Carolyn Whiskin took us through a review of the commonly used DMARDs in rheumatic diseases. Most of the actions and interactions with these medications can be found on www.rheuminfo.com. Some clinical pearls from her presentation include the following…
Methotrexate is the most used and well-tolerated medication in rheumatic disease. 30% of patients will achieve low disease activity on MTX monotherapy. It is the anchor medication for combination therapy and a first-line treatment for RA. Absorption is equivalent for oral and subcutaneous doses up to 15 mg/wk. When doses greater than 15 mg/wk are needed, the oral dose must be given in divided doses. Subcutaneous MTX is recommended for better absorption and reduced GI upset. Contraception should be used by both males and females during treatment with MTX and for 3 months after discontinuation. It is thought that MTX affects the quantity but not the quality of sperm, but more research is needed in this area.
Many patients have a ″sick day″ post MTX treatment. Folic acid can help with symptoms and does not decrease the efficacy of MTX. There are no recommended guidelines for prescribing folic acid, and both folic acid and folinic acid have similar efficacy. Folic acid needs to be metabolized, so if a patient is not obtaining benefit from folic acid then try folinic acid.
Pharmacists may flag a problem because of interactions with MTX since the pharmacy print-outs do not discriminate between high-dose MTX for cancer and the smaller doses we use for rheumatic diseases. Low-dose NSAIDs are generally safe to use with MTX. Side effects of PPIs may be increased with high-dose MTX. Sulfa antibiotics such as Septra may increase bone marrow suppression in patients so they should not be used. Sulfasalazine and leflunomide may be flagged as an interaction with MTX but should not be a problem in the dosages we use in rheumatology. A courtesy statement to the pharmacist stating that you are aware of the potential interaction and that you are monitoring the patient can be helpful.
Hydroxychloroquine may decrease insulin degradation therefore blood sugar monitoring is important since your patient may need less treatment. The generic for Plaquenil causes much more nausea and vomiting. Be aware! A side effect of hydroxychloroquine is retinal toxicity but this is likely only in older people or those with diabetes. Therefore, some clinicians do a baseline eye test and then another test after 5 years for younger people. The loss of red light perception is one of the first signs of retinal toxicity.
Sulfasalazine requires a properly functioning gut in order for it to work properly.
Interactions with MTX can increase the level of sulfasalazine through competition for renal clearance.
Leflunomide can be comparable to MTX in terms of effectiveness. The US and UK do not use MTX and leflunomide together. Maybe this should be considered in Canada?
Tofacitinib is considered a DMARD and needs the same monitoring as other agents in this class. There is a low incidence of bowel perforation and increases in cholesterol. There are potential interactions with fluconazole and ketoconazole.
A helpful tool for assessing risk of infection for patients on DMARDs is the RABBIT risk score:
Most increase in infection risk is due to the disease state itself, not the medication
Controlling disease may decrease the incidence of infection
Higher doses of steroids may increase the risk for infections
Vaccinate RA patients before starting medications because they are at higher risk than the general population
Patients receiving MTX doses of less than 0.4 mg/kg/week can receive shingles vaccination (see vaccine protocol).