Mellistin

Each vial contains Colistimethate sodium equivalent to Colistin 150 mg.
Each gram of Colistin contains sodium 0.099 mg (0.0043 mmol).

Pharmacology: Pharmacodynamics: Colistimethate sodium is the sulfamethyl derivative of Colistin. Colistin or Polymyxin E is a Polymyxin antibiotic obtained from Bacillus polymyxa var. Colistinus that is active against many gram-negative bacilli and inactive against gram-positive bacteria, fungi, and viruses. The mechanism of action is bactericidal. Colistimethate (Colistin-methanesulfonate) is hydrolyzed to Colistin which acting like a cationic detergent and binds to the bacterial cytoplasmic membrane of susceptible bacteria. This alters permeability and causes leakage of bacterial cell wall. This leads to bacterial death. In vitro, Colistin is active against these bacteria as follows.
Aerobic gram-negative bacteria: Acinetobacter sp., Acinetobacter baumannii, Citrobacter sp., Escherichia coli, Enterobacter aerogenes, Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella sp., Shigella sp. and some strains of Bordetella sp., Vibrio sp.
Some bacteria have been reported resistance to Colistin. Those are Proteus sp., Providencia sp., Serratia sp., Neisseria gonorrhoeae, N. meningitidis, and Bacteriodes fragilis.
Pharmacokinetics: Colistimethate sodium is not absorbed from the GI tract and must be given parenterally. The drug is widely distributed into body tissues such as the liver, kidneys, lung, heart, and muscle. In patients with normal or inflamed meninges, only minimal concentrations of antimicrobial activity are attained in cerebrospinal fluid (CSF). More than 50% of Colistin bound to serum proteins. It also crosses the placenta and is distributed into milk. Colistimethate sodium is hydrolyzed to Colistin and possibly other metabolites with fewer substituted amino groups. The plasma half-life of Colistimethate sodium is 1.5-8 hours in adults with normal renal function and is prolonged in patients with impaired renal function. Both Colistimethate sodium and metabolites of the drug are excreted mainly by the kidneys.
Colistimethate sodium may be removed by hemodialysis and, to a lesser extent, by peritoneal dialysis.

Colistimethate sodium is used parenterally for the treatment of acute or chronic infections caused by certain susceptible gram-negative bacilli such as Acinetobacter baumannii (including Acinetobacter baumannii which resistant to all antibiotics), Pseudomonas aeruginosa (including Pseudomonas aeruginosa which resistant to all antibiotics), Escherichia coli (including ESBL-producing Escherichia coli), Klebsiella pneumoniae (including ESBL-producing Klebsiella pneumoniae), Enterobacter aerogenes, Citrobacter sp., Haemophilus influenzae, Salmonella sp., Shigella sp., Proteus sp., Providencia sp., Serratia sp. and some strains of Bordetella sp., Vibrio sp. Colistimethate sodium is administered by oral inhalation via nebulization for the treatment of Pseudomonas aeruginosa in respiratory tract infections among patients with cystic fibrosis.

Mode of administration: MELLISTIN 150 MG injection is administered by IM injection, IV injection, continuous IV infusion or oral inhalation.
With concern of microbial contamination, the drug should be used promptly after the preparation and the remaining mixed solution should be discarded.
Color changing or any precipitation should be observed before use.
Preparation for intramuscular (IM) and intravenous (IV) injection: MELLISTIN 150 MG injection is reconstituted by adding 2 ml of sterile water for injection to a vial, the resultant solution contains 75 mg of Colistin per ml. The vial should be swirled gently to avoid frothing.
The drug should be injected directly into a vein over 3-5 minute period every 12 hours.
Preparation for intravenous (IV) infusion: For continuous IV infusion, one-half of the total daily dose should be injected directly into vein over 3-5 minute period every 12 hours. The remaining one-half of the total daily dose should be added to a compatible IV solutions as the following: 0.9% sodium chloride injection, 5% dextrose, 5% dextrose and 0.225% sodium chloride injection, 5% dextrose and 0.45% sodium chloride injection, 5% dextrose and 0.9% sodium chloride injection, lactated Ringer's solution or 10% invert sugar. Swirl gently to avoid frothing.
Intravenous (IV) infusion administration: The drug should be administered 1-2 hours after the initial dose by slow IV infusion over the next 22-23 hours. The infusion rate should be 5-6 mg/hour in patients with normal renal function. For patients with impaired renal function, the infusion rate should be reduced depending on the degree of renal impairment.
Preparation for oral inhalation: For oral inhalation via nebulization, an isotonic solution of Colistimethate sodium has been prepared by diluting the appropriate dose in 2-4 ml of preservative-free 0.9% sodium chloride injection or sterile water and should be used promptly after being prepared.
Stability: Following reconstitution with sterile water for injection, Colistimethate sodium solutions containing 75 mg of Colistin per ml should be stored at 2-8°C or 25°C and used within 10 days. For the reconstitution with 0.9% NSS or D5W, Colistimethate sodium solutions containing 1.5 mg of Colistin per ml should be stored at 2-8°C or 25°C and used within 72 hours. However, Solutions of Colistimethate sodium should be used promptly after being mixed.
Recommendation dose: Dosage and administration depend on severity of infection, patient status, renal function, and causative organism or follow physician's instruction.
The usual IM or IV dosage of Colistimethate sodium for adults and children with normal renal function is 2.5-5 mg/kg of Colistin daily given in 2-4 divided doses.
The maximum IM or IV dosage of Colistimethate sodium is 5 mg/kg of Colistin daily.
For early treatment of Pseudomonas aeruginosa respiratory infections in adults and pediatric cystic fibrosis patients, Colistimethate sodium has been given by oral inhalation via nebulization in a dosage of 33.33-66.66 mg of Colistin 2 or 3 times daily.
Dosage in renal impairment: In patients with renal impairment, the dose and frequency of Colistimethate sodium should be decreased in proportion to the degree of renal impairment. (See table.)

