"The U.S. Food and Drug Administration today approved Orbactiv (oritavancin), a new antibacterial drug to treat adults with skin infections.
Orbactiv is approved to treat patients with acute bacterial skin and skin structure infections (ABSS"...
Increased Mortality In Patients With HABP/VABP And Pre-existing Moderate To Severe Renal Impairment (CrCl ≤ 50 mL/min)
In the analysis of patients (classified by the treatment received) in the two combined HABP/VABP trials with pre-existing moderate/severe renal impairment (CrCl ≤ 50 mL/min), all-cause mortality within 28 days of starting treatment was 95/241 (39%) in the VIBATIV group, compared with 72/243 (30%) in the vancomycin group. All-cause mortality at 28 days in patients without pre-existing moderate/severe renal impairment (CrCl > 50 mL/min) was 86/510 (17%) in the VIBATIV group and 92/510 (18%) in the vancomycin group. Therefore, VIBATIV use in patients with baseline CrCl ≤ 50 mL/min should be considered only when the anticipated benefit to the patient outweighs the potential risk [see ADVERSE REACTIONS, Clinical Trials Experience and Clinical Trials, HABP/VABP].
Decreased Clinical Response In Patients With cSSSI And Pre-existing Moderate/Severe Renal Impairment (CrCl ≤ 50 mL/min)
In a subgroup analysis of the combined cSSSI trials, clinical cure rates in the VIBATIVtreated patients were lower in patients with baseline CrCl ≤ 50 mL/min compared with 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 cSSSI and with baseline moderate/severe renal impairment.
Table 2: Clinical Cure by Pre-existing Renal
Impairment - Clinically Evaluable Population
|CrCl > 50 mL/min||87.0% (520/598)||85.9% (524/610)|
|CrCl ≤ 50 mL/min||67.4% (58/86)||82.7% (67/81)|
In both the HABP/VABP trials and the cSSSI trials, renal 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 rates were also higher in patients who received concomitant medications known to affect kidney function (e.g., non-steroidal antiinflammatory drugs, ACE inhibitors, and loop diuretics).
Monitor renal function (i.e., serum creatinine, creatinine clearance) in all patients receiving VIBATIV. 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 versus discontinuing and initiating therapy with an alternative agent should be assessed [see DOSAGE AND ADMINISTRATION, ADVERSE REACTIONS, and CLINICAL PHARMACOLOGY].
In patients with renal dysfunction, accumulation of the solubilizer hydroxypropyl-betacyclodextrin can occur [see Patients with Renal Impairment and CLINICAL PHARMACOLOGY].
Pregnant Women And Women Of Childbearing Potential
Avoid use of VIBATIV during pregnancy unless the potential benefit to the patient outweighs the potential risk to the fetus. VIBATIV caused adverse developmental outcomes in 3 animal species at clinically relevant doses. This raises concern about potential adverse developmental outcomes in humans.
Women of childbearing potential should have a serum pregnancy test prior to administration of VIBATIV. If not already pregnant, women of childbearing potential should use effective contraception during VIBATIV treatment [see Use In Specific Populations].
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 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. Blood samples for coagulation tests unaffected by VIBATIV may be collected at any time [see DRUG INTERACTIONS].
For patients who require aPTT monitoring while being treated with VIBATIV, a non phospholipid dependent coagulation test such as a Factor Xa (chromogenic) assay or an alternative anticoagulant not requiring aPTT monitoring may be considered.
Table 3: Coagulation Tests Affected and Unaffected by
|Affected by Telavancin||Unaffected by Telavancin|
|Prothrombin time/international normalized ratio||Thrombin time|
|Activated partial thromboplastin time||Whole blood (Lee-White) clotting time|
|Activated clotting time||Platelet aggregation study|
|Coagulation based factor X activity assay||Chromogenic anti-factor Xa assay|
|Functional (chromogenic) factor X activity assay|
|Fibrin degradation products|
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 have normal levels of D-dimer and fibrin degradation products.
Serious and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, may occur after first or subsequent doses. Discontinue VIBATIV at first sign of skin rash, or any other sign of hypersensitivity. Telavancin is a semi-synthetic derivative of vancomycin; it is unknown if patients with hypersensitivity reactions to vancomycin will experience crossreactivity to telavancin. VIBATIV should be used with caution in patients with known hypersensitivity to vancomycin [see Postmarketing Experience].
VIBATIV 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. Hypertoxin- 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 more than 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 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 may result in overgrowth of nonsusceptible organisms, including fungi. Patients should be carefully monitored during therapy. If superinfection occurs, appropriate measures should be taken.
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 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. Use of VIBATIV should be avoided in patients with these conditions.
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
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 1-855-6338479.
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.
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 Category C
Pregnancy Exposure 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 VIBATIV pregnancy registry by calling 1-855633- 8479.
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 use in pregnant women. In 3 animal species, VIBATIV 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).
Given the lack of human data and the risks suggested by animal data, avoid using VIBATIV in pregnant women unless the benefits to the patient outweigh the potential risks to thefetus.
There are no data on human pregnancies exposed to VIBATIV.
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.
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 is administered to a nursing woman.
The safety and effectiveness of VIBATIV in pediatric patients has not been studied.
Of the 929 patients treated with VIBATIV at a dose of 10 mg/kg once daily in clinical trials of cSSSI, 174 (19%) were ≥ 65 years of age and 87 (9%) 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 (9%) patients ≥ 65 years of age treated with VIBATIV had adverse events indicative of renal impairment compared with 16 of 755 (2%) patients < 65 years of age [see WARNINGS AND PRECAUTIONS, Clinical Trials].
Of the 749 HABP/VABP patients treated with VIBATIV at a dose of 10 mg/kg once daily in clinical trials of HABP/VABP, 397 (53%) were ≥ 65 years of age and 230 (31%) were ≥ 75 years of age. 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 treatment groups.
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 HABP/VABP and 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].
In the HABP/VABP studies higher mortality rates were observed in the VIBATIV-treated patients with baseline CrCl ≤ 50 mL/min. Use of VIBATIV in patients with pre-existing moderate/severe renal impairment should be considered only when the anticipated benefit to the patient outweighs the potential risk [see WARNINGS AND PRECAUTIONS].
VIBATIV-treated patients in the cSSSI studies with baseline creatinine clearance ≤ 50 mL/min had lower clinical cure rates. Consider these data when selecting antibacterial therapy in patients with baseline moderate/severe renal impairment (CrCl ≤ 50 mL/min) [see WARNINGS AND PRECAUTIONS].
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 HABP/VABP and 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].This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 12/19/2014
Additional Vibativ Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.