Note: Recommendations often change due to epidemiology (resistance) and emerging information; consult CDC and WHO for current recommendations, as appropriate.
Active TB infection, treatment: Note: Always use as part of a multidrug regimen. Any regimens using less than once daily dosing should administer dosing as directly observed therapy (DOT). Treatment regimens for pulmonary tuberculosis consist of an initial 2-month intensive phase of a 4-drug regimen, followed by a continuation phase of an additional 4 to 7 months of isoniazid and rifampin. Pyrazinamide frequency and dosing differs depending on treatment regimen selected; consult current drug-sensitive TB guidelines for detailed information (ATS/CDC/IDSA [Nahid 2016]).
ATS/CDC/IDSA Recommendations (ATS/CDC/IDSA [Nahid 2016]):
Once daily or 5-times-weekly (DOT):
Infants, Children, and Adolescents weighing <40 kg: Oral: 35 mg/kg/dose once daily or 5 times weekly DOT; suggested range: 30 to 40 mg/kg/dose
Children and Adolescents weighing ≥40 kg: Note: Doses should be based on lean body weight for patients within a normal weight range for their height (optimal dosing for obese patients has not been established): Oral: Weight-band dosing for whole tablets:
40 to 55 kg: 1,000 mg (18.2 to 25 mg/kg/dose) once daily or 5-times-weekly (DOT)
56 to 75 kg: 1,500 mg (20 to 28.6 mg/kg/dose) once daily or 5-times-weekly (DOT)
76 to 90 kg: 2,000 mg (22.2 to 26.3 mg/kg/dose) once daily or 5-times-weekly (DOT)
Three-times-weekly DOT: Note: Although suggested dosing based on experience with twice-weekly regimen; experts suggest three-times-weekly regimens are more effective than twice-weekly DOT regimens; pyrazinamide-containing three-times-weekly DOT may be used as part of an intensive phase; consult guidelines for specific information
Infants, Children, and Adolescents weighing <40 kg: Oral: 50 mg/kg/dose three times weekly
Children and Adolescents weighing ≥40 kg: Note: Doses should be based on lean body weight for patients within a normal weight range for their height (optimal dosing for obese patients has not been established) Oral: Weight-band dosing for whole tablets:
40 to 55 kg: 1,500 mg (27.3 to 37.5 mg/kg/dose) three-times-weekly
56 to 75 kg: 2,500 mg (33.3 to 44.6 mg/kg/dose) three-times-weekly
76 to 90 kg: 3,000 mg (33.3 to 39.5 mg/kg/dose) three-times-weekly
Twice-weekly DOT: Note: Regimen not generally recommended; do not use in HIV patients or those with smear-positive and/or cavitary disease. This therapy should only be used following completion of a 2-week intensive phase once-daily (or 5-times-weekly) regimen. Missed doses result in the equivalent of once-weekly dosing which has been shown to be inferior and is associated with treatment failure, relapse, and development of drug resistance.
Infants, Children, and Adolescents weighing <40 kg: Oral: 50 mg/kg/dose twice weekly
Children and Adolescents weighing >40 kg: Oral:
40 to 55 kg: 2,000 mg (36.4 to 50 mg/kg/dose) twice weekly
56 to 75 kg: 3,000 mg (40 to 53.6 mg/kg/dose) twice weekly
76 to 90 kg: 4,000 mg (44.4 to 52.6 mg/kg/dose) twice weekly
There are no pediatric specific recommendations; based on experience in adult patients, dosing adjustment suggested
There are no dosage adjustments provided in the manufacturer’s labeling. Use is contraindicated in cases of severe hepatic impairment.
(For additional information see "Pyrazinamide: Drug information")
Tuberculosis, treatment (drug-susceptible): Oral: Note: Always administer in combination with other antitubercular drugs (AST/CDC/IDSA [Nahid 2016]).
Dosing: Doses should be based on lean body weight for patients within a normal weight range for their height (optimal dosing for obese patients has not been established) (AST/CDC/IDSA [Nahid 2016]):
Once-daily therapy (ATS/CDC/IDSA [Nahid 2016]):
40 to 55 kg: 1,000 mg once daily Note: The preferred frequency of administration is once daily; however, 5-days per week administration by directly-observed therapy (DOT) is an acceptable alternative.
