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A


Acarbose — (Precose)

International Brand Names

Glibose (Taiwan); Glicobase (Italy); Glucobay (Argentina, Austria, Bangladesh, Belgium, Brazil, Bulgaria, Chile, Colombia, Costa Rica, Czech Republic, Denmark, Dominican Republic, Ecuador, El Salvador, England, Germany, Greece, Guatemala, Honduras, Hungary, India, Israel, Italy, Japan, Korea, Malaysia, Mexico, Netherlands, Nicaragua, Norway, Pakistan, Panama, Peru, Poland, Portugal, Spain, Sweden, Switzerland); Gluconase (Philippines); Glumida (Spain); Prandase (Canada, Israel); Rebose (India)

Drug Class α-Glucosidase inhibitor; Antidiabetic agents; Oral hypoglycemics
Indications Diabetes mellitus, type 2
Mechanism An oral pancreatic α-amylase and intestinal α-glucoside hydrolase inhibitor that delays bowel carbohydrate metabolism, slowing the postprandial rise in glucose
Dosage With Qualifiers Diabetes mellitus, type 2—begin 25 mg (50 mg if > 60 kg); thereafter, 50–100 mg PO ac tid based on glucose levels

  • Contraindications —hypersensitivity to drug or class, DKA, cirrhosis, intestinal obstruction or malabsorption syndromes

  • Caution —renal dysfunction

Maternal Considerations Acarbose has been shown to reduce/delay the onset of type 2 diabetes in patients with impaired glucose intolerance. There are no adequate reports or well-controlled studies of acarbose in pregnant women. Two studies of pregnant women with impaired glucose tolerance compare acarbose to other oral hypoglycemic agents . Acarbose produced outcomes as good or superior to insulin and glyburide.
Side effects include intestinal discomfort consisting of pain, diarrhea, flatulence, elevated LFTs, and jaundice.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Only 2% of the oral dose is absorbed. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses almost 10 × higher than those used clinically.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether acarbose enters human breast milk. However, < 2% of acarbose is bioavailable. It is unlikely any would be excreted into the milk and/or absorbed by the neonate. The drug and/or its metabolites have been found in the milk of lactating rats at levels reaching 10 times the maternal plasma levels. A single rat study suggests acarbose might alter the composition of breast milk by inhibiting lipogenesis.
Drug Interactions Some drugs such as thiazides (and similar class diuretics), corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin , nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid can cause hyperglycemia. Women taking both acarbose and one of these drugs should be monitored closely for loss of glucose control. Discontinuation of such drugs may lead to hypoglycemia.
Intestinal adsorbents (e.g., charcoal) and digestive enzyme such as amylase and pancreatin may reduce the effect of acarbose and should not be taken together.
Acarbose may alter digoxin bioavailability when they are co-administered.
Neomycin may decrease acarbose metabolism.
Quinolone antibiotics, SSRIs, salicylates, and MAO inhibitors may enhance the hypoglycemic effect of acarbose and other blood glucose lowering agents.
References Hanefeld M, Schaper F, Koehler C. Cardiovasc Drugs Ther 2008; 22:225-31.
Mercer SW, Williamson DH. Biochem J 1987; 242:235-43.
Product information. Precose, Bayer Corp., 1997.
Zarate A, Ochoa R, Hernandez M, Basurto L. Ginecol Obstet Mex 2000; 68:42-5.
Bertini AM, Silva J, Taborda W, et al. J Perinat Med, 2005, 33:519-23
Summary Pregnancy Category: B
Lactation Category: S (likely)

  • Insulin and diet regulation remain the standard treatments for glucose intolerance during pregnancy.

  • There is a growing interest in the use of oral hypoglycemic agents during pregnancy, and acarbose is an interesting candidate.

Acetaminophen — (APAP; Acephen; Aceta; Acetaminophen Uniserts; Anapark; Apacet; Asidon; Calip; Dapacin; Ed-Apap; Feverall; Genapap; Genebs; Mapap; Maranox; Neopap; Oraphen-PD; Panadol; Redutemp; Ridenol; Silapap; Tapanol; Tempra; Tylenol; Uni-Ace)

International Brand Names

Abenol (Canada); Acamol (Chile, Israel); Acamoli Forte suppositories for Kids (Israel); Acet (Malaysia, Philippines); Acetalgin (Switzerland); Acetam (Peru); Acetamol (Italy); ACET suppositories (Singapore); Adorem (Colombia); Afebrin (Hong Kong, Indonesia, Philippines); Algiafin (Chile); Alphagesic (Indonesia); Alvedon (Sweden); Amol (Israel); A-Mol (Thailand); Anaflon (Germany); Analgiser (Israel); Apirex (France); Arfen (Malaysia, South Africa); Atamel (Peru); Benuron (Japan); Ben-U-Ron (Belgium, Germany, Portugal, Switzerland); Biogesic (Indonesia, Philippines, Thailand); Biogesic Suspension (Hong Kong); Bodrex (Indonesia); Brenal (Philippines); Calapol (Indonesia); Calodol (Philippines); Calpol (India, Ireland, Israel, Japan, Puerto Rico, South Africa, Thailand); Causalon (Argentina); Cemol (Thailand); Christamol (Hong Kong); Claradol (Morocco); Clocephen (Philippines); Crocin (India); Daga (Thailand); Datril (Mexico, Venezuela); Depyretin (Taiwan); Dirox (Argentina); Dismifen (Mexico); Dolex (Uruguay); Dolex 500 (Colombia, Uruguay); Doliprane (France, Morocco); Dolitabs (France); Dolofen (Colombia); Dolomol (Israel); Dolorol (South Africa); Dolotemp (Mexico); Doltem (Peru); Drilan (Philippines); Dymadon (Australia); Efferalgan 500 (Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Israel, Nicaragua, Panama); Efferalganodis (France); Eraldor (Ecuador); Expandol (France); Fervex (Brazil); Flurinol (Philippines); Fortolin (China); Gelocatil (Spain); Geluprane 500 (France); Gunaceta (Indonesia); Kamolas (Indonesia); Kyofen (Colombia); Lemgrip (Belgium); Lotemp (Thailand); Malidens (India); Mebinol (Peru); Meforagesic (Philippines); Metagesic (Philippines); Mexalen (Austria, Czech Republic, Hungary); Milidon 500 (Singapore); Minopan (Korea); Mypara (Thailand); Nalgesik (Indonesia); Napa (Singapore); Napamol (South Africa); Naprex (Indonesia); NEBS (Japan); Nektol 500 (Philippines); Nilapur (Indonesia); Pacemol (Brazil, Singapore); Pacimol (India); Pamol (Denmark, New Zealand); Panadol (Belgium, Brazil, Bulgaria, Chile, England, Finland, France, Greece, Hong Kong, Indonesia, Ireland, Italy, Korea, Netherlands, South Africa, Switzerland, Taiwan, Thailand, Uruguay); Panadol Actifast (Malaysia, Singapore); Panamax (Australia); Panodil (Denmark, Norway, Sweden); Paracet (Norway); Parageniol (Paraguay); Paragin (Thailand); Paralgin (Australia); Paralief (Ireland); Paramidol (Peru); Paramol (Israel, Taiwan); Parapaed (Germany); Parapaed Junior (New Zealand); Parapaed Six Plus (New Zealand); Paratabs (New Zealand); Parvid (Philippines); Paximol (Singapore); Pedipan (Korea); Penral-Night (Korea); Pinex (Norway); Poro (Malaysia); Predimol (India); Puernol (Italy); Raperon (Korea); Rapidol (Chile); Reliv (Sweden); Remedol (Puerto Rico); Revanin (South Africa); Rhinapen elixir (Korea); Roxamol Gelcaps (Israel); Salzone (South Africa); Saridon (Colombia); Serimol (Hong Kong); Setamol (Australia); Sinedol (Dominican Republic); Taganopain (Korea); Tamifen (Ecuador); Tempra (Belgium, Canada, Costa Rica, Ecuador, El Salvador, Greece, Guatemala, Honduras, Indonesia, Japan, Mexico, Nicaragua, Panama, Spain, Thailand); Tempte (Taiwan); Temzzard (Mexico); Termofren (Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua, Panama); Turpan (Indonesia); Tylenol (Australia, Austria, Brazil, Bulgaria, Canada, China, France, Germany, Hong Kong, Israel, Japan, Korea, Mexico, Philippines, Portugal, Spain, Switzerland, Thailand, Venezuela); Tylenol Extra Fuerte (Paraguay, Peru); Tylex (Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua, Panama); Winadol (Colombia, Venezuela); Winasorb (Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua, Panama); Xebramol (Thailand); Zetifen (Philippines); Zolben (Venezuela); Zydinol (Philippines)

Drug Class Analgesics, non-narcotic; Antipyretics; NSAID
Indications Mild pain, fever, menstrual cramps, osteoarthritis, tension headache
Mechanism Nonspecific cyclooxygenase inhibitor
Dosage With Qualifiers Pain and/or fever—650–1000 mg PO/PR q4–6 h; max 4 g/d
NOTE: Included in many combinations.

