Drugs List

Therapeutic Indications

Uses

Prophylaxis of MAC infection in HIV pts. with CD4 less than 75 cells/mcl
Treatment of Mycobacterium infection (non-tuberculous)
Tuberculosis - pulmonary

Contraindications

Neonates under 1 month
Breastfeeding
Pregnancy

Precautions and Warnings

Children 1 month to 18 years
Porphyria
Renal impairment - creatinine clearance below 30 ml/minute
Severe hepatic impairment

Reduce dose in patients with creatinine clearance below 30ml/min
Ensure absence of Mycobacterial disease before starting prophylaxis
Monitor for occurrence of uveitis, esp. if used with macrolides/triazoles
Monitor hepatic function
Perform regular white blood cell and platelet counts
Advise patient of possible colour changes to skin and body secretions
Advise patient that this medicine may discolour the urine pink or orange
Consider C. difficile if diarrhoea occurs within 2 months of treatment
Uveitis: distinguish from other ocular complications of HIV
Consider dose reduction in severe hepatic impairment
Lifetime MAC prophylaxis may be required
Female: Barrier or non-hormonal contraception advised during treatment
Female: Oral contraception may not be adequate during treatment
Advise patients on the importance of taking treatment regularly
Discolours soft contact lenses

Rifabutin is a potent enzyme-inducing drug and oral contraception may not be adequate during therapy. Women of childbearing age should be advised to use alternative family planning methods unaffected by enzyme inducing drugs during treatment. Since enzyme activity does not return to normal for several weeks after stopping an enzyme-inducing drug, appropriate contraceptive measures are required for 4 weeks after stopping.

Monitor for occurrence of uveitis, particularly if used with macrolides or triazoles. If such an event occurs, the patient should be referred to an ophthalmologist and, if considered necessary, rifabutin treatment should be suspended. Uveitis associated with rifabutin must be distinguished from other ocular complications of HIV.

Clostridium difficile associated diarrhoea (CDAD) has been reported with the use of rifabutin. CDAD must be considered in all patients who present with diarrhoea following antibiotic use.

Pregnancy and Lactation

Pregnancy

Rifabutin is contraindicated in pregnancy as insufficient safety data available.

It is not known if rifabutin or its active metabolite crosses the human placenta. The molecular weight of rifabutin (about 847), moderate plasma protein binding, high lipid solubility, and prolonged terminal half-life (45hours) suggest the passage to the embryo/foetus will occur. Schaefer (2007) concludes that inadvertent use of rifabutin does not require termination of pregnancy or invasive diagnostic procedures. However, a detailed ultrasound may be considered after first trimester exposure.

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 use of rifabutin is contraindicated in breastfeeding women.

The molecular weight of rifabutin (about 847), moderate plasma protein binding, and prolonged terminal half-life (45hours) suggest that excretion into breast milk should be expected. Milk may be stained brown-orange colour, and the effects on a nursing infant are unknown but serious toxicity is a potential complication. In addition, HIV patients taking rifabutin for prophylaxis of MAC infection, may put the infant at risk of exposure to the HIV virus, therefore women with HIV should not breastfeed.

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

Agranulocytosis
Anaemia
Arthralgia
Bronchospasm
Chest pain
Clostridium difficile diarrhoea
Corneal opacities
Dyspnoea
Elevation of liver enzymes
Eosinophilia
Granulocytopenia
Haemolysis
Hepatitis
Hypersensitivity reactions
Influenza-like syndrome
Jaundice
Leucopenia
Lymphopenia
Myalgia
Nausea
Neutropenia
Pancytopenia
Pyrexia
Rash
Reddish discolouration of body fluids
Reduced neutrophil count
Reduced platelet count
Shock
Skin discolouration
Thrombocytopenia
Uveitis
Vomiting
White blood cell count decreased

Presentation

Oral formulations of rifabutin.

