Oritavancin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gloria Picoy [2]
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Overview
Oritavancin is an antibiotic that is FDA approved for the treatment of acute bacterial skin and skin structure infections caused by Gram-positive microorganisms. Common adverse reactions include nausea, vomiting and headache
limb and subcutaneous abscesses, and diarrhea.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Acute Bacterial Skin and Skin Structure Infections
- Oritavancin is indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive microorganisms:
- Staphylococcus aureus (including methicillin-susceptible and methicillin–resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus group (includes S. anginosus, S. intermedius, and S. constellatus), and Enterococcus faecalis (vancomycin-susceptible isolates only).
- Dosage: a single 1200 mg dose administered by intravenous infusion over 3 hours
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Oritavancin in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Oritavancin in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Safety and efficacy are not established in pediatric patients
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Oritavancin in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Oritavancin in pediatric patients.
Contraindications
Intravenous Unfractionated Heparin Sodium
Use of intravenous unfractionated heparin sodium is contraindicated for 48 hours after ORBACTIV administration because the activated partial thromboplastin time (aPTT) test results are expected to remain falsely elevated for approximately 48 hours after ORBACTIV administration.
Hypersensitivity
ORBACTIV is contraindicated in patients with known hypersensitivity to ORBACTIV.
Warnings
Potential Risk of Bleeding with Concomitant Use of Warfarin
Co-administration of ORBACTIV and warfarin may result in higher exposure of warfarin, which may increase the risk of bleeding. Use ORBACTIV in patients on chronic warfarin therapy only when the benefits can be expected to outweigh the risk of bleeding. Frequently monitor for signs of bleeding.
ORBACTIV has been shown to artificially prolong PT and INR for up to 24 hours, making the monitoring of the anticoagulation effect of warfarin unreliable up to 24 hours after an ORBACTIV dose.
Coagulation Test Interference
ORBACTIV has been shown to artificially prolong aPTT for 48 hours and the PT and INR for 24 hours by binding to and preventing action of the phospholipid reagents which activate coagulation in commonly used laboratory coagulation tests.
For patients who require aPTT monitoring within 48 hours of ORBACTIV dosing, a non-phospholipid dependent coagulation test such as a Factor Xa (chromogenic) assay or an alternative anticoagulant not requiring aPTT monitoring may be considered.
Effects by ORBACTIV on activated clotting time (ACT) are expected since the phospholipid reagents are also utilized in this coagulation test. ORBACTIV has no effect on the coagulation system.
Hypersensitivity
Serious hypersensitivity reactions have been reported with the use of ORBACTIV. If an acute hypersensitivity reaction occurs during ORBACTIV infusion, discontinue ORBACTIV immediately and institute appropriate supportive care. Before using ORBACTIV, inquire carefully about previous hypersensitivity reactions to glycopeptides. Due to the possibility of cross-sensitivity, carefully monitor for signs of hypersensitivity during ORBACTIV infusion in patients with a history of glycopeptide allergy. In the Phase 3 ABSSSI clinical trials, the median onset of hypersensitivity reactions in ORBACTIV-treated patients was 1.2 days and the median duration of these reactions was 2.4 days.
Infusion Related Reactions
Infusion related reactions have been reported with ORBACTIV including pruritus, urticaria or flushing. If reactions do occur, consider slowing or interrupting ORBACTIV infusion.
Clostridium difficile-associated Diarrhea
Clostridium difficile-associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial drugs, including ORBACTIV, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal 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, as these infections can be refractory to antibacterial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial 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, antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Osteomyelitis
In Phase 3 ABSSSI clinical trials, more cases of osteomyelitis were reported in the ORBACTIV treated arm than in the vancomycin-treated arm. Monitor patients for signs and symptoms of osteomyelitis. If osteomyelitis is suspected or diagnosed, institute appropriate alternate antibacterial therapy}.
Development of Drug Resistant Bacteria
Prescribing ORBACTIV 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.
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Oritavancin Clinical Trials Experience in the drug label.
Postmarketing Experience
There is limited information regarding Oritavancin Postmarketing Experience in the drug label.
Drug Interactions
Effect of ORBACTIV on CYP Substrates
A cocktail drug-drug interaction study was conducted in healthy volunteers (n=16) evaluating the concomitant administration of a single 1200 mg dose of ORBACTIV with probe substrates for several CYP450 enzymes. ORBACTIV was found to be a nonspecific, weak inhibitor (CYP2C9 and CYP2C19) or inducer (CYP3A4 and CYP2D6) of several CYP isoforms.
Caution should be used when administering ORBACTIV concomitantly with drugs with a narrow therapeutic window that are predominantly metabolized by one of the affected CYP450 enzymes (e.g., warfarin), as co-administration may increase (e.g. for CYP2C9 substrates) or decrease (e.g. for CYP2D6 substrates) concentrations of the narrow therapeutic range drug. Patients should be closely monitored for signs of toxicity or lack of efficacy if they have been given ORBACTIV while on a potentially affected compound (e.g. patients should be monitored for bleeding if concomitantly receiving ORBACTIV and warfarin).
