Labopharm Sees FDA OK for Tramadol Drug in Four Months

Apr. 09, 2008

Labopharm Inc's lengthy struggle to get U.S. Food and Drug Administration approval for its once-daily version of the pain killer tramadol could be over in about four months, its president and chief executive, James Howard-Tripp, told Reuters on Tuesday.

The company, which has been seeking the approval since May 2007, expects to meet with the director of the FDA's Center for Drug Evaluation and Research sometime this month. After the meeting, the FDA has another 30 days to hand down a decision.

Once the decision is announced, the company must complete ...

http://www.therapeuticsdaily.com/news/article.cfm?contentValue=1762538&contentType=sentryarticle&channelID=29

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Patients left in the lurch as drips dry up in civic hospitals

Saturday, May 03, 2008 03:37 IST

The shrinking public health facilities at two civic hospitals — KEM and Sion
hospital — have left several patients and their families in a lurch.
Handling a flow of over 10,000 patients every day, the two BMC hospitals have exhausted their stock of basic saline, which is crucial in any healthcare set-up.

For the last two weeks even the emergency services department at KEM hospital has been functioning without saline. Sion hospital, on the other hand, has been
witnessing a similar crunch from the last few days.

Supply of basic medicines like paracetamols, cough syrups and calcium tablets have been irregular at both hospitals for over a year. Sion hospital does not have a supply of live saving drugs like tramadol, voveron, anti-bacterial tablets, etc, for over
six months.

Patients and their families, however, are left with no option but to purchase the medicines themselves. Anand Ghopre’s son Ashish is being treated at KEM hospital for a fractured leg. He said, “We have been purchasing saline bottles worth Rs1,000 everyday. The nurses and doctors also made me buy hand-gloves, antiseptic bottles and even cotton from the nearby chemist.”

Similarly, Rajnish Patel was in for a rude shock when he shifted his father from a private nursing home to KEM hospital since he could not afford private care anymore. “I was practically paying for everything. These civic hospitals should stop saying that they provide free treatment,” he said.

With around 3,000 patients admitted in the hospital at any given time, lack of saline has become a cause of worry even for the doctors. “With the temperatures soaring, there has been a steady flow of dehydrated patients.

Saline is a must for them and it is sad that we have to rush even the daily wage labourers to chemists,” said one of the resident doctors at KEM hospital. He added that about 70 per cent of the scheduled life-saving drugs were not available in the hospitals.

Interestingly, the Sree Swami Samarth chemist shop located opposite KEM hospital has been doing good business over the last two weeks. An employee who did not wish to be named said they had kept an extra stock of saline bottles due to the sudden increase in demand. When contacted, dean of KEM hospital Dr ME Yeolekar said that they had taken adequate steps to deal with the problem.

“Saline has been made available to all the emergency departments and gradually the supply will be streamlined,” he said, adding, that there was a procedural problem in procuring the drugs and saline.

http://www.dnaindia.com/report.asp?newsid=1162480&pageid=2

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Cipher provides regulatory update for CIP-TRAMADOL ER

Tuesday, May 13, 2008

Cipher Pharmaceuticals Inc. (TSX: DND: 78.89, -0.81, -1.01%) today announced that a revised New Drug Application (NDA) has been submitted to the U.S. Food and Drug Administration (FDA) for CIP-TRAMADOL ER, its extended-release formulation of tramadol. In May 2007, the Company received an approvable letter from the FDA pertaining to its NDA for CIP-TRAMADOL ER.

Cipher's revised NDA includes data from additional pharmacokinetic studies conducted by the Company comparing CIP-TRAMADOL ER to Ultram(R: 73.05, -0.38, -0.51%) ER.

After considering feedback from the FDA appeal process and the results of the additional statistical sensitivity analysis of existing data suggested by the FDA, Cipher and its advisors concluded that submitting the revised NDA provided the most expeditious path to final regulatory approval.

Subject to FDA acceptance for filing, Cipher expects the review to be completed by October 2008. It is possible that the submission could trigger patent infringement litigation and a stay of up to 30 months under the Hatch-Waxman Act.

About Cipher Pharmaceuticals Inc.

Cipher Pharmaceuticals is a drug development company focused on commercializing novel formulations of successful, currently marketed molecules using advanced drug delivery technologies. Cipher's strategy is to in-license products that incorporate proven drug delivery technologies and advance them through the clinical development and regulatory approval stages, after which the products are out-licensed to international partners. Because Cipher's products are based on proven technology platforms applied to currently marketed drugs, they are expected to have lower approval risk, shorter development timelines and significantly lower development costs. The Company's lead compound, CIP-FENOFIBRATE, received final approval from the U.S. Food and Drug Administration and Health Canada in the first quarter of 2006. The product is being marketed in the United States by ProEthic Pharmaceuticals under the label Lipofen(R: 73.05, -0.38, -0.51%). In addition, Cipher is developing formulations of the pain reliever tramadol (FDA approvable letter in May 2007) and the acne treatment isotretinoin (FDA approvable letter in April 2007).

Cipher is listed on the Toronto Stock Exchange under the symbol 'DND' and has approximately 24 million shares outstanding. For more information, please visit www.cipherpharma.com.

http://www.foxbusiness.com/story/markets/industries/health-care/cipher-provides-regulatory-update-cip-tramadol-er/-512036520

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Cipher Submits Revised NDA for CIP-Tramadol ER

Wednesday, 14 May 2008

Cipher Pharmaceuticals has submitted a revised new drug application to the FDA for CIP-Tramadol ER, its extended-release formulation of tramadol.

The company's revised new drug application (NDA) includes data from additional pharmacokinetic studies conducted by the company comparing CIP-Tramadol ER to Ultram ER. Subject to FDA acceptance for filing, the company expects the review to be completed by October 2008.


After considering feedback from the FDA appeal process and the results of the additional statistical sensitivity analysis of existing data suggested by the FDA, the company and its advisors concluded that submitting the revised NDA provided the most expeditious path to final regulatory approval.

http://www.redorbit.com/news/health/1385206/cipher_submits_revised_nda_for_ciptramadol_er/

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Power of the Mind

There should be some clarification of exactly what we are talking about when we use the term "placebo."

Several definitions can be found, but for the purpose of this discussion, we will define placebo as "any therapeutic procedure which has an effect on a patient, symptoms, syndrome or disease but which is objectively without specific activity for the condition being treated."1

The placebo effect should be defined as "a change in the body, or body-mind unit, that occurs as a result of the symbolic significance that one attributes to an event or object in the healing environment."2

Before scientific medicine, those physicians with the most convincing approach and professional charisma were the most effective.

"Physicians clearly knew that even a plain sugar pill - once given to patients with a reassuring and compassionate attitude - could alleviate their suffering."3

Study of the placebo effect was launched by Henry Beecher in 1955 with his paper "The Powerful Placebo," in which he determined that an average of 32 percent of patients respond to a placebo.4

Since that time, research into the placebo effect has flourished. Many have confirmed the one-third placebo response found by Beecher. There have been studies that have attempted to explain away the one-third placebo response due to spontaneous remission.

This attempt was somewhat successful except in the areas related to pain.5 Response to placebo in patients with motor disorders such as Parkinson's disease has also emerged as reproducible.

