8 Interactions found for:

The following applies to the ingredients: Hydrocodone (found in Norco)

Benefit should outweigh risk

US FDA pregnancy category: Not assigned

Risk Summary: Based on animal data, may cause fetal harm; prolonged maternal use of opioids during pregnancy may cause neonatal opioid withdrawal syndrome.

Comments:
-Women should be advised of the risk of neonatal abstinence syndrome and ensure that appropriate treatment will be available.
-Long-acting opioids should not be used during and immediately prior to labor, when short acting analgesics or other analgesic techniques are more appropriate.

Rats administered this drug during gestation and lactation showed increases in stillborn pups and decreases in pup survival at doses equivalent to the human dose of 100 mg/day. Reduced nursing behavior and decreased body weights were observed at 2 times the human dose. Reduced fetal weights were observed in rabbits given this drug during the period of organogenesis at doses equivalent to 5 times the human dose of 100 mg/day. Additionally, increases in the number of umbilical hernias, irregularly shaped bones, and delays in fetal skeletal maturation were observed in the study at doses 15 times the human dose of 100 mg/day. No fetal malformations were observed in rats and rabbits at doses approximately 2 (rats) and 10 (rabbits) times a human dose of 100 mg/day. Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes may cause neonatal opioid withdrawal syndrome. There are no controlled data in human pregnancy.

Chronic opioid use may cause reduced fertility in males and females; it is unknown whether these effects on fertility are reversible.

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: Acetaminophen-Hydrocodone (found in Norco)

Benefit should outweigh risk

US FDA pregnancy category: C

Comments:
-Prolonged use of opioids during pregnancy can result in physical dependence in the neonate; women should be advised of the risk of neonatal abstinence syndrome and ensure that appropriate treatment will be available.
-Monitor neonates exposed to opioid analgesics for signs of excess sedation and respiratory depression.

Opioid analgesics cross the placenta. Hydrocodone use during labor may cause respiratory depression in the newborn infant. Prolonged use of opioids during pregnancy can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. The onset, duration, and severity of the condition will vary based on maternal use (duration of use, timing, and amount of last use) and rate of elimination in the newborn. Acetaminophen has not been associated with major congenital malformations, although animal studies have identified adverse effects at clinically relevant doses. Epidemiologic data do not clearly report an association with oral acetaminophen and major birth defects, miscarriage, or adverse maternal or fetal outcomes when this drug is used during pregnancy, but due to methodological limitations cannot definitively establish the absence of any risk. In pregnant rats receiving oral drug at doses up to 0.88 times maximum human daily dose (MHDD) during organogenesis, fetotoxicity (reduced fetal weight and length) and dose-related increases in bone variations (reduced ossification and rudimentary rib changes) were observed. Areas of necrosis in both the liver and kidney of pregnant rats and fetuses were observed when pregnant rats were given oral drug throughout gestation at doses 1.2 times the maximum human daily dose. There are no controlled data in human pregnancy.

Chronic use of opioids may cause reduced fertility; it is unknown whether these effects are reversible.

FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

The following applies to the ingredients: Acetaminophen (found in Norco)

Benefit should outweigh risk

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

Risk Summary: A clear association of drug use and birth defects, miscarriage, or adverse maternal or fetal outcomes has not been shown with human use; animal studies have demonstrated adverse events at clinically relevant doses.

In pregnant rats receiving oral drug at doses up to 0.85 times maximum human daily dose (MHDD) during organogenesis, fetotoxicity and dose-related increases in bone variations (reduced ossification and rudimentary rib changes) were observed. Areas of necrosis in both the liver and kidney of pregnant rats and fetuses were observed when pregnant rats were given oral drug throughout gestation at doses 1.2 times the maximum human daily dose. Animal studies using the IV formulation have not been performed. In humans, this drug and its metabolites cross the placental barrier. Large cohort studies have not found an association between maternal use in the first trimester and either adverse pregnancy outcomes or congenital malformations. Some evidence of increased risk of neurodevelopmental disorders (e.g., attention deficit hyperactivity disorder [ADHD]), respiratory illness (e.g., asthma) and reproductive toxicity (e.g., androgen disruption) has been suggested in epidemiologic studies. However, extrapolating causation from pharmaco-epidemiological studies to humans is tricky considering various confounders and biases inherent in the study design. Associations seen in clinical cohort studies need clarification with randomized clinical trials (RCTs), which would be difficult to perform ethically in pregnant populations. The mechanism by which this drug or its metabolites affect neurological development, asthma, or endocrine/reproductive toxicity is poorly understood. It is important to factor in the risk of untreated febrile illness in mother and child when evaluating risks and benefits of using this drug. There are no controlled data in human pregnancy.

Epidemiologic data, including a population based case-control study from the National Birth Defects Prevention Study (n= 11,610) and data from 26,424 live singleton births have shown no increased risk of major birth defects in children with first trimester prenatal exposure. In 2015, the US Food and Drug Administration released results of their evaluation on published research studies looking at mothers who took this drug as either an over the counter or prescription product at any time during their pregnancy and the risk of attention deficit hyperactivity (ADHD) in their babies. They found all studies reviewed had potential limitations in their designs that prevented drawing reliable conclusions. In a prospective birth cohort study (Avon Longitudinal Study or Parents and Children [ALSPAC]) maternal drug exposure was assessed by questionnaire at 18 and 32 weeks, children were assessed at 61 months. Mothers were questioned about behavioral problems in their children at 7 years old; children's behavioral problems were assessed using the Strengths and Difficulties Questionnaire (SDQ). A number of confounders were evaluated although a limitation of the study was lack of information for drug use. The authors suggest there may be an association between drug use during pregnancy and behavioral problems in childhood that may be due to an intrauterine mechanism. Further studies are needed to test alternatives to a causal explanation.

