Kanamycin Sulfate

Class: Aminoglycosides
VA Class: AM300
CAS Number: 25389-94-0

• Neurotoxicity and Ototoxicity


• 
  

  Neurotoxicity (manifested as both auditory and vestibular ototoxicity) can occur.¹ Other neurotoxicity manifestations include vertigo, numbness, skin tingling, muscle twitching, and seizures.¹

  
  


• 
  

  Eighth-cranial nerve impairment develops principally in patients with preexisting renal damage and in those with normal renal function who receive doses higher or treatment longer than recommended.¹

  
  


• 
  

  Aminoglycoside-induced ototoxicity is irreversible, usually bilateral, and may be partial or total.¹

  
  


• 
  

  Risk of hearing loss increases with degree of exposure to either high peak or high trough serum concentrations.¹

  
  


• 
  

  Adjust dosage or discontinue kanamycin if evidence of ototoxicity (e.g., dizziness, vertigo, tinnitus, roaring in the ears, hearing loss) occurs.¹

  
  


• 
  

  Patients developing cochlear damage may not have symptoms during aminoglycoside treatment to warn them of eighth-cranial nerve toxicity and total or partial, irreversible, bilateral deafness may occur after drug discontinued.¹

  
  

• Nephrotoxicity


• 
  

  Potentially nephrotoxic.¹

  
  


• 
  

  Oliguria may indicate renal impairment.¹

  
  


• 
  

  Nephrotoxicity develops principally in patients with preexisting renal damage and in those with normal renal function who receive doses higher or treatment longer than recommended.¹

  
  

• Patient Monitoring


• 
  

  Patients should be under close clinical observation because of potential toxicities.¹

  
  


• 
  

  Closely monitor renal and eighth-cranial nerve function, especially in patients with known or suspected renal impairment at start of treatment and also in those whose renal function is initially normal but who develop renal dysfunction during treatment.¹

  
  


• 
  

  Periodically monitor serum kanamycin concentrations to ensure adequate concentrations and avoid potentially toxic and prolonged peak concentrations (>35 mcg/mL).¹

  
  


• 
  

  Rising trough concentrations (>10 mcg/mL) may indicate tissue accumulation.¹ Tissue accumulation, excessive peak concentrations, cumulative dose, advanced age, and dehydration may contribute to ototoxicity and nephrotoxicity.¹

  
  


• 
  

  Evaluate urine for decreased specific gravity and increased excretion of protein, cells, and casts; periodically determine BUN, S_cr, and CL_cr.¹

  
  


• 
  

  When feasible, perform serial audiograms in patients old enough to be tested, particularly high-risk patients.¹

  
  


• 
  

  Discontinue kanamycin or adjust dosage if there is evidence of impaired renal, vestibular, or auditory function.¹

  
  

• Neuromuscular Blockade


• 
  

  Concomitant use of an aminoglycoside with anesthesia and muscle-relaxing drugs may cause neuromuscular blockade with respiratory paralysis.¹ May occur with aminoglycosides given by any route, including intraperitoneal instillation.¹

  
  


• 
  

  Consider possibility of neuromuscular blockade and respiratory paralysis when administering aminoglycosides, especially concurrently with anesthetics or neuromuscular-blocking agents (e.g., tubocurarine, succinylcholine, decamethonium) or in patients receiving massive transfusions of citrate-anticoagulated blood.¹ (See Interactions.)

  
  


• 
  

  Calcium salts may reduce neuromuscular blockade, but mechanical respiratory assistance may be necessary.¹

  
  

• Interactions


• 
  

  Avoid concurrent and/or sequential use of other neurotoxic or nephrotoxic drugs, particularly other aminoglycosides (including paromomycin), amphotericin B, bacitracin, cisplatin, colistimethate/colistin, polymyxin B, vancomycin, and viomycin.¹ (See Interactions.)

  
  


• 
  

  Avoid concurrent use of potent diuretics (e.g., ethacrynic acid, furosemide, meralluride sodium [not commercially available in the US], sodium mercaptomerin [not commercially available in the US], mannitol) since diuretics themselves may cause ototoxicity and IV diuretics enhance toxicity by altering serum and tissue aminoglycoside concentrations.¹ (See Interactions.)

  
  

Introduction

Antibacterial and antituberculosis agent; aminoglycoside antibiotic obtained from cultures of Streptomyces kanamyceticus.^{1 4 21}

Uses for Kanamycin Sulfate

Serious Bacterial Infections

Has been used for short-term treatment of serious bacterial infections caused by susceptible Acinetobacter, Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Proteus, or Serratia marcescens.^{1 4} Not a drug of choice; use only when causative agent is susceptible and other anti-infectives are ineffective or contraindicated.²¹ When a parenteral aminoglycoside is indicated, amikacin, gentamicin, or tobramycin usually is preferred.^{4 21}

Has been used in conjunction with a penicillin or cephalosporin for initial therapy of serious infections when the causative agent is unknown.¹ If anaerobic bacteria are suspected, consider using a suitable anti-infective in conjunction with kanamycin.¹ Adjust therapy based on in vitro susceptibility testing.¹

Has been used for treatment of known or suspected staphylococcal infections in certain situations.¹ This includes initial treatment of severe infections when the causative organisms may be either gram-negative bacteria or staphylococci, treatment of infections caused by susceptible staphylococci in patients hypersensitive to other more appropriate anti-infectives, and treatment of mixed infections that may involve both gram-negative bacteria and staphylococci.¹ Not a drug of choice for staphylococcal infections.¹

Mycobacterial Infections

Treatment of active (clinical) tuberculosis† (TB) in conjunction with other antituberculosis agents.^{6 7 21}

Second-line agent used in the treatment of TB in patients with relapse, treatment failure, or Mycobacterium tuberculosis resistant to isoniazid and/or rifampin or when first-line drugs cannot be tolerated.⁶

Patients with treatment failure or drug-resistant M. tuberculosis, including multidrug-resistant (MDR) TB (resistant to both isoniazid and rifampin) or extensively drug-resistant (XDR) TB (resistant to both isoniazid and rifampin and also resistant to a fluoroquinolone and at least one parenteral second-line antimycobacterial such as capreomycin, kanamycin, or amikacin), should be referred to or managed in consultation with experts in the treatment of TB as identified by local or state health departments or CDC.^{6 e}

Kanamycin Sulfate Dosage and Administration

Administration

Administer by IV infusion or IM injection.¹

IV administration generally is recommended in patients with life-threatening infections, septicemia, shock, severe hypotension, CHF, hematologic disorders, severe burns, or reduced muscle mass.^b

Has been administered by inhalation via a nebulizer.¹

Has been administered by intraperitoneal instillation^{1 4} or irrigation (abscess cavities, pleural space, peritoneal and ventricular cavities).¹

Has been administered orally,² but a preparation for oral administration is no longer commercially available in the US.

Patient should be well hydrated prior to and during therapy to minimize chemical irritation of renal tubules from high urine kanamycin concentrations.¹

Assess renal function prior to and daily or more frequently during therapy.¹ Keep patients under close clinical observation because of the risk of ototoxicity and nephrotoxicity.¹ (See Neurotoxicity and Ototoxicity under Cautions.)

