Figure 1.  Monitoring Patients Receiving Isoniazid

 


 

Table 1.   Dosages, Pharmacokinetics and Minimal Inhibitory Concentrations of Antituberculosis Medications



Drug


Usual Adult

Daily Dosage*

Peak Serum Concentration

(µg/ml)

Usual MIC

(range)†

(µg/ml)

First-line oral drugs:

 

 

 

   Isoniazid

300 mg

3 - 5

0.01 - 0.025

   Rifampin

600 mg

8 - 29

0.06 - 0.25

   Rifabutin

300 mg

0.3-0.9

0.125-1.0

   Pyrazinamide

30 mg/kg

20 - 60

6.2 - 50

   Ethambutol

15 - 25 mg/kg

3 - 5

0.5 - 2.0

Injectable drugs:

 

 

 

   Streptomycin

15 mg/kg

35 - 45

0.25 - 2.0

   Amikacin

15 mg/kg

35 - 45

0.5 - 1.0

   Kanamycin

15 mg/kg

35 - 45

1.5 - 3.0

   Capreomycin

15 mg/kg

35 - 45

1.25 - 2.5

Second-line oral drugs:

 

 

 

   Ofloxacin**

400 mg b.i.d.

4-6

0.25 - 2.0

   Levofloxacin**

500 mg qd

­3-5

0.12-1.0

   Moxifloxacin**

400 mg qd

3-5

0.031-0.12

   Gatifloxacin**

400 mg qd

3-5

0.007-0.12

   Ethionamide

250 mg b.i.d. or t.i.d.

1 - 5

0.3 - 1.2

   Aminosalicylic acid

3 g q.i.d.

40 - 70

Not known

   Cycloserine

250 mg b.i.d. or t.i.d.

20 - 35

Not known

* Q.D. denotes daily, b.i.d. denotes twice a day, t.i.d. three times a day, and q.i.d. four times a day.

** Expect a 1 ug/ml increase in peak serum concentration for every 100 mg/dose

+MIC denotes minimal inhibitory concentration for drug-susceptible organisms.

Sources: Adapted from reference 99 (with permission) and personal communication with Charles Peloquin, Pharm.D.

 

Table 2. First Line Drugs [Download PDF]

Drug

Dose in mg/kg

(Maximum Dose)

Adverse Reactions

Comments

 

Daily

2 Times/Week*

3 Times/Week*

 

 

Isoniazid

Children

10-20

 

(300 mg)

Adults

5

 

(300 mg)

 

Children

20-40

 

(900 mg)

Adults

15

 

(900 mg)

Children

20-40

 

(900 mg)

Adults

15

 

(900 mg)

Hepatic enzyme elevation

Hepatitis

Peripheral neuropathy

Central nervous system (mild)

Drug interactions

Hepatitis risk increases with age and alcohol consumption

Pyridoxine can prevent peripheral neuropathy

Rifampin

Children

10-20

 

(600 mg)

Adults

10

 

(600 mg)

 

Children

10-20

 

(600 mg)

Adults

10

 

(600 mg)

Children

10-20

 

(600 mg)

Adults

10

 

(600 mg)

GI upset

Drug interactions

Hepatitis

Bleeding problems

Flu-like symptoms

Rash

Significant interactions with
-methadone
-birth control pills
-many other drugs

Colors body fluids orange

May permanently discolor soft contact lenses

Rifabutin

Children

–

Adults

5

 

(300 mg)

Children

–

 

Adults

5

 

(300 mg)

Children

–

Adults

5

 

(300 mg)

Rash

Hepatitis

Fever

Thrombocytopenia

With increased levels:

  Arthralgias, uveitis, leukopenia

 

Significant interactions with
-methadone
-birth control pills
-many other drugs

Colors body fluids orange

May permanently discolor soft contact lenses

Rifapentine**

Children

–

 

Adults

–

Children

–

Adults

–

Children

–

Adults

–

Rash

Hepatitis

Fever

Thrombocytopenia

Significant interactions with
-methadone
-birth control pills
-many other drugs

Colors body fluids orange

May permanently discolor soft contact lenses

Pyrazinamide

Children

15-30

 

