|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
Pronunciation
(peer a ZIN a mide)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Adjunctive treatment of tuberculosis in combination with other antituberculosis agents
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic effects have not been observed in animal reproduction studies. Due to the risk of tuberculosis to the fetus, treatment is recommended when the probability of maternal disease is moderate to high. Although not recommended as the initial treatment regimen, the use of pyrazinamide during pregnancy is recommended by The World Health Organization (Blumberg, 2003).
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
Low concentrations of pyrazinamide have been detected in breast milk; concentrations are less than maternal plasma concentration (Holdiness, 1984). The amount of drug in breast milk is considered insufficient for the treatment of tuberculosis in breast-fed infants.
Contraindications
Hypersensitivity to pyrazinamide or any component of the formulation; acute gout; severe hepatic damage
Warnings/Precautions
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 pre-existing 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).
Adverse Reactions
1% to 10%:
Central nervous system: Malaise
Gastrointestinal: Anorexia, nausea, vomiting
Neuromuscular & skeletal: Arthralgia, myalgia
<1%: Acne, angioedema (rare), anticoagulant effect, dysuria, fever, gout, hepatotoxicity, interstitial nephritis, itching, photosensitivity, porphyria, rash, sideroblastic anemia, thrombocytopenia, urticaria
Metabolism/Transport Effects
None known.
Drug Interactions
CycloSPORINE: Pyrazinamide may decrease the serum concentration of CycloSPORINE. Risk C: Monitor therapy
CycloSPORINE (Systemic): Pyrazinamide may increase the serum concentration of CycloSPORINE (Systemic). 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. Risk D: Consider therapy modification
Storage
Store at controlled room temperature of 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Converted to pyrazinoic acid in susceptible strains of Mycobacterium which lowers the pH of the environment; exact mechanism of action has not been elucidated
Pharmacodynamics/Kinetics
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: 9-10 hours
Time to peak, serum: Within 2 hours
Excretion: Urine (4% as unchanged drug)
Dosage
Oral: Treatment of tuberculosis:
Note: Used as part of a multidrug regimen. Treatment regimens consist of an initial 2-month phase, followed by a continuation phase of 4 or 7 additional months; pyrazinamide is administered in the initial phase of treatment.
Children:
HIV negative (CDC, 2003):
Daily therapy: 15-30 mg/kg/day (maximum: 2 g/day)
Twice weekly directly observed therapy (DOT): 50 mg/kg/dose (maximum: 2 g/dose)
HIV-exposed/-infected: Daily therapy: 20-40 mg/kg/dose once daily (maximum: 2 g/day) (CDC, 2009)
Adults: Suggested dosing based on lean body weight (Blumberg, 2003; CDC, 2003):
Daily therapy:
40-55 kg: 1000 mg
56-75 kg: 1500 mg
76-90 kg: 2000 mg (maximum dose regardless of weight)
Twice weekly directly observed therapy (DOT):
40-55 kg: 2000 mg
56-75 kg: 3000 mg
76-90 kg: 4000 mg (maximum dose regardless of weight)
Three times/week DOT:
40-55 kg: 1500 mg
56-75 kg: 2500 mg
76-90 kg: 3000 mg (maximum dose regardless of weight)
Dosing adjustment in renal impairment: Adults: Clcr <30 mL/minute or receiving hemodialysis: Treatment of TB: 25-35 mg/kg/dose 3 times per week administered after dialysis (Blumberg, 2003; CDC, 2003)
Monitoring Parameters
Periodic liver function tests, serum uric acid, sputum culture, chest x-ray 2-3 months into treatment and at completion
Test Interactions
Reacts with Acetest® and Ketostix® to produce pinkish-brown color
Patient Education
You will need regular medical follow-up and laboratory tests while taking this medication. May cause nausea or loss of appetite. Report change in color of urine, pale stools, easy bruising or bleeding, blood in urine or difficulty urinating, yellowing of skin or eyes, extreme joint pain, unusual fever, or unresolved nausea or vomiting.
Geriatric Considerations
Pyrazinamide is used in the 2-month intensive treatment phase of a 6-month treatment plan. Most elderly acquired their Mycobacterium tuberculosis infection before effective chemotherapy was available; however, older persons with new infections (not reactivation), or who are from areas where drug-resistant M. tuberculosis is endemic, or who are HIV-infected should receive 3-4 drug therapies including pyrazinamide.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause drowsiness
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Assess patient history for use cautions and evaluate any history of alcohol intake prior to beginning treatment. Administer with at least one other effective agent for tuberculosis (other than rifampin). Evaluate results of chest x-ray regularly.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral: 500 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Pyrazinamide)
500 mg (30): $47.24
Extemporaneously Prepared
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.