According to published animal studies, this drug may cause reduced fertility in both males and females described as decreased testicular weights, reduced spermatogenesis, reduced fertility; and reduced implantation sites, respectively.

AU TGA pregnancy category A: Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.

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: Metformin

Benefit should outweigh risk

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

Risk Summary: Data are not sufficient to inform a drug-associated risk for major birth defects or miscarriage; published studies have not reported an increased risk. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy.

Comments:
-Maternal glucose levels should be well controlled prior to conception and throughout pregnancy to avoid maternal and fetal diabetes-associated risks.
-Premenopausal women should understand the potential for unintended pregnancy with use of this drug as ovulation may occur in some anovulatory women.

Animal studies do not indicate harmful effects with respect to pregnancy, embryo or fetal development, birth or postnatal development. Poorly-controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, stillbirth and delivery complications. Poorly controlled maternal diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. Published evidence suggests this drug has a good safety profile in women with no increased long-term effects in offspring up to 18 months; however, much of the evidence is from observational, small, and/or nonrandomized studies, and therefore data must be interpreted cautiously.

Many experts continue to recommend insulin as the drug of choice for type 1, type 2, and gestational diabetes when diet alone is unsuccessful in controlling blood sugars. The estimated background risk for major birth defects in women with pre-gestational diabetes mellitus with an HbA1C greater than 7 is 6% to 10% and for women with a HbA1C greater than 10, this risk has been reported to be as high as 20% to 25%. In the US, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The estimated risk of miscarriage for pregnant women with diabetes is unknown. There are no adequate and well-controlled studies in pregnant women.

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: Hydrocodone (found in Norco)

Use is not recommended and a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

Excreted into human milk: Yes

Comments: Infants exposed to this drug through breast milk should be closely monitored for excess sedation and respiratory depression; withdrawal symptoms can occur when maternal administration of hydrocodone is stopped or breastfeeding is stopped.

Maternal use of oral narcotics during breastfeeding can cause infant drowsiness, central nervous system depression, and even death. Newborns are particularly sensitive. Once a mother's milk comes in, it is best to provide pain control with a nonnarcotic analgesic. There are no studies describing drug levels of extended-release hydrocodone or its metabolites in breast milk. Hydrocodone is metabolized to 6 active metabolites including hydromorphone.

The following applies to the ingredients: Acetaminophen-Hydrocodone (found in Norco)

A decision should be made to discontinue breast-feeding or discontinue this drug, considering the importance of the drug to the mother

Excreted into human milk: Yes (acetaminophen) Yes (hydrocodone)

Comments:
-Breastfed infants should be monitored for excess sedation and respiratory depression; immediate medical attention should be sought if infant develops breathing difficulties or limpness.
-Withdrawal symptoms can occur in breastfed infants when maternal drug use or breastfeeding are stopped.

Breastfed infants of mothers who receive opioids, especially newborns, can experience drowsiness and CNS depression, even death. A study in 30 breastfeeding women found mean and median hydrocodone infant daily doses of 3.9 and 2.1 mcg/kg, respectively, which calculates to 2.4% and 1.6% of weight-adjusted maternal doses. Hydrocodone is metabolized to 6 active metabolites including hydromorphone. Mean and median hydromorphone daily doses of 2.1 and 0.3 mcg/kg, respectively, were found. Of interest was that 2 women excreted much more hydromorphone than others which might represent ultrarapid CYP450 2D6 metabolizers.

The following applies to the ingredients: Acetaminophen (found in Norco)

Caution is recommended.

Excreted into human milk: Yes

Comments;
-This drug has been used without apparent harmful effects.
-This drug is considered compatible with breastfeeding by the American Academy of Pediatrics.

This drug is excreted into breast milk in very small amounts. Published reports reveal peak levels occur 1 to 2 hours after dosing and are undetectable after 12 hours. Reports have also shown infants ingesting 90 mL of breast milk every 3 hours would receive an average of 0.14% (range 0.04% to 0.23%) of the mother's dose; calculated to be a maximum maternal weight-adjusted dose of around 2%. Other studies have shown similar calculated maximal maternal weight adjusted doses (1.1% to 3.6%); these doses are about 0.5% of the lowest recommended infant dose of this drug. A single case of a maculopapular rash has been reported in a 2-month old nursing infant; the rash recurred on rechallenge.

The following applies to the ingredients: Metformin

Benefit should outweigh risk

Excreted into human milk: Yes

Comments:
-Available data have not reported adverse effects in breastfed infants, however, this data is limited.
-Due to this limited data, product manufacturers recommend a decision should be made to discontinue nursing or discontinue the drug, considering the importance of the drug to the mother.
-Published data suggest this drug is compatible with breastfeeding; they recommend caution when nursing a newborn or premature infant, and those with renal impairment.

Drug levels are expected to be 0.5% (range 0.11% to 1%) of the mother's weight-adjusted dosage and milk/plasma ratio range between 0.13 and 1. Since milk levels are expected to be relatively constant, timing of breastfeeding with drug administration is expected to be of little benefit. One large prospective study found no adverse effects in breastfed infants. Low detectable serum levels were found in some breastfed infants.