Aceclofenac/paracetamol/tramadol Uses

• Aceclofenac indications
• Uses of Aceclofenac in details
• Aceclofenac description
• Aceclofenac dosage
• Aceclofenac interactions
• Aceclofenac side effects
• Aceclofenac contraindications
• Paracetamol indications
• Uses of Paracetamol in details
• Paracetamol description
• Paracetamol dosage
• Paracetamol interactions
• Paracetamol side effects
• Paracetamol contraindications
• Tramadol indications
• Uses of Tramadol in details
• Tramadol description
• Tramadol dosage
• Tramadol interactions
• Tramadol side effects
• Tramadol contraindications

Consists of aceclofenac, paracetamol, tramadol

Aceclofenac indications

Articular syndrome (rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gout), degenerative and chronic inflammatory diseases of musculoskeletal system (osteochondrosis, osteoarthritis, periartropatii), post-traumatic inflammation of soft tissue and musculoskeletal system (sprains, bruises). Pain in the spine, neuralgia, myalgia, arthralgia, pain and inflammation after surgery or injury, pain in gout, migraine, algomenorrhea, pain with Bursitis, proctitis, colic (biliary and renal), pain in infectious and inflammatory diseases of ENT organs.

For local use: the inhibition of miosis during surgery for cataract prevention of cystoid macular edema associated with removal and lens implantation, inflammatory eye non-infectious nature, post-traumatic inflammation in penetrating and nonpenetrating wound of the eyeball.

Uses of Aceclofenac in details

It is used to relieve pain and swelling of joints (osteoarthritis), swelling of the small joints of hands and feet (rheumatoid arthritis), arthritis that mainly affect the spine (ankylosing spondylitis).

Aceclofenac description

Aceclofenac also contains the following excipients: Medium chain triglycerides, hard fat, gelatin, D-sorbitol, concentrated glycerin, titanium dioxide, yellow no. 5, red no. 40 and purified water.

Aceclofenac dosage

FC tab: Usual Dose: 100 mg twice daily.

Renal Insufficiency: There is no evidence that the dosage of aceclofenac needs to be modified in patients with mild renal impairment, but as with other NSAIDs, caution should be exercised.

Hepatic Insufficiency: There is some evidence that the dose of aceclofenac should be reduced in patients with hepatic impairment and it is suggested that an initial dose of 100 mg be used.

SR tab: Adults: 1 tablet daily.

Children: There are no clinical data on the use of aceclofenac in children.

Gel: Adults: Gently rub 2-4 g (a circular shaped mass approximately 2-2.5 cm in diameter) 3-4 times daily. Maximum Daily Dose: 16 g. Maximum Weekly Dose: 112 g. A period of at least 4 hrs should be left between applications. The dose should not be applied >4 times in a 24-hr period. After application, the hands should be washed unless this is the treated site. Do not use for >14 days unless recommended by the physician.

Aceclofenac interactions

Lithium: Aceclofenac may increase plasma concentrations of lithium.

Cardiac Glycosides: NSAIDs may exacerbate cardiac failure and reduce the glomerular filtration rate in patients receiving glycosides due to increase plasma glycoside (including digoxin) levels.

Diuretics: Aceclofenac, like other NSAIDs, may inhibit the activity of diuretics. Diuretics can increase the risk of nephrotoxicity of NSAIDs.

Anticoagulants: Like other NSAIDs, Aceclofenac may enhance the activity of anticoagulants.

Methotrexate: Since NSAIDs may increase plasma levels, resulting in increased toxicity, caution should be exercised if NSAIDs and methotrexate are administered within 24 hrs of each other.

Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.

Other NSAIDs and Steroids: Concomitant therapy with aspirin, other NSAIDs and steroids may increase the frequency of adverse reactions, including the risk of gastrointestinal bleeding.

Cyclosporin: Cyclosporin nephrotoxicity may be increased by the effect of NSAIDs on renal prostaglandins.

