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Drug Interactions between propranolol and roflumilast topical

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

propranolol roflumilast topical

Applies to: propranolol and roflumilast topical

MONITOR: Coadministration with CYP450 3A4 inhibitors or dual CYP450 3A4/1A2 inhibitors may increase the systemic exposure (AUC) to roflumilast following topical administration. According to the prescribing information, N-oxidation of roflumilast by CYP450 3A4 and 1A2 is a major step in the metabolism of the drug. In vitro, roflumilast is 3 times more potent than its N-oxide metabolite at inhibition of the phosphodiesterase 4 (PDE4) enzyme, but on average, the roflumilast N-oxide AUC is approximately 8-fold greater than the parent drug AUC following IV or topical administration and about 10-fold greater following oral administration. In a pharmacokinetic study of 18 adults and 6 adolescents with plaque psoriasis and a mean body surface area involvement of 26.8% (adults) and 13.0% (adolescents), the mean AUC of roflumilast and roflumilast N-oxide following application of 3 to 6.5 g once daily for 15 days was 72.7 and 628 h*ng/mL, respectively, for adults and 25.1 and 140 h*ng/mL, respectively, for adolescents. Data regarding concomitant use of CYP450 3A4 or dual CYP450 3A4/1A2 inhibitors have been reported for oral roflumilast (500 mcg single dose). When coadministered with the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 13 days), roflumilast peak plasma concentration (Cmax) and AUC increased by 23% and 99%, respectively, while roflumilast N-oxide Cmax decreased by 38% and AUC increased by 3%. When coadministered with erythromycin (500 mg three times daily for 13 days), a moderate CYP450 3A4 inhibitor, roflumilast Cmax and AUC increased by 40% and 70%, respectively, while roflumilast N-oxide Cmax decreased by 34% and AUC increased by 4%. When coadministered with the dual CYP450 3A4/1A2 inhibitors fluvoxamine (50 mg daily for 14 days) or cimetidine (400 mg twice daily for 7 days), roflumilast Cmax increased by 12% and 46% and its AUC increased by 156% and 85%, respectively, while the roflumilast N-oxide Cmax decreased by 210% and 4% and its AUC increased by 52% and 27%, respectively.

MANAGEMENT: Treatment with topical roflumilast should be re-evaluated if an interaction is suspected and persistent intolerability occurs. Patients should be advised to contact their physician if they experience increased frequency and/or severity of side effects such as diarrhea, headache, insomnia, nausea, upper respiratory tract infection, or urinary tract infection.

References (2)
  1. (2011) "Product Information. Daliresp (roflumilast)." Astra-Zeneca Pharmaceuticals
  2. (2022) "Product Information. Zoryve (roflumilast topical)." Arcutis Biotherapeutics, Inc, 1

Drug and food interactions

Moderate

propranolol food

Applies to: 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 (2)
  1. Olanoff LS, Walle T, Cowart TD, et al. (1986) "Food effects on propranolol systemic and oral clearance: support for a blood flow hypothesis." Clin Pharmacol Ther, 40, p. 408-14
  2. Byrne AJ, McNeil JJ, Harrison PM, Louis W, Tonkin AM, McLean AJ (1984) "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, s45-50
Moderate

propranolol food

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

propranolol food

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

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.

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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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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