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Medicines公司8月6日宣布，FDA已批准抗生素Orbactiv（oritavancin，奥利万星，IV）注射液，用于由敏感革兰氏阳性菌（包括耐甲氧西林金黄色葡萄球菌，MRSA）导致的急性细菌性皮肤和皮肤结构感染（ABSSSIs）成人患者的治疗。Orbactiv是FDA批准用于ABSSSIs治疗的首个和唯一一种单剂量治疗方案的抗生素。患者仅接受一次Orbactiv输液，整个治疗方案便已结束。此次Orbactiv的获批，也代表着细菌性皮肤和皮肤结构感染疾病治疗方面远超当前临床标准的重大进步。目前，患者往往需要多次静脉输注抗生素，而Orbactiv单剂量治疗方案，将显著减少患者的剂量负担。
ORBACTIV is a lipoglycopeptide antibacterial drug indicated for the treatment of adult patients with acute bacterial skin and skin structure infections caused or suspected to be caused by susceptible isolates of designated Gram-positive microorganisms. (1.1) To reduce the development of drug-resistant bacteria and maintain the effectiveness of ORBACTIV and other antibacterial drugs, ORBACTIV should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. (1.2) DOSAGE AND ADMINISTRATION A 1200 mg single dose is administered by intravenous infusion over 3 hours. (2.1) DOSAGE FORMS AND STRENGTHS For injection: 400 mg of lyophilized powder in a single-use vial for reconstitution. (3) CONTRAINDICATIONS Use of intravenous unfractionated heparin sodium is contraindicated for 120 hours (5 days) after ORBACTIV administration. (4.1, 5.2) Known hypersensitivity to ORBACTIV (4.2, 5.3) WARNINGS AND PRECAUTIONS Concomitant warfarin use: 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. (5.1) Coagulation test interference: ORBACTIV has been shown to artificially prolong aPTT for up to 120 hours, and may prolong PT and INR for up to 12 hours and ACT for up to 24 hours. For patients who require aPTT monitoring within 120 hours of ORBACTIV dosing, consider a non phospholipid dependent coagulation test such as a Factor Xa (chromogenic) assay or an alternative anticoagulant not requiring aPTT. (5.2, 7.2) Hypersensitivity reactions have been reported with the use of antibacterial agents including ORBACTIV. Discontinue infusion if signs of acute hypersensitivity occur. Monitor closely patients with known hypersensitivity to glycopeptides. (5.3) Infusion-related reactions have been reported. Slow the rate or interrupt infusion if infusion reaction develops. (5.4) Clostridium difficile-associated diarrhea: Evaluate patients if diarrhea occurs. (5.5) Osteomyelitis: Institute appropriate alternate antibacterial therapy in patients with confirmed or suspected osteomyelitis. (5.6) ADVERSE REACTIONS The most common adverse reactions (≥ 3%) in patients treated with ORBACTIV were headache, nausea, vomiting, limb and subcutaneous abscesses, and diarrhea. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact The Medicines Company at 1-888-977-6326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. See 17 for PATIENT COUNSELING INFORMATION. Revised: 1/2016 FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 1.1 Acute Bacterial Skin and Skin Structure Infections ORBACTIV® (oritavancin) for injection 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). 1.2 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of ORBACTIV and other antibacterial drugs, ORBACTIV should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosage The recommended dosing for ORBACTIV is a single 1200 mg dose administered by intravenous infusion over 3 hours in patients 18 years and older. 2.2 Preparation of ORBACTIV for Intravenous Infusion ORBACTIV is intended for intravenous infusion, only after reconstitution and dilution. Three ORBACTIV 400 mg vials need to be reconstituted and diluted to prepare a single 1200 mg intravenous dose. Reconstitution: Aseptic technique should be used to reconstitute three ORBACTIV 400 mg vials. Add 40 mL of sterile water for injection (WFI) to reconstitute each vial to provide a 10 mg/mL solution per vial. For each vial, gently swirl to avoid foaming and ensure that all ORBACTIV powder is completely reconstituted in solution. Each vial should be inspected visually for particulate matter after reconstitution and should appear to be clear, colorless to pale yellow solution. Dilution: Use ONLY 5% dextrose in sterile water (D5W) for dilution. Do NOT use Normal Saline for dilution as it is incompatible with ORBACTIV and may cause precipitation of the drug. Use aseptic technique to: Withdraw and discard 120 mL from a 1000 mL intravenous bag of D5W. Withdraw 40 mL from each of the three reconstituted vials and add to D5W intravenous bag to bring the bag volume to 1000 mL. This yields a concentration of 1.2 mg/mL. Since no preservative or bacteriostatic agent is present in this product, aseptic technique must be used in preparing the final intravenous solution. Diluted intravenous solution in an infusion bag should be used within 6 hours when stored at room temperature, or used within 12 hours when refrigerated at 2 to 8°C (36 to 46°F). The combined storage time (reconstituted solution in the vial and diluted solution in the bag) and 3 hour infusion time should not exceed 6 hours at room temperature or 12 hours if refrigerated. 