Amikacin

Type of Medication: Antibiotic

Indications: Treatment of Pseudomonas aeruginosa, Burkholderia cepacia complex and Mycobacterium abscessus infections

Side Effects: Vestibular and auditory damage, irreversible vestibulocochlear nerve damage, nephrotoxicity, less frequently hypomagnesaemia with prolonged therapy, colitis, nausea, vomiting, hypersensitivity, headaches, rash, fever, paraesthesia, hypocalcaemia, hypomagnesaemia and hypokalaemia, neuromuscular blockade and respiratory paralysis.

Route of administration: Adult (Intravenous)

Dose: 15 mg/kg once daily or 7.5 mg/kg twice daily or 15–25 mg/kg three times per week (BTS guidelines – 2107)

Administration: Give over 60 minutes in 50ml NaCl 0.9%.

Levels: daily dosing – trough: <5 mg/L, peak: 25–35 mg/L. Three time a weeks- 65–80 mg/L  – (BTS guidelines – 2107)

Monitoring: Renal function – Monitor twice weekly during month 1, weekly during month 2, then fortnightly to the end of treatment. Consider increasing frequency of monitoring if there is evidence of renal impairment. Auditory and vestibular monitoring Loss of hearing usually occurs first and is detected by regular audiometric testing. Vertigo, loss of balance and auditory disturbances (tinnitus) are also signs of ototoxicity. Ototoxicity on audiogram is defined as a 20 dB loss from baseline at any one test frequency or a 10 dB loss at any two adjacent test frequencies. If this occurs, amikacin should be discontinued or dosing reduced in frequency to avoid further hearing loss, although the hearing loss that has occurred is likely to be permanent.

FBC, U&Es, LFTs should be performed intermittently throughout antibiotic treatment

Route of administration: Adult (Nebulised)

Dose: 500 mg twice daily. In cases of intolerance after an initial initiation period, a dose reduction may be considered to 250–500 mg once or twice daily. In the UK, the injectable preparation is given via the nebulised route, using a suitable nebuliser with filter attachment . The 250 mg/mL injection should be used and made up to 4 mL with sodium chloride 0.9%. Formal assessment with test dose should be undertaken. Amikacin for injection may only be mixed with sodium chloride 0.9%. It must not be nebulised as a mixture with other nebulised drugs (eg, salbutamol, dornase alfa or other nebulised antibiotics).

(Amikacin is not licensed for the treatment of NTM in the UK)

BTS guidelines

Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations

Route of administration: Paediatric (Intravenous)

Dose: children: usually 15–30 mg/kg daily or 15–30 mg/kg three times per week. Maximum dose 1500 mg daily

Administration: Give over 60 minutes in 50ml NaCl 0.9%.

Levels: daily dosing – trough: <5 mg/L, peak: 25–35 mg/L. Three time a weeks- 65–80 mg/L – (BTS guidelines – 2107)

Monitoring: Renal function – Monitor twice weekly during month 1, weekly during month 2, then fortnightly to the end of treatment. Consider increasing frequency of monitoring if there is evidence of renal impairment. Auditory and vestibular monitoring Loss of hearing usually occurs first and is detected by regular audiometric testing. Vertigo, loss of balance and auditory disturbances (tinnitus) are also signs of ototoxicity. Ototoxicity on audiogram is defined as a 20 dB loss from baseline at any one test frequency or a 10 dB loss at any two adjacent test frequencies. If this occurs, amikacin should be discontinued or dosing reduced in frequency to avoid further hearing loss, although the hearing loss that has occurred is likely to be permanent.

FBC, U&Es, LFTs should be performed intermittently throughout antibiotic treatment

Route of administration: Paediatric (Nebulised)

Dose: 500 mg twice daily. In cases of intolerance after an initial initiation period, a dose reduction may be considered to 250–500 mg once or twice daily. In the UK, the injectable preparation is given via the nebulised route, using a suitable nebuliser with filter attachment . The 250 mg/mL injection should be used and made up to 4 mL with sodium chloride 0.9%. Formal assessment with test dose should be undertaken. Amikacin for injection may only be mixed with sodium chloride 0.9%. It must not be nebulised as a mixture with other nebulised drugs (eg, salbutamol, dornase alfa or other nebulised antibiotics).

(Amikacin is not licensed for the treatment of NTM in the UK)

BTS guidelines

Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations

Examples of some Drug Interactions

Interacting drug: Alendronate (Bisphosphonates)

increased risk of hypocalcaemia

Interacting drug: Amphotericin

increase risk of nephrotoxicity

Interacting drug: Capreomycin

increased nephrotoxicity and ototoxicity

Interacting drug: Colistin

increased risk of ototoxicity and nephrotoxicity

Interacting drug: Cyclosporin

increased risk of nephrotoxicity and increased levels of both drugs. Reduce aminoglycoside dose is essential and monitor cyclosporin levels carefully

Interacting drug: Frusemide (Loop diuretics)

increase risk of ototoxicity

Interacting drug: Indomethacin

increased plasma concentration of amikacin

Interacting drug: Neostigmine/pyridostigmine

antagonism of effect

Interacting drug: Non-depolarising muscle relaxants

enhances effect e.g. atracurium, vecuronium, pancuronium

Interacting drug: Teicoplanin

increased nephrotoxicity and ototoxicity

Interacting drug: Vancomycin

increased risk of nephrotoxicity and ototoxicity