  • Contraindications —hypersensitivity to drug or class

  • Caution —hepatic or renal dysfunction, chronic alcohol use, G6PD deficiency, PKU

Maternal Considerations Acetaminophen is a component of a long list of OTC medications and is used by 40%–70% of pregnant women. It is metabolized in the liver and excreted by the kidneys. During the first trimester, the mean t/2 is significantly lower and oral clearance is significantly higher compared to nonpregnant control subjects. Only during pregnancy is weight related to clearance, suggesting the dose may need to be adjusted in obese women. Ibuprofen provides more rapid relief of perineal pain after vaginal delivery. In one RCT, acetaminophen plus oxycodone was superior to patient-controlled morphine for the relief of postcesarean pain. There are no obvious differences in clearance at term. Chronic abuse and overdose are the most common problems. The damage appears secondary to free radical toxicity with consumption of glutathione. N -acetylcysteine is the treatment of choice for acute overdose. In one prospective case-control study, use of prenatal ibuprofen, naproxen, and aspirin, but not acetaminophen, increased the risk of spontaneous abortion by 80% (adjusted hazard ratio 1.8 [95% CI 1.0–3.2]). The association was stronger if the initial use occurred around conception or if the use lasted more than a week. Acetaminophen may interfere with sex and thyroid hormone function. Human trials reveal a correlation between acetaminophen use during pregnancy and increased risk for childhood wheezing and asthma.
Side effects include hepatotoxicity, nephrotoxicity, agranulocytosis, pancytopenia, hemolytic anemia, pancreatitis, rash, angioedema, and urticaria.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Acetaminophen crosses the human placenta, reaching steady state in the isolated perfused model within 1 h. The F:M ratio for acetaminophen approximated 0.12 in the pregnant ewe, and neither sulfate nor glucuronide metabolites crossed. Acetaminophen use during labor to treat the fever of chorioamnionitis is associated with improved fetal umbilical blood gases, presumably by reducing fetal oxygen demand as the maternal core temperature declines. Although it was previously suggested that exposure to acetaminophen was associated with clubfoot and digital abnormalities, these reports are not sustained in large series. Unlike aspirin, acetaminophen has no antiplatelet activity and does not pose a hemorrhagic risk to the fetus. There does appear to be a link between acetaminophen and gastroschisis/small bowel atresia.
Two studies based on population-level trends suggest acetaminophen use is associated with the incidence/prevalence of autism. One large prospective observational study concluded that the use of acetaminophen (especially when the exposure was 28 d or more) was associated with motor milestone delay, gross and fine motor impairment, communication impairment, impairments in internalizing and externalizing behaviors, and hyperactivity. Two other large cohort studies based on the Danish National Birth cohort are especially concerning. In the first, acetaminophen use during pregnancy is associated with an increased risk of autism spectrum disorder, but only when a hyperkinetic disorder was also present. This report was recently confirmed in a UK study. In the second Danish National cohort report, acetaminophen use in the first and second trimesters had a negative impact on IQ at age 5 y when taken for pain or inflammation, but not fever. Fever alone had a negative impact on IQ at age 5 y, and acetaminophen use for fever eliminated the effect of fever.
Breastfeeding Safety Acetaminophen is excreted in low concentrations into breast milk. The amount of the drug administered to the mother estimated to be available to the neonate ranges from 0.04% to 0.23%, and it is generally considered compatible with breastfeeding.
Drug Interactions Tramadol may increase the risk of acetaminophen toxicity.
Local anesthetics may increase the risk of methemoglobinemia.
Excessive use of acetaminophen and alcohol increases risk of hepatotoxicity.
There is an increased risk of acetaminophen hepatotoxicity if used with barbiturates, carbamazepine, hydantoins, and sulfinpyrazone.
References Avella-Garcia CB, Julvez J, Fortuny J et al. Int J Epidemiol. 2016 Jun 28. pii: dyw115. [Epub ahead of print]
Beaulac-Baillargeon L, Rocheleau S. Eur J Clin Pharmacol 1994; 46:451-4.
Cleves MA, Savell VH Jr, Raj S, et al; National Birth Defects Prevention Study. Birth Defects Res Part A Clin Mol Teratol 2004; 70:107-13.
Committee on Drugs, American Academy of Pediatrics. Pediatrics 1994; 93:137-50.
Davis KM, Esposito MA, Meyer BA. Am J Obstet Gynecol 2006; 194:967-71.
Eyers S, Weatherall M, Jefferies S, Beasley R. Clin Exp Allergy 2011; 41:482-89
Kamandetdecha R, Tanninandorn Y. J Med Assoc Thai 2008; 91:282-6.
Kirshon B, Moise KJ Jr, Wasserstrum N. J Reprod Med 1989; 34:955-9.
Li DK, Liu L, Odouli R. BMJ 2003; 327:368-73.
Liew Z, Ritz B, Virk J, Arah OA, Olsen J. Epidemiology. 2016 Jul 28. [Epub ahead of print]
Liew Z, Ritz B, Virk J, Olsen J. Autism Res. 2015 Dec 21. [Epub ahead of print]
Rayburn W, Shukla U, Stetson P, Piehl E. Am J Obstet Gynecol 1986; 155:1353-6.
Stergiakouli E, Thapar A, Smith GD. JAMA Pediatr. Published online August 15, 2016.
Wang LH, Rudolph AM, Benet LZ. J Pharmacol Exp Ther 1986; 238:198-205.
Weigand UW, Chou RC, Maulik D, Levy G. Pediatr Pharmacol (New York) 1984; 4:145-53.
Werler MM, Mitchell AA, Hernandez-Diaz S, Honein MA. Am J Obstet Gynecol 2005;193:771-7.
Werler MM, Sheehan JE, Mitchell AA. Am J Epidemiol 2002; 155:26-31.
Summary Pregnancy Category: B (?)
Lactation Category: S

  • Acetaminophen has been used throughout pregnancy for analgesia and to reduce fever.

  • Though generally considered safe for use during pregnancy, human studies consistently raise concern that acetaminophen may be associated with either ADHD or autism. And although it may offset the impact of maternal fever on child IQ at age 5 y, acetaminophen used for other indications in the first and second trimesters may negatively affect the child’s IQ at age 5 y. Caution is warranted.

  • Like most drugs, it should be used during the first and second trimesters only when clearly necessary.

Acetazolamide — (Acetadiazol; Acetamide; Azomid; Dehydratin; Diamox; Diamox Sequels; Diamox Sodium; Ederen; Glauconox; Inidrase; Nephramid; Oratrol)

International Brand Names

Acetadiazol (Mexico); Albox (Japan); Apo-Acetazolamide (Malaysia); Carbinib (Portugal); Cetamid (Philippines); Defiltran (Germany); Diamox (Argentina, Bangladesh, Brazil, Bulgaria, Canada, Chile, Czech Republic, Ecuador, Germany, Greece, Hungary, Korea, Mexico, Pakistan, Peru, Poland, Portugal, Slovenia, South Africa, Turkey, Venezuela); Diamox Sustets (Colombia); Diluran (Czech Republic); Diural (Uruguay); Diuramid (Germany, Poland); Edemox (Spain); Genephamide (Peru); Glaucomed (Colombia); Glaucomide (New Zealand); Glaupax (Denmark, Ireland, Japan, Netherlands, Norway, Sweden, Switzerland, Thailand); Huma-Zolamide (Hungary); Ledamox (Japan); Lediamox (Portugal); Ledimox (Japan, Portugal); Stazol (Paraguay)

Drug Class Carbonic anhydrase inhibitors; Diuretics
Indications Glaucoma, open and closed angle; altitude sickness, prevention and treatment; epilepsy; CHF; drug-induced edema; urinary alkalinization
Mechanism Carbonic anhydrase inhibitor
Dosage With Qualifiers Glaucoma—125–250 mg PO/IV bid to qid
Altitude sickness—250–500 mg PO bid beginning 48 h before ascent
Epilepsy—375–1000 mg (8–30 mg/kg/d) PO qd if sole agent; begin 250 mg qd if with other agents
Congestive heart failure—250–375 mg PO/IV qd (for best results, take on alternate days)
Drug-induced edema—250–375 mg PO/IV qd (for best results, take on alternate days)
Urinary alkalinization—5 mg/kg PO/IV bid or tid to maintain alkaline urine pH

  • Contraindications —hypersensitivity to drug or class, hyponatremia, hypokalemia, depressed respiratory function, cirrhosis, hyperchloride acidosis, adrenocortical insufficiency

  • Caution —hepatic and/or renal dysfunction

Maternal Considerations There are no adequate reports or well-controlled studies of acetazolamide in pregnant women. Pregnancy is not known to alter the impact, efficacy, and dosing of acetazolamide .
Side effects include aplastic anemia, Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatitis, paresthesias, loss of appetite, taste changes, dyspepsia, and polyuria.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Acetazolamide apparently crosses the human placenta. There is no suggestion of teratogenicity in humans despite a long clinical experience. One case report documents a preterm infant whose mother was treated for glaucoma throughout pregnancy with oral acetazolamide . When renal tubular acidosis developed, acetazolamide was detected in the child’s serum, confirming transplacental passage. In another case report, the fetus was born with a sacrococcygeal teratoma. And in a third, the exposed infant demonstrated metabolic complications including metabolic acidosis, hyperbilirubinemia, hypocalcemia, and hypomagnesemia. In some rodents, acetazolamide is teratogenic (skeletal abnormalities consisting variably of ossification defects or some form of postaxial forelimb ectrodactyly in rats, urinary malformations in mice when combined with amiloride ). The prevalence of defects is enhanced when combined with ibuprofen .
Breastfeeding Safety Acetazolamide is not concentrated in the milk, and the neonatal exposure is < 0.5% of the maternal dose. It is generally considered compatible with breastfeeding.
Drug Interactions Acetazolamide may modify phenytoin metabolism and increase the serum level of phenytoin . By decreasing the GI absorption of primidone, it may decrease serum concentrations of primidone .
Acetazolamide reduces urinary excretion of quinidine and may enhance its effect. It increases lithium excretion.
Acetazolamide may elevate cyclosporine levels.
Acetazolamide may reduce urinary excretion of amphetamine and may enhance its effect.
Additive effects of concomitant carbonic anhydrase inhibitor use.
Acetazolamide may potentiate the effects of folic acid antagonists.
Concomitant use of aspirin may lead to toxicity by enhancing tissue penetration.
Acetazolamide may potentiate effects of oral anticoagulants.
References Academy of Pediatrics. Pediatrics 1994; 93:137-50.
Lee GS, Liao X, Cantor RM, Collins MD. Birth Defects Res A Clin Mol Teratol 2006;76:19-28.
Nakatsuka T, Komatsu T, Fujii T. Teratology 1992; 45:629-36.
Ozawa H, Azuma E, Shindo K, et al. Eur J Pediatr 2001; 160:321-2.
Summary Pregnancy Category: C
Lactation Category: S

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

Acetylcysteine — (Acetyst; Alveolux; Bromuc; Mucomyst; Mucosil; Mucosol; Mukosil; Respaire)

International Brand Names

ACC (Mexico); Acerac (Korea); Acetain (Korea); Acypront (Hong Kong); Alveolex (Ireland); Bromuc (Brazil); Cetilan (Korea); Drenaflen (Ecuador); Ecomucyl (Switzerland); Eloamin (Czech Republic); Encore (Taiwan); Exomuc (France, Hong Kong); Fabrol (Austria, England, Finland, Greece, Ireland, Sweden); Flemex-AC (Thailand); Fluimicil (Germany, Hungary, Switzerland); Fluimucil (Brazil, China, Colombia, Ecuador, France, Hong Kong, Indonesia, Italy, Morocco, Netherlands, Peru, Singapore, Spain, Taiwan, Thailand); Fluimucil A (Malaysia); Flutafin (Taiwan); Hidonac (Philippines); Libramucil (Ecuador); M.C.T. (Korea); Menaxol (Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua, Panama); Mucidin (Korea); Mucofillin (Japan); Mucolator (Malaysia); Mucolitico (Chile); Mucomiste (Portugal); Mucomyst (Australia, Austria, Belgium, Canada, Denmark, France, Netherlands); Mucoserin (Korea); Mucosof (China); Mucosten (Korea); Mucoza (Singapore, Thailand); Mukolit (Indonesia); Muteran (Korea); Parvolex (Canada, Philippines); Parvolex DBL (Malaysia); Reolin (Israel); Siran 200 (Israel); Solmucol (Singapore); Spatam (Singapore); Stecin (Korea); Zifluvis (Colombia)

