Gentamicin

Indications : gentamicin is indicated in bacteraemia, urinary tract infections, chest infections, severe neonatal infections and other serious systemic infections due to susceptible organisms, in adults and children including neonates.

1. Consideration should be given to official local guidance on the appropriate use of antibacterial agents.

Adults:

Systemic infections: if renal function is not impaired, 3-5 mg/kg/day in divided doses according to severity of infection, adjusting according to clinical response and body weight. Serious infections: if renal function is not impaired, 5mg/kg daily in divided doses at six or eight hourly intervals.

The total daily dose may be subsequently increased or decreased as clinically indicated. Urinary tract infections: as 'systemic infections'. Or, if renal function is not impaired, 160mg once daily may be used.

Paediatric Patients:

The daily dose recommended in children (aged 1 year and above) and adolescents with normal renal function, is 3-6 mg/kg body weight per day as 1 single dose (preferred) or up to 2 single doses. 5 mg/kg body weight per day as 1 single dose (preferred) or up to 2 single doses.

The daily dose in neonates is 4-7 mg/kg body weight per day. Due to the longer half- life, neonates are given the required daily dose in 1 single dose.

Elderly:

There is some evidence that elderly patients may be more susceptible to aminoglycoside toxicity whether secondary to previous auditory/vestibular impairment or borderline renal dysfunction. Accordingly, therapy should be closely monitored by frequent determination of gentamicin serum levels, assessment of renal function and signs of toxicity.

Renal impairment:

Gentamicin is excreted by simple glomerular filtration. In impaired renal function, the recommended daily dose has to be decreased and adjusted to the renal function. Nomograms are available for the calculation of the dose, which depends on the patient's age, weight, and renal function The following table may be useful when treating adults.

Blood Urea Creatine clearance (mg/100ml) (mmol/I) (GFR) (ml/min) Dose and frequency of administration <40 6-7 >70 80mg* 8 hourly 40-100 6-17 30-70 80mg* 12 hourly 100-200 17-34 10-30 80mg* daily >200 >34 5-10 80mg* every 48 hours Twice weekly intermittent haemodialysis <5 80mg* after dialysis *60mg if body weight <60kg.

Frequency of dosage in hours may also be approximated as serum creatine (mg%) x eight or in SI units, as serum creatine (μmol/l) divided by 11. If these dosage guides are used peak serum levels must be measured. Peak levels of gentamicin occur approximately one hour after intramuscular injectable and intravenous injectable.

Trough levels are measured just prior to the next injectable. Assay of peak serum levels gives confirmation of adequacy of dosage and also serves to detect levels above 10mg/l, at which the possibility of ototoxicity should be considered.

One hour concentrations of gentamicin should not exceed 10mg/l (but should reach 4mg/l), while the pre-dose trough concentration should be less than 2mg/l Method of administration The recommended dose and precautions for intramuscular and intravenous administration are identical.

Gentamicin when given intravenously should be injected directly into a vein or into the drip set tubing over no less than three minutes. If administered by infusion, this should be over no longer than 20 minutes and in no greater volume of fluid than 100ml.

Monitoring advice:

Serum concentration monitoring of gentamicin is recommended, especially in elderly, in newborns and in patients with impaired renal function. Samples are taken at the end of a dosing interval (trough level). Trough levels should not exceed 2 μg/ml administering gentamicin twice daily and 1 μg/ml for a once daily dose.

4

The following CIOMS frequency rating is used, when applicable: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10 000 to <1/1000); very rare (<1/10 000), not known (cannot be estimated from the available data).

4).

Gastrointestinal disorders:

Very common: vomiting Not known: stomatitis, nausea Hepatobiliary disorders: Not known: abnormal liver function, transaminases increased Skin and subcutaneous tissue disorders: Not known: Stevens-Johnson syndrome, toxic epidermal necrosis, rash, purpura, urticaria, pruritus Renal and urinary disorders: Very rare: acute renal failure, Fanconi-like syndrome in patients treated with a prolonged course of high dose Not known: nephrotoxicity (usually reversible) has been reported.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

1. Myasthenia gravis.

Gentamicin Injection USP (gentamicin sulfate) is clinically effective in serious infections caused by susceptible strains of the following bacteria: Pseudomonas aeruginosa, Proteus species (indole negative and indole positive), Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Serratia marcescens, and Staphylococcus species (methicillin-susceptible strains only).

