Analgesics

This page covers some of the most widely used classes of analgesics in dental pain management. Women should not suffer unnecessarily from pain during pregnancy and lactation.

Animal studies have indicated that a rise in maternal core body temperature of 1.5°C may be associated with an increased risk of neural tube defects (NTDs). Severe or chronic pain, if inadequately treated, may also impact on maternofetal outcome through alteration of both maternal cardiovascular function and uteroplacental perfusion. 

While human data is limited, effective treatment of a high temperature during early pregnancy is important. As fever can be a consequence of odontogenic infections, dentists need to be aware that hesitation to treat pregnant women can potentially have adverse consequences on maternofetal health. In general, the first-line treatment of pain management for dental pain is paracetamol (McCullough 2011).

Paracetamol

READ SUMMARY

Paracetamol is an analgesic indicated for the treatment of mild-to-moderate pain. In interpreting pregnancy safety studies, it is important to appreciate the possible adverse effects due to the underlying maternal condition for which paracetamol is used. 

Paracetamol is generally the first-line analgesic for dental pain because 

While it readily crosses the placenta but doesn’t appear to raise the increase the risk of birth defects or other adverse pregnancy outcomes (Kennedy, 2011).

• Several studies have found no increase in risk in overall congenital malformation rates following in utero exposure. A registry-based study from Denmark of 26 424 first trimester exposures found no increase in either the specific or the overall rate of birth defects (Rebordosa et. al, 2008). Although some retrospective studies including the US Collaborative Perinatal Project found a possible association with congenital dislocation of the hip based on 226 first trimester exposures (Heinonen 1977).
• use during any stage of pregnancy was not statistically associated with preterm birth or small for gestational age. These results came from a small prospective cohort study (760 pregnant women) (de Castro et al., 2022).
• a recent meta-analysis of 185,909 children exposed during pregnancy found no association with children’s risk of autism, ADHD, or intellectual disability using sibling control analysis  (Ahlqvist et al., 2024). This indicates that the findings of previous studies have suggested that acetaminophen (paracetamol) use during pregnancy may increase risk of neurodevelopmental disorders in children is not reliable. Note: the quality of these studies have been questioned in the literature. Current literature suggests there is no proof that paracetamol exposure affects a child’s behaviour.
• Two meta-analyses did find an increased risk for childhood asthma following first trimester exposure although no causal relationship between paracetamol and neurodevelopmental outcomes has been found  (Fan et al., 2017; Baranska et al., 2023). However, an increased incidence of wheezing or childhood asthma following frequent paracetamol use during late pregnancy (20-32 weeks) has been found in some, but not all, studies.
• A case-control study of 322 mother-child pairs found no link with first trimester exposure and cerebral palsy (Thacher et al., 2024). 

Administration in breastfeeding

Paracetamol is considered to be safe for use during lactation. The amount of paracetamol that the baby would receive through breastfeeding is much less than what they would get from a direct dosing. However, combination products containing paracetamol with codeine, ibuprofen, aspirin) are generally not recommended during breastfeeding (see specific monographs).

NSAIDs (Non-steroidal anti-inflammatory drugs)

Nonsteroidal anti-inflammatory drugs (NSAIDs; including aspirin, ibuprofen, naproxen, indomethacin and diclofenac), are available as “over-the counter” medications and are used to decrease pain and swelling (Kennedy 2011, Bloor and Paech 2013, Black, Khor et al. 2019). 

NSAIDs are inhibitors of cyclo-oxygenase/prostaglandin synthesis.

Effects on fertility

Laboratory animal evidence suggests that drugs that inhibit cyclo-oxygenase/prostaglandin synthesis may interfere with female fertility by disrupting ovulation. This effect is reversible on ceasing treatment. A human case series suggest an association between NSAID use and reduced female fertility (Norman and Wu 2004). Consequently, it is recommended that women planning pregnancy should avoid or reduce the dose of aspirin, NSAIDs, or COX-2 inhibitors (Bloor and Paech 2013).

Administration in pregnancy

Women who have accidentally used anti-inflammatory medicines can be generally reassured but there are various reasons to avoid NSAIDs at different stages of pregnancy (FDA 2022). 

All NSAIDs easily cross the placenta, and their safety profile in pregnancy depends on the timing, dose, and duration of exposure.

First Trimester

It is unclear whether taking ibuprofen during the first 8 weeks of pregnancy increases the risk of having a miscarriage, malformation or preterm delivery. A recent meta-analysis found no increased risk of spontaneous abortion and a small increase congenital anomalies and birth defects (Chen, Yang et al. 2024). However, the evidence is likely to be confounded and. did not control for the indications of use of NSAIDs (such as underlying fever or viral illness) (Kennedy 2011).. Some inflammatory illnesses that NSAIDs are used to treat, increase the chance of miscarriage (Bumps 2024). 