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer concomitant anti-infectives (e.g., cephalosporins, penicillins) separately; do not admix.¹

Dilution

Prepare IV infusions by adding 500 mg of kanamycin to 100–200 mL or 1 g to 200–400 mL of compatible diluent (e.g., 0.9% sodium chloride, 5% dextrose).¹

Rate of Administration

Administer slowly over 30–60 minutes.¹

IM Administration

Inject deeply into the upper outer quadrant of the gluteal muscle.¹

Intraperitoneal Instillation

Instill into the peritoneal cavity through a polyethylene catheter sutured into the wound at closure (e.g., following exploration for established peritonitis or after peritoneal contamination due to fecal spill during surgery).¹

Consider risk of toxicity with this route; closely monitor serum concentrations.¹ If possible, postpone until patient has fully recovered from the effects of anesthesia and skeletal muscle relaxants.¹ (See Interactions.)

Dilution

Prepare intraperitoneal solution by diluting 500 mg kanamycin in 20 mL sterile water for injection.¹

Irrigation

If used as an irrigating solution in abscess cavities, pleural space, or peritoneal and ventricular cavities, consider risk of toxicity with this route; closely monitor serum concentrations.¹

Dilution

Prepare a solution for irrigation containing 2.5 mg kanamycin per mL.¹

Nebulization

Monitor serum concentrations carefully during nebulization therapy.¹

Dilution

Prepare a solution for nebulization by diluting 1 mL of kanamycin injection (250 mg/mL) in 3 mL of 0.9% sodium chloride injection.¹

Dosage

Available as kanamycin sulfate; dosage expressed in terms of kanamycin.¹

Dosage is identical for either IV or IM administration.¹

Base dosage on patient's pretreatment body weight and renal status.¹ For obese patients, base dosage on lean body mass.¹

Many clinicians recommend that dosage be determined using appropriate pharmacokinetic methods for calculating dosage requirements and patient-specific pharmacokinetic parameters (e.g., elimination rate constant, volume of distribution) derived from serum concentration-time data; susceptibility of the causative organism; severity of the infection; and the patient's immune and clinical status.^b Because of potential toxicity, fixed-dosage recommendations not based on patient weight or serum drug concentrations are not advised.^b

Determine peak and trough serum kanamycin concentrations periodically during therapy.^{1 b} Adjust dosage to maintain desired serum concentrations whenever possible, especially in patients with life-threatening infections, suspected toxicity or nonresponse to treatment, decreased or varying renal function, and/or when increased aminoglycoside clearance (e.g., patients with cystic fibrosis, burns) or prolonged therapy is likely.^{4 200 201 202 203}

In general, desirable peak kanamycin concentrations (30–60 minutes following IM injection or 15–30 minutes after completion of an IV infusion)^b during parenteral therapy are 15–30 mcg/mL^{1 4 8 b} and trough concentrations (just prior to the next dose) should not exceed 5–10 mcg/mL.^{1 4 8 b} Some evidence suggests that an increased risk of toxicity may be associated with prolonged peak kanamycin concentrations >30–35 mcg/mL.^{4 8} Manufacturer recommends avoiding peak serum concentrations (30–90 minutes after injection) >35 mcg/mL and trough concentrations (just prior to the next dose) >10 mcg/mL.¹

Once daily† administration of kanamycin is recommended for the treatment of tuberculosis†;⁶ once-daily regimens are rarely used for other indications.⁴

Usual duration of parenteral treatment for serious bacterial infections is 7–10 days.¹ In difficult and complicated infections, reevaluate use of kanamycin if treatment duration >14 days is being considered.^{1 4} Long-term use is not recommended.^{1 4}

If the drug is continued, closely monitor serum kanamycin concentrations and renal, auditory, and vestibular functions if the drug is continued.¹

Well-hydrated patients with normal kidney function who receive a total kanamycin dose of ≤15 g have a low risk of toxic reactions.¹

Pediatric Patients

General Pediatric Dosage

Use with caution in premature infants and neonates because renal immaturity may prolong serum half-life.¹

AAP states kanamycin is inappropriate for treatment of mild to moderate infections.⁷

Serious Bacterial Infections

Uncomplicated infections usually respond within 24–48 hours; if definite clinical response does not occur within 3–5 days, discontinue kanamycin and reevaluate susceptibility of the causative organism.¹ Failure to respond may be caused by resistance or the presence of septic foci requiring surgical drainage.¹

IV

15 mg/kg daily given in 2 or 3 equally divided doses every 8 or 12 hours.¹

Infants and children >4 weeks of age: AAP recommends 15–22.5 mg/kg daily given in 3 divided doses;⁷ some clinicians recommend 30 mg/kg daily given in 3 divided doses.⁷

IM

15 mg/kg daily given in 2 equally divided doses every 12 hours; alternatively, use 3 or 4 equally divided doses every 6 or 8 hours if continuously high blood concentrations desired.¹

Infants and children >4 weeks of age: AAP recommends 15–22.5 mg/kg daily given in 3 divided doses;⁷ some clinicians recommend 30 mg/kg daily given in 3 divided doses.⁷

Tuberculosis†

Treatment of Active (Clinical) Tuberculosis†

Should not be used alone for treatment of TB; must be given in conjunction with other antituberculosis agents.⁶

IV or IM

Children <15 years of age weighing ≤40 kg: 15–30 mg/kg daily (up to 1 g) given once daily or twice weekly recommended by ATS, CDC, and IDSA.⁶

Children ≥15 years of age or weighing >40 kg: ATS, CDC, and IDSA recommend 15 mg/kg daily (up to 1 g) given as a single daily dose 5–7 times weekly for the first 2–4 months or until culture conversion;⁶ dosage can then be reduced to 15 mg/kg daily (up to 1 g) given as a single daily dose 2–3 times weekly.⁶

AAP recommends 15–30 mg/kg daily (up to 1 g) in infants, children, or adolescents.⁷

Adults

Serious Bacterial Infections

Uncomplicated infections usually respond within 24–48 hours; if definite clinical response does not occur within 3–5 days, discontinue kanamycin and reevaluate susceptibility of the causative organism.¹ Failure to respond may be caused by resistance or the presence of septic foci requiring surgical drainage.¹

IV

15 mg/kg daily in 2 or 3 equally divided doses given every 8 or 12 hours for 7–10 days.¹

IM

15 mg/kg (up to 1.5 g) daily given in 2 equally divided doses every 12 hours for 7–10 days; alternatively, 3 or 4 equally divided doses every 6 or 8 hours if continuously high blood concentrations desired.¹

Intraperitoneal

Instill 500 mg into the peritoneal cavity for established peritonitis or after peritoneal contamination due to fecal spill during surgery.¹

Irrigation

Instill 2.5 mg/mL solution into abscess cavities, pleural space, or peritoneal or ventricular cavities.¹

Inhalation

250 mg 2–4 times daily.¹ Administer diluted in 3 mL of 0.9% sodium chloride using a nebulizer.¹

Tuberculosis†

Treatment of Active (Clinical) Tuberculosis†

Should not be used alone for treatment of TB; must be given in conjunction with other antituberculosis agents.⁶

IV or IM

ATS, CDC, and IDSA recommend 15 mg/kg (up to 1 g) given once daily 5–7 times weekly for 2–4 months or until culture conversion;⁶ dosage can then be reduced to 15 mg/kg once daily (up to 1 g) 2–3 times weekly.⁶

Prescribing Limits

Pediatric Patients

Serious Bacterial Infections

All Routes

Maximum: 1.5 g daily.¹ Total dose ≤15 g.¹

Treatment of Active (Clinical) Tuberculosis†

IV or IM

Maximum 1 g.⁶

Adults

Serious Bacterial Infections

All Routes

Maximum: 1.5 g daily.¹ Total dose ≤15 g.¹

Treatment of Active (Clinical) Tuberculosis†

IV or IM

Maximum 1 g.⁶

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.¹

Renal Impairment

Serious Bacterial Infections

Dosage adjustments necessary in patients with renal impairment.^{1 4 8 15} Whenever possible, monitor serum kanamycin concentrations, especially in patients with changing renal function.¹

Various methods have been used to determine aminoglycoside dosage for patients with renal impairment, and there is wide variation in dosage recommendations for these patients.^{1 8 15}

Manufacturer recommends an initial dosage of 7.5 mg/kg given at intervals (in hours) calculated by multiplying the patient’s steady-state serum creatinine (in mg/dL) by 9.¹

The dosing method of Sarubbi and Hull (based on corrected Cl_cr) also has been recommended.^b Consult specialized references for specific information on dosage for patients with renal impairment.

