Nelin

Netilmicin sulfate.

Each 2 mL vial contains Netilmicin Sulfate equivalent to Netilmicin 100 mg.
Each 1.5 mL vial contains Netilmicin Sulfate equivalent to Netilmicin 150 mg.
Excipients/Inactive Ingredients: 100 mg/2 mL: Methylparaben, Propylparaben, Sodium sulfate, Edetate disodium, Sodium sulfite, Sodium metabisulfite, Water for injection.
150 mg/1.5 mL: Methylparaben, Propylparaben, Edetate disodium, Sodium sulfite, Sodium metabisulfite, Water for injection.
Preservative: Methylparaben 1.3 mg/mL and Propylparaben 0.20 mg/mL in NELIN injection 100 mg/2 mL and NELIN injection 150 mg/1.5 mL.
Netilmicin is a rapidly acting bactericidal antibiotic, it acts by inhibiting normal protein synthesis in susceptible organisms, such as E. coli; Salmonella sp.; Citrobacter sp.; Pseudomonas aeruginosa; Enterobacter sp.; Proteus sp. (indole-positive); Serratia sp.; Acinetobacter sp.; Providencia sp.; Penicillinase and non-penicillinase-producing Staphylococcus-including methicillin-resistant strains; Klebsiella sp.; Shigella sp.; Proteus mirabilis; Pseudomonas sp.; Yersinia (Pasteurella) pestis; Neisseria sp.; S. faecalis.

Pharmacology: Pharmacodynamics: Netilmicin is classified as aminoglycosides which are bactericidal inhibitors of protein synthesis. Netilmicin irreversibly bind to the 30S subunit of bacterial ribosomes, blocking the recognition step in protein synthesis and causing misreading of the genetic code. The ribosomes separate from messenger RNA; cell death ensues.
Pharmacokinetics: Netilmicin is poorly absorbed from the gastrointestinal tract after oral administration. Absorption from IM injection is rapid, with peak blood levels achieved within 1 hour.
Netilmicin is widely distributed in extracellular fluids, cross the placental barrier and exhibit low protein binding. Concentrations are found in bile, tissues, sputum, bronchial secretions and synovial, interstitial, peritoneal, abscess and pleural fluids. Newborn infants, postpartum females and patients with ascites, spinal cord injury and cystic fibrosis may have an enlarged apparent volume of distribution.
Netilmicin is excreted by glomerular filtration, largely as unchanged drug. Probenecid does not affect renal tabular transport. Netilmicin half-life is 2 - 2.7 hours in patients with normal renal function and 40 hours in patients with ESRD.
When renal function is impaired, significant accumulation and subsequent toxicity may occur rapidly if dosage is not adjusted. Netilmicin is removed by hemodialysis. The serum half-life is longer in young infants, as the immature renal system is unable to excrete these drugs rapidly. Prolonged half-life may also be noted in the elderly. In severely burned patients, the half-life may be significantly decreased and result in serum concentrations lower than anticipated. Because of the narrow range between therapeutic and toxic serum levels, careful attention to dosage calculation is essential.

NELIN injection is indicated in the treatment of infections caused by susceptible strains of the previously mentioned microorganisms. Clinical studies have shown NELIN to be effective in: Septicemia; Complicated urinary tract infections; Lower respiratory tract infections; Biliary tract infections; Skin, soft tissue infections; Bone, joint infections; Intra-abdominal infection (including peritonitis); Infections of central nervous system (including meningitis).
NELIN injection is recommended as initial therapy in suspected or confirmed gram-negative infection. In serious infections when the causative organisms are unknown. NELIN injection may be administered as initial therapy in conjunction with a penicillin- or cephalosporin-type drug before, obtaining results of susceptibility testing. If anaerobic organisms are suspected, suitable antimicrobial therapy in conjunction with NELIN injection should be given. Following identification of the organism and its susceptibility, NELIN injection or other appropriate antibiotic therapy should then be continued.
Netilmicin is not indicated in the treatment of uncomplicated initial episodes of urinary tract infection unless the causative organisms are resistant to antimicrobial agents having less potential toxicity. NELIN injection has been used effectively in combination with carbenicillin or ticarcillin for the treatment of life-threatening infections caused by Pseudomonas aeruginosa.