Drug Class Antidotes; Antioxidants; Mucolytics
Indications Treatment of acetaminophen or Amanita phalloides toxicity; mucolytic in patients with cystic fibrosis
Mechanism A glutathione precursor that breaks disulfide bonds caused by oxidation
Dosage With Qualifiers Acetaminophen toxicity—begin 140 mg/kg PO by NG tube; thereafter, 70 mg/kg PO q4h × 15–20 doses
Mucolytic—1 nebulizer ampule q6–8 h; alternatively 2–5 mL of 10% solution or 600 mg in 3 divided doses

  • Contraindications —hypersensitivity to drug or class

  • Caution —severe respiratory failure, asthma

Maternal Considerations N -acetylcysteine is a prototype antioxidant presently used nearly exclusively during pregnancy for the treatment of maternal drug toxicity associated with free radical excess such as that occurring with acetaminophen . There are no adequate reports or well-controlled studies of N -acetylcysteine in pregnant women. It has been used for the treatment of acetaminophen toxicity during pregnancy. N -acetylcysteine or another like compound may have a role in the treatment of several disorders associated with excess free radical generation, including preterm labor and preeclampsia. For example, its administration reduced maternal hypertension after uterine artery ligation in rats.
Side effects include bronchospasm, anaphylaxis, N/V, stomatitis, rhinorrhea, urticaria, and rash.
Fetal Considerations N -acetylcysteine rapidly crosses the human placenta, reaching equilibrium with maternal sera. In one trial, laboring women with chorioamnionitis were given 100 mg/kg of NAC every 6 h until delivery as part of an effort to protect the fetal brain. NAC was associated with benefit, and there were no untoward events. In laboratory studies, it reduces embryo toxicity associated with hyperglycemia, hypoxia, and sepsis. In other studies, it reduces the adverse fetal effects of maternal inflammation by in part blocking the inflammation-stimulated release of cytokines. Further, N -acetylcysteine prevents neuronal loss in chronically hypoxic mouse and guinea pig fetuses.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether N -acetylcysteine enters human breast milk. It is unlikely short-term administration for an acute problem would pose a risk to the nursing infant.
Drug Interactions N -acetylcysteine should not be mixed in solution with tetracycline, oxytetracycline, and erythromycin lactobionate .
Intestinal absorbants such as charcoal may reduce the absorption of N -acetylcysteine.
References Beloosesky R, Gayle DA, Ross MG. Am J Obstet Gynecol 2006; 195:1053-7.
Bisseling TM, Maria Roes E, Raijmakers MT, et al. Am J Obstet Gynecol 2004; 191:328-33.
Boyer JC, Hernandez F, Estorc J, et al. Clin Chem 2001; 47:971-4.
Buhimschi IA, Buhimschi CS, Weiner CP. Am J Obstet Gynecol 2003; 188:203-8.
Chang EY, Barbosa E, Paintlia MK, et al. Am J Obstet Gynecol 2005; 193:952-6.
Horowitz RS, Dart RC, Jarvie DR, et al. J Toxicol Clin Toxicol 1997; 35:447-51.
Jenkins DD, Wiest DB, Mulvihill DM, et al. J Pediatr. 2016;168: 67-76.
McElhatton PR, Sullivan FM, Volans GN. Reprod Toxicol 1997; 11:85-94.
Summary Pregnancy Category: B
Lactation Category: S (likely)

  • N -acetylcysteine is indicated for the treatment of either cystic fibrosis or acetaminophen overdose during pregnancy.

  • Future investigation may demonstrate a role for N -acetylcysteine in the treatment of the fetus for a myriad of pathologic conditions that share excess free radical generation.

Acyclovir — (Acivir Cream; Acivir Eye; Avirax; Avorax; Clovicin; Clovix; Entir; Supra-Vir; Zovirax)

International Brand Names

ACERPES (Germany); Acevir (Philippines); Acic Creme (Germany); Acicloftal (Italy); Aciclor (Venezuela); Aciclosina (Peru); Aciclovir-BC IV (Australia); Acihexal (Australia); Acilax cream (Hong Kong); Acitop (South Africa); Acivir Cream (India, Israel); Acivir Eye (India); Aclova (Korea); Aclovir (Taiwan, Thailand); Aclovirax (Hong Kong); Activir (France); Acyclo-V (Bahrain); Acylene (Malaysia); Acyron (Korea); Acyrova (Korea); Acyvir (Ecuador, Hong Kong, Italy, Korea); Aias (Korea); Apicol (Colombia); Avirax (Canada); Avorax (Hong Kong, Malaysia, Singapore); Avorax Cream (Malaysia); Azovir (Indonesia); Bearax (Singapore); Cicloferon (Mexico); Cicloviral (Colombia); Clinovir (Indonesia, Thailand); Clovicin (Taiwan); Clovir (Brazil); Cloviran (Chile); Colsor (Thailand); Cusiviral (Hong Kong, Malaysia, Singapore, Spain); Cyclivex (South Africa); Cyclo (Korea); Cyclomed (Israel); Cyclorax (Hong Kong); Cyclostad (Philippines); Cyclovir (India, South Africa); Cyllanvir (Philippines); Danovir (Singapore); Deherp (Taiwan, Thailand); Dravyr (Singapore); Dumophar (Indonesia); Eduvir (Indonesia); Entir (Singapore, Thailand); Erlvirax (Singapore); Eurovir (Paraguay); Exavir (Brazil); Expit (Uruguay); Herpefug (Germany); Herpex (Bahrain, India, Philippines); Herpoviric (Germany); Herpoviric Rp Creme (Germany); Inmerax (Chile); Innovirax (Philippines); Isavir (Mexico); Juviral (Germany); Laciken (Mexico); Leramex (Thailand); Lermex (Thailand); Lesaclor (Mexico); Libravir (Ecuador); Lisovyr (Argentina, Chile); Lovir (Malaysia, Singapore); Lovire (South Africa); Maclov (Mexico); Marvir (Thailand); Matrovir (Indonesia); Maynor (Spain); Medovir (Bulgaria, Israel, Malaysia, Singapore, Taiwan); Norum (Thailand); Olvit (Mexico); Oppvir (Taiwan, Thailand); Opthavir (Mexico); Poviral (Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Indonesia, Nicaragua, Panama); Proviral (Argentina); Qualiclovir (Hong Kong); Quavir (Indonesia); Ranvir (Thailand); Raxclo (Philippines); Supra-Vir (Israel); Supraviran (Germany); Supraviran Creme (Germany, Israel); Syntovir (Hong Kong); Vacrax (Malaysia); Vacrovir (Korea); Vermis (Thailand); Vicorax (Taiwan, Thailand); Viraban (New Zealand); Viralex (Philippines); Viralex-DS (Philippines); Virax (Korea); Vircella (Indonesia); Virest (Malaysia, Singapore); Virex (Colombia); Virless (China, Singapore, Taiwan); Viroclear (Hong Kong); Virogon (Thailand); Virolan (Taiwan); Viromed (Thailand); Vironida (Peru); Virucid (Hong Kong); Virules (Hong Kong); Virupos Eye Oint (Korea); Vivir (Korea); Warviron (Hong Kong); Zetavir (Mexico); Zeven Cream (Malaysia); Zevin (Hong Kong, Thailand); Zodiac (Korea); Zoral (Hong Kong, Singapore); Zoral Cream (Malaysia); Zorax (Singapore); Zorel (Indonesia); Zoter (Indonesia); Zovir (Denmark); Zoylex (Korea); Zumasid (Indonesia); Zyclir (Australia); Zyvir (Kenya)

Drug Class Antivirals
Indications Primary or secondary herpes infection/suppression; treatment or prevention of Varicella pneumonia
Mechanism A synthetic, acyclic purine nucleoside that inhibits DNA polymerase by direct incorporation
Dosage With Qualifiers Genital herpes, recurrent—200 mg PO 5 ×/d × 10 d
Genital herpes, suppressive—400 mg PO bid for up to a year, or during pregnancy, from 36 w onward; with HIV, 400–800 mg PO 2–3 ×/d, or IV 5–10 mg/kg q8h × 5–10 d
Herpes zoster—800 mg PO 5 ×/d × 7–10 d
Ocular herpes—3% ointment 5 ×/d × 7–10 d
Varicella, acute—800 mg PO qid × 5 d