56 to 75 kg: 1,500 mg once daily.
76 to 90 kg: 2,000 mg once daily.
Three-times-weekly DOT (ATS/CDC/IDSA [Nahid 2016]):
40 to 55 kg: 1,500 mg 3 times weekly.
56 to75 kg: 2,500 mg 3 times weekly.
76 to 90 kg: 3,000 mg 3 times weekly.
Twice-weekly DOT (ATS/CDC/IDSA [Nahid 2016]):
40 to 55 kg: 2,000 mg twice weekly.
56 to 75 kg: 3,000 mg twice weekly.
76 to 90 kg: 4,000 mg twice weekly.
Regimens: Treatment regimens for pulmonary tuberculosis and tuberculous meningitis consist of an initial 2-month phase of a 4-drug regimen that includes pyrazinamide, followed by a continuation phase of a 2-drug regimen (does not include pyrazinamide) of an additional 4 to 7 months for pulmonary tuberculosis and a continuation phase of an additional 7 to 10 months of a 2-drug regimen (does not include pyrazinamide) for tuberculous meningitis (optimal duration is not defined although continuation phase must continue for a minimum of 7 additional months). Adjunctive corticosteroid therapy (eg, dexamethasone, prednisolone) tapered over 6 to 8 weeks is also recommended for tuberculous meningitis; pyrazinamide frequency and dosing differs depending on treatment regimen selected; consult current drug-sensitive TB guidelines (ATS/CDC/IDSA [Nahid 2016]).
Tuberculosis, treatment (drug-resistant) (alternative agent):
Note: Expert consultation for optimal regimen and duration of treatment is advised.
Oral: 25 to 40 mg/kg once daily (AST/CDC/IDSA [Nahid 2019]).
CrCl <30 mL/minute or receiving intermittent hemodialysis: Treatment of drug-susceptible tuberculosis: 25 to 35 mg/kg/dose 3 times per week administered after dialysis (do not administer daily) (ATS/CDC/IDSA [Nahid 2016]).
There are no dosage adjustments provided in the manufacturer's labeling. Use is contraindicated in cases of severe hepatic impairment.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 500 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Tebrazid: 500 mg
Generic: 500 mg
Oral: May take without regard to food (Zent 1995).
Oral: May take without regard to food (Zent 1995).
Store at controlled room temperature of 15°C to 30°C (59°F to 86°F).
Adjunctive treatment of Mycobacterium tuberculosis infection in combination with other antituberculosis agents (FDA approved in children and adults)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Central nervous system: Malaise
Gastrointestinal: Anorexia, nausea, vomiting
Neuromuscular & skeletal: Arthralgia, myalgia
<1%, postmarketing, and/or case reports: Acne vulgaris, acquired blood coagulation disorder (anticoagulant effect), angioedema (rare), dysuria, fever, gout, hepatotoxicity, interstitial nephritis, porphyria, pruritus, sideroblastic anemia, skin photosensitivity, skin rash, thrombocytopenia, urticaria
Hypersensitivity to pyrazinamide or any component of the formulation; acute gout; severe hepatic damage
Concerns related to adverse effects:
• Hepatotoxicity: Dose-related hepatotoxicity ranging from transient ALT/AST elevations to jaundice, hepatitis and/or liver atrophy (rare) has occurred.
Disease-related concerns:
• Alcoholism: Due to concerns for preexisting hepatic dysfunction, use with caution in patients with a history of alcoholism (even if ethanol consumption is discontinued during therapy).
• Diabetes: Use with caution in patients with diabetes mellitus.
• Gout: May inhibit uric acid excretion; acute gouty attacks have been reported. Use with caution in patients with chronic gout; contraindicated with acute gout.
• Porphyria: Use with caution in patients with porphyria.
• Renal impairment: Use with caution in patients with renal failure.