Nahata MC, Morosco RS, and Peritre SP, “Stability of Pyrazinamide in Two Suspensions,” Am J Health Syst Pharm, 1995, 52(14):1558-60.
References
Ad Hoc Committee of the Scientific Assembly on Microbiology, Tuberculosis and Pulmonary Infections, “Treatment of Tuberculosis and Tuberculosis Infection in Adults and Children,” Clin Infect Dis, 1995, 21:9-27.
American Academy of Pediatrics, Committee on Infectious Diseases, “Chemotherapy for Tuberculosis in Infants and Children,” Pediatrics, 1992, 89(1):161-5.
American Thoracic Society, “Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection,” MMWR Recomm Rep, 2000, 49(RR-6):1-51.
Bass JB Jr, Farer LS, Hopewell PC, et al, “Treatment of Tuberculosis and Tuberculosis Infection in Adults and Children,” Am J Respir Crit Care Med, 1994, 149(5):1359-74.
Blumberg HM, Burman WJ, Chaisson RE, et al, “American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Treatment of Tuberculosis,” Am J Respir Crit Care Med, 2003, 167(4):603-62.
Centers for Disease Control and Prevention (CDC) and American Thoracic Society, “Update: Adverse Event Data and Revised American Thoracic Society/CDC Recommendations Against the Use of Rifampin and Pyrazinamide for Treatment of Latent Tuberculosis Infection - United States, 2003,” MMWR, 2003, 52(31):735-9. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5231a4.htm. Last accessed February 16, 2005.
Centers for Disease Control and Prevention, “Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Children: Recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics,” MMWR Recomm Rep, 2009, 58(RR-11):1-166. Available at http://aidsinfo.nih.gov/contentfiles/Pediatric_OI.pdf.
Centers for Disease Control and Prevention, “Treatment of Tuberculosis. American Thoracic Society, CDC, and Infectious Diseases Society of America,” MMWR Recomm Rep, 2003, 52(RR-11):1-77.
Combs DL, O'Brien RJ, and Geiter LJ, “USPHS Tuberculosis Short-Course Chemotherapy Trial 21: Effectiveness, Toxicity, and Acceptability: The Report of Final Results,” Ann Intern Med, 1990, 112(6):397-406.
Davidson PT and Le HQ, “Drug Treatment of Tuberculosis - 1992,” Drugs, 1992, 43(5):651-73.
“Drugs for Tuberculosis,” Med Lett Drugs Ther, 1993, 35(908):99-101.
Havlir DV and Barnes PF, “Tuberculosis in Patients With Human Immunodeficiency Virus Infection,” N Engl J Med, 1999, 340(5):367-73.
Herlevsen P, Nielsen C, and Pedersen JT, “Convulsions After Treatment With Pyrazinamide,” Tubercle, 1987, 68(2):145-6.
Holdiness MR, "Antituberculosis Drugs and Breast-Feeding," Arch Intern Med, 1984, 144(9):1888.
Iseman MD, “Treatment of Multidrug-Resistant Tuberculosis,” N Engl J Med, 1993, 329(11):784-91.
Lacroix C, Hoang TP, Nouveau J, et al, “Pharmacokinetics of Pyrazinamide and Its Metabolites in Healthy Subjects,” Eur J Clin Pharmacol, 1989, 36(4):395-400.
“Prevention and Treatment of Tuberculosis Among Patients Infected With Human Immunodeficiency Virus: Principles of Therapy and Revised Recommendations. Centers for Disease Control and Prevention,” MMWR Recomm Rep, 1998, 47(RR-20):1-58.
Starke JR and Correa AG, “Management of Mycobacterial Infection and Disease in Children,” Pediatr Infect Dis J, 1995, 14(6):455-70.
Starke JR, “Modern Approach to the Diagnosis and Treatment of Tuberculosis in Children,” Pediatr Clin North Am, 1988, 35(3):441-64.
Starke JR, “Multidrug Therapy for Tuberculosis in Children,” Pediatr Infect Dis J, 1990, 9(11):785-93.
“Treatment of Latent Tuberculosis Infection (LTBI), Last Updated: April 8, 2004.” Available at http://www.cdc.gov/nchstp/tb/pubs/tbfactsheets/250110.htm. Last accessed February 16, 2005.
Van Scoy RE and Wilkowske CJ, “Antituberculous Agents,” Mayo Clin Proc, 1992, 67(2):179-87.
Yoshikawa TT, “Tuberculosis in Aging Adults,” J Am Geriatr Soc, 1992, 40(2):178-87.
International Brand Names
Lexi-Comp.com
Last full review/revision January 2012
Content last modified January 2012
| 
