34/18. Eravacycline -(XERAVA)- (Aug 2018)- to treat intra-abdominal infections
Drug Name:34/18. Eravacycline -(XERAVA)- (Aug 2018)- to treat intra-abdominal infections
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
DRUG INTERACTIONS-(summary)
1. Effect of Strong CYP3A Inducers on XERAVA- Concomitant use of strong CYP3A inducers decreases the exposure of eravacycline, which may reduce the efficacy of XERAVA [
• Patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage
Indication:
BRIEF SUMMARY
ERAVACYLINE-(Aug 2018)
Indn- To treat complicated intra-abdominal infections in patienrs 18 years and older
Comp- • For injection: 50 mg of eravacycline (equivalent to 63.5 mg eravacycline dihydrochloride) as a lyophilized powder in a single-dose vial for reconstitution and further dilution. • Administer XERAVA for injection 1 mg/kg by intravenous infusion over approximately 60 minutes every 12 hours for a total duration of 4 to 14 days.
ADR- Most common adverse reactions (incidence = 3%) are infusion site reactions, nausea, and vomiting.
CI- CONTRAINDICATIONS-
WARNINGS -
• Hypersensitivity Reactions: Life-threatening hypersensitivity (anaphylactic) reactions have been reported with tetracycline antibacterial drugs, including XERAVA. Avoid use in patients with known hypersensitivity to tetracyclines
Pat Inform-
Serious Allergic Reactions- Advise patients that allergic reactions, including serious allergic reactions, could occur and that serious reactions require immediate treatment
Ask patient about any previous hypersensitivity reactions to antibacterial drugs including tetracycline or other allergens
. Tooth Discoloration and Inhibition of Bone Growth
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U.S. FDA APPROVED DRUGS DURING 2018
Sr.No- 34
• For injection: 50 mg of eravacycline (equivalent to 63.5 mg eravacycline dihydrochloride) as a lyophilized powder in a single-dose vial for reconstitution and further dilution.
Adverse Reaction:
ADVERSE REACTIONS-
Most common adverse reactions (incidence = 3%) are infusion site reactions, nausea, and vomiting.
Contra-Indications:
WARNINGS AND PRECAUTIONS-
• Hypersensitivity Reactions: Life-threatening hypersensitivity (anaphylactic) reactions have been reported with tetracycline antibacterial drugs, including XERAVA. Avoid use in patients with known hypersensitivity to tetracyclines.
• Tooth Discoloration and Enamel Hypoplasia: The use of XERAVA during tooth development (last half of pregnancy, infancy and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown) and enamel hypoplasia.
• Inhibition of Bone Growth: The use of XERAVA during the second and third trimester of pregnancy, infancy and childhood up to the age of 8 years may cause reversible inhibition of bone growth
• Clostridium difficile-associated diarrhea: Evaluate if diarrhea occurs.
Dosages/ Overdosage Etc:
Patient Information:
PATIENT COUNSELING INFORMATION-
Serious Allergic Reactions-
Advise patients that allergic reactions, including serious allergic reactions, could occur and that serious reactions require immediate treatment
. Ask patient about any previous hypersensitivity reactions to antibacterial drugs including tetracycline or other allergens
. Tooth Discoloration and Inhibition of Bone Growth
Advise patients that XERAVA, like other tetracycline-class drugs, may cause permanent tooth discoloration of deciduous teeth and reversible inhibition of bone growth when administered during the second and third trimesters of pregnancy.
Tell your healthcare provider right away if you become pregnant during treatment
Lactation- Advise women not to breastfeed during treatment with XERAVA and for 4 days after the last dose
Diarrhea- Diarrhea is a common problem caused by antibacterial drugs, including XERAVA, which usually ends when the antibacterial drug is discontinued.
Sometimes after starting treatment with antibacterial drug, patients can develop watery and bloody stools (with or without stomach cramps and fever) which may be a sign of a more serious intestinal infection, even as late as 2 or more months after having taken the last dose of the antibacterial drug.
If this occurs, instruct patients to contact their healthcare provider as soon as possible
Tetracycline Class Adverse Reactions= Inform patients that XERAVA is similar to tetracycline-class antibacterial drugs and may have similar adverse reactions
Overgrowth of Non-susceptible Microorganisms- Inform patients that antibacterial drugs including XERAVA may promote the overgrowth of non-susceptible microorganisms, including fungi
Antibacterial Resistance- Inform patients that antibacterial drugs including XERAVA should only be used to treat bacterial infections. They do not treat viral infections (for example, the common cold).
