APR AM 100 2ml

NC-302:

INFORMATION FOR THE USER

Amikacin Injection

Read all of this information carefully before you start taking this medicine because it contains important information for you.
• Keep this information. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine is prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this information.

1. COMPOSITION:
Eachvial contains:
Amikacin sulphate eq. to Amikacin – 50mg
Methyl paraben – 0.08% w/v
Propyl paraben – 0.02% w/v

For IV/IM use only.

2. DESCRIPTION:
Amikacin is an antibiotic that is used to treat bacterial infections.

3. PHARMACOLOGICAL ACTION:
Amikacin is a semi-synthetic aminoglycoside antibiotic derived from Kanamycin A. It is active against a broad spectrum of Gram-negative organisms, including pseudomonas, E. coli and some Gram-positive organisms, e.g. S. aureus. It is bactericidal in action. Although the exact mechanism of action has not been fully elucidated, the drugs appear to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits.
4. CLINICAL PHARMACOKINETICS:
Amikacin is rapidly absorbed after IM injection. Peak plasma conc. eq. to ~20 mg/ml are achieved 1 hr after IM doses of 500mg, reducing to ~2 µg/ml 10 hrs after injections. 20% or less is bound to serum protein & serum conc. remain in the bactericidal range for sensitive organisms for 10-12 hrs. Single doses of 500mg administered as an IV infusion over 30 min produce a mean peak serum conc. of 38 µg/ml. Repeated infusions do not produce drug accumulation in adults with normal renal function. Decreased renal function will lead to accumulation. In adults with normal renal function the plasma elimination half-life is usually 2-3 hrs. 94-98% of a single IM/IV dose is excreted unchanged by glomerular filtration within 24 hrs. Urine conc. averages 563 µg/ml in the first 6 hrs following a single 250mg IM dose & 163 µg/ml over 6-12 hrs. Following a single 500 mg IM dose urine conc. averages 832 µg/ml in adults with normal renal function. It diffuses readily through extracellular fluids & is excreted in the urine unchanged, primarily by glomerular filtration. It has been found in pleural fluid, amniotic fluid & in the peritoneal cavity following parenteral administration. Data from multiple daily dose trials show that spinal fluid levels in normal infants are approx. 10-20% of the serum conc. & may reach 50% in meningitis.
5. INDICATIONS:
Amikacin injection is indicated for the treatment of susceptible infections of:
– Bronchiectasis
– Bone & joint infections
– Intra-abdominal infections
– Meningitis
– Mycobacterium infections
– Respiratory tract infections
– Sepsis
– Skin and suture site infections
– Urinary tract infections
6. CONTRAINDICATIONS:
– Patients with known allergy to amikacin or any component of the formulation.
– A history of hypersensitivity/serious toxic reactions to aminoglycosides may contraindicate the use of any aminoglycoside because of the known cross sensitivities of patients to drugs in this class.
– May impair neuromuscular transmission & should not be given to patients with myasthenia gravis.

