Optimizing the care of the care of the reproductively active rheumatic patient Salahuddin Kazi

Optimizing the care of the Optimizing the care of the care of the reproductively care of the reproductively active rheumatic patientactive rheumatic patient

Salahuddin KaziSalahuddin Kazi

The Epidemiology of The Epidemiology of Fertility, Pregnancy and Fertility, Pregnancy and Outcomes in Rheumatic Outcomes in Rheumatic

PatientsPatients

Pregnancy and lupusPregnancy and lupus~4500 pregnancies in women with SLE ~4500 pregnancies in women with SLE each year in the United Stateseach year in the United States

one third will result in a cesarean sectionone third will result in a cesarean section

33% will have preterm birth33% will have preterm birth

more than 20% will be complicated by more than 20% will be complicated by preeclampsiapreeclampsia

Pregnancy in sclerodermaPregnancy in sclerodermathe overall success rate ( live birth) was:the overall success rate ( live birth) was:

84% in women who had limited scleroderma 84% in women who had limited scleroderma

77% in women who had diffuse scleroderma 77% in women who had diffuse scleroderma

84% in the historical controls.84% in the historical controls.

Clowse M.E.B., Jamison M.G., Myers E., et al: National study of medical complications in SLE pregnancies. Arthritis Rheum 54. (9 Suppl): S263-S264.2006

Steen V.D.: Pregnancy in women with systemic sclerosis. Obstet Gynecol 94. (1): 15-20.1999

The spectrum of The spectrum of reproductionreproduction

The patient preventing/postponing The patient preventing/postponing reproductionreproduction

The patient preserving fertilityThe patient preserving fertility

The patient actively planning pregnancyThe patient actively planning pregnancy

The pregnant patientThe pregnant patient

The postpartum patientThe postpartum patient

The lactating/nursing patientThe lactating/nursing patient

The patient The patient preventing/postponing preventing/postponing

pregnancypregnancyOral Contraceptives – likely safeOral Contraceptives – likely safe

SELENA trail – 1 year placebo controlled study in SLESELENA trail – 1 year placebo controlled study in SLEPatients with inactive or stable active lupusPatients with inactive or stable active lupusWomen with moderate anticardiolipin or the lupus Women with moderate anticardiolipin or the lupus anticoagulant were excludedanticoagulant were excludedNo increase in lupus flaresNo increase in lupus flares

Depo-Progesterone – effective and safe for short term Depo-Progesterone – effective and safe for short term useuse

FDA advised that the use be limited to 2 years FDA advised that the use be limited to 2 years because of an increased risk of osteoporosis with because of an increased risk of osteoporosis with long-term uselong-term use

IUD - a woman with SLE who has a single partner and IUD - a woman with SLE who has a single partner and who is not on immunosuppressive drugs other than who is not on immunosuppressive drugs other than low-dose prednisone is considered an appropriate low-dose prednisone is considered an appropriate candidatecandidate

The patient The patient preserving fertilitypreserving fertilityLess important issue with decreasing use of Less important issue with decreasing use of cyclophosphamide and shorter durtaion of cyclophosphamide and shorter durtaion of therapytherapy

The PREGO study – ongoing – will compare The PREGO study – ongoing – will compare monthly injection of gonadotropin-releasing monthly injection of gonadotropin-releasing hormone analogue (GnRH-a) to placebo in hormone analogue (GnRH-a) to placebo in young SLE patients during cyclophosphamide young SLE patients during cyclophosphamide therapytherapy

The only established method for preservation The only established method for preservation of child-bearing potential in women at risk of of child-bearing potential in women at risk of gonadal failure is embryo cryopreservationgonadal failure is embryo cryopreservation

Immunosuppressive Immunosuppressive Drugs in PregnancyDrugs in Pregnancy

Contraindicated Potentially Safe: Caution Advised

Insufficient Data

Methotrexate Glucocorticoids TNF inhibitors

Leflunomide Azathioprine Anakinra

CellCept 6- mercaptopurine Rituximab

?NSAIDs Sulfasalazine Abatacept

Cytoxan Hydroxychloroquine

Intravenous immune globulin

The patient actively The patient actively planning pregnancyplanning pregnancy

When to discontinue medicationsWhen to discontinue medicationsMethotrexate – 3 monthsMethotrexate – 3 months

Leflunomide – 2 years! + washout if < 2 Leflunomide – 2 years! + washout if < 2 yearsyears

