Zemdri (plazomicin) 500 mg/10mL Injection
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Other aminoglycosides class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Plazomicin injection is used to treat serious urinary tract infections, including kidney infections, that are caused by bacteria. Plazomicin injection is in a class of medications called aminoglycoside antibiotics. It works by killing bacteria. Antibiotics such as plazomicin injection will not work for colds, flu, or other viral infections. Taking or using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.
Read the full MedlinePlus article ↗- Zemdri is only available as an IV infusion — there's no oral version. It's used for complicated urinary tract infections, including serious kidney infections like pyelonephritis, a...
- Why am I getting this antibiotic instead of a pill?
- Most patients receive Zemdri for 4 to 7 days by IV. After that, your doctor may switch you to an antibiotic pill to finish out a total course of about 7 to 10 days. The maximum tim...
- How long will I need to be on this medication?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Plazomicin Sulfate — tap one for details:
Plazomicin Sulfate may be associated with lower levels of 8 nutrients — worth a chat with your pharmacist, not a cause for alarm.
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Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
2 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $33.02 | $330.21 / 10 vials |
| Medicare Part B allowsASP · J0291 | $3.519 / J0291 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Zemdri (plazomicin) 500 mg/10mLthis 69097-0820-96 | Cipla | 10 vials | — | — | FDA listed | — |
| Zemdri (plazomicin) 500 mg/10mL 71045-0010-02 | Achaogen, | 10 vials | — | — | FDA listed | — |
| Zemdri (plazomicin) 500 mg/10mL 80735-0820-96 | Cipla | 10 vials | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 9688711 ↗ | Drug substance | U-2328 | Nov 21, 2028 |
| US 9266919 ↗ | Method of use | U-2328 | Nov 21, 2028 |
| US 8383596 ↗ | Drug substance | U-2328 | Jun 25, 2032 |
| US 8822424 ↗ | Drug product | — | Nov 21, 2028 |
| Code | What it grants | Expires |
|---|---|---|
| NCE | New Chemical Entity (5-year) | Jun 25, 2023 |
| GAIN | Qualified Infectious Disease Product (+5-year) | Jun 25, 2028 |
Is there a generic version of ZEMDRI 500 MG/10 ML VIAL?
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🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 69097-0820-96 You're viewing this | 10 VIAL in 1 CARTON (69097-820-96) / 10 mL in 1 VIAL (69097-820-37) | 2018-07-16 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
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 )
🎯 Indications and Usage ▾
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 )
1.1Complicated 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) ].
1.2Usage 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 )
2.1Recommended 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.
2.2Monitoring 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) ] .
2.3Dosage 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. Patients with CLcr greater than or equal to 15 and less than 90 mL/min receiving ZEMDRI may require subsequent dosage adjustments based on change in renal function and/or Therapeutic Drug Monitoring (TDM) as appropriate [ see Dosage and Administration (2.4) ] . 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. 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].
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 l…
💊 Dosage Forms and Strengths ▾
3. DOSAGE FORMS AND STRENGTHS ZEMDRI injection 500 mg/10 mL (50 mg/mL) is a sterile, clear, colorless to yellow solution supplied in a single-dose vial. Each single-dose vial contains plazomicin sulfate equivalent to 500 mg plazomicin freebase. ZEMDRI injection 500 mg/10 mL (50 mg/mL) is a single-dose vial containing plazomicin sulfate equivalent to 500 mg plazomicin free base. ( 3 )
⛔ 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 )
⚠️ Warnings and Cautions ▾
5. WARNINGS AND PRECAUTIONS Hypersensitivity Reactions, including anaphylaxis: Reported for aminoglycosides. If an allergic reaction occurs, discontinue ZEMDRI. ( 5.4 ) Clostridium difficile -Associated Diarrhea : Reported for nearly all systemic antibacterial drugs. Evaluate if diarrhea occurs. ( 5.5 )
5.1Nephrotoxicity Nephrotoxicity has been reported with the use of ZEMDRI [see Adverse Reactions (6.1) ]. Most serum creatinine increases were ≤ 1 mg/dL above baseline and reversible. In Trial 1, the incidence of adverse reactions associated with renal function (acute kidney injury, serum creatinine increased, chronic kidney disease, creatinine clearance decreased, renal failure, renal impairment) was 3.6% (11/303) in ZEMDRI-treated patients compared with 1.3% (4/301) in meropenem-treated patients [see Adverse Reactions (6.1) ].
Serum creatinine increases of 0.5 mg/dL or greater above baseline occurred in 7% (21/300) of ZEMDRI-treated patients compared with 4% (12/297) of meropenem-treated patients. These increases mainly occurred in patients with CLcr ≤ 90 mL/min and were associated with a plazomicin trough level (C min ) greater than or equal to 3 mcg/mL [see Adverse Reactions (6.1) and Clinical Pharmacology (12.2) ] . 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.
