Safety of Anti-Itch Medications During Pregnancy

Some of us have dealt with itchiness our entire lives and have become masters at deciding which medications we can use to control those itching urges. However, whether or not you’ve had experience with itchiness, pregnancy can be a challenging time and many women have questions about medication safety when trying to control their symptoms. This article aims to give you the information you need about systemic (medications that get into the bloodstream) therapies for itch and their safety for a developing baby. Antihistamines are the major category of drugs which will be discussed.

Antihistamines can be divided into two major categories: first-generation and second-generation. The major difference is that the first-generation drugs have been around longer and have greater penetration into the circulation of the central nervous system. This means that they have greater sedative effects compared to second-generation agents (why many people feel sleepy after taking a medication with diphenhydramine). For the same reason, the first generation drugs are also used to control nausea and vomiting during pregnancy.^[1] Some common first-generation agents include Diphenhydramine (ingredient in Benadryl), hydroxyzine (ingredient in Vistaril and Atarax), and chlorpheniramine (ingredient in Aller-Chlor, and Teldrin). Common second-generation agents include Loratadine (ingredient in Claritin), cetirizine (ingredient in Zyrtec), and fexofenadine (ingredient in Allegra).^[2] 

Pregnancy Category B Antihistamines 

Pregnancy category B indicates that there are very few human studies, if any, but animal studies do not show an increased risk of adverse effects on the fetus with use of the medication.

The first generation antihistamines - diphenhydramine and chlorpheniramine - and the second-generation antihistamines - loratadine and cetirizine - are considered pregnancy category B medications. The “Allergic Rhinitis and its Impact on Asthma” guidelines recommend using second-generation antihistamines over first-generations because of fewer sedative and other side effects in the general population.^[3] However, it can be argued that first-generation agents are preferred during pregnancy since there is a greater amount of safety data published for these medications in pregnant women.^[2]

Several large meta-analyses (combines the results of many reports/studies on one topic and presents the major conclusion) on safety data of antihistamine use in pregnancy have concluded there is no definitive risk of an increased rate of birth defects or other adverse fetal outcomes compared to the general population. Overall, these reports have indicated the relative safety of these medications in pregnancy. One recent large report that included 32 individual studies stated no significant correlation between antihistamine use and fetal malformations, prematurity, spontaneous abortions, low birth weight, or stillbirths. This report went on to further state that 3 cases in which expectant mothers were accidentally exposed to overdoses of medication did not result in any adverse fetal outcomes.^[4]

Current recommendations are that first-generation antihistamines are preferred over second-generation agents in pregnant women. However, care should be used with all antihistamines in the third trimester close to the time of birth. IV antihistamines and high doses should be avoided especially during this time, as they are known to stimulate uterine contractions which can result in lack of oxygen to the baby (especially diphenhydramine). Of the second-generation medications, loratadine should be used before trying cetirizine.^[2] 

In terms of lactation safety, diphenhydramine and cetirizine are considered L2 (safer), but the baby should be monitored for effects of sedation. Chlorpheniramine is L3 (moderately safe), and again the baby should be monitored for excessive sedation. Loratadine is considered L1 (safest), but the baby should be monitored for effects of sedation, fast heart rate, and dry mouth.^[2]

Pregnancy Category C Antihistamines 

Pregnancy category C includes medications for which there is no human data, and animal studies do not exist or show adverse effects to the fetus.

This category includes the first-generation antihistamine, hydroxyzine, and the second-generation antihistamine, fexofenadine.

Care should be used when using these agents during pregnancy, as there have been reports of adverse fetal outcomes in human reports and/or animal studies with both medications. High doses of hydroxyzine use in pregnant mothers have been associated with withdrawal symptoms in newborns, including tonic-clonic seizures in one report. Currently, hydroxyzine is not prescribed to pregnant women by allergists.^[5] There is limited data on the use of fexofenadine in pregnant women, but a few reports have correlated its use with low birth weight in animal studies. Since there is very little known about this drug, it is not recommended as a first-line agent in pregnant women with an itch.^[5]

Hydroxyzine is L1 in lactation safety (safest), but the baby should be monitored for sedation, dry mouth, and high heart rate. Fexofenadine is L2 (safer), and the baby should be monitored for sedation.^[2]

A Word About Oral Doxepin

This drug is known as tricyclic antidepressant, and its original use was to treat depression and sleep disorders. However, it has also been found to be useful in the treatment of itch. No animal studies have demonstrated fetal malformations or adverse fetal side effects with the use of this drug. This being said, there are very few, if any, human studies evaluating this drug during pregnancy. There has been one report of polydactyly, heart defects, and oral cleft abnormalities correlated with maternal exposures to the medication in the first trimester. It is recommended to use antihistamines before attempting to use this medication to control the itch. This drug should especially be avoided in the third trimester due to the risk of reduced muscle tone, vomiting, and weak suck in the newborn.^[2] 

In terms of lactation safety, it is considered L5 (contraindicated), as this drug is thought to be secreted in breast milk and can cause an infant to experience breathing difficulties, loss of muscle tone, decreased suckling and vomiting.^[6]