Dosage calculation methods should not be used in patients undergoing hemodialysis or peritoneal dialysis.^a

In adults with renal failure undergoing hemodialysis, some clinicians recommend supplemental doses of 50–75% of the initial loading dose at the end of each dialysis period.⁸

Dialysis patients: monitor serum kanamycin concentrations and adjust dosage to maintain desired concentrations.^a

Treatment of Active (Clinical) Tuberculosis†

Adults

IV or IM

ATS, CDC, and IDSA recommend that usual doses be given at less frequent intervals; lower doses may reduce efficacy.⁶ These experts recommend 12–15 mg/kg daily given 2 or 3 times weekly.⁶

Hemodialysis patients: Give dose after hemodialysis is finished.⁶ Monitor serum kanamycin concentrations and adjust dosage to maintain desired concentrations.⁶

Geriatric Patients

Treatment of Active (Clinical) Tuberculosis†

IV or IM

>59 years of age: 10 mg/kg daily (up to 750 mg).⁶

Select dosage with caution and closely monitor renal function because of age-related decreases in renal function.^a

Cautions for Kanamycin Sulfate

Contraindications

• 
  

  History of hypersensitivity or serious toxic reactions to kanamycin or other aminoglycosides.¹

  
  


• 
  

  Long-term therapy (e.g., tuberculosis) because of toxic hazards associated with extended administration.¹

  
  

Warnings/Precautions

Warnings

Neurotoxicity and Ototoxicity

Patients receiving aminoglycosides should be under close clinical observation because of possible ototoxicity.¹

Vestibular and permanent bilateral auditory ototoxicity occurs most frequently in those with past or present history of renal impairment, those receiving other ototoxic drugs, and those who receive high dosages or prolonged treatment.¹

Serial audiograms should be obtained, if feasible, in patients old enough to be tested, particularly in high-risk patients.¹

Discontinue kanamycin or adjust dosage if there is evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, hearing loss).¹

Some aminoglycosides have caused fetal ototoxicity when administered to pregnant women.¹ (See Pregnancy under Cautions.)

Nephrotoxicity

Patients receiving aminoglycosides should be under close clinical observation because of possible nephrotoxicity.¹ Renal function should be assessed prior to therapy and daily, or more frequently, during therapy.¹

Nephrotoxicity occurs most frequently in those with past or present history of renal impairment, those receiving other nephrotoxic drugs, and those who receive high dosage or prolonged treatment.¹

Monitor urine for increased protein excretion and the presence of cells and casts.¹ Obtain Cl_cr, S_cr, and/or BUN at the onset of therapy, frequently during therapy, and at or shortly after the end of therapy.¹ If renal function is changing, test more frequently.¹

Dosage reduction and increased hydration may be desirable if other evidence of renal dysfunction occurs (e.g., decreased Cl_cr, decreased urine specific gravity, increased BUN or serum creatinine, oliguria).¹

If azotemia increases or if a progressive decrease in urinary output occurs, discontinue kanamycin.¹

Aminoglycoside-induced nephrotoxicity usually is reversible.¹

Neuromuscular Blockade

Neuromuscular blockade and respiratory paralysis reported with high kanamycin dosage.¹

Possibility of neuromuscular blockade should be considered, especially in patients receiving anesthetics or neuromuscular blocking agents (e.g., tubocurarine, succinylcholine, decamethonium) or in those receiving massive transfusions of citrate-anticoagulated blood.¹

Calcium salts may reverse neuromuscular blockade, but mechanical respiratory assistance may be necessary.¹

Sensitivity Reactions

Hypersensitivity

Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, reported with aminoglycosides.¹

Cross-sensitivity

Cross-sensitivity occurs among the aminoglycosides.^{1 b}

Sulfite Sensitivity

Kanamycin injection contains sodium metabisulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.¹

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of kanamycin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.¹

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.¹ In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.¹

Usually used in conjunction with other anti-infectives (e.g., penicillins, cephalosporins) for empiric treatment of serious infections pending results of in vitro susceptibility tests.¹ If anaerobic bacteria are suspected, concomitant use of an anti-infective active against anaerobes is necessary.¹

Topical Instillation

Aminoglycosides may be absorbed in substantial quantities from body surfaces after topical instillation or local irrigation and may cause neurotoxicity, nephrotoxicity, neuromuscular blockade, or respiratory paralysis.^{1 b} Carefully monitor serum levels during treatment.¹

Hydration

Patient should be well hydrated before treatment to prevent irritation of the renal tubules by the high concentrations of kanamycin in the urinary excretory system.¹

Risk of toxic reactions is low in well-hydrated patients with normal kidney function who receive a total kanamycin dose ≤15 g.¹

Neuromuscular Disorders

Use with caution in patients with neuromuscular disorders such as myasthenia gravis, parkinsonism, or infant botulism; may aggravate muscle weakness because of potential curare-like effect on the neuromuscular junction.¹

Superinfection

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.¹ Discontinue drug and institute appropriate therapy if superinfection occurs.¹

Specific Populations

Pregnancy

Category D.¹

Possibility of fetal harm if administered to a pregnant woman.¹ Complete, irreversible, bilateral congenital deafness reported when another aminoglycoside (i.e., streptomycin) was used during pregnancy.¹

If used during pregnancy or if patient becomes pregnant while receiving kanamycin, patient should be apprised of the potential hazard to the fetus.¹

Lactation

Distributed into milk.¹ Use with caution.¹

Pediatric Use

Use with caution in neonates and premature infants because renal immaturity in these patients may result in prolonged serum half-life.¹

Geriatric Use

Increased risk of toxicity; select dosage with caution and closely monitor renal function because of age-related decreases in renal function.¹

When assessing renal function in geriatric patients, Cl_cr may be more useful than BUN or S_cr.¹

Renal Impairment

Risk of neurotoxicity (manifested as vestibular and permanent bilateral auditory ototoxicity) is greater in patients with renal damage than in other patients.¹

Renal function should be assessed prior to and during therapy.¹

Eighth-cranial nerve function should be monitored closely, especially in patients who have known or suspected renal impairment at the start of treatment and also in those whose renal function is initially normal but who develop signs of renal dysfunction during treatment.¹

Common Adverse Effects

Ototoxicity, neurotoxicity.¹

Interactions for Kanamycin Sulfate

Neurotoxic, Ototoxic, or Nephrotoxic Drugs

Concomitant or sequential use with other drugs that have neurotoxic, ototoxic, or nephrotoxic effects may result in additive toxicity and should be avoided, if possible.^{1 b}

Because of the possibility of an increased risk of ototoxicity due to additive effects or altered serum and tissue aminoglycoside concentrations, do not give concurrently with potent diuretics.^{1 b}

