Codeine is converted to morphine in the liver by the CYP2D6 enzyme. There are many genetic variations of CYP2D6, which affect the extent of this conversion in individuals. This leads to differences in the plasma levels of morphine and different levels of pain relief.
For some this can result in no benefit from the drug, for others that they experience excessive drowsiness and constipation. For breastfeeding mothers in the latter group this may also lead their babies to experience respiratory depression.
Initial cautious recommendation of use during breastfeeding followed an adverse event report from Canada, where a breastfed baby died at 12 days of age. At post mortem he was found to have very high levels of morphine in his blood because his mother had multiple copies of the gene which metabolises codeine into morphine and was taking compound codeine analgesics for episiotomy pain.
The mother had reported side effects of constipation and somnolence sleepiness in herself. In another study vanderVaart it was found that ultra rapid metabolisers chose to take less codeine than their counterparts complaining of dizziness and constipation.
They chose instead, to take paracetamol and naproxen or naproxen alone which were options in the study protocol. The MHRA have reported that to date, at least 44 cases of neonatal respiratory depression in breastfed infants of codeine-using mothers have been published MHRA Codeine combinations have in the past formed the mainstay of analgesic use, particularly in the early postpartum period.
The genotype producing ultra rapid metabolism is rare but is impossible to identify without genetic testing. If a mother has never taken codeine preparations before she would be unaware of whether she might be an ultra rapid metaboliser putting herself and her baby at risk of adverse effects.
Madadi et al the group who have published most papers on codeine use during breastfeeding Motherisk. They suggested that:. The UKMI Specialist Pharmacy Service issued information in May that dihydrocodeine and tramadol may be considered where breastfeeding mothers require opioids but that the possibility of a mother being an ultrarapid metaboliser cannot be ignored even with these drugs. If opioids are prescribed and adverse effects develop in breastfeeding infants, the possibility of opioid toxicity should be considered regardless of the maternal dose.
In such cases, the opioid should preferably be replaced by an alternative non-opioid analgesic and breastfeeding interrupted until the cause of the symptoms is clear. SPS The data demonstrated that opioids could have been a factor as 10 of the 12 infants were exposed to opioids and most of their mothers received more doses than the control group Naumburg Use of any opioid by breastfeeding mothers, if necessary and only as third line choice of medication after the use of regular paracetamol and non steroidal anti-inflammatories — see Information sheet on Analgesics and breastfeeding on www.
If adverse effects develop in breastfeeding infants the possibility of opioid toxicity should be considered, regardless of maternal dose. The opioid should be replaced by a suitable non-opioid analgesic LactMed Hale. Breastfeeding should not be interrupted unless the symptoms are extreme e. Mothers should be fully informed of the risks before being sold or prescribed codeine or any opioid and to watch their nursling carefully for any signs of increased drowsiness — sleeping longer or more frequently.
This can be evident whatever the age of the nursling and it should not be assumed that an older baby is not at risk. Using the half life of codeine as 3 hours — it takes 15 hours for a dose to be regarded as no longer in breastmilk. They suggested that: In most cases, the occurrence of CNS depression is consistent between the mother and the baby. If the mother suffers from symptoms of CNS depression e.
If the baby is not feeding well, does not wake up to be fed, does not gain weight, or shows limpness, he or she should be examined by a physician. Central nervous system depression in the baby appears to worsen after 4 days probably, owing to the accumulation of morphine with more breastfeeding.
If possible, codeine should not be used for longer than 4 days. Healthcare professionals should be aware that breastfeeding is not recommended during treatment with codeine or tramadol due to the risk of serious adverse reactions in breastfed infants such as excess sleepiness, difficulty breastfeeding, and serious breathing problems, which may result in death. We also encourage health care professionals to read the Drug Safety Communication regarding all new warnings the FDA is communicating about these products.
The signs of opioid overdose in the breastfeeding mother are the same as can occur with any person taking an opioid. These include trouble breathing, shortness of breath, extreme drowsiness, light-headedness when changing positions, or feeling faint. Breastfeeding mothers who are ultra-rapid metabolizers may have symptoms of too much opioid, even if they are taking a dose that would not otherwise be expected to cause an overdose.
If any of these symptoms occur, the mother, family members, or other close contacts should call her doctor or right away. It is important for health care professionals and breastfeeding women to discuss the use of pain medicines and to consider alternatives to codeine or tramadol. Because most people do not know if they are ultra-rapid metabolizers, and because early signs of opioid overdose in an infant may be difficult to notice, breastfeeding is not recommended during treatment with codeine or tramadol.
These tests are not routinely done but may help healthcare professionals make individualized treatment decisions for a patient. The mother should discuss her concerns with her doctor, and her doctor may select another pain medication that is not subject to the risks associated with CYP2D6 ultra-rapid metabolism.
Visit the Codeine Information page. Index to Drug-Specific Information. What is codeine and how is it used? When codeine enters the body, it is changed metabolized in the liver to morphine, the active form. Morphine relieves pain and cough and is also responsible for side effects that some people may experience. What is tramadol and how is it used?
0コメント