AMIKACIN KABI

Posology Amikacin Kabi is commonly used in combination with other appropriate antibiotics to cover the bacterial spectrum encountered in the respective infection. The dosage as well as the use of amikacin would notably depend on the type of infection and the patient status.

Local therapeutic guidance should be taken into consideration. e. 5 mg/kg body weight every 12 hours. 5 g. In endocarditis and in febrile neutropenic patients dosing should be twice daily, as there is not enough data to support once daily dosing.

5 mg/kg body weight every 12 hours. In endocarditis and in febrile neutropenic patients dosing should be twice daily, as there is not enough data to support once daily dosing. 2). 2). 00 ml Accuracy of dosing is improved if Amikacin 5 mg/ml solution for infusion is administered with an Accuracy of dosing is improved if Amikacin 5 mg/ml solution for infusion is administered with an infusion pump.

Maximum daily dose:

The daily dose of amikacin is based on body weight, consequently the maximum dose should equally be based on body weight unless otherwise justified. 5 g per day but should not be administered for a period longer than 10 days and only under constant monitoring.

A maximum total adult dose of 15 g should not be exceeded; other aminoglycoside treatment given previously must be included in this calculation. Due to the requirement for dose adjustments once daily dosing of amikacin is not recommended for patients with febrile neutropenia, renal failure.

Duration of treatment The total duration of therapy should be limited to 7 to 10 days, depending on severity of infection. In severe and complicated infections, where treatment with amikacin exceeds 10 days, the suitability of treatment with amikacin should be re-evaluated, as eventual treatment continuation requires the monitoring of serum amikacin levels and of renal, auditory and vestibular functions.

Patients with infections caused by susceptible microorganisms should respond to therapy within 24 to 48 hours with the recommended dosage regime. When no clinical response is seen within three to five days an alternative therapy should be considered.

Monitoring advice Assessment of renal function should be performed at the start of therapy and should be re- evaluated at regular intervals during treatment. Monitoring of amikacin plasma concentrations is strongly recommended in all patients, and especially in the elderly, newborns, obese patients and those with renal impairment or cystic fibrosis.

4). Blood samples are taken at the end of a dosage interval (trough level) and 30- 90 minutes after the end of the infusion (peak level). In case of multiple daily doses, peak levels should not exceed 30 - 35 micrograms/ml. The trough level should be less than 10 micrograms/ml.

For once daily dose regimens, local guidelines on serum concentration monitoring should be considered. Patients with impaired renal function Renal function should be monitored in all patients receiving amikacin and is mandatory in those with renal impairment.

Note:

Once daily administration of amikacin is not recommended in patients with renal function disorders (creatinine clearance <50 ml/min). In renal impairment with a glomerular filtration rate of less than 70 ml/minute, dose reduction or longer dose intervals are advised, because an accumulation of amikacin can be expected.

5 mg/kg body weight. The dose interval for individual patients is calculated as 9 times the serum creatinine level. 5 mg/kg body weight) must be administered every 2 x 9 = 18 hours. 5 mg/kg body weight. The values presented in the following table may be taken as guidance.

Creatinine clearance Daily dose of […]

Under certain conditions amikacin shows ototoxic and/or nephrotoxic effects. Renal impairment is uncommonly observed in patients treated with amikacin and is usually reversible upon withdrawal of the medicinal product.

Important note on therapy:

Renal impairment and hearing impairment due to neurological effects can be for the most part avoided with the observance of precautionary measures. Control renal status as well as the senses of hearing and equilibrium before, during and after therapy.

Maintain adequate hydration and ensure adequate urine production. 2). The adverse reactions considered at least possibly related to treatment are listed below by body system organ class and absolute frequency. The following terminologies have been used in order to classify the occurrence of undesirable effects: – 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: Uncommon: Superinfection or colonisation (with resistant microbes or yeast-like fungi) Blood and lymphatic system disorders: Rare: anaemia, leukopaenia, granulocytopenia, thrombocytopenia, eosinophilia Immune system disorders: Rare: Hypersensitivity reactions3 Very rare: Anaphylactic shock Not known Cross-allergy between aminoglycosides Metabolism and nutrition disorders: Rare: Hypomagnesaemia Nervous system disorders: Uncommon: Dizziness1, vertigo1 Rare: Headache, migraine, paraesthesia, tremor Eye disorders: Uncommon: Nystagmus1 Rare: Blindness5, retinal infarction5 Ear and labyrinth disorders: Uncommon: Tinnitus1, pressure in the ears1, hearing impairment1 Very rare: Deafness1 Vascular disorders: Rare: Hypotension Respiratory, thoracic and mediastinal disorders: Rare: Respiratory function depression4 Very rare: Respiratory paralysis4 Not known: Apnoea, bronchospasm Gastrointestinal disorders: Uncommon: Nausea1 Rare: Vomiting Skin and subcutaneous tissue disorders: Rare: Skin rash, exanthema, pruritus, urticaria (hypersensitivity reactions)3 Musculoskeletal and connective tissue disorders: Rare: Arthralgia Very rare: Neuromuscular blockage Renal or urinary disorders: Uncommon: Damage to renal tubuli2, renal impairment2 Very rare: Toxic nephropathy, acute renal failure General disorders and administration site conditions: Rare: Drug-related fever3 Investigations: Rare: Aspartate aminotransferase increased, Alanine aminotransferase increased, alkaline phosphatase increased (slight and transient) Further information on particular undesirable effects (1) These effects were seen in particular when the recommended dosage level was exceeded, in treatment lasting longer than 10 days, or when the dose was not adequately reduced for patients with renal dysfunction.

