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Zemdri (Plazomicin) is a brand name for Plazomicin. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1. INDICATIONS AND USAGE ZEMDRI is an aminoglycoside antibacterial indicated for the treatment of patients 18 years of age or older with Complicated Urinary Tract Infections (cUTI) including Pyelonephritis. ( 1.1 ) As only limited clinical safety and efficacy data are available, reserve ZEMDRI for use in patients who…
Verbatim from this product's FDA label. Tap a section to expand.
2. DOSAGE AND ADMINISTRATION Administer ZEMDRI 15 mg/kg every 24 hours by intravenous (IV) infusion over 30 minutes to patients 18 years of age or older with creatinine clearance greater than or equal to 90 mL/min. 1 ) Recommended duration of treatment is 4 to 7 days for cUTI, including pyelonephritis.
1 ) Assess creatinine clearance in all patients prior to initiating therapy and daily during therapy. 2 ) Recommended initial dosage regimen for patients with renal impairment is shown in the table below. 3 ) Estimated CLcr CLcr estimated by the Cockcroft-Gault formula.
3 ) (mL/min) Recommended Dosage for ZEMDRI Calculate dosage using Total Body Weight (TBW). For patients with TBW greater than IBW by 25% or more, use adjusted body weight. 3 ) 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 See Full Prescribing Information for subsequent dosage adjustment based on changes in renal function or Therapeutic Drug Monitoring (TDM).
4 ). See Full Prescribing Information for instructions on preparation of the solution, stability in intravenous fluids and drug compatibilities. 1 Recommended Dosage The recommended dosage regimen of ZEMDRI is 15 mg/kg administered every 24 hours by intravenous (IV) infusion over 30 minutes in patients 18 years of age or older and with creatinine clearance (CLcr) greater than or equal to 90 mL/min (Table 1).
The duration of therapy should be guided by the severity of infection and the patient's clinical status for up to 7 days. 4) ].
Table 1:
Dosage Regimen of ZEMDRI in Adults With CLcr CLcr estimated by the Cockcroft-Gault formula using total body weight (TBW). For patients with TBW greater than ideal body weight (IBW) by 25% or more, use IBW. Greater Than or Equal to 90 mL/min cUTI Infection Dosage Regimen Calculate dosage using TBW.
4 × [TBW – IBW]. Duration of Treatment Complicated Urinary Tract Infections, including Pyelonephritis 15 mg/kg every 24 hours 4 to 7 days An appropriate oral therapy may be considered after 4 to 7 days of ZEMDRI therapy to complete a total duration of 7 to 10 days (IV plus oral).
The maximum duration of ZEMDRI for cUTI is 7 days. 6) ] . 3 Dosage in Adult Patients With Renal Impairment The recommended initial dosage regimen of ZEMDRI in adult patients with CLcr greater than or equal to 15 and less than 90 mL/min, estimated by the Cockcroft-Gault formula, is described in Table 2.
6. 6) ] Most common adverse reactions (≥ 1% of patients treated with ZEMDRI) are decreased renal function, diarrhea, hypertension, headache, nausea, vomiting and hypotension. gov/medwatch. 1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be compared directly to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
ZEMDRI was evaluated in two comparator-controlled clinical trials (Trial 1, NCT02486627 and Trial 2, NCT01096849) in patients with cUTI, including pyelonephritis. 1) ] . Trial 1 included 303 patients treated with ZEMDRI and 301 patients treated with meropenem.
1 days). In some patients, parenteral therapy was followed by a switch to an oral antibacterial drug. 2% of patients were 65 years of age or older. 3%). 0%) had mild or moderate renal impairment (CLcr >30 to 90 mL/min) at baseline. Patients with CLcr of 30 mL/min or less were excluded.
0% of patients receiving ZEMDRI (6/303) and meropenem (6/301), respectively. Common Adverse Reactions in Trial 1 Table 3 lists adverse reactions occurring in 1% or more of patients receiving ZEMDRI in Trial 1.
Table 3:
Incidence (%) of Adverse Reactions Occurring in 1% or More of cUTI Adult Patients Treated With ZEMDRI in Trial 1 Adverse Reactions ZEMDRI (N=303) n (%) Meropenem 1 g IV every 8 hours. (N=301) n (%) Decreased Renal Function Combined term that corresponds to adverse reactions associated with renal function described in Nephrotoxicity section below.
7) The adverse reactions profile for the cUTI patients in Trial 2 were similar to those observed in Trial 1. 0% (12/297) of meropenem-treated patients. 0% (9/297) in ZEMDRI- and meropenem-treated patients, respectively. By the last follow-up visit (between 8 to 43 days after completion of IV therapy), the majority of ZEMDRI-treated patients (9/11) and all meropenem treated patients (9/9) with serum creatinine increases while on therapy had fully recovered renal function.
5.
WARNINGS AND PRECAUTIONS Hypersensitivity Reactions, including anaphylaxis:
Reported for aminoglycosides. If an allergic reaction occurs, discontinue ZEMDRI. 4 ) Clostridium difficile -Associated Diarrhea : Reported for nearly all systemic antibacterial drugs. Evaluate if diarrhea occurs. 1) ]. Most serum creatinine increases were ≤ 1 mg/dL above baseline and reversible.