The Mind Connection
There have been two psychological theories proposed to explain the placebo effect. Classical conditioning suggests that repeated exposure to a given stimulus can evoke a conditioned response over time, even when the stimulus is similar to the original but devoid of its actual therapeutic properties.

An example of this is a sugar pill evoking the same conditioned response as a pain pill because the patient associates the small, round, white pill with pain relief.

This can then be broadened to include nearly anything in the patient/provider environment. The stimulus might be a lab coat, treatment table, modality machine or even the presence of the provider, if these have been previously associated with pain relief.

Expectation theory is the second theory on how the placebo effect works. It contends that if a patient expects or believes he will have a positive response to a treatment, then he will. This positive response occurs even when the treatment has no therapeutic property.

This theory also goes another step, suggesting that the patient will have a negative response if he expects or believes a negative outcome will be obtained from the treatment. This is commonly called the "nocebo" effect. The expectation theory has been shown to operate through the body's endogenous opioid system.6

More recent studies have shown that the placebo effect works through both opioid and non-opioid systems.7 Though it is beyond the scope of this article, there is considerable ongoing research that is tracing the neural pathways that mediate the placebo effect.

One interesting study has even shown specificity in the body's response to placebo effect. Benedetti, et al., have shown that the opioid-mediated placebo response can be directed to specific areas of the body based on specific verbal instructions regarding that body part.8 This was also shown through application of a placebo cream to a specific area of the body.

An important final research finding is that the placebo effect is also able to magnify a legitimate medical treatment. In one example, researchers evaluated the use of four pain medications (buprenorphine, tramadol, ketorolac and metamizol) using open injection with positive verbal cues versus hidden injection through automatic infusion pumps.9 The medication dosage to give 50 percent pain relief was considerably higher in the hidden injection group compared to the open injection group.

Healthcare Meaning
So what does all this mean to the provider? First and foremost, it should remind us that we are treating the whole patient, not just a body part or an injury.

Many times we say things to patients that can have a great positive or negative effect on their outcomes. When someone says to a patient, "Well, your X-ray shows some arthritis, so you may have to learn to live with it," they may have punched that patient's ticket for a lifetime of pain expectation.

Many therapists are familiar with studies that show similar radiology findings in groups of people, some of whom have pain while others have none. We have seen X-rays on patients who have only the slightest amount of arthritic change and they have severe pain. At the same time, we have seen severe arthritic changes on the radiograph, for instance in the hip joint, and wonder how the person even walks - yet they report only mild discomfort.

Is this all based on an individual's natural pain tolerance, or have these patients been given two different sets of expectations?

As we explain our treatment programs to patients, do we meagerly explain what the outcome might be or what we hope it will be, and miss out on great expectations?

Have we seen providers with outstanding knowledge and skills have only mediocre outcomes with patients? Have we seen those with average clinical skills who can almost literally talk a patient into getting better? What we say, how we say it and the environment in which we say it can have an impact on the patient's outcome.

http://lpn.advanceweb.com/editorial/content/editorial.aspx?cc=115908

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Cipher Files Revised NDA for Opioid Pain Drug

Cipher Pharmaceuticals has submitted a revised NDA for CIP-Tramadol ER, an opioid pain reliever, after receiving an approvable letter for the drug a year ago.

The revised NDA includes data from additional pharmacokinetic studies comparing the company’s drug with opioid Ultram ER (tramadol HCl) marketed by Ortho-McNeil and for which Biovail is the patent holder, Cipher President Larry Andrews said.

Last December, Cipher appealed the FDA’s approvable letter, which said an additional clinical trial was needed for the drug. The FDA defended its letter but later told the company a new analysis could be an alternative to a new trial. In February, Cipher said the FDA asked it to do additional statistical sensitivity analysis of existing clinical data on CIP-Tramadol ER (tramadol HCl).

After considering feedback from the FDA appeal process and the results of the additional analysis, Cipher concluded that submitting the revised NDA was the fastest path to final regulatory approval, it said.

CIP-Tramadol ER is a biphasic, extended-release formulation of tramadol, which is used to manage moderate to moderately severe pain. Tramadol is a synthetic opioid molecule developed to have the analgesic efficacy of the opioid family of drugs without the well-known side effects, including addiction, Cipher said.

http://fdanews.com/newsletter/article?issueId=11607&articleId=106928

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Overdosage can induce seizures & respiratory depression

In overdose, tramadol produces significant neurologic toxicity such as seizures, coma and respiratory depression, while cardiovascular toxicity seems to be limited to mild tachycardia and hypertension. When seizures do occur with tramadol use, they are commonly of short duration and are easily treatable. In one reported case of a seizure, the convulsions were induced by naloxone administration. Hence, although respiratory depression in overdose can be treated with the opioid antagonist, naloxone, reversal of all opioid poisoning should be conducted with low doses, repeated as clinically indicated, to avoid rebound effects including pain, hypertension, tachycardia and seizures.

Tramadol contraindicated in patients on MAOIs

There are now a number of case reports, which suggest induction of a serotonin syndrome by combination of tramadol with SSRIs. Such combinations may be used with caution. Although no reports of drug interactions with MAO inhibitors have been published, the concomitant use of MAOIs with tramadol is contraindicated as a safety precaution. Other relevant interactions between tramadol and concomitant medication have not been described. Initial reports of an interaction between tramadol and coumarins with prolongation of INR could not be confirmed.

Caution in epileptics & those on tricyclics, SSRIs, high dose opioids

The issue of possible tramadol-induced seizures has been discussed increasingly in international literature. Overall, there is no good evidence that tramadol use by itself can induce idiopathic seizures, except possibly in excessive doses. However, tramadol should be used with caution in patients with a history of epilepsy and those on concomitant seizure threshold-lowering medication (e.g. tricyclics, selective serotonin re-uptake inhibitors, high dose opioids).

Other adverse effects: nausea, vomiting, sweating

The most common adverse events reported in clinical trials and post-marketing studies were, in decreasing order of frequency (range 7 to 1%): nausea, dizziness, drowsiness, tiredness, fatigue, sweating, vomiting, dry mouth and postural hypotension. Nausea, a well-documented opioid side effect, seems to occur with an incidence comparable to that in other opioids, while vomiting is less common. The incidence of nausea varied with route and setting of administration from 3% in controlled trials of oral medication, to 21% with IV use via patient controlled analgesia (PCA) pumps in the postoperative period. Avoidance of early mobilisation after IV administration, initiation of oral treatment at low doses with gradual increase, and use of antiemetics (phenothiazines and/or 5-HT3-antagonists) can reduce the incidence and severity of this side effect.

Sweating is a side effect specific to tramadol, due to its monoaminergic effects, and it can be quite distressing to a small number of patients. In rare situations, sweating may be severe enough to necessitate discontinuation.

Low dependence potential

The effects of long-term opioid intake on the development of tolerance, physical dependence and psychological addiction are reduced with tramadol use. In an experimental setting, it was demonstrated that even experienced opioid users could not recognise tramadol in lower doses as an opioid, whereas in higher doses they could recognise it, but did not “like” it, presumably due to its tricyclic-like properties. Hence, the incidence of abuse of tramadol is low in all post-marketing surveys; the FDA reports a rate of abuse in the range of 1 in 100,000 patient exposures. Furthermore, tramadol is not registered as a controlled drug in any country. However, this does not mean that its use in “at-risk” patients should be encouraged. Rare cases of withdrawal reactions after abrupt discontinuation of tramadol have also been reported.

