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[Pandora II]

Kama_s - I wish I''d known about the ibuprofen being safe up to 32 weeks, I was desperate to take some for an inflamed costovertebral joint and the pain team told me it was a big no-no. I was already on 125mg lamotrigine, 200mg SR tramadol and around 60mg codeine and they just suggested upping the codeine a bit. Are opiates significantly safer that other things in pregnancy?


Not particularly, especially not in the 3rd trimester. There isn''t much conern for birth defects with either. But opiate use in the 3rd trimester is not suggested because of withdrawal symptoms in the newborn. Most of the concern with opiates is during breastfeeding though. A % of people have a variation of a liver enzyme that makes you less efficient in breaking down the drug and flushing it out of your system. So you end up having more in your blood, which gets passed on via breast milk. Plus, chances are the baby too has the same variation, causing an overdose.
Ibuprofen, when used AFTER week 35 (I say 32 to stay on the safe side), prematurely closes the ductus arteriosus (DA). The DA normally closes automatically soon after birth. Ibuprofen causes it to close prior to birth, again, when used after week 35 only. So technically, it''s safe to use until that point.


Kama, thought I''d put this in a new thread so as not to hijack the other.

I''m really interested in this as it''s very different from the advice I was given - I know you are a specialist in neo-natal toxicology and probably have far more up-to-date info than my pain specialist who doesn''t see pregnant people very often except to give them epidurals!

My daughter was born opiate dependent as I couldn''t come off the meds while I was pregnant or afterwards. She had Apgars of 10 and 10 at birth, but started withdrawing about 24 hours later - hideous high pitched cry and generally miserable so they put her on oramorph for a day. The hospital was very keen for me to breastfeed to help with the withdrawal - plus they were giving me 20mg of morphine on top of the rest due to the damage her delivery caused - so she was getting a fair whack through the milk. They weren''t totally happy about breastfeeding on lamotrigine (SJS risk), but we couldn''t find anything definitive against in any research papers, but nothing was mentioned about the opiates being a problem...

If she''s been breastfeed now for nearly a year, can I be pretty sure that she''s okay with them? Can they suddenly start to have problems?

(ETA: Any chance of my thinking I''d get a nice placid doped-out baby was checked within minutes of meeting her - I have the child who NEVER sleeps or stops.

)

 

[kama_s]

So sorry you had to go through all that

First of all, I need to correct myself on something I said earlier. I was wondering why your Dr. gave morphine to D and that''s when I realized I got the pathway wrong. Let me explain. Codeine is broken down by your body to morphine. Some people have a liver enzyme variation (CYP2D6 for your interest) that makes them break down codeine FASTER (not slower, as I incorrectly mentioned before). So more morphine is in the system. Hence, more morphine goes into the baby as well. Now, you would know if you''re one of them. If you feel extremely drowsy and sleepy after you''ve taken codeine, then you''re a fast metabolizer. If you notice same in D, then do NOT breastfeed while on codeine. I don''t think this is the case for you, but something for you to keep an eye out for.

Now, for lamotrigine (let''s call it LTG). A significant amount crosses through the breast membranes. The problem, however, is that there aren''t very many studies done on LTG use while nursing. When I finished up my degree, we were in the middle of conducting a study on LTG - we asked women to donate their breast milk so we can determine how much LTG was in it. I''ll try and give a friend a call to see if the study has been completed. I don''t think there is much issue with LTG for you, because you would have noticed something by now. Some of the side effects to look out for are: apnea, rash, drowsiness or poor sucking. If you notice a rash, discontinue breastfeeding until you can see a Dr. to establish the cause of the rash. Unfortunately, this is all the information that is available for LTG at this moment.

Hope this info helps.

 

[Pandora II]

Date: 4/28/2010 10:58:08 AM
Author: kama_s
So sorry you had to go through all that

First of all, I need to correct myself on something I said earlier. I was wondering why your Dr. gave morphine to D and that''s when I realized I got the pathway wrong. Let me explain. Codeine is broken down by your body to morphine. Some people have a liver enzyme variation (CYP2D6 for your interest) that makes them break down codeine FASTER (not slower, as I incorrectly mentioned before). So more morphine is in the system. Hence, more morphine goes into the baby as well. Now, you would know if you''re one of them. If you feel extremely drowsy and sleepy after you''ve taken codeine, then you''re a fast metabolizer. If you notice same in D, then do NOT breastfeed while on codeine. I don''t think this is the case for you, but something for you to keep an eye out for.

Now, for lamotrigine (let''s call it LTG). A significant amount crosses through the breast membranes. The problem, however, is that there aren''t very many studies done on LTG use while nursing. When I finished up my degree, we were in the middle of conducting a study on LTG - we asked women to donate their breast milk so we can determine how much LTG was in it. I''ll try and give a friend a call to see if the study has been completed. I don''t think there is much issue with LTG for you, because you would have noticed something by now. Some of the side effects to look out for are: apnea, rash, drowsiness or poor sucking. If you notice a rash, discontinue breastfeeding until you can see a Dr. to establish the cause of the rash. Unfortunately, this is all the information that is available for LTG at this moment.

