Aminosalicylates contain the compound 5-aminosalicylic acid, or 5-ASA, which helps reduce inflammation. These drugs are used to prevent relapses and maintain remission in mild-to-moderate Crohn’s disease.
The standard aminosalicylate drug is sulfazine (Azulfidine). This drug combines the 5-ASA drug mesalamine with sulfapyridine, a sulfa antibiotic. While sulfazine is cheap and effective, the sulfa component of the drug can cause unpleasant side effects, including headache, nausea, and rash.
Patients who cannot tolerate sulfazine, or who are allergic to sulfa drugs, have other options for aminosalicylate drugs, including mesalamine (Asacol, Pentasa), olsalazine (Dipentum), and balsalazide (Colazal). These drugs, like sulfazine, are available as pills. Mesalamine is also available in enema (Rowasa) and suppository (Canasa) forms.
Mesalamine can cause kidney problems and should be used with caution by patients with kidney disease. Common side effects of aminosalicylate drugs include:
- Abdominal pain and cramps (mesalamine, balsalazide)
- Diarrhea (mesalamine, olsalazine)
- Gas (mesalamine)
- Nausea (mesalamine)
- Hair loss (mesalamine)
- Headache (mesalamine, balsalazide)
- Dizziness (mesalamine)
All mesalamine preparations, including sulfasalazine, appear to be safe for children, and for women who are pregnant or nursing.
Corticosteroids (commonly called steroids) are powerful anti-inflammatory drugs used for treating Crohn's disease in adults. Because of their severe side effects, steroids should be reserved for those with moderate-to-severe disease or those who relapse after other therapies. Steroids appear to be safe for pregnant women and can be used if necessary during pregnancy. Long-term usage is avoided if possible because of side effects.
Corticosteroids are frequently combined with other drugs, such as 5-ASA drugs, to produce more rapid symptom relief and to allow quicker withdrawal, although such combinations do not improve remission time.
In general, corticosteroids are recommended only for short-term use for achieving remission in active Crohn's disease. The lowest effective dose should be used for the shortest amount of time. Long-term treatments cause significant side effects, and alternative drugs exist. Corticosteroids do not prevent flare-ups and are rarely used for maintenance treatment.
Patients who are malnourished are less likely to respond to steroids, and those who had an initial inadequate response to steroids are also less likely to do well with repeat therapy. Some patients who have had Crohn's disease for a long time may have partial or complete resistance to corticosteroids.
Corticosteroid Types. Prednisone (Deltasone), methylprednisolone (Medrol), and hydrocortisone (Cortef, Cortisol) are the most common corticosteroids. Newer steroids, such as budesonide (Entocort), affect only local areas in the intestine and do not circulate throughout the body, which may help reduce widespread side effects.
Administering Corticosteroids. Most corticosteroids can be taken as a pill. For patients who cannot take oral forms, methylprednisolone and hydrocortisone may also be given intravenously, or rectally as a suppository, enema, or foam. The severity or location of the condition often determines the form.
Side Effects of Corticosteroids. Standard steroids can have distressing and sometimes serious long-term side effects, including:
- Susceptibility to infection
- Weight gain (particularly increased fatty tissue on the face and upper trunk and back)
- Excess hair growth
- High blood pressure (hypertension)
- Weakened bones (osteoporosis)
- Cataracts and glaucoma
- Muscle wasting
- Menstrual irregularities
- Upper gastrointestinal ulcers
- Personality change, including irritability, insomnia, depression, and psychosis
Withdrawing from Corticosteroids. Once the intestinal inflammation has subsided, steroids must be withdrawn very gradually. Withdrawal symptoms, including fever, malaise, and joint pain, may occur if the dosage is lowered too rapidly. If this happens, the dosage is increased slightly and maintained until symptoms are gone. More gradual withdrawal is then resumed.
For very active inflammatory bowel disease that does not respond to standard treatments, immunosuppressant drugs are used for long-term therapy. Such drugs suppress or limit actions of the immune system and therefore the inflammatory response that causes Crohn's disease. Immunosuppressants may help maintain remission in Crohn's disease and heal fistulas and intestinal ulcers caused by this disease. These drugs are sometimes combined with a corticosteroid drug for treating active disease flares.
Azathioprine (Imuran, Azasan) and 6-mercaptopurine (6-MP, Purinethol) are the standard oral immunosuppressant drugs. However, it can take 3 - 6 months for these drugs to have an effect. To speed up the response, they are sometimes prescribed along with a corticosteroid drug. Lower steroid doses are then needed, resulting in fewer side effects. Corticosteroids may also be withdrawn more quickly. For this reason, immunosuppressants are sometimes referred to as steroid-sparing drugs.
Other pill forms of immunosuppressants include cyclosporine A (Sandimmune, Neoral) and tracrolimus (Prograf). These drugs are quicker-acting than azathiopine and 6-mercaptopurine. Cyclosporine A generally takes 1 - 2 weeks to take effect. For patients who have Crohn’s disease accompanied by fistulas, Cyclosporine A may be given intravenously. For patients whose condition affects the mouth or area around the anus, tracrolimus is available as a topical ointment.
