Drugs List

Therapeutic Indications

Uses

Tuberculosis: continuation phase treatment
Tuberculosis: initial phase treatment in combination with other drugs

Contraindications

Hereditary fructose intolerance
Jaundice

Precautions and Warnings

Elderly
Predisposition to seizures
Alcoholism
Breastfeeding
Chronic renal failure
Diabetes mellitus
Epileptic disorder
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of psychosis
Immunodeficiency syndromes
Malnutrition
Peripheral neuropathy
Porphyria
Positive HIV status
Pregnancy
Slow acetylator status

Consider vitamin K supplementation risk of vitamin K dependent coagulopathy
Intermittent therapy increases the risk of hypersensitivity reactions
Treatment to be initiated and supervised by a specialist
Preparation contains sucrose
Monitor hepatic function before treatment and regularly during treatment
Monitor platelets before starting and during treatment
Monitor renal function prior to initiating treatment
Monitor hepatic function frequently in patients with hepatic impairment
Perform blood counts in patients with alcohol dependence
Perform blood counts in patients with hepatic impairment
Perform blood counts on prolonged use of this treatment
Adverse effects may be seen after ingestion of high-tyramine foods/drinks
Advise patient that red discolouration of body fluids may occur
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Discontinue if hepatitis develops
Discontinue if thrombocytopenia occurs
May cause convulsions
May cause hyperbilirubinaemia
May cause vitamin K dependent coagulopathy and severe bleeding
Discontinue if haemolytic anaemia occurs
Discontinue if renal failure develops
Discontinue if significant/persistent hepatic function abnormalities occur
Female: Barrier or non-hormonal contraception advised during treatment
Advise patient of importance of full compliance
Discolours soft contact lenses

Patients should be seen monthly during therapy and should be questioned regarding symptoms associated with adverse effects. All abnormalities should be investigated including laboratory testing when necessary.

Monitor transaminase monthly in patients over 35 years on a monthly basis, there is an increased risk of isoniazid-associated hepatitis in this patient population.

The following factors are also associated with an increased risk of hepatitis; daily intake of alcohol, chronic liver disease, intravenous drug use, black or hispanic women.

Rifampicin should be used with caution and under strict medical supervision in patients with hepatic impairment. Hepatic function should be monitored (especially serum alanine aminotransferase (ALT) and serum aspartate transaminase (AST)) before therapy and every two to four weeks during therapy.

Pregnancy and Lactation

Pregnancy

Use rifampicin with isoniazid with caution in pregnancy.

Animal studies have reported spina bifida in mice and rats and cleft palates in mice when administered rifampicin. Teratogenicity has been reported in rats. Rifampicin crosses the human placenta to the foetus. No controlled studies link the use of rifampicin to congenital defects in humans. One report described a 4.4% incidence of malformations, which is similar to the expected frequency of defects in the healthy population, but higher than the rate noted for other tuberculosis patients (Briggs, 2011).

Several reviews have concluded that rifampicin was not a proven teratogen and recommended the use of rifampicin with isoniazid and ethambutol if necessary. Schaefer (2007) concludes that rifampicin is a drug of choice for the treatment of tuberculosis during pregnancy, Schaefer (2007) also suggests the use of rifampicin as prophylaxis against meningococcal infection. When administered during the last few weeks of pregnancy, post-natal haemorrhage in the mother and neonate may occur and therapy with vitamin K1 may be required.

Animal studies in mice, rats and rabbits have not revealed teratogenic effects, but embryocidal effects were observed in rats and rabbits. Isoniazid crosses the human placenta to the foetus. Briggs (2011) concludes that isoniazid does not appear to be a human teratogen. Schaefer (2007) states isoniazid as the drug of choice for prophylaxis and treatment of tuberculosis in pregnancy and recommends combination with pyridoxine (vitamin B6) and monthly liver function tests. The American Thoracic Society recommends the use of the drug for tuberculosis during pregnancy as "Untreated tuberculosis represents a far greater hazard to a pregnant woman and her foetus than does treatment of the disease."

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 to 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

Use rifampicin with isoniazid with caution in breastfeeding.

The Centres for Disease Control and prevention state that breastfeeding should not be discouraged in patients taking pyrazinamide, rifampicin or isoniazid. Low levels of all three drugs are excreted in breast milk, the concentrations of these drugs is not considered sufficient for treatment of tuberculosis in the breastfed infant.

Schaefer (2007) 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.