Constipation & respiratory depression: less likely, less pronounced

Respiratory depression with tramadol is less pronounced, and occurs less often, in comparison to equianalgesic doses of morphine. In large clinical and post-marketing studies including over 21,000 patients, no clinically relevant respiratory depression was reported. However, respiratory depression can occur, in particular with overdose (as described in children) or with impaired renal function,10 possibly due to retention of the active metabolite M1.

Another opioid side effect, which is reduced with tramadol use, is constipation. Clinically this has proven to be a significant advantage with long-term therapy, but could also be beneficial in the prevention of ileus postoperatively.

Dual mechanism may explain improved side effect profile

The novel way in which tramadol provides analgesia with fewer side effects may be explained by its dual mechanism of action, opioid and monoaminergic. Its major metabolite O-desmethyl tramadol (M1) has a weak affinity at μ-opioid receptors as an agonist. The monoaminergic activity comes through the two stereoisomers of tramadol itself, which act synergistically on serotonergic and noradrenergic mechanisms of pain transmission. More specifically, tramadol enhances spinal pain inhibitory pathways by inhibiting neuronal re-uptake of serotonin (5-HT) and noradrenaline (NA), and stimulating 5-HT release. This added monoaminergic component possibly allows tramadol’s efficacy to stretch over a wider range of painful pathologies than other opioids.

Proven efficacy in a broad range of painful conditions

Tramadol has a dose-dependent efficacy that lies between that of codeine and morphine, with a parenteral potency comparable to that of pethidine, i.e. about 10-20% of the gold standard morphine. Oral bioavailability is high (85-100%) and permits easy conversion from the oral to the parenteral route and visa versa. Surprisingly, the efficacy of tramadol is not associated with the usual serious opioid side effects which can often be dose-limiting. Furthermore, unlike nonsteroidal anti-inflammatory drugs, tramadol has no serious adverse gastrointestinal effects, such as gastrointestinal bleeding. Numerous clinical trials have proven its efficacy and safety over a broad range of painful conditions, both acute and chronic; however, in severe pain morphine may be superior to tramadol. It is this combination of safety with good efficacy that has made tramadol a unique addition to the analgesic armamentarium.

Tramal

Tramadol (Tramal™) is a synthetic, centrally acting analgesic used parenterally and orally for the treatment of moderate to severe pain. It was approved in New Zealand in 1997, but it is not currently funded. Its potency is comparable to that of pethidine, but in severe pain morphine is possibly superior.
Respiratory depression and constipation are less common with tramadol and less pronounced than with other opioids. However, respiratory depression can occur, in particular, after overdose and with impaired renal function. Unlike other opioids, tramadol is not usually associated with the development of tolerance, physical dependence or psychological addiction. In clinical trials the most common adverse reactions, in decreasing frequency, were nausea, dizziness, drowsiness, tiredness, fatigue, sweating, vomiting, dry mouth and postural hypotension. Tramadol may possibly increase the risk of seizures in those with a history of epilepsy or those on medication, which lowers the seizure threshold, but it appears that tramadol does not induce idiopathic seizures except at very high doses. Tramadol is contraindicated in users of MAO inhibitors as a safety precaution and, because of the risk of serotonin syndrome, should be used with caution in combination with SSRIs.
In overdose, tramadol induces significant neurological toxicity (seizures, coma, respiratory depression), but cardiovascular toxicity is mild.

Tramadol (Tramal™) is a synthetic, centrally-acting analgesic used parenterally and orally for the treatment of moderate to severe pain. While tramadol was not granted marketing consent in New Zealand until 1997, and it is not currently listed in the Pharmaceutical Schedule, experience in other countries dates back more than 20 years. In 1998, tramadol became the most used centrally-acting analgesic worldwide; outselling morphine in dollars turned over.1 The success of tramadol is mainly a result of its favourable side effect profile, which differs significantly from that of other opioids.

What other information should I know?

Keep all appointments with your doctor.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

What should I do if I forget a dose?

If your doctor has told you to take tramadol regularly, take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What special precautions should I follow?

Before taking tramadol,

* tell your doctor and pharmacist if you are allergic to tramadol or other opiate pain or cough medications such as meperidine (Demerol), morphine (Avinza, Kadian, MS Contin), codeine (in some pain medications and cough syrups), hydrocodone (in Vicodin), hydromorphone (Dilaudid), oxycodone (OxyContin, in Percocet), propoxyphene (Darvon, Darvon N, in Darvocet), any other medications, or any of the ingredients in tramadol tablets or extended-release tablets. Ask your pharmacist for a list of ingredients in tramadol tablets or extended release tablets.
* tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking. Be sure to mention any of the following: antifungal medications such as ketoconazole (Nizoral); digoxin (Lanoxin); erythromycin (E.E.S., E-Mycin, Erythrocin); monoamine oxidase (MAO) inhibitors, including isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate); medications for anxiety, mental illness, nausea, and pain; medications for seizures, such as carbamazepine (Tegretol); muscle relaxants such as cyclobenzaprine (Flexeril); promethazine (Phenergan); quinidine; rifampin (Rifadin, Rifamate, Rimactane, others); sedatives; sleeping pills; selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft); tranquilizers; tricyclic antidepressants such as amitriptyline (Elavil), amoxapine (Asendin), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Adapin, Sinequan), imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil);and warfarin (Coumadin). Many other medications may also interact with tramadol, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
* tell your doctor what herbal products you are taking, especially St. John's wort.
* tell your doctor if you have or have ever had seizures; an infection in your brain or spine; a head injury, a brain tumor, a stroke, or any other condition that caused high pressure inside your skull; depression or thoughts about harming or killing yourself or planning or trying to do so; diabetes; breathing problems or lung disease; or kidney or liver disease. Also tell your doctor if you drink or have ever drunk large amounts of alcohol, use or have ever used street drugs, or have overused prescription medications.
* tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking tramadol, call your doctor.
* if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking tramadol.
* you should know that this medication may make you drowsy and may affect your coordination. Do not drive a car or operate machinery until you know how this medication affects you.
* talk to your doctor about the safe use of alcohol while you are taking this medication. Alcohol can make the side effects from tramadol worse.
* you should know that tramadol may cause dizziness, lightheadedness, and fainting when you get up from a lying position. To avoid this, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.

How should this medicine be used?

Tramadol comes as a tablet and an extended-release (long-acting) tablet to take by mouth. The regular tablet is usually taken with or without food every 4-6 hours as needed. The extended-release tablet should be taken once a day. Take the extended-release tablet at about the same time of day every day, and either always take it with food or always take it without food. Take tramadol exactly as directed. Do not take more medication as a single dose or take more doses per day than prescribed by your doctor. Taking more tramadol than prescribed by your doctor may cause serious side effects or death.

Your doctor may start you on a low dose of tramadol and gradually increase the amount of medication you take, not more often than every 3 days if you are taking the regular tablets or every 5 days if you are taking the extended-release tablets.

