The Lupus Group of WA

Medications

John "Jack" H. Klippel, MD, Medical Director, The Arthritis Foundation
A reprint from Lupus Foundation of America Article Library 2001

Introduction
Medications play an important role in the care of most people with systemic lupus erythematosus ( SLE ). This pamphlet ( see Table 1 ) discusses the principal drugs used in the primary management of lupus :

Anti-inflammatory drugs
Corticosteroids
Anti-malarials
Cytotoxic, or immunosuppressive, drugs
Investigational ( research ) drugs :
- hormone modifications
- more selective immunosuppressive drugs
- biologic agents.

Which medications are right for my lupus ?
The choice of drugs is highly individualized and typically changes often during the course of the disease. Factors that are considered in treatment decisions include :

the type and severity of lupus symptoms
the person's response to treatment
risks of drug side effects.

In addition, it is important to note that people with lupus often require other drugs for the treatment of conditions commonly seen with the disease. Examples of these types of medications include :

diuretics for fluid retention
anti-hypertensive drugs for increased blood pressure
anti-convulsants for seizure disorders
antibiotics for infections
drugs for osteoporosis.

Anti-inflammatory drugs
Anti-inflammatory drugs relieve the symptoms of lupus by reducing the inflammation responsible for the pain and discomfort. Anti-inflammatory medications are the most commonly used drugs for lupus treatment, particularly for symptoms such as :

fever,
arthritis, or
pleurisy

Improvement in symptoms is generally noted within several days of beginning treatment. In the majority of people with lupus, anti-inflammatory drugs are the only medication that is ever required to control their lupus. Anti-inflammatory drugs fall into two categories ( see Table 1 )

non-steroidal anti-inflammatory drugs
corticosteriods

Non-steroidal anti-inflammatory drugs
The NSAIDs include both salicylates ( aspirin ) and related drugs that may be purchased over the counter ( brand names : Advil, Nuprin, Aleve ) or that require a physician's prescription.

When should my doctor prescribe NSAIDs ?
NSAIDs are especially useful for :

musculoskeletal symptoms, such as arthritis, arthralgia, joint stiffness or pain
fever and chest pain from mild pleurisy ( inflammation of the lining of the lung )
pericarditis ( inflammation of the sac around the heart ).

For reasons that are not known, people often respond better to one non-steroidal drug than another. Thus, it may be necessary to treat a person with several different drugs to determine the most effective one.

NSAID side effects
The most common side effect of non-steroidal medications is irritation of the stomach or bowel which causes abdominal pain.
Infrequently, this may lead to serious complications such as an ulcer with bleeding.
To reduce the chance of these problems, non-steroidal drugs are usually taken with meals or given along with other medications that protect the stomach and bowel.
Occasionally, side effects from non-steroidal drugs may be mistaken for signs of active lupus :

fever
skin rashes
abnormal urine studies
severe headache.

It is important to recognize these NSAID side effects that might mimic findings seen in lupus, since the symptoms are promptly reversed simply by stopping the drug.

Corticosteroids ( Cortisone )
Corticosteroids are naturally occurring hormones with very potent anti-inflammatory properties.
In high doses, corticosteroids also suppress immune functions.
They may be used as creams or ointments for lupus skin rashes.
They may be given as pills or injections.
Most signs of lupus respond rapidly to corticosteroid treatment.
At times, treatment with corticosteroids may actually be life-saving.

When should my doctor prescribe corticosteroids ?
The decision to begin corticosteroids, and the details as to what type and dose of corticosteroid to use, are highly individualized :
If a person has symptoms such as fever, arthritis, or pleurisy that have not responded to non-steroidal drugs, he or she could then be treated with low doses of an oral corticosteroid, such as prednisone or methylprednisolone ( brand name : prednisolone ).
Individuals with more severe or serious lupus symptoms, such as kidney disease, seizures, anemia, or low platelets ( thrombocytopenia ) may require high doses of corticosteroids.
In most instances, the corticosteroid is given as a single dose in the morning.
Other ways of giving corticosteroids include :

Doses given several times each day
Doses only on alternate days
High doses given intravenously ( called bolus therapy ).

How long will I take corticosteroids ?
Once the symptoms of lupus have responded to treatment, the dose of corticosteroids is gradually reduced ( tapered ). Meanwhile the individual is carefully watched for evidence of relapse of the disease.
The longer a person has been on corticosteroids, the more difficult it becomes to lower the dose.
It is very important that corticosteroids are taken exactly as prescribed.
Treatment should never be stopped abruptly without consulting with a physician.

