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Medications for Arthritis by Dr. Humeira Badsha

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There are 2 main kinds of medications for arthritis: Anti-Ifnlammartory Non-Steroidal (NSAIDA), steroids, and disease modifying drugs (DMARDS, specific treatment for inflammatory arthritis)

NSAIDS OR ANTI-INFLAMMATORIES:

This is a group of drugs that are commonly referred to as ‘pain-killers’ but actually also reduce swelling and inflammation. While these drugs may control the pain and symptoms of arthritis they do not control the disease or prevent joint damage. It is generally not recommended to take these medications for long term (> 3-6 months).

If it is necessary to take these medications long term it should be done under the supervision of a doctor.

Some of the side effects of NSAIDs are:

  • High blood pressure
  • Stomach ulcers (this is more common in those over 60 years, who also taking steroids, who have previous stomach ulcers or bleeds, who need high doses of pain killers). If one is at risk of stomach complications then medicines to protect the stomach such as omeprazole (losec, omez), pantoprozole, etc. should be used. Celecoxib (celebrex) and Etoricoxib (Arcoxia) have a decreased risk of stomach problems.
  • Kidney and liver problems in the elderly
  • Increased risk of heart attack in the elderly and those at risk of heart attack.
  • Other possible side effects include dizziness, sleepiness, ringing in ears, bloating.

Some of the commonly available NSAIDs are:

Ibuprofen (Brufen, advil, motrin, prufen). 600 – 800 mg three times daily

Diclofenac (Voltaren) 75 mg twice daily, 50 mg three times daily, 100 mg once a day

Indomethacin (indocid) 25- 50 mg three times daily

Meloxicam (mobic) 7.5 -15 mg once daily

Naproxen (naprosyn) 375 – 500 mg twice daily

Piroxicam (Feldene) 20 mg once daily

Celecoxib 200 mg twice daily

Etoricoxib (Arcoxia) 60 or 90 mg once daily

NSAIDs work by a different mechanism than steroid medications (such as prednisone) to decrease inflammation and pain. It is important to discuss with your doctor the goal of using the N|SAID. If the goal of taking the NSAID is to suppress inflammation then it will need to be taken at higher doses and on a regular dosing interval. If it is to relieve pain and not necessarily inflammation, then often lower doses and an as needed dosing interval are sufficient.

I heard that these medications can cause heart attacks?

In the last 2 or 3 years there has been controversy regarding a subset of NSAIDs called cox-2 inhibitors. Cox-2 inhibitors are safer for the stomach and have a reduced risk of stomach ulcers or bleeding. However, they had an increased risk of heart attacks and in 2004 Viox and subsequently Bextra were withdrawn from the market. Subsequent research with Arcoxia has shown that it is as safe as Diclofenac or Voltaren for the heart. Arcoxia remains safer than traditional NSAIDs for the stomach. Hence people who have had heart attacks, strokes or are over the age of 65, have uncontrolled high blood pressure, or multiple risk factors for heart attack or stroke should avoid ANY painkillers. This becomes a difficult issue in older people who are at risk for heart attacks and have severe arthritis. These patients should not receive brufen, voltaren, or other painkillers because of multiple risks involved. In this case the safest option would be to use plain pain killers which do not have anti-inflammatory actions such as tramadol or tramal, or even paracetamol.

Doctor, why should I use these medications if they have so many side effects?

