Plazomicin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous, as sulfate [preservative free]:

Zemdri: 500 mg/10 mL (10 mL)

Pharmacology

Mechanism of Action

Interferes with bacterial protein synthesis by binding to 30S ribosomal subunit resulting in a defective bacterial cell membrane.

Pharmacokinetics/Pharmacodynamics

Distribution

0.24 +/- 0.04 L/kg (Cass 2011)

Excretion

Urine (97.5% as unchanged drug); feces (<0.2%)

Clearance: 1.1 ± 0.1 mL/minute/kg (Cass 2011)

Time to Peak

IV: At the end of or just after infusion (Cass 2011)

Half-Life Elimination

3 to 4 hours (Cass 2011)

Protein Binding

~20%

Use in Specific Populations

Special Populations: Renal Function Impairment

AUC is increased and clearance is decreased in renal impairment.

Use: Labeled Indications

Urinary tract infection, complicated (including pyelonephritis): Treatment of complicated urinary tract infections (UTI), including pyelonephritis caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae in patients ≥18 years. Note: Reserve for use in complicated UTI patients who have limited or no alternative treatment options.

Contraindications

Hypersensitivity to plazomicin, any aminoglycoside, or any component of the formulation

Dosage and Administration

Dosing: Adult

Urinary tract infection (UTI), complicated: IV: 15 mg/kg once daily for 4 to 7 days; may follow with appropriate oral therapy to complete a total of 7 to 10 days of therapy (IV plus oral). Note: Use total body weight (TBW) to calculate dose in non-obese patients. For patients with TBW greater than ideal body weight (IBW) by ≥25%, see Dosing: Obesity.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Obesity

For patients with TBW greater than ideal body weight (IBW) by ≥25%, use adjusted body weight (ABW) for dosing. ABW = IBW + 0.4 x (TBW-IBW).

Reconstitution

IV: Dilute in NS or LR to total volume of 50 mL (maximum concentration: 45 mg/mL).

Administration

IV: Infuse over 30 minutes.

Storage

Store intact vials refrigerated at 2°C to 8°C (36°F to 46°F). IV infusion solutions mixed in NS or LR at concentrations of 2.5 to 45 mg/mL are stable for 24 hours at room temperature.

Drug Interactions

Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Arbekacin: May enhance the nephrotoxic effect of Aminoglycosides. Arbekacin may enhance the ototoxic effect of Aminoglycosides. Monitor therapy

Ataluren: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, an increased risk of nephrotoxicity may occur with the concomitant use of ataluren and aminoglycosides. Avoid combination

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Monitor therapy

Botulinum Toxin-Containing Products: Aminoglycosides may enhance the neuromuscular-blocking effect of Botulinum Toxin-Containing Products. Monitor therapy

Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Monitor therapy

CARBOplatin: Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Monitor therapy

Cefazedone: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephalosporins (2nd Generation): May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephalosporins (3rd Generation): May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephalosporins (4th Generation): May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephalothin: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cephradine: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination

CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Consider therapy modification

CycloSPORINE (Systemic): Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Monitor therapy

Distigmine: Aminoglycosides may diminish the therapeutic effect of Distigmine. Monitor therapy

Foscarnet: May enhance the nephrotoxic effect of Aminoglycosides. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Monitor therapy

Mannitol (Systemic): May enhance the nephrotoxic effect of Aminoglycosides. Avoid combination

Mecamylamine: Aminoglycosides may enhance the neuromuscular-blocking effect of Mecamylamine. Avoid combination

Methoxyflurane: Aminoglycosides may enhance the nephrotoxic effect of Methoxyflurane. Avoid combination

Neuromuscular-Blocking Agents: Aminoglycosides may enhance the respiratory depressant effect of Neuromuscular-Blocking Agents. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Monitor therapy

