-002-01)
• Cartons of 10 individually packaged 750 mg single-dose vials (NDC 52118-001-01)

Store original packages at refrigerated temperatures of 2 to 8°C (35 to 46 °F). Excursions to ambient temperatures (up to 25 °C (77 °F)) are acceptable. Avoid excessive heat.

17 PATIENT COUNSELING 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 is used during pregnancy
• Have a pregnancy test prior to administration of VIBATIV
• If not pregnant, use effective contraceptive methods to prevent pregnancy during VIBATIV treatment
• Notify their prescribing physician/ healthcare provider if they become pregnant during VIBATIV treatment

Pregnancy Registry

There is a pregnancy registry that monitors pregnancy outcomes in women exposed to VIBATIV during pregnancy. Physicians are encouraged to register pregnant patients, or pregnant women may enroll themselves in the pregnancy registry by calling 1-855-MED-THRX (1-855-633-8479).

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 should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When VIBATIV 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 or other antibacterial drugs in the future.

Common Adverse Effects

Patients should be informed about the common adverse effects of VIBATIV including diarrhea, 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, including over-the-counter medications.

Manufactured for:
Theravance, Inc.
South San Francisco, CA  94080

US Patent Nos. 6,635,618 B2; 6,858,584 B2; 6,872,701 B2; 7,008,923 B2; 7,208,471 B2; 7,351,691 B2; 7,531,623 B2; 7,544,364 B2; 7,700,550 B2; 8,101,575 B2; 8,158,580 B2.

THERAVANCE^®, the Theravance logo, and VIBATIV^® are registered trademarks of Theravance, Inc.

MEDICATION GUIDE
VIBATIV ^® (vy-'ba-tiv)
(telavancin)
for injection

Read this Medication Guide before you receive VIBATIV. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about VIBATIV?

VIBATIV can cause serious side effects, including:

• Increased risk of death. VIBATIV was associated with an increased risk of death compared to vancomycin in people who already had kidney problems and were treated for bacterial pneumonia that you can get when you are in the hospital.
• New or worsening kidney problems. Your healthcare provider should do a blood test to check your kidneys before you start, while you receive, and after you stop receiving VIBATIV.
• VIBATIV may harm your unborn baby. Women who can become pregnant should have a blood pregnancy test before receiving VIBATIV.
  • Talk to your healthcare provider if you are pregnant or plan to become pregnant. Your healthcare provider will decide if VIBATIV is the right medicine for you.
  • Women who can become pregnant should use effective birth control (contraception) while receiving VIBATIV.
  • If you become pregnant while receiving VIBATIV, tell your healthcare provider right away. Talk to your healthcare provider about taking part in the VIBATIV Pregnancy Registry. This is a study to learn how VIBATIV affects pregnancy and babies. You can enroll in this registry by calling 1-855-MED-THRX (1-855-633-8479).

What is VIBATIV?

VIBATIV is a prescription antibacterial medicine used alone, or with other medicines, to treat adults with certain types of germs (bacteria) that cause:

• Serious skin infections
• Hospital-Acquired Bacterial Pneumonia (HABP)
• Ventilator-Associated Bacterial Pneumonia (VABP)

It is not known if VIBATIV is safe or effective in children under 18 years of age.

Who should not take VIBATIV?

Do not take VIBATIV if you:

• are allergic to telavancin or any of the ingredients in VIBATIV. See the end of this Medication Guide for a complete list of ingredients in VIBATIV.

What should I tell my healthcare provider before receiving VIBATIV?

Before you receive VIBATIV, tell your healthcare provider if you:

• have had a serious allergic reaction to VIBATIV or vancomycin
• have kidney problems
• have diabetes
• have or have had heart problems, including QTc prolongation or a family history of it
• have high blood pressure
• have any other medical conditions
• are breastfeeding or plan to breastfeed. It is not known if VIBATIV passes into breast milk. You and your healthcare provider should decide if you will breastfeed while receiving VIBATIV.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. VIBATIV and other medicines can affect each other causing side effects.

Especially tell your healthcare provider if you take:

• a Non-Steroidal Anti-Inflammatory Drug (NSAID)
• certain blood pressure medicines called ACE Inhibitors or ARBs
• water pills (diuretics)
• a blood thinner
• medicine to control your heart rate or rhythm (antiarrhythmics)

Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure.

Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.

How will I receive VIBATIV?

• VIBATIV is given by your healthcare provider through a needle placed into your vein (IV infusion) slowly over 1 hour, 1 time each day, for 7 to 21 days.
• Do not stop receiving VIBATIV unless your healthcare provider tells you to, even if you feel better.
• Your healthcare provider will do blood tests before you start and while you receive VIBATIV.

What are the possible side effects of VIBATIV?

VIBATIV may cause serious side effects, including:

See “What is the most important information I should know about VIBATIV?”

• Serious allergic reactions. Allergic reactions can happen in people who take VIBATIV, even after only one dose. Stop taking VIBATIV and get emergency medical help right away if you get any of the following symptoms of a severe allergic reaction:
  • hives
  • trouble breathing or swallowing
  • swelling of the lips, tongue, face
  • throat tightness, hoarseness
  • rapid heartbeat
  • faint
• Infusion-related reactions. People who receive VIBATIV too quickly can have a certain type of skin reaction called “Red-man Syndrome”. Signs and symptoms of Red-man Syndrome can include:
  • red color (flushing)
  • rash
  • itching
• Problems with the electrical system of your heart (QTc prolongation). Tell your healthcare provider right away if you have a change in your heartbeat such as a fast or irregular heartbeat or if you had a fainting episode.

Call your healthcare provider right away if you have any of the serious side effects listed above.

The most common side effects of VIBATIV include:

• change in your sense of taste
• nausea
• vomiting
• foamy urine
• diarrhea

Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of VIBATIV. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store VIBATIV?

• Store VIBATIV in the original package
• Keep VIBATIV refrigerated between 35°F to 46°F (2°C to 8°C)
• Keep out of heat

Keep VIBATIV and all medicines out of the reach of children.

General Information about the safe and effective use of VIBATIV.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use VIBATIV for a condition for which it is not prescribed.

This Medication Guide summarizes the most important information about VIBATIV. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about VIBATIV that is written for health professionals.

For more information, go to www.vibativ.com or call 1-855-MED-THRX (1-855-633-8479).

What are the ingredients in VIBATIV?

Active ingredient: telavancin hydrochloride

Inactive ingredients: hydroxypropylbetadex, Ph. Eur (hydroxypropyl-beta-cyclodextrin), mannitol, sodium hydroxide and hydrochloric acid

This Medication Guide has been approved by the U.S. Food and Drug Administration

Manufactured for:

Theravance, Inc.

South San Francisco, CA 94080

VIBATIV^® is a registered trademark of Theravance, Inc.

Revised: 06/2013

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 250 MG/VIAL UNIT CARTON

NDC 52118-002-01

1 Carton containing 1 Vial of 250 mg

Vibativ^®

(telavancin hydrochloride)

Equivalent to 250 mg telavancin per vial

Rx only

Theravance, Inc.