AMIKACIN

Posology The dose must be adjusted individually, based on body weight and renal function, and the serum concentration must be monitored regularly. Amikacin can be given intramuscularly or intravenously in the same dosage. 6) and administered as an infusion over 30-60 minutes.

g. 5 mg/kg all 12 hours, or 2 mg/kg every 8 hours). 5 g. For endocarditis and febrile neutropenic patients, dosing should be done twice a day, as there is insufficient data for once-daily dosing. 5 mg/kg every 12 hours. For endocarditis and febrile neutropenic patients, dosing should be done twice a day, as there is insufficient data for once-daily dosing.

2). 2). 2).

Endocarditis:

In endocarditis caused by Enterococcus faecalis or alpha streptococcus, Amikacin should be combined with ampicillin and benzylpenicillin, respectively. In case of endocarditis caused by staphylococci, Amikacin should be combined with an isoxazolyl penicillin.

Neutropenic patients:

When treating neutropenic patients, Amikacin should be combined with piperacillin and tazobactam. In the case of serious infections of unknown etiology, Amikacin should be combined with a beta-lactam antibiotic while waiting for a culture and resistance report.

5 g/day nor be administered for a period longer than 10 days. 5 g should not be exceeded. In case of systemic infection caused by Pseudomonas aeruginosa, Amikacin can be combined with a beta-lactam antibiotic effective against Pseudomonas aeruginosa.

When treating infections caused by both aerobic and anaerobic bacteria, Amikacin should be combined with a preparation active against anaerobic bacteria. 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. Impaired renal function It is especially important in the case of impaired renal function that the serum concentration of amikacin is monitored regularly.

Since amikacin is mainly eliminated by the renal by glomerular filtration, the rate of elimination depends on the patient's renal function and the recommended daily dose should therefore be adapted to renal function. If renal function is impaired and the dose is not reduced and/or the dosing intervals are not extended, abnormally high and possibly toxic concentrations can be achieved in blood and tissues due to accumulation.

The degree of renal impairment should be controlled by determining serum creatinine or creatinine clearance. 1), all patients are initially given a normal dose (15mg/kg body weight). In patients with mild to moderate renal impairment, the dosing interval is based on the trough value, see “Treatment control”.

e. where an adequate trough value is not reached within 48 hours.

Haemodialysis:

The documentation for dosing in patients undergoing haemodialysis is deficient. Commonly used dosage is 5 mg/kg body weight given after each dialysis session.

Peritoneal dialysis:

Patients who undergo peritoneal dialysis twice a week are given 5 mg/kg body weight after each dialysis session. 5 mg/kg after the following dialysis sessions. 5 mg/ml) may be used satisfactorily as an irrigating solution in abscess cavities, the pleural space, the peritoneum and the cerebral ventricles.

5 mg/ml). If instillation is desired in adults, a single dose of 500 mg is diluted in 20 ml of sterile distilled water and may be instilled through a polyethylene catheter sutured into the wound at closure. If possible, instillation should be postponed until the patient has fully recovered from the effects of anaesthesia and muscle- relaxing drugs.

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, if high doses are being given, the elderly and in cystic […]

All aminoglycosides can induce ototoxicity, renal toxicity and neuromuscular blockade. 4 "Special warnings and precautions for use"). The frequency of the side effects listed below is defined using the following conventions: 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).

MedDRA system organ class Frequency Adverse event Infections and infestations Uncommon Super infection or colonization with resistant bacteria or yeastsa Blood and lymphatic system disorders Rare Anaemia, eosinophilia, granulocytopenia, leukopenia, thrombocytopenia Immune system disorders Not known Anaphylactic response (anaphylactic reaction, anaphylactic shock and anaphylactoid reaction), hypersensitivity Metabolism and nutrition disorders Rare Hypomagnesemia Common Dizziness Rare Tremora , paraesthesiaa, headache, balance disorders Nervous system disorders Not known Acute muscular paralysisa Eye disorders Rare Blindnessb, retinal infarctionb Common Vestibular disorders with nausea Rare Tinnitusa, hearing lossa Ear and labyrinth disorders Not known Deafnessa, neurosensory deafnessa Cardiovascular disorders Rare Hypotension, hypotonia, thrombophlebitis, tachycardia, myocarditis Respiratory, thoracic and mediastinal disorders Not known Apnoea, bronchospasm Gastrointestinal disorders Uncommon Vomiting, nausea Hepatobiliary disorders Rare Elevation of liver enzymes in plasma (SGOT, SGPT, LDH, alkaline phosphatase and bilirubin) Uncommon RashSkin and subcutaneous tissue disorders Rare Pruritus, urticaria Musculoskeletal and connective tissue disorders Rare Arthralgia, myokymiaa Common Proteinuria, urea increase Rare Oliguriaa, serum creatinine increasea,albuminuriaa, azotemiaa, presence of red and white blood cells in the urinea Renal and urinary disorders Not known Acute renal failure, toxic nephropathy, cells in the urinea Rare FeverGeneral disorders and administration site conditions Not known Pain in the injection site a.

