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Interactions between Hyrimoz and Paclitaxel

1 drug interaction and 21 additional warnings found for the following 2 drugs:

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Drug interactions

Major drug interactions

Major:

PACLitaxel adalimumab

Applies to: paclitaxel and Hyrimoz (adalimumab)
Monitor closely

The use of tumor necrosis factor (TNF) blockers with other immunosuppressive or myelosuppressive agents may increase the risk of infections. Serious infections and sepsis, including fatalities, have been reported with the use of TNF blockers, particularly in patients on concomitant immunosuppressive therapy. Agents that may be significantly myelo- or immunosuppressive include antineoplastic agents, radiation, zidovudine, linezolid, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents (greater than 10 mg/day to 1 mg/kg/day, whichever is less, of prednisone or equivalent for more than 2 weeks), and long-term topical or inhaled corticosteroids. Concomitant use of TNF blockers with other immunosuppressants such as azathioprine or mercaptopurine may also increase the risk of a rare and often fatal cancer of white blood cells known as hepatosplenic T-Cell lymphoma (HSTCL), which has primarily been reported in adolescent and young adult males receiving treatment for Crohn's disease or ulcerative colitis. Cases of HSTCL have also occurred during use of these agents alone. Because individuals with rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, or plaque psoriasis may be more likely to develop lymphoma than the general population, it is difficult to assess the added risk of TNF blockers, azathioprine, and/or mercaptopurine.

Management

Patients receiving a TNF blocker alone or with other immunosuppressive or myelosuppressive agents should be monitored closely for the development of infections. TNF blocker therapy should be discontinued if a serious infection or sepsis occurs. Close monitoring for signs and symptoms of HSTCL (e.g., splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss) is also recommended during use of TNF blockers, particularly in combination with other immunosuppressants such as azathioprine and mercaptopurine.

References (6)
  1. (2001) "Product Information. Remicade (infliximab)." Centocor Inc
  2. (2001) "Product Information. Enbrel (etanercept)." Wyeth-Ayerst Laboratories
  3. (2003) "Product Information. Humira (adalimumab)." Abbott Pharmaceutical
  4. (2008) "Product Information. Cimzia (certolizumab pegol)." UCB Pharma Inc
  5. (2009) "Product Information. Simponi (golimumab)." Centocor Inc
  6. FDA. U.S. Food and Drug Administration (2012) FDA Drug Safety Communication: Drug labels for the Tumor Necrosis Factor-alpha (TNFa) blockers now include warnings about infection with Legionella and Listeria bacteria. http://www.fda.gov/Drugs/DrugSafety/ucm270849.htm

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

PACLitaxel Food/Lifestyle

Applies to: paclitaxel
Monitor

Coadministration with inhibitors of CYP450 3A4, such as grapefruit juice, may increase the plasma concentrations of paclitaxel, which is a substrate of the isoenzyme. Current data suggest that consumption of large quantities of grapefruit juice inhibit both intestinal and hepatic CYP450 3A4 due to certain compounds present in grapefruit. Specific data for paclitaxel are lacking; however, in a case report of a 52-year-old woman with esophageal squamous cell carcinoma receiving a twice weekly chemotherapy regimen including intravenous docetaxel (40 mg/m2) reported that docetaxel systemic exposure (AUC) increased by 65% compared with the AUC target of 1.96 mg*h/L and clearance decreased by 63%, with a 71% reduction in the patient's neutrophil count. In the absence of other CYP450 3A4 inhibitors, these effects were attributed to daily consumption of 250 mL of grapefruit juice, which the patient had been consuming for at least 3 months. Two weeks after the patient ceased the grapefruit juice, the docetaxel AUC was closer to the target value and the neutrophil count reduction was less than 35%. In addition, in a pharmacokinetic study consisting of 7 cancer patients, mean dose-normalized docetaxel AUC increased by 2.2-fold and clearance decreased by 49% when intravenous docetaxel was given at a reduced dosage of 10 mg/m2 in combination with the potent CYP450 3A4 inhibitor ketoconazole (200 mg orally once daily for 3 days) compared to docetaxel administered alone at 100 mg/m2.

Management

Caution is recommended if paclitaxel is to be used in combination with grapefruit and grapefruit juice. Patients should be closely monitored for the development of paclitaxel toxicity, including diarrhea, mucositis, myelosuppression, and peripheral neuropathy and dose adjustment considered per local treatment protocols.