2.3 Incompatibilities ORBACTIV is administered intravenously. ORBACTIV should only be diluted in D5W. Do NOT use normal saline for dilution as it is incompatible with ORBACTIV and may cause precipitation of the drug. Therefore other intravenous substances, additives or other medications mixed in normal saline should not be added to ORBACTIV single-use vials or infused simultaneously through the same IV line or through a common intravenous port. In addition, drugs formulated at a basic or neutral pH may be incompatible with ORBACTIV. ORBACTIV should not be administered simultaneously with commonly used intravenous drugs through a common intravenous port. If the same intravenous line is used for sequential infusion of additional medications, the line should be flushed before and after infusion of ORBACTIV with D5W. 3 DOSAGE FORMS AND STRENGTHS ORBACTIV is supplied as sterile, white to off-white lyophilized powder equivalent to 400 mg of oritavancin in a single use 50 mL clear glass vial. 4 CONTRAINDICATIONS 4.1 Intravenous Unfractionated Heparin Sodium Use of intravenous unfractionated heparin sodium is contraindicated for 120 hours (5 days) after ORBACTIV administration because the activated partial thromboplastin time (aPTT) test results may remain falsely elevated for up to 120 hours (5 days) after ORBACTIV administration [see Warnings and Precautions (5.2) and Drug Interactions (7.2)]. 4.2 Hypersensitivity ORBACTIV is contraindicated in patients with known hypersensitivity to ORBACTIV. 5 WARNINGS AND PRECAUTIONS 5.1 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 [see Drug Interactions (7.1), Clinical Pharmacology (12.3)]. ORBACTIV has been shown to artificially prolong prothrombin time (PT) and international normalized ratio (INR) for up to 12 hours, making the monitoring of the anticoagulation effect of warfarin unreliable up to 12 hours after an ORBACTIV dose [see Warnings and Precautions (5.2)]. 5.2 Coagulation Test Interference ORBACTIV has been shown to artificially prolong aPTT for up to 120 hours, PT and INR for up to12 hours, and activated clotting time (ACT) for up to 24 hours following administration of a single 1200 mg dose by binding to and preventing action of the phospholipid reagents commonly used in laboratory coagulation tests. ORBACTIV has also been shown to elevate D dimer concentrations up to 72 hours after ORBACTIV administration. For patients who require aPTT monitoring within 120 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 [see Contraindications (4.1) and Drug Interactions (7.2)]. ORBACTIV has no effect on the coagulation system in vivo. 5.3 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 [see Adverse Reactions (6.1)]. 5.4 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 [see Adverse Reactions (6.1)]. 5.5 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. 5.6 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 [see Adverse Reactions (6.1)]. 5.7 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 [see Patient Counseling Information (17)]. 6 ADVERSE REACTIONS The following adverse reactions are also discussed in the Warnings and Precautions section of labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.3)] Infusion Related Reactions [see Warnings and Precautions (5.4)] Clostridium difficile-associated Diarrhea [see Warnings and Precautions (5.5)] Osteomyelitis [see Warnings and Precautions (5.6)] 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of ORBACTIV cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. ORBACTIV has been evaluated in two, double-blind, controlled ABSSSI clinical trials, which included 976 adult patients treated with a single 1200 mg intravenous dose of ORBACTIV and 983 patients treated with intravenous vancomycin for 7 to 10 days. The median age of patients treated with ORBACTIV was 45.6 years, ranging between 18 and 89 years of age with 8.8% ≥65 years of age. Patients treated with ORBACTIV were predominantly male (65.4%), 64.4% were Caucasian, 5.8% were African American, and 28.1% were Asian. Safety was evaluated for up to 60 days after dosing. In the pooled ABSSSI clinical trials, serious adverse reactions were