Zombistin

Uses

Zombistin is used for the treatment of acute or chronic infections caused by sensitive strains of certain gram-negative bacilli. It is particularly used for the infection caused by sensitive strains of Pseudomonas aeruginosa. Zombistin is not used for infections due to Proteus or Neisseria. Zombistin is very effective in the treatment of infections due to the following gram-negative organisms: Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa.

Zombistin is also used to associated treatment for these conditions: Bacterial Infections

How Zombistin works

Zombistin is a surface active agent which penetrates into and disrupts the bacterial cell membrane. Zombistin is polycationic and has both hydrophobic and lipophilic moieties. It interacts with the bacterial cytoplasmic membrane, changing its permeability. This effect is bactericidal. There is also evidence that polymyxins enter the cell and precipitate cytoplasmic components, primarily ribosomes.

Dosage

Zombistin dosage

Maintenance dose: 9 MIU/day in 2-3 divided doses. In patients who are critically ill, a loading dose of 9 MIU should be administered.

Renal impairment patients: Dose adjustments in renal impairment patients are necessary. Dose reductions are recommended for patients with creatinine clearance < 50 ml/min. Twice daily dosing is recommended.

• Creatinine clearance <50-30 ml/min: daily dose 5.5-7.5 MIU
• Creatinine clearance <30-10 ml/min: daily dose 4.5-5.5 MIU
• Creatinine clearance <10 ml/min: daily dose 3.5 MIU

• No-HD days: 2.25 MIU/day (2.2-2.3 MIU/day).
• HD days: 3 MIU/day (Should be given after the HD session) Twice daily dosing is recommended.

• Children ≤40 kg: 75,000-150,000 IU/kg/day divided into 3 doses.
• Children >40 kg: >150,000 IU/kg/day has been reported in children with cystic fibrosis.

Direct Intermittent Administration- Slowly inject one-half of the total daily dose over a period of 3 to 5 minutes every 12 hours.

Continuous Infusion- Slowly inject one-half of the total daily dose over 3 to 5 minutes. Add the remaining half of the total daily dose of Zombistin for injection to one of the following:

• 0.9% NaCl
• 5% dextrose in 0.9% NaCl
• 5% dextrose in water
• 5% dextrose in 0.45% NaCl
• 5% dextrose in 0.225% NaCl
• Lactated Ringer's solution

Side Effects

The following adverse reactions have been reported: gastrointestinal upset, tingling of extremities and tongue, slurred speech, dizziness, vertigo and paresthesia, generalized itching, urticaria and rash, fever, increased blood urea nitrogen (BUN), elevated creatinine and decreased creatinine clearance, respiratory distress and apnea, nephrotoxicity and decreased urine output.

Toxicity

Oral LD₅₀ in rats is 5450 mg/kg. Overdosage with colistimethate can cause neuromuscular blockade characterized by paresthesia, lethargy, confusion, dizziness, ataxia, nystagmus, disorders of speech and apnea. Respiratory muscle paralysis may lead to apnea, respiratory arrest and death.

Precaution

Zombistin should be used with caution in patient with impaired renal function. When actual renal impairment is present, Zombistin may be used, but the greatest caution should be exercised and the dosage should be reduced in proportion to the extent of the impairment. Zombistin should be used with caution in neonates, infants and children.

Interaction

Zombistin should not be given with certain antibiotics like- aminoglycosides and polymyxin due to report of interfere with the nerve transmission at the neuromuscular junction. It should not be given with muscle relaxants e.g., tubocurarine and other drugs including ether, succinylcholine, gallamine, decamethonium and sodium citrate. The concomitant use of Sodium Cephalothin and Zombistin should be avoided.

Food Interaction

Zombistin Drug Interaction

Moderate: sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprimUnknown: pancrelipase, pancrelipase, heparin, heparin, acetaminophen, acetaminophen, budesonide, budesonide, dornase alfa, dornase alfa, montelukast, montelukast, valproic acid, valproic acid, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol

Zombistin Disease Interaction

Major: colitisModerate: renal dysfunction

Elimination Route

Very poor absorption from gastrointestinal tract.

Half Life

2-3 hours following either intravenous or intramuscular administration in adults and in the pediatric population, including premature infants.

Pregnancy & Breastfeeding use

There are no adequate and well-controlled studies about the use of Zombistin in pregnant women. Since colistimethate is transferred across the placental barrier in humans, it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether Zombistin is excreted in human breast milk. Therefore, caution should be exercised when administered to nursing women.

Contraindication

The use of Zombistin Sodium Parenteral is contraindicated for patients with a history of sensitivity to the drug or any of its components.

Acute Overdose

Overdosage with colistimethate sodium can cause neuromuscular blockade characterized by paresthesia, lethargy, confusion, dizziness, ataxia, nystagmus, disorders of speech and apnea. Respiratory muscle paralysis may lead to apnea, respiratory arrest and death. Overdosage with the drug can also cause acute renal failure, manifested as decreased urine output and increases in serum concentrations of B.U.N and creatinine. As in any case of overdose, Zombistin Sodium therapy should be discontinued and general supportive measures should be utilized.

Storage Condition

Before reconstitution: Store below 30°C. After reconstitution: Store at 2°C to 8°C (Do not freeze) and use within 24 hours.

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