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Nabumetone — (Nabuco; Relafen)

International Brand Names

Aflex (Thailand); Anfer (Thailand); Arthaxan (Germany); Bumetone (Korea, Thailand); Consolan (Denmark); Deku (Taiwan); Goflex (Indonesia); Labuton (Taiwan); Mebutan (Netherlands); Nabentac (Korea); Nabone (Thailand); Nabonet (Thailand); Nabuco (Israel); Nabuflam (India); Naburen (Colombia); Nabuser (Italy); Nacton (Korea); Nadorex (Colombia); Naflex (Thailand); Nametone (Thailand); Noac (Uruguay); No-Ton (Taiwan); Prodac (Korea); Relafen (Canada, Korea); Relif (Spain); Relifen (Japan, South Africa); Relifex (Brazil, Bulgaria, Costa Rica, Czech Republic, Denmark, Dominican Republic, Ecuador, El Salvador, England, Finland, Greece, Guatemala, Honduras, Hong Kong, Hungary, Ireland, Italy, Mexico, Nicaragua, Panama, Philippines, Poland, Sweden, Taiwan, Thailand, Turkey); Relisan (South Africa); Relitone (South Africa); Subuton (Taiwan); Tanleeg (Taiwan); Tontec (Taiwan); Unimetone (Korea)

Drug Class Analgesics, non-narcotic; NSAIDs
Indications Osteoarthritis or rheumatoid arthritis, antiinflammatory
Mechanism Inhibits cyclooxygenase and lipoxygenase, reducing prostaglandin synthesis
Dosage With Qualifiers Osteoarthritis—1 g PO qd or bid
Rheumatoid arthritis—1 g PO qd or bid
Antiinflammatory—1 g bid × 7–14 d; begin 2 g/d × 1 d; max 2 g/d

  • Contraindications —hypersensitivity to drug or class, NSAID-induced asthma

  • Caution —nasal polyps, GI bleeding, hypertension, CHF

Maternal Considerations Upon absorption, nabumetone is rapidly metabolized to its active metabolite 6MNA. There is no published experience with nabumetone or 6MNA during pregnancy.
Side effects include thrombocytopenia, GI bleeding, renal failure, Stevens-Johnson syndrome, interstitial nephritis, hepatotoxicity, agranulocytosis, abdominal pain, diarrhea, constipation, increased sweating, nervousness, insomnia, somnolence, tinnitus, cholestatic jaundice, duodenal ulcer, dysphagia, gastric ulcer, gastroenteritis, increased appetite, increased LFTs, melena, edema, urticaria, rash, dizziness, and headache.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether nabumetone or 6MNA 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. There is evidence, however, of increased embryo resorption.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether nabumetone or 6MNA enters human breast milk. According to the manufacturer, 6MNA is secreted into the milk of rodents.
Drug Interactions Caution should be exercised with warfarin because enhancement has been observed in association with other NSAIDs.
There is more rapid absorption if administered with food or milk; however, the total amount in the plasma is unchanged.
References There is no published experience in pregnancy or during lactation.
Summary Pregnancy Category: C
Lactation Category: U

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

  • Nabumetone is not recommended for use in the third trimester due to the known effects of NSAIDs on the human fetal cardiovascular system (closure of ductus arteriosus).

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

Nadolol — (Corgard)

International Brand Names

Apo-Nadol (Hong Kong); Apo-Nadolol (New Zealand); Corgard (Argentina, Belgium, Brazil, Canada, Chile, Colombia, England, France, Greece, Ireland, Italy, Kenya, Malaysia, Mexico, Nigeria, Peru, Philippines, Poland, Russia, South Africa, Spain, Switzerland, Taiwan, Tanzania, Turkey, Uganda, Uruguay, Venezuela, Zambia); Farmagard (Indonesia); Nadic (Japan); Solgol (Austria, Germany, Spain)

Drug Class Adrenergic antagonists; β-Blockers
Indications Hypertension, angina, arrhythmia, headache prophylaxis (vascular)
Mechanism Nonselective β-adrenergic receptor antagonist
Dosage With Qualifiers Hypertension—begin 20–40 mg/d; increase 40–80 mg qd × 2–14 d; max 240–320 mg/d
Angina—begin 20–40 mg/d; increase 40–80 mg qd × 3–7 d; max 160–240 mg/d
Arrhythmia—60–640 mg PO qd
Headache (migraine) prophylaxis (vascular)—20–80 mg PO qd; max 120 mg/d

  • Contraindications —hypersensitivity to drug or class, sinus bradycardia, asthma, second- to third-degree AV block

