7 Interactions found for:

The following applies to the ingredients: Gabapentin (found in Neurontin)

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Benefits should clearly outweigh risks

AU TGA pregnancy category: B3
US FDA pregnancy category: Not assigned

Risk Summary: There are no data on the developmental risks associated with use of this drug in pregnant women; in animal studies, developmental toxicity was observed at doses estimated to be similar or lower than those used clinically.

Comments:
-The risk of having a child with a congenital defect as a result of antiepileptic medication is far outweighed by the dangers to the mother and fetus of uncontrolled epilepsy; folic acid supplementation (5 mg) should be started 4 weeks prior to and continued for 12 weeks after conception.
-Women of childbearing potential should receive counseling on the risk of fetal abnormalities with use of antiepileptic drugs (AEDs) during pregnancy; AEDs should generally be continued during pregnancy utilizing monotherapy at the lowest effective dose as this has been shown to minimize risks of fetal abnormalities compared to combination AED therapy.
-A pregnancy exposure registry is available.

Animal studies have revealed evidence of developmental toxicity (increased fetal skeletal and visceral abnormalities, and increased embryofetal mortality) when administered at doses similar to, or lower than expected clinical doses. In rats, an increased incidence of hydroureter and/or hydronephrosis have been observed in offspring at all doses, the lowest dose being similar to the maximum recommended human dose on a mg/m2 basis. This drug crosses the human placenta. From the limited amount of data in human pregnancy, it is not possible to inform an associated increased risk of congenital malformations because epilepsy itself and the presence of concomitant antiepileptic medicinal products have their own risks. There are no controlled data in human pregnancy.

To provide information regarding the effects of in utero exposure to this drug, pregnant patients should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll-free number 1-888-233-2334 and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/.

AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D and X are being phased out.

The following applies to the ingredients: Tramadol

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According to some authorities: Use is not recommended.

AU TGA pregnancy category: C
US FDA pregnancy category: Not Assigned

Risk Summary: Insufficient data are available in humans to inform a drug-related risk; however, prolonged use of opioids during pregnancy for medical or nonmedical purposes can result in respiratory depression and physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.

Comments:
-Use is not recommended in pregnant women immediately prior to or during labor when other analgesic techniques are more appropriate.
-If prolonged use is required in a pregnant woman, advise the patient of the risk for neonatal opioid withdrawal syndrome, which could be life-threatening if not recognized and treated, and ensure appropriate monitoring and treatment will be available.
-Monitor newborns exposed to this drug for signs of excess sedation, respiratory depression, and neonatal opioid withdrawal syndrome and manage accordingly. An opioid overdose reversal agent must be available for reversal of opioid-induced respiratory depression in the neonate.

Animal studies have revealed decreased fetal weights, reduced ossification, and structural abnormalities in the brains of fetuses. This drug has been shown to cross the placental barrier with an umbilical vein to maternal vein serum concentration ratio of 0.83. There are no controlled data in human pregnancy; however, there have been postmarketing reports of neonatal seizures, neonatal withdrawal syndrome, fetal death, and still birth.

Chronic use of opioids may cause reduced fertility in females and males; however, it is unknown whether these effects are reversible.

AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

The following applies to the ingredients: Gabapentin (found in Neurontin)

Professional Content

Benefits should clearly outweigh risks

Excreted into human milk: Yes

Comments:
-Breastfed infants should be monitored for drowsiness, adequate weight gain, and developmental milestones, especially when used in combination with other anticonvulsant or psychotropic drugs and in younger, exclusively breastfed infants.
-Some authorities suggest discontinuing nursing or discontinuing use of this drug while breastfeeding due to the potential for serious adverse reactions in the breastfed infant.

With maternal doses up to 2.1 g/day, estimated doses for fully breastfed infants are 0.2 to 1.3 mg/kg/day (equivalent to 1.3 to 3.8% of the maternal weight-adjusted dose). An expert panel has deemed this drug is an acceptable choice for refractory restless leg syndrome during lactation. Until more data becomes available, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for this drug and any potential adverse effects on the breastfed infant from this drug or from the underlying maternal condition.

The following applies to the ingredients: Tramadol

Professional Content

Breastfeeding is not recommended during use of this drug.

