Drugs and devices forincreasing milk supply

I What's the evidence?

Where there is lowsupply .

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Iconditions to consider:

• Anaemia (Hx and FBP) -hypopituitarism

• Hypothyroidism (TSH)

• Retained placenta (HCG)

• pcas (androgens, glucose metabolism TSH, prolactin,etc)

• Gestational ovarian theca cysts (testosterone)

• Delayed lactogenesis II: SSRls" stress, birthinterventions

• Frequent removal of milk

• Facilitating the normal hormonal milieu

• Always advise normal physiologicalstrategies BEFORE interventions

I:'.: FlaUM 4-7 Hormonelevelsduringp~(."y:and

, Lewton. Adapted from 1.l:M:'., S: In-. Susan Lout-'s B~t i

Bf~ AdtHson·Wesley, Boston, 1990. p. 34. .~

Mechanisms of action - usuallyrelated to prolactin secretion

Complex, may be achieved by:

• Direct stimulation of prolactin production

• Stimulation of prolactin releasing hormone (TSH egosulpride)

• Suppression of prolactin inhibitory factor (dopamine)

- Inhibiting dompamine-producing neurons

- Blocking hypothamic dopaminergic receptors (eg maxalon)

- Blocking peripheral dopamine receptors (eg motilium)

~utical galactagogues(I I

• Antiemetics (dopamine antagonists)- domperidone (Motilium)- metoclopramide (Maxalon)

• Neuroleptics- chlorpromazine- sulpride

• Hormones- Oxytocin- Growth hormone (GH, somatotrophin)- Thyrotrophin releasing hormone (TRH)

Herbal andnatural preparations

• Fenugreek

• Silmarin (Milk Thistle, Bio-C)

• Galega (Goat's rue)

• alfalfa, mulanggay, blessed thistle, shatarvi,anise, basil, fennel, mauve, verbena, grapeand coffee

~ Lactation ~iSkCategories

• L5: contraindicated• L4: possibly hazardous• L3: moderately safe• L2: safer• L1: safest

Drug queries see Dr Tom Hale's website:http://neonatal.ttuhsc.edu/lactlindex.htmlor

10 KEMH Obstetric Drug Information Service 9340 2723

I ~harmaCeUtiCalS

IMetoclopromide, LRC:L2

• Antagonizes the release of dopamine in the CNS

• Commonly used for GORD in infants

• Dose 10 mg tds (up to 45mg/day) for 10 -14 daysand taper off over 5-7 days

• Side effects: restlessness, anxiety, drowsiness andfatigue: (10%) diarrhoea, headache, insomnia andcaution with extrapyramidal effects (1%)

• Contraindications: epilepsy, depression11 hypertension intestinal bleeding, pheochromocytoma

I Pharmaceuticals I

IDomperidone (LRC: L1)

• Approved for use in 80 countries but not the USA

• Dose 10-20 mg tds to qid

• Side effects very rare, oral dryness, abdominal cramping & headache

121'

I• Pre-term mothers with low supply <300ml/day (n=7,

mean of 53 days post partum)

• Double blind, 3 phase randomised crossover trial, no ITT(n=6)

• Volume increased 215% (30mg) to 367% (60mg) in theresponders

LrWan et aI., 2008. DOS~ effect study of domperidone as agalactagogue in preterm mothers with insufficient milk suppl

1 and its transfer into milk. British Journal of Pharmacology

$1) r G 2.50 )'PrOlaCtin before and 45 mlns after expressing

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Mean pre-pumping prolactin levels higher at both doses (p<.007) but thete was no difference at

45 mins between non-responders (n=2 -+1) and responders (n=4)

Not powered to detect a statistical dtfference

Domperidone studies Ida Silva et aI., 2001)

I• Pre-term infants N=20, 32-33days pp, low supply

despite extensive LC assistance.

• Increase in milk production of 44.5% (motilium) vs16.6% (control)

• Prolactin was similar at baseline in both with asignificant increase in the motilium group:119.3 ug/Lvs 18.1ug/L (p<.008) returning to baseline 3 daysafter the last dose

Randomised, double blinded, drug (11); placebo (9)

Similar baseline prolactins, although not consistent sampling.

When were prolactin levels taken?

36% drop out in intervention group (n=4), no intention to treat

No follow up after 7 days

Such a huge difference in outcome is concerning in a smallsample (?more severe problems were randomised to placebogroup?)

• FDA banned the compounding of domperidone citing significant sideeffects where pts were receiving high doses of IV domperidone duringcancer therapy (1985 studies)

• 2004 FDA issues a warning on its use, despite the AAPrecommendatio"n that it is "usually compatible with breastfeeding~

• However: Domperidone is only 13-17% bioavailable orally due tosignificantfirst-pass hepatic and intestinal metabolism .