  • Contraindications —hypersensitivity to drug or class

  • Caution —renal dysfunction or concurrent nephrotoxic drug

Maternal Considerations Some 22% of pregnant women have genital HSV infection, and most of them are unaware. There is a long clinical experience free of obvious adverse effects. Treatment is not curative, but rather intended to reduce the duration of symptoms and viral shedding. Meta-analysis indicates prophylactic acyclovir beginning at 36 w reduces the risks for a clinical recurrence of genital herpes at delivery, cesarean section for recurrence, and herpes shedding at delivery. Suppression therapy is clinically effective and cost effective whether or not the primary infection occurred during the current pregnancy. Though it has not been specifically studied, the t/2 of acyclovir may be reduced during pregnancy, as it is excreted by the kidneys. Its combination with zidovudine alters the clearance of both agents in pregnant rats.
Side effects include seizures, coma, leukopenia, thrombocytopenia, renal dysfunction, N/V, diarrhea, headache, dizziness, lethargy, rash, and confusion.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether acyclovir crosses the human placenta. It is unclear whether maternal prophylaxis actually reduces the incidence of neonatal herpes. Postmarketing surveillance by Glaxo-Wellcome has not revealed any increase in or pattern of malformations after acyclovir exposure during the first trimester (756 pregnancies). A population-based study from Denmark that included 90 systemic and 995 topical exposures was likewise reassuring. Avoidance is preferred, as the death rate from neonatal herpes may exceed 25% despite high-dose acyclovir therapy. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety Acyclovir is passively secreted and achieves concentrations in breast milk higher than maternal serum, and it is used to treat neonatal herpetic infection. It is generally considered compatible with breastfeeding. It has been estimated that the unsupplemented newborn would ingest 1–3 mg/d.
Drug Interactions Probenecid and cimetidine increases the mean acyclovir t/2 and AUC. Urinary excretion and renal clearance are correspondingly lower.
References Academy of Pediatrics. Pediatrics 1994; 93:137-50.
Bork K, Kaiser T, Benes P. Arzneimittelforschung 2000; 50:656-8.
Braig S, Luton D, Sibony O, et al. Eur J Obstet Gynecol Reprod Biol 2001; 96:55-8.
Brown SD, Bartlett MG, White CA. Antimicrob Agents Chemother 2003; 47:991-6.
Eldridge RR, Ephross SA, Heffner CR, et al. Prim Care Update Obstet Gynecol 1998; 5:190-1.
Heuchan AM, Isaacs D. Med J Aust 2001; 174:288-92.
Hollier LM, Wendel GD. Cochrane Database Syst Rev 2008; (1):CD004946.
Leung DT, Sacks SL. Drugs 2000; 60:1329-52.
Little SE, Caughey AB. Am J Obstet Gynecol 2005; 193:1274-9.
Meyer LJ, de Miranda P, Sheth N, et al. Am J Obstet Gynecol 1988; 158:586-8.
Ratanajamit C, Vinther Skriver M, Jepsen P, et al. Scand J Infect Dis 2003; 35:255-9.
Scott LL, Alexander J. Am J Perinatol 1998; 15:57-62.
Scott LL, Hollier LM, McIntire D, et al. Infect Dis Obstet Gynecol 2001; 9:75-80.
Sheffield JS, Holier LM, Hill JB, et al. Obstet Gynecol 2003; 102:1396-403.
Taddio A, Klein J, Koren G. Ann Pharm 1994; 28:585-7.
Summary Pregnancy Category: B
Lactation Category: S

  • Acyclovir significantly reduces the duration of shedding and the number of recurrent HSV outbreaks during pregnancy.

  • Prophylaxis to prevent recurrence should be initiated at 36 weeks.

Adalimumab — (Humira)

International Brand Names

None identified.

Drug Class Immunosuppressant; antirheumatic
Indications Arthritis, plaque psoriasis, ankylosing spondylitis, Crohn’s disease, and ulcerative colitis
Mechanism Binds to tumor necrosis factor alpha (TNF-alpha) to interfere with the inflammatory processes
Dosage With Qualifiers Crohn’s disease and ulcerative colitis—160 mg SC × 1 on day1, then 80 mg SC × 1 on day 15, then 40 mg SC q2w on day 29.
Rheumatoid arthritis—begin 1 mg/kg PO qd; increase 0.5 mg/kg/d after 6–8 w; max 2.5 mg/kg/d; alternatively, 40mg SC q2wk

  • Contraindications —hypersensitivity to drug or class, chronic or localized infections

  • Caution —tuberculosis, infection, sepsis, neurologic events, malignancies

Maternal Considerations There are no adequate reports or well-controlled studies of adalimumab in pregnant women. Reports from more than 2000 pregnancies exposed to TNF-α inhibitors during the first trimester reveal minimal risks of spontaneous abortion, low birth weight, prematurity, or congenital malformations. According to the Adalimumab Pregnancy Registry, serious infections and tuberculosis occurred at a rate of 4.7 and 0.3 events/100 patient-years, respectively. No significant laboratory abnormalities were reported with adalimumab -plus- methotrexate compared with placebo-plus- methotrexate . Influenza-related AEs occurred in 5% of vaccinated patients compared with 14% of patients not vaccinated during the study.
Side effects include headache, hypertension, nausea.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. In one series, 24/38 (71%) pregnancies were exposed to anti-TNFα at conception/first trimester, 11/38 (29%) prior to conception, and 3 (11%) after paternal exposure. According to the Adalimumab Pregnancy Registry, relative risk of major birth defects and spontaneous abortions in adalimumab-exposed women was similar to that of unexposed women with RA and healthy women. There were no differences in outcomes among the groups. Adalimumab crosses the placenta and is detected in cord blood at birth at concentrations higher than in maternal serum and remains detectable for up to 6 months after birth. Neonatal exposure is expected to be highest in the third trimester. Animal studies are reassuring, revealing no evidence of teratogenicity or IUGR. In one prospective multicenter study, offspring of mothers who received combination therapy with adalimumab plus AZA/6-MP had a 35% increase in risk of infection at 9–12 months of age compared to those receiving monotherapy.
Breastfeeding Safety There is no published experience in nursing women. Low concentrations of adalimumab are detected in breast milk.
Drug Interactions No drug-drug interactions have been reported.
References Hoxha A, Calligaro A, Di Poi E et al. Joint Bone Spine. 2016 Jun 22. pii: S1297-319X(16)30096-3.
Julsgaard M, Christensen LA, Gibson PR, et al. Gastroenterology 2016; epub
Ostensen M. Ann N Y Acad Sci 2014; 1317:32-8
Summary Pregnancy Category: B
Lactation Category: U

Adapalene — (Differin; Differine)

International Brand Names

Adaferin (India, Mexico); Adaferin Gel (Israel); Differine (France); Differin Gel (Austria, Germany, Ireland, Italy, Spain, Sweden, Switzerland)

Drug Class Dermatologics; Retinoids
Indications Acne vulgaris
Mechanism Binds retinoid nuclear receptors to interfere with cellular differentiation, keratinization, and inflammatory processes
Dosage With Qualifiers Acne vulgaris—apply (0.1%) cream or gel to the affected area once daily at night

  • Contraindications —hypersensitivity to drug or class

  • Caution —unknown

Maternal Considerations Systemic absorption of adapalene across human skin is low, with none being detected in the plasma of six patients treated for acne in a standardized fashion for 5 d with 2 g. There are no adequate reports or well-controlled studies of adapalene in pregnant women. Women of childbearing age should be fully informed of the risks and the importance of effective contraception. This also applies to patients with moderate forms of psoriasis, for which topical tazarotene is indicated.
Side effects include erythema, dryness, burning, scaling, and photosensitivity.
Fetal Considerations There are no adequate studies of adapalene in human pregnancy. It is unknown whether adapalene crosses the human placenta. Though the pharmacology is encouraging, there are several reports in humans associating adapalene with fetal malformation after cutaneous exposure. A meta-analysis, including 654 pregnant women exposed to topical retinoids and 1375 unexposed control pregnant women, revealed no major increase in the rates of major congenital malformation, spontaneous abortions, low birth weight, and prematurity. The available information is insufficient to conclude cause and effect. Oral administration to rodents at 100–200 × the MRHD increased the risk of malformation. No abnormalities were seen in pregnancies exposed to lower concentrations.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether adapalene enters human breast milk. Considering the dose and route, it is unlikely to pose a significant risk to the breastfeeding neonate.
Drug Interactions As adapalene may cause local irritation, simultaneous use of other topical agents such as medicated or abrasive soaps and cleansers, soaps and cosmetics with a strong drying effect, and products with high concentrations of alcohol should be avoided if possible. Caution is also recommended in using preparations containing sulfur, resorcinol, or salicylic acid in combination with adapalene . Other cutaneous antiacne treatments may be used in the morning when adapalene topical is used at night.
References Autret E, Berjot M, Jonville-Bera AP, et al. Lancet 1997; 350:339.
Kaplan YC, Ozsarfati J, Etwel F, et al. Br J Dermatol 2015; 173:1132-41.
[No authors]. Prescrire Int 1998; 7:148-9.
[No authors]. Prescrire Int 2005; 14:100-1.
Summary Pregnancy Category: C
Lactation Category: U

  • It is best to avoid topical retinoids in early pregnancy, as the disease process is rarely life threatening.

  • Women of childbearing age should be fully informed of the risks and the importance of effective contraception.

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

Adenosine — (Adenic; Adenocar; Adenocard; Adeno-Jec; Adenoscan; Adenosine Phosphate; ATP)

International Brand Names

Adenocard (Brazil, Canada); Adenocor (Belgium, Bulgaria, China, Colombia, Denmark, Ecuador, Egypt, England, Ireland, Korea, Malaysia, Norway, Peru, South Africa, Spain, Taiwan, Thailand); Adenocur (Netherlands); Adenoject (India); Adenoscan (Hong Kong); Adenosina Biol (Argentina, Paraguay); Adrekar (Austria, Germany); Cardiovert (Philippines); Krenosin (France, Italy, Mexico); Krenosine (Switzerland)

Drug Class Antiarrhythmics; Diagnostics
Indications Paroxysmal SVT
Mechanism Interrupts reentry pathways by slowing AV node conduction
Dosage With Qualifiers Paroxysmal SVT conversion—3–6 mg IV over 1–2 sec; may double to 6 mg and then 12 mg if no response after 1–2 min

  • Contraindications —hypersensitivity to drug or class, second- or third-degree heart block or sick sinus syndrome

  • Caution —asthma, chronic obstructive pulmonary disease

Maternal Considerations An endogenous purine-based nucleoside, IV adenosine is the first choice for short-term management of paroxysmal supraventricular arrhythmia after a vagal maneuver fails. Co-administration of midazolam safely reduces recall of the unpleasant effects of adenosine . For long-term therapy, β-blocking agents with β 1 selectivity are first-line drugs; class Ic agents and the class III drug sotalol are also effective therapeutic alternatives. Adenosine has been used on multiple occasions during pregnancy to treat paroxysmal SVT. There are reports of preterm labor associated with adenosine administration.
Side effects include arrhythmia (bradycardia, VF or ventricular tachycardia, asystole, complete heart block), bronchospasm, flushing, chest or groin pressure, dizziness, N/V, apprehension, palpitations, and headache.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Adenosine crosses the human placenta and enhances placental perfusion. Rodent studies reveal no evidence of teratogenicity. Adenosine can be administered directly into the umbilical vein to achieve control of a fetal SVT. Although adenosine has a very short elimination t/2 (< 10 s), transient fetal bradycardia has been observed during treatment of a maternal SVT with intravenous adenosine.
Breastfeeding Safety There are no adequate reports or well-controlled studies in nursing women. Adenosine is a normal constituent of human breast milk, though the short t/2 suggests little, if any, of the exogenously administered adenosine will enter the milk.
Drug Interactions Adenosine may be rarely associated with VF when combined with digoxin and verapamil use. Because of the potential for additive or synergistic depressant effects on the SA and AV nodes, however, adenosine should be used with caution in the presence of these agents.
The effects of adenosine are antagonized by methylxanthines such as caffeine and theophylline .
Adenosine effects are enhanced by dipyridamole. Carbamazepine may increase the degree of heart block produced by other agents.
References Acevedo CG, Huambachano A, Perez E, et al. Placenta 1997; 18:387-92.
Canlorbe G, Azria E, Michel D, et al. Ann Fr Anesth Reanim 2011; 30:372-4.
Chow T, Galvin J, McGovern B. Am J Cardiol 1998; 82:581-621.
Dunn JS, Brost BC. Am J Emerg Med 2000; 18:234-5.
Elkayam U, Goodwin TM. Am J Cardiol 1995; 75:521-3.
Hourigan C, Safih S, Rogers I, et al. Emerg Med (Fremantle) 2001; 13:51-6.
Matsubara S, Kuwata T, Mitsuhashi T. TJ Obstet Gynaecol Can 2011; 22:794-5.
Robins K, Lyons G. Br J Anaesth 2004; 92:140-3.
Tan HL, Lie KI. Eur Heart J 2001; 22:458-64.
Trappe HJ, Pfitzner P. Z Kardiol 2001; 90:36-44.
Summary Pregnancy Category: C
Lactation Category: U

  • Useful for the short-term treatment of either maternal or fetal tachycardia.

