18/18. Plazomicin- (ZEMDRIL)- (June 2018)- to treat adults with complicated urinary tract infections
Drug Name:18/18. Plazomicin- (ZEMDRIL)- (June 2018)- to treat adults with complicated urinary tract infections
List Of Brands:
Indication Type Description:
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Indication:
BRIEF SUMMARY
PLAZOMICIN-(June 2018)
Indn- To treat adults with complicated urinary tract infections
Comp- ZEMDRI injection 500 mg/10 mL (50 mg/mL) is a single-dose vial containing plazomicin sulfate equivalent to 500 mg plazomicin free base Recommended initial dosage regimen for patients with renal impairment is shown in the table below.
Estimated CLcr a (mL/min) Recommended Dosage for a. Dosing Interval Greater than or equal to 60 to less than 90 15 mg/kg Every 24 hours Greater than or equal to 30 to less than 60 10 mg/kg Every 24 hours Greater than or equal to 15 to less than 30 10 mg/kg Every 48 hours a CLcr estimated by the Cockcroft-Gault formula.
b. Calculate dosage using Total Body Weight (TBW). For patients with TBW greater than IBW by 25% or more, use adjusted body weight.
ADR- Most common adverse reactions (? 1% of patients treated with ZEMDRI) are decreased renal function, diarrhea, hypertension, headache, nausea, vomiting and hypotension
CI- is contraindicated in patients with known hypersensitivity to any aminoglycoside
WARNINGS-
Hypersensitivity Reactions, including anaphylaxis: Reported for aminoglycosides. If an allergic reaction occurs, discontinue ZEMDRI.
Clostridium difficile-Associated Diarrhea: Reported for nearly all systemic antibacterial drugs. Evaluate if diarrhea occurs.
Pat Infm
Nephrotoxicity - Advise patients, their families, or caregivers that nephrotoxicity has been reported with therapy.
Counsel patients to follow their physician’s directions regarding renal function laboratory tests, maintenance of adequate hydration, and avoidance of potentially nephrotoxic agents while receiving therapy
Ototoxicity-
Advise patients, their families, or caregivers that hearing loss, vertigo, and tinnitus have been reported with therapy.
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U.S. FDA APPROVED DRUGS DURING 2018
Sr.No- 18
Adverse Reaction:
ADVERSE REACTIONS -
Most common adverse reactions (? 1% of patients treated with ZEMDRI) are decreased renal function, diarrhea, hypertension, headache, nausea, vomiting and hypotension
Contra-Indications:
CONTRAINDICATIONS-
ZEMDRI is contraindicated in patients with known hypersensitivity to any aminoglycoside
WARNINGS AND PRECAUTIONS-
Hypersensitivity Reactions, including anaphylaxis: Reported for aminoglycosides. If an allergic reaction occurs, discontinue ZEMDRI.
Clostridium difficile-Associated Diarrhea: Reported for nearly all systemic antibacterial drugs. Evaluate if diarrhea occurs.
Dosages/ Overdosage Etc:
Recommended initial dosage regimen for patients with renal impairment is shown in the table below.
Estimated CLcr a (mL/min) Recommended Dosage for ZEMDRI b Dosing Interval Greater than or equal to 60 to less than 90 15 mg/kg Every 24 hours Greater than or equal to 30 to less than 60 10 mg/kg Every 24 hours Greater than or equal to 15 to less than 30 10 mg/kg Every 48 hours a CLcr estimated by the Cockcroft-Gault formula. (2.3) b Calculate dosage using Total Body Weight (TBW). For patients with TBW greater than IBW by 25% or more, use adjusted body weight.
See Full Prescribing Information for subsequent dosage adjustment based on changes in renal function or Therapeutic Drug Monitoring (TDM).
See Full Prescribing Information for instructions on preparation of the solution, stability in intravenous fluids and drug compatibilities.
DOSAGE FORMS AND STRENGTHS-
ZEMDRI injection 500 mg/10 mL (50 mg/mL) is a single-dose vial containing plazomicin sulfate equivalent to 500 mg plazomicin free base
Patient Information:
PATIENT COUNSELING INFORMATION-
Nephrotoxicity Advise patients, their families, or caregivers that nephrotoxicity has been reported with ZEMDRI therapy.
Counsel patients to follow their physician’s directions regarding renal function laboratory tests, maintenance of adequate hydration, and avoidance of potentially nephrotoxic agents while receiving ZEMDRI therapy
Ototoxicity-
Advise patients, their families, or caregivers that hearing loss, vertigo, and tinnitus have been reported with ZEMDRI therapy.
Counsel patients to inform their physician if they experience changes in hearing or balance, or if they experience new onset or changes in preexisting buzzing or roaring in their ear(s), even if it occurs after the completion of ZEMDRI therapy
Aggravation of Neuromuscular Disorders
Advise patients, their families, or caregivers that aggravation of muscle weakness has been reported for other aminoglycosides, particularly in patients with underlying neuromuscular disease or receiving neuromuscular blocking agents.