7. WARNINGS AND PRECAUTIONS:
Patients should be well hydrated during amikacin therapy.
Caution should be applied to patients with pre-existing renal insufficiency, pre-existing hearing or vestibular damage & diminished glomerular filtration. Patients treated with parenteral aminoglycosides should be under close clinical observation because of the potential ototoxicity & nephrotoxicity associated with their use. Safety for treatment periods which are longer than 14 days has not been established.
If therapy is expected to last 7 days or more in patients with renal impairment, or 10 days in other patients, a pre-treatment audiogram should be obtained and repeated during therapy.
Renal Toxicity: Aminoglycosides are potentially nephrotoxic. Renal toxicity is independent of plasma obtained at the peak (Cmax). The risk of nephrotoxicity is greater in patients with impaired renal function, and in those who receive higher doses, or in those whose therapy is prolonged.
Patients should be well hydrated during treatment and renal function should be assessed by the usual methods prior to starting therapy & daily during the course of treatment.
Neuro/Ototoxicity: Neurotoxicity, manifested as vestibular and/or bilateral ototoxicity, can occur in patients treated with aminoglycosides. The risk of aminoglycoside-induced ototoxicity is greater in patients with impaired renal function, and in those who receive high doses, or in those whose therapy is prolonged over 5-7 days of treatment, even in healthy patients. Aminoglycoside-induced ototoxicity is usually irreversible.
Neuromuscular Toxicity: Neuromuscular blockade & respiratory paralysis have been reported following parenteral injection, topical instillation & following oral use of aminoglycosides. The possibility of respiratory paralysis should be considered if aminoglycosides are administered by any route, especially in patients receiving anaesthetics, neuromuscular blocking agents such as tubocurarine, succinylcholine, decamethonium or in patients receiving massive transfusions of citrate-anticoagulated blood.
Must not be used in patients with myasthenia gravis. Should be used with caution in patients with muscular disorders such as Parkinsonism since these drugs may aggravate muscle weakness because of their potential curare-like effect on the neuromuscular junction.
Allergic reactions: The use 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 such as streptomycin, dihydrostreptomycin, gentamicin, , neomycin, polymyxin B, colistin, cephaloridine or viomycin 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.
Large doses administered during surgery have been responsible for a transient myasthenic syndrome.
Paediatric use: Should be used with caution in premature & neonatal infants because of the renal immaturity of these patients & the resulting prolongation of serum half-life of these drugs.
Aminoglycosides are quickly & almost totally absorbed when they are applied topically, except to the urinary bladder, in association with surgical procedures. Irreversible deafness, renal failure & death due to neuromuscular blockade have been reported following irrigation of both small & large surgical fields with an aminoglycoside preparation.
Use of amikacin may result in overgrowth of non-susceptible organisms.
Macular infarction sometimes leading to permanent loss of vision has been reported following IV administration.
8. ADVERSE EFFECTS:
Side effects include: Superinfections, Anaemia, Eosinophilia, Anaphylaxis & hypersensitivity reactions, Hypomagnesemia, Tremor, Tinnitus, Deafness, Hypotension, Apnoea, Nausea & vomiting, Rash, Urticaria, Renal failure, Oliguria, Increased creatinin levels, Pain at injection site

9. DRUG INTERACTIONS:
The concurrent or serial use of other neurotoxic, ototoxic/nephrotoxic agents, particularly bacitracin, cisplatin, amphotericin B, ciclosporin, tacrolimus, cephaloridine should be avoided either systemically/ topically because of the potential for additive effects.
Increased nephrotoxicity has been reported following concomitant parenteral administration of aminoglycoside antibiotics & cephalosporins.
Concurrent use with potent diuretics (furosemide) should be avoided since diuretics by themselves may cause ototoxicity.
In Vitro admixture with beta-lactam antibiotics (penicillins/cephalosporins) may result in significant mutual inactivation. A reduction in serum activity may also occur when an aminoglycoside or penicillin-type drug is administered in vivo by separate routes
Increased risk of hypocalcaemia when administered with bisphosphonates.
Increased risk of nephrotoxicity & possibly of ototoxicity when administered with platinum compounds.
Concomitantly administered thiamine may be destroyed by the reactive sodium bisulfite component of the amikacin sulfate formulation.
Intraperitoneal use is not recommended in patients under the influence of anaesthetics/muscle-relaxing drugs (halothane) as neuromuscular blockade & consequent respiratory depression may occur.
Indomethacin may increase the plasma conc. of amikacin in neonates.

10. DOSAGE:The recommended dose is 15mg/kg/day which may be administered as a single dose or in 2 equally divided doses. The total daily dose should not exceed 1.5g.

11. ADMINISTRATION:
For IV/IM use only.
Administration to be done by a registered medical practitioner/nurse in a proper sterile and hospital setting only.
12. STORAGE:
Do not store above 25°C. Store in the original package. Keep away from children. Do not expose to direct sunlight.

13. MANUFACTURED BY:

14. MARKETED BY:

Last revised on August 2020.