Specific Drugs and Laboratory Tests

Drug	Interaction	Comments
Amphotericin B	Possible increased incidence of nephrotoxicity and/or neurotoxicity1	Avoid concurrent or sequential use, if possible1
Anti-emetics (e.g., dimenhydrinate, meclizine)	Anti-emetics that suppress nausea and vomiting of vestibular origin and vertigo may mask symptoms of vestibular ototoxicity8
Bacitracin	Possible increased incidence of nephrotoxicity and/or neurotoxicity1	Avoid concurrent or sequential use, if possible1
β-Lactam antibiotics (cephalosporins, penicillins)	In vitro evidence of additive or synergistic antibacterial effects between penicillins and aminoglycosides against some enterococci, Enterobacteriaceae, or Ps. aeruginosa; used to therapeutic advantage (e.g., treatment of endocarditis)b Possible increased incidence of nephrotoxicity reported with some cephalosporins; cephalosporins may spuriously elevate creatinine concentrations1 b Potential in vitro and in vivo inactivation of aminoglycosides1	Do not admix; administer IV solutions of the drugs separately1 Monitor serum aminoglycoside concentrations, especially when high penicillin doses are used or patient has renal impairment1 Promptly assay, freeze, or treat specimens with beta-lactamase1
Carbapenems (imipenem)	In vitro evidence of additive or synergistic antibacterial effects with aminoglycosides against some gram-positive bacteria (Enterococcus faecalis, S. aureus, Listeria monocytogenes)b
Chloramphenicol	Some in vitro evidence of antagonism with aminoglycosides; in vivo antagonism has not been demonstrated and the drugs have been administered concomitantly with no apparent decrease in activityb
Cisplatin	Possible increased incidence of nephrotoxicity and/or neurotoxicity1	Avoid concurrent or sequential use, if possible1
Clindamycin	Some in vitro evidence of antagonism with aminoglycosides; in vivo antagonism has not been demonstrated and the drugs have been administered concomitantly with no apparent decrease in activityb
Colistimethate/Colistin	Possible increased incidence of nephrotoxicity and/or neurotoxicity1	Avoid concurrent or sequential use, if possible1
Diuretics (ethacrynic acid, furosemide, meralluride sodium, sodium mercaptomerin, mannitol)	Possible increased risk of ototoxicity (diuretics themselves may cause ototoxicity) or increased risk of other aminoglycoside-related adverse effects (diuretics may alter aminoglycoside serum or tissue concentrations)1 b
Neuromuscular blocking agents and general anesthetics (succinylcholine, tubocurarine, decamethonium)	Possible potentiation of neuromuscular blockade and respiratory paralysis1	Use concomitantly with caution; closely observe for signs of respiratory depression1
NSAIAs	Possible increased serum aminoglycoside concentrations reported with indomethacin in premature neonates; may be related to indomethacin-induced decreases in urine output	Closely monitor aminoglycoside concentrations and adjust dosage accordingly
Polymyxin B	Possible increased incidence of nephrotoxicity and/or neurotoxicity1	Avoid concurrent or sequential use, if possible1
Tetracyclines	Some in vitro evidence of antagonism with aminoglycosides; in vivo antagonism has not been demonstrated and the drugs have been administered concomitantly with no apparent decrease in activityb
Vancomycin	Possible increased incidence of nephrotoxicity and/or neurotoxicity1	Avoid concurrent or sequential use, if possible1

Kanamycin Sulfate Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed from the GI tract.^{4 16 17 21}

Rapidly absorbed following IM injection;^{1 13 21} peak serum concentrations attained within 1 hour.¹

Aminoglycosides are quickly and almost totally absorbed from body surfaces (except the urinary bladder) after local irrigation or intraoperative topical application in association with medical procedures.^{1 b} Also rapidly absorbed from the bronchial tree, wounds, or denuded skin after local instillation, or when used to irrigate joints; use of large doses at these sites may result in substantial plasma concentrations of the drugs.^b

Plasma Concentrations

Following a single IM dose of 7.5 mg/kg in adults with normal renal function, peak plasma concentrations average 22 mcg/mL within 1 hour;¹ 8 hours after the dose, plasma concentrations average 3.2 mcg/mL.¹ Plasma concentrations are similar following IV infusion over 1 hour.¹

Premature infants: Single IM dose of 6.3–8.5 mg/kg resulted in peak plasma concentrations averaging 17.5 mcg/mL within 1 hour and 5.8 mcg/mL at 12 hours.¹⁸

Neonates 1–7 days of age: Single IM dose of 7.5 mg/kg or 10 mg/kg resulted in peak serum concentrations of 21.8 or 26.8 mcg/mL, respectively, 30 minutes after dose.¹⁹ When given by IV infusion over 20 minutes, plasma concentrations were 21.4 or 29.3 mcg/mL, respectively.¹⁹

Intraperitoneal instillation of 500 mg in 20 mL of 0.9% sodium chloride: Peak plasma concentration of 19 mcg/mL within 15 minutes.¹⁴

Special Populations

Plasma concentrations may be lower in pregnant women.⁴

Plasma concentrations are higher in patients with renal impairment.^{1 4 15}

Plasma concentrations may be decreased in patients with severe burns.¹

Distribution

Extent

Distributed into most body tissues and fluids including pleural fluid, synovial fluid, ascitic fluid, gallbladder, and bile.^{1 4} Low concentrations in saliva and bronchial secretions.⁴

Low concentrations in CSF in adults with uninflamed meninges.^{1 4}

Infants: CSF concentration is 10–20% of serum concentrations if normal meninges; may be 50% if meninges are inflamed.¹

Crosses the placenta and is distributed into cord blood and amniotic fluid.^{1 4}

Distributed into milk.¹

Elimination

Elimination Route

Excreted principally in urine by glomerular filtration; not reabsorbed by renal tubules.¹

Removed by hemodialysis^{4 10 15} and peritoneal dialysis.^{4 15}

Half-life

Adults: 2–4 hours.^{1 4 8 9 11 13 15}

Special Populations

Geriatric patients: Half-life may be prolonged.⁴

Premature neonates: 9 hours.¹⁸

Neonates 1–7 days of age: 4.3–5.1 hours.¹⁹

Severe burn patients: Possible decreased half-life.¹

Renal impairment: Prolonged half-life.^{1 4 15}

Severe renal impairment: 27–80 hours.^{4 8 15}

Stability

Storage

Parenteral

Injection

20–25°C.¹

Stable for 24 hours at room temperature in most IV fluids (e.g., 0.9% sodium chloride, 5% dextrose).⁵

Solution may darken during storage; does not indicate a loss of potency.¹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^HID

Compatible

Amino acids 4.25%, dextrose 25%

Dextrose 5% in sodium chloride 0.9%

Dextrose 5 or 10% in water

Isolyte M or P with dextrose 5%

Ringer’s injection, lactated

Sodium chloride 0.9%

Drug Compatibility

Manufacturer states that kanamycin should not be admixed with β-lactam antibiotics because of possible mutual inactivation.¹

Admixture CompatibilityHID

Compatible

Ascorbic acid injection

Cefoxitin sodium

Chloramphenicol sodium succinate

Clindamycin phosphate

Dopamine HCl

Furosemide

Penicillin G potassium

Penicillin G sodium

Polymyxin B sulfate

Sodium bicarbonate

Vitamin B complex with C

Incompatible

Amphotericin B

Chlorpheniramine maleate

Colistimethate sodium

Heparin sodium

Methohexital sodium

Variable

Hydrocortisone sodium succinate

Y-Site CompatibilityHID

Compatible

Cyclophosphamide

Furosemide

Heparin sodium with hydrocortisone sodium succinate

Hydromorphone HCl

Magnesium sulfate

Meperidine HCl

Morphine sulfate

Perphenazine

Potassium chloride

Vitamin B complex with C

Actions and SpectrumActions

• 
  

  Usually bactericidal.¹

  
  