Generally, these drugs are safe if used for limited periods of time and under supervision of a doctor. Patients should not be using them over the counter or self medicating. The doctor recognizes side effects and will monitor you. You should be especially cautious if you have any of the following conditions:

  • liver problem (e.g., hepatitis)
  • ulcer, gastritis, or bleeding from the intestines or stomach
  • take blood thinners like Coumadin (warfarin), heparin, aspirin, or Plavix
  • take steroids like prednisone
  • have a low platelet count
  • have had stroke, heart attack, hypertension, or congestive heart failure
  • are allergic to aspirin or other NSAIDs
  • have acid reflux disease or indigestion
  • are pregnant, may become pregnant, or breast feeding
  • are over the age of 65

STEROIDS (CORTISONE):

There are many different ways patients refer to these drugs: cortisone, prednisolone, steroids. Patients are either very afraid to take these medications at all or some are taking them long term. Steroids in various forms are very useful for the following situations:

  1. In patients with newly diagnosed inflammatory arthritis to gain rapid control of the disease.
  2. To quickly control flares of the disease.
  3. To inject into joints for control of a single, swollen or inflamed joint.

Some commonly used forms of steroids:

Cortisone – 5 -150 mg daily

Dexamethasone (decadron) 0.5 to 9 mg per day

Hydrocortisone (cortef) 20- 240 mg daily

Methylprednisolone (Medrol) 4 -160 mg per day

Prednisolone (gupisone) 5 -100 mg daily

Common side effects of steroids:

  • Weight gain
  • Increased hunger
  • Moon face
  • Skin changes, stretch marks
  • Bruising
  • Hypertension
  • Muscle weakness
  • Cataracts
  • Mood changes
  • Difficulty sleeping
  • Increased blood pressure
  • Cholesterol
  • Weak bones or osteoporosis
  • Necrosis of bone

STEROD SIDE EFFECTS

Although the list of steroid side effects are long it should be remembered that these usually occur when the medications are taken for long periods of time and at high doses. They should always be taken under supervision by a doctor and should be tapered down slowly, rather than stopped suddenly. It is generally not advisable to take these on a long term basis.

DMARD (DISEASE MODIFYING DRUGS):

These are the medications which are used for long term control of all inflammatory arthritis. All medications have side effects but the main goal of these medications is TO PREVENT JOINT DAMAGE. Generally the disease is worse than the medication and it is safe to take these as long as the patient is under the supervision of a specialist.

NAME DOSE COMMON SIDE EFFECTS
METHOTREXATE (tablet/ injection) 7.5 – 25 MG Lowers blood counts, liver irritation, immune suppression
SULFASALAZINE (SALAZOPYRIN) 1000 – 3000 mg daily Allergic skin rashes, low blood counts, irritated liver
HYDROXYCHLOROQUINE (PLAQUENIL) 200 – 400 mg daily Pigmentation in eye (reversible)
AZATHIPRINE (IMURAN) 75-150 mg daily low blood counts, irritated liver, , immune suppression
LEFLUNOMIDE (ARAVA) 10-20 mg daily Lowers blood counts, liver irritation, immune suppression
AURONOFIN (GOLD) 6-9 mg daily Rashes, diarrhoea
CYCLOPHOSPHAMIDE 50-150 mg daily Lowers blood counts, liver irritation, immune suppression
CYCLOSPORINE (NEORAL/ SANDIMMUNE) 100-400 MG daily High BP, swollen gums, kidney problems
MINOCYCLINE 200 mg daily Rashes, nausea
PENICILLAMINE 150- 1000 mg daily Diarrhea, joint pains, stomach problems, bleeding brusing
BIOLOGICAL RESPONSE MODIFIERS (ENBREL, HUMIRA, REMICADE, MABTHERA, ORENCIA, KINERET) Various (see below) Infections, skin irritation

METHOTREXATE has become the GOLD STANDARD or most preferred drug for rheumatoid arthritis. Generally it is safe. Research has shown that patients who take these medication have less chances of joint damage, death and that it also prolongs the life span of those who have rheumatoid arthritis. The risks are acceptable and benefits are great.

Methotrexate is an ‘antimetabolite’ which interferes with folic acid production, DNA production and cellular reproduction. It is commonly used in the treatment of rheumatoid arthritis to suppress an overactive immune system that is causing inflammation and damage to the joints and other organs. Methotrexate is one of several Disease-Modifying Antirheumatic Drugs (DMARDs) which are able to slow the progression of the disease.

