CIDOMYCIN

Posology 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. 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.

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). 4).

Gastrointestinal disorders:

Very common: vomiting Not known: stomatitis, nausea Hepatobiliary disorders: Not known: abnormal liver function, transaminases increased Skin and subcutaneous tissue disorders: Not known: Stevens-Johnson syndrome, Toxic Epidermal Necrosis, rash, purpura, urticaria, pruritus 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Ototoxicity and nephrotoxicity Ototoxicity has been reported following the use of aminoglycosides, including gentamicin. 8). Important risk factors include renal impairment, high doses, prolonged duration of treatment and age (neonates/infants and possibly the elderly).

8). Serum levels are determined so as to avoid peak concentrations above 10 mg/L and troughs above 1 mg/L when administering 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. In patients with a maternal history of relevant mutations or aminoglycoside induced deafness, alternative treatments or genetic testing prior to administration should be considered.

Mitochondrial mutations are rare, and the penetrance of this observed effect is unknown. In cases of significant obesity gentamicin serum concentrations should be closely monitored and a reduction in dose should be considered. To avoid adverse events, continuous monitoring (before, during and after treatment) of hepatic and laboratory parameters is also recommended.

6). Gentamicin should be used with care in conditions characterised by muscular weakness. Superinfection Treatment with gentamicin may produce an excessive growth of drug-resistant micro- organisms. If this happens, an appropriate treatment should be initiated.

1. • Myasthenia gravis.