Swallow the extended-release tablets whole; do not split, chew, or crush them. Do not snort (inhale powder from crushed tablet) or inject the dissolved extended-release tablets. Taking this medication in a way that is not recommended may cause serious side effects or death.

Tramadol can be habit-forming. Do not take a larger dose, take it more often, or take it for a longer period of time than prescribed by your doctor. Call your doctor if you find that you want to take extra medication or if you notice any other unusual changes in your behavior or mood.

Do not stop taking tramadol without talking to your doctor. Your doctor will probably decrease your dose gradually. If you suddenly stop taking tramadol you may experience withdrawal symptoms such as nervousness; panic; sweating; difficulty falling asleep or staying asleep; runny nose, sneezing, or cough; numbness, pain, burning, or tingling in your hands or feet; hair standing on end; chills; nausea; uncontrollable shaking of a part of your body; diarrhea; or rarely, hallucinations (seeing things or hearing voices that do not exist).

Why is this medication prescribed?

Tramadol is used to relieve moderate to moderately severe pain. Tramadol extended-release tablets are only used by people who are expected to need medication to relieve pain around-the-clock for a long time. Tramadol is in a class of medications called opiate agonists. It works by changing the way the body senses pain.

Risks Associated With Buying Tramadol Online

We've all heard of the great benefits of buying Tramadol online; better prices, fast FedEx Next Day delivery, and easy prescription approval (if any at all). But with this great convenience comes certain risks of possible catastrophe and disaster. So how does one avoid these risks, yet keep the benefits associated with online pharmacies?

Quality Of Online Tramadol Medication

Since many online pharmacies are foreign-based, there are some conflicting levels of standards implemented in production environment and value. The FDA, for instance, generally holds a high standard on how drugs are produced, developed, and manufactured. The same drug in a third world country, however, may have far less standards in comparison.

As far as quality goes, the resulting product may be of lesser quality. As Tramadol is used as a pain killer, this could be a poor show for buyers. But buying from a reputable foreign online source can help remedy this possible catastrophe.

Risks of Gaming With Tramadol Prescriptions

Another popular fad among some online pharmacies is gaming customers. Since the laws in foreign countries are different, it is almost next to impossible to actually take a person to court over a trivial drug problem and still turn a profit from the ordeal. For this reason, it is recommended that consumers make sure that an online pharmacy is legit and has been running for a couple of years before buying from them.

Some other online pharmacies may also steal financial information from customers, and not be a real pharmacy at all. In this case, the best defense is to verify a pharmacy via various means. The best test to verify a successful and dependable online pharmacy is to check their contact details. If they have a real address and phone number, this is usually an indicator that they are legit (although exceptions are always present).

Possible Legal Issues With Buying Tramadol Online

The Food and Drug Administration, or FDA, claims that it is illegal for United States citizens to buy Tramadol without a prescription. To get around this, customers must obtain a prescription from an online pharmacy. This usually involves having a phone or email interview with an actual pharmacist, in which case the customer will receive the medication up successful conferencing.

But some online pharmacies employ surveys or use pharmacists that are not properly licensed. If this is the case, buyers may be in legal trouble as technically they are buying prescription medication without a real prescription. Customers can get around this catastrophe the same way they can bypass the rest of the problems- ask around and see which online pharmacy is the most dependable. Also do Internet searches to see which online pharmacy has the best reputation, yet still offers the best prices and shipping methods.

Final Thoughts on Risks Associated with Buying Tramadol Online

Tramadol prescriptions are truly a blessing when they can be bought online and delivered to your doorstep the next day via FedEx Next Day shipping. Customers will often find that the savings found in buying online can be seen as a Free Prescription since it is in fact so easy to obtain and costs less money in doing so.

But as stated earlier, it can't be stressed enough that Tramadol should be taken with care and only with a prescription. Be sure to verify an online pharmacy's reputation before buying from them. And if all else fails, there is always the doctor's office visit!

Daniel Millions

Resources For Tramadol Users To Get Prescription Medication

Tramadol is a successful drug used to treat mild to severe pain. It functions much like codeine or morphine would. In comparison to morphine, it is around one tenth as potent. It also has less to no dependency risks- making Tramadol a wise choice in pain medication. But where can Tramadol users get the drug, exactly?

Getting Tramadol The Old-Fashioned Way

If you haven?t been blessed with Internet access (and our condolences if you aren?t), you are more than likely going to be making a visit to the pharmacist. This will require fuel to drive there, extra costs that go to pharmacy services, and of course the inconvenience of leaving one?s own home is present.

But the old-fashioned way isn?t the only option, even if one doesn?t have Internet access. Tramadol users can go online in public libraries to get recurring prescriptions and deliveries of the drug straight to their doorstep via FedEx Next Day. And if Internet access is available at your home- you don?t even have to leave the house!

How To Get Tramadol Online

Tramadol requires a prescription, which means a doctor?s approval is needed. Tramadol users have two choices: visit a real doctor to get the prescription and use it to get Tramadol online, or conference with an online pharmacist to get the prescription.

If a Tramadol user wishes to conference with an online pharmacist, all that is needed is an email account or even a telephone. This allows the pharmacist to ask relevant questions to make sure there will be no complications or unnecessary risks involved with taking Tramadol.

In a sense, online users are getting a Free Prescription. They do not have to pay a doctor for the actual physical and checkup that doctors perform. Instead, a simple phone call or online chat can cut the costs completely. This Free Prescription is a great benefit to those who aren?t too keen on spending more money than they have to.

Special Scenarios For Offline Tramadol Users

If you don?t have the Internet access needed for online pharmacies, there are still options to get the necessary prescription. As stated before, using a public library will allow a recurring billing and shipment to be enabled. The pharmacist can then call a cell phone or home phone at a certain time and date to make sure the prescription will go through.

Although many online pharmacies push email as the number one means of communication because of its lack of cost, most do offer the telephone conferencing option. This simplifies the process even more for Tramadol users, since return visits to the public library will be unnecessary. All that will be needed is a telephone and the number to the online pharmacy.

Final Thoughts On Resources For Tramadol Users

If you;re comfortable with spending unnecessary money on fuel, services, and fees- the old fashioned way may suit you. But for the technology savvy and thrifty individuals, which accounts for most of the population, online pharmacies are fast becoming a new precedent in prescription medication.

It is strongly recommended that Tramadol users take advantage of online pharmacies. As time goes on, the online pharmacy will eventually take over most of the pharmaceutical market. This will be a great gift to consumers who will enjoy the cheaper prices, convenience, and reliability that online pharmacies provide.

Daniel Millions

A New Pharmacy Delivery Service

How easy would it be to get every medication you?ve ever needed delivered directly to your door? It?s fun to think that we can bypass the doctor visit altogether and just get prescription Tramadol via the Internet. But with the advent of new Internet technology, this fun idea has become a reality for prescription Tramadol users all over the world.

Buying Tramadol Medication Online

There is a long list of reasons why one would need to buy Tramadol online. Making the doctors visit may not be plausible due to disability or humiliation. One might also just use the Internet pharmacy as a resource to save money from bloated doctor fees. Whatever the case, there are certain benefits and drawbacks to getting prescription Tramadol delivered to your doorstep.

