Amikacin

Name: Amikacin

Amikacin Side Effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • hearing loss, or a roaring sound in your ears;
  • severe or ongoing dizziness;
  • kidney problems--little or no urinating; painful or difficult urination; swelling in your feet or ankles; feeling tired or short of breath;
  • weak or shallow breathing;
  • numbness or tingly feeling;
  • muscle twitching or seizure (convulsions); or
  • severe stomach pain, diarrhea that is watery or bloody.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Side Effects of Amikacin

Serious side effects have been reported with amikacin. See the “Amikacin Precautions” section.

Common side effects of amikacin include the following:

  • rash
  • fever
  • headache
  • tingling or numbness in the extremities
  • tremor
  • nausea
  • vomiting
  • joint pain
  • decreased blood pressure
  • vision changes

This is not a complete list of amikacin side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Amikacin and Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X - are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Amikacin falls into category D. It has been shown that use of amikacin in pregnant women caused some babies to be born with problems. However, in some serious situations, the benefit of using this medication may be greater than the risk of harm to the baby.

Other Requirements

  • Store amikacin at room temperature.
  • Keep this and all medicines out of the reach of children.

Amikacin FDA Warning

WARNINGS

Patients treated with parenteral aminoglycosides should be under close clinical observation because of the potential ototoxicity and nephrotoxicity associated with their use. Safety for treatment periods which are longer than 14 days has not been established.

Neurotoxicity, manifested as vestibular and permanent bilateral auditory ototoxicity, can occur in patients with preexisting renal damage and in patients with normal renal function treated at higher doses and/or for periods longer than those recommended. The risk of aminoglycoside-induced ototoxicity is greater in patients with renal damage. High frequency deafness usually occurs first and can be detected only by audiometric testing. Vertigo may occur and may be evidence of vestibular injury. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and convulsions. The risk of hearing loss due to aminoglycosides increases with the degree of exposure to either high peak or high trough serum concentrations. Patients developing cochlear damage may not have symptoms during therapy to warn them of developing eighth-nerve toxicity, and total or partial irreversible bilateral deafness may occur after the drug has been discontinued. Aminoglycoside-induced ototoxicity is usually irreversible.

Aminoglycosides are potentially nephrotoxic. The risk of nephrotoxicity is greater in patients with impaired renal function and in those who receive high doses or prolonged therapy.

Neuromuscular blockade and respiratory paralysis have been reported following parenteral injection, topical instillation (as in orthopedic and abdominal irrigation or in local treatment of empyema), and following oral use of aminoglycosides. The possibility of these phenomena should be considered if aminoglycosides are administered by any route, especially in patients receiving anesthetics, neuromuscular blocking agents such as tubocurarine, succinylcholine, decamethonium, or in patients receiving massive transfusions of citrate-anticoagulated blood. If blockage occurs, calcium salts may reverse these phenomena, but mechanical respiratory assistance may be necessary.

Renal and eighth-nerve function should be closely monitored especially in patients with known or suspected renal impairment at the onset of therapy and also in those whose renal function is initially normal but who develop signs of renal dysfunction during therapy. Serum concentrations of amikacin should be monitored when feasible to assure adequate levels and to avoid potentially toxic levels and prolonged peak concentrations above 35 micrograms per mL. Urine should be examined for decreased specific gravity, increased excretion of proteins, and the presence of cells or casts. Blood urea nitrogen, serum creatinine, or creatinine clearance should be measured periodically. Serial audiograms should be obtained where feasible in patients old enough to be tested, particularly high risk patients. Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, and hearing loss) or nephrotoxicity requires discontinuation of the drug or dosage adjustment.

Concurrent 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.

The concurrent use of amikacin with potent diuretics (ethacrynic acid, or furosemide) should be avoided since diuretics by themselves may cause ototoxicity. In addition, when administered intravenously, diuretics may enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.

Amikacin side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • hearing loss, or a roaring sound in your ears;

  • severe or ongoing dizziness;

  • kidney problems--little or no urinating; painful or difficult urination; swelling in your feet or ankles; feeling tired or short of breath;

  • weak or shallow breathing;

  • numbness or tingly feeling;

  • muscle twitching or seizure (convulsions); or

  • severe stomach pain, diarrhea that is watery or bloody.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect amikacin?

Amikacin can harm your kidneys. This effect is increased when you also use certain other medicines, including: antivirals, chemotherapy, injected antibiotics, medicine for bowel disorders, medicine to prevent organ transplant rejection, injectable osteoporosis medication, and some pain or arthritis medicines (including aspirin, Tylenol, Advil, and Aleve).

