2nd Line Medications

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Treatment regimens that include four different first-line antituberculosis medications are recommended for the initial treatment of TB in adults.  The initial regimen should include INH, RIF, PZA and EMB unless there are contraindications to any of the drugs or if the patient is pregnant.  Rifampin should not be used in patients who are receiving HIV medications.

Ciprofloxacin, Clarithromycin, Clofazamine & Ofloxacin are not considered 2nd-line drugs, but can be used as alternatives to the listed options in cases of drug resistance/intolerance.

All patients with drug-resistant TB should be placed on directly observed therapy (DOT).  Second-line drugs are not intended for intermittent use and should be given on a daily basis.  Exercise extreme caution when using these drugs during pregnancy due to known and unknown risk to the fetus.  The following drugs are listed alphabetically. 

Amikacin/kanamycin (AM/KM) 

Not yet approved by the U.S. Food and Drug Administration for use in the treatment of tuberculosis.

Daily Dose (Max)
15mg/kg (1g)
Usual dose is 750-1000mg IV/IM; given as a single dose 5-7 days/week & reduced to 2-3 days/week after the first 2-4 months or after culture conversion, depending on efficacy of drug regimen.

Adverse Reactions
Rental toxicity, vestibular dysfunction, hearing loss, electrolyte abnormalities, dizziness

Monitoring
Baseline and monthly auditory and renal function

Comments
Avoid or reduce dose in adults over age 59 (10mg/kg with a maximum dose of 750mg).  Should not be used concurrently with other aminoglycosides or Capreomycin.

Capreomycin (CM)

Daily Dose (Max)
15mg/kg (1g)
Usual dose is 750-1000mg IV/IM; given as a single dose 5-7 days/week & reduced to 2-3 days/week after the first 2-4 months or after culture conversion, depending on efficacy of drug regimen.

Adverse Reactions
Auditory, vestibular, and renal toxicity, electrolyte abnormalities

Monitoring
Baseline and monthly auditory and renal function as well as serum K+ and Mg++ levels

Comments
Avoid or reduce dose in adults over age 59 (10mg/kg with a maximum dose of 750mg).  Decrease dose with renal insufficiency.  Should not be used with aminoglycosides.

Cycloserine (CS)

Daily Dose (Max)
10-15mg/kg (1g)
500-750 mg divided BID

Adverse Reactions
CNS effects, perhipheral neuritis, psychosis, seizures, depression, headaches, rash, drug interactions

Monitoring
Neuropsychiatric status assessed monthly.

Comments
Use cautiously in patients with renal insuffiency.  Pyridoxine may decrease CNS effects.  Avoid sunlight.  Consider dosing at mealtimes.  Although recommended, it is unusual for patients to tolerate this dosage.  Drug serum concentration measurements are useful in determining the optimal dose.

Ethionamide (ETA)

Daily Dose (Max)
15-20mg/kg (1g)
Usuallly 500-750mg QD or divided BID

Adverse Reactions
GI intolerance, hepatoxicity, neurotoxicity, endocrine effects, metallic taste, hypersensitivity

Monitoring
Baseline LFTs recommended in all patients.  For patients with pre-existing liver disease or who develop abnormal liver function that does require discontinuation of the drug, LFTs should be measured monthly & when symptoms occur.

Comments
Reduce dosage in patients with creatine clearance of <30mL/min; start with low dosage and increase as tolerated.  To reduce GI upset, give in divided dose.  May cause hypothyroid condition, especially if used with PAS.

Levofloxacin (LEV)

Not yet approved by the U.S. Food and Drug Administration for use in the treatment of tuberculosis.

Daily Dose (Max)
500-750mg

Adverse Reactions
GI intolerance, headache, dizziness, rash, vaginitis, drug interactions, hypersensitivity

Comments
Cross resistance with Ciprofloxacin and Olfloxacin.  Should not be administered within 2 hours of taking antacid/medications containing divalent cations.
Ciprofloxacin, Clarithromycin, Clofazamine & Ofloxacin are not considered 2nd-line drugs, but can be used as alternatives to the listed options in cases of drug resistance/intolerance.

Moxifloxacin (MOX)

Not yet approved by the U.S. Food and Drug Administration for use in the treatment of tuberculosis.

Daily Dose (Max)
400ng

Adverse Reactions
GI intolerance, headache, dizziness, rash, vaginitis, drug interactions, hypersensitivity

Comments
Cross resistance with Ciprofloxacin and Olfloxacin.  Should not be administered within 2 hours of taking antacid/medications containing divalent cations.
Ciprofloxacin, Clarithromycin, Clofazamine & Ofloxacin are not considered 2nd-line drugs, but can be used as alternatives to the listed options in cases of drug resistance/intolerance.

p-Aminosalicylic acid (PAS)

Daily Dose (Max)
8-12g in 2-3 doses

Adverse Reactions
GI intolerance, hypersensitivity, hepatoxicity, malabsorption syndrome, coagulopathy

Monitoring
Baseline hepatic enzymes and thyroid function

Comments
May causehypothyroid condition if used with ETA.  Monitor cardiac patients for sodium load.  Doubling of prothrombin time lessened with use of SM.

Streptomycin (SM)

Daily Dose (Max)
15mg/kg (1g)
Usual dose is 750-1000mg IV/IM; given as a single dose 5-7 days/week & reduced to 2-3 days/week after the first 2-4 months or after culture conversion, depending on efficacy of drug regimen.

Adverse Reactions
Ototoxicity (hearing loss or vestibular dysfunction), neurotoxicity, renal toxicity

Monitoring
Baseline hearing & serum creatine measurement.  Monthly renal function assessment and questioning regarding auditory or vestibular symptoms.

Comments
Avoid or reduce dose in adults over age 59 (10mg/kg daily with a maximum dose of 750mg).  Decrease dose with renal insufficiency.