Bremelanotide for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women

[FDA News Release, June 21, 2019] – The U.S. Food and Drug Administration today approved Vyleesi (bremelanotide) to treat acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women.

“There are women who, for no known reason, have reduced sexual desire that causes marked distress, and who can benefit from safe and effective pharmacologic treatment. Today’s approval provides women with another treatment option for this condition,” said Hylton V. Joffe, M.D., M.M.Sc., director of the Center for Drug Evaluation and Research’s Division of Bone, Reproductive and Urologic Products. “As part of the FDA’s commitment to protect and advance the health of women, we’ll continue to support the development of safe and effective treatments for female sexual dysfunction.”

HSDD is characterized by low sexual desire that causes marked distress or interpersonal difficulty and is not due to a co-existing medical or psychiatric condition, problems within the relationship or the effects of a medication or other drug substance. Acquired HSDD develops in a patient who previously experienced no problems with sexual desire. Generalized HSDD refers to HSDD that occurs regardless of the type of sexual activity, situation or partner.

Vyleesi activates melanocortin receptors, but the mechanism by which it improves sexual desire and related distress is unknown. Patients inject Vyleesi under the skin of the abdomen or thigh at least 45 minutes before anticipated sexual activity and may decide the optimal time to use Vyleesi based on how they experience the duration of benefit and any side effects, such as nausea. Patients should not use more than one dose within 24 hours or more than eight doses per month. Patients should discontinue treatment after eight weeks if they do not report an improvement in sexual desire and associated distress.

The most common side effects of Vyleesi are nausea and vomiting, flushing, injection site reactions and headache. About 40% of patients in the clinical trials experienced nausea, most commonly with the first Vyleesi injection, and 13% needed medications for the treatment of nausea. About 1% of patients treated with Vyleesi in the clinical trials reported darkening of the gums and parts of the skin, including the face and breasts, which did not go away in about half the patients after stopping treatment. Patients with dark skin were more likely to develop this side effect.

In the clinical trials, Vyleesi increased blood pressure after dosing, which usually resolved within 12 hours. Because of this effect, Vyleesi should not be used in patients with high blood pressure that is uncontrolled or in those with known cardiovascular disease. Vyleesi is also not recommended in patients at high risk for cardiovascular disease.

When naltrexone is taken by mouth, Vyleesi may significantly decrease the levels of naltrexone in the blood. Patients who take a naltrexone-containing medication by mouth to treat alcohol or opioid dependence should not use Vyleesi because it could lead to naltrexone treatment failure.

Research and writing made possible thanks to the generous sponsorship from Pemason Pharmaceutical Limited – owned by Pharmacists and operated by a team of Pharmacists with a commitment to quality pharmaceuticals & drug information

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Source: FDA News Release, June 21, 2019

Co-amoxiclav (Augmentin) is classified as FDA Pregnancy Risk Category B i.e., animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women. Augmentin package insert published in DailyMed states it should be used during pregnancy only if clearly needed.

The association between early maternal exposure to amoxicillin and oral clefts remains controversial. One study finds that amoxicillin use in early pregnancy may be associated with an increased risk of oral clefts. The same study did not find associations between first-trimester exposure to amoxicillin and the risk of most other major birth defects, such as cardiovascular system, central nervous system, gastrointestinal system, urinary system defects and musculoskeletal system defects.

A rational pharmacotherapy approach will be:

INDICATION: Does the mother have a condition for which co-amoxiclav is clearly indicated?

EFFICACY: Is co-amoxiclav shown to be effective for the diagnosed condition? What is the place of co-amoxiclav for the treatment of the condition?

SAFETY: What are the common side effects of co-amoxiclav? Are there safer alternatives for the management of the condition? For instance, amoxicillin vs co-amoxiclav?

COMPLIANCE: Is the mother able to take the prescribed course i.e., cost & convenience?

Research and writing made possible thanks to the generous sponsorship from Pemason Pharmaceutical Limited – owned by Pharmacists and operated by a team of Pharmacists with a commitment to quality pharmaceuticals & drug information

To sponsor EMDEX Topic(s) i.e., Medication Management of Diseases, Therapeutic Notes or Development of Drug Monographs, please contact Editor@EmdexOnline.com

Footnote (Medscape.com):

We all know to be cautious when prescribing antibiotics to women who are pregnant. A new CDC analysis looked at a commercial insurance database to assess this further.

Among almost 35,000 pregnant women treated for urinary tract infections (UTIs) in their first trimester, nearly 35% received nitrofurantoin and about 8% received trimethoprim-sulfamethoxazole (TMP/SMX).

