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Information

Editors

PaulaMaasilta
TuulaVasankari

Antitubercular Medication in Ambulatory Care

Essentials

  • The combination of drugs used is mainly the same irrespective of the location of tuberculous changes in the body. The choice of medication is affected by the possibility of drug resistance and any previous treatment; the duration of treatment depends on the location of tuberculous changes.
  • Depending on the local policies, the medication, hospital treatment and/or follow-up visits required for the treatment of tuberculosis may be free of charge for the patient.
  • The standard treatment regimen consists of rifampicin (RIF) and isoniazid (INH) for 6 months, combined with ethambutol (EMB) and pyrazinamide (PZA) during the first 2 months.
  • Regular intake of the drugs is essential for treatment success.
  • Some information in this article describes the organization and implemenation of care in Finland. Consult also local (national, regional) guidelines concerning the use of antitubercular medication.

Principles of drug treatment Steroids for Tuberculous Pleurisy, Rifabutin for Treating Pulmonary Tuberculosis, Length of Tuberculosis Chemotherapy, Intermittent Dosing with Drugs for Tuberculosis, Strategies to Promote Adherence to Tuberculosis Treatment, Directly Observed Therapy (Dot) in Tuberculosis Treatment

  • The organization of care may be directed by national legislation and other policies. Consult them for locally relevant details.
    • In Finland, for example, the treatment of tuberculosis is started and monitored within specialized care. Supervised outpatient care is carried out within primary care in collaboration with specialized care.
  • Except for certain patient groups (e.g. patients with AIDS), the standard treatment regimen consists of rifampicin (RIF) and isoniazid (INH) for 6 months, combined with ethambutol (EMB) and pyrazinamide (PZA) during the first 2 months.
  • The normal daily dose for RIF is 600 mg (450 mg for patients under 50 kg), for INH 300 mg, for PZA 1 500 mg (1 000 mg for patients under 55 kg and 2 000 mg for patients over 75 kg), and for EMB 1 250 mg (750 mg for patients under 55 kg and 1 600 mg for patients over 75 kg), respectively.
  • Fluoroquinolones should not be used as first-line antitubercular drugs, but in skeletal tuberculosis they are recommended and they may be necessary also in specific cases Fluoroquinolones for Treating Tuberculosis.
  • The treatment of central nervous system tuberculosis Meningitis in Adults should be started as soon as meningeal tuberculosis is suspected because it will take time to obtain the result of bacterial culture. Fluoroquinolone is usually incorporated into the treatment.
  • GPs and specialists in other fields should take the patient's antitubercular medication into consideration.
    • Symptoms or laboratory findings may be due to the medication.
    • Interactions with other medicines should be considered (warfarin treatment should be reviewed when starting or ending the administration of RIF).
  • All drugs should be taken at the same time, in the morning. Regular intake of the drugs is the most important prerequisite for recovery.

Supervised medication

  • Supervised medication should be organized for all patients. Patients should take (swallow) their medication under the supervision of a nurse or video surveillance. Since tuberculosis is usually defined as a dangerous communicable disease, specific regulations with regard to the treatment apply. Consult local instructions.
    • In Finland, supervised medication is, as far as possible, carried out 7 days a week particularly in drug- or alcohol-addicted patients, in elderly patients and in patients with multiple problems. In other patients, supervised medication is carried out on 5 days a week (Monday to Friday).
  • What supervised medication involves
    • Encouragement and motivation of patients throughout treatment
    • Teaching patients and those responsible for treatment about the administration of medication, particularly emphasizing that it should be administered regularly every day
    • Checking that the medication is administered as prescribed
    • Supervising and recording that patients swallow their medication, and regular reporting of this to the unit responsible for their treatment
    • Monitoring of the adverse effects of medication and quick response to such effects, as necessary
    • Recording of any deviations in therapy and reporting of such deviations to the unit responsible for treatment
  • Telling patients that supervised medication is part of the good treatment of tuberculosis, aimed at supporting the patient, and does not represent a doubt about the patient's reliability.
  • Supervised medication under video surveillance can be either live or recorded. In the latter case, a nurse can check afterwards that the medication was taken.

Adverse effects of antitubercular drugs

  • Always consult locally available drug information regarding interactions and adverse effects of antitubercular drugs.

Rifampicin

  • Stains all excretions red (may stain contact lenses).
  • Liver reactions
  • Gastrointestinal symptoms
  • Skin symptoms
  • Immunologically mediated symptoms
    • Flu-like syndrome
    • Thrombocytopenia
    • Haemolytic anaemia
  • Anuria
  • Shock, dyspnoea
  • Interactions occur with the following pharmaceutical agents, for example (impairing their efficacy):
    • oral contraceptives
    • anticoagulants
    • glucocorticoids
    • tolbutamide
    • barbiturates
    • cyclosporin.