Tell your doctor about all your current medicines and any you start or stop using, especially:

  • a diuretic or "water pill";

  • any other antibiotic.

This list is not complete. Other drugs may interact with amikacin, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

What do I need to tell my doctor BEFORE I take Amikacin?

  • If you have an allergy to amikacin or any other part of this medicine.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are breast-feeding or plan to breast-feed.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take amikacin with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take Amikacin?

  • Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
  • If you are allergic to sulfites, talk with your doctor. Some products have sulfites.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Do not use longer than you have been told. A second infection may happen.
  • If you are 65 or older, use amikacin with care. You could have more side effects.
  • Use with care in newborns. Talk with the doctor.
  • This medicine may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking this medicine, call your doctor right away.

How is this medicine (Amikacin) best taken?

Use amikacin as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • It is given as a shot into a muscle or vein.
  • Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.

What do I do if I miss a dose?

  • Call your doctor to find out what to do.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Change in balance.
  • Feeling confused.
  • Dizziness or passing out.
  • Hearing loss.
  • Change in hearing.
  • Ringing or roaring in the ears.
  • Muscle weakness.
  • A burning, numbness, or tingling feeling that is not normal.
  • Twitching.
  • Seizures.
  • Trouble breathing, slow breathing, or shallow breathing.
  • Feeling very tired or weak.
  • It is common to have diarrhea when taking this medicine. Rarely, a very bad form of diarrhea called Clostridium difficile (C diff)–associated diarrhea (CDAD) may occur. Sometimes, this has led to a deadly bowel problem (colitis). CDAD may happen while you are taking amikacin or within a few months after you stop taking it. Call your doctor right away if you have stomach pain or cramps, very loose or watery stools, or bloody stools. Do not try to treat loose stools without first checking with your doctor.

Contraindications

Hypersensitivity to amikacin, other aminoglycosides, or any component of the formulation

Dosing Adult

Individualization is critical because of the low therapeutic index

In underweight and nonobese patients, use of total body weight (TBW) instead of ideal body weight for determining the initial mg/kg/dose is widely accepted (Nicolau, 1995). Ideal body weight (IBW) also may be used to determine doses for patients who are neither underweight nor obese (Gilbert 2009).

Initial and periodic peak and trough plasma drug levels should be determined, particularly in critically-ill patients with serious infections or in disease states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery). Manufacturer recommends a maximum daily dose of 15 mg/kg/day (or 1.5 g/day in heavier patients). Higher doses may be warranted based on therapeutic drug monitoring or susceptibility information.

Usual dosage range:

IM, IV: 5 to 7.5 mg/kg/dose every 8 hours; Note: Some clinicians suggest a daily dose of 15 to 20 mg/kg/day for all patients with normal renal function. This dose is at least as efficacious with similar, if not less, toxicity than conventional dosing.

Intrathecal/intraventricular (off-label route): Meningitis (susceptible gram-negative organisms): 5 to 50 mg/day (Gilbert, 1986; Guardado 2008; IDSA 2004; Kasiakou 2005)

Indication-specific dosing:

Cystic fibrosis exacerbation (off-label use/route): Inhalation for nebulization:

Monotherapy: 500 mg twice daily (Le 2010)

Adjunctive therapy: 100 mg twice daily with concomitant IV amikacin and ceftazidime (Schaad 1987)

Endophthalmitis, bacterial (off-label use): Intravitreal: 0.4 mg/0.1 mL NS in combination with vancomycin

Meningitis (susceptible gram-negative organisms):

IV: 5 mg/kg every 8 hours (administered with another bactericidal drug) (IDSA 2004)

Intrathecal/intraventricular (off-label route): Usual dose: 30 mg/day (IDSA 2004); Range: 5 to 50 mg/day (with concurrent systemic antimicrobial therapy) (Gilbert, 1986; Guardado 2008; IDSA 2004; Kasiakou 2005)

Mycobacterium avium complex (MAC) (off-label use): IV: Adjunct therapy (with macrolide, rifamycin, and ethambutol): 8 to 25 mg/kg 2 to 3 times weekly for first 2 to 3 months for severe disease (maximum single dose for age >50 years: 500 mg) (Griffith 2007)

Mycobacterium fortuitum, M. chelonae, or M. abscessus: IV: 10 to 15 mg/kg daily for at least 2 weeks with high dose cefoxitin

Pneumonia, hospital-acquired (HAP) or ventilator-associated (VAP) (alternative therapy) (off-label dose): IV: 15 to 20 mg/kg/dose once every 24 hours for 7 days; may consider shorter or longer durations depending on rate of clinical improvement. When used as empiric therapy, use in combination with an agent active against S. aureus and an additional antipseudomonal agent. Note: Aminoglycosides are not recommended as monotherapy in patients with HAP or VAP due to P. aeruginosa (Kalil 2016).