• 
  

  Inhibits protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits.^{1 b}

  
  


• 
  

  In vitro spectrum of activity includes many gram-negative aerobic bacteria (including most Enterobacteriaceae and Pseudomonas aeruginosa), some mycobacteria, and some aerobic gram-positive bacteria.^{1 b} Inactive against fungi, viruses, and most anaerobic bacteria.^b

  
  


• 
  

  Gram-positive aerobes: Active in vitro against penicillinase-producing and nonpenicillinase-producing Staphylococcus aureus,¹ S. epidermidis,¹ Streptococcus pyogenes (group A β-hemolytic streptococci),¹ S. pneumoniae,¹ and group D streptococci.¹

  
  


• 
  

  Gram-negative aerobes: Active in vitro and in clinical infections against Acinetobacter,¹ Citrobacter,¹ Enterobacter aerogenes,¹ Escherichia coli,¹ Haemophilus influenzae,¹ Klebsiella pneumoniae,¹ Neisseria gonorrhoeae,¹ Proteus,¹ Providencia,¹ Salmonella,¹ Shigella,¹ and Serratia marcescens.¹

  
  


• 
  

  Mycobacteria: Active against Mycobacterium tuberculosis^{4 6} and may be active against multidrug-resistant strains.⁶ Active in vitro against some strains of M. abscessus.

  
  


• 
  

  Partial cross-resistance occurs between kanamycin and other aminoglycosides.^b

  
  


• 
  

  Some M. tuberculosis resistant to streptomycin may be susceptible to kanamycin,⁶ but M. tuberculosis demonstrates complete cross-resistance between kanamycin and amikacin.^{4 6} Cross-resistance also can occur between kanamycin and capreomycin.^f

  
  


• 
  

  There have been recent reports of extensively drug-resistant (XDR) TB.^{c d e} XDR TB is caused by M. tuberculosis resistant to both rifampin and isoniazid that also are resistant to

quetiapine

Generic Name: quetiapine (kwe TYE a peen)

Brand Names: SEROquel, SEROquel XR

What is quetiapine?

Quetiapine is an antipsychotic medicine. It works by changing the actions of chemicals in the brain.

Quetiapine is used to treat schizophrenia in adults and children who are at least 13 years old.

Quetiapine is used to treat bipolar disorder (manic depression) in adults and children who are at least 10 years old.

Quetiapine is also used together with antidepressant medications to treat major depressive disorder in adults.

Extended-release quetiapine (Seroquel XR) is for use only in adults and should not be given to anyone younger than 18 years old.

Quetiapine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about quetiapine?

Never take quetiapine in larger amounts, or for longer than recommended by your doctor. High doses or long-term use of quetiapine can cause a serious movement disorder that may not be reversible. Symptoms of this disorder include tremors or other uncontrollable muscle movements. Quetiapine is not for use in psychotic conditions related to dementia. Quetiapine may cause heart failure, sudden death, or pneumonia in older adults with dementia-related conditions. Stop using quetiapine and call your doctor at once if you have the following symptoms: very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, uncontrolled muscle movements, feeling light-headed, blurred vision, eye pain, increased thirst and urination, excessive hunger, fruity breath odor, weakness, nausea and vomiting.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Video: Treatment for Depression

Treatments for depression are getting better everyday and there are things you can start doing right away.

What should I discuss with my healthcare provider before taking quetiapine?

Quetiapine is not for use in psychotic conditions related to dementia. Quetiapine may cause heart failure, sudden death, or pneumonia in older adults with dementia-related conditions.

To make sure you can safely take quetiapine, tell your doctor if you have any of these other conditions:

• 
  

  liver or kidney disease;

  
  


• 
  

  heart disease, high blood pressure, heart rhythm problems, a history of heart attack or stroke;

  
  


• 
  

  a history of low white blood cell (WBC) counts;

  
  


• 
  

  a thyroid disorder;

  
  


• 
  

  seizures or epilepsy;

  
  


• 
  

  cataracts;

  
  


• 
  

  high cholesterol or triglycerides;

  
  


• 
  

  a personal or family history of diabetes; or

  
  


• 
  

  trouble swallowing.

  
  

You may have thoughts about suicide when you first start taking an antidepressant, especially if you are younger than 24 years old. Tell your doctor if you have worsening symptoms of depression or suicidal thoughts during the first several weeks of treatment, or whenever your dose is changed.

Your family or other caregivers should also be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.

FDA pregnancy category C. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. Quetiapine can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are using quetiapine. Taking antipsychotic medication during the last 3 months of pregnancy may cause problems in the newborn, such as withdrawal symptoms, breathing problems, feeding problems, fussiness, tremors, and limp or stiff muscles. However, you may have withdrawal symptoms or other problems if you stop taking your medicine during pregnancy. If you become pregnant while taking quetiapine, do not stop taking it without your doctor's advice. Do not give quetiapine to a child without a doctor's advice. Extended-release quetiapine (Seroquel XR) is for use only in adults and should not be given to anyone younger than 18 years old.

How should I take quetiapine?

Never take quetiapine in larger amounts, or for longer than recommended by your doctor. High doses or long-term use of quetiapine can cause a serious movement disorder that may not be reversible. Symptoms of this disorder include tremors or other uncontrollable muscle movements.

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results.

Take this medicine with a full glass of water. You may take quetiapine with or without food. Do not crush, chew, or break an extended-release tablet. Swallow the pill whole. Breaking the pill may cause too much of the drug to be released at one time.

Quetiapine may cause you to have high blood sugar (hyperglycemia). Talk to your doctor if you have any signs of hyperglycemia such as increased thirst or urination, excessive hunger, or weakness. If you are diabetic, check your blood sugar levels on a regular basis while you are taking quetiapine.

This medication can cause you to have a false positive drug screening test. If you provide a urine sample for drug screening, tell the laboratory staff that you are taking quetiapine. Store at room temperature away from moisture and heat.

See also: Quetiapine dosage (in more detail)

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of quetiapine can be fatal. Overdose symptoms may include extreme drowsiness, fast heart rate, feeling light-headed, or fainting.

What should I avoid while taking quetiapine?

Quetiapine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Avoid becoming overheated or dehydrated during exercise and in hot weather. You may be more prone to heat stroke.

Avoid drinking alcohol. It can increase certain side effects of quetiapine.

Quetiapine side effects

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

Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Stop using quetiapine and call your doctor at once if you have a serious side effect such as:

• 
  

  very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors;

  
  


• 
  

  feeling like you might pass out;

  
  


• 
  

  jerky muscle movements you cannot control, trouble swallowing, problems with speech;

  
  


• 
  

  tremors, or restless muscle movements in your eyes, tongue, jaw, neck, arms, or legs;

  
  


• 
  

  mask-like appearance of the face, trouble swallowing, problems with speech;

  
  


• 
  

  blurred vision, eye pain, or seeing halos around lights;

  
  


• 
  

  increased thirst and urination, excessive hunger, fruity breath odor, weakness, nausea and vomiting; or

  
  


• 
  

  fever, chills, body aches, flu symptoms, white patches or sores inside your mouth or on your lips.

  
  

Less serious side effects may include:

• 
  

  dizziness, drowsiness, tired feeling;

  
  


• 
  

  dry mouth, sore throat;

  
  


• 
  

  stomach pain, upset stomach, nausea, vomiting, constipation;

  
  


• 
  

  breast swelling or discharge;

  
  


• 
  

  missed menstrual periods; or

  
  


• 
  

  increased appetite, weight gain.

  
  

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.

Quetiapine Dosing Information

Usual Adult Dose for Schizophrenia:

Immediate-release tablets:
Initial Dose: 25 mg orally twice a day.

