guidelines for treatment of tuberculosis

8/3/2019 Guidelines for Treatment of Tuberculosis

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Queensland Tuberculosis Control Centre 26 June 2006 1

Queensland Tuberculosis Control CentreGUIDELINES FOR TREATMENT OF TUBERCULOSIS

IN PREGNANCY

The decision to treat tuberculosis in pregnancy must take into account the potential risks to mother

and foetus from medication, and the benefits to mother, foetus and community of adequatetreatment. It is widely considered that the benefits of treating tuberculosis in pregnancy outweighany risk of treatment.

Untreated tuberculosis represents a far greater hazard to a pregnant woman and her fetus than does treatment of the disease CDC (2003, 62)

INTERNATIONAL GUIDELINESThe British Thoracic Society ( www.brit-thoracic.org.uk ), International Union Against Tuberculosisand Lung Disease ( www.iuatld.org ) and the World Health Organisation ( www.who.int ) all supportthe use of standard first-line drug regimens in pregnant women with tuberculosis.

The Centers for Disease Control (USA) ( www.cdc.gov ) does not specifically endorse the use ofpyrazinamide in pregnancy, citing the absence of detailed teratogenicity data, but states that it canprobably be used safely during pregnancy. An alternative 9(E)HR regimen is endorsed by theCDC.

EFFECTS OF TUBERCULOSIS ON PREGNANCYMaternal tuberculosis has been associated with an increased risk of spontaneous abortion,perinatal mortality, small for gestational age and low birth weight in some studies. Outcome isunfavourably influenced by delays in diagnosis or treatment, along with disease other than that inlymph nodes (Ormerod, 2001).

Congenital tuberculosis is a rare complication of in utero tuberculosis infection as a result ofmaternal haematogenous spread. Congenital tuberculosis is difficult to diagnose as it is seldomdistinguishable from other neonatal or congenital infections. Symptoms usually arise in the secondor third weeks' post-partum. Hepatosplenomegaly, respiratory distress and fever are common, andchest radiography is almost universally abnormal (Ormerod, 2001).

FIRST-LINE DRUGSIsoniazid : (Pregnancy Category A). Recommended for use in pregnancy. As isoniazid may beassociated with an increased risk of hepatotoxicity in pregnant women, symptoms should beassessed, and it is recommended by some that liver function tests be performed fortnightly duringthe first two months of treatment, and monthly thereafter (Bothamley, 2001).

Isoniazid given for treatment of latent tuberculosis (chemoprophylaxis) is considered safe, and isrecommended especially where the risk of developing disease is higher, such as with HIV co-infection or with a history of recent contact (Bothamley, 2001).

Pyridoxine : Pyridoxine supplementation is recommended for all pregnant women taking isoniazidas deficiency is more likely in pregnant women than in the general population (CDC 2003, 62;Bothamley 2001). The Queensland Tuberculosis Control Centre recommends the routine use ofpyridoxine in all patients taking isoniazid.

Rifampicin : (Pregnancy Category C). Bleeding attributed to hypoprothrominaemia has beenreported in infants and mothers following the use of rifampicin in late pregnancy. The use ofrifampicin is indicated in pregnant women with tuberculosis, with the recommendation that vitaminK be given to both the mother and the infant postpartum if rifampicin is used in the last few weeksof pregnancy (Bothamley 2001).

Ethambutol : (Pregnancy Category A). Recommended for use in pregnancy.
http://www.brit-thoracic.org.uk/http://www.iuatld.org/http://www.who.int/http://www.cdc.gov/http://www.cdc.gov/http://www.who.int/http://www.iuatld.org/http://www.brit-thoracic.org.uk/


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Pyrazinamide : (Pregnancy Category n/a only available on SAS). There are no reports of foetalmalformations attributable to pyrazinamide, although there are additionally no animal orepidemiological studies reported to support the safety of this drug in pregnancy. The absence ofsuch safety data is the reason that the CDC (USA) guidelines do not endorse pyrazinamide inpregnancy. Its use is supported by other tuberculosis authorities, including the IUATLD and theBTS. To date, there are no reports of significant adverse events from the use of this drug in thetreatment of TB in pregnant women despite the fact that the drug is used as part of the standardregimen in many countries. However, additionally, insufficient data are available about the numberof pregnant women treated for TB in these many settings. If the treating doctor elects not to usepyrazinamide, a nine-month regimen containing isoniazid and rifampicin throughout (supplementedby ethambutol until drug susceptibility results are available) is recommended.

