Usage
Sisomicin is an aminoglycoside antibiotic primarily used to treat serious bacterial infections, especially those caused by susceptible gram-negative bacteria like Escherichia coli and Pseudomonas aeruginosa. It is often reserved for infections resistant to other antibiotics or when other antibiotics are contraindicated. It can also be used for certain infections such as sepsis, respiratory tract infections, and urinary tract infections, as well as some gram-positive infections like staphylococcal infections. Topically, it is used for pyoderma. Its pharmacological classification is antibiotic.
Sisomicin works by irreversibly binding to the bacterial 30S ribosomal subunit and also to the 50S subunit in some bacteria. This action disrupts protein synthesis by interfering with the decoding site, ultimately leading to bacterial cell death by making the bacterial cell membrane defective.
Alternate Names
Sisomicin is also known as sisomicin sulfate. Brand names include Sisomin and Sisowill (cream).
How It Works
Pharmacodynamics: Sisomicin exerts its bactericidal effect by inhibiting protein synthesis in susceptible bacteria. It binds to the 30S ribosomal subunit, interfering with the messenger RNA translation and causing misreading of the genetic code. This results in the production of non-functional proteins and ultimately leads to bacterial cell death. Additionally, in some cases, it also binds to the 50S ribosomal subunit.
Pharmacokinetics: While some pharmacokinetic data is available from studies, certain aspects are not fully elucidated. Absorption details following intramuscular administration have been studied, showing peak serum concentrations reached approximately 1 hour after injection. Intravenous administration achieves higher peak levels more quickly. Elimination occurs primarily through renal excretion with a mean half-life ranging between 90 and 120 minutes in children. Metabolism data is limited.
Mode of Action: Sisomicin’s bactericidal action targets the bacterial ribosome. By binding to the 30S subunit, it disrupts the accurate reading of messenger RNA codons, leading to the incorporation of incorrect amino acids during protein synthesis. The resulting abnormal proteins compromise cellular functions and eventually cause bacterial cell death.
Receptor binding, enzyme inhibition, or neurotransmitter modulation: The primary mechanism of action is ribosomal binding leading to protein synthesis inhibition. Specific information on receptor binding, enzyme inhibition, or neurotransmitter modulation is not readily available.
Elimination pathways: Sisomicin is primarily excreted unchanged through the kidneys, making renal function a critical factor in dosage adjustment.
Dosage
Standard Dosage
Adults:
- Intramuscular/Intravenous: 3 mg/kg daily, divided into 2-3 doses.
- Topical (0.1% cream): Apply to the affected area twice daily.
Children:
Pediatric dosing should be carefully determined based on the child’s weight and the severity of the infection. Consultation with a pediatrician or neonatologist is highly recommended. Neonates and infants require specific dosing adjustments according to age and weight:
- Neonates: 2-3 mg/kg twice daily (IM or IV)
- Infants and School children: 2.5 mg/kg thrice daily.
Special Cases:
- Elderly Patients: Dosage adjustments may be necessary due to age-related decline in renal function. Careful monitoring of renal function is essential.
- Patients with Renal Impairment: Dosage must be reduced and/or dosing intervals prolonged based on creatinine clearance. Close monitoring of renal function is crucial.
- Patients with Hepatic Dysfunction: Caution is advised as hepatic metabolism data is limited. Monitor liver function tests.
- Patients with Comorbid Conditions: Careful evaluation and dose adjustments may be needed for patients with myasthenia gravis, Parkinsonism, hypotension, or dehydration.
Clinical Use Cases:
Dosing considerations for specific situations:
- Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: Dosage adjustments based on individual needs and close physiological monitoring.
- Emergency Situations: Initial doses might be higher, followed by adjustments based on patient response and renal function.
Dosage Adjustments:
Dose adjustments are necessary based on renal function, age, and other patient-specific factors.
Side Effects
Common Side Effects:
- Nausea
- Vomiting
- Diarrhea
- Dizziness
- Injection site reactions (pain, redness)
Rare but Serious Side Effects:
- Nephrotoxicity (kidney damage)
- Ototoxicity (hearing loss, balance problems, tinnitus)
- Neurotoxicity (peripheral neuropathy, confusion, lethargy, hallucinations, seizures, mental depression)
- Neuromuscular blockade (muscle weakness, respiratory paralysis)
- Hypersensitivity reactions (rash, urticaria, anaphylaxis)
Long-Term Effects:
- Potential for irreversible hearing loss and kidney damage with prolonged use.
