Drugs List

Therapeutic Indications

Uses

Active tuberculosis caused by mycobacterium tuberculosis(adjunct treatment)

Contraindications

Acute gout attack
Hyperuricaemia
Severe hepatic impairment

Precautions and Warnings

Acute porphyria
Breastfeeding
Diabetes mellitus
History of alcohol abuse
History of gout
Mild hepatic impairment
Pregnancy
Renal impairment

Reduce dose and/or alter dose interval in patients with renal impairment
Must be used in combination with other anti-tuberculous drugs
Monitor renal and hepatic function before and during treatment
Take cultures for sensitivity testing before and regularly during treatment
Monitor patients at risk of gout
Monitor uric acid levels
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Advise patients to seek medical advice if signs of hepatotoxicity occur
Consider discontinuing treatment if ALT/AST > 5 times upper limit of normal
Discontinue immediately following signs of acute hepatotoxicity
May cause hyperuricaemia
Discontinue and do not restart if hyperuricaemia + gouty arthritis develop

Monitor hepatic function prior to therapy and then every two to four weeks during therapy. Discontinue and do not reinstate therapy if signs of hepatocellular damage occur.

Use in Porphyria

Use with caution in patients with acute porphyria.

The manufacturer contraindicates pyrazinamide in patients with acute porphyria. The European Porphyria Network lists pyrazinamide on drugs unsafe to use in the acute porphyrias. However, the Drug Database for Acute Porphyria (NAPOs) list pyrazinamide as probably not porphyrinogenic, suggesting it is most probably neither an inducer or an inhibitor of CYP enzymes.

Pregnancy and Lactation

Pregnancy

Pyrazinamide should only be used during pregnancy if the potential benefits outweigh the potential risk to the foetus.

The risk of therapy is not known due to a lack of specific human clinical data and in the absence of animal studies.

Briggs suggests because active tuberculosis is a far greater risk to the foetus than the drug, pyrazinamide should not be withheld in pregnancy.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

The manufacturer suggests pyrazinamide is contraindicated during pregnancy. If it use is deemed essential, the patient should stop breastfeeding.

Briggs suggests breastfed infants should be monitored for rare cases of jaundice, fever, loss of appetite, nausea and vomiting, thrombocytopenia, rash and arthralgia.

The amount of pyrazinamide excreted in breast milk is insufficient to treat tuberculosis in the breastfed infant.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Aggravation of peptic ulcer
Anorexia
Arthralgia
Death
Dysuria
Fever
Flushing
Gout
Hepatic failure
Hepatic impairment
Hepatic tenderness
Hepatocellular damage
Hepatomegaly
Hypersensitivity reactions
Jaundice
Malaise
Nausea
Photosensitivity
Pruritus
Rash
Sideroblastic anaemia
Splenomegaly
Urticaria
Vomiting

Presentation

Tablets containing pyrazinamide

Drugs List

Therapeutic Indications

Uses

Active tuberculosis caused by mycobacterium tuberculosis(adjunct treatment)

Dosage

Multi-resistant M. tuberculosis may be present in immunocompromised patients. The organism should be cultured to confirm its type and drug sensitivity. Confirmed M. tuberculosis infection sensitive to first line drugs should be treated with a standard six month regimen. Patients should be closely monitored after completing treatment.

In meningeal or pericardial tuberculosis, a corticosteroid should be started at the same time as anti-tuberculosis therapy.

Adults

Children

Patients with Renal Impairment

Contraindications

Acute gout attack
Hyperuricaemia
Severe hepatic impairment

Precautions and Warnings

Acute porphyria
Breastfeeding
Diabetes mellitus
History of alcohol abuse
History of gout
Mild hepatic impairment
Pregnancy
Renal impairment

Reduce dose and/or alter dose interval in patients with renal impairment
Must be used in combination with other anti-tuberculous drugs
Monitor renal and hepatic function before and during treatment
Take cultures for sensitivity testing before and regularly during treatment
Monitor patients at risk of gout
Monitor uric acid levels
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Advise patients to seek medical advice if signs of hepatotoxicity occur
Consider discontinuing treatment if ALT/AST > 5 times upper limit of normal
Discontinue immediately following signs of acute hepatotoxicity
May cause hyperuricaemia
Discontinue and do not restart if hyperuricaemia + gouty arthritis develop

Monitor hepatic function prior to therapy and then every two to four weeks during therapy. Discontinue and do not reinstate therapy if signs of hepatocellular damage occur.

Use in Porphyria

Use with caution in patients with acute porphyria.

The manufacturer contraindicates pyrazinamide in patients with acute porphyria. The European Porphyria Network lists pyrazinamide on drugs unsafe to use in the acute porphyrias. However, the Drug Database for Acute Porphyria (NAPOs) list pyrazinamide as probably not porphyrinogenic, suggesting it is most probably neither an inducer or an inhibitor of CYP enzymes.

Pregnancy and Lactation

Pregnancy

Pyrazinamide should only be used during pregnancy if the potential benefits outweigh the potential risk to the foetus.

The risk of therapy is not known due to a lack of specific human clinical data and in the absence of animal studies.

Briggs suggests because active tuberculosis is a far greater risk to the foetus than the drug, pyrazinamide should not be withheld in pregnancy.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

The manufacturer suggests pyrazinamide is contraindicated during pregnancy. If it use is deemed essential, the patient should stop breastfeeding.

Briggs suggests breastfed infants should be monitored for rare cases of jaundice, fever, loss of appetite, nausea and vomiting, thrombocytopenia, rash and arthralgia.

The amount of pyrazinamide excreted in breast milk is insufficient to treat tuberculosis in the breastfed infant.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Aggravation of peptic ulcer
Anorexia
Arthralgia
Death
Dysuria
Fever
Flushing
Gout
Hepatic failure
Hepatic impairment
Hepatic tenderness
Hepatocellular damage
Hepatomegaly
Hypersensitivity reactions
Jaundice
Malaise
Nausea
Photosensitivity
Pruritus
Rash
Sideroblastic anaemia
Splenomegaly
Urticaria
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: April 2013

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Zinamide 500 mg tablets. Genus Pharmaceuticals. Revised August 2010.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

European Porphyria Network.
Available at https://www.porphyria-europe.com/03-drugs/selecting-drug-unsafe.asp
Pyrazinamide.
Last accessed: March 14, 2014.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 14 September 2017

The Drug Database for Acute Porphyria (NAPOs).
Available at https://www.drugs-porphyria.org/languages/UnitedKingdom/s1.php?l=gbr
Pyrazinamide. Last revised: July 19, 2013.
Last accessed: March 14, 2014.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Pyrazinamide. Last revised: January 4, 2011
Last accessed: April 15, 2013