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Rabeprazole — (Aciphex)

International Brand Names

Gastrodine (Chile); Pariet (Australia, Colombia, France, Germany, Indonesia, Mexico, Peru, Philippines, South Africa, Taiwan, Thailand); Rabec (Argentina); Rabeloc (India)

Drug Class Antiulcer agents; Gastrointestinals; Proton pump inhibitors
Indications GERD, esophagitis, duodenal ulcer, hypersecretory conditions, stress ulcer, ulcer prophylaxis
Mechanism Hydrogen-potassium ATP-ase inhibitor
Dosage With Qualifiers GERD—20 mg PO qd or bid × 4–8 w; may repeat for an additional 8 w if needed
Erosive esophagitis—20 mg PO qd or bid × 4–8 w; may repeat for an additional 8 w if needed
Duodenal ulcer—20 mg PO qd or bid × 4 w; may repeat for an additional 4 w if needed
Hypersecretory conditions—60 mg PO qd
NOTE: Do not crush or chew.

  • Contraindications —hypersensitivity to drug or class

  • Caution —hepatic dysfunction, long-term use

Maternal Considerations GERD or heartburn occurs in 45%–85% of women during pregnancy. The effect of estrogen and progesterone on lower esophageal sphincter tone is a recognized factor. The treatment for GERD is the reduction of gastric acidity. There is no published experience with rabeprazole during pregnancy. Other proton pump inhibitors are generally considered effective treatment for GERD during pregnancy. There are no reported adverse effects. Proton pump inhibitors are first-line agents for the prevention of “aspiration syndrome” during general anesthesia.
Side effects include hepatic failure, blood dyscrasias, headache, and diarrhea.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether rabeprazole 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.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether rabeprazole enters human breast milk. It is concentrated in rodent breast milk.
Drug Interactions May augment the INR and PT increase when used with coumadin.
Produces sustained inhibition of gastric acid secretion. An interaction with compounds that are dependent on gastric pH for absorption may occur due to the magnitude of acid suppression. For example, it decreases by almost one-third the bioavailability of ketoconazole and increases the AUC and C max for digoxin by 19% and 29%, respectively. Therefore patients may need to be monitored when such drugs are taken concomitantly.
In a clinical study in patients categorized by CYP2C19 genotype (n = 6 per genotype category), gastric acid suppression was higher in poor metabolizers compared with extensive metabolizers.
Also a substrate of CYP3A4. Inducers of this enzyme (e.g., rifampin, phenobarbital ) may increase the metabolism of rabeprazole, whereas inhibitors (e.g., ketoconazole , clarithromycin, nelfinavir ) may increase serum concentrations.
Use with amoxicillin and clarithromycin resulted in increased plasma levels of rabeprazole and 14-hydroxyclarithromycin. Use with clarithromycin or pimozide is contraindicated.
Prolonged treatment (≥ 2 y) with rabeprazole may lead to malabsorption of dietary vitamin B 12 and subsequent vitamin B 12 deficiency.
References There is no published experience in pregnancy or during lactation.
Summary Pregnancy Category: B
Lactation Category: U

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

  • Proton pump inhibitors are agents of choice for the treatment of GERD in nonpregnant patients.

  • Safety data are limited to animal studies and case reports. As a result, proton pump inhibitors are recommended during pregnancy only for the treatment of severe, intractable GERD.

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

Rabies immune globulin, human — (BayRab; Hyperab; Imogam rabies)

International Brand Names

Bayer Bayrab Rabies Immune Globulin (Philippines); Bayrab (Canada); Imogam (Australia); Imogan Rabia (Spain); Rabigam (South Africa); Rabuman Berna (Philippines, Thailand)

Drug Class Antivirals; Immune globulins
Indications Rabies exposure
Mechanism Passive immunization
Dosage With Qualifiers Rabies exposure—20I U/kg (0.133 mL/kg) concurrent with the first vaccine dose; if feasible, up to half the dose should be thoroughly infiltrated in the area of the wound and the rest IM in the gluteus
NOTE: May also be given up to day 7 after first vaccine dose; never give in the same syringe or site as vaccine.

