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):
  • In patients older than 18 years of age, it is approved for the treatment of serious urinary tract infections (UTI), including pyelonephritis brought on by:
    • Escherichia coli,
    • Klebsiella pneumoniae,
    • Proteus mirabilis, and
    • Enterobacter cloacae.
  • Note: After the IV treatment is finished, the patient may get the appropriate oral treatment to finish the 7–10 day course of therapy (IV plus oral).

Plazomicin (Zemdri) Dose in Adults

Plazomicin (Zemdri) Dose for complicated Urinary tract infection (UTI):

• 15 mg/kg IV once a day for 4 - 7 days.
• When there are no other therapeutic choices for complex UTI, the treatment should only be used.
• Note:
  • Total body weight (TBW) should be used to calculate the dose in non-obese patients.

Use in Children:

The drug's effectiveness and safety in children have not been determined.

Pregnancy Risk Category: Not assigned

• [US Boxed Warning]
  • When used during pregnancy, aminoglycosides such as plazomicin can cause harm to fetuses.
• Children whose moms took streptomycin during pregnancy have been documented to suffer entire irreversible bilateral congenital deafness.
• There is a chance of injury even if there haven't been any reports of serious side effects for the child or the foetus after maternal usage of all aminoglycosides.

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.
• The manufacturer advises weighing the advantages and disadvantages of treatment for the mother and child.

Plazomicin (Zemdri) Dose in Kidney Disease:

Note:

• Using the total body weight (or ideal body weight for patients whose total body weight is less than 25% of their IBW), the Cockcroft-Gault formula estimates CrCl.
• 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:
  • Patients with severe renal impairment have not been investigated, and dosage modifications have not been given.
• End-stage renal disease (ESRD) requiring hemodialysis:
  • Patients with severe renal impairment have not been investigated, and dosage modifications have not been given.
• Continuous renal replacement therapy (CRRT):
  • Patients with severe renal impairment have not been investigated, and dosage modifications have not been given.

Note:

• In individuals with a CrCl of 15 to 90 ml/minute, measure plasma trough concentrations (within 30 minutes of the next planned dosage).
• Dosing intervals for patients with plasma trough concentrations above 3 mcg/ml should be 1.5 times longer (from every 24 hours to every 36 hours or from 48 to 72 hours).

Plazomicin (Zemdri) Dose in Liver disease:

Patients with liver disease have not been studied with it. The manufacturer hasn't offered any dose modifications.

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's critical to keep an eye on how the renal system is performing.
  • 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.
  • Patients may not detect ototoxicity symptoms, which might take up to a year to appear.
• 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 who have significant renal impairment might need to change their dosage.
  • It should not be used in patients with preexisting kidney dysfunction.

Plazomicin: Drug Interaction

Monitoring parameters:

• Urinalysis,
• urine output,
• BUN,
• Plasma plazomicin trough concentrations (for patients with CrCl 90 mL/min);
• Serum creatinine before treatment commencement and every day while receiving treatment;
• 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.

After intravenous injection, the time at which serum concentrations peak:

• 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.