Aceclofenac side effects

The majority of adverse reactions reported have been reversible and of a minor nature. The most frequent are gastrointestinal disorders, in particular dyspepsia, abdominal pain, nausea and diarrhea, and occasional occurrence of dizziness. Dermatological complaints including pruritus and rash, and abnormal hepatic enzyme and serum creatinine levels have also been reported.

If serious adverse reactions occur, Aceclofenac should be withdrawn.

Inform the physician or pharmacist in case of adverse effects related to Aceclofenac used.

Aceclofenac contraindications

Hypersensitivity to aceclofenac, acetylsalicylic acid or to any of the excipients of Aceclofenac.

FC tab/SR tab: Active or history of recurrent peptic ulcer/haemorrhage (≥2 distinct episodes of proven ulceration or bleeding); NSAIDs are contraindicated in patients who have previously shown hypersensitivity reactions (eg, asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin or other NSAIDs; severe heart, hepatic and renal failure; history of gastrointestinal (GI) bleeding or perforation, related to previous NSAIDs therapy.

Gel: Patients with or without chronic asthma in whom attacks of asthma, urticaria or acute rhinitis are precipitated by aspirin or other NSAIDs; concomitant use of other products containing aceclofenac; concomitant use of oral NSAIDs.

Do not use in children and adolescents <14 years.

Use in pregnancy & lactation: FC tab/SR tab: NSAIDs should not be used during pregnancy or labour unless the potential benefit to the patient outweighs the potential risk to the fetus.

In limited studies available, NSAIDs can appear in the breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breastfeeding.

Gel: Since no experience has been acquired with Aceclofenac gel in pregnancy or lactation, it is not recommended for use in these circumstances.

What is Paracetamol?

Paracetamol (acetaminophen) is a pain reliever and a fever reducer. The exact mechanism of Paracetamol of is not known.

Paracetamol is used to treat many conditions such as headache, muscle aches, arthritis, backache, toothaches, colds, and fevers. It relieves pain in mild arthritis but has no effect on the underlying inflammation and swelling of the joint.

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

Paracetamol indications

For systemic use of Paracetamol Sante Naturelle: prevention and treatment of hypo- and avitaminosis of vitamin C; providing increased need for vitamin C during growth, pregnancy, lactation, with heavy loads, fatigue and during recovery after prolonged severe illness; in winter with an increased risk of infectious diseases.

For intravaginal use: chronic or recurrent vaginitis (bacterial vaginosis, nonspecific vaginitis) caused by the anaerobic flora (due to changes in pH of the vagina) in order to normalize disturbed vaginal microflora.

How should I use Paracetamol?

Use paracetamol exactly as directed on the label, or as prescribed by your doctor.

Do not use more of this medication than is recommended. An overdose of paracetamol can cause serious harm. The maximum amount for adults is 1 gram (1000 mg) per dose and 4 grams (4000 mg) per day. Using more paracetamol could cause damage to your liver. If you drink more than three alcoholic beverages per day, talk to your doctor before taking paracetamol and never use more than 2 grams (2000 mg) per day. If you are treating a child, use a pediatric form of paracetamol. Carefully follow the dosing directions on the medicine label. Do not give the medication to a child younger than 2 years old without the advice of a doctor.

Measure the liquid form of paracetamol with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one. You may need to shake the liquid before each use. Follow the directions on the medicine label.

The paracetamol chewable tablet must be chewed thoroughly before you swallow it.

Make sure your hands are dry when handling the paracetamol disintegrating tablet. Place the tablet on your tongue. It will begin to dissolve right away. Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing.

To use the paracetamol effervescent granules, dissolve one packet of the granules in at least 4 ounces of water. Stir this mixture and drink all of it right away. To make sure you get the entire dose, add a little more water to the same glass, swirl gently and drink right away.

Do not take a paracetamol rectal suppository by mouth. It is for use only in your rectum. Wash your hands before and after inserting the suppository.