  • Contraindications —none known

  • Caution —hypersensitivity to drug or class, asthma

Maternal Considerations Over 50% of the rabies cases among Americans result from exposure to dogs outside the United States. Prevention is key. Rabies is almost universally fatal once it occurs. Rabies immune globulin is prepared from the plasma of donors hyperimmunized with rabies vaccine. The product is standardized to an average potency of 150 IU/mL. Rabies vaccine and rabies immune globulin should be given to anyone suspected of rabies exposure unless previously immunized with rabies vaccine and with confirmed adequate antirabies titers. It has been used successfully without complication during pregnancy. The reported adverse reaction rate is similar in pregnant and nonpregnant women.
Side effects include injection site reaction and mild fever.
Fetal Considerations There are no adequate reports or well-controlled studies of rabies immune globulin in human fetuses. Antirabies IgG likely crosses the human placenta. Fetal infection with rabies is reported. It is not known whether transfer provides any level of protection to the perinate. Animal reproduction studies have not been performed.
Breastfeeding Safety There is no published experience in pregnancy. It is unknown whether rabies immune globulin enters human breast milk. However, other IgG antibodies are excreted into breast milk.
Drug Interactions Repeated doses of rabies immune globulin should not be administered once vaccine treatment has been initiated, as this could prevent the full expression of active immunity expected from the rabies vaccine.
Other antibodies in the rabies immune globulin preparation may interfere with the response to live vaccines such as measles, mumps, polio, or rubella. Immunization with live vaccines should not be given within 3 mo after rabies immune globulin administration.
References Chabala S, Williams M, Amenta R, Ognjan AF. Am J Med 1991; 91:423-4.
Chutivongse S, Wilde H, Benjavongkulchai M, et al. Clin Infect Dis 1995; 20:818-20.
Sipahioglu U, Alpaut S. Mikrobiyol Bul 1985; 19:95-9.
Sudarshan MK, Giri MS, Mahendra BJ, et al. Hum Vaccin 2007; 3:87-9.
Summary Pregnancy Category: C
Lactation Category: S (likely)

  • Rabies remains a problem in many locales; it is almost uniformly fatal once it manifests.

  • Postexposure prophylaxis with both rabies immune globulin and vaccine reduces the risk of disease.

  • Pregnant women respond to rabies immune globulin.

Rabies vaccine — (Imovax Rabies; RabAvert)

International Brand Names

Berirab P (Philippines); Imovax Rabbia (Italy); Lyssavac N Berna (Ecuador, Hong Kong, Malaysia, Peru, Philippines, Thailand); Rabies-Imovax (Finland, Sweden); Rabipur (Austria, Czech Republic, England, Germany, India, Ireland, Israel); Rabuman Berna (Ecuador); Rasilvax (Italy); Vacuna Antirrabica Humana (Colombia)

Drug Class Vaccines
Indications Rabies exposure
Mechanism Active immunization
Dosage With Qualifiers Rabies exposure, booster immunization—1 mL IM on days 0, 7, 21, and 28 after exposure
Rabies exposure, immunization—1 mL IM booster
NOTE: For IM use only.

  • Contraindications—none known

  • Caution—hypersensitivity to bovine gelatin, chicken protein, neomycin, chlortetracycline, amphotericin B

