Are Triptans Safe To Take While Breastfeeding?

Are Triptans Safe To Take While Breastfeeding?

Triptans are the best drugs for acute therapy of migraine and have been so since Glaxo brought out injectable Imitrex 6 mg subcutaneous in 1991.  There are now 7 triptans, 5 that are commonly used for acute therapy of migraine-sumatriptan, zomatriptan, eletriptan, rizatriptan, and almotriptan.  These are all quickly acting drugs that work within 30 minutes.  The drugs naratriptan and frovatriptan are marked for menstrual migraine chiefly because of their long duration.  Frovatriptan is the star here as it last 26 hours, but like naratriptan has an onset of 1-2 hours.

 
The Migraine Timing Cycle

The Migraine Timing Cycle

 

There are 4 steps in the migraine process--called the migraine timing cycle.  The first step is trigeminal nerve pain fiber inflammation by the brainstem.  The second step occurs at 20-40 minutes when the ganglion of the nerve and artery in the brain start to release the Neuropeptides--Neurokinin A, Substance P, and CGRP.  The 3rd step occurs at about 2 hours as the inflammatory chemicals cause meningeal artery vasodilatation.  The 4th step occurs at 3-4 hours with inflammation of the thalamus, the deep nucleus in the center of the brain called the “pain center.”  The 4th step is also called “Central Sensitization” because steps 1,2, and 3 occur in the skull but are outside the brain while step 4 inflames the thalamus in the brain.

An episode of migraine lasts 4-72 hours because that’s how long it takes the body to metabolize the inflammatory neuropeptides.  They released into the brain and then drain down the veins to the liver, and are discharged in the toilet after 3 days.  If one treats migraine with over-the-counter drugs like Advil or Tylenol, they don’t stop the release of the neuropeptides and the inflammation, yet triptans will do that and that’s why triptans are such important and effective drugs for treating migraine.

Patients with migraine should treat with triptans but never with opiate drugs or drugs with butalbital, like Fioricet.  Butalbital is a barbiturate drugs and has been banned in every country in the world except in Canada and the United States because it causes medication overuse headache. There are no research articles published that show that butalbital helps migraine, but one reports its use with tension type headache.  The sarcastic joke at headache meetings is that butalbital is the only drug that persons from Mexico go to the United States to get.

Use of too much Caffeine, Tylenol, Advil, Aleve, triptans, butalbital, or opioid narcotics like hydrocodone or tramadol can cause medication overuse headache.  The general rule of migraine patients to prevent medication overuse headache is to limit over-the-counter painkillers and triptans to no more than 2 days a month.  Opioid narcotics and butalbital should not be used for migraine headaches.  Medication overuse headache is the current term for persons who have chronic migraine from overuse of medication.  It used to be called rebound headache which is an old term.

Chronic migraine is defined by the International Classification of Headache as being 15 headaches or more per month, 8 of which have migraine features.  Episodic headache is defined as 14 or less headache days per month.

If the patient uses over-the-counter medications or a triptan, a transition occurs so that after several migraine headaches have occurred within a week or 2, every time the patient takes caffeine or Tylenol or a triptan, the inflammatory neurochemicals are released and they stay in the body for 3 more days and so the migraine process becomes continuous.  It is sort of like putting lighter fluid on a fire which makes the fire continue to burn.  If one considers that migraine can generate chemicals that last 3 days and multiple that by 2 days, the result may be 6 days of neurochemical release per week.  So, if the doctor allowed his patient to take Tylenol or a triptan 3 days a week that’s 9 days with chemical inflammation, more than the 7 days in a week, and explains the limitation of all painkillers and triptans to no more than 2 days a week.

Imitrex (sumatriptan)

Oral tablet PO 50-100 mg

Nasal Spray 5-20 mg

Subcutaneous 6mg 

Zomig (zolmitriptan)

Oral tab ZMT  2.5-5 mg       

Nasal Spray 5 mg              

Maxalt (rizatriptan) 10-20 mg          

Axert (almotriptan) 6.25-12.5 mg    

Relpax (eletriptan) 40 mg               

Amerge (naratriptan) 2.5 mg               

Frova (frovatriptan) 2.5 mg              

I have a more thorough discussion of the migraine timing cycle on my webpage at www.doctormigraine.com/blog/categories/general migraine.  However, this timing cycle points to the reason why migraine should be treated early with a triptan.  The patient has only 20-40 minutes after the onset of pain before the neurochemicals are released and a triptan drug will block the release of these chemicals.  It’s just that simple.