In the setting of worsening renal function, the benefit of continuing ZEMDRI should be assessed [see Dosage and Administration (2.2 , 2.4) , Adverse Reactions (6.1) and Use in Specific Populations (8.5 , 8.6) ] . Adjust the initial dosage regimen in cUTI patients with CLcr ≥ 15 mL/min and < 60 mL/min [see Dosage and Administration (2.3) ] . For subsequent doses, TDM is recommended for patients with CLcr ≥15 mL/min and < 90 mL/min [see Dosage and Administration (2.4) ] .
5.2Ototoxicity Ototoxicity with use of ZEMDRI 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. Regarding the incidence of adverse reactions associated with cochlear or vestibular function, in Trial 1, there was one case of reversible hypoacusis (1/303;0.3%) in ZEMDRI-treated patients and one case of tinnitus (1/301;0.3%) in meropenem-treated patients [see Adverse Reactions (6.1) ] .
In Trial 2, one case each of irreversible tinnitus and reversible vertigo was reported in ZEMDRI-treated patients, and one case of an abnormal audiogram occurred in a levofloxacin-treated patient [see Adverse Reactions (6.1) ] . 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. Risk of Ototoxicity Due to Mitochondrial DNA Variants Cases of ototoxicity with aminoglycosides have been observed in patients with certain variants in the mitochondrially encoded 12S rRNA gene ( MT-RNR1 ), particularly the m.1555A>G variant. Ototoxicity occurred in some patients even when their aminoglycoside serum levels were within the recommended range.
Mitochondrial DNA variants are present in less than 1% of the general US population, and the proportion of the variant carriers who may develop ototoxicity as well as the severity of ototoxicity is unknown. In case of known maternal history of ototoxicity due to aminoglycoside use or a known mitochondrial DNA variant in the patient, consider alternative treatments other than amino…
🤒 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 Cipla USA, Inc. at 1-866-604-3268 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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) ZE…
👥 Use in Specific Populations ▾
8. USE IN SPECIFIC POPULATIONS
8.1Pregnancy 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 approximately 2.5-fold the human AUC at the recommended clinical dose. In a pre- and postnatal development study in rats, maternal animals received subcutaneous plazomicin at 0, 3, 8, or 30 mg/kg/day from the start of organogenesis through lactation. There were no adverse effects on maternal function or pre- and postnatal survival, development, behavior, or reproductive function of the offspring at up to 30 mg/kg/day (0.32-fold human AUC at the clinical daily dose of 15 mg/kg).
8.2Lactation 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. 8.4.
Pediatric Use The safety and effectiveness of ZEMDRI in patients less than 18 years of age have not been established.
8.5Geriatric 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. In Trial 1, for ZEMDRI- treated patients ≥ 65 years old, the incidence rate of adverse reactions was 27% (37/137) versus 18.9% (27/143) in the meropenem-treated patients ≥ 65 years old. For ZEMDRI- treated patients < 65 years old, the incidence rate of adverse reactions was 13.3% (22/166) versus 24.1% (38/158) in the meropenem-treated patients < 65 years old.
The rate of adverse reactions a…
🤰 Pregnancy ▾
8.1Pregnancy 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 approximately 2.5-fold the human AUC at the recommended clinical dose. In a pre- and postnatal development study in rats, maternal animals received subcutaneous plazomicin at 0, 3, 8, or 30 mg/kg/day from the start of organogenesis through lactation. There were no adverse effects on maternal function or pre- and postnatal survival, development, behavior, or reproductive function of the offspring at up to 30 mg/kg/day (0.32-fold human AUC at the clinical daily dose of 15 mg/kg).
🧒 Pediatric Use ▾
8.4. Pediatric Use The safety and effectiveness of ZEMDRI in patients less than 18 years of age have not been established.
🧓 Geriatric Use ▾
8.5Geriatric 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. In Trial 1, for ZEMDRI- treated patients ≥ 65 years old, the incidence rate of adverse reactions was 27% (37/137) versus 18.9% (27/143) in the meropenem-treated patients ≥ 65 years old. For ZEMDRI- treated patients < 65 years old, the incidence rate of adverse reactions was 13.3% (22/166) versus 24.1% (38/158) in the meropenem-treated patients < 65 years old.
The rate of adverse reactions associated with renal function for the ZEMDRI-treated patients ≥ 65 years old was 6.6% (9/137) versus 2.8% (4/143) in the meropenem-treated patients. For ZEMDRI- treated patients < 65 years old, the incidence rate of adverse reactions associated with renal function was 1.2% (2/166), versus 0% (0/158) in the meropenem-treated patients [see Clinical Studies (14.1) and Adverse Reactions (6.1) ] . ZEMDRI is substantially excreted by the kidneys, and the risk of adverse reactions to ZEMDRI may be greater in patients with renal impairment.