Gentamicin Injection USP (gentamicin sulfate) may be considered for the treatment of Staphylococcus infections when other less potentially toxic drugs are contraindicated and bacterial susceptibility tests and clinical judgment indicate its use.

The use of gentamicin is indicated in the treatment of serious infections caused by laboratory determined susceptible bacteria, with due regard for relative antibiotic toxicity. Therefore, the drug should be considered for treatment of:  Bacteremia  Respiratory tract infections  Urinary tract infections  Infected wounds: surgical and traumatic  Bone and soft tissue infections, including peritonitis and burns complicated by sepsis In the majority of cases bacteriologic cultures should be obtained initially to identify the causative organism(s) and to determine susceptibility to gentamicin.

Sensitivity discs of 2 mcg and 10 mcg are available for this purpose. In suspected or documented gram-negative septicemia, particularly when shock or hypotension is present, gentamicin should be considered for initial antimicrobial therapy.

If anaerobic organisms are suspected, additional antimicrobial therapy should be added to the gentamicin regimen. The decision to continue therapy with gentamicin should be based on results of the antimicrobial susceptibility tests, clinical response of the patient, and consideration of relative antibiotic toxicity.

Clinical studies have shown that organisms previously sensitive to gentamicin have become resistant during therapy. Acquired resistance to one aminoglycoside does not necessarily confer resistance to other agents in the class. If susceptibility tests indicate the causative organism is resistant to gentamicin, other tests or additional antimicrobial therapy should be instituted.

Combined therapy with gentamicin and a penicillin type of drug has been used in suspected sepsis until bacteriological studies have identified the etiological organism. 1 Pediatrics Pediatrics (≤ 12 years): Based on the data submitted and reviewed by Health Canada, the safety and efficacy of Gentamicin Injection USP in pediatric patients has been established.

Therefore, Health Canada has authorized an indication for pediatric use. Gentamicin Injection USP (gentamicin sulfate) should not be used in newborns, infants and neonates except for the treatment of life-threatening infections. Dose adjustments for children are necessary (see WARNINGS AND PRECAUTIONS and DOSAGE AND ADMINISTRATION).

2 Geriatrics Geriatrics (> 65 years of age): Dose adjustment may be required for elderly patients due to age related decline in glomerular filtration rate. Gentamicin Injection USP should be used with caution in patients with auditory, vestibular or neuromuscular dysfunction (see WARNINGS AND PRECAUTIONS and DOSAGE AND ADMINISTRATION).

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Gentamicin Injection USP and other antibacterial drugs, Gentamicin Injection USP should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.

When culture and susceptibility information are available, they should be considered in selecting or modifying antimicrobial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

1 Dosing Considerations Gentamicin Injection USP is usually given intramuscularly. g. shock, hemorrhagic disorders, extensive burns, reduced muscle mass, renal impairment, large injection volumes). Using the recommended doses, considerable variation in the serum concentration between individual patients has been observed.

Monitoring of peak and trough gentamicin serum concentrations is important to insure adequate therapeutic concentration which may be critical, while at the same time avoiding potentially toxic concentrations. Following intravenous or intramuscular administration, 2 or 3 times daily, the peak concentration, measured 30 minutes to 1 hours after administration, is expected to be in the range of 4 to 6 mcg/mL.

With once daily administration, transient, high peak concentrations can be anticipated. With all regimens, the dosages should be adjusted to avoid prolonged concentrations above 10 to 12 mcg/mL. Trough levels above 2 mcg/mL, measured just before the next dose, should also be avoided.

Determination of the adequacy of a serum level for a particular patient must take into consideration susceptibility of the causative microorganism, severity of infection, and the status of the patient's host-defence mechanisms. The patient’s pre-treatment body weight should be obtained for calculation of correct dosage.