Methotrexate is available as oral tablets or injection. The tablets are usually taken once a week with or after food. Methotrexate can cause nausea and vomiting at the start of therapy, but if the weekly dose is increased slowly, your body system will usually get used to it.

This drug does not work immediately. It may be weeks to months before you notice any benefit. Thus it is important that you take your medication regularly, otherwise you may not receive any benefit at all.

Methotrexate can be taken with other medicines used for rheumatoid arthritis, such as corticosteroids. Avoid immunization (vaccination), especially with live vaccines, unless approved by your doctor. Also, avoid direct contact with persons who have taken oral polio vaccine or those with infections.

Do not drink alcohol while on this medicine as alcohol can increase the chance of liver problems.

Please inform your doctor or pharmacist if you are taking other medications, including traditional remedies, that he is not aware of.

Many methotrexate users experience no, or minor, side effects when the drug is taken according to your doctor’s instruction. However certain unwanted effects may occur. You may be given folic acid supplements to prevent these side effects or folinic acid to reverse them.

Side effect Warning signs To reduce this side effect
Nausea or Vomiting or Diarrhoea or Stomach pain Take medication after food or divide the dose to be taken within the day. Inform your doctor immediately if you see bloody vomit or stools.

Consult your doctor or pharmacist if you vomit shortly after taking a dose of methotrexate or if you have forgotten to take your medication for a few days

Loss of hair May not be obvious Reversible when the drug is discontinued
Allergic reaction or Photosensitivity

Is very rare

skin rashes or itching, flushing or redness of skin, severe sunburn These usually resolve readily on stopping treatment or with dose reduction. Stay out of strong sunlight.
Lung inflammation is very rare Persistent coughing or breathlessnes or chest pain The drug should be stopped
Liver disorder or irritation is very rare when the doctor is monitoring you Yellow eyes or skin or dark urine or constant abdominal pain The drug should be stopped. Avoid all alcohol

Tell your doctor if you previously had jaundice or hepatitis

Blood disorder

(rare)

There may be no warning signs but unusual bleeding or bruising, lip or mouth ulcers with ‘flu-like’ symptoms may occur

(Note: occasional minor mouth ulcers without fever is harmless)

Inform your doctor immediately if these symptoms occur

Monitoring of the effects of your new treatment is important, particularly during the first three months of treatment. To do this we may need to check your blood tests regularly. The monitoring is for your safety

SPECIAL PRECAUTIONS

While taking methotrexate, you may be more susceptible to infections; see a doctor immediately if you develop fever or if you feel generally unwell.

You (or your spouse if you are male) SHOULD NOT get pregnant when on this medication..

As with all medicines, it is important to inform your doctor if you intend to conceive or breast-feed while taking this medicine.

SULFASALAZINE

Sulphasalazine is a medicine that is used to control rheumatoid arthritis or psoriatic arthritis.

This is a disease-modifying antirheumatic drug [DMARD] (also called slow-acting antirheumatic drug [SAARD]) which helps to reduce the inflammation in the joints and prevent joint and cartilage destruction in the long term. It has no direct pain relieving effect. Hence, it will not reduce the pain and swelling acutely.

HOW IS SULFASALAZINE TAKEN ?

Sulfasalazine should be taken with or after food. Sometimes the tablets upset the stomach at the start of therapy, but if the dose is increased slowly, your body will usually get used to it.

Do not crush or chew the tablets as they are enteric-coated in order to reach the colon. They should be swallowed whole with a full glass of water (unless otherwise directed).

This drug does not work immediately. It may be weeks to months before you notice any benefit. Thus it is important that you take your medication regularly, otherwise you may not receive any benefit at all

You will need to continue your other arthritis and anti-inflammatory tablets unless your doctor advises otherwise.

If you need to take sulfasalazine with iron supplements or antacids, space them at least 2 hours apart.

Please inform your doctor or pharmacist if you are taking other medications, including traditional remedies, that he is not aware of.

