Skip to Content
Looking to save on your medications?  Find out how 

8 Interactions found for:

metformin and Symbicort
Interactions Summary
  • 3 Major
  • 2 Moderate
  • 3 Minor
  • metformin
  • Symbicort

Drug Interactions

Moderate
Metformin + Symbicort

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

MONITOR: The efficacy of insulin and other antidiabetic agents may be diminished by certain drugs, including atypical antipsychotics, corticosteroids, diuretics, estrogens, gonadotropin-releasing hormone agonists, human growth hormone, phenothiazines, progestins, protease inhibitors, sympathomimetic amines, thyroid hormones, L-asparaginase, alpelisib, copanlisib, danazol, diazoxide, isoniazid, megestrol, omacetaxine, phenytoin, sirolimus, tagraxofusp, temsirolimus, as well as pharmacologic dosages of nicotinic acid and adrenocorticotropic agents. These drugs may interfere with blood glucose control because they can cause hyperglycemia, glucose intolerance, new-onset diabetes mellitus, and/or exacerbation of preexisting diabetes.

MANAGEMENT: Caution is advised when drugs that can interfere with glucose metabolism are prescribed to patients with diabetes. Close clinical monitoring of glycemic control is recommended following initiation or discontinuation of these drugs, and the dosages of concomitant antidiabetic agents adjusted as necessary. Patients should be advised to notify their physician if their blood glucose is consistently high or if they experience symptoms of severe hyperglycemia such as excessive thirst and increases in the volume or frequency of urination. Likewise, patients should be observed for hypoglycemia when these drugs are withdrawn from their therapeutic regimen.