References (9)
  1. (2001) "Product Information. Taxotere (docetaxel)." Rhone Poulenc Rorer
  2. Aronson JK, Grahame-Smith DG (1981) "Clinical pharmacology: adverse drug interactions." Br Med J, 282, p. 288-91
  3. McInnes GT, Brodie MJ (1988) "Drug interactions that matter: a critical reappraisal." Drugs, 36, p. 83-110
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  5. Yong WP, Wang LZ, Tham LS, et al. (2008) "A phase I study of docetaxel with ketoconazole modulation in patients with advanced cancers." Cancer Chemother Pharmacol, 62, p. 243-51
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Engels FK, Mathot RA, Loos WJ, van Schaik RH, Verweij J (2006) "Influence of high-dose ketoconazole on the pharmacokinetics of docetaxel." Cancer Biol Ther, 5, p. 833-9
  8. Valenzuela B, Rebollo J, Perez T, Brugarolas A, Perez-Ruixo JJ (2011) "Effect of grapefruit juice on the pharmacokinetics of docetaxel in cancer patients: a case report." Br J Clin Pharmacol
  9. Starr SP, Hammann F, Gotta V, et al. (2016) "Pharmacokinetic interaction between taxanes and amiodarone leading to severe toxicity." Br J Clin Pharmacol, 450, p. 22-27

Disease interactions

20 potential interactions Applies to: 18 conditions, including Heart Failure, COPD, Peripheral Neuropathy, Arrhythmia, and Fever.

Anaphylaxis

Moderate:

paclitaxel

PACLitaxel has a moderate potential interaction with Anaphylaxis.

Anaphylaxis and severe hypersensitivity reactions characterized by dyspnea and hypotension requiring treatment, angioedema, and generalized urticaria have occurred in patients receiving paclitaxel. It is recommended that all patients should be pretreated with corticosteroids, diphenhydramine, and H2 antagonists. Patients who have developed severe hypersensitivity reactions should not be rechallenged with paclitaxel injection.

Arrhythmia

Major:

paclitaxel

PACLitaxel has a major potential interaction with Arrhythmia.

Severe conduction abnormalities, some requiring pacemaker placement, have been reported during paclitaxel therapy. Therapy with paclitaxel should be administered cautiously in patients with or predisposed to conduction disorders. Clinical monitoring of cardiac function is recommended during subsequent paclitaxel therapy.

Bleeding Disorder

Major:

paclitaxel

PACLitaxel has a major potential interaction with Bleeding Disorder.

Paclitaxel induces dose-dependent myelosuppression, primarily affecting neutrophils. Anemia characterized as a red blood cell count <11 g/dl has been reported in 78% of patients administered paclitaxel. Thrombocytopenia is uncommon and rarely severe. Therapy with paclitaxel should be administered cautiously in patients whose bone marrow reserve may be severely depressed and should be withheld when neutrophil counts fall below 1500/mm3 and/or platelet counts fall below 100,000/mm3. Paclitaxel injection should not be used in patients with solid tumors with baseline neutrophil counts less than 1500/mm3 or in patients with AIDS-related Kaposi's sarcoma with baseline neutrophil counts of less than 1000/mm3. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Close clinical monitoring of hematopoietic function is recommended.

Bone Marrow Depression/Low Blood Counts

Major:

paclitaxel

PACLitaxel has a major potential interaction with Bone Marrow Depression/Low Blood Counts.

Paclitaxel induces dose-dependent myelosuppression, primarily affecting neutrophils. Anemia characterized as a red blood cell count <11 g/dl has been reported in 78% of patients administered paclitaxel. Thrombocytopenia is uncommon and rarely severe. Therapy with paclitaxel should be administered cautiously in patients whose bone marrow reserve may be severely depressed and should be withheld when neutrophil counts fall below 1500/mm3 and/or platelet counts fall below 100,000/mm3. Paclitaxel injection should not be used in patients with solid tumors with baseline neutrophil counts less than 1500/mm3 or in patients with AIDS-related Kaposi's sarcoma with baseline neutrophil counts of less than 1000/mm3. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Close clinical monitoring of hematopoietic function is recommended.

Moderate:

Hyrimoz

The adalimumab in Hyrimoz has a moderate potential interaction with Bone Marrow Depression/Low Blood Counts.

Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia, some with a fatal outcome, have been reported in patients treated with TNF blocking agents. Caution should be exercised when treating patients who have ongoing or a history of significant hematologic abnormalities. Discontinuation of therapy should be considered in patients with confirmed significant hematologic abnormalities.

Central Nervous System Disorders

Major:

Hyrimoz

The adalimumab in Hyrimoz has a major potential interaction with Central Nervous System Disorders.

The use of TNF blocking agents has been associated with rare cases of CNS manifestations of systemic vasculitis, seizure and new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Care should be exercised when considering the use of these agents in patients with neurologic disorders and discontinuing the agent is recommended if these disorders develop during therapy.

COPD

Moderate:

Hyrimoz

The adalimumab in Hyrimoz has a moderate potential interaction with COPD.

In controlled trials of other TNF blockers, other than adalimumab, in adult patients at higher risk for malignancies (i.e., patients with COPD with a significant smoking history and cyclophosphamide-treated patients with Wegener's granulomatosis), a greater portion of malignancies occurred in the TNF blocker group compared to the control group.

Fever

Major:

paclitaxel

PACLitaxel has a major potential interaction with Fever.

Paclitaxel induces dose-dependent myelosuppression, primarily affecting neutrophils. Anemia characterized as a red blood cell count <11 g/dl has been reported in 78% of patients administered paclitaxel. Thrombocytopenia is uncommon and rarely severe. Therapy with paclitaxel should be administered cautiously in patients whose bone marrow reserve may be severely depressed and should be withheld when neutrophil counts fall below 1500/mm3 and/or platelet counts fall below 100,000/mm3. Paclitaxel injection should not be used in patients with solid tumors with baseline neutrophil counts less than 1500/mm3 or in patients with AIDS-related Kaposi's sarcoma with baseline neutrophil counts of less than 1000/mm3. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Close clinical monitoring of hematopoietic function is recommended.

Heart Failure

Moderate:

Hyrimoz

The adalimumab in Hyrimoz has a moderate potential interaction with Heart Failure.

Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers. Cases of worsening CHF have also been observed with adalimumab. Adalimumab has not been formally studied in patients with CHF; however, in clinical trials of another TNF blocker, a higher rate of serious CHF-related adverse reactions was observed. Exercise caution when using adalimumab in patients who have heart failure and monitor them carefully.

History, Skin Cancer

Major:

Hyrimoz

The adalimumab in Hyrimoz has a major potential interaction with History, Skin Cancer.

In clinical trials malignancies have been observed in patients receiving TNF-blockers agents. Patients with psoriasis should be monitored for non-melanoma skin cancers (NMSCs), particularly those patients who have had prior prolonged phototherapy treatment. Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker therapy. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. Postmarketing cases of fatal hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with TNF blockers. Caution should be exercised when considering these agents in the treatment of patients with a history of malignancies or in continuing treatment in patients who develop malignancies while receiving these agents.

Infection

Major:

Hyrimoz

The adalimumab in Hyrimoz has a major potential interaction with Infection.

There have been reports of serious infections, including sepsis and opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis and tuberculosis with TNF blockers. Treatment with these agents should not be initiated in patients with an active infection, including clinically important localized infections. Caution and close monitoring is recommended when considering their use in patients with a history of recurrent infections, underlying conditions which may predispose them to infections, or chronic, latent, or localized infections. Administration of these agents should be discontinued if a patient develops a serious infection or sepsis.

Major:

paclitaxel

PACLitaxel has a major potential interaction with Infection.

Because of their cytotoxic effects on rapidly proliferating tissues, antineoplastic agents frequently can, to varying extent, induce myelosuppression. The use of these drugs may be contraindicated in patients with known infectious diseases. All patients should be instructed to immediately report any signs or symptoms suggesting infection such as fever, sore throat, or local infection during antineoplastic therapy. Close clinical monitoring of hematopoietic function is recommended.

Infectious Hepatitis

Moderate:

Hyrimoz

The adalimumab in Hyrimoz has a moderate potential interaction with Infectious Hepatitis.

The use of TNF blockers has been associated with reactivation of hepatitis B, in some cases fatal, in patients who were previously infected with the hepatitis B virus (HBV). Therefore, screening for viral hepatitis should be performed in accordance with published guidelines before starting therapy with these agents. Monitor patients at risk or with evidence of current or prior HBV infection for clinical and laboratory signs of hepatitis or HBV reactivation. Prescribers should exercise caution in prescribing TNF blockers in patients previously infected with HBV. It is recommended to monitor patients with evidence of current or prior HBV infection for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following therapy. In patients who develop HBV reactivation, therapy should be stopped and antiviral therapy with appropriate supportive treatment should be initiated. The safety of resuming these agents after HBV reactivation is controlled is not known. Therefore, prescribers should weigh the risks and benefits when considering resumption of therapy.

