FACTS OF TRAMADOL

1. Tramadol is in a group of drugs called opiate agonists. It is used to treat moderate to severe pain by changing the way the body senses pain.
2. Tramadol can either be taken as a normal tablet or an extended-release (long-acting) tablet to be taken through the mouth. The regular tablet can be taken with or without food every four to six hours or as needed. 
3. The extended-release tablet should only be taken once a day around the same time every day.
4. When using extended-release the patient either needs to always take it with food or always take it without food. 
5. The extended-release tablets should only be taken whole. It is dangerous to split, chew, crush, snort or inject the dissolved form of the tablet.
6. It is important to only take the medication as the doctor prescribes because it is a highly dependent drug.

WHY TRAMADOL?

•  Grünenthal established that Tramadol has a weak respiratory depressant effect when compared with morphine. it changes the way human body feels pain.
• Tramadol provides adequate pain relief in patients with different types of pain.
• Tramadol has many clinical trials have showed that is more effective than other analgesics in some particulars kinds of pain.
• Tramadol has many other trials have demonstrated the acceptable safety profile of a well administered dosage schedule of Tramadol in patients with low back pain and hip or knee osteoarthritis.

TRAMADOL - ADVANTAGES IN BRIEF

• generally well tolerated
• proven efficacy in a broad range of painful conditions
• respiratory depressionis less common and less pronounced than with other opioids 
• lesser constipation effect than with other opioids 
• withdrawal not considered to be as severe as that produced by other opioids
• low abuse and dependence potential 
• more effective than NSAIDs for controlling post operative pain
• antidepressant-like (mood improving) activity 
• local anesthetic activity 
• low interaction potential
• devoid of immunosuppressive activity
• reasonably priced - available generic formulation

HOW TO GET RID OF TRAMADOL ADDICTION?

• Your doctor's advice is the best way to prevent from the tramadol. 

• A popular way to overcome the addiction is the use of  the Waismann Method of Accelerated Neuro-Regulation program.

• This approach requires a stay in hospital for a few days, but is able to handle drug tramadol opioid receptors with the cleaning. 

• A healthy lifestyle in conjunction with the exercises and diet can help control the symptoms. 

• You can also reduce the dependence of tramadol by using the Ginko biloba , fish oil, green tea and vitamin b supplements. 

• In addition, your doctor may recommend counseling and drug treatment program for combating drug tramadol.

SYMPTOMS OF TRAMADOL DRUG ADDICTION

1. If you are addicted to tramadol and are trying to quit the habit, you may end up feeling withdrawal symptoms.
2. Symptoms can vary from moderate to very severe and includeTremors
   Anxiety
   Inability to sleep
   Sweating
   Diarrhea
   Hallucinations
   Pain.
   
3. It is recommended that you do not stop taking the medication abruptly.
4. You will need to gradually get off the drug in order to avoid withdrawal symptoms and not relapse.

TRAMADOL - SIGNS OF ADDICTION

• If a patient is using tramadol in a manner that is inconsistent with treatment, they are addicted to the drug. 
• Inconsistencies include taking higher dosages of the drug or taking tramadol more frequently then you are supposed to. 
• Other signs of addiction include a patient getting multiple prescriptions from different doctors to get more tramadol. 
• You may also be addicted if you are stealing tramadol or you are acquiring the drug from outside sources.

SIGNS OF TRAMADOL DEPENDENCY

1. Experts claim that there is a major difference in the definition of dependency and addiction. Patients who are dependent on the drug only use it because of a condition that is still being treated.
2. Patients who are self-medicating run a higher risk of dependency.
3. In some states, this drug can be purchased over the counter and is another reason for the abuse of tramadol.
4. There is also an increased chance of dependency if the patient is using tramadol for an extended amount of time. 
5. Many doctors report that the dependency for this drug is purely psychological and increased dosage may cause the user to become accustomed to the lessened pain.
6. Anything above the recommended dosage will cause side effects that can harm you. This drug is used to control pain and is not intended for other health conditions

TRAMAOL IS ADDICTIVE OR NOT?

• Tramadol is classified as a narcotic but is not a drug like morphine. 

• Many patients are weary of taking this drug due to its likelihood for addiction. 

• If tramadol is used as recommended, you will not become dependent or addicted to the drug.

• Many patients who use tramadol have claimed that the drug is addicting. 

• A recent study by the Journal of Family Practice found that tramadol has a low risk of addiction. 

• Tramadol is considered to be one of the better pain relievers that is available, but dependence can become an issue if prescriptions are not monitored.

PURPOSE OF TRAMADOL WHO USED IT

1. Generally speaking, people who need relief from pain are the ones who use Tramadol. 
2. This is a drug that goes into your body and slowly releases the pain-killing ingredients over a long period of time. These go to the nerve endings and change the way that you feel the pain, making it so that you are not in agony any longer.
3. Anyone who has felt enduring pain that will not abate on its own is a candidate for this type of a drug.
4. If you are looking for more specific examples, those exist as well. First off, people who have been hurt in car accidents often use Tramadol while they try to heal; this drug lets them sleep so that they can rest and get better. 
5. People who have had surgery will also use it if the surgery was rather invasive and left them with a long recovery time. 
6. People who are growing older and who have been injured through falls and other such accidents will also take this drug for their pain.