References

  1. Greenstone MA, Shaw AB "Alternate day corticosteroid causes alternate day hyperglycaemia." Postgrad Med J 63 (1987): 761-4
  2. Pollare T, Lithell H, Berne C "A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension." N Engl J Med 321 (1989): 868-73
  3. Carter BL, Small RE, Mandel MD, Starkman MT "Phenytoin-induced hyperglycemia." Am J Hosp Pharm 38 (1981): 1508-12
  4. Al-Rubeaan K, Ryan EA "Phenytoin-induced insulin insensitivity." Diabet Med 8 (1991): 968-70
  5. Chaudhuri ML, Catania J "A comparison of the effects of bumetanide (Burinex) and frusemide on carbohydrate metabolism in the elderly." Br J Clin Pract 42 (1988): 427-9
  6. Goldman JA, Neri A, Ovadia J, Eckerling B, Vries A, de "Effect of chlorothiazide on intravenous glucose tolerance in pregnancy." Am J Obstet Gynecol 105 (1969): 556-60
  7. Miller NR, Moses H "Transient oculomotor nerve palsy. Association with thiazide-induced glucose intolerance." JAMA 240 (1978): 1887-8
  8. Kansal PC, Buse J, Buse MG "Thiazide diuretics and control of diabetes mellitus." South Med J 62 (1969): 1372-9
  9. Andersen OO, Persson I "Carbohydrate metabolism during treatment with chlorthalidone and ethacrynic acid." Br Med J 2 (1968): 798-801
  10. Curtis J, Horrigan F, Ahearn D, Varney R, Sandler SG "Chlorthalidone-induced hyperosmolar hyperglycemic nonketotic coma." JAMA 220 (1972): 1592-3
  11. Chowdhury FR, Bleicher SJ "Chlorthalidone--induced hypokalemia and abnormal carbohydrate metabolism." Horm Metab Res 2 (1970): 13-6
  12. Diamond MT "Hyperglycemic hyperosmolar coma associated with hydrochlorothiazide and pancreatitis." N Y State J Med 72 (1972): 1741-2
  13. Jones IG, Pickens PT "Diabetes mellitus following oral diuretics." Practitioner 199 (1967): 209-10
  14. Black DM, Filak AT "Hyperglycemia with non-insulin-dependent diabetes following intraarticular steroid injection." J Fam Pract 28 (1989): 462-3
  15. Gunnarsson R, Lundgren G, Magnusson G, Ost L, Groth CG "Steroid diabetes--a sign of overtreatment with steroids in the renal graft recipient?" Scand J Urol Nephrol Suppl 54 (1980): 135-8
  16. Murphy MB, Kohner E, Lewis PJ, Schumer B, Dollery CT "Glucose intolerance in hypertensive patients treated with diuretics: a fourteen-year follow-up." Lancet 2 (1982): 1293-5
  17. Seltzer HS, Allen EW "Hyperglycemia and inhibition of insulin secretion during administration of diazoxide and trichlormethiazide in man." Diabetes 18 (1969): 19-28
  18. Jori A, Carrara MC "On the mechanism of the hyperglycaemic effect of chlorpromazine." J Pharm Pharmacol 18 (1966): 623-4
  19. Erle G, Basso M, Federspil G, Sicolo N, Scandellari C "Effect of chlorpromazine on blood glucose and plasma insulin in man." Eur J Clin Pharmacol 11 (1977): 15-8
  20. "Product Information. Thorazine (chlorpromazine)." SmithKline Beecham PROD (2002):
  21. "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  22. "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  23. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  24. "Product Information. Synthroid (levothyroxine)." Abbott Pharmaceutical PROD (2002):
  25. "Product Information. Carafate (sucralfate)." Hoechst Marion Roussel PROD (2001):
  26. Stambaugh JE, Tucker DC "Effect of diphenylhydantoin on glucose tolerance in patients with hypoglycemia." Diabetes 23 (1974): 679-83
  27. Malherbe C, Burrill KC, Levin SR, Karam JH, Forsham PH "Effect of diphenylhydantoin on insulin secretion in man." N Engl J Med 286 (1972): 339-42
  28. Javier Z, Gershberg H, Hulse M "Ovulatory suppressants, estrogens, and carbohydrate metabolism." Metabolism 17 (1968): 443-56
  29. Sotaniemi E, Kontturi M, Larmi T "Effect of diethylstilbestrol on blood glucose of prostatic cancer patients." Invest Urol 10 (1973): 438-41
  30. Bell DS "Insulin resistance. An often unrecognized problem accompanying chronic medical disorders." Postgrad Med 93 (1993): 99-103,
  31. Berlin I "Prazosin, diuretics, and glucose intolerance." Ann Intern Med 119 (1993): 860
  32. Rowe P, Mather H "Hyperosmolar non-ketotic diabetes mellitus associated with metolazone." Br Med J 291 (1985): 25-6
  33. Haiba NA, el-Habashy MA, Said SA, Darwish EA, Abdel-Sayed WS, Nayel SE "Clinical evaluation of two monthly injectable contraceptives and their effects on some metabolic parameters." Contraception 39 (1989): 619-32
  34. Virutamasen P, Wongsrichanalai C, Tangkeo P, Nitichai Y, Rienprayoon D "Metabolic effects of depot-medroxyprogesterone acetate in long-term users: a cross-sectional study." Int J Gynaecol Obstet 24 (1986): 291-6
  35. Dimitriadis G, Tegos C, Golfinopoulou L, Roboti C, Raptis S "Furosemide-induced hyperglycaemia - the implication of glycolytic kinases." Horm Metab Res 25 (1993): 557-9
  36. Goldman JA, Ovadia JL "The effect of estrogen on intravenous glucose tolerance in woman." Am J Obstet Gynecol 103 (1969): 172-8
  37. Hannaford PC, Kay CR "Oral contraceptives and diabetes mellitus." BMJ 299 (1989): 1315-6
  38. Spellacy WN, Ellingson AB, Tsibris JC "The effects of two triphasic oral contraceptives on carbohydrate metabolism in women during 1 year of use." Fertil Steril 51 (1989): 71-4
  39. Ludvik B, Clodi M, Kautzky-Willer A, Capek M, Hartter E, Pacini G, Prager R "Effect of dexamethasone on insulin sensitivity, islet amyloid polypeptide and insulin secretion in humans." Diabetologia 36 (1993): 84-7