Counsel patients to inform their physician if they have an underlying neuromuscular disorder such as myasthenia gravis or are receiving neuromuscular blocking agents [see
Fetal Harm-
Aminoglycosides, including ZEMDRI, can cause fetal harm when administered to a pregnant woman.
Counsel women of childbearing potential about the potential risk of fetal harm if ZEMDRI is used during pregnancy. Advise pregnant women that aminoglycosides can cause irreversible congenital deafness when administered to a pregnant woman
Tell women of childbearing potential to notify their prescribing physician/ healthcare provider if they become pregnant during ZEMDRI treatment [see Warnings and Precautions (5.4)].
Hypersensitivity Reactions-
Advise patients, their families, or caregivers that allergic reactions, including serious allergic reactions, could occur and that serious reactions require immediate treatment. Ask them about any previous hypersensitivity reactions to ZEMDRI or other aminoglycosides
Potentially Serious Diarrhea-
Advise patients, their families, or caregivers that diarrhea is a common problem caused by antibacterial drugs, including ZEMDRI. 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, tell patient to contact his or her healthcare provider
Antibacterial Resistance-
Counsel patients, their families, or caregivers that antibacterial drugs, including ZEMDRI, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold).
When ZEMDRI 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 ZEMDRI or other antibacterial drugs in the future
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Manufactured for: Achaogen, Inc. South San Francisco, CA 94080
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1 Mechanism of Action-
ZEMDRI is an antibacterial drug [see Microbiology (12.4)].
2. Pharmacodynamic-
The ratio of area under the plasma concentration-time curve to the minimum inhibitory concentration (AUC:MIC) for plazomicin has been shown to best correlate with efficacy in animal and in vitro models of infection against Enterobacteriaceae.
Cardiac Electrophysiology-
The effect of ZEMDRI on the QTc interval was evaluated in a Phase 1 randomized, placebo and positive controlled, double-blind, single-dose, crossover thorough QTc study in 56 healthy adult subjects.
3.Pharmacokinetics-
The pharmacokinetic (PK) parameters of plazomicin are similar for single- and multiple-dose administration of ZEMDRI in healthy subjects. No appreciable accumulation of plazomicin was observed following multiple IV infusions of 15 mg/kg administered every 24 hours in subjects with normal renal function.
Metabolism- Plazomicin does not appear to be metabolized to any appreciable extent.
Excretion - Plazomicin is primarily excreted by the kidneys.
Specific Populations-
No clinically significant differences in the pharmacokinetics of plazomicin were observed based on age (18 to 90 years of age), sex, or race/ethnicity.
Geriatric Patients-
No clinically relevant trend in plazomicin exposure (Cmax and AUC0-24h) was observed with regard to age alone.
Drug Interaction Studies-
Clinical Studies Based on the results of a clinical drug-drug interaction (DDI) study that evaluated the effect of a single dose of plazomicin (15 mg/kg) on the single dose plasma PK of metformin, plazomicin did not affect the PK of metformin, which is a substrate of OCT and MATE transporters.
In Vitro Studies-
Drug-Metabolizing Enzymes Plazomicin does not inhibit the following cytochrome P450 isoforms: CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5. Plazomicin does not induce CYP1A2, CYP2B6, and CYP3A4.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS-
1. Pregnancy Risk Summary-
Aminoglycosides, including ZEMDRI, can cause fetal harm when administered to a pregnant woman.
There are no available data on the use of ZEMDRI in pregnant women to inform a drug associated risk of adverse developmental outcomes.
Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown.
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-
There are no data on the presence of ZEMDRI in human milk, the effects on the breastfed infant, or the effects on milk production. Plazomicin was detected in rat milk (see Data).
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ZEMDRI and any potential adverse effects on the breastfed infant from ZEMDRI or from the underlying maternal condition.
Data In a pre- and postnatal development study in rats, low concentrations of plazomicin in maternal milk were detected, with mean concentrations representing 2% to 4% of maternal plasma concentrations. In nursing pups, the systemic exposure (AUC) to plazomicin through lactational exposure was approximately 0.04% of maternal systemic exposure
4. Pediatric Use-
The safety and effectiveness of ZEMDRI in patients less than 18 years of age have not been established.
5. Geriatric Use Of the 425 patients treated with ZEMDRI in Trials 1 and 2, 40% (170/425) were 65 years of age and older, including 17.2% (73/425) patients 75 years of age and older.
6. Renal Impairment-
Plazomicin total body clearance was significantly decreased in patients with CLcr greater than or equal to 15 to less than 60 mL/min compared to patients with CLcr greater than or equal to 60 mL/min
OVERDOSAGE-
In the event of overdosage, ZEMDRI should be discontinued and supportive care is advised. Maintenance of glomerular filtration and careful monitoring of renal function is recommended.
Hemodialysis may aid in the removal of ZEMDRI from the blood, especially if renal function is, or becomes, compromised.
No clinical information is available on the use of hemodialysis to treat ZEMDRI overdosage. 11.