Pregnancy and over-the-counter cough, cold, and pain relievers (2023)

FOR USPharmacy. 2006;3:33-47.

In the last 20 years, more drugs than ever have been available over the counter.¹Despite the large number of patients who self-medicate, only a small percentage seek advice from a doctor when choosing a product.^2,3This is a concern given the size of this potential patient population. This population includes many patients with chronic health conditions that can be aggravated by improper use of over-the-counter medications. Of particular concern is the safe use of over-the-counter medications in pregnant women. A recent study showed that 92.6% and 45.2% of women took over-the-counter and herbal medicines, respectively, during pregnancy. Pain relievers and cough and cold remedies are two of the most common categories of over-the-counter products bought during pregnancy.⁴

Safety and Pregnancy Data
There is currently limited safety data on the use of over-the-counter medications during pregnancy. Due to ethical concerns, most available safety data come from post-marketing surveillance reports and retrospective studies. The FDA has developed pregnancy categories for over-the-counter and prescription drugs. This classification system allows physicians to make informed decisions about the use of medications during pregnancy. The system is divided into five categories: A, B, C, D and X. Each letter indicates the level of safety evidence available to support the use of a drug during pregnancy (Table 1).^5,6The safety of a drug during pregnancy generally depends on the trimester or stage of fetal embryonic development.

Benefits vs scratches
In the United States, approximately 150,000 babies are born with birth defects each year.⁷Birth defects can occur due to many non-drug factors. Some of the most common defects are spina bifida, microtia, hypoplastic left heart, cleft palate, cleft lip, esophageal atresia, anencephaly, omphalocele, and reduced limbs.⁷Doctors must weigh the benefits against the risks when recommending over-the-counter pain relievers and cough and cold medicines to pregnant women. Because medical conditions treated with over-the-counter and herbal products in pregnant women are not generally life-threatening, physicians should also consider suggesting nondrug remedies such as rest and hydration.

This article provides information on some common OTC pain relievers and cough and cold remedies. Each section covers the product, pregnancy category, pregnancy safety information, dosage, side effects, and contraindications. The comparison of risks and benefits must be considered for each individual patient. Information on when patients should be referred to a physician (Tables 2 and 3) is included to support the decision-making process.

In general, acetaminophen is widely used during pregnancy and few side effects have been reported. Patients may be advised to take 325 to 1000 mg every four to six hours as needed (maximum 4000 mg/day). Pregnant patients should be instructed to use the lowest effective dose of the medicinal product. If the drug is ineffective or the required use exceeds 10 days, the patient should be referred to the doctor. Other pregnant women who should consult a doctor before starting self-treatment include those with kidney or liver dysfunction, high-risk pregnancies, complaints of third trimester headache (a possible sign of elevated blood pressure and eclampsia), pain scored greater than 6 on a scale of 1 to 10, presence of fever or other signs of infection or pain associated with any type of trauma.¹¹Depending on the nature of the pain, non-pharmacological recommendations can be made. For example, a patient complaining of a headache should try to rest and lie down in a dark, quiet room.

AINE:Nonprescription nonsteroidal anti-inflammatory drugs (NSAIDs) include ibuprofen, naproxen, and ketoprofen. All three are pregnancy category B in the first and second trimester and category D in the third trimester. The best-researched NSAID in pregnancy is the prescription product indomethacin. Like over-the-counter products, indomethacin is a pregnancy category B in the first trimester and D in the third trimester. The indomethacin data could be extrapolated to the entire class of NSAIDs, as studies on other drugs in this class are lacking.⁸Compared to acetaminophen, NSAIDs have been associated with a slightly higher risk of gastroschisis.¹⁰In addition, all NSAIDs used near labor are associated with oligohydramnios (low amniotic fluid), premature closure of the ductus arteriosus, and inhibition of labor.⁹Unfortunately, complications such as pulmonary hypertension, fetal nephrotoxicity and periventricular hemorrhage can also occur in the newborn.⁸

In general, NSAIDs should not be used during pregnancy without the consent of the patient's physician. However, if patients require NSAID self-treatment, appropriate doses may be recommended: ibuprofen 200 to 400 mg every four to six hours (maximum 1200 mg/day); naproxen 220 mg every 8 to 12 hours (maximum 660 mg/day); and ketoprofen 12.5 mg every six to eight hours, repeating the initial dose after one hour if there is no effect (maximum 75 mg/day).¹¹

Whenever possible, the lowest effective dose should be used. The patient should be evaluated and, if necessary, referred to her doctor. Eligible referrals include, but are not limited to, the criteria listed for acetaminophen, history of gastrointestinal ulceration, blood pressure problems, and history of NSAID-responsive asthma. Pregnant women should not take NSAIDs for more than 48 hours without consulting their doctor.

