Hydroxychloroquine Methotrexate

Clinically important, potentially hazardous interactions with acitretin, antacids, cholestyramine, dapsone, furazolidone, halofantrine, hydroxychloroquine, methotrexate, methoxsalen, mivacurium, nilotinib, penicillamine, sulfonamides... 

D. Pharmacokinetics and Clinical Use Sulfasalazine, hydroxychloroquine, methotrexate, cyclosporine, penicillamine and leflunomide are given orally. Infliximab and etanercept are given by injection. Gold compounds are available for parenteral use (gold sodium thiomalate and au-rothioglucose) and for oral administration (auranofin). 

Older disease-modifying antirheumatic drugs (DMARDs) used frequently in rheumatoid arthritis include hydroxychloroquine, methotrexate, steroids, and sulfasalazine. Gold salts and penicillamine may be effective but cause severe toxicity (see Chapter 36). 

The miscellaneous drugp are used to treat a variety of musculoskeletal disorders. Ffenicillamine, methotrexate (MTX), and hydroxychloroquine are used to treat rheumatoid arthritis in patients who have had an insufficient therapeutic response to or are intolerant of other antirheumatic drugp such as the sailcylates and NSAIDs. The Summary Drug Table Drug s Used to Tream Musculoskeletal Disorders provides additional information about these and other drug s. One compound, hylan G-F 20, listed in the Summary Drug Table is not used for rheumatoid arthritis, but rather, for osteoarthritis knee pain. It is a viscous, elastic... 

In addition to relying on safety and efficacy data, the initial DMARD choice depends on disease severity, patient characteristics (i.e., comorbidities, likelihood of adherence), cost, and clinician experience with the medication.1,7 Methotrexate alone or in combination therapy is the initial treatment of choice for patients with aggressive disease. Patients with early, mild disease may receive monotherapy with sulfasalazine or hydroxychloroquine. Agents such as azathioprine, D-penicillamine, and gold salts are used rarely today because of concerns about toxicity and reduced efficacy.1,15... 

Cyclization adrenaline azathioprine calciferol chlordiazepoxide cholecalciferol clomiphene hydroxychloroquine levodopa methotrexate phenylalanine tyrosine... 

The most recent treatment paradigm calls for earher, more aggressive treatment of rheumatoid arthritis. DMARDs are frequently employed along with NSAIDs in the initial treatment of the disease. The COX-2 inhibitors are often used because they are less likely to cause serious GI toxicity than are the nonspecihc COX inhibitors. The usual DMARD of choice for patients with mild rheumatoid arthritis is hydroxychloroquine or sulfasalazine methotrexate is used for those with moderate to serious disease. Other DMARDs are used if these agents are poorly tolerated or do not produce suf-hcient response. Combination therapy of methotrexate and another agent is also used to treat disease that is not responsive to individual DMARDs. 

The disease modifying drugs (DMDs/ DMARDs) used are gold, d-penicillamine, hydroxychloroquine, sulfasalazine and immuno-suppressants like methotrexate, azathioprine, cyclosporin etc. 

The drug is approximately 70% absorbed after oral administration (see Chapter 54). It is metabolized to a less active hydroxylated metabolite, and both the parent compound and the metabolite are polyglutamated within cells, where they stay for prolonged periods. Methotrexate s serum half-life is usually only 6-9 hours, although it may be as long as 24 hours in some individuals. Methotrexate s concentration is increased in the presence of hydroxychloroquine, which can reduce the clearance or increase the tubular reabsorption of methotrexate. This drug is excreted principally in the urine, but up to 30% may be excreted in bile. 

When added to methotrexate background therapy, cyclosporine, chloroquine, hydroxychloroquine, leflunomide, infliximab, adalimumab, rituximab, and etanercept have all shown improved efficacy. In contrast, azathioprine, auranofin, or sulfasalazine plus methotrexate results in no additional therapeutic benefit. Other combinations have occasionally been used, including the combination of intramuscular gold with hydroxychloroquine. 

Originally used in the treatment of malaria, the drugs chloroquine (Aralen) and hydroxychloroquine (Pla-quenil) have also been used to treat rheumatoid arthritis. In the past, these drugs have been used reluctantly because of the fear of retinal toxicity (see Adverse Side Effects ).25 There is now evidence, however, that these agents can be used safely, but they are only marginally effective when compared to other DMARDs. These drugs are therefore not usually the first choice, but they can be used in patients who cannot tolerate other DMARDs, or in combination with another DMARD (e.g., methotrexate) for more comprehensive treatment. 

Therapy for SEE is both complex and, in many instances, disappointing for both patient and practitioner. Management of the systemic signs and symptoms may not improve the ocular manifestations of the disease. The most common therapy for the arthritic and cardiac complications is NSAID use. Hydroxychloroquine and chloroquine are particularly effective in treating the discoid rash associated with the disease. In some cases oral steroids are used either alone or in combination with other immunosuppressive agents. Methotrexate can effectively reduce the need for systemic steroids in the treatment of mild to moderate SEE. Cyclophosphamide and... 

Furst DE. The combination of methotrexate, sulfasalazine and hydroxychloroquine is highly effective in rheumatoid... 

Combination therapy with two or more DMARDs may be effective when single-DMARD treatment is unsuccessful. The combinations of cyclosporine plus methotrexate and methotrexate plus sulfasalazine and hydroxychloroquine have been shown to be particularly effective. ... 

Disease-modifying antirheumatic drugs (DMARDs) are thought to slow disease progression and may be started with NSAIDs at the time of initial diagnosis, especially if symptoms are severe. Hydroxychloroquine is often recommended for mild arthritis and methotrexate (MTX) for moderate to severe RA. Other DMARDs (see Table VI-1-3) are used less frequently, sometimes in combination regimens for refractory cases. 

Answer C. Ocular toxicity is characteristic of chloroquine and hydroxychloroquine. Corneal deposits are reversible, but retinal pigmentation can ultimately lead to blindness. Patients will complain about GI distress, visual dysfunction, ringing in the ears (note that tinnitus aiso occurs in salicylism), and itchy skin. Hydroxychloroquine also promotes oxidative stress that can lead to hemolysis in G6PD deficiency. DMARDs include gold salts (e.g., auranofin), methotrexate, and etanercept, but thioridazine is a phenothiazine used as an antipsychotic it lacks anti-inflammatory effect, but does cause retinal pigmentation. 

---