Hope this info helps.

Thanks for that, it was very helpful.

Don''t worry, I knew what the situation would be long before I got pregnant and had a lot of consultations before doing so as I knew she''d be opiate dependent. I was quite prepared for them to tell me that we''d be unwise to do it and was suprised just how positive and encouraging they were about going ahead and they spent a lot of time explaining that they''d step in straight away to avoid her being in any pain - I know how bad withdrawal can be so I felt awful about that idea.

I did reduce the LTG to 25mg until week 14 and then titrated up over 8 weeks to reduce any cleft palate risk). She actually did better than we were expecting - my hospital sees a lot of heroin babies, so they were relieved to actually know what one of their patients was actually on!

I''m guessing that since 60mg of codeine at a time doesn''t even make me yawn that I''m not a fast metaboliser.

I''d be interested to know more on the LTG and breastmilk - I think I read that it''s about a 45% crossover? I did ring GlaxoSmithCline and offered to complete any forms or anything for their pregnancy register and they said they had just closed it.

D did get a rash twice - and I was on the phone to my father instantly to see if it was one to worry about and took her to her own GP (was common or garden post-viral). I''ve seen photos of SJS, but who knows what it looks like in small babies...

 

[kama_s]

I''m glad you had a great team of physicians that took good care of D!

The risk for cleft palate is actually very minimal (to none) with LTG. A previous registry showed an increased risk, but they actually didn''t have a proper control group. They used a negative control - that is women who had an uneventful pregnancy. The reason why this would give a higher risk is because very often the underlying disease in itself can cause an icnreased risk for birth defects. So really, you should compare with women who don''t use the drug but DO have the underlying disease. Several big studies were conducted after this one (one being the GSK/Kendle study you mentioned that I believe included almost 1500 women on LTG) and none of them showed an increased risk for cleft palate. We do, however, recommend additional folic acid (5mg/day). Some other anticonvulsants have been shown to cause neural tube defects, but again, nothing was noted with LTG. That said, folate is a water soluble vitamin, so if you have excess, you''ll just pee it out. So it doesn''t hurt to up the folate dose. In fact, last year Health Canada officially increased the recommended folate dose to 5mg/day for ALL planning/pregnant women.

From the top of my head, the amount of LTG found in the baby''s plasma was 30-50% of maternal levels. Which is very high. Usually we are concerned with anything more than 10%. I don''t think there have been any reports of a newborn breastfed with LTG who actually had TEN rashes. At this point, I think, it is more of a theoretical risk - so just something to keep an eye out for.

Not even a yawn?! Haha, slow poke

P.S.: Sorry if my last few posts are all over the place. I''ve been SO exhausted last few days, I can barely keep my eyes open.

 

[Pandora II]

Date: 4/28/2010 9:03:57 PM
Author: kama_s
I''m glad you had a great team of physicians that took good care of D!

The risk for cleft palate is actually very minimal (to none) with LTG. A previous registry showed an increased risk, but they actually didn''t have a proper control group. They used a negative control - that is women who had an uneventful pregnancy. The reason why this would give a higher risk is because very often the underlying disease in itself can cause an icnreased risk for birth defects. So really, you should compare with women who don''t use the drug but DO have the underlying disease. Several big studies were conducted after this one (one being the GSK/Kendle study you mentioned that I believe included almost 1500 women on LTG) and none of them showed an increased risk for cleft palate. We do, however, recommend additional folic acid (5mg/day). Some other anticonvulsants have been shown to cause neural tube defects, but again, nothing was noted with LTG. That said, folate is a water soluble vitamin, so if you have excess, you''ll just pee it out. So it doesn''t hurt to up the folate dose. In fact, last year Health Canada officially increased the recommended folate dose to 5mg/day for ALL planning/pregnant women.

From the top of my head, the amount of LTG found in the baby''s plasma was 30-50% of maternal levels. Which is very high. Usually we are concerned with anything more than 10%. I don''t think there have been any reports of a newborn breastfed with LTG who actually had TEN rashes. At this point, I think, it is more of a theoretical risk - so just something to keep an eye out for.

Not even a yawn?! Haha, slow poke

P.S.: Sorry if my last few posts are all over the place. I''ve been SO exhausted last few days, I can barely keep my eyes open.

I went on 5mg/day as soon as we started TTC - it was ridiculous before I got the Rx, I was buying it over the counter in the usual dosage and taking more than a months supply a week to get the 5mg a day!

I''m now on 5mg/day on a permanent basis. As far as I know there are no adverse effects of bigger doses of folic acid so I don''t understand why they don''t give everyone a bigger whack - I suppose it might make pernicious anaemia harder to detect or something...

They were extra cautious as my sister''s daughter had cleft palate, I was also sent for extra ultrasounds with the cardiologists which I thought a bit odd.

I actually OD''d my husband on codeine once as I forgot how tolerant I am and gave him 60mg after he came off his motorbike and injured his ankle. Poor guy, he could barely speak!

Thanks for the info on the LTG - are there any new papers out/coming out. I gave my consultant copies of everything I found at the time - I know I''m a bit of a case study for them, which is fine by me - so would be good to flag it up if there are.