Download Effects of antiinflammatory and immunosuppressive Medicines on

EFFECTS OF ANTIINFLAMMATORY AND
IMMUNOSUPPRESSIVE MEDICINES ON FERTILITY,
PREGNANCY AND LACTATION.
DR SULTAN ALMOGAIRIN
CONSULTANT RHEUMATOLOGIST
1
Effects of antiinflammatory
and immunosuppressive
Medicines on Fertility,
Pregnancy and Lactation
1.
2.
3.
4.
5.
6.
7.
Aspirin
NSAID
Corticosteroids
SAS
HQ
Gold
PCA
8. Cyclosporin
9. MTX
10. Leflun
11. AZO
12. MMF
13. CYP
14. Antibiologic agents
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FDA Use-in-Pregnancy ratings for drugs
Category Interpretation
A
Controlled studies show no riskAdequate, well-controlled studies in
preg women have failed to demonstrate
risk to the fetus.
B
No evidence of risk in humansEither animal findings show risk (but human
findings do not) or, if no adequate human
studies have been done, animal findings are
negative.
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Category Information
C
Risk cannot be ruled out –
Human studies are lacking and animal studies
studies are either +ve for fetal risk or lacking as
as well. However, pot. benef. may justify the
potential risk.
D
Positive evidence of risk –
Investigational or postmarketing data show risk to
the fetus. Nevertheless, pot. benef. may outweigh
the risk.
X
Contraindicated in pregnancyStudies in animals por humans, or investig. or
postmarketing reports have shown fetal risk which
clearly outweighs any possible benef to the patient.
4
Many rheumatic disease affects women
of child age and meds used to treat
these disease may affect
Concep – Preg – Fetal develop and lact.
Physicians who care for these women
need to be aware of the poten S/E.
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Safety of Drug each stage and
benefit to risk ratio
In general, most of drugs however are not
tested in preg women and are not
labelled for use during preg.
The lack of available information presents
a problem for both physician and the
woman.
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Aspirin
A. Fertility and conception:
- remain most common drug
- Asp can cross the placenta and cause
cong A (rare)
- several large prosp studies failed to
confirm a significant  in cleft palate or
cong A.
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ASPIRIN
B. Preg (M) Effects
- higher dose  3 Gm/d inhibits uterine
contraction and prolong labor and gestation
 ant and post P Hg → complicated D +
anemia
- low dose Asp throughout P
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ASPIRIN
C. Preg (F)
- Possible premat closure of DA may
also causes  PLt aggreg and  risk
of IC Hgg.
- transient NEON RF and oligohy have
been described
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ASPIRIN
D. LACT
- After single Asp dose of 450 mg to 650 mg 0.1 to 21%
reaches the inf over 24-hours.
- Peak salicyl level in milk 2-hours after peak S. level
- However, with ch. Maternal intake of antiinfl. Doses and
immature NEON metab the infant can potent develop salicyl
intox. and bleed
AAP: Asp be used cautiously by the mother of nursing inf and large
doses should be avoided.
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ASPIRIN
E. RECOMMEND:
- Anti inflam doses of Asp should be
avoided the last (4 to 8 weeks) of preg
to avoid complications and for lactation low
doses (caution)
ASPIRIN
FDA (C, D3rd)
BF ©
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2. NSAID
A. Concept of F
- use in P has not been investigated in
depth for many of the newer Ag.
- NSAID not known to be teratog. in
human and prophylactic cessation of
therapy is not necessary.
- Women plan to conceive (implant)
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2. NSAID
C. Preg (F)
- 1448 newborn has been exposed to Naprox
during the 1st T. And results do not support an
assoc between the drug and Cong A.
- Another study showed only assoc with
spontaneous abortion.
- There will be  IC bleed + cut blood.
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2. NSAID
D. Preg (F)
-
Premature closure DA
Pulm HTN
Impaired renal function,  amniotic fluid
The dose, duration and period of gestation are
important determinants of these effects
- Above are uncommon with D/C weeks
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2. NSAID
E. LACT
- Milk to plasman ration 0.01 trace amount of Nap,
Ibup, Diclo have been reported in milk.