  • Caution —diabetes mellitus, hepatic failure, CHF

Maternal Considerations Nadolol is a nonselective β-blocker offering the advantage of once-daily dosing. It is popular for migraine prophylaxis. There are no adequate reports or well-controlled studies of nadolol in pregnant women. The published literature is limited to case reports. In one instance, it was used to treat hypertension associated with primary hyperaldosteronism.
Side effects include fatigue, dizziness, slurred speech, bradycardia, rash, CHF, bronchospasm, constipation, dry mouth, nausea, diarrhea, weight gain, cough, nasal stuffiness, sweating, tinnitus, facial swelling, and blurred vision.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether nadolol crosses the human placenta. Other drugs in this class do cross. Case reports suggest fetal exposure may increase the risk of cardiorespiratory depression, mild hypoglycemia, and IUGR. Its long duration of action and the fact that it is only 30% protein bound make nadolol less desirable during pregnancy than other β-blockers such as propranolol. Nadolol crosses the rodent placenta. Rodent studies are generally reassuring, revealing no evidence of teratogenicity despite the use of doses higher than those used clinically. There is evidence of embryotoxicity and IUGR.
Breastfeeding Safety Nadolol is excreted into human breast milk. The relative infant dose is estimated to be 2%–7%. If a woman elects to continue nursing while taking nadolol, the child should be observed for evidence of β-blockade.
Drug Interactions May exaggerate the hypotension induced by general anesthetic agents.
May enhance hypoglycemia or hyperglycemia; adjust antidiabetic drug dosage accordingly.
References Devlin RG, Duchin KL, Fleiss PM. Br J Clin Pharmacol 1981; 12:393-6.
Fox RE, Marx C, Stark AR. Am J Obstet Gynecol 1985; 152:1045-6.
Solomon CG, Thiet M, Moore F Jr, Seely EW. J Reprod Med 1996; 41:255-8.
Wilson AL, Matzke GR. Drug Intell Clin Pharm 1981; 15:21-6.
Summary Pregnancy Category: C
Lactation Category: S (likely)

  • Nadolol 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 regarding use during pregnancy and lactation.

Nafcillin — (Nafcil; Nallpen; Unipen)

International Brand Names

Vigopen (Philippines)

Drug Class Antibiotics; Penicillins
Indications Bacterial infections, especially penicillinase-producing Staphylococcus
Mechanism Bactericidal—inhibits cell wall synthesis
Dosage With Qualifiers Bacterial infections—500 mg–2 g IV/IM q4–6 h; max 12 g/d IM or 20 g/d IV
NOTE: Hepatic and renal dosing; concurrent administration of nafcillin and probenecid increases and prolongs serum levels.

  • Contraindications —hypersensitivity to drug or class

  • Caution —cephalosporin allergy, renal or hepatic dysfunction, neonate

Maternal Considerations Nafcillin is a penicillinase-resistant antibiotic eliminated primarily by nonrenal routes, namely hepatic inactivation and excretion in the bile. There are no adequate reports or well-controlled studies of nafcillin in pregnant women. The published literature consists of scattered case reports. Other penicillins have proved safe during pregnancy.
Side effects include pain, swelling, inflammation, interstitial nephritis, pseudomembranous colitis, hepatotoxicity, seizures, tissue necrosis, N/V, diarrhea, candidiasis, urticaria, thrombophlebitis, neutropenia, leukopenia, thrombocytopenia, hypokalemia, and rash.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether nafcillin 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 nafcillin enters human breast milk. It is generally considered compatible with breastfeeding. Nafcillin is frequently used to treat mastitis of cows.
Drug Interactions Tetracycline may antagonize the bactericidal effect of penicillins and should be avoided.
High-dose regimens (e.g., 2 g q4h) may decrease the effects of warfarin for up to 30 d after the nafcillin has been discontinued. The PT should be monitored closely.
May cause subtherapeutic cyclosporine levels. Cyclosporine levels should be monitored when used with nafcillin .
References Takeba K, Fujinuma K, Miyazaki T, et al. J Chromatogr 1998; 812:205-11.
Summary Pregnancy Category: B
Lactation Category: S (likely)

  • Nafcillin is an alternative for the treatment of puerperal mastitis.

  • There are alternative agents if necessary during pregnancy for almost all indications.

Naftifine — (Naftin)

International Brand Names

Exoderil (Austria, Bulgaria, Costa Rica, Dominican Republic, El Salvador, Germany, Greece, Guatemala, Honduras, Hong Kong, Hungary, Indonesia, Malaysia, Nicaragua, Panama, Poland, Russia, Taiwan, Turkey); Jia Mei (Taiwan); Suadian (Italy)

Drug Class Antifungals; Dermatologics
Indications Fungal and candidal infections (fungal infections: T. rubrum, T. mentagrophytes, T. tonsurans; Epidermophyton floccosum, M. canis, M. audouinii, M. gypseum; Candida species: C. albicans ), skin infections
Mechanism Inhibits biosynthesis of ergosterol, and thus the fungal cell wall
Dosage With Qualifiers Skin infections—apply to affected area qd
NOTE: Available as 1% cream or gel.

  • Contraindications —hypersensitivity to drug or class

  • Caution —unknown

Maternal Considerations Clotrimazole , miconazole and nystatin are the primary antifungal agents to be used during pregnancy. Naftifine may be effective should they fail. There is no published experience with naftifine during pregnancy.
Side effects include burning, dryness, erythema, and itching.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether naftifine crosses the human placenta. Considering the dose and route, it is unlikely the maternal systemic concentration will reach a clinically relevant level. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether naftifine enters human breast milk. However, considering the dose and route, it is unlikely to pose a clinically significant risk to the breastfeeding neonate.
Drug Interactions No clinically relevant interactions identified.
References Patel VM, Schwartz RA, Lambert WC. J Eur Acad Dermatol Venereol 2017; 31:1440-6.
Summary Pregnancy Category: B
Lactation Category: S (probably)