WHAT ARE THE IMPORTANT SIDE EFFECTS OF SULFASALAZINE ?

Side effects can occur with any drug and this drug is no exception. When taken according to your doctor’s instructions, they are infrequent.

Side effect Warning signs To reduce this side effect
Nausea or loss of appetite or diarrhoea Take medication after food.
Headache or dizziness Improves as you get used to the medication or with dose reduction.
Staining of urine, skin and tears Orange-yellow staining This is harmless. However staining of soft contact lenses can occur and you may opt to wear spectacles instead.
Allergic reaction Generalised skin rashes or peeling, itching,

swelling of the eyes.

Inform your doctor immediately. These usually resolve readily on stopping treatment.

Tell your doctor if you have ever had any unusual or allergic reaction to any sulfa medicines, aspirin or tartrazine dye before starting treatment.

Photosensitivity Skin rashes, redness or other discolouration of the skin, severe sunburn Stay out of direct sunlight between 10am and 3pm if possible. Wear protective clothing or sunglasses. Apply sunblock when necessary and do not use a sunlamp.
Liver disorder

(rare)

Yellow eyes or skin or constant abdominal pain The drug should be stopped. Avoid all alcohol.
Blood disorder

(rare)

There may be no warning signs but unusual bleeding or bruising, mouth ulcers with ‘flu-like’ symptoms may occur Inform your doctor immediately if these symptoms occur.

Inform your doctor if you have G6PD deficiency.

WHY DO I NEED REGULAR BLOOD TESTS WHEN TAKING THIS DRUG?

Although blood and liver disorders are rare, abnormal blood counts and liver function tests can arise especially during the first month of treatment and whenever the dose of medication is increased.

Even if you have been on treatment for a long time, you need to have your blood tests checked every 3 months.

Regular blood tests ensure that these abnormalities are detected early, before the “warning signs” occur. These reverse when treatment is stopped.

I AM “ALLERGIC” TO SULFA DRUGS. CAN I TAKE SULPHASALAZINE?

Your doctor will verify your sulfa drug allergy with you as not all sulfa-containing drugs cross react. Inform your doctor is you have G6PD deficiency (a blood disorder).

SPECIAL PRECAUTIONS

As with all medicines, it is important to inform your doctor if you intend to conceive or breast-feed while taking this medicine.

If you are male and planning a family, you should be aware that the tablets may cause a drop in sperm count. This is usually reversible when the treatment is stopped.

Hydroxychloroquine Sulfate

Chloroquine Phosphate

Hydroxychloroquine Sulfate and Chloroquine Phosphate are anti-malarial drugs found to be useful in the treatment of autoimmune diseases like discoid and systemic lupus erythematosus, rheumatoid arthritis and juvenile chronic arthritis, chronic cutaneous vasculitis. These drugs are particularly effective in treating skin and joint symptoms and they have been demonstrated to reduce inflammation and improve muscle or joint pain. However they are not effective when used alone for more severe manifestations of these diseases which involve the major organs.

Hydroxychloroquine or chloroquine tablets should be taken with or after food to reduce stomach upset.

This drug does not work immediately. It may be weeks to months before you notice any benefit. Thus it is important that you take your medication regularly, otherwise you may not receive any benefit at all.

These drugs can be taken with other medication, e.g. corticosteroids or NSAIDS, used for the treatment of lupus erythematosus or rheumatoid arthritis. In fact, they are sometimes given in combination with prednisolone to reduce the amount of steroid that is needed to improve symptoms.

Do not consume these drugs together with antacids, space them apart by at least 2 hours.

Please inform your doctor or pharmacist if you are taking other medications, including traditional remedies, that he is not aware of.

Side effects can occur with any drug and these drugs are no exception. When taken according to the doctor’s instruction, they are infrequent. Hydroxychloroquine and chloroquine are not equivalent in their side effects. Side effects with hydroxychloroquine are generally rare.

