Galactagogues

=Galactagogues=

How they work
Galactagogues are medications that can induce or enhance breastmilk production; hence, they are often prescribed when a mother has an inadequate milk supply.

Dopamine is a physiologic inhibitor of prolactin release from the pituitary gland. Blocking dopamine receptors prevent inhibition of prolactin release and help increase the milk supply.



- In clinical practice, domperidone side effects in breastfeeding women have occurred rarely when compared to metoclopramide. Breastfeeding women taking metoclopramide may experience symptoms such as depression and drowsiness. For this reason, domperidone is a preferred galactagogue
 * Domperidone (Motilium®)** is a peripheral dopamine antagonist. It blocks dopamine receptors in the gastrointestinal tract and the brainstem. It does not enter the brain compartment as it does not cross the blood brain barrier. It is generally used for the treatment of nausea, vomiting or reflux. As it increases prolactin levels, it is accepted for use as a galactagogue to increase breast milk supply.

**Metoclopramide (Maxolon®, Pramin®)** is a central dopamine antagonist. It has an effect in the gastrointestinal tract and in the brain. It is generally used for the treatment of nausea, vomiting or reflux but may also be used as a galactagogue to increase breast milk supply, as it increases prolactin levels like domperidone.



**Herbal preparations** There are many purported natural galactagogues such as caffeine, hops, fenugreek, fennel seed, blessed thistle and alfalfa which have traditionally been used to increase breastmilk production, but none of these have reliable clinical evidence that they work for this purpose. At present, there is mainly anecdotal evidence that they are effective. A study found the high use of herbal galactogogues by women previously having breastfed (43.3%) was surprising. This use may be related to the fact that 20–40% of breast-feeding women have perceived lactation deficiency.

None of these herbs have been studied to determine how well they stimulate lactation; nor has their safety in lactation been shown the attention it deserves, although there is at least some preliminary evidence supporting the utility of these herbs.Nonetheless, as shown in the box, Botanical Galactagogue Formulas, these herbs are common ingredients in herbal formulas used by many lactating women.

Fenugreek is especially popular for this use. Although many swear by it for increasing milk production, there is no reliable research demonstrating this effect. The mechanism of action is unknown, but there have been suggestions that fenugreek may affect milk production because the breast is a modified sweat gland, and the herb is known to stimulate sweat production.

Beer has been recommended for decades as a galactagogue (agent to increase breast milk supply). It is thought that the B vitamins in beer are good for supply, others think that the alcohol content helps mothers relax and achieve more let-down reflexes. Studies have shown that babies consume less milk at a feeding where alcohol is present. Mother’s should use their discretion on this topic.

__Alcohol and breastfeeding__ Studies have shown that within thirty minutes of its ingestion, the equivalent of one standard drink changes the smell of breastmilk and has a mildly sedative effect on the baby. Excessive amounts may lead to drowsiness, deep sleep and weakness. A drowsy baby may not suck well which may lead to a reduction in supply. One recent report suggests a 23% reduction (156 ml to 120 ml) in breastmilk production following ingestion of beer. The altered smell of the milk may account for any fussiness. Any drug that causes drowsiness in the infant may be implicated in SIDS.

Alcohol may theoretically inhibit oxytocin release. Oxytocin is the hormone that causes contraction of the cells surrounding the alveoli and interlobular ducts, forcing milk out into the larger ducts for the baby to remove. Anecdotally, one drink relaxes the mother and improves the let-down reflex whereas large doses of alcohol are believed to have an adverse effect on the let-down or milk ejection reflex. Studies have shown that maternal doses of alcohol greater than 1-2 g/kg can interfere with the let-down reflex, though there is considerable variation between individual mothers.

Questions to Ask
__Domperidone__ - If used with dopamine agonists (bromocriptine, cabergoline, pergolide and pramipexole) domperidone may antagonise their effects; may rarely worsen symptoms of Parkinson’s disease; as it does not usually cross the blood-brain barrier use in preference to other dopamine antagonists in this situation. However, it has been used in conjunction with dopamine agonists for suppression of unwanted peripheral effects such as digestive disorders, nausea and vomiting, without affecting their central activity. - As domperidone in high concentrations may prolong the QT interval, the manufacturer contraindicates its use with erythromycin and other inhibitors of CYP3A4 that prolong the QT interval. - Ketoconazole inhibits the metabolism of domperidone, increasing its concentration; in high concentration domperidone may prolong the QT interval; combination contraindicated
 * Medications**

__Metoclopramide__ - Metoclopramide is a dopamine antagonist; administration with dopamine agonists (bromocriptine, cabergoline, pergolide and pramipexole) in Parkinson’s disease will reduce the therapeutic effect of the dopamine agonist; avoid these combinations by using an antiemetic which is not a dopamine antagonist (although domperidone may be a suitable alternative). - Absorption of some drugs may be altered due to increased gastric motility caused by metoclopramide.