CellCept – 3 monthsCellCept – 3 months

NSAIDS – 2 weeksNSAIDS – 2 weeks

Anti-TNF – after pregnancy confirmedAnti-TNF – after pregnancy confirmed

The pregnant The pregnant patientpatient

The patient with well controlled diseaseThe patient with well controlled disease

The patient with active diseaseThe patient with active disease

The special case of the SSA/Ro positive The special case of the SSA/Ro positive patientpatient

The patient with antiphospholipid The patient with antiphospholipid antibodiesantibodies

Patient with well Patient with well controlled RA on an anti-controlled RA on an anti-

TNF agentTNF agentJW is a 32 year old woman with RF+ve, JW is a 32 year old woman with RF+ve, CCP + RACCP + RA

She avoided methotrexate and has been She avoided methotrexate and has been on Humira monotherapy – with well on Humira monotherapy – with well controlled disease for 18 monthscontrolled disease for 18 months

She is now keen to start a familyShe is now keen to start a family

Should she stop/continue anti-TNF Should she stop/continue anti-TNF therapy?therapy?

Table 1 Table 1 Pregnancy risk categories (adapted Pregnancy risk categories (adapted from FDA Consumerfrom FDA Consumer6060) associated with ) associated with

antirheumatic drugsantirheumatic drugs

Skomsvoll JF et al. (2007) Drug Insight: anti-tumor necrosis factor therapy for inflammatory arthropathies during reproduction, pregnancy and lactation

Nat Clin Pract Rheumatol 3: 156–164 doi:10.1038/ncprheum0426

Skomsvoll JF et al. (2007) Drug Insight: anti-tumor necrosis factor therapy for inflammatory arthropathies during reproduction, pregnancy and lactation

Nat Clin Pract Rheumatol 3: 156–164 doi:10.1038/ncprheum0426

Key PointsKey PointsNo increased risk of adverse pregnancy No increased risk of adverse pregnancy outcome has been demonstrated in patients outcome has been demonstrated in patients treated with anti-tumor necrosis factor (anti-treated with anti-tumor necrosis factor (anti-TNF) drugsTNF) drugs

In general, anti-TNF therapy should be In general, anti-TNF therapy should be stopped before pregnancy, as there are stopped before pregnancy, as there are limited data concerning the risk to the fetuslimited data concerning the risk to the fetus

Anti-TNF therapy might, however, be used in Anti-TNF therapy might, however, be used in selected patients with inflammatory selected patients with inflammatory arthropathies where there is high disease arthropathies where there is high disease activity, according to an individual risk–benefit activity, according to an individual risk–benefit analysis, until early pregnancy is detected analysis, until early pregnancy is detected (although this might result in possible (although this might result in possible exposure in early pregnancy)exposure in early pregnancy)

VACTERL and anti-TNF VACTERL and anti-TNF therapytherapy

The authors examined reports of congenital The authors examined reports of congenital abnormalities submitted to the US FDA over a 5–abnormalities submitted to the US FDA over a 5–10 year period, and identified 41 children with 10 year period, and identified 41 children with birth defects born to mothers who received birth defects born to mothers who received infliximab or etanercept at some point during infliximab or etanercept at some point during their pregnancytheir pregnancy

Of these children, 24 had a set of anomalies Of these children, 24 had a set of anomalies that, in the view of the authors, constituted part that, in the view of the authors, constituted part of the so-called VACTERL association, a of the so-called VACTERL association, a nonrandom association of birth defects nonrandom association of birth defects comprising vertebral, anal, cardiac, tracheal, comprising vertebral, anal, cardiac, tracheal, esophageal and renal malformations or problemsesophageal and renal malformations or problems

Carter, J. D. et al. A safety assessment of tumor necrosis factor antagonists during pregnancy: a review of the FDA database. J. Rheumatol. doi:10.3899/jrheum.080545 (2008)

VACTERL and anti-TNF VACTERL and anti-TNF therapytherapy

The VACTERL association occurs spontaneously in The VACTERL association occurs spontaneously in 0.3–2.1 per 10,000 live births, and its multiple 0.3–2.1 per 10,000 live births, and its multiple malformations originate during the early weeks malformations originate during the early weeks of pregnancyof pregnancy