Albuterol — (Airet; Albuterol Sulfate; Asmalin; Asmanil; Asmavent; Butamol; Buventol; Proventil; Salbusian; Salbutamol; Theosal; Ventolin; Ventolin Rotacaps; Volmax)

International Brand Names

Aerolin (Brazil, Chile, Greece); Airhexal (Philippines); Airomir (Australia, Canada, France, Hong Kong, Malaysia, Singapore, Taiwan, Thailand); Almotex (Philippines); Asmacaire (Philippines); Asmadil (South Africa); Asmalin Pulmoneb (Philippines); Asmasal (Thailand); Asmatol (Argentina); Asmaven (England); Asmavent (Canada); Asmidon (Japan); Asmol CFC-Free (Australia); Asmol Uni-Dose (New Zealand); Asmovent (Malaysia); Assal (Mexico); Asthalin (India); Azmasol (Singapore); Broncho-Spray (Germany); Broncovaleas (Italy); Bronter (Colombia); Brytolin (Philippines); Butahale (Singapore); Buto-Asma (Singapore, Spain, Thailand); Butomix (Peru); Butotal (Chile); Buventol (Singapore, Taiwan); Buventol Easyhaler (France, Indonesia, Thailand); Cletal (Philippines); Cobutolin (England); Cybutol (Hong Kong); Dilatamol (Indonesia); Emplusal (Philippines); Epaq Inhaler (Australia); Exafil (Mexico); Glisend (Indonesia); Grafalin (Indonesia); Hivent DS (Philippines); Krosalburol (Ecuador); Libretin (Philippines); Medolin (Singapore); Mozal (Taiwan); Novosalmol (Canada); Parasma (Colombia); Provexel NS (Philippines); Prox-S (Philippines); Pulmol-S (Peru); Respax (New Zealand); Respreve (Hong Kong); Sabutol (Singapore); Salbetol (India); Salbron (Indonesia); Salbulin (Costa Rica, Dominican Republic, El Salvador, England, Guatemala, Honduras, Panama); Salbutalan (Mexico); Salbutan (Venezuela); Salbutin (Israel); Salbutol (Korea, Peru); Salbutron SR (Korea); Salbuven (Indonesia); Salbuvent (Norway); Salda (Thailand); Salden (Costa Rica, Ecuador, El Salvador, Guatemala, Honduras, Nicaragua, Panama); Salmaplon (India); Salmol (China); Salmundin Retard (Germany); Salomol (Taiwan); Sedalin (Philippines); Sultanol (Austria, Germany, Japan); Suprasma (Indonesia); Teoden (Brazil); Tobybron (Indonesia); Venalax (Philippines); Vencronyl (Philippines); Venetlin (Japan); Ventilan (Colombia, Portugal); Ventilastin Novolizer (Germany); Ventimax (South Africa); Ventodisks (China); Ventol (Israel); Ventolin (Argentina, Belgium, Bulgaria, Canada, China, Costa Rica, Czech Republic, Ecuador, El Salvador, Guatemala, Honduras, Hong Kong, Hungary, Indonesia, Ireland, Italy, Malaysia, Mexico, Netherlands, Nicaragua, Panama, Paraguay, Peru, Philippines, Spain, Switzerland, Taiwan, Thailand, Uruguay, Venezuela); Ventolin CFC-Free (Australia); Ventoline (Denmark, Finland, France, Norway, Sweden); Volmax (China, Ecuador, Hong Kong, New Zealand); Zebu (Thailand); Zenmolin (Hong Kong); Zibil (Mexico)

Drug Class Adrenergic agonists; Bronchodilators
Indications Bronchospasm; exercise-induced asthma
Mechanism A selective β 2 -agonist
Dosage With Qualifiers Bronchospasm—1–2 puffs MDI q4–6 h, max 12 puffs/d; or 2–4 mg PO tid or qid
Exercise-induced asthma—2 puffs MDI × 1 given 15–30 min before exercise
NOTE: Numerous drug interactions are known. The reader should consult a detailed reference if the patient is or has recently been on a MAOI or TCA, a β-adrenoceptor antagonist, a diuretic, or digoxin .

  • Contraindications —hypersensitivity to drug or class

  • Caution —hyperthyroidism, CV disease, diabetes mellitus, seizure disorder

Maternal Considerations Albuterol has been used as a tocolytic in some countries given IV, SC, or PO (also see terbutaline or ritodrine, whose efficacy it compares to). There is no quality evidence it can halt preterm or term labor. β-Mimetic tocolysis is associated with pulmonary edema, especially with multiple gestation, or in women concurrently receiving glucocorticoid therapy to hasten fetal lung maturation, or in association with infection. The mechanism is unclear. Treatment consists of oxygen supplementation and diuresis. Maternal serum glucose and plasma insulin levels peak soon after cessation of therapy and return to preinfusion levels within 2–3 h. The decline in potassium is gradual and plateaus after 2 h. Once the albuterol infusion is stopped, the potassium returns to normal by 2 h. Total WBC counts increase within an hour of initiating therapy. There is no need to administer insulin for hyperglycemia and/or potassium for hypokalemia unless the patient is a known diabetic or is severely affected and requires immediate surgery.
Side effects include bronchospasm with inhaler form, arrhythmia, tremor, nervousness, tachycardia, dizziness, headache, hypertension, nausea, hyperactivity, hypokalemia, and hyperglycemia.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Albuterol appears to cross the human placenta, though the kinetics remain to be elucidated. Less than 10% is absorbed after inhalation. There is no convincing evidence of teratogenicity after first-trimester exposure. In general, long-term follow-up studies of infants exposed to β-mimetic tocolysis are reassuring. Albuterol, like other β-adrenoceptor agonists, is associated with a reduction in the incidence of RDS. Animal studies reveal ~ 10% of the circulating maternal albuterol reaches the fetus, but the amount in the fetal lungs is comparable to that in the maternal lungs. A single abstract suggests an increased risk of newborn retinopathy. Albuterol is teratogenic in mice at doses lower than those used in humans.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether albuterol enters human breast milk. Other β-adrenoceptor agonists such as ritodrine and terbutaline are considered safe for breastfeeding. Systemic absorption after inhalation is 10% or less.
Drug Interactions Use with other sympathomimetic agents may lead to deleterious CV effects. This does not preclude the judicious use of an adrenergic agonist aerosol bronchodilator.
Albuterol should be administered with extreme caution to women using either MAOIs or TCAs (or within 2 w of discontinuation).
β-Blockers may trigger severe bronchospasm in asthmatic women. However, under certain circumstances (e.g., as prophylaxis after MI), there may be no acceptable alternative to the use of a β-blocker in women with asthma.
The ECG changes and/or hypokalemia secondary to non–potassium-sparing diuretics may be acutely worsened by β-agonists.
Serum digoxin levels decrease about 20% after a single dose of either IV or oral albuterol to normal volunteers who ingested digoxin for 10 d.
References Ashworth MF, Spooner SF, Verkuyl DA, et al. Br J Obstet Gynaecol 1990; 97:878-82.
Chua S, Razvi K, Wong MT, et al. J Obstet Gynaecol Res 1997; 23:381-7.
Michie CA, Braithwaite S, Schulenberg E, Harvey D. Arch Dis Child 1994; 71:F149.
Milliez JM, Flouvat B, Delhotal B, Jannet D. Obstet Gynecol 1992; 80:182-5.
[No authors]. Ann Allergy Asthma Immunol 2000; 84:475-80.
The Worldwide Atosiban versus Beta-agonists Study Group. BJOG 2001; 108:133-42.
Van Zutphen AR, Bell EM, Browne ML et al. Birth Defects Res A Clin Mol Teratol. 2015 Nov;103(11):951-61.
Summary Pregnancy Category: C
Lactation Category: S

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

  • As a tocolytic, albuterol has no advantage over any other β-adrenoceptor agonist, prolonging pregnancy on average 48 h over placebo.

  • It is ineffective, as are all β-adrenoceptor agonists, when used for preterm labor prophylaxis.

  • β-Adrenoceptor agonists should be avoided in diabetic women. If unavoidable, the patient should be aggressively covered with a short-acting insulin.

Alendronate — (Fosamax)

International Brand Names

Aldrox (Chile); Alenato (Argentina); Alend (Korea); Alnax (Paraguay); Alovell (Indonesia); Arendal (Peru); Armol (Colombia); Bifemelan (Colombia); Bifosa (India); Bonapex (Egypt); Defixal (Costa Rica, Dominican Republic, El Salvador, Guatemala, Nicaragua, Panama); Endronax (Brazil); Eucalen (Colombia); Fixopan (Ecuador); Fosalan (Israel); Fosamax (Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Costa Rica, Czech Republic, Denmark, Ecuador, Egypt, El Salvador, England, France, Germany, Guatemala, Honduras, Hong Kong, Hungary, Indonesia, Ireland, Italy, Korea, Malaysia, Mexico, Netherlands, Nicaragua, Norway, Panama, Peru, Philippines, Poland, Singapore, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Venezuela); Fosmin (Peru); Fosval (Paraguay); Marvil (Peru, Uruguay); MaxiBone (Israel); MaxiBone 70 (Israel); Neobon (Colombia); Osdron (Brazil); Osdronat (Colombia); Oseotenk (Argentina); Osficar (Colombia); Oslene (Indonesia); Osteofar (Indonesia); Osteofos (Hong Kong); Osteopor (Uruguay); Osteosan (Chile); Osteovan (Costa Rica); Osticalcin (Colombia); Porosal (Venezuela); Tibolene (Colombia); Voroste (Indonesia)

Drug Class Bisphosphonates; Calcium metabolism
Indications Osteoporosis
Mechanism Inhibits osteoclast resorption
Dosage With Qualifiers Osteoporosis, postmenopausal treatment—10 mg PO qd, or 70 mg PO once a week taken with meals
Osteoporosis, postmenopausal prevention—5 mg PO qd, or 35 mg PO once per week taken with meals
Osteoporosis, steroid induced—5 mg PO qd taken with meals
NOTE: Avoid supine position.

