Home › Drugs › Plazomicin

Plazomicin

FDA Drug Information • Also known as: Zemdri (Plazomicin)

Brand Names
Zemdri (Plazomicin)
Route
INTRAVENOUS
Dosage Form
INJECTION
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: NEPHROTOXICITY, OTOTOXICITY, NEUROMUSCULAR BLOCKADE and FETAL HARM Nephrotoxicity has been reported with ZEMDRI. The risk of nephrotoxicity is greater in patients with impaired renal function, the elderly, and in those receiving concomitant nephrotoxic medications. Assess creatinine clearance in all patients prior to initiating therapy and daily during therapy [see Dosage and Administration (2.2) and Warnings and Precautions (5.1) ] . Therapeutic Drug Monitoring (TDM) is recommended for complicated urinary tract infection (cUTI) patients with CLcr less than 90 mL/min to avoid potentially toxic levels [see Dosage and Administration (2.3 , 2.4) ] . 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. Aminoglycoside-associated ototoxicity has been observed primarily in patients with a family history of hearing loss, patients with renal impairment, and in patients receiving higher doses and/or longer durations of therapy than recommended [see Warnings and Precautions (5.2) ] . Aminoglycosides have been associated with neuromuscular blockade. 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 in patients concomitantly receiving neuromuscular blocking agents [see Warning and Precautions (5.3) ] . Aminoglycosides, including ZEMDRI, can cause fetal harm when administered to a pregnant woman [see Warnings and Precautions (5.4) , Use in Specific Populations (8.1) ] . WARNING: NEPHROTOXICITY, OTOTOXICITY, NEUROMUSCULAR BLOCKADE and FETAL HARM See full prescribing information for complete boxed warning. Nephrotoxicity has been reported with ZEMDRI. The risk of nephrotoxicity is greater in patients with impaired renal function, the elderly, and in those receiving concomitant nephrotoxic medications. ( 5.1 ) 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. ( 5.2 ) Aminoglycosides have been associated with neuromuscular blockade. During therapy with ZEMDRI, monitor for adverse reactions associated with neuromuscular blockade particularly in high-risk patients. ( 5.3 ) Aminoglycosides, including ZEMDRI can cause fetal harm when administered to a pregnant woman. ( 5.6 , 8.1 )

Description

11. DESCRIPTION ZEMDRI contains plazomicin sulfate, a semi-synthetic aminoglycoside antibacterial derived from sisomicin. The chemical name of plazomicin sulfate is (2" R ,3" R ,4" R ,5" R )-2"-[(1 S ,2 S ,3 R ,4 S ,6 R )-4-amino-6-[(2'" S )-4'"-amino-2'"-hydroxybutanamido)amino]-3-[(2' S ,3' R )-3'-amino-6'-((2-hydroxyethylamino)methyl)-3',4'-dihydro-2H-pyran-2'-yloxy]-2-hydroxycyclohexyloxy]-5''-methyl-4''-(methylamino)tetrahydro-2H-pyran-3'',5''-diol sulfate. Plazomicin sulfate contains a theoretical 2.5 molar equivalents of sulfate relative to the freebase, based on complete protonation. The molecular weight of plazomicin sulfate is calculated based on 1:2.5 stoichiometry. The corresponding empirical formula is C 25 H 48 N 6 O 10 ∙2.5 H 2 SO 4 (plazomicin sulfate) and the molecular weight of the plazomicin sulfate salt is 837.89 g/mol and the molecular weight of the freebase is 592.69 g/mol. Figure 1: Chemical Structure of Plazomicin Sulfate ZEMDRI injection 500 mg/10 mL is a sterile, clear, colorless-to-yellow liquid for intravenous administration supplied in 10-mL single-dose Type 1 glass vials. Each vial contains plazomicin sulfate equivalent to 500 mg plazomicin freebase at a concentration of 50 mg/mL adjusted to pH 6.5. Each vial also contains Water for Injection and sodium hydroxide for pH adjustment. This sterile, nonpyrogenic solution is formulated without preservatives. Chemical Structure

What Is Plazomicin 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 have limited or no alternative treatment options. ( 1.1 ) To reduce the development of drug-resistant bacteria and maintain effectiveness of ZEMDRI and other antibacterial drugs, ZEMDRI should be used only to treat infections that are proven or strongly suspected to be caused by susceptible microorganisms. ( 1.2 ) 1.1 Complicated Urinary Tract Infections (cUTI), including Pyelonephritis ZEMDRI is indicated in patients 18 years of age or older for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis caused by the following susceptible microorganism(s): Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis , and Enterobacter cloacae . As only limited clinical safety and efficacy data for ZEMDRI are currently available, reserve ZEMDRI for use in cUTI patients who have limited or no alternative treatment options [see Clinical Studies (14.1) ]. 1.2 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZEMDRI and other antibacterial drugs, ZEMDRI should be used only to treat or prevent 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.

Dosage and Administration

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. ( 2.1 ) Recommended duration of treatment is 4 to 7 days for cUTI, including pyelonephritis. ( 2.1 ) Assess creatinine clearance in all patients prior to initiating therapy and daily during therapy. ( 2.2 ) Recommended initial dosage regimen for patients with renal impairment is shown in the table below. ( 2.3 ) Estimated CLcr CLcr estimated by the Cockcroft-Gault formula. ( 2.3 ) (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. ( 2.3 ) 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). ( 2.3 , 2.4 ). See Full Prescribing Information for instructions on preparation of the solution, stability in intravenous fluids and drug compatibilities. ( 2.5 , 2.6 , 2.7 ) 2.1 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. During treatment, dosage adjustments may be required based on change in renal function [see Dosage and Administration (2.3 , 2.4) ]. 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. For patients with TBW greater than IBW by 25% or more, use adjusted body weight based on the equation: Adjusted body weight = IBW + 0.4 × [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. 2.2 Monitoring of Renal Function Assess creatinine clearance in all patients prior to initiating therapy and daily during therapy with ZEMDRI [see Dosage and Administration (2.3) , Warnings and Precautions (5.1) and Use in Specific Populations (8.6) ] . 2.3 Dosage in Adult Patients With Renal Impairment The recommended initial dosage regimen of ZEMDRI in adult patients with CLcr greater...

