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Oral Medications For IC

An Expanded Treatment Arsenal

There was once a time when IC patients had a very limited selection of prescription oral medications available to them to help with the symptoms of IC. Thankfully, times have changed. More interest in IC treatments, both oral and intravesical (instilled into the bladder), has been generated by the medical and research communities and the pharmaceutical industries.

Here is a closer look at several of the prescription oral medications currently available to help you with your symptoms. Most of these medications are used "off-label" for IC, meaning that the Food & Drug Administration (FDA) has not approved them specifically for use in IC. However, many of these medications have been investigated by researchers to observe their effects on IC patients, and the results have been published in medical journals. Often times a combination of these treatments is needed to provide adequate symptom relief. [Note: Please consult with your physician before taking or combining any of these medications.]
 
Mucosal Surface Protectants
Elmiron® (pentosan polysulfate sodium), first FDA-approved in 1996, is the only oral medication approved specifically for use in IC. Elmiron is thought to work by restoring a damaged, thin, or "leaky" bladder surface, easing the pain and discomfort of IC.

It is important to remember that Elmiron must be taken continually for several months before improvement may be seen. Physicians will often combine Elmiron with more immediate-acting medications so that patients can get relief from their symptoms sooner.

References:

  • Parsons CL. Epithelial coating techniques in the treatment of interstitial cystitis. Urology. 1997 May;49(5A Suppl):100-4.
  • Hanno PM. Analysis of long-term Elmiron therapy for interstitial cystitis. Urology. 1997 May;49(5A Suppl):93-9.

Tricyclic Antidepressants 
Tricyclic antidepressants are used for their many beneficial side effects, and prescribed in lower dosages for treating IC than would be used for treating depression. These beneficial side effects include: anti-pain properties; anticholinergic effects which help decrease urinary frequency; sedative effects; and the blockage or re-uptake of certain neurotransmitters that cause the brain to misinterpret or ignore pain impulses. The most common tricyclic antidepressants used to treat IC are: Elavil® (amitriptyline), Norpramin® (desipramine), Pamelor® (nortriptyline), Sinequan® (doxepin), and Tofranil® (imipramine).

Newer classes of antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), have not been researched for use in treating IC. While these newer medications are being used for the treatment of many chronic pain conditions, including fibromyalgia, there is no evidence that they are more helpful than the tricyclics for the treatment of IC. Some IC patients have reported that SSRIs have not helped with their symptoms, or have increased their IC symptoms. However, patients who are unable to tolerate certain side effects of the tricyclic antidepressants, such as dry mouth, constipation and urinary retention, may want to consider trying SSRIs.

References:

  • Pranikoff K, Constantino G. The use of amitriptyline in patients with urinary frequency and pain. Urology. 1998 May;51(5A Suppl):179-81.
  • Hanno PM. Amitriptyline in the treatment of interstitial cystitis. Urol Clin North Am. 1994 Feb;21(1):89-91. Review.


Medications That Block Mast Cell Degranulation
Antihistamines

Antihistamines have been found to be useful in the treatment of IC, especially for IC patients who suffer from allergies. The most widely used antihistamine to treat IC is hydroxyzine. It inhibits mast cell degranulation which is thought to play a part in some IC patients’ symptoms. It also has sedative and anxiety reducing effects. Hydroxyzine is available in two oral forms -- Vistaril® (hydroxyzine pamoate), and Atarax ® (hydroxyzine hydrochloride). Vistaril has a slightly higher absorption rate. Atarax is also available in liquid oral form for patients allergic to fillers or dyes used in the capsules or pills.

References:

  • Minogiannis P, El-Mansoury M, Betances JA, Sant GR, Theoharides TC. Hydroxyzine inhibits neurogenic bladder mast cell activation. Int J Immunopharmacol. 1998 Oct;20(10):553-63.
  • Theoharides TC, Sant GR. Hydroxyzine therapy for interstitial cystitis. Urology. 1997 May;49(5A Suppl):108-10.
  • Theoharides TC. Hydroxyzine in the treatment of interstitial cystitis. Urol Clin North Am. 1994 Feb;21(1):113-9.

H2 Blockers
Histamine 2 blockers (H2 Blockers) are used primarily to treat heartburn, ulcers and acid indigestion. They work by blocking the production of a type of histamine in the stomach known as histamine-2. Tagamet® (cimetidine) and similar H2 blockers such as Zantac® (ranitidine) are being used by some IC patients to help to reduce their IC symptoms. Small studies have been conducted using Tagamet to successfully treat IC. However, the exact mechanism by which this class of medication works to relieve IC is uncertain.