Maternal Considerations Over 50% of the rabies cases among Americans result from exposure to dogs outside the United States. It is almost universally fatal once manifest. Rabies vaccine is an inactivated vaccine grown in chicken fibroblasts. Rabies vaccine and rabies immune globulin should be given to anyone suspected of rabies exposure unless previously immunized with rabies vaccine producing confirmed adequate antirabies titers. There are no data on the interchangeable use of different rabies vaccines in a single pre- or postexposure series. Thus vaccine from a single manufacturer should be used for the complete series if possible. The vaccine has been used successfully during pregnancy, and pregnant women respond immunologically at least as well as nonpregnant women. The reported adverse reaction rate is similar in pregnant and nonpregnant women.
Side effects include anaphylaxis, paralysis, and muscular sclerosis.
Fetal Considerations There are no adequate reports or well-controlled studies of rabies vaccine in human fetuses. Fetal rabies is reported. It is likely the IgG antibody produced in response to the vaccine crosses the placenta. It is not known whether transfer provides any level of perinatal protection. Several trials have reported normal intrauterine growth and pregnancy outcome in women vaccinated for postexposure prophylaxis. There were no adverse vaccine effects reported in more than 250 pregnancies.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether rabies vaccine enters human breast milk. It is likely the antibodies produced in response to the vaccine are excreted into the milk. It is generally accepted that the woman can resume breastfeeding once the vaccination series has begun.
Drug Interactions Corticosteroids, other immunosuppressive agents, antimalarials, and immunosuppressive illnesses interfere with the development of active immunity after vaccination and may diminish the protective efficacy of the vaccine. Preexposure prophylaxis should be administered to such persons with the understanding that their immune response may be inadequate.
Immunosuppressive agents should not be administered during postexposure therapy unless essential for the treatment of other conditions. When rabies postexposure prophylaxis is administered to persons receiving corticosteroids or other immunosuppressive therapy, or who are immunosuppressed, it is important that a serum sample be tested for rabies antibody to ensure that an acceptable antibody response has been induced.
Rabies immune globulin must not be administered at more than the recommended dose, because the response to active immunization may be impaired.
References Chabala S, Williams M, Amenta R, Ognjan AF. Am J Med 1991; 91:423-4.
Chutivongse S, Wilde H, Benjavongkulchai M, et al. Clin Infect Dis 1995; 20:818-20.
Huang G, Liu H, Cao Q, et al. Hum Vaccin Immunother 2013 Jan; 9:177-83.
Sipahioglu U, Alpaut S. Mikrobiyol Bul 1985; 19:95-9.
Sudarshan MK, Giri MS, Mahendra BJ, et al. Hum Vaccin 2007; 3:87-9.
Sudarshan MK, Madhusudana SN, Mahendra BJ. J Commun Dis 1999; 31:229-36.
Sudarshan MK, Madhusudana SN, Mahendra BJ, et al. Indian J Publ Health 1999; 43:76-8.
Toouey S. Travel Med Infect Dis 2007; 5:327-48.
Summary Pregnancy Category: C
Lactation Category: U

  • Rabies remains a problem in many locales; it is almost uniformly fatal.

  • Postexposure prophylaxis with both immune globulin and vaccine reduces the risk of disease and may be lifesaving.

  • Rabies vaccine is a heat-killed product and not contraindicated during pregnancy.

  • Pregnant women respond to rabies vaccine at least as well as matched nonpregnant women.

  • There is no evidence of fetal jeopardy from vaccination.

Raloxifene — (Evista)

International Brand Names

Bonmax (India); Celvista (Thailand); Evista (Hong Kong, Indonesia, Israel, Korea, Malaysia, Philippines, Singapore, Taiwan); Loxar (Uruguay); Loxifen (Paraguay); Raxeto (Argentina)

Drug Class Calcium metabolism agents; SERMs
Indications Postmenopausal osteoporosis, prophylaxis and treatment
Mechanism Estrogen receptor modulator inhibiting bone resorption and turnover
Dosage With Qualifiers Postmenopausal osteoporosis—60 mg PO qd
NOTE: Take with vitamin D (400 U qd) and calcium.

  • Contraindications —hypersensitivity to drug or class, pregnancy, DVT, HRT or OCP use

  • Caution —unknown

Maternal Considerations The decline in estrogen after oophorectomy and menopause enhances bone resorption and accelerates bone loss. Osteoporosis is underdiagnosed and undertreated. SERMs are a family of drugs used to manage estrogen-related pathology. Raloxifene decreases resorption of bone and reduces biochemical markers of bone turnover to the premenopausal range. It has antiestrogenic actions on the uterus and breast. Raloxifene does not stimulate the endometrium and may reduce the risk of ovarian cancer. It does not appear to affect the patient’s interest in sex, desire for or frequency of sexual activity, or the frequency or intensity of orgasm. Nor does raloxifene interfere with estrogen and nonhormonal vaginal cream moisturizers in postmenopausal vaginal atrophy. Long-term effects are under study. There is no published experience during pregnancy.
Side effects include PE, DVT, hot flashes, arthralgia, flulike symptoms, sinusitis, nausea, weight gain, pharyngitis, depression, cough, leg cramps, insomnia, and dyspepsia.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is not known whether raloxifene crosses the human placenta. Studies in rodents reveal an increase in several types of defects, including heart, brain, and skeleton. Unlike estrogen, raloxifene does not alter the organization of the neuronal system related to sexual receptivity in rodents.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether raloxifene enters human breast milk.
Drug Interactions Use with cholestyramine is not recommended. Cholestyramine is an anion exchange resin and causes a 60% reduction in the absorption and enterohepatic cycling of raloxifene.
Use with coumadin was assessed in a single-dose study where it had no effect on the pharmacokinetics of coumadin, but decreased the PT some 10%. The PT should be monitored more closely when starting or stopping therapy with raloxifene. In the osteoporosis treatment trial, there were no clinically relevant effects of warfarin co-administration on plasma concentrations of raloxifene .
References Modugno F, Ness RB, Ewing S, Causley JA. Obstet Gynecol 2003; 101:353-61.
Parsons A, Merritt D, Rosen A, et al. Obstet Gynecol 2003; 101:346-52.
Pinilla L, Barreiro ML, Tena-Sempere M, Aguilar E. Neurosci Lett 2002; 329:285-8.
Vestergaard P, Rejnmark L, Mosekilde L. Osteoporos Int 2005; 16:134-41.
Summary Pregnancy Category: X
Lactation Category: U

