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Econazole nitrate — (Spectazole)

International Brand Names

Amicel (Italy); Bismultin (Greece); Derma-Coryl (Israel); Dermazole (Australia, Hong Kong, Singapore); Ecanol (India); Econ (Thailand); Econite (Hong Kong); Ecosone (Hong Kong); Ecostatin (Canada, England, Ireland, New Zealand); Ecotam (Spain); Ecreme (New Zealand); Epi-Pevaryl (Germany); Fongeryl (France); Fungazol (Korea); Gyno-Coryl (Israel); Micolak (Mexico); Micolis (Argentina, Chile, Ecuador, Paraguay, Peru, Uruguay); Micos (Italy); Micostyl (Brazil, Mexico); Palavale (Japan); Penicomb (Greece); Pevaryl (Bahrain, Cyprus, Egypt, Germany, Greece, Hong Kong, Ireland, Jordan, Malaysia, New Zealand, Philippines, Poland, Slovenia, Sudan, Turkey, Venezuela)

Drug Class Antifungals; Dermatologics
Indications Tinea and cutaneous candidiasis
Mechanism An imidazole derivative that changes fungal cell wall permeability
Dosage With Qualifiers Tinea—apply cream to affected area qd
Cutaneous candidiasis—apply cream to affected area bid

  • Contraindications —hypersensitivity

  • Caution —unknown

Maternal Considerations Econazole is less effective than clotrimazole for the treatment of Candida vaginitis . Systemic absorption of econazole is extremely low. There are no adequate reports or well-controlled studies of econazole in pregnant women. Econazole prolongs pregnancy in rats when given orally.
Side effects include burning, itching, redness, and rash.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether econazole crosses the human placenta. One epidemiologic study of women using vaginally administered econazole is reassuring. Considering the dose and route, it is unlikely the maternal systemic concentration will reach a clinically relevant level. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically. Embryotoxic effects were noted in rodents after oral administration of 10–40 × the MRHD.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether econazole enters human breast milk. It is present in rodent breast milk after high oral doses. Considering the indication, dosing, and route, it seems unlikely to pose a clinically significant risk to the breastfeeding neonate.
Drug Interactions No clinically significant interactions identified.
References Czeizel AE, Kazy Z, Vargha P. Eur J Obstet Gynecol Reprod Biol 2003; 111:135-40.
Guaschino S, Michelone G, Stola E, et al. Biol Res Pregnancy Perinatol 1986; 7:20-2.
Summary Pregnancy Category: C
Lactation Category: S (likely)

  • There are other antifungal agents with higher clinical efficacy and more experience during pregnancy.

Edrophonium — (Enlon; Reversol; Tensilon)

International Brand Names

Enlon (Canada)

Drug Class Cholinesterase inhibitors; Musculoskeletal agents
Indications Diagnosis of myasthenia gravis, anesthesia adjunct
Mechanism Parasympathetic, cholinesterase inhibitor
Dosage With Qualifiers Myasthenia gravis, diagnosis—2 mg IV test dose over 15–30 sec; if no response after 1 min, repeat with 8 mg; if a reaction, halt infusion and administer atropine 0.5 mg IV
Anesthesia, adjunct—reversal of nondepolarizing neuromuscular blockade: 500 mcg/kg IV given 1 min after atropine 0.02 mg/kg IV push

  • Contraindications —hypersensitivity, intestinal obstruction

  • Caution —asthma, arrhythmia

Maternal Considerations Edrophonium is a short- and rapid-acting cholinergic drug. There are no adequate reports or well-controlled studies of edrophonium in pregnant women. Older literature suggests anticholinesterases may trigger preterm labor.
Side effects include severe cholinergic reaction, arrhythmias, respiratory paralysis, diplopia, tearing, seizures, dysphagia, dysarthria, dysphonia, hypotension, diarrhea, and abdominal pain.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether edrophonium crosses the human placenta; the chemical structure suggests it will not. There are no reports of either fetal toxicity or teratogenicity. Rodent teratogenicity studies apparently have not been performed.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether edrophonium enters human breast milk. The chemical structure suggests it will not be excreted into the breast milk. Considering the indication and rapid breakdown, one-time edrophonium use is unlikely to pose a clinically significant risk to the breastfeeding neonate.
Drug Interactions May trigger a cholinergic crisis if combined with cholinergic drugs.
Aspirin and or dipyridamole may decrease cholinesterase inhibitory activity.
β-Blockers may increase the risk of an arrhythmia (heart block).
Will prolong the duration of neuromuscular blockade from succinylcholine.
Avoid atropine -like agents if there is a prolongation of the QT time.
Aminoglycosides may decrease muscle-stimulating efficacy.
References Drachman DB. N Engl J Med 1978; 298:186-93.
Summary Pregnancy Category: C
Lactation Category: S (probably)

  • Edrophonium should be used during pregnancy and lactation only if the benefit justifies the potential perinatal risk.