Salicylate
Aspirin is a pregnancy category C at doses less than 150 mg per day and a standard category D dose in all three trimesters.⁹Salicylates have been associated with increased mortality, neonatal hemorrhage, decreased birth weight, prolonged gestation and labor, and possible birth defects. A pregnant patient should never take aspirin without the approval and guidance of her doctor.

decongestants
Oral:Pseudoephedrine and phenylephrine are the only over-the-counter oral decongestants available in the United States. These oral decongestants are available as monotherapy and combination drugs. Combination cough and cold products usually contain an analgesic, antihistamine, cough suppressant and/or decongestant. These combination products are often more convenient for the patient due to the reduced tablet load and cost. However, like non-pregnant patients, pregnant women should only use pain relievers and cough and cold products that treat their symptoms. This will help minimize the potential risks of using unnecessary medication.

Pseudoephedrine and phenylephrine are pregnancy category C in all three trimesters of pregnancy.¹²The American College of Obstetricians and Gynecologists (ACOG) and the American College of Allergy, Asthma and Immunology (ACAAI) recommend the use of pseudoephedrine during pregnancy. However, they advise against using oral decongestants during the first trimester because of the possible increased risk of gastroschisis (a defect in the abdominal wall).¹²Retrospective studies have shown an increased risk of gastroschisis with pseudoephedrine.^10,13,14However, gastroschisis is a relatively rare condition and the increased risk does not guarantee the occurrence of the adverse event. A prospective study of 453 women who used decongestants in the first trimester showed no increased risk of birth defects.¹⁴Unfortunately, the study population may not have been large enough to exclude the risk of gastroschisis.

Oral decongestants can also cause vasoconstriction, which can lead to maternal hypertension and poor fetal blood flow. Because poor circulation can stunt fetal growth, the risks of taking oral decongestants in the first trimester may outweigh the benefits.

In the second and third trimester, pseudoephedrine can be recommended for pregnant women in an appropriate dose. To minimize exposure to the fetus, pregnant patients should take the immediate-release (rather than extended-release) formulation and the lowest effective dose for the shortest possible time. A reasonable dose is 30 to 60 mg every four to six hours as needed (maximum 240 mg/day).¹¹

Oral decongestants are vasoconstrictors and should not be used in patients with certain cardiac conditions, such as uncontrolled hypertension and acute myocardial infarction. They also have sympathomimetic properties and can aggravate some conditions such as diabetes mellitus and hyperthyroidism. The patient should contact her doctor if she has a high-risk pregnancy, fever, or other signs of infection, if congestion lasts more than seven days, or if medications do not relieve symptoms.¹¹

Nasal:Oxymetazoline, phenylephrine, naphazoline, and xylometazoline are nasal sprays commonly available in the United States. All of these nasal sprays/drops fall under category C for pregnancy. The amount of fetal exposure is minimal as only a small amount of the drug is absorbed systemically. There are only a few studies available for any of the nasal preparations. However, a prospective study of 197 and 56 women who received intranasal oxymetazoline and phenylephrine, respectively, showed no increased risk of malformations.¹⁴

American Association of PharmacistsOver-the-counter medication handbookIt is recommended to use oxymetazoline during pregnancy as the preferred nasal decongestant.¹¹Appropriate doses of oxymetazoline can be recommended for patients during pregnancy provided the patient has no contraindications to the drug. Contraindications are high-risk pregnancy, fever or other signs of infection, and congestion for more than seven days. These products should be used with caution, if at all, in patients who cannot take oral decongestants. The presence of underlying conditions (eg, diabetes mellitus) and the level of control of these conditions must be assessed before recommending nasal sprays or drops. A suitable dose of oxymetazoline is two to three sprays in each nostril every 10 to 12 hours (maximum two doses per day). It is important that patients are advised not to use the drug more often than recommended or for more than three days due to the risk of rebound congestion. If the drug does not work, the patient should consult his doctor.¹¹

Antitussive expectorants
Guaifenesina:Coughing is a protective reflex. Guaifenesin breaks down the mucus in the patient's chest, making the cough more productive. If the patient is able to cough up more phlegm, the frequency of coughing is likely to decrease as the phlegm is removed. However, guaifenesin has not been shown to be effective against coughs in patients with cold symptoms.^11,15,16Suitable alternative recommendations include a humidifier or vaporizer, hydration, and hard candy.