Therefore, a causal relationship between NSAID use in pregnancy and adverse outcomes is not considered unproven.

Second Trimester

After week 20 of pregnancy exposure to NSAIDs has been associated with kidney problems in the foetus which can lead to low levels of amniotic fluid that surrounds the baby (oligohydramnios).  After 20 weeks, the foetus’ kidneys produce most of the amniotic fluid of pregnancy, therefore kidney problems can lead to low levels of amniotic fluid. Amniotic fluid provides a protective cushion and helps in the development of the fetus’ lungs, digestive system, and muscles (FDA 2022). Oligohydramnios is often, but not always, reversible with treatment discontinuation.[uktis]

Third Trimester

After 30 weeks, NSAIDs could cause premature closure of the fetal ductus arteriosus (an opening between the two major blood vessels leading from the heart) (FDA 2022, Bumps 2024, MotherToBaby 2024). NSAIDs are inhibitors of cyclo-oxygenase which is a is a potent dilator of the ductus arteriosus and pulmonary resistance vessels in the fetus and newborns.  oxygenase. Its inhibition could potentially cause premature closure of these vessels (Kennedy 2011). These adverse outcomes are generally only seen after days to weeks of treatment and only infrequently reported as soon as 48 hours after NSAID initiation. 

Topical NSAIDs generally result in negligible blood levels and would be considered to be relatively safe in pregnancy although absorption is increased by use over a large surface area or the application of heat (Kennedy 2011).

Administration in breastfeeding

At recommended doses, anti-inflammatory medicines such as ibuprofen and diclofenac are considered to be compatible with breastfeeding.  The infant dose relative to the maternal dose is very low,  0.65% and 1% respectively, (Kennedy 2011).  Of the NSAIDs, ibuprofen and diclofenac are the preferred choices due to their shorter half-lives (UK Drugs In Lactation Advisory Service (UKDILAS) 2024).

Ibuprofen

Ibuprofen is a painkiller that can be bought from a pharmacy or may sometimes be prescribed by a doctor. It belongs to a class of drug called non-steroidal anti-inflammatory drugs (NSAIDs).
Use of ibuprofen during pregnancy is not advised unless prescribed by a doctor, especially if you are 30 or more weeks pregnant. Paracetamol is usually recommended to control pain or fever during pregnancy.

Administration in pregnancy

Evidence on the safety of ibuprofen is conflicting. 

It is unclear whether taking ibuprofen during the first 8 weeks of pregnancy increases the chance of having a miscarriage. Some (but not all) studies have suggested that ibuprofen use in early pregnancy might be linked to an increased chance of miscarriage. However, one explanation for this is that some inflammatory illnesses that ibuprofen is used to treat increase the chance of miscarriage (Bumps 2024). A recent meta-analysis found no increased risk of spontaneous abortion (Chen, Yang et al. 2024). 

A few studies have suggested that using ibuprofen in the first trimester might lead to a small increased chance for gastroschisis (when the intestines stick out of a hole in the stomach wall). A recent meta-analysis re-iterated this finding however, the analysis did not restrict cases to first trimester and many of the studies were acknowledged to have a high risk of bias (Baldacci, Santoro et al. 2024, Chen, Yang et al. 2024). 

Ibuprofen after week 20 of pregnancy can cause kidney problems in the foetus which can lead to low levels of amniotic fluid that surrounds the baby (oligohydramnios).  This is because, after around 20 weeks of pregnancy, the foetus’ kidneys produce most of the amniotic fluid, therefore kidney problems can lead to low levels of this amniotic fluid. Amniotic fluid provides a protective cushion and helps the unborn babies’ lungs, digestive system, and muscles develop (FDA 2022). These adverse outcomes are generally only seen after days to weeks of treatment and only infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation. 

After 30 weeks, can cause premature closure of the fetal ductus arteriosus (an opening between the two major blood vessels leading from the heart) (FDA 2022, Bumps 2024, MotherToBaby 2024).

If use for longer than 48 hours cannot be avoided between 20- and 30-weeks’ gestation, seek medical or obstetric advice.

Administration in breastfeeding

Ibuprofen appears in breast milk in very low concentrations and the amounts of ibuprofen in breastmilk are less than the doses given to infants directly. At least 23 cases are reported in the literature in which infants (ages not stated) were breastfed during maternal ibuprofen use with no adverse effects reported. Because of its extremely low levels in breastmilk, short half-life and safe use in infants in doses much higher than those excreted in breastmilk, ibuprofen is a preferred choice as an analgesic or anti-inflammatory agent in nursing mothers (LactMed 2006).