Drugs List

Therapeutic Indications

Uses

Prophylaxis of MAC infection in HIV pts. with CD4 less than 75 cells/mcl
Treatment of Mycobacterium infection (non-tuberculous)
Tuberculosis - pulmonary

Dosage

When rifabutin is used in combination therapy this should always be with other anti-mycobacterial drugs not belonging to the family of rifamycins.

Adults

Children

Patients with Renal Impairment

Contraindications

Neonates under 1 month
Breastfeeding
Pregnancy

Precautions and Warnings

Children 1 month to 18 years
Porphyria
Renal impairment - creatinine clearance below 30 ml/minute
Severe hepatic impairment

Reduce dose in patients with creatinine clearance below 30ml/min
Ensure absence of Mycobacterial disease before starting prophylaxis
Monitor for occurrence of uveitis, esp. if used with macrolides/triazoles
Monitor hepatic function
Perform regular white blood cell and platelet counts
Advise patient of possible colour changes to skin and body secretions
Advise patient that this medicine may discolour the urine pink or orange
Consider C. difficile if diarrhoea occurs within 2 months of treatment
Uveitis: distinguish from other ocular complications of HIV
Consider dose reduction in severe hepatic impairment
Lifetime MAC prophylaxis may be required
Female: Barrier or non-hormonal contraception advised during treatment
Female: Oral contraception may not be adequate during treatment
Advise patients on the importance of taking treatment regularly
Discolours soft contact lenses

Rifabutin is a potent enzyme-inducing drug and oral contraception may not be adequate during therapy. Women of childbearing age should be advised to use alternative family planning methods unaffected by enzyme inducing drugs during treatment. Since enzyme activity does not return to normal for several weeks after stopping an enzyme-inducing drug, appropriate contraceptive measures are required for 4 weeks after stopping.

Monitor for occurrence of uveitis, particularly if used with macrolides or triazoles. If such an event occurs, the patient should be referred to an ophthalmologist and, if considered necessary, rifabutin treatment should be suspended. Uveitis associated with rifabutin must be distinguished from other ocular complications of HIV.

Clostridium difficile associated diarrhoea (CDAD) has been reported with the use of rifabutin. CDAD must be considered in all patients who present with diarrhoea following antibiotic use.

Pregnancy and Lactation

Pregnancy

Rifabutin is contraindicated in pregnancy as insufficient safety data available.

It is not known if rifabutin or its active metabolite crosses the human placenta. The molecular weight of rifabutin (about 847), moderate plasma protein binding, high lipid solubility, and prolonged terminal half-life (45hours) suggest the passage to the embryo/foetus will occur. Schaefer (2007) concludes that inadvertent use of rifabutin does not require termination of pregnancy or invasive diagnostic procedures. However, a detailed ultrasound may be considered after first trimester exposure.

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 use of rifabutin is contraindicated in breastfeeding women.

The molecular weight of rifabutin (about 847), moderate plasma protein binding, and prolonged terminal half-life (45hours) suggest that excretion into breast milk should be expected. Milk may be stained brown-orange colour, and the effects on a nursing infant are unknown but serious toxicity is a potential complication. In addition, HIV patients taking rifabutin for prophylaxis of MAC infection, may put the infant at risk of exposure to the HIV virus, therefore women with HIV should not breastfeed.

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

Agranulocytosis
Anaemia
Arthralgia
Bronchospasm
Chest pain
Clostridium difficile diarrhoea
Corneal opacities
Dyspnoea
Elevation of liver enzymes
Eosinophilia
Granulocytopenia
Haemolysis
Hepatitis
Hypersensitivity reactions
Influenza-like syndrome
Jaundice
Leucopenia
Lymphopenia
Myalgia
Nausea
Neutropenia
Pancytopenia
Pyrexia
Rash
Reddish discolouration of body fluids
Reduced neutrophil count
Reduced platelet count
Shock
Skin discolouration
Thrombocytopenia
Uveitis
Vomiting
White blood cell count decreased

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: March 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 (2012) 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.

Summary of Product Characteristics: Mycobutin. Pharmacia Limited. Revised March 2012.

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