- Some NSAID circulate entero hep (C/E) because
most NSAID displace BIL they can  risk of
kern and are C/E in NEON J.
AAP
Ibup, Diclof to be comp to BF.
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2. NSAID
RECOMMEND
- When administered to preg patient
NSAID should be given in
1. Lowest effective dose.
2. Intermittently, if possible
3. Tt should be D/C at least 6 to 8
weeks prior to expected delivery
NSAID
FDA(B, D near term) BF ©
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3. Cortecosteroid
Flurinated prep such as dex and Betam less
metabolized in placenta so greater dose to
fetus so preferred for immature lung.
Agent such as Pred and Methyl Pred only
10% of maternal dose to F so preferred for
maternal dis.
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3. Cortecosteroid
A. Concept and F:
CST in high doses have causes cleft P in
experimental animals and low birth weight in
human.
No evidence that pred or methyl pred are
teratog in humans.
B. Preg (M)
as non-preg, DM, HTN, AVN.
 Premature rupture of membrane
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3. Cortecosteroid
C. Preg (F)
Small % of maternal dose of prednisone,
prednisolone, + methyl Pr reaches F and
NEON monitoring for incidence of Adr. Supp
and infection (very low).
Several large studies have not found 
incidence of cong A.
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3. Cortecosteroid
D. Lact
Small amount of CST in BrM
For maternal doses of 20 mg once or twice daily.
The nursing infant would be exposed to minimal
amount of steroid. At higher dose they
recommended waiting at least 4 hours. However,
even at 80 mg ld. The nursing infant would have
<0.1% of the dose which corresponds to <10% of the
infant’s end of cortisol product.
AAP
Compatible with BF
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3. Cortecosteroid
E. RECOMMEND
Routine use of POCa + Vitamin D supp is
recommended
Stress dose for any stressful event such as
surgery
Lactation (four hours)
CST
FDA (B/C)
BF ©
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Sulfasalaz
30% of oral dose is absorbed in small
intestine. The test passes into the colon.
SAS will be cleared into 5 AM SA and Sulfa
+ fetal conc. are approx. the same as
maternal conc. but 5 AM SA has very limited
placental transfer.
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Sulfasalaz
A. Concept + F
In (W) no reports of problem to F.
In (M) SAS induces oligosp., impaired
sperm motilits.
Temporary and reversible infertility with
D/C drug.
B. Preg (F) most experience in IBD patients no
 in fetal abortion or spontaneous abortion
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Sulfasalaz
C. Lact
Drug is excreted in Br M (45% of maternal S.
level). No adverse effects in 16 nursing infants. An
exclusively Br Fed infant developed bloody diarrhea
attributed to his mother SAS and mother was slow
acetylator who has relatively high S. level. Based on
this report.
AAP Classifies SAS as a drug should be given with
caution to nursing W because substantial S/E may
occur in same inf. It may be the first choice in treat
RA in child age who are planning to get preg.
SAS
FDA (B, D near term)
BF © caution
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HYDROXY CH
A. Concept + F
No adverse effects on F
B. Preg (F)
No report of cong malf in children exposed to the
drug used to treat RA and SLE.
9 preg in 8 SLE patient on HQ Tt thought preg.
9 livebirths with no cong malf. And F/U 33 Ms
Conclusion: it is safer to continue Tt with HQ than to
D/C it during preg + risk aflare up of the dis.
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HYDROXY CH
Retrospec
36 preg in 33 patients (SLE) exposed to
HQ and compared them with preg in 53
control W.
The obstetric outcome of two groups were
similar. There was no evidence of
teratogenic effect of HQ.
