Drug Eluting Stents Balancing Risk and Benefits Prof. Alfredo E. Rodriguez Director Cardiovascular Research Centre (CECI) Head Cardiac Unit/Otamendi Hospital Postgraduate Buenos Aires School of Medicine Buenos Aires, Argentina firstname.lastname@example.org Pull quotes: “New randomised trials with the latest DES generation are showing significant improvements in safety/efficacy”,
American people can buy antibiotics in Australia online here: https://buyantibiotics-24h.com/ No prescription required and cheap price!
C683966.r66.cf2.rackcdn.comDisclaimer: This newsletter, provided by ITIS, is funded by a grant from the Illinois Department of Public Health and
supported by Northwestern Memorial Hospital and Northwestern University Medical School. It is for educational purposes
only and is meant to summarize the information available at the time of its creation. It should be construed neither as
medical advice nor opinion on any specific clinical situation. For more information on a specific clinical situation, or
updated information, please consult your health care provider.
Acne and Pregnancy
Vol 7#5, February 2000
Kathleen O’Connell, BA; Megan Shepard, BA; Kelly Ormond, MS, CGC; Eugene Pergament, MD,
A variety of medications are prescribed for the treatment of acne, some taken orally, others topically.
When assessing the possible risk of these medications during pregnancy, the route of the exposure is
important to consider. Topical creams and gels are less systemically available than medicines taken
orally, ultimately meaning that the fetus is exposed to less of the medication. As with any decision
about medication during pregnancy, the potential risks must be weighed against its benefits for the
patient. Since there are various acne medications available, it may be possible for a woman to find a
combination of medications that is both effective and does not put her pregnancy at risk for major
malformations. This newsletter examines various medications used in the treatment of acne.
Benzoyl Peroxide (Benzac, Benzamycin, Beroxyl, Desquam, Triaz, Vanoxide)
Benzoyl peroxide is a topical treatment for acne that has antibacterial effects and induces skin peeling.
About 5% of each topical dose is absorbed sytemically. There are not any animal or human
reproductive studies on benzoyl peroxide, and therefore its potential teratogenic risk is undetermined.
However, benzoyl peroxide is commonly used, and there are no case reports about benzoyl peroxide
and birth defects in the literature. This, combined with its topical exposure, provides some reassurance
that the risk of malformations is likely to be low.
Hydrocortisone (Vanoxide-HC; w/ benzoyl peroxide)
Hydrocortisone is a corticosteroid used topically to treat acne and other dermatologic conditions. There
have been no reproductive studies on topical exposures to hysdrocortisone specifically, and as such its
risk in pregnancy is undetermined.
A literature review of oral cortisol exposures during pregnancy did not find an increased risk for
malformations in the exposed group, but it was found that the exposed group did have an increased risk
for prematurity and other complications for the mother and fetus (Aron et al., 1990). The doses in the
studies reviewed were presumably much larger than a dose from a topical exposure. Fraser et al. (1995)
surveyed 468 women exposed to all corticosteroids in general, and noted no significant increase in birth
defects. However, this study did note an increase in cleft palate versus that expected (2 vs. 0.2).
Because an increase in clefting has been observed in mice exposed to corticosteroids (Fraser et al.,
1951), this finding is of potential concern.
Most other studies of oral and inhaled corticosteroids have not found a significant increase in birth
defects or in clefts specifically (Czeizel and Rockenbauer, 1997; Fitzsimons et al., 1986; Rodriquesz-
Pinella and Martinez-Frias, 1998; Schatz et al., 1997). Finally, a retrospective study by Czeizel et al.
(1997) followed 191 women exposed to topical cortisone during pregnancy and found no significant
increase in birth defects. In summary, although there is a potential connection between oral
corticosteroids and cleft palate identified in the human and animal studies by Fraser et al. (1951 and
1995), it is unlikely that a topical exposure to hydrocortisone significantly increases the risk of birth
defects, including oral clefts.
Salicylic Acid (Sal Ac)
Salicylic acid is used to treat acne, warts and other dermatological problems. There are no studies
specifically looking at topical salicylic acid in pregnancy. Oral salicylic acid (aspirin) has not been
associated with an increase in malformations if used during the first trimester, but use in late in
pregnancy has been associated with bleeding, especially intracranial bleeding (Rumack et al., 1981).
