4 Interactions found for:

The following applies to the ingredients: Budesonide (found in Symbicort)

Professional Content

Benefit should outweigh risk
-Some authorities, recommend avoiding the use of rectal formulations during pregnancy.

AU TGA pregnancy category: A (inhalation powder); B3 (oral and rectal foam)
US FDA pregnancy category: Not assigned

Risk Summary: The possibility of fetal harm with inhaled corticosteroids appears remote; but data are insufficient with oral and rectal administration to inform a drug-associated risk for major birth defects and miscarriage.

Comments:
-Hypoadrenalism may occur in neonates exposed to glucocorticosteroids in utero; carefully observe neonates for signs and symptoms of hypoadrenalism.

Teratogenicity and embryocidal effects have been observed in rabbits and rats administered subcutaneous doses that represent 0.05 and 0.5 times the maximum recommended human doses, respectively. These effects have been reported as increased fetal loss, decreased pup weights, and skeletal abnormalities. Higher doses administered by inhalation to rats have not shown to be teratogenic. Experience with oral corticosteroids at pharmacologic doses suggests rodents are more prone to teratogenic effect than humans.

Results from a large population-based prospective cohort epidemiological study reviewing data from 3 Swedish registries covering approximately 99% of the pregnancies from 1995-1997 indicate no increased risk for congenital malformations from the use of inhaled drug during early pregnancy. These same data were used in a second study bringing the total to 2,534 infants whose mothers were exposed to inhaled budesonide. In this study, the rate of congenital malformations among infants whose mother were exposed to inhaled budesonide during early pregnancy was not different from the rate for all newborn babies during the same period (3.6%).

There are few data on pregnancy outcomes after oral or rectal administration in humans. The maximal concentration of budesonide in plasma is expected to be higher with oral compared to inhaled use. Prolonged or repeated exposure may increase the risk of intra-uterine growth retardation. When considering use, risk benefit analysis should take into consideration disease-associated maternal and/or embryo/fetal risks. Inhaled glucocorticosteroids offer lower systemic effects compared to oral glucocorticosteroids and achieve similar pulmonary responses. There are no adequate and well controlled studies in pregnant women. The background birth defect and miscarriage risk for the indicated population is not known. In the US general population, the estimated major birth defect risk is 2 to 4% and the miscarriage risk is 15 to 20%.

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.

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: Formoterol (found in Symbicort)

Professional Content

This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus.

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

Comment:
-Beta-agonists, including this drug, may potentially interfere with uterine contractility due to a relaxant effect on uterine smooth muscle; use during labor and delivery only if benefits outweigh risks.

Animal reproduction studies showed teratogenicity, including increased fetal malformations, decreased fetal weights, and increased neonatal mortality at oral doses approximately 730 to 29000 times the maximum recommended human dose (MRHD); no effects were seen with the inhalation route at 300 times the MRHD. Doses approximately 50 times the MRHD administered during organogenesis caused delayed ossification, and decreased fetal weight was seen at approximately 1500 times the MRHD. Animals given 1500 times the MRHD during late pregnancy had increased stillbirths and neonatal mortality, however no effects were seen at approximately 50 times the MRHD. There are no controlled data in human pregnancy.

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: Budesonide-Formoterol (found in Symbicort)

Professional Content

This drug should be used during pregnancy only if the benefit outweighs the potential risks.

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

Risk Summary:
-There are no adequate and well-controlled studies of this drug or one of its individual components, formoterol, in pregnant women.
-Disease-Associated Maternal and/or Embryo/Fetal risk: In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes such as preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control.
-Labor or Delivery: There are no well-controlled human studies that have investigated the effects of this drug during labor and delivery. Due to the potential for beta-agonist interference with uterine contractility, this drug should be used during labor only if the benefits clearly outweigh the risk.

In animal reproduction studies, administration of budesonide-formoterol by the inhalation route, was teratogenic, embryocidal, and reduced fetal weights in rats at less than the maximum recommended human daily inhalation dose (MRHDID) on a mcg/m2 basis.

Budesonide alone, administered by the subcutaneous route, was teratogenic, embryocidal, and reduced fetal weights in rats and rabbits at less than the MRHDID, but these effects were not seen in rats that received inhaled doses up to 4 times the MRHDID. Studies of pregnant women have not shown that inhaled budesonide alone increases the risk of abnormalities when administered during pregnancy. Experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than humans.

Formoterol alone, administered by the oral route, was teratogenic in rats and rabbits at 1600 and 65,000 times the MRHDID, respectively. Formoterol was also embryocidal, increased pup loss at birth and during lactation, and decreased pup weight in rats at 110 times the MRHDID. These adverse effects generally occurred at large multiples of the MRHDID when formoterol was administered by the oral route to achieve high systemic exposures. No teratogenic, embryocidal, or developmental effects were seen in rats that received inhalation doses up to 375 times the MRHDID.

AU TGA pregnancy category B1: 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 not shown evidence of an increased occurrence of fetal damage.

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: Budesonide (found in Symbicort)

Professional Content

Benefit should outweigh risk.
-Some authorities consider the use acceptable during breastfeeding.

Excreted into human milk: Yes

Comment:
-Lactation studies have not been conducted with oral or rectal budesonide. However, some experts consider inhaled, nasal, oral and rectal corticosteroids acceptable to use during breastfeeding, as bioavailability in the infant is likely to be very low for any drug that enters the breastmilk.
-The breastfed infant is exposed to approximately 0.3 to 1% of the dose received via a dry powder inhaler by the patient.
-Extrapolating from inhaled drug exposure, data suggest therapeutic oral and rectal doses could expose a breastfeeding infant to drug levels 2.5 to 10 times higher respectively, than those from inhalation.
-Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for this medication as well as any potential adverse effects from this drug or the underlying maternal condition.

The following applies to the ingredients: Budesonide-Formoterol (found in Symbicort)

Professional Content

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 (budesonide); Unknown (formoterol)
Excreted into animal milk: Yes (formoterol); Data not available (budesonide)

Comments:
-The effects in the nursing infant are unknown.

Budesonide:
Human data with dry powder inhaler indicates that the total daily oral dose available in breast milk to the infant is approximately 0.3% to 1% of the dose inhaled by the mother.

Formoterol:
In the fertility and reproduction study in rats, the maximum plasma concentration that the pups received from the maternal animal after nursing was estimated at 4.4%.

The following applies to the ingredients: Formoterol (found in Symbicort)

Professional Content

Caution is recommended. Benefit should outweigh risk.

Excreted into human milk: Unknown
Excreted into animal milk: Yes

Comments:
-Women should contact their physician if they are nursing while taking the inhalation solution.
-The effects in the nursing infant and on milk production are unknown.
-Consider the developmental and health benefits of breastfeeding, along with the mother's clinical need for this medication, as well as any potential adverse effects on the child from the medication or the underlying maternal condition.

This drug and its metabolites was excreted in the breast milk of lactating rats given oral doses of 50 mcg/kg, and growth and survival of the pups were decreased when lactating rats were given oral doses greater than 1 mg/kg/day. A study in rats showed increased postnatal mortality at maternal oral doses of 0.2 mg/kg/day or greater, and retardation of pup growth at 15 mg/kg/day. The amount of drug found in animal milk was less than 2% of that in maternal plasma.