4 "Special warnings and precautions for use". b. Amikacin is not formulated for intravitreal use. Blindness and retinal infarction have been reported following intravitreal administration (injection into the eye) of amikacin. Description of selected adverse reactions Cases of skin and mucosal reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported, however with an unclear connection.

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. As with all aminoglycosides, there have been reports of nephrotoxicity and acute renal failure following approval of amikacin. 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.

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Allergic reactions Amikacin contains sodium metabisulfite which may rarely cause severe hypersensitivity reactions in susceptible individuals, including anaphylactic symptoms and life-threatening bronchial spasms (bronchospasm). Sulfite sensitivity is generally uncommon and more frequent in asthmatics than in non-asthmatics.

Caution should be applied to patients with existing renal insufficiency, or with existing auditory or vestibular damage. Patients treated with parenteral aminoglycosides should be under close clinical observation due to potential ototoxicity and nephrotoxicity associated with treatment.

The safety of treatment for longer than 14 days has not been established. Neuro/Ototoxicity Neurotoxicity manifesting as vestibular and/or bilateral auditory ototoxicity may occur in patients treated with aminoglycosides. The risk of aminoglycoside-induced ototoxicity is greater in patients with impaired renal function or in those where the duration of treatment is extended beyond 5-7 days, even in healthy patients.

Often, deafness at high frequencies appears first and can only be detected by audiometric testing. Dizziness may occur and may be evidence of vestibular damage. Other signs of neurotoxicity may include numbness, skin tingling, muscle twitching, and convulsions.

Patients who develop cochlear or vestibular damage do not need to have symptoms during treatment that alert them of eighth cranial nerve damage. Total or partially irreversible bilateral deafness or disabling vertigo may occur after discontinuation of the drug.

Aminoglycoside Induced ototoxicity is usually irreversible. 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 family history of relevant mutations or aminoglycoside induced deafness, alternative treatments or genetic testing prior to administration, should be considered.

Neuromuscular toxicity Neuromuscular blockade and respiratory paralysis have been reported following parenteral injection, topical installation as in orthopaedic flushing and abdominal lavage, or with local empyema treatment) and after oral administration of aminoglycosides.

5 “Interactions with other medications and other forms of interaction"). If neuromuscular blockade occurs, calcium salts may relieve respiratory paralysis but mechanical ventilation may be necessary. In animal studies, neuromuscular blockade and muscular paralysis have been reported after administration of high doses of amikacin.

Aminoglycosides should be used with caution in patients with muscular disorders such as myasthenia gravis or parkinsonism, as these drugs may aggravate muscle weakness due to their potential curare-like effect on the neuromuscular junction.

Renal toxicity Aminoglycosides are potentially nephrotoxic. Renal toxicity appears independent of plasma obtained at the peak (Cmax). The risk of nephrotoxicity is increased in patients with impaired renal function and in patients receiving high doses or prolonged treatment.

Patients should be well hydrated during treatment and renal function should be assessed by the usual methods prior to starting therapy and daily during the course of treatment. A reduction of dosage is required if evidence of renal dysfunction occurs, such as presence of urinary casts, white or red cells, albuminuria, decreased creatinine clearance, decreased urine specific gravity, increased BUN, serum creatinine, or oliguria.

If azotemia increases, or if a progressive decrease in urinary output occurs, treatment should be stopped. Elderly patients may have reduced renal function which may not be seen in the routine screening tests such as BUN (blood urea nitrogen) or serum creatinine.

A creatinine clearance determination may be more helpful. Monitoring of renal function in elderly patients during treatment with aminoglycosides is particularly important. Renal function and function of the eighth cranial nerve should be closely monitored, especially in patients with known or suspected renal impairment at the onset of treatment and also in those whose renal function is initially normal but who develop signs of renal impairment during treatment.

Serum concentrations of amikacin should be monitored (when possible) to ensure adequate levels and to avoid potential toxic levels. The urine should be examined for decreased density, increased excretion of proteins and the presence of cells or casts.

BUN (blood urea nitrogen), serum creatinine, or creatinine clearance should be measured periodically. Repeat audiograms should be performed (if possible), especially in high-risk patients. Evidence of ototoxicity (dizziness, tinnitus, ringing in the ears and hearing loss) or nephrotoxicity require discontinuation of the drug or dose adjustment.

Concomitant and/or sequential systemic, oral, or topical use of other neurotoxic or nephrotoxic products, particularly bacitracin, cisplatin, amphotericin B, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, vancomycin, or other aminoglycosides, should be avoided.

Other factors that may increase risk of toxicity are advanced age and dehydration. Inactivation of aminoglycosides is clinically significant only in patients with severe renal impairment. Inactivation may persist in body fluid samples collected for analysis, resulting in incorrect aminoglycoside readings.

Such samples should be handled properly (analyzed immediately, frozen, or treated with beta-lactamase). Diarrhoea/pseudomembranous colitis caused by Clostridium difficile occurs. Patients […]

1. - Due to the known cross sensitivities previous hypersensitivity reactions or serious toxic reactions with any aminoglycosides may be a contraindication for the use of other aminoglycosides. - Because of its sulfite content, Amikacin must not be used in asthmatics with sulfite hypersensitivity.