Pyrazinamide (pyrazinamide)

No dosing information is available for this tab.

Pyrazinamide is administered orally. The fixed-combination preparation containing isoniazid, rifampin, and pyrazinamide (Rifater(R)) should be given either 1 hour before or 2 hours after a meal with a full glass of water.

There is no enhanced messaging for this drug.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Antibiotics/Fecal Microbiota

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota is a suspension of live bacteria, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota. Antibacterial treatment should be completed for 24 to 72 hours before initiating treatment with fecal microbiota. Do not use antibiotics for up to 8 weeks after fecal microbiota.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota.

Antibiotics/Fecal Microbiota Spores

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota spores is a suspension of live bacterial spores, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota spores.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota spores. Antibacterial treatment should be completed for 2 to 4 days before initiating treatment with fecal microbiota spores.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota spores.

Antimicrobials/Live Typhoid Vaccine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The antimicrobial may be active against the organism in the live-vaccine. Antimicrobial therapy may prevent the vaccine organism from replicating enough to trigger an immune response.(1)

CLINICAL EFFECTS: Vaccination may be ineffective.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Do not give oral typhoid vaccine until 72 hours after the last dose of antimicrobial. If possible, to optimize vaccine effectiveness, do not start antibacterial drugs for 72 hours after the last dose of oral typhoid vaccine. A longer interval should be considered for long-acting antimicrobials, such as azithromycin.(3)

DISCUSSION: Because antimicrobial therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of live-attenuated typhoid vaccine and the Centers for Disease Control (CDC) state that the vaccine should not be administered to patients receiving antimicrobial therapy.(1-3)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Pyrazinamide/Rifampin

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The concurrent use of rifampin and pyrazinamide for the treatment of latent tuberculosis (TB prophylaxis) may result in additive or synergistic hepatotoxicity.(1,2)

CLINICAL EFFECTS: The concurrent use of rifampin and pyrazinamide for the treatment of latent tuberculosis (TB prophylaxis) may result in hepatotoxicity and death.(2)

PREDISPOSING FACTORS: Underlying liver disease, concurrent therapy with agents associated with liver injury, alcoholism, and/or a previous history of isoniazid-associated liver injury may predispose patients to liver damage from the combination of rifampin and pyrazinamide when used for the treatment of latent tuberculosis (TB prophylaxis).(1)

PATIENT MANAGEMENT: The combination of rifampin and pyrazinamide is recommended by the Centers for Disease Control (CDC) as part of a standard 4-drug regimen for the treatment of active TB disease.(1,2) The American Thoracic Society (ATS) and the CDC state that the combination of rifampin and pyrazinamide should generally not be offered to patients with latent tuberculosis infection for either HIV-negative or HIV-positive persons.(2) The combination of rifampin and pyrazinamide for the treatment of latent tuberculosis should never be offered to patients who are 1) concurrently taking other medicines associated with liver injury, 2) drink excessive amounts of alcohol (even if alcohol use is discontinued during therapy), 3) have underlying liver disease, or 4) have a history of underlying isoniazid associated liver injury.(2) The combination of rifampin and pyrazinamide for the treatment of latent tuberculosis may be considered if the potential benefit outweigh the risk of severe liver injury and death, but only if 1) the preferred or alternative regimens are not likely to be completed and 2) oversight by a clinician with experience in the treatment of latent tuberculosis can be provided.(1) When used as therapy for latent TB (TB prophylaxis), the ATS and CDC recommend that the combination of rifampin and pyrazinamide be used with the following cautions. No more than a two-week supply of rifampin-pyrazinamide should be dispensed at one time. The daily pyrazinamide dose should not exceed 20 mg/kg/day or a maximum of 2 grams/day and the twice weekly dose should not exceed 50 mg/kg/day or a maximum of 4 grams/day. Patients, serum AT, and bilirubin should be assessed at 2, 4, 6, and 8 weeks of therapy. Therapy should be discontinued and should not be resumed if the AT is 5 times the upper limit of normal range in asymptomatic patients, or if the AT is above normal range when accompanied by symptoms of hepatitis, or if serum bilirubin is greater than the normal range. Patients should be instructed to stop taking the combination and seek medical attention if they develop abdominal pain, emesis, jaundice, or other hepatitis symptoms.(2) These recommendations have been endorsed by the Infectious Diseases Society of America (IDSA).(2)

DISCUSSION: From October of 2000 to June of 2003, 48 cases of liver injury (defined as clinical and laboratory findings consistent with hepatitis leading to hospital admission or death) associated with the combination of rifampin and pyrazinamide for the treatment of latent tuberculosis were were reported to the CDC. Of these 48 cases, 37 patients recovered and 11 died of liver failure. Of these 48 cases, 33% occurred in the second month of treatment. Of the 7,737 patients who started combination rifampin and pyrazinamide during this period, 204 discontinued the regimen because of elevated AST concentration greater than 5 times the upper limit of normal (rate 26.4 per 1,000 initiations) and an additional 146 patients discontinued the regimen because of symptoms of hepatitis (rate 18.9 per 1,000 initiations). The estimated rates of hospitalization and death during this period were 3.0 per 1,000 initiations and 0.9 per 1,000 initiations, respectively.(2)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Pyrazinamide/Probenecid

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Pyrazinamide has been shown to inhibit urate secretion.(1)

CLINICAL EFFECTS: May observe hyperuricemia and gout resulting from reduced probenecid response.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitor patients receiving concurrent probenecid and pyrazinamide for signs and symptoms of gout flares.

DISCUSSION: In a study in 18 males, pyrazinamide inhibited urate secretion, but had no effect on probenecid secretion.(1)

There is no enhanced messaging for this drug.

There are no contraindication contraindications for this drug.

• Alcohol use disorder
• Porphyria
• Severe hepatic disease

• Diabetes mellitus
• Gout

There is no enhanced messaging for this drug.

Rare or Very Rare

• Abnormal hepatic function tests
• Acute gouty arthritis
• Angioedema
• Bronchospastic pulmonary disease
• DRESS syndrome
• Gout
• Hepatitis
• Hypersensitivity drug reaction
• Hyperuricemia
• Hypotension
• Interstitial nephritis
• Jaundice
• Porphyria
• Sideroblastic anemia
• Thrombocytopenic disorder

More Frequent

• Arthralgia
• Myalgia

Less Frequent

• Anorexia
• Nausea
• Vomiting

Rare or Very Rare

• Acne vulgaris
• Conjunctivitis
• Dysuria
• Eosinophilia
• Erythema
• Fever
• Flu-like symptoms
• Neutropenic disorder
• Pruritus of skin
• Skin photosensitivity
• Skin rash
• Urticaria

No enhanced messaging available.

No enhanced messaging available.

Animal reproduction studies have not been performed with pyrazinamide, and it is also not known whether the drug can cause fetal harm when administered to pregnant women or whether it can affect reproduction capacity. Pyrazinamide should be used during pregnancy only when clearly needed. The American Thoracic Society (ATS), US Centers for Disease Control and Prevention (CDC), and Infectious Diseases Society of America (IDSA) state that routine use of pyrazinamide in pregnant women is not recommended. However, the benefits of pyrazinamide may outweigh the possible (but unquantified) risk in some pregnant women with tuberculosis, especially when resistance to other drugs but susceptibility to pyrazinamide is likely.

Because pyrazinamide is distributed into milk in small amounts, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

No enhanced messaging available.