Side Effects (Adverse Reactions)

6. ADVERSE REACTIONS The following important adverse reactions are discussed in greater detail in the Warnings and Precautions section: Nephrotoxicity [see Warnings and Precautions (5.1) ] Ototoxicity [see Warnings and Precautions (5.2) ] Neuromuscular Blockade [see Warnings and Precautions (5.3) ] Fetal Harm [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.5) ] Clostridium difficile -Associated Diarrhea [see Warnings and Precautions (5.6) ] Most common adverse reactions (≥ 1% of patients treated with ZEMDRI) are decreased renal function, diarrhea, hypertension, headache, nausea, vomiting and hypotension. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Achaogen at 1-833-252-6402 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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. In both trials, patients with CLcr greater than 60 mL/min received ZEMDRI 15 mg/kg IV once daily as a 30-minute infusion [ see Clinical Studies (14.1) ] . Trial 1 included 303 patients treated with ZEMDRI and 301 patients treated with meropenem. Patients were to receive 4 to 7 days of ZEMDRI (mean duration of 5.1 days). In some patients, parenteral therapy was followed by a switch to an oral antibacterial drug. The median age of patients treated with ZEMDRI in Trial 1 was 62 years (range 18 to 90 years) and 45.2% of patients were 65 years of age or older. Patients treated with ZEMDRI were predominantly female (56.1%) and White (99.3%). A majority of patients (68.0%) 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. Adverse Reactions Leading to Treatment Discontinuations in Trial 1 In Trial 1, treatment discontinuation from IV study drug due to an adverse reaction occurred in 2.0% 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. 11 (3.6) 4 (1.3) Diarrhea 7 (2.3) 5 (1.7) Hypertension 7 (2.3) 7 (2.3) Headache 4 (1.3) 9 (3.0) Nausea 4 (1.3) 4 (1.3) Vomiting 4 (1.3) 3 (1.0) Hypotension 3 (1.0) 2 (0.7) The adverse reactions profile for the cUTI patients in Trial 2 were similar to those observed in Trial 1. Nephrotoxicity Reported in Trial 1 In Trial 1, serum creatinine increases of 0.5 mg/dL or greater above baseline occurred in 7.0% (21/300) of ZEMDRI-treated patients compared with 4.0% (12/297) of meropenem-treated patients. Of these, the incidence during IV therapy was 3.7% (11/300) vs 3.0% (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. Serum creatinine increases of 0.5 mg/dL or greater above baseline were observed following completion of IV therapy. These increases were generally ≤ 1.0 mg/dL above baseline and recovered by the next measurement. In cUTI patients with CLcr of greater than 30 and less than or equal to 90 mL/min, 9.7% (20/207)...

Contraindications

4. CONTRAINDICATIONS ZEMDRI is contraindicated in patients with known hypersensitivity to any aminoglycoside [see Warnings and Precautions (5.5) ] . ZEMDRI is contraindicated in patients with known hypersensitivity to any aminoglycoside ( 4 , 5.4 )

Pregnancy and Breastfeeding

8.1 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. Published literature reports of streptomycin, an aminoglycoside, state that it can cause total, irreversible, bilateral congenital deafness in children whose mothers received streptomycin during pregnancy. No drug-related visceral or skeletal malformations were observed in pregnant rats and rabbits administered subcutaneous plazomicin during organogenesis at maternal exposures approximately 0.8-fold (rats) and 2.5-fold (rabbits) of the human AUC at the clinical dose of 15 mg/kg/day . Auditory function of offspring was not measured in animal studies (see Data ) . 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. Data Animal Data In an embryo-fetal development study in rats, plazomicin doses of 0, 8, 25, or 50 mg/kg/day administered subcutaneously during organogenesis did not cause drug-related visceral or skeletal malformations, or reduce survival of fetuses. The mid and high doses caused maternal toxicity (reductions in food consumption and body weight gain; increased kidney weight). The high dose resulted in maternal exposure (AUC) approximately 0.8-fold the human AUC at the clinical dose of 15 mg/kg once daily. In an embryo-fetal development study in rabbits, plazomicin administered subcutaneously at doses of 0, 10, 30, or 50 mg/kg/day did not cause visceral or skeletal malformations or reduced fetal survival. At the high dose, significant maternal toxicity was observed (including renal injury and lethality) and exposure was...

Overdosage

10. 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.

How Supplied

16. HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied ZEMDRI injection 500 mg/10 mL (50 mg/mL) is supplied in single-dose, 10-mL vials fitted with flip-off seals with royal blue polypropylene buttons as a clear, colorless to yellow, sterile solution. Each vial contains plazomicin sulfate equivalent to 500 mg plazomicin freebase at a concentration of 50 mg/mL plazomicin in Water for Injection. Each vial contains sodium hydroxide for pH adjustment to 6.5. The solution may become yellow in color; this does not indicate a decrease in potency. NDC number Package/Volume Units per carton Plazomicin content 71045-010-02 Single use, fliptop vial, 10-mL 10 500 mg in 10 mL (50 mg/mL) 16.2 Storage and Handling Store ZEMDRI injection 500 mg/10 mL (50 mg/mL) refrigerated at 2°C to 8°C (36°F to 46°F).

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.