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1.
Expert Rev Clin Pharmacol ; 4(6): 743-50, 2011 Nov.
Article in English | MEDLINE | ID: mdl-22111860

ABSTRACT

Methotrexate is an antifolate agent used in the treatment of various cancers and some autoimmune diseases. In oncology, methotrexate is frequently administered at a high dose (>1 g/m(2)) and comes with various procedures to reduce the occurrence of toxicity and particularly to ensure optimal renal elimination. Drug-drug interactions involving methotrexate are the origin of severe side effects owing to delayed elimination of the antifolate and, more rarely, of decreased efficacy in relation to suboptimal exposure. Most of these interactions are driven by membrane drug transporters whose activity/expression can be inhibited by the interacting medication. In the last 10 years, research on drug transporters has permitted retrospective identification of the molecular mechanisms underlying drug-drug interactions with methotrexate. This article summarizes reported drug-drug interactions involving methotrexate in clinical oncology with reference to the role of drug transporters that control the disposition of the antifolate agent.


Subject(s)
Drug Interactions/physiology , Medical Oncology , Methotrexate/pharmacokinetics , Neoplasms/metabolism , Animals , Humans , Medical Oncology/methods , Methotrexate/therapeutic use , Neoplasms/drug therapy , Organic Anion Transporters/metabolism
2.
Bull Cancer ; 98(2): 176-81, 2011 Feb.
Article in French | MEDLINE | ID: mdl-21382797

ABSTRACT

The aim of our work was to assess the potential clinical impact of therapeutic education in patients treated with anticancer drugs. One hundred-one ambulatory adult patients (mean age: 60 years, range: 24-88) treated by anticancer chemotherapy were included. The occurrence of adverse events was reported by 83% of the patients. Twenty-one percent (14/67) of the patients were not compliant with their supportive care treatment, 60% (60/101) took over-the-counter medications (one contraindication identified) and 14% (14/101) claimed they had received no counsel on risk behaviour (UV exposure, lack of contraception, driving) from health care professionals. Overall, 11% (44/397) of adverse events were associated with a lack of information. Twelve percent (4/33) of the calls to the doctor, 6% (1/17) of the visits to the physician and 21% (3/14) of the hospitalizations could be associated with a lack of therapeutic education. These data enlighten the importance of therapeutic education of cancer patients treated by chemotherapy.


Subject(s)
Antineoplastic Agents/adverse effects , Neoplasms/drug therapy , Patient Compliance , Patient Education as Topic , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Contraindications , Female , Health Surveys , Humans , Male , Middle Aged , Prospective Studies , Risk-Taking , Self Medication , Young Adult
3.
Anticancer Res ; 30(3): 963-5, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20393020

ABSTRACT

BACKGROUND: Delayed elimination of methotrexate associated with serious side-effects has been attributed to the co-administration of benzimidazole proton pump inhibitors. PATIENTS AND METHODS: We have retrospectively analyzed the causes of delayed methotrexate elimination in patients who had received the rescue agent glucarpidase to evaluate the potential implication of benzimidazoles. RESULTS: Between 2002 and 2008, six patients (mean age: 30 years; range: 4-74 years) were treated with glucarpidase. Delayed elimination associated with impaired renal function occured after the first cycle except in 2 patients (2nd and 8th administration of high-dose methotrexate). The possible causes of delayed elimination identified were: insufficient hydration (n=1) and drug-drug interactions (n=5). The potential drug-drug interactions included the co-administration of piperacillin/tazobactam (n=1) and proton pump inhibitors (omeprazole, n=3; esomeprazole, n=2). Impaired elimination of methotrexate was not observed either in the 3 patients who were treated further or during the previous cycles of the 2 pretreated patients in relation to the absence of co-prescription of proton pump inhibitors. CONCLUSION: In line with the recent literature and given the prohibitive cost of glucarpidase, we have advocated the cessation of proton pump inhibitors administration during methotrexate treatment.