Guaifenesin is considered pregnancy category C. Guaifenesin has not been studied as extensively as other over-the-counter products. In a study of 197 pregnant women, there was an association between first trimester exposure to guaifenesin and an increased incidence of inguinal hernia.¹⁷This hernia association was not found in other studies with guaifenesin.⁶

Guaifenesin is contraindicated in patients with chronic cough due to asthma, smoking, emphysema, chronic bronchitis, heart failure, or use of angiotensin converting enzyme (ACE) inhibitors. Fortunately, emphysema, chronic bronchitis, and heart failure are relatively uncommon in women of childbearing age. In addition, the use of ACE inhibitors is also traditionally avoided in this subgroup of patients. Other types of cough that should not be self-treated are coughs that last longer than seven days, coughs that subside/disappear and come back, and coughs in combination with symptoms of infection such as fever. As with other over-the-counter cough and cold products, long-acting, delayed-release, and/or alcohol-containing preparations should be avoided to minimize exposure to the fetus. A reasonable dose is 200 to 400 mg every four hours as needed (maximum 2400 mg/day). See Table 3 for the special circumstances when patients should not self-medicate and refer to a physician for cough.

Dextrometorfano:Because coughing can be protective, it should generally not be suppressed except in specific situations. If the cough is unproductive and disrupts sleep or is severe in nature, it can be suppressed.

Like guaifenesin, dextromethorphan has not been shown to be effective in patients with cold symptoms.^11,16,18A non-drug treatment similar to guaifenesin may be recommended. Dextromethorphan is equivalent to codeine as a cough suppressant and is a category C pregnancy drug. Exposure to dextromethorphan in the first trimester has been studied and no increased risk of birth defects has been identified.⁶However, one study showed teratogenicity when dextromethorphan was injected into avian embryos.¹⁹It was questioned and investigated whether data from avian embryos can be extrapolated to humans. Three major and seven minor malformations occurred in 128 women exposed to dextromethorphan during the first trimester (compared to five major and eight minor malformations in the control group).²⁰This study showed that the risk of birth defects with dextromethorphan was similar to the baseline rate of birth defects. However, there is still a theoretical concern that an antagonist in theNorte- The methyl-d-aspartate receptor can affect fetal brain growth. To date, this side effect has not been studied in humans.

Concomitant use of dextromethorphan with central nervous system (CNS) depressants and monoamine oxidase (MAO) inhibitors (within 14 days) should be avoided. It has the same contraindications as guaifenesin therapy. An appropriate dose of dextromethorphan is 10 to 20 mg every four hours as needed (maximum 120 mg/day).

In 2006, the American College of Chest Physicians (ACCP) issued new guidelines addressing proper cough management. Because available over-the-counter cough medicines do not relieve the underlying cause, the ACCP does not recommend the use of cough suppressants and cough sputum for postnasal fluids. For postnasal drip, an antihistamine or decongestant is recommended. Since the effectiveness of guaifenesin and dextromethorphan for coughing up a cold is questionable, they should be used sparingly in pregnant women. Non-pharmacological measures for cough may be more effective with less risk to the patient.²¹

Antihistamines
Antihistamines can relieve a runny nose and sneezing, but they don't affect other symptoms of the common cold.¹¹The main OTC exception is loratadine, which lacks potent anticholinergic activity. Therefore, loratadine does not treat allergic rhinorrhea or sneezing. According to the ACAAI and ACOG opinion, chlorpheniramine was selected as one of two antihistamines recommended during pregnancy (the other is not available in the US).¹²

Chlorpheniramine, clemastine, diphenhydramine, and loratadine are considered pregnancy category B. Bronpheniramine and triprolidine belong to pregnancy category C. The most common concerns about the use of antihistamines during pregnancy are cleft palate (loratadine and diphenhydramine), polydactyly (diphenhydramine), retrolental, and uterine fibroplasia. Contractions (diphenhydramine).²²A cause-effect relationship could not be established for cleft palate and polydactyly due to the small number of cases. An association has been established between the use of antihistamines in the last two weeks of pregnancy and an increased risk of retrolental fibroplasia.²³When used in the third trimester, high-dose diphenhydramine may have oxidative properties. This can lead to uterine contractions. Due to a lack of information and some theoretical risks, antihistamines should be avoided in late pregnancy.

Several studies have examined the use of antihistamines in the first trimester and have not shown an increased risk of major birth defects over that expected at baseline. Two possible exceptions are brompheniramine and clemastine (limb reduction defects). However, a cause-and-effect relationship has yet to be found. Chlorpheniramine and diphenhydramine have not been associated with major birth defects in the first trimester or at any time during pregnancy. Exposure to triprolidine (plus pseudoephedrine) in the first trimester was studied in 628 women.⁶Of the patients studied, nine had an important congenital anomaly. Whether this was caused by triprolidine or pseudoephedrine could not be determined due to the simultaneous use.