This is despite recommendations that these antibiotics should be avoided during the first trimester unless there are no alternatives. Options thought to be safe during pregnancy are amoxicillin-clavulanate, cephalosporins, and Fosfomycin…

Further Footnote from MotherToBaby.com:

See the Q&As from Amoxicillin/Clavulanate factsheet here: https://mothertobaby.org/fact-sheets/amoxicillin-clavulanate/

References:

1. DailyMed – AUGMENTIN – amoxicillin and clavulante potassium tablet, film coated AUGMENTIN – amoxicillin and clavulante potassium tablet [Internet]. [cited 2019 Jun 20]. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d567412a-e5ed-4c7f-90f0-ea3039786480
2. Lin KJ, Mitchell AA, Yau W-P, Louik C, Hernández-Díaz S. Maternal Exposure to Amoxicillin and the Risk of Oral Clefts. Epidemiol Camb Mass. 2012 Sep;23(5):699–705.
3. Avoid These Antibiotics in the First Trimester of Pregnancy [Internet]. Medscape. [cited 2019 Jun 20]. Available from: http://www.medscape.com/viewarticle/891799

Liraglutide (Victoza) shown to improve blood sugar control in pediatric patients with type 2 diabetes

[June 17, 2019] – The U.S. Food and Drug Administration today approved Victoza (liraglutide) injection for the treatment of pediatric patients 10 years or older with type 2 diabetes. Victoza is the first non-insulin drug approved to treat type 2 diabetes in pediatric patients since metformin was approved for pediatric use in 2000. Victoza has been approved to treat adult patients with type 2 diabetes since 2010.

“Victoza has now been shown to improve blood sugar control in pediatric patients with type 2 diabetes. The expanded indication provides an additional treatment option at a time when an increasing number of children are being diagnosed with this disease,” said Lisa Yanoff, M.D, acting director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research.

Type 2 diabetes is the most common form of diabetes, occurring when the pancreas cannot make enough insulin to keep blood sugar at normal levels. Although type 2 diabetes primarily occurs in patients over the age of 45, the prevalence rate among younger patients has been rising dramatically over the past couple of decades. In the U.S., more than 5,000 new cases of type 2 diabetes are diagnosed each year among youths younger than age 20.

Victoza improves blood sugar levels by creating the same effects in the body as the glucagon-like peptide (GLP-1) receptor protein in the pancreas. GLP-1 is often found in insufficient levels in type 2 diabetes patients. Like GLP-1, Victoza slows digestion, prevents the liver from making too much glucose (a simple sugar), and helps the pancreas produce more insulin when needed. As noted on the label, Victoza is not a substitute for insulin and is not indicated for patients with type 1 diabetes or those with diabetic ketoacidosis, a condition associated with diabetes where the body breaks down fat too quickly because there is inadequate insulin or none at all. Victoza is also indicated to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease; however, its effect on major adverse cardiovascular events in paediatrics was not studied and it is not indicated for this use in children.

The efficacy and safety of Victoza for reducing blood sugar in patients with type 2 diabetes was studied in several placebo-controlled trials in adults and one placebo-controlled trial with 134 pediatric patients 10 years and older for more than 26 weeks. Approximately 64% of patients in the pediatric study had a reduction in their haemoglobin A1c (HbA1c) below 7% while on Victoza, compared to only 37% who achieved these results with the placebo. HbA1c is a blood test that is routinely performed to evaluate how well a patient’s diabetes is controlled, and a lower number indicates better control of the disease. These results occurred regardless of whether the patient also took insulin at the same time. Adult patients who took Victoza with insulin or other drugs that increase the amount of insulin the body makes (e.g., sulfonylurea) may have an increased risk of hypoglycemia (low blood sugar). Meanwhile, pediatric patients 10 years and older taking Victoza had a higher risk of hypoglycemia regardless of whether they took other therapies for diabetes.

The prescribing information for Victoza includes a Boxed Warning to advise health care professionals and patients about the increased risk of thyroid C-cell tumours. For this reason, patients who have had, or have family members who have ever had medullary thyroid carcinoma (MTC) should not use Victoza, nor should patients who have an endocrine system condition called multiple endocrine neoplasia syndrome type 2 (MEN 2). In addition, people who have a prior serious hypersensitivity reaction to Victoza or any of the product components should not use Victoza. Victoza also carries warnings about pancreatitis, Victoza pen sharing, hypoglycemia when used in conjunction with certain other drugs known to cause hypoglycemia including insulin and sulfonylurea, renal impairment or kidney failure, hypersensitivity and acute gallbladder disease. The most common side effects are nausea, diarrhoea, vomiting, decreased appetite, indigestion and constipation.

Source: FDA News Release, June 17, 2019

June 3, 2019: U.S. Food and Drug Administration issued a warning advising pregnant women and women who could become pregnant to not take dietary supplements containing vinpocetine due to possible reproductive safety risks. According to data reviewed by the FDA, including a recent report by the National Institute of Health’s (NIH) National Toxicology Program (NTP), consumption of vinpocetine is associated with adverse reproductive effects – in other words, vinpocetine may cause a miscarriage or harm fetal development.

Vinpocetine is a synthetically produced compound marketed in Nigeria under the brand names Cognitol® and Innovitol®. It may also be contained in certain products marketed as dietary supplements, either by itself or combined with other ingredients. Vinpocetine may be referred to on product labels as

• Vinca minor extract,
• Lesser periwinkle extract, or
• Common periwinkle extract.

Dietary supplements containing vinpocetine are often marketed for uses that include enhanced memory, focus, or mental acuity; increased energy; and weight loss.