The recommended dosage for intravenous and intramuscular administration is identical. The patient's pretreatment body weight should be obtained for calculation of correct dosage. Aminoglycoside dosage in obese patients should be based on an estimate of lean body mass.
Patients with normal renal function: Adults: 4.0 - 6.0 mg/kg/day given in three equal doses every 8 hours, 2 equal doses every 12 hours or once daily.
For adults weighing 40 - 50 kg, a dose of 100 mg given every 12 hours or 200 mg once daily.
For adults weighing 50 - 90 kg, a dose of 150 mg given every 12 hours or 100 mg every 8 hours or 300 mg once daily.
For patients with life-threatening infections, dosages up to 7.5 mg/kg/day may be administered in three equal doses every 8 hours. This dosage should be reduce to 6 mg/kg/day or less as soon as clinically indicated, usually within 48 hours.
Children: 6.0 - 7.5 mg/kg/day (2.0 to 2.5 mg/kg administered every 8 hours)
Duration: The usual duration of treatment for all patients is 7 - 14 days. In complicated infections, a longer course of therapy may be necessary. Although prolonged courses of netilmicin have been well tolerated, it is important that patients treated beyond the usual time period be monitored carefully for changes in renal, auditory and vestibular function. Dosage should be reduced if clinically indicated.
Measure serum concentrations: Generally, to measure peak levels, draw a serum sample about 30 minutes after IV infusion or 1 hour after an IM dose. For trough levels, obtain serum samples at 8 hours or just prior to the next dose. Toxic peak serum level and trough serum level of netilmicin are higher than 16 and 4 mcg/mL, consecutively.
Generally, desirable peak and trough concentrations range from 6 to 10 and 0.5 to 2 mcg/mL, respectively.
Deteriorating renal function may require a greater reduction in dosage than that specified in the guidelines given as follows for patients with stable renal impairment.
The initial or loading dose is the same as that for patient with normal renal function. Three suggested methods to adjust the total daily dosage for the degree of renal impairment are: 1) Divided the suggested suggested dosage value for patients with normal renal function by serum creatinine level to obtain the adjusted size of each dose.
2) Determine the adjusted daily dose of netilmicin as the equation as follows. (See Equation 1.)

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3) Alternatively, use the following graph to obtain the percentage of the dose selected; administer at 8 hours intervals: (See figure.)

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Ccr can be estimated from serum creatinine levels by the following formula: (See Equation 2.)

Click on icon to see table/diagram/image

The adjusted total daily dose may be administered as one dose at 24 hours intervals. Or as 2 or 3 equally divided doses at 12 hours or 8 hours intervals, respectively. Generally each interval dose should not exceed 3.25 mg/kg.
NELIN injection is physically compatible with the following parenteral solution, such as Sterile water for injection; 5% Dextrose in water; 5% Dextrose and 0.9% Sodium chloride injection; Ringer's injection; Normal Saline; 10% Dextrose in water; Lactated ringer's injection; Lactated ringer's injection with 5% Dextrose.
IV administration: In adults, single dose may be diluted in 50 to 200 mL of one.of the parenteral solutions as listed. In infants and children, the volume of diluent should be less, according to the fluid requirements of the patient. The solution must be infused over a period of ½ - 2 hours.
The intravenous administration of NELIN is useful for treating patients with septicemia or shock. It may also be the preferred route of administration for some patients with congestive heart failure, hematologic disorders, severe bums, or those with reduced muscle mass.
Hemodialysis: In adults with renal failure undergoing hemodialysis, the amount of netilmicin removed from the blood may vary depending upon several factors, including the dialysis method and equipment used. The dose of 2 mg/kg at the end of each dialysis period is recommended until the results of tests measuring serum levels become available. Adjust dosage appropriately based on these tests.

Symptoms: Auditory and vestibular toxicities have been associated with aminoglycoside overdose. These toxicities may occur in patients treated > 10 days, in patients with reduced renal function, in dehydrated patients, or patients receiving medications with additive auditory toxicities. These patients may not have signs or symptoms or may experience dizziness, tinnitus, vertigo and lose of high-tone acuity as ototoxicity progresses. Ototoxicity signs and symptoms may not begin to occur until long after the drug has been discontinued.
Neuromuscular blockage or respiratory paralysis may occur following aminoglycoside administration. If neuromuscular blockade occurs, it may be reversed by the administration of calcium salts but mechanical assistance may be necessary.
Treatment: The initial treatment intervention is to establish an airway and ensure oxygenation and ventilation. Adequately hydrate patients and carefully monitor fluid balance, Ccr and plasma levels.
In the even of overdose or toxic reactions, hemodialysis or peritoneal dialysis will aid in the removal of netilmicin sulfate from the blood. Hemodialysis is preferable because it is more efficient in reducing serum levels.

Hypersensitivity and serious toxic reaction to netilmicin or other aminoglycosides contraindicated its use.

