Ryzolt

• Store Ryzolt between 59°F to 86°F (15°C to 30°C).
• Keep Ryzolt and all medicines out of the reach of children.

This section provides information on the proper use of a number of products that contain tramadol. It may not be specific to Ryzolt. Please read with care.

Take this medicine only as directed by your doctor. 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.

This medicine should come with a Medication Guide. Read and follow the instructions carefully. Ask your doctor if you have any questions.

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 doctor.

If you are using the disintegrating tablet, make sure your hands are dry before you handle the tablet. Do not open the blister pack that contains the tablet until you are ready to take it. Remove the tablet from the blister pack by peeling back the foil, then taking the tablet out. Do not push the tablet through the foil. Do not break, crush, or chew it. Place the tablet in your mouth. It should melt quickly. After the tablet has melted, swallow or take a sip of water.

Swallow the extended-release tablet and tabletwhole with liquids. Do not break, crush, or chew it.

Dosing

The dose of this medicine 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 this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, 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 using the medicine.

• For chronic pain:
  • For oral dosage form (extended-release tablets):
    • Adults—At first, 100 milligrams (mg) once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 300 mg per day.
    • Children—Use and dose must be determined by your doctor.
• For moderate to severe pain:
  • For oral dosage form (disintegrating tablets):
    • Adults and children 16 years of age and older—At first, 50 to 100 milligrams (mg) every four to six hours as needed. Your doctor may increase your dose as needed. However, the dose is usually not more than 400 mg per day.
    • Children younger than 16 years of age—Use and dose must be determined by your doctor.
  • For oral dosage form (tablets):
    • Adults and children 16 years of age and older—At first, 25 milligrams (mg) per day, taken every morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 400 mg per day.
    • Children younger than 16 years of age—Use and dose must be determined by your doctor.

Missed Dose

If 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

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Ryzolt® was studied in four 12-week, randomized, double-blind, controlled studies in patients with moderate to severe pain due to osteoarthritis. Efficacy was demonstrated in one double-blind, placebo-controlled, randomized withdrawal design study. In this study, patients who experienced a reduction of pain and were able to tolerate Ryzolt® during an open-label titration period, were then randomized to Ryzolt® or to placebo for 12 weeks. Sixty-five percent of patients were able to successfully titrate onto Ryzolt®. After a washout, patients randomized to Ryzolt® were titrated to 200 mg or 300 mg of Ryzolt® based on tolerability and remained on that dose for the following 12-week period. Approximately 24% of patients discontinued during the randomized period of the study, with more patients discontinuing from the Ryzolt® arm than the placebo arm due to adverse events (10% vs. 5%, respectively) and more patients discontinuing from the placebo arm than the Ryzolt® arm due to lack of efficacy (10% vs. 8%, respectively). Patients treated with Ryzolt® demonstrated a greater improvement in pain intensity, measured on an 11-point numerical rating scale, at the end of treatment compared to patients randomized to placebo. Figure 3 shows the fraction of patients achieving various degree of improvement in pain from baseline to the end of treatment (week 12). The figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement.

Figure 3. Proportion of Patients Achieving Various Levels of Pain Relief as Measured by 12-Week Pain Intensity.  

Abuse

Ryzolt® is a mu-agonist opioid. Tramadol, like other opioids used in analgesia, can be abused and is subject to criminal diversion.

Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a treatable disease, utilizing a multidisciplinary approach, but relapse is common.

Concerns about abuse and addiction should not prevent the proper management of pain. However all patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use.

“Drug-seeking” behavior is very common in addicts and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. Ryzolt®, like other opioids, may be diverted for non-medical use. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Ryzolt® is intended for oral use only. The crushed tablet poses a hazard of overdose and death. This risk is increased with concurrent abuse of alcohol and other substances. With parenteral abuse, the tablet excipients can be expected to result in local tissue necrosis, infection, pulmonary granulomas, and increased risk of endocarditis and valvular heart injury. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

Dependence

Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Physical dependence is manifested by withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an antagonist.

The opioid abstinence or withdrawal syndrome is characterized by some or all of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. Generally, tolerance and/or withdrawal are more likely to occur the longer a patient is on continuous opioid therapy.

Risk of Overdosage

Serious potential consequences of overdosage with Ryzolt® are central nervous system depression, respiratory depression and death. In treating an overdose, primary attention should be given to maintaining adequate ventilation along with general supportive treatment (see OVERDOSAGE).