Scientists who have studied the effects of vinpocetine on pregnant animals concluded that vinpocetine decreased fetal weight and increased the chances of a miscarriage. The blood levels of vinpocetine measured in the pregnant animals were similar to those reported in people after taking a single dose of vinpocetine, indicating that pregnant women may experience adverse effects from vinpocetine similar to those seen in the pregnant animals.

FDA is advising firms marketing dietary supplements containing vinpocetine to evaluate their product labeling to ensure that it provides safety warnings against use by pregnant women and women who could become pregnant.

Source:

FDA Statement on warning for women of childbearing age about possible safety risks of dietary supplements containing vinpocetine

Energy drinks significantly prolong the QTc interval and are associated with an increase in blood pressure, according to a study published online May 29 in the Journal of the American Heart Association.

Energy drinks are commonly promoted as supplements that can boost performance and cognition but have also been reported to have numerous detrimental side effects, particularly cardiovascular and neurological in nature. Their consumption has been associated with cardiac arrest, myocardial infarction, spontaneous coronary dissection, and coronary vasospasm. They have been linked to an increase in emergency room visits and deaths.

The study aims to determine the impact of energy drinks on electrocardiographic and hemodynamic parameters in young healthy volunteers.

Sachin A. Shah, Pharm.D., from the University of the Pacific in Stockton, California, and colleagues randomly assigned 34 healthy volunteers (age, 22.1 ± 3.0 years) to 32 ounces of energy drink A, energy drink B, or placebo on three study days with a six-day washout period in between. At baseline and every 30 minutes for 240 minutes, the authors assessed the primary endpoint of the QTc interval and the secondary endpoints of the QT interval, PR interval, QRS interval, heart rate, and brachial and central blood pressures.

The researchers found that the maximum change from baseline in Bazett’s corrected QT interval was 17.9 ± 13.9 ms, 19.6 ± 15.8 ms, and 11.9 ±11.2 ms for drink A, drink B, and placebo, respectively. Compared with placebo, the maximum changes from baseline in peripheral and central systolic and diastolic blood pressure were statistically significantly different, with significantly higher systolic blood pressure changes with drinks A and B versus placebo.

“The public should be aware of the impact of energy drinks on their body, especially if they have other underlying health conditions,” Shah said in a statement.

In Nigeria, commonly available energy drinks include Monster, MAMBA, Matador, Power Horse, Red Bull, Bullet, Fearless, Lacoco, Rox, etc.

Conclusions

Caffeinated energy drinks significantly prolong the QTc interval and raise brachial and central blood pressure post‐acute exposure. Further investigation is warranted on whether an individual ingredient or a unique combination leads to the observed electrophysiological and hemodynamic changes. The impact of long‐term energy drinks consumption remains unknown.

ADDENDUM

Caffeine meter

• 8 oz (240 mL) brewed coffee has about 133 mg caffeine (range: 102-200 mg)
• 8 oz (240 mL) instant coffee has about 93 mg caffeine (range: 27-173 mg)
• 8 oz (240 mL) tea has about 53 mg caffeine (range: 40-120 mg)
• A 12 oz or 355 mL can of Cola beverage (regular or diet) has about 35-50 mg caffeine
• The amount of caffeine in energy drinks varies widely. 8 oz (240 mL) of Red Bull or Monster energy drink contains 80 mg caffeine.
• Sports drinks do NOT usually contain caffeine. Herbal teas, decaffeinated drinks are caffeine free.
• OTC medicines are another source of caffeine e.g., 1 tablet of Paracetamol plus Caffeine contains about 60 mg caffeine
• Recommended maximum caffeine intake for adult is 400 mg/day (from all sources)
• Children under 12 should not exceed 2.5 mg/kg/day, based on Health Canada recommendations

Source:

1. Shah Sachin A., Szeto Andy H., Farewell Raechel, Shek Allen, Fan Dorothy, Quach Kathy N., et al. Impact of High Volume Energy Drink Consumption on Electrocardiographic and Blood Pressure Parameters: A Randomized Trial. J Am Heart Assoc. 2019 Jun 4;8(11):e011318.

Diet-controlled patients.

In patients with type 2 diabetes who are well controlled with diet alone, the risk associated with fasting is quite low. Distributing calories over two to three smaller meals during the non-fasting interval may help prevent excessive postprandial hyperglycemia. Patients controlled with diet alone usually combine this with a regular daily exercise program.

The exercise program should be modified in its intensity and timing to avoid hypoglycemic episodes; the timing of the exercise could be changed to ∼2 hours after the sunset meal. Finally, in this usually older age-group, often with hypertension and dyslipidemia, fluid restriction and dehydration may increase the risk of thrombotic events.

Patients treated with oral agents.

The choice of oral agents should be individualized. In general, agents that act by increasing insulin sensitivity are associated with a significantly lower risk of hypoglycemia than compounds that act by increasing insulin secretion.

• Metformin. Patients treated with metformin alone may safely fast because the possibility of hypoglycemia is minimal. However, it is suggested that the timing of the doses be modified.

Two-thirds of the total daily dose be administered in iftar, while the other third be given in sehri.

