Digestive Health Newsletter

Mind Your Meds -- An Updated Review

Nisa Kubiliun, MD and Jamie S. Barkin, MD

Volume 16, 
October 01, 2009

by Nisa Kubiliun, MD and Jamie S. Barkin, MD

Nisa Kubiliun, MD Nisa Kubiliun, MD, is currently Chief Fellow in the Division of Gastroenterology at Jackson Memorial Hospital in Miami, Florida. She received her medical degree from the University of Miami Miller School of Medicine and completed her residency in Internal Medicine at the University of Texas Southwestern where she was Chief Medical Resident.




Jamie S. Barkin, MD Jamie S. Barkin, MD, is a Professor of Medicine in the Departments of Medicine, Oncology, and Pediatrics at the University of Miami, Miller School of Medicine and Chief, Division of Gastroenterology, at Mount Sinai Medical Center, Miami Beach. He is also a staff physician at Jackson Memorial Hospital, the V.A. Medical Center, and the University of Miami Hospitals and Clinics in Miami. The author of over 400 scientific papers and texts in gastroenterology, Dr. Barkin serves on several editorial boards and is a reviewer for many major medical journals. His research and reviews have been published in leading peer–reviewed journals. He lectures at national and international scientific meetings.


Table of Contents

Introduction

Medication for ulcerative colitis (UC) and Crohn's disease (CD) can help control your symptoms. The goals of inflammatory bowel disease (IBD) therapy are to reduce inflammation, relieve symptoms, maintain remission, and prevent flare–ups. It's important to remember that, for your medication to do its job, you must take it as prescribed. IBD is a chronic disease, therefore long–term treatment will likely be necessary, and you need to take your medication even if you are feeling well. This newsletter will describe the many effective drugs available and provide tips for taking your medicine.

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What is the standard treatment for IBD?

When it comes to IBD, each person responds differently to treatment, and medication is therefore tailored to your specific situation. Because there is no "one–size–fits–all" medication, what works well for one person may not work for another. What's more, people vary with respect to the side effects they may experience and the kinds of side effects they are willing to tolerate. Finally, different people prefer different methods of medication administration, e.g., pills, liquid suspension, injection, suppository, or enema. Your doctor's recommendation will depend on your symptoms, the severity and the course of your disease, and your prognosis. You may find that you need to try several different medications before figuring out what works best for you. It is important to keep track of how well your medication is working for you and report any concerns to your doctor.

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What types of medication might my doctor consider?

 

    · Aminosalicylates

    If you have mild to moderate IBD, aminosalicylates (e.g., mesalamine, sulfasalazine, olsalazine, and balsalazide) will likely be your first line of defense for achieving and maintaining remission, in accordance with their FDA–approved indications. Aminosalicylates (which are also referred to as 5–ASAs) decrease inflammation at the cellular level. Most are administered orally in dosages that require you to take a number of pills several times each day. Mesalamine is also available as an enema (Rowasa®) or suppository (Canasa®), which can be inconvenient to use, so many physicians will try to switch patients from these medications.

    A major concern physicians have about mesalamines is that it is difficult for patients to take multiple pills at numerous times throughout the day. To address this concern, new formulations have been created to allow for once daily dosing. For example, Apriso,™ a locally–acting aminosalicylate indicated for the maintenance of remission of ulcerative colitis in adults, is a mesalamine–based 5–ASA that uses a patented technology to provide extended and delayed 5–ASA delivery. Apriso gradually distributes mesalamine throughout your entire colon in a once–a–day formulation – which can be a plus if you find it difficult to remember to take your pills. The following table describes Apriso and other extended–and/or delayed–release 5–ASAs.

