Treating Pain Effectively - New Study Results Confirm Improved Gastrointestinal Tolerability Of Tapentadol

Results from two phase III clinical studies of tapentadol immediate release tablets ( IR ) suggest a significantly improved gastrointestinal tolerability ( 1 ) as well as safety ( 2 ) profile compared to oxycodone HCl IR. The data were presented by German pharmaceutical company Grunenthal at this year's Annual Congress of the European League against Rheumatism ( EULAR, June 11-14, Paris, France ) .

In Europe, one in five adults experiences chronic pain ( 3 ) in their life. To reduce pain effectively, especially with chronic pain conditions, the use of strong analgesics such as opioids is expanding. ( 4 ) However, a substantial number of patients receiving pain therapy do not feel satisfied with their treatment ( 5 ) , ( 6 ) , ( 7 ) and stop their opioid therapy against medical recommendation. ( 8 ) The most important reasons for this are gastrointestinal ( GI ) side effects like nausea and vomiting in first few days and constipation in course of ongoing treatment ( 9 ) ; GI tolerability is one of the leading causes of treatment discontinuation for patients who take prescription pain medications.

Tapentadol is a novel centrally acting analgesic that acts by two mechanisms of action, combining mu-opioid receptor agonism and noradrenaline reuptake inhibition properties in a single molecule. New results from two phase III studies with tapentadol were presented at EULAR meeting. A study in patients with end-stage joint disease showed that treatment with a 50 mg or 75 mg tapentadol IR resulted in significantly higher pain relief compared to placebo ( P <0. 001 ) when assessed over five days of treatment. ( 1 ) In addition, patients treated with tapentadol experienced significantly less GI side effects compared to patients treated with 10 mg of oxycodone IR.

The 50 mg and 75 mg tapentadol IR treatment groups showed similar efficacy to that seen in patients treated with 10 mg of oxycodone HCl IR. The most common adverse events in both treatment groups included nausea, dizziness and vomiting. However, compared to oxycodone IR, both doses of tapentadol studied were associated with a significant reduction in incidence of gastrointestinal side effects such as nausea, vomiting and constipation. 26 percent of patients treated with 10 mg of oxycodone IR experienced constipation compared to only 4 and 7 percent of the tapentadol IR groups, treated with 50 mg and 75 mg, respectively ( P <0. 001 ) .

In addition, 18 percent of the patients in tapentadol IR 50 mg group and 21 percent in tapentadol IR 75 mg group reported nausea compared to 41 percent in oxycodone IR group ( P < 0. 001 ) . There also were fewer reports of vomiting with both doses of tapentadol IR, 50 mg and 75 mg: 7 or 14 percent respectively versus 34 percent with oxycodone IR ( P <0. 001 ) .

While in the oxycodone HCl IR 10 mg group discontinuation rate was 29 percent, only 13 and 18 percent of the patients in tapentadol IR 50- and 75 mg group, respectively, discontinued treatment before end of the study.

The second study presented at EULAR congress further demonstrates improved tolerability profile of tapentadol IR in comparison to oxycodone HCl IR; for the first time data was collected over a treatment period of 90 days. ( 2 )

The objective of this phase III, randomized 4: 1 vs. oxycodone IR, double-blind, flexible dose study was to assess the safety of tapentadol IR for treating low back pain or osteoarthritis pain of hip or knee over a period of 90 days. Treatment included tapentadol IR ( 50 or 100 mg ) every four to six hours as needed up to 600 mg per day or oxycodone HCl IR ( 10 or 15 mg ) every four to six hours as needed up to 90 mg per day. A total of 679 and 170 patients in the tapentadol IR and oxycodone HCl IR groups, with average pain intensity at inclusion on an 11-point numerical rating scale of 7. 0 and 7. 2, respectively ( 10 ) , were included in efficacy and safety analyses.

Both treatment groups indicated a comparable analgesic effect at specified doses. The incidences of nausea, vomiting, constipation, and composite of nausea and/or vomiting in tapentadol IR group were significantly lower than in oxycodone HCl IR group ( P <0. 001 for all treatment comparisons ) .

Significant differences ( P <0. 05 ) were found between groups for time to first onset of nausea, vomiting, and constipation, with time-to-event being consistently shorter in the oxycodone HCl IR group.

In conclusion, two studies showed the high efficacy of tapentadol IR as well as its significantly improved gastrointestinal tolerability profile in comparison to oxycodone IR.

About Tapentadol

Tapentadol is a next generation centrally-acting analgesic, which is currently being developed for relief of moderate to severe pain. It has a unique profile with two mechanisms of action, combining mu-opioid receptor agonism and noradrenaline reuptake inhibition properties in a single molecule. It demonstrates an efficacy comparable to classical strong opioids, like oxycodone or morphine, and an improved tolerability profile, especially in regard to gastro-intestinal side effects like nausea, vomiting, and constipation. Tapentadol is being developed as immediate-release formulation for acute pain and prolonged-release formulation for chronic pain; once approved, it'll be used in hospital and outpatient settings.

