UKMi Q&A 29.7

Which medicines can be used to treat intermittent allergic rhinitis during pregnancy?

Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals

Before using this Q&A, read the disclaimer at

Date prepared: December 2015

Summary

Women with Intermittent Allergic Rhinitis (IAR) during pregnancy can be treated with a number of medicines without increasing the risk of an adverse pregnancy outcome. However, the decision to treat should always be based on a risk versus benefit assessment of each case.

The choice of medicine should be based on symptom type and severity, evidence of foetal safety, product efficacy as well as patient preference. Rhinitis and especially rhinitis during pregnancy is not always due to allergens and may not respond to standard therapies.

Treatment:

  • Avoid / minimise precipitating allergens, if known and if practical.
  • Assess risks and benefits – particularly in relation to trimester.
  • The preferred treatment for IAR in pregnancy is the application of topical preparations as this act locally and haslower systemic exposure, therefore reducing the risk posed to the foetus.
  • If nasal congestion predominates, intranasal corticosteroids are the treatments of choice during pregnancy. Sodium cromoglicate nasal spray is also suitable for use during pregnancy but may be less effective.
  • If an intranasal preparationdoes not fully relieve symptoms or is not tolerated, consider an oral antihistamine. Chlorphenamine has traditionally been the antihistamine of choice in pregnancy but can cause sedation. Loratadine or cetirizine are the antihistamines now recommended for use during pregnancy.
  • Intranasal decongestants are of limited benefit in IAR and are generally only recommended in pregnancy for relieving nasal congestion prior to the use of topical corticosteroids.
  • Any medication prescribed during pregnancy should be at the lowest effective dose for the shortest time necessary.

Background

Many people with allergic rhinitis are sensitised to more than one allergen. As well as the occasional flare up, polysensitisation can cause a mild persistent rhinitis throughout most if not all of the year. The occasional exacerbations, known under the banner term “intermittent allergic rhinitis” (IAR) are not always due to seasonal allergens and recent allergic rhinitis guidelines do not include seasonality as a defining aspect of IAR (1). Although the terms “hayfever” and “seasonal allergic rhinitis” are no longer included in the formal definition, they remain clinically useful (2).

Rhinitis during pregnancy is not necessarily the result of allergen exposure. In up to 20% of pregnancies symptoms are thought to be related to the effects that elevated levels of oestrogen and placental growth factor have on the nasal mucosa (2,3). Rhinitis of pregnancycan start during any gestational week but the severity may increase in the last trimester as the blood oestrogen levels increase. It tends to be self-limiting and symptoms usually resolve after delivery, soit is important to establish whether rhinitis in a pregnant woman is allergen related(2,3).

IAR can have a significant impact on a person’s quality of life. A blocked or runny, itchy nose is obviously unpleasant, but IAR can also affect sleep, causing sleep loss and snoring, exacerbation of asthma, and maybe even obstructive sleep apnoea (1).

Very few medications used for the treatment of IAR are licensed for use in pregnancy. General information about prescribing in pregnancy, notes on the risks posed by drugs, and the limitations with the data available are discussed in Medicines Q&A 34.6"What should you think about when prescribing to pregnant women?". If you are not familiar with this information, you are advised to review it before reading further.

Answer

The choice of treatment usually depends on the predominant symptoms, their severity and persistence, as well as patient preference and cost (1). Allergen avoidance is usually recommended but it is not always practical or acceptable and no single method of allergen avoidance in isolation has been proven effective (1). Drug therapy is indicated if symptoms persist and topical administration should be considered first-line since there is minimal systemic absorption(4).

CORTICOSTEROIDS – Intranasal

Intranasal corticosteroids, such as beclometasone, budesonide and fluticasone, are the treatment of choice for IAR during pregnancy particularly when nasal congestion predominates or exacerbations are frequent (2-5).

Although studies of intranasal corticosteroid use in pregnancy are limited there is no convincing evidence that the use of systemic or inhaled corticosteroids during pregnancy is associated with an increased risk of malformations (6,7). These data could be extrapolated to intranasal use, since the resulting blood concentrations from this route would be considerably less than when the drugs are used systemically.

There is little difference in efficacy and safety between the intranasal corticosteroid formulations available but there are differences in cost and patient preference that will influence choice (2,8).

SODIUM CROMOGLICATE – Eye drops and intranasal

Intranasal sodium cromoglicate has not been shown to be teratogenic and, although its efficacy may be modest when compared with the intranasal corticosteroids, it is considered by some to be a first line therapy for allergic rhinitis in pregnancy, especially in the first trimester (1,4,5).

Although there are few published data on the use of chromones, such as sodium cromoglicate, during pregnancy(2,3)it is unlikely that ocular administration will lead to an increased risk of an adverse pregnancy outcome(9). The manufacturers of sodium cromoglicate eye drops state that it has no adverse effects on foetal development, and the eye drops can be used in pregnancy where there is a clear need (9). Sodium cromoglicate eye drops are poorly absorbed through mucosal surfaces at therapeutic doses (approximately 0.03% is absorbed) and the amount reaching the systemic circulation is very small (9).