Initial symptoms of vestibular disturbances are dizziness, nausea and vomiting. The clinical examination often reveals a nystagmus. Vestibular disturbances are reversible in almost any case. The first symptoms of cochlear dysfunction often include a loss of high-tone perception (≥4,000 Hertz) that precedes hearing loss and is detected only by audiometry.

(2)Another uncommon adverse effect is damage to the renal tubules with renal impairment. The mechanism of renal damage involves accumulation in the lysosomes, phospholipase inhibition and necrosis of tubular cells after repeated administration of amikacin.

Once daily dosing may reduce the risk of nephrotoxicity. Renal damage is reversible to varying degrees but exacerbates the risk of accumulation which may cause or intensify ototoxic effects. An increase in the serum creatinine concentration, the presence of albumin, red and white blood cells or cylinders in urine, uraemia and oliguria are possible.

(3)Rare adverse effects are hypersensitivity reactions such as exanthema, itching, hives, and drug fever. (4)In rare cases, if intravenous infusion of the medicinal product is too fast, respiratory functions may be seriously depressed.

5). (5) Amikacin is not formulated for intavitreal use. Blindness and retinal infarction have been reported following intravitreous administration (injection into the eye) of amikacin. 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.

Caution is necessary on administration to patients with renal impairment, to patients with auditory or vestibular damage, to patients with neuromuscular disorders, and if patients were treated with another aminoglycoside active substance immediately prior to amikacin.

Neuro/Ototoxicity Neurotoxicity, manifested as vestibular and/or bilateral auditory ototoxicity, can occur in patients treated with aminoglycosides. The risk of aminoglycoside-induced ototoxicity is greater in patients with impaired renal function, or in those whose therapy is prolonged over 5-7 days of treatment, even in healthy patients.

High frequency deafness usually occurs first and can be detected only by audiometric testing. Vertigo and loss of balance may occur and may be evidence of vestibular injury. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and convulsions.

Patients developing cochlear or vestibular damage may not have symptoms during therapy to warn them of developing eighth nerve toxicity, and total or partial irreversible bilateral deafness or disabling vertigo may occur after the medicinal product has been discontinued.

Aminoglycoside-induced ototoxicity is usually irreversible. The use of amikacin in patients with a history of allergy to aminoglycosides or in patients who may have subclinical renal or eighth nerve damage induced by prior administration of nephrotoxic and/or ototoxic agents should be considered with caution, as toxicity may be additive.

In these patients amikacin should be used only if, in the opinion of the physician, therapeutic advantages outweigh the potential risks. 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.

Renal toxicity Aminoglycosides are potentially nephrotoxic. Renal toxicity is independent of plasma obtained at the peak (Cmax). The toxic effects of aminoglycosides, including amikacin, are more frequent in patients with renal impairment, if doses in excess of those recommended are administered, and if the recommended duration of treatment is exceeded.

The safety of treatment over periods longer than 14 days has not been established. Other factors that increase the risk of aminoglycoside toxicity include advanced age and dehydration. Daily doses should be reduced and/or the interval between doses extended in the case of signs of renal dysfunction such as: cylindruria, the presence of leukocytes or red blood cells, albuminuria, reduction in creatinine clearance, decreased urine specific gravity, azotaemia, elevation of serum creatinine and oliguria.

Treatment must be discontinued if azotaemia increases or if urine volume decreases gradually. Elderly patients may have reduced renal function which may not be evident in routine screening tests such as BUN (blood urea nitrogen) or serum creatinine.

A creatinine clearance determination may be more useful. Monitoring of renal function in elderly patients during treatment with aminoglycosides is particularly important. During treatment the patient must be well-hydrated and renal function should be determined at the onset of treatment, particularly in patients with renal impairment.

Renal function should also be monitored closely during treatment. It is recommended to perform repeat audiometric examinations, especially in the case of patients at high risk. 2). Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, and hearing loss) or nephrotoxicity requires discontinuation of the medicinal product or dose adjustment.

Inactivation of the aminoglycoside is clinically significant only in patients with severely impaired renal function. Inactivation may continue in specimens of body fluids collected for assay, resulting in inaccurate aminoglycoside readings.

Such specimens should be properly handled (assayed promptly, frozen, or treated with beta-lactamase). Neuromuscular toxicity Neuromuscular blockade and respiratory paralysis have been reported following parenteral injection, topical instillation (as in orthopaedic and abdominal irrigation or in local treatment of empyema) and following oral use of aminoglycosides.

5). If neuromuscular blockade occurs, calcium salts may reverse respiratory paralysis, but mechanical respiratory assistance may be necessary. Neuromuscular blockade and muscular paralysis have been demonstrated in laboratory animals given high doses of amikacin.

Administration of aminoglycosides to patients with neuromuscular disease such as myasthenia gravis or parkinsonism requires extreme caution, as aminoglycosides act on the neuro-muscular junction similarly to curare and they may thus worsen muscle weakness.

Other Aminoglycosides applied locally as part of a surgical procedure are quickly and nearly completely absorbed (with the exception of the urinary bladder). In association with irrigation of the surgical field using aminoglycoside preparations (regardless of the extent) development of irreversible deafness, renal failure and death due to neuromuscular blockade have been reported.

Paediatric population Aminoglycosides should be used with caution in premature and neonatal infants because of the renal immaturity of these patients and […]

1. - Hypersensitivity to other aminoglycosides.