Corticosteroid side effects
There are many complications of corticosteroid treatment, and the risks of these complications are increased when :

high doses of corticosteroids are required
corticosteroids are used for an extended period.

Corticosteroids may :

produce changes in physical appearance :
- weight gain
- puffy cheeks
- thinning of the skin and hair
- easy bruising.
cause stomach discomfort such as dyspepsia or heartburn. These may be minimized by giving the drug with meals or along with medications that prevent stomach damage.
cause marked changes in mood, including :
- depression
- mood swings.
cause diabetes.
increase the risk of infections, muscle weakness, or cataracts.
have an effect on the bones including :
- joint damage of the hips, knees, or other joints ( osteonecrosis ).
- produce osteoporosis ( thinning of bone ) when given over long periods. In most people, calcium or other medications to prevent osteoporosis are given along with the corticosteroids.

Anti-malarial drugs
Drugs used for the treatment of malaria are widely used in the management of lupus symptoms. The drug hydroxychloroquine ( brand name : Plaquenil ) is the most commonly used of the anti-malarial agents.

When should my doctor prescribe anti-malarials ?
Anti-malarials are particularly effective in the treatment of :

lupus arthritis
skin rashes
mouth ulcers.

Other possible benefits of anti-malarials include :

reducing the risk of blood clots
lowering cholesterol levels.

Anti-malarials are considered to have a small risk of causing birth defects.
Anti-malarials are generally not recommended for women who want to become pregnant.

Anti-malarial side effects
- low-dose therapy

gastric symptoms ( stomach pain or dyspepsia )
rashes or darkening of the skin
muscle weakness
shortly after starting treatment, there may be a temporary mild blurring of vision, which goes away entirely on its own.

- high-dose therapy
In high doses ( such as those used in the treatment of malaria ), certain anti-malarial drugs may damage the retina of the eye, causing vision problems. With the low doses of anti-malarials used in the treatment of lupus, the risk of this complication is extremely low.

However, as a precaution, people treated with anti-malarials generally have a thorough eye examination before the drug is started, and then every 6-12 months during therapy.
This is so that any sign of damage to the retina can be detected early and, if needed, the drug can be stopped.

Cytotoxic ( immunosuppressive ) drugs
Cytotoxic, or immunosuppressive, drugs are used to suppress the immune system in people with lupus. The most commonly used drugs of this type are :

azathioprine ( brand name : Imuran )
cyclophosphamide ( brand name : Cytoxan )
methotrexate ( brand name : Rheumatrex )
cyclosporine ( brand names : Sandimmune, Neoral ).

When should my doctor prescribe immunosuppressive drugs ?
These drugs are generally reserved for people with more serious manifestations of lupus, such as lupus nephritis or neurologic disease, in whom treatment with corticosteroids has failed. It is very important that cytotoxic drugs only be given by physicians who are experienced with the use of these medications.

Immunosuppressive side effects
The possible toxicities of cytotoxic drugs are considerable and individuals treated with these drugs must be very carefully monitored. The drugs have a major effect on cells produced by the bone marrow, including :

white blood cells
red blood cells
platelets.

Thus, people treated with cytotoxic drugs must have regular complete blood counts ( CBCs ) to make certain that levels of these cells do not become too low.
In addition, cytotoxic drugs reduce a person's ability to fight off infections.
Those receiving cytotoxic drugs are more likely to contract viral infections such as shingles ( herpes zoster )
Other more serious infections may also develop.

Specific toxicities
There are distinct toxicities that are unique to each cytotoxic drug :

Cyclophosphamide may cause : :
- hair loss
- bladder complications
- sterility.
Azathioprine may cause :
- an allergic-type of hepatitis
- pancreatitis.
Methotrexate may cause :
- liver damage, including cirrhosis
- serious lung toxicity.
Cyclosporine :
- commonly produces hypertension
- may lead to kidney damage.

In addition, all cytotoxic drugs are thought to increase a person's risk for developing cancer.

Investigational drugs
A number of investigational ( research ) drugs for lupus are currently being studied in clinical trials. Promising new treatments include :

hormone modifications
more selective immunosuppressive drugs
biologic agents.