ANTIHISTAMINES – Oral

Oral antihistamines are particularly suited to relieving symptoms mediated by histamine including ocular symptoms, rhinorrhoea, sneezing and nasal itching, but have little effect on nasal congestion (1,3). They are absorbed into the systemic circulation and are considered a greater risk to the foetus than intranasal treatments (4).

First Generation (or sedating antihistamines)

Chlorphenamine has traditionally been the antihistamine of choice in pregnancy because the large amount of outcome data do not indicate a risk to the foetus (4,10). However concerns about excessive drowsiness have led to the second generation antihistamines being recommended for treating IAR - including IAR during pregnancy (1,11).

Second Generation (or non-sedating antihistamines)

Due to concerns about the adverse effect profile of the first generation antihistamines, when an antihistamine is needed a second generation agent is now preferred (1,7). In the past, second generation antihistamines werenot recommended in pregnancy because of a lack of safety data.However, more data are now available which support the safe use of second generation antihistamines in pregnancy. (4,10).

Loratadine is the most studied second-generation antihistamine during pregnancy with data from more than 5000 exposures not suggesting a teratogenic risk (12,13). Data from a registry study (n=292), a prospective comparative study (n=161 taking loratadine and n=161 controls) and a second comparative study (n=210 taking loratadine, n=267 taking other antihistamines, and n=929 controls) showed no adverse effects of loratadine exposure during pregnancy on the infant(10).

Cetirizine is an active metabolite of hydroxyzine, which has not been associated with human teratogenicity. The limited data available do not indicate foetal toxicity therefore cetirizine could be used as a second option if loratadine is not tolerated (4,12). Data from 97 women who used cetirizine during early pregnancy showed no increase in teratogenic effects, and there was an incidental finding of significantly less pregnancy-related nausea and vomiting. The largest study, in 917 women taking cetirizine during pregnancy, also showed no increase in malformation or in delivery complications when compared with the general population (10).

Fexofenadine is the active metabolite of terfenadine, which used to be considered the non-sedating antihistamine of choice in pregnancy(14). The very limited data on the use of fexofenadine during pregnancy do not suggest an increase in risk, but loratadine or cetirizine are the preferred options (12,14).

ANTIHISTAMINES – Intranasal

Intranasal antihistamines are effective in reducing nasal itching, sneezing, runny nose and nasal congestion but they do not appear to improve ocular symptoms (1). In the UK, azelastine is the only antihistamine licensed for intranasal use and studies and experience in human pregnancy are lacking (5,6).

In animal reproductive studies, oral doses of azelastine 240 - 500 times that intended for human use have led to skeletal abnormalities and growth retardation in the offspring(6). In humans, the nasal route of administration and the low dose delivered implies minimal systemic exposure, however the manufacturers of Rhinolast® Nasal Spray advise caution if used during pregnancy (15).

The clinical relevance of these animal studies to nasal use during human pregnancy is dubious. There is no evidence to date to support a link between use in human pregnancy at recommended doses and an increased risk of adverse pregnancy outcomes therefore inadvertent exposure during pregnancy does not require intervention (12,16)

SYMPATHOMIMETIC DECONGESTANTS – Oral and Intranasal

Intranasal decongestants are of limited benefit in IAR and are generally only recommended for relieving nasal congestion prior to the use of topical corticosteroids (2,5). Prolonged use can give rise to rebound congestion when stopped (rhinitis medicamentosa) therefore they should only be used for 7 to 10 days at most (2,3). As these agents are effective in the short term for relieving the symptoms of rhinitis of pregnancy, they have been extensively and often inappropriately used by pregnant women. Oxymetazoline does not appear to pose a risk to the foetus when used at recommended doses(6,7)and xylometazoline, being similar, is unlikely to pose a risk either. However, as data for their use in pregnancy are limited, use should be reserved until after the first trimester.

Oral decongestants such as pseudoephedrine are not recommended in allergic rhinitis due to lack of efficacy and adverse effects, e.g. agitation, insomnia, tachycardia (2).Due to a lack of studies and a theoretical risk ofdisruptive malformations such as such as gastroschisis, intestinal atresia, and hemifacial microsomia, oral decongestants should be avoided during pregnancy (12).

COMPLEMENTARY THERAPIES

The use of complementary and alternative therapies, such as homeopathy, herbal medicines and acupuncture for the treatment of allergic rhinitis is popular and many patients who use it appear to be satisfied however there is insufficient evidence to support claims of efficacy (1,17). Due to a lack of clinical data and insufficient reliable information, patients should be advised to avoid all such therapies during pregnancy.

Limitations

The above outline is presented for guidance. In general, prescribing in pregnancy should be considered on an individual basis, particularly if there are unusual circumstances (e.g. complicated obstetric history, requirement for high doses etc.). In these instances, further advice can be sought from your local (or Regional) medicines information service.

