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Drug Interactions between RCK and tofacitinib

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

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Interactions between your drugs

Moderate

cloNIDine tofacitinib

Applies to: RCK (clonidine / ketorolac / ropivacaine) and tofacitinib

GENERALLY AVOID: Tofacitinib has been shown to decrease heart rate and prolong the PR interval of the electrocardiogram in some patients. Theoretically, coadministration with other agents that prolong the PR interval (e.g., beta-blockers, digoxin, alpha-2 adrenoceptor agonists) may result in elevated risk of conduction disturbances and atrioventricular block. In clinical trials, use of tofacitinib (10 to 20 mg daily; at steady-state) was associated with significant decreases in heart rate (4 to 7 bpm) and increases in PR interval (4 to 10 ms) compared with placebo.

MANAGEMENT: According to the manufacturer, concomitant use of tofacitinib with other agents that lower heart rate and/or prolong the PR interval should be avoided when possible. Caution is advised if concomitant use is necessary, particularly in patients with known conduction problems or severe cardiac disease. An ECG should be considered in these patients before initiating concomitant therapy and after titration to steady-state. Patients should be advised to notify their physician if they experience dizziness, lightheadedness, fainting, or irregular heartbeats.

References (2)
  1. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  2. Cerner Multum, Inc. "Australian Product Information."
Moderate

ketorolac tofacitinib

Applies to: RCK (clonidine / ketorolac / ropivacaine) and tofacitinib

MONITOR: Coadministration of Janus kinase (JAK) inhibitors with corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and/or opioids may increase the risk of gastrointestinal (GI) perforation. Patients with a prior history of peptic ulceration or diverticular disease may also have an increased risk. Adverse events of diverticulitis and GI perforation have been infrequently reported in clinical studies and postmarketing use of JAK inhibitors such as baricitinib, ruxolitinib, tofacitinib, and upadacitinib. However, the role of JAK inhibition in these events has not been determined. In studies with rheumatoid arthritis and ulcerative colitis patients, many were receiving background therapy with NSAIDs or corticosteroids.

MANAGEMENT: Caution is recommended when using JAK inhibitors in patients with a history of peptic ulceration or diverticular disease and in patients receiving concomitant treatment with drugs associated with an increased risk of GI perforation such as corticosteroids, NSAIDs, and opioids. Patients should be advised to contact their healthcare provider if they experience signs and symptoms of GI perforation such as severe abdominal pain, fever, chills, nausea, or vomiting.

References (15)
  1. Strate LL, Liu YL, Huang ES, Giovannucci EL, Chan AT (2011) "Use of aspirin or nonsteroidal anti-inflammatory drugs increases risk for diverticulitis and diverticular bleeding." Gastroenterology, 140, p. 1427-33
  2. Medicines and Healthcare products Regulatory Agency (2020) Baricitinib (Olumiant¥): increased risk of diverticulitis, particularly in patients with risk factors. https://www.gov.uk/drug-safety-update/baricitinib-olumiant-increased-risk-of-diverticulitis-particularly-in-patients-with-risk-factors
  3. (2021) "Product Information. Olumiant (bARICITinib)." Eli Lilly Australia Pty Ltd, vA7_April2021
  4. (2023) "Product Information. Olumiant (baricitinib)." Eli Lilly and Company Ltd
  5. Hoisnard L, Lebrun-Vignes B, Maury S, et al. (2022) "Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database." Sci Rep, 12, p. 7140
  6. (2023) "Product Information. Olumiant (baricitinib)." Lilly, Eli and Company, DailyMed
  7. (2023) "Product Information. Xeljanz (tofacitinib)." Pfizer U.S. Pharmaceuticals Group
  8. (2023) "Product Information. Xeljanz (tofacitinib)." Pfizer Ltd
  9. (2023) "Product Information. Xeljanz (tOFACitinib)." Pfizer Australia Pty Ltd, pfpxelja10423
  10. (2023) "Product Information. Rinvoq (upadacitinib)." AbbVie US LLC
  11. (2023) "Product Information. Rinvoq (upadacitinib)." AbbVie Ltd
  12. (2023) "Product Information. Rinvoq (upadacitinib)." AbbVie Pty Ltd, 8
  13. (2022) "Product Information. Olumiant (baricitinib)." Eli Lilly Canada Inc, 260967
  14. (2022) "Product Information. Xeljanz (tofacitinib)." Pfizer Canada ULC, 258173
  15. (2022) "Product Information. Rinvoq (upadacitinib)." AbbVie Corporation, 262176

Drug and food interactions

Moderate

tofacitinib food

Applies to: tofacitinib

MONITOR: Grapefruit juice may increase the plasma concentrations of tofacitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The extent and clinical significance are unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Until more information is available, some authorities recommend avoiding consumption of grapefruit juice during tofacitinib therapy (Canada). Patients receiving tofacitinib therapy who ingest grapefruits or grapefruit juice should be monitored for adverse effects and undue fluctuations in plasma drug levels.

References (1)
  1. (2024) "Product Information. Xeljanz (tofacitinib)." Pfizer Canada ULC
Moderate

cloNIDine food

Applies to: RCK (clonidine / ketorolac / ropivacaine)

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.

References (10)
  1. Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
  3. Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
  4. Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
  8. Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
  9. (2023) "Product Information. Buprenorphine (buprenorphine)." G.L. Pharma UK Ltd
  10. (2023) "Product Information. Temgesic (buprenorphine)." Reckitt Benckiser Pty Ltd
Moderate

ketorolac food

Applies to: RCK (clonidine / ketorolac / ropivacaine)

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

References (1)
  1. (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn

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

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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

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