• Glitazones. Patients on insulin sensitizers (pioglitazone) have a low risk of hypoglycemia. Usually, no change in dose is required. Taken at night or iftar.
• Sulfonylureas. Newer members of the sulfonylurea family (gliclazide MR or glimepiride) have been shown to be effective, resulting in a lower risk of hypoglycemia. If taken once daily before Ramadan then should be taken full dose in iftar. If taken twice a day then full morning dose in iftar and half of the night dose in sehri.
• Short-acting insulin secretagogues. Members of this group (repaglinide and nateglinide) are useful because of their short duration of action. They could be taken twice daily in iftar and in sehri.
• Incretin-based therapy. Glucagon-like peptide-1 receptor agonists (GLP-1ras) exenatide and liraglutide and dipeptidylpeptidase-4 inhibitors (DPP-4is) alogliptin, saxagliptin, sitagliptin, and vildagliptin. These classes of agents are not independently associated with hypoglycemia, though they can increase the hypoglycemic effects of sulfonylureas, glinides, and insulin. During Ramadan, these drugs do not require dose titration. Can be taken at night or in iftar
• α-Glucosidase inhibitors. Acarbose, miglitol, and voglibose slow the absorption of carbohydrates when taken with the first bite of a meal. Because they are not associated with an independent risk of hypoglycemia, particularly in the fasting state, they may be particularly useful during Ramadan. α-Glucosidase inhibitors are associated with frequent mild to moderate gastrointestinal effects, particularly flatulence. Using modest doses and slowly initiating therapy are reported to minimize the frequency of these adverse effects

Patients treated with insulin.

Problems facing patients with type 2 diabetes who administer insulin are similar to those with type 1 diabetes, except that the incidence of hypoglycemia is less. A major objective is to suppress hepatic glucose output to near-physiologic levels during the fasting period. Judicious use of intermediate- or long-acting insulin preparations plus a short-acting insulin administered before meals would be an effective strategy.

There is some evidence suggesting that the use of insulin lispro instead of regular insulin before meals in patients with type 2 diabetes who fast during Ramadan is associated with less hypoglycemia and smaller postprandial glucose excursions.

• Short/Rapid-acting insulin, take the usual dose in iftar and 25-50% reduced dose in sehri.

Using one injection of a long-acting insulin analog, such as insulin glargine, or two injections of NPH, lente, or detemir insulin before the sunset and predawn meals may provide adequate coverage as long as the dosage of each injection is appropriately individualized.

• Basal analogues (intermediate/long-acting) once daily, same time at night or in iftar by 20-30% dose reduction.
• Intermediate-acting insulin twice daily, full morning dose in iftar and half of the night dose in sehri.

A single injection of intermediate-acting insulin administered before the sunset meal may be sufficient to provide acceptable glycemic control in patients with reasonable basal insulin secretion. However, most patients will still require short-acting insulin administered in combination with the intermediate- or long-acting insulin at the sunset meal to cover the large caloric load of iftar. Moreover, many will need an additional dose of short-acting insulin at predawn.

• Premixed insulin or split mixed insulin dose during Ramadan should be in iftar full pre-Ramadan morning dose and in sehri half of the night dose.

Pregnancy and fasting during Ramadan

Pregnancy is a state of increased insulin resistance and insulin secretion and of reduced hepatic insulin extraction. Fasting glucose concentrations are lower but postprandial glucose and insulin levels are substantially higher in healthy pregnant women than those who are not pregnant. Elevated blood glucose and A1C levels in pregnancy are associated with increased risk for major congenital malformations.

Fasting during pregnancy would be expected to carry a high risk of morbidity and mortality to the fetus and mother, although controversy exists. While pregnant Muslim women are exempt from fasting during Ramadan, some with known diabetes (type 1, type 2, or gestational) insist on fasting during Ramadan. These women constitute a high-risk group, and their management requires intensive care.

In general, women with pre-gestational or gestational diabetes should be strongly advised to not fast during Ramadan. However, if they insist on fasting, then special attention should be given to their care. The management of pregnant patients during Ramadan is based on an appropriate diet and intensive insulin therapy. The issues discussed above concerning the management of type 1 and type 2 diabetes also apply to this group, with the exception that more frequent monitoring and insulin dose adjustment is necessary

Congenital anomalies – WHO defines congenital anomalies as…

Research and writing made possible thanks to the generous sponsorship from Pemason Pharmaceutical Limited – owned by Pharmacists and operated by a team of Pharmacists with a commitment to quality pharmaceuticals & drug information

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Proven teratogenic drugs in humans – see the link to Table 1 below

OTC medication use during pregnancy & lactation – see the link to Table 2 below

Prescription drugs of choice during pregnancy and lactation – see the link to Table 3 below

Congenital anomalies

WHO (World Health Organization) defines congenital anomalies as structural or functional anomalies (e.g. metabolic disorders) that occur during intrauterine life and can be identified prenatally, at birth or later in life.

There are a variety of causes of congenital malformations namely:

Socioeconomic and demographic factors: Congenital anomalies are more frequent among resource-constrained families and countries. This may be associated with lack of access to sufficient, nutritious food and increased exposure to agents or factors such as infection and alcohol that induce or increase the incidence of abnormal prenatal development.

Genetic factors: Consanguinity (when parents are related by blood) increases the prevalence of rare genetic congenital anomalies and nearly doubles the risk for neonatal and childhood death, intellectual disability and other anomalies in first-cousin unions.

