Usual Adult Dose for Pyelonephritis

15 mg/kg IV infusion (given over 30 minutes) every 24 hours

• Duration of therapy: 4 to 7 days

Comment: Appropriate oral therapy should be considered after 4 to 7 days of treatment to complete a total (IV and oral) treatment duration of 7 to 10 days.

Use: Treatment of complicated urinary tract infections (cUTI), including pyelonephritis caused by susceptible strains of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae

Usual Adult Dose for Urinary Tract Infection

15 mg/kg IV infusion (given over 30 minutes) every 24 hours

• Duration of therapy: 4 to 7 days

Comment: Appropriate oral therapy should be considered after 4 to 7 days of treatment to complete a total (IV and oral) treatment duration of 7 to 10 days.

Use: Treatment of complicated urinary tract infections (cUTI), including pyelonephritis caused by susceptible strains of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae

Renal Dose Adjustments

RENAL DOSE ADJUSTMENTS:
Initial dose:

• CrCl 60 to less than 90 mL/min: 15 mg/kg IV infusion (given over 30 minutes) every 24 hours
• CrCl 30 to less than 60 mL/min: 10 mg/kg IV infusion (given over 30 minutes) every 24 hours
• CrCl 15 to less than 30 mL/min: 10 mg/kg IV infusion (given over 30 minutes) every 48 hours
• CrCl less than 15 mL/min: Data not available

Maintenance dose: Determined by therapeutic drug monitoring (TDM)
Duration of therapy: 4 to 7 days

Comments:

• Trough levels should be measured approximately 30 minutes prior to the second dose of this drug.
• Dose adjustments based on TDM include extending the dosage interval by 1.5-fold (e.g., from every 24 hours to every 36 hours OR from every 48 hours to every 72 hours) in patients with trough concentrations 3 mcg/mL or higher.

Liver Dose Adjustments

Data not available

Dose Adjustments

Therapeutic drug monitoring/range: Trough concentrations below 3 mcg/mL

Dosing:

• Dosing should be determined by the patient's total body weight (TBW).
• If the patient's TBW is 25% greater than the ideal body weight (IBW), the dosing weight should be determined by the following: IBW plus 0.4 times (TBW weight minus IBW).

Precautions

US BOXED WARNINGS:
NEPHROTOXICITY:

• Nephrotoxicity has been reported with this drug.
• The risk of nephrotoxicity is greater in patients with renal dysfunction, the elderly, and in those receiving concomitant nephrotoxic medications.
• Assess creatinine clearance in all patients prior to initiation of therapy and daily during therapy.
• Therapeutic drug monitoring (TDM) is recommended for cUTI patients with CrCl less than 90 mL/min to avoid potentially toxic levels.

OTOTOXICITY:

• Ototoxicity, manifested as hearing loss, tinnitus, and/or vertigo, has been reported with this drug.
• 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 dysfunction, and in patients receiving higher doses and/or longer durations of therapy than recommended.

NEUROMUSCULAR BLOCKADE:

• Aminoglycosides have been associated with neuromuscular blockade.

During therapy with this drug, 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.

FETAL HARM:

• Aminoglycosides, including this drug, can cause fetal harm when administered to a pregnant woman.

NARROW THERAPEUTIC INDEX:

• This drug should be considered a narrow therapeutic index (NTI) drug as small differences in dose or blood concentrations may lead to serious therapeutic failures or adverse drug reactions.

Recommendations:

• Generic substitution should be done cautiously, if at all, as current bioequivalence standards are generally insufficient for NTI drugs.
• Additional and/or more frequent monitoring should be done to ensure receipt of an effective dose while avoiding unnecessary toxicities.

CONTRAINDICATIONS:

• Hypersensitivity to the active component, any aminoglycoside, or any of the ingredients

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Continuous renal replacement therapy: Data not available
Hemodialysis: Data not available

Other Comments

Administration advice:

• Other drugs should not be infused simultaneously through the same IV line.

Storage requirements:

• Undiluted vials should be stored refrigerated (2 to 8C).
• Once diluted, the solution is stable for up to 24 hours at room temperature.

Reconstitution/preparation techniques:

• This drug should be diluted to 2.5 to 45 mg/mL with a compatible solution.

IV compatibility:

• Compatible: 0.9% sodium chloride or Lactated Ringer's solution; compatibility with other drugs has not been established
• This drug should not be physically mixed or added to other drugs.

General:

• Limitation of use: This drug should be reserved for patients with cUTI who have limited/no alternative treatment options.

Monitoring:

• General: Trough levels
• Renal: Regular renal function monitoring

Patient advice:

• Patients should be told to report any unusual or severe side effects, including signs/symptoms of ototoxicity and nephrotoxicity.
• Patients should be directed to take the full course of treatment, even if they feel better.
• Advise patients to speak to their healthcare provider if they become pregnant, intend to become pregnant, or are breastfeeding.

Frequently asked questions

• What type of drug is Zemdri?