The risks of aspirin late in pregnancy are probably not relevant for a topical exposure to salicylic acid,
even late in the pregnancy, because of its low systemic levels. Topical salicylic acid is common in
many over-the-counter dermatological agents, and the lack of adverse reports suggests a low
Erythromycin (A/T/S 2% acne gel, Benzamycin, Emgel, Erycette, T-Stat, Theramycin)
Erythromycin is an antibiotic that is commonly prescribed in pregnancy. Although often taken orally to
treat infection, it is also used topically for acne. Erythromycin crosses the placenta minimally; the fetal
blood concentration is only 2-10% of the maternal serum concentration, and the medication is quickly
metabolized by the body.Takaya et al. (1965) found no increased malformations in mice exposed to 1-
20 times the human dose. Human studies on erythromycin have all examined oral exposures.
Retrospective studies of 79 and 6972 women exposed in first trimester had no significant increase in
birth defects (Heinonen et al., 1977; Briggs, 1998). Jick et al. (1981) examined the prescription records
of women exposed to erythromycin during the first trimester and also found no increase in birth defects
(n=100-200). Because of these studies and the fact that this medication is commonly prescribed, it is
generally assumed that topical erythromycin does not pose a significant increased risk for birth defects.
Clindamycin is an antibiotic related to erythromycin and available both orally and topically for the
treatment of acne. It has been studied in both mice and rats at doses up to 180 mg/kg/day without
teratogenic effects (Weinstein et al., 1976; Philipson et al., 1976).The retrospective Michigan Medicaid
study identified 647 women exposed to clindamycin in the first trimester (both oral and topical
exposures) and did not note an increased risk for major malformations. Furthermore, a study of 104
women exposed to clindamycin in the second and third trimesters did not suggest an increased risk for
prematurity or placental complications (McCormack et al., 1987). This medication is unlikely to
significantly increase the risk for birth defects in either its oral or topical form.
Tetracycline is an antibiotic taken orally to treat acne. This medication belongs to a family of
antibiotics that includes minocycline and doxycycline. The half-life of tetracycline is 11-22 hours, so
most of the medication is removed from the body in 5 days.Two retrospective studies found no increase
in the incidence of major malformations when women were exposed to tetracycline in the first trimester
(Heinonen et al., 1977; Briggs, 1998). However, discoloration of deciduous teeth and the crowns of
permanent teeth was seen in children who were exposed to tetracycline after the fourth month of
gestation. Studies performed by Cohlan et al. (1961), Kline et al. (1964) and Kutscher et al. (1966)
established that infants exposed to tetracycline in utero after the fourth month of gestation may have discoloration of deciduous (”baby”) teeth, cavities, and enamel hypoplasia in their teeth. It is believed that tetracycline causes dental discoloration and bone depression because it acts on the calcification process in development. The critical period for calcification begins at four months’ gestation and ends twelve months post-partum. Therefore, tetracyline should be avoided after the sixteenth week of gestation and throughout lactation.
The degree of dental staining appears to proportional to the dose of the medication (Egerman et al., 1992). Cohlan et al. (1961) also found that tetracycline caused long bone growth depression of 40% which normalized when the use of the medication was suspended.
Doxycycline and minocycline, two medications structurally-related to tetracycline, are also used to treat acne. These medications have not been as well-studied as tetracycline; it is, however, generally assumed that doxycycline and minocycline similarly affect the fetal calcification process. Therefore, these medications should also be avoided after the first trimester of pregnancy through the breastfeeding period.
Sodium Sulfacetamide (Sulfaset, Klaron, Novacet, Sebizon)Sodium sulfacetamide is a topical anti-infective medication used to treat acne and seborrheic skin conditions. It belongs to the class of medications termed sulfonamides, and most reproductive studies examine sulfonamides as a class and in oral dosages, making it difficult to extrapolate the potential risk for a topical medication such as sulfacetamide.
The maternal use of sulfonamides near delivery can lead to newborn toxicity, resulting in anemia and jaundice and, theoretically, kernicterus, although this has yet to be documented in the literature. (Briggs, 1998). There have been two large retrospective studies of sulfonamide exposure, which involved 1445 and 3465 women exposed in the first trimester; neither study found an increased risk for malformations from the class in general (Heinonen et al., 1977; Briggs, 1998).