  40. Domenet JG "Diabetogenic effect of oral diuretics." Br Med J 3 (1968): 188
  41. Coni NK, Gordon PW, Mukherjee AP, Read PR "The effect of frusemide and ethacrynic acid on carbohydrate metabolism." Age Ageing 3 (1974): 85-90
  42. Schmitz O, Hermansen K, Nielsen OH, Christensen CK, Arnfred J, Hansen HE, Mogensen CE, Orskov H, Beck-Nielsen H "Insulin action in insulin-dependent diabetics after short-term thiazide therapy." Diabetes Care 9 (1986): 631-6
  43. Blayac JP, Ribes G, Buys D, Puech R, Loubatieres-Mariani MM "Effects of a new benzothiadiazine derivative, LN 5330, on insulin secretion." Arch Int Pharmacodyn Ther 253 (1981): 154-63
  44. Elmfeldt D, Berglund G, Wedel H, Wilhelmsen L "Incidence and importance of metabolic side-effects during antihypertensive therapy." Acta Med Scand Suppl 672 (1983): 79-83
  45. Winchester JF, Kellett RJ, Boddy K, Boyle P, Dargie HJ, Mahaffey ME, Ward DM, Kennedy AC "Metolazone and bendroflumethiazide in hypertension: physiologic and metabolic observations." Clin Pharmacol Ther 28 (1980): 611-8
  46. Petri M, Cumber P, Grimes L, Treby D, Bryant R, Rawlins D, Ising H "The metabolic effects of thiazide therapy in the elderly: a population study." Age Ageing 15 (1986): 151-5
  47. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb PROD (2001):
  48. Harper R, Ennis CN, Heaney AP, Sheridan B, Gormley M, Atkinson AB, Johnston GD, Bell PM "A comparison of the effects of low- and conventional-dose thiazide diuretic on insulin action in hypertensive patients with NIDDM." Diabetologia 38 (1995): 853-9
  49. "Product Information. Precose (acarbose)." Bayer PROD (2001):
  50. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):
  51. "Product Information. Amaryl (glimepiride)." Hoechst Marion Roussel PROD (2001):
  52. Charan VD, Desai N, Singh AP, Choudhry VP "Diabetes mellitus and pancreatitis as a complication of L- asparaginase therapy." Indian Pediatr 30 (1993): 809-10
  53. Seifer DB, Freedman LN, Cavender JR, Baker RA "Insulin-dependent diabetes mellitus associated with danazol." Am J Obstet Gynecol 162 (1990): 474-5
  54. "Product Information. Crixivan (indinavir)." Merck & Co., Inc PROD (2001):
  55. Pickkers P, Schachter M, Hughes AD, Feher MD, Sever PS "Thiazide-induced hyperglycaemia: a role for calcium-activated potassium channels?" Diabetologia 39 (1996): 861-4
  56. "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc PROD (2001):
  57. Dube MP, Johnson DL, Currier JS, Leedom JM "Protease inhibitor-associated hyperglycaemia." Lancet 350 (1997): 713-4
  58. "Product Information. Oncaspar (pegaspargase)." Rhone Poulenc Rorer PROD (2001):
  59. "Product Information. Prandin (repaglinide)." Novo Nordisk Pharmaceuticals Inc PROD (2001):
  60. "Product Information. Elspar (asparaginase)." Merck & Co., Inc PROD (2001):
  61. "Product Information. Hyperstat (diazoxide)." Apothecon Inc (2022):
  62. "Product Information. Megace (megestrol)." Bristol-Myers Squibb PROD (2001):
  63. Walli R, Demant T "Impaired glucose tolerance and protease inhibitors." Ann Intern Med 129 (1998): 837-8
  64. "Product Information. Agenerase (amprenavir)." Glaxo Wellcome PROD (2001):
  65. Mauss S, Wolf E, Jaeger H "Impaired glucose tolerance in HIV-positive patients receiving and those not receiving protease inhibitors." Ann Intern Med 130 (1999): 162-3
  66. Kaufman MB, Simionatto C "A review of protease inhibitor-induced hyperglycemia." Pharmacotherapy 19 (1999): 114-7
  67. "Product Information. Tolinase (tolazamide)." Pharmacia and Upjohn PROD (2001):
  68. "Product Information. Orinase (tolbutamide)." Pharmacia and Upjohn PROD (2001):
  69. "Product Information. Dymelor (acetohexamide)." Lilly, Eli and Company PROD (2001):
  70. Wehring H, Alexander B, Perry PJ "Diabetes mellitus associated with clozapine therapy." Pharmacotherapy 20 (2000): 844-7
  71. Tsiodras S, Mantzoros C, Hammer S, Samore M "Effects of protease inhibitors on hyperglycemia, hyperlipidemia, and lipodystrophy - A 5-year cohort study." Arch Intern Med 160 (2000): 2050-6
  72. "Product Information. Fortovase (saquinavir)." Roche Laboratories PROD (2001):
  73. "Product Information. Starlix (nateglinide)." Novartis Pharmaceuticals PROD (2001):
  74. Hardy H, Esch LD, Morse GD "Glucose disorders associated with HIV and its drug therapy." Ann Pharmacother 35 (2001): 343-51
  75. Leary WP, Reyes AJ "Drug interactions with diuretics." S Afr Med J 65 (1984): 455-61
  76. "Product Information. NovoLOG Mix 70/30 (insulin aspart-insulin aspart protamine)." Novo Nordisk Pharmaceuticals Inc (2022):
  77. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb (2003):
  78. "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline (2003):
  79. "Product Information. Apidra (insulin glulisine)." Aventis Pharmaceuticals (2004):
  80. "Product Information. Prezista (darunavir)." Ortho Biotech Inc (2006):
  81. "Product Information. Zolinza (vorinostat)." Merck & Co., Inc (2006):
  82. "Product Information. Torisel (temsirolimus)." Wyeth-Ayerst Laboratories (2007):
  83. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
  84. "Product Information. Elzonris (tagraxofusp)." Stemline Therapeutics (2019):
  85. "Product Information. Piqray (alpelisib)." Novartis Pharmaceuticals (2019):