The dosage may be increased in increments of 25 to 50 mg two times a day or three times a day on the second and third days (as tolerated). By the fourth day a dosage range of 300 mg to 400 mg daily (divided into 2 or 3 doses a day) may be achieved. Additional dosage adjustments (increases or decreases) of 25 to 50 mg twice a day may be made, as needed. However, at least 2 days should pass between the additional dosage adjustments.

Efficacy in schizophrenia has been reported with doses ranging from 150 to 750 mg/day. Maximum clinical effect has been reported at 300 mg/day. The safety of doses above 800 mg/day has not been evaluated in clinical trials.

Extended-release tablets:
Initial dose: 300 mg orally once daily without food or with a light meal.
Maintenance dose: 400 to 800 mg orally once daily depending on response and tolerance.
Maximum dose: Doses above 800 mg daily have not been studied.

The dosage of the extended-release tablets may be increased in increments of up to 300 mg daily at intervals as short as 1 day.

The efficacy of quetiapine in long-term use (over 6 weeks) has not been studied in clinical trials. Patients who respond favorably to quetiapine may be continued on the lowest dose which is effective in maintaining their remission. Patients should be periodically reassessed to determine their need for maintenance treatment.

Usual Adult Dose for Bipolar Disorder:

Immediate-release tablets:
Mania associated with bipolar I disorder as monotherapy or as adjunct therapy to lithium or divalproex:
Initial Dose: 50 mg orally twice a day

The dose may be increased to 200 mg orally twice daily on day 4 in increments of up to 50 mg twice daily. Further dosage adjustments up to 800 mg per day by day 6 should be in increments of no greater than 200 mg/day. Data has been reported to indicate that the majority of patients responded between 400 mg per day to 800 mg per day. The safety of doses above 800 mg per day has not been evaluated in clinical trials.

Immediate-release tablets:
Depressive episodes associated with bipolar disorder:
Initial dose: 50 mg orally once a day

The dose may be increased to reach 300 mg orally once a day by day 4. Some patients may require a further increase to 600 mg once a day by increasing the daily dose to 400 mg on day 5 and 600 mg on day 8 of treatment. Efficacy was demonstrated in this patient population at both 300 mg and 600 mg per day. However, no additional benefit was observed in patients receiving 600 mg per day as compared to those patients receiving 300 mg per day.

Extended-release tablets:

Bipolar Depression:
(Depressive Episodes Associated with Bipolar Disorder)
Usual dose for Acute Treatment: administer orally once daily in the evening starting with 50 mg per day and increasing doses to reach 300 mg per day by day 4.
Recommended Dosing Schedule: Day 1 - 50 mg, Day 2 - 100, mg, Day 3 - 200 mg, & Day 4 - 300 mg

Bipolar Mania:
Usual dose for Acute Monotherapy or Adjunct Therapy (with lithium or divalproex): administer orally once daily in the evening starting with 300 mg on day 1, 600 mg on day 2, and adjust between 400 mg and 800 mg per day thereafter depending on the clinical response and tolerance of the individual patient.

Bipolar Maintenance:
Continue treatment at the dosage required to maintain symptom remission.
While there is no body of evidence available to specifically address how long patients should remain on quetiapine extended-release tablets, maintenance of efficacy in Bipolar I Disorder has been demonstrated with quetiapine (administered orally twice daily totaling 400 to 800 mg per day) as adjunct therapy to lithium or divalproex. Generally, in the maintenance phase, patients continued on the same dose on which they were stabilized during the stabilization phase. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.

Usual Adult Dose for Depression:

As adjunctive therapy to antidepressants for use in the treatment of major depressive disorder:

Extended-release tablets:

Initial dose: 50 mg orally once daily in the evening

On day 3, the dose can be increased to 150 mg once daily in the evening.

Range: 150 mg to 300 mg orally daily. Doses above 300 mg have not been studied.

Usual Geriatric Dose for Schizophrenia:

Immediate-release tablets:
Initial Dose: 25 mg orally once a day.

The dose may be increased daily in increments of 25 mg/day to 50 mg/day to an effective dose, depending on the clinical response and tolerability of the patient.

Efficacy in schizophrenia has been reported with doses ranging from 150 to 750 mg/day. Maximum clinical effect has been reported at 300 mg/day. The safety of doses above 800 mg/day has not been evaluated in clinical trials.

Extended-release tablets:
When an effective immediate-release dose has been reached (above 200 mg), the patient may be switched to the extended-release formulation at an equivalent dose.

The efficacy of quetiapine in long-term use (over 6 weeks) has not been studied in clinical trials. Patients who respond favorably to quetiapine may be continued on the lowest dose which is effective in maintaining their remission. Patients should be periodically reassessed to determine their need for maintenance treatment.

Usual Geriatric Dose for Bipolar Disorder:

Extended-release tablets:
Initial dose: 50 mg/day
The dose can be increased in increments of 50 mg/day depending on the response and tolerance of the individual patient.

What other drugs will affect quetiapine?

Before using quetiapine, tell your doctor if you regularly use other medicines that make you sleepy (such as cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by quetiapine.

Tell your doctor about all other medicines you use, especially:

• 
  

  a medication to treat high blood pressure or a heart condition;

  
  


• 
  

  medications to treat Parkinson's disease;

  
  


• 
  

  steroids (prednisone and others);

  
  


• 
  

  an antibiotic or antifungal medication such as clarithromycin (Biaxin), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin, Pediazole), levofloxacin (Levaquin), ketoconazole (Nizoral), rifampin (Rifadin, Rimactane, Rifater), and others;

  
  


• 
  

  anti-malaria medications such as chloroquine (Aralen) or mefloquine (Lariam);

  
  


• 
  

  heart rhythm medicine such as amiodarone (Cordarone, Pacerone), dofetilide (Tikosyn), disopyramide (Norpace), procainamide (Procan, Pronestyl), propafenone (Rythmol), quinidine (Quin-G), and others;

  
  


• 
  

  medications to treat HIV or AIDS;

  
  


• 
  

  migraine headache medicine such as sumatriptan (Imitrex, Treximet) or zolmitriptan (Zomig);

  
  


• 
  

  narcotic medication such as methadone (Methadose, Diskets, Dolophine);

  
  


• 
  

  seizure medication such as carbamazepine (Carbatrol, Tegretol), divalproex (Depakote), phenobarbital (Luminal, Solfoton), phenytoin (Dilantin), or valproic acid (Depakene, Stavzor); or

  
  


• 
  

  other antidepressant or medicines to treat psychiatric disorders, such as amitriptylline (Elavil, Vanatrip, Limbitrol), clozapine (FazaClo, Clozaril), fluoxetine (Prozac, Sarafem, Symbyax), haloperidol (Haldol), risperidone (Risperdal), thioridazine (Mellaril), and others.

  
  

This list is not complete and other drugs may interact with quetiapine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More quetiapine resources

• Quetiapine Side Effects (in more detail)
• Quetiapine Dosage
• Quetiapine Use in Pregnancy & Breastfeeding
• Quetiapine Drug Interactions
• Quetiapine Support Group
• 277 Reviews for Quetiapine - Add your own review/rating

• quetiapine Advanced Consumer (Micromedex) - Includes Dosage Information


• Quetiapine MedFacts Consumer Leaflet (Wolters Kluwer)


• Quetiapine Fumarate Monograph (AHFS DI)


• Seroquel Prescribing Information (FDA)


• Seroquel Consumer Overview


• Seroquel XR Prescribing Information (FDA)


• Seroquel XR Sustained-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)

Compare quetiapine with other medications

• Bipolar Disorder
• Borderline Personality Disorder
• Depression
• Generalized Anxiety Disorder
• Insomnia
• Obsessive Compulsive Disorder
• Paranoid Disorder
• Post Traumatic Stress Disorder
• Schizoaffective Disorder
• Schizophrenia
• Tourette's Syndrome

Where can I get more information?