Because we are ordering from the Internet, we have to get the prescription Tramadol shipped to us. At this point, many Tramadol users are thinking that the shipping would take an elongated amount of time- certainly too long compared to a simple trip to the local pharmacy.

But what many Tramadol users don?t understand is that the worldwide shipping service has become incredibly reliable- and fast! FedEx Next Day shipping is available for shipping prescription Tramadol to users all over the world- and overnight no less. Given, there will be a night?s wait in which the Tramadol user would have to wait longer as compared to the local pharmacy visit, but the benefits at this point outweigh any pitfalls.

Another reason some Tramadol users haven?t made the switch just yet is because of shipping costs. Sure, Tramadol could be shipped to a doorstep overnight, but what about the price? Of course, there is a higher price for faster shipping, but this price can be justified though the savings achieved through purchasing online. Since we are indeed purchasing online, there is no need to pay labor and running costs associated with doctor?s visits, pharmacies, and we even bypass paying for fuel. You could look at it as getting a Free Prescription, since we aren?t paying the doctor a dime!

Lastly, Tramadol users claim that they don?t buy online because they are worried about risks involved with being scammed or buying illegal medication. While it is true there are shady pharmacies online, and pharmacies online without licenses, there are hundreds that provide services in a professional and timely manner. With a little research and good will, there will be not problem at all in finding a worthy online pharmacy for your prescription Tramadol.

To help limit risks, Tramadol users also ask their doctors, family, and friends of good sources they have used on the Internet. It just goes to show that any online source can be shady but all that is needed is perseverance and perhaps a little socialization on your part.

Final Thoughts on Delivery Prescription Tramadol

As it stands, the thought of prescription Tramadol is very exciting indeed. If the extra costs aren?t necessary, why pay them? Tramadol users have been migrating to online services in record numbers. And as time moves on, these numbers will only increases.

Following the reasoning provided in the preceding paragraphs comes down to one single conclusion: buying online prescription Tramadol isn?t risky, it?s thrifty, it?s legal, and above all else- it saves you time and effort otherwise required to get a prescription medication.

Daniel Millions

Pain Medication And Dependency Are You At Risk?

Pain medication is used to relieve surgery patients, those who have been in accidents, and even those with chronic illnesses from different types of aches and sores. But as history has shown, pain medication can cause dependency and addiction in a large majority of its users. So how do you know if you are at risk or not?

Why Pain Medication Is Addicting

Pain medication blocks pain receptors, which gives the human body a sense of euphoria in some instances. This is a rather addicting feeling to have, for obvious reasons. But the interesting part is that once this feeling is achieved, a user starts to become accustomed to the feeling. Therefore, a bigger dosage of medicine is needed- which creates further dependency and addiction issues.

These simple facts are the reason why pain medication has become some of the most widely abused drugs in the world. In many cases, this abuse leads to critical accidents such as overdosing. This goes to show that pain killers can be just as deadly as they are addicting.

Safe Forms of Pain Killers

There are certain forms of prescription medication that allows users to get the best of both worlds: potent pain killing power and little to no risk of dependency or addiction. So how do these safe forms of pain killers work?

One of the newer pain killers on the market, Tramadol, provides around 10% of the power obtained from morphine, but is devoid of the risk and dependency associated with pain killers. Thus, Tramadol has become very popular among the pain killer users. Tramadol still requires a prescription, however, as it is not over the counter medication.

Where To Obtain Safe Pain Killers

Safe pain killers can be acquired over the Internet for easy ordering and receiving. The handy part about ordering online is that FedEx Next Day shipping can be obtained to get the prescription medication the very next day.

Internet users enjoy the online pharmacy craze that has spawned in recent years. Many view it as a way to get a Free Prescription, since the actual doctor's visit is unnecessary. Instead hopeful pain killer users will conference with an online pharmacist that prescribes the medication. Because the online pharmacist will suffer less running and labor costs, the fee is much less than what a normal office visit would be.

Of course, not everyone has Internet access. If that is the case, the trip to the doctor's office and local pharmacy is still viable. Tramadol, as mentioned before requires a prescription. If you do not qualify for Tramadol (which almost everyone should) you should ask your doctor for other alternatives to non habit forming drugs. After all, we are trying to fix problems, not create them!

Final Thoughts On Pain Killers, Dependency, and Addiction

Whatever the solution becomes to relieving pain, take steps to ensure you do not become dependent or addicted to pain killers. Alternatives such as Tramadol are great for those who might be at risk for such behavior. Otherwise, doctor supervision may be required to ensure health use of a drug or product.

If the resulting medication is prescription based, don't forget about the wonders of the Internet- it might just end up saving you some money and wasted effort in getting to the local pharmacy or doctors office.

Daniel Millions

How To Get Tramadol Without A Prescription Legally

There are several reasons as to why one would want to avoid obtaining a prescription for Tramadol. Some don't have the money to pay for a doctor's visit, in addition to the steep fees pharmacies demand for prescriptions such as Tramadol. Others have other reasons, but the goal is the same: how does one get a Tramadol shipment without the prescription?

How To Get Tramadol Without A Prescription

Getting Tramadol without a prescription can be a little tricky, depending on where you live. In the United States, for example, the Food and Drug Administration, or FDA, claims that it is illegal to obtain the drug without a prescription.

There is an interesting loophole to this, however. In foreign countries there are no laws dictating the legality of selling prescription drugs over the Internet to those who live in countries where it is illegal to obtain prescription drugs without the prescription.

Of course, it is completely illegal to buy prescription drugs from a foreign source even if one does import the drug. This hasn't stopped many Tramadol users, however. While some can claim ignorance of drug laws, which may be excusable, most know what they are doing.

Tramadol Without A Prescription: The Process Of Obtaining The Drug

Foreign online pharmacies work much like legal United States online pharmacies do. Although instead of a pharmacist that conducts questions, there is usually a survey that can be taken. It's important to note that surveys aren't always the most accurate source of dictating whether or not a drug is safe to use and a real doctor or pharmacist should be consulted first.

After the survey or conference with an online pharmacist, the order is filled and shipped to the buyer. The buyer at this point enjoys a lot of financial freedom. The prescription is practically a Free Prescription, with the savings incurred from shopping both online and from a foreign source. With these savings, many consumers opt to get FedEx Next Day delivery, which enables the drugs to be at the buyer's doorstep the very next day.

It's important to note that since the FDA does indeed outlaw buying prescription drugs from foreign sources, it may be potentially problematic if one were to get caught doing this. For this reason, it is strongly recommended that consumers instead find a legal United States pharmacy that conforms to FDA standards.

A Legal Way Of Obtaining Tramadol Without A Prescription

As mentioned before, some pharmacies offer surveys instead of pharmacists to conference with. Since surveys do not usually require extensive background checks, almost anyone can get a prescription drug online, although technically it is just like not having a prescription at all since there is no work involved in obtaining the prescription.

Final Thoughts of Obtaining Tramadol Online Without A Prescription

Tramadol, being a prescription drug, may be out of reach for those who need it most. In these trying times, these individuals look for ways to obtain the drug without a prescription. In some cases, there are legal ways- others are less legal. It is highly recommended only legal methods be flowed, and be sure to ultimately give precedence to your own health and safety above all else.