Subject(s)
Antimetabolites, Antineoplastic/pharmacokinetics , Antimetabolites, Antineoplastic/poisoning , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Benzimidazoles/pharmacology , Methotrexate/pharmacokinetics , Methotrexate/poisoning , Proton Pump Inhibitors/pharmacology , Adolescent , Adult , Aged , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Benzimidazoles/administration & dosage , Bone Neoplasms/drug therapy , Bone Neoplasms/metabolism , Child , Child, Preschool , Drug Interactions , Humans , Lymphoma/drug therapy , Lymphoma/metabolism , Methotrexate/administration & dosage , Middle Aged , Neuroblastoma/drug therapy , Neuroblastoma/metabolism , Osteosarcoma/drug therapy , Osteosarcoma/metabolism , Proton Pump Inhibitors/administration & dosage , Retrospective Studies , Young Adult , gamma-Glutamyl Hydrolase/therapeutic use
5.
Br J Clin Pharmacol ; 70(5): 762-4, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21545633

ABSTRACT

AIMS: To report a case of severe delayed methotrexate elimination attributable to consumption of a cola beverage. METHODS: To investigate unexplained low urinary pH in a lymphoma patient treated with high-dose methotrexate. RESULTS: Unexpected urinary acidity, despite administration of large amounts of sodium bicarbonate, could be attributed to repeated consumption of a cola beverage. It resulted in a delayed elimination of methotrexate and acute renal failure. Discontinuation of cola drinks, increase in calcium folinate rescue and in sodium bicarbonate allowed satisfactory elimination of methotrexate on day 12 after infusion and recovery from renal impairment without other severe toxicity. No other cause of delay in methotrexate elimination could be identified. CONCLUSIONS: Cola beverages have a low pH due to their phosphoric acid content that is excreted by renal route. We recommend patients receiving high dose methotrexate abstain from any cola drink within 24 h before and during methotrexate administration and until complete elimination of the drug.


Subject(s)
Carbonated Beverages/adverse effects , Cola/adverse effects , Food-Drug Interactions , Methotrexate/pharmacokinetics , Antimetabolites, Antineoplastic , Biological Transport/drug effects , Humans , Hydrogen-Ion Concentration , Kidney/metabolism , Liver/metabolism , Lymphoma/drug therapy , Lymphoma/urine , Male , Methotrexate/therapeutic use , Middle Aged , Urine/chemistry
6.
Pharm World Sci ; 31(6): 619-21, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19757141

ABSTRACT

CASE DESCRIPTION: A French Caucasian man aged 39 with HIV infection was treated with abacavir/lamivudine and ritonavir/lopinavir. The patient (normal renal and liver functions) was diagnosed with a Burkitt lymphoma for which he was treated with cyclophosphamide day 1 to 5; doxorubicin day 1; methotrexate day 10; and vincristine day 1 and 8. At day 12, he suffered from abdominal pain associated with constipation. Paralytic ileus was diagnosed by study imaging. Ileus lasted 10 days necessitating parenteral feeding. Later on, a further cycle of chemotherapy with etoposide replacing vincristine was given and was well tolerated. CONCLUSION: We speculate that an interaction between ritonavir/lopinavir and vincristine was responsible for this severe toxicity. Vincristine is transported by P-gp and is metabolized via CYP3A5. Ritonavir is a potent CYP3A5 isoenzyme and P-gp inhibitor. Lopinavir is also a P-gp inhibitor. Ritonavir and lopinavir might have delayed vincristine elimination. Clinicians should be aware of this possible interaction.


Subject(s)
Antineoplastic Agents, Phytogenic/adverse effects , Burkitt Lymphoma/drug therapy , HIV Infections/drug therapy , HIV Protease Inhibitors/adverse effects , Intestinal Pseudo-Obstruction/chemically induced , Pyrimidinones/adverse effects , Ritonavir/adverse effects , Vincristine/adverse effects , Abdominal Pain/chemically induced , Adult , Antineoplastic Agents, Phytogenic/pharmacokinetics , Burkitt Lymphoma/complications , Constipation/chemically induced , Drug Interactions , HIV Infections/complications , Humans , Lopinavir , Male , Vincristine/pharmacokinetics
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