Side effect Warning signs To reduce this side effect
Nausea, Anorexia

Or Diarrhoea

Take medication after food
Headache or Dizziness or Ringing in the ears or Muscle weakness Improves as you get used to the medication or with dose reduction.

Check with your doctor if you experience muscle weakness that progresses from your legs and upwards

Blurred vision

Retinal damage

(uncommon if the recommended daily dose is not exceeded)

Visual disturbances, photophobia, light flashes and streaks, missing or blacked-out areas in the visual field, difficulty in focusing Transient blurring of vision may occur but this usually resolves in 1 to 2 weeks

Inform your doctor immediately. Retinal damage is usually reversible when treatment is stopped. Hydroxychloroquine has a lower risk compared to chloroquine

You will have to undergo an eye examination before treatment is initiated and at least 6 monthly thereafter

Allergic reaction or Pigmentary changes in the skin and mucous membranes

(rare)

Generalized skin rashes, itching, discolourationof the skin, fingernails and inside of the mouth These usually resolve readily on stopping treatment
Blood disorder

(rare)

There may be no warning signs but unusual bleeding or bruising, mouth ulcers with ‘flu-like’ symtoms may occur Inform your doctor immediately if these symptoms occur.

Monitoring of the effects of your new treatment is important, particularly during the first three months of treatment. To do this we may need to check your blood tests regularly. The monitoring is for your safety

Inform your doctor if you have G6PD deficiency

AZATHIOPRINE

Azathioprine is a potent drug that can partially suppress the body’s natural defence mechanism known as the immune response. Azathioprine acts to prevent the body’s immune system from rejecting ‘foreign’ tissues (such as a transplanted organ) or attacking its own tissues or organs (which happens in autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, polyarteritis nodosa). Azathioprine is not normally used as a first-line agent in the treatment of milder forms of such diseases as there are safer medications available.

HOW IS AZATHIOPRINE TAKEN ?

Azathioprine is usually taken orally, with or after food to reduce stomach upset. Azathioprine can cause nausea and vomiting at the start of therapy, but if the dose is increased slowly, your system will usually get used to it.

This drug does not work immediately. It may be weeks to months before you notice any benefit. Thus it is important that you take your medication regularly, otherwise you may not receive any benefit at all

CAN AZATHIOPRINE BE TAKEN WITH OTHER MEDICATIONS ?

Azathioprine is often given together with corticosteroids in the treatment of autoimmune diseases when steroid therapy alone has provided inadequate control.

Azathioprine should not be used together with other immunosuppressive agents. Nonetheless, if this is done, it should be borne in mind that over-immunosuppression may occur, thus increasing the risk to infections. Avoid immunization (vaccination), especially with live vaccines, unless approved by your doctor. Also, avoid direct contact with persons who have taken oral polio vaccine or those with infections.

Allopurinol (gout medication) may interfere with removal of azathioprine from the body and increase its effects/side effects.

Do not drink alcohol while on this medicine as alcohol can increase the chance of liver problems.

Please inform your doctor or pharmacist if you are taking other medications, including traditional remedies, that he is not aware of.

WHAT ARE THE IMPORTANT SIDE EFFECTS OF AZATHIOPRINE ?

Many of the adverse effects of azathioprine only occur at higher dosages and they are usually reversible with dose reduction. Due to the way that azathioprine works, some side effects may present only years after the medication is used.

Side effect Warning signs To reduce this side effect
Nausea or Vomiting or Anorexia or Diarrhoea Take medication after food or divide the dose to be taken within the day.
Loss of hair May not be obvious This is harmless and often resolves spontaneously
Allergic reaction skin rashes or itching These usually resolve readily on stopping treatment or with dosage reduction
Liver disorder Yellow eyes or skin or dark urine or constant abdominal pain The drug should be stopped. Avoid all alcohol

Tell your doctor if you previously had jaundice or hepatitis

Blood disorder

(rare)

There may be no warning signs but unusual bleeding or bruising, lip or mouth ulcers with ‘flu-like’ symptoms may occur

(Note: occasional minor mouth ulcers without fever is harmless)

Inform your doctor immediately if these symptoms occur

Monitoring of the effects of your new treatment is important, particularly during the first three months of treatment. To do this we may need to check your blood tests regularly. The monitoring is for your safety

SPECIAL PRECAUTIONS

While taking azathioprine, you may be more susceptible to infections; see a doctor immediately if you develop fever or if you feel generally unwell.