BENEFITS OF TRAMADOL

•	Relieves various causes of pain, including post-surgery pain
•	Used to treat chronic pain
•	Can be used with or as an alternative to non-steroidal anti-inflammatory drugs (NSAIDs)

OTHER DRUGS THAT AFFECT TRAMADOL IN PET ANIMALS

• Seizure will appear more if you give tramadol while giving certain other medications. 
• Tell your veterinarian if you are also giving your pet or using any of the following medications: 

1. an MAO inhibitor such as selegiline (Anipryl), Mitaban, or a Preventic Collar; an antidepressant such as amitriptyline, clomipramine (Clomicalm), fluoxetine (Prozac, Reconcile), or acepromazine.
2.  warfarin (Coumadin) 
3. digoxin (Lanoxin) 
4. ketoconazole (Nizoral) 
5. drugs that can cause drowsiness such as other pain medications, muscle relaxants, and herbal products.

• This list is not complete and there may be other medications that can interact with tramadol.

• Tell your veterinarian about all the prescription and over-the-counter medications you give your pet.

• This includes vitamins, minerals and herbal products.

SIDE EFFECTS OF TRAMADOL IN PET ANIMALS

1. Get emergency veterinary medical help if your pet develops these signs of an allergic reaction: hives; difficulty breathing; swelling of the face, lips, tongue, or throat. 
2. Stop using tramadol and call your veterinarian at once if your pet has any of these serious side effects: seizure; a red, blistering, peeling skin rash; or shallow breathing.  
3. Less serious side effects may include: 

• drowsiness, and weakness; 

• vomiting

• constipation

• loss of appetite

• blurred vision

• insomnia.

OVERDOSAGE SYMPTOMS OF TRAMADOL IN PET ANIMALS

Overdose symptoms may include

• drowsiness, 

• shallow breathing, 

• slow heartbeat, 

• extreme weakness, 

• fainting,  

• coma.

Seek emergency veterinary medical attention if you think you have given your pet too much medicine.
An overdose of tramadol can be fatal.

THINGS TO DO WHEN YOU MISS THE DOSAGE OF TRAMADOL IN PET ANIMALS

• Don't forgot to give the correct dosage of tramadol to your pet animals as prescribed by the veterinarian.

• If you miss the dosage,Give the missed dose as soon as you remember.

• If it is almost time for the next dose, skip the missed dose and give the medicine at the next regularly scheduled time. 

• Do not give extra medicine to make up the missed dose.
  

HOW TO GIVE TRAMADOL TO YOUR PET ANIMALS

• Give tramadol exactly as directed by your veterinarian. 

• Do not give it in larger doses or for longer than recommended by your veterinarian. 

• Allow plenty of water for your pet to drink. 

• Tramadol can be given with or without food. 

• Do not crush the tramadol tablet. 

• Do not stop giving tramadol suddenly. 

• Symptoms of sudden withdrawal may include anxiety, nausea, diarrhea, tremors, chills, and breathing problems. Talk to your veterinarian about how to avoid withdrawal symptoms when stopping this medication. 

• Store tramadol at room temperature away from moisture and heat.

THINGS TO KNOW BEFORE GIVING TRAMADOL TO YOUR PET ANIMALS

Do not give tramadol if you are giving your pet any of the following drugs;  

• a narcotic pain medicine, 

• sedatives or tranquilizers (such as Valium),

• medicine for anxiety. 

1. Seizures have occurred in humans taking tramadol. Your pet's risk of seizure may be higher if your pet has any of these conditions; a history of epilepsy or other seizure disorder, a metabolic disorder, or if your pet is being given an antidepressant, muscle relaxer, or medicine for nausea and vomiting. 
2. Tell your veterinarian if your pet is allergic to any medications, or if your pet has kidney disease, liver disease, or a stomach disorder. 
3. Tell your veterinarian if your pet is pregnant or lactating.

INGREDIENTS OF TRAMADOL

1. Tramadol hydrochloride is the main ingredient in any tramadol medication.This is the ingredient that makes it tramadol rather than something else.
2. Other ingredients include corn starch, hypromellose, lactose, magnesium stearate, polysorbate 80, wax, polyethylene glycol, titanium dioxide, sodium starch glycolate and microcrystalline cellulose.  
3. Any other ingredients in medications vary by brand, pill size and any other necessary components of the medication.

BREAST FEEDING WARNIGS OF TRAMADOL

• Tramadol is found in breast milk.

• Do not breast-feed while taking Tramadol.

• Tramadol is excreted into human milk in small amounts.

• The manufacturer suggests that tramadol should not be administered to nursing women.

PREGNANCY WARNINGS OF TRAMADOL

Tramadol has been shown to cause harm to the feotus. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of taking Tramadol while you are pregnant.

Pregnancy warning:

• Tramadol has been assigned to pregnancy category C by the FDA. 
• Animal studies have revealed evidence of embryotoxicity and fetotoxicity. There are no controlled data in human pregnancy. 
• Tramadol should only be given during pregnancy when benefit outweighs risk.
• Tramadol has been shown to cross the placental barrier, with an umbilical vein to maternal vein serum concentration ratio of 0.83.
• A case of tramadol withdrawal in a neonate has been reported following long-term analgesic treatment of the mother.
• At 35 hours of age, the infant showed signs of a severe withdrawal syndrome with high-pitched crying, trembling, and shortened sleeping hours.

DIFFERENCE BETWEEN TRAMADOL AND ULTRAM

TRAMADOL:

• Tramadol is a synthetic opioid pain reliever and it is used to relieve moderate to severe pain.

• Tramadol is an active ingredient (drug substance).

ULTRAM:

• Ultram are immediate release tablets that are used in the management of pain.

• Ultram is a finished pharmaceutical product (tablets: the most common way of administering a medicine). 

They are different things but they have a strong link: Ultram contains Tramadol.

