Interaction With Methotrexate

The worldwide prevalence of diabetes mellitus (DM) has increased dramatically in the past 20 years. Insulin resistance occurs early in type 2 disease. This leads to progressive beta cell failure and overt diabetes. Though monotherapy can slow down this process, it does not prevent the progression of the disease. To address, both insulin resistance and beta cell dysfunction, combination therapy is required.

In a meta-analysis conducted by Westlake et al. (2009), studies that investigated the association between methotrexate in patients with RA and the risk of cardiovascular disease. INclusion criteria for being studied in the meta-analysis conducted by Westlake et al. (2009) included adult patients suffering from RA for more than 18 years. Adults over the age of 30-40 with a long history of RA were of concern because of the high prevalence in this particular group. Studies that examined the form of MTX consumed were also included in the meta-analysis to help assess the importance of form and dose of MTX used. Outcome variables measured in studies that were included in the review included common cardiovascular outcomes such as cerebrovascular disease, peripheral vascular disease and ischaemic heart disease (Westlake et al., 2009). In order to assess the efficiency of methotrexate in treating rheumatoid arthritis, studies manipulated the dosage or administration of methotrexate in adults who were suffering from rheumatoid arthritis. “ Effect sizes and odds ratios for clinical, radiological and toxicity outcomes were calculated and directly or indirectly compared between study groups using methotrexate in different dosages or by different routes”(Visser & Van Der Heijde,

Methotrexate is an antimetabolite of folic acid that blocks the formation of thymine within the cell, rendering it incapable of DNA replication. As a chemotherapeutic agent, it is also employed as an alternative treatment for psoriasis and rheumatoid arthritis when they are unresponsive to conventional therapies. Methotrexate (MTX) induces an effect similar to 5-fluorouracil (5-FU) by interrupting the formation of thymine within the cell, which leads to the inability to replicate DNA. Unlike 5-FU, which inhibits the action of thymidylate synthetase, MTX binds tightly to dihydrofolate reductase (DHFR) and blocks the formation of tetrahydrofolate, leading to the depletion of associated folate co-factors (126).

Metformin is a diabetic medication that’s typically used for type 2 diabetic patients. “Metformin works by helping to restore your body's proper response to the insulin that is naturally produced. It also decreases the amount of sugar that the liver makes and that the stomach and intestines absorb (Rx List, 2017).”In the endocrine system, the body either doesn't produce enough insulin or doesn't respond properly to insulin causing an imbalance between the effects of insulin and glucagon. Metformin then help decrease the insulin output to the body. Metformin is taking orally and absorbed into the body and blood stream to decrease the amount of glucose made by the liver and it decreases the amount of absorption in the body (Campbell, 2006).”

Co-administration of statins with cyclosporine, erythromycin, niacin or fibrates carries an increased risk for myopathy. Cyclosporin and erythromycin interact with statins via the CYP3A4 pathway and by interfering with OAT1B1 – a membrane transporter that helps regulate drug influx to the liver.

Methotrexate is a competitive inhibiter of binding of dihydrofolic acid (FH2) to the enzyme dihydrofolate reductase (DHFR). METHOTREXATE is a structural analogue of folic acid which make it can easily bind to the same receptor. DHFR is responsible for reducing FH2 to folinic acid (FH4), the active intracellular metabolite. Thus, METHOTREXATE decreases the amount of intracellular FH4 available and affects the metabolic pathways within the cell that are FH4 dependent. These pathways include pyrimidine metabolism and purine, polyamine synthesis and amino

A study published in The Journal of Clinical Endocrinology & Metabolism compared the effects of metformin monotherapy, glyburide monotherapy and glyburide-metformin therapy in 486 patients whose

Do’s and don’t related to drug therapy/ administration: Before taking this medication check for your radial pulse for a full minute. If your heartbeat is less than 60 beats per minute do not take the dosage and contact your provider. This drug should be taken once a day at the same time. This drug can be taken with or without food. If taken with food avoid taking it with foods that are rich in fiber (oats, raspberries, artichokes, lentils and

The primary endpoint behind the study is to determine the possible toxicities that may be encountered while on methotrexate therapy. The study aims to identify whether MTX administration is following the five rights of medication administration (the right patient, the right drug, the right dose, the right route, and the right time). After all, the ultimate purpose is to optimize patient care.

Medications that can cause interactions include anticoagulants, probenecid, bisphosphonates, angiotensin-converting enzyme (ACE) inhibitors, anticoagulants (Warfarin), antiplatelet medicines (Clopidogrel), aspirin, corticosteroids (Prednisone), heparin, other NSAIDs (Ibuprofen), Rivaroxaban, or Selective Serotonin Reuptake Inhibitors (SSRIs) (Fluoxetine) due to the risk of stomach bleeding may be increased. Bisphosphonates (Alendronate), Cyclosporine, Hydantoins (Phenytoin), Lithium, Methotrexate, Quinolones (Ciprofloxacin), Sulfonamides (Sulfamethoxazole), and Sulfonylureas (Glipizide) side effects may be increased by Naproxen. The effectiveness of Angiotensin-converting enzyme (ACE) inhibitors (Enalapril), Beta-blockers (Propranolol), or diuretics (Furosemide, Hydrochlorothiazide) may be decreased by Naproxen (Lexi-Comp,

To avoid dangerous drug-drug interactions, people should consult a pharmacist or doctor before they take prescription drugs and OTC drugs at the same time. People who have chronic disorders should also consult a pharmacist or doctor. OTC drugs are not designed to treat serious disorders and can make some disorders worse. An unanticipated reaction, such as a rash or insomnia, is a signal to stop taking the drug immediately and obtain medical

An interaction between two medications does not mean that you have to stop using one of them. Speak to your doctor on how you can manage the interaction.

In vitro and in vivo studies have identified OATP1B1’s clinical importance in drug drug interactions (DDI) as some drugs which inhibit them have been observed to cause DDIs12. These drugs inhibit OATP1B1 and thus increasing the plasma concentrations of other OATP1B1 substrates12. The hepatic uptake rate is determinant of overall hepatic clearance for OATP1B1 substrates which are metabolised in the liver. Thus, DDIs can be cause only by inhibition of OATP1B112. Examples of compounds which causing DDI are Gemfibrozil, Rimfampicin and Cyclosporine

Metformin hydrochloride is available as immediate-release, extended-release oral tablet and oral solution. There are different brands available such as Glumetza, Fortamet, Glucophage (U.S. brands), Diabex, Diaformin and Terry White Chemists Metformin (Australian brands).

Clarify the order with the Physician involved. Refer to the drug guide or any reliable source if necessary.