Use contraceptives when you are taking azathioprine, regardless of your gender, as this medicine can cause harm to the foetus.

As with all medicines, it is important to inform your doctor if you intend to conceive or breast-feed while taking this medicine.

New Treatments

Biological Response Modifiers (BRM):

In the last decade we have ssen the introduction of new medications for RA which sometimes have produced dramatic results. These act on blocking the chemicals, called cytokines that are involved in inflammation. The goal of treatment in 2000 is REMISSION and these BRMs give patients the best chance to be disease free.

In a study at Dubai Bone and Joint Center we found that the best predictor of being in disease remission was treatment with a BRM.

TNF inhibitors act by decreasing a chemical called tumor necrosis factor (TNF).

ANTI-TNF Dose Route
Enbrel (Etarnercept) 50 mg once weekly Subcutaneously

(under the skin)

Self adminstered
Humira (Adalimumab) 40 mg every 2 weeks Subcutaneously

(under the skin)

Self adminstered
Remicade (Infliximab) 3-5mg/ kg. body weight

Once every 2 months ( 1 dose at 0, 2, 4 weeks and then 8 weekly)

Intravenously In hospital

These medication work by blocking the production of joint inflammation. They usually work better when used in combination with standard medications such as methotrexate or sulfasalazine. They are highly effective but not everyone needs them. They are usually reserved for those who are unable to take or have inadequate response to the standard treatments for rheumatoid arthritis. They have been shown to prevent joint damage and give excellent outcomes in rheumatoid arthritis.

The commonest side effects are injection site reactions or irritation. Rarely latent tuberculosis can get reactivated. Patients are always screened prior to treatment with a skin test for TB and a chest x-ray. Immune system gets suppressed and hence there is a higher chance of infections. Most of these infections are classified as ‘non-serious’. Patients taking these medicines should not have live vaccines. It is sometimes recommended that these are stopped 2-4 weeks before major surgery.

Very rare side effects include heart failure, lupus or neurological diseases. Some of the other disadvantages are that these medications are expensive and insurance companies do not pay for them. They need to be kept refrigerated. With Remicade there can be infusion reactions occurring during or after the drug administration. Patients can feel dizzy, short of breath. These reactions subside usually by slowing the rate of infusion.

Mabthera (Rituximab or Rituxan) is a new class of BRM which inhibits CD20 B cells (a kind of white cell). It was initially used for the treatment of lymphoma but has now emerged as a powerful new tool for rheumatoid arthritis treatmet. It is given as 2 injections of 1000 mg of intravenous infusions (separated by 2 weeks). This treatment is repeated 6 -12 months later. Infusion reactions such as low blood pressure, itching, difficulty breathing can occur but the chances are usually greater with the first infusion. Mabthera also carries the risk of infections.

Abatacept (Orencia) works by blocking the T cells which in turn activate B cells to produce TNF. Abatacept is used in patients who have not responded to methotrexate or anti-TNF medications. Side effects include cough, dizziness, infections and infusion reactions. The initial dose is 500 – 1000 mg intravenously, 2nd dose 2 weeks later and 4 weekly thereafter.

This is one of a set of articles by Dr. Humeira Badsha, Specialist Rheumatologist, for patient awareness.

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This web site is run by an Arthritis Specialist based in Dubai, United Arab Emirates. On this site you will find news about the latest in arthritis, information about research results in the field, tips and information and diet and exercise, and much more.

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