1) ]. 5 mg/dL or greater above baseline occurred in 7% (21/300) of ZEMDRI-treated patients compared with 4% (12/297) of meropenem-treated patients. 2) ] . Assess CLcr in all patients prior to initiating therapy and daily during therapy with ZEMDRI, particularly in those at increased risk of nephrotoxicity, such as those with renal impairment, the elderly, and those receiving concomitant potentially nephrotoxic medications.
6) ] . 3) ] . 4) ] . 2 Ototoxicity Ototoxicity, manifested as hearing loss, tinnitus, and/or vertigo, has been reported with ZEMDRI. Symptoms of aminoglycoside-associated ototoxicity may be irreversible and may not become evident until after completion of therapy.
1) ] . 1) ] . Aminoglycoside-associated ototoxicity has been observed primarily in patients with a family history of hearing loss (excluding age-related hearing loss), patients with renal impairment, and in patients receiving higher doses and/or for longer periods than recommended.
In Trial 1 and Trial 2, patients with a history of hearing loss, with the exception of age-related hearing loss, were excluded. The benefit-risk of ZEMDRI therapy should be considered in these patients. 3 Neuromuscular Blockade Aminoglycosides have been associated with exacerbation of muscle weakness in patients with underlying neuromuscular disorders, or delay in recovery of neuromuscular function in patients receiving concomitant neuromuscular blocking agents.
4. 5) ] . 4 )
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4) ] .
Table 2:
Dosage Regimen of ZEMDRI in Adults With CLcr Less Than 90 mL/min Estimated CLcr CLcr estimated by the Cockcroft-Gault formula using total body weight (TBW). For patients with TBW greater than ideal body weight (IBW) by 25% or more, use IBW.
(mL/min) Dosage Calculate dosage using TBW. 4 × [TBW – IBW]. 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 There is insufficient information to recommend a dosage regimen in patients with CLcr less than 15 mL/min or on renal replacement therapy, including hemodialysis or continuous renal replacement therapy.
4 TDM in cUTI Patients With Renal Impairment For cUTI patients with CLcr greater than or equal to 15 mL/min and less than 90 mL/min, TDM is recommended to maintain plasma trough concentrations below 3 mcg/mL. Measure plazomicin plasma trough concentration within approximately 30 minutes before administration of the second dose of ZEMDRI.
2) ] . 5 Preparation of Diluted Solutions of ZEMDRI ZEMDRI is supplied as a single-dose fliptop 10-mL vial that contains plazomicin sulfate equivalent to 500 mg plazomicin freebase in 10 mL Water for Injection (concentration of 50 mg/mL).
9% Sodium Chloride Injection, USP or Lactated Ringer's Injection, USP to achieve a final volume of 50 mL for intravenous infusion. 7) ] . ZEMDRI does not contain preservatives. Aseptic technique must be followed in preparing the infusion solution.
Discard unused portion of the ZEMDRI vial. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. 7 Drug Compatibility Compatibility of ZEMDRI for administration with other drugs has not been established.
ZEMDRI should not be mixed with other drugs or physically added to solutions containing other drugs. Other medications should not be infused simultaneously with ZEMDRI through the same IV line.
5 mg/dL or greater above baseline were observed following completion of IV therapy. 0 mg/dL above baseline and recovered by the next measurement. 5 mg/dL or greater above baseline. 6) ] . Ototoxicity Pure tone audiometry was evaluated in Phase 1 trials and in Trial 2.
0% (1/49) of comparator- or placebo-exposed adults. Other Adverse Reactions Reported with ZEMDRI The following selected adverse reactions were reported in more than one ZEMDRI-treated patient in Trials 1 and 2 and are not described elsewhere in the labeling: Gastrointestinal disorders : constipation, gastritis Laboratory Investigations : alanine aminotransferase increased Metabolism and nutrition disorders : hypokalemia Nervous system disorders: dizziness Renal and urinary disorders: hematuria Respiratory, thoracic and mediastinal disorders : dyspnea
During therapy with ZEMDRI, monitor for adverse reactions associated with neuromuscular blockade, particularly in high-risk patients, such as patients with underlying neuromuscular disorders (including myasthenia gravis) or those patients concomitantly receiving neuromuscular blocking agents.
4 Fetal Harm Aminoglycosides, including ZEMDRI, can cause fetal harm when administered to a pregnant woman. Aminoglycosides cross the placenta, and streptomycin has been associated with several reports of total, irreversible, bilateral congenital deafness in pediatric patients exposed in utero .
1) ] . 5 Hypersensitivity Reactions Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving aminoglycoside antibacterial drugs. Before therapy with ZEMDRI is instituted, careful inquiry about previous hypersensitivity reactions to other aminoglycosides should be made.
A history of hypersensitivity to other aminoglycosides is a contraindication to the use of ZEMDRI, because cross-sensitivity among aminoglycoside antibacterial drugs has been established. Discontinue ZEMDRI if an allergic reaction occurs.
6 Clostridium difficile -Associated Diarrhea Clostridium difficile- associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial drugs and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial drugs alters the normal flora of the colon and may permit overgrowth of C.
difficile. C. difficile produces toxins A and B that contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial 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 drugs.
If CDAD is suspected or confirmed, antibacterial drugs not directed against C. difficile may need to be discontinued. Manage fluid and electrolyte levels as appropriate, supplement protein intake, monitor antibacterial treatment of C.
difficile, and institute surgical evaluation as clinically indicated. 7 Development of Drug-Resistant Bacteria Prescribing ZEMDRI 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 .