LIST OF VETENARY ANIMALS THAT ARE USING TRAMADOL FOR THEIR PAIN RELIEF

1. Tramadol may be used to treat post-operative, injury-related, and chronic (e.g., cancer-related) pain in 

• Dogs 

• Cats  

• Rabbits

• Coatismany 

• Rats  

• Flying squirrels

• Guinea pigs

• Ferrets

• Raccoons

AVAILABILITY OF TRAMADOL

Tramadol comes in many forms, including:

• capsules (regular and extended release)

• tablets (regular, extended release, chewable, low-residue and/or uncoated tablets that can be taken by the sublingual and buccal routes)

• suppositories

• effervescent tablets and powders

• ampules of sterile solution for SC, IM, and IV injection

• preservative-free solutions for injection by the various spinal routes (epidural, intrathecal, caudal, and others)

• powders for compounding

• liquids both with and without alcohol for oral and sub-lingual administration, available in regular phials and bottles, dropper bottles, bottles with a pump similar to those used with liquid soap and phials with droppers built into the cap

• tablets and capsules containing (acetaminophen/APAP), aspirin and other agents.

HOW TO BUY TRAMADOL ONLINE WITH PRESCRIPTION

Tramadol requires a prescription, which means a doctor’s approval is needed. Tramadol users have two choices: 

1. Visit a real doctor to get the prescription and use it to get Tramadol online, or
2. 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 question 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 fantastic benefit to those who aren’t too keen on spending more money than they have to.

CLINICAL RESULT OF TRAMADOL [ULTRAM]

• Ultracet has been evaluated for efficacy and safety in pivotal single-dose trials in subjects with acute pain.

•  In these trials, subjects with pain following oral surgical procedures who received two tablets of Ultracet experienced greater relief than placebo-treated subjects. 

• Additionally, subjects treated with Ultracet experienced greater relief than subjects on either of the individual components given at the same dose.

• The onset of pain relief after Ultracet (occurring in less than one hour) was faster than with tramadol alone, whereas the duration of pain relief after Ultracet was longer than with acetaminophen alone. Analgesia was found to be generally comparable to ibuprofen.

TRAMADOL IN CHRONIC PAIN MANAGEMENT

• Tramadol extended-release in the management of chronic pain

 

• Chronic, noncancer pain such as that associated with osteoarthritis of the hip and knee is typically managed according to American College of Rheumatology guidelines.

  

• Patients unresponsive to first-line treatment with acetaminophen receive nonsteroidal antiinflammatory drugs (NSAIDs), including cyclooxygenase-2 (COX-2) inhibitors.

DRUG ABUSE AND DEPENDENCE OF TRAMADOL

• Although tramadol can produce drug dependence of the ?-opioid type (like codeine or dextropropoxyphene) and potentially may be abused, there has been little evidence of abuse in foreign clinical experience.

• In clinical trials, tramadol produced effects similar to an opioid, and at supratherapeutic doses was recognized as an opioid in subjective/behavioral studies. 

• Tolerance development has been reported to be relatively mild and withdrawal when present, is not considered to be as severe as that produced by other opioids. 

• Part of tramadol's activity and some extension of the duration of ?-opioid activity. Delayed ?-opioid activity is believed to reduce a drug's abuse liability.

• An assay for tramadol is not included in routine urine screens for drugs of abuse.

CMEMICAL STRUCTURE OF TRAMADOL

TRAMADOL

 

 

Chemical Name:
 

trans-(+/-)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl) cyclohexanol

 

Classification:
 

Non-opiate synthetic analgesic

 

Primary Uses:
 

Analgesia

 

Brand Names:
 

• Ultram

• Ultracet

• Tramal

 

Slang:
 

Tram cars

LEGAL STATUS OF TRAMADOL

• The DEA currently has tramadol listed as a Chemical of Concern, and several states have enacted legislation placing restrictions on the drug.

• In the United States, this drug is not currently controlled under the Controlled Substances Act (CSA). Because it is not controlled, there are no CSA regulations regarding distribution, manufacturing, or prescription of this chemical. 

• According to FDA regulations, sales and distribution are only allowed by those with a valid license. 

• Possession is not illegal for those without a prescription; however, law may differ from state-to-state

THINGS TO AVOID WHILE TAKING TRAMADOL

• Do not drink alcohol. 

• It may cause a dangerous decrease in your breathing when used together with this medicine. 

• Tramadol may impair your thinking or reactions. 

• Be careful if you drive or do anything that requires you to be alert

TRAMADOL INJECTION - A COMPLETE VIEW

            Tramadol is a weak against at all types of opiod receptors with some selectivity for neuroreceptors. It is a good analgesic. But has little respiratory depression and GI effects. No drug dependence or tolerance to analgesic effects occurs.

Indications:
             Severe acute and chronic pain in diagnostic procedures and surgical pain, arthralgia, pain associated with fractures and osteoarthritis.

Dosage:

•   Oral :50-100 mg 2-3 times daily. Maximum 400mg divided doses . 

•    IV/IM/SC 100 mg Child 1.15 mg/kg Maximum 500 mg.

Adverse effects:

•   Sweating 

•    nausea 

•    vomiting 

•   animation 

•   dizziness.

Drug interactions:

            Concomitantly administered tranquillisers and other CNS depressants sedative effects potentiated. MAOI’s fatal interaction occurs opioid analgesics like buprenorphine, butorphanol ans pentazocine may precipitate with drawal symptoms.

CONTRAINDICATIONS OF TRAMADOL

• ULTRAM® (tramadol hcl) should not be administered to patients who have previously demonstrated hypersensitivity to tramadol, any other component of this product or opioids.

• ULTRAM® (tramadol hcl) is contraindicated in any situation where opioids are contraindicated, including acute intoxication with any of the following: 

1. alcohol
2. hypnotics
3. narcotics
4. centrally acting analgesics
5. opioids or psychotropic drugs.