Infant should be monitored for toxicity including hepatitis and vision changes. Observe for fatigue, weakness, malaise, anorexia, nausea and vomiting.

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

Abdominal discomfort
Acute interstitial nephritis
Acute renal failure
Acute tubular necrosis
Adrenal suppression
Aggravation of porphyria
Agranulocytosis
Anaemia
Anaphylaxis
Anorexia
Bone pain
Cerebral haemorrhage
Chills
Collapse
Constipation
Convulsions
Diarrhoea
Dizziness
Drowsiness
Dry mouth
Encephalopathy
Eosinophilia
Erythema multiforme
Exfoliative dermatitis
Fever
Flushing
Gynaecomastia
Haemolytic anaemia
Headache
Hepatic impairment
Hepatitis
Hyperglycaemia
Hypersensitivity reactions
Hypotension
Increase in antinuclear antibodies (ANA)
Influenza-like syndrome
Intravascular coagulation (disseminated)
Itching
Jaundice
Leucopenia
Lyell's syndrome
Menstrual disturbances
Micturition disorders
Muscle weakness
Myopathy
Nausea
Oedema
Optic neuritis
Pancreatitis
Pellagra
Pemphigoid reaction
Polyneuritis
Possible staining of soft contact lenses
Pseudomembranous colitis
Psychoses
Purpura
Pyrexia
Rash
Reddish discolouration of body fluids
Reflex disorders
Renal impairment
Respiratory symptoms
Shock
Shortness of breath
Skin reactions
Stevens-Johnson syndrome
Superficial tooth discolouration
Systemic lupus erythematosus-like syndrome
Thrombocytopenia
Toxic epidermal necrolysis
Urticaria
Vasculitis
Vertigo
Vomiting
Wheezing

Presentation

Oral formulations of rifampicin and isoniazid.

Drugs List

Therapeutic Indications

Uses

Tuberculosis: continuation phase treatment
Tuberculosis: initial phase treatment in combination with other drugs

Dosage

Rifampicin and isoniazid must be used in combination with other anti-tuberculous drugs during the initial phase of treatment until the susceptibility of the infecting organism to rifampicin and isoniazid has been confirmed.

Adults

Elderly

Children

Contraindications

Hereditary fructose intolerance
Jaundice

Precautions and Warnings

Elderly
Predisposition to seizures
Alcoholism
Breastfeeding
Chronic renal failure
Diabetes mellitus
Epileptic disorder
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of psychosis
Immunodeficiency syndromes
Malnutrition
Peripheral neuropathy
Porphyria
Positive HIV status
Pregnancy
Slow acetylator status

Consider vitamin K supplementation risk of vitamin K dependent coagulopathy
Intermittent therapy increases the risk of hypersensitivity reactions
Treatment to be initiated and supervised by a specialist
Preparation contains sucrose
Monitor hepatic function before treatment and regularly during treatment
Monitor platelets before starting and during treatment
Monitor renal function prior to initiating treatment
Monitor hepatic function frequently in patients with hepatic impairment
Perform blood counts in patients with alcohol dependence
Perform blood counts in patients with hepatic impairment
Perform blood counts on prolonged use of this treatment
Adverse effects may be seen after ingestion of high-tyramine foods/drinks
Advise patient that red discolouration of body fluids may occur
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Discontinue if hepatitis develops
Discontinue if thrombocytopenia occurs
May cause convulsions
May cause hyperbilirubinaemia
May cause vitamin K dependent coagulopathy and severe bleeding
Discontinue if haemolytic anaemia occurs
Discontinue if renal failure develops
Discontinue if significant/persistent hepatic function abnormalities occur
Female: Barrier or non-hormonal contraception advised during treatment
Advise patient of importance of full compliance
Discolours soft contact lenses

Patients should be seen monthly during therapy and should be questioned regarding symptoms associated with adverse effects. All abnormalities should be investigated including laboratory testing when necessary.

Monitor transaminase monthly in patients over 35 years on a monthly basis, there is an increased risk of isoniazid-associated hepatitis in this patient population.

The following factors are also associated with an increased risk of hepatitis; daily intake of alcohol, chronic liver disease, intravenous drug use, black or hispanic women.

Rifampicin should be used with caution and under strict medical supervision in patients with hepatic impairment. Hepatic function should be monitored (especially serum alanine aminotransferase (ALT) and serum aspartate transaminase (AST)) before therapy and every two to four weeks during therapy.

Pregnancy and Lactation

Pregnancy

Use rifampicin with isoniazid with caution in pregnancy.

