Part 15 (2/2)

No studies have been published on congenital anomalies after exposure to naltrexone during embryogenesis. Three case series comprising reportedly nonoverlapping patients contained 31 infants whose mothers used naltrexone during the first trimester, and there were no congenital anomalies present (Hulse and O'Neil, 2002; Hulse et al et al., 2001, 2004). Notably, these gravidas were given naltrexone as part of a treatment regimen for heroin addiction. According to its manufacturer, this agent was shown to be embryocidal in animal studies. Independent investigators have reported no increased frequency of congenital anomalies among rats or rabbits exposed during embryogenesis.

160.

a.n.a.lgesics during pregnancy OTHER a.n.a.lGESICS.

Butalbital Butalbital is a short-acting barbiturate that is contained in a variety (over 40) of available prescription a.n.a.lgesic compounds. Butalbital is usually combined with aspirin or acetaminophen (with or without caffeine). The most common indication for butalbital-containing a.n.a.lgesic compounds is tension headaches. All barbiturates cross the placenta, as do acetaminophen and aspirin. Barbiturate use in the first trimester was not a.s.sociated with an increase in the frequency of congenital anomalies in exposed offspring. However, barbiturates have been a.s.sociated with fetal dependence and newborn withdrawal symptoms when used chronically by the mother in the third trimester.

Medical compounds comprised of isometheptene, dichloralphen.a.z.ine and acetaminophen (Midrin, Amidrin, Migratine) are used to treat vascular headaches or migraines.

Isometheptene, a sympathomimetic drug, causes vasoconstriction. Dichloralphenazone is a mild sedative. This combination is commonly used during pregnancy, but no studies of the risk of congenital anomalies are available for two of the components (isometheptene, dichloralphen.a.z.ine).

Sumatriptan and other triptans Sumatriptan (Imitrex) is a selective 5-hydroxytryptamine receptor agonist. It is used primarily as acute therapy for migraine headaches. Among 658 infants born to women who used sumatriptan during the first trimester, the frequency of congenital anomalies was no greater than expected (Kallen and Lynger, 2001). According to its manufacturer, it has been shown to cause malformations in rabbits but was not teratogenic in rats. Using the ex vivo ex vivo isolated perfused cotyledon technique, sumatriptan crossed the placenta by pa.s.sive transport in the isolated perfused cotyledon technique, sumatriptan crossed the placenta by pa.s.sive transport in the ex vivo ex vivo isolated perfused cotyledon technique (Schenker isolated perfused cotyledon technique (Schenker et al et al., 1995). This drug is listed as an FDA category C agent, but seems to be safe for use during pregnancy (Table 8.2). Other triptans include nartriptan, almotriptan, rizatriptan, zolmitriptan. None have been adequately studied during pregnancy.

SPECIAL CONSIDERATIONS.

Labor a.n.a.lgesics MEPERIDINE.

Meperidine provides effective pain relief for 24 h in most patients who need systemic labor a.n.a.lgesics. The usual dose is 2550 mg IV or 5075 mg IM. Promethazine, in a dose of 25 mg, is also usually given as an adjunct to prevent nausea (Table 8.3).

BUTORPHENOL.

Butorphenol is also a very effective narcotic for systemic a.n.a.lgesia and is usually given in a dose of 12 mg either IV or IM. This agent provides pain relief for up to 4 h.

Special considerations 161.

Table 8.2 Comparison of Teratogen Information System (TERIS) risk and Food and Drug Administration (FDA) pregnancy risk ratings Comparison of Teratogen Information System (TERIS) risk and Food and Drug Administration (FDA) pregnancy risk ratings Drug Risk Risk rating Acetaminophen None B.

Butalbital Unlikely C*

Butorphanol Undetermined C *

m Fenoprofen Undetermined B*

Fentanyl Undetermined C *

m Hydrocodone Unlikely C*

Hydromorphone Unlikely B*

Ibuprofen Minimal B *

m Indomethacin None to minimal B*

Isometheptene Undetermined C.

Meclofenamate Undetermined B*

Meperidine Unlikely B*

Methadone Unlikely B*

Morphine Congenital anomalies: unlikely neonatal neurobehavioral C *

m Effects: moderate Nalbuphine Undetermined B *

m Naloxone Undetermined Bm Naltrexone Undetermined Cm Naproxen Undetermined B *

m Oxycodone Undetermined B *

m Oxymorphone Undetermined B*

Pentazocine Unlikely C*

Phenacetin None B.