(2 g)

Adults

15-30

 

(2 g)

 

Children

50-70

 

(4 g)

Adults

50-70

 

(4 g)

Children

50-70

 

(3 g)

Adults

50-70

 

(3 g)

Hepatitis

Rash

GI upset

Joint aches

Hyperuricemia

Gout (rare)

Treat hyperuricemia only if patient has symptoms

Ethambutol

Children

15-25

 

Adults

15-25

 

Children

50

Adults

50

Children

25-30

 

Adults

25-30

Optic neuritis

Not recommended for children too young to be monitored for changes in vision unless tuberculosis is drug resistant

Streptomycin

Children

20

 

(1 g)

Adults

15

 

(1 g)

Children

25-30

 

(1.5 g)

Adults

25-30

 

(1.5 g)

Children

25-30

 

(1.5 g)

Adults

25-30

 

(1.5 g)

Ototoxicity

Renal toxicity

Avoid or reduce dose in adults
> 60 years old

Notes:  Children ≤ 12 years old. Adjust weight-based dosages as weight changes.

*All regimens administered 2 or 3 times a week should be used with directly observed therapy (DOT)

**Rifapentine is dosed once weekly at 10 mg/kg (max 900 mg daily) during the continuation phase, only.

Source. Adapted from reference #7

 

 

Table 3. Second Line Drugs [Download PDF]

Drug

Daily Dose
(Max. Dose)

Adverse Reactions

Monitoring

Comments

Capreomycin

15 mg/kg

 (1 g)

Toxicity-auditory
         -vestibular
         -renal

Assess vestibular and hearing
function

Measure renal function and serum drug levels

After bacteriologic conversion, dosage may be reduced to 2-3 times per week

 

Kanamycin

15 mg/kg

 (1 g)

Toxicity-auditory
           -vestibular
           -renal

Assess vestibular and hearing
function

Measure renal function and serum drug levels

After bacteriologic conversion, dosage may be reduced to 2-3 times per week

Amikacin

15 mg/kg

(1 g)

 

Renal toxicity         

Chemical imbalance

Hearing loss            

Dizziness

Vestibular dysfunction

Assess hearing function

Measure renal function and serum drug levels

Not approved by FDA for TB treatment

After bacteriologic conversion, dosage may be reduced to 2-3 times per week

Ethionamide

15-20 mg/kg

 (1 g)

GI upset                 

Metallic taste

Hepatotoxicity          

Bloating

Hypersensitivity

Measure hepatic enzymes

Start with low dosage and increase as tolerated

May cause hypothyroid condition, especially if used with PAS

Para-aminosalicylic acid

150 mg/kg (12 g)

GI upset

Hypersensitivity

Hepatotoxicity

Sodium load

Measure hepatic enzymes

Assess volume status

Start with low dosage and increase as tolerated

Monitor cardiac patients for sodium load

Cycloserine

15-20 mg/kg

(1 g)

Psychosis                

Headaches

Convulsions            

Rash

Depression               

Drug interactions

Assess mental status

Measure serum drug levels

Start with low dosage and increase as tolerated

Pyridoxine may decrease CNS effects

Ofloxacin

400-800 mg/day

GI upset                 

Drug interactions

Dizziness                

Headaches

Hypersensitivity       

Restlessness

 

Drug interactions

Not approved by FDA for TB treatment

Should not be used in children

Avoid: antacids, zinc, iron, sucralfate

Levofloxacin

500-750 mg/day

GI upset                 

Drug interactions

Dizziness                 

Headaches

Hypersensitivity       

Restlessness

 

Drug interactions

Not approved by FDA for TB treatment

Should not be used in children

Avoid: antacids, iron, zinc, sucralfate

Moxifloxacin

400 mg/day

GI upset                 

Drug interactions

Dizziness               

Headaches

Hypersensitivity       

Restlessness

Drug interactions

Not approved by FDA for TB treatment

Should not be used in children

Avoid: antacids, iron, zinc, sucralfate

Gatifloxacin

400 mg/day

GI upset                 

Drug interactions

Dizziness                

Headaches

Hypersensitivity       

Restlessness

Drug interactions

Not approved by FDA for TB treatment

Should not be used in children

Avoid: antacids, iron, zinc, sucralfate

Notes: Doses for children same as for adults. Use these drugs only in consultation with a clinician experienced in the management of

drug-resistant TB.