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

Nalbuphine

International Brand Names

Bufigen (Mexico); Nalbufina (Uruguay); Nalcryn SP (Mexico); Nubain (Austria, Brazil, Bulgaria, Canada, Costa Rica, Czech Republic, Dominican Republic, Ecuador, El Salvador, England, Germany, Greece, Guatemala, Honduras, Hungary, Netherlands, New Zealand, Nicaragua, Panama, Philippines, Poland, Switzerland, Taiwan, Thailand, Venezuela); Nubaina (Argentina); Nubain SP (Mexico); Onfor (Argentina, Paraguay)

Drug Class Analeptics; Narcotic agonist-antagonists
Indications Pain, anesthesia (adjunct)
Mechanism Binds to opiate receptors
Dosage With Qualifiers Pain—10 mg IV/IM/SC q3–6 h prn; max 20 mg/dose or 160 mg/d
Anesthesia (adjunct)—0.25–0.5 mg/kg prn; begin 0.3–3 mg/kg IV

  • Contraindications —hypersensitivity to drug or class

  • Caution —opiate dependency; renal, hepatic, or pulmonary dysfunction; biliary surgery; sulfite allergy

Maternal Considerations Nalbuphine (formerly marketed as Nubain) is a synthetic opioid agonist-antagonist analgesic commonly used for intrapartum analgesia. Its potency is essentially equivalent to morphine on a milligram basis. Nalbuphine acts within minutes after IV administration, and < 15 min after SC or IM injection; the duration of analgesia ranges from 3 to 6 h. There are no well-controlled studies of nalbuphine in pregnant women. It is, however, a popular agent in some areas for analgesia during labor, comparable to meperidine. Concerns for fetal safety were raised by a pharmaceutical company that no longer manufactures nalbuphine (see http://www.fda.gov/medwatch/safety/2005/aug_PI/Nubain_PI.pdf ). There is insufficient information to support these concerns or to recommend any change in the administration of this medication for analgesia in labor. Due to its ability to bind the same opiate receptor as morphine, IV nalbuphine is sometimes used to treat intrathecal morphine -induced pruritus after cesarean delivery.
Side effects include headache, nervousness, depression, restlessness, crying, feeling of floating, hostility, unusual dreams, confusion, euphoria, faintness, hallucinations, dysphoria, feeling of heaviness, numbness, tingling, dizziness, bradycardia, hypotension, respiratory depression, dyspepsia, N/V, sweating, dry mouth, urticaria, cramps, dyspnea, asthma, bitter taste, speech difficulty, urinary urgency, blurred vision, pruritus, and substance abuse.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Nalbuphine crosses the human placenta, achieving an F:M ratio approximating 0.75. Nalbuphine decreases the number of FHR accelerations and variability, but it does not affect the fetal response to vibroacoustic stimulation. The neonatal t/2 is estimated at 4 h. Nalbuphine can cause respiratory depression and should be used with caution in women delivering preterm. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety The mean and maximum nalbuphine milk concentrations are 42 ± 26 and 61 ± 26 ng/mL, respectively. Assuming a milk volume of 150 mL/kg/d, the mean and maximum doses a breastfed neonate would ingest in 1 d are 7 ± 3.2 and 9 ± 3.8 mcg/kg/d. That equates to a relative infant dose of 0.59 ± 0.27% of the weight-adjusted maternal daily dose.
Drug Interactions Concomitant use with other drugs that affect the serotonergic neurotransmitter system, such as SSRIs, SNRIs, TCAs, triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system, and MAOIs, may result in serotonin syndrome.
References Committee on Obstetric Practice, American College of Obstetricians and Gynecologists. Obstet Gynecol 2007; 110:449.
Charuluxananan S, Kyokong O, Somboonviboon W, et al. Anesth Analg 2001; 93:162-5.
Culebras X, Gaggero G, Zatloukal J, et al. Anesth Analg 2000; 91:601-5.
Frank M, McAteer EJ, Cattermole R, et al. Anaesthesia 1987; 42:697-703.
Giannina G, Guzman ER, Lai YL, et al. Obstet Gynecol 1995; 86:441-5.
Jacqz-Aigrain E, Serreau R, Boissinot C, et al. Ther Drug Monit 2007; 29:815-8.
Nicolle E, Devillier P, Delanoy B, et al. Eur J Clin Pharmacol 1996; 49:485-9.
Poehlmann S, Pinette M, Stubblefield P. J Reprod Med 1995; 40:707-10.
Sherer DM, Cooper EM, Spoor C, et al. Am J Perinatol 1994; 11:367-8.
Somrat C, Oranuch K, Ketchada U, et al. J Obstet Gynaecol Res 1999; 25:209-13.
Wischnik A, Wetzelsberger N, Lucker PW. Arzneimittelforschung 1988; 38:1496-8.
Summary Pregnancy Category: B
Lactation Category: S

  • Nalbuphine is a popular labor analgesic and an efficacious treatment of side effects secondary to epidural morphine.

Nalmefene — (Cervene; Revex)

International Brand Names

None identified.