Patients treated with aminoglycosides should be under close clinical observation because of the potential toxicity associated with their use.
As with other aminoglycosides, renal function should be closely monitored during therapy. The risk of nephrotoxicity is greater in patients with impaired renal function, in those who receive high dosage or prolonged therapy and the elderly, concurrent use of other nephrotoxic agents, frequent dosing, potassium depletion and decreased intravascular volume. Renal toxicity, may characterized by decreased creatinine clearance, cells or casts in the urine, decreased urine specific gravity, oliguria, proteinuria or evidence of nitrogen retention (increasing BUN, nonprotein nitrogen [NPN] or serum creatinine). Renal damage is usually reversible.
Neurotoxicity, manifested as both auditory (cochlear) and vestibular ototoxicity, can occur with any of these agents. Auditory changes are irreversible, usually bilateral and may be partial or total. Risk of hearing loss increases with the degree of exposure to either high peak or high trough serum concentrations and continues to progress after drug withdrawal. The risk is greater in patients with renal-impairment and with preexisting hearing loss. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and convulsions.
Monitoring of renal and eighth cranial nerve functions is recommended during therapy particularly for patients with known or suspected reduced renal function and also in those renal function is initially normal, but who develops signs of renal dysfunction.
Evidence of renal impairment or ototoxicity requires drug discontinuation or appropriate dosage adjustments. When feasible, monitor, drug serum concentrations. Avoid concomitant use with other ototoxic, neurotoxic or nephrotoxic drugs. Other factors which may increase risk of toxicity are dehydration and advanced age. Patients should be well hydrated during treatment.
Aminoglycosides should be used with caution in patients with neuromuscular disorders, such as Myasthenia gravis, Parkinsonism or infant botulism since these drugs theoretically may aggravate muscle weakness because of their potential curare-like effects on the neuromuscular junction. Neuromuscular blockage resulting in respiratory, paralysis has occurred with aminoglycosides, especially if given with or soon after anesthesia or muscle relaxants.
Extemporaneous admixtures of aminoglycosides with beta-lactam-type antibiotics (penicillins or cephalosporins) may result in inactivation.
NELIN injection contains sodium metabisulfite and sodium sulfite; these may cause allergic type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people.
Use in Children: Use with caution in premature infants and neonates because of their renal immaturity and the resulting prolongation of serum half-life of these drugs.
Use in the Elderly: These patients may have reduced renal function. Monitoring renal function and drug levels during treatment is particularly important.

Pregnancy: Pregnancy category D.
Serious side effects to the mother, fetus or newborn have not been reported, but the potential of harm exists. Therefore, risk-benefit must be carefully considered when this medication is required in life-threatening situations or in serious disease for which other medications cannot be used or are ineffective.
If netilmicin is used during pregnancy or if the patient becomes pregnant while taking netilmicin, the patient should be apprised of the potential hazard to the fetus.
Lactation: Small amounts of netilmicin are excreted in breast milk. Decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking to account the importance of the drug to the mother.

Central/Peripheral nervous system: Headache, encephalopathy, fever, disorientation, neuromuscular blockage, paresthesia, convulsion, muscle twitching, myasthenia gravis-like syndrome, numbness, peripheral neuropathy, skin tingling.
Gastrointestinal tract: Vomiting, diarrhea.
Hematologic: Anemia, eosinophilia, leukopenia, thrombocytopenia.
Skin: Rash, Itching.
Renal: Oliguria, proteinuria, casts, red and white cells in urine.
Special senses: Dizziness, tinnitus, vertigo, visual disturbances/blurred vision.
Miscellaneous: Apnea, pain/irritation at injection site, hypotension, severe, pain induration and hematomas following injection, prolonged PT, hyperkalemia, palpitation, immature, circulating WBCs, leukemoid reaction, nystagmus, a Fanconi-like syndrome, with aminoaciduria and metabolic acidosis.
LAB TEST ABNORMALITIES: Lab test abnormalities include: increased alkaline phosphatase, increased AST or ALT, bilirubin, increased serum-creatinine, BUN,-decreased creatinine clearance.

Cephalosporins, Enflurane, Methoxyflurane, Vancomycin: Risk of neprotoxicity may increase above that with aminoglycoside alone. Monitor patients.
Indomethacin IV: In preterm infants, the use of indomethacin for closure of patent ductus arteriosus resulted in aminoglycoside accumulation in one study.
Loop diuretics: Auditory toxicity appears to increase during concomitant use. Hearing loss of vary degrees may occur; it may be irreversible. Monitor patients.
Neuromuscular blockers, depolarizing and non-depolarizing: The neuromuscular blocking effects are enhanced by aminoglycosides. Prolonged respiratory, depression may occur.
Penicillins: Synergism of these agents is well documented; however, certain penicillins may inactivate certain aminoglycosides. The problein may be greatest in vitro.
Polypeptide antibiotics: Concurrent use of these agents may increase the risk of respiratory paralysis and renal dysfunction.

Store at room temperature not exceeding 30°C. Protect from light and excessive heat.

Aminoglycosides

J01GB07 - netilmicin ; Belongs to the class of other aminoglycosides. Used in the systemic treatment of infections.

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