6.5. Management of reactions to anti-tuberculosis drugs


These are important because they cause discomfort to patients and because they interrupt treatment. Hypersensitivity (allergic) reactions. These rarely occur in the first week of treatment. They are commonest in the second to fourth week. They are much less frequent with isoniazid, rifampicin and ethambutol than they are with streptomycin and thioacetazone. Very rarely patients become allergic to all three drugs in a regimen.

There are various degrees of reaction:

  1. Mild: itching of the skin only: this is often the only sign of rifampicin allergy.
  2. Moderate: fever and rash. The rash is often mistaken for measles or scarlet fever. If severe the skin looks blistered and resembles urticaria.
  3. Severe: In addition to fever and rash there may be generalized swelling of lymph nodes, enlargement of liver and spleen, swelling round the eyes and swelling of the mucous membranes of the mouth and lips.
  4. High fever, a generalized blistering rash and ulceration of the mucous membranes of the mouth, genitals and eyes (Stevens-Johnson syndrome). This is a rare but dangerous reaction, particularly to thioacetazone, and particularly in patients with HIV infection.
  5. Very rarely there may be chronic eczema involving the limbs occurring after the eighth week. This is almost always due to allergy to streptomycin.

This is discussed in two parts: immediate and desensitization.

  1. If the only complaint is mild itching you can usually continue drug treatment, as the patient desensitizes himself; give anti-histamine drug (if available).
  2. If there are fever and rash stop all drugs; give anti-histamine drug (if available).
  3. If there is a very severe reaction, stop all drugs.
  4. If the patient seems seriously ill, it may be necessary to send the patient to hospital for active desensitization therapy.

Approximate methods of desensibilization, (desensitization) to antituberculous drugs.
Management of desensitization is best done in hospital. If possible give two anti-tuberculosis drugs, which the patient has not previously received while you are carrying out desensitization. Test all drugs the patient has received before starting desensitization. There are so many effective drugs now that, if you have other drugs available, it is often easier to substitute another drug for the one, which has caused the reaction.

If alternative drugs are not available, below is a guide to desensitization (table 5.5.1.).

Table 5.5.1.

Challenge doses for detecting cutaneous or generalized hypersensitivity to anti-tuberculosis drugs

Drug Challenge doses
Day 1 Day 2
Isoniazid 50 mg 300 mg
Rjfampicin 75 mg 300 mg
Pyrazinamide 250 mg 1.0 g
Ethambutol 100 mg 500 mg
Thioacetazone 25 mg 50 mg
Streptomycin or other aminoglycosides 125 mg 500 mg

If a reaction occurs with the first challenge dose drug (as shown on Table 5.5.1.) you know the patient is hypersensitive to that drug. When starting to desensitize it is usually safe to begin with a tenth of the normal dose. Then increase the dose by a tenth each day.

If he has a mild reaction to a dose (tabl. 5.5.1), give the same dose (instead of a higher dose) next day. If there is no reaction, go on increasing by a tenth each day.

If the reaction is severe a lower dose should be returned and increase the doses should be done more gradually.

If the patient is in hospital, or can attend at 12 hourly intervals, you can give the doses twice a day. In most cases you can easily complete the desensitization within 7-10 days.

As soon as you have completed the desensitization to that drug, begin giving it regularly but make sure that it is combined with at least one other drug (to which the patient is not hypersensitive) so as to prevent drug resistance.


All anti-tuberculosis drugs can cause damage to the liver. It is very difficult to decide whether hepatitis is due to drugs or to infectious hepatitis. Hepatitis as a side-effect occurs in about 1 per cent of treated patients, and is probably commonest with thioacetazone and pyrazinamide. Mild asymptomatic increase in serum enzymes is a common occurrence. This is not an indication to stop drugs. If there is loss of appetite, jaundice and liver enlargement, treatment should be stopped until liver function has returned to normal. In most patients the same drugs can be given again without return of hepatitis. If the hepatitis has been severe don’t use pyrazinamide or rifampicin for retreatment. Give streptomycin, isoniazid and ethambutol for 2 months, followed by 10 months of isoniazid and ethambutol (2SHE/10HE).

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