Drug Class Antidotes; Narcotic agonist-antagonists
Indications Opiate overdose, postoperative opiate reversal
Mechanism Opiate receptor antagonist
Dosage With Qualifiers Opiate overdose—0.5 mg IV; over 70 kg, dose individually; max 1.5 mg
Postoperative opiate reversal—0.25 mcg/kg IV; increase 0.25 mcg/kg increments q2–5 min; max 1 mcg/kg IV

  • Contraindications —hypersensitivity to drug or class

  • Caution —renal or hepatic dysfunction, opiate addiction, concomitant usage of cardiotoxic drugs

Maternal Considerations Nalmefene is a long-acting opioid antagonist used to treat an overdose. It has also been used to provide long-term relief from side effects of intrathecal morphine, but it failed in the one prospective trial to reduce the incidence of pruritus, N/V, and the level of sedation.
Side effects include arrhythmia, tachycardia, bradycardia, fever, postoperative pain, N/V, headache, vasodilation, dizziness, somnolence, confusion, and chills.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether nalmefene 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 Nalmefene is excreted into human breast milk, though the kinetics remain to be elucidated. However, considering the indication and dosing, one-time nalmefene use is unlikely to pose a clinically significant risk to the breastfeeding neonate.
Drug Interactions No clinically relevant interactions identified.
References Pellegrini JE, Bailey SL, Graves J, et al. AANA J 2001; 69:199-205.
Summary Pregnancy Category: B
Lactation Category: S (likely)

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

  • There are superior agents to treat the side effects of intrathecal morphine.

Naloxone — (Narcan)

International Brand Names

Antioplaz (Argentina); Mapin (Hong Kong, Malaysia); Nalone (France); Naloxon (Germany); Naloxona (Ecuador); Narcan (Belgium, Brazil, Canada, England, Greece, Ireland, Italy, Korea, Netherlands, Philippines, Switzerland, Taiwan, Venezuela); Narcan Neonatal (France); Narcanti (Argentina, Austria, Bulgaria, Czech Republic, Denmark, Finland, Germany, Hungary, Mexico, Norway, Poland, Sweden, Uruguay); Narcotan (India); Naxone (Israel); Zynox (South Africa)

Drug Class Antidotes; Narcotic agonist-antagonists
Indications Opiate overdose, postoperative opiate reversal
Mechanism Antagonizes various opiate receptors (opiate antagonist)
Dosage With Qualifiers Opiate overdose—0.4–2 mg SC/IV/IM q2–3 min; if no response by 10 min, the diagnosis should be questioned
Postoperative opiate reversal—0.1–0.2 mg IV q2–3 min prn

  • Contraindications —hypersensitivity to drug or class

  • Caution —opiate addiction, renal or hepatic dysfunction, cardiotoxic drugs

Maternal Considerations Naloxone is a popular opioid antagonist. Pregnant heroin users have poor maternal and neonatal outcome. Medically supervised heroin withdrawal is generally discouraged during pregnancy because of the fetal risk and a high likelihood of failure with return to regular illicit heroin use. More recently, a number of withdrawal procedures developed using naloxone or naltrexone have met with some success in users who continue the antagonist throughout pregnancy.
Maternal respiratory arrest is a rare but potentially life-threatening complication associated with intrathecal opioids for labor analgesia. Resuscitation should include IV naloxone. Very-low-dose IV naloxone is often used to treat neuraxially injected morphine -associated pruritus. It is not effective when given SC as prophylaxis.
The combination of buprenorphine / naloxone ( B/N ) is used to treat opioid use disorder and prevent buprenorphine abuse. During pregnancy, however, the use of buprenorphine as a single agent is preferred to prevent prenatal naloxone exposure. Women who become pregnant while taking B/N are advised to discontinue the naloxone but to continue the buprenorphine . The use of implant naltrexone is not associated with higher rates of poor birth outcomes compared with methadone - and buprenorphine -exposed neonates.
Side effects include cardiac arrest, VF, tachycardia, hypertension, hypotension, seizures, N/V, tremor, diaphoresis, pulmonary edema, withdrawal symptoms, and sweating.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Naloxone crosses the human placenta and may precipitate withdrawal in the fetus. Naloxone does not alter the placental transfer or clearance of morphine in humans. Neonates of women given parenteral opioids in labor that require naloxone have lower 1-min Apgar scores than neonates whose mothers have epidural analgesia. Physicians practicing in community vs. university hospitals use naloxone more often to resuscitate the neonate. It is unclear whether this increased use reflects adherence to the American Academy of Pediatrics’ guidelines for resuscitation or whether the neonates delivered in community hospitals require resuscitation more frequently. Either way it is clear this practice is poorly supported and should be examined. Porcine studies suggest that increased opioid “tonus” lowers the FHR and decreases fetal movement. Naloxone antagonizes the inhibitory effect of morphine on fetal heart rhythm and stimulates fetal hypermotility. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety There are no adequate reports or well-controlled studies in nursing women. It is unknown whether naloxone enters human breast milk. However, considering the indication and dosing, one-time naloxone use is unlikely to pose a clinically significant risk to the breastfeeding neonate. Endogenous opioids inhibit oxytocin neurons until parturition, and naloxone increases oxytocin secretion in pregnant rats. In humans, oxytocin secretion is inhibited in breastfeeding women by exogenous morphine compared with the control. Naloxone does not reverse the process.
Drug Interactions No clinically relevant interactions identified.
References Douglas AJ, Bicknell RJ, Russell JA. Adv Exp Med Biol 1995; 395:381-94.
Douglas AJ, Leng G, Russell JA. Reproduction 2002; 123:543-52.
Douglas AJ, Neumann I, Meeren HK, et al. J Neurosci 1995; 15:5049-57.
Head BB, Owen J, Vincent RD Jr, et al. Obstet Gynecol 2002; 99:452-7.
Herschel M, Khoshnood B, Lass NA. Pediatrics 2000; 106:831-4.
Hulse GK, O’Neill G, Pereira C, Brewer C. Aust N Z J Obstet Gynaecol 2001; 41:424-8.
Katsiris S, Williams S, Leighton BL, Halpern S. Can J Anaesth 1998; 45:880-3.
Kopecky EA, Simone C, Knie B, Koren G. Life Sci 1999; 65:2359-71.
Laslo J, Brunner JM, Burns D, et al. Matern Health Neonatol Perinatol 2017; 3:4.
Leighton BL, Halpern SH. Am J Obstet Gynecol 2002; 186(Suppl):S69-77.
Leighton BL, Halpern SH. Semin Perinatol 2002; 26:122-35.
Lindow SW, Hendricks MS, Nugent FA, et al. Gynecol Obstet Invest 1999; 48:33-7.
Lockington PF, Fa’aea P. Anaesthesia 2007; 62:672-6.
Summary Pregnancy Category: B
Lactation Category: S