__Fenugreek__ - There is some concern that fenugreek might have additive effects when used with anticoagulant or antiplatelet drugs, resulting in increased risk of bruising and bleeding. Some of the constituents in fenugreek have antiplatelet effects, although these might not be present in concentrations that are clinically significant. - Fenugreek may reduce blood glucose levels and might have additive effects on glucose levels when used with antidiabetes drugs. Monitor blood glucose levels closely.

__Domperidone__ - Reduce dose if using repeatedly in severe renal impairment (urinary excretion amounts to 33% of the oral dose) - Caution in hepatic impairment (extensively metabolised)
 * Medical Conditions**

__Metoclopramide__ - Postpartum mothers are at a relatively high risk for postpartum depression and metoclopramide can cause depression as a side effect. Therefore, metoclopramide should probably be avoided in women with a history of major depression and not used for prolonged periods in any mothers during this time of high susceptibility. Long-term uses of metoclopramide also increases the risk of tardive dyskinesia. Other reported side effects in nursing mothers include tiredness, nausea, headache, vertigo, intestinal gas, hair loss and anxiety - Reduce dose in moderate and severe renal impairment; EPSE are common. - Contraindicated in phaeochromocytoma (neuroendocrine tumour of the medulla of the adrenal glands), probably due to the release of catecholamines from the tumour. Such hypertensive crises may be controlled by phentolamine.

__Fenugreek__ Research on the use of fenugreek by non-insulin diabetic patients has shown a small reduction in fasting and post-prandial blood sugar levels, but a more statistically significant decrease in total cholesterol and triglyceride levels of patients with coronary artery disease __Fenugreek__ - An article in the Annals of Allergy, Asthma and Immunology reported two cases of immediate allergy following ingestion, inhalation, and external application of fenugreek seed powder. In the first case, inhalation of the fenugreek seed powder resulted in rhinorrhea, wheezing, and fainting. The second case was of a patient with chronic asthma who developed numbness of head, facial angioedema, and wheezing after application of fenugreek paste to her scalp as a treatment for dandruff. Skin scratch test was performed with fenugreek and other members of the Leguminosae family as fenugreek also belongs to Leguminosae. - Allergic reactions may be due to allergenic chemicals occurring naturally within the plant, or to the presence of substances such as nitrates from the soil in which the plant is grown, as has occurred in certain areas of Jordan. - Exercise caution if you have allergies to peanut, chickpea or other legumes
 * Allergies**

__Domperidone__ Safe to use; ADEC category B2.
 * Pregnancy**

__Metoclopramide__ Safe to use; ADEC category A.

__Fenugreek__ Fenugreek should not be used during pregnancy because it can stimulate the uterus. Consumption of fenugreek by pregnant women just before delivery may cause the neonate to have an unusual body odor, which may be confused with maple syrup disease. It does not appear to cause long-term sequelae.

__Domperidone__ The milk:serum ratio of Domperidone has been reported to be 0.4. This relatively low value is likely related to domperidone’s high protein binding (greater than 90%) and to its relatively high molecular weight. The amount of domperidone that would be ingested by the infant would be extremely small (less than 0.2 μ g/kg daily, assuming a daily milk intake of 150 mL/kg and a milk domperidone concentration of 1.2 ng/mL found in this study). This amount is much lower than the level of metoclopramide (approximately 125 ng/mL) that has been measured in the breast milk of nursing mothers treated with this drug.
 * Breastfeeding**

Clinical trials of domperidone have been conducted on breastfeeding women to establish its role as a galactagogue. Very small concentrations of domperidone were found in breastmilk samples and side effects in infants and children have not been reported. The amount ingested by the infant through the breastmilk would be extremely low (less than .2micrograms/kg/day) as compared to doses used to treat infants and children. Numerous studies that have been conducted found that the amount of domperidone in the breastmilk represents an infant dose of 0.01-0.08% of the maternal adjusted dose.

In clinical practice, domperidone side effects in breastfeeding women have occurred rarely when compared to metoclopramide (Maxolon®), another galactagogue. Breastfeeding women taking metoclopramide may experience symptoms such as depression and drowsiness. For this reason, domperidone is a preferred galactagogue. __Metoclopramide__ - Metoclopramide is excreted in variable amounts in breastmilk. Most infants would receive less than 10% of the maternal weight-adjusted dosage, but some receive doses that achieve pharmacologically active serum levels, elevated serum prolactin and possible gastrointestinal side effects. Although most studies have found no adverse effects in breastfed infants during maternal metoclopramide use, many did not adequately observe for side effects. - Available clinical trials have not reported side effects in infants who are breastfed by women taking metoclopramide. However, due to metoclopramide's potential side effects on breastfeeding women, it is generally not recommended for use as a galactagogue. See domperidone if a galactagogue is required.