  • There are no indications for raloxifene during pregnancy.

Ramipril — (Altace)

International Brand Names

Cardace (India); Corpril (Thailand); Delix (Germany); Hytren (Austria); Pramace (Sweden); Quark (Italy); Ramace (Australia, Belgium, Denmark, Finland, Korea, Mexico, Netherlands, Philippines, South Africa, Thailand); Triatec (Denmark, France, Greece, Indonesia, Ireland, Italy, Portugal, Sweden, Switzerland); Tritace (Austria, Belgium, Colombia, Costa Rica, Czech Republic, Denmark, Dominican Republic, Ecuador, El Salvador, England, Guatemala, Honduras, Hong Kong, Ireland, Korea, Mexico, Netherlands, New Zealand, Nicaragua, Panama, Philippines, Puerto Rico, Taiwan); Unipril (Italy); Vesdil (Germany)

Drug Class ACEI/A2R-antagonists
Indications Hypertension, post-MI CHF, CV risk reduction
Mechanism ACE inhibition
Dosage With Qualifiers Hypertension—begin 2.5 mg PO qd; max 20 mg PO qd
Post-MI CHF—begin 2.5 mg PO bid × 7 d, then 5 mg PO bid
CV risk reduction—begin 2.5 mg PO qd × 7 d, then 10 mg PO qd; indicated for patients > 55 y with either CAD, CVA, or PVD or with diabetes mellitus and at least one other risk factor
NOTE: Renal dosing.

  • Contraindications —hypersensitivity to drug or class, angioedema

  • Caution —severe CHF, renal dysfunction, renal artery stenosis, collagen vascular disease, hyponatremia, and volume depletion

Maternal Considerations Some ACEIs decrease proteinuria and preserve renal function in patients with hypertension and diabetes mellitus to a greater extent than other antihypertensive agents. They have been shown to decrease the progression of nephropathy in normotensive patients with type 2 diabetes mellitus. There are no adequate reports or well-controlled studies of ramipril in pregnant women. In general, ACEIs are avoided during pregnancy because of fetal risks. The lowest effective dose should be used if ramipril is required for BP control during pregnancy.
Side effects include angioedema, severe hypotension, hyperkalemia, hepatotoxicity, pancreatitis, agranulocytosis, neutropenia, cough, dizziness, fatigue, N/V, myalgias, arthralgias, and URI symptoms.
Fetal Considerations There is no published experience in human fetuses. Ramipril likely crosses the human placenta, as similar agents do. Transfer was described as low in one rodent study. Adverse fetal effects occur even after first-trimester exposure to ACEIs, for which the relative risk is 2.7. Exposure is associated with CV and CNS disorders. No such increase is seen with other classes of antihypertensive agents. Later exposure is associated with cranial hypoplasia, anuria, reversible or irreversible renal failure, death, oligohydramnios, prematurity, IUGR, and PDA. The mechanism of renal dysfunction is likely related to fetal hypotension associated with prolonged decreased glomerular filtration. There is inadequate study to decide whether ramipril is typical of ACEIs. However, the one published rodent study is reassuring. If oligohydramnios is detected, ramipril should be discontinued unless lifesaving for the mother. Antenatal surveillance should be initiated (e.g., BPP) if the fetus is potentially viable. Oligohydramnios may not appear until after the fetus has irreversible injury. Neonates exposed in utero to ACEIs should be observed closely for hypotension, oliguria, and hyperkalemia. If oliguria occurs despite adequate pressure and renal perfusion, exchange transfusion or peritoneal dialysis may be required.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether ramipril enters human breast milk. Its presence is described as low in rodents.
Drug Interactions Use with NSAIDs has been associated with worsening of renal failure and increased serum potassium.
May be associated with hypotension when used with diuretics, especially if the diuretic was recently initiated. The possibility can be minimized by either discontinuing the diuretic or increasing the salt intake prior to initiation of ramipril.
May attenuate potassium loss caused by thiazide diuretics. Potassium-sparing diuretics (e.g., amiloride, spironolactone, triamterene ) or potassium supplements can increase the risk of hyperkalemia. The patient’s serum potassium should be monitored frequently.
Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACEIs during therapy with lithium. These drugs should be used together with caution and frequent monitoring of serum lithium levels.
Telmisartan may increase the serum concentration of ramipril and its active metabolite, leading to adverse/toxic effects.
References Cooper WO, Hernandez-Diaz S, Arbogast PG, et al. N Engl J Med 2006; 354:2443-51.
Eckert HG, Badian MJ, Gantz D, et al. Arzneimittelforschung 1984; 34:1435-47.
Summary Pregnancy Category: C (first trimester), D (second and third trimesters)
Lactation Category: U