Drug-Laboratory Test Interactions
ORBACTIV has been shown to artificially prolong aPTT for 48 hours and PT and INR for up to 24 hours by binding to and preventing action of the phospholipid reagents which activate coagulation in commonly used laboratory coagulation tests. Effects by ORBACTIV on ACT are expected since the phospholipid reagents are also utilized in this coagulation test. ORBACTIV has no effect on the coagulation system.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): C Reproduction studies performed in rats and rabbits have revealed no evidence of harm to the fetus due to oritavancin at the highest concentrations administered, 30 mg/kg/day and 15 mg/kg/day, respectively. Those daily doses would be equivalent to a human dose of 300 mg, or 25% of the single clinical dose of 1200 mg. Higher doses were not evaluated in nonclinical developmental and reproductive toxicology studies.
There are no adequate and well-controlled trials in pregnant women. ORBACTIV should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Oritavancin in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Oritavancin during labor and delivery.
Nursing Mothers
It is unknown whether oritavancin is excreted in human milk. Following a single intravenous infusion in lactating rats, radio-labeled [14C]-oritavancin was excreted in milk and absorbed by nursing pups. Caution should be exercised when ORBACTIV is administered to a nursing woman.
Pediatric Use
Safety and effectiveness of ORBACTIV in pediatric patients (younger than 18 years of age) has not been studied.
Geriatic Use
The pooled Phase 3 ABSSSI clinical trials of ORBACTIV did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Gender
There is no FDA guidance on the use of Oritavancin with respect to specific gender populations.
Race
There is no FDA guidance on the use of Oritavancin with respect to specific racial populations.
Renal Impairment
No dosage adjustment of ORBACTIV is needed in patients with mild or moderate renal impairment. The pharmacokinetics of ORBACTIV in severe renal impairment have not been evaluated. ORBACTIV is not removed from blood by hemodialysis.
Hepatic Impairment
No dosage adjustment of ORBACTIV is needed in patients with mild or moderate hepatic impairment. The pharmacokinetics of ORBACTIV in patients with severe hepatic insufficiency has not been studied.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Oritavancin in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Oritavancin in patients who are immunocompromised.
Administration and Monitoring
Administration
Intravenous
Monitoring
There is limited information regarding Oritavancin Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Oritavancin and IV administrations.
Overdosage
In the ORBACTIV clinical program there was no incidence of accidental overdose of ORBACTIV.
Based on an in vitro hemodialysis study, ORBACTIV is unlikely to be removed from blood by hemodialysis. In the event of overdose, supportive measures should be taken.
Pharmacology
There is limited information regarding Oritavancin Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Oritavancin Mechanism of Action in the drug label.
Structure
There is limited information regarding Oritavancin Structure in the drug label.
Pharmacodynamics
The antimicrobial activity of oritavancin appears to correlate with the ratio of area under the concentration-time curve to minimal inhibitory concentration (AUC/MIC) based on animal models of infection.
Exposure-response analyses from both preclinical and clinical studies support the treatment of clinically relevant Gram-positive microorganisms (e.g. S. aureus and S. pyogenes) causative of ABSSSI with a single 1200 mg dose of ORBACTIV.
Cardiac Electrophysiology
In a thorough QTc study of 135 healthy subjects at a dose 1.3 times the 1200 mg recommended dose, ORBACTIV did not prolong the QTc interval to any clinically relevant extent.
Pharmacokinetics
There is limited information regarding Oritavancin Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Oritavancin Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Oritavancin Clinical Studies in the drug label.
How Supplied
There is limited information regarding Oritavancin How Supplied in the drug label.
Storage
There is limited information regarding Oritavancin Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Oritavancin Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Oritavancin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
- Orbactiv
Look-Alike Drug Names
There is limited information regarding Oritavancin Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.
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| Formula | C86H97Cl3N10O26 |
| Molar mass | 1793.1 g/mol |
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Oritavancin (INN, also known as LY333328) is an investigational glycopeptide antibiotic with bactericidal activity effective in treating infections caused by Gram-positive organisms. It treats complicated skin and skin structure infections. This new drug will be tested for treatment of bacteraemia and nosocomial pneumonia.
It demonstrates similar activity to vancomycin, but it has stronger activity against Staphylococcus and Enterococcus. The pharmacokinetics and pharmacodynamics of oritavancin appear to be favourable and once-daily dosing is likely. The incidence of multi-drug resistant bacteria is increasing and explorations into additional treatment options are essential. The clinical efficacy of oritavancin has not yet been determined.
References
- Ward K, Mersfelder T, LaPlante K (2006). "Oritavancin--an investigational glycopeptide antibiotic". Expert Opin Investig Drugs. 15 (4): 417&ndash, 29. PMID 16548791.
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- Glycopeptide antibiotics