For obese patients, the dosage calculation should be based on an estimate of lean body mass. The usual duration of treatment for all patients is 7 to 10 days. In complicated infections, a longer course of therapy may be necessary. In such cases, monitoring of renal, auditory and vestibular functions is recommended, since toxicity is more likely to occur with treatment extended over 10 days.

Dosage should be reduced if clinically indicated. 2 Recommended Dose and Dosage Adjustment INTRAMUSCULAR INJECTION - Patients with Normal Renal Function Urinary Tract Infections: Gentamicin is highly concentrated in urine and renal tissue.

In patients with lower urinary tract infection, particularly if chronic or recurrent and without Gentamicin Injection USP Page 7 of 37 evidence of impairment of renal function, Gentamicin Injection USP may be administered intramuscularly either in a dose of 160 mg once a day or 80 mg twice a day for 7 to 10 days.

0 mg/kg of body weight. Upper urinary tract infections, such as pyelonephritis, and more particularly if there are signs of systemic involvement, should be treated according to one of the dosage schedules for systemic infections. 5, it may be advantageous to alkalinize the urine of patients for urinary tract infections.

Systemic Infections:

Adults: The recommended dosage of Gentamicin Injection USP for adult patients with serious infections and normal renal function is 3 mg/kg/day administered intramuscularly in three equal doses. Therefore, for patients weighing over 60 kg, the usual dosage is 80 mg three times daily.

For patients weighing 60 kg or less, the usual dosage is 60 mg three times a day. The usual duration of treatment is 7 to 10 days. In difficult and complicated infections, a longer course of therapy may be necessary. In such cases, monitoring of renal, auditory and vestibular functions is advisable.

Life-Threatening Infections:

In patients with life-threatening infections, dosages up to 5 mg/kg/day should be administered in three or four equally divided doses. This dosage should be reduced to 3 mg/kg/day as soon as clinically indicated. Special Populations Pediatrics (≤ 12 years of age) The precautions for the treatment of infection in children are the same as those for adults.

5 mg/kg administered every eight (8) hours). 5 mg/kg administered every 8 hours) is recommended. Using these recommended doses, considerable variation in the serum levels between individual children has been observed therefore monitor serum levels regularly.

A serum level in excess of 10-12 mcg/mL following intramuscular administration should be considered potentially toxic. 5 mg/kg administered every 12 hours) is recommended. Use Gentamicin Injection USP with caution in pre-term newborns (post conceptional age of ≤ 38 weeks) because of their renal immaturity.

The above dosage schedules are not intended as rigid recommendations but are provided as guides to dosage. , microbiologic, enzymatic and radioimmunoassay techniques) are available to measure gentamicin concentrations in body fluids.

Gentamicin Injection USP Page 8 of 37 The usual duration of treatment is 7 to 10 days. In difficult and complicated infections, a longer course of therapy may be necessary. In such cases monitoring of renal, auditory and vestibular functions is advisable since they are at greater risk of gentamicin-related toxicities (See Monitoring and Laboratory Tests).

Patients with Impaired Renal Function Dosage must be adjusted in patients with impaired renal function (Table 1). Since the creatinine clearance rate and serum creatinine concentration have high correlation with the serum half-life of gentamicin, these laboratory tests may provide the guidance necessary for adjustment of the interval between doses of gentamicin.

The serum half-life (in hours) of gentamicin may be estimated by multiplying the serum creatinine (mg/100 mL) by four. The frequency of administration (in hours) may be approximated by doubling the serum half-life.

Table 1:

Approximate Dosage Guidelines for […]

1 Adverse Reaction Overview The most frequently reported serious adverse drug reactions associated with gentamicin includes nephrotoxicity (including acute renal failure, renal tubular necrosis, toxic nephropathy) and ototoxicity (including irreversible hearing loss).

Gentamicin may cause specific damage to the lining cells of renal proximal tubules. The incidence of reported nephrotoxic damage in aminoglycoside-treated patients ranges from 5 to almost 40% depending on the type of patients studied, the definition of nephrotoxicity, and intensity of renal monitoring.