Infections: Maternal infections such as syphilis and rubella are a significant cause of congenital anomalies in low- and middle-income countries.

Maternal nutritional status: Iodine deficiency, folate insufficiency, obesity and diabetes mellitus are linked to some congenital anomalies. For example, folate insufficiency increases the risk of having a baby with a neural tube defect. Also, excessive vitamin A intake may affect the normal development of an embryo or fetus.

Environmental factors: Maternal exposure to certain pesticides and other chemicals, as well as certain medications, alcohol, tobacco, psychoactive drugs and radiation during pregnancy, may increase the risk of having a fetus or neonate affected by congenital anomalies.

Despite widespread concern about drug safety, it is estimated that only 2 to 3% of birth defects are related to medications, leaving 97% to 98% to other causes namely genetic, environmental, or unknown causes.

A drug’s effect on the fetus is determined largely by fetal age at exposure, drug potency, and drug dosage. Fetal age affects the type of drug effect:

• Before the 20^th day after fertilization i.e., Week 1 to 2 or the period between the last menstrual period (LMP) and fertilization: Drugs given during this period typically have an “all-or-nothing effect.” That is, the effect of the teratogen is either to kill the embryo & cause spontaneous abortion or have no effect at all. Teratogenesis is unlikely during this stage.
• During organogenesis (between 20 & 56 days after fertilization) i.e., Week 3 to 8 or the embryonic period: The developing embryo is most susceptible to teratogenic agents during this stage of rapid cell division and differentiation. Virtually all organs of the body are formed during this period. Each organ of an embryo has a critical period during which its development may be disrupted (see Figure 1 above).
• After organogenesis (in the 2nd and 3rd trimesters) i.e., Week 9 to birth or the fetal period: Teratogenesis is unlikely, but drugs may alter growth and function of normally formed fetal organs and tissues. As placental metabolism increases, doses must be higher for fetal toxicity to occur.

From the foregoing, the damage caused by medications can be classified into 2 broad categories:

• those that are teratogens, and
• those that cause adverse fetal effects.

Teratogens cause alteration of tissue development or organ formation and occur approximately 2 to 8 weeks post conception i.e., during the embryonic period. It is therefore important for clinicians to ascertain the stage of pregnancy when considering medication use in pregnancy.

The most common teratogenic effects are neural tube defects, congenital heart abnormalities, cleft lip or palate, and fetal stillbirth.

Conversely, adverse fetal effects result in the dysfunction of an organ or tissue after that organ or tissue has been formed. Some examples include difficult postnatal adaptation, withdrawal, electrolyte abnormalities, and altered glucose metabolism.

Medications that may cause adverse fetal effects include some antipsychotics, antidepressants, and opioid medications.

Relatively few medications are known teratogens (see Table 1 below).

Although the number of medications associated with teratogenicity is small, it is important because many of the underlying causes of congenital anomalies cannot be affected or changed, whereas drug exposure can be controlled.

The placental “barrier”?

The placenta is the lifeline of the developing fetus. It is a semipermeable barrier through which all nutrients and waste products must pass. Teratogenicity depends upon the ability of the agent to cross the placenta.

Drugs diffuse across the placenta similarly to the way they cross other epithelial barriers. Several factors affect a medication’s ability to cross the placenta, although the majority of drugs are transported by passive diffusion based on the concentration gradient. Medications most likely to cross are lipophilic, unionized in maternal blood, have low molecular weight (<600 Daltons), and are not highly protein bound. Conversely, if a medication is hydrophilic, ionized in maternal serum and highly protein bound, little to no medication will cross.

Not all maternal drugs cross the placenta to the fetus. Drugs that cross the placenta may have a direct toxic effect or a teratogenic effect. Drugs that do not cross the placenta may still harm the fetus by:

• Constricting placental vessels and thus impairing gas and nutrient exchange
• Producing severe uterine hypertonia that results in anoxic injury
• Altering maternal physiology (e.g., causing hypotension)

In evaluating a medication for use during pregnancy, the clinician should:

• first, consider the stage of pregnancy
• second, review the information available regarding exposure of the fetus during that time.
• finally, consider the risk to the mother and infant if the disease state is left untreated.

Principles of Safe Drug Prescribing in Pregnancy

• All drugs carry some risk during pregnancy. It is important to balance the benefits and harms to both mother and fetus before recommending drug use during pregnancy.
• Discuss the possible fetal effects of any medication prescribed to women of childbearing age and ask about their reproductive plans.
• Avoid the use of nonessential medications (for relief of mild symptoms) in pregnancy.
• Confirm the diagnostic indication for drug therapy during pregnancy and continue drugs which are essential for maternal health.
• Consider the known risks of the medication and the consequences of withdrawing the medication during pregnancy.
• Consult a reliable source of information about drug safety during pregnancy.
• Consider non-drug alternatives and safer medications for the treatment of conditions during pregnancy.
• Because drug metabolism and distribution may be altered during pregnancy, consider necessary dosing changes and follow drug levels when necessary.

