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Drug Interactions between ocrelizumab and Proben-C

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

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Interactions between your drugs

Moderate

colchicine ocrelizumab

Applies to: Proben-C (colchicine / probenecid) and ocrelizumab

MONITOR: The concomitant use of the CD20-directed cytolytic antibody ocrelizumab with other immune-modulating or immunosuppressive therapies, including immunosuppressant doses of corticosteroids, may result in an increased risk of immunosuppression. However, data is conflicting. Factors that appear to be associated with a risk of serious infections include higher doses of ocrelizumab than those recommended for multiple sclerosis (MS), other comorbidities, and concomitant use in patients on chronic immunosuppressants/corticosteroids. Ocrelizumab alone has been reported to increase the risk for respiratory tract infections and herpes-related infections in MS trials. In the postmarketing setting, hepatitis B reactivation, cases of progressive multifocal leukoencephalopathy (PML), and immune-mediated colitis have been reported. In relapsing MS (RMS) studies, 58% of ocrelizumab-treated patients experienced infections compared to 52% of interferon-treated patients. However, the proportion of patients reporting serious infection was higher in the interferon-treated group (2.9% versus 1.3%). On the other hand, when ocrelizumab is used concomitantly with immunosuppressants in other autoimmune conditions (e.g., rheumatoid arthritis) some studies have reported an increase in serious infections such as atypical pneumonia, pneumocystis jirovecii pneumonia, varicella pneumonia, tuberculosis, and histoplasmosis have been reported from some studies, including rare reports of fatalities.

MANAGEMENT: The increased risk of additive immunosuppression should be considered if co-administering ocrelizumab with other immunosuppressive therapy. Some authorities recommend avoiding concomitant use of other immunosuppressive therapies with ocrelizumab, except for the use of corticosteroids for symptomatic treatment of a MS relapse. Patients should be advised to notify their doctor if they develop signs or symptoms of infection, including upper or lower respiratory tract infection, skin infection, herpes related infection, or PML. If switching from a drug with prolonged immune effects (e.g., daclizumab, fingolimod, natalizumab, teriflunomide, mitoxantrone), the duration and mechanism of action should be considered prior to starting ocrelizumab therapy. The product labeling should be consulted for more specific recommendations.

References

  1. Emery P, Rigby W, tak pp, et al. (2023) Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3911947/
  2. (2022) "Product Information. Ocrevus (ocrelizumab)." Roche Products Ltd
  3. (2023) "Product Information. Ocrevus (oCRELizumab)." Roche Products Pty Ltd
  4. (2023) "Product Information. Ocrevus (ocrelizumab)." Genentech
  5. (2017) "Product Information. Ocrevus (ocrelizumab)." Hoffmann-La Roche Limited
View all 5 references

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Drug and food interactions

Major

colchicine food

Applies to: Proben-C (colchicine / probenecid)

GENERALLY AVOID: Coadministration with grapefruit juice may increase the serum concentrations of colchicine. Clinical toxicity including myopathy, neuropathy, multiorgan failure, and pancytopenia may occur. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism and P-glycoprotein efflux in the gut wall by certain compounds present in grapefruits. A published case report describes an eight-year-old patient with familial Mediterranean fever who developed acute clinical colchicine intoxication after ingesting approximately one liter of grapefruit juice per day for two months prior to hospital admission while being treated with colchicine 2 mg/day. Her condition progressed to circulatory shock and multiorgan failure, but she recovered with supportive therapy after 24 days in the hospital. In a study of 21 healthy volunteers, administration of 240 mL grapefruit juice twice a day for 4 days was found to have no significant effect on the pharmacokinetics of a single 0.6 mg dose of colchicine. However, significant interactions have been reported with other CYP450 3A4 inhibitors such as clarithromycin, diltiazem, erythromycin, ketoconazole, ritonavir, and verapamil.

MANAGEMENT: Patients treated with colchicine should be advised to avoid the consumption of grapefruit and grapefruit juice, and to contact their physician if they experience symptoms of colchicine toxicity such as abdominal pain, nausea, vomiting, diarrhea, fatigue, myalgia, asthenia, hyporeflexia, paresthesia, and numbness.

References

  1. Pettinger WA (1975) "Clonidine, a new antihypertensive drug." N Engl J Med, 293, p. 1179-80
  2. Caraco Y, Putterman C, Rahamimov R, Ben-Chetrit E (1992) "Acute colchicine intoxication: possible role of erythromycin administration." J Rheumatol, 19, p. 494-6
  3. Schiff D, Drislane FW (1992) "Rapid-onset colchicine myoneuropathy." Arthritis Rheum, 35, p. 1535-6
  4. Putterman C, Ben-Chetrit E, Caraco Y, Levy M (1991) "Colchicine intoxication: clinical pharmacology, risk factors, features, and management." Semin Arthritis Rheum, 21, p. 143-55
  5. Boomershine KH (2002) "Colchicine-induced rhabdomyolysis." Ann Pharmacother, 36, p. 824-6
  6. (2003) "Severe colchicine-macrolide interactions." Prescrire Int, 12, p. 18-9
  7. Tateishi T, Soucek P, Caraco Y, Guengerich FP, Wood AJ (1996) "Colchicine biotransformation by human liver microsomes. Identification of CYP3A4 as the major isoform responsible for colchicine demethylation." Biochem Pharmacol, 53, p. 111-6
  8. Dogukan A, Oymak FS, Taskapan H, Guven M, Tokgoz B, Utas C (2001) "Acute fatal colchicine intoxication in a patient on continuous ambulatory peritoneal dialysis (CAPD). Possible role of clarithromycin administration." Clin Nephrol, 55, p. 181-2
  9. Rollot F, Pajot O, Chauvelot-Moachon L, Nazal EM, Kelaidi C, Blanche P (2004) "Acute colchicine intoxication during clarithromycin administration." Ann Pharmacother, 38, p. 2074-7
  10. Wilbur K, Makowsky M (2004) "Colchicine myotoxicity: case reports and literature review." Pharmacotherapy, 24, p. 1784-92
  11. Hung IF, Wu AK, Cheng VC, et al. (2005) "Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency: a retrospective study." Clin Infect Dis, 41, p. 291-300
  12. Cheng VC, Ho PL, Yuen KY (2005) "Two probable cases of serious drug interaction between clarithromycin and colchicine." South Med J, 98, p. 811-3
  13. Akdag I, Ersoy A, Kahvecioglu S, Gullulu M, Dilek K (2006) "Acute colchicine intoxication during clarithromycin administration in patients with chronic renal failure." J Nephrol, 19, p. 515-7
  14. van der Velden W, Huussen J, Ter Laak H, de Sevaux R (2008) "Colchicine-induced neuromyopathy in a patient with chronic renal failure: the role of clarithromycin." Neth J Med, 66, p. 204-6
  15. Goldbart A, Press J, Sofer S, Kapelushnik J (2000) "Near fatal acute colchicine intoxication in a child. A case report." Eur J Pediatr, 159, p. 895-7
  16. (2008) "Colchicine: serious interactions." Prescrire Int, 17, p. 151-3
  17. (2009) "Product Information. Colcrys (colchicine)." AR Scientific Inc
  18. Dahan A, Amidon GL (2009) "Grapefruit juice and its constitueants augment colchicine intestinal absorption: potential hazardous interaction and the role of p-glycoprotein." Pharm Res, 26, p. 883-92
  19. McKinnell J, Tayek JA (2009) "Short term treatment with clarithromycin resulting in colchicine-induced rhabdomyolysis." J Clin Rheumatol, 15, p. 303-5
View all 19 references

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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.

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