If you end up questioning as to whether or not a pharmacy is legal or safe, the best resource to go to is your usual doctor as a first resort.

Buy pain medications FedEx next day and free prescription Buy Tramadol online FedEx next day and free prescription

Author: Daniel Millions

Storage

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

Special dietary instructions

Talk to your doctor about drinking grapefruit juice while you are taking ULTRAM (tramadol hydrochloride tablets).

Labor and delivery

ULTRAM (tramadol hydrochloride tablets) should not be used in pregnant women prior to or during labor unless the potential benefits outweigh the risks. Safe use in pregnancy has not been established. Chronic use during pregnancy may lead to physical dependence and post-partum withdrawal symptoms in the newborn. Tramadol has been shown to cross the placenta. The mean ratio of serum tramadol in the umbilical veins compared to maternal veins was 0.83 for 40 women given tramadol during labor.

The effect of ULTRAM (tramadol hydrochloride tablets), if any, on the later growth, development, and functional maturation of the child is unknown.

Elderly patient use

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy. In patients over 75 years of age, daily doses in excess of 300 mg are not recommended.

A total of 455 elderly (65 years of age or older) subjects were exposed to ULTRAM (tramadol hydrochloride tablets) in controlled clinical trials. Of those, 145 subjects were 75 years of age and older.

In studies including geriatric patients, treatment-limiting adverse events were higher in subjects over 75 years of age compared to those under 65 years of age. Specifically, 30% of those over 75 years of age had gastrointestinal treatment-limiting adverse events compared to 17% of those under 65 years of age. Constipation resulted in discontinuation of treatment in 10% of those over 75.

Possible side effects

Tramadol may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

* dizziness
* weakness
* sleepiness
* difficulty falling asleep or staying asleep
* headache
* nervousness
* agitation
* uncontrollable shaking of a part of the body
* muscle tightness
* changes in mood
* drowsiness
* heartburn or indigestion
* nausea
* vomiting
* diarrhea
* constipation
* itching
* sweating
* chills
* dry mouth

Some side effects can be serious. If you experience any of these symptoms or those listed in the SPECIAL PRECAUTIONS section , call your doctor immediately:

* seizures
* sores on the inside of your mouth, nose, eyes, or throat
* flu-like symptoms
* hives
* rash
* difficulty swallowing or breathing
* swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
* hoarseness
* hallucinations (seeing things or hearing voices that do not exist)

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online [at http://www.fda.gov/MedWatch/report.htm] or by phone [1-800-332-1088].

Tramadol may cause other side effects. Tell your doctor if you have any unusual problems while you are taking this medication.

Children

Tramadol should not be used in CHILDREN younger than 16 years old; safety and effectiveness in these children have not been confirmed. The use of ULTRAM (tramadol hydrochloride tablets) in the pediatric population is not recommended.

Breastfeeding

Nursing Mothers

ULTRAM (tramadol hydrochloride tablets) is not recommended for obstetrical preoperative medication or for post-delivery analgesia in nursing mothers because its safety in infants and newborns has not been studied. Following a single IV 100 mg dose of tramadol, the cumulative excretion in breast milk within 16 hours postdose was 100 g of tramadol (0.1% of the maternal dose) and 27 µg of M1.

Pregnancy

Tramadol has been shown to be embryotoxic and fetotoxic in mice, (120 mg/kg or 360 mg/m²), rats (≥25 mg/kg or 150 mg/m²) and rabbits (≥75 mg/kg or 900 mg/m²) at maternally toxic dosages, but was not teratogenic at these dose levels. These dosages on a mg/m² basis are 1.4, ≥0.6, and ≥3.6 times the maximum daily human dosage (246 mg/m²) for mouse, rat and rabbit, respectively.

No drug-related teratogenic effects were observed in progeny of mice (up to 140 mg/kg or 420 mg/m²), rats (up to 80 mg/kg or 480 mg/m²) or rabbits (up to 300 mg/kg or 3600 mg/m²) treated with tramadol by various routes. Embryo and fetal toxicity consisted primarily of decreased fetal weights, skeletal ossification and increased supernumerary ribs at maternally toxic dose levels. Transient delays in developmental or behavioral parameters were also seen in pups from rat dams allowed to deliver. Embryo and fetal lethality were reported only in one rabbit study at 300 mg/kg (3600 mg/m²), a dose that would cause extreme maternal toxicity in the rabbit. The dosages listed for mouse, rat and rabbit are 1.7, 1.9 and 14.6 times the maximum daily human dosage (246 mg/m²), respectively.

Missed dose

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

Overdose

In case of Tramadol overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of Tramadol overdose may include:

* decreased size of the pupil (the black circle in the center of the eye)
* difficulty breathing
* extreme drowsiness
* unconsciousness
* coma
* seizure
* heart attack

Dosing instructions

Adults (17 years of age and over)

For patients with moderate to moderately severe chronic pain not requiring rapid onset of analgesic effect, the tolerability of ULTRAM (tramadol hydrochloride tablets) can be improved by initiating therapy with the following titration regimen: ULTRAM (tramadol hydrochloride tablets) should be started at 25 mg/day qAM and titrated in 25 mg increments as separate doses every 3 days to reach 100 mg/day (25 mg q.i.d.). Thereafter the total daily dose may be increased by 50 mg as tolerated every 3 days to reach 200 mg/day (50 mg q.i.d.). After titration, ULTRAM (tramadol hydrochloride tablets) 50 to 100 mg can be administered as needed for pain relief every 4 to 6 hours not to exceed 400 mg/day. For the subset of patients for whom rapid onset of analgesic effect is required and for whom the benefits outweigh the risk of discontinuation due to adverse events associated with higher initial doses, ULTRAM (tramadol hydrochloride tablets) 50 mg to 100 mg can be administered as needed for pain relief every four to six hours, not to exceed 400 mg per day.

Individualization of Dose

Good pain management practice dictates that the dose be individualized according to patient need using the lowest beneficial dose. Studies with tramadol in adults have shown that starting at the lowest possible dose and titrating upward will result in fewer discontinuations and increased tolerability.

* In all patients with creatinine clearance less than 30 mL/min, it is recommended that the dosing interval of ULTRAM (tramadol hydrochloride tablets) be increased to 12 hours, with a maximum daily dose of 200 mg. Since only 7% of an administered dose is removed by hemodialysis, dialysis patients can receive their regular dose on the day of dialysis.
* The recommended dose for adult patients with cirrhosis is 50 mg every 12 hours.
* In general, dose selection for an elderly patient over 65 years old should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy. For elderly patients over 75 years old, total dose should not exceed 300 mg/day.

Warnings and precautions

You should not take tramadol if you have ever been addicted to drugs or alcohol, if you are currently intoxicated (drunk), or if you have recently used any of the following drugs:

*alcohol;
*narcotic pain medicine;
*sedatives or tranquilizers (such as Valium);
*medicine for depression or anxiety;
*medicine for mental illness (such as bipolar disorder, schizophrenia); or
*street drugs.