  • Ramipril and other ACEIs should be avoided throughout pregnancy if possible.

  • First-trimester exposure is likely associated with an increase in CV and CNS abnormalities.

  • Neonatal skull hypoplasia and reversible or irreversible renal failure are the most frequent fetal consequences of ACEIs during late pregnancy.

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

Ranitidine — (Ranitiget; Zantac)

International Brand Names

Azanplus (Colombia); Pylorid (Australia, Canada, Denmark, England, Hong Kong, Ireland, Israel, Netherlands, Thailand); Pylorid 400 (Philippines); Pylorisin (Austria)

Drug Class Antihistamines, H 2 ; Antiulcer agents; Gastrointestinals
Indications Duodenal or gastric ulcer, erosive esophagitis, GERD, dyspepsia
Mechanism H 2 antagonist
Dosage With Qualifiers Duodenal or gastric ulcer—150 mg PO bid
Erosive esophagitis—150 mg PO qid
GERD—150 mg PO bid
Dyspepsia—75 mg PO qd or bid
NOTE: Renal dosing; may be combined with bismuth subsalicylate (Tritec).

  • Contraindications —hypersensitivity to drug or class, porphyria

  • Caution —hepatic or renal dysfunction

Maternal Considerations Pregnant women with symptomatic GERD should be managed aggressively with lifestyle and dietary modification. Antacids are first-line therapy. Should they fail, ranitidine and cimetidine are second-line options during pregnancy. Ranitidine has also been used successfully during pregnancy for the treatment of Zollinger-Ellison syndrome. It is used in many labor wards every 6 h to reduce the risk of acid aspiration.
Side effects include hepatotoxicity, thrombocytopenia, myalgia, headache, N/V, diarrhea, constipation, vertigo, dizziness, malaise, dry skin, rash, and confusion.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Ranitidine crosses the human placenta, achieving about 40% of the level of antipyrine in the isolated perfused cotyledon. Epidemiologic study reveals no increased prevalence of adverse fetal outcomes following first-trimester exposure. Rodent studies are reassuring, noting no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically. Ranitidine reduces fetal gastric pH when administered to pregnant rabbits, suggesting placental transfer.
Breastfeeding Safety There is no published experience in nursing women. Although ranitidine is concentrated in human breast milk, no adverse effects are reported. Ranitidine is approved for use in pediatric practice.
Drug Interactions Clarithromycin increases plasma ranitidine concentrations by 50%–60% and 14-hydroxyclarithromycin plasma concentrations by almost one-third.
Prolonged treatment (≥ 2 y) with rabeprazole may lead to malabsorption of dietary vitamin B 12 and subsequent vitamin B 12 deficiency.
References Aslan A, Karaguzel G, Uysal N, et al. Am J Perinatol 1999; 16:209-15.
Dicke JM, Johnson RF, Henderson GI, et al. Am J Med Sci 1988; 295:198-206.
Garbis H, Elefant E, Diav-Citrin O, et al. Reprod Toxicol 2005; 19:453-8.
Hagemann TM. J Hum Lact 1998; 14:259-62.
Kearns GL, McConnell RF Jr, Trang JM, Kluza RB. Clin Pharm 1985; 4:322-4.
Larson JD, Patatanian E, Miner PB Jr, et al. Obstet Gynecol 1997; 90:83-7.
Matok I, Gorodischer R, Koren G, et al. J Clin Pharmacol 2010; 50:81-7.
Ruigomez A, Garcia Rodriguez LA, Cattaruzzi C, et al. Am J Epidemiol 1999; 150:476-81.
Stewart CA, Termanini B, Sutliff VE, et al. Am J Obstet Gynecol 1997; 176:224-33.
Summary Pregnancy Category: B
Lactation Category: S (likely)

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

  • Medications used for treating GERD are not routinely tested in randomized, controlled trials in pregnant women.

