Skip to main content

Drug Interactions between Dilt-XR and roflumilast topical

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

Edit list (add/remove drugs)

Interactions between your drugs

Moderate

dilTIAZem roflumilast topical

Applies to: Dilt-XR (diltiazem) 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

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

Switch to consumer interaction data

Drug and food interactions

Moderate

dilTIAZem food

Applies to: Dilt-XR (diltiazem)

MONITOR: Like many CNS-active agents, alcohol can exhibit hypotensive effects. Coadministration with antihypertensive agents including diltiazem may result in additive effects on blood pressure and orthostasis.

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered diltiazem in some patients. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In a study of ten healthy male volunteers, administration of a single 120 mg oral dose of immediate-release diltiazem in combination with 250 mL of grapefruit juice increased the diltiazem peak plasma concentration (Cmax) and systemic exposure (AUC) by an average of 22% and 20%, respectively, compared to administration with water. The time to reach Cmax (Tmax) and the terminal half-life were not affected, and no statistically significant differences in blood pressure and heart rate were observed during administration with grapefruit juice relative to water. In a different study, repeated administration of 200 mL of grapefruit juice at 0, 2, 4, 8 and 12 hours had no significant effect on the Cmax or AUC of a single 120 mg oral dose of diltiazem, but increased its half-life from 4.1 to 5.1 hours. The ratios for the N-demethyl and deacetyl metabolites to diltiazem were also not affected by grapefruit juice. However, because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients should be advised that alcohol may potentiate the hypotensive effects of diltiazem, especially during the initiation of therapy and following a dosage increase. Caution should be exercised when rising from a sitting or recumbent position, and patients should notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients who regularly consume grapefruit or grapefruit juice should be monitored for increased adverse effects of diltiazem such as such as headache, irregular heartbeat, edema, unexplained weight gain, and chest pain. Grapefruit and grapefruit juice should be avoided if an interaction is suspected.

References

  1. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  2. Sigusch H, Henschel L, Kraul H, Merkel U, Hoffmann A (1994) "Lack of effect of grapefruit juice on diltiazem bioavailability in normal subjects." Pharmazie, 49, p. 675-9
  3. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  4. Christensen H, Asberg A, Holmboe AB, Berg KJ (2002) "Coadministration of grapefruit juice increases systemic exposure of diltiazem in healthy volunteers." Eur J Clin Pharmacol, 58, p. 515-520
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics."
View all 5 references

Switch to consumer interaction data

Moderate

dilTIAZem food

Applies to: Dilt-XR (diltiazem)

MONITOR: Calcium-containing products may decrease the effectiveness of calcium channel blockers by saturating calcium channels with calcium. Calcium chloride has been used to manage acute severe verapamil toxicity.

MANAGEMENT: Management consists of monitoring the effectiveness of calcium channel blocker therapy during coadministration with calcium products.

References

  1. Henry M, Kay MM, Viccellio P (1985) "Cardiogenic shock associated with calcium-channel and beta blockers: reversal with intravenous calcium chloride." Am J Emerg Med, 3, p. 334-6
  2. Moller IW (1987) "Cardiac arrest following intravenous verapamil combined with halothane anaesthesia." Br J Anaesth, 59, p. 522-6
  3. Oszko MA, Klutman NE (1987) "Use of calcium salts during cardiopulmonary resuscitation for reversing verapamil-associated hypotension." Clin Pharm, 6, p. 448-9
  4. Schoen MD, Parker RB, Hoon TJ, et al. (1991) "Evaluation of the pharmacokinetics and electrocardiographic effects of intravenous verapamil with intravenous calcium chloride pretreatment in normal subjects." Am J Cardiol, 67, p. 300-4
  5. O'Quinn SV, Wohns DH, Clarke S, Koch G, Patterson JH, Adams KF (1990) "Influence of calcium on the hemodynamic and anti-ischemic effects of nifedipine observed during treadmill exercise testing." Pharmacotherapy, 10, p. 247
  6. Woie L, Storstein L (1981) "Successful treatment of suicidal verapamil poisoning with calcium gluconate." Eur Heart J, 2, p. 239-42
  7. Morris DL, Goldschlager N (1983) "Calcium infusion for reversal of adverse effects of intravenous verapamil." JAMA, 249, p. 3212-3
  8. Guadagnino V, Greengart A, Hollander G, Solar M, Shani J, Lichstein E (1987) "Treatment of severe left ventricular dysfunction with calcium chloride in patients receiving verapamil." J Clin Pharmacol, 27, p. 407-9
  9. Luscher TF, Noll G, Sturmer T, Huser B, Wenk M (1994) "Calcium gluconate in severe verapamil intoxication." N Engl J Med, 330, p. 718-20
  10. Bar-Or D, Gasiel Y (1981) "Calcium and calciferol antagonise effect of verapamil in atrial fibrillation." Br Med J (Clin Res Ed), 282, p. 1585-6
  11. Lipman J, Jardine I, Roos C, Dreosti L (1982) "Intravenous calcium chloride as an antidote to verapamil-induced hypotension." Intensive Care Med, 8, p. 55-7
  12. McMillan R (1988) "Management of acute severe verapamil intoxication." J Emerg Med, 6, p. 193-6
  13. Perkins CM (1978) "Serious verapamil poisoning: treatment with intravenous calcium gluconate." Br Med J, 2, p. 1127
  14. Moroni F, Mannaioni PF, Dolara A, Ciaccheri M (1980) "Calcium gluconate and hypertonic sodium chloride in a case of massive verapamil poisoning." Clin Toxicol, 17, p. 395-400
View all 14 references

Switch to consumer interaction data

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.

See also

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer