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 These stronger medications are often called slow acting anti-rheumatic drugs (SAARDs), disease modifying anti-rheumatic drugs (DMARDs) or “second line” drugs. 

 This booklet is intended to be a general guide to the DMARDs commonly used to treat rheumatoid arthritis. However, they are also used to treat other forms of arthritis, for example psoriatic arthritis.Each DMARD may be given on its own, but if it does not control your arthritis, a second one may be added. Using more than one DMARD is called combination therapy. Your doctor may also prescribe corticosteroids (Prednisone, Prednisolone, Depo-Medrol, Kenacort) for the treatment of rheumatoid arthritis. 

 The slow acting anti-rheumatic drugs include:

The benefits of DMARDs are not felt straight away. It may be 6-10 weeks, sometimes a little longer before you may notice any benefit from these slow-acting medications. There is often a reduction in swelling, stiffness and pain together with a decrease in tiredness. Some of the blood tests that measure inflammation also improve.
It is important to remember that each person is different and each of us responds to medications in different ways.

 Pregnancy  

Talk to your doctor if you are planning to have a baby, as most (but not all) second line medications will need to be stopped before you become pregnant. DMARDs may be started again once you have finished breast-feeding.

Side Effects

 DMARDs tend to have a greater effect on arthritis than NSAIDs and there are some side effects, which are associated with taking this type of medication. Careful monitoring of the dose, together with regular routine blood and urine testing will enable any possible problems to be picked up very quickly and appropriate action taken. The following is a list of side effects which are sometimes seen in slow acting medications. 

• Nausea and/or diarrhoea:
This is usually related to the dose and reducing the dose will often ease these symptoms.

• Rashes:These may come and go while you are taking DMARDs. If they continue, the medication is stopped.

• Mouth ulcers, sore or bleeding gums:These may occur with some of the medications and must be reported to your doctor at once.

• Changes in the blood cells:
a. White blood cells: These cells are important for fighting infection and may be reduced while taking any DMARD.
b. Platelets: These are necessary for blood clotting and may also be reduced.• Changes in the liver:Some functions of the liver may be affected while taking some DMARDs. 

• Changes in the kidney:The kidneys can sometimes allow protein and small amounts of blood to leak into the urine during treatment.How Often Are Tests Done?When the medication is started, blood tests (full blood count, liver and kidney function) and urine testing for protein and blood may be performed weekly or less frequently depending on what DMARD you are taking.
Your doctor will organize the tests for you.  

Recording Your ResultsYou may be given a booklet, which contains information on the dosage of medication, and details of each blood and urine sample tested. In this way it is easy for your doctor to see the information he needs to know. Any changes in the tests will also show if your doctor needs to take any action. It is important that you keep this booklet with you and take it each time you visit your doctor.Please remember – the benefits that can be gained from taking slow acting anti-rheumatic drugs outweigh the possible side effects. Simple precautions on a regular basis, as mentioned, will prevent side effects from becoming a problem.  

Following is information on individual DMARDs being used in Malaysia.  

METHOTREXATE (LEDERTREXATE)

• Taken as a tablet.
• This medication is taken once a week with a usual starting dose of 5.0-7.5mg. It is usually taken on the same day each week, with the dose slowly increased.
• The dosage may be changed by your doctor, depending on how well your arthritis responds and whether you have side effects.
• It is best taken with food to avoid stomach upsets.Potential side effects of Methotrexate• Mouth ulcers or sore gums.
• Nausea – this usually only lasts 24 hours following medication.
• Reduction in white blood cells and platelet numbers in the blood.
• Changes in the liver.Special precautions while taking Methotrexate• Only take the medication weekly (never daily)
• Routine regular blood tests, as arranged by your doctor.
• It is very important to limit your intake of alcohol while taking Methotrexate. Your doctor will advise you what is considered an acceptable amount.
• It is very important to avoid pregnancy while taking methotrexate.