Adjust weight-based dosages as weight changes.  Source: Adapted from reference #7

 

Table  4.  Drug Regimen For Culture-positive Pulmonary Tuberculosis [Download PDF]

INITIAL PHASE

CONTINUATION PHASE
Regimen Drugs Interval and Doses‡ Regimen Drugs Interval and Doses‡ #

    1

INH

RIF

PZA

EMB

Seven days per week

for 56 doses (8 weeks)

     1A

     1B

    

INH /RIF

INH/RIF

 

Seven days per week for 126 doses (18 weeks)            Twice-weekly for 36 doses (18 weeks)                           

    2

 

 

 

INH

RIF

PZA

EMB

Seven days per week for 14 doses (2 weeks)

then twice-weekly for 12 doses (6 weeks)

    2

   

INH/RIF

 

Twice-weekly for 36 doses (18 weeks)

 

    3

INH

RIF

PZA

EMB

Thrice-weekly for 24 doses (8 weeks)

    3

 

INH/RIF/ PZA/EMB*

Thrice-weekly for 54 doses

(18 weeks)

    4+

INH

RIF

EMB

Seven days per week for 56 doses (8 weeks)

    4 A

    4 B

INH/RIF

INH/RIF

Seven days per week for 196 doses (28 weeks)

Twice-weekly for 56 doses (28 weeks)

INH = isoniazid, RIF = rifampin, RPT = rifapentine, PZA = pyrazinamide, EMB = ethambutol

‡When DOT is used drugs may be given 5 days per week and the necessary number of doses adjusted accordingly.

#Patients with cavitation on initial chest radiograph and positive cultures at completion of 2 months of therapy should receive a 7-month continuation phase.

* Options 1 C and 2B should only be used in HIV-negative patients who have negative sputum smears at the time of completion of 2 months of therapy and who do not have cavitation on initial the chest radiograph (see text).

Source:  Adapted from reference 7.

*Same experts believe that INH and RIF can be confirmed without PZA and EMB in the continuation phase.

+This regimen should be used only in special circumstances (see text)

 

 

 

Table 5.Selected Treatment Regimens for Drug-Resistant Tuberculosis. [Download PDF]

 

Resistance to:

 Treatment Regimen

 Duration of Therapy

Comments

Isoniazida

Rifampin

Ethambutol

Pyrazinamide

6 -9 months

Pyrazinamide for entire duration

Isoniazida

Rifampin

Ethambutol

12 months

Consider addition of pyrazinamide

Rifampina

Isoniazid

Ethambutol

18 months

Consider addition of pyrazinamide

Isoniazid and ethambutola

Rifampin

Pyrazinamide

Fluoroquinolone

Injectableb

9 -12 months

 

Isoniazid and rifampina

Ethambutol

Pyrazinamide

Fluoroquinolone

Injectableb

18 months after culture conversion

Consider surgery

Isoniazid, rifampin, ethambutola

Pyrazinamide

Fluoroquinolone

Injectableb

Plus 2 othersc

24 months after culture conversion

Consider surgery

Isoniazid

rifampin, pyrazinamide†

Ethambutol

Fluoroquinolone

Injectableb

Plus 2 othersc

24 months after culture conversion

Consider surgery

Isoniazid, rifampin, ethambutol, pyrazinamide†

Fluoroquinolone

Injectableb

Plus 3 othersc

24 months after culture conversion

Surgery if possible

Adapted from Iseman MD. Treatment of multidrug-resistant tuberculosis. N Engl J Med 1993;329:784-791, with permission.

a ± streptomycin resistance

b streptomycin, amikacin, kanamycin, or capreomycin.  Injectable should be continued for at least 6 months, if possible.

c ethionamide, cylcoserine, or para-aminosalicylic acid.  In some cases, rifabutin, amoxacillin/cavulanic acid, imipenem, clofazamine, thiacetazone.