Most patients don’t know to treat early and therefore the chemicals are released and inflame the trigeminal nerve, the arteries, and the thalamus.  The patient returns and states that the triptan doesn’t work.  It is reported that triptans well help migraine headache any time during a migraine, even if is treated late, but unless migraine is treated at onset, the patient will not be headache free within 2 hours.

Headache free means that all migraine symptoms are gone--headache, nausea, sound sensitivity, light sensitivity, olfactory sensitivity, and mental cloudiness.  In my office I go over and over again this point with patients to treat early and then the next time they in they report that they did well with the triptan, and the migraine was gone early.  Many patients tell me that they get relief within 15 or 30 minutes, which is less than the reported time it takes the drug to work.

Triptan contraindications.  This means if you have these medical problems, don’t take triptans.

Triptans should not be used with a personal or strong family history of coronary artery disease.  They shouldn’t be used with uncontrolled hypertension.  Doses should be limited for children, the elderly (defined here as over 65 years old.), and patients with basilar artery or complicated migraine (aura symptoms over 60 minutes.)  Also, triptans should not be mixed with ergotamine or DHE within 24 hours.

Common triptan side effects:

Side effects may be--chest tightness or pressure, near fainting, neck/back pain which may be burning, a warm or hot feeling, dizziness, or drowsiness.

Are Triptans Safe To Take While Breastfeeding?  Yes, triptans are safe to take while breastfeeding.  Nursing infant absorption of medication from their mother’s milk is low and not enough to harm the baby.  Recent medical studies support the safety of triptans during pregnancy.

1. A Canadian Family Physician article in 2010 reported on 5 nursing women who had received subcutaneous sumatriptan.  Drug concentrations in milk and plasma over the next 8 hours were measured by high-performance liquid chromatography.  It was estimated that the infants received 3.5% of the maternal dose.  Adjusting the dose for infants in comparison with adults, gave a dose of 0.49% for very premature neonate to 0.7% for a 30-week-old infant. 

As a rule, a medication with a relative infant dose of less than 10% of the administered maternal dose is considered compatible with breastfeeding. In addition, given the low oral bioavailability of sumatriptan of 14% when compared with the subcutaneous route of 96%, it is expected that the amounts ingested by suckling infants would be small and would most likely not cause adverse effects.

Also, sumatriptan is usually delivered as a single dose at infrequent intervals and it was thought that the low-level excretion in breast milk would not bring a significant risk to the suckling infant.  This minor exposure could be avoided by pumping and then discarding all milk for 8 hours after the dose of sumatriptan.

2.The American Academy of Pediatrics also considers sumatriptan as usually compatible with breastfeeding.

3. Another small study indicates that a single 80-mg oral dose of eletriptan results in a relative infant dose of 0.02% of the maternal dose; however, the concentration of the active metabolite (with a longer plasma half-life) was not measured in the breast milk.

4.Triptans are now generally considered to be safe to use during pregnancy.

5.The accumulated evidence from sumatriptan’s pregnancy registry and other studies suggest that this drug is a safe therapeutic option for the treatment of migraine attacks in pregnant women. More studies are needed to confirm the safety of the other triptans in pregnancy; however, evidence to date is reassuring. In addition, sumatriptan is considered compatible with breastfeeding, as minimal amounts are excreted into milk.

6.Women who suffer from migraine headaches, which often render them unable to carry out tasks of daily living, can use triptans during pregnancy and breastfeeding without fear of harming their unborn children or infants.

Related questions

Is there a decreased risk of migraine in women who breastfeed?  Yes, one study reported that 100% of women who bottle-fed their babies had their migraines return within one month, while only 43% of those who breastfed did.  This indicates a protective effect from breastfeeding. Not all studies have confirmed this, however.

Does migraine get better during pregnancy?  Fifty to seventy-five percent of women have fewer or less intense attacks during pregnancy.  Decreased migraine headaches during pregnancy is especially noted with women who had “menstrually related migraine without aura or pure menstrual migraine.” 