References

(1) Bousquet J, Khaltaev N, Cruz A et al. Allergic rhinitis and its impact on asthma (ARIA) 2008. Allergy 2008; 63(Suppl 86):8-160.

(2) Scadding GK, Durham SR, Mirakian R et al. BSACI guidelines for the management of allergic and non-allergic rhinitis. Clin Exp Allergy 2008; 38:19-42.

(3) Loock JW. Allergic rhinitis and pregnancy - a review of the literature, with recommendations for management. Curr Allergy Clin Immunol 2009; 22(1):11-16.

(4) UK Teratology Information Service.Allergic rhinitis in pregnancy. September 2014. Accessed via on 01/12/2015.

(5) Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. Accessed via on 01/12/2015

(6) Briggs GG, Freeman RK, Sumner JY. Drugs in Pregnancy and Lactation. 10th ed. Philadelphia: Wolters Kluwer Health, 2015.

(7) Yawn B, Knudtson M. Treating asthma and comorbid allergic rhinitis in pregnancy. J Am Board Fam Med 2007; 20:289-298.

(8) London New Drugs Group APC/DTC briefing document: Intranasal corticosteroids for allergic rhinitis. Denby, A. 2008. Accessed via: on 04/12/2015

(9) Summary of Product Characteristics. Opticrom Allergy Eye Drops. Sanofi. Date of revision of the text: 9 January 2014. Accessed via: on 01/12/2015.

(10) Hoyte FCL, Katial RK. Antihistamine therapy in allergic rhinitis. Immunol Allergy Clin N Am 2011; 31:509-543.

(11) Sato K. Treatment of allergic rhinitis during pregnancy. Clin Exp Allergy 2012; 12:31-36.

(12) Schaefer C, Peters P, Miller R. Drugs During Pregnancy and Lactation: Treatment options and risk assessment. 3rd ed. London: Academic Press, 2015.

(13) Golightly L, Greos L. Second Generation Antihistamines. Actions and Efficacy in the Management of Allergic Disorders. Drugs 2005; 65(3):341-384.

(14) UK Teratology Information Service. Fexofenadine in pregnancy. September 2014. Accessed via: on 01/12/2015.

(15) Summary of Product Characteristics. Rhinolast Nasal Spray. Meda Pharmaceuticals. Date of revision of the text: January 2014. Accessed via: on 01/12/2015

(16) Salib RJ, Howarth PH. Safety and Tolerability Profiles of Intranasal Antihistamines and Intranasal Corticosteroids in the Treatment of Allergic Rhinitis. Drug Saf 2003; 26(12):863-893.

(17) Brozek JL, Bousquet J, Baena-Cagnani CE et al. Allergic Rhinitis and its impact on asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol 2010; 126:466-476.

Quality Assurance

Prepared by

Elizabeth Uhegwu, Medicines Information Pharmacist, London Medicines Information Service (Northwick Park Hospital). [Based on earlier work by staff of theLondon Medicines Information Service.]

Contact

Date Prepared

December 8th 2015

Checked by

Sheena Vithlani, Regional Medicines Information Manager, London Medicines Information Service (Northwick Park Hospital).

Search strategy

  • Embase:[*HAY FEVER/ OR *ALLERGIC RHINITIS/] AND exp PREGNANCY/ [Limit to: Publication Year 2014-CURRENT and Human and English Language];
  • Embase: [*HAY FEVER/ OR *ALLERGIC RHINITIS/] AND exp PREGNANCY/ AND *ALTERNATIVE MEDICINE/; [Limit to: Publication Year 2014-CURRENT and Human and English Language]
  • Embase: CROMOGLYCATE DISODIUM/ AND exp PREGNANCY/ [Limit to: Human and English Language and Publication Year 2014-CURRENT and (Routes of Drug Administration Topical)]
  • Medline: *RHINITIS, ALLERGIC, SEASONAL/ OR *RHINITIS, ALLERGIC, PERENNIAL/ OR *RHINITIS ALLERGIC/; AND exp PREGNANCY/ [Limit to: Publication Year 2014-CURRENT and Human and English Language]
  • Medline: *RHINITIS, ALLERGIC, SEASONAL/ OR *RHINITIS, ALLERGIC, PERENNIAL/ OR *RHINITIS, ALLERGIC/; AND exp PREGNANCY/ AND *COMPLEMENTARY THERAPIES/
  • Toxbase (01/12/2015)
  • NHS Evidence: "allergic rhinitis" AND pregnancy (01/12/2015)
  • Briggs GG, Freeman RK, Sumner JY. Drugs in Pregnancy and Lactation. 10th ed. Philadelphia: Wolters Kluwer Health, 2015.
  • Schaefer C, Peters P, Miller R. Drugs During Pregnancy and Lactation: Treatment options and risk assessment. 3rd ed. London: Academic Press, 2015.
  • Summary of Product Characteristics for products mentioned.

1

From the NHS Evidence website