Efavirenz — (Sustiva)

International Brand Names

Efavir (India); Filginase (Argentina); Stocrin (Colombia, Hong Kong, Israel, Mexico, Peru, Singapore, South Africa, Taiwan, Thailand); Sustiva (Canada); Virorrever (Argentina)

Drug Class Antivirals; Non-nucleoside reverse transcriptase inhibitors
Indications HIV infection
Mechanism NNRTI
Dosage With Qualifiers HIV—600 mg PO qd

  • Contraindications —hypersensitivity

  • Caution —hepatic dysfunction, cisapride use, triazolam use, midazolam use, astemizole use

Maternal Considerations There are no adequate reports or well-controlled studies of efavirenz in pregnant women. However, there are several case series of HIV-infected women who conceived while taking efavirenz. It is often prescribed in combination with tenofovir and emtricitabine ; it is the first choice in many second and third world countries. It is common practice to switch women on efavirenz to another NNRTI prior to a planned pregnancy or if the patient presents in the early first trimester. The majority of these pregnancies are unintended, stressing the importance of contraceptive counseling. Hepatotoxicity may be more common during pregnancy. Perhaps the most relevant consideration when initiating a pregnant woman on an NNRTI is whether normally tolerated side effects will be magnified by pregnancy.
Side effects include Stevens-Johnson syndrome, dermatitis, erythema multiforme, rash, drowsiness, insomnia, abnormal dreams, hyperlipidemia, diarrhea, N/V, fever, and hepatic dysfunction.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Efavirenz crosses the placenta, achieving an F:M ratio approximating unity. Its use has been associated with CNS malformations in monkey fetuses at doses that approximate those in humans and with NTDs in exposed human fetuses. Although these studies led to a reclassification of the drug to category D, postmarketing studies reveal efavirenz is not a significant human teratogen. Rodent studies reveal an increased frequency of reabsorptions.
Breastfeeding Safety Efavirenz enters human breast milk. In one study with a mean efavirenz maternal plasma concentration of 6.6 mg/L, the milk concentration was 3.5 mg/L and the relative infant dose 6.1%. Breastfeeding is generally contraindicated in HIV-infected women where formula is available to reduce the risk of neonatal transmission. However, none of the children studied became infected while breastfeeding. Efavirenz is excreted in the breast milk of rats.
Drug Interactions Efavirenz is a CYP3A4 inducer. Thus substrates of CYP3A4 may have lower than normal plasma concentrations when used in tandem. It also inhibits CYP2C9, 2C19, and 3A4. Co-administration of drugs primarily metabolized by these isozymes may result in altered plasma concentrations of the co-administered drug, necessitating dose adjustments.
Drug inducers of CYP3A4 (e.g., phenobarbital, rifampin, rifabutin ) may increase efavirenz clearance and lower plasma concentrations.
Astemizole, midazolam, triazolam, cisapride, ergot derivatives, and voriconazole should not be administered with efavirenz.
Efavirenz may decrease concentrations of atazanavir, clarithromycin, indinavir, lopinavir, methadone, saquinavir, and sertraline.
Saquinavir should not be used as sole protease inhibitor in combination with efavirenz.
Ritonavir increases the efavirenz concentration. The combination results in a higher frequency of adverse clinical affects (e.g., dizziness, nausea, paresthesia) and laboratory abnormalities (elevated liver enzymes).
References Bussmann H, Wester CW, Wester CN, et al. J Acquir Immune Defic Syndr 2007; 45:269-73.
Cadman J. GMHC Treat Issues 1998; 12:12.
De Santis M, Carducci B, De Santis L, et al. Arch Intern Med 2002; 162:355.
Floridia M, Tamburrini E, Ravizza M, et al; The Italian Group on Surveillance on Antiretroviral Treatment in Pregnancy. Antivir Ther 2006; 11:941-6.
Fundaro C, Genovese O, Rendeli C, et al. AIDS 2002; 16:299-300.
Hill JB, Sheffield JS, Zeeman GG, Wendel GD Jr. Obstet Gynecol 2001; 98:909-11.
Phiri K, Hernandez-Diaz S, Dugan KB, et al. Pediatr Infect Dis J 2014; 33:741-6.
Schneider S, Peltier A, Gras A, et al. J Acquir Immune Defic Syndr 2008; 48:450-4.
Taylor GP, Low-Beer N. Drug Saf 2001; 24:683-702.
Summary Pregnancy Category: D (reclassified from category C in 2004)
Lactation Category: S (possibly)

  • The goal of HIV treatment during pregnancy is achievement and maintenance of a zero viral load.

  • Breastfeeding is generally contraindicated in HIV-infected women where formula is available to reduce the risk of neonatal transmission.

  • Efavirenz should be used during pregnancy and lactation only if the benefit justifies the potential perinatal risk.

  • Physicians are encouraged to register pregnant women under the Antiretroviral Pregnancy Registry (1-800-258-4263) for a better follow-up of the outcome while under treatment with efavirenz.