     

                                                                 5-ASAs

     

    5-ASA

     Delayed       Controlled

    Release

     Extended Release

     Once Daily

    Apriso™1

    x

     

    x

    x

    Asacol®2

    x

     

     

     

    Colazal®3

    x

     

     

     

    Lialda™4

    x

     

     

    x

    Pentasa®5

     

    x

     

     



    References



    1. Apriso Prescribing Information http://www.salix.com/assets/pdf/prescribe_info/aprisopi.pdf
    2. Asacol Prescribing Information http://www.asacol.com/pdf/asacol-info.pdf
    3. Colazal Prescribing Information http://www.salix.com/assets/pdf/prescribe_info/colazalpi.pdf
    4. Lialda Prescribing Information http://www.lialda.com/docs/lialda-prescribing-information.pdf
    5. Pentasa Prescribing Information http://pi.shirecontent.com/PI/PDFs/Pentasa_USA_ENG.pdf

    · Corticosteroids

    Corticosteroids are powerful, fast–acting anti–inflammatory drugs that suppress the immune system. They are generally used to treat disease flare–ups in people with moderate to severe, active IBD. Unfortunately, steroids do not prevent flare–ups and, in our opinion, they should not be taken chronically.

    When taken orally, corticosteroids like prednisone, methylprednisone, and hydrocortisone have systemic effects – they affect more than just your gastrointestinal tract. Other oral options, like budesonide, have minimal systemic effects because they are metabolized by your liver.

    If your healthcare provider prescribes oral corticosteroids, but you continue to experience local symptoms (e.g., urgency, rectal bleeding, or passing only gas when you feel like you need to pass stool) your physician may prescribe a local mesalamine enema or corticosteroid enema (e.g., budesonide).

    Corticosteroids are prescribed only for short periods of time, due to side effects which can include risk of infection, bone loss, diabetes, weight gain, high blood pressure, mood swings and insomnia, and increased facial hair. To minimize side effects, your dosage should decrease once your symptoms are under control. Once you have taken corticosteroids for more than ten to fourteen days, be careful to gradually decrease your dosage instead of suddenly going "cold turkey." Stopping too quickly can cause feelings of weakness, lightheadedness, muscle and joint pain, abdominal pain, and diarrhea. It may also result in a flare of your symptoms.

    If you are prescribed corticosteroids, it is important to monitor your caloric intake, since corticosteroids can increase your appetite. Maintaining a healthy weight will decrease your risk for developing diabetes and high blood pressure.

    · Immunomodulators

    Your doctor may prescribe immunomodulators if you 1) do not respond to other medications, 2) frequently need to use corticosteroids, 3) have side effects with corticosteroids, or 4) have perianal disease or fistulas that don't respond to antibiotics. Like corticosteroids, immunomodulators also suppress the immune system. Some can take up to six months to have their full effect, but others are faster acting. To speed up their effect, immunomodulators are sometimes combined with lower than normal doses of steroids. Immunomodulators can be administered orally (azathioprine, 6–mercaptopurine) or by injection (methotrexate or cyclosporine). Side effects may include risk of infection, nausea, vomiting, and headache. Your physician will monitor your blood counts and liver tests when you take these medications.

    · Antibiotics

    Antibiotics are typically used to treat CD, but not UC. They may be particularly effective if you have fistulas or abscesses. Antibiotics can help control your symptoms by decreasing intestinal bacteria and suppressing your immune system. They are most often taken orally (e.g., ciprofloxacin or metronidazole), but can also be injected (ciprofloxacin or metronidazole). If your symptoms are successfully treated with antibiotics, your doctor may prescribe them as maintenance therapy. Side effects can include headaches, vomiting, nausea, and diarrhea.

    · Biologic Therapies

    Biologic therapies are genetically engineered medications that interfere with your body's inflammatory response. Unlike most immunosuppressive medication, biologic therapies act selectively instead of systemically. There are two categories of biologic therapies, anti–tumor necrosis factor (anti–TNF) therapy and integrin receptor agonists. Anti–TNF therapy (e.g., infliximab, adalimumab, certolizumab, and pegol) works by binding to and inactivating a protein that is responsible for intestinal inflammation. Infliximab is administered by intravenous infusion over a period of two to three hours. Adalimumab and certolizumab are given as a shot into the fatty part of the skin. Side effects include injection site reactions, risk of infection, headaches, rashes, and nausea. Integrin receptor agonists (e.g., natalizumab) work by binding to cells that play a role in inflammation. Because of potentially serious side effects (e.g., neurological disease, allergic reactions, and increased infection risk), if you take natalizumab, you must enroll in a special FDA monitoring program.