 

  

 

Table 6:  Dosing Recommendations in Patients Receiving Chronic Hemodialysis [Download PDF]

 Drug

Recommended dose* 

Isoniazid

5-10mg/kg/day daily (max 300 mg/day) or 900 mg three times/week

Rifampin

600 mg/day or three times/week (max 600 mg/day)

Pyrazinamide

25-35 mg/kg/day three times/week

Ethambutol**

15-25 mg/kg/day three times/week

Levofloxacin

750-1000 mg/day three times/week

Cycloserine**

250-500 mg three times/week

Ethionamide

250-500 mg qd

PAS

4 gm b.i.d

Clofazimine

100-200 mg qd

Streptomycin**

12-15 mg/kg/dose two-three times/week

Capreomycin**

12-15 mg/kg/dose two-three times/week

Kanamycin**

12-15 mg/kg/dose two-three times/week

Amikacin**

12-15 mg/kg/dose two-three times/week

 

*The medications may be given after dialysis

** Monitor serum drug concentrations to avoid drug toxicity.

 

 

Table 7. Criteria for Positive Tuberculin Skin Test, By Risk Group [Download PDF]

 

Reaction ≥ 5 mm 

Reaction ≥ 10 mm

Reaction ≥ 15 mm

HIV infection

Immigration within the past 5 years from high prevalence country

Persons with no risk factors

Recent contact to infectious case

Injection drug users

 

Fibrotic lesions on chest radiograph consistent with prior TB

Residents and employees of high-risk settingsb

 

Patients with organ transplants or other immunosuppressed patientsc

Mycobacteriology laboratory personnel

 

 

Persons with high-risk clinical conditionsd

 

 

Children younger than 4 yr of age or infants, children, and adolescents exposed to adults at high-risk

 

 

a For persons who are otherwise at low risk and are tested at the start of employment, a reaction of ≥15 mm is considered positive.

b Prisons and jails, nursing homes and other long-term facilities for the elderly, hospitals and other health-care facilities, residental facilities for patients with acquiried immunodeficiency syndrome (AIDS), and homeless shelters.

c Receiving the equivalent of ≥ 15 mg/d of prednisone for one month or more. Risk of TB in patients treated with corticosteroids increases with higher dose and longer duration.

d Silicosis, diabetes mellitus, chronic renal failure, some hematologic disorders (e.g, leukemias and lymphomas), other specific malignancies (e.g., carcinomas of the head and neck), weight loss of ≥ 10 % of ideal body weight, gastrectomy, and jejunoileal bypass

Adapted from reference 5 with permission

 

 

 

Table 8.  Recommended Treatment Regimens for LTBI [Download PDF]

Drug

Dose

(max. dose)

Interval and Duration

Comments

INH

5 mg/kg/day

(300 mg)

Daily for 9 m

Preferred regimen

INH

15 mg/kg/day

(900 mg)

Twice-weekly for 9 m

Directly observed therapy must be used

INH

5 mg/kg/day

(300 mg)

Daily for 6 m

Not for HIV + patients

INH

 15 mg/kg/day

(900 mg)

Twice-weekly for 6 m

Not for HIV + patients. Directly observed therapy must be used

RIF

10 mg/kg/day

  (600 mg)

Daily for 4 mo

For persons who do not tolerate isoniazid or pyrazinamide or contacts to isoniazid-resistant cases

RIF

 

+

PZA

10 mg/kg/day

 (600 mg)

 + 

15-20 mg/kg/day

Daily for 2 m

Should generally not be used (see text)

RIF

 

+

PZA

10 mg/kg/day

(600 mg)

+

40 mg/kg/day

Twice-weekly for 3 m

Should generally not be used (see text). Directly observed therapy must be used.

 

INH = isoniazid, RIF = rifampin, PZA = pyrazinamide

Source: Adapted from reference 5 and 31a.