Management of TB special cases

Presenter: Dr. Afaf Ageed

Pulmonologist

Alshaab teaching hospital

 Pregnancy
• Untreated tuberculosis represents a greater
hazard to a pregnant woman and the fetus than
treatment of the disease.
• Most TB drugs, except for streptomycin, are
safe for use in pregnant women
• Pyridoxine supplementation is recommended

Streptomycin should not be used in

pregnancy
 Breastfeeding women

• All the TB drugs are safe.

• Pyridoxine supplementation is recommended
 The newborn baby
Manage the newborn baby as follows.
• Do not separate the baby from the mother unless she is
desperately ill. Advise on cough etiquette
• If the mother is sputum-smear negative and the baby is
well, give the baby BCG immediately (if it has not already
been given).
• If the mother was sputum -smear positive during
pregnancy or still is at the time of delivery:
– If the baby is well, prescribe isoniazid 10 mg/kg in a single dose
daily for 6 months. If the infant remains healthy, stop isoniazid
and give BCG. Do not vaccinate with BCG at the same time as
isoniazid is being administered.
– If the baby is ill at birth and you suspect congenital tuberculosis
give full anti-tuberculosis treatment.
 Women using contraceptives

• Rifampicin reduces the effectiveness of oral

contraceptives:
Two options for contraception:
1- oral contraceptive pill containing a higher
dose of estrogen (50 μg).
2- a non-hormonal method of contraception
throughout Rifampicin treatment and for at least
one month subsequently
Liver disorders
1- TB treatment in patients with pre-existing
liver disease:
Patients with the following conditions can receive
the usual TB regimens:
 Hepatitis virus carrier.
 Patients with a past history of acute hepatitis,

• Hepatotoxic reactions to anti-TB drugs may be

more common among these patients and should
therefore be anticipated and closely monitored.
 In patients with unstable or advanced liver
disease:
• liver function tests should be done at the start
of treatment. .

• If the serum alanine aminotransferase(ALT)

level is more than 3 times normal before the
initiation of treatment the following regimens
should be considered:
 One hepatotoxic drug:
• The more unstable or severe the liver disease
is, the fewer hepatotoxic drugs should be
used:
2 months of Isoniazid, Ethambutol and
streptomycin, followed by 10 months of
Isoniazid and Ethambutol. (2HES/10HE)
 Two hepatotoxic drugs
a) 9 months of Isoniazid and Rifampicin, plus
Ethambutol (until or unless Isoniazid
susceptibility is documented) . (2HRE/7HR)
b) 2 months of Isoniazid, Rifampicin,
streptomycin and Ethambutol, followed by 6
months of Isoniazid and
Rifampicin.(2HRES/6HR)
 No hepatotoxic drugs:
• streptomycin ,Ethambutol and
Fluoroquinolone ,for 12-24
months.(2SEFq/16-22 EFq)
TB Regimens for patients with liver disorders

Instruction Regimen
Two hepatotoxic drugs: LPA 9HRE
must be performed for INH and
Rifampicin 2HRSE/6HR

9RZE

One hepatotoxic drug 2HES/10HE

No hepatotoxic drugs 18–24SEFQ
Liver diseases expert consultation is advisable in
treating patients with advanced or unstable liver
disease.
Proposed treatment options according to Child’s class
(could be evaluated with Liver diseases specialist)
Child’s class Suggested Treatment

A Two hepatotoxic drugs

B one hepatotoxic drug

C No hepatotoxic drugs.
 2-Management of drug-induced hepatitis

• From the first-line anti-TB drugs, pyrazinamide is

the most hepatotoxic followed by isoniazid, and
rifampicin.

