APR GENTOMET 30 Ml

AB-21:

INFORMATION FOR THE USER

Gentamicin Injection

 

Read all of this information carefully before you start taking this medicine because it contains important information for you.

• Keep this information. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine is prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this information.

COMPOSITION:

Each vial contains:

Gentamicin sulphate eq. to gentamicin – 40mg

Methyl paraben – 0.18% w/v

Propyl paraben – 0.02% w/v

For IV/IM use only.

DESCRIPTION:

Gentamicin is a bactericidal antibiotic that is used to treat bacterial infections.

PHARMACOLOGICAL ACTION:

Gentamicin is usually bactericidal in action. The exact mechanism of action has not been fully elucidated, it appears to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits. In general, it is active against many aerobic gram-negative bacteria & some aerobic gram-positive bacteria. It is inactive against fungi, viruses, & most anaerobic bacteria. In vitro, conc. of 1-8 µg/ml inhibit most susceptible strains of E. coli, H. influenzae, M. lacunata, Neisseria, indole positive & indole negative Proteus, Pseudomonas (including most strains of P. aeruginosa), S. aureus, S. epidermidis & Serratia. However, different species & different strains of the same species may exhibit wide variations in susceptibility in vitro. In addition, in vitro susceptibility does not always correlate with in vivo activity. It is only minimally active against Streptococci. Natural & acquired resistance to gentamicin has been demonstrated in both gram-negative & gram-positive bacteria. Resistance may be due to decreased permeability of the bacterial cell wall, alteration in the ribosomal binding site, or the presence of a plasmid-mediated resistance factor which is acquired by conjugation. Plasmid-mediated resistance enables the resistant bacteria to enzymatically modify the drug by acetylation, phosphorylation, or adenylation & can be transferred between organisms of the same or different species. Resistance to other aminoglycosides & several other anti-infectives (e.g. chloramphenicol) may be transferred on the same plasmid. There is partial cross-resistance between gentamicin & other aminoglycosides.

CLINICAL PHARMACOKINETICS:

The distribution volume is about eq. to the volume of extracellular water. In newborns 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 per kg bodyweight is affected & 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 conc. a higher dose per kg bodyweight needs to be administered. It 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 hrs. In neonates elimination rate is reduced due to immature renal function. Elimination half-life averages approx. 8 hrs 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 to 0.2 L/h in neonates at a gestational age of 40 weeks.

INDICATIONS:

Gentamicin injection is indicated for the treatment of susceptible infections of:

• Upper & lower urinary tract infections
• Burn & wound infections
• Septicaemia & bacteraemia
• Abscesses
• Subacute bacterial endocarditis
• Neonatal infections
• Gynaecological infections

CONTRAINDICATIONS:

• Patients being treated with gentamicin should be under close clinical observation because of its potential toxicity
• Hypersensitivity to gentamicin, any other ingredient or other aminoglycosides
• Myasthenia gravis
• Should be used with caution in premature infants because of their renal immaturity, in elderly people and generally in patients with impaired renal function. Diabetes, auditory vestibular dysfunctions, otitis media, a history of otitis media, previous use of ototoxic drugs and a genetically determined high sensitivity to aminoglycoside induced ototoxicity, are other main factors which may pre-dispose the patient to toxicity.

WARNINGS AND PRECAUTIONS:

Patients should be under close clinical observation because of its potential toxicity.

As with other aminoglycosides toxicity is related to serum conc. At serum levels more than 10 micrograms/ml the vestibular mechanism may be affected. Evidence of toxicity requires adjustment of dosage or withdrawal of the drug.

As there is some evidence that the risk of both ototoxicity & nephrotoxicity is related to the level of total exposure, duration of therapy should be the shortest possible compatible with clinical recovery.

In some patients with impaired renal function, there has been a transient rise in blood- urea-nitrogen, which has usually reverted to normal during or following cessation of therapy. It is important to adjust the frequency of dosage according to the degree of renal function.

Should be used with care in conditions characterised by muscular weakness.

In significant obesity serum conc. should be closely monitored & a reduction in dose should be considered.

Concurrent use of other neurotoxic and/or nephrotoxic drugs can increase the possibility of gentamicin toxicity. Co-administration with the following agents should be avoided:

• Neuromuscular blocking agents such as succinylcholine & tubocurarine.
• Other potentially nephrotoxic or ototoxic drugs such as cephalosporins & methicillin.
• Potent diuretics such as ethacrynic acid & furosemide.
• Other aminoglycosides.

To avoid adverse events, continuous monitoring of renal function (serum creatinin, creatinin clearance), control of function of vestibule & cochlea as well as hepatic & laboratory parameters is recommended.

Sulphites can cause allergic-type reactions including anaphylactic symptoms & bronchospasm in susceptible people, especially those with a history of asthma or allergy.

ADVERSE EFFECTS:

Common side effects include: Vestibular damage & ototoxicity, Nephrotoxicity, Hypersensitive reactions, Anaphylaxis, Anaemia, Blood dyscarias, Granulocytopenia, CNS toxicity, abnormal hepatic function, Hypomagnesemia, Stomatitis, Nausea & vomiting, Urticria
DRUG INTERACTIONS:

• Increased risk of nephrotoxicity with cephalosporins notably cephalothin.
• Has been known to potentiate anticoagulants such as warfarin & phenindione.
• Increased risk of nephrotoxicity with amphotericin B.
• Antagonism of effect of neostigmine & pyridostigmine.
•  Cyclosporin, cisplatin: increased risk of nephrotoxicity.
• Increased risk of nephrotoxicity & possible risk of ototoxicity with cisplatin.
• Increased risk of ototoxicity with loop diuretics.
• Effect of non-depolarising muscle relaxants such as tubocurarine enhanced. Neuromuscular blockade & respiratory paralysis have been reported from administration of aminoglycosides to patients who have received curare-type muscle relaxants during anesthesia.
• Indomethacin possibly increases plasma conc. in neonates.
• Concurrent use of bisphosphonates may increase the risk of hypocalcaemia.
• Concurrent use with Botulinum Toxin may increase the risk of toxicity due to enhanced neuromuscular block.

DOSAGE: The recommended dose is 3-6mg/kg body weight per day as 1 (preferred) or 2 single doses.

ADMINISTRATION:

For IV/IM use only.

Administration to be done by a registered medical practitioner/nurse in a proper sterile and hospital setting only.

STORAGE:

Do not store above 25°C. Store in the original package. Keep away from children. Do not expose to direct sunlight.

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Last revised on August 2020.