2 Post-Market Adverse Reactions Since clinical studies are not available for Gentamicin Injection USP, all adverse drug reactions are presented in the post-market adverse drug reactions section. Adverse reactions reported and possibly related to gentamicin are summarized in Table 3: Gentamicin Injection USP Page 16 of 37 Table 3: Adverse Reactions Reported and Possibly Related to Gentamicin Blood and Lymphatic System Increased reticulocyte counts; decreased reticulocyte counts; anaemia; haemolytic anemia; pancytopenia; granulocytopenia; thrombocytopenia; leukopenia; eosinophilia; transient agranulocytosis; decreased hemoglobin and hematocrit; purpura, splenomegaly; haemolysis; febrile neutropenia; haemolysis.

Cardiac tachycardia Ear and Labyrinth Vertigo; vestibular disorder; tinnitus; deafness; ototoxicity; and impaired hearing. Ophthalmologic Blurred vision; visual disturbances; vision impairment; diplopia; oscillopsia. Gastrointestinal Vomiting; nausea; decreased appetite; increased salivation; weight loss; gastrointestinal hemorrhage; laryngeal edema and spasm; stomatitis.

General Disorders and Administration Site Conditions Gait disturbance; fatigue; pyrexia; feeling abnormal; generalized burning; local swelling; abasia. Hepatic Increased serum transaminase (AST, ALT); increased serum bilirubin; transient hepatomegaly.

Immune System Drug fever, anaphylactoid reactions; anaphylactic reaction. Infections and Infestations Bacteraemia; citrobacter infection; gastroenteritis viral; pathogen resistance; sepsis neonatal. Injury, Poisoning and Procedural Complications Fall; pain at the injection site; toxicity to various agents; maternal exposure during pregnancy; foetal exposure during pregnancy; 8th nerve injury.

Investigations Blood calcium increased; decrease in serum calcium, magnesium, sodium and potassium; increased blood pressure; increased serum LDH Metabolism and nutrition disorders hypervolemia Musculoskeletal and Connective Tissue Back pain; joint pain; alopecia and muscle twitching.

Gentamicin Injection USP Page 17 of 37 Nervous System Lethargy; skin tingling; numbness; headache; confusion; dizziness; balance disorder; speech disorder; cognitive disorder; tremor; memory impairment; fifth nerve paresthesia; convulsions; pseudotumor cerebri; acute organic brain syndrome; speech disorder developmental; hydrocephalus; neuromuscular blockade.

Psychiatric Disorientation; insomnia; depression; abnormal thinking. Renal and Urinary Renal failure, acute renal failure; tubulointerstitial nephritis; nephropathy toxic; increased blood creatinine; haemodialysis; renal tubular necrosis; renal impairment; renal pain.

Respiratory, thoracic and mediastinal disorders Respiratory depression; pulmonary fibrosis. Skin and Subcutaneous Tissue Rash; itching; rash erythematous; urticaria; subcutaneous atrophy or fat necrosis; Red man syndrome. Surgical and Medical Procedures Haemodialysis.

Vascular disorders hypotension; hypertension

The use of Gentamicin Injection USP (gentamicin sulfate) is contraindicated in patients with:  A history of hypersensitivity or serious toxic reactions to gentamicin or to other aminoglycosides because of the known cross-sensitivity of patients to drugs in this class.

 A history of hypersensitivity to gentamicin or any ingredient in the formulation or component of the container. For a complete listing, see the DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING section of the product monograph.

INDICATIONS AND USAGE:

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Gentamicin Injection, USP and other antibacterial drugs, Gentamicin Injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Gentamicin Injection, USP is indicated in the treatment of serious infections caused by susceptible strains of the following microorganisms: Pseudomonas aeruginosa, Proteus species (indole-positive and indole-negative), Escherichia coli, Klebsiella-Enterobacter-Serratia species, Citrobacter species and Staphylococcus species (coagulase-positive and coagulase-negative).

Clinical studies have shown gentamicin injection to be effective in bacterial neonatal sepsis; bacterial septicemia and serious bacterial infections of the central nervous system (meningitis), urinary tract, respiratory tract, gastrointestinal tract (including peritonitis), skin, bone and soft tissue (including burns).

