pyrazinamide

Converted to pyrazinoic acid in susceptible strains of Mycobacterium, which lowers the pH of the environment.

Therapeutic effects:

Bacteriostatic action against susceptible mycobacteria.

Spectrum:

Active against mycobacteria only.

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed after oral administration.

Distribution: Widely distributed. Reaches high concentrations in the CNS (same as plasma).

Metabolism/Excretion: Mostly metabolized by the liver. Metabolite (pyrazinoic acid) has antimycobacterial activity; 3–4% excreted unchanged by the kidneys.

Half-Life: Pyrazinamide: 9.5 hr. Pyrazinoic acid: 12 hr. Both are ↑ in renal impairment.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1–2 hr (4–5 hr‡)	24 hr

‡For pyrazinoic acid.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Cross-sensitivity with ethionamide, isoniazid, niacin, or nicotinic acid may exist;
Severe hepatic impairment.

Use Cautiously in:

Gout;
Renal failure;
Diabetes mellitus;
Acute intermittent porphyria;
OB: Use during pregnancy only if clearly needed;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: acne, photosensitivity, rash

GI: anorexia, diarrhea, HEPATOTOXICITY, nausea, vomiting

GU: dysuria

Hemat: anemia, thrombocytopenia

Metab: hyperuricemia

MS: arthralgia, gouty arthritis

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with rifampin may result in life-threatening hepatotoxicity; avoid concurrent use.
May ↓ levels and effectiveness of cyclosporine.
May ↓ effectiveness of antigout agents.

Route/Dosage ⬆ ⬇

PO (Adults and Children ): 15–30 mg/kg/day as a single dose. Up to 60 mg/kg/day has been used in isoniazid-resistant TB (not to exceed 2 g/day as a single dose or 3 g/day in divided doses). May also be given as 50–70 mg/kg 2–3 times weekly (not to exceed 2 g/dose on daily regimen, 3 g/dose for 3-times-weekly regimen, or 4 g/dose for twice-weekly regimen). Patients with HIV: 20–40 mg/kg/day for first 2 mo of therapy (maximum: 2 g/day); further dosing depends on regimen employed.

Availability ⬆ ⬇

(Generic available)

Tablets: 500 mg

Assessment ⬆ ⬇

Perform mycobacterial studies and susceptibility tests before and periodically during therapy to detect possible resistance.

Lab Test Considerations:

Evaluate hepatic function before and every 2–4 wk during therapy. Increased AST and ALT may not be predictive of clinical hepatitis and may return to normal levels during treatment. Patients with impaired liver function should receive pyrazinamide therapy only if crucial to treatment.
- Monitor serum uric acid concentrations during therapy. May cause ↑ resulting in precipitation of acute gout.
- May interfere with urine ketone determinations.

Implementation ⬆ ⬇

PO: May be given concurrently with isoniazid.

Patient/Family Teaching ⬆ ⬇

Advise patient to take medication as directed and not to skip doses or double up on missed doses. Take missed doses as soon as remembered unless almost time for next dose. Emphasize the importance of continuing therapy even after symptoms have subsided. Length of therapy depends on regimen being used and underlying disease states.
Inform patients with diabetes that pyrazinamide may interfere with urine ketone measurements.
Advise patients to notify health care professional if no improvement is noticed after 2–3 wk of therapy or if fever, anorexia, malaise, nausea, vomiting, darkened urine, yellowish discoloration of the skin and eyes, pain, or swelling of the joints occurs.
Advise patients to use sunscreen and protective clothing to prevent photosensitivity reactions.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Monitor infants exposed to pyrazinamide via breast milk for jaundice.
Emphasize the importance of regular follow-up exams to monitor progress and check for side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