Reconstitution

For intravenous administration, dilute in a compatible solution (eg, NS, D5W) to a final concentration of 0.25 to 5 mg/mL.

For Healthcare Professionals

Applies to amikacin: compounding powder, injectable solution, intravenous solution

General

All aminoglycosides have the potential to cause auditory, vestibular, and renal toxicity and neuromuscular blockade. Such side effects occurred more often in patients with current or past history of renal impairment, of treatment with other ototoxic or nephrotoxic agents, and in patients treated for longer periods and/or with higher doses than recommended.[Ref]

Renal

Frequency not reported: Nephrotoxicity, elevated serum creatinine, albuminuria, presence of red and white cells, casts, azotemia, oliguria[Ref]

Such renal function changes were usually reversible when the drug was discontinued.

Predisposing factors have included advanced age, preexisting renal insufficiency, dehydration, and concomitant use of other potentially nephrotoxic drugs. One study has shown that hyperbilirubinemia in patients with biliary obstruction may also be a predisposing factor to aminoglycoside nephrotoxicity.

In one prospective, nonrandomized study, patients developed nephrotoxicity in 25% of amikacin courses.[Ref]

Nervous system

Rare (less than 0.1%): Headache, paresthesia, tremor
Frequency not reported: Neurotoxicity, ototoxicity (including vestibular and permanent bilateral auditory ototoxicity), neuromuscular blockade, toxic effects on the eighth cranial nerve, hearing loss, loss of balance, cochlear damage, high frequency deafness, total or partial irreversible bilateral deafness, acute muscular paralysis due to neuromuscular blockade, numbness, skin tingling, muscle twitching, convulsions, dizziness, vertigo, tinnitus, roaring in the ears[Ref]

Ototoxicity may be irreversible and usually includes loss of auditory function secondary to cochlear hair cell damage. Damage may also be vestibular.

High frequency deafness usually occurs before hearing loss can be detected. Hearing loss may be permanent.

Rare neurologic side effects have included neuromuscular blockade, particularly in patients who are predisposed, including patients with myasthenia gravis, hypocalcemia, and patients on concomitant neuromuscular blocking agents.

A case of irreversible sensorineural hearing loss has been reported in a patient with diabetic end stage renal disease, after using an amikacin-heparin lock for 16 weeks (25 mg amikacin three times a week).[Ref]

Respiratory

Frequency not reported: Respiratory paralysis/apnea due to neuromuscular blockade[Ref]

Musculoskeletal

Rare (less than 0.1%): Arthralgia[Ref]

Gastrointestinal

Rare (less than 0.1%): Nausea, vomiting[Ref]

Hematologic

Rare (less than 0.1%): Anemia, eosinophilia[Ref]

Cardiovascular

Rare (less than 0.1%): Hypotension
Frequency not reported: Hypersensitivity myocarditis[Ref]

Dermatologic

Rare (less than 0.1%): Skin rash, pruritus, exfoliative dermatitis[Ref]

Other

Rare (less than 0.1%): Fever, drug fever[Ref]

Hypersensitivity

Rare (less than 0.1%): Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome (at least 1 case)[Ref]

Hepatic

Frequency not reported: Elevations in liver function tests (clinical significance unknown)[Ref]

Some side effects of amikacin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Usual Adult Dose for Joint Infection

15 to 22.5 mg/kg/day IV or IM in 1 to 3 divided doses, depending on severity of infection (initial maximum of 1.5 g/day, then adjust dose based on desired serum levels)

Usual Adult Dose for Peritonitis

Peritoneal dialysis-related peritonitis:
CAPD intermittent dosing: 2 mg/kg in 1 exchange/day (based on ideal body weight) intraperitoneally for anuric patients and 2.5 mg/kg/bag for nonanuric patients (investigational)
CAPD continuous dosing: 24 mg/L exchange intraperitoneally for anuric patients and 30 mg/L for nonanuric patients