Ranolazine — (Ranexa)

International Brand Names

Drug Class Antianginal agent
Indications Chronic angina
Mechanism Unknown
Dosage With Qualifiers Chronic angina—500 mg PO bid; increase to 1000 mg PO bid as needed
NOTE: May be combined with β-blockers, nitrates, calcium channel blockers, antiplatelet therapy, lipid-lowering therapy, ACE inhibitors, and angiotensin receptor blockers.

  • Contraindications —hypersensitivity to drug or class, hepatic cirrhosis, CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, nelfinavir ) and inducers (e.g., rifampin, phenobarbital, St. John’s wort )

  • Caution — plasma levels increased ~ 40% to 50% in patients with renal dysfunction, QT interval prolongation

Maternal Considerations Chronic angina is a sign of cardiovascular disease, which is rare in the obstetric population. However, patients with chronic angina in pregnancy should be considered high risk to develop MI and managed accordingly. There are no published reports of ranolazine use during pregnancy.
Side effects include dizziness, headache, constipation, nausea.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is not known whether ranolazine crosses the human placenta, Rodent studies are reassuring, noting 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 ranolazine enters human breast milk. It is excreted into rodent breast milk.
Drug Interactions CYP3A inhibitors will increase ranolazine plasma concentrations. Strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir ) are contraindicated, whereas moderate inhibitors (e.g., diltiazem, verapamil, erythromycin, fluconazole, and grapefruit juice) require a ranolazine dosing adjustment.
Concomitant use of CYP3A inducers such as rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and St. John’s wort is contraindicated.
P-gp inhibitors (e.g., cyclosporine ) may increase ranolazine concentrations. Titrate dosage based on clinical response.
The exposure to CYP2D6 substrates, such as tricyclic antidepressants and antipsychotics, may be increased during co-administration with ranolazine , and lower doses may be required.
The dose of simvastatin should be lowered to 20 mg when used with ranolazine .
Limit the dose of metformin to 1700 mg daily when used with ranolazine .
References There is no published experience in pregnancy or during lactation.
Summary Pregnancy Category: C
Lactation Category: U (unknown)

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

Remifentanil — (Ultiva)

International Brand Names

None identified.

Drug Class Analgesics, narcotic
Indications Anesthesia
Mechanism Binds opiate receptors
Dosage With Qualifiers Anesthesia:
Induction—0.5–1 mcg/kg/min IV; anesthesia induced when given with a hypnotic and a muscle relaxant to avoid chest rigidity
Maintenance—0.05–2 mcg/kg/min IV; usually given along with inhaled or IV anesthetic agent
Postoperative—0.025–0.2 mcg/kg/min IV
Sedation—0.025–0.2 mcg/kg/min IV; usually given with sedative-hypnotic (e.g., propofol )
NOTE: Onset < 1 min, duration 5–10 min, peak 1–5 min.

  • Contraindications —hypersensitivity to drug or class, epidural or intrathecal use