•  ULTRAM® may worsen central nervous system and respiratory depression in these patients.

STORAGE CONDITIONS OF TRAMADOL

• 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.

TRAMADOL IN ANIMALS - GENERAL VIEW

1. For humans, it is sometimes difficult to understand, classify or even study their own pain, so trying to know and relieve animal pain is a difficult task. 
2. It is important to remember that pain perception is similar in all species. Perhaps, the most obvious in animals is the pain after a surgical procedure. To get good results when treating physical pain in animals may take more time because they can’t communicate verbally with us.  
3. Veterinarians and owners should pay attention to all suitable signs of pain through painful behavior. 
4. There are two main types of pains: acute and chronic pain. The first appears on suddenly because of an injury, surgery or an infection. This sort of pain can limit animals’ mobility. The second one is a long lasting pain. Many of the causes of chronic pain are disorders connected with age.

 To investigate pain in animals many clinical studies have been performed for many years. Most of them have used dogs and cats. However, small rodents and rabbits are the main subjects of these studies. Benefits of using painkillers in animals include better surgery recovery, shorter hospitalization time and improvement of respiratory function. Many other treatments and therapies are focused on relieving different kinds of pains. In veterinary medicine, several reasons caused animals suffering. Some of them are: osteoarthritis, cancer pain and neuropathic pain.

    Management of chronic pain can be difficult and sometimes therapy schedules must be designed by combining analgesics with adjuvant medications.There are many products to alleviate pain. The group of drugs called opioids receptors give beneficial relief in suffering animals. Although it is difficult to interpret animal suffering, we all know that providing pain relief, animals will improve their quality of life. Pain is a symptom that should be treated on suspicion. It should be administered up to the veterinarian makes sure that the level of pain has fallen.

    Tramadol for animals is one of the most reliable and useful active principles available to veterinarians for treating animals in pain. It has a dual mode of action: mu agonism and monoamine reuptake inhibition, which produces mild anti-anxiety results. Tramadol may be utilized for relieving pain in cats and dog and this is an advantage because the use of some non-steroidal anti-inflammatory substances in cats may be dangerous.

ADVERSE REACTION OF TRAMADOL IN ANIMALS

When animals are administered Tramadol, adverse reactions can occur.

          

     The most common are:  

• constipation 
  

• upset stomach  
  

• decreased heart rate. 

      In case of overdose:

• mental alteration

• pinpoint pupils 

• seizures                       

       may appear. In such case, veterinarians should evaluate the correct treatment for these events.

               Tramadol can’t be co-administered with Deprenyl or any other psychoactive active ingredient such as: serotonin reuptake inhibitors, tricyclic antidepressants, or monoamine oxidase inhibitors.            

              
               Tramadol for animals is removed from the body via liver and kidney excretion. Thus, if animals suffer from any disease in these systems, it may be necessary to adjust the dose.

DOSAGE AND ADMINISTRATION OF TRAMADOL IN ANIMALS

Dosage of Tramadol for animals:

•  In dogs a starting dosage of 1-2 mg/kg twice a day will be useful for pain management.  

•  Cats are administered 2-4 mg/kg twice a day.

Tramadol for animals overdose: 

•   Owners should take care of veterinarians’ recommendations and follow them strictly. Symptoms associated with overdose may be serious, so it is important to contact the animal’s veterinarian in order to treat it properly.

•   Animal distress and pain may result in physiological changes and the use of Tramadol for animals in such cases should be accompanied by good nursing care to get a better recovery.

•    Veterinary nurse also has an important role in getting the total recuperation for sick animals. 

•    Tramadol for animals is involved in the ethical and compassionate care of animals suffering from pain.     

•    Throughout the results obtained in clinical researches, veterinarians have improved their knowledge of animal pain. This understanding can be added to all the techniques and drug therapies they use everyday for a better animal assistance.

PROPER USE OF TRAMADOL MEDICINE

If you think that this medicine is not working as well after you have been taking it for a few weeks, do not increase the dose . Instead, check with your medical doctor or dentist.

Dosing:
The dose of tramadol will be different for different patients. Follow your doctor's orders or the directions on the label . The following information includes only the average doses of tramadol. If your dose is different, do not change it unless your doctor tells you to do so.

The number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are taking tramadol .

Take this medicine only as directed. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. Using too much of this medicine increases the chance of unwanted effects.

• For chronic pain:
  • For oral dosage form (long-acting tablets):
    • Adults—100 mg once a day. Your doctor may increase your dose as needed. You should not take more than 300 mg per day. 
     
    • Children up to 18 years of age—Use and dose must be determined by your doctor.

 

• For pain:
  • For oral dosage form (tablets):
    • Adults—One-half to two 50-milligram (mg) tablets every four to six hours as needed, no more than 8 tablets in a day
       
    • Your healthcare professional may want you to break the tablets in half for the first dose and increase your dose by half-tablets, up to a maximum of 2 full tablets per dose. By starting at a lower dose and slowly increasing the amount of medicine you take, this will help you get used to the medicine gradually.
      Your healthcare professional may want you to take 2 tablets for the first dose if you are having severe pain. This helps the medicine start working a little faster. 
     
    • Children up to 16 years of age—Use and dose must be determined by your doctor.

Missed dose:

If your medical doctor or dentist has directed you to take this medicine according to a regular schedule and you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage:

To store this medicine:

• Keep out of the reach of children. 

•  Store away from heat and direct light. 

•  Do not store tramadol tablets in the bathroom, near the kitchen sink, or in other damp places. Heat or moisture may cause the medicine to break down. 

•  Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of the reach of children.