The design of the Carter study makes it The design of the Carter study makes it impossible to judge whether or not TNF inhibitors impossible to judge whether or not TNF inhibitors taken during pregnancy increase the risk for taken during pregnancy increase the risk for birth defectsbirth defects

The main limitation is the unknown number of The main limitation is the unknown number of total pregnancy exposures to TNF inhibitors, total pregnancy exposures to TNF inhibitors, which precludes a meaningful assessment of the which precludes a meaningful assessment of the magnitude of risk (if any)magnitude of risk (if any)

Carter, J. D. et al. A safety assessment of tumor necrosis factor antagonists during pregnancy: a review of the FDA database. J. Rheumatol. doi:10.3899/jrheum.080545 (2008)

The Patient with active The Patient with active disease/flare in disease/flare in

pregnancypregnancyPrednisonePrednisone is largely metabolized by the placenta - fetal is largely metabolized by the placenta - fetal exposure is smallexposure is small

Doses greater ≥20 mg increase the risk of both Doses greater ≥20 mg increase the risk of both preeclampsia and of gestational diabetes in SLE preeclampsia and of gestational diabetes in SLE pregnancypregnancy

Intravenous methylprednisolone, 1000 mg daily for 3 Intravenous methylprednisolone, 1000 mg daily for 3 days, given over 90 minutes, can help achieve quick days, given over 90 minutes, can help achieve quick control of an SLE flarecontrol of an SLE flare

Fetal exposure to corticosteroids may not be completely Fetal exposure to corticosteroids may not be completely benignbenign

Cognitive impairment has been found in premature Cognitive impairment has been found in premature infants exposed to corticosteroidsinfants exposed to corticosteroids

This must be balanced against the severe risks This must be balanced against the severe risks experienced by very preterm babiesexperienced by very preterm babies


pregnancypregnancyIt is well know that nonsteroidal anti-It is well know that nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided inflammatory drugs (NSAIDs) should be avoided during the second and third trimesters because during the second and third trimesters because of their effect on the ductus arteriosusof their effect on the ductus arteriosus

NSAIDs must be avoided even in the first NSAIDs must be avoided even in the first trimestertrimester

NSAIDs rarely have a deleterious effect on NSAIDs rarely have a deleterious effect on fertilityfertility

Ofori B., Oraichi D., Blais L., et al: Risk of congenital anomalies in pregnant users of non-steroidal anti-inflammatory drugs: a nested case-control study. Birth Defects Res B Dev Reprod Toxicol 77. (4): 268-279.2006


pregnancypregnancyAntimalarialsAntimalarials: Initially, there was concern : Initially, there was concern because of case reports of congenital because of case reports of congenital malformations in pregnancies with chloroquine malformations in pregnancies with chloroquine exposureexposure

Both chloroquine and hydroxychloroquine cross Both chloroquine and hydroxychloroquine cross the placenta, and both are also present in the placenta, and both are also present in breast milkbreast milk

Hydroxychloroquine should be continued Hydroxychloroquine should be continued during pregnancy because cessation of during pregnancy because cessation of hydroxychloroquine leads to increased disease hydroxychloroquine leads to increased disease activity, lupus flares, and preterm birthactivity, lupus flares, and preterm birth


pregnancypregnancyAzathioprineAzathioprine has a long track record of use in has a long track record of use in pregnancy with an acceptable safety profile – rare pregnancy with an acceptable safety profile – rare reports of neonatal immunosuppression.reports of neonatal immunosuppression.

Mycophenolate mofetil Mycophenolate mofetil has been associated with has been associated with rare fetal malformations of the corpus callosum and rare fetal malformations of the corpus callosum and digit - advisable to switch to azathioprine before digit - advisable to switch to azathioprine before conceptionconception

CyclophosphamideCyclophosphamide must be avoided during the first must be avoided during the first and early second trimesters – use in the third and early second trimesters – use in the third trimester in several patients who had severe lupus trimester in several patients who had severe lupus nephritis not responding to high-dose nephritis not responding to high-dose corticosteroids and other immunosuppressive corticosteroids and other immunosuppressive drugs was followed by intrauterine fetal demisedrugs was followed by intrauterine fetal demise

CyclosporineCyclosporine has been associated with growth has been associated with growth restriction - may reflect the underlying maternal restriction - may reflect the underlying maternal diseases for which it was prescribeddiseases for which it was prescribed

The patient with SSA/Ro The patient with SSA/Ro antibodiesantibodies

ML is a 22 year old nursing student with ML is a 22 year old nursing student with SLE (+ANA, +dsDNA, + SSA/Ro, SLE (+ANA, +dsDNA, + SSA/Ro, pericarditis) – on HCQ alonepericarditis) – on HCQ alone

She is now 12 weeks pregnantShe is now 12 weeks pregnant

What is the risk for neonatal lupus What is the risk for neonatal lupus syndromes?syndromes?