Aspirin

Aspirin is used to treat mild pain and fever, and low-dose aspirin is also prescribed by some obstetricians (often with heparin) to reduce the risk of adverse outcomes in pregnant women with recurrent miscarriages (Kozer, Nikfar et al. 2002). Aspirin is a Cox1 and Cox2 inhibitor. Aspirin is rapidly metabolised to salicylic acid which is of lower potency (Hale 2023).

Administration in pregnancy

Overall, aspirin is not associated with an increased risk of congenital malformations, although one meta-analysis suggested an association between first trimester aspirin use and increased risk of gastroschisis (Kozer, Nikfar et al. 2002) (Kennedy, 2011). However, a large random, control trial with low dose aspirin in a first trimester trial, also found no difference in the risk of congenital anomalies or gastroschisis (Hoffman, Goudar et al. 2020).  A more recent meta-analysis restricting analysis to low dose aspirin before 14 weeks (first trimester) found no increased risk for any congenital malformations or gastroschisis (Garza-Galvan, Ferrigno et al. 2023).  A third meta-analysis lacked information on aspirin dose, exposure period, and duration of treatment, finding an increased the risk of exomphalos/gastroschisis in infants while acknowledging publication bias in the included studies (Chen, Yang et al. 2024). 

As with other NSAIDs, aspirin should be avoided after 20 weeks due to the potential risk of oligohydramnios and persistent pulmonary hypertension of the newborn.

Administration in breastfeeding

Aspirin is excreted into breastmilk, with higher doses resulting in disproportionately higher milk levels. 

Although the direct use of aspirin in infants with viral infections has been associated with Reye syndrome, the risk from indirect exposure via breastmilk is unknown.  There was also one case metabolic acidosis in one breastfed infant after long-term, high-dose maternal aspirin ingestion.

For this reason, aspirin is generally not recommended for treatment of pain during breastfeeding and safer alternatives are available (Kennedy 2011).

Diclofenac

Administration in pregnancy

Diclofenac is a NSAID used for the treatment of arthritis, acute and chronic pain, and primary dysmenorrhea. Similar to other agents in this class, it also has antipyretic activity (Briggs, Freeman et al. 2022). NSAIDs are inhibitors of cyclo-oxygenase/prostaglandin synthesis.  

As with other Cox-2 inhibitors, women attempting to conceive should not use diclofenac because of the potential impact on blastocyst implantation. 

Diclofenac crosses the human placenta. However, a recent meta-analysis found no increased risk of major congenital malformations nor spontaneous abortion with exposure during pregnancy (Chen, Yang et al. 2024). 

Like other NSAIDs, diclofenac should be avoided after 20 weeks due to the potential risk of oligohydramnios and persistent pulmonary hypertension of the newborn.

Administration in breastfeeding

The manufacturer states that diclofenac is excreted into the milk of nursing mothers but does not cite quantitative data. Other small studies, showed very low or undetectable breastmilk levels (LactMed 2006). Diclofenac is one the preferred NSAIDS (Ibuprofen is the other)  to be used by nursing mothers due to its shorter half-life (UK Drugs In Lactation Advisory Service (UKDILAS) 2024).

Naproxen

Administration in pregnancy

Naproxen is a NSAID used for pain relief and fever. (Briggs, Freeman et al. 2022). NSAIDs are inhibitors of cyclo-oxygenase/prostaglandin synthesis.  

As with other Cox-2 inhibitors, women attempting to conceive should not use diclofenac because of the potential impact on blastocyst implantation. 

Naproxen crosses the human placenta (Briggs, Freeman et al. 2022). 

Although, some studies have reported a small increased risk for miscarriage and congenital malformations, a recent meta-analysis found no increased risk of spontaneous abortion or major congenital malformations following exposure to naproxen during pregnancy (Chen, Yang et al. 2024). 

Similar to other NSAIDs, naproxen should be avoided after 20 weeks due to the potential risk of oligohydramnios and persistent pulmonary hypertension of the newborn.

Administration in breastfeeding

Naproxen passes into breast milk in small amounts. Although only very small amounts pass into breastmilk, due to its longer half-life the risk of accumulation in breastfed infants increases  (LactMed 2006). Although adverse effects in breastfed infants are uncommon, the long half-life suggest that other medications may be preferred while breastfeeding.

Celecoxib

Celecoxib is a second-generation NSAID that reduces inflammation (swelling) and relieve pain. It is indicated for the relief of the signs and symptoms of osteoarthritis and rheumatoid arthritis as well as acute pain in adults [briggs].