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HYDROXY CH
27 preg in 23 W with M to mod SLE
In 17 of the preg the drug was used at a dose 200-400
mg OD through gestation. The outcome of these
cases included two abortion, two prenatal, one infant
with CHB
Six patient HQ was started during the 1st trimester and in
the remaining four therapy was stopped after dx of
preg resulting in a worsening of the dis and higher
dose of CST and preg termination in one because of
severe renal lupus F/U of 20 newborn (healthy + no
S/E) so benefit of continu of HQ risks and dis exac
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HYDROXY CH
Preg (M)
Available data suggest that HQ can be continued safely
throuh preg. It seems that because of the risk of
SLE flare, discontinuing therapy during preg
represent a greater danger to the fetus and mother
than continuing H. Moreover, cessation of therapy
at the time preg is detected would not stop
exposure of the embryo and fetus to the drug
because of the very long elimination half life.
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HYDROXY CH
Preg (L)
Low conc. of HQ are found in Br milk because
of slow elimination rate and potential of
accummul of atoxic amount in the infant,
breast feeding during daily therapy with HQ
should be undertaken cautiously.
AAP classified the drug as compatible with
breast feeding.
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HYDROXY CH
RECOMMEND
HQ does not seem to pose a significant risk to the fetus
especially with low doses. It may be most prudent to
avoid its use during preg in patient with RA since the
patient can be managed safely with CST.
However, with patients with SLE already taking HQ, the
benefit of continuing Tt with this medication, though
preg seem to outweigh the risk associated with its
use.
HQ
FDA ©
BF © caution
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GOLD
A. Concept + F
There are limited reports of preg outcome in W
taking G for Tt of RA. G doesn’t seem to
impair fertility use adeq cc.
One approach for patients undergoing long
term IMG is to time each monthly inject on
the 1st day of period. Such regimen assure
that G can be withdrawn as soon as preg is
recognized.
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GOLD
B. Preg (F)
G cross the placenta and have been found
in the fetal liver and kid. There is no
evidence of  in neon malformation in the
small number of pregnancy reported.
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GOLD
C. Lact
There are small number of reports of rash, nephritis,
hepatitis and immunological problems and it is
difficult to ascribe a cause effect relationship.
AAP considers G compatible with Breast feeding but
because of prolonged retention of G in the mother
body and the potential for toxic effect in the infant, it
may most prudent to avoid nursing.
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GOLD
D. RECOMMEND
Because preg freq improved during preg,
the potential risks of the drug seem to
outweigh the benefit. However, in apt who is
stable on G many rheumatologist are
reluctant to risk a flare either during or after
preg and may wish to have these patients
continue taking the drug in that case a
careful discussion with the patient and
monitoring of the preg are essential.
GOLD
FDA ©
BF © caution
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P C A
Teratogenic and skin laxity, have been observed in
animal studies and exposure of the human fetus to
PCA has resulted in serious disorders including
growth retard, hip dislocate, hernia.
In general, other drugs (NSAID or low dose CST) are
effective and safer for pregnant or lactating patient
with RA.
PCA its role in pregnant for W with sclerod is unknown
and Tt should be D/C before conception or as soon
as preg is confirmed.
36
CSP
Experience in the Tt of RA is
limited although it is approved by
FDA for this use. Most of preg
outcome data are from preg transpl
recipient.
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CSP
A. Preg (M)
51 preg in 48 W treated have been reported
and 11 patients have been conceived from
men on CSP.
BP, G, Pyelon, uterine dyst, SZ,
encephalopathy and Cr. Complicated
almost 50% of these high risk preg.
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CSP
B. Preg (F)
In the study of 51 preg, 2 spontaneous and
6 elec abortions occurred, 1 for fetal an
encephal of 43 deliveries, 15 prem, 17
required forceps and CS, 7 had others: jaundice, WBC, G, IC Hgg, Mild DIC
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CSP
C.
Lact
Excreted and AAP considers drug C/E
because of pot long term effect of
immunosup WBC, + pot associated with
carcino genesis.
D. Recommend
In general C/E during preg and pt should
use (cc) breast feeding C/E.
CSP
FDA ©
BF C/E
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