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and renal function should be monitored. Dosage adjustment in elderly patients should take into account renal function and plazomicin concentrations as appropriate [see Dosage and Administration (2.2 , 2.3 , 2.4) and Clinical Pharmacology (12.3) ] .
🆘 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.
🧬 Clinical Pharmacology ▾
12. CLINICAL PHARMACOLOGY
12.1Mechanism of Action ZEMDRI is an antibacterial drug [see Microbiology (12.4) ] .
12.2Pharmacodynamics 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. Exposure- Response Relationship for Nephrotoxicity in cUTI Patients Based on exposure-response analysis for nephrotoxicity, defined as serum creatinine increases greater than or equal to 0.5 mg/dL from baseline, using the data from two cUTI clinical trials (Trial 1 and Trial 2), development of nephrotoxicity was associated with estimated plazomicin exposure (i.e., the plasma trough concentration [C min ]) in patients with CLcr greater than 30 mL/min and less than or equal to 90 mL/min (N=243).
The incidence of nephrotoxicity was higher in patients with plazomicin C min greater than or equal to 3 mcg/mL (36%, 10/28) compared to patients with plazomicin C min less than 3 mcg/mL (5%, 11/215). 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. At a single dose of 20 mg/kg (1.3 times the maximum recommended dose), ZEMDRI did not prolong the QTc interval to any clinically relevant extent.
12.3Pharmacokinetics 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. The AUC, maximum plasma concentration (C max ), and C min increased in proportion to the dose over the dose range of 4 to 15 mg/kg.
The plazomicin AUC, C max , and C min are summarized in Table 4. Table 4: Pharmacokinetic Parameters (Geometric Mean [±SD]) of Plazomicin Following Administration of ZEMDRI 15 mg/kg by 30-Minute IV Infusion in Healthy Subjects and cUTI Patients with CLcr Greater than or Equal to 90 mL/min Healthy Subjects PK parameters following a single dose of 15 mg/kg; Based on non-compartmental analysis of PK data; AUC 0-inf is reported; C min is concentration at 24 hours. Geometric mean (±SD) N=54 cUTI Patients Day 1 PK parameters following administration of 15 mg/kg; Derived based on population PK model; AUC 0-24h is reported.
Geometric mean (±SD) N=87 AUC (mcg∙h/mL) 257 (±67.0) 226 (±113) C max (mcg/mL) 73.7 (±19.7) 51.0 (±26.7) C min (mcg/mL) 0.3 (±0.2) 0.5 (±1.2) Distribution The mean (±SD) volume of distribution of plazomicin in healthy adults and cUTI patients is 17.9 (±4.8) and 30.8 (±12.1) L, respectively. The average binding of plazomicin to human plasma proteins is approximately 20%. The degree of protein binding was concentration-independent across the range tested in vitro (5 to 100 mcg/mL).
Elimination The mean (±SD) total body clearance of plazomicin in healthy adults and cUTI patients is 4.5 (±0.9) and 5.1 (±2.01) L/h, respectively. The mean (±SD) half-life of plazomicin was 3.5 h (±0.5) in healthy adults with normal renal function (n=54). Metabolism Plazomicin does not appear to be metabolized to any appreciable extent.
Excretion Plazomicin is primarily excreted by the kidneys. Following a single 15 mg/kg IV dose of radiolabeled plazomicin in healthy subjects, 56% of the total administered radioactivity was recovered in urine within 4 hours, 89.1% was recovered within 168 hours, with less than 0.2% in feces. In total, 97.5% of the dose was recovered in the urine as unchanged plazomicin.
The mean renal clearance (±SD) of plazomicin (4.6 [±1.2] L/h) was similar to total body clearance, suggesting that plazomicin is eliminated by the kidneys. Specific Populations No clinically significant differences in the pharmacokinetics of plazomicin were observed based…
🧬 Mechanism of Action ▾
12.1Mechanism of Action ZEMDRI is an antibacterial drug [see Microbiology (12.4) ] .
📦 How Supplied / Storage and Handling ▾
16. HOW SUPPLIED/STORAGE AND HANDLING
16.1How 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 69097-820-96 Single use, fliptop vial, 10-mL 10 500 mg in 10 mL (50 mg/mL)
16.2Storage and Handling Store ZEMDRI injection 500 mg/10 mL (50 mg/mL) refrigerated at 2°C to 8°C (36°F to 46°F).
📦 Storage and Handling ▾
16.2Storage and Handling Store ZEMDRI injection 500 mg/10 mL (50 mg/mL) refrigerated at 2°C to 8°C (36°F to 46°F).
📋 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
💬 Information for Patients ▾
17. 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 [see Warnings and Precautions (5.1) ] .
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 [see Warnings and Precautions (5.2) ] . 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 Warnings and Precautions (5.3) ] . 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 [see Use in Specific Populations (8.1) ]. 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 [see Warnings and Precautions (5.5) ] . 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 [see Warnings and Precautions (5.6) ] . 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 [see Warnings and Precautions (5.7) ] .