__Fenugreek__ - The safety of fenugreek after pregnancy and during breast-feeding is not known (although fenugreek is used to promote lactation), however, there are no known reports of adverse events in the nursing baby - Studies have shown fenugreek to have potential as an anxiolytic and antidepressant. Given that anxiety is often part of the problem in insufficient milk production, these aspects of the plant may have a role in its use as a galactagogue as well

How to take
- Current dosage at the WCH is one tablet three times a day for 5 days, then one tablet twice a day for 3 days, then one tablet once a day for 4 days - It is not necessary to take the medication prior to meals (as it is not being taken for its anti-nausea effect). - Discontinuing domperidone slowly appears to cause no reduction in milk production.
 * Domperidone**

- Currently not recommended by BESS (Breastfeeding Education & Support Services), RWH (Royal Women's Hospital) - The dose is one tablet three to four times a day. Commence with one tablet twice a day and increase to one tablet three to four times a day as required. Once breastmilk is supply is adequate, reduce dose slowly. - AMH: 10 mg 3 times daily, taper dose over 7–10 days before stopping
 * Metoclopramide**

- The usual dose is two to three capsules three times a day, and can be discontinued once adequate milk production is attained - Another study lists the recommended dose of fenugreek as a single herb to promote milk production as a 1200-mg capsule 2–3 times daily.
 * Fenugreek**

Side effects
Uncommon - dry mouth, headache, urticarial rash. Rare - loss of balance, palpitations, swelling of feet.
 * Domperidone**

Common: restlessness, dizziness, drowsiness, headache. Uncommon: extrapyramidal adverse effects, hypertension, hypotension, diarrhoea, constipation, depression Rare: agranulocytosis, supraventricular tachycardia, hyperaldosteronism, neuroleptic malignant syndrome, tardive dyskinesia.
 * Metoclopramide**

- Orally, fenugreek can cause diarrhoea, dyspepsia, abdominal distention, and flatulence - Lactating women who take fenugreek in quantities required to increase their milk supply often notice that their sweat and urine exudes a maple syrup odour
 * Fenugreek**

Other advice?
__Domperidone__ //Domperidone has been shown to significantly increase milk production without evidence of adverse effects in the infant:// - has been shown to raise the serum prolactin level in non-lactating women from 8.1 to 110.9 ng/ml after one 20 mg dose - in a double-blind placebo controlled trial, 32 mothers of full term infants experiencing failure of lactogenesis were randomized to receive either domperidone (10 mg TID) or placebo. Prolactin levels were reported as significantly higher after the 2 nd day of treatment in the domperidone group (p < 0.01). The mean daily milk yield was also increased significantly in the domperidone group (P < 0.01), with a corresponding higher infant weight gain. - in a small double blind, randomized controlled trial (n = 16), a 7 day course of domperidone (10 mg TID) given to mothers of preterm infants experiencing insufficient milk production resulted in a significantly increased milk supply (P < 0.05), low levels of drug detected in breast milk (< 0.2 mcg/kg/d) and significantly higher maternal prolactin level when compared to the placebo group. No infant or maternal side effects were reported in the above trials.
 * Galactagogues and increased breast milk production**

- During oral administration of 30 mg daily for two weeks the plasma prolactin level measured 90 minutes after drug intake remained fairly constant at 25 ng/mL in males (normal value was 5 ng/mL) whilst in females the level of 117 ng/mL after the first dose decreased to 56 ng/mL after 14 doses (pretreatment normal value was 9 ng/mL).

__Metoclopramide__ - A study of 20 primiparous mothers whose infant were not gaining weight adequately compared metoclopramide (n = 10) to placebo (n = 10) for increasing milk supply. All mothers passed a brief training course on improving breastfeeding technique and the benefits of breastfeeding before entering the study. All infants gained weight over the next 2 weeks. The increase in weight in the metoclopramide group was not different from the placebo group

CMI
[|AMH - Domperidone] [|AMH - Metoclopramide] [|Resources for Clinicians - Galactagogues] [|Pharmacoepidemiology and Drug Safety - Use of herbal drugs in pregnancy] [|RCHM - Medications and herbal preparations to increase breastmilk production] [|Natural Medicines Database - Natural Medicines Used for Lactation-Related Conditions] [|Lactmed - Domperidone] [|Lactmed - Metoclopramide] [|Breastfeeding.org - Fenugreek and low milk production] [|Annals of Allergy, Asthma and Immunology - Allergy to Fenugreek] [|Alternative and Complementary Therapies - Botanical Galactagogues]