In United States a New Drug Application ( NDA ) has been submitted to U. S. Food and Drug Administration ( Food and Drug Administration ) for tapentadol immediate release ( IR ) tablets by Grunenthal's co-development partner Johnson & Johnson Pharmaceutical Research & Development, L. L. C. ( J&JPRD ) . Grunenthal is preparing submission of tapentadol IR to regulatory authorities in Europe, Mexico, and South America.

Two Mechanisms of Action

Tapentadol acts by two mechanisms of action, combining mu-opioid receptor agonism and noradrenaline reuptake inhibition properties in a single molecule. Mu-receptor agonists are drugs that bind to mu-opioid receptors in central nervous system. These drugs modify sensory and affective ( mood ) aspects of pain, inhibit the transmission of pain on spinal cord level and affect activity in parts of brain that control how pain is perceived. Noradrenaline reuptake inhibitors are a type of central nervous system medication that increases level of noradrenaline in brain by inhibiting its reabsorption into nerve cells; these compounds have analgesic properties.

Tapentadol Co-Development Partnership

Grunenthal discovered and began development of tapentadol. Grunenthal and J&JPRD are conducting phase IIb and III development programs for tapentadol for acute and chronic pain conditions. Grunenthal licensed rights to tapentadol to Ortho-McNeil-Janssen Pharmaceuticals, Inc. , and J&JPRD, for the United States, Canada and Japan. Grunenthal maintains marketing rights in Europe and rest of world.

About Grunenthal

Grunenthal is an expert in pain therapy and gynaecology and a pioneer in intelligent, user-friendly drug delivery technologies. Founded in 1946, company employs 1, 900 people in Germany and 4, 800 worldwide. In 2006, Grunenthal achieved revenues of 813 million Euro. http: //www. grunenthal. com

References

( 1 ) Upmalis D, Okamoto A, Van Hove I, Stegmann J, Haeussler J. Efficacy and Tolerability Data Supporting Use of Tapentadol Immediate Release for the Relief of Pain From End-Stage Joing Disease. Abstract AB0744, 9th Annual European Congress of Rheumatology ( EULAR 2008 ) , 11-14 June 2008, Paris, France.

( 2 ) Oh C, Upmalis D, Okamoto A, Stegmann J. Flexible Use of Tapentadol Immediate Reelease for 90 Days for the Treatment of Low Back Pain and Osteoarthritis Pain: A Safety Study. Abstract FRI0335, 9th Annual European Congress of Rheumatology ( EULAR 2008 ) , 11-14 June 2008, Paris, France.

( 3 ) Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2006; 10: 287-333.

( 4 ) Rowbotham MC, Lindsey CD. How effective is long-term opioid therapy for chronic noncancer pain? Clin J Pain. 2007; 23: 300-2.

( 5 ) McDermott AM, Toelle TR, Rowbotham DJ, Schaefer CP, Dukes EM. The burden of neuropathic pain: results from a cross-sectional survey. Eur J Pain. 2006; 10: 127-35.

( 6 ) Eriksen J, Sjogren P, Bruera E, Ekholm O, Rasmussen NK. Critical issues on opioids in chronic non-cancer pain: an epidemiological study. Pain. 2006; 125: 172-.

( 7 ) OPEN Minds. The white paper on opioids and pain: a pan-European challenge. 2005. Available from here. [Last accessed 09 Apr 2008].

( 8 ) Nicholson B. Responsible prescribing of opioids for management of chronic pain. Drugs. 2003; 63: 17-32.

( 9 ) Harris JD. Management of expected and unexpected opioid-related side effects. Clin J Pain 2008; 24: S8-S13.

( 10 ) Oh C. , Upmalis D. , Okamoto A. , Stegmann J. Tapentadol Immediate Release for 90 Days for the Treatment of Low Back Pain and Osteoarthritis Pain: A Safety Study. Johnson & Johnson Pharmaceutical Research & Development, L. L. C. , Raritan, NJ, USA; Research and Development, Grunenthal GmbH, Aachen, Germany. Poster presented at the 9th Annual European Congress of Rheumatology ( EULAR 2008 ) , 11-14 June 2008, Paris, France.

Grunenthal

Medical advises for your health improvement

Tramadol and our health.

uses of Tramadol

Tramadol is used to relieve ongoing, moderate pain in people who need all-day pain relief ( " around clock " dosing ) . It's similar to narcotic pain medications. It works on certain nerves in brain that control how you experience pain.

how to use of Tramadol

Take Tramadol by mouth, either always with food or always without food, usually once daily or as directed by your doctor. If nausea occurs, consult your doctor or pharmacist about ways to decrease it ( e. g. , antihistamines, lying down for 1 to 2 hours with as little head movement as possible ) .

Swallow Tramadol whole. Don't crush, chew, or split tablet. Doing so would release the Tramadol into your bloodstream all at once, possibly causing serious ( sometimes fatal ) side effects.

The dosage is based on your medical condition and response to treatment. To reduce risk of side effects, your doctor may tell we to gradually increase your dose when starting long-acting Tramadol. The maximum recommended dose is 300 milligrams a day.

