ZEMDRI (plazomicin sulfate)

There are 1 contraindications. Absolute contraindication.

Contraindication List
Mt-RNr1 increased risk of aminoglycoside-induced hearing loss

There are 8 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Clostridioides difficile infection
Disorder of the vestibulocochlear nerve
Myasthenia gravis
Pregnancy

There are 3 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Kidney disease with likely reduction in glomerular filtration rate (GFr)
Tinnitus
Vertigo

There are 11 severe adverse reactions.

More Frequent	Less Frequent
Hypertension Hypotension Kidney disease with reduction in glomerular filtration rate (GFr)	Auditory neurotoxicity Nephrotoxicity

Rare/Very Rare
Abnormal hepatic function tests Clostridioides difficile infection Hypersensitivity drug reaction Hypokalemia Neuromuscular blockade Ototoxicity

There are 10 less severe adverse reactions.

More Frequent	Less Frequent
Diarrhea Headache disorder Nausea Vomiting	None.

Rare/Very Rare
Constipation Dizziness Dyspnea Gastritis Hematuria Tinnitus

Aminoglycosides, including plazomicin, can cause fetal harm when administered to pregnant women. (See Fetal/Neonatal Morbidity under Warnings/Precautions: Warnings, in Cautions.) Data are not available regarding use of plazomicin in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Pregnant women should be advised of the potential risk to a fetus.

In animal studies, no plazomicin-related visceral or skeletal malformations were observed in pregnant rats or rabbits receiving plazomicin at doses that resulted in maternal exposures 0.8- or 2.5-fold higher, respectively, than human exposures at the recommended dosage; auditory function was not measured in the offspring of these animals.

Plazomicin is distributed into milk in rats. It is not known if the drug is distributed into human milk, affects the breast-fed infant, or affects milk production. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for plazomicin and any potential adverse effects on the breast-fed infant from the drug or the underlying maternal condition.

In phase 2 and 3 clinical studies evaluating plazomicin, 40% of patients were 65 years of age and older; 17.2% of patients were 75 years of age and older. In patients 65 years of age or older in the phase 3 study (Trial 1), adverse effects were reported in 27 or 18.9%

of those receiving plazomicin or meropenem, respectively; in those younger than 65 years of age, adverse effects were reported in 13.3 or 24.1%, respectively.

The rate of adverse renal effects in patients 65 years and older was 6.6 or 2.8% in those receiving plazomicin or meropenem, respectively; in those younger than 65 years of age, such adverse effects were reported in 1.2

or 0%, respectively. Clinically relevant age-related differences in plazomicin exposures have not been observed. Although trough plasma concentrations of plazomicin reported in geriatric patients 65-90 years of age were higher than those reported in younger adults, these increased trough plasma concentrations were mainly attributed to age-related changes in renal function.

Since the risk of adverse effects may be greater in patients with renal impairment and geriatric patients are more likely to have decreased renal function, plazomicin dosage should be selected carefully in geriatric patients and renal function should be monitored. Dosage adjustments in geriatric patients should take into account renal function and plazomicin plasma concentrations as appropriate. (See Renal Impairment under Dosage and Administration: Special Populations.)