Maximum dose: 1.5 g/day by all routes

Precautions

The use of aminoglycosides may result in nephrotoxicity and ototoxicity. The risk is greatest in patients with impaired renal function, those receiving high doses for prolonged periods of time, the elderly, and dehydrated patients. Aminoglycosides have been associated with permanent bilateral auditory and/or vestibular toxicity. Onset of ototoxicity may be delayed and cochlear damage may be asymptomatic, so deafness may not occur until after the drug has been discontinued. Monitoring patients for the development of toxicity is recommended: Serial, vestibular, audiometric, and renal function tests (creatinine clearance, BUN, urinalysis for proteinuria, decreased specific gravity, casts, and cells) should be performed before and during therapy. Patients should be well-hydrated. Patients and their family members should be informed of possible eighth cranial nerve toxicity. Tinnitus may be a sentinel symptom of ototoxicity.

NARROW THERAPEUTIC INDEX:
-This drug should be considered a narrow therapeutic index (NTI) drug as small differences in dose or blood concentrations may lead to serious therapeutic failures or adverse drug reactions.
Recommendations:
- Generic substitution should be done cautiously, if at all, as current bioequivalence standards are generally insufficient for NTI drugs.
-Additional and/or more frequent monitoring should be done to ensure receipt of an effective dose while avoiding unnecessary toxicities.

Caution should be used when aminoglycosides are given with other potentially nephrotoxic drugs, such as nonsteroidal anti-inflammatory agents or antineoplastic agents.

Caution should also be used when giving aminoglycosides with other potentially ototoxic drugs, such as loop diuretics. Concomitant use of potent diuretics should be avoided.

The sodium bisulfite preservative in some formulations of amikacin may cause allergic, anaphylactic, or asthmatic reactions in sulfite-sensitive patients.

Aminoglycosides may aggravate muscle weakness due to their potential curare-like effects on neuromuscular function, therefore amikacin should be used cautiously in patients with muscular disorders such as myasthenia gravis or Parkinson's disease.

Dialysis

Adults:
Hemodialysis or peritoneal dialysis patients: 3 to 7.5 mg/kg as a loading dose; calculate subsequent doses based on serum concentrations

Amikacin is dialyzable by hemo- and peritoneal dialysis. A supplemental dose is recommended after dialysis.

Amikacin Breastfeeding Warnings

Amikacin is excreted into human milk in small amounts. Due to poor oral bioavailability, systemic toxicity in the nursing infant is unlikely.

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Yes Excreted into animal milk: Unknown The effects in the nursing infant are unknown.

Administrative Information

LactMed Record Number

8

Last Revision Date

20150310

Disclaimer

Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.

Warnings

Black Box Warnings

Neurotoxicity, manifested as both bilateral auditory and vestibular ototoxicity, can occur in patients with preexisting renal damage and in patients with normal renal function treated at higher doses and/or for periods longer than those recommended. High-frequency deafness usually occurs first and can be detected only by audiometric testing

Vertigo may occur and may be evidence of vestibular injury

Aminoglycosides are potentially nephrotoxic

Risk is greater in patients with impaired renal function and in those who receive high doses or prolonged therapy. Rarely, nephrotoxicity may not become apparent until the first few days after cessation of therapy

Use with caution in premature infants and neonates because of renal immaturity and the resulting prolongation of serum half-life of the drug

Neuromuscular blockade and respiratory paralysis have been reported following parenteral injection, topical instillation (as in orthopedic and abdominal irrigation or in local treatment of empyema), and oral use of aminoglycosides, especially when given soon after anesthesia or muscle relaxants

If blockage occurs, calcium salts may reverse these phenomena, but mechanical respiratory assistance may be necessary

Avoid concurrent or sequential use of neurotoxic and/or nephrotoxic drugs including other aminoglycosides (eg, amikacin, streptomycin, neomycin, kanamycin, gentamicin, paromomycin

Cumulative listing of drugs to avoid from all aminoglycoside package inserts include amphotericin B, bacitracin, cephaloridine, cisplatin, colistin, polymyxin B, vancomycin, and viomycin

Avoid potent diuretics (eg, ethacrynic acid, furosemide) because they increase risk of ototoxicity

When administered intravenously, diuretics may enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue

Contraindications

Documented hypersensitivity

Cautions

Renal impairment

Risk of neurotoxicity, ototoxicity, nephrotoxicity - risk of ototoxicity increase with concurrent loop diuretics

Not intended for long-term therapy; caution in patients with renal failure (not on dialysis), hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission

Pregnancy & Lactation

Pregnancy Category: D

Lactation: excretion in milk unknown/not recommended

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

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