 

CLINICAL PHARMACOLOGY OF ULTRAM [TRAMADOL HCL]

Pharmacodynamics

ULTRAM® (tramadol hcl) contains tramadol, a centrally acting synthetic opioid analgesic. Although its mode of action is not completely understood, from animal tests, at least two complementary mechanisms appear applicable: binding of parent and M1 metabolite to μ-opioid receptors and weak inhibition of3reuptake of norepinephrine and serotonin.

Opioid activity is due to both low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabolite M1 to μ-opioid receptors. In animal models, M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in μ-opioid binding. Tramadol-induced analgesia is only partially antagonized by the opiate antagonist naloxone in several animal tests. The relative contribution of both tramadol and M1 to human analgesia is dependent upon the plasma concentrations of each compound .

Tramadol has been shown to inhibit reuptake of norepinephrine and serotonin in vitro, as have some other opioid analgesics. These mechanisms may contribute independently to the overall analgesic profile of ULTRAM® (tramadol hcl) . Analgesia in humans begins approximately within one hour after administration and reaches a peak in approximately two to three hours.

Apart from analgesia, ULTRAM® (tramadol hcl) administration may produce a constellation of symptoms (including dizziness, somnolence, nausea, constipation, sweating and pruritus) similar to that of other opioids. In contrast to morphine, tramadol has not been shown to cause histamine release. At therapeutic doses, ULTRAM® (tramadol hcl) has no effect on heart rate, left-ventricular function or cardiac index. Orthostatic hypotension has been observed.

Pharmacokinetics

The analgesic activity of ULTRAM® (tramadol hcl) is due to both parent drug and the M1 metabolite (see CLINICAL PHARMACOLOGY, Pharmacodynamics). Tramadol is administered as a racemate and both the [-] and [+] forms of both tramadol and M1 are detected in the circulation. Linear pharmacokinetics have been observed following multiple doses of 50 and 100 mg to steady-state.

Absorption

The mean absolute bioavailability of a 100 mg oral dose is approximately 75%. The mean peak plasma concentration of racemic tramadol and M1 occurs at two and three hours, respectively, after administration in healthy adults. In general, both enantiomers of tramadol and M1 follow a parallel time course in the body following single and multiple doses although small differences (~10%) exist in the absolute amount of each enantiomer present.

Steady-state plasma concentrations of both tramadol and M1 are achieved within two days with four times per day dosing. There is no evidence of self-induction (see Figure 1 and Table 1 below).

Food Effects

Oral administration of ULTRAM® (tramadol hcl) with food does not significantly affect its rate or extent of absorption, therefore, ULTRAM® (tramadol hcl) can be administered without regard to food.

Distribution

The volume of distribution of tramadol was 2.6 and 2.9 liters/kg in male and female subjects, respectively, following a 100 mg intravenous dose. The binding of tramadol to human plasma proteins is approximately 20% and binding also appears to be independent of concentration up to 10 μg/mL. Saturation of plasma protein binding occurs only at concentrations outside the clinically relevant range.

Metabolism

Tramadol is extensively metabolized after oral administration by a number of pathways, including CYP2D6 and CYP3A4, as well as by conjugation of parent and metabolites. Approximately 30% of the dose is excreted in the urine as unchanged drug, whereas 60% of the dose is excreted as metabolites. The remainder is excreted either as unidentified or as unextractable metabolites. The major metabolic pathways appear to be N- and O-demethylation and glucuronidation or sulfation in the liver. One metabolite (O-desmethyltramadol, denoted M1) is pharmacologically active in animal models. Formation of M1 is dependent on CYP2D6 and as such is subject to inhibition, which may affect the therapeutic response

Approximately 7% of the population has reduced activity of the CYP2D6 isoenzyme of cytochrome P-450. These individuals are “poor metabolizers” of debrisoquine, dextromethorphan, tricyclic antidepressants, among other drugs. Based on a population PK analysis of Phase I studies in healthy subjects, concentrations of tramadol were approximately 20% higher in “poor metabolizers” versus “extensive metabolizers”, while M1 concentrations were 40% lower. Concomitant therapy with inhibitors of CYP2D6 such as fluoxetine, paroxetine and quinidine could result in significant drug interactions. In vitro drug interaction studies in human liver microsomes indicate that inhibitors of CYP2D6 such as fluoxetine and its metabolite norfluoxetine, amitriptyline and quinidine inhibit the metabolism of tramadol to various degrees, suggesting that concomitant administration of these compounds could result in increases in tramadol concentrations and decreased concentrations of M1. The full pharmacological impact of these alterations in terms of either efficacy or safety is unknown. Concomitant use of SEROTONIN re-uptake INHIBITORS and MAO INHIBITORS may enhance the risk of adverse events, including seizure .

Elimination

Tramadol is eliminated primarily through metabolism by the liver and the metabolites are eliminated primarily by the kidneys. The mean terminal plasma elimination half-lives of racemic tramadol and racemic M1 are 6.3 ± 1.4 and 7.4 ± 1.4 hours, respectively. The plasma elimination half-life of racemic tramadol increased from approximately six hours to seven hours upon multiple dosing.

Special Populations

Renal

Impaired renal function results in a decreased rate and extent of excretion of tramadol and its active metabolite, M1. In patients with creatinine clearances of less than 30 mL/min, adjustment of the dosing regimen is recommended . The total amount of tramadol and M1 removed during a 4-hour dialysis period is less than 7% of the administered dose.

Hepatic

Metabolism of tramadol and M1 is reduced in patients with advanced cirrhosis of the liver, resulting in both a larger area under the concentration time curve for tramadol and longer tramadol and M1 elimination half-lives (13 hrs. for tramadol and 19 hrs. for M1). In cirrhotic patients, adjustment of the dosing regimen is recommended .