Excreted into human milk: Yes

Comments:
-The effects in the nursing infant are unknown; there is the potential for serious adverse reactions (including excess sedation and respiratory depression) in breastfed infants.
-According to some authorities: This drug is not recommended for obstetrical preoperative medication or for postdelivery analgesia in nursing mothers because its safety in infants and newborns has not been studied.
-If infants are exposed through breast milk, they should be monitored for excess sedation and respiratory depression; withdrawal symptoms can occur in breastfed infants when maternal use of an opioid analgesic or breastfeeding is stopped.

In adults, this drug has 70% to 100% oral bioavailability and is metabolized to the active O-desmethyltramadol (M1); both parent drug and M1 are present in human milk. The parent drug has a more potent monoamine reuptake inhibitory effect while M1 has a more potent opioid mu-agonist effect (i.e., M1 is more potent than the parent drug in mu opioid receptor binding); M1 is about 10% as potent as morphine in mu-opiate binding, although some experts have reported a 450-fold potency difference. Women who are extensive metabolizers of this drug (CYP450 2D6 ultrarapid metabolizers) may have higher than expected M1 serum levels, potentially leading to higher M1 levels in breast milk which can be dangerous in their breastfed infants; the capacity of preterm and newborn infants to metabolize this drug to M1 is limited. In women with normal metabolism of this drug, the amount of parent drug secreted into human milk is low and dose dependent.

Excretion of this drug into milk is low and even lower amounts of the active metabolite (M1) are excreted. With usual maternal dosage, the amount excreted into breast milk is much less than the dose that has been given to neonates for analgesia and is unlikely to adversely affect nursing infants. Maternal use of oral opioids during breastfeeding can cause infant drowsiness, which may progress to rare but severe central nervous system depression; neonates appear particularly sensitive to the effects of even small dosages narcotic analgesics. The US FDA and the manufacturer recommend against the use of this drug during breastfeeding. If newborn's mother requires this drug, it is not a reason to discontinue breastfeeding; however, once the mother's milk comes in, pain control should be provided with a nonnarcotic analgesic and oral intake of this drug should be limited to 2 to 3 days at a low dosage with close infant monitoring. If this drug is used, infants should be monitored for excess sleepiness, difficulty breastfeeding, breathing difficulties, or limpness, and a physician should be contacted immediately if any of these occur.

After a single 100 mg IV dose, the cumulative excretion in breast milk within 16 hours postdose was 100 mcg of parent drug (0.1% of the maternal dose) and 27 mcg of M1.

Detectable levels (greater than 12 mcg/L) of this drug were found in samples of breast milk collected 10 hours after a 50 mg maternal dose (IV or oral); no other clinical details or milk levels were reported.

At 2 to 4 days postpartum, 75 mothers provided 3 milk samples from both breasts during the 6 hours following a 100 mg oral dose after taking at least 4 doses. The milk level averaged 748 mcg/L (parent drug) and 203 mcg/L (M1); these values translate to an infant dosage averaging 112 and 30 mcg/kg/day of the drug and metabolite, respectively. An exclusively breastfed infant would receive maternal weight-adjusted dosages of 2.24% of this drug and 0.64% of its metabolite. Reanalysis of this data using a population pharmacokinetic model showed a simulated maternal dosage of 100 mg every 6 hours yielded average milk levels of 0.82 mg/L (parent drug) and 0.36 mg/L (M1) in extensive metabolizers and 0.99 mg/L (parent drug) and 0.18 mg/L (M1) in poor metabolizers. Infant exposure to this drug and its metabolite was the same in both phenotype groups and represented 3.1% of the maternal weight-adjusted dose of this drug. Based on this analysis, the dosage of this drug excreted in milk in poor metabolizers would average 0.15 mg/kg/day, which is 2.6% of the weight-adjusted dose of this drug, and 1.5% of the recommended neonatal IV dose of 10 mg/kg/day; the dosage of M1 excreted in milk in extensive metabolizers would average 0.054 mg/kg/day, which represents 2% to 3% of the normal daily neonatal IV morphine equivalent dosage.

This drug can increase prolactin levels; however, the prolactin level in a mother with established lactation may not affect her ability to breastfeed.