Adverse Drug Reactions (ADR):
- Acute renal failure
- Anaphylaxis
Contraindications:
- Hypersensitivity to sisomicin or any aminoglycoside antibiotic
- Myasthenia gravis
- Severe renal impairment (except with careful monitoring and dose adjustment)
- Pre-existing neuromuscular disorders that could be exacerbated by the drug.
Drug Interactions:
- Nephrotoxic drugs: Increased risk of kidney damage (e.g., vancomycin, amphotericin B, cisplatin, loop diuretics).
- Ototoxic drugs: Increased risk of hearing loss (e.g., other aminoglycosides, ethacrynic acid, furosemide, vancomycin).
- Neuromuscular blocking agents: Enhanced neuromuscular blockade (e.g., pancuronium, vecuronium, atracurium).
- Certain anti-inflammatory drugs: (e.g. indomethacin) increases sisomicin plasma levels.
- Beta-lactam antibiotics: Incompatibility when mixed in the same IV solution.
- Antihistamines (H1 receptor blockers): May mask the early signs of ototoxicity.
Pregnancy and Breastfeeding:
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Pregnancy: Sisomicin should be used with caution during pregnancy. Animal studies suggest a potential risk of fetal harm, including ototoxicity. Consult with a specialist if use is essential during pregnancy.
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Breastfeeding: While limited information is available, sisomicin is believed to be present in breast milk. It is generally considered safe to use during breastfeeding, but it’s essential to monitor the infant for potential adverse effects.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit.
- Side Effects: Nausea, vomiting, diarrhea, nephrotoxicity, ototoxicity, neurotoxicity, neuromuscular blockade, hypersensitivity.
- Contraindications: Hypersensitivity to aminoglycosides, myasthenia gravis, severe renal impairment.
- Drug Interactions: Nephrotoxic and ototoxic drugs, neuromuscular blocking agents, some beta-lactam antibiotics.
- Pregnancy & Breastfeeding: Use with caution; monitor infant.
- Dosage: Adults: 3 mg/kg/day divided; Topical: 0.1% cream twice daily. Pediatric dosing requires careful adjustment.
- Monitoring Parameters: Renal function, hearing tests, serum sisomicin levels.
Popular Combinations
Specific information on popular drug combinations is not readily available. Concurrent use with other antibiotics should be carefully considered based on individual case specifics and potential for interactions.
Precautions
- General Precautions: Assess renal and hepatic function, screen for pre-existing neuromuscular disorders.
- Specific Populations: Closely monitor pregnant or breastfeeding women and adjust dosage in elderly patients and those with renal impairment. Monitor neonates and children carefully for adverse reactions.
- Lifestyle Considerations: Limited data on interaction with alcohol.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Sisomicin?
A: Adults: 3 mg/kg/day IM/IV divided into 2-3 doses; Topical: 0.1% cream twice daily. Pediatric dosing requires careful individual adjustment based on age, weight and renal function. Neonates: 2-3mg/kg twice daily. Infants and older children: 2.5 mg/kg thrice daily.
Q2: What are the serious side effects of Sisomicin?
A: Nephrotoxicity, ototoxicity, neurotoxicity, and neuromuscular blockade are the most serious potential side effects.
Q3: What are the contraindications for Sisomicin use?
A: Known hypersensitivity to aminoglycosides, myasthenia gravis, and severe renal impairment.
Q4: How does Sisomicin interact with other medications?
A: It can interact with other nephrotoxic or ototoxic drugs, neuromuscular blocking agents, and some beta-lactam antibiotics.
Q5: Can Sisomicin be used during pregnancy or breastfeeding?
A: It should be used with caution in pregnancy due to the potential risk to the fetus. It’s generally considered safe during breastfeeding, but the infant should be monitored.
Q6: What is the mechanism of action of Sisomicin?
A: It inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit.
Q7: What infections is Sisomicin commonly used to treat?
A: Serious gram-negative bacterial infections, including sepsis, respiratory tract infections, and urinary tract infections, when other antibiotics are ineffective or contraindicated. It can also treat staphylococcal and other infections.
Q8: How should renal function be monitored in patients receiving Sisomicin?
A: Regular monitoring of serum creatinine and creatinine clearance is essential to adjust dosage and prevent nephrotoxicity.
Q9: What is the onset of action for Sisomicin?
A: The onset of action is relatively rapid, typically within 30 minutes to 1 hour after intravenous administration.
Q10: Are there any specific monitoring parameters for patients on Sisomicin?
A: Yes, renal function, hearing tests (audiometry), and serum sisomicin levels should be monitored, especially during prolonged therapy.