• Domperidone has been used in more than 33 countries world-wide formore than 30 years including England, Australia, Canada and isavailable over-the-counter in many countries

• Never the first line of choice due to eNSeffects and possible risk for extra pyramidalside effects

• See Zuppa, A. A. , et al. 2010. Safety and efficacy ofgalactogogues: substances that induce, maintain and increasebreast m ilk production J Pharm Pharmaceu! Sci 13(2): 162-174,

I I ~ - IlnoeW..,w. ~, niSt ~:;:j Trust

l( ; :;im~! " Altruism{.~ Sexual~~~ " OnDER attractiveness~ NOW ;

I Oxytocin ~ .l'l;1\J'u.r~lJYli Communication

( I

• Stimulates the MER

• Dose - 1 spray (3 drops)/nostril (40U/ml solt'n)before expression or feeding

· Fewtrell et al., Randomised double trial of of oxytocin nasal spray inmothers expressing breastmilk for pre-term infants Arch Dis ChildFetal Neonatal Ed, 2006· MacDonald et aI., A review of safety, side-effects and subjectivereactions to intranasal oxytocin in human researchPsychoneuroendocn'nofogy, 2011

· Does not significantly improve outcomes in lactation, nor producedetectable subjective changes in recipients

19

• An herb is a plant or plant part used for its scent,flavour or therapeutic properties.

• sold as tablets, capsules, powders, teas, ex1racts andfresh or dried plants.

• However, some cause healthproblems, some are noteffective and some mayinteract with other drugs

l1Herbs and

lNatural Remedies

( r

• Small amount of human studies are of poormethodological quality

• 20% pregnant women believed that herbs andvitamins were safer than prescription medicines orbetter at treating medical problems

• 30% did not disclose use to their doctor

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~ Herbs and Natural Remedies

While there is some regulation of herbs,quality/potency varies:• Standardized vs non-standardized products• Part of plant used or % of parts in mix used

(Different parts can have different effects)• Freshness of the herb• Shelf life• Exposure to light• Interactions and potentiating

effects

est reference aidSafety Ratings

A- no safety issues identified; generallyconsidered safe when used appropriately

B- May not be appropriate for self-use bysome individuals, or may cause side-effects if misused. Seek reliable safetyand dose info.

C- Moderate potential for toxicITy, mainlydose related

0- Use only with supervision ofknOWledgeable physician

E-Avoid. Toxic plant with no justifiablemedical use.

lIi Fenugreek

\. II • From the pea family

• Used to flavour curries, Chutneys, artificialmaple syrup

• Used to alleviate coughs, bronchitis, sorethroat and dysmenorrhoea

• Mechanism of action ?R!T stimulates sweatproduction, ?growth hormone

24 • GRAS

• A standard dose has not been defined

• *1 - 4 caps (580-61 Omg) tds to qid, or

• *One cup of strained tea tds (1/4 tsp seedssteeped in 8 oz water for 10 mins)

• Transfer of fenugreek into milk is unknown

• Hale Risk = L3, herbal safety rating = B

• Maple syrup smell to urine and sweat

• Possible side effects: diarrhea (mother or baby),stomach upset, hypoglycemia, allergy. Could worsenasthma.

• Care in diabetics? Potentiates the actionshypoglycaemics

• Contraindicated in pregnancy

Evidence for the use offenugreek

• Reeder et al. (ILeA 2010 conference poster)

• N=26, preterm mothers <31weeks,randomised double blind, fenugreek for 21days from Day 5, pumping 8-10 times/day

• Prolactin levels measured every 5 - 7 days

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Reeder, C. The effect ofFenugreek on milkproduction & prolactinlevels in mothers of pre-term infants

No statistical difference in milkvolume, prolactin, perceivedstress, sleep, energy, calmness,expressing or kangaroo carebetween Fenugreek and placebogroups

Turkyilmaz et aI., 2011. The Effect of Galactagogue Herbal Teaon Breast Milk Production and Short-Term Catch-Up of BirthWeight in the First Week of Life

66 exclusively BF healthy mothers of healthy termneonates randomised into 3 groups

• Group 1 - 3 cups of herbal tea/day containingfenugreek; Group 2 - a placebo; Group - nointervention

• Group 1 had lower maximum wi loss, regained theirBW quicker and had higher mean expressedbreastmilk volume expressed on Day 3

Turkyilmaz et aI., 2011. The Effect of Galactagogue Herbal Teaon Breast Milk Production and Short·Term Catch·Up of BirthWeight in the First Week of Life

BreM! l:l:!k \"Chmll! (mU~uimlr.".\\.bf;hl.IMS j":\, rllf.to_~••••~gM}Tla.('.to~:nb'_"thl\~:(di;yl.......................... -.- ... --.------------- .... _ ....

·Similar education received by the same LC for both groups·No significant difference in demographics between groups·A Choice of 2 different herbal teas recommended by a paediatricanforthe intervention group and an apple tea for the placebo group·Blinding details unclear·Breastmilk was expressed (consecutively) for 15 mins on the 3rd day

30 using the same pump

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lFor moreI

• Commonly used herbal galactagogues by Lisa Marasco

http://www.ilca.org/files/resources/HealthCareP rov iders/Ga lactogogue%20Dosage%20& %20Reference%20T able%20V2. pdf

• ABM Protocol 9 (revised Jan 2011 )

http://www.bfmed.org/Resources/Protocols.aspx

• Gabay, MP. 2002. Galactagogues that induce lactation. J HumLact. 18, 274-9

• Zuppa, A. A. , et al. 2010. Safety and efficacy of galactogogues:substances that induce, maintain and increase breast milkproduction J Pharm Pharmaceut Sct 13(2): 162-174,

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