Patients should be instructed that:

• Ryzolt® is for oral use only and should be swallowed whole with a sufficient quantity of liquid and not split, chewed, dissolved or crushed.
• Ryzolt® may cause seizures and/or serotonin syndrome with concomitant use of serotonergic agents (including SSRIs, SNRIs and triptans) or drugs that significantly reduce the metabolic clearance of tramadol.
• Ryzolt®should be taken once daily, at approximately the same time every day and that exceeding these instructions can result in respiratory depression, seizures or death.
• Ryzolt®should not be taken in doses exceeding the maximum recommended daily dose as exceeding these recommendations can result in respiratory depression, seizures or even death (see DOSAGE AND ADMINISTRATION)
• Ryzolt®may impair the mental and physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Patients using this drug should be cautioned accordingly.
• Ryzolt®should not be taken with alcohol-containing beverages.
• Ryzolt®should be used with caution when taking medications such as tranquilizers, hypnotics or other opiate containing analgesics.
• Female patients should be instructed to inform the physician if they are pregnant, think they might become pregnant, or are trying to become pregnant (see PRECAUTIONS,Pregnancy and Labor and Delivery).
• Clinical experience suggests that signs and symptoms of withdrawal may be reduced by tapering medication when discontinuing tramadol therapy.
• Patients should be informed to keep Ryzolt®out of reach of children.

Use in Drug and Alcohol Addiction

Ryzolt® is an opioid with no approved use for the management of addictive disorders. Its proper usage in individuals with drug or alcohol dependence, either active or in remission is for the management of pain requiring opioid analgesia.

Drug Interactions

CYP2D6 and CYP3A4 Inhibitors: Concomitant administration of CYP2D6 and/or CYP3A4 inhibitors (see CLINICAL PHARMACOLOGY, Pharmacokinetics), such as quinidine, fluoxetine, paroxetine and amitriptyline (CYP2D6 inhibitors), and ketoconazole and erythromycin (CYP3A4 inhibitors), may reduce metabolic clearance of tramadol increasing the risk for serious adverse events including seizures and serotonin syndrome.

Serotonergic Drugs: There have been postmarketing reports of serotonin syndrome with use of tramadol and SSRIs/SNRIs or MAOIs and α2-adrenergic blockers. Caution is advised when Ryzolt® is coadministered with other drugs that may affect the serotonergic neurotransmitter systems, such as SSRIs, MAOIs, triptans, linezolid (an antibiotic which is a reversible non-selective MAOI), lithium, or St. John’s Wort. If concomitant treatment of Ryzolt® with a drug affecting the serotonergic neurotransmitter system is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases (see WARNINGS, Serotonin Syndrome).

Triptans: Based on the mechanism of action of tramadol and the potential for serotonin syndrome, caution is advised when Ryzolt®is coadministered with a triptan. If concomitant treatment of Ryzolt®with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases (see WARNINGS, Serotonin Syndrome).

Patients taking carbamazepine, a CYP3A4 inducer, may have a significantly reduced analgesic effect. Because carbamazepine increases tramadol metabolism and because of the seizure risk associated with tramadol, concomitant administration of Ryzolt®and carbamazepine is not recommended.

Tramadol is metabolized to M1 by CYP2D6. Quinidine is a selective inhibitor of that isoenzyme, so that concomitant administration of quinidine and tramadol products results in increased concentrations of tramadol and reduced concentrations of M1. The clinical consequences of these findings are unknown. In vitro drug interaction studies in human liver microsomes indicate that tramadol has no effect on quinidine metabolism.

Use with Digoxin and Warfarin

Post-marketing surveillance of tramadol has revealed rare reports of digoxin toxicity and alteration of warfarin effect, including elevation of prothrombin times.

Interaction With Central Nervous System (CNS) Depressants

Ryzolt® should be used with caution and in reduced dosages when administered to patients receiving CNS depressants such as alcohol, opioids, anesthetic agents, narcotics, phenothiazines, tranquilizers or sedative hypnotics. Ryzolt® increases the risk of CNS and respiratory depression in these patients.

Potential of Other Drugs to Affect Tramadol

In vitro drug interaction studies in human liver microsomes indicate that concomitant administration with inhibitors of CYP2D6 such as fluoxetine, paroxetine, and amitriptyline could result in some inhibition of the metabolism of tramadol.

Tramadol is partially metabolized by CYP3A4. Administration of CYP3A4 inhibitors, such as ketoconazole and erythromycin, or inducers, such as rifampin and St. John’s Wort, with Ryzolt®may affect the metabolism of tramadol leading to altered tramadol exposure.