HYDROXYCHLOROQUINE (PLAQUENIL)

• Taken as a tablet.
• The dosage is usually taken once daily (based on your weight)
• A higher dose may be used at first, 400-600 mg daily.
• Regular dosage is usually between 200-400mg daily. Potential side effects of Plaquenil 

• Skin rashes, particularly on the areas exposed to the sun.
• May affect the eyes. This is unlikely at dosages used today.
• Stomach effects such as nausea, cramps, and diarrhoea. Special precautions while taking Plaquenil 

• Regular eye checkup, at least every 12 months. Your doctor may refer you to an eye specialist.
• Use SPF 30+ sunblock in the sun, and long sleeved clothing when exposed to the sun.
• Use a hat and good quality sunglasses.
• Plaquenil is best taken with meals.

SULPHASALAZINE (SALAZOPYRIN-EN)  

• Taken as a tablet.
• The dosage depends on your response to treatment.
• At first, dosage is usually 500mg a day (one tablet).
• The dosage is increased slowly over a number of weeks until the full dosage is reached (often 4-6 tablets daily).
  

The dosage may be changed from time to time depending on how your arthritis responds.   

Potential side effects of Sulphasalazine  

• Nausea and indigestion.
• Dizziness and headache.
• Skin rashes.
• Reduction of white blood cells and platelet numbers in your blood. This is a rare side effect.
• Slight changes in the liver.
• May stain contact lenses yellow, particularly soft lenses.
• Urine may have an orange color.
• May reduce the sperm count in men and could cause temporary infertility. This effect only occurs while taking sulphasalazine. The sperm counts returns to normal once the medication is stopped.
• There is no effect on fertility in women.  

Special precautions while taking Sulphasalazine  

• Routine blood test will be performed. Your doctor will indicate how often he/she wants you to have your blood tested.
• Tell your doctor of any symptoms you may have. Change of dosage of sulphasalazine may ease the symptom.  

• Always take your medication after meals and use the enteric-coated EN brand.  

AZATHIOPRINE (IMURAN)  

• Taken as a tablet.
• The tablets are usually in doses of 25 or 50 mg.
• The dosage may be increased slowly over a few weeks until the full dose is reached – usually between 100-150 mg per day. The dosage may be changed from time to time depending on how well your arthritis has responded, and if you are experiencing any side effects.  

Potential side Effects of Azathioprine  

• Nausea.
• Mouth ulcers or sore gums.
• A reduction of white blood cells or platelets.
• Changes in the liver.
Special precautions while taking Azathioprine
• Routine blood tests as arranged by your doctor.
• Take your medication after meals to avoid stomach upsets.  

LEFLUNOMIDE (ARAVA)  

• Taken as a tablet.
• The dosage consists of loading dose – normally 100mg once daily for 3 days.
• The usual dose is 20mg once daily. If 20mg is poorly tolerated, it may be reduced to 10mg daily may be used if other DMARDs are also being used.  

Potential side effects of Leflunomide  

• Diarrhoea – generally mild and will stop with time.
• A reduction in the white blood cells or platelets.
• Changes in the liver.
• Skin rashes.
• Minor hair loss.  

Special precautions while taking Leflunomide  

• Routine regular blood tests, as arranged by your doctor.
• Leflunomide should not be given to pregnant and breastfeeding women or women of childbearing potential who are not using reliable contraception.
• You must not start a family (both men & women) while on Arava. Pregnancy should be avoided for 2 years after cessation of therapy with Arava unless a special wash out procedure is carried out. Consult your doctor if you wish to become pregnant or father a child.  

D-Penicillamine (D-Penamine)  

• Taken as a tablet.
• Dosage is usually once or twice daily with starting dose between 125-250 mg daily.
• Dosage is increased gradually until the full dose is reached. This is usually between 500-1000mg per day.
• Dosage may be changed by your doctor depending on how your arthritis responds, or whether you have any side effects.
  

D-Penicillamine is not an antibiotic and an allergy to penicillin should not prevent you from taking it.  

Potential side effects of D-Penilcillamine  

• Mouth ulcers.
• Nausea and indigestion.
• Skin rashes.
• Changes in taste – this usually disappears after a few weeks.
• Reduction of white blood cells and platelet numbers.
• Changes in the kidneys. This may result in protein in the urine.  