Menstrually related migraine is migraine that occurs during menstruation and at other times during the month, not related to menstruation.  Pure menstrual migraine patients only have their migraines at the start of their cycle.  Both menstrually related migraine and pure menstrual migraine are headaches that occur, by definition, 2 days before bleeding starts, the day of start of bleeding, or 2 days after. 

Estrogen levels are high for the first 3 weeks of a woman’s cycle and then when estrogen levels drop and progesterone levels rise, menstrual headaches occur.  Falling levels of estrogen after delivery may be associated with postpartum depression.

Pregnancy is a high estrogen level time, and this is why migraine attacks for many women improves during pregnancy.  It is usually women who have migraine with or without aura, that is non-estrogen related migraine for women, who have trouble with migraine during pregnancy.  Their migraine is not especially helped by the high estrogen level of pregnancy.

What happens to migraine during the postpartum period?  Thirty to forty percent of all women have migraine headaches occur after their baby is born.  This usually occurs during the first week after delivery and these migraines for about 6 weeks postpartum last longer and are more severe.  Then in 55 percent of women, migraine headaches improve back to their pre-pregnancy level.

Importance of breast-feeding for the infant.  Breast-feeding has important health and emotional benefits for both mother and infant and should be encouraged. The mother bonds with her child and provides important immune therapy through her breast milk.  Breast-feeding stabilizes estrogen levels because without it they plunge to zero, aggravating migraine.

While there are some data to suggest migraine may improve during breast-feeding, more than half of women experience migraine recurrence with 1 month of delivery. Thus, a thorough knowledge base of the safety and recommended use of common acute and preventive migraine drugs during breast-feeding is vital to clinicians treating migraine sufferers. Choice of treatment should take into account the balance of benefit and risk of medication.

Breastfeeding is recommended by both the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics.

 
548980db59655_-_rbk-2012-mom-judgement-breastfeeding-s2+%281%29.jpg
 

Are there references for lactating mothers that gives helpful information regarding medications?  Useful references are:

The American Academy of Pediatrics publication "The Transfer of Drugs and Other Chemicals Into Human Milk.”

Thomas Hale's manual Medications and Mothers Milk.

Briggs, Freeman, and Yaffe's reference book, Drugs in Pregnancy and Lactation.

National Library of Medicine's Drugs and Lactation Database (LactMed) is a fully referenced database available online.

The LactMed database contains information on drugs and other chemicals to which breastfeeding mothers may be exposed.  It includes information on the levels of such substances in breast milk and infant blood, and the possible adverse effects in the nursing infant.  Suggested therapeutic alternatives to those drugs are provided, where appropriate.  All data are derived from the scientific literature and fully referenced.  A peer review panel checks the data to assure scientific validity and currency.

What other simpler drugs may be used for treatment of migraine with breastfeeding?   Ibuprofen, diclofenac, and eletriptan are among acute medications with low levels in breast milk, but studies of triptans are limited. Toxicity is a concern with aspirin due to an association with Reye's syndrome; sedation or apnea is a concern with opioids.

What about use of the new CGRP antibody drugs for pregnancy or lactation?  There is no current indication for the use of CGRP antibody drugs during pregnancy or while breastfeeding.

The FDA statement regarding CGRP antibody drugs is: 

Pregnancy-caution is advised during pregnancy.  No human data is available, no known risk of fetal harm based on animal data at 20 times recommended human dose.

Lactation–caution is advised for breast-feeding.  No human data available to assess risk of infant harm or effects on milk production.

General advice for caring for the migraine mother postpartum.

The migraine lifestyle should be followed.  That is no caffeine, 3 meals a day, setting the sleep-wake cycle to be 7-8 hours at night as best as possible considering getting up at night to nurse the infant.  Naps for the mother will be needed.  Recruitment of the spouse to help with the baby will be helpful.  On rare occasions breast milk may be pumped and given by bottle by a family member or friend so the mother may sleep.  All known migraine triggers should be avoided if possible.

Ice bags over the head can be helpful.  Comforting massage may help with neck pain.

 
Ice bag

Ice bag

 

General aerobic exercise like walking or water aerobics may be helpful.  Attention to stress, depression, anxiety, and emotional issues is important.  CBT or cognitive behavioral therapy may be helpful for anxiety or depression.  In the YouTube search engine enter CBT and depression or CBT and anxiety and then watch the videos to learn how to use CBT.

