AMIKACIN

5mg/kg every 12 hours). 5g. In endocarditis and febrile neutropenic patients, dosing should be done twice daily, as there is insufficient data for once-daily dosing. 5 mg/kg every 12 hours. In endocarditis and febrile neutropenia patients, dosing should be done twice a daily, as there is insufficient data for once-daily dosing.

2 "Pharmacokinetic properties"). 2).

Dosage in elderly patients (≥ 65 years):

Dose should be adjusted as described under impaired renal function if necessary. 5mg/kg (max. 5 g/day nor be administered for a period longer than 10 days. 5 g should not be exceeded. 5 mg/kg/day in two equally divided doses (equivalent to 250 mg twice daily in adults).

As the activity of amikacin is enhanced by increasing the pH, a urinary alkalizing agent may be administered concurrently. Monitoring The renal function status should be evaluated by measuring the serum creatinine concentration or preferably by estimation of creatinine clearance.

Blood urea nitrogen (BUN) is far less reliable for this purpose. Assessment of renal function should be performed at the start of therapy and should be re-evaluated at regular intervals during treatment. Amikacin concentrations in serum should be measured in all patients receiving parenteral amikacin and must be measured in obesity, neonates, if high doses are being given, the elderly and in cystic fibrosis.

Both peak and trough serum concentrations should be measured intermittently during therapy to ensure adequate but not excessive serum levels. In patients receiving multiple daily dosing peak concentrations (30-90 minutes after injection) should not exceed 35μg/ml and trough concentrations (just before the next dose) should not exceed 10μg/ml.

In patients receiving once daily (or extended interval) dosing pre-dose ('trough') concentration should be less than 5 mcg/ml. Peak concentrations (approximately 60 minutes after administration) may exceed 35 mcg/ml. If the pre-dose ('trough') concentration is high, the interval between doses must be increased.

If the post-dose ('peak') concentration is high, the dose must be decreased. Auditory and vestibular function should also be monitored during treatment, in particular if longer treatment duration (>7-10 days) is considered.

Dosage in renal impairment:

NOTE: In patients with impaired renal function (creatinine clearance <50ml/min) the recommended dose has to be decreased and adjusted to the renal function. This can be achieved by increasing the dose interval and/or reducing the dose.

In all patients with renal impairment, serum amikacin peak and trough concentration and renal function must be monitored regularly and the dose regimen altered as necessary (see below). Once daily/extended interval dosing Patients with renal impairment in whom once daily dosing would be considered appropriate if their renal function were normal may receive extended interval dosing.

The initial dose may be the same as in normal renal function. The dose interval should be at least 24 hours and extended according to the degree of renal impairment and the results of serum amikacin level measurements (see Monitoring Advice).

In severe renal impairment, the initial dose may have to reduced in addition. g. 5 mg/kg) should be administered every 18 hours. 5 6 54 Once daily or extended interval dosing should be avoided in patients with a creatinine clearance less than 20 ml/minute.

73 m2.

Reduced dose at fixed intervals:

If patients with renal impairment are given amikacin at fixed time intervals, the dose must be reduced. In these patients, the serum amikacin concentration should be measured to ensure accurate administration and to avoid excessive serum concentrations.

If a determination of serum concentration is not possible and the patient's condition is stable, serum creatinine and creatinine clearance rates are the most readily available indicators of the extent of renal dysfunction and the consequent reduction in dose.

As renal function may alter appreciably during therapy, the serum creatinine should be checked frequently and the dosage regimen modified as necessary. Multiple daily dosing In patients […]

All aminoglycosides have oto-, nephro- and neurotoxic potential. 4 "Special warnings and precautions for use ").

Frequency is defined using the following convention:

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 (frequency cannot be estimated from the available data) Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

* Changes in renal function are usually reversible at the end of therapy. ** Amikacin is not intended for administration to the vitreous body. When amikacin was injected directly into the eye, maculopathies were observed, occasionally leading to complete loss of vision.

MedDRA system organ class Frequency Adverse event Infections and Infestations Uncommon Super infection or colonization with resistant bacteria or yeasts a. g. alanine aminopeptidase, glutamine transferase, β-galactosidase, N-acetyl-glucosaminidase), azotemia, decrease in urine osmolarity, increase in blood urea nitrogen and serum creatinine, decrease in creatinine clearance.

In case of minor irritations (albumin, erythrocytes, leukocytes or cylinders in urine) the fluid intake should be increased. After discontinuation of the drug, renal impairment is usually reversible. 5 - 5% of the treated patients. 4 "Special warnings and precautions for use").

When treating with amikacin, special attention should be paid to cochlear damage. These are manifested as tinnitus, pressure in the ears and initially merely as audiometrically detectable decrease of acoustic perceptions in the high frequency range (> 4000 Hertz) above the speech range.

However, hearing loss can develop to complete, irreversible deafness despite discontinuation of the aminoglycoside. Vestibular disorders manifest in initial symptoms such as dizziness, nausea, and vomiting. In the clinical examination usually a nystagmus is detected.

At the first sign of hearing or balance disorders, amikacin therapy should be discontinued.

Disorder of the nervous system Neuromuscular blockades:

Specific risks are very rare when taking aminoglycosides. The occurrence of neuromuscular blockade, which can lead to respiratory arrest, can occur especially with intrapleural or intraperitoneal administration. The neuromuscular blocking properties of the aminoglycosides are enhanced by inhalation narcotics or muscle relaxants or curare-like drugs.

Particularly at risk are patients with myasthenia gravis. Respiratory paresis requires artificial respiration. In addition, the application of potassium salts may be considered as a countermeasure. Immune system disorders Due to the content of sulfite it can lead to hypersensitivity reactions that may manifest as vomiting, diarrhoea, wheezing, acute asthma attack, disturbance of consciousness or shock in individual cases, especially in bronchial asthma.

These reactions can vary widely individually and can lead to life-threatening conditions 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.

Allergic reactions Amikacin contains sodium metabisulfite. Sodium metabisulfite may rarely cause severe hypersensitivity reactions in susceptible individuals, including anaphylactic symptoms and life- threatening bronchial spasms (bronchospasm).

Sulphite hypersensitivity is generally uncommon and more common in asthmatics than non-asthmatics. Neuromuscular toxicity Neuromuscular blockade and respiratory paresis have been reported following parenteral injection, topical lavage (such as orthopaedic and abdominal irrigation, or with local empyema treatment) or after oral administration of aminoglycosides.

The risk of respiratory paresis when administering aminoglycosides irrespective of the route of administration should be considered, especially in patients receiving anaesthetics or neuromuscular blocking agents (see section

1 or other aminoglycoside antibiotics. • Due to the known cross sensitivities in this class of drugs, a history of hypersensitivity or serious toxic reactions to aminoglycosides may be a contraindication to all aminoglycosides.