Drugs List

Therapeutic Indications

Uses

Tuberculosis - extra pulmonary
Tuberculosis - pulmonary

Unlicensed Uses

Tuberculosis - prophylaxis

Contraindications

Drug induced hepatic disorder
Galactosaemia

Precautions and Warnings

Acute porphyria
Alcoholism
Breastfeeding
Diabetes mellitus
Epileptic disorder
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of psychosis
Lactose intolerance
Malnutrition
Positive HIV status
Pregnancy
Renal impairment - glomerular filtration rate below 10ml/minute
Seizures
Slow acetylator status

Consult national/regional policy on the use of anti-infectives
Must be used in combination with other anti-tuberculous drugs
Contains lactose
Advise patient to take at least 30 minutes before a meal
Monitor hepatic function before treatment and regularly during treatment
Adverse effects may be seen after ingestion of high-tyramine foods/drinks
Advise patients to discontinue therapy if signs of hepatotoxicity occur
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Consider treatment with pyridoxine to prevent peripheral neuritis
Discontinue if hepatitis develops
May cause convulsions
Discontinue if AST level exceeds 3 times the upper limit of normal
Discontinue if substantial increase in bilirubin occurs
Discontinue if symptoms of hepatic disease occur
Advise patient to seek medical advice before taking paracetamol products
Advise patient of importance of full compliance

Specialist advice should be sought about tuberculosis treatment in immunocompromised patients. Dosage regimens should be chosen carefully and potentially hazardous interactions should be avoided.

Isoniazid may increase the formation of toxic metabolites of paracetamol if paracetamol is taken during isoniazid treatment. Advise patients that they should limit the use of paracetamol-containing products during treatment with isoniazid and, preferably, seek medical advice before taking paracetamol-containing products.

Patients receiving isoniazid may experience adverse effects (such as headache, sweating, palpitations, flushing and hypotension) after consuming certain foods or drinks. Tyramine-containing foods may cause an interaction due to the weak monoamine oxidase inhibiting activity of isoniazid and high-tyramine foods such as cheese, red wine, lager and preserved foods should be considered if a patient presents with such a reaction. Isoniazid may also inhibit diamine oxidase, causing an enhanced response to histamine-containing foods such as cheese or fish that is not fresh. The diet of the patient should be examined and advice to avoid such foodstuffs should be given in the event of such a reaction.

Pregnancy and Lactation

Pregnancy

Isoniazid should be only be used in pregnancy when the potential benefit justifies the potential risk to the foetus. If used in pregnancy, pyridoxine supplementation is recommended.

It is considered that untreated tuberculosis is a greater hazard to a pregnant woman and her foetus than treatment with isoniazid.

It is known that isoniazid crosses the human placenta to the foetus. Briggs states that isoniazid does not appear to be a human teratogen. Schaefer states that isoniazid is the drug of choice for prophylaxis and treatment of tuberculosis in pregnancy and recommends combination with pyridoxine (vitamin B6) and monthly liver function tests. Animal studies in mice, rats and rabbits have not revealed teratogenic effects, but embryocidal effects were observed in rats and rabbits.

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 ).

Licensed in pregnancy? - No

Recommended for use in pregnancy? - Drug of choice for prophylaxis and treatment of tuberculosis in pregnancy

Lactation

The manufacturer advises caution when treating with isoniazid during breastfeeding.

At least one review concludes that women can safely breastfeed their infants while taking isoniazid if the infant is periodically examined for signs and symptoms of peripheral neuritis and hepatitis. The Centres for Disease Control and Prevention (USA) state that breastfeeding should not be discouraged in patients taking isoniazid. Low levels of isoniazid are excreted in breast milk, it is unlikely to cause adverse reactions in infants. The concentration of isoniazid in milk is not considered sufficient for treatment of tuberculosis in the breastfed infant.

Schaefer concludes that isoniazid (in combination with 0.5 to 1 mg of vitamin B6 prophylaxis per day for the infant), rifampicin and pyrazinamide are the tuberculostatics of choice during breastfeeding. Ethambutol is also acceptable.

Infant should be monitored for toxicity including hepatitis and vision changes. Administration of pyridoxine to the breastfeeding mother and infant may be considered.

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

Drug excreted in breast milk? - Yes

Considered suitable or recommended by manufacturer? - Yes

Side Effects

Acidosis
Acute pancreatitis
Agranulocytosis
Aplastic anaemia
Constipation
Convulsions
Difficulty in micturition
Dry mouth
Elevation of liver enzymes
Erythema multiforme
Fever
Fulminant hepatitis
Gastro-intestinal disturbances
Gynaecomastia
Haemolytic anaemia
Hearing loss
Hepatic damage
Hepatic necrosis
Hepatitis
Hyperglycaemia
Hyperreflexia
Hypersensitivity reactions
Interstitial pneumonitis
Jaundice
Lupus erythematosus-like syndrome
Mood changes
Nausea
Optic neuritis
Pellagra
Peripheral neuropathy
Personality change
Psychotic episodes
Purpura
Stevens-Johnson syndrome
Systemic lupus erythematosus
Tinnitus
Toxic epidermal necrolysis
Vertigo
Vomiting
Withdrawal symptoms

Presentation

Tablets containing isoniazid

Drugs List

Therapeutic Indications

Uses

Tuberculosis - extra pulmonary
Tuberculosis - pulmonary

Unlicensed Uses

Tuberculosis - prophylaxis

Dosage

Adults

Children

Neonates

Patients with Renal Impairment

Contraindications

Drug induced hepatic disorder
Galactosaemia

Precautions and Warnings

Acute porphyria
Alcoholism
Breastfeeding
Diabetes mellitus
Epileptic disorder
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of psychosis
Lactose intolerance
Malnutrition
Positive HIV status
Pregnancy
Renal impairment - glomerular filtration rate below 10ml/minute
Seizures
Slow acetylator status