  • Contraindications —hypersensitivity to drug or class, hypocalcemia, severe renal dysfunction

  • Caution —upper GI disease

Maternal Considerations There are no adequate reports or well-controlled studies of alendronate in pregnant women. Alendronate is superior to conjugated estrogens (with or without medroxyprogesterone ) for the prevention of bone loss in older adult women, though the combination is superior. Drug levels may persist in bone for long periods of time, leading to inadvertent pregnancy exposure.
Side effects include esophagitis, gastritis, dysphagia, esophageal ulcer, N/V, abdominal pain, arthralgia, myalgias, back pain, constipation, diarrhea, headache, chest pain, flulike syndrome, and peripheral edema.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Adverse effects of bisphosphonates on fetal outcomes have been seen in animal studies, but the doses used were much higher than those typically used in clinical practice. One review identified 15 reports of bisphosphonate use before and/or during pregnancy (in total, 65 mother-child pairs); the agents used included alendronate, ibandronate, and risedronate, among many, with the reported durations of use ranging from one-time treatments to months or years. Adverse outcomes observed included marginal decreases in gestational age and birth weight and transient neonatal electrolyte abnormalities (e.g., hypocalcemia, hypercalcemia, hyperphosphatemia); however, no long-term health consequences were reported in any infant. Alendronate crosses the rodent placenta, decreasing bone density and delaying delivery. Both the total and ionized calcium are reduced in the rodent mother and fetus. The toxic effects are reversed by calcium administration.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether alendronate enters human breast milk. However, the risk to the breastfed neonate is likely low considering the low maternal systemic levels.
Drug Interactions Combined use of HRT and alendronate in postmenopausal osteoporotic women revealed the suppression of bone turnover was greater with the combination.
Calcium supplements, antacids, and some oral medications interfere with absorption of alendronate . Women should wait at least 1⁄2 h after taking alendronate before taking any other oral medications.
The incidence of upper GI adverse events is increased in women receiving daily doses of alendronate greater than 10 mg and aspirin -containing products.
Food, beverages (other than water), and herbal products may interfere with the absorption of alendronate. Women should wait at least 1⁄2 h after taking alendronate before consuming.
References Greenspan SL, Resnick NM, Parker RA. JAMA 2003; 289:2525-33.
Minsker DH, Manson JM, Peter CP. Toxicol Appl Pharmacol 1993; 121:217-23.
Ornoy A, Wajnberg R, Diav-Citrin O. Reprod Toxicol 2006; 22:578-9.
Patlas N, Golomb G, Yaffe P, et al. Teratology 1999; 60:68-73.
Rutgers-Verhage AR, deVries TW, Torringa MJ. Clin Mol Teratol 2003; 67:203-4.
Samdani A, Lachmann E, Nagler W. Am J Phys Med Rehabil 1998; 77:153-6.
Summary Pregnancy Category: C
Lactation Category: U

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

Alfentanil — (Alfenta; Alfentanyl; Rapifen)

International Brand Names

Alfenil (Korea); Alfenta (Brazil, Canada); Brevafen (Argentina); Fanaxal (Spain); Fentalim (Italy); Rapifen (Bulgaria, Brazil, Chile, Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Hong Kong, Ireland, Israel, Mexico, Nicaragua, Panama, Paraguay, Poland, Slovenia, South Africa, Spain, Taiwan, Turkey, Uruguay, Venezuela)

Drug Class Analgesics, narcotic
Indications Analgesia either alone or in combination for labor or gynecologic pain
Mechanism A short-acting lipophilic opioid
Dosage With Qualifiers Anesthesia, induction—130–245 mcg/kg IV (primarily with underlying cardiac disease undergoing a prolonged surgical procedure); more commonly 8–50 mcg/kg at induction to blunt the pressor response to tracheal intubation
Anesthesia, maintenance—3–15 mcg/kg IV prn, or 0.5–1 mcg/kg/min continuous infusion
NOTE: Chest wall rigidity is common, and neuromuscular blockers are usually given to enable mask ventilation before tracheal intubation.
Conscious sedation—3–8 mcg/kg IV × 1

  • Contraindications —hypersensitivity to drug or class

  • Caution —chest wall rigidity; N/V; bradycardia; hepatic, renal, or pulmonary dysfunction; head injury; bowel obstruction

Maternal Considerations Alfentanil is a short-acting narcotic with rapid onset. As with other lipophilic opioids, alfentanil reduces the total dose of local anesthetic analgesic needed to provide comfort when combined with bupivacaine for epidural analgesia while diminishing the likelihood of an undesired motor blockade. IV alfentanil given just prior to intubation reduces the associated pressor response in both healthy and preeclamptic women.
Side effects include respiratory arrest or depression, arrhythmia, seizure, coma, abuse or dependency, muscle rigidity, N/V, dizziness, hypertension, hypotension, tachycardia, bradycardia, confusion, sweating, dry mouth, constipation, and urinary retention.
Fetal Considerations Alfentanil crosses the placenta when given IV, though its transfer rate is lower than fentanyl (which approximates antipyrine ). Neither human embryo toxicity nor teratogenicity is reported, though first-trimester human data are limited. Alfentanil is embryotoxic in rodents when given for 10–30 d at doses 2–3 × the MRHD. One limited monkey study concluded offspring had impaired ability to do simple cognitive tasks at 2–3 mo of age after exposure at 14 w gestation. Lipophilic and hydrophilic characteristics of the drug influence placental transfer, as do fluctuations in maternal flow. Neonatal depression characterized by reduced active and passive tone is reported when alfentanil is given shortly before delivery. Occasionally, a narcotic antagonist is necessary. There are no reported fetal or neonatal effects after its use for conduction anesthesia.
Breastfeeding Safety Alfentanil is excreted into human breast milk, though the amount excreted is too small to have any significant effect on the newborn.
Drug Interactions The magnitude and duration of CNS and CV system effects may be enhanced when administered with other CNS depressants such as barbiturates, tranquilizers, opioids, or inhalation general anesthetics. Postoperative respiratory depression may be enhanced or prolonged.
Erythromycin may inhibit alfentanil clearance and increase the risk of prolonged or delayed respiratory depression. Cimetidine reduces the alfentanil clearance.
Fluconazole reduces the alfentanil clearance.
Diltiazem reduces the alfentanil clearance.
Perioperative administration of drugs affecting hepatic blood flow or enzyme function may reduce plasma alfentanil clearance and prolong recovery.
References Ashton WB, James MF, Janicki P, Uys PC. Br J Anaesth 1991; 67:741-7.
Cooper RA, Devlin E, Boyd TH, Bali IM. Eur J Anaesthesiol 1993; 10:183-7.
Giesecke AH, Rice LJ, Lipton JM. Anesthesiology 1985; 63:A284.
Giroux M, Teixera MG, Dumas JC, et al. Biol Neonate 1997; 72:133-41.
Golub MS, Eisele JH Jr, Donald JM. Am J Obstet Gynecol 1988; 159:1280-6.
Rout CC, Rocke DA. Br J Anaesth 1990; 65:468-74.
Scherer R, Holzgreve W. Eur J Obstet Gynecol Reprod Biol 1995; 59:S17-29.
Zakowski MI, Ham AA, Grant GJ. Anesth Analg 1994; 79:1089-93.
Summary Pregnancy Category: C
Lactation Category: S

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

Allopurinol — (Aipico; Alloremed; Alloscan; Alonol; Aloral; Aluline; Aluprin; Apurol; Isanol; Lopurin; Lysuron; Unizuric; Uricemil; Uriconorm-E; Zyloprim; Zyroric)

International Brand Names

Aceprax (Paraguay, Uruguay); Adenock (Japan); Alinol (Thailand); Allnol (Hong Kong); Allo 300 (Germany); Allo-Basan (Switzerland); Allohexal (Australia); Allopin (Thailand); Allopur (Norway, Switzerland); Allo-Puren (Germany); Alloril (Israel); Allorin (New Zealand); Allosig (Australia); Allozym (Japan); Allurase (Philippines); Allurit (Italy); Alopron (Puerto Rico); Alositol (Japan); Alpurase (Philippines); Alpurin (Philippines); Alunlan (Philippines, Taiwan); Alurin (Guatemala); Aluron (Venezuela); Anoprolin (Japan); Anzief (Japan); Apo-Allopurinol (Canada); Aprinol (Japan); Apurin (Denmark, Finland, Greece, Netherlands); Atisuril (Mexico); Bleminal (Germany); Caplenal (England, Ireland); Capurate (Australia, Taiwan); Cellidrin (Germany); Clint (South Africa); Erloric (Singapore); Etindrax (Mexico); Foligan (Germany, Switzerland); Gichtex (Austria); Hamarin (England); Isoric (Indonesia); Kemorinol (Indonesia); Ketanrift (Japan); Ketobun-A (Japan); Litinol (Venezuela); Llanol (Indonesia, Philippines); Lopurine (Philippines); Lo-Uric (South Africa); Lysuron 300 (Switzerland); Masaton (Japan); Medoric (Thailand); Mefanol (Ecuador); Mephanol (Hong Kong, Israel, Malaysia, South Africa, Switzerland); Milurit (Bulgaria, Hong Kong, Hungary); Miniplanor (Japan); Neufan (Japan); Nipurol (Venezuela); No-Uric (Israel); Progout (China, Hong Kong, Singapore); Proxuric (Indonesia); Puricemia (Indonesia); Puricos (South Africa); Purinase (Philippines); Purinol (Ireland, Malaysia); Purinox (Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua, Panama); Puristen (Philippines); Ranpuric (South Africa); Remid (Germany); Riball (Japan); Rinolic (Indonesia); Salterprim (South Africa); Takanarumin (Japan); Tonsaric (Taiwan); Trianol (Philippines); Unizuric 300 (Mexico); Uric (Japan); Uricad (Thailand); Uriconorm (Switzerland); Urinol (Malaysia); Uripurinol (Germany); Urogquad (Argentina); Uroquad (Indonesia, Puerto Rico, South Africa); Urosin (Austria, Ecuador, Germany); Valeric (Singapore); Vitralgin (Peru); Xanturic (France); Xylonol (Taiwan); Zylapour (Greece); Zylol (Israel); Zyloprim (Canada, Paraguay, Philippines, South Africa); Zyloric (Argentina, Austria, Brazil, Chile, China, Greece, Hong Kong, India, Indonesia, Korea, Malaysia, Mexico, Peru, Poland, Slovenia, South Africa, Taiwan, Thailand, Turkey, Uruguay, Venezuela); Zyroric (Korea)

Drug Class Antigouts; Antioxidants; Purine analogs
Indications Gout, nephrolithiasis secondary to urate or calcium oxalate stones
Mechanism A xanthine oxidase inhibitor that interferes with the conversion of xanthine and hypoxanthine to uric acid
Dosage With Qualifiers Gout prophylaxis—100–800 mg PO qd; titrate dose until uric acid < 6 mg/dL
Urate nephrolithiasis prophylaxis—100–800 mg PO qd
Calcium oxalate calculi—200–300 mg PO qd
NOTE: Renal dosing.