  • Caution —respiratory depression

Maternal Considerations Unlike other opioids, remifentanil undergoes rapid hydrolysis by nonspecific blood and tissue esterases. Even after a 4-h infusion, the functional t/2 is only 4 min. This characteristic suggests a potential for use in obstetrics. The pharmacokinetic profile of remifentanil in midtrimester pregnant women was similar to that in the general population. In a pilot study, remifentanil provided superior pain relief to laboring women when given by PCA compared with IM meperidine. There are contradictory reports that remifentanil improves the success rate of external cephalic version in women at term. However, remifentanil is difficult to titer in clinical practice, and it produces high levels of sedation and excess rates of maternal oxygen desaturation. It is more often used as a supplement to neuraxial anesthesia during cesarean delivery.
Side effects include apnea, chest wall rigidity, ventricular arrhythmia, bradycardia, hypotension, dependency, seizures, N/V, shivering, fever, dizziness, constipation, headache, blurred vision, pruritus, oliguria, confusion, tachycardia, agitation, anxiety, and biliary spasm.
Fetal Considerations Remifentanil crosses the human placenta, achieving an F:M ratio approximating 0.5. Mean clearance approximates 93 mL/min/kg. Thus although remifentanil crosses the placenta, it appears to be rapidly metabolized, redistributed, or both. Neonatal sedation is reported. 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 remifentanil enters human breast milk. It is excreted into rodent breast milk. Considering the indication and t/2, one-time remifentanil use is unlikely to pose a clinically significant risk to the breastfeeding neonate.
Drug Interactions Remifentanil may enhance the effect of other CNS depressants.
References Burgos J, Pijoan JI, Osuna C, et al. Acta Obstet Gynecol Scand 2016; 95:547-54.
Kan RE, Hughes SC, Rosen MA, et al. Anesthesiology 1998; 88:1467-74.
Smith JA, Donepudi RV, Argoti PS, et al. Front Pharmacol 2017; 8:11.
Thurlow JA, Laxton CH, Dick A, et al. Br J Anaesth 2002; 88:374-8.
Volmanen P, Akural EI, Raudaskoski T, Alahuhta S. Anesth Analg 2002; 94:913-7.
Wang ZH, Yang Y, Xu GP. Medicine (Baltimore) 2017; 96:e6256.
Summary Pregnancy Category: C
Lactation Category: S (likely)

  • There are alternative agents with a higher safety profile for which there is more experience regarding use during pregnancy and lactation.

Repaglinide — (Prandin)

International Brand Names

GlucoNorm (Canada); NovoNorm (Argentina, Australia, Brazil, Chile, China, Colombia, Hong Kong, Indonesia, Korea, Malaysia, Mexico, Paraguay, Philippines, Singapore, Taiwan, Thailand, Uruguay); Prandin (Brazil); Rapilan (India); Sestrine (Argentina)

Drug Class Adrenergic antagonists; Antidiabetic agents
Indications Diabetes mellitus type 2
Mechanism ATP-dependent potassium channel antagonist that stimulates islet cell insulin release in a glucose-dependent manner
Dosage With Qualifiers Diabetes mellitus type 2—0.5–4 mg PO 5–30 min qac; max 16 mg/d
NOTE: Titer to glucose profile.

  • Contraindications —hypersensitivity to drug or class, IDDM, ketoacidosis

  • Caution —severe renal disease

Maternal Considerations The published experience during pregnancy with repaglinide is limited to isolated case reports. Its clearance is lower in women than in men. Insulin remains the standard agent for the treatment of hyperglycemia during pregnancy. However, a growing body of research indicates that some oral hypoglycemic agents such as glyburide may be equally effective and safe though more convenient.
Side effects include hypoglycemia, pancreatitis, Stevens-Johnson syndrome, hemolytic anemia, hepatic dysfunction, headache, URI symptoms, N/V, constipation, diarrhea, dyspepsia, myalgias, and chest pain.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Low levels of repaglinide crossed the human placenta in an ex vivo perfusion model. Rodent studies are reassuring, revealing no evidence of teratogenicity. However, an increased risk of IUGR may be secondary to chronic maternal hypoglycemia.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether repaglinide enters human breast milk. It does enter rat milk and is associated with skeletal deformities in the feeding pups.
Drug Interactions Metabolism may be inhibited by CYP3A4 inhibitors (e.g., ketoconazole, miconazole ) and antibacterial agents (e.g., clarithromycin, erythromycin ). Drugs that induce CYP3A4 (e.g., barbiturates, carbamazepine, rifampin ) may increase repaglinide metabolism.
Use with gemfibrozil may significantly increase repaglinide levels. Patients taking repaglinide should not start taking gemfibrozil; patients taking gemfibrozil should not start taking repaglinide. Concomitant use may enhance and prolong the blood glucose–lowering effects of repaglinide. Rare postmarketing events of serious hypoglycemia have been reported.
The hypoglycemic action of oral blood glucose–lowering agents may be potentiated by certain drugs, including β-adrenergic blocking agents, chloramphenicol, coumarins, MAOIs, NSAIDs and other drugs that are highly protein bound, probenecid, salicylates, and sulfonamides. The patient should be observed closely for hypoglycemia. When such drugs are withdrawn, the patient should be observed closely for loss of glycemic control.
Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the calcium channel blocking drugs, corticosteroids, estrogens, isoniazid, nicotinic acid, oral contraceptives, phenothiazines, phenytoin, thiazides and other diuretics, sympathomimetics, and thyroid products. When these drugs are withdrawn, the patient should be observed closely for hypoglycemia.
When given with food, repaglinide AUC is decreased, and taking it without eating may cause hypoglycemia. It is recommended that repaglinide be taken 30 min prior to a meal.
References Mollar-Puchades MA, Martin-Cortes A, Perez-Calvo A, Diaz-Garcia C. Diabetes Obes Metab 2007; 9:146-7.
Napoli A, Ciampa F, Colatrella A, Fallucca F. Diabetes Care 2006; 29:2326-7.
Tertti K, Petsalo A, Niemi M, et al. Eur J Pharm Sci 2011; 44:181-6.
Viertel B, Guttner J. Arzneimittelforschung 2000; 50:425-40.
Summary Pregnancy Category: C
Lactation Category: U

