Dextromethrophan Pseudoephedrine Chlorpheniramine Phenylpropanolamine Oxymetazoline
During the winter months, when colds and flus are more frequent, many women have questions about whether over-the-counter cold and flu remedies are safe to take during pregnancy. As with the use of any medication during pregnancy, the lowest therapeutic dose is recommended, and chronic use of any cold medication is not recommended. Following is a list of common ingredients in these remedies, and the available information about their use during pregnancy:
Dextromethorphan
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Dextromethorphan is a
common ingredient in cough syrups.
The Collaborative Perinatal
Project identified 300 women exposed to dextromethorphan during the first
trimester and did not find an increased risk for birth defects. Two additional
cohort studies involving 59 and 184 women, respectively, who used
dextromethorphan during pregnancy did not find an association between this agent
and congenital defects. More recently, a group of Spanish investigators
published epidemiologic data that did not support a possible association between
the use of dextromethorphan during pregnancy and increased risk of neural tube
defects, heart defects, or an altered risk of all other congenital defects.
There were 70 dextromethorphan-exposed pregnancies in this report. There have
not been adequate studies in human pregnancy and more data is required before a
thorough risk assessment is possible.
In 1998, an animal study involving chick embryos suggests that early exposure to dextromethorphan is associated with an increased risk for neural tube defects, craniofacial defects, and embryotoxicity. In addition to this study a pediatric research group is in the process of conducting a prospective study involving the use of Dextromethorphan. Preliminary findings suggest that Dextromethorphan use during pregnancy does not increase the rates of major malformations above the risk of 1-3%. The highest dose used in this study is greater than the amount ingested by a person taking dextromethorphan to treat a cough, but may be comparable to the amount received by a person abusing dextromethorphan recreationally. The moderate and low doses are comparable to that received from cough syrup. While animal data can be useful it is important to remember that different species have different levels of sensitivity following exposure to the same agent. In general, it is thought that therapeutic dextromethorphan use during pregnancy does not pose a high risk for malformation.
Pseudoephedrine
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Pseudoephedrine is a
sympathomimetic used in various cold medications, most often medications with
several active ingredients. Thus it is often difficult to separate the effects
of pseudoephedrine from those of other agents. An epidemiological study
evaluating 902 women exposed to pseudoephedrine during the first trimester did
not find an increased risk for congenital malformations. Another study evaluated
39 women who were exposed to pseudoephedrine during the first trimester and 194
women who were exposed to pseudoephedrine any time during the pregnancy, and did
not find the rate of congenital malformations to be increased. An association
between maternal use of Pseudoephedrine in pregnancy and an increase risked for
gastroschisis (abdomen does not close fully allowing intestines to stick out)
has been observed in one study of 76 children born with this anomaly. However,
this study did not account for recall bias, dosage, or timing. Additional
investigation is required before the significance of this report can be
established. There is a case report of a woman who received 480 – 840 mL per day
of a cough syrup containing pseudoephedrine throughout her pregnancy. The infant
displayed features of fetal alcohol syndrome, irritability, tremors, and low
tone. The fact that there were three other agents including ethanol in this
medication does not allow for a causal relationship to be made.
Chlorpheniramine
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Chlorpheniramine is a
widely used antihistamine that helps
relieve red,
itchy, watery eyes; sneezing; and runny nose caused by allergies, hay fever, and
the common cold. This product can be found in sinus,
nasal decongestants
and allergy medicines and is currently the antihistamine of choice during
pregnancy; however it is not know if it crosses the placenta.
There have been no adequate or well-controlled studies of the use of this agent
during human pregnancy. The Collaborative Perinatal Project identified 1070
women who were exposed to chlorpheniramine during the first trimester and found
no significant increase in birth defects. A teratology information service
followed 68 pregnancies that had been exposed to chlorpheniramine and identified
one child with congenital hip dysplasia.
Animal studies involving mice did not detect teratogenic effects in the
offspring. Due to the limited amount of information available, further
investigation is required to accurately determine the safety of chlorpheniramine
use during human pregnancy.
Phenylpropanolamine
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Phenylpropanolamine or PPA (Dexatrim) is a commonly used drug in
non-prescription cold pills and diet pills. Currently the Food and Drug
Administration (FDA) is issuing a public health advisory concerning PPA. FDA is
taking steps to remove PPA from all drug products and has requested that all
drug companies discontinue marketing products containing this agent, due to a
recent study that has reported that taking phenylpropanolamine increases the
risk of hemorrhagic stroke (bleeding into the brain or into tissue surrounding
the brain) in women. Men may also be at risk. Although the risk of hemorrhagic
stroke is very low, FDA recommends that consumers not use any products that
contain PPA.
The Collaborative Perinatal Project initially found a possible association between use of this medication during the first trimester and various birth defects, including hypospadias, ear and eye malformations, polydactyly, and pectus excavatum. The study design used by this project does not permit the conclusion that phenylpropanolamine was the causative agent in these abnormalities. In addition, the number of malformations in this particular study was small. An additional retrospective study was unable to find an association between this agent and an increased incidence of any birth defects. In a case-controlled study of 76 children born with gastroschisis, there was no significant association between maternal exposure to Phenylpropanolamine during the first trimester and this particular birth defect.
Although not demonstrated in clinical reports, there is a theoretical concern that the excessive use of phenylpropanolamine might impair blood flow to the fetus. Uterine blood vessels contain only alpha adrenergic receptors, which are capable of causing constriction when stimulated. Normally, these vessels are maximally dilated.
A growing number of cases have been reported suggesting that myocardial injury and intracranial hemorrhage have been associated with the ingestion of recommended doses of phenylpropanolamine. One case of intracerebral hemorrhage occurred in a patient 3 weeks after childbirth. Before her pregnancy this patient had used phenylpropanolamine as a dieting aid without incident. The hypertensive effects of phenylpropanolamine may be particularly troubling for patients with pre-existing high blood pressure or those who are ingesting other medications that may enhance the effects of phenylpropanolamine, such as monoamine oxidase inhibitors. The use of phenylpropanolamine as a diet aid during pregnancy is particularly inappropriate in the light of clinical observations that it lacks effectiveness for this indication and the belief that weight loss during pregnancy is contraindicated. Due to the limited amount of information available on phenylpropanolamine, further investigation is required to accurately determine the safety of its use in human pregnancy and is recommended to be avoided during pregnancy.
Oxymetazoline
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Oxymetazoline (Afrin) is an alpha adrenergic agonist used in non-prescription
nasal decongestants. To date, there have been no reports associating
oxymetazoline with congenital anomalies. The Collaborative Perinatal
Project identified a handful of mothers exposed to this medication
during pregnancy. They did not find an increase in physical birth
defects or adverse pregnancy outcomes; however, the number of
women exposed is too small to draw any conclusions. There has
been a study in which 12 pregnant women received single doses
of oxymetazoline nasal spray and then were monitored regarding
blood flow velocity in the uterus, as well as fetal blood flow.
The data from this study did not find the use of oxymetazoline
nasal spray, at the recommended dose, to cause any alterations
in blood flow. In addition, no significant changes are observed
in maternal blood pressure or fetal heart rate. There is one case
report of excessive use of oxymetazoline nasal spray by a women
late in the third trimester of her pregnancy. This was associated
with a non-reactive no stress test and deceleration of fetal heart
rate. Thus, the majority of the data suggest that the use of oxymetazoline
nasal spray at the recommended dose is safe for the healthy pregnant
patient. Caution is warranted with the use of oxymetazoline nasal
spray in excessive amounts, as it has been associated with bradycardia
(irregular heart beat) and hypotension (decreased blood pressure).