  • Contraindications —hypersensitivity to drug or class

  • Caution —renal dysfunction

Maternal Considerations Allopurinol is rarely indicated for traditional indications in pregnant or lactating women, and there are no adequate reports or well-controlled studies of allopurinol in pregnant women. There are several case reports. One woman treated for primary gout during pregnancy with allopurinol delivered a healthy child at 35 w. Another documents a woman treated for a gout flare associated with gestational diabetes, also without adverse events. A report documents 13 cases of allopurinol and thiopurine co-therapy used successfully to manage inflammatory bowl diseases during pregnancy without attributable adverse fetal effects. Allopurinol is also used during pregnancy for women undergoing treatment of acute leukemia. Of future interest is its potential as an antioxidant. Allopurinol was used unsuccessfully in one trial for the treatment of established preeclampsia.
Side effects include agranulocytosis, aplastic anemia, thrombocytopenia, hepatic dysfunction, urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis, rash, diarrhea, pruritus, nausea, and gout flare.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Allopurinol readily crosses the ovine placenta, where it reaches equilibrium within 30 min. It reduces superoxide generation in the brains of fetuses subject to intermittent umbilical cord occlusion. One multicenter randomized placebo controlled trial concluded that maternal treatment with allopurinol during fetal hypoxia lowered neuronal damage markers in female but not male cord blood; developmental outcome was not reported. There is no evidence that allopurinol is teratogenic in humans. Cleft palate and skeletal defects are reported in some rodents. In 31 prospectively identified pregnancies with allopurinol exposure during at least the first trimester, an overall rate of major malformations (3.7%) and of spontaneous abortions (cumulative incidence 11%, 95% CI 3–40)—each within normal range—was reported.
Breastfeeding Safety Allopurinol and its metabolite oxypurinol are excreted into breast milk to a limited degree and are considered compatible with breastfeeding. The average daily dose of allopurinol consumed by a 3-kg neonate would be 0.6 mg and that of oxypurinol would be 24 mg.
Drug Interactions Allopurinol inhibits xanthine oxidase–catalyzed oxidation of mercaptopurine and azathioprine to 6-thiouric acid. Women taking allopurinol require a one-fourth to one-third reduction in their dose of mercaptopurine / azathioprine .
Allopurinol prolongs the t/2 of dicumarol . The PT should be reassessed periodically in women receiving both drugs.
Chlorpropamide’s t/2 may be prolonged by allopurinol, as allopurinol and chlorpropamide compete for excretion by the renal tubule. The risk of hypoglycemia secondary to this mechanism may be increased in women with renal insufficiency.
Allopurinol may increase the t/2 of vidarabine .
Allopurinol may inhibit hepatic oxidation of phenytoin.
High doses of allopurinol (300 mg bid) inhibit the clearance of theophylline in normal subjects.
Co-administration of allopurinol may increase the plasma concentration of cyclosporine .
References Coddington CC, Albrecht RC, Cefalo RC. Am J Obstet Gynecol 1979; 133:107-8.
Committee on Drugs. Pediatrics 1994; 93:137-50.
Fujii T, Nishimura H. Jpn J Pharmacol 1972; 22:201-6.
Gulmezoglu AM, Hofmeyr GJ, Oosthuisen MM. Br J Obstet Gynaecol 1997; 104:689-96.
Hoeltzenbein N, Stieler K, Panse M et al. PLoS One 2013; 19:8 201
Kaandorp JJ, Benders MJ, Schuit E, et al. Arch Dis Child Fetal Neonatal Ed 2014; 100:F216-23.
Kamilli I, Gresser U. Clin Investig 1993; 71:161-4.
Kozenko M, Grynspan D, Oluyomi-Obi T, et al. Am J Med Genet A 2011; 155A:2247-52.
Masaoka N, Nakajima Y, Hayakawa Y, et al. J Matern Fetal Neonatal Med 2005; 18:1-7.
Van Veen TR, Haeri S. Gynecol Obstet Invest 2015; 79:217-21
Sheikh, MNelson-Piercy C, Duley J, et al. J Crohns Colitis 2015; 9:680-4
Summary Pregnancy Category: C
Lactation Category: S

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

Almotriptan — (Axert)

International Brand Names

Almogran (Belgium, Denmark, England, France, Germany, Ireland); Axert (Canada)

Drug Class Serotonin receptor agonists
Indications Migraine headache, acute
Mechanism Binds with high affinity to 5-HT 1D , 5-HT 1B , and 5-HT 1F receptors, causing cranial vessel constriction
Dosage With Qualifiers Migraine headache, acute—6.25–12.5 mg PO × 1; may repeat × 1 q2h; max 25 mg/24 h
NOTE: Renal and hepatic dosing.

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

  • Caution— cerebrovascular disease, PVD, ischemic bowel, cardiac risk factors, hepatic or renal dysfunction

Maternal Considerations Migraine is a paroxysmal disorder with attacks of headache, N/V, photo- and phonophobia, and malaise. There is no published experience with almotriptan during pregnancy. Similar agents such as sumatriptan are associated with an increased risk of preterm birth. It is likely the metabolism of almotriptan is decreased during pregnancy, thus increasing the risk of toxicity.
Side effects include hypertensive crisis, MI, coronary spasm, ventricular arrhythmias, CVA, peripheral vascular ischemia, bowel ischemia, N/V, 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 almotriptan crosses the human placenta. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically, though embryo lethality was observed at 1000 × the MRHD, and prolongation of pregnancy at 160 × the MRHD.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether almotriptan enters human breast milk. Almotriptan is concentrated in rat milk (7 × higher rat plasma).
Drug Interactions SSRIs (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline ) may rarely cause weakness, hyperreflexia, and incoordination when given with 5-HT 1 agonists. MAOIs (e.g., moclobemide) may decrease almotriptan clearance. Verapamil may increase almotriptan plasma concentrations. Ketoconazole and other potent CYP3A4 inhibitors increased the AUC for almotriptan by 60%. Although the interaction between almotriptan and other potent CYP3A4 inhibitors (e.g., itraconazole, ritonavir, erythromycin ) has not been studied, increased levels to almotriptan are to be expected when used with these medications.
References There is no published experience in pregnancy or during lactation.
Summary Pregnancy Category: C
Lactation Category: U

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

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

Aloe Vera — (Aloe Vera; Cape; Zanzibar; Socotrine)

International Brand Names

None identified.

Drug Class Dermatologics
Indications Wound healing
Mechanism May neutralize or bind to the fibroblast growth factor-2 receptor
Dosage With Qualifiers Wound healing—applied topically using a variety of formulations

  • Contraindications— hypersensitivity to drug or class

  • Caution —unknown

Maternal Considerations Aloe vera gel is extracted from the inner layer of the leaf and contains a myriad of compounds. Two FDA advisory panels concluded there was insufficient evidence that aloe vera is useful for the treatment of minor burns, cuts, or vaginal irritation. However, one study suggested aloe vera may accelerate wound healing by promoting gap junctional intercellular communication and proliferation of human skin fibroblasts. There are no adequate reports or well-controlled studies in pregnant women. It should never be ingested.
Side effects include severe gastric cramping and diarrhea if taken internally.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses.
Breastfeeding Safety There is no published experience in pregnancy. However, considering the topical route, it is unlikely the breastfed neonate would ingest clinically relevant amounts.
Drug Interactions No drug-drug interaction studies in human subjects have been conducted.
References There is no published experience in pregnancy or during lactation.
Summary Pregnancy Category: C
Lactation Category: S (likely)

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

Alosetron Hydrochloride — (Lotronex)

International Brand Names

Liminos (Mexico)

Drug Class Antidiarrheals; Gastrointestinals; Serotonin receptor antagonist
Indications Diarrhea-predominant irritable bowel syndrome
Mechanism A selective and potent antagonist of the serotonin 5-HT 3 receptor
Dosage With Qualifiers Diarrhea associated with irritable bowel syndrome—1 mg PO bid

  • Contraindications —hypersensitivity to drug or class, constipation

  • Caution —unknown

Maternal Considerations There are no published reports of alosetron use during pregnancy.
Side effects include ischemic colitis, constipation, hypertension, allergic rhinitis, dyspepsia, and depressive disorders.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether alosetron crosses the human placenta. Rodent studies are generally reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically, with the exception of the mouse, where cleft palate and skeletal defects were reported.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether alosetron enters human breast milk. Alosetron is excreted into the milk of lactating rats.
Drug Interactions Co-administration of alosetron and fluvoxamine is contraindicated. Alosetron is metabolized by a variety of hepatic CYP drug-metabolizing enzymes. Fluvoxamine inhibits CYP1A2, CYP3A4, CYP2C9, and CYP2C19. Fluvoxamine increases mean alosetron plasma AUC some sixfold and prolongs the t/2 threefold. Other moderate CYP1A2 inhibitors, including quinolone antibiotics and cimetidine , should also be avoided unless necessary.
Ketoconazole is a strong inhibitor of CYP3A4 and increases alosetron plasma AUC by close to one-third. Other strong CYP3A4 inhibitors, such as clarithromycin, telithromycin, protease inhibitors, voriconazole, and itraconazole, have not been evaluated but should be used with caution with alosetron .
Based on several in vitro and in vivo studies, it is unlikely alosetron will inhibit the hepatic metabolic clearance of drugs metabolized by the major CYP enzyme 3A4, as well as the CYP enzymes 2D6, 2C9, 2C19, 2E1, or 1A2.
References There is no published experience in pregnancy or during lactation.
Summary Pregnancy Category: B
Lactation Category: U

  • Alosetron is rarely indicated during pregnancy and should be used only when the benefits outweigh any theoretic risks.

