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7 Interactions found for:

Cymbalta and propranolol
Interactions Summary
  • 3 Major
  • 3 Moderate
  • 1 Minor
  • Cymbalta
  • propranolol

Drug Interactions

Moderate
Propranolol + Cymbalta

The following applies to the ingredients: Propranolol and Duloxetine (found in Cymbalta)

MONITOR: Duloxetine is a moderate inhibitor of CYP450 2D6 and may increase the plasma concentrations of drugs that are substrates of the isoenzyme. According to the product labeling, when duloxetine (60 mg twice a day) was administered in conjunction with a single 50 mg dose of desipramine, a CYP450 2D6 substrate, the systemic exposure (AUC) of desipramine increased 3-fold. Conversely, many CYP450 2D6 substrates can also be competitive or noncompetitive inhibitors of the isoenzyme and may increase the plasma concentrations of duloxetine, which is partially metabolized by CYP450 2D6.

MANAGEMENT: Caution is advised if duloxetine must be used concomitantly with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range such as tricyclic antidepressants, phenothiazines, beta blockers, and class IC antiarrhythmic agents (e.g., propafenone, flecainide). A lower initial dosage, as well as clinical and laboratory monitoring, may be appropriate for some drugs.

References

  1. Skinner MH, Kuan HY, Pan A, et al. "Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers." Clin Pharmacol Ther 73 (2003): 170-7
  2. "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company (2004):

Drug and Food Interactions

Moderate
Propranolol + Food

The following applies to the ingredients: Propranolol

ADJUST DOSING INTERVAL: The bioavailability of propranolol may be enhanced by food.

MANAGEMENT: Patients may be instructed to take propranolol at the same time each day, preferably with or immediately following meals.

References

  1. Olanoff LS, Walle T, Cowart TD, et al. "Food effects on propranolol systemic and oral clearance: support for a blood flow hypothesis." Clin Pharmacol Ther 40 (1986): 408-14
  2. Byrne AJ, McNeil JJ, Harrison PM, Louis W, Tonkin AM, McLean AJ "Stable oral availability of sustained release propranolol when co-administered with hydralazine or food: evidence implicating substrate delivery rate as a determinant of presystemic drug interactions." Br J Clin Pharmacol 17 (1984): s45-50

The following applies to the ingredients: Propranolol

ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers. The exact mechanism of interaction is unknown. In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively. The elimination half-life increased by 44%. Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone. However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments. The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.

MANAGEMENT: It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours. Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.

References

  1. Kirch W, Schafer-Korting M, Axthelm T, Kohler H, Mutschler E "Interaction of atenolol with furosemide and calcium and aluminum salts." Clin Pharmacol Ther 30 (1981): 429-35

The following applies to the ingredients: Propranolol

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.

References

  1. "Product Information. Cytisine (cytisinicline)." Consilient Health Ltd (2024):
  2. jeong sh, Newcombe D, sheridan j, Tingle M "Pharmacokinetics of cytisine, an a4 b2 nicotinic receptor partial agonist, in healthy smokers following a single dose." Drug Test Anal 7 (2015): 475-82
  3. Vaughan DP, Beckett AH, Robbie DS "The influence of smoking on the intersubject variation in pentazocine elimination." Br J Clin Pharmacol 3 (1976): 279-83
  4. Zevin S, Benowitz NL "Drug interactions with tobacco smoking: an update" Clin Pharmacokinet 36 (1999): 425-38

Moderate
Cymbalta + Food

The following applies to the ingredients: Duloxetine (found in Cymbalta)

GENERALLY AVOID: Use of duloxetine in conjunction with chronic alcohol consumption may potentiate the risk of liver injury. Duloxetine alone can increase serum transaminase levels. In clinical trials, 0.3% of patients discontinued duloxetine due to liver transaminase elevations. The median time to detection was about two months. Three duloxetine-treated patients had liver injury as manifested by transaminase and bilirubin elevations, with evidence of obstruction. Substantial intercurrent ethanol use was present in each of these cases, which may have contributed to the abnormalities observed. Duloxetine does not appear to enhance the central nervous system effects of alcohol. When duloxetine and ethanol were administered several hours apart so that peak concentrations of each would coincide, duloxetine did not increase the impairment of mental and motor skills caused by alcohol.