  • Repaglinide should be avoided during pregnancy and lactation until additional research supports its use.

Reserpine — (Reserpaneed; Serpalan; Serpasil; Serpatabs; Serpate; Serpivite)

International Brand Names

Maviserpin (Mexico); Rauserpine (Taiwan); Rauverid (Philippines); Serpasil (Canada, Indonesia); Serpasol (Spain)

Drug Class Adrenergic antagonists, other; Antihypertensives
Indications Hypertension, adjunct for psychosis
Mechanism Depletes catecholamine and 5-HT stores
Dosage With Qualifiers Hypertension—begin 0.5 mg PO qd × 1–2 w, then 0.1–0.25 mg PO qd
Psychiatric disorders—begin 0.5 mg PO qd
NOTE: Discontinue with first signs of depression.

  • Contraindications —hypersensitivity to drug or class, depression (especially with suicidal tendencies), active peptic ulcer, active ulcerative colitis, electroconvulsive therapy

  • Caution —history of either peptic ulcer or ulcerative colitis; gallstones; renal insufficiency; anesthesia; use of digoxin , quinidine, or other antihypertensives

Maternal Considerations Reserpine is a pure crystalline alkaloid of rauwolfia. It is a second-line agent for the treatment of hypertension. Reserpine is also used to treat cerebral vasospasm, migraines, Raynaud’s syndrome, refractory depression, tardive dyskinesia, and thyrotoxic crisis. There is only limited study during pregnancy.
Side effects include N/V, diarrhea, anorexia, dryness of mouth, hypersecretion, arrhythmias, syncope, angina-like symptoms, bradycardia, edema, dyspnea, epistaxis, nasal congestion, dizziness, headache, paradoxical anxiety, depression, nervousness, nightmares, drowsiness, myalgias, weight gain, deafness, and pruritus.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Reserpine crosses the human placenta. It can increase neonatal respiratory tract secretions and cause nasal congestion, cyanosis, and anorexia. Although it is unclear whether reserpine is a human teratogen, rodent studies reveal evidence of teratogenicity and embryotoxicity. It is also tumorigenic.
Breastfeeding Safety Reserpine is excreted in human breast milk. Increased respiratory tract secretions, nasal congestion, cyanosis, and anorexia can occur in breastfed infants.
Drug Interactions MAOIs should be avoided or used with extreme caution.
Should be used cautiously with digitalis and quinidine, because cardiac arrhythmias have occurred with rauwolfia preparations.
Use with other antihypertensive agents necessitates careful titration of dosage with each agent.
Use with TCAs may decrease the antihypertensive effect of reserpine.
The action of direct-acting amines (e.g., epinephrine, isoproterenol, metaraminol, phenylephrine ) may be prolonged. The action of indirect acting amines (e.g., amphetamines, ephedrine, tyramine ) is inhibited.
References Southern African Hypertension Society Executive Committee 2000. S Afr Med J 2001; 91:163-72.
Mirmiran M, Swaab DF. Neurotoxicology 1986; 7:95-102.
Summary Pregnancy Category: C
Lactation Category: NS

  • Reserpine should probably be avoided during pregnancy and lactation unless there is no other option.

  • Reserpine is no longer available in the United States.

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

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