Potential for Tramadol to Affect Other Drugs

In vitro studies indicate that tramadol is unlikely to inhibit the CYP3A4-mediated metabolism of other drugs when administered concomitantly at therapeutic doses. Tramadol is a mild inducer of selected drug metabolism pathways measured in animals.

Carcinogenesis, Mutagenesis and Impairment of Fertility

A slight, but statistically significant increase in two common murine tumors, pulmonary and hepatic, was observed in a mouse carcinogenicity study, particularly in aged mice. Mice were dosed orally up to 30 mg/kg (90 mg/m2 or 0.5 times the maximum daily human dosage of 185 mg/m2) for approximately two years, although the study was not done with the Maximum Tolerated Dose. This finding is not believed to suggest risk in humans. No such finding occurred in a rat carcinogenicity study (dosing orally up to 30 mg/kg - 180 mg/m2 equal to the maximum daily human dosage of tramadol).

Tramadol was not mutagenic in the following assays: Ames Salmonella microsomal activation test, CHO/HPRT mammalian cell assay, mouse lymphoma assay (in the absence of metabolic activation), dominant lethal mutation tests in mice, chromosome aberration test in Chinese hamsters, and bone marrow micronucleus tests in mice and Chinese hamsters. Positive mutagenic results occurred in the presence of metabolic activation in the mouse lymphoma assay and micronucleus test in rats. Relevance of the finding in humans is unknown.

No effects on fertility were observed for tramadol at oral dose levels up to 50 mg/kg (300 mg/m2) in male rats and 75 mg/kg (450 mg/m2) in female rats. These dosages are 1.6 and 2.4 times the maximum daily human dosage of 185 mg/m2, respectively.

Pregnancy

Teratogenic Effects: Pregnancy Category C

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 (≥75mg/kg or 900 mg/m2) at maternally toxic dosages, but was not teratogenic at these dose levels. These dosages on an mg/m2 basis are 1.9, 0.8 and 4.9 times the maximum daily human dosage (185 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 in 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 2.2, 2.6 and 19.4 times the maximum daily human dosage (185 mg/m2), respectively.

Tramadol was evaluated in peri- and post-natal studies in rats. Progeny of dams receiving oral (gavage) dose levels of 50 mg/kg (300 mg/m2 or 1.6 times the maximum daily human Ryzolt dosage) or greater had decreased weights, and pup survival was decreased early in lactation at 80 mg/kg (480 mg/m2 or 2.6 times the maximum daily human dose).

There are no adequate and well-controlled studies in pregnant women. Ryzolt® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonatal seizures, neonatal withdrawal syndrome, fetal death and stillbirth have been reported during post-marketing surveillance of tramadol immediate-release products.

Labor and Delivery

Ryzolt® 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 (see DRUG ABUSE AND ADDICTION). 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 Ryzolt®, if any, on the later growth, development and functional maturation of the child is unknown.

Nursing Mother

Ryzolt®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 µg of tramadol (0.1% of the maternal dose) and 27 µg of M1.

Pediatric Use

The safety and efficacy of Ryzolt®in patients under 16 years of age has not been established. The use of Ryzolt®in the pediatric population is not recommended.

Geriatric Use

In general, caution should be used when selecting the dose for an elderly patient. Usually, dose administration should start 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 (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

In 12-week clinical trials, Ryzolt®was administered to 534 patients aged 65 years and older. Of those, 68 patients were 75 years of age and older. Comparable incidence rates of patients experiencing adverse events were observed for patients older than 65 years of age compared with younger patients (< 65 years of age), except constipation for which the incidence was higher in older patients. Ryzolt®should be used with caution in patients older than 75 years of age (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

Ryzolt®was administered to a total of 2707 subjects (2406 patients and 301 healthy volunteers) during clinical studies, including four randomized double-blind studies (treatment ≥ 12 weeks) and two open-label long-term studies (treatment up to 12 months) in patients with moderate to severe pain due to osteoarthritis of the knee. A total of 844 patients were exposed to Ryzolt®for 12 weeks, 493 patients for 6 months and 243 patients for 12 months. Treatment emergent adverse events increased with dose from 100 mg to 300 mg in the three twelve-week, randomized, double-blind, placebo-controlled studies (Table 2).

The majority of patients who experienced the most common adverse events (≥5%) reported mild to moderate symptoms. Less than 3% of adverse events were rated as severe. Overall, onset of these adverse events usually occurred within the first two weeks of treatment.

