Home » 2022 » July

Monthly Archives: July 2022

Ulipristal Acetate (EllaOne) as an emergency hormonal contraceptive and Breastfeeding

Ulipristal is used as an emergency contraceptive for up to 120 hours (5 days) after intercourse. It is a single tablet.

The manufacturer (patient information leaflet and SPC)  recommends that breastfeeding should be avoided for 1 week after administration as it is present in milk.

This does not seem to be justified by pharmacokinetic data which supports the recommendations by expert sources that breastfeeding can continue as normal.

Pharmacokinetics

It is highly plasma protein bound (98-99.5%)

Relative Dose     0.8 – 1    % (significantly below 10% regarded as compatible with breastfeeding)

The manufacturer reports that after this medication was given to 12 breastfeeding women for emergency contraception mean levels in milk were measured as shown

 ulipristal level in breastmilk
24 hours22.7 ng/mL
24-48 hours2.6ng/ml
48-72 hours1.56 ng/mL
72-96 hours1.04 ng/mL
96-120 hours0.69 ng/mL

The manufacturer did not report any neonatal outcomes as the infants in this report were not breastfed.

Recommendations on compatibility of breastfeeding

  • No information is available on the clinical use of ulipristal during breastfeeding; however, amounts in milk are low. If ulipristal is required by the mother, it is not a reason to discontinue breastfeeding. Some older sources recommend withholding breastfeeding for 24 hours after a dose,[ Curtis KM, Jatlaoui TC, Tepper NK, et al. U.S. selected practice recommendations for contraceptive use, 2016. MMWR Recomm Rep. 2016;65:1–66]but this is no longer a requirement according to current FDA-approved labeling. https://www.ncbi.nlm.nih.gov/books/NBK500655/
  • Intestinal absorption by the infant of the low dose excreted in breastmilk would be hindered, since oral bioavailability decreases up to 45% if administered with fat-rich foods, such as breastmilk.

Given the minimal excretion of the product in breastmilk and the absence of adverse effects recorded during breastfeeding, it is difficult to justify the recommendation proposed by other authors or health agencies such as CDC to interrupt breastfeeding for 24 hours (Curtis 2016 CDC) or 36 hours (Mansour 2009).

https://www.e-lactancia.org/breastfeeding/ulipristal-acetate-contraceptive/product/
  • A single dose of 30mg ulipristal acetate is licensed to be taken within 120 hours (5 days) after unprotected intercourse or contraceptive failure. Ulipristal is not the preferred emergency contraceptive during breastfeeding, however, based on pharmacokinetic data, UKDILAS do not consider it necessary to withhold breastfeeding if a single dose has been taken. https://www.sps.nhs.uk/articles/emergency-contraception-and-breast-feeding/

Patient advice

  • if vomiting occurs within 3 hours of taking a dose, a replacement dose should be taken;
  • the next period may be early or late;
  • seek medical attention promptly if any lower abdominal pain occurs because this could signify an ectopic pregnancy.
  • Take a pregnancy test if the next menstrual period is delayed by more than 7 days, is lighter than usual, or is associated with abdominal pain which is not normal for a period pain

Further sources of information

Topirimate in pregnancy and breastfeeding

In July 2022 MHRA issued new guidance on the use of topirimate in women of childbearing age both in the treatment of epilepsy and prevention of migraine

https://www.gov.uk/drug-safety-update/topiramate-topamax-start-of-safety-review-triggered-by-a-study-reporting-an-increased-risk-of-neurodevelopmental-disabilities-in-children-with-prenatal-exposure#:~:text=Topiramate%20and%20current%20pregnancy%20prevention%20requirements,-Before%20the%20initiation&text=For%20migraine%20prophylaxis%2C%20topiramate%20is,a%20patient%20who%20is%20pregnant.