reported in 57/976 (5.8%) patients treated with ORBACTIV and 58/983 (5.9%) treated with vancomycin. The most commonly reported serious adverse reaction was cellulitis in both treatment groups: 11/976 (1.1%) in ORBACTIV and 12/983 (1.2%) in the vancomycin arms, respectively. The most commonly reported adverse reactions (≥3%) in patients receiving a single 1200 mg dose of ORBACTIV in the pooled ABSSSI clinical trials were: headache, nausea, vomiting, limb and subcutaneous abscesses, and diarrhea. In the pooled ABSSSI clinical trials, ORBACTIV was discontinued due to adverse reactions in 36/976 (3.7%) of patients; the most common reported reactions leading to discontinuation were cellulitis (4/976, 0.4%) and osteomyelitis (3/976, 0.3%). Table 1 provides selected adverse reactions occurring in ≥ 1.5% of patients receiving ORBACTIV in the pooled ABSSSI clinical trials. There were 540 (55.3%) patients in the ORBACTIV arm and 559 (56.9%) patients in the vancomycin arm, who reported ≥1 adverse reaction. Table 1: Incidence of Selected Adverse Reactions Occurring in ≥ 1.5% of Patients Receiving ORBACTIV in the Pooled ABSSSI Clinical Trials
Blood and lymphatic system disorders: anemia, eosinophilia General Disorders and administration site conditions: infusion site erythema, extravasation, induration, pruritis, rash, edema peripheral Immune system disorders: hypersensitivity Infections and infestations: osteomyelitis Investigations: total bilirubin increased, hyperuricemia Metabolism and nutrition disorders: hypoglycemia Musculoskeletal and connective tissue disorders: tenosynovitis, myalgia Respiratory, thoracic and mediastinal disorders: bronchospasm, wheezing Skin and Subcutaneous Tissue Disorders: urticaria, angioedema, erythema multiforme, pruritis, leucocytoclastic vasculitis, rash. 7 DRUG INTERACTIONS 7.1 Effect of ORBACTIV on CYP Substrates ORBACTIV is a nonspecific, weak inhibitor (CYP2C9 and CYP2C19) or inducer (CYP3A4 and CYP2D6) of several CYP isoforms [see Clinical Pharmacology (12.3)]. 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) [see Warnings and Precautions (5.1)]. 7.2 Drug-Laboratory Test Interactions ORBACTIV may artificially prolong certain laboratory coagulation tests (see Table 2) by binding to and preventing the action of the phospholipid reagents which activate coagulation in commonly used laboratory coagulation tests [see Contraindications (4.1) and Warnings and Precautions (5.2)]. For patients who require monitoring of anticoagulation effect within the indicated time after 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. ORBACTIV does not interfere with coagulation in vivo. In addition, ORBACTIV does not affect tests that are used for diagnosis of Heparin Induced Thrombocytopenia (HIT). Table 2: Coagulation Tests Affected and Unaffected by ORBACTIV
8.1 Pregnancy Pregnancy Category 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. 8.3 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. 8.4 Pediatric Use Safety and effectiveness of ORBACTIV in pediatric patients (younger than 18 years of age) has not been studied. 8.5 Geriatric 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. 8.6 Renal Impairment No dosage adjustment of ORBACTIV is needed in patients with mild or moderate renal impairment [see Dosage and Administration (2.1), Clinical Pharmacology (12.3)]. The pharmacokinetics of ORBACTIV in severe renal impairment have not been evaluated. ORBACTIV is not removed from blood by hemodialysis. 8.7 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 [see Dosage and Administration (2.1), Clinical Pharmacology (12.3)]. 10 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. 11 DESCRIPTION ORBACTIV (oritavancin) for injection contains oritavancin diphosphate, a semisynthetic lipoglycopeptide antibacterial drug. The chemical name for oritavancin is [4"R]-22-O-(3-amino-2,3,6-trideoxy-3-C-methyl-α-L-arabino-hexopyranosyl)-N3''-[(4'-chloro[1,1'-biphenyl]-4-yl)methyl] vancomycin phosphate [1:2] [salt]. The empirical formula of oritavancin diphosphate is C86H97N10O26Cl3•2H3PO4 and the molecular weight is 1989.09. The chemical structure is represented below:
Oritavancin exhibits linear pharmacokinetics at a dose up to 1200 mg. The mean, population-predicted oritavancin concentration-time profile displays a multi-exponential decline with a long terminal plasma half-life as shown in Figure 1 Figure 1: Population Mean Plasma Concentration-Time Profile after a Single 1200 mg dose of Oritavancin Administered Intravenously Over 3 Hours – Semi-Log Scale