Drug and Food Interactions

Major
Metformin + Food

The following applies to the ingredients: Metformin

GENERALLY AVOID: Alcohol can potentiate the effect of metformin on lactate metabolism and increase the risk of lactic acidosis. In addition, alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes. Although hypoglycemia rarely occurs during treatment with metformin alone, the risk may increase with acute consumption of alcohol. Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise. The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia. Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion. By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia. Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes.

Food may have varying effects on the absorption of metformin from immediate-release versus extended-release formulations. When a single 850 mg dose of immediate-release metformin was administered with food, mean peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 40% and 25%, respectively, and time to peak plasma concentration (Tmax) increased by 35 minutes compared to administration under fasting conditions. By contrast, administration of extended-release metformin with food increased AUC by 50% without affecting Cmax or Tmax, and both high- and low-fat meals had the same effect. These data may not be applicable to formulations that contain metformin with other oral antidiabetic agents.

MANAGEMENT: Metformin should be taken with meals, and excessive alcohol intake should be avoided during treatment. Diabetes patients in general should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis. Alcohol should not be consumed on an empty stomach or following exercise, as it may increase the risk of hypoglycemia. Patients should contact their physician immediately if they experience potential signs and symptoms of lactic acidosis such as malaise, myalgia, respiratory distress, increasing somnolence, and nonspecific abdominal distress (especially after stabilization of metformin therapy, when gastrointestinal symptoms are uncommon). With more marked acidosis, there may also be associated hypothermia, hypotension, and resistant bradyarrhythmias. Metformin should be withdrawn promptly if lactic acidosis is suspected. Serum electrolytes, ketones, blood glucose, blood pH, lactate levels, and blood metformin levels may be useful in establishing a diagnosis. Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia).