Administration in pregnancy

There is little specific information regarding celecoxib in pregnancy. The general recommendation is to follow generally guidelines for NSAIDs.

(see above)

Administration in breastfeeding

Low levels of this drug are excreted in breastmilk. The elimination half-life range was 4.0-6.5 hours. These data suggest that celecoxib would be eliminated from breast milk about 24 hours after the last dose Knoppert DC, Stempak D, Baruchel S, Koren G. Celecoxib in human milk: a case report. Pharmacotherapy 2003;23:97-100. In Brigs].

Celecoxib is not expected to cause adverse effects in breastfed infants (Drugs and lactation database 2021).  No infant side effects were noted by the mothers of 2 infants aged 17 and 22 months who were breastfed during long-term maternal use of celecoxib 200 mg daily. No infant side effects were observed in these infants ((Hale, McDonald et al. 2004); https://pubmed.ncbi.nlm.nih.gov/15479658/).

Opioids

Opioids are stronger pain relieving medicines used to treat moderate to severe pain that can result from some dental procedures, such as tooth extraction, gum and other dental surgery, or placement of dental implants, dentists may prescribe medications for pain relief, including opioids. Commonly prescribed opioid medications for relief of dental pain include hydrocodone, oxycodone, and acetaminophen with codeine.

Overall, opioid analgesics have not been associated with an increase in birth defects or other adverse outcomes such as miscarriage. There is also reassuring data on longer-term neurodevelopmental follow-up in exposed infants.

The main concern about these drugs is that persistent use may lead to dependence and tolerance in the mother with resultant withdrawal (neonatal abstinence syndrome) in the neonate.

In the general population, paracetamol and codeine is not the analgesic of choice for dental pain. [mothersafe]

Codeine

Administration in pregnancy

Codeine crosses the human placenta [briggs].

Various reports have described associations between 1st trimester exposure to codeine, and congenital defects. Many of these studies contain confounders that could have affected the results, such as doses used, the reasons for use (e.g., pain, antitussive or addiction), and exposures to other drugs. 

A few studies looking at codeine use in pregnancy suggest a possible small increased chance of some birth defects such as heart defects and spina bifida [m2b], a recent meta-analysis did not support this finding a small increase in atrial septal defects and no increased risk of neural tube defects or major congenital malformations overall [varney]. Overall, no studies have found a specific pattern of birth defects caused by codeine use. If there is an increased chance of birth defects with codeine use in pregnancy, it is likely to be small [m2b].

The use of codeine may prolong labour and cause postpartum haemorrhage in some women (Nezvalová-henriksen, Spigset et al. 2011). 

Using codeine around the time of delivery has been associated with withdrawal symptoms in the baby (Neonatal Abstinence Syndrome). This depends on length of time and/or the dose of taken during pregnancy.  The baby can affect the baby for a while after birth, meaning that they may need to be looked after in a neonatal unit. The baby may be irritable, have feeding problems, and initially need some help with breathing. These problems usually settle within the first few days.[bumps]

Administration in breastfeeding

Codeine is partially metabolised by CYP2D6 into morphine, which is excreted into breast milk . The amount of codeine and morphine secreted into milk is dependent on the dose and maternal metabolism. If nursing mothers are CYP2D6 ultra-rapid metabolisers, higher levels of morphine may be present in their breast milk. In addition, infants are more susceptible to adverse events during the neonatal period (first or second week) And can present with infant drowsiness [hale].  For these reasons, codeine (and other opioids) are not the preferred medication during breastfeeding.

Combination medications

Ibuprofen with Codeine

When reading about combination drugs, precautions are generally considered for both drug effects. Please read ibuprofen as well as codeine monographs. 

In brief, NSAIDs are to be avoided after 20 weeks due to risk of oligohydramnios and after 30 weeks due to risk of premature closure of ductus arteriosus. At or near term, codeine may prolong labour, cause postpartum haemorrhage and produce neonatal withdrawal symptoms.

Ibuprofen and codeine both appear in breast milk in low concentrations. Codeine is contraindicated during breastfeeding (risk of increased morphine in ultra-rapid CYP2D6 metabolisers) due to risk of respiratory depression in the infant.

Paracetamol with codeine

Precautions are generally summative. Paracetamol is safe to sue in pregnancy and breastfeeding, read the codeine monographs. 

In brief, at or near term, codeine may prolong labour, cause postpartum haemorrhage and produce neonatal withdrawal symptoms. Codeine is contraindicated during breastfeeding (risk of increased morphine in ultra-rapid CYP2D6 metabolisers) due to risk of respiratory depression in the infant.

Last Updated: 2024 June 20

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