a As determined by broth microdilution with 0.002% polysorbate-80 during oritavancin dissolution and dilution and in the final assay. b The current absence of resistant isolates precludes defining any results other than "Susceptible". Isolates yielding test results other than "Susceptible" should be retested, and if the result is confirmed, the isolate should be submitted to a reference laboratory for further testing. A report of “Susceptible” indicates that the antimicrobial drug is likely to inhibit growth of the microorganism if the antimicrobial drug reaches the concentration usually achievable at the site of infection. Quality Control Standardized susceptibility test procedures require the use of laboratory control microorganisms to monitor and ensure the accuracy and precision of supplies and reagents used in the assay and the techniques of the individuals performing the test. Acceptable oritavancin MIC ranges for the quality control strains are shown in Table 5. Quality control microorganisms are specific strains of organisms with intrinsic biological properties, and are very stable strains that will give a standard and reproducible susceptibility pattern. The specific strains used for microbiological quality control are not clinically significant. Table 5: Acceptable Quality Control Ranges for Oritavancin Susceptibility Testinga
a As determined by broth microdilution with 0.002% polysorbate-80 during oritavancin dissolution and dilution and in the final assay.1,2 Diffusion technique The use of the disk diffusion method is not recommended since quality control ranges have not been defined for oritavancin. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long term studies in animals have not been conducted to determine the carcinogenic potential of oritavancin. No mutagenic or clastogenic potential of oritavancin was found in a battery of tests, including an Ames assay, in vitro chromosome aberration assay in Chinese hamster ovary cells, in vitro forward mutation assay in mouse lymphoma cells and an in vivo mouse micronucleus assay. Oritavancin did not affect the fertility or reproductive performance of male rats (exposed to daily doses up to 30 mg/kg for at least 4 weeks) and female rats (exposed to daily doses up to 30 mg/kg for at least 2 weeks prior to mating). Those daily doses would be equivalent to a human dose of 300 mg, or 25% of clinical dose. Higher doses were not evaluated in nonclinical fertility studies. 14 CLINICAL STUDIES 14.1 Acute Bacterial Skin and Skin Structure Infections (ABSSSI) A total of 1987 adults with clinically documented ABSSSI suspected or proven to be due to Gram-positive pathogens were randomized into two identically designed, randomized, double-blind, multi-center, multinational, non-inferiority trials (Trial 1 and Trial 2) comparing a single 1200 mg intravenous dose of ORBACTIV to intravenous vancomycin (1 g or 15 mg/kg every 12 hours) for 7 to 10 days. The primary analysis population (modified intent to treat, mITT) included all randomized patients who received any study drug. Patients could receive concomitant aztreonam or metronidazole for suspected Gram-negative and anaerobic infection, respectively. Patient demographic and baseline characteristics were balanced between treatment groups. Approximately 64% of patients were Caucasian and 65% were males. The mean age was 45 years and the mean body mass index was 27 kg/m2. Across both trials, approximately 60% of patients were enrolled from the United States and 27% of patients from Asia. A history of diabetes was present in 14% of patients. The types of ABSSSI across both trials included cellulitis/erysipelas (40%), wound infection (29%), and major cutaneous abscesses (31%). Median infection area at baseline across both trials was 266.6 cm2. The primary endpoint in both trials was early clinical response (responder), defined as cessation of spread or reduction in size of baseline lesion, absence of fever, and no rescue antibacterial drug at 48 to 72 hours after initiation of therapy. Table 6 provides the efficacy results for the primary endpoint in Trial 1 and Trial 2 in the primary analysis population. Table 6: Clinical Response Rates in ABSSSI Trials using Responders1, 2 at 48-72 Hours after Initiation of Therapy