References

  1. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb PROD (2001):
  2. "Position Statement: evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes related complications. American Diabetes Association." Diabetes Care 25(Suppl 1) (2002): S50-S60

Moderate
Symbicort + Food

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

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations and systemic effects of orally administered budesonide. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the manufacturer, the systemic exposure of oral budesonide approximately doubles after extensive intake of grapefruit juice.

MANAGEMENT: Patients receiving budesonide should avoid the regular consumption of grapefruits and grapefruit juice to prevent undue increases in plasma budesonide levels and systemic effects.

References

  1. "Product Information. Entocort (budesonide)." AstraZeneca Pharma Inc (2001):

Drug and Pregnancy Interactions

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

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.

References

  1. "Product Information. Pulmicort Respules (budesonide)." Astra-Zeneca Pharmaceuticals PROD (2001):
  2. "Product Information. Uceris (budesonide)." Santarus Inc (2013):
  3. "Product Information. Pulmicort Flexhaler (budesonide)." A-S Medication Solutions (2016):
  4. "Product Information. Entocort EC (budesonide)." Perrigo, L. Company (2016):

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

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.

References

  1. "Product Information. Foradil (formoterol)." Novartis Pharmaceuticals PROD (2001):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. "Product Information. Perforomist (formoterol)." Dey Laboratories (2016):

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

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.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. "Product Information. Symbicort (budesonide-formoterol)." Astra-Zeneca Pharmaceuticals (2006):
  3. Cerner Multum, Inc. "Australian Product Information." O 0

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.

References

  1. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb PROD (2001):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. "Product Information. Fortamet (metformin)." Physicians Total Care (2014):
  5. "Product Information. Glumetza (metformin)." Biovail Pharmaceuticals Canada (2014):
  6. "Product Information. Riomet (metformin)." Ranbaxy Pharmaceuticals (2014):
  7. Lindsay RS, Loeken MR "Metformin use in pregnancy: promises and uncertainties" Diabetologia 60 (2017): 1612-9
  8. Kelley KW, Carroll DG, Meyer A "A review of current treatment strategies for gestational diabetes mellitus." Drugs Context 4 (2015): epub

Drug and Breastfeeding Interactions

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

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.

References

  1. "Product Information. Pulmicort Respules (budesonide)." Astra-Zeneca Pharmaceuticals PROD (2001):
  2. "Product Information. Uceris (budesonide)." Santarus Inc (2013):
  3. "Product Information. Pulmicort Flexhaler (budesonide)." A-S Medication Solutions (2016):
  4. "Product Information. Entocort EC (budesonide)." Perrigo, L. Company (2016):

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

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%.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. "Product Information. Symbicort (budesonide-formoterol)." Astra-Zeneca Pharmaceuticals (2006):
  3. Cerner Multum, Inc. "Australian Product Information." O 0

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.

References

  1. "Product Information. Glucophage (metformin)." Bristol-Myers Squibb PROD (2001):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Feig DS, Briggs GG, Koren G "Oral antidiabetic agents in pregnancy and lactation: a paradigm shift?" Ann Pharmacother (2007): 1174-80
  4. Cerner Multum, Inc. "Australian Product Information." O 0
  5. United States National Library of Medicine "Toxnet. Toxicology Data Network. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT" (2013):
  6. "Product Information. Fortamet (metformin)." Physicians Total Care (2014):
  7. "Product Information. Glumetza (metformin)." Biovail Pharmaceuticals Canada (2014):
  8. "Product Information. Riomet (metformin)." Ranbaxy Pharmaceuticals (2014):
  9. Kelley KW, Carroll DG, Meyer A "A review of current treatment strategies for gestational diabetes mellitus." Drugs Context 4 (2015): epub

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

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.

References

  1. "Product Information. Foradil (formoterol)." Novartis Pharmaceuticals PROD (2001):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. "Product Information. Perforomist (formoterol)." Dey Laboratories (2016):

Therapeutic Duplication Warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

Switch to: Consumer Interactions

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Disclaimer: This content should not be considered complete and should not be used in place of a call or visit to a healthcare professional. Use of this content is subject to our terms of use & medical disclaimer.