If we have severe kidney disease ( e. g. , on dialysis ) or severe liver disease ( e. g. , cirrhosis ) , regular-release Tramadol is recommended instead of long-acting form.

Pain medications work best if they're used as first signs of pain occur. If we wait until pain has worsened, medication may not work as well.

Follow your doctor's or pharmacist's instructions for safe use of non-narcotic pain relievers ( e. g. , acetaminophen, ibuprofen ) . Ask your doctor or pharmacist for more details regarding your treatment.

Tramadol may cause dependence, especially if it has been used regularly for an extended time or if it has been used in high doses. In such cases, withdrawal reactions ( e. g. , anxiety, sweating, sleeplessness, shaking, diarrhea, rapid breathing ) may occur while use Tramadol if you suddenly stop Tramadol. Also, if you are taking regular doses of narcotic medications for ongoing pain ( e. g. , cancer pain ) , starting Tramadol may cause a withdrawal reaction. To prevent withdrawal reactions when stopping extended, regular treatment with Tramadol, gradually reduce dosage as directed. Consult your doctor or pharmacist for more details, and report any withdrawal reactions immediately.

Rarely, abnormal drug-seeking behavior ( addiction ) is possible with Tramadol. Don't increase your dose, take it more frequently, or use it for a longer time than prescribed. Properly stop medication when so directed.

When used for an extended period, Tramadol mayn't work as well and may require different dosing. Talk with your doctor if Tramadol stops working well.

Tell your doctor if your pain does not decrease or if it worsens.

side effects of Tramadol

Nausea, vomiting, constipation, lightheadedness, dizziness, drowsiness, headache, or weakness may occur while use Tramadol. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

To prevent constipation, maintain a diet adequate in fiber, drink plenty of water, and exercise. If we are taking Tramadol regularly, it may be useful to start using a laxative right away instead of waiting until we become constipated. Consult your pharmacist for details regarding correct use of laxatives ( e. g. , stimulant-type with stool softener ) .

Remember that your doctor has prescribed Tramadol because he or she has judged that benefit to you is greater than risk of side effects. Many people using Tramadol don't have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur:

Tell your doctor immediately if any of these rare but very serious side effects occur:

A very serious allergic reaction to Tramadol ( which may occur while use Tramadol as early as the first dose ) is rare. However, seek immediate medical attention if we notice any of the following symptoms:

This isn't a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

precautions of Tramadol

Before taking long-acting Tramadol, tell your doctor or pharmacist if we are allergic to it; or to other narcotics ( e. g. , codeine ) ; or if we have any other allergies.

Tramadol shouldn't be used if we have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if we have:

Before using Tramadol, tell your doctor or pharmacist your medical history, especially of:

Tramadol may make you dizzy or drowsy. Use caution while driving, using machinery, or doing any activity that requires alertness. Avoid alcoholic beverages because they may increase risk of Tramadol's side effects.

To reduce dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Before having surgery, tell your doctor or dentist that we are using Tramadol.

Caution is advised when using Tramadol in elderly because they may be more sensitive to its effects, especially slow/shallow breathing and drowsiness.

During pregnancy, Tramadol should be used only when clearly needed. It is not recommended for use for long periods or in high doses late in pregnancy because of possible serious harm to your baby. Discuss the risks and benefits with your doctor. Infants born to mothers who have been using Tramadol for an extended time may have seizures or withdrawal symptoms such as irritability, abnormal/persistent crying, or diarrhea. Tell your doctor immediately if we notice any of these symptoms in your newborn.

Tramadol passes into breast milk. While there have been no reports of harm to nursing infants, consult your doctor before breast-feeding.

interactions of Tramadol

Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring we for them. Don't start, stop, or change dosage of any medicine before checking with them first.

Tramadol shouldn't be used with following medications because very serious ( possibly fatal ) interactions may occur while use Tramadol:

Avoid taking MAO inhibitors within 2 weeks before, during, and after treatment with Tramadol.

If you're currently using any of these medications listed above, tell your doctor or pharmacist before starting Tramadol.

Before using Tramadol, tell your doctor or pharmacist of all prescription and nonprescription/herbal products we may use, especially of:

Also report use of drugs that might increase seizure risk when combined with Tramadol such as isoniazid ( INH ) , phenothiazines ( e. g. , thioridazine, chlorpromazine, promethazine ) , theophylline, or tricyclic antidepressants ( e. g. , amitriptyline ) , among others. Consult your doctor or pharmacist for details.

Tell your doctor or pharmacist if we also take drugs that cause drowsiness such as certain antihistamines ( e. g. , diphenhydramine ) , anti-anxiety drugs ( e. g. , diazepam ) , anti-seizure drugs ( e. g. , phenytoin ) , medicine for sleep ( e. g. , zolpidem ) , muscle relaxants ( e. g. , cyclobenzaprine ) .

Check labels on all your medicines ( e. g. , cough-and-cold products ) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

This document doesn't contain all possible interactions. Therefore, before using Tramadol, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share list with your doctor and pharmacist.

Tramadol with EU delivery

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