Isoniazid

  • Liver reactions
  • Rash
  • Fever
  • Neurological symptoms
    • Peripheral neuropathy
    • Convulsions, psychological symptoms

Ethambutol

  • Optic neuritis; visual acuity and colour vision may be impaired
  • Rash
  • In patients with renal failure, the dose should be reduced.

Pyrazinamide

  • Liver reactions
  • Arthralgias (asymptomatic increase in serum urate concentration is more common)
  • Gastrointestinal symptoms
  • Sensitization to sunlight
  • Flush
  • Nausea

Investigations during treatment

  • Check local instructions regarding follow-up.
  • Laboratory tests
    • At treatment start
      • ESR, basic blood count with platelets, plasma ALT, alkaline phosphatase, bilirubin, creatinine,CRP, HIV antibodies
    • After 2 weeks and 1, 2, 4, and 6 months from treatment start and as indicated
      • basic blood count with platelets, plasma ALT, bilirubin, CRP (if elevated)
      • if EMB is used, visual acuity and colour vision before beginning the medication, 2 weeks after the beginning and subsequently once a month.
  • Chest x-rays for follow-up of pulmonary tuberculosis
    • Before the treatment, 2 and 6 months after starting treatment, and as indicated on clinical grounds (suspicion of poor response, for example).
  • Sputum smear microscopy and sputum culture in pulmonary tuberculosis
    • Before treatment, also for determination of drug resistance
    • Tb staining and culture of sputum should be performed at 2 weeks and subsequently once a month in series of 3 samples.
    • Other samples should be taken as clinically indicated.
  • Patients can be considered cured after adequate treatment and no routine follow-up examinations are indicated. If problems occurred in the treatment or if substantial changes remain in the chest x-ray or if the patient is HIV-positive, the follow-up may be continued for 1-2 years after the treatment.

Treatment of latent infection in adults

  • About a third of the population worldwide has been infected with tuberculosis. These people have a latent tuberculosis infection (LTBI) but no symptoms or active disease.
  • The life-time cumulative risk of developing tuberculosis is about 10%, and in half of cases this occurs within 2 years of infection.
  • The assessment concerning the need for treatment is performed in specialized care.
  • Treatment of latent tuberculosis infection should be considered if the risk of developing symptomatic disease is increased, for example, if initiation of TNF-alpha inhibitor treatment is planned.
    • Treatment of asymptomatic LTBI should also be considered after recent significant exposure to tuberculosis. In such cases, antitubercular treatment is used to prevent symptomatic disease after primary infection.
    • The treatment of patients with LTBI should always be started, monitored and ended in specialized care.
    • Consult local instructions regarding the investigations and treatment of persons exposed to tuberculosis.
  • Treatment alternatives
  • After recent exposure to infection, treatment should be considered in patients with
    • clearly impaired immune response
    • age below 35 years
    • HIV infection
    • planned organ transplantation
    • medication impairing the immune response
      • TNF-alpha inhibitors
      • cytotoxic drugs
      • long-term high-dose glucocorticoid medication (15-20 mg prednisolone daily)
      • Other biological drugs depending on the mechanism of action.
    • leukaemia, lymphoma, cancer of the head/neck region or lung
    • silicosis
    • chronic renal failure requiring dialysis treatment.

Treatment of multiresistant tuberculosis

  • Check local epidemiology (including nearby countries) and local guidelines.
  • Effective and regular medication prevents the development of drug resistance.
    • Multiresistant strains are therefore so far rare in Finland but they do occur close to Finland, in Russia and in the Baltic countries, as well as in countries where the treatment of tuberculosis is inadequate.
  • If the patient has received antituberculous drugs in the past, if there is no reliable record of the treatment, if the medication has been discontinued, or if the patient arrives from a region where drug resistance is common, the risk of drug resistance must be taken into account when the treatment is planned
  • When drug resistance is suspected, a stain-positive sputum sample is always tested using a rapid test based on nucleic acid detection in order to detect drug resistance. The test may also be perfomed in a stain-negative sputum sample, but in such a case its sensitivity is not as good. A culture with growth can also be examined using a rapid test based on nucleic acid detection, but the actual results regarding sensitivity to different drugs is only acquired through the culture method.
  • Simply adding a further drug if the disease responds poorly to the combination of drugs used represents malpractice!
  • Patients with multiresistant tuberculosis should be treated, in the infectious stage, in an isolated, hypobaric space. The treatment is long and expensive.

Evidence Summaries

Related Keywords

ATC Code:

J04AC01

J04AB02

J01MA01

J01MA02

J01MA06

J01MA12

J01MA14

J01MA23

J04AK01

J04AK02

Primary/Secondary Keywords