  • Naloxone reverses the effect of narcotics on the fetus and newborn. It should be given within minutes of delivery.

Naltrexone — (ReVia; Trexan)

International Brand Names

Antaxone (Italy, Spain); Celupan (Spain); Nalerona (Chile, Peru); Nalorex (England, France, Ireland, Netherlands); Nemexin (Austria, Denmark, Finland, Germany, Poland, Switzerland); Nodict (India); Nutrexon (Indonesia); Phaltrexia (Indonesia); Regental (Uruguay); Revez (Argentina); Re-Via (Mexico); Revia (Brazil, Denmark, France, Hong Kong, Hungary, Israel, Korea, Taiwan); ReVia (Canada)

Drug Class Antidotes; Narcotic agonist-antagonists
Indications Opiate addiction, alcohol dependence
Mechanism Opioid receptor antagonist
Dosage With Qualifiers Opiate addiction—begin 25 mg PO × 1, repeat in 1 h if no withdrawal; alternatively 100 mg PO qd, then 150 mg PO q3d
NOTE: Patient must be opiate free × 7–10 d and pass the naloxone challenge test.
Alcohol dependence—50 mg PO qd

  • Contraindications —hypersensitivity to drug or class, hepatitis, hepatic failure, opiate use, failed naloxone challenge, failed naltrexone challenge, acute opiate dependence, acute opiate withdrawal

  • Caution —unknown

Maternal Considerations Naltrexone is a synthetic congener of oxymorphone with no opioid agonist properties. There are no adequate reports or well-controlled studies of naltrexone in pregnant women. Pregnant opiate users have poorer maternal and neonatal outcome. Medically supervised heroin withdrawal is generally discouraged during pregnancy because of the fetal risk and a high likelihood of failure with return to regular illicit heroin use. A number of withdrawal procedures have been developed using naloxone or naltrexone . Neither naltrexone nor buprenorphine is associated with the high rates of neonatal mortality or congenital anomalies seen in methadone -exposed neonates. Ovarian failure of hypothalamic origin is a consequence of an inappropriate increase in opioid tone of the neurons that release GnRH in a pulsatile manner. Naltrexone administration to these women can lead to pregnancy. After cesarean section, naltrexone is effective against the pruritus and vomiting associated with intrathecal morphine for analgesia, but it shortens the duration of analgesia.
Side effects include suicidal ideation, opiate withdrawal symptoms, insomnia, N/V, headache, anxiety, chills, anorexia, somnolence, constipation, abdominal pain, muscle aches, rash, dizziness, fatigue, restlessness, bone or joint pain, myalgia, and nasal symptoms.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Naltrexone crosses the human and rodent placenta. Rodent studies are generally reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically. There is evidence of embryo and early fetal toxicity. Rodents exposed to naltrexone during prenatal life are larger in weight and length, confirming that native opioids are important growth-inhibiting regulators. Naltrexone has no behavioral affect on exposed rabbit pups.
Breastfeeding Safety The excretion of naltrexone and its primary metabolite 6,β-naltrexol has been measured in the breast milk of one patient—an opiate-dependent woman undergoing oral naltrexone pharmacotherapy (5 mg/d). The total relative infant dose was < 1.4%. Only 6,β-naltrexol was detected in infant plasma and at a very low concentration of 1.1 mcg/L. These levels pose little risk to the newborn.
Drug Interactions Patients taking the XR injectable suspension may not benefit from opioids.
References Abboud TK, Lee K, Zhu J, et al. Anesth Analg 1990; 71:367-70.
Chan CF, Page-Sharp M, Kristensen JH, et al. J Hum Lact 2004; 20:322-6.
Christian MS. J Clin Psychiatry 1984; 45:7-10.
Farid WO, Dunlop SA, Tait RJ, et al. Curr Neuropharmacol 2008; 6:125-50.
Hulse G, O’Neil G. Aust N Z J Obstet Gynaecol 2002; 42:569-73.
Hulse GK, O’Neill G, Pereira C, Brewer C. Aust N Z J Obstet Gynaecol 2001; 41:424-8.
Kelty E, Hulse G. Drugs 2017; 77:1211-9.
McLaughlin PJ, Tobias SW, Lang CM, Zagon IS. Physiol Behav 1997; 62:501-8.
Saia KA, Schiff D, Wachman EM, et al. Curr Obstet Gynecol Rep 2016; 5:257-263.
Wildt L, Leyendecker G, Sir-Petermann T, Waibel-Treber S. Hum Reprod 1993; 8:350-8.
Zagon IS, Hurst WJ, McLaughlin PJ. Life Sci 1997; 61:1261-7.
Zagon IS, Hurst WJ, McLaughlin PJ. Life Sci 1998; 62:221-8.
Summary Pregnancy Category: C
Lactation Category: S (probably)

  • Naltrexone reduces the adverse symptoms associated with morphine analgesia but shortens the duration.