Eletriptan — (Relpax)

International Brand Names

Relert (Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Israel, Nicaragua, Panama); Relpax (England, France, Ireland, Mexico)

Drug Class Serotonin receptor agonists
Indications Migraine headache, acute
Mechanism Binds with high affinity to 5-HT 1B , 5-HT 1D , and 5-HT 1F receptors, causing cranial vessel constriction
Dosage With Qualifiers Migraine headache, acute—20–40 mg PO × 1; may repeat q2h × 1 if recurs; max 80 mg/24 h

  • Contraindications— hypersensitivity to drug or class, uncontrolled hypertension, cerebrovascular disease, ischemic heart disease, coronary spasm, basilar or hemiplegic migraines, PVD, ischemic bowel, 5-HT 1 agonist or ergot use < 24 h, CYP3A4 inhibitor use < 7 d

  • Caution— cardiac risk factors

Maternal Considerations Migraine is a paroxysmal disorder with attacks of headache, N/V, photo- and phonophobia, and malaise. There is no published experience with eletriptan during pregnancy.
Side effects include hypertensive crisis, MI, coronary spasm, ventricular arrhythmias, CVA, peripheral vascular ischemia, bowel ischemia, N/V, cramping, dyspepsia, dysphagia, somnolence, headache, paresthesias, and chest or jaw or neck pain or pressure.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether eletriptan crosses the human placenta. A pregnancy registry that included 528 women with first-trimester sumatriptan exposure revealed no evidence of teratogenicity. In mice and rabbits, eletriptan at 6–12 × the MRHD during organogenesis is associated with IUGR and skeletal abnormalities.
Breastfeeding Safety According to the manufacturer, eletriptan is excreted in human breast milk. The relative infant dose was 0.02%. The M:P ratio was 1:4 but showed great variability.
Drug Interactions Eletriptan is metabolized primarily by CYP3A4.
Ergot-containing drugs (e.g., dihydroergotamine, methysergide ) are reported to cause prolonged vasospastic reactions that may be additive. Use of ergot-type medications within 24 h of eletriptan is not recommended
Propranolol increases both the C max and AUC by 10% and 33%, respectively.
Use of other 5-HT 1 agonists within 24 h of eletriptan is not recommended.
References Ephross SA, Sinclair SM. Headache. 2014; 54: 1158-72.
Summary Pregnancy Category: C
Lactation Category: S (probably)

  • Eletriptan should be used during pregnancy and lactation only if the benefit justifies the potential perinatal risk.

  • There are alternative agents with a more reassuring safety profile.

Enalapril — (Vasotec)

International Brand Names

Acetec (Malaysia); Acetensil (Spain); Alapren (South Africa); Alphapril (Australia); Alphrin (Korea); Analept (Bulgaria, Greece); Anapril (Hong Kong, Singapore); Antens (Korea); Auspril (Australia); Bajaten (Chile); Beartec (Korea); Benalipril (Germany); Biocronil (Colombia); BQL (India, South Africa); Cardiopril (Peru); Controlvas (Spain); Converten (India); Convertin (Israel); Corprilor (Singapore); Elfonal (Korea); EnaABZ (Germany); Enahexal (New Zealand); Enaladil (Mexico); Enalagamma (Germany); Enalapril (Germany, Spain); Enaldun (Hong Kong); Enalin (Korea); Enaloc (Finland); Enalpapril (Israel); Enam (China); Enap (Singapore); Enapren (Italy); Enapril (Thailand); Enaprin (Korea); Enaril (Korea, Thailand); Enetil (Colombia); Enpril (Korea); Envas (India); Erotec (Korea); Etron (Korea); Glioten (Brazil, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru); Hipertal (Philippines); Hypace (Philippines, South Africa); Hytrol (India); Innovace (England, Ireland); Inoprilat (Indonesia); Invoril (China, India, Malaysia, Singapore, South Africa, Thailand); Kenopril (Mexico); Lapril (Thailand); Lenipril (Korea); Lepril (Korea); Lotrial (Argentina, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Nicaragua, Panama, Peru); Lowtril (Korea); Malepril (Korea); Meipril (Indonesia); Naprilene (Italy); Naritec (Korea, Thailand); Nuril (India); Pharmapress (Hong Kong); Pres (Germany); Presil (Colombia); Renallapin (Korea); Renaton (Korea); Renavace (Japan); Renitec (Argentina, Austria, Belgium, Brazil, Bulgaria, China, Colombia, Czech Republic, Denmark, Ecuador, Egypt, Finland, France, Greece, Hong Kong, Hungary, Malaysia, Mexico, Netherlands, New Zealand, Norway, Peru, Philippines, Poland, Portugal, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, Venezuela); Renitek (Russia); Reniten (Switzerland); Renivace (Indonesia); Repantril (Indonesia); Sintec (Taiwan); Tenace (Indonesia); Unaril (Taiwan); Unipril (Colombia); Vasopress (Philippines); Vasotec (Canada); Xanef (Germany)

Drug Class ACEI/A2R-antagonists
Indications Hypertension, CHF, MI, nephropathy
Mechanism ACEI
Dosage With Qualifiers Hypertension—begin 5 mg PO qd (max 40 mg qd); alternatively, 0.625–1.25 mg IV, then up to 5 mg IV q6h
CHF—begin 2.5 mg PO qd (max 40 mg qd)
MI—begin 2.5 mg PO qd (max 40 mg qd), and quickly titrate dose up
Nephropathy—5–20 mg PO qd
NOTE: Also combined with either hydrochlorothiazide or felodipine.