In contrast, other case controlled studies raised concerns about sulfonamide use in pregnancy. A 1971 case-control study by Nelson et al. determined the pregnancy exposures of 1369 patients, 468 of whom had babies with congenital malformations. They observed that significantly more mothers of the babies with birth defects took sulfonamides than the control mothers (Nelson et al., 1971). Saxon et al. (1975) looked retrospectively at 599 children born with oral clefts. The mothers of children with malformations in addition to the oral clefts were more likely to have taken sulfonamides than mothers of children with isolated oral clefts.
Because topical sulfacetamide has never been specifically studied to determine its potential teratogenic risk, one cannot definitively conclude that it does not cause birth defects. However, because it is topical and, for the most part, sulfonamides as a class do not appear to significantly increase the risk for birth defects, it is unlikely that topical sulfacetamide causes a significantly increased risk for malformations.
Breastfeeding while using sulfonamides is probably not a risk to a healthy infant. At most 1-2% of a maternal, oral dose of sulfonamides enters the breastmilk (Adair, 1938; Hac, 1939). However, sulfonamides can potentially cause anemia and jaundice in stressed, premature or hyperbilirubinemic infants. In addition, if an infant has G-6-PD deficiency breastfeeding should be avoided while taking sulfonamides , as sulfonamides act as oxidative stressors and can result in a hemolytic crisis.
Retinoids Isotretinoin (Accutane, Roaccutane)Isotretinoin is an oral retinoid used to treat cystic acne. A known teratogen, this medication is contraindicated during pregnancy due to the characteristic malformations it causes. The pattern includes defects of the CNS, thymus, craniofacial and cardiovascular systems, as well as conotruncal malformations. Isotretinoin is thought to affect initial differentiation and migration of cephalic neural
crest cells, and the critical period for this medication is 2-5 weeks post conception. Because the
teratogenicity of Accutane is fairly well-known, we have chosen to focus upon other common acne
medications in this review, rather than summarizing the literature about isotretinoin (for more details,
see RISK/NEWSLETTER 3/96). Despite the half-life of approximately 1 day (manufacturer insert),
due to the teratogenicity of this medication it is recommended that isotretinoin be discontinued at least
one month prior to attempting pregnancy (Braun et al., 1984; Benke, 1984; Rosa, 1983; McBride,
1985; Rizzo et al., 1991).
Tretinoin (Avita cream, Retin A)
Tretinoin is a component of various topical acne creams. Because this medication is related to
isotretinoin, there is concern that tretinoin could potentially have similar teratogenic effects on the
fetus. Two case reports have described infants born to women using topical tretinoin during the first
trimester of pregnancy. The infants had malformations that mimic the birth defects associated with
isotretinoin (Camera et al., 1992; Lipson et al., 1993). In contrast, a prospective cohort study failed to
find an association between birth defects and 215 women exposed to tretinoin in the first trimester (Jick
et al., 1993). Shapiro et al. (1997) did not find a significant increase in number of livebirths, SAB’s,
low birth weight, major malformations, duration of pregnancy, and cesarean sections in 94 women
exposed to tretinoin versus controls.
A dose-response relationship potentially could play a role in the effects of tretinoin; it is of note that 5-
31% of tretinoin is absorbed sytemically, depending on whether the skin is healthy or dermatitic.
Although prospective studies have shown no increase in congenital anomalies, the case reports and
biological plausibility of the anomalies raise concern about this medication. While such risks are likely
to be low given the low topical absorption, health professionals should encourage women to weigh the
risk and benefits of tretinoin during pregnancy.
Adapalene (Differin Gel)
Adapalene is a retinoid used in a topical gel form for the treatment of acne. As such, there are
theoretical risks for retinoid embryopathy. However, the manufacturer reports that only trace amounts
of adapalene are absorbed from the skin (trace is defined as less than 0.25 ng/ml). The manufacturer’s
studies on pregnant rats and rabbits using doses 120-150 times the maximum human topical dose did
not show an increased risk of adverse outcome or malformations. There has been one human case
report of adapalene use during weeks 4-13 of pregnancy; the fetus had IUGR, anophthalmia and
agenesis of the optic chiasm, and the pregnancy was aborted at 13 weeks (Autret et al., 1997). The
anomalies seen in this pregnancy are not typical of those seen with other retinoid exposures. In
addition, as with any case report, the malformations could be coincidental and unrelated to the
adapalene. There have not been any other human studies or case reports to date. The overall risk of
adapalene is undetermined because there have not been any human studies. However, because only
trace amounts of the gel are absorbed into the skin, it is unlikely that doses large enough to induce
malformations could reach a fetus.