Seizures have occurred in some people taking tramadol. Your risk of a seizure may be higher if you have any of these conditions:

*a history of drug or alcohol addiction;
*a history of epilepsy or other seizure disorder;
*a history of head injury;
*a metabolic disorder; or
*if you are also taking an antidepressant, muscle relaxer, or medicine for nausea and vomiting.

Talk with your doctor about your individual risk of having a seizure while taking tramadol.

Before taking tramadol, tell your doctor if you are allergic to any drugs, or if you have:

*kidney disease;
*liver disease;
*a stomach disorder; or
*a history of depression, mental illness, or suicide attempt.

If you have any of these conditions, you may need a dose adjustment or special tests to safely take tramadol.
FDA pregnancy category C. This medication may be harmful to an unborn baby. Tramadol may also cause serious or fatal side effects in a newborn if the mother uses the medication during pregnancy or labor. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Tramadol can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. Tramadol should not be given to a child younger than 18 years of age.

Take tramadol exactly as it was prescribed for you. Do not take it in larger doses or for longer than recommended by your doctor. Do not take more than 300 milligrams of tramadol in one day.
Seek emergency medical attention if you think you have used too much of this medicine. A tramadol overdose can be fatal. Overdose symptoms of a tramadol overdose may include drowsiness, shallow breathing, slow heartbeat, extreme weakness, cold or clammy skin, feeling light-headed, fainting, or coma. Tramadol may be habit-forming and should be used only by the person it was prescribed for. Tramadol should never be given to another person, especially someone who has a history of drug abuse or addiction. Keep the medication in a secure place where others cannot get to it. Tramadol can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Do not stop using tramadol suddenly, or you could have unpleasant withdrawal symptoms such as anxiety, sweating, nausea, diarrhea, tremors, chills, hallucinations, trouble sleeping, or breathing problems. Talk to your doctor about how to avoid withdrawal symptoms when stopping the medication. Do not crush the tramadol tablet. This medicine is for oral (by mouth) use only. Powder from a crushed tablet should not be inhaled or diluted with liquid and injected into the body. Using this medicine by inhalation or injection can cause life-threatening side effects, overdose, or death.

Description

ULTRAM® (tramadol hydrochloride tablets) is a centrally acting analgesic. The chemical name for tramadol hydrochloride is (±)cis-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl) cyclohexanol hydrochloride.

The molecular weight of tramadol hydrochloride is 299.8. Tramadol hydrochloride is a white, bitter, crystalline and odorless powder. It is readily soluble in water and ethanol and has a pKa of 9.41. The n-octanol/water log partition coefficient (logP) is 1.35 at pH 7. ULTRAM tablets contain 50 mg of tramadol hydrochloride and are white in color. Inactive ingredients in the tablet are corn starch, hydroxypropyl methylcellulose, lactose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, sodium starch glycolate, titanium dioxide and wax.

What is?

Tramadol is a narcotic-like pain reliever.

Tramadol is used to treat moderate to severe pain. Tramadol extended-release is used to treat moderate to severe chronic pain when treatment is needed around the clock.

Tramadol may also be used for other purposes not listed in this medication guide.

efficacy of once-daily tramadol formulation

Labopharm Inc. (NASDAQ:DDSS) (TSX:DDS) Wednesday said the Food and Drug Administration hasn't overturned the approvable letter it sent the company in May regarding Labopharm's formulation of the analgesic tramadol.

Labopharm said it plans to appeal the matter to the next supervisory level at the FDA.

In May, the FDA sent Labopharm a second approvable letter that said the Canadian company hadn't demonstrated the efficacy of its once-daily tramadol formulation because the statistical methods used to analyze the data didn't adequately address missing data related to subjects who dropped out of the clinical trials.

The first approvable letter from the FDA came in September 2006 and gave the same decision. Labopharm's first appeal led to the second approvable letter in May.

Usage

I - Tramadol is prescribed to treat moderate to moderately severe pain.

Tramadol belongs to the class of drugs known as opiate agonists. Primarily, tramadol works by changing the way the body senses pain. Some people mistakenly believe that tramadol is an NSAID (nonsteroidal anti-inflammatory drug), but it is not.
II - Tramadol is available in immediate release and extended release formulations.

Tramadol may be prescribed as an immediate release tablet (50 mg.) or as an extended release tablet (100, 200, or 300 mg.).

The extended release tablets are usually reserved for patients with chronic pain who require continuous, long-term treatment. Your doctor will determine the appropriate dosage schedule for you.
III - Tramadol extended release tablets must be taken whole, not split, chewed or crushed.

It is important to take tramadol properly and to follow prescribing instructions. If taken improperly or in a way that is not recommended, serious side effects and even death can result.
IV - Tramadol can be habit-forming for some people.

Do not take more tramadol than has been prescribed for you. Taking more tramadol or taking it more often can cause dependency on it. You should also not stop taking tramadol without first consulting your doctor. You may experience withdrawal symptoms if you stopped it suddenly. You doctor will likely decrease your dose of tramadol gradually.
V - Drug interactions are possible with tramadol.

Be aware of the following possible drug interactions:

* Carbamazepine reduces the effect of tramadol
* Quinidine increases the concentration of tramadol by 50-60%
* Combining tramadol with an MAO (monoamine oxidase inhibitor) inhibitor or SSRI (selective serotonin reuptake inhibitors) can lead to seizures or other serious side effects.

Be sure to tell your doctor about all medications you are taking.
VI - Tramadol, when combined with certain other substances, can increase central nervous system and respiratory depression.

In other words, breathing may be affected or even stop if tramadol is combined with alcohol, narcotic drugs, anesthetics, tranquilizers, or sedatives.
VII - The use of tramadol during pregnancy should be avoided.

Because the safety of tramadol use during pregnancy has not been established, the medication should not be used during pregnancy. The safe use of tramadol in nursing mothers has also not been established.
VIII - Tramadol is usually well-tolerated. Any side effects are usually temporary.

Some of the common side effects associated with tramadol include:

* nausea
* constipation
* dizziness
* headache
* drowsiness
* vomiting

There are also less common side effects including: itching, sweating, diarrhea, rash, dry mouth, and vertigo. There have been patients who developed seizures after taking tramadol.
ix - A Cochrane Review of tramadol to treat osteoarthritis revealed some small benefit.

The Cochrane Review stated that when tramadol is taken for up to 3 months, there may be decreased pain, improvements in function and stiffness and overall well-being. However, tramadol can cause side effects that are significant enough to require that the patient must stop taking the medication. Risks outweigh benefits for many people who have tried tramadol.
X - If an overdose of tramadol has occurred, call your local poison control center, or call 911 if it appears to be an emergency situation.

Symptoms of an overdose include decreased pupil size, difficulty breathing or staying awake, unconscious, coma, heart attack, or seizure. Call for help, even if you are unsure about what to do.

