(peer a ZIN a mide)
Adjunctive treatment of tuberculosis in combination with other antituberculosis agents
Hypersensitivity to pyrazinamide or any component of the formulation; acute gout; severe hepatic damage
Tuberculosis treatment: Oral: 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.
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)
Tuberculosis treatment: Oral: 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.
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: CrCl <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)
No dosage adjustment provided in manufacturer 's labeling. Use is contraindicated in cases of severe hepatic impairment.
Store at controlled room temperature of 15 � �C to 30 � �C (59 � �F to 86 � �F).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 500 mg
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.[PMID: 7552903]Benzbromarone: Pyrazinamide may diminish the therapeutic effect of Benzbromarone. Monitor therapy
CycloSPORINE (Systemic): Pyrazinamide may decrease the serum concentration of CycloSPORINE (Systemic). 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. Consider therapy modification
Periodic liver function tests, serum uric acid, sputum culture, chest x-ray 2-3 months into treatment and at completion
Reacts with Acetest � � and Ketostix � � to produce pinkish-brown color
1% to 10%:
Central nervous system: Malaise
Gastrointestinal: Anorexia, nausea, vomiting
Neuromuscular & skeletal: Arthralgia, myalgia
<1% (Limited to important or life-threatening): Acne, angioedema (rare), anticoagulant effect, dysuria, fever, gout, hepatotoxicity, interstitial nephritis, itching, photosensitivity, porphyria, rash, sideroblastic anemia, thrombocytopenia, urticaria
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.
C
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).
Converted to pyrazinoic acid in susceptible strains of Mycobacterium which lowers the pH of the environment; exact mechanism of action has not been elucidated
Well absorbed
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%
Hepatic
Urine (4% as unchanged drug)
Serum: Within 2 hours
9 to 10 hours, prolonged with reduced renal or hepatic function
50%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), severe bone pain, severe joint pain, severe muscle pain, urinary retention, or change in amount of urine passed (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.