Aminoglycosides, including gentamicin, are not indicated in uncomplicated initial episodes of urinary tract infections unless the causative organisms are susceptible to these antibiotics and are not susceptible to antibiotics having less potential for toxicity.

Specimens for bacterial culture should be obtained to isolate and identify causative organisms and to determine their susceptibility to gentamicin. Gentamicin injection may be considered as initial therapy in suspected or confirmed gram-negative infections, and therapy may be instituted before obtaining results of susceptibility testing.

The decision to continue therapy with this drug should be based on the results of susceptibility tests, the severity of the infection and the important additional concepts contained in the BOXED WARNINGS . If the causative organisms are resistant to gentamicin, other appropriate therapy should be instituted.

In serious infections when the causative organisms are unknown, gentamicin injection may be administered as initial therapy in conjunction with a penicillin-type or cephalosporin-type drug before obtaining results of susceptibility testing.

If anaerobic organisms are suspected as etiologic agents, consideration should be given to using other suitable antimicrobial therapy in conjunction with gentamicin. Following identification of the organism and its susceptibility, appropriate antibiotic therapy should then be continued.

Gentamicin injection has been used effectively in combination with carbenicillin for the treatment of life-threatening infections caused by Pseudomonas aeruginosa. It has also been found effective when used in conjunction with a penicillin-type drug for treatment of endocarditis caused by group D streptococci.

Gentamicin injection has also been shown to be effective in the treatment of serious staphylococcal infections. While not the antibiotic of first choice, gentamicin injection may be considered when penicillins or other less potentially toxic drugs are contraindicated and bacterial susceptibility tests and clinical judgment indicate its use.

It may also be considered in mixed infections caused by susceptible strains of staphylococci and gram-negative organisms. In the neonate with suspected bacterial sepsis or staphylococcal pneumonia, a penicillin-type drug is also usually indicated as concomitant therapy with gentamicin.

DOSAGE AND ADMINISTRATION:

Gentamicin injection may be given IM or IV. The patient’s pretreatment body weight should be obtained for calculation of correct dosage. The dosage of aminoglycosides in obese patients should be based on an estimate of the lean body mass.

It is desirable to limit the duration of treatment with aminoglycosides to short term. PATIENTS WITH NORMAL RENAL FUNCTION Adults The recommended dosage of gentamicin injection for patients with serious infections and normal renal function is 3 mg/kg/day, administered in three equal doses every eight hours (Table 3) .

For patients with life-threatening infections, dosages up to 5 mg/kg/day may be administered in three or four equal doses. This dosage should be reduced to 3 mg/kg/day as soon as clinically indicated (Table 3) . It is desirable to measure both peak and trough serum concentrations of gentamicin to determine the adequacy and safety of the dosage.

When such measurements are feasible, they should be carried out periodically during therapy to assure adequate but not excessive drug levels. For example, the peak concentration (at 30 to 60 minutes after IM injection) is expected to be in the range of 4 to 6 mcg/mL.

When monitoring peak concentrations after IM or IV administration, dosage should be adjusted so that prolonged levels above 12 mcg/mL are avoided. When monitoring trough concentrations (just prior to the next dose), dosage should be adjusted so that levels above 2 mcg/mL are avoided.

Determination of the adequacy of a serum level for a particular patient must take into consideration the susceptibility of the causative organism, the severity of the infection and the status of the patient’s host-defense mechanisms.

In patients with extensive burns, altered pharmacokinetics may result in reduced serum concentrations of aminoglycosides. In such patients treated with gentamicin, measurement of serum concentrations is recommended as a basis for dosage adjustment.

2 *The dosage of aminoglycosides in obese patients should be based on an estimate of the lean body mass. **for q6h schedules, dosage should be recalculated. 5 mg/kg administered every eight hours). 5 mg/kg administered every eight hours).

5 mg/kg administered every 12 hours). For further information concerning the use of gentamicin in infants and children, see gentamicin injection (pediatric) product information. The usual duration of treatment for all patients is 7 to 10 days.