Source: Powrie R, Hingle S. Drug prescribing in pregnancy. American College of Physicians; 2015 Jan. Available from: http://smartmedicine.acponline.org/

Quick reference tables

Click the links below to access the PDF Tables

Proven teratogenic drugs in humans (Table 1)

• Table 1_Proven teratogenic drugs in humans

OTC medication use during pregnancy & lactation (Table 2)

• Table 2_OTC medication use during pregnancy & lactation

Prescription drugs of choice during pregnancy and lactation (Table 3)

• Table 3_Prescription drugs of choice during pregnancy and lactation

Important links

Drugs in Pregnancy and Breastfeeding – Perinatology.com. Collection of several resources and links

URL: https://www.perinatology.com/exposures/druglist.htm

MotherToBaby – Medications & More during Pregnancy & Breastfeeding. US-based site offers evidence-based information for mothers, health-care professionals and members of the general public

URL: https://mothertobaby.org/

Infant Risk Center – Texas Tech University Health Sciences Center

URL: https://www.infantrisk.com/categories/breastfeeding

References:

1. World Health Organization (WHO). Congenital anomalies. Fact sheet No. 370; 2015 Apr. Available from: http://www.who.int/mediacentre/factsheets/fs370/en/
2. Gunatilake R, Patil AS. Drugs in pregnancy. Merck Manual; 2013 Jan. Available from: http://www.merckmanuals.com/professional/gynecology-and-obstetrics/drugs-in-pregnancy/drugs-in-pregnancy
3. Burkey BW, Holmes AP. Evaluating medication use in pregnancy and lactation: what every pharmacist should know. J Pediatr Pharmacol Ther 2013;18(3):247–258
4. Chung W. Teratogens and their effects. Available from: http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt23-Teratogens.pdf
5. Kosar L. Peri‐pregnancy: drug treatment considerations. RxFiles; 2014 Oct. Available from: rxfiles.ca (login required).
6. Dutta S. Human teratogens and their effects: a critical evaluation. International Journal of Information Research and Review; 2015 Mar. Available from: http://www.ijirr.com/sites/default/files/issues/0296.pdf
7. Diav-Citrin O. Human teratogens: a critical evaluation. The Motherisk Program, the Hospital for Sick Children, Toronto, ON Canada. Available from: http://www.nvp-volumes.org/p2_4.htm
8. Koren G. Medication safety in pregnancy and breastfeeding. McGraw Hill Medical; 2007
9. Powrie R, Hingle S. Drug prescribing in pregnancy. American College of Physicians; 2015 Jan. Available from: http://smartmedicine.acponline.org/

Medications and mother’s milk

Research and writing made possible thanks to the generous sponsorship from Pemason Pharmaceutical Limited – owned by Pharmacists and operated by a team of Pharmacists with a commitment to quality pharmaceuticals & drug information

To sponsor EMDEX Topic(s) i.e., Medication Management of Diseases, Therapeutic Notes or Development of Drug Monographs, please contact Editor@EmdexOnline.com

Drugs generally considered incompatible with breastfeeding – see the link to Table 1 below

OTC medication use during pregnancy & lactation – see the link to Table 2 below

Prescription drugs of choice during pregnancy and lactation – see the link to Table 3 below

Breastfeeding has many proven benefits for both the mother and the infant. Mothers who breastfeed experience less postpartum bleeding and return to pre-pregnancy weight more rapidly. They also have a lower risk for postpartum depression, type 2 diabetes, and breast and ovarian cancer. Infants who are breastfed have fewer infections, most notably otitis media, as well as a lower incidence of sudden infant death syndrome, necrotizing enterocolitis, childhood leukaemia, diabetes, asthma, and obesity. Exclusive breastfeeding until the age of 4 months and partially thereafter has been associated with a significant reduction in respiratory and gastrointestinal morbidity in infants.

The American Academy of Pediatrics recommends breastfeeding for the first year of life, including breast milk exclusively for the first 6 months. Breastfeeding should be promoted by health care professionals. Breastfeeding mothers should be adequately counselled on safe medication use. Breastfeeding should not be stopped unnecessarily when a medication is prescribed.

Absolute contraindications to breastfeeding are rare and may include human immunodeficiency virus (HIV) infection, illicit drug use, galactosemia in the infant, herpes simplex virus lesion on the breast, active tuberculosis or human T-cell lymphocytic virus infection, radioactive isotopes/radioactive material exposure, and antimetabolite or other chemotherapy use.

Conditions that are not prohibitive of breastfeeding include herpes simplex virus infection that does not include a lesion on the breast, hepatitis B infection, and cytomegalovirus infection.

The use of medications, either prescription or over-the-counter, is seldom a contraindication to breastfeeding. Short courses of medication may require that a mother use a pump to collect her milk to continue to stimulate the milk production, alleviate symptoms of engorgement, and then discard it rather than feeding it to the infant.

Counselling Tip

If a drug must be taken by a mother while breastfeeding, scheduling the doses so that peak plasma and milk levels of the drug do not coincide with breastfeeding sessions may be possible. Advise the mother to breastfeed just before taking a dose of a drug and/or at least 2 hours after taking a dose. This may help reduce infant exposure

Drug transfer into milk

The transfer of medication into human milk shares some of the same principles as crossing the placenta, with most by passive diffusion. A medication may cross through the placenta into the fetal circulation and back on the concentration gradient, just as a drug may pass into milk and diffuse back into the bloodstream as serum concentrations decrease.