To improve lupus symptoms and reduce the need for corticosteroids :

the hormone dehydroepiandrosterone ( DHEA )
blocking secretion of the hormone, prolactin, with bromocriptine.

For lupus nephritis, newer, more potent immunosuppressive drugs may be effective. Drugs that show less risk of serious side effects compared to more conventional cytotoxic drugs are :

mycophenolate mofetil ( CellCept )
2-chlorodeoxyadenosine.

Biologic agents are being used to selectively block the immune system from forming autoantibodies that develop in lupus, a new and exciting approach for both treating and preventing the disease.

Conclusion
There is a need for people with lupus to know about the drugs used in the treatment of their disease. This pamphlet briefly reviews the major drugs currently being used. If you have any questions about the information presented here, you should check with your physician, your pharmacist.

Table 1 Principal drugs used in the management of systemic lupus erythematosus (SLE)
category	drug ( brand ) name	major side effects
I - Non-Major Organ Involvement ( fever, arthritis, pleurisy/pericarditis, rash )
Non-Steroidal Anti-inflammatory Drugs ( NSAIDs )	celecoxib ( Celebrex ) diclofenac ( Cataflam, Voltaren ) etodolac ( Lodine ) fenprofen ( Nalfon ) flurbiprofen ( Ansaid ) ibuprofen ( Motrin, Advil, Nuprin ) ketoprofen ( Orudis, Actron ) meclofamate ( Meclomen ) meloxicam ( Mobic ) nabumetone ( Relafen ) naproxen ( Naprosyn, Anaprox, Aleve ) oxaprozin ( Daypro ) piroxicam ( Feldene ) rofecoxib ( Vioxx ) salicylates ( Aspirin, Arthopan ) sulindac ( Clinoril ) tolmetin ( Tolectin )	Abdominal pain, heartburn, gastric ulcers and bleeding, fluid retention, rashes, kidney or liver damage, dizziness or confusion, headache
Anti-Malarials	Hydroxychloroquine ( Plaquenil ) chloroquine ( Aralen ) quinicrine ( Atabrine )	Nausea, abdominal pain/cramps, rash, skin pigmentation, weakness, blurred vision, headache, eye damage.
Corticosteriods	Topical Creams/Ointments ( for lupus rashes ) clobetasol ( Temovate ) halobetasol ( Ultravate ) hydrocortisone ( Cortef, Cortaid ) triamcinolone ( Aristocort, Kenalog ) betamethasone ( Valisone, Diprosone ) fluocinolone ( Synalar ) fluocinonide ( Lidex )	Skin thinning and pigment changes, superficial blood vessel formation
	Tablets Prednisone ( Deltasone ) prednisolone ( Prelone ) methylprednisolone ( Medrol )	Weight gain, round or moon shaped face, mood changes, thin/fragile skin, acne, diabetes, facial hair, cataracts, osteoporosis, osteonecrosis, muscle weakness, hypertension, gastric ulcers, infections
	Intravenous Methylprednisolone ( Solu-Medrol ) hydrocortisone ( Solu-Cortef )	Metallic taste, infections, nervousness
Cytotoxics and Immunosuppressives	Methotrexate ( Rheumatrex )	Nausea, abdominal pain, mouth ulcers, rashes, cough, shortness of breath, lung or bone marrow damage
Cytotoxics and Immunosuppressives	Azathioprine ( Imuran )	Nausea or vomiting, pancreatitis, infection, liver disease, cancer
II - Major Organ Involvement ( nephritis, neurologic disease, etc )
Corticosteroids	See above; typically used in higher doses or as intravenous infusion	See above
Cytotoxics and Immunosuppressives	Azathioprine ( Imuran )	See above
	cyclophosphamide ( Cytoxan )	Nausea or vomiting, rash, infection, hair loss, bladder damage, infertility, cancer
	chlorambucil ( Leukeran )	Nausea or vomiting, rash, infection, hair loss, infertility, cancer
	cyclosporine ( Sandimmune, Neoral )	Hypertension, hair growth, tremors, tender or enlarged gums, kidney damage
	mycophenolate mofetil ( Cellcept )	Diarrhea, nausea

Chart courtesy of John H. Klippel, MD; updated by Robert S. Katz, MD

Disclaimer :
The Lupus Group of WA (Inc) does not recommend or endorse any products, drugs, treatments, procedures, medical or health professional in this article. We suggest you discuss this information with your doctor or specialist.