  • Contraindications —hypersensitivity, renal artery stenosis

  • Caution —renal dysfunction, hypovolemia, severe CHF, collagen vascular disease

Maternal Considerations There are no adequate reports or well-controlled studies of enalapril in pregnant women. It is generally well tolerated, and pregnancy does not alter dosing. However, enalapril should be discontinued immediately when pregnancy is diagnosed and replaced with another suitable hypotensive agent to prevent or minimize the fetal risks.
Side effects include angioedema, hypotension, renal failure, hyperkalemia, hepatotoxicity, neutropenia, pancreatitis, dizziness, N/V, fatigue, dyspepsia, rash, urticaria, and myalgia.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Enalapril crosses the human placenta, but it does not equilibrate, even after 6 h, at least in the isolated perfused model. Relative to laboratory-tested species, the human fetus has higher vulnerability to enalapril and other ACEIs, exhibiting a syndrome not seen in experimental animals because humans develop these systems prior to calvarial ossification at the end of the first trimester. Exposure to agents that interfere with angiotensin actions are associated with cranial hypoplasia, anuria, reversible or irreversible renal failure, death, oligohydramnios, prematurity, IUGR, and patent ductus arteriosus, even if taken only during the first trimester. Long-term renal disease is reported in survivors. Enalapril produces fetal hypotension in rhesus macaques.
Breastfeeding Safety There are no adequate reports or well-controlled studies in nursing women. Trace amounts of enalapril are detected in breast milk, and the relative infant dose is < 0.2%. It is unlikely a term infant would experience any adverse effects. Captopril and benazepril are reasonable alternatives.
Drug Interactions Diuretics, especially if recently initiated, may be associated with hypotension after initiation of enalapril . The possibility can be minimized by volume loading, discontinuing the diuretic, or increasing salt intake before enalapril .
The antihypertensive effect appears augmented by agents that release renin (e.g., diuretics).
In patients with preexisting renal disease, NSAIDs may cause a further decline that is usually reversible if enalapril is discontinued.
Attenuates potassium loss caused by thiazide-type diuretics when given IV. Potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride ), potassium supplements, or potassium-containing salt substitutes may cause significant increases in the serum potassium and should be used with caution.
Lithium toxicity has been reported in patients receiving ACEIs, including enalapril. Serum lithium levels should be monitored frequently.
References Burrows RF, Burrows EA. Aust N Z J Obstet Gynaecol 1998; 38:306-11.
Ducsay CA, Umezaki H, Kaushal KM, et al. Am J Obstet Gynecol 1996; 175:50-5.
Miller RK, Jessee L, Barrish A, et al. Teratology 1998; 58:76-81.
Redman CW, Kelly JG, Cooper WD. Eur J Clin Pharmacol 1990; 38:99.
Tabacova S. Crit Rev Toxicol 2005; 35:747-55.
Tabacova S, Little R, Tsong Y, et al. Pharmacoepidemiol Drug Saf 2003; 12:633-46.
Summary Pregnancy Category: D
Lactation Category: S (probably)

  • Enalapril and other inhibitors of angiotensin’s actions should be avoided during pregnancy if possible.

  • There are alternative agents for which there is more experience during pregnancy and lactation.

  • When the mother’s disease requires treatment with enalapril, the lowest doses should be used followed by close monitoring of the fetus.

Enoxaparin — (Lovenox)

International Brand Names

Aerotina (Argentina); Clexane (Belgium, Bulgaria, China, Czech Republic, England, Germany, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Korea, Malaysia, Netherlands, Paraguay, Philippines, Poland, Russia, Spain, Switzerland, Turkey, Uruguay, Venezuela); Clexane 40 (South Africa); Clexane Forte (Israel); Klexane (Canada, Denmark, Finland, Norway, Sweden); Lovenox (Austria, Canada, France, Indonesia, Portugal)

Drug Class Anticoagulants; Low-molecular-weight heparins
Indications Prevention and treatment of venous thrombosis in the maternal or placental circulation
Mechanism Binds ATIII, accelerates inhibition of factor Xa
Dosage With Qualifiers DVT prophylaxis (episode greater than 12 mo before pregnancy, no thrombophilia)—begin at 20–40 mg SC qd; DVT/PE within 12 mo pregnancy; therapeutic levels 30-80 mg SC bid
DVT prophylaxis (associated with thrombophilia)—depends on the thrombophilia and medical history. Consult a specialty text such as High Risk Pregnancy: Management Options .
Antiphospholipid syndrome—begin at 20–40 mg SC qd
Cesarean section—at least 40 mg SC qd until patient is active
Treatment of acute thrombosis—1–1.5 mg/kg SC q12h
NOTE: Target for anti-Xa activity depends on indication and laboratory test used.
NOTE: Does not significantly influence bleeding time, PT, or PTT.
NOTE: Manufacturer has specifically sought to discourage its use during pregnancy.