SECOND- LINE DRUGSStreptomycin : (Pregnancy Category n/a only available on SAS). Streptomycin has a wellestablished association with foetal ototoxicity and IS NOT RECOMMENDED for the treatment oftuberculosis in pregnant women.

Fluoroquinolones : (Pregnancy Category B3 for Ciprofloxacin, Gatifloxacin, Moxifloxicin andNorfloxacin). There is no evidence of increased incidence of abnormalities in babies of motherstreated with fluoroquinolones. Animal studies of ciprofloxacin suggest that there is a risk ofdamage to articular cartilage and subsequent juvenile arthritis with short courses of treatment, andthe possibility of joint damage with longer courses of treatment used for tuberculosis must beseriously considered (Bothamley, 2001). Fluoroquinolones should only be used in pregnantwomen with tuberculosis where the benefits of treatment are judged to outweigh the potential risksand the decision to use such drugs in this setting should only be made after discussion withclinicians experienced in the management of TB.

Amoxycillin/Clavulanic Acid (pregnancy category B1). There is no evidence of teratogenicity inanimal studies. Amoxycillin/clavulanic acid has been used in late pregnancy as prophylaxis inwomen with prolonged rupture of membranes without any problems documented, but there islimited experience with its use in the first trimester. There is only likely to be a minor role foramoxycillin/clavulanic acid in the treatment of pregnant women with MDR-TB where insufficientalternatives are available (Bothamley 2001). MDR-TB should only be treated after closeconsultation with clinicians experienced in the management of TB.

Para-Aminosalicylic Acid (PAS) (Pregnancy Category n/a only available on SAS). There isinsufficient animal and human safety data relating to the use of PAS in pregnancy. It has beenassociated with a slightly higher incidence of limb and ear abnormalities in one report involving 123patients taking PAS with other anti-TB drugs (Bothamley, 2001). However, an increased risk ofcongenital defects has not been found in other studies. PAS should not be used to treat TB inpregnant women unless the benefit/risk ratio (after discussion with a clinician experienced in the

management of difficult TB cases) is favourable.Amikacin (Pregnancy Category D). There is concern that all aminoglycosides are potentiallynephrotoxic and ototoxic to the foetus and their use IS NOT RECOMMENDED in tuberculosis inpregnant women. Maternal drug levels do not appear to correlate with foetal safety (MIMS 2003).Use of aminoglycosides in pregnancy should only be as a last resort after due consideration of therisks and benefits (WHO 2003) and close discussion with experts in the clinical management ofTB.

Capreomycin (Pregnancy Category C). There is evidence of teratogenicity in studies wherecapreomycin was given to pregnant rats. Capreomycin is generally contraindicated in pregnancyand should only be used following consideration of its risks and benefits (MIMS 2003, WHO 2003)

in consultation with an expert in the clinical management of TB.Ethionamide and Prothionamide (Pregnancy category n/a only available on SAS). Thesedrugs have been shown to be teratogenic in animal studies and their use IS NOTRECOMMENDED in pregnancy (Ormerod 2001).


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Cycloserine (Pregnancy Category n/a only available on SAS). There is no evidence ofteratogenicity in rats, but there is insufficient study in humans to confirm the safety of cycloserine inpregnancy. Its use should only be considered where the benefits outweigh the potential risks(MIMS 2003) after discussion with an expert in the clinical management of TB.

