Treatment of Tuberculosis Drugs, side effects and interactions

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Treatment of Tuberculosis(Drugs, side effects
and interactions)

• Alison Haigh
• Lead Pharmacist (Antimicrobial Therapy),
• Bradford Teaching Hospitals NHS Foundation Trust

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Introduction

• Principles of treatment
• Aims of treatment
• Current treatment guidelines
• Characteristics of drugs
• Side effects
• Interactions
• Pharmaceutical care

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Principles of treatment

• Adequate and effective treatment essential in
  order to cure patient, prevent recurrence and
  control spread to the wider population.
• Use combination therapy reduce risk of
  resistance to single agent emerging
• Consider all relevant factors to ensure
  appropriate regimen
• Extended course of treatment to ensure eradication

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Current Guidelines (NICE 2006)

• Recommend use of
• Rifampicin
• Isoniazid
• Ethambutol
• Pyrazinamide
• Streptomycin
• Glucocorticocoids in active meningeal disease
• (Protionamide, cycloserine,capreomycin
  reserved for MDRTB)

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NICE guidelinesStandard recommended regimen

• Six month course of treatment
• 4 drug combination for first 2 months (isoniazid
  rifampicin, pyrazinamide, ethambutol)
  initiation phase -followed by 4 months of two
  drug combination (rifampicin, isoniazid)
  continuation phase

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Standard recommended regimen

• Appropriate for treatment of
• Pulmonary TB (adults, adults with HIV and paeds)
• Peripheral lymph node TB
• Bone and joint (incl. Spinal)TB
• Miliary/disseminated TB
• Pericardial TB
• Genito-urinary TB

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NICE guidelinesMeningeal/CNS TB

• 12 month regimen- isoniazid, pyrazinamide
  rifampicin ethambutol for 2/12, (initiation
  phase) glucocorticoid for first 2-3 weeks
• then
• 10/12 of isoniazid rifampicin (continuation
  phase)

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NICE guidelinesManaging Drug resistance

• MDR-TB- resistance to rifampicin and isoniazid
  with considerable consequences

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Characteristics of drugsRifampicin

• Semi-synthetic agent
• Sterilising effect
• Rapidly absorbed (reduced by concurrent food
  intake) and widely distributed in body
• Penetrates into CSF when meninges inflamed
• Undergoes first pass metabolism in liver
• Excreted in bile
• Usual dose 450-600mg daily

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Rifampicin Side effects

• Discoloration of urine, sweat, tears
• GI disturbances
• Minor elevation of liver enzymes (transient,
  reversible)
• Flu-syndrome
• Thrombocytopenia
• Allergic reactions (urticaria, rash)
• CNS effects- fatigue, ataxia

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Rifampicin- interactions

• Potent inducer of hepatic enzymes so many
  clinically relevant interactions including
• Antiarrhythmics
• Anticoagulants
• Oral hypoglycaemics
• Anti-epileptics
• Antifungals
• Antivirals
• Oral contraceptive- alternative method necessary
• Thyroxine

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Characteristics of drugsIsoniazid

• Bactericidal
• Rapidly absorbed, widely distributed
• Penetrates CSF
• Metabolised in liver-genetically controlled
• Usual dose 300mg daily

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Isoniazid side effects

• Relatively few but include
• GI disturbances
• Peripheral neuropathy (give prophylactic
  pyridoxine 50mg weekly)
• Optical neuritis
• Hypersensitivity reactions
• Mild liver function disturbances
• Rarely hyperglycaemia, gynaecomastia

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Isoniazid - Interactions

• Inhibits cytochrome P450
• Increases plasma concentration of carbamazepine,
  ethosuximide, phenytoin
• Possible reduced effect of oral contraceptive
• Possibly increases plasma levels of theophylline
• Absorption reduced by antacids

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Characteristics of drugsPyrazinamide

• Bactericidal, kills semidormant bacilli
• Use reduces later relapse rates so allows shorter
  continuation phase
• Well absorbed, penetrates CSF
• Metabolised in liver

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Pyrazinamide- side effects

• Not always well tolerated
• Hepatotoxicity (anorexia, fever hepatomegaly
  jaundice)
• Nausea, dyspepsia
• Arthralgia
• Occasionally photosensitivity

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Pyrazinamide- interactions

• Only significant one possible effect on
  contraceptive effect of oestrogens

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Characteristics of drugsEthambutol

• Bacteriostatic agent
• Well absorbed
• Excreted unchanged in urine
• Dose- 15mg/kg (reduce in renal impairment)

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Ethambutol- side effects

• Dose related retrobulbar neuritis- stop drug
  immediately. Visual acuity tested before starting
  treatment
• Red/green colour blindness
• Peripheral neuritis

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Ethambutol - Interactions

• None documented in BNF/SmPC

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Aspects of Pharmaceutical Care

• Supply quantities
• Timing of daily doses
• Pyridoxine- prophylaxis of peripheral neuritis
• Formulations
• Use of combination products
• Monitored dosing systems
• Exemption from prescription charges