Azelaic Acid (Azelex)
Azelaic acid is a topical cream for acne. The manufacturer’s studies in animals do not show an increase
in malformations at doses much higher than the maximum human dose. There have not been any
human reproductive studies to date. While it is reassuring that animal studies do not show
teratogenicity and that the fetal dose is small because the medication is topical, the risk of azelaic acid
is undetermined because there have been no human studies.
In summary, acne medications present a range of risks during pregnancy. Because of its proven
teratogenicity, it is well known that isotretinoin (Accutane) should not be taken during pregnancy.
Additionally, tetracycline and its derivatives should not be used after 16 weeks gestation due to its
effects on calcium-containing tissue, particularly teeth. The risks of other medications such as tretinoin
are less certain, while some commonly used medications, like benzoyl peroxide, do not appear to pose
a significant risk for malformations. Because of the widely known teratogenic effects of isotretinoin,
many women are wary of acne medications in general during pregnancy. However, there are a wide
variety of medications available for the treatment of acne, many of which pose a minimal risk if applied
topically during pregnancy.
Adair (1938). JAMA. 111:766-70.Aron et al. (1990)
Autret et al. (1997). Lancet. 350:339.
Benke PJ (1984). JAMA. 251:3267-9.
Braun JT et al. (1984). Lancet 1:506-7.
Briggs et al. (1993). Drugs in Pregnancy and
Lactation 5th Ed. Williams and Wilkins, 1998.
Camera, G et al (1992). Lancet, 339:687.
Cohlan SQ et al. (1961). Antimicrobial Agents and
Czeizel and Rockenbauer (1997). Teratology. 56(5): 335-40.
Egerman et al. (1992). Obstet Gynecol Clin NA. 19(3):551-61.
Fitzsimons et al. (1986) J Allergy Clin Immunol 78:349-53.
Fraser et al. (1951). Pediatrics. 8:527-33.
Fraser et al. (1995). Teratology. 51(1):45-6.
Hac (1939). Am J Obstet Gynecol. 38:57-66.
Heinonen et al., Birth Defects and Drugs in Pregnancy.
Littleton, MA:Publishing Sciences Grp, 1977
Hill RM (1984). Lancet. 1:1465.
Jick H. et al. (1981). JAMA. 246(4):343-6.
Jick S et al. (1993). Lancet, 341:1181-1182.
Kline et al. (1964). JAMA. 188:178-80.
Kutscher et al. (1966). Am J Obstet Gynecol. 96:291-2.
Lipson AH et al (1993). Lancet, 341:1352-3.
McBride WG. (1985). Lancet. 1:1276.
McCormack et al. (1987). Obstet Gynecol. 69:202-7.
Nelson et al. (1971). BMJ. 1:523-7.
Philipson et al. (1976). Clin Pharm Ther. 19:68-77.
Rizzo R et al. (1991). Teratology. 44:599-604.
Rodriquez-Pinella and Martinez-Frias (1998)
Rosa FW. (1983). Lancet. 2:513.
Rumack et al. (1981). Obstet Gynecol. 58(Sup):52S-6S
Saxon et al. (1975). Int J Epidem. 4:37-44.
Schatz et al. (1997) J Allergy Clin Immunol 100:301-6
Shapiro L et al (1997). Lancet, 350:1143-4.
Weinstein et al. (1976) Am J Obstet Gynecol. 124:688-91
Additional Useful Review Articles:
Duff, P. (1992). “Antibiotic use in Obstetrics andGynecology.” Obstet Gynecoly Clin NA 19(3).
Reed BR. (1997). Dermatologic drug use during pregnancy and lactation. Derm Clinics, 15(1):197-206.
Robert E and Scialli A (1994). Topical medications during pregnancy. Reproductive Toxicology
fufonk dzekad 119 ds varxZr tkjh dh tkus okyh vkS"kf/k;ksa dh lwph 1 Ether, Anaesthetic Inhalation, Volatile Liquid 500ml 1 Thiopentone Sodium Injection , powder for solution , 1.0g(sodium salt) in Ampoules1 Bupivacaine Injection ,0.25% (Hydrochloride) in 10 ml Vial1 Lidocaine Injection, 2%,(Hydrochloride) in 30 ml Vial Lidocaine Injection for spinal anaesthesia , 5% (Hydrochloride) in