The most important factor in infant exposure through breast milk is the amount of medication in the mother’s serum. Next, the properties that affect the transfer of medication from serum into milk should be considered. These include bioavailability, molecular weight, protein binding, pKa, and lipid solubility.

Similar to crossing the placenta, molecular weight and protein binding can predict a medication’s likelihood to cross into breast milk. Medications with small molecular weights (<200 Da) are more likely to pass, and those that have a large molecular weight exhibit reduced entry into breast milk

In general, the properties necessary for a medication to cross into the central nervous system (CNS) also predict diffusion into breast milk. Medications that are highly lipid soluble easily pass into breast milk and cross the blood-brain barrier. If a medication is a centrally active medication, advising the mother to watch for CNS side effects in the infant is important.

Galactogogues

Galactogogues are chemical substances used to aid in breast milk production. Medications should never replace support, education and assessment of breastfeeding technique. Frequent feeds and complete milk removal at regular intervals will increase milk production.

Domperidone, like Metoclopramide, increases milk production by increasing prolactin. Usual dose 10 mg orally 3 times daily for 7-10 days; max. 60 mg/day. There is no evidence that doses >30 mg/day is more effective and may be associated with increased risk of side effects (e.g., QT prolongation). May take up to 4 days for improvement. Preferred over metoclopramide due to fewer side effects.

Metoclopramide 10 mg orally three times a day for 7 to 14 days, then taper by reducing 1 tablet q5‐7 days. Concerns about efficacy and safety limit use. May be associated with rare incidences of tardive dyskinesia, depression or dysthymia in the nursing mother.

Herbals: Not usually recommended due to inadequate data vs. prescription galactagogues. Fenugreek: Most commonly used herbal galactogogue; mother and baby may smell like maple syrup. Rare incidence of GI bleeding suspected in premature infants. Avoid use if allergic to peanuts or legumes.

Beer: Barley contained in beer may increase prolactin, but not enough evidence to recommend. Alcohol content not responsible for the effect on prolactin secretion and may decrease milk production.

Bromocriptine is not recommended for the suppression of lactation due to an increased risk of stroke and myocardial infarctions when used postpartum

Does drinking beer help increase your milk supply?

Beer and breastfeeding

There are clear indications that beer can stimulate prolactin secretion which may enhance lactogenesis both in non-lactating humans and in experimental animals. The component in beer responsible for the effect on prolactin secretion is not the alcohol content but apparently a polysaccharide from barley, which explains that the effect on prolactin can also be induced by non-alcoholic beer. Studies have shown a reduced breast milk intake by infants after moderate alcohol consumption of their mothers. Regular use of alcoholic drinks during lactation should be discouraged and instead, mothers may be referred to non-alcoholic beer.

Source: Koletzko B, Lehner F. Beer and breastfeeding. Advances in Experimental Medicine and Biology [serial online]. 2000;478:23-28. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed July 26, 2015

Quick reference tables

Click the links below to access the PDF Tables

Drugs generally considered incompatible with breastfeeding (Table 1)

• Table 1_Drugs generally considered incompatible with breastfeeding

OTC medication use during pregnancy & lactation (Table 2)

• Table 2_OTC medication use during pregnancy & lactation

Prescription drugs of choice during pregnancy and lactation (Table 3)

• Table 3_Prescription drugs of choice during pregnancy and lactation

Important links

Drugs in Pregnancy and Breastfeeding – Perinatology.com. Collection of several resources and links

URL: https://www.perinatology.com/exposures/druglist.htm

MotherToBaby – Medications & More during Pregnancy & Breastfeeding. US-based site offers evidence-based information for mothers, health-care professionals and members of the general public

URL: https://mothertobaby.org/

Infant Risk Center – Texas Tech University Health Sciences Center

URL: https://www.infantrisk.com/categories/breastfeeding

References:

1. World Health Organization (WHO). Congenital anomalies. Fact sheet No. 370; 2015 Apr. Available from: http://www.who.int/mediacentre/factsheets/fs370/en/
2. Gunatilake R, Patil AS. Drugs in pregnancy. Merck Manual; 2013 Jan. Available from: http://www.merckmanuals.com/professional/gynecology-and-obstetrics/drugs-in-pregnancy/drugs-in-pregnancy
3. Burkey BW, Holmes AP. Evaluating medication use in pregnancy and lactation: what every pharmacist should know. J Pediatr Pharmacol Ther 2013;18(3):247–258
4. Chung W. Teratogens and their effects. Available from: http://www.columbia.edu/itc/hs/medical/humandev/2004/Chpt23-Teratogens.pdf
5. Kosar L. Peri‐pregnancy: drug treatment considerations. RxFiles; 2014 Oct. Available from: rxfiles.ca (login required).
6. Dutta S. Human teratogens and their effects: a critical evaluation. International Journal of Information Research and Review; 2015 Mar. Available from: http://www.ijirr.com/sites/default/files/issues/0296.pdf
7. Diav-Citrin O. Human teratogens: a critical evaluation. The Motherisk Program, the Hospital for Sick Children, Toronto, ON Canada. Available from: http://www.nvp-volumes.org/p2_4.htm
8. Koren G. Medication safety in pregnancy and breastfeeding. McGraw Hill Medical; 2007

US Food & Drug Administration (FDA) is advising that rare but serious injuries have happened with certain common prescription insomnia medicines because of sleep behaviours, including sleepwalking, sleep driving, and engaging in other activities while not fully awake. These complex sleep behaviours have also resulted in deaths. These behaviours appear to be more common with Z-drugs (zopiclone, zolpidem, zaleplon, eszopiclone) than other prescription medicines used for sleep.