When XERAVA 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 the immediate treatment and
(2) increase the likelihood that bacteria will develop resistance and will not be treatable by XERAVA or other antibacterial drugs in the future
Distributed by: Tetraphase Pharmaceuticals, Inc. 480 Arsenal Way, Ste 110 Watertown, MA 02472 XERAVA™ is a trademark of Tetraphase Pharmaceuticals, In
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action- Eravacycline is an antibacterial drug
2. Pharmacodynamics- The AUC divided by the MIC of eravacycline has been shown to be the best predictor of activity.
Based on the flat exposure-response relationship observed in clinical studies, eravacycline exposure achieved with the recommended dosage regimen appears to be on the plateau of the exposure-response curve
. Cardiac Electrophysiology - The effect of XERAVA on the QTc interval was evaluated in a Phase 1 randomized, placebo and positive controlled, double-blind, single-dose, crossover thorough QTc study in 60 healthy adult subjects. At the 1.5 mg/kg single dose (1.5 times the maximum approved recommended dose), XERAVA did not prolong the QTc interval to any clinically relevant extent.
3. Pharmacokinetics- Following single-dose intravenous administration, eravacycline AUC and Cmax increase approximately dose-proportionally over doses from 1 mg/kg to 3 mg/kg (3 times the approved dose).
Distribution- Protein binding of eravacycline to human plasma proteins increases with increasing plasma concentrations, with 79% to 90% (bound) at plasma concentrations ranging from 100 to 10,000 ng/mL.
The volume of distribution at steady-state is approximately 321 L. Elimination The mean elimination half-life is 20 hours.
Metabolism- Eravacycline is metabolized primarily by CYP3A4- and FMO-mediated oxidation.
Excretion- Following a single intravenous dose of radiolabeled eravacycline 60 mg, approximately 34% of the dose is excreted in urine and 47% in feces as unchanged eravacycline (20% in urine and 17% in feces) and metabolites.
Specific Populations- No clinically significant differences in the pharmacokinetics of eravacycline were observed based on age (18-86 years), sex, and race.
Patients with Renal Impairment- The geometric least square mean Cmax for eravacycline was increased by 8.8% for subjects with end stage renal disease (ESRD) versus healthy subjects with 90% CI -19.4, 45.2.
Patients with Hepatic Impairment - Eravacycline Cmax was 13.9%, 16.3%, and 19.7% higher in subjects with mild (Child-Pugh Class A), moderate (Child-Pugh Class B), and severe (Child-Pugh Class C) hepatic impairment versus healthy subjects, respectively.
Drug Interaction Studies- Clinical Studies Concomitant use of rifampin (strong CYP3A4/3A5 inducer) decreased eravacycline AUC by 35% and increased eravacycline clearance by 54%
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy Risk Summary- XERAVA, like other tetracycline-class antibacterial drugs, may cause discoloration of deciduous teeth and reversible inhibition of bone growth when administered during the second and third trimester of pregnancy
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
2. Lactation Risk Summary - It is not known whether XERAVA is excreted in human breast milk. Eravacycline (and its metabolites) is excreted in the milk of lactating rats (s
3 Females and Males of Reproductive Potential- Infertility Based on animal studies, XERAVA can lead to impaired spermiation and sperm maturation, resulting in abnormal sperm morphology and poor motility. The effect is reversible in rats.
4. Pediatric Use The safety and effectiveness of XERAVA in pediatric patients have not been established.
Due to the adverse effects of the tetracycline-class of drugs, including XERAVA on tooth development and bone growth, use of XERAVA in pediatric patients less than 8 years of age is not recommended
5. Geriatric Use- Of the total number of patients with cIAI who received XERAVA in Phase 3 clinical trials (n = 520), 158 subjects were = 65 years of age, while 59 subjects were = 75 years of age.
No overall differences in safety or efficacy were observed between these subjects and younger subjects.
6. Hepatic Impairment- No dosage adjustment is warranted for XERAVA in patients with mild to moderate hepatic impairment (Child Pugh A and Child Pugh B). Adjust XERAVA dosage in patients with severe hepatic impairment (Child Pugh C) .
7. Renal Impairment- No dosage adjustment is necessary for XERAVA in patients with renal impairment
OVERDOSAGE- No reports of overdose were reported in clinical trials. In the case of suspected overdose, XERAVA should be discontinued and the patient monitored for adverse reactions. Hemodialysis is not expected to remove significant quantities of XERAVA