How should she be managed?How should she be managed?

Neonatal Lupus SyndromesNeonatal Lupus Syndromes95%95%

SLESLE35%35%

SSSS70%70%

SCLESCLE80%80%

AsymptomaticAsymptomaticWomenWomen0.44%0.44%

Frequency ofAnti-Ro Antibodies

Frequency ofAnti-Ro Antibodies

The patient with The patient with SSA/Ro antibodiesSSA/Ro antibodies

Neonatal lupus is a passively transferred Neonatal lupus is a passively transferred autoimmune disease that occurs in about 1 autoimmune disease that occurs in about 1 to 2 percent of babies born to mothers with to 2 percent of babies born to mothers with SSA/Ro antibodiesSSA/Ro antibodies

The incidence of congenital complete heart The incidence of congenital complete heart block appears to be more common in women block appears to be more common in women with high titers of anti-Ro/SSA and with high titers of anti-Ro/SSA and anti-La/SSBanti-La/SSB

The incidence of heart block rises to about The incidence of heart block rises to about 18 percent in women with anti-Ro/SSA 18 percent in women with anti-Ro/SSA and/or anti-La/SSB antibodies who have had and/or anti-La/SSB antibodies who have had a previous child with congenital heart blocka previous child with congenital heart block


Antibodies with a specificity for the 52 Antibodies with a specificity for the 52 kD component of the Ro/SSA protein are kD component of the Ro/SSA protein are more frequently found and are present more frequently found and are present at higher concentrations in the serum of at higher concentrations in the serum of children with congenital heart block and children with congenital heart block and their mothers their mothers

The combination of anti-Ro/SSA and The combination of anti-Ro/SSA and anti-La/SSB antibodies may increase the anti-La/SSB antibodies may increase the likelihood of cutaneous manifestations likelihood of cutaneous manifestations of neonatal lupusof neonatal lupus


Complete heart block generally persists Complete heart block generally persists despite steroid therapydespite steroid therapy

incomplete heart block often is incomplete heart block often is reversible, but may progress to reversible, but may progress to complete heart block despite therapy complete heart block despite therapy

Glucocorticoids may suppress the Glucocorticoids may suppress the associated pleuropericardial effusion or associated pleuropericardial effusion or hydrops, and may improve outcomes hydrops, and may improve outcomes


Complete heart block generally persists despite steroid Complete heart block generally persists despite steroid therapytherapy

incomplete heart block often is reversible, but may incomplete heart block often is reversible, but may progress to complete heart block despite therapy progress to complete heart block despite therapy

Glucocorticoids may suppress the associated Glucocorticoids may suppress the associated pleuropericardial effusion or hydrops, and may improve pleuropericardial effusion or hydrops, and may improve outcomes outcomes

There are no formal guidelines for the type or the There are no formal guidelines for the type or the frequency of testing to detect fetal heart blockfrequency of testing to detect fetal heart block

Dr. Jill Buyon recommends performing weekly pulsed Dr. Jill Buyon recommends performing weekly pulsed Doppler fetal echocardiography from the 16th through Doppler fetal echocardiography from the 16th through the 25th week of pregnancy and then every other week the 25th week of pregnancy and then every other week until 32 weeksuntil 32 weeks

Dr. Buyon is a great Dr. Buyon is a great resource if you have resource if you have

questionsquestionsDear Dr. Buyon,

I'm following a very interesting 33 year old patient with Sjogren's syndrome who is positive for ANA, anti-SSA and anti-SSB. She is especially interesting because she presented with hypokalemia and was found to have a renal tubular acidosis approximately 11 years ago. She subsequently developed sicca symptoms and in 2006 successfully delivered a baby without any complications. She has a Masters in Library Sciences and read about the differences between 52 kD and 60 kD Ro and the varying risk for congenital heart block. She is interested in determining what kind of anti-SSA/Ro antibody she may be carrying. I recognize that this is a research assay and not commercially available. All the same, both she and I are curious if your lab or any other lab that you are aware off is able to perform this determination. She would also be interested in participating in any research study that would enroll her.