Consult national/regional policy on the use of anti-infectives
Must be used in combination with other anti-tuberculous drugs
Contains lactose
Advise patient to take at least 30 minutes before a meal
Monitor hepatic function before treatment and regularly during treatment
Adverse effects may be seen after ingestion of high-tyramine foods/drinks
Advise patients to discontinue therapy if signs of hepatotoxicity occur
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Consider treatment with pyridoxine to prevent peripheral neuritis
Discontinue if hepatitis develops
May cause convulsions
Discontinue if AST level exceeds 3 times the upper limit of normal
Discontinue if substantial increase in bilirubin occurs
Discontinue if symptoms of hepatic disease occur
Advise patient to seek medical advice before taking paracetamol products
Advise patient of importance of full compliance

Specialist advice should be sought about tuberculosis treatment in immunocompromised patients. Dosage regimens should be chosen carefully and potentially hazardous interactions should be avoided.

Isoniazid may increase the formation of toxic metabolites of paracetamol if paracetamol is taken during isoniazid treatment. Advise patients that they should limit the use of paracetamol-containing products during treatment with isoniazid and, preferably, seek medical advice before taking paracetamol-containing products.

Patients receiving isoniazid may experience adverse effects (such as headache, sweating, palpitations, flushing and hypotension) after consuming certain foods or drinks. Tyramine-containing foods may cause an interaction due to the weak monoamine oxidase inhibiting activity of isoniazid and high-tyramine foods such as cheese, red wine, lager and preserved foods should be considered if a patient presents with such a reaction. Isoniazid may also inhibit diamine oxidase, causing an enhanced response to histamine-containing foods such as cheese or fish that is not fresh. The diet of the patient should be examined and advice to avoid such foodstuffs should be given in the event of such a reaction.

Pregnancy and Lactation

Pregnancy

Isoniazid should be only be used in pregnancy when the potential benefit justifies the potential risk to the foetus. If used in pregnancy, pyridoxine supplementation is recommended.

It is considered that untreated tuberculosis is a greater hazard to a pregnant woman and her foetus than treatment with isoniazid.

It is known that isoniazid crosses the human placenta to the foetus. Briggs states that isoniazid does not appear to be a human teratogen. Schaefer states that isoniazid is the drug of choice for prophylaxis and treatment of tuberculosis in pregnancy and recommends combination with pyridoxine (vitamin B6) and monthly liver function tests. Animal studies in mice, rats and rabbits have not revealed teratogenic effects, but embryocidal effects were observed in rats and rabbits.

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 ).

Licensed in pregnancy? - No

Recommended for use in pregnancy? - Drug of choice for prophylaxis and treatment of tuberculosis in pregnancy

Lactation

The manufacturer advises caution when treating with isoniazid during breastfeeding.

At least one review concludes that women can safely breastfeed their infants while taking isoniazid if the infant is periodically examined for signs and symptoms of peripheral neuritis and hepatitis. The Centres for Disease Control and Prevention (USA) state that breastfeeding should not be discouraged in patients taking isoniazid. Low levels of isoniazid are excreted in breast milk, it is unlikely to cause adverse reactions in infants. The concentration of isoniazid in milk is not considered sufficient for treatment of tuberculosis in the breastfed infant.

Schaefer concludes that isoniazid (in combination with 0.5 to 1 mg of vitamin B6 prophylaxis per day for the infant), rifampicin and pyrazinamide are the tuberculostatics of choice during breastfeeding. Ethambutol is also acceptable.

Infant should be monitored for toxicity including hepatitis and vision changes. Administration of pyridoxine to the breastfeeding mother and infant may be considered.

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

Drug excreted in breast milk? - Yes

Considered suitable or recommended by manufacturer? - Yes

Side Effects

Acidosis
Acute pancreatitis
Agranulocytosis
Aplastic anaemia
Constipation
Convulsions
Difficulty in micturition
Dry mouth
Elevation of liver enzymes
Erythema multiforme
Fever
Fulminant hepatitis
Gastro-intestinal disturbances
Gynaecomastia
Haemolytic anaemia
Hearing loss
Hepatic damage
Hepatic necrosis
Hepatitis
Hyperglycaemia
Hyperreflexia
Hypersensitivity reactions
Interstitial pneumonitis
Jaundice
Lupus erythematosus-like syndrome
Mood changes
Nausea
Optic neuritis
Pellagra
Peripheral neuropathy
Personality change
Psychotic episodes
Purpura
Stevens-Johnson syndrome
Systemic lupus erythematosus
Tinnitus
Toxic epidermal necrolysis
Vertigo
Vomiting
Withdrawal symptoms

Withdrawal Symptoms and Signs

On discontinuation of treatment, effects such as headache, insomnia, excessive dreaming, irritability or nervousness may occur.

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.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

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

Summary of Product Characteristics: Isoniazid tablets 50 mg. Focus Pharmaceuticals Limited. Revised March 2010.
Summary of Product Characteristics: Isoniazid tablets 100 mg. Focus Pharmaceuticals Limited. Revised March 2010.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 12 September 2017

The Drug Database for acute Porphyria (NAPOS)
Available at: https://www.drugs-porphyria.com/languages/UnitedKingdom/index2.php?l=gbr
Isoniazid Last revised: October 1, 2004
Last accessed: July 15, 2010

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
Isoniazid. Last revised: October 2, 2012
Last accessed: April 17, 2013