 

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Is it ok to take medication for IBD if I am also taking other medication?

With the exception of sulfasalazine, which can react with other sulfa drugs, it is unlikely that your IBD medication will interact with other medication you are taking. However, since drug interactions can cause side effects or either decrease or intensify drug activity, it is always important to tell your doctor about any other prescription or over–the–counter medication. Be sure to also mention any vitamin or herbal supplements.

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What should I do if my medication makes me feel sick?

Don't suffer unnecessarily – talk to your doctor. It is sometimes difficult to know if you are experiencing a disease symptom or the side effect of a medication. Be sure to contact your doctor immediately if you experience any of the following:

  • Severe joint pain
  • Tingling in your hands or feet
  • Dizziness or fainting
  • Chills or sweating
  • Difficulty breathing
  • Swelling of your lips, tongue, or face
  • Hives
  • Severe worsening of symptoms
  • Severe headache or blurred vision

Here is a good rule of thumb: If a new symptom occurs after beginning a medication, stop taking the medication and call your physician.

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Why do I have to take my medication even when I feel fine? Why not wait until I feel a flare–up coming?

Once your symptoms are under control and you are feeling well, you may think that your disease is cured and you can cut back on your medication or stop taking it completely. But, unfortunately, there is currently no cure for IBD. Studies show that continuing to take your medication, even when you are feeling fine, decreases your risk of relapse, disease progression, and colorectal cancer (if you have UC), and increases your quality of life. For more information, refer to the newsletter titled "Staying on Medication – Your Health Depends on It" by Dr. Stephen Hanauer.

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How can I remember to take my medicine, especially when I'm in remission?

If you find that it's challenging to remember to take your medication, especially when you're in remission, there are a number of strategies you can try to help you remember. For example:

  • Take your medication at the same time(s) each day. You can use a Mind Your Meds chart to help you keep track.
  • Use pill boxes to organize daily doses.
  • Keep your medication visible – on the counter instead of in a drawer.
  • Use electronics to your advantage – program your watch, cell phone, or computer to remind you.

If you are having trouble remembering to take your medication, be honest with your doctor. Try asking for advice about improving your compliance and if there might be a similar medication that is easier for you to take. Also be sure to refill your prescriptions – it's no good remembering to take your medication if you've run out. Your pharmacy may have a refill reminder program. Again, for more information, refer to the newsletter titled "Staying on Medication – Your Health Depends on It" by Dr. Stephen Hanauer.

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Conclusion

There are many medications for treating the symptoms of IBD that will allow you to live life to its fullest. Always be sure to check with your healthcare provider about which options are most appropriate for you. Remember that every patient is different and that your needs may change over time. What's more, each year, another group of drugs enters the research pipeline, and new and improved medications make their debut in the pharmacy. It is important to keep up–to–date about all of the treatment options available, and reading this newsletter is a great first step.

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Important Safety Information about AZASAN

WARNING: Chronic immunosuppression with this purine antimetabolite increases risk of neoplasia in humans. Physicians using this drug should be very familiar with this risk as well as with the mutagenic potential to both men and women and with possible hematologic toxicities. See WARNINGS section in complete Prescribing Information.