Adverse reactions with an incidence of 1.0% to <5.0%

Ear and labyrinth disorders: vertigo

Gastrointestinal disorders: abdominal pain, diarrhea, dry mouth, dyspepsia, upper abdominal pain

General disorders: fatigue, weakness

Investigations: weight decreased

Metabolism and nutrition disorders: anorexia

Musculoskeletal and connective tissue disorders: arthralgia

Nervous system disorders: headache, tremor

Psychiatric disorders: anxiety, insomnia

Skin and subcutaneous tissue disorders: pruritus, sweating increased

Vascular disorders: hot flushes

Adverse reactions with an incidence of <1.0%

Blood and lymphatic system disorders: anemia, thrombocytopenia

Cardiac disorders: bradycardia

Eye disorders: blurred vision, visual disturbance

Gastrointestinal disorders: abdominal discomfort, abdominal distension, abdominal tenderness, change in bowel habit, constipation aggravated, diverticulitis, diverticulum, dyspepsia aggravated, dysphagia, fecal impaction, gastric irritation, gastritis, gastrointestinal hemorrhage, gastrointestinal irritation, gastro-esophageal reflux disease, lower abdominal pain, pancreatitis aggravated, rectal hemorrhage, rectal prolapse, retching

General disorders: asthenia, malaise

Hepatobiliary disorders: biliary tract disorder, cholelithiasis

Immune system disorders: hypersensitivity

Investigations: alanine aminotransferase decreased, alanine aminotransferase increased, aspartate aminotransferase decreased, aspartate aminotransferase increased, blood amylase increased, blood creatinine increased, blood in stool, blood potassium abnormal, blood pressure increased gamma glutamyltransferase increased

Metabolism and nutrition disorders: appetite decreased, dehydration

Nervous system disorders: ataxia, disturbance in attention, dysarthria, gait abnormal, headache aggravated, mental impairment, sedation, seizure, sleep apnea syndrome, syncope, tremor

Psychiatric disorders: abnormal behavior, agitation, anxiety, confusion, depression, emotional disturbance, euphoric mood, indifference, irritability, libido decreased, nervousness, sleep disorder

Renal and urinary disorders: difficulty in micturition, urinary hesitation, urinary retention

Reproductive system and breast disorders: erectile dysfunction, sexual dysfunction

Respiratory, thoracic and mediastinal disorders: dyspnea

Skin and subcutaneous tissue disorders: allergic dermatitis, cold sweat, dermatitis, night sweats, pallor, generalized pruritus, urticaria

Vascular disorders: flushing, hypertension, hypotension, orthostatic hypotension

You should not take Ryzolt if you are allergic to tramadol, or if you have:

• severe asthma or breathing problems;

• a blockage in your stomach or intestines;

• if you have recently used alcohol, sedatives, tranquilizers, or narcotic medications.

Seizures have occurred in some people taking tramadol. Talk with your doctor about your seizure risk, which may be higher if you have:

• a history of head injury, epilepsy or other seizure disorder;

• a history of drug or alcohol addiction;

• a metabolic disorder; or

• if you are also using certain medicines to treat migraine headaches, muscle spasms, depression, mental illness, or nausea and vomiting.

To make sure Ryzolt is safe for you, tell your doctor if you have:

• liver or kidney disease;

• a stomach disorder; or

• a history of drug abuse, alcohol addiction, mental illness, or suicide attempt.

Ryzolt is more likely to cause breathing problems in older adults and people who are severely ill, malnourished, or otherwise debilitated.

Tramadol may be habit forming and should be used only by the person it was prescribed for. Never share Ryzolt 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. Selling or giving away Ryzolt to any other person is against the law.

It is not known whether Ryzolt will harm an unborn baby. If you use tramadol while you are pregnant, your baby could become dependent on the drug. This can cause life-threatening withdrawal symptoms in the baby after it is born. Babies born dependent on habit-forming medicine may need medical treatment for several weeks. Tell your doctor if you are pregnant or plan to become pregnant.

Tramadol can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are taking Ryzolt.

Do not give this medication to anyone younger than 16 years old without the advice of a doctor. Ultram ER should not be given to anyone younger than 18 years old.

Take Ryzolt exactly as prescribed. Follow all directions on your prescription label. Tramadol can slow or stop your breathing, especially when you start using this medicine or whenever your dose is changed. Never take Ryzolt in larger amounts, or for longer than prescribed. Tell your doctor if the medicine seems to stop working as well in relieving your pain.

Ryzolt can be taken with or without food, but take it the same way each time.

Do not crush or break an extended-release Ryzolt tablet. Swallow it whole to avoid exposure to a potentially fatal dose.

Never crush or break a Ryzolt pill to inhale the powder or mix it into a liquid to inject the drug into your vein. This practice has resulted in death with the misuse of tramadol and similar prescription drugs.