Geriatric

Healthy elderly subjects aged 65 to 75 years have plasma tramadol concentrations and elimination half-lives comparable to those observed in healthy subjects less than 65 years of age. In subjects over 75 years, maximum serum concentrations are elevated (208 vs. 162 ng/mL) and the elimination half-life is prolonged (7 vs. 6 hours) compared to subjects 65 to 75 years of age. Adjustment of the daily dose is recommended for patients older than 75 years.

Gender

The absolute bioavailability of tramadol was 73% in males and 79% in females. The plasma clearance was 6.4 mL/min/kg in males and 5.7 mL/min/kg in females following a 100 mg IV dose of tramadol. Following a single oral dose, and after adjusting for body weight, females had a 12% higher peak tramadol concentration and a 35% higher area under the concentration-time curve compared to males. The clinical significance of this difference is unknown.

Clinical Studies

ULTRAM® (tramadol hcl) has been given in single oral doses of 50, 75 and 100 mg to patients with pain following surgical procedures and pain following oral surgery (extraction of impacted molars).
In single-dose models of pain following oral surgery, pain relief was demonstrated in some patients at doses of 50 mg and 75 mg. A dose of 100 mg ULTRAM® (tramadol hcl) tended to provide analgesia superior to codeine sulfate 60 mg, but it was not as effective as the combination of aspirin 650 mg with codeine phosphate 60 mg.

ULTRAM® (tramadol hcl) has been studied in three long-term controlled trials involving a total of 820 patients, with 530 patients receiving ULTRAM® (tramadol hcl) . Patients with a variety of chronic painful conditions were studied in double-blind trials of one to three months duration. Average daily doses of approximately 250 mg of ULTRAM® (tramadol hcl) in divided doses were generally comparable to five doses of acetaminophen 300 mg with codeine phosphate 30 mg (TYLENOL® with Codeine #3) daily, five doses of aspirin 325 mg with codeine phosphate 30 mg daily, or two to three doses of acetaminophen 500 mg with oxycodone hydrochloride 5 mg (TYLOX®) daily.

Titration Trials

In a randomized, blinded clinical study with 129 to 132 patients per group, a 10-day titration to a daily ULTRAM® (tramadol hcl) dose of 200 mg (50 mg four times per day), attained in 50 mg increments every 3 days, was found to result in fewer discontinuations due to dizziness or vertigo than titration over only 4 days or no titration. In a second study with 54 to 59 patients per group, patients who had nausea or vomiting when titrated over 4 days were randomized to re-initiate ULTRAM® (tramadol hcl) therapy using slower titration rates.

A 16-day titration schedule, starting with 25 mg qAM and using additional doses in 25 mg increments every third day to 100 mg/day (25 mg four times per day), followed by 50 mg increments in the total daily dose every third day to 200 mg/day (50 mg four times per day), resulted in fewer discontinuations due to nausea or vomiting and fewer discontinuations due to any cause than did a 10-day titration schedule.

SIMPLE MECHANISM

Mechanism of Action

Tramadol is a centrally acting synthetic opioid analgesic. Although its mode of action is not completely understood, from animal tests, at least two complementary mechanisms appear applicable: binding of parent and M1 metabolite to mu-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin.
Opioid activity is due to both low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabolite M1 to mu-opioid receptors. In animal models, M1 is up to six times more potent than tramadol in producing analgesia and 200 times more potent in mu-opioid binding. Tramadol-induced analgesia is only partially antagonized by the opiate antagonist naloxone in several animal tests. The relative contribution of both tramadol and M1 to human analgesia is dependent upon the plasma concentrations of each compound.

Tramadol has been shown to inhibit reuptake of norepinephrine and serotonin in vitro, as have some other opioid analgesics. These mechanisms may contribute independently to the overall analgesic profile of tramadol.

Acetaminophen is a non-opiate, non-salicylate analgesic. (from Ultracet Prescribing Information)

TRAMADOL WARNINGS

Risk of convulsions may also increase in patients with epilepsy, those with a history of seizures, or in patients with a recognized risk for seizure (such as head trauma, metabolic disorders, alcohol and drug withdrawal, CNS infections). In tramadol overdose, naloxone administration may increase the risk of seizure.

Suicide Risk

• Do not prescribe ULTRAM ER for patients who are suicidal or addiction-prone. 

•  Prescribe ULTRAM ER with caution for patients taking tranquilizers or antidepressant drugs and patients who use alcohol in excess.

• Tell your patients not to exceed the recommended dose and to limit their intake of alcohol.

Serotonin Syndrome Risk

The development of a potentially life-threatening serotonin syndrome may occur with use of tramadol products, including ULTRAM ER, particularly with concomitant use of serotonergic drugs such as SSRIs, SNRIs, TCAs, MAOIs and triptans, with drugs which impair metabolism of serotonin (including MAOIs) and with drugs which impair metabolism of tramadol (CYP2D6 and CYP3A4 inhibitors). This may occur within the recommended dose.

Serotonin syndrome may include mental-status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

BRAND NAMES

• Conzip^®

• Ryzolt^®

• Ultram^®

• Ultram^® ER

10 THINGS YOU SHOULD KNOW ABOUT TRAMADOL

Tramadol Safety Decreases Unwanted Side Effects

Tramadol, the generic version of Ultram, is a synthetic analgesic medication. The exact mode of action of tramadol is unknown but it is said to work like morphine. Tramadol binds to opioid receptors in the brain -- receptors that transmit the sensation of pain throughout the body. Here are 10 things you should know about tramadol to ensure its safe use.

 

1 - 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.