  • Contraindications —hypersensitivity, active bleeding, thrombocytopenia

  • Caution —diabetic retinopathy, renal dysfunction

Maternal Considerations The incidence of PE and DVT is higher in pregnant compared with nonpregnant patients, reaching a rate of 0.05%–1% in all pregnancies and as high as 3% after cesarean section. Pregnancy increases the clearance of both heparin and LMW heparinoids such as enoxaparin. Though it is logical to assume dosing should be periodically adjusted during pregnancy, an RCT using a composite outcome concluded there was no benefit. This conclusion differs from another RCT of a different at-risk population. Until additional information is available, it is suggested periodic monitoring continue throughout pregnancy (anti-Xa activity of 0.20–0.40 U/mL for prophylaxis, and 0.4–0.7 U/mL for full anticoagulation). The mean maximum dose required to achieve a therapeutic anti-Xa level at 5–6 h after injection in one study was 38.1 mg every 12 h (range 30–75 mg every 12 h). The mean anti-Xa level was 0.28 IU/mL (median 0.3, range 0.05–0.8 IU/mL). The risk of osteoporosis is similar to that with unfractionated heparin, though the risk of thrombocytopenia may be lower. Acute thrombosis should be treated with therapeutic anticoagulation for the remainder of pregnancy and for at least 6 w postpartum (a minimum of 3 mo total).
Enoxaparin has been used for prophylaxis during pregnancy in women with thrombophilia or mechanical heart valve or antiphospholipid syndrome. There have been multiple deaths of treated pregnant women with a mechanical heart valve, and the manufacturer specifically discourages its use for this indication. Women treated with LMWHs for prevention of thromboembolic complications are at risk of developing an epidural or spinal hematoma after neuraxial anesthesia. Unlike unfractionated heparin, enoxaparin is not predictably reversed with protamine. Preferably, LMWHs are replaced with unfractionated heparin at 36 w. Otherwise, patients should be instructed to withhold their next injection once contractions begin or 12 h prior to a planned induction of labor. Enoxaparin should be discontinued 12–24 h (depending on daily dose) before placement of neuraxial (epidural or spinal) anesthesia. Enoxaparin should not be (re)instituted until at least 12 h after removal of an indwelling epidural catheter.
Side effects include epidural/spinal hematoma, thrombocytopenia, paralysis, CHF, pneumonia, anemia, hemorrhage, fever, injection site hematoma or bruising, hematuria, and elevated transaminases.
Fetal Considerations Neither unfractionated nor fractionated heparin crosses the human placenta, and thus enoxaparin does not pose a direct risk to the human fetus. Epidemiologic studies are reassuring. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety There are no well-controlled studies in nursing women. One investigation found no anti-Xa activity in the breast milk from a single patient, and another in a population of 12 women. Enoxaparin is unlikely to cross in light of its high MW, and if it does cross and is ingested by the nursing newborn, it is likely to be degraded.
Drug Interactions Agents that can enhance the risk of bleeding (e.g., anticoagulants; platelet inhibitors including aspirin; salicylates; NSAIDs, including ketorolac; dipyridamole; sulfinpyrazone ) should be discontinued prior to beginning enoxaparin.
References Backos M, Rai R, Baxter N, et al. Br J Obstet Gynaecol 1999; 106:102-7.
Bar J, Mashiah R, Cohen-Sacher B, et al. Thromb Res 2001; 101:235-41.
Carlin AJ, Farquharson RG, Quenby SM, et al. Hum Reprod 2004; 19:1211-4.
Casele H, Haney EI, James A, et al. Am J Obstet Gynecol 2006; 195:1109-13.
Casele HL, Laifer SA, Woelkers DA, Venkataramanan R. Am J Obstet Gynecol 1999; 181:1113-7.
Dimitrakakis C, Papageorgiou P, Papageorgiou I, et al. Haemostasis 2000; 30:243-8.
Huxtable LM, Tafreshi MJ, Ondreyco SM. Clin Appl Thromb Hemost. 2005;11:171-81.
James D, Steer P, Weiner CP, Gonik B (Eds.) High Risk Pregnancy: Management Options, 2nd ed. Philadelphia: WB Saunders, 2006.
Ko A, Harada MY, Barmparas G, et al. JAMA Surg 2016 Jul 6. [Epub ahead of print]
Laurent P, Dussarat GV, Bonal J, et al. Drugs 2002; 62:463-77.
Lepercq J, Conard J, Borel-Derlon A, et al. BJOG 2001; 108:1134-40.
Rowan JA, McCowan LM, Raudkivi PJ, North RA. Am J Obstet Gynecol 2001; 185:633-7.
Salim R, Nachum Z, Gavish I, et al. Thromb Haemost 2016 Jul 21;116(4). [Epub ahead of print]
Torricelli M, Reis FM, Florio P, et al. Ultrasound Med Biol 2006; 32:1431-5.
Summary Pregnancy Category: B
Lactation Category: S (probably)

  • Enoxaparin is a more costly alternative to unfractionated heparin with likely equal efficacy and a similar risk of osteoporosis complicating long-term therapy.

  • The dose of enoxaparin administered must be monitored periodically throughout pregnancy and the puerperium by the measurement of anti-Xa activity to assure appropriate levels.

Ephedrine

International Brand Names

None identified.