Click on icon to see table/diagram/image

Overdosage of Colistimethate sodium can cause neuromuscular blockade characterized by paresthesia, lethargy, confusion, dizziness, ataxia, nystagmus, disorder of speech, apnea, respiratory muscle paralysis, respiratory arrest, and death. Overdosage of the drug may also cause acute renal failure, manifested as decreased urine output and increase in serum concentrations of BUN and creatinine.
Treatment for overdosage: The drug should be discontinued and initiate supportive treatment.
Colistimethate sodium may be removed by hemodialysis and, to a lesser extent, by peritoneal dialysis.

Colistimethate sodium is contraindicated in individuals who are hypersensitive to the drug or Polymyxins.

1. Colistimethate sodium is contraindicated in individuals who are hypersensitive to the drug.
2. Colistimethate sodium may cause transient neurological disturbances and nephrotoxicity.

Maximum dosage: Do not exceed 5 mg/kg/day in patients with normal renal function.
Colistimethate sodium may cause nephrotoxicity, manifested as decreased urine output, increased serum concentrations of BUN and creatinine, proteinuria, hematuria, and casts in the urine. If these symptoms occur, dosing should be adjusted or the drug should be discontinued immediately.
Colistimethate sodium may cause transient nervous system effect, including circumoral or peripheral paresthesia or numbness, tingling or formication of the extremities or tongue, dizziness, vertigo, giddiness, ataxia, blurred vision, and slurred speech. These adverse nervous system effects generally appear within the first 4 days of therapy and disappear when the drug is discontinued. The patient should be monitored closely; some of these adverse nervous system effects may be alleviated by reducing dosage of the drug.
Treatment with Colistimethate sodium alters the normal flora in the gut leading to overgrowth of Clostridium difficile. C. difficile produces toxins which contribute to the development of CDAD that must be considered in all patients who present with diarrhea following Colistimethate sodium use. Mild cases of colitis may respond to discontinuance of the drug alone, but management of moderate to severe case should include treatment with fluid, electrolyte, protein supplementation, and appropriate anti-infective therapy.
Since nephrotoxic effects may additive, concurrent or sequential use of Colistimethate sodium with other drugs which have similar toxic potentials and with neuromuscular blocking agents should be avoided.
Patients who received Colistimethate sodium by oral inhalation via nebulization may cause bronchoconstriction. It has been suggested that premedication with bronchodilators may reduce the potentials for development of bronchoconstriction.

There are no adequate and well-controlled study in pregnant women. Use during pregnancy only when the potential benefits justify the possible risks to the fetus.
It is not known whether Colistimethate sodium is distributed into milk. The drug should be temporarily discontinue during nursing administration.

Adverse reactions which may occur during the use of the drug are: Renal effects: nephrotoxicity, manifested as decreased urine output, increased serum concentrations of BUN and creatinine, protenuria, hematuria, and casts in the urine.
Nervous system effects: circumoral or peripheral paresthesia or numbness, tingling or formication of the extremities or tongue, dizziness, vertigo, giddiness, ataxia, blurred vision, and slurred speech.
Respiratory effects: Respiratory arrest, Apnea, Bronchoconstriction, Respiratory distress.
Other adverse effects: generalized pruritus or urticaria, rash, drug fever, dysphonia, and pain at the site of injection. Moreover, leucopenia and granulocytopenia may be found (rare).

1. Since nephrotoxic effects may be additive, concurrent or sequential use of Colistimethate sodium and other drugs with similar toxic potentials (e.g., aminoglycosides, amphotericin B, capreomycin, cephalothin, methoxyflurane, polymyxin B sulfate, vancomycin) should be avoided, if possible.
2. Neuromuscular blocking agents (e.g., tubocurarine, succinylcholine, ether, decamethonium, gallamine) and other drugs (e.g., sodium citrate) potentiate neuromuscular blockade. These drugs should be used with extreme caution in patients receiving Colistimethate sodium.

Dry powder should be kept below 30°C before reconstitution.
Do not freeze the solution.

Other Antibiotics

J01XB01 - colistin ; Belongs to the class of polymyxins. Used in the systemic treatment of infections.

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