Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (www.bnf.org).

• Antacids and alginates are considered safe in pregnancy when used at the correct dosage, despite a lack of evidence from controlled or observational studies. They are considered to be an unclassified risk in pregnancy by the United States Food and Drug Administration [American Gastroenterological Association, 2006], and pregnancy is not listed as a contraindication or caution to antacid use in the British National Formulary (BNF) [BNF 54, 2007]. Some products, such as Gaviscon^®, are licensed for use in pregnancy [ABPI Medicines Compendium, 2005; ABPI Medicines Compendium, 2007].
• The recommended antacids and alginates are listed in Table 1. Liquids are generally preferred as they are considered more effective [BNF 54, 2007], and tablets are not as widely available on the NHS.
• Antacids and alginates are usually used as required or just before symptoms are expected (e.g. before meals and sleep).
• Taking antacids with food may prolong their duration of action.
• Antacids may impair the absorption of some drugs, and they can prevent the absorption of iron supplements. If an interaction is anticipated, the drug should ideally be taken at least 2 hours after the antacid is used.
• Antacids and alginates are well tolerated with few adverse effects when used at the correct dosage:
• Magnesium products tend to cause diarrhoea, whereas aluminium products cause constipation [BNF 54, 2007]. Taking a product with both minerals may alleviate these symptoms, although CKS found no evidence to support this.
• Some alginate products have a high sodium content. If hypertension or pre-eclampsia is likely to be problematic, it may be better to avoid these, although there is a lack of evidence to support this [Duley, 2004].

• Ranitidine is not licensed for use in pregnant women, but is considered safe on the basis of several years of use without incident, and supporting evidence from observational studies.
• The British National Formulary (BNF) states 'Manufacturer advises avoid unless essential, but not known to be harmful' [BNF 54, 2007]. This is in accordance with the product license stated in the Summary of Product Characteristics [ABPI Medicines Compendium, 2009].
• It is classed as a group B drug in terms of risk to pregnancy by the United States Food and Drug Administration (i.e. 'animal studies shown no risk but human studies inadequate or animal studies show some risk not supported by human studies') [Ali and Egan, 2007].
• CKS recommends the usual dosage of ranitidine; 150 mg, twice a day [Schaefer et al, 2007]. This is consistent with an RCT which found a lower dosage (150 mg, once a day) to be ineffective [Larson et al, 1997]. If this dosage provides insufficient protection, consider switching to omeprazole or seeking specialist advice.
• Ranitidine is well tolerated by most women. Some adverse effects were reported following post-marketing surveillance (rather than data from controlled trials, so they were not necessarily causal associations) and are estimated to occur rarely (affecting less than one person in 1000) [ABPI Medicines Compendium, 2009].

• Omeprazole is licensed for use in pregnancy [ABPI Medicines Compendium, 2008] and is likely to be safe for use in all trimesters:
• The British National Formulary states it is 'not known to be harmful (in pregnancy)' [BNF 54, 2007].
• It is considered to be a class C drug in pregnancy by the United States Food and Drug Administration (i.e. 'Animal studies show risk but human studies are inadequate or no studies in humans or animals'). This is in contrast to the other proton pump inhibitors (namely esomeprazole, lansoprazole, pantoprazole, and rabeprazole), which are all class B [Madanick and Katz, 2006]. However, this classification is based on animal studies where very high doses were found to be teratogenic; recent evidence from observational studies in humans show that the drug is unlikely to be harmful to the fetus.
• CKS recommends the use of standard doses of omeprazole as used for other people with acid reflux disease, as there is an absence of evidence on dosage in pregnancy from controlled trials [ABPI Medicines Compendium, 2008]. This is a relatively conservative regimen, using low doses. The maximal effect develops after 5 days [Christopher, 2005].
• The starting dose is 10 mg, once a day [Christopher, 2005].
• This can be increased to 20 mg, once a day, if symptoms are not fully improved after 5 days or if they return.
• If symptoms persist, seek specialist advice.
• Omeprazole is well tolerated. The most common adverse effects are headache or gastrointestinal effects (e.g. diarrhoea), including symptoms often seen in pregnancy (e.g. nausea and vomiting). It therefore may not be clear if it is the drug that is causing these adverse effects [ABPI Medicines Compendium, 2008]. If in doubt, stop the drug, and seek specialist advice if symptoms are severe or persistent.

• Advise that:
• The best available evidence suggests that omeprazole is a safe treatment in pregnancy, and the baby will not be harmed by its use.
• If symptoms are severe, treating symptoms will lead to a more fulfilling and pleasant pregnancy.
• Treatment can usually be discontinued after delivery as the condition resolves spontaneously.
• Adverse effects are unusual with omeprazole and rarely serious. If severe gastrointestinal symptoms or headache begin shortly after starting the drug, advise the woman to return for advice.