Drug Class Adrenergic agonists; Bronchodilators; Decongestants, nasal
Indications Nasal decongestant, pressor support after epidural analgesia
Mechanism Causes release of epinephrine and NE from nerve endings, resulting in mainly β-adrenergic stimulation; also a weak direct-acting vasopressor
Dosage With Qualifiers Decongestant—25–50 mg PO q6h (max 150 mg/d)
NOTE: May be combined with theophylline, pentobarbital, or potassium iodide.

  • Contraindications —hypersensitivity, thyroid toxicosis, porphyria, CAD, hypertension, use of an MAOI within 14 d

  • Caution —glaucoma, arrhythmia, hyperthyroidism

Maternal Considerations There are no adequate reports or well-controlled studies of ephedrine in pregnant women. When abused as a decongestant, ephedrine may exacerbate the hypertension associated with preeclampsia. There is a long clinical experience with the use of ephedrine during labor to treat hypotension associated with neuraxial anesthesia. It is considered the vasopressor of choice unless contraindicated by maternal condition (e.g., tachycardia or coexisting valvular stenosis) and is protective of the uterine circulation, perhaps through release of NO in the placental vessels. But although interventions such as colloids, ephedrine, phenylephrine, or lower leg compression reduce the incidence of hypotension, none has been shown to eliminate the need to treat maternal hypotension during spinal anesthesia for cesarean section. An RCT demonstrated that adjusting the dose of bupivacaine to a patient’s height and weight decreases the incidence and severity of maternal hypotension while reducing the use of ephedrine . The need for ephedrine can also be reduced by arranging the patient in the left lateral position with the head elevated while placing the spinal. Women with preeclampsia are less likely to experience hypotension at the time of spinal anesthesia and require significantly less ephedrine when they do.
Side effects include arrhythmias, insomnia, nervousness, dizziness, and tachycardia.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Ephedrine apparently crosses the placenta, though the kinetics remain to be elucidated. Rodent teratogenicity studies have not been conducted. The long clinical experience with the drug, both in OTC preparations and in the labor suite, is reassuring.
Breastfeeding Safety There are no adequate reports or well-controlled studies in nursing women. Ephedrine is excreted and concentrated into breast milk, but < 1% of the ingested dose is excreted. Thus it is generally considered safe for breastfeeding women. However, a single dose of pseudoephedrine reduces 24-h milk production by as much as 25%. Therefore it is best to avoid repeated use while breastfeeding.
Drug Interactions Bromocriptine may increase the risk of hypertension, stroke, and MI.
Cyclobenzaprine may decrease the pressor effect.
Atomoxetine may increase the pressor response.
May decrease the hypoglycemic effect of insulin.
References Aljazaf K, Hale TW, Ilett KF, et al. Br J Clin Pharmacol 2003; 56:18-24.
Aya AG, Vialles N, Tanoubi I, et al. Anesth Analg 2005; 101:869-75.
Cooper DW, Carpenter M, Mowbray P, et al. Anesthesiology 2002; 97:1582-90.
Cyna AM, Andrew M, Emmett RS, et al. Cochrane Database Syst Rev 2006; (4):CD002251.
Ducros L, Bonnin P, Cholley BP, et al. Anesthesiology 2002; 96:612-6.
Findlay JW, Butz RF, Sailstad JM, et al. Br J Clin Pharmacol 1984; 18:901-6.
Li P, Tong C, Eisenach JC. Anesth Analg 1996; 82:288-93.
Siddiqui KM, Ali MA, Ullah H. Korean J Anesthesiol. 2016; 69:143-8.
Summary Pregnancy Category: C
Lactation Category: S

  • Ephedrine is commonly found in many OTC preparations.

  • It is a popular agent for the treatment of hypotension associated with neuraxial anesthesia.

Epinephrine — (Adrenalin Chloride; Ana-Guard; Epifrin; EpiPen; Glaucon; Philip; Racepinephrine; Sus-Phrine)

International Brand Names

Adrenalin (Bulgaria, Canada, Finland, Norway, Sweden, Turkey); Adrenalina (Italy); Adrenalina Sintetica (Switzerland); Adrenaline (Greece, Russia); Adrenaline Aguettant (France); Adrenalini Bitarticas (Indonesia); Adrenalin Medihaler (Denmark, Finland); Ana-Guard (South Africa); Anapen (France); Bosmin (Taiwan); Epifrin (New Zealand); Epinefrina (Chile); Epipen (Canada, Israel, South Africa); Epipen Jr. 0.15mg Adrenaline Auto-Injector (Australia); Epipen Junior (Israel); Eppy (Bulgaria, Ireland, Italy, South Africa, Sweden); Eppy “N” (Israel); Eppystabil (Austria); Glaucon (Czech Republic); Glaufrin (Sweden); Isopto Epinal (Spain); L-Adrenalin (Austria); Medihaler-Iso (South Africa); Posumin (Taiwan); Simplene (England, Ireland, South Africa); Suprarenin (Austria); Weimer Adrenaline (Hong Kong, Philippines); Weradren (Philippines)

Drug Class Adrenergic agonists; Bronchodilators; Inotropes; Ophthalmics; Pressors
Indications Severe asthma, anaphylaxis, cardiac arrest
Mechanism Potent activator of α- and β-adrenoceptors
Dosage With Qualifiers Severe asthma—0.1–0.5 mg SC q10–15 min
Anaphylaxis—0.1–0.5 mg SC q10–15 min (or 0.1–0.25 mg IV over 5–10 min)
Cardiac arrest—0.5–1 mg IV q3–5 min prn (or 1 mg via ET tube, 0.1–1 mg intracardiac); may follow with 1–4 mcg/min constant infusion
NOTE: Usually a 1:10,000 solution; may be combined with a local anesthetic.