Alprazolam — (Alpralid; Alprazolam Intensol; Altraxic; Apo-Alpraz; Xanax; Xanax TS; Xanolam; Zoldac; Zolam; Zopax)

International Brand Names

Aceprax (Paraguay, Uruguay); Alcelam (Thailand); Alganax (Indonesia); Alnax (Thailand); Alpaz (Peru); Alplax (Argentina); Alpralid (Israel); Alpram (Korea); Alpranax (Israel); Alprax (Australia, India, Thailand); Alprocontin (India); Alprox (Israel, Taiwan); Altraxic (Philippines); Alviz (Indonesia); Alzam (South Africa); Alzax (Korea); Alzolam (India); Anax (Thailand); Anpress (Thailand); Ansiopax (Chile); Anxirid (South Africa); Anzion (Thailand); Apo-Alpraz (Canada, Singapore); Apraz (Brazil); Azor (South Africa); Calmlet (Indonesia); Cassadan (Germany); Constan (Japan); Daclor (Dominican Republic); Dixin (Colombia); Dizolam (Singapore); Drimpam (South Africa); Feprax (Indonesia); Frixitas (Indonesia); Frontal (Brazil); Kalma (Taiwan); Kinax (Taiwan); Marzolam (Thailand); Nalion (Hong Kong); Neupax (Mexico); Nirvan (Colombia); Pacyl (India); Panix (South Africa); Pharnax (Thailand); Prinox (Argentina); Renax (Hong Kong); Restyl (Israel); Sapram (Korea); Solanax (Japan); Tafil (Costa Rica, Denmark, El Salvador, Germany, Guatemala, Honduras, Mexico, Nicaragua, Panama, Venezuela); Tafil D (Mauritius); Tensivan (Colombia); Trankimazin (Spain); Tranquinal (Brazil, Ecuador, Paraguay, Peru, Uruguay); Tricalma (Chile, Peru); Valeans (Italy); Xanacine (Thailand); Xanagis (Israel); Xanax (Argentina, Belgium, Bulgaria, Canada, Colombia, Czech Republic, Ecuador, England, France, Germany, Greece, Hong Kong, Hungary, Ireland, Italy, Malaysia, Netherlands, Peru, Poland, Portugal, Switzerland, Taiwan, Thailand); Xanax SR (Singapore); Xanax TS (Canada); Xanax XR (Taiwan); Xanolam (South Africa); Xanor (Austria, Finland, Norway, Philippines, South Africa, Sweden); Xanor XR (Philippines); Zacetin (Korea); Zanapam (Korea); Zolam (India); Zopax (South Africa); Zotran (Chile); Zypraz (Indonesia)

Drug Class Anxiolytics; Benzodiazepines; Sedatives
Indications Acute anxiety
Mechanism A short-acting benzodiazepine that reduces anxiety by enhancing GABA effects
Dosage With Qualifiers Antianxietal—0.25–0.5 mg PO tid, max 4 mg/d
Panic disorder—0.5 mg PO tid, up to 1 mg after 3–4 d

  • Contraindications —hypersensitivity to drug or class, glaucoma, pregnancy, CNS depression

  • Caution —hepatic or renal dysfunction

Maternal Considerations The number of pregnant women using alprazolam seems to be growing, yet there remain few published reports of its use during pregnancy. Abrupt cessation of therapy is associated with a discontinuation-emergent syndrome that includes neuropsychiatric, GI, dermatologic, CV, and visual symptoms.
Side effects include physical dependence, syncope, tachycardia, seizures, respiratory depression, coma, drowsiness, light-headedness, dry mouth, depression, headache, constipation, diarrhea, N/V, insomnia, blurred vision, hypotension, increased salivation, and dermatitis.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Although there is no evidence that alprazolam is a human teratogen by either case reports or postmarketing surveillance, diazepam has been associated with fetal malformations. There is also concern based on studies with other benzodiazepines that postnatal behavior might be altered by antenatal exposure. Neonatal withdrawal has been reported. Treatment with phenobarbital is beneficial. Mice exposed to alprazolam demonstrate more individual than group activities and avoid open areas, and the males are more aggressive.
Breastfeeding Safety Alprazolam enters breast milk by passive diffusion, achieving an M:P ratio of 0.36. This is approximately 3% of the weight-adjusted maternal dose. Though the risk is reasonably small, alprazolam should be avoided during lactation because of the potential that it might alter neurodevelopment and because of the documented risks of withdrawal.
Drug Interactions Benzodiazepines such as alprazolam can produce additive CNS depressant effects when given with other psychotropic medications, anticonvulsants, antihistaminics, ethanol, and other drugs that themselves produce CNS depression.
Drugs or diseases that cause dry mouth or raise stomach pH may slow disintegration or dissolution, resulting in slowed or decreased absorption.
Alprazolam metabolism requires CYP3A hydroxylation. Drugs that inhibit this pathway can profoundly affect the clearance of alprazolam . Known drugs of concern include fluoxetine, propoxyphene, and oral contraceptives.
Clinical studies of other benzodiazepines suggest a possible drug interaction between alprazolam and diltiazem, isoniazid, macrolide antibiotics such as erythromycin and clarithromycin, and grapefruit juice. In vitro studies of other benzodiazepines suggest possible interactions with ergotamine, cyclosporine, amiodarone, nicardipine, and nifedipine .
Carbamazepine can increase alprazolam metabolism and thus decrease plasma levels.
Co-administration of nefazodone or fluvoxamine with alprazolam increases the peak concentrations, AUC, and t/2 of alprazolam.
Cimetidine impairs clearance of alprazolam and increases t/2.
HIV protease inhibitors (e.g., ritonavir ) may impair alprazolam clearance, prolong t/2, and enhance clinical effects.
References Anderson PO, McGuire GG. DICP Ann Pharmacother 1989; 23:614.
Christensen HD, Gonzalez CL, Rayburn WF. Am J Obstet Gynecol 2003; 189:1452-7.
Gidal J, Acs N, Banhidy F, Czeizel A. Toxicol lnd Health 2008; 24:53-60.
Oo CY, Kuhn RJ, Desai N, et al. Br J Clin Pharmacol 1995; 40:231-6.
St. Clair SM, Schirmer RG. Obstet Gynecol 1992; 80:843-6.
Summary Pregnancy Category: D
Lactation Category: NS (likely)

  • Alprazolam should be avoided during pregnancy and lactation unless there are no safer options.

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

Alteplase — (Actilyse; Activacin; Activase; TPA)

International Brand Names

Actilyse (Austria, Bangladesh, Belgium, Brazil, Bulgaria, Colombia, Czech Republic, Denmark, England, Finland, France, Germany, Greece, Hungary, Italy, Japan, Mexico, Netherlands, Norway, Pakistan, Poland, Portugal, South Africa, Spain, Sweden, Switzerland); Activacin (Japan)

Drug Class Thrombolytics
Indications Acute MI, pulmonary embolus, acute ischemic stroke
Mechanism Human recombinant tissue plasminogen activator is a serine protease that converts plasminogen to plasmin in the presence of fibrin.
Dosage With Qualifiers Acute MI—within 4 h of symptom onset and based on weight: < 67 kg, 15 mg bolus IV, followed by 0.75 mg/kg IV over the next 30 min (not to exceed 50 mg), then 0.5 mg/kg over the next 60 min (not to exceed 35 mg); > 66 kg, 15 mg bolus IV, followed by 50 mg IV over 30 min, then 35 mg over the next 60 min
Pulmonary embolus—100 mg IV over 120 min; initiate heparin therapy near the end or immediately following the alteplase when either the PTT or TT returns to < 2 × normal
Acute ischemic stroke—given within 4 h of symptom onset: 0.9 mg/kg IV over 60 min; begin with 10% of dose as an IV bolus over 1 min (max total dose 90 mg)

  • Contraindications —hypersensitivity to drug or class, intracranial hemorrhage, seizure at onset of stroke, internal bleeding, intracranial neoplasm, aneurysm, hypertension (> 185/110 mmHg S/D)

  • Caution —unknown

Maternal Considerations There are no adequate reports or well-controlled studies of alteplase in pregnant women. There are case reports of its use during pregnancy for the treatment of PE, MI, and peripheral thrombosis without an apparent increase in risk for hemorrhage, abruption, and PROM or preterm labor.
Side effects include cerebral hemorrhage, arrhythmias, severe bleeding, anaphylaxis, hypotension, N/V, and fever.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether alteplase crosses the human placenta. It could theoretically interfere with implantation. In light of its high molecular weight, alteplase is unlikely to cross the placenta. No maternal or fetal toxicity was evident at 0.65 times (1 mg/kg) the human dose in pregnant rats and rabbits dosed during organogenesis. Rodent teratogenicity studies have not been conducted.
Breastfeeding Safety There is no published experience in nursing women. Although tissue plasminogen activator is a normal constituent of human breast milk, it is unknown whether alteplase increases that level.
Drug Interactions Drugs that alter platelet function (e.g., aspirin, dipyridamole, abciximab ), in addition to heparin and vitamin K antagonists, may increase the risk of bleeding if administered prior to, during, or after alteplase .
There are postmarketing reports of orolingual angioedema associated with alteplase .
References Baudo F, Caimi TM, Redaelli R, et al. Am J Obstet Gynecol 1990; 163:1274-5.
Grand A, Ghadban W, Perret SP, et al. Ann Cardiol Angeiol 1996; 45:517-22.
Huang WH, Kirz DS, Gallee RC, Gordey K. Obstet Gynecol 2000; 96:838.
Nassar AH, Abdallah ME, Moukarbel GV, et al. J Perinat Med 2003; 31:257-60.
Schumacher B, Belfort MA, Card RJ. Am J Obstet Gynecol 1997; 176:716-9.
Summary Pregnancy Category: C
Lactation Category: U

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

  • It is effective for acute thrombotic events that place the patient’s survival in question.

Amantadine — (Contenton; Endantadine; Infectoflu; Mantandan; Shikitan; Symmetrel; Topharmin)

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