The Ryzolt tablet shell may pass into your stools (bowel movements). This is normal and does not mean that you are not receiving enough of the medicine.

Do not stop using Ryzolt suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using tramadol.

Store at room temperature away from moisture and heat.

Keep track of the amount of medicine used from each new bottle. Tramadol is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.

Do not drink alcohol. Dangerous side effects or death can occur when alcohol is combined with Ryzolt. Check your food and medicine labels to be sure these products do not contain alcohol.

Ryzolt may impair your thinking or reactions. Avoid driving or operating machinery until you know how this medicine will affect you. Dizziness or severe drowsiness can cause falls or other accidents.

Applies to tramadol: oral capsule extended release, oral suspension, oral tablet, oral tablet disintegrating, oral tablet extended release

Along with its needed effects, tramadol (the active ingredient contained in Ryzolt) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking tramadol:

• Abdominal or stomach fullness
• abnormal or decreased touch sensation
• blisters under the skin
• bloating
• blood in the urine
• blood pressure increased
• blurred vision
• change in walking and balance
• chest pain or discomfort
• chills
• convulsions (seizures)
• darkened urine
• difficult urination
• dizziness or lightheadedness when getting up from a lying or sitting position
• fainting
• fast heartbeat
• frequent urge to urinate
• gaseous abdominal or stomach pain
• indigestion
• irregular heartbeat
• loss of memory
• numbness and tingling of the face, fingers, or toes
• numbness, tingling, pain, or weakness in the hands or feet
• pain in the arms, legs, or lower back, especially pain in the calves or heels upon exertion
• pain or discomfort in the arms, jaw, back, or neck
• pains in the stomach, side, or abdomen, possibly radiating to the back
• pale bluish-colored or cold hands or feet
• recurrent fever
• seeing, hearing, or feeling things that are not there
• severe cramping
• severe nausea
• severe redness, swelling, and itching of the skin
• sweats
• trembling and shaking of the hands or feet
• trouble performing routine tasks
• weak or absent pulses in the legs
• yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur while taking tramadol:

• Change in consciousness
• decreased awareness or responsiveness
• difficulty with breathing
• lack of muscle tone
• lightheadedness
• loss of consciousness
• pinpointed pupils of the eyes
• severe sleepiness
• slow or irregular heartbeat
• unusual tiredness

Some side effects of tramadol may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abdominal or stomach pain
• agitation
• constipation
• cough
• diarrhea
• discouragement
• drowsiness
• dry mouth
• feeling of warmth
• feeling sad or empty
• feeling unusually cold
• fever
• general feeling of discomfort or illness
• headache
• heartburn
• irritability
• itching or skin rash
• joint pain
• loss of appetite
• loss of interest or pleasure
• loss of strength or weakness
• muscle aches and pains
• nausea
• redness of the face, neck, arms, and occasionally, upper chest
• restlessness
• runny nose
• shivering
• sleepiness or unusual drowsiness
• sore throat
• stuffy nose
• sweating
• tiredness
• trouble concentrating
• unusual feeling of excitement
• weakness

• Abnormal dreams
• appetite decreased
• back pain
• bladder pain
• blistering, crusting, irritation, itching, or reddening of the skin
• bloody or cloudy urine
• body aches or pain
• change in hearing
• clamminess
• cold flu-like symptoms
• confusion
• cough producing mucus
• cracked, dry, or scaly skin
• decreased interest in sexual intercourse
• difficult, burning, or painful urination
• difficulty with moving
• disturbance in attention
• ear congestion
• ear drainage
• earache or pain in ear
• excessive gas
• fall
• false or unusual sense of well-being
• feeling hot
• feeling jittery
• flushing or redness of the skin
• general feeling of bodily discomfort
• goosebumps
• headache, severe and throbbing
• hoarseness
• hot flashes
• inability to have or keep an erection
• itching, pain, redness, swelling, tenderness, or warmth on the skin
• joint sprain
• joint stiffness
• joint swelling
• loss in sexual ability, desire, drive, or performance
• loss of voice
• lower back or side pain
• muscle aching or cramping
• muscle injury
• muscle pain or stiffness
• muscle spasms or twitching
• nasal congestion
• neck pain
• night sweats
• pain
• pain in the limbs
• pain or tenderness around the eyes and cheekbones
• pain, swelling, or redness in the joints
• skin discoloration
• swelling
• swelling of the hands, ankles, feet, or lower legs
• tightness of the chest
• trouble in holding or releasing urine
• trouble with sleeping
• weight increased or decreased