AZASAN® (azathioprine tablets) 75/100 mg is indicated as an adjunct for the prevention of rejection in renal homotransplantations, and also for the management of active rheumatoid arthritis to reduce signs and symptoms.The most commonly reported side effects associated with AZASAN therapy are leukopenia and/or thrombocytopenia, secondary infections, neoplasia, nausea, vomiting, diarrhea, fever, myalgias, skin rashes, and hepatotoxicity. AZASAN therapy should be given cautiously when used concomitantly with allopurinol, ACE inhibitors, and other agents affecting myelopoiesis. AZASAN is contraindicated in pregnant and lactating women and in patients who have shown hypersensitivity to this product.

Consult with your physician to see if this product is right for you.

Complete Prescribing Information for AZASAN, including BOXED WARNINGpdf

Important Safety Information about METOZOLV® ODT

WARNING: TARDIVE DYSKINESIA

See full prescribing information for complete boxed warning.

Treatment with metoclopramide can cause tardive dyskinesia, a serious movement disorder that is often irreversible. The risk of developing tardive dyskinesia increases with the duration of treatment and the total cumulative dose.

Metoclopramide therapy should be discontinued in patients who develop signs or symptoms of tardive dyskinesia. There is no known treatment for tardive dyskinesia. In some patients, symptoms may lessen or resolve after metoclopramide treatment is stopped.

Treatment with metoclopramide for longer than 12 weeks should be avoided in all but rare cases where therapeutic benefit is thought to outweigh the risk of developing tardive dyskinesia.

METOZOLV® ODT (metoclopramide HCl) is indicated as short-term (4 to 12 weeks) therapy for adults with symptomatic, documented gastroesophageal reflux disease (GERD) who fail to respond to conventional therapy and for the relief of symptoms associated with acute and recurrent diabetic gastroparesis (diabetic gastric stasis) in adults. Therapy should not exceed 12 weeks in duration. Take on an empty stomach up to four times daily, at least 30 minutes before eating and at bedtime.

METOZOLV ODT is contraindicated in patients with intestinal obstruction, hemorrhage, or perforation; pheochromocytoma; known sensitivity or intolerance to metoclopramide; epilepsy; or are receiving concomitant medications with extrapyramidal reactions.

Extrapyramidal symptoms (EPS), manifested primarily as acute dystonic reactions, occur in approximately 1 in 500 patients treated with the usual adult dosages of 30 to 40 mg/day of metoclopramide. These usually are seen during the first 24 to 48 hours of treatment with metoclopramide, occur more frequently in pediatric patients and adult patients less than 30 years of age and are even more frequent at higher doses.

Drug-induced Parkinsonism can occur during metoclopramide therapy, more commonly within the first 6 months after beginning treatment, but also after longer periods. Patients with a history of Parkinson’s disease should be given metoclopramide cautiously, if at all, since such patients can experience exacerbation of Parkinsonian symptoms when taking metoclopramide.

There have been rare reports of an uncommon but potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) associated with metoclopramide. Clinical manifestations of NMS include hyperthermia, muscle rigidity, altered consciousness, and evidence of autonomic instability. The management of NMS should include immediate discontinuation of metoclopramide and other drugs not essential to concurrent therapy.

Depression associated with metoclopramide use has occurred in patients with and without a history of depression. For those patients with a prior history of depression, metoclopramide should only be given if the expected benefits outweigh the potential risks.

In one study in hypertensive patients, intravenously administered metoclopramide was shown to release catecholamines; hence, caution should be exercised when metoclopramide is used in patients with hypertension. Any rapid rise in blood pressure associated with METOZOLV ODT use should result in immediate cessation of metoclopramide use in those patients.

Since metoclopramide produces a transient increase in plasma aldosterone, patients with cirrhosis or congestive heart failure may be at risk of developing fluid retention and volume overload. If these side effects occur at any time in any patients during metoclopramide therapy, the drug should be discontinued.

Adverse reactions, especially those involving the nervous system, may occur after stopping the use of METOZOLV ODT.

In clinical studies, the most frequently reported adverse events (≥2% occurrence) were headache, nausea, fatigue, somnolence, and vomiting.