 

2 - 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.

 

3 - 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.

 

4 - 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.

 

5 - 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% to 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.

 

6 - 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.

 

7 - 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.

 

8 - 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

Less common side effects include: itching, sweating, diarrhea, rash, dry mouth, and vertigo. There have been patients who developed seizures after taking tramadol.

 

9 - 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.

 

10 - 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.

OVERDOSAGE CAUSES OF TRAMADOL

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.

MECHANISM OF TRAMADOL

What does “mechanism of action” mean? This phrase refers to the effect that a drug substance causes on a living organism or in a biochemical system. The drug substance can produce four main actions: depressing, stimulating, destroying cells and replacing substances.


The desired activities may be cellular membrane disruption, chemical reaction, interaction with enzyme proteins, interaction with structural proteins, interaction with carrier proteins, interaction with ion channels, binding to receptors, hormone receptors, neuromodulator receptors and neurotransmitter receptors.

Although there are many studies performed on thousands of volunteers to know more about analgesics, Tramadol mechanism of action is not completely understood. From studies with animals, at least two complementary mechanisms seem to be valid: binding of parent and M1 metabolite to µ-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin. The comparative contribution of both Tramadol and M1 to human analgesia depends on the plasma concentrations of each compound. Apart from analgesia, Tramadol may cause a group of symptoms similar to that of an opioid.

The mechanism explained above seems to be a little bit complicated if you are not a scientist but its objective is to clarify why Tramadol can work for treating pain. The different way in which Tramadol provides analgesia with less side effects than the ones caused by other similar products may be explained by Tramadol dual mechanism of action.

In animal and human models both opioid and monaminergic mechanisms contribute to the analgesic efficacy of Tramadol, with the monaminergic mechanism likely accounting for more than half of the analgesic effect.

Tramadol is related to the uptake inhibition of the neurotransmitters noradrenaline and serotonin. Its dual mechanism of action differentiates it from prototypic opioids such as morphine or codeine. This mechanism of action allows Tramadol to have a significant therapeutic importance to improve pain. Tramadol has no clinically related effect on respiratory or cardiovascular parameters. Tramadol may demonstrate particularly useful in patients with poor cardiopulmonary function and in other special patient groups.

Drugs may be classified like any other chemical agent that affects life process. The relationship between the dose administered to a patient and the usefulness on the treatment of the disease he or she suffers from.

Differences between Pharmacokinetics and Pharmacodynamics: The first one is focused on drug quantitative performance in the body. The second one studies the biochemical and physiological effects of the drugs and their mechanism of actions. So, Tramadol mechanism of action explains the effect that Tramadol has on human body functions. In general, drugs can’t create new functions but they are able to modulate the ones that already exist. It has been observed that the drug effects are the result of their relationship with molecules.
Tramadol mechanism of action allows pharmaceutical products that contained Tramadol to produce analgesia that can be compared to Codeine or Dextropropoxyphene. In addition, it produces the beneficial effects that may improve post-surgical pain, obstetric pain, cancer pain and chronic pain of mechanical and neurogenic origin.

Since 2004, there has been a state of uncertainty and controversy about the use of nonsteroidal anti-inflamatory medications and cyclooxygenase (COX)-2 inhibitors, so other analgesics have started to be used for treating moderate to severe pain. This is Tramadol case. Although it was launched in 1977, new uses have been discovered for this active principle.

At the same time, products manufactured with Tramadol may be habit forming. Patients should not take more doses than the ones recommended by their physicians. On the other hand, if they feel that Tramadol mechanism of action is not acting properly, they should contact their healthcare providers immediately.
Because of its mechanism of action, Tramadol may be coadministered with other analgesics, especially those with peripheral action. Drug substances that depress CNS function may enhance the sedative result of Tramadol. When facing a treatment to get pain management, patients should know everything about the drug they will use. Physicians are in charge of providing them with the necessary information to make them feel more confident.

Tramadol mechanism of action is available for those patients who need relief for their pain and suffering. This “mechanism” seems to really “act” as a loyal ally.

IMPORTANT INFORMATION OF TRAMADOL

• You should not take this medication if you are allergic to tramadol, if you have ever been addicted to drugs or alcohol, or if you have ever attempted suicide.

•  Do not take tramadol while you are intoxicated (drunk) or taking any of the following: alcohol or street drugs, narcotic pain medicine, sedatives or tranquilizers, or medicine for depression, anxiety, or mental illness.

•  Seizures (convulsions) have occurred in some people taking this medicine. Tramadol may be more likely to cause a seizure if you have a history of seizures or head injury, a metabolic disorder, or if you are taking certain medicines such as antidepressants, muscle relaxers, narcotic, or medicine for nausea and vomiting.

• Seek emergency medical attention if you think you have used too much of this medicine. A tramadol overdose can be fatal.

• Tramadol may be habit-forming. Tell your doctor if you feel the medicine is not working as well in relieving your pain. Never share tramadol with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it.

• 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.

ADVERSE REACTIONS OF TRAMADOL

ADVERSE REACTIONS

Tramadol hydrochloride tablets were administered to 550 patients during the double-blind or open-label extension periods in U.S. studies of chronic nonmalignant pain. Of these patients, 375 were 65 years old or older. Table 2 reports the cumulative incidence rate of adverse reactions by 7, 30 and 90 days for the most frequent reactions (5% or more by 7 days). The most frequently reported events were in the central nervous system and gastrointestinal system. Although the reactions uled in the table are felt to be probably related to tramadol administration, the reported rates also include some events that may have been due to underlying disease or concomitant medication. The overall incidence rates of adverse experiences in these trials were similar for tramadol and the active control groups, TYLENOL^® with Codeine #3 (acetaminophen 300 mg with codeine phosphate 30 mg), and aspirin 325 mg with codeine phosphate 30 mg, however, the rates of withdrawals due to adverse events appeared to be higher in the tramadol groups.