References:

  • Dasgupta P, Sharma SD, Womack C, Blackford HN, Dennis P. Cimetidine in painful bladder syndrome: a histopathological study. BJU Int. 2001 Aug;88(3):183-6.
  • Lewi H. Cimetidine in treatment of interstitial cystitis. Urology. 1995 Jun;45(6):1088.
  • |eshadri P, Emerson L, Morales A. Cimetidine in the treatment of interstitial cystitis. Urology. 1994 Oct;44(4):614-6.
Leukotriene Inhibitors
IC patients with asthma may be familiar with the asthma medication, Singulair® (montelukast). Singulair belongs to a class of medications called leukotriene inhibitors. Like histamines, leukotrienes are released from mast cells and are thought to play a role in inflammation. And as we all know, inflammation is thought to be a part of the "IC picture." In a recent small study, patients who took a single daily dose of oral montelukast had significant improvement of urinary frequency, urgency and pain.

Placebo-controlled clinical trials are needed to understand more about the use of leukotriene inhibitors in the treatment of IC.

Another leukotriene-inhibitor, Accolate® (zafirkulast), which is also an asthma medication, may, in theory, be helpful in fighting IC symptoms, but no research has been conducted to determine its effect on IC.

References:

  • Bouchelouche K, Kristensen B, Nordling J, Horn T, Bouchelouche P. Increased urinary leukotriene E4 and eosinophil protein X excretion in patients with interstitial cystitis. J Urol. 2001 Dec;166(6):2121-5.
  • Bouchelouche K, Nordling J, Hald T, Bouchelouche P. The cysteinyl leukotriene D4 receptor antagonist montelukast for the treatment of interstitial cystitis. J Urol. 2001 Nov;166(5):1734-7.
Mast Cell Inhibitors
Oral Gastrocrom® (cromolyn sodium), a mast cell inhibitor, has also been reported to help to relieve IC symptoms in some patients. However, very little research has been published on the use of cromolyn sodium to treat IC. Gastrocrom blocks the release of histamines and leukotrienes from the mast cell. Gastrocrom is designed for use in treating mastocytosis, a condition caused by the presence of too many mast cells in various tissues in the body, resulting in diarrhea, flushing, headaches, vomiting, urticaria (hives), abdominal pain, nausea, itching and other symptoms. It is thought that a subgroup of IC patients may suffer from mastocytosis, yet more research is needed in this area to learn more about the connection between IC and mastocytosis.
 
Anticonvulsants
Anti-seizure medications have become a mainstay of chronic pain management, especially in relieving neuropathic (nerve-related) pain, such as reflex sympathetic dystrophy and diabetic neuropathy. Neurontin® (gabapentin) and Klonopin® (clonazepam) are two types of these medications that are currently being used to treat IC.

References:

  • Sasaki K, Smith CP, Chuang YC, Lee JY, Kim JC, Chancellor MB. Oral gabapentin (neurontin) treatment of refractory genitourinary tract pain. Tech Urol. 2001 Mar;7(1):47-9.
  • Hansen HC. Interstitial cystitis and the potential role of gabapentin. South Med J. 2000 Feb;93(2):238-42. Review. 
Opioid Analgesics/Pain Medications
Most IC specialists agree that for some IC patients (those with severe, intractable chronic pain), management of their pain with opioid analgesics (narcotics) is necessary. While there has been significant controversy surrounding the use of opioids to treat chronic, non-malignant pain conditions such as IC, more and more physicians, especially pain management specialists, will prescribe opioid therapy when needed for their IC patients.

There are many types of narcotic pain medications. The one thing that they have in common is that they are derived or synthesized from the opium-producing poppy plant, and they work on the opioid receptors in the brain to control pain. Short-acting opioid analgesics, such as Percocet® or Vicodin®, may be used to treat moderate, occasional IC pain. These medications are typically combined with aspirin, acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs), and because of this, may be taxing to the liver, kidneys and/or gastrointestinal lining.

Long-acting opioid analgesics, such as OxyContin®, MS-Contin® and Duragesic® are useful in treating chronic, severe IC pain, and do not typically contain aspirin, acetaminophen or NSAIDs.

