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Applications Oral Hypoglycemics and Insulin The pregnant women who have pre-existing type 2 diabetes or develop gestational diabetes (GDM) may need antidiabetics. The increased insulin resistance may cause preeclampsia, macrosomia, fetal organ hepatomegaly and caesarian delivery. Women with GDM have increased risk to develop DM after pregnancy. To diagnose gestational diabetes, the blood glucose concentrations are listed:  For gestational diabetic patients, the most common oral antidiabetic is glyburide which is usually effective as single agent, and only 4-16% will need supplemental insulin. Metformin is considered safe for short-term use during 2nd and 3rd trimesters. Other alternatives, like acarbose is limited by abdominal cramping. Also, other classes of antidiabetics, like TZDs and glinides are still experimental. In term of insulin selection, NPH and regular insulin are preferred, and insulin detemir and insulin aspart/lispro have some safety data than others. The insulin dosing varies due to obesity, ethnicity, degree of hyperglycemia from 0.7 units -2 units/kg/day based on present pregnant weight, then titrate by self-monitoring blood glucose. Antihypertension Treatment of severe hypertension has a well-established maternal benefit of reduction in stroke risk when SBP>=160 mmHg and DBP >= 110 mmHg. All antihypertensives cross placenta, so the risks and benefits to start the treatment need to be evaluated. The options in pregnancy are methyldopa, labetalol, long-acting nifedipine, IV hydralazine for pre-eclampsia, thiazides(controversial), clonidine (less preferred). ACEi, ARBs, direct renin inhibitors are contraindicated in pregnancy because fetal renal/cardiac abnormalities. Also, IV nitroprusside should not be used since cyanide poisoning. In lactation, propranolol, metoprolol and labetalol have lowest transfer to milk in beta blockers, and atenolol and acebutolol are extensively excreted by lactation. For other classes, the lactation compatibilities are listed in table:  Antidepressants The risks of untreated moderate to severe maternal major depression often outweigh the risks associated with antidepressants to both mother and fetus. The most commonly used antidepressants during pregnancy are SSRIs. The risks information of antidepressants in pregnancy comes from low to moderate quality studies. In practice, regimen starts from lowest effective dose and needs to titrate carefully. ▶ MAO inhibitor: limited data was studies for this class, and seldom prescribed due to drug-drug/food interactions. In animal studies, MAO inhibitors associated with fetal growth restriction, but few human data available for pregnancy use. For lactation, this class generally not been used. ▶ TCAs: low risk of teratogenicity in pregnancy. It is compatible during lactation. Nortriptyline is preferred agent, and doxepin is generally avoided. ▶ SSRIs: low risk of teratogenicity. Paroxetine associated with a small increased risk for congenital cardiovascular malformations in some studies. SSRIs is compatible in lactation, and paroxetine and sertraline are the preferred agents. ▶ SNRIs: don’t appear to be associated with congenital fetal malformations, and safe to use in lactation. ▶ Atypical antidepressants  Anticoagulants ⏩ For pregnant women who are on high risk of DVT, prosthetic heart valves, or have A Fib, cerebral venous sinus thrombosis, left ventricular dysfunction, and fetal loss, they need anticoagulant during pregnancy and lactation. During pregnancy, warfarin can cross placenta. It is teratogenic reported following 1st trimester exposure. Use is contraindicated during pregnancy (pregnancy X) except in women with mechanical heart valve who are at high risk for thromboembolism (pregnancy D). Warfarin does not cross into the break milk, so it is compatible with lactation. ⏩ Heparin is compatible use in pregnancy and lactation but requires dose adjustment since lower maximum enoxaparin concentrations and anti-factor Xa activity levels occur during pregnancy. ⏩ Other oral anticoagulants are lack of human data in use during pregnancy and lactation. With available animal studies, they suggest moderate risk for dabigatran and rivaroxaban, and low risk for apixaban during pregnancy. All of them are potential toxic for lactating women. Progesterone therapy ⏩ Progesterone reduces risk of preterm birth (<37 weeks or < 259 days of gestation) in one-third of women with singleton pregnancy. In the US, 1 in 8 pregnancies can have preterm birth complications. If the women have previous spontaneous preterm birth, IM progesterone is recommended. Or, if the women have shorter cervix than normal on current pregnancy, vaginal progesterone is recommended. Minor side effects include injection site reaction if given by IM, or irritation or discharge if applied vaginally.  Conclusion In conclusion, many pregnant women are using OTC and prescription products during their pregnancy. The available evidence and studies vary on products. As a pharmacist, using clinical judgement, assessing risk and benefits, consulting patients with write drug reference, and providing patient-centered discussion and decision-making process are very important. |
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