 
¹ "CNS Stimulation" is a composite of nervousness, anxiety, agitation, tremor, spasticity, euphoria, emotional lability and hallucinations.

Incidence 1% to less than 5%, possibly causally related: the following uls adverse reactions that occurred with an incidence of 1% to less than 5% in clinical trials, and for which the possibility of a causal relationship with tramadol exists.

Body as a Whole: Malaise.

Cardiovascular: Vasodilation.

Central Nervous System: Anxiety, Confusion, Coordination disturbance, Euphoria, Miosis, Nervousness, Sleep disorder.

Gastrointestinal: Abdominal pain, Anorexia, Flatulence.

Musculoskeletal: Hypertonia.

Skin: Rash.

Special Senses: Visual disturbance.

Urogenital: Menopausal symptoms, Urinary frequency, Urinary retention.

Incidence less than 1%, possibly causally related: the following uls adverse reactions that occurred with an incidence of less than 1% in clinical trials and/or reported in post-marketing experience.

Body as a Whole: Accidental injury, Allergic reaction, Anaphylaxis, Death, Suicidal tendency, Weight loss, Serotonin syndrome (mental status change, hyperreflexia, fever, shivering, tremor, agitation, diaphoresis, seizures and coma).

Cardiovascular: Orthostatic hypotension, Syncope, Tachycardia.

Central Nervous System: Abnormal gait, Amnesia, Cognitive dysfunction, Depression, Difficulty in concentration, Hallucinations, Paresthesia, Seizure , Tremor.

Respiratory: Dyspnea
.
Skin: Stevens-Johnson syndrome/Toxic epidermal necrolysis, Urticaria, Vesicles.

Special Senses: Dysgeusia.

Urogenital: Dysuria, Menstrual disorder.

Other adverse experiences, causal relationship unknown: A variety of other adverse events were reported infrequently in patients taking tramadol hydrochloride tablets during clinical trials and/or reported in post-marketing experience. A causal relationship between tramadol hydrochloride tablets and these events has not been determined. However, the most significant events are uled below as alerting information to the physician.

Cardiovascular: Abnormal ECG, Hypertension, Hypotension, Myocardial ischemia, Palpitations, Pulmonary edema, Pulmonary embolism.

Central Nervous System: Migraine, Speech disorders.

Gastrointestinal: Gastrointestinal bleeding, Hepatitis, Stomatitis, Liver failure.

Laboratory Abnormalities: Creatinine increase, Elevated liver enzymes, Hemoglobin decrease, Proteinuria.

Sensory: Cataracts, Deafness, Tinnitus.

OTHER DRUGS THAT AFFECTS TRAMADOL

You may be more likely to have a seizure (convulsions) if you take tramadol while you are using certain other medicines. Do not take tramadol without telling your doctor if you also use any of the following medications:

• an MAO inhibitor such as isocarboxazid (Marplan), tranylcypromine (Parnate), phenelzine (Nardil), or selegiline (Eldepryl, Emsam); or

•  an antidepressant such as amitriptyline (Elavil, Vanatrip), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), imipramine (Tofranil), nortriptyline (Pamelor), paroxetine (Paxil), or sertraline (Zoloft)

Cold or allergy medicine, sleeping pills, muscle relaxers, and medicine for seizures or anxiety can add to sleepiness caused by tramadol. Tell your doctor if you regularly use any of these medicines, or any other pain medication.
Tell your doctor about all other medicines you use, especially:

• carbamazepine (Tegretol)

•  lithium (Eskalith, LithoBid)

•  ADHD medications (Adderall, Ritalin, Strattera)

•  an antibiotic such as clarithromycin (Biaxin), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin), linezolid (Zyvox), rifampin (Rifadin, Rimactane, Rifater); or telithromycin (Ketek)

•  antifungal medication such as clotrimazole (Mycelex Troche), itraconazole (Sporanox), ketoconazole (Extina, Ketozole, Nizoral, Xolegal), or voriconazole (Vfend)

•  cancer medications such as gefitinib (Iressa), imatinib (Gleevec), or nilotinib (Tasigna)

•  a heart rhythm medication such as amiodarone (Cordarone, Pacerone), flecainide (Tambocor), propafenone (Rythmol), or quinidine (Quin-G)

•  heart or blood pressure medication such as diltiazem (Cartia, Cardizem), felodipine (Plendil), nifedipine (Nifedical, Procardia), verapamil (Calan, Covera, Isoptin, Verelan), and others

• HIV/AIDS medicine such as atazanavir (Reyataz), delavirdine (Rescriptor), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), saquinavir (Invirase), or ritonavir (Norvir, Kaletra); or

• migraine headache medicine such as sumatriptan (Imitrex, Treximet)

This list is not complete and there are many other drugs that can interact with tramadol. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you.

DOSAGE AND ADMINISTRATION

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 tramadol can be improved by initiating therapy with initiating therapy with a titration regimen.

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, 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 per 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, 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 tramadol 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.

SIDE EFFECTS OF TRAMADOL

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)
  

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

WHAT PRECAUTIONS SHOULD U FOLLOW BEFORE TRAMADOL

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 tablet. 

• 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.

TRAMADOL GENERAL

What class of treatment is Ultram (Tramadol)?

Category :  Central Nervous System Agents / Analgesics / Miscellaneous Analgesics.

Type        :   Prescription.

TRAMADOL VACINE IMAGE

TRAMADOL VACINAL IMAGES