Concurrent drug therapy issues:
• Hepatotoxic agents: Use with caution in patients receiving concurrent medications associated with hepatotoxicity (particularly with rifampin). The 2-month rifampin-pyrazinamide regimen for the treatment of latent tuberculosis infection (LTBI) has been associated with severe and fatal liver injuries; incidence increased with pyrazinamide doses >30 mg/kg/day. The Infectious Diseases Society of America and Centers for Disease Control and Prevention recommend that the 2-month rifampin-pyrazinamide regimen should not generally be used in patients with LTBI.
None known.
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Benzbromarone: Pyrazinamide may diminish the therapeutic effect of Benzbromarone. Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
CycloSPORINE (Systemic): Pyrazinamide may enhance the myopathic (rhabdomyolysis) effect of CycloSPORINE (Systemic). Pyrazinamide may decrease the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
Favipiravir: May enhance the adverse/toxic effect of Pyrazinamide. Specifically, the risk for increased uric acid concentrations may be increased. Risk C: Monitor therapy
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
RifAMPin: Pyrazinamide may enhance the hepatotoxic effect of RifAMPin. Severe (even fatal) liver injury has been reported in patients receiving these 2 drugs as a 2-month treatment regimen for latent TB infection. Management: Rifampin-pyrazinamide is generally not preferred for the treatment of latent tuberculosis (TB) due to the risk of hepatotoxicity. However, it is an option for patients at high risk of developing active TB who are unlikely to complete preferred treatment. Risk D: Consider therapy modification
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Evaluate pregnancy status prior to treatment of multidrug-resistant tuberculosis in females of reproductive potential. Females of reproductive potential should use effective contraception during treatment for multidrug-resistant tuberculosis (Esmail 2018).
Active tuberculosis infection is associated with adverse fetal outcomes including intrauterine growth restriction, low birth weight, preterm birth, and perinatal death (Esmail 2018; Miele 2020) as well as adverse maternal outcomes, including increased risks for anemia and cesarean delivery. Placental transmission may rarely occur with active maternal disease (Miele 2020).
Due to the risks of untreated tuberculosis, pyrazinamide may be used as part of the initial treatment regimen of drug-susceptible active tuberculosis when the probability of maternal disease is moderate to high; however, risks and benefits of use during pregnancy should be considered for each individual patient. The addition of pyrazinamide may be of benefit in pregnant patients with HIV, extrapulmonary or severe tuberculosis (ATS/CDC/IDSA [Nahid 2016]).
Use of pyrazinamide may also be considered in the treatment of multidrug-resistant tuberculosis. The treatment of multidrug-resistant tuberculosis in pregnant patients should be individualized; evidence to support a specific regimen is not available (ATS/CDC/ERS/IDSA [Nahid 2019]; WHO 2020).
Pregnancy-induced physiologic changes do not alter the pharmacokinetic properties of pyrazinamide in a clinically significant way; dose adjustment is not needed in pregnant patients (Abdelwahab 2020).
Periodic liver function tests, serum uric acid
Converted to pyrazinoic acid in susceptible strains of Mycobacterium which lowers the pH of the environment; exact mechanism of action has not been elucidated
Note: Bacteriostatic or bactericidal depending on drug's concentration at infection site
Absorption: Well absorbed
Distribution: Widely into body tissues and fluids including liver, lung, and CSF
Relative diffusion from blood into CSF: Adequate with or without inflammation (exceeds usual MICs)
CSF:blood level ratio: Inflamed meninges: 100%
Protein binding: 50%
Metabolism: Hepatic
Half-life elimination: 9 to 10 hours, prolonged with reduced renal or hepatic function
Time to peak, serum: Within 2 hours
Excretion: Urine (4% as unchanged drug)
100 mg/mL Oral Suspension (ASHP Standard Concentration) (ASHP 2017)
A 100 mg/mL oral suspension may be made with tablets. Crush two-hundred pyrazinamide 500 mg tablets and mix with a suspension containing 500 mL methylcellulose 1% and 500 mL simple syrup. Add to this a suspension containing one-hundred forty crushed pyrazinamide tablets in 350 mL methylcellulose 1% and 350 mL simple syrup to make 1.7 L suspension. Label "shake well" and "refrigerate". Stable for 60 days refrigerated (preferred) and 45 days at room temperature.
Tablets (Pyrazinamide Oral)
500 mg (per each): $6.15 - $6.50
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