MANAGEMENT: Due to the risk of liver injury, patients prescribed duloxetine should be counseled to avoid excessive use of alcohol. Duloxetine should generally not be prescribed to patients with substantial alcohol use.

References

  1. "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company (2004):

Drug and Pregnancy Interactions

The following applies to the ingredients: Duloxetine (found in Cymbalta)

This drug should not be used during pregnancy unless the benefit outweighs the risk to the fetus.

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

Risk summary: Observational study data have not produced clear drug-associated risks regarding adverse events or major birth defects.

Comments:
-A pregnancy exposure registry is available.
-Neonates exposed to this drug late in the third trimester may require respiratory support, tube feeding, and/or prolonged hospitalization.
-Exposed neonates should be monitored after delivery for direct toxic effects of this drug, drug discontinuation syndrome, and serotonin syndrome.
-Women who discontinued antidepressant use during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressant use.

Animal studies have revealed increased perinatal toxicity and fetotoxicity at doses potentially correlated with maternal toxicity. There are no controlled data in human pregnancy.

Some neonates exposed to SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors), or SSRIs (Selective Serotonin Reuptake Inhibitors) late in the third trimester had clinical findings including respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. This clinical picture is consistent with either direct toxic effect of SSRIs and SNRIs, drug discontinuation syndrome, or serotonin syndrome.

A less than 2-fold increase in postpartum hemorrhage was determined by observational data in patients exposed to the drug within 1 month before birth.

A study of women with a history of major depression who were euthymic at the beginning of pregnancy, showed women who discontinued antidepressant medication during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressant medication.

To monitor maternal-fetal outcomes of pregnant women exposed to antidepressant therapy, a National Pregnancy Registry for Antidepressants has been established. Healthcare providers are encouraged to prospectively register patients. For additional information: https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/

Healthcare providers are encouraged to register patients receiving Cymbalta by calling the Cymbalta Pregnancy Registry at 1-866-814-6975 or by visiting www.cymbaltapregnancyregistry.com.

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. Cymbalta (duloxetine)." Lilly, Eli and Company (2004):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0

The following applies to the ingredients: Propranolol

This drug is only recommended for use during pregnancy when there are no alternatives and the benefit outweighs the risk.

AU TGA pregnancy category: C
US FDA pregnancy category: C

Beta blockers may cause decreased placental perfusion, fetal and neonatal bradycardia, and hypoglycemia.

Propranolol has been used safely to treat a variety of conditions during pregnancy, including hypertension and pheochromocytoma in the mother, and tachyarrhythmias in both the mother and fetus. There are a number of abnormalities associated with the use of propranolol during pregnancy, but many of these may be attributable to underlying diseases. These abnormalities include some signs of beta-blockade, such as bradycardia, hypoglycemia, and respiratory depression. Other abnormalities that may be due to propranolol include intrauterine growth retardation, small placentas, polycythemia, thrombocytopenia, and hypocalcemia.

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 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.