Z-drugs registered by Nigeria’s NAFDAC include Zopiclone (Zopice, Zopimax) and Zolpidem (Stilnox).

Serious injuries and death from complex sleep behaviours have occurred in patients with and without a history of such behaviours, even at the lowest recommended doses, and the behaviours can occur after just one dose. These behaviours can occur after taking these medicines with or without alcohol or other CNS depressants that may be sedating such as tranquilizers, opioids, and anti-anxiety medicines.

Z-drugs are medicines used to treat insomnia in adults who have difficulty falling asleep or staying asleep. They are in a class of medicines called sedative-hypnotics and have been approved and on the market for many years. These insomnia medicines work by slowing activity in the brain to allow sleep. Quality sleep can have a positive impact on physical and mental health.

Health care professionals should not prescribe zopiclone, zolpidem, zaleplon, or eszopiclone to patients who have previously experienced complex sleep behaviours after taking any of these medicines. Advise all patients that although rare, the behaviours caused by these medicines have led to serious injuries or death. Tell the patient to discontinue taking these medicines if they experience an episode of complex sleep behaviour.

Patients should stop taking your insomnia medicine and contact your health care professional right away if you experience a complex sleep behaviour where you engage in activities while you are not fully awake or if you do not remember activities you have done while taking the medicine

Zopiclone monograph in EMDEX has been updated to reflect this important safety information. See Zopiclone (under Pharmacovigilance, Advice to Patients and Contra-indications).

Source: FDA Drug Safety Communication, April 30, 2019

US National Institutes of Health (NIH) study suggests supplement that reduces risk of birth defects may also have maternal health benefit.

Taking a folic acid supplement daily before pregnancy may reduce the risk of gestational, or pregnancy-related, diabetes, according to a study by researchers at the National Institutes of Health and other institutions. The findings appear in Diabetes Care.

Folic acid is the synthetic form of folate, or vitamin B9, which is found in leafy green vegetables, nuts, peas, beans and other foods. The U.S. Preventive Services Task Force (USPSTF) recommends that all women of reproductive age take a daily supplement containing 400 to 800 micrograms of folic acid to reduce the risk of conceiving a child with a neural tube defect, a class of birth defects affecting the brain and spinal cord.

Gestational diabetes results when the level of blood sugar, or glucose, rises too high. It increases a woman’s chances for cesarean delivery and for blood pressure disorders during pregnancy. It also raises the risk of cardiovascular disease and type 2 diabetes later in life. For infants, gestational diabetes increases the risk of large birth size and of obesity during childhood and adulthood.

In the current study, researchers analyzed data from nearly 15,000 women enrolled in the Nurses’ Health Study II, a long-term study of diet, lifestyle factors and disease outcomes among female nurses. Among more than 20,000 pregnancies, there were 824 cases of gestational diabetes. Compared to women who did not take a folic acid supplement, those who took less than 400 micrograms were 22% less likely to develop gestational diabetes. Those who took 600 micrograms were 30% less likely to develop the condition.

“In addition to reducing the risk for neural tube defects, our findings suggest that taking folic acid supplements before pregnancy might provide a low-cost way to reduce the risk of gestational diabetes,” said the study’s senior author, Cuilin Zhang, M.D., Ph.D., of the Division of Intramural Population Health Research at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

The researchers did not find a lower risk of gestational diabetes associated with consumption of foods that contain high amounts of folate. They cited earlier studies showing that folic acid is absorbed more easily into the body, compared to the naturally occurring form of the vitamin. Researchers also noted that previous studies have found that insufficient folate is associated with insulin resistance (difficulty using insulin to lower blood glucose), which may precede the development of type 2 diabetes in non-pregnant people.

CONCLUSIONS

Higher habitual intakes of supplemental folate before pregnancy were significantly associated with lower GDM risk. If confirmed, these findings indicate that prepregnancy folic acid supplementation could offer a novel and low-cost avenue to reduce GDM risk

References:

1. Daily folic acid supplement may reduce risk of gestational diabetes [Internet]. National Institutes of Health (NIH). 2019 [cited 2019 Apr 30]. Available from: https://www.nih.gov/news-events/news-releases/daily-folic-acid-supplement-may-reduce-risk-gestational-diabetes
2. Li M, Li S, Chavarro JE, Gaskins AJ, Ley SH, Hinkle SN, et al. Prepregnancy Habitual Intakes of Total, Supplemental, and Food Folate and Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study. Diabetes Care. 2019 Apr 11;dc182198.