Methotrexate (MTX, Rheumatrex, Mexate) is another fast-acting type of immunosuppressant. It is given weekly and may be an option for patients with severe Crohn’s disease who have not been helped by other immunosuppressant drugs. However, methotrexate can cause miscarriages and birth defects (as well as liver damage). Because of these complications, both men and women who take methotrexate should use birth control.
General side effects of immunosuppressants may include nausea, vomiting, and liver or pancreatic inflammation. Patients should receive frequent blood tests to monitor bone marrow, liver, and kidneys. Patients who take cyclosporine A or tacrolimus need to have their blood pressure and kidney function checked regularly.
Biologic response modifiers are genetically engineered drugs that target specific proteins involved with the body's inflammatory response.
The American Gastroenterological Association recommends that, in general, biologic drugs should not be used as first-line treatment for most patients with Crohn's disease. However, some patients with moderate-to-severe disease -- especially those who have not responded to corticosteroids or who suffer from fistulas -- may benefit from initial treatment with infliximab or other biologic drugs. In all cases, the benefits of biologic drugs need to be weighed against their potential risks, which can include increased risk for infections, lymphoma, and drug-related side effects.
Tumor necrosis factor (TNF) blockers, which include infliximab, adalimumab, and certolizumab, can increase the risk for cancer, particularly lymphomas, in children and adolescents. They can also increase the risk for leukemia in patients of all ages.
Some patients who take anti-TNF drugs develop psoriasis. Fungal infections and tuberculosis are also serious concerns for patients who take anti-TNF drugs. Doctors should carefully monitor patients on anti-TNF therapy for any signs of infection. Symptoms of fungal infections include fever, malaise, weight loss, sweating, cough, and shortness of breath.
Infliximab. Infliximab (Remicade) is an anti-TNF drug that was the first biologic drug approved for treating adults and children with Crohn's disease.
Infliximab is used to help control symptoms and to induce and keep the disease in remission. Infliximab is also used to reduce the number of fistulas and maintain fistula closure. Common side effects of infliximab include respiratory infections (sinus infections and sore throat), headache, rash, cough, and stomach pain. Like all anti-TNF drugs, inflixmab can potentially cause serious severe side effects, including increased susceptibility to viral, fungal, and bacterial infections (including tuberculosis). Other severe side effects may include lymphoma (a type of cancer), heart failure, liver failure aplastic anemia, nervous system disorders, and allergic reactions.
Adalimumab. Adalimumab (Humira) is a biologic drug used for inducing and achieving remission in adult patients with moderate-to-severe Crohn's disease. Like infliximab, adalimumab blocks TNF. Also approved for treating symptoms of rheumatoid arthritis, adalimumab requires injections to initiate treatment, followed by a maintenance shot every other week.
In addition to pain at the injection site, common side effects of adalumimab include upper respiratory infections, headache, rash, and nausea. Adalimumab’s potential severe side effects are similar to those of infliximab. In addition, adalimumab may reactivate hepatitis B in patients who carry the virus in their blood.
Certolizumab. Certolizumab (Cimzia) is another anti-TNF drug given by injection. Patients receive an injection every 2 weeks for the first 3 weeks. Once patients show signs of improvement, they receive an injection once a month. Certolizumab’s side effects are similar to those of adalimumab and infliximab.
Natalizumab. Natalizumab (Tysabri) is also a biologic drug, but it does not target TNF. Instead, natalizumab affects white blood cells involved in the inflammatory response. Natalizumab is given by intravenous infusion once a month in a doctor’s office or hospital infusion clinic.
Because natalizumab carries some serious potential risks, patients who take this medication must enroll in a special program that helps the FDA monitor side effects of the drug. The most serious side effect is increased risk for a rare neurological condition called progressive multifocal leukoencephalopathy (PML), which can lead to death or severe disability. Other serious side effects of natalizumab include allergic reactions, and increased susceptibility to infections including serious herpes infections. In general, natalizumab should not be used by patients who are currently taking immunosuppressant drugs.
Natalizumab may cause liver injury within a week of starting the drug. Other less serious side effects may include headache, fatigue, urinary tract infections, joint and limb pain, rash, and infusion reactions.
Antibiotics. Antibiotics may be used as a first-line treatment for fistulas, bacterial overgrowth, abscesses, and any infections around the anus and genital areas. Standard antibiotics include ciprofloxacin (Cipro) and metronidazole (Flagyl). Ciprofloxacin is the antibiotic of choice.
Over time, metronidazole can cause peripheral neuropathy, a nerve disorder that can cause numbness and tingling in the hands and feet. Other side effects associated with metronidazole include nausea, vomiting, diarrhea, loss of appetite, dizziness, and headaches.
Although ciprofloxacin causes fewer side effects than metrondizaole, it can interact with antacids (Rolaids, Tums) and vitamin and mineral supplements that contain calcium, iron, or zinc. Do not take antacids or vitamin supplements at the same time as the ciprofloxacin dose.
Anti-Diarrheal Drugs. Mild-to-moderate diarrhea may be reduced by daily use of psyllium (Metamucil). Standard anti-diarrheal medications include loperamide (Imodium) or a combination of atropine and diphenoxylate (Lomotil). In some cases, codeine may be prescribed.