Complete Prescribing Information for METOZOLV ODT, including BOXED WARNING pdf

Important Safety Information about OSMOPREP

WARNINGS

There have been rare, but serious reports of acute phosphate nephropathy in patients who received oral sodium phosphate products for colon cleansing prior to colonoscopy. Some cases have resulted in permanent impairment of renal function and some patients required long–term dialysis. While some cases have occurred in patients without identifiable risk factors, patients at increased risk of acute phosphate nephropathy may include those with increased age, hypovolemia, increased bowel transit time (such as bowel obstruction), active colitis, or baseline kidney disease, and those using medicines that affect renal perfusion or function (such as diuretics, angiotensin converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], and possibly nonsteroidal anti–inflammatory drugs [NSAIDs]).

It is important to use the dose and dosing regimen as recommended (PM/AM split dose).

OSMOPREP® (sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) Tablets are indicated for cleansing of the colon as a preparation for colonoscopy in adults 18 years of age or older. Considerable caution should be advised before OSMOPREP is used in patients with severe renal insufficiency, congestive heart failure, ascites, unstable angina, gastric retention, ileus, severe chronic constipation, bowel perforation, toxic megacolon, gastric bypass or stapling surgery, or hypomotility syndrome. Use with caution in patients with impaired renal function, patients with a history of seizures or at higher risk of seizure, patients with higher risk of cardiac arrhythmias, known or suspected electrolyte disturbances (such as dehydration), or people taking drugs that affect electrolyte levels. Patients with electrolyte abnormalities such as hypernatremia, hyperphosphatemia, hypokalemia, or hypocalcemia should have their electrolytes corrected before treatment with OSMOPREP.

OSMOPREP is contraindicated in patients with a known allergy or hypersensitivity to sodium phosphate salts or any of its ingredients, and in patients with biopsy–proven acute phosphate nephropathy. In clinical trials, the most commonly reported adverse reactions (reporting frequency >3%) were abdominal bloating, nausea, abdominal pain, and vomiting. It is recommended that patients receiving OSMOPREP be advised to adequately hydrate before, during, and after the use of OsmoPrep.

For complete Prescribing Information for OSMOPREP including BOXED WARNING.pdf

Important Safety Information about VISICOL

WARNINGS

There have been rare, but serious reports of acute phosphate nephropathy in patients who received oral sodium phosphate products for colon cleansing prior to colonoscopy. Some cases have resulted in permanent impairment of renal function and some patients required long-term dialysis. While some cases have occurred in patients without identifiable risk factors, patients at increased risk of acute phosphate nephropathy may include those with increased age, hypovolemia, increased bowel transit time (such as bowel obstruction), active colitis, or baseline kidney disease, and those using medicines that affect renal perfusion or function (such as diuretics, angiotensin converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], and possibly nonsteroidal anti-inflammatory drugs [NSAIDs]).

It is important to use the dose and dosing regimen as recommended (PM/AM split dose).

VISICOL® (sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) Tablets are indicated for cleansing of the colon as a preparation for colonoscopy in adults 18 years of age or older. VISICOL is not to be used in patients with congestive heart failure, ascites, unstable angina pectoris, gastric retention, ileus or acute obstruction or pseudo-obstruction, severe chronic constipation, bowel perforation, acute colitis, toxic megacolon, or hypomotility syndrome. Use with caution in patients with impaired renal function, pre-existing electrolyte disturbances, or people taking drugs that affect electrolyte levels. VISICOL is contraindicated in patients with a known allergy or hypersensitivity to sodium phosphate salts or any of its ingredients. In clinical trials, the most commonly observed (≥1%) adverse reactions occurring with use of VISICOL were generally transient and self-limited and included nausea, vomiting, abdominal bloating, abdominal pain, dizziness and headache.

Consult with your physician to see if this product is right for you.

Complete Prescribing Information for VISICOL, including BOXED WARNING pdf

The information contained on this page is intended for US patients, healthcare professionals, and pharmacists only.

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