Liver Disease

Major:

paclitaxel

PACLitaxel has a major potential interaction with Liver Disease.

Paclitaxel is extensively metabolized by the liver. Patients with moderate to severe hepatic impairment may be at increased risk for hepatotoxicity. Additionally, myelotoxicity of paclitaxel may be exacerbated in patients with serum total bilirubin >2 times ULN. Therapy with paclitaxel should be administered cautiously and at a reduced dosage in patients with compromised hepatic function.

Lymphoma

Major:

Hyrimoz

The adalimumab in Hyrimoz has a major potential interaction with Lymphoma.

In clinical trials malignancies have been observed in patients receiving TNF-blockers agents. Patients with psoriasis should be monitored for non-melanoma skin cancers (NMSCs), particularly those patients who have had prior prolonged phototherapy treatment. Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker therapy. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. Postmarketing cases of fatal hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with TNF blockers. Caution should be exercised when considering these agents in the treatment of patients with a history of malignancies or in continuing treatment in patients who develop malignancies while receiving these agents.

Pancytopenia

Moderate:

Hyrimoz

The adalimumab in Hyrimoz has a moderate potential interaction with Pancytopenia.

Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia, some with a fatal outcome, have been reported in patients treated with TNF blocking agents. Caution should be exercised when treating patients who have ongoing or a history of significant hematologic abnormalities. Discontinuation of therapy should be considered in patients with confirmed significant hematologic abnormalities.

Peripheral Neuropathy

Major:

paclitaxel

PACLitaxel has a major potential interaction with Peripheral Neuropathy.

Dose-dependent peripheral neuropathy has been reported in 60% of patients during paclitaxel therapy. Severe peripheral neuropathy is rare and requires a 20% reduction in dosage of paclitaxel. Therapy with paclitaxel should be administered cautiously in patients with or predisposed to peripheral neuropathy.

Skin Cancer

Major:

Hyrimoz

The adalimumab in Hyrimoz has a major potential interaction with Skin Cancer.

In clinical trials malignancies have been observed in patients receiving TNF-blockers agents. Patients with psoriasis should be monitored for non-melanoma skin cancers (NMSCs), particularly those patients who have had prior prolonged phototherapy treatment. Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker therapy. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. Postmarketing cases of fatal hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with TNF blockers. Caution should be exercised when considering these agents in the treatment of patients with a history of malignancies or in continuing treatment in patients who develop malignancies while receiving these agents.

Tuberculosis, Active

Major:

Hyrimoz

The adalimumab in Hyrimoz has a major potential interaction with Tuberculosis, Active.

Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving TNF blocking agents, including patients who have previously received treatment for latent or active tuberculosis. Cases of active tuberculosis have also occurred in patients being treated with these agents during treatment for latent tuberculosis. Prior to initiating TNF blocking agents, patients should be screened for latent tuberculosis infection with a tuberculin skin test and periodically during therapy. Patients testing positive in tuberculosis screening should be treated by standard medical practice prior to therapy with TNF blocking agents. Anti-tuberculosis therapy should also be considered prior to initiation of therapy in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Tuberculosis should be strongly considered in patients who develop a new infection during treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis.

Tuberculosis, Latent

Major:

Hyrimoz

The adalimumab in Hyrimoz has a major potential interaction with Tuberculosis, Latent.

Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving TNF blocking agents, including patients who have previously received treatment for latent or active tuberculosis. Cases of active tuberculosis have also occurred in patients being treated with these agents during treatment for latent tuberculosis. Prior to initiating TNF blocking agents, patients should be screened for latent tuberculosis infection with a tuberculin skin test and periodically during therapy. Patients testing positive in tuberculosis screening should be treated by standard medical practice prior to therapy with TNF blocking agents. Anti-tuberculosis therapy should also be considered prior to initiation of therapy in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Tuberculosis should be strongly considered in patients who develop a new infection during treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis.

More resources

Hyrimoz

A total of 574 drugs are known to interact with Hyrimoz.

paclitaxel

A total of 554 drugs are known to interact with paclitaxel.

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.