• Your pharmacist can provide more information about quetiapine.

See also: quetiapine side effects (in more detail)

Soloxine

Dosage Form: FOR ANIMAL USE ONLY
Soloxine®

(LEVOTHYROXINE SODIUM)

TABLETS

Description

Each Soloxine® (Levothyroxine Sodium, USP) Tablet provides synthetic crystalline levothyroxine sodium (L-thyroxine).

The structural formula for levothyroxine sodium is:

Levothyroxine Sodium Action

Levothyroxine sodium acts, as does endogenous thyroxine, to stimulate metabolism, growth, development and differentiation of tissues. It increases the rate of energy exchange and increases the maturation rate of the epiphyses. Levothyroxine sodium is absorbed rapidly from the gastrointestinal tract after oral administration. Following absorption, the compound becomes bound to the serum alpha globulin fraction. For purposes of comparison, 0.1 mg of levothyroxine sodium elicits a clinical response approximately equal to that produced by one grain (65 mg) of desiccated thyroid.

Indications

Provides thyroid replacement therapy in all conditions of inadequate production of thyroid hormones. Hypothyroidism is the generalized metabolic disease resulting from deficiency of the thyroid hormones levothyroxine (T4) and liothyronine (T3). Soloxine (levothyroxine sodium) will provide levothyroxine (T4) as a substrate for the physiologic deiodination to liothyronine (T3). Administration of levothyroxine sodium alone will result in complete physiologic thyroid replacement.

Canine hypothyroidism is usually primary, i.e., due to atrophy of the thyroid gland. In the majority of cases the atrophy is associated with lymphocytic thyroiditis and in the remainder it is non-inflammatory and as of yet unknown etiology. Less than 10 percent of cases of hypothyroidism are secondary, i.e., due to deficiency of thyroid stimulating hormone (TSH). TSH deficiency may occur as a component of congenital hypopituitarism or as an acquired disorder in adult dogs, in which case it is invariably due to the growth of a pituitary tumor.

Hypothyroidism in the Dog

Hypothyroidism usually occurs in middle-aged and older dogs although the condition will sometimes be seen in younger dogs of the larger breeds. Neutered animals of either sex are also frequently affected, regardless of age. The following are clinical signs of hypothyroidism in dogs:

 

Lethargy, lack of endurance, increased sleeping

 

Reduced interest, alertness and excitability

 

Slow heart rate, weak apex beat and pulse, low voltage on ECG

 

Preference for warmth, low body temperature, cool skin

 

Increased body weight

 

Stiff and slow movements, dragging of front feet

 

Head tilt, disturbed balance, unilateral facial paralysis

 

Atrophy of epidermis, thickening of dermis

 

Surface and follicular hyperkeratosis, pigmentation

 

Puffy face, blepharoptosis, tragic expression

 

Dry, coarse, sparse coat, slow regrowth after clipping

 

Retarded turnover of hair (carpet coat of boxers)

 

Shortening or absence of estrus, lack of libido

 

Dry feces, occasional diarrhea

 

Hypercholesterolemia

 

Normochromic, normocytic anemia

 

Elevated serum creatinine phosphokinase

Contraindications

Levothyroxine sodium therapy is contraindicated in thyrotoxicosis, acute myocardial infarction and uncorrected adrenal insufficiency. Use in pregnant bitches has not been evaluated.

Precautions

The effects of levothyroxine sodium therapy are slow in being manifested. Overdosage of any thyroid drug may produce the signs and symptoms of thyrotoxicosis including, but not limited to: polydipsia, polyuria, polyphagia, reduced heat tolerance and hyperactivity or personality change. Administer with caution to animals with clinically significant heart disease, hypertension or other complications for which a sharply increased metabolic rate might prove hazardous.

Adverse Reactions

There are no particular adverse reactions associated with levothyroxine sodium therapy at the recommended dosage levels. Overdosage will result in the signs of thyrotoxicosis listed above under precautions.

Dosage

The initial recommended dose is 0.1 mg/10 lb. (4.5 kg) body weight twice daily. Dosage is then adjusted by monitoring the thyroid blood levels of the dog every four weeks until an adequate maintenance dose is established. The usual maintenance dose is 0.1 mg/10 lb. (4.5 kg) once daily.

A maximum of 0.8 mg to 1.0 mg total daily dose will be sufficient in most dogs over 80 pounds in body weight.

Administration

Soloxine tablets may be administered orally or placed in the food.

Dosage forms available

0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.8 mg and 1.0 mg tablets in bottles of 250 and 1,000.

Storage

Store at controlled room temperature 15°C to 30°C (59°F to 86°F).

References

1. Evinger, J.V. and Nelson, R.W.; JAVMA 314. 1984, pg 185, 314-316.


2. Richard Nelson, DVM; Current Veterinary Therapy X. Edited by R. W. Kirk, W. B. Saunders, Co., Philadelphia, PA 1989, pg 994.


3. Edward Feldman, DVM and Richard Nelson, DVM; Canine and Feline Endocrinology and Reproduction. W. B. Saunders 1987, pg 82.

Virbac AH, Inc.

Fort Worth, TX 76137

For More Information Call

1-800-338-3659

11/09

301787-02

PRINCIPAL DISPLAY PANEL - 0.1 mg Tablet Bottle Label

Virbac

ANIMAL HEALTH

NDC 051311-831-25

Soloxine®

(LEVOTHYROXINE SODIUM)

TABLETS

0.1 mg

250 TABLETS

CAUTION: Federal law restricts this drug to use

by or on the order of a licensed veterinarian.

Virbac AH, Inc. • P.O. Box 162059

Fort Worth, TX 76161 • (800) 338-3659

PRINCIPAL DISPLAY PANEL - 0.2 mg Tablet Bottle Label

Virbac

ANIMAL HEALTH

NDC 051311-832-25

Soloxine®

(LEVOTHYROXINE SODIUM)

TABLETS

0.2 mg

250 TABLETS

CAUTION: Federal law restricts this drug to use

by or on the order of a licensed veterinarian.

Virbac AH, Inc. • P.O. Box 162059

Fort Worth, TX 76161 • (800) 338-3659

PRINCIPAL DISPLAY PANEL - 0.3 mg Tablet Bottle Label

Virbac

ANIMAL HEALTH

NDC 051311-833-25

Soloxine®

(LEVOTHYROXINE SODIUM)

TABLETS

0.3 mg

250 TABLETS

CAUTION: Federal law restricts this drug to use

by or on the order of a licensed veterinarian.

Virbac AH, Inc. • P.O. Box 162059

Fort Worth, TX 76161 • (800) 338-3659

PRINCIPAL DISPLAY PANEL - 0.4 mg Tablet Bottle Label

Virbac

ANIMAL HEALTH

NDC 051311-834-25

Soloxine®

(LEVOTHYROXINE SODIUM)

TABLETS

0.4 mg

250 TABLETS

CAUTION: Federal law restricts this drug to use

by or on the order of a licensed veterinarian.

Virbac AH, Inc. • P.O. Box 162059

Fort Worth, TX 76161 • (800) 338-3659

PRINCIPAL DISPLAY PANEL - 0.5 mg Tablet Bottle Label

Virbac

ANIMAL HEALTH

NDC 051311-835-25

Soloxine®

(LEVOTHYROXINE SODIUM)

TABLETS

0.5 mg

250 TABLETS

CAUTION: Federal law restricts this drug to use

by or on the order of a licensed veterinarian.