Thanks!Dino Kazi

Dr. Buyon is a great Dr. Buyon is a great resource if you have resource if you have

questionsquestionsDear Dino,

Thank you for your email. The long and short of it is that I am not in agreement that your patient really needs any testing beyond anti-Ro and La. Here is why. Her risk of a child with CHB is 2% if she has high titer anti-Ro (almost all anti-Ro is high titer). If she also has anti-La it may be 4-5%, no more. The presence of antibodies to Ro52 is common in mothers of children with CHB but in FACT it does not jack the risk up any higher than 5%. Almost every mother in our PRIDE study (Circulation) had anti-52Ro and as you will see the incidence was as expected, no higher. She should have weekly PR intervals done on her fetus from 16-26 weeks if possible. Thereafter the risk is decreased. If PR greater than 150msec she should have her Peds Cards call me urgently. There is no reliable prophylactic med and we are currently studying HCQ and IVIG. The recurrence rate is about 19%. Hope this all helps.

Jill


If the fetus develops incomplete heart block, prenatal If the fetus develops incomplete heart block, prenatal treatment should be considered with the treatment should be considered with the administration of fluorinated glucocorticoids that are administration of fluorinated glucocorticoids that are not inactivated by placental 11-beta hydroxysteroid not inactivated by placental 11-beta hydroxysteroid dehydrogenase (eg, oral dexamethasone 4 mg daily or dehydrogenase (eg, oral dexamethasone 4 mg daily or betamethasone 2 or 3 mg per day), beginning as soon betamethasone 2 or 3 mg per day), beginning as soon after detection as feasible, and continuing through the after detection as feasible, and continuing through the end of pregnancy. end of pregnancy.

If heart block does not improve despite several weeks If heart block does not improve despite several weeks of glucocorticoid therapy, and if there is no other of glucocorticoid therapy, and if there is no other indication for their use, they may be discontinued. indication for their use, they may be discontinued.

Careful observation of infants whose atrioventricular Careful observation of infants whose atrioventricular block has been reversed in utero is necessary in the block has been reversed in utero is necessary in the postnatal period, as there is still a risk of progression postnatal period, as there is still a risk of progression to a higher degree heart block, even with clearance of to a higher degree heart block, even with clearance of maternal autoantibodies maternal autoantibodies

The patient with positive The patient with positive antiphospholipid antiphospholipid

antibodiesantibodiesAntibodies aloneAntibodies alone

Antibodies + pregnancy-related event Antibodies + pregnancy-related event (early severe preclampsia, IUGR)(early severe preclampsia, IUGR)

Antibodies + recurrent embryonic lossAntibodies + recurrent embryonic loss

Antobodies + late fetal lossAntobodies + late fetal loss

Antibodies + prior VTEAntibodies + prior VTE

Antiphospholipid Antiphospholipid antibodies aloneantibodies alone

Therapeutic options for these women include no Therapeutic options for these women include no therapy, low dose ASA alone, or low dose ASA and therapy, low dose ASA alone, or low dose ASA and prophylactic heparinprophylactic heparin

Advisory Board of the 10th International Congress on Advisory Board of the 10th International Congress on aPL favored using low dose ASA alone in these aPL favored using low dose ASA alone in these patients patients

The American College of Chest Physicians Evidence-The American College of Chest Physicians Evidence-Based Clinical Practice Guidelines concluded these Based Clinical Practice Guidelines concluded these women are probably at increased risk of developing women are probably at increased risk of developing pregnancy-related venous thrombosis and suggested pregnancy-related venous thrombosis and suggested they be managed antepartum with either close clinical they be managed antepartum with either close clinical surveillance, prophylactic unfractionated heparin, or surveillance, prophylactic unfractionated heparin, or prophylactic low molecular weight heparin, and that prophylactic low molecular weight heparin, and that they receive postpartum anticoagulationthey receive postpartum anticoagulation

APL + history of APL + history of severe pre-severe pre-

eclampsia or IUGReclampsia or IUGRLow dose aspirin (50-100 mg) in 2Low dose aspirin (50-100 mg) in 2ndnd and and 33rdrd trimester trimester

Consider prophylactic LMWH or UFH in Consider prophylactic LMWH or UFH in cases of ASA failure or when placental cases of ASA failure or when placental examination shows extensive examination shows extensive thrombosisthrombosis