In difficult and complicated infections, a longer course of therapy may be necessary. In such cases monitoring of renal, auditory and vestibular functions is recommended, since toxicity is more apt to occur with treatment extended for more than 10 days.

Dosage should be reduced if clinically indicated. FOR INTRAVENOUS ADMINISTRATION The IV administration of gentamicin may be particularly useful for treating patients with bacterial septicemia or those in shock. It may also be the preferred route of administration for some patients with congestive heart failure, hematologic disorders, severe burns or those with reduced muscle mass.

For intermittent IV administration in adults, a single dose of gentamicin injection may be diluted in 50 to 200 mL of sterile isotonic saline solution or in a sterile solution of dextrose 5% in water; in infants and children, the volume of diluent should be less.

The solution may be infused over a period of one-half to two hours. The recommended dosage for IM and IV administration is identical. Gentamicin injection should not be physically premixed with other drugs, but should be administered separately in accordance with the recommended route of administration and dosage schedule.

PATIENTS WITH IMPAIRED RENAL FUNCTION Dosage must be adjusted in patients with impaired renal function to assure therapeutically adequate, but not excessive blood levels. Whenever possible serum concentration of gentamicin should be monitored.

One method of dosage adjustment is to increase the interval between administration of the usual doses. Since the serum creatinine concentration has a high correlation with the serum half-life of gentamicin, this laboratory test may provide guidance for adjustment of the interval between doses.

The interval between doses (in hours) may be approximated by multiplying the serum creatinine level (mg/100 mL) by 8. For example, a patient weighing 60 kg with a serum creatinine level of 2 mg/100 mL could be given 60 mg (1 mg/kg) every 16 hours (2 x 8).

In patients with serious systemic infections and renal impairment, it may be desirable to administer the antibiotic more frequently but in reduced dosage. In such patients, serum concentrations of gentamicin should be measured so that adequate but not excessive levels result.

A peak and trough concentration measured intermittently during therapy will provide optimal guidance for adjusting dosage. After the usual initial dose, a rough guide for determining reduced dosage at eight-hour intervals is to divide the normally recommended dose by the serum creatinine level (Table 4) .

For example, after an initial dose of 60 mg (1 mg/kg), a patient weighing 60 kg with a serum creatinine level of 2 mg/100 mL could be given 30 mg every eight hours (60 ÷ 2). It should be noted that the status of renal function may be changing over the course of the infectious process.

It is important to recognize that deteriorating renal function may require a greater reduction in dosage than that specified in the above guidelines for patients with stable renal impairment. 7 to 8 < 10 10 In adults with renal failure undergoing hemodialysis, the amount of gentamicin removed from the blood may vary depending upon several factors including the dialysis method used.

An eight-hour hemodialysis may reduce serum concentrations of gentamicin by approximately 50%. 7 mg/kg depending upon the severity of the infection. In children, a dose of 2 mg/kg may be administered. The above dosage schedules are not intended as rigid recommendations but are provided as guides to dosage when measurement of gentamicin serum level is not feasible.

A variety of methods are available to measure gentamicin concentrations in body fluids; these include microbiologic, enzymatic and radioimmunoassay techniques. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

gov/medwatch. Nephrotoxicity Adverse renal effects, as demonstrated by the presence of casts, cells or protein in the urine or by rising BUN, NPN, serum creatinine or oliguria, have been reported. They occur more frequently in patients with a history of renal impairment (especially if dialysis is required) and in patients treated for longer periods or with larger doses than recommended.

Neurotoxicity Serious adverse effects on both vestibular and auditory branches of the eighth nerve have been reported, primarily in patients with renal impairment (especially if hemodialysis is required) and in patients on high doses and/or prolonged therapy.

Symptoms include dizziness, vertigo, tinnitus, roaring in the ears and also hearing loss, which, as with the other aminoglycosides, may be irreversible. Hearing loss is usually manifested initially by diminution of high-tone acuity.

Other factors which may increase the risk of toxicity include excessive dosage, dehydration and previous exposure to other ototoxic drugs. Peripheral neuropathy or encephalopathy, including numbness, skin tingling, muscle twitching, convulsions and a myasthenia gravis-like syndrome have been reported.