Virbac AH, Inc. • P.O. Box 162059

Fort Worth, TX 76161 • (800) 338-3659

PRINCIPAL DISPLAY PANEL - 0.6 mg Tablet Bottle Label

Virbac

ANIMAL HEALTH

NDC 051311-836-25

Soloxine®

(LEVOTHYROXINE SODIUM)

TABLETS

0.6 mg

250 TABLETS

CAUTION: Federal law restricts this drug to use

by or on the order of a licensed veterinarian.

Virbac AH, Inc. • P.O. Box 162059

Fort Worth, TX 76161 • (800) 338-3659

PRINCIPAL DISPLAY PANEL - 0.7 mg Tablet Bottle Label

Virbac

ANIMAL HEALTH

NDC 051311-837-25

Soloxine®

(LEVOTHYROXINE SODIUM)

TABLETS

0.7 mg

250 TABLETS

CAUTION: Federal law restricts this drug to use

by or on the order of a licensed veterinarian.

Virbac AH, Inc. • P.O. Box 162059

Fort Worth, TX 76161 • (800) 338-3659

PRINCIPAL DISPLAY PANEL - 0.8 mg Tablet Bottle Label

Virbac

ANIMAL HEALTH

NDC 051311-838-25

Soloxine®

(LEVOTHYROXINE SODIUM)

TABLETS

0.8 mg

250 TABLETS

CAUTION: Federal law restricts this drug to use

by or on the order of a licensed veterinarian.

Virbac AH, Inc. • P.O. Box 162059

Fort Worth, TX 76161 • (800) 338-3659

PRINCIPAL DISPLAY PANEL - 1.0 mg Tablet Bottle Label

Virbac

ANIMAL HEALTH

NDC 051311-830-25

Soloxine®

(LEVOTHYROXINE SODIUM)

TABLETS

1.0 mg

250 TABLETS

CAUTION: Federal law restricts this drug to use

by or on the order of a licensed veterinarian.

Virbac AH, Inc. • P.O. Box 162059

Fort Worth, TX 76161 • (800) 338-3659

Soloxine  levothyroxine sodium  tablet

Product Information Product Type PRESCRIPTION ANIMAL DRUG NDC Product Code (Source) 51311-831 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength levothyroxine sodium (levothyroxine) levothyroxine sodium 0.1 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color YELLOW Score 2 pieces Shape OVAL Size 10mm Flavor Imprint Code 0;1 Contains

Packaging # NDC Package Description Multilevel Packaging 1 51311-831-10 1000 TABLET In 1 BOTTLE None 2 51311-831-25 250 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
UNAPPROVED DRUG OTHER		12/07/2009

Soloxine  levothyroxine sodium  tablet

Product Information Product Type PRESCRIPTION ANIMAL DRUG NDC Product Code (Source) 51311-832 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength levothyroxine sodium (levothyroxine) levothyroxine sodium 0.2 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color PINK Score 2 pieces Shape OVAL Size 10mm Flavor Imprint Code 0;2 Contains

Packaging # NDC Package Description Multilevel Packaging 1 51311-832-10 1000 TABLET In 1 BOTTLE None 2 51311-832-25 250 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
UNAPPROVED DRUG OTHER		12/07/2009

Soloxine  levothyroxine sodium  tablet

Product Information Product Type PRESCRIPTION ANIMAL DRUG NDC Product Code (Source) 51311-833 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength levothyroxine sodium (levothyroxine) levothyroxine sodium 0.3 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color GREEN Score 2 pieces Shape OVAL Size 10mm Flavor Imprint Code 0;3 Contains

Packaging # NDC Package Description Multilevel Packaging 1 51311-833-10 1000 TABLET In 1 BOTTLE None 2 51311-833-25 250 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
UNAPPROVED DRUG OTHER		12/07/2009

Soloxine  levothyroxine sodium  tablet

Product Information Product Type PRESCRIPTION ANIMAL DRUG NDC Product Code (Source) 51311-834 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength levothyroxine sodium (levothyroxine) levothyroxine sodium 0.4 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color RED (Maroon) Score 2 pieces Shape OVAL Size 10mm Flavor Imprint Code 0;4 Contains

Packaging # NDC Package Description Multilevel Packaging 1 51311-834-10 1000 TABLET In 1 BOTTLE None 2 51311-834-25 250 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
UNAPPROVED DRUG OTHER		12/07/2009

Soloxine  levothyroxine sodium  tablet

Product Information Product Type PRESCRIPTION ANIMAL DRUG NDC Product Code (Source) 51311-835 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength levothyroxine sodium (levothyroxine) levothyroxine sodium 0.5 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color WHITE Score 2 pieces Shape OVAL Size 10mm Flavor Imprint Code 0;5 Contains

Packaging # NDC Package Description Multilevel Packaging 1 51311-835-10 1000 TABLET In 1 BOTTLE None 2 51311-835-25 250 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
UNAPPROVED DRUG OTHER		12/07/2009

Soloxine  levothyroxine sodium  tablet

Product Information Product Type PRESCRIPTION ANIMAL DRUG NDC Product Code (Source) 51311-836 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength levothyroxine sodium (levothyroxine) levothyroxine sodium 0.6 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color PURPLE Score 2 pieces Shape OVAL Size 10mm Flavor Imprint Code 0;6 Contains

Packaging # NDC Package Description Multilevel Packaging 1 51311-836-10 1000 TABLET In 1 BOTTLE None 2 51311-836-25 250 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
UNAPPROVED DRUG OTHER		12/07/2009

Soloxine  levothyroxine sodium  tablet

Product Information Product Type PRESCRIPTION ANIMAL DRUG NDC Product Code (Source) 51311-837 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength levothyroxine sodium (levothyroxine) levothyroxine sodium 0.7 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color ORANGE Score 2 pieces Shape OVAL Size 10mm Flavor Imprint Code 0;7 Contains

Packaging # NDC Package Description Multilevel Packaging 1 51311-837-10 1000 TABLET In 1 BOTTLE None 2 51311-837-25 250 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
UNAPPROVED DRUG OTHER		12/07/2009

Soloxine  levothyroxine sodium  tablet

Product Information Product Type PRESCRIPTION ANIMAL DRUG NDC Product Code (Source) 51311-838 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength levothyroxine sodium (levothyroxine) levothyroxine sodium 0.8 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color BLUE Score 2 pieces Shape OVAL Size 10mm Flavor Imprint Code 0;8 Contains

Packaging # NDC Package Description Multilevel Packaging 1 51311-838-10 1000 TABLET In 1 BOTTLE None 2 51311-838-25 250 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
UNAPPROVED DRUG OTHER		12/07/2009

Soloxine  levothyroxine sodium  tablet

Product Information Product Type PRESCRIPTION ANIMAL DRUG NDC Product Code (Source) 51311-830 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength levothyroxine sodium (levothyroxine) levothyroxine sodium 1 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color BROWN (Beige) Score 2 pieces Shape OVAL Size 10mm Flavor Imprint Code 1 Contains

Packaging # NDC Package Description Multilevel Packaging 1 51311-830-10 1000 TABLET In 1 BOTTLE None 2 51311-830-25 250 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
UNAPPROVED DRUG OTHER		12/07/2009

Labeler - Virbac AH, Inc. (131568396)

Establishment
Name	Address	ID/FEI	Operations
Virbac Bridgeton		808558100	MANUFACTURE

Revised: 12/2009Virbac AH, Inc.