The new safety review was triggered by a large observational study ( Bjørk M et al 2022) reporting that prenatal exposure to topiramate is associated with an increased risk of autism spectrum disorders, intellectual disability, and neurodevelopmental disorders (https://jamanetwork.com/journals/jamaneurology/fullarticle/2793003

Use of Topiramate

  • to prevent migraine headaches in adults after consideration of possible alternative treatment options
  • alone to treat seizures in adults and children aged older than 6 years
  • with other medicines to treat seizures in adults and children aged 2 years and older

Advice if a pregnancy is planned

If you are taking topiramate for epilepsy and are planning a pregnancy, urgently talk to your doctor for a specialist review – there are other epilepsy medicines that are not associated with an increased risk of birth defects in pregnancy

If you are taking topiramate for migraine and planning a pregnancy, talk to your prescriber about alternative treatments that can be used in pregnancy as soon as possible

NB topiramate can reduce the effectiveness of hormonal contraception in preventing unplanned pregnancy – talk to a healthcare professional about the best contraception for you while you are taking topiramate

MHRA review 2021

Following a comprehensive national review by the Commission on Human Medicines into the safety of antiepileptic drugs in pregnancy, including topiramate, in January 2021 a new safety advice in Drug Safety Update with patient advice, and a Public Assessment Report were published.

The review showed topiramate exposure in-utero to be associated with an increased risk of congenital malformations (approximately 4 or 5 cases per 100 babies, compared with 2 or 3 in the general population). Topiramate was also shown to be associated with an increased risk of the baby being born of low birth weight and small for gestational age (fetal growth restriction).

At the time of the 2021 review, some data had raised concerns that topiramate use during pregnancy may be associated with an increased risk of autism spectrum disorder and poorer developmental outcomes. However, the numbers in the available studies were limited and further data were needed to reach firm conclusions.

Details on the findings of the Bjørk study

The study by Bjørk and colleagues is a large, well-conducted study using established data sources from 5 Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden). It reports that children whose mothers use topiramate or valproate during pregnancy are at an increased risk of autism spectrum disorder, intellectual disability, and a composite outcome of any neurodevelopmental disorder. These risks are known for valproate (see section on valproate below).

Data from around 4.5 million mother-child pairs were examined and this included 24,825 children (0.6%) who were prenatally exposed to antiepileptic drugs. Of these, 16,170 were born to mothers who had epilepsy. These data were analysed to estimate the risk of autism spectrum disorder and intellectual disability after exposure to the 10 most frequently used antiepileptic drugs when used as monotherapy (one medicine) and the 5 most frequently used antiepileptic drugs when used as duotherapy (two medicines at the same time).

In unexposed children of mothers with epilepsy, the 8-year cumulative incidence of autism spectrum disorder and intellectual disability were 1.5% and 0.8% respectively compared with 4.3% and 3.1% in children of mothers with epilepsy exposed to topiramate. The adjusted hazard ratios for autism spectrum disorder and intellectual disability were 2.8 (95% CI 1.4 to 5.7) and 3.5 (95% CI 1.4 to 8.6).

A range of sensitivity analyses were conducted that broadly showed consistent and statistically significant effect estimates of a greater than 2-fold increase in risk of neurodevelopmental disorders across most of the analyses. The data also showed a dose-dependent effect for topiramate.

Topiramate and current pregnancy prevention requirements

  • Before the initiation of topiramate in a woman of childbearing potential, pregnancy testing should be performed, and the patient should be fully informed of the risks if used during pregnancy.
  • For epilepsy, alternative therapeutic options should be considered for women of childbearing potential. If topiramate is used, a highly effective contraception is strongly recommended, and the discussion with the patient should include information on both the risks associated with taking topiramate and of uncontrolled epilepsy during pregnancy.
  • For migraine prophylaxis, topiramate is contraindicated in pregnancy and in women of childbearing potential if not using a highly effective method of contraception. As such, topiramate should not be prescribed for migraine prevention in a patient who is pregnant

Topirimate and Breastfeeding

  • Maternal doses of topiramate up to 200 mg daily produce relatively low levels in infant serum. Sedation and diarrhoea have been reported occasionally in breastfed infants, but most infants tolerate the drug in milk well. In a few infants, no long-term adverse effects on growth and development have been seen. Monitor the infant for diarrhoea, drowsiness, irritability, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of anticonvulsant or psychotropic drugs. (https://www.ncbi.nlm.nih.gov/books/NBK501259/
  • Öhman et al 2002. observed five babies at delivery and followed three of them through lactation. Two to three weeks after delivery two of the breastfed infants had detectable but unquantifiable levels of topiramate and one had an undetectable concentration; m/p ratios of around 0.86 were determined throughout the study period and no adverse events noted. Observe for sedation, poor feeding and diarrhoea. https://breastfeeding-and-medication.co.uk/fact-sheet/anti-epilepsy-medication-and-breastfeeding
  • Topirimate is moderately excreted into breast milk with the infant receiving just over 10% of the maternal weight-adjusted dose. Neither clinical nor psychomotor developmental effects have been observed in infants whose mothers were treated. Only a possibly related case of gastroenteritis that resolved after discontinuation of mother’s medication. Plasma levels of infants whose mothers were treated with topiramate have shown to be undetectable or pretty below (<1 mg / L) the recommended therapeutic level (5-20 mg / L). Check up the occurrence of diarrhoea, irritability and lethargy in infants ( https://www.e-lactancia.org/breastfeeding/topiramate/product/)

Adequate precautions against pregnancy must be used even when breastfeeding exclusively.

