Gentamicin

Gentamicin Intrathecal 5mg/ml Solution for Injection,

Each ampoule (1ml) contains Gentamicin Sulphate Ph Eur equivalent to 5mg Gentamicin base.

For the full list of excipients, see section 6.1.

Injection.

Gentamicin is an aminoglycoside antibiotic with broad-spectrum bactericidal activity. 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.

Gentamicin Intrathecal Injection is indicated as a supplement to systemic therapy in bacterial meningitis, ventriculitis and other bacterial infections of the central nervous system.

Consideration should be given to official local guidance on the appropriate use of antibacterial agents.

Posology

Bacterial meningitis and ventriculitis:

The starting dose of Gentamicin Intrathecal Injection for both children and adults is 1 mg daily, intrathecally or intraventricularly, together with 1 mg/kg every eight hours intramuscularly.

The MIC of the infecting organism in the C.S.F. should be assessed and, if necessary, the intrathecal/intraventricular dose increased to 5 mg daily, whilst keeping the intramuscular dose at 1 mg/kg eight-hourly.Treatment should be continued for at least 7 days but longer if necessary.Periodic serum and C.S.F. gentamicin assays should be carried out to ensure that adequate antibiotic levels are maintained and that serum and C.S.F. levels do not exceed 10 mg/l.

Method of administration

Intrathecal or intraventricular.

• Known hypersensitivity to the active substance (gentamicin), other aminoglycosides or any of the excipients listed in section 6.1.

• Myasthenia gravis and related conditions (evidence exists that gentamicin may cause neuromuscular blockade).

Ototoxicity and nephrotoxicity

Ototoxicity has been reported following the use of aminoglycosides, including gentamicin. Symptoms include loss of balance and hearing loss, which may be irreversible (see section 4.8). Important risk factors include renal impairment, high doses, prolonged duration of treatment and age (neonates/infants and possibly the elderly). Due to the potential for ototoxicity and nephrotoxicity, monitoring of vestibule, cochlea and renal function is recommended before, during and shortly after treatment (see section 4.8). Serum levels are determined so as to avoid peak concentrations above 10 mg/l and troughs above 1 mg/l when administrating gentamicin once daily and 2 mg/l when administering gentamicin twice daily.

As there is some evidence that risk of both ototoxicity and 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.

There is an increased risk of ototoxicity in patients with mitochondrial DNA mutations, (particularly the nucleotide 1555 A to G substitution in the 12S rRNA gene), even if aminoglycoside serum levels are within the recommended range during treatment. Alternative treatment options should be considered in such patients. Mitochondrial mutations are rare, and the penetrance of this observed effect is unknown.

To avoid adverse events, continuous monitoring (before, during and after treatment) of hepatic and laboratory parameters is also recommended.

In patients with a maternal history of relevant mutations or aminoglycoside induced deafness, alternative treatments or genetic testing prior to administration should be considered.

Drug-resistant microorganisms

Treatment with gentamicin may produce an excessive growth of drug-resistant microorganisms. If this happens, an appropriate treatment should be initiated.

Clostridium difficile infection

Diarrhoea and pseudomembranous colitis have been observed when gentamicin is combined with other antibiotics. These diagnoses should be considered in every patient that develops diarrhoea during or immediately after treatment. Gentamicin should be discontinued if the patient suffers severe diarrhoea and/or bloody diarrhoea during treatment and an appropriate treatment should be initiated. Drugs that inhibit peristalsis should not be administered (see section 4.8).

Pregnancy

Gentamicin should only be used in pregnancy if considered essential by the physician (see section 4.6).

Conditions characterised by muscular weakness.

Gentamicin should be used with care in conditions characterised by muscular weakness.

Obesity

In cases of significant obesity gentamicin serum concentrations should be closely monitored and a reduction in dose should be considered

Important information about the ingredients of Gentamicin

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially “sodium-free

Concurrent administration of gentamicin and other potentially ototoxic or nephrotoxic drugs should be avoided. Potent diuretics such as etacrynic acid and furosemide are believed to enhance the risk of ototoxicity whilst amphotericin B, cisplatin and ciclosporin are potential enhancers of nephrotoxicity.