Try to empty your bowel and bladder just before using the paracetamol suppository. Remove the outer wrapper from the suppository before inserting it. Avoid handling the suppository too long or it will melt in your hands.

For best results from the suppository, lie down and insert the suppository pointed tip first into the rectum. Hold in the suppository for a few minutes. It will melt quickly once inserted and you should feel little or no discomfort while holding it in. Avoid using the bathroom just after inserting the suppository.

Stop using paracetamol and call your doctor if:

• you still have a fever after 3 days of use;

• you still have pain after 7 days of use (or 5 days if treating a child);

• you have a skin rash, ongoing headache, or any redness or swelling; or

• if your symptoms get worse, or if you have any new symptoms.

Urine glucose tests may produce false results while you are taking paracetamol. Talk to your doctor if you are diabetic and you notice changes in your glucose levels during treatment.

Store paracetamol at room temperature away from heat and moisture. The rectal suppositories can be stored at room temperature or in the refrigerator.

Uses of Paracetamol in details

This drug is used to treat mild to moderate pain (from headaches, menstrual periods, toothaches, backaches, osteoarthritis, or cold/flu aches and pains) and to reduce fever.

How to use Paracetamol

Take this product by mouth as directed. Follow all directions on the product package. If you are uncertain about any of the information, consult your doctor or pharmacist.

There are many brands and forms of acetaminophen available. Read the dosing instructions carefully for each product because the amount of acetaminophen may be different between products. Do not take more acetaminophen than recommended.

If you are giving acetaminophen to a child, be sure you use a product that is meant for children. Use your child's weight to find the right dose on the product package. If you don't know your child's weight, you can use their age.

For suspensions, shake the medication well before each dose. Some liquids do not need to be shaken before use. Follow all directions on the product package. Measure the liquid medication with the provided dose-measuring spoon/dropper/syringe to make sure you have the correct dose. Do not use a household spoon.

For rapidly-dissolving tablets, chew or allow to dissolve on the tongue, then swallow with or without water. For chewable tablets, chew thoroughly before swallowing.

Do not crush or chew extended-release tablets. Doing so can release all of the drug at once, increasing the risk of side effects. Also, do not split the tablets unless they have a score line and your doctor or pharmacist tells you to do so. Swallow the whole or split tablet without crushing or chewing.

For effervescent tablets, dissolve the dose in the recommended amount of water, then drink.

Pain medications work best if they are used as the first signs of pain occur. If you wait until the symptoms have worsened, the medication may not work as well.

Do not take this medication for fever for more than 3 days unless directed by your doctor. For adults, do not take this product for pain for more than 10 days (5 days in children) unless directed by your doctor. If the child has a sore throat (especially with high fever, headache, or nausea/vomiting), consult the doctor promptly.

Tell your doctor if your condition persists or worsens or if you develop new symptoms. If you think you may have a serious medical problem, get medical help right away.

Paracetamol description

Paracetamol is an organic compound that consists of a six-membered ring containing two opposing nitrogen atoms. Paracetamol exists as small alkaline deliquescent crystals with a saline tasteacinol was introduced to medicine as a solvent for uric acid. When taken into the body the drug is partly oxidized and partly eliminated unchanged. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successfulacinol was first introduced as an anthelmintic in 1953. A large number of piperazine compounds have anthelmintic Paracetamol. Their mode of Paracetamol is generally by paralysing parasites, which allows the host body to easily remove or expel the invading organism.

Paracetamol dosage

Usual Adult Paracetamol Dose for Fever:

General Dosing Guidelines: 325 to 650 mg every 4 to 6 hours or 1000 mg every 6 to 8 hours orally or rectally.

Paracetamol 500mg tablets: Two 500 mg tablets orally every 4 to 6 hours

Usual Adult Paracetamol Dose for Pain:

General Dosing Guidelines: 325 to 650 mg every 4 to 6 hours or 1000 mg every 6 to 8 hours orally or rectally.