Technetium 99 studies and Breastfeeding

Earlier this year I had the pleasure of working with Rachel Bidder and others at Swansea Bay University Health Board on compiling information on Having a Tc‑99m Diagnostic Study whilst breastfeeding. Subsequently the information was shared in a presentation to the BNMS conference. In addition, the local team amended their information on MRI and CT to be more breastfeeding friendly.

The information from the Swansea team is reproduced here with their permission. If you have questions regarding expressing and storing, please contact your local breastfeeding team. My thanks to Rachel for allowing me to share this

https://breastfeeding-and-medication.co.uk/wp-content/uploads/2022/07/technetium-scans-and-breastfeeding.pdf

Buscopan (Hyoscine) and Breastfeeding

Buscopan is compatible with breastfeeding

Hyoscine which is most frequent referred to by mothers under the trade name of Buscopan ™. It is used to resolve smooth muscle spasm often in irritable bowel syndrome. It can also help bladder 0cramps and period pain.

The BNF states that the amount in breastmilk is too small to be harmful.

It’s unusual to have any side effects, but some people get a dry mouth, constipation and blurred vision.

See also factsheet on irritable bowel syndrome and breastfeeding https://breastfeeding-and-medication.co.uk/fact-sheet/irritable-bowel-syndrome-ibs-and-breastfeeding

Pharmacokinetics

Plasma protein binding 50%, oral bio-availability 81%, licensed in children.

Further information

https://www.nhs.uk/medicines/buscopan-hyoscine-butylbromide/

Rescue Remedy and Breastfeeding

Many people like to take Rescue Remedy when they are anxious or more frequently, I have found, when taking a driving test or exam. There are no research studies that I am aware of. However, the Rescue Remedy site is quite reassuring.

“The Rescue Remedy® formula contains a carefully selected blend of five flower remedies and is prepared according to natural and traditional methods at the Bach Centre in Oxfordshire. While Rescue Remedy® should be safe to take even while pregnant or breastfeeding  you should always talk to your doctor before taking any Rescue® product, especially if you are currently taking any medication.”

https://www.rescueremedy.com/en-us/explore/faqs/can-i-take-rescue-while-pregnant-or-breastfeeding/

https://www.rescueremedy.com/en-us/explore/faqs/can-i-take-rescue-while-pregnant-or-breastfeeding/

Omeprazole and Breastfeeding

Omeprazole is compatible with breastfeeding

Omeprazole (Losec™) is a proton pump inhibitor used to block acid secretion for a variety of reasons including:

  • Reflux
  • Oesaphagitis
  • To protect the stomach against drugs like ibuprofen or prednisolone

The capsules contain gastro-resistant granules, the tablets are also gastro-resistant so that very little of the drug can pass into breastmilk. We also give omeprazole solution to babies with symptoms of reflux. Omeprazole is extremely acid labile with a half-life of 10 minutes at pH values below 4.[ Pilbrant A, Cederberg C. Development of an oral formulation of omeprazole. Scand J Gastroenterol Suppl 1985; 108:113-120.]

Virtually all omeprazole ingested via milk would probably be destroyed in the stomach of the infant prior to absorption.

Relative infant dose 1.1%, Plasma protein bound 95%, oral bioavailability 30-40% (Hale Medications and Mother’s Milk)

Narcolepsy and Breastfeeding

This is a topic on which I confess I had no knowledge. I havent had many queries over the years but most were focussed on asking about modenafil. So a question this week prompted me to do some more research and add it into a factsheet. Hope it helps

wendy@breastfeeding-and-breastfeeding.co.uk

Factsheet narcolepsy and breastfeeding

https://breastfeeding-and-medication.co.uk/wp-content/uploads/2022/07/narcolepsy.pdf

https://breastfeeding-and-medication.co.uk/wp-content/uploads/2022/07/narcolepsy.pdf