  • Contraindications —hypersensitivity, narrow-angle glaucoma, CAD, CV disease, sulfite allergy

  • Caution —asthma, hyperthyroidism

Maternal Considerations Epinephrine is commonly used for the relief of severe bronchospasm secondary to allergy. There are no adequate reports or well-controlled studies of epinephrine in pregnant women. Theoretically, it could lead to a decrease in uterine blood flow. Epinephrine in solution with local anesthetic decreases vascular absorption of local anesthetic, intensifying neural blockade and in some cases prolonging the duration of the block. The maternal response may be potentiated by a variety of drugs and by preeclampsia.
Side effects include stroke, cerebral hemorrhage, arrhythmias, hypertension, tachycardia, tremor, N/V, and headache.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Epinephrine apparently rapidly crosses the human placenta, which is rich in catecholamine receptors. It is teratogenic in mice at 25 × the MRHD.
Breastfeeding Safety There is no published experience with epinephrine in nursing women. Based on its molecular size, epinephrine is likely excreted into human breast milk. However, any epinephrine would be rapidly destroyed when orally ingested. It is unlikely to pose a clinical risk to the breastfeeding neonate.
Drug Interactions Use with excessive digitalis, mercurial diuretics, or other drugs that sensitize the heart to arrhythmias is not recommended.
May be potentiated by TCAs, certain antihistamines (e.g., chlorpheniramine, diphenhydramine, tripelennamine ), and levothyroxine.
References Nguyen TT, Tseng YT, McGonnigal B, et al. Placenta 1999; 20:3-11.
Summary Pregnancy Category: C
Lactation Category: S

  • Epinephrine should be used during pregnancy and lactation only if the benefit justifies the potential perinatal risk.

Epoetin alfa — (EPO; Epogen; Eprex; Erythropoietin; Procrit)

International Brand Names

Epoade (Japan); Epokine (Philippines); Epoxitin (Italy); Eprex (Belgium, Bulgaria, Czech Republic, Denmark, England, Finland, France, Greece, Hungary, Italy, Netherlands, Norway, Portugal, Russia, South Africa, Spain, Sweden, Switzerland, Turkey); Erypo (Austria, Germany, Switzerland); Espo (Japan); Hemapo (Indonesia)

Drug Class Hematopoietic agents; Hormones
Indications Transfusion reduction or severe hyporegenerative anemia secondary to AZT therapy, chronic renal failure, or chemotherapy
Mechanism Stimulates RBC production
Dosage With Qualifiers Transfusion reduction—300 U/kg SC 3 ×/w beginning 10 d preoperative
AZT-related anemia—150 U/kg SC/IV 3 ×/w beginning for 8 w; may increase to 300 U/kg for 3 w if poor response
Renal failure–related anemia—50–100 U/kg IV/SC 3 ×/w
Chemotherapy-related anemia—150 U/kg SC/IV 3 ×/w beginning for 8 w; may increase to 300 U/kg for 3 w if poor response

  • Contraindications —hypersensitivity

  • Caution —hypertension; iron, folate, or vitamin B 12 deficiency; CHF; CAD; seizure disorder; sickle cell anemia

Maternal Considerations There are no adequate reports or well-controlled studies of epoetin in pregnant women. Case series suggest hypertension may complicate as many as 20% of cases, perhaps reflecting the fact it is most often prescribed for pregnant women under going chronic renal dialysis. Adjuvant epoetin safely enhances the efficacy of iron sucrose in the treatment of gestational iron deficiency anemia resistant to orally administered iron alone. In one case report, it was used successfully to treat a pregnant Jehovah’s Witness with sickle cell disease.
Side effects include severe hypertension, CHF, MI, stroke, DVT, seizures, headache, arthralgia, tachycardia, fever, diarrhea, N/V, dyspnea, dizziness, rash, and paresthesias.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether epoetin crosses the human placenta. It does not cross the isolated placental cotyledon. In the offspring of rats treated with 500 U/kg, a diverse group of abnormalities was observed, including delayed ossification. There were no effects below that dose.
Breastfeeding Safety There is no published experience in nursing women. The molecular weight makes it unlikely that synthetic epoetin enters human breast milk, though erythropoietin is a normal component of breast milk.
Drug Interactions No clinically significant interactions identified.
References Breymann C, Visca E, Huch R, Huch A. Am J Obstet Gynecol 2001; 184:662-7.
Danko J, Huch R, Huch A. Lancet 1990; 335:737-8.
Reisenberger K, Egarter C, Kapiotis S, et al. Obstet Gynecol 1997; 89:738-42.
Sifakis S, Angelakis E, Vardaki E, et al. Gynecol Obstet Invest 2001; 51:150-6.
Tan TL, Ahmad H, Jhavar R, et al. J Obstet Gynaecol 2007; 27:82-3.
Summary Pregnancy Category: C
Lactation Category: S (probably)

  • Epoetin should be used during pregnancy and lactation only if the benefit justifies the potential perinatal risk.