APL + late fetal APL + late fetal lossloss

For women with laboratory criteria for For women with laboratory criteria for aPL and one or more fetal losses after 10 aPL and one or more fetal losses after 10 weeks of gestationweeks of gestation

Combined therapy with low dose ASA (81 Combined therapy with low dose ASA (81 mg per day begun as soon as conception mg per day begun as soon as conception is attempted) and prophylactic LMWHis attempted) and prophylactic LMWH

Low dose ASA and prophylactic or Low dose ASA and prophylactic or intermediate dose unfractionated heparin intermediate dose unfractionated heparin is a reasonable alternativeis a reasonable alternative

APL + recurrent APL + recurrent embryonic lossesembryonic losses

Management of women with laboratory Management of women with laboratory criteria for aPL and multiple embryonic criteria for aPL and multiple embryonic losses (less than 10 weeks of gestation) is losses (less than 10 weeks of gestation) is controversial, as there are many causes of controversial, as there are many causes of early recurrent pregnancy lossearly recurrent pregnancy loss

If the woman has had three or more such If the woman has had three or more such losses and a structurally normal uterus and losses and a structurally normal uterus and documentation of euploid lossesdocumentation of euploid losses

low dose ASA and prophylactic or low dose ASA and prophylactic or intermediate-dose heparin therapy or low intermediate-dose heparin therapy or low dose ASA and prophylactic LMWH heparin dose ASA and prophylactic LMWH heparin during pregnancy can be offeredduring pregnancy can be offered

APL + prior VTEAPL + prior VTEWomen with laboratory criteria for aPL Women with laboratory criteria for aPL and a prior history of arterial or venous and a prior history of arterial or venous thrombosis are at high risk of thrombosis are at high risk of recurrence and are generally on lifelong recurrence and are generally on lifelong anticoagulation with warfarinanticoagulation with warfarin

These women should receive These women should receive thromboprophylaxis during pregnancy thromboprophylaxis during pregnancy and postpartum and postpartum

Dosing Heparin Dosing Heparin with prior VTEwith prior VTE

For most pregnant women a low For most pregnant women a low molecular weight heparin (LMWH)-molecular weight heparin (LMWH)-based regimen, rather than an based regimen, rather than an unfractionated heparin (UFH)-based unfractionated heparin (UFH)-based regimen is recommendedregimen is recommended

Continue therapy postpartum for 6 Continue therapy postpartum for 6 weeksweeks

The postpartum The postpartum patientpatient

Watch for disease flaresWatch for disease flares

Screen for thyroid diseaseScreen for thyroid disease

Continue anticoagulation (if applicable) Continue anticoagulation (if applicable) for 6 weeksfor 6 weeks

Discuss resumption of medicationsDiscuss resumption of medications

Discuss resumption of contraceptionDiscuss resumption of contraception

Lactation/NursingLactation/NursingPrednisone is excreted into the breast milk, but use during Prednisone is excreted into the breast milk, but use during lactation is deemed compatible by the American Academy of lactation is deemed compatible by the American Academy of Pediatrics (AAP) if justified by the potential benefit to the Pediatrics (AAP) if justified by the potential benefit to the health of the motherhealth of the mother

Azathioprine is likely safe – very low levels in infantsAzathioprine is likely safe – very low levels in infants

Sulfasalazine is safe – folate supplementation recommendedSulfasalazine is safe – folate supplementation recommended

HCQ - HCQ is found in human breast milk. Breastfed infants HCQ - HCQ is found in human breast milk. Breastfed infants may be exposed to 2 percent of the maternal dose The AAP may be exposed to 2 percent of the maternal dose The AAP considers use of HCQ compatible with breastfeedingconsiders use of HCQ compatible with breastfeeding

CSA is excreted in breast milk, and therapeutic levels have CSA is excreted in breast milk, and therapeutic levels have been reported in breastfed infants - the use of CSA by been reported in breastfed infants - the use of CSA by lactating mothers is not recommendedlactating mothers is not recommended

Methotrexate, leflunomide, CellCept and Cytoxan are all Methotrexate, leflunomide, CellCept and Cytoxan are all contraindicatedcontraindicated

The The lactating/nursing lactating/nursing

patientpatient

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Optimizing the care of the care of the reproductively active rheumatic patient Salahuddin Kazi