Oxatomide: May enhance the ototoxic effect of Aminoglycosides. Monitor therapy

Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Exceptions: Amoxicillin; Ampicillin; Bacampicillin; Cloxacillin; Dicloxacillin; Nafcillin; Oxacillin; Penicillin G (Parenteral/Aqueous); Penicillin G Benzathine; Penicillin G Procaine; Penicillin V Benzathine; Penicillin V Potassium. Consider therapy modification

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Tenofovir Products: Aminoglycosides may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Adverse Reactions

1% to 10%:

Cardiovascular: Hypertension (2%), hypotension (1%)

Central nervous system: Headache (1%)

Gastrointestinal: Diarrhea (2%), nausea (1%), vomiting (1%)

Genitourinary: Nephrotoxicity (4%)

Otic: Ototoxicity (2%)

Renal: Increased serum creatinine (4%; CrCl: 30 to 90 mL/minute: ≤10%), acute renal failure (≤4%), decreased creatinine clearance (≤4%), renal disease (≤4%), renal failure syndrome (≤4%), renal insufficiency (≤4%)

Frequency not defined:

Central nervous system: Dizziness

Endocrine & metabolic: Hypokalemia

Gastrointestinal: Constipation, gastritis

Genitourinary: Hematuria

Hepatic: Increased serum alanine aminotransferase

Respiratory: Dyspnea

<1%, postmarketing, and/or case reports: Hypoacusis (reversible), tinnitus (irreversible), vertigo

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Serious and occasionally fatal hypersensitivity reactions have been reported in patients receiving aminoglycosides; before therapy, inquire about previous hypersensitivity to other aminoglycosides. Discontinue plazomicin if an allergic reaction occurs.
• Nephrotoxicity: [US Boxed Warning]: May cause nephrotoxicity; risk factors include preexisting renal impairment, elderly patients, and concomitant nephrotoxic agents. Monitor renal function closely and reassess continuation of therapy if nephrotoxicity occurs. Most serum creatinine increases were ≤1 mg/dL above baseline and usually reversible; increases mainly occurred in patients with CrCl ≤90 mg/dL and were associated with plazomicin trough concentrations ≥3 mcg/mL.
• Neuromuscular blockade: [US Boxed Warning]: May cause neuromuscular blockade, especially in patients with underlying neuromuscular disorders and/or in patients receiving concomitant neuromuscular blocking agents.
• Ototoxicity: [US Boxed Warning]: May cause ototoxicity manifested as hearing loss, tinnitus, and/or vertigo; risk factors include family history of hearing loss, renal impairment, and receipt of higher doses and/or longer durations of therapy than recommended. Symptoms of ototoxicity may be irreversible and may not become evident until after therapy is complete.
• Superinfection: May cause superinfection of Clostridioides (formerly Clostridium) difficile infection (CDI) and pseudomembranous colitis; CDI has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Hearing impairment: Use with caution in patients with hearing loss or a family history of hearing loss.
• Neuromuscular disorders: Use with caution in patients with neuromuscular disorders, including myasthenia gravis.
• Renal impairment: Use with caution in patients with preexisting renal insufficiency; dosage modification required.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pregnancy: [US Boxed Warning]: Aminoglycosides may cause fetal harm if administered to a pregnant woman.

Monitoring Parameters

Urinalysis, urine output, BUN, serum creatinine (prior to initiation of therapy and daily during therapy), plasma plazomicin trough (for patients with CrCl <90 mL/min); symptoms of ototoxicity or neuromuscular blockade

Pregnancy

Pregnancy Considerations

[US Boxed Warning]: Aminoglycosides may cause fetal harm if administered to a pregnant woman.

There are several reports of total irreversible bilateral congenital deafness in children whose mothers received another aminoglycoside (streptomycin) during pregnancy. Although serious side effects to the fetus/infant have not been reported following maternal use of all aminoglycosides, a potential for harm exists.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Have patient report immediately to prescriber signs of kidney problems (unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain), hearing loss, noise or ringing in the ears, severe dizziness, change in balance, muscle weakness, or signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.