  • A growing body of evidence suggests it is advantageous for certain women with iron deficiency.

Epoprostenol — (Flolan)

International Brand Names

Flolan (Australia, Austria, Belgium, Canada, Denmark, England, France, Ireland, Israel, Italy, Netherlands, Singapore, Spain)

Drug Class Antihypertensives; Platelet inhibitors; Prostaglandins; Vasodilators
Indications Pulmonary hypertension
Mechanism Prostacyclin is a direct vasodilator.
Dosage With Qualifiers Pulmonary hypertension—2 ng/kg/min IV, increase 1–2 ng/min q15min; infuse through a central line

  • Contraindications —hypersensitivity, CHF, pulmonary edema

  • Caution —unknown

Maternal Considerations Epoprostenol is prostacyclin. Primary pulmonary hypertension is a rare, progressive condition aggravated by the physiologic changes of pregnancy. Epoprostenol has been used to successfully treat women with either primary or secondary pulmonary hypertension during pregnancy and in the immediate postpartum period. The maternal mortality rate ranges from 30% to 50%.
Side effects include pulmonary edema, rebound pulmonary hypertension, thrombocytopenia, headache, N/V, anxiety, tachycardia, hypotension, chest pain, diarrhea, paresthesias, and dyspnea.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether epoprostenol crosses the human placenta. The placenta and fetus synthesize large quantities of prostacyclin. There is no reason to suspect toxicity. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether epoprostenol is excreted into breast milk. However, prostacyclin is a normal component of human breast milk and its short t/2 makes it unlikely synthetic prostacyclin would enter breast milk and have a clinical effect after ingestion by the infant.
Drug Interactions Hypotension may occur when given with diuretics, antihypertensive agents, or other vasodilators.
May decrease the clearance of furosemide and digoxin by about 15%.
References Badalian SS, Silverman RK, Aubry RH, Longo J. J Reprod Med 2000; 45:149-52.
Kuhn DC, Walenga RW, Stuart MJ. Am J Perinatol 1991; 8:179-84.
Stewart R, Tuazon D, Olson G, Duarte AG. Chest 2001; 119:973-5.
Summary Pregnancy Category: B
Lactation Category: S (probably)

  • Epoprostenol has been successfully employed in several women with life-threatening pulmonary hypertension.

Eprosartan mesylate — (Teveten)

International Brand Names

Epratenz (Belgium); Teveten (Australia, Austria, Canada, Denmark, England, France, Germany, Hong Kong, Ireland, Korea, Netherlands, Philippines, Sweden)

Drug Class Antihypertensive; AT-1 antagonists
Indications Hypertension
Mechanism Highly specific AT-1 receptor antagonist
Dosage With Qualifiers Hypertension—600–800 mg PO qd

  • Contraindications —hypersensitivity, pregnancy

  • Caution —renal artery stenosis, volume depletion, CHF

Maternal Considerations There is no published human experience with eprosartan during pregnancy. Extensive experiences with other compounds that inhibit aspects of the angiotensin-renin system indicate it should be considered a human teratogen and avoided during pregnancy.
Side effects include severe hypertension, CHF, MI, stroke, DVT, seizures, headache, arthralgia, tachycardia, fever, diarrhea, N/V, dyspnea, dizziness, rash, and paresthesias.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether eprosartan crosses the human placenta. Similar class drugs cross the placenta and are known teratogens. Later exposure to agents that interfere with angiotensin action is associated with cranial hypoplasia, anuria, reversible or irreversible renal failure, death, oligohydramnios, prematurity, IUGR, and patent ductus arteriosus. This “ACEI fetopathy” does not have a counterpart in experimental animals because humans develop these systems prior to calvarial ossification at the end of the first trimester.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether eprosartan enters human breast milk. Eprosartan is excreted into rodent breast milk. Until further study, it should be avoided if the infant is very premature, and if term, the infant should be monitored for possible adverse effects. Eprosartan should be given at the lowest effective dose and breastfeeding avoided at times of peak drug levels if breastfeeding continues.
Drug Interactions No clinically significant interactions identified.
References There is no published experience in pregnancy or during lactation.
Summary Pregnancy Category: D
Lactation Category: U

  • Eprosartan and other inhibitors of angiotensin’s actions should be avoided during pregnancy if possible as they are likely human teratogens and clearly cause a fetopathy that is often not reversible.

  • There are alternative agents for which there is more experience during pregnancy and lactation such as benazepril , captopril , and enalapril .

  • When the mother’s disease requires treatment with eprosartan, the lowest doses should be used, followed by close monitoring of the fetus.

Ergocalciferol — (Biocatines D2 masiva; Deltalin; Drisdol; Radiostol; Vitamin D)

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