References

  1. O'Hare MF, Kinney CD, Murnaghan GA, McDevitt DG "Pharmacokinetics of propranolol during pregnancy." Eur J Clin Pharmacol 27 (1984): 583-7
  2. Levitan AA, Manion JC "Propranolol therapy during pregnancy and lactation." Am J Cardiol 32 (1973): 247
  3. Taylor EA, Turner P "Anti-hypertensive therapy with propranolol during pregnancy and lactation." Postgrad Med J 57 (1981): 427-30
  4. "Product Information. Inderal (propranolol)." Wyeth-Ayerst Laboratories PROD (2001):
  5. O'Connor PC, Jick H, Hunter JR, Stergachis A, Madsen S "Propranolol and pregnancy outcome." Lancet 2 (1981): 1168
  6. Caldroney RD "Beta-blockers in pregnancy." N Engl J Med 306 (1982): 810
  7. Livingstone I, Craswell PW, Bevan EB "Propranolol in pregnancy three year prospective study." Clin Exp Hypertens B 2 (1983): 341-50
  8. Eliahou HE, Silverberg DS, Reisin E, Romem I, Mashiach S, Serr DM "Propranolol for the treatment of hypertension in pregnancy." Br J Obstet Gynaecol 85 (1978): 431-6
  9. Redmond GP "Propranolol and fetal growth retardation." Semin Perinatol 6 (1982): 142-7
  10. Frishman WH, Chesner M "Beta-adrenergic blockers in pregnancy." Am Heart J 115 (1988): 147-52
  11. Belpaire FM, Wynant P, Vantrappen P, Dhont M, Verstraete A, Bogaert MG "Protein binding of propranolol and verapamil enantiomers in maternal and foetal serum." Br J Clin Pharmacol 39 (1995): 190-3
  12. Page RL "Treatment of arrhythmias during pregnancy." Am Heart J 130 (1995): 871-6
  13. "Product Information. InnoPran XL (propranolol)." Reliant Pharmaceuticals LLC (2003):
  14. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  15. TGA. Therapeutic Goods Administration. Australian Drug Evaluation Committee "Prescribing medicines in pregnancy: an Australian categorisation of risk of drug use in pregancy. http://www.tga.gov.au/docs/pdf/medpreg.pdf" (2007):
  16. Cerner Multum, Inc. "Australian Product Information." O 0

Drug and Breastfeeding Interactions

The following applies to the ingredients: Propranolol

Use is not recommended.

Excreted into human milk: Yes

Comments: Propranolol levels in breast milk are low and would not be expected to cause any adverse effects in breastfed infants.

Propranolol milk to maternal plasma ratios as high as 1.5 has been reported. While no adverse effects in the nursing infant have been reported, experts advise monitoring the infant for signs and symptoms of beta-blockade and to schedule feedings at least three hours after maternal propranolol administration.

References

  1. Roberts RJ, Blumer JL, Gorman RL, et al. "American Academy of Pediatrics Committee on Drugs: Transfer of drugs and other chemicals into human milk." Pediatrics 84 (1989): 924-36
  2. Levitan AA, Manion JC "Propranolol therapy during pregnancy and lactation." Am J Cardiol 32 (1973): 247
  3. Bauer JH, Pape B, Zajicek J, Groshong T "Propranolol in human plasma and breast milk." Am J Cardiol 43 (1979): 860-2
  4. Taylor EA, Turner P "Anti-hypertensive therapy with propranolol during pregnancy and lactation." Postgrad Med J 57 (1981): 427-30
  5. "Product Information. Inderal (propranolol)." Wyeth-Ayerst Laboratories PROD (2001):
  6. "Product Information. InnoPran XL (propranolol)." Reliant Pharmaceuticals LLC (2003):
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  8. Cerner Multum, Inc. "Australian Product Information." O 0
  9. United States National Library of Medicine "Toxnet. Toxicology Data Network. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT" (2013):

The following applies to the ingredients: Duloxetine (found in Cymbalta)

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:
-Some experts state that a more thoroughly studied alternative agent (e.g., nortriptyline, paroxetine, sertraline) may be preferred while breastfeeding premature or neonates.
-The American Academy of Pediatrics classifies other antidepressants as agents for which the effect on nursing infants is unknown but may be of concern.
-Exposed infants should be monitored for developmental milestones, feeding, sedation, weight gain, especially in younger infants who are exclusively breastfed and/or when breastfed infants are exposed to multiple antipsychotropic agents.

The estimated neonatal dose is approximately 0.1% to 0.3% of the maternal dose.

References

  1. "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company (2004):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. United States National Library of Medicine "Toxnet. Toxicology Data Network. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT" (2013):
  5. Briggs GG, Freeman RK. "Drugs in Pregnancy and Lactation." Philadelphia, PA: Wolters Kluwer Health (2015):
  6. National Library of Medicine (US) "Drugs and Lactation Database (LactMed) https://www.ncbi.nlm.nih.gov/books/NBK501922/" (2019):

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.

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