Antihistamines should be used with caution with CNS depressants, MAO inhibitors, and phenytoin. Caution should also be exercised when using antihistamines if the patient has angle-closure glaucoma, peptic ulcer disease, asthma, pulmonary emphysema, or chronic bronchitis. Patients should be warned that they may have motor impairments even if they do not feel drowsy. Other anticholinergic side effects are also possible. Adult dosages are as follows (as needed): brompheniramine 4 mg every four to six hours (maximum 24 mg/day), chlorpheniramine 4 mg every four to six hours (maximum 24 mg/day), 1, clemastine 34 mg every 12 hours (maximum 2.68 mg/day), triproline 2.5 mg every four to six hours (maximum 10 mg/day), and diphenhydramine 25 to 50 mg every four to six hours (maximum 300 mg/day)

Several
Menthol and Camphor:Menthol and camphor have not been well studied during pregnancy. Menthol is a common ingredient in many throat drops, sprays, and ointments. There are no human studies on the use of menthol during pregnancy; therefore your risk is indeterminate. The concentration of menthol in these products is low, so the risk of birth defects is considered to be low. Retrospective studies with a camphor-based product (Vicks VapoRub) have not shown developmental toxicity associated with exposures during pregnancy.⁶This product is not to be taken orally. However, the American Pharmacists AssociationHandbook of over-the-counter medicinesrecommends that patients consult their doctor before using these drugs.

coneflower:Echinacea is a common herbal medicine used to boost the immune system. The available evidence supporting the use of echinacea to reduce the severity and duration of cold symptoms is controversial. A lack of product standardization, different preparations used, problems with the study design and conflicting results complicate the interpretation of efficacy.²⁴A small study showed that using echinacea in the first trimester did not increase the risk of serious birth defects. The study results showed that echinacea was safe as a short-term (five to seven days) treatment.²⁵Due to questionable efficacy and limited safety data, echinacea should be avoided in pregnant women.

Zink:Zinc is commonly used to reduce the signs and symptoms of a cold when given within 24 hours of the onset of symptoms.²⁶Zinc lozenges have been shown to be effective in slightly reducing the duration of cold symptoms.²⁷Trials with zinc nasal sprays have not been as promising.^28,29

However, due to the unpleasant taste of zinc lozenges, these are not easy to take. Used to treat cold symptoms, these often uncomfortable lozenges need to be taken every two hours to be effective. The most commonly reported side effect of zinc lozenges is nausea, which may be a pre-existing problem in this patient population.³⁰Zinc nasal gel may reduce the likelihood of these side effects, but additional safety and efficacy data are lacking.³¹

There is limited safety data to support the use of zinc lozenges. However, several studies have shown that zinc supplementation in vitamins during pregnancy can improve fetal development.^32,33Zinc has been shown to be safe in reasonable doses during pregnancy. Doses for pregnant women over 19 years of age should not exceed 40 mg per day (34 mg/day for patients 14 to 18 years of age). Six drops per day are recommended for some over-the-counter zinc lozenges, which works out to 79.9 mg per day. Taking higher doses, especially in the third trimester, increases the risk of complications, such as preterm labor.³⁴Pregnant women should be educated on the importance of adequate dosing from all sources, including prenatal vitamins.

Vitamin C
The evidence supporting the use of vitamin C to reduce the severity and duration of cold symptoms is controversial. In studies supporting the use of vitamin C for this indication, the effects are small (reduction in symptoms in less than 24 hours). To achieve this result, the patient needs to take 1-3 g of vitamin C per day. Doses greater than 1g have been associated with increased side effects such as nausea and diarrhea.^35,36Many pregnant patients may find that the burden associated with taking large doses of vitamin C may not outweigh the potential benefits.

There is only a limited amount of safety data to support vitamin C in pregnancy. However, in reasonable doses, vitamin C appears to be safe during pregnancy.³⁷It is recommended that pregnant women over the age of 19 consume no more than 2 g of vitamin C per day (and less than 1,800 mg/day for pregnant women between the ages of 14 and 18).³⁸Physicians and patients must weigh the benefits against the risks when considering vitamin C during pregnancy.

role of pharmacist
Because the common cold is a self-limiting, non-life-threatening condition and there is some risk associated with taking medications during pregnancy, non-drug treatment should be recommended over over-the-counter medications. Hydration, rest, vaporizers or humidifiers, nasal irrigation, and saline nasal sprays help relieve symptoms. See Tables 2 and 3 for conditions where the patient should be referred to the physician and not self-treated.

If a patient is a suitable candidate for self-treatment, see Tables 4 and 5 for suitable product options. Pharmacists can help patients avoid combination therapy by recommending medications that directly address the patient's symptoms. The pharmacist may advise the patient to avoid products that may not work or may be harmful. By educating the patient about long-acting alcohol-containing products and encouraging dosing if necessary, the pharmacist can help the patient minimize fetal drug exposure. As such, pharmacists play a crucial role in guiding pregnant women through the maze of over-the-counter cough and cold products.

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