Labopharm target

globeandmail.com: MarketsBlog - Labopharm target halved to $1: "For years, verbal jousting between Biovail and Labopharm about the merits of their respective once-daily pain pills has lost its edge these days. In Biovail’s latest quarterly update, U.S. sales of its tramadol pain reliever were lower for the second quarter in a row. That prompted Blackmont Capital to drop its “conversion assumption (generic-to-once-daily tramadol) from 45 per cent to 20 per cent in 2010,” which reduces the overall size of the U.S. market. While Labopharm’s competitive tramadol drug hasn’t cracked the U.S. market because of a dispute with the FDA, lower quarter-over-quarter sales in Europe prompt analyst Laurence Terrisse-Rulleau to suggest the market overseas isn’t responding as quickly as expected. As a result, she halved her Labopharm target price to $1, keeping the stock at “sell.” She figures the drug developer will be forced to conduct additional clinical trials to win U.S. clearance or drop the U.S. market altogether. Labopharm is fractionally higher at $1.24 on the TSX Monday afternoon."

once-daily painkiller tramadol

Print Story - canada.com network: "Labopharm Inc. and Paladin Labs Inc. said on Thursday they sealed a Canadian licensing and distribution agreement giving Paladin exclusive right to market and sell Labopharm's once-daily painkiller tramadol. Under the terms of the deal, Labopharm will receive a transfer price on packaged product supply based on a percentage of the anticipated selling price, as well as up front and milestone payments of up to $1.5-million from Paladin. Labopharm will retain co-promotion rights. The two companies said they expect the product to be launched in Canada this year. Once-daily tramadol, Labopharm's key product, has received regulatory approval in 22 European countries."

once-a-day pill

Print Story - canada.com network: "A pair of local pharmaceutical firms expect considerable financial gain from helping Canadians control their pain with a newly approved, once-a-day prescription pill.

Brass at Paladin Labs Inc. in Montreal and Laval-based Labopharm Inc. jointly announced yesterday a licensing and distribution agreement for a sustained-release version of tramadol, a centrally acting analgesic pain-treatment product.

'With considerable sales potential, Labopharm's once-daily tramadol will become the flagship product in our pain portfolio,' said Jonathan Goodman, president and chief executive officer of Paladin.

'We look forward to launching this unique product into the large and growing Canadian pain-treatment market, which in 2006 reached almost 26 million prescriptions representing sales of more than $800 million.'

Sue Cavallucci at IMS Health Canada in Kirkland, a leading provider of market intelligence to the pharmaceutical and health-care industries, acknowledged the pain-treatment class 'is huge and encompasses several categories.'

But as far as the class that tramadol belongs to - non-narcotic, non-injectable synthetic pain-killer - the public relations manager said there were an estimated 1.46 million prescriptions dispensed from Canadian retail pharmacies last year valued at more than $54 million.

Goodman said the total tramadol market outside Canad"

Labopharm and Palatin Technologies Ink Tramadol Agreement

Labopharm and Palatin Technologies Ink Tramadol Agreement - News, Search Jobs, Events: "Labopharm Inc. (TSX: DDS - News; NASDAQ: DDSS - News) and Paladin Labs Inc. (TSX:PLB - News) today announced that they have completed a licensing and distribution agreement under which Labopharm has granted Paladin the exclusive right to market and sell Labopharm's once-daily tramadol product in Canada. Labopharm will retain co-promotion rights.

'With sales and marketing expertise specific to the pain and central nervous system areas and a strong commitment to our product, Paladin is the right marketing partner for our once-daily tramadol in Canada,' said James R. Howard-Tripp, President and Chief Executive Officer, Labopharm Inc. 'We believe that our once-daily tramadol product will fulfill a need not currently being met within the pain treatment landscape in Canada.'

'With considerable sales potential, Labopharm's once-daily tramadol will become the flagship product in our pain portfolio,' said Jonathan Ross Goodman, President and Chief Executive Officer of Paladin Labs Inc. 'We look forward to launching this unique product into the large and growing Canadian pain treatment market, which in 2006 reached almost 26 million prescriptions representing sales of more than $800 million.'

Under the terms of the agreement, Labopharm will receive a transfer price on packaged product supply based on a percenta"

Once-Daily Tramadol

Labopharm Completes South Korean Licensing and Distribution Agreement for Once-Daily Tramadol: "Labopharm Inc. today announced that it has completed a licensing and distribution agreement for South Korea for its once-daily tramadol product with WhanIn Pharmaceutical Co., Ltd.

'This agreement marks our first foray into Asia as we continue to establish sales channels in key markets around the world as part of the global commercialization program for our once-daily tramadol product,' said James R. Howard-Tripp, President and Chief Executive Officer, Labopharm Inc. 'Standard unit sales of tramadol products in South Korea have grown at a compounded annual rate of 28% over the last five years, reaching 97 million in 2006. We look forward to working with our partner WhanIn toward launch of our once-daily tramadol in this growing market in 2008.'

Under the terms of the agreement, WhanIn will have the exclusive right to market and sell Labopharm's once-daily tramadol product in South Korea. Labopharm will supply WhanIn with product and will receive revenue at rates commensurate with those of previous licensing and distribution agreements that Labopharm has entered into for European markets. Labopharm will also receive an up front payment.

South Korea is the 11th largest pharmaceutical market in the world. For the 12 month period ended September 2005, total pharmaceutical sales were US$7 billion"

Par Pharmaceutical Files Form 10-Q/As for First and Second Quarters of 2006

Par Pharmaceutical Files Form 10-Q/As for First and Second Quarters of 2006: "Par Pharmaceutical Companies, Inc. today filed with the U.S. Securities and Exchange Commission its Form 10-Q/A that restates previously issued consolidated financial statements for the first quarters of 2006 and 2005. Par previously disclosed that, due to inadvertent accounting errors, it would restate its consolidated financial statements for certain prior periods. Today, Par also filed its Form 10-Q/A for the second quarter of 2006. This filing supplements the company's original Form 10-Q filing which did not include Part I, Item 1 (Condensed Consolidated Financial Statements) and Item 2 (Management's Discussion and Analysis of Financial Condition and Results of Operations). Par intends to file its Form 10-Q/A for the third quarter of 2006, its Form 10-K for 2006 and its Form 10-Q for the first quarter of 2007 at the earliest practicable date.

The table below sets forth the impact of the restatement adjustments on the company's reported net income for the three months ended April 1, 2006.


Net Income
(in millions)

2006

"

dose titration of once-daily tramadol at 3rd International Forum on Pain Medicine

Labopharm to present poster on dose titration of once-daily tramadol at 3rd International Forum on Pain Medicine: "Labopharm Inc. today announced that it will present a poster discussing the dose titration of its once-daily formulation of tramadol at the 3rd International Forum on Pain Medicine to be held June 28 to July 1, 2007 in Montreal, Canada.

The poster compares two different titration schedules for Labopharm's once-daily formulation of tramadol in three Phase III clinical trials: a six-day titration to a 300 mg dose (clinical trials MDT3-002 and MDT3-003) and a nine-day titration to a 300 mg dose (clinical trial MDT3-005). The comparison showed that percentage of adverse events and discontinuations due to adverse events was similar regardless of the titration schedule.

These results, in addition to the fact that Labopharm's once-daily tramadol formulation achieves steady state plasma levels after two days, suggest that a shorter titration schedule may be adequate for most patients. A previous study showed that most patients achieve pain control using Labopharm's once-daily tramadol at a dose of 200 mg. The data in this poster suggest that, for most patients, after starting with a dose of 100 mg for two days, the therapeutic dose of 200 mg could be achieved after two days without increased risk of side effects. If a patient requires a higher dose (300 mg), the therapeutic dose"