NOTE:

The risk of toxic reactions is low in patients with normal renal function who did not receive gentamicin sulfate at higher doses or for longer periods of time than recommended. Other reported adverse reactions possibly related to gentamicin include: respiratory depression, lethargy, confusion, depression, visual disturbances, decreased appetite, weight loss and hypotension and hypertension; rash, itching, urticaria, generalized burning, laryngeal edema, anaphylactoid reactions, fever and headache; nausea, vomiting, increased salivation and stomatitis; purpura, pseudotumor cerebri, acute organic brain syndrome, pulmonary fibrosis, alopecia, joint pain, transient hepatomegaly and splenomegaly.

Laboratory abnormalities possibly related to gentamicin include: increased levels of serum transaminase (SGOT, SGPT), serum LDH and bilirubin; decreased serum calcium, magnesium, sodium and potassium; anemia, leukopenia, granulocytopenia, transient agranulocytosis, eosinophilia, increased and decreased reticulocyte counts and thrombocytopenia.

While clinical laboratory test abnormalities may be isolated findings, they may also be associated with clinically related signs and symptoms. For example, tetany and muscle weakness may be associated with hypomagnesemia, hypocalcemia and hypokalemia.

While the local tolerance of gentamicin sulfate is generally excellent, there has been an occasional report of pain at the injection site. Subcutaneous atrophy or fat necrosis suggesting local irritation has been reported rarely. Nephrotoxicity Adverse renal effects, as demonstrated by the presence of casts, cells or protein in the urine or by rising BUN, NPN, serum creatinine or oliguria, have been reported.

They occur more frequently in patients with a history of renal impairment (especially if dialysis is required) and in patients treated for longer periods or with larger doses than recommended. Neurotoxicity Serious adverse effects on both vestibular and auditory branches of the eighth nerve have been reported, primarily in patients with renal impairment (especially if hemodialysis is required) and in patients on high doses and/or prolonged therapy.

Symptoms include dizziness, vertigo, tinnitus, roaring in the ears and also hearing loss, which, as with the other aminoglycosides, may be irreversible. Hearing loss is usually manifested initially by diminution of high-tone acuity.

Other factors which may increase the risk of toxicity include excessive dosage, dehydration and previous exposure to other ototoxic drugs. Peripheral neuropathy or encephalopathy, including numbness, skin tingling, muscle twitching, convulsions and a myasthenia gravis-like syndrome have been reported.

NOTE:

The risk of toxic reactions is low in patients with normal renal function who did not receive gentamicin sulfate at higher doses or for longer periods of time than recommended. Other reported adverse reactions possibly related to gentamicin include: respiratory depression, lethargy, confusion, depression, visual disturbances, decreased appetite, weight loss and hypotension and hypertension; rash, itching, urticaria, generalized burning, laryngeal edema, anaphylactoid reactions, fever and headache; nausea, vomiting, increased salivation and stomatitis; purpura, pseudotumor cerebri, acute organic brain syndrome, pulmonary fibrosis, alopecia, joint pain, transient hepatomegaly and splenomegaly.

Laboratory abnormalities possibly related to gentamicin include: increased levels of serum transaminase (SGOT, SGPT), serum LDH and bilirubin; decreased serum calcium, magnesium, sodium and potassium; anemia, leukopenia, granulocytopenia, transient agranulocytosis, eosinophilia, increased and decreased reticulocyte counts and thrombocytopenia.

While clinical laboratory test abnormalities may be isolated findings, they may also be associated with clinically related signs and symptoms. For example, tetany and muscle weakness may be associated with hypomagnesemia, hypocalcemia and hypokalemia.

While the local tolerance of gentamicin sulfate is generally excellent, there has been an occasional report of pain at the injection site. Subcutaneous atrophy or fat necrosis suggesting local irritation has been reported rarely.

CONTRAINDICATIONS:

Hypersensitivity to gentamicin is a contraindication to its use. A history of hypersensitivity or serious toxic reactions to other aminoglycosides may contraindicate use of gentamicin because of the known cross-sensitivity of patients to drugs in this class.