Paracetamol 500mg tablets: Two 500 mg tablets orally every 4 to 6 hours

Usual Pediatric Dose for Fever:

Oral or Rectal:

<=1 month: 10 to 15 mg/kg/dose every 6 to 8 hours as needed.

>1 month to 12 years: 10 to 15 mg/kg/dose every 4 to 6 hours as needed (Maximum: 5 doses in 24 hours)

Fever: 4 months to 9 years: Initial Dose: 30 mg/kg (Reported by one study (n=121) to be more effective in reducing fever than a 15 mg/kg maintenance dose with no difference regarding clinical tolerance.)

>=12 years: 325 to 650 mg every 4 to 6 hours or 1000 mg every 6 to 8 hours.

Usual Pediatric Dose for Pain:

Oral or Rectal:

<=1 month: 10 to 15 mg/kg/dose every 6 to 8 hours as needed.

>1 month to 12 years: 10 to 15 mg/kg/dose every 4 to 6 hours as needed (Maximum: 5 doses in 24 hours)

Fever: 4 months to 9 years: Initial Dose: 30 mg/kg (Reported by one study (n=121) to be more effective in reducing fever than a 15 mg/kg maintenance dose with no difference regarding clinical tolerance.)

>=12 years: 325 to 650 mg every 4 to 6 hours or 1000 mg every 6 to 8 hours.

Paracetamol interactions

See also:
What other drugs will affect Paracetamol?

With the simultaneous use with inducers of microsomal liver enzymes, means having hepatotoxic effect, increasing the risk of hepatotoxic Paracetamol of paracetamol.

With the simultaneous use of anticoagulants may be slight to moderate increase in prothrombin time.

With the simultaneous use of anticholinergics may decrease absorption of paracetamol.

With the simultaneous use of oral contraceptives accelerated excretion of paracetamol from the body and may reduce its analgesic Paracetamol.

With the simultaneous use with urological means reduced their effectiveness.

With the simultaneous use of activated charcoal reduced bioavailability of paracetamol.

When Paracetamol applied simultaneously with diazepam may decrease excretion of diazepam.

There have been reports about the possibility of enhancing mielodepression effect of zidovudine while applying with paracetamol. A case of severe toxic liver injury.

Described cases of toxic effects of paracetamol, while the use of isoniazid.

When applied simultaneously with carbamazepine, phenytoin, phenobarbital, primidonom decreases the effectiveness of paracetamol, which is caused by an increase in its metabolism and excretion from the body. Cases of hepatotoxicity, while the use of paracetamol and phenobarbital.

In applying cholestyramine a period of less than 1 h after administration of paracetamol may decrease of its absorption.

At simultaneous application with lamotrigine moderately increased excretion of lamotrigine from the body.

With the simultaneous use of metoclopramide may increase absorption of paracetamol and its increased concentration in blood plasma.

When applied simultaneously with probenecid may decrease clearance of paracetamol, with rifampicin, sulfinpyrazone - may increase clearance of paracetamol due to increasing its metabolism in the liver.

At simultaneous application of Paracetamol with ethinylestradiol increases absorption of paracetamol from the gut.

Enhances the effect of indirect anticoagulants (coumarin derivatives and indandione). Antipyretic and analgesic activity of caffeine increases, reduce - rifampicin, phenobarbital and alcohol (accelerated biotransformation, inducing microsomal liver enzymes).

Paracetamol side effects

See also:
What are the possible side effects of Paracetamol?

Effects due to the presence of acetylsalicylic acid.

Accidents awareness with respiratory or skin reactions (angioedema, urticaria, asthma, anaphylactic shock);

Cross hypersensitivity reactions with NSAIDs and with tartrazine;

At low doses recommended for the use of Paracetamol, side effects of aspirin are generally limited to some irritation of the gastro-intestinal tract.