TREATMENT OF TUBERCULOSIS IN WOMEN WHO AREBREASTFEEDING

There is general consensus that although small concentrations of anti-tuberculosis drugs areexcreted in breast milk, treatment for tuberculosis is not a contraindication to breastfeeding. It isalso important to note that the concentrations of TB drugs in breast milk are so low that theycannot be relied upon for treatment of the infant. If an infant requires treatment for active diseaseor primary prophylaxis, the weight-based guidelines for children should be followed in selecting asuitable treatment regimen. In general, mothers with fully drug susceptible pulmonary TB cancontinue breast feeding their infants providing the infant has been given appropriate anti-mycobacterial cover (isoniazid, if no evidence of disease in the infant, or full treatment if active TB

disease cannot be excluded.)

Explanation of Pregnancy Categories (MIMS 2003)

Category ExplanationCategory A Drugs which have been taken by a large number of pregnant women and women of

childbearing age without any proven increase in the frequency of malformations or otherdirect or indirect harmful effects on the foetus having been observed

Category B1 Drugs that have been taken by only a limited number of pregnant women and women ofchildbearing age, without an increase in the frequency of malformation or other direct orindirect harmful effects on the human foetus having been observed. Studies in animals[1]have not shown evidence of an increased occurrence of foetal damage

Category B2 Drugs that have been taken by only a limited number of pregnant women and women ofchildbearing age, without an increase in the frequency of malformation or other direct orindirect harmful effects on the human foetus having been observed. Studies in animals[1]are inadequate or may be lacking, but available data show no evidence of an increasedoccurrence of foetal damage

Category B3 Drugs that have been taken by only a limited number of pregnant women and women ofchildbearing age, without an increase in the frequency of malformation or other direct orindirect harmful effects on the human foetus having been observed. Studies in animals[1]have shown evidence of an increased occurrence of foetal damage, the significance ofwhich is considered uncertain in humans

Category C Drugs that, owing to their pharmacological effects, have caused, or may be suspected ofcausing harmful effects on the human foetus or neonate without causing malformations.These effects may be reversible

Category D Drugs that have caused, are suspected to have caused, or may be expected to cause anincreased incidence of human foetal malformations, or irreversible damage. These drugsmay also have adverse pharmacological effects

Category X Drugs that have such a high risk of causing permanent damage to the foetus that theyshould not be used in pregnancy, or when there is a possibility of pregnancy

Note: For drugs in categories B1, B2 and B3, human data are lacking or inadequate and sub-categorisation istherefore based on available animal data. The allocation of a B category does not imply greater safety thanthe C category. Drugs in category D are not absolutely contraindicated in pregnancy (e.g. anticonvulsants).Moreover, in some cases the D category has been assigned on the basis of `suspicion'.

Due to legal considerations in this country, sponsor companies have, in some cases, applied a more

restrictive category than can be justified on the basis of available data. In some cases there may bediscrepancies between the official product information appearing in MIMS Annual and the information in theMedicines in Pregnancy booklet due to the lead times involved in printing.[1] Animal studies submitted in support of new drug applications must conform to the Australian Guidelinesfor the Registration of Drugs - Volume 1, Prescription and other specified Drug Products, 2nd Edition.


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References:Bothamley G (2001) Drug Treatment for Tuberculosis during Pregnancy: Safety ConsiderationsDrug Safety 24 (7):553-65

British Thoracic Society (1998) Chemotherapy and management of tuberculosis in the UnitedKingdom: recommendations 1998 Thorax 53 :536-48

Centers for Disease Control (2003) Treatment of Tuberculosis MMWR 52 (RR-11):1-77

Enarson DA, Rieder HL, Arnadottir T and Trbucq A (2000) Management of Tuberculosis: AGuide for Low Income Countries IUATLD, Paris 5 th Ed.

MIMS Online (2003) accessed electronically via http://ckn.health.qld.gov.au in January 2006.

Ormerod P (2001) Tuberculosis in pregnancy and the puerperium Thorax 56 :494-9

World Health Organisation (2003) Treatment of Tuberculosis: Guidelines for National Programs

WHO, Geneva 3rd

Ed
http://www.ckn.health.qld.gov.au/http://www.ckn.health.qld.gov.au/

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