Phenylbutazone Undetermined C *

m Promethazine None C.

Propoxyphene None C*

Propranolol Undetermined C *

m Sulindac Undetermined B*

Sumatriptan Unlikely Cm Compiled from: Friedman et al., 1990; Briggs et al., 2005; Friedman and Polifka, 2006.

a.n.a.lgesia following minor procedures Several oral narcotic agents (hydrocodone, oxycodone) provide satisfactory relief for moderate pain a.s.sociated with minor surgical procedures, such as dental procedures. Narcotic agents should not be used over a protracted period of time (more than 7 days) late in pregnancy because of the potential for neonatal dependence or withdrawal symptoms.

Headache Headaches are common during pregnancy and may increase in frequency during gestation. In all headache syndromes, potential identifiable causes of headaches should be ruled out before a long-term treatment plan is implemented. Headache etiology in most 162 162 a.n.a.lgesics during pregnancy patients is unknown. Headaches are divided into two major categories: (1) tension and (2) vascular (migraine). For mild to moderate headaches, aspirin, acetaminophen, ibuprofen, or naproxen usually provide satisfactory relief. Acetaminophen is the preferred a.n.a.lgesic for use during pregnancy. Aspirin should be avoided during pregnancy for hematologic reasons, and especially when headaches occur close to term. Aspirin increases the potential for increased bleeding from salicylcate use. More generally, NSAIDS should not be used after 34 weeks gestational age because of the theoretical potential for premature closure of the ductus arteriosus and other potential adverse effects. If other agents have failed, ibuprofen appears to pose the least risk for increased bleeding and premature ductus closure.

Migraine (vascular) headaches are difficult to treat during pregnancy, and they seem to increase in frequency during gestation. The vasoconstrictive agent, ergotamine, is one of the agents used to treat migraine headaches in the nonpregnant patient; however, it is not recommended for use during pregnancy because it has (1) vasoconstrictive and (2) oxytocin-like actions. Propranolol at a dose of 40 mg or higher per day (several divided doses) has been effective for the treatment of some migraines in the pregnant patient, and poses a negligible risk to the unborn child.

Amitriptyline, a tricyclic antidepressant, has been used to treat migraine headaches in pregnant women. However, this agent should be used as a third line of medical treatment for migraine headaches among pregnant women with vascular headaches who have not responded to a.n.a.lgesics or propranolol.

The combination of isomethertene, dichloralphenazone, and acetaminophen is also used for treatment of migraine headaches during pregnancy. However, the effects of isomethertene and dichloralphenazone are unknown. Importantly, this combination of drugs should be avoided in women with hypertension. The usual dose is two capsules orally at the beginning of an attack and then one capsule every hour; up to five capsules in any one 12-h period (see manufacturer's prescribing recommendations).

Sumatriptan (Imitrex) has been studied sufficiently to state that the risk of congenital anomalies following first trimester exposure is not greater than that in the general population (Kallen and Lygner, 2001).

As emphasized earlier, narcotic a.n.a.lgesics should not be utilized on a chronic basis for headaches because of the potential for addiction in the mother and withdrawal symptoms in the fetus. However, narcotic a.n.a.lgesics may be efficacious for the treatment of an acute migraine episode with little to no risk to the fetus.

Table 8.3 Suggested dosage regimens for some commonly used parenteral narcotic a.n.a.lgesic agents for postoperative paina Suggested dosage regimens for some commonly used parenteral narcotic a.n.a.lgesic agents for postoperative paina Agent Dosage Butorphanol 24 mg IM q 34 h, or 0.51 mg IV q 34 h Hydromorphone 12 mg IM q 34 h, or 0.51 mg IV q 3 h Meperidine 50100 mg IM q 34 h Morphine 10 mg (520 mg) IM q 4 h Nalbuphine 10 mg IM or IV q 36 h Pentazocine 30 mg IM or IV q 34 h aRefer to manufacturer's recommendations.

Key references 163.

a.n.a.lgesia following operative procedures The most common indication for acute narcotic a.n.a.lgesic therapy is for postoperative pain relief. Women who require surgery during pregnancy can be safely treated with a variety of a.n.a.lgesic agents for postoperative pain with relative safety for the fetus. Two commonly used regimens are meperidine (Demerol), 50100 mg IM every 34 h, or hydromorphone (Dilaudid), 12 mg every 34 h. Dosage regimens for various parenteral preparations are summarized in Table 8.3.

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