3 .5 Make referral to Treatment Center physician as necessary for moderate or severe ADRs

If a patient has one of the moderate to severe ADRs listed in table 4, a physician should examine the patient immediately to take proper action. Refer the patient to a physician at the Treatment Center for care and follow-up.

TABLE 5 Moderate to Severe ADRs

Adverse Reactions Suspected Agents

Acute renal failure S, Km, Am, Cm

Bartter-like syndrome (decrease in serum potassium, magnesium and calcium) Cm, Km, Am, S

Suggested Management

Discontinue suspect drug. Consider using Cm if an aminoglycoside had been the prior injectable in the regimen. Consider dosing 2 to 3 times a week if drug is essential to the regimen and patient can tolerate (close monitoring of creatinine). Adjust the dose according to creatinine clearance. See Annex A: Recommended Dosages. Check electrolytes (K, Mg, Ca). Replace electrolytes as needed.

Generalized hypersensitivity (Stevens-Johnson syndrome) Hearing loss

Hemolysis Hepatitis/jaundice

Hypothyroidism Any drug Withdrawal of the drugs and refer to specialist.

S, Km, Am, Cm, Clr • Document hearing loss and compare with baseline audiometry if available. • change parenteral treatment to Cm if appropriate (no resistance confirmed or suspected). • Increase frequency and/or lower dose of suspected agent if this can be done without compromising the regimen. • Discontinue suspected agent if this can be done without compromising the regimen.

R

Discontinue drug and referral to specialist

Z, H, R, Eto/Pto, PAS, E, FQ Discontinue therapy pending resolution of hepatitis. Eliminate other potential causes of hepatitis. Consider suspending most likely agent permanently. Reintroduce remaining drugs, one at a time with the most hepatotoxic agent first, while monitoring liver function.

PAS, Eto/Pto

Initiate thyroxine therapy.

Intractable vomiting Eto/Pto, PAS, H, E, Z • Assess for dehydration, initiate rehydration if indicated. • Divide the dose (AM and PM) as long as it is supervised. • Discontiue suspected agent if this can be done without compromising the regimen.

Optic neuritis

E

Discontinue drug and refer to ophthalmologist.

Adverse Reactions Suspected Agents

Psychosis/psychotic symptoms (violent/suicidal tendencies)

Cs, H

Purpura

R Suggested Management

Discontinue suspected agent for a short period of time (1-4 weeks) while psychotic symptoms are brought under control. Antipsychotic treatment, referral to psychiatrist. Lower the dose of suspected agent if this can be done without compromising regimen. Discontinue drug and refer to specialist

Seizures Cs, H, FQ

Discontinue suspected agents pending resolution of seizures. Anticonvulsant therapy (phenytoin, valproic acid). Discontinue suspected agent if this can be done without compromising regimen. The main objective is to identify these possible reactions, detect them in an early stage and refer the patient to Treatment Center physician for study and further action.

**Note: Dose adjustments or drug withdrawal must always be done at the Treatment Center.

The preceding tables summarize the adverse drug reactions during treatment. It can also serve as a guide to the health worker as to whether anti-TB drugs will be discontinued or not. The drugs in bold font are more strongly associated with the adverse effect than the other drugs not in the group.

There are a number of measures that can be taken for patients with ADRs in general. • Since most ADRs occurring most frequently during the early months of treatment diminish with time, informing patients of this fact reassures them. • Giving small doses of the oral SLDs then slowly increasing the dose until the full recommended dosages are reached. For example, for a patient requiring 3 tablets of Pto, give 1 tablet each for 3 days, then 2 tablets for the next 3 days then 3 tablets thereafter. The same can be followed for Cycloserine and PAS. • Giving of ancillary drugs for symptomatic treatment, e.g., an anti-emetic for nausea, or a pain reliever for arthralgia, is a necessary step in most patients. • Splitting the dose into morning and afternoon dosages is an alternative for the Pto, Cs and PAS as long as both doses are supervised either at a Treatment Center or by atrained health worker during home-based supervised therapy. Splitting of doses is not applicable to Z, E and the FQs. • Reducing the drug dose to the lower acceptable limit, may be an alternative. Refer to Annex A for the dose range of certain drugs. • Withdrawal of the drug may be done as long as it does not compromise the regimen, i.e., still four reliable drugs are included; otherwise, another drug should be given as a replacement. Discontinuing a drug should be done as a last resort measure.

It is important to be aware that without an adequate regimen MDR-TB mortality is very high and in cases in which there is resistance to multiple drugs, and therefore only a few drugs are effective, to stop using one of them may result in treatment failure.

Reminder: If at any time you observe that a patient’s condition has significantly worsened, refer the patient to a physician at the Treatment Center for further assessment and treatment.