References:

  • Ratner, V. Pain in Interstitial Cystitis: Changing Attitudes, Changing Treatments. Pain Forum, vol. 8, no. 3: 154-7, autumn 1999.
  • Brookoff D. Chronic pain: 2. The case for opioids. Hosp Pract (Off Ed). 2000 Sep 15;35(9):69-72, 75-6, 81-4. Review.
  • Brookoff D. Chronic pain: 1. A new disease? Hosp Pract (Off Ed). 2000 Jul 15;35(7):45-52, 59.
  • Brookoff D. The causes and treatment of pain in interstitial cystitis, p. 177. In Sant, GR (ed): Interstitial cystitis. Lippincott-Raven, New York, 1997.
Muscle Relaxants & Antianxiety Medications
Valium® (diazepam), Baclofen® (lioresal), and Klonopin® (clonazepam - also classed as an anti-seizure medication) are considered muscle relaxants. Some IC patient have reported that this class of medications helps with their IC symptoms. They may be especially helpful if the IC patient also suffers from pelvic floor dysfunction (PFD). No research has been conducted using these medications specifically to treat IC.

Xanax® and Ativan® represent a class of medications called benzodiazepines, which were designed originally to treat anxiety and panic disorder. In recent years these medications have been found to help in the treatment of chronic fatigue syndrome, fibromyalgia, restless leg syndrome and many other chronic illnesses, some of which are thought to be related to IC. Some IC patients have reported that these medications can help with their IC symptoms, as well as the symptoms from other related illnesses. These medications appear to work by "down-regulating" the central nervous system.

While opioid therapy is becoming more accepted for use in chronic pain, benzodiazepines, unfortunately, are not yet as accepted. Like opioids, there is the potential for addiction with these medications. However, many experts who treat prolonged chronic illness, for which there is no known cause or cure, do rely on benzodiazepines to help their patients’ myriad of frustrating symptoms. Little published research is available regarding the use of benzodiazepines in the treatment of IC and/or related conditions (with the exception of panic disorder).
 
Bladder Antispasmodics, Analgesics & Anticholinergics
While not specifically designed to treat IC, several different types of medications may be helpful in treating these related symptoms, or treating concurrent urinary tract infections. Some of these medications contain single active ingredients, while others combine several different medications to help to relieve more symptoms. These medications may not work for all IC patients because they can cause urinary retention (difficulty in urinating), which may already be a problem for some IC patients. They can also cause dry eyes and mouth, which can be troublesome for IC patients with co-existing conditions such as Sjogren’s syndrome.

Urimax® contains both an analgesic to help to control the pain and an antispasmodic to relieve the spasms that frequently accompany and aggravate the urgency, frequency, pain and burning syndrome of an inflamed bladder. Urimax also contains an antiseptic/antibacterial agent to help reduce bacteria in urine.

Pyridium-Plus® is a combination of a pain reliever, an antispasmodic and butabarbital, which is a sedative.

Pyridium® (available by prescription, and in an over-the counter lower dose formula) is a non-narcotic urinary tract analgesic used for short-term relief of bladder pain.

Urised® combines urinary antiseptics with antispasmodics to help to relieve the discomfort of urinary inflammation and pain.

The above medications are meant for short-term use only.

Bladder Antispasmodics/Anticholinergics: If bladder spasms, causing urinary urgency and frequency, are your main IC symptoms (and pain is not a significant component), you may want to try one of the following medications. These medications are sometimes used to treat incontinence and "over-active" bladder, as well.

Examples of antispasmodic/anticholinergic medications include: oxybutinin: Ditropan®, Ditropan XL® (extended-release formula); tolterodine: Detrol®, Detrol LA® (time-released); Levsin®, Levbid® (sublingual), Levsinex® (time-released); hyoscyamine: Cystospaz®, Cystospaz-M® (time-released); flavoxate: Urispas®; dicyclomine: Bentyl®; propantheline: Pro-Banthine ®.
 
An Oral Medication in the Research Pipeline
IPD-1151T

A Th2 cytokine inhibitor, known as IPD-1151T, is under investigation by a Japanese team of researchers as a possible oral treatment for non-ulcerative IC. The December issue of Urology Times reported that IPD-1151 showed promise in treating non-ulcerative IC in a small study conducted in Japan. Further studies of this medication are planned for Japan and the US.

References:

  • Ueda T, Tamaki M, Ogawa O, Yoshimura N. Over expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in patients with interstitial cystitis and bladder carcinoma. J Urol. 2002 Jan;167(1):347-51.
  • Ueda T, Tamaki M, Ogawa O, Yoshimura N. Overexpression of platelet-derived endothelial cell growth factor (PD-ECGF) factor/thymidine phosphorylase (TP) in interstitial cystitis. Urology. 2001 Jun;57(6 Suppl 1):130-1.
  • Ueda T, Tamaki M, Ogawa O, Yamauchi T, Yoshimura N. Improvement of interstitial cystitis symptoms and problems that developed during treatment with oral IPD-1151T. J Urol. 2000 Dec;164(6):1917-20.



ICA Update, May/June 2002
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