The mother shouldn’t take over-the-counter medications such as caffeine, Tylenol, Advil, or Aleve more than 2 days a week to avoid medication overuse headache.  Adequate hydration is important also.

Mothers should check with their pediatricians before taking any drugs during breastfeeding. It may be possible to not take any medication for migraine during breast-feeding.

How long do women breastfeed?

Older, higher educated women breastfed a longer time.

Sixty-eight percent of women who breastfed longer than one year returned to employment before their infant was 1 year old.

The most common reason for long-term breastfeeding was that it was a special time for mother and baby that the mother was not ready to give up.

Half of nursing mothers breastfed on demand.

By 12 to 15 months, fifty-four percent of babies slept in a crib in a separate room while thirty-seven percent slept in the same bed with their mother all or part of the night.

Fifty-seven percent of mothers considered their support group to be lightly or moderately important in influencing their decision to breastfeed beyond a year. 10% considered it to be extremely important.

Regarding medication given first-line for the nursing mother.  Tylenol (acetaminophen) is the preferred first-line drug that may be given for migraine since it is well known and may be safely used.

If preventive drugs are to be used propranolol and metoprolol are suggested first-line treatments because so little of the drug gets into breast milk.  Low dose amitriptyline and nortriptyline which are antidepressant drugs used for migraine prevention may also be tried.

Preventive medications that are not recommended include zonisamide, atenolol, and tizanidine.

Second-line medications for breast-feeding mothers would be sumatriptan and eletriptan which have been most successfully used in medical studies.

Short courses of prednisone as 20 mg 3 times a day for 7 days or Medrol Dosepak for 6 days may be used for episodes of medication overuse headache and detoxing from painkillers.

Botox may be tried although there are no reference studies because it’s doubtful that Botox gets into the mother’s milk.

Medications to be avoided during breast-feeding are:

Aspirin which is also found in Excedrin and BC powder should not be given because it may cause gastric irritation and possible bleeding problems in babies.

Ergotamine drugs such as Migranal and DHE 45 vasoconstriction and may restrict milk production.

Can breastfeeding cause headaches even in women no previous history of migraine?  Non-migrainous women along with women with a previous diagnosis of migraine may get headaches from breastfeeding due to the release of the hormone oxytocin.  This type of headache is called “lactation headache” and it may be treated in the same way as regular postpartum migraine. 

Lactation headache for some women will resolve after a few weeks, but for others it may continue until the child is weaned.  Lactation headache may also develop if the breasts become hard, swollen, and overfilled with milk.  Oxytocin secretion is associated with breast engorgement which may be relieved by frequent breastfeeding or pumping often.

Are there other causes of Postpartum Headache besides migraine?

A study in the American Journal of Obstetrics & Gynecology reviewed the outcomes of 95 women with postpartum headache.  The postpartum period in this group was defined as 24 hours from the time of delivery to 42 days after delivery.

This study found that about 50 percent of postpartum headaches were either migraines or tension-type headaches.  Twenty-four percent were caused by pre-eclampsia/eclampsia and 16 percent were post-spinal headaches after lumbar puncture for anaesthesia or mistakenly performed epidural punctures which resulted in through the dura lumbar puncture for anaesthesia.

 
Right sided throbbing migraine

Right sided throbbing migraine

 

Ten percent of the headaches related to more serious brain abnormalities such as cerebral hemorrhage or stroke.  These headaches were due to:

1.Subarachnoid hemorrhage—a serious, possibly life-threatening bleed into subarachnoid space which is along with the dura mater is one of the covers of the brain.  Subarachnoid hemorrhage is usually due to a ruptured cerebral aneurysm and is diagnosed by severe headache, a stiff neck, and blood in the brain noted by CAT scan and a bloody spinal tap.  Cerebral aneurysms are treated usually by neurosurgeons.

2.Meningitis.  The covering of the brain is called the meninges and a bacterial or viral infection can occur there causing headache, a stiff neck, and a lumbar puncture positive for bacteria or a virus.

3.Pituitary apoplexy is hemorrhage or lack of blood in the pituitary gland that occurs in the postpartum period causing severe headache, double vision, or visual field defects.  It is usually related to a tumor in the pituitary gland.

4.Arterial dissection means blood piercing through one of the layers of an artery going to the brain which usually blocks circulation to part of the brain and resulting in a stroke.

Good luck with this.

Britt Talley Daniel M.D.

www.doctormigraine.com