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

Naphazoline — (Ak-Con; Albalon; Allersol; I-Naphline; Murine; Muro’s Opcon; Nafazair; Naphacel; Naphazole; Naphcon Forte; Nazil; Ocu-Zoline; Opcon; Spectro-Con; Vasocon)

International Brand Names

Albalon (Belgium, Hong Kong, South Africa); Albalon Liquifilm (Netherlands, Philippines); Albasol (Chile, Colombia, Ecuador, Peru); All Clear (Hong Kong); Dazolin (Argentina); Idril N sine augentropfen (Germany); Imizol (Italy); Mirafrin (Colombia); Naftazolina (Italy); Naphacel Ofteno (Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama); Naphasal (Israel); Naphazolin (Germany); Naphcon (Greece, Israel, South Africa, Venezuela); Naphcon Forte (Belgium, Canada, Thailand); Naphtears (Paraguay, Uruguay); Nazil Ofteno (Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama); Privina (Brazil); Rintal (Peru); Vasocon (Canada); Vistalbalon (Germany); Zolin (Peru)

Drug Class Decongestants; Sympathomimetics
Indications Ocular congestion
Mechanism Stimulates α-adrenergic receptors (sympathomimetic)
Dosage With Qualifiers Ocular congestion—1–2 gtt OS/OD q3–4 h; max 4 doses/d

  • Contraindications —hypersensitivity to drug or class, glaucoma

  • Caution —CV disease, diabetes mellitus, hyperthyroidism, hypertension

Maternal Considerations There are no adequate reports or well-controlled studies of naphazoline in pregnant women.
Side effects include hyperemia, headache, dizziness, blurred vision, large pupils, increased sweating, weakness, and nervousness.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. It is unknown whether naphazoline crosses the human placenta. Considering the dose and route, it is unlikely the associated maternal systemic concentration will reach a clinically relevant level.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether naphazoline enters human breast milk. However, considering the indication and dosing, occasional naphazoline use is unlikely to pose a clinically significant risk to the breastfeeding neonate.
Drug Interactions No clinically relevant interactions identified.
References There are no current relevant references.
Summary Pregnancy Category: C
Lactation Category: S (likely)

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

Naproxen — (EC-Naprosyn; Ec-Naprosyn; Flexipen; Napoton; Napren; Naprosyn; Sutony)

International Brand Names

Acusprain (South Africa); Aflamax (Peru); Agilxen (Colombia); Aleve (Paraguay, Poland, Singapore, Uruguay); Alpron (Philippines); Anax (Korea); Anexopen (Greece); Antalgin (Spain); Apo-Naproxen (Canada); Apranax (Bulgaria, France, Israel, Russia, Venezuela); Apraxin (Turkey); Apronax (Colombia, Ecuador, Peru); Artagen (India); Artron (Mexico); Artroxen (Italy); Babel (Korea); Bipronyl (Singapore); Bonyl (Denmark); Complement (Peru); Congex (Argentina); Crysanal (Australia); Dafloxen (Mexico); Daprox (Denmark); Deflamox (Mexico); Diferbest (Mexico); Diocodal (Argentina); Dysmenalgit (Germany); Femex (Netherlands); Flanax (Brazil, Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua, Panama, Philippines); Flanax Forte (Peru); Floginax (Italy); Flonax (Peru); Fuxen (Mexico); Gibixen (Italy); Headlon (Japan); Inza (Australia, Hong Kong, Malaysia); Iraxen (Peru); Laraflex (England); Laser (Italy); Lefaine (Philippines); Leniartil (Italy); Licorax (Korea); Nafasol (South Africa); Naixan (Japan); Napolon (Korea); Naposin (Taiwan); Naprius (Italy); Naproflam (Germany); Naprong (Korea); Naprontag (Argentina); Naprorex (Hong Kong); Naprosyn (Canada, Czech Republic, Denmark, Ecuador, England, Finland, Greece, Hong Kong, India, Ireland, Italy, Malaysia, Norway, Peru, Portugal, Russia, Spain, Sweden, Switzerland, Turkey); Naprosyne (Belgium, France, Netherlands); Naprosyn LE (Thailand); Naprosyn LLE (Philippines); Naprosyn LLE Forte (Philippines); Naproxi 250 (Israel); Naproxi 500 (Israel); Naprux (Argentina); Napxen (Thailand); Narma (Japan); Narocin (Israel); Naxen (Canada, Indonesia, Mexico, South Africa); Naxen F (Korea); Naxen-F CR (Korea); Naxopren (Finland); Naxyn 250 (Israel); Naxyn 500 (Israel); Novo-naprox (Canada); Novonaprox (Canada); Nuprafem (Singapore); Nycopren (Austria, Denmark, Finland); Prexan (Italy); Primeral (Italy); Prodilor (Germany); Pronaxen (Malaysia, Sweden); Proxen (Austria, Germany, Spain, Switzerland); Proxen LLE (Taiwan); Proxidol (Israel); Rahsen (Japan); Roxen (Thailand); Sanomed (Philippines); Saritilron (Japan); Seladin (Malaysia); Shiprosyn (Philippines); Sutolin (Taiwan); Synflex (England, Hong Kong, Ireland); Tohexen (Japan); Uniflam (Peru); U-Ritis (Taiwan); Velsay (Mexico); Veradol (Argentina); Vinsen (Thailand); Wintrex (Peru); Xenar (Italy); Xenobid (India)