2Patients who died at 48 to 72 hours, after initiation of therapy or who had increase in lesion size at 48 to 72 hours, after initiation of therapy or who used non-study antibacterial therapy during first 72 hours or who had an additional, unplanned, surgical procedure or who had missing measurements during the first 72 hours from initiation of study drug were classified as non-responders. 3 95% CI based on the Normal approximation to Binomial distribution. A key secondary endpoint in these two ABSSSI trials evaluated the percentage of patients achieving a 20% or greater reduction in lesion area from baseline at 48-72 hours after initiation of therapy. Table 7 summarizes the findings for this endpoint in the two ABSSSI trials. Table 7: Clinical Response Rates1 in ABSSSI Trials using Reduction in Lesion Area of 20% or Greater at 48-72 Hours after Initiation of Therapy
2 95% CI based on the Normal approximation to Binomial distribution. Another secondary efficacy endpoint in the two trials was investigator-assessed clinical success at post therapy evaluation at day 14 to 24 (7 to 14 days from end of blinded therapy). A patient was categorized as a clinical success if the patient experienced a complete or nearly complete resolution of baseline signs and symptoms related to primary ABSSSI site (erythema, induration/edema, purulent drainage, fluctuance, pain, tenderness, local increase in heat/warmth) such that no further treatment with antibacterial drugs was needed. Table 8 summarizes the findings for this endpoint in the mITT and clinically evaluable population in these two ABSSSI trials. Note that there are insufficient historical data to establish the magnitude of drug effect for antibacterial drugs compared with placebo at the post therapy visits. Therefore, comparisons of ORBACTIV to vancomycin based on clinical success rates at these visits cannot be utilized to establish non-inferiority conclusions. Table 8: Clinical Success Rates1 in ABSSSI Trials at the Follow-Up Visit (7-14 days after end of therapy)
2 95% CI based on the Normal approximation to Binomial distribution 3 mITT population consisted of all randomized patients who received study drug; CE population consisted of all mITT patients who did not have violations of inclusion and exclusion criteria, completed treatment and had investigator assessment at the Follow-Up Visit. Outcomes by Baseline Pathogen: Table 9 shows outcomes in patients with an identified baseline pathogen in the microbiological Intent-to-Treat (microITT) population in a pooled analysis of Trial 1 and Trial 2. The outcomes shown in the table are clinical response rates at 48 to 72 hours and clinical success rates at follow-up study day14 to 24. Table 9: Outcomes by Baseline Pathogen (microITT)
2 Patients achieving a 20% or greater reduction in lesion area from baseline at 48-72 hours after initiation of therapy 3 Clinical success was defined if the patient experienced a complete or nearly complete resolution of baseline signs and symptoms as described above. 4Baseline bacteremia in the oritavancin arm with relevant microorganisms causing ABSSSI included four subjects with MSSA and seven subjects with MRSA. Eight of these eleven subjects were responders at 48 to 72 hours after initiation of therapy. 15 REFERENCES 1.Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard – Ninth Edition. CLSI document M7-A09, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, PA 19087, 2012. 2.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 16.1 How Supplied/Storage ORBACTIV is supplied as single use 50 mL capacity glass vials containing sterile lyophilized powder equivalent to 400 mg of oritavancin (NDC 65293-015-01). Three vials are packaged in a carton to supply a single 1200 mg dose treatment (NDC 65293-015-03). ORBACTIV vials should be stored at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP, Controlled Room Temperature (CRT)]. 17 PATIENT COUNSELING INFORMATION Patients should be advised that allergic reactions, including serious allergic reactions, could occur and that serious reactions require immediate treatment. They should inform their healthcare provider about any previous hypersensitivity reactions to ORBACTIV, other glycopeptides (vancomycin, telavancin, or dalbavancin) or other allergens. Patients should be advised that diarrhea is a common problem caused by antibacterial drugs including ORBACTIV, which usually resolves when the drug is discontinued. Sometimes, frequent watery or bloody diarrhea may occur and may be a sign of a more serious intestinal infection. If severe watery or bloody diarrhea develops, patients should contact their healthcare provider. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=085d6d1a-21c2-11e4-8c21-0800200c9a66 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
