Pregnancy Neonatal Opioid Withdrawal Syndrome Inform female patients of reproductive potential that use of Levorphanol Tartrate Tablets for an extended period of time during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated [see WARNINGS , PRECAUTIONS; Pregnancy ]. Embryo-Fetal Toxicity Inform female patients of reproductive potential that Levorphanol Tartrate Tablets can cause fetal harm and to inform the prescriber of a known or suspected pregnancy [see WARNINGS , PRECAUTIONS; Pregnancy ].
Pregnancy Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see WARNINGS ]. Available data with Levorphanol Tartrate Tablets in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, oral levorphanol produced malformations and nearly 50% embryo lethality in mice at 10 and 12 times the human daily dose of 12 mg/day, respectively.
Paternal exposure to levorphanol prior to mating to an untreated female resulted in reduced litter birth weights, developmental delays, and aberrant behavior in a swim maze at 34 times the human daily dose of 12 mg/day. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Clinical Considerations Fetal/Neonatal Adverse Reactions Use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight.
The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see WARNINGS ]. Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates.
An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. Levorphanol Tartrate Tablets are not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including Levorphanol Tartrate Tablets can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions.
However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Animal Data In a published study, levorphanol has been shown to cause central nervous system malformations consistent with neural tube defects (kinking of the spinal cord, hydromyelia, dilation of the fourth ventricle, and brachyury) in pregnant mice when given a single subcutaneous dose of 25 mg/kg (10 times the human daily dose of 12 mg/day based on a body surface area comparison) on Gestation Day 9.
Subcutaneous administration of 30 mg/kg levorphanol to pregnant mice on Gestation Day 9 resulted in approximately 50% mortality of the mouse embryos (12 times the human daily dose of 12 mg/day). In another published study, male mice were injected subcutaneously twice daily with increasing daily doses of levorphanol up to 42 mg/kg/day (34 times the human daily dose of 12 mg based on body surface area) for 5.5 to 8.5 days prior to mating with an untreated female.
Paternal exposure to levorphanol resulted in reduced birth weights of the litters, developmental delays in the offspring, and aberrant swim patterns in the progeny when measured at 6.5 to 8.5 weeks of age. Lactation Risk Summary The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Levorphanol Tartrate Tablets and any potential adverse effects on the breastfed infant from Levorphanol Tartrate Tablets or from the underlying maternal condition.
Clinical Considerations Infants exposed to Levorphanol Tartrate Tablets through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breastfeeding is stopped. Data Studies of levorphanol concentrations in breast milk have not been performed. However, morphine, which is structurally similar to levorphanol, is excreted in human milk.
Because of the potential for serious adverse reactions from levorphanol in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Levorphanol Tartrate Tablets are not recommended in children under the age of 18 years as the safety and efficacy of the drug in this population has not been established.
Geriatric Use Elderly patients (aged 65 years or older) may have increased sensitivity to levorphanol. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. The initial dose of Levorphanol Tartrate Tablets should be reduced by 50% or more in the infirm elderly patient.
Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were coadministered with other agents that depress respiration. Titrate the dosage of Levorphanol Tartrate Tablets slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see WARNINGS ].
This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function.
