Plazomicin (Zemdri) is an aminoglycoside antibiotic that is administered intravenously to treat patients with complicated urinary tract infections.

Plazomicin (Zemdri) Uses:

• Complicated Urinary tract infection (including pyelonephritis):
  • It is indicated for the treatment of complicated urinary tract infections (UTI) in patients older than 18 years of age, including pyelonephritis caused by:
    • Escherichia coli,
    • Klebsiella pneumoniae,
    • Proteus mirabilis, and
    • Enterobacter cloacae.
  • Note: The treatment should be reserved for use in complicated UTI when no alternative treatment options are available.

Plazomicin (Zemdri) Dose in Adults

Plazomicin (Zemdri) Dose in the treatment of complicated Urinary tract infection (UTI):

• 15 mg/kg IV once a day for 4 - 7 days.
• Appropriate oral treatment may follow after the completion of IV treatment to complete a total course of 7 to 10 days of therapy (IV plus oral).
• Note:
  • Total body weight (TBW) should be used to calculate the dose in non-obese patients.

Use in Children:

The safety and efficacy if the drug in children have not been established.   

Pregnancy Risk Category: Not assigned

• [US Boxed Warning]
  • When used during pregnancy, aminoglycosides such as plazomicin can cause harm to fetuses.
• Case reports of total irreversible bilateral congenital deafness have been reported in children whose mothers streptomycin during pregnancy.
• While no reports of serious side effects for the infant or the fetus have been made following maternal use all aminoglycosides, there is still the possibility of harm.

Use of plazomicin while breastfeeding

• It is unknown if the drug will be excreted into breastmilk.
• Aminoglycosides do not usually get into breastmilk, so infant exposure is unlikely.
• Manufacturer suggests that you weigh the risks and benefits of treatment for the mother and baby.

Plazomicin (Zemdri) Dose in Kidney Disease:

Note:

• CrCl estimated by Cockcroft-Gault formula using Total Bodyweight (or Ideal body weight for patients when the total body weight is ≥25% than the IBW)
• CrCl ≥60 mL/minute:
  • Adjustment in the dose is not necessary.
• CrCl 30 to <60 mL/minute:
  • 10 mg/kg once daily
• CrCl 15 to <30 mL/minute:
  • 10 mg/kg once every other day (every 48 hours)
• CrCl <15 mL/minute:
  • It has not been studied in patients with severe renal impairment and dosage adjustments have not been provided.
• End-stage renal disease (ESRD) requiring hemodialysis:
  • It has not been studied in patients with severe renal impairment and dosage adjustments have not been provided.
• Continuous renal replacement therapy (CRRT):
  • It has not been studied in patients with severe renal impairment and dosage adjustments have not been provided.

Note:

• Measure plasma trough concentrations (within 30 minutes prior to the next scheduled dose) in patients with a CrCl of 15 - 90 ml/minute.
• Patients who have plasma trough concentrations exceeding 3 mcg/ml the dosing intervals should be extended by 1.5 fold (from every 24 hours to every 36 hours or from 48 to 72 hours).   

Plazomicin (Zemdri) Dose in Liver disease:

It has not been studied in patients with liver disease. Adjustments in the dose have not been provided by the manufacturer.   

Side Effects of Plazomicin (Zemdri):

• Cardiovascular:
  • Hypertension
  • Hypotension
• Central Nervous System:
  • Headache
• Gastrointestinal:
  • Diarrhea
  • Nausea
  • Vomiting
• Genitourinary:
  • Nephrotoxicity
• Otic:
  • Ototoxicity
• Renal:
  • Increased Serum Creatinine
  • Acute Renal Failure
  • Decreased Creatinine Clearance
  • Renal Disease
  • Renal Failure Syndrome
  • Renal Insufficiency

Rare Side effects of Plazomicin (Zemdri):

• Central Nervous System:
  • Dizziness
• Endocrine & Metabolic:
  • Hypokalemia
• Gastrointestinal:
  • Constipation
  • Gastritis
• Genitourinary:
  • Hematuria
• Hepatic:
  • Increased Serum Alanine Aminotransferase
• Respiratory:
  • Dyspnea

Contraindications to Plazomicin (Zemdri):

• Allergies to plazomicin or other aminoglycosides or any component of the formulations

Warnings and precautions

• Hypersensitivity reactions
  • It can cause severe and sometimes fatal allergic reactions.
  • It is important to ask patients about any previous hypersensitivity reactions to other aminoglycosides. If there are any, discontinue use of the drug.
• Nephrotoxicity: [US Boxed Warning]
  • It can cause nephrotoxicity.
  • Patients taking concomitant nephrotoxic medications, patients with preexisting kidney impairment, and elderly people are at greater risk for developing nephrotoxicity.
  • It is important to monitor the function of the renal system.
  • Most patients who participated in clinical trials experienced mild reversible renal dysfunction (creatinine levels less than 1 mg/dl higher than the baseline).
  • Patients with a baseline CrCl less than 90 mg/dl or a trough drug concentration greater than 3 mg/ml were more likely to have renal dysfunction.
• Neuromuscular blockade: [US Boxed Warning]:
  • It can cause neuromuscular blockade, which could lead to weakness.
  • Patients with myasthenia Gravis and other neuromuscular disorders should be cautious when using the drug.
• Ototoxicity: [US Boxed Warning]
  • Ototoxicity can result from its use, manifesting as vertigo, hearing loss, and/or tinnitus.
  • Ototoxicity is more common in patients with a history of cytotoxicity, either from their family or their own.
  • When higher doses of the drug are taken for a longer time, there is a greater risk of developing ototoxicity.
  • Ototoxicity symptoms may not be noticed by patients and may take up to a year to manifest.
• Superinfection
  • Superinfections can result from prolonged use of the drug.
  • Clostridium difficile infection can cause diarrhea, cramps and bloody stool.
  • Clostridioides difficile infections have been reported after only two months of treatment with antibiotics.
• Hearing impairment:
  • Patients who have a history of hearing loss in their family or personal should not use this drug.
• Neuromuscular disorders:
  • Patients suffering from neuromuscular disorders like myasthenia gravis or other neurological conditions should be cautious when taking the drug.
• Renal impairment
  • Patients with severe renal impairment may require dosage modification.
  • It should not be used in patients with preexisting kidney dysfunction.

Plazomicin: Drug Interaction

Monitoring parameters:

• Urinalysis,
• urine output,
• BUN,
• Serum creatinine before treatment initiation and daily during therapy,
• Plasma plazomicin trough concentrations (for patients with CrCl <90 mL/min);
• Features of ototoxicity or neuromuscular blockade

How to administer Plazomicin (Zemdri)?

It is infused intravenously over thirty minutes.   

Mechanism of action of Plazomicin (Zemdri):

• It binds with the 30S subunit of the ribosomal ribosomal subunit, interfering in bacterial protein synthesis.
• This results in defective bacterial cell membranes.

Protein binding:

• About 20%

Half-life elimination:

• 3 to 4 hours.

Time to peak serum concentrations after intravenous administration:

• After the infusion or at the end of the injection.

Excretion:

• It is excreted in urine (97.5% as unchanged drug);
• feces (<0.2%);

International Brand Names of Plazomicin:

• Zemdri

Plazomicin Brand Names in Pakistan:

No Brands Available in Pakistan.