TRADE NAME: GARAMYCIN 40MG/1ML AMPOULE. GARAMYCIN 80MG/2ML AMPOULE. GENERIC NAME:Gentamicin sulphate. COMPOSITION OF GARAMYCIN 40MG/1ML AMPOULE: Each ampoule(1ml) contains: Active ingredient: Gentamicin sulphate (equivalent to gentamicin base) 40mg Excipients: Methyl paraben, propyl paraben, Sodium metabisulphite, Disodium Edetate, Water for injection. COMPOSITION OF GARAMYCIN 80MG/2ML AMPOULE: Each ampoule(2ml) contains: Active ingredient: Gentamicin sulphate (equivalent to gentamicin base) 80mg Excipients: Methyl para-hydroxybenzoate, propyl para-hydroxybenzoate, Sodium metabisulphite, Sodium Edetate, Water for injection. PHARMACEUTICAL FORM:Solution in ampoule for I.M./I.V. injection or I.V. infusion. PHARMACOLOGICAL ACTION: PHARMACODYNAMICS: Pharmacotherapeutic group: Antibacterials for systemic use. Gentamicin is a mixture of antibiotic substances produced by the growth of micromonospora purpurea. It is bactericidal with greater antibacterial activity than streptomycin, neomycin or kanamycin. Gentamicin exerts a number of effects on cells of susceptible bacteria. It affects the integrity of the plasma membrane and the metabolism of RNA, but its most important effects is inhibition of protein synthesis at the level of the 30s ribosomal subunit. PHARMACOKINETICS: Gentamicin is not readily absorbed from the gastro-intestinal tract. Gentamicin is 70 – 85% bound to plasma albumin following administration and is excreted 90% unchanged in urine. The half-life for its elimination in normal patients is 2 – 3 hours. Effective plasma concentration is 4 – 8 μg/ml. The volume of distribution (vd) is 0.3 l/kg. The elimination rate constant is: 1. 0.02 hr-1 for anuric patients* 2. 0.30 hr-1 normal * Therefore in those with anuria care must be exercised following the usual initial dose, any subsequent administration being reduced in-line with plasma concentrations of gentamicin. Paediatric population (premature infants and neonates) Distribution The distribution volume of gentamicin is about equivalent to the volume of extracellular water. In the newborn water makes up 70 – 75% of bodyweight, compared with 50 – 55% in adults. The extracellular water compartment is larger (40% of body weight compared with 25% of body weight in adults). Therefore, the volume of distribution of gentamicin per kg bodyweight is affected and decreases with increasing age from 0.5 – 0.7 l/kg for a premature newborn to 0.25 l/kg for an adolescent. The larger volume of distribution per kg bodyweight means that for adequate peak blood concentration a higher dose per kg bodyweight needs to be administered. Elimination Gentamicin is not metabolized in the body but is excreted unchanged in microbiologically active form predominantly via the kidneys. In patients with normal renal function the elimination half-life is about 2 – 3 hours. In neonates elimination rate is reduced due to immature renal function. Elimination half-life averages approximately 8 hours in neonates at a gestational age of 26 – 34 weeks compared with about 6.7 hours in neonates at a gestational age of 35 – 37 weeks. Correspondingly, clearance values increase from about 0.05 l/h in neonates at a gestational age of 27 – 0.2 l/h in neonates at a gestational age of 40 weeks. INDICATIONS: Gentamicin is an aminoglycoside antibiotic with broad-spectrum bactericidal activity. It is indicated to treat severe infections caused by bacteria susceptible to gentamicin such as, but not limited to: Urinary tract infections Respiratory tract infections Intra-abdominal infections CNS infections Severe neonatal infections It is usually active against most strains of the following organisms: Escherichia coli, Klebsiella spp., Proteus spp. (indole positive and indole negative), Pseudomonas aeruginosa, Staphylococci, Enterobacter spp., Citrobacter spp. and Providencia spp. Consideration should be given to official local guidance on the appropriate use of antibacterial agents. DOSAGE AND ADMINISTRATION: Dosage Adults The recommended dose in adults with normal renal function is 3 – 5 mg/kg/day, depending on the severity of infection, administered as one single dose (preferred) or in two divided doses. The dose should be adjusted according to clinical response and serum concentration levels (see below). Dose calculations should be based on ideal body weight. A dosing frequency of more than twice daily may be adopted for some specific pathogens or some sites of infection as recommended in national and local guidance. Once daily dosing is not recommended in cases of endocarditis, depending on the responsible pathogens. National and local guidance on treatment with gentamicin and serum level monitoring in endocarditis should be followed. In patients with normal renal function, 160 mg once daily may be used for the treatment of urinary tract infections. Paediatric population The daily dose recommended in children aged 1 year and above and adolescents with normal renal function, is 3 – 6 mg/kg/day as one single dose (preferred) or two divided doses. The daily dose in infants after the first month of life is 4.5 – 7.5 mg/kg/day as one single dose (preferred) or two divided doses. The daily dose in neonates and pre-term infants (aged 0 – 4 weeks old) is 4 – 7 mg/kg/day. Due to the longer half-life, newborns are given the required daily dose in one 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 ototoxicity. Renal impairment In impaired renal function, the recommended daily dose has to be decreased and adjusted to the renal function. This can be achieved by reducing the dose and/or increasing the dose interval. In all patients with renal impairment, serum gentamicin peak and trough concentration and renal function must be monitored frequently (see below). Nomograms are available for the calculation of dose, which depends on the patient’s age, weight and renal function. Local guidance should be followed where available. No clear recommendation can be made for once daily dosing; dosing should be guided by plasma concentration levels. In patients with moderate renal impairment, in whom once daily dosing would be considered appropriate if their renal function were normal, the dose interval should be at least 24 hours and extended according to the degree of renal impairment and the results of serum gentamicin monitoring. Limited data are available in patients with severe renal impairment (creatinine clearance < 30 ml/min) after once daily dose