Drug Class Analgesics, non-narcotic; NSAIDs
Indications Osteoarthritis or rheumatoid arthritis, dysmenorrhea, pain, ankylosing spondylitis, antiinflammatory effect
Mechanism Inhibits cyclooxygenase and lipoxygenase, leading to reduced prostaglandin synthesis
Dosage With Qualifiers Osteoarthritis—250–500 mg PO bid; max 1500 mg/d × 3–5 d
Rheumatoid arthritis—250–500 mg PO bid; max 1500 mg/d × 3–5 d
Dysmenorrhea—250 mg PO q6–8 h prn; begin 500 mg × 1; max 1250 mg/d
Pain—250–500 mg PO bid; max 1500 mg/d × 3–5 d
Ankylosing spondylitis—250–500 mg PO bid; max 1500 mg/d × 3–5 d
Antiinflammatory effect—250–500 mg PO bid; max 1500 mg/d × 3–5 d

  • Contraindications —hypersensitivity to drug or class, NSAID-induced asthma, renal or hepatic dysfunction

  • Caution —GI bleeding, hypertension, CHF, nasal polyps, chronic alcoholic liver disease, anemia

Maternal Considerations NSAIDs are widely distributed in OTC preparations, and their use during pregnancy is underestimated. About 5% of women report using either ibuprofen or naproxen near conception or during pregnancy. In a prospective, case-control study, prenatal ibuprofen or naproxen use 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 was around conception or if it lasted more than 1 w. The increased spontaneous abortion rate could be secondary to pain prior to the actual passage of tissue thus biasing the studies. The use of naproxen or opioids was associated with a small but significant reduction in fecundability, but there was little association between other pain-relieving medications and fecundability. Naproxen may be used with sumatriptan for the treatment of acute migraine.
Naproxen offers no distinct clinical advantage after the first trimester over other NSAIDs on the market. It provides analgesic relief similar to acetaminophen after vaginal delivery. One randomized trial suggests the addition of regular doses of naproxen to prn requests for acetaminophen-codeine provides small reductions in pain on day 2 after cesarean delivery, with the greatest effects at 36 h, when pain typically peaks.
Side effects include headache, dyspnea, dizziness, drowsiness, light-headedness, vertigo, skin eruption, ecchymosis, sweating, purpura, edema, palpitations, tinnitus, hearing disturbances, visual disturbances, renal failure, bronchospasm, Stevens-Johnson syndrome, interstitial nephritis, hepatotoxicity, thrombocytopenia, agranulocytosis, constipation, rash, increased hepatic transaminases, urticaria, and fluid retention.
Fetal Considerations Naproxen crosses the human placenta, achieving an F:M ratio of 0.92 during the second trimester. Fetal levels are dependent on the maternal levels, as NSAIDs are not metabolized by the fetal kidney. A large prospective cohort study found no associations between the use of naproxen during the first trimester and an increased risk of overall or major congenital malformation rates. However, a meta-analysis of 30 studies that included 22 case-control studies, seven cohort studies, and one RCT concluded that exposure to aspirin or NSAIDs during the first trimester of pregnancy is associated with an increased risk of gastroschisis ( aspirin ), cardiac malformations ( NSAIDs ), and orofacial malformations ( naproxen ). Other NSAIDs can cause premature closure of the fetal ductus arteriosus. Although the ductal response to naproxen remains to be studied, there are several case reports of neonatal pulmonary hypertension after its use in the third trimester. Rodent studies are reassuring, revealing no evidence of teratogenicity or IUGR despite the use of doses higher than those used clinically.
Breastfeeding Safety Naproxen is excreted into human breast milk; the relative infant dose is 3.3%. Despite the low transfer, there have been a few reports of adverse effects including a 7-d-old newborn with prolonged bleeding and acute anemia.
Drug Interactions Displaced from its binding sites by aspirin , resulting in lower plasma concentrations and peak plasma levels.
NSAIDs reduce the tubular secretion of methotrexate in an animal model, possibly increasing the toxicity of methotrexate.
NSAIDs may diminish the antihypertensive effect of ACEIs.
NSAIDs may reduce the natriuretic effect of furosemide and thiazides. This response is attributed to inhibition of renal prostaglandin synthesis.
Increases the minimum lithium concentration some 15% and decreases renal clearance some 20%, presumably secondary to the inhibition of renal prostaglandin synthesis. Patients should be observed carefully for signs of lithium toxicity.
The effects of warfarin and NSAIDs on GI bleeding are synergistic. Caution is advised even though no significant interactions have been observed in clinical studies with naproxen and coumarin-type anticoagulants.
NSAIDs may reduce the antihypertensive effect of β-blockers.
Probenecid increases plasma levels and extends the t/2 significantly.
Use of naproxen delayed-release tablets are not recommended with H 2 blockers, sucralfate, or intensive antacid therapy due to the increase in gastric pH.
Naproxen absorption may be decreased with food.
References Angle PJ, Halpern SH, Leighton BL, et al. Anesth Analg 2002; 95:741-5.
Davies NM, Anderson KE. Clin Pharmacokinet 1997; 32:268-93.
Li DK, Liu L, Odouli R. BMJ 2003; 327:368-73.
McInerney KA, Hatch EE, Wesselink AK, et al. Hum Reprod 2017; 32:103-11.
Nakhai-Pour HR, Bérard A. Expert Rev Clin Pharmacol 2008; 1:605-16.
Nezvalová-Henriksen K, Spigset O, Nordeng H. BJOG 2013; 120:948-59.
Siu SS, Yeung JH, Lau TK. Hum Reprod 2002; 17:1056-9.
Skovlund E, Fyllingen G, Landre H, Nesheim BI. Eur J Clin Pharmacol 1991; 40:539-42.
Talati AJ, Salim MA, Korones SB. Am J Perinatol 2000; 17:69-71.
Summary Pregnancy Category: B
Lactation Category: S