Any potential nephrotoxicity of cephalosporins, and in particular cephaloridine, may also be increased in the presence of gentamicin. Consequently, if this combination is used monitoring of kidney function is advised.Neuromuscular blockade and respiratory paralysis have been reported from administration of aminoglycosides to patients who have received curare-type muscle relaxants during anaesthesia.

Pregnancy

There are no proven cases of intrauterine damage caused by gentamicin. However, in common with most drugs known to cross the placenta, usage in pregnancy should only be considered in life threatening situations where expected benefits outweigh possible risks.

Breast-feeding

In the absence of gastro-intestinal inflammation, the amount of gentamicin ingested from the milk is unlikely to result in significant blood levels in breast-fed infants.

Not known.

The following CIOMS frequency rating is used, when applicable: Very common (≥ 1/10); common (≥ 1/100 to ≤ 1/10); uncommon (≥ 1/1,000 to ≤ 1/100); rare (≥ 1/10,000 to ≤ 1/1,000); very rare (≤ 1/10,000); not known (cannot be estimated from the available data).

Infections and infestations:

Not known: antibiotic-associated colitis, pseudomembranous colitis, Superinfection (caused by gentamicin-resistant bacteria)

Blood and lymphatic system disorders:

Not known: anaemia, blood dyscrasia

Immune system disorders:

Not known: hypersensitivity, anaphylaxis/anaphylactic reaction (including anaphylactic shock)

Metabolism and nutrition disorders:

Not known: hypomagnesaemia on prolonged therapy

Psychiatric disorders:

Not known: depression, hallucinations, confusion

Nervous system disorders:

Not known: central neuropathy (including convulsions, lethargy, encephalopathy), peripheral neuropathy

Ear and labyrinth disorders:

Not known: transitory hearing loss, irreversible hearing loss, deafness, particularly after exposure to ototoxic drugs or in the presence of renal dysfunction (see section 4.4).

Gastrointestinal disorders:

Not known: stomatitis, nausea, vomiting

Hepatobiliary disorders:

Not known: abnormal liver function, transaminases increased

Skin and subcutaneous tissue disorders:

Not known: rash, purpura, urticaria, pruritus, Steven Johnson syndrome, toxic epidermal necrosis

Renal and urinary disorders:

Very rare: acute renal failure, Fanconi-like syndrome in patients treated with a prolonged course of high-dose

Not known: nephrotoxicity (usually reversible) has been reported.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Haemodialysis and peritoneal dialysis will aid the removal from blood but the former is probably more efficient. Calcium salts given intravenously have been used to counter the neuromuscular blockade caused by gentamicin

Pharmacotherapeutic group: Antibacterials for systemic use, ATC Code: J01GB03

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.

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 to 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:

0.02 hr^-1 for anuric patients *

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.

Not applicable.

Sodium Chloride BP

Water for Injections BP

In general, gentamicin injection should not be mixed. In particular the following are incompatible in mixed solution with gentamicin injection: penicillins, cephalosporins, erythromycin, heparins, sodium bicarbonate.

* Dilution in the body will obviate the danger of physical and chemical incompatibility and enable gentamicin to be given concurrently with the drugs listed above either as a bolus injection into the drip tubing, with adequate flushing, or at separate sites. In the case of carbenicillin, administration should only be at a separate site.

* Carbon dioxide may be liberated on addition of the two solutions. Normally this will dissolve in the solution but under some circumstances small bubbles may form.

36 months

Store below 25°C, do not refrigerate or freeze.

Gentamicin Intrathecal Injection is supplied in 1 ml neutral glass ampoules in packs of 5.

Not applicable.

Zentiva Pharma UK Limited

12 New Fetter Lane

London

EC4A 1JP

United Kingdom

PL 17780/0506

28/07/2010

27/03/2024