• Signs / symptoms:
– Anorexia; nausea; vomiting; jaundice; abdominal
pain
 When to suspect Drug induced
hepatitis
• It is suspected when the ALT level is ≥3 times
the upper limit of normal in the presence of
hepatitis symptoms, or ≥5 the upper limit of
normal in the absence of symptoms.
• In either situation, hepatotoxic drugs are
stopped immediately and the patient is
evaluated carefully.
• Other causes of abnormal liver function tests
must be excluded before diagnosing drugs
induced hepatotoxicity
 Anti- TB drugs Rechallenge Priciples
• If TB treatment has been stopped, it is necessary to wait
for liver function tests to revert to normal and clinical
symptoms (nausea, abdominal pain) to resolve before
reintroducing the anti-TB drugs.
• Starts after ALT returns to less than two times the ULN,
• Rifampin may be restarted with or without ethambutol.
• After 3 to 7 days, isoniazid may be reintroduced,
subsequently
• rechecking ALT.
• If symptoms recur or ALT increases, the last drug added
should be stopped.
 Rechallenge Priciples cont
• For those who have experienced prolonged or severe
hepatotoxicity, but tolerate reintroduction with rifampin
and isoniazid, rechallenge with pyrazinamide may be
hazardous.
• In this circumstance, pyrazinamide may be permanently
discontinued, with treatment extended to 9 months.
• Although pyrazinamide can be reintroduced in some milder
cases of hepatotoxicity the benefit of a shorter treatment
course likely does not outweigh the risk of severe
hepatotoxicity from pyrazinamide rechallenge/ be
causious.
 Recommended steps in Sudan
• INH 100 mg /day increase to 300mg/day in 2-3 days. if
no reaction continue .
• After 2-3 days Rif can be added, started with 150 mg
/day,up to 300mg /day in 2-3 days,then to 450mg/day
(wt<50 kg) or 600 mg(wt>50) after further 2-3 days,if
no reaction.and then continue
• Finally Z can be added.Started with 200mg/day
increasing to 800gm after 2-3days then to 1600g /day.
• If there is no further reaction standard chemotherapy
can be contiued.
 If it is not possible to perform liver
function tests, it is advisable to wait an
extra 2 weeks after resolution of jaundice
and upper abdominal tenderness before
restarting TB treatment
 Management of drug-induced hepatitis

Tolerance to INH & RIF 9RHE (2RHE+7RH)

(2SHRE/6HR)
Tolerance to INH only 12 HES (2 HES/ 10 HE)
Tolerance to IRIF only 9 RZE (2RZE/7RE)

No tolerance to RIF, (2SEFq/16-22 EFq)

INH or Z
If All tolerated again 2RHZE+4RH
Renal failure and severe renal
insufficiency
 Renal disease
• Uremia and post renal transplant are state of
acquired immune deficiency , have higher risk
of developing TB. And should received
treatment for latent tuberculosis.
• dialysis patient have 10-30 fold higher risk to
develop TB.
• R, H , Z are excreted mainly by the biliary route ,
and so are safe in normal dosage in mild renal
impairment and CKD patient .
• Patient with creatinine clearance < 30ml/min
or ESRD on Z , is given in dose of 25 – 35
mg/dose 3times weekly after HD.
• S and others aminoglycoside are mainly
excreted by the kidneys and should be avoided
in CKD .
E is excreted mainly by the kidneys , should be
used in reduced dosages .
• Patient with CrCL < 30ml/min the dose is 15-
20mg/kg 3 times weekly .
• Patient on HD should received the dose after
HD.
• Dosage of quinolones also should be reduced
• Pyridoxine 10- 20mg/d should be used in
patient with CKD to reduce the risk of
peripheral neuropathy .
• 2RHZ / 4RH recommended regmin by WHO
for TB in patient with CKD.
 Drugs-Induced Renal Insufficiency
• Likely cause: streptomycin
• Asymptomatic; or ↓ urine, volume overload, uraemia, serositis
• Management:
– Stop agent
– Rule out other causes
– (Monitor renal function weekly)
– Once stable, restart at 3x weekly dosing for adjusted
drugs(Z,E)
 Epilepsy

• INH may be associated with an increased risk

of seizure .
• pyridoxine should be given to all epileptic
patient taking INH.
• There are many drug interaction of anti TB and
antiepileptic drugs.
• Close monitoring of serum drug level is
advised.
 Diabetes mellitus
• The drug regimen is same as in non-diabetic.
control of blood glucose is mandatory.
• oral hypoglycemic drugs may need to be
increased due to interaction with Rifampicin.
• Prophylactic pyridoxine is indicated.
THE END

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