Animal studies have reported spina bifida in mice and rats and cleft palates in mice when administered rifampicin. Teratogenicity has been reported in rats. Rifampicin crosses the human placenta to the foetus. No controlled studies link the use of rifampicin to congenital defects in humans. One report described a 4.4% incidence of malformations, which is similar to the expected frequency of defects in the healthy population, but higher than the rate noted for other tuberculosis patients (Briggs, 2011).

Several reviews have concluded that rifampicin was not a proven teratogen and recommended the use of rifampicin with isoniazid and ethambutol if necessary. Schaefer (2007) concludes that rifampicin is a drug of choice for the treatment of tuberculosis during pregnancy, Schaefer (2007) also suggests the use of rifampicin as prophylaxis against meningococcal infection. When administered during the last few weeks of pregnancy, post-natal haemorrhage in the mother and neonate may occur and therapy with vitamin K1 may be required.

Animal studies in mice, rats and rabbits have not revealed teratogenic effects, but embryocidal effects were observed in rats and rabbits. Isoniazid crosses the human placenta to the foetus. Briggs (2011) concludes that isoniazid does not appear to be a human teratogen. Schaefer (2007) states isoniazid as the drug of choice for prophylaxis and treatment of tuberculosis in pregnancy and recommends combination with pyridoxine (vitamin B6) and monthly liver function tests. The American Thoracic Society recommends the use of the drug for tuberculosis during pregnancy as "Untreated tuberculosis represents a far greater hazard to a pregnant woman and her foetus than does treatment of the disease."

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 to 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

Use rifampicin with isoniazid with caution in breastfeeding.

The Centres for Disease Control and prevention state that breastfeeding should not be discouraged in patients taking pyrazinamide, rifampicin or isoniazid. Low levels of all three drugs are excreted in breast milk, the concentrations of these drugs is not considered sufficient for treatment of tuberculosis in the breastfed infant.

Schaefer (2007) 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.

Infant should be monitored for toxicity including hepatitis and vision changes. Observe for fatigue, weakness, malaise, anorexia, nausea and vomiting.

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

Abdominal discomfort
Acute interstitial nephritis
Acute renal failure
Acute tubular necrosis
Adrenal suppression
Aggravation of porphyria
Agranulocytosis
Anaemia
Anaphylaxis
Anorexia
Bone pain
Cerebral haemorrhage
Chills
Collapse
Constipation
Convulsions
Diarrhoea
Dizziness
Drowsiness
Dry mouth
Encephalopathy
Eosinophilia
Erythema multiforme
Exfoliative dermatitis
Fever
Flushing
Gynaecomastia
Haemolytic anaemia
Headache
Hepatic impairment
Hepatitis
Hyperglycaemia
Hypersensitivity reactions
Hypotension
Increase in antinuclear antibodies (ANA)
Influenza-like syndrome
Intravascular coagulation (disseminated)
Itching
Jaundice
Leucopenia
Lyell's syndrome
Menstrual disturbances
Micturition disorders
Muscle weakness
Myopathy
Nausea
Oedema
Optic neuritis
Pancreatitis
Pellagra
Pemphigoid reaction
Polyneuritis
Possible staining of soft contact lenses
Pseudomembranous colitis
Psychoses
Purpura
Pyrexia
Rash
Reddish discolouration of body fluids
Reflex disorders
Renal impairment
Respiratory symptoms
Shock
Shortness of breath
Skin reactions
Stevens-Johnson syndrome
Superficial tooth discolouration
Systemic lupus erythematosus-like syndrome
Thrombocytopenia
Toxic epidermal necrolysis
Urticaria
Vasculitis
Vertigo
Vomiting
Wheezing

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: May 2015

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 (online) London: Brayfield A (ed). Pharmaceutical Press Accessed on 21 May 2015.

Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

Summary of Product Characteristics: Rifinah 150mg/100mg. Sanofi-Aventis. Revised March 2019.
Summary of Product Characteristics: Rifinah 150mg/300mg. Sanofi-Aventis. Revised March 2019.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 13 September 2017

The Norwegian Porphyria Centre (NAPOS).
Available at: https://www.drugs-porphyria.com/languages/UnitedKingdom/s1.php?l=gbr
Last revised: 01 October 2004
Last accessed: 21 May 2015

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
Rifampin Last revised: 7 September, 2013
Last accessed: 21 May, 2015

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: 7 September, 2013
Last accessed: 21 May, 2015