Special precautions while taking D-Penicillamine  

• Routine blood and urine tests which will be arranged by your doctor.
• It is important to take D-Penicillamine on an empty stomach as food interferes with its absorption in the body. Take the tablets 1/2hour before meal, or at least two hours following a meal.
• Take your D-Penicillamine record booklet each time you visit your doctor.
• Antacids and iron tablets can slow the absorption of D-Penicillamine. Take these medications at different times of the day to D-Penicillamine.  

ETANERCEPT (ENBREL)  

• Given as a subcutaneous injection 50mg once weekly or 25mg twice weekly.
   

Potential side effects of Etanercept  

• Injection site reaction – mild to moderate reactions (rash, itch, swelling) that normally last for 3 to 5 days.
• You may be more likely to get severe infections while taking this class of medication.
• A very small percentage of patients developed lumps or tumours (cancers). Please see your doctor if you discover any new lumps.  

Special precautions when using Etanercept  

• Routine regular blood tests, as arranged by your doctor.
• Etanercept should be used during pregnancies only if absolutely needed.
• Nursing mother – It is not known whether Etanercept is excreted in human milk.  

INFLIXIMAB (REMICADE)  

• This drug is given in the form of intravenous infusion (injection into the veins) at an interval that will determined by your doctor. It is usually given together with methotrexate.  

Potential side effects of Infliximab  

• Difficulty in breathing.
• Skin itching
• Headache
• You may be more likely to get severe infections while taking this class of medication.
• A very small percentage of patients developed lumps or tumours (cancers). Please see your doctor if you discover any new lumps.  

Special precautions when using Infliximab  

• Similar to Etanercept.  

ADALIMUMAB (HUMIRA)  

• Given as a subcutaneous injection 40mg every two weeks  

Potential side effects of Adalimumab  

• Injection site reactions
• You may be more likely to get severe infections while taking this class of medication
• A very small percentage of patients developed lumps or tumours (cancers). Please see your doctor if you discover any new lumps  

Special precautions when using Adalimumab  

• Similar to Etanercept and Infliximab  

RITUXIMAB (MABTHERA)  

• Given usually as a course of two intravenous infusions, which may be repeated after 6 to 12 months  

Potential side effects of Rituximab  

• During the infusion, headaches and chills can occur.
• Rarely, breathing difficulties and low blood pressure can also happen
• Increased risk of infections  

Special precautions when using Rituximab  

• Routine blood tests determined by your doctor
• Women should not become pregnant at least 12 months after Rituximab treatment
• Women should not breast-feed at least 12 months after Rituximab treatment
  

CORTICOSTEROIDS  

Although corticosteroids reduce inflammation they are not disease modifying drugs like the other DMARDs. These medications have the ability to decrease inflammation more quickly than DMARDs. The side effects are not the same as those of DMARD medications.  

Prednisone, Prednisolone  

• Taken as a tablet.
• Dosage varies from person to person, but the aim is to keep the dose below 5 mg per day.
• May be given in high doses over a short period of time to control severe arthritis. The dose will then be adjusted by your doctor.  

Special Precautions while taking Corticosteroid  

• Treat any infections early.
• Maintain a well balanced diet.
• Maintain adequate calcium in the diet.
• Increase your exercise level.
• Best taken in the morning.
  

Never stop taking steroids suddenly. The dosage should be decreased slowly over a number of weeks. Your doctor will advise you about this.  

Injection of corticosteroid into a joint  

Joints commonly injected are fingers, toes, knees, and shoulders. Most of the steroid stays in the joint and dissolves over a few days, however a small amount is absorbed into the bloodstream. This may give an added relief to other joints, lasting up to six weeks and sometimes longer. Injecting corticosteroids into a joint does not produce the side effects associated with taking steroid by mouth.  

Special precautions with injections into a joint  

• Injections must be given by an experienced doctor, either your general practitioner or specialist.
• Usually no more than three or four injections are given into the same joint over a 12 months period.