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

  • Periconceptual naproxen may increase the risk of spontaneous abortion or decrease fertility.

  • First-trimester exposure should be minimized until completion of future studies in light of the association with orofacial malformations.

  • Acetaminophen ( paracetamol ) is the analgesic of choice in the first trimester.

  • Naproxen probably poses minimal risk when taken occasionally outside the first trimester.

Naratriptan — (Amerge)

International Brand Names

Amerge (Canada); Antimigrin (Austria); Naragran (Denmark); Naramig (Argentina, Australia, Belgium, Brazil, Bulgaria, Chile, Colombia, England, France, Germany, Ireland, Korea, Mexico, Netherlands, Peru, Singapore, South Africa, Thailand, Uruguay)

Drug Class Serotonin receptor agonists
Indications Migraine headache
Mechanism Selective 5-HT 1B/1D agonist
Dosage With Qualifiers Migraine headache—1–2.5 mg PO × 1; may repeat in 4 h after first dose; max 5 mg/d

  • Contraindications —hypersensitivity to drug or class, hypertension, CAD, hepatic failure, significant renal or hepatic dysfunction, MAOIs < 14 d, ergot derivatives < 24 h

  • Caution —CVD, mild hepatic dysfunction

Maternal Considerations Migraine headaches are a frequent complaint during pregnancy, and ergot compounds are generally considered contraindicated. From 55%–90% of pregnant women experience an improvement in headache symptoms during the second and third trimesters. A higher percentage of women with menstrual migraine find they improve during pregnancy. There are no adequate reports or well-controlled studies of naratriptan in pregnant women. The clearance of naratriptan is modestly reduced (22%) in women on oral contraceptives; clearance during pregnancy is unstudied. Smoking increases clearance by one-third. The manufacturer, Glaxo-Wellcome, maintained a registry for post-marketing information on pregnancy outcomes. Although the final results from the 16-y Glaxo-Wellcome pregnancy registry revealed no detectable increase in the rate of major birth defects after naratriptan exposure, the sample size was too small (57) to permit definitive conclusions of the risks.
Side effects include malaise, fatigue, abnormal ECG, acute MI, stroke, coronary vasospasm, cardiac arrest, palpitations, tachyarrhythmia, hypertensive crisis, colonic ischemia, hyposalivation, vomiting, tracheitis, asthma, pleuritis, tremors, cognitive function disorders, sleep disorders, disorders of equilibrium, anxiety, depression, hallucinations, panic, polyuria, diuresis, and inflammation of the breast, vagina, or bladder.
Fetal Considerations There are no adequate reports or well-controlled studies in human fetuses. Epidemiologic information is limited but reassuring. There is more experience with sumatriptan . It is unknown whether naratriptan crosses the human placenta. Rodent studies reveal embryotoxicity and skeletal abnormalities at doses producing maternal plasma levels only a few multiples of the MRHD. However, the frequencies of these adverse outcomes are not dose dependent.
Breastfeeding Safety There is no published experience in nursing women. It is unknown whether naratriptan enters human breast milk. It does enter rodent milk. However, considering the indication and dosing, one-time naratriptan use is unlikely to pose a clinically significant risk to the breastfeeding neonate. The patient may choose to pump her breasts for 24 h for added safety.
Drug Interactions Use of ergotamine-containing or ergot-type medications (e.g., dihydroergotamine, methysergide ) within 24 h is contraindicated as there is a theoretic concern the effects may be additive.
SSRIs (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline ) are reported, rarely, to cause weakness, hyperreflexia, and incoordination when co-administered with 5-HT 1 agonists.
MAOIs increase the systemic effects and elimination and raise plasma levels of naratriptan .
References Ephross SA, Sinclair SM. Headache 2014; 54:1158-72.
Evans EW, Lorber KC. Ann Pharmacother 2008; 42:543-9.
Källén B, Nilsson E, Otterblad Olausson P. Drug Saf 2011; 34:691-703.
Nezvalová-Henriksen K, Spigset O, Nordeng H. Headache 2010; 50:563-75.
Nezvalová-Henriksen K, Spigset O, Nordeng HM. Headache 2012; 52:1319-20.
Pfaffenrath V, Rehm M. Drug Saf 1998; 19:383-8.
Summary Pregnancy Category: C
Lactation Category: U

  • Naratriptan 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 regarding use during pregnancy and lactation.

Nateglinide — (Starlex)

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