Pyrazinamide

Registered South African indications:

• Tuberculosis

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Breastfeeding
• Hepatic disease
• Hyperuricaemia and/or gouty arthritis
• Acute porphyria

Cautions 

• Pregnancy
• Severe renal impairment
• Hepatic impairment
• Gout 
• Diabetes mellitus

Forms avail. in SA and covered in this monograph: tab

Drug sensitive mycobacterium tuberculosis (in combination with other medication)

Less than 30kg

• Oral (tab): 20-30mg/kg; Max: 2g/24hrs

Between 30-37kg

• Oral (tab): 800mg, dly; Max: 2g/24hrs

Between 38-54kg

• Oral (tab): 1200mg, dly; Max: 2g/24hrs

Between 55-70kg

• Oral (tab): 1600mg, dly; Max: 2g/24hrs

Greater than 71kg

• Oral (tab): 2000mg, dly; Max: 2g/24hrs

Drug resistant mycobacterium tuberculosis (in combination with other medication)

Less than 30kg

• Oral (tab): 30-40mg/kg; Max: 2,5g/24hrs

Between 33-50kg

• Oral (tab): 1000-1750mg, dly; Max: 2,5g/24hrs

Between 51-70kg

• Oral (tab): 1750-2000mg, dly; Max: 2,5g/24hrs

Greater than 70kg

• Oral (tab): 2000-2500mg, dly; Max: 2,5g/24hrs

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From intensive phase until at least 18 months after tuberculous culture conversion

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Isoniazid monoresistant tuberculosis

• Oral (tab): 25mg/kg, dly

Paed. forms avail. in SA and covered in this monograph: tab

Drug sensitive tuberculosis

Younger than 8 years and less than 30kg

• Oral (tab): 30-40mg/kg, dly; Max: 2g/24hrs 

Weight	Dose (mg)
2-2.9kg	75
3-3.9kg	125
4-5.9kg	150
6-7.9kg	250
8-11.9kg	250
12-14.9kg	500
15-19.9kg	500
20-24.9kg	750
25-29.9kg	1000

Older than 8 years and greater than 30kg

• See adult dosage

Drug resistant tuberculosis

• Oral (tab): 30-40mg/kg, dly; Max: 2g/24hrs 

Decisions related to dose adjustment/discontinuing TB regimen must be discussed in advance with Pulmonologists/Infectious Disease specialists, and cases must be dealt with individually

Pregnancy 

• Caution
• There have been no well-controlled studies in pregnant women. Pyrazinamide continuation as part of TB treatment is recommended. Do not exceed maximum doses

Breastfeeding 

• Contraindicated

Renal Impairment

• eGFR ≥30-89ml/min/1.73m²: No dose adjustment recommended 
• eGFR ≤29ml/min/1.73m² or scheduled dialysis: Caution; dose adjustment recommended
  25-35 mg/kg/dose (lean body weight), 3 times per week
  Administer after dialysis session for target patients
  Daily dosing must be avoided

Hepatic Impairment

• Mild to severe: Caution; dose adjustment recommended 
  Baseline (pre-therapy) LFT is recommended for safety and monitoring (esp. serum ALT); Doses should be based on lean body weight (LBW/mg)
  PZA-DILI (Pyrazinamide/Drug-Induced Liver Injury):
  All potentially offending agents should be stopped (incl. other anti-TB agents and ARVs), and re-introduced (re-challenged) in the following order: Rifampicin, Isoniazid, Pyrazinamide, Ethambutol
  On day 9: Re-introduce Pyrazinamide 250mg/day (as 3rd rechallenge agent after Rifampicin and Isoniazid)
  On day 10: Pyrazinamide 1000mg/day
  On day 11: Pyrazinamide full recommended dose
  Discontinue Pyrazinamide as soon as the patient experiences minor skin involvement. No further re-challenge is recommended
• Hepatic disease: Contraindicated

Elderly

• No dose adjustment recommended 

Porphyria Information

• Probably not porphyrinogenic (PNP)
• Acute porphyria: Contraindicated

Drugs in Sport

• Permitted - No warnings

Gastrointestinal Disorders

• Anorexia 
• Nausea and vomiting 
• Peptic ulcer 

Hepatobiliary Disorders

• Hepatic reaction
• Liver tenderness
• Hepatomegaly 
• Splenomegaly
• Jaundice
• Hepatic failure 

Genitourinary Disorders

• Dysuria 

Musculoskeletal Disorders

• Gout 
• Arthralgia

Skin and Subcutaneous Tissue Disorders

• Flushing
• Rash
• Urticaria 
• Pruritus
• Photosensitivity 

Immune, Blood and Lymphatic System Disorders 

• Sideroblastic anaemia

• Uricosuric agents  
• Oestrogens
• Oral typhoid vaccination

• Renal function
• Hepatic function
• Baseline uric acid levels

Pyrazinamide exhibits tuberculostatic activity. It is active only at an low pH, and it is therefore active mainly on the tubercle bacilli located within the cell. It is these bacteria which are probably responsible for microbial persistence and thus for relapses after chemotherapy has stopped. Pyrazinamide has low bacterial activity compared with isoniazid. It is thought that when these are used in combination, isoniazid is the key bactericidal drug, whilst pyrazinamide has a sterilising role, acting on a special bacterial population inhibited by the acid environment inside the macrophage or the walls of tuberculous cavities.

Tablet 500mg

• Macleods Pyrazinamide (Macleods)
• Sandoz Pyrazinamide (Sandoz)
• Pyrazide (Sanofi)

COMBINATION PREPARATIONS

Isoniazid/ Rifampicin/ Pyrazinamide/ Ethambutol hcl

Tablet 75mg/150mg/400mg/275mg

• Antib-4 (Medicine Dev)
• Rifafour E-275 (Sanofi)
• Rimstar 4-Fdc (Sandoz)

Isoniazid/ Rifampicin/ Pyrazinamide

Tablet 30mg/60mg/150mg

• Rimcure Paed 3-Fdc (Sandoz)