At higher doses, side effects include gastrointestinal mucosal erosions, gastric ulcer or duodenal ulcer, occult blood loss, melena.

Acetylsalicylic acid may also increase the tendency to bleeding and bleeding time (the lengthening of bleeding continues 4-6 days after stopping the drug).

It may also worsen renal function including cases of pre-existing condition (the long-term use can cause chronic kidney disease).

The signs of salicylic overdose described under.

Effects due to the presence of paracetamol.

At the doses and duration of recommended treatment, side effects are usually negligible, but the prolonged use of paracetamol in therapeutic doses large (2-4 g per day, or 10-20 tablets Paracetamol) may cause the appearance chronic hepatitis. This justifies the recommendations of caution especially in patients with liver disease prior.

Very rarely, it can produce thrombocytopenia.

The acute liver toxicity in overdose massive (doses greater than 8 g of paracetamol) is described in paragraph overdose.

Paracetamol contraindications

See also:
What is the most important information I should know about Paracetamol?

Paracetamol should not be used in patients who have previously exhibited hypersensitivity to aspirin and/or nonsteroidal antiinflammatory agents. Paracetamol should not be given to patients with a recent history of gastrointestinal bleeding or in patients with bleeding disorders (e.g., hemophilia).

What is Tramadol?

Tramadol is an pain medicine similar to an opioid. Tramadol is used to treat moderate to severe pain.

The extended-release form of tramadol is for around-the-clock treatment of pain. This form of tramadol is not for use on an as-needed basis for pain.

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

Tramadol indications

Adults

Tramadol® (tramadol hydrochloride) is indicated for the management of moderate to moderately severe pain in adults.

Geriatrics ( > 65 Years of Age)

Healthy elderly subjects aged 65 to 75 years administered tramadol have plasma concentrations and elimination half-lives comparable to those observed in healthy subjects less than 65 years of age. Tramadol® should be administered with greater caution in patients older than 75 years, due to the greater potential for adverse events in this population.

Pediatrics ( < 18 Years of Age)

The safety and effectiveness of Tramadol® have not been studied in the pediatric population. Therefore, use of Tramadol® tablets is not recommended in patients under 18 years of age.

How should I use Tramadol?

Use Tramadol as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Tramadol by mouth with or without food.
• To open the blister pack, peel back the foil on the blister. Do NOT push the tablet through the foil.
• Do NOT chew, break, or split the tablet.
• To take Tramadol, place the tablet in your mouth. Let it dissolve, and then swallow it with saliva. Tramadol may be taken with or without water.
• If you miss a dose of Tramadol and you are taking it regularly, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Tramadol.

Uses of Tramadol in details

Use: Labeled Indications

Pain management:

Extended release: Management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

Immediate release: Management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Limitations of use: Reserve tramadol for use in patients for whom alternative treatment options (eg, nonopioid analgesics) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Tramadol ER is not indicated as an as-needed analgesic.

Off Label Uses

Premature ejaculation

Data from mostly placebo-controlled clinical trials suggest that tramadol may be beneficial for the treatment of premature ejaculation.

Tramadol description

A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of morphine. It also has a depressant Tramadol on the cough center and may be given to control intractable cough associated with terminal lung cancer. Tramadol is also used as part of the treatment of dependence on opioid drugs, although prolonged use of methadone itself may result in dependence. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3)

Tramadol dosage

Tramadol should not be used in patients with:

•

creatinine clearance less than 30 mL/min,

•

severe hepatic impairment (Child-Pugh Class C)

.

Tramadol must be swallowed whole and must not be chewed, crushed, or split.

Adults (18 years of age and over)

Patients Not Currently on Tramadol Immediate-Release Products

For patients not currently treated with tramadol immediate-release (IR) products, Tramadol should be initiated at a dose of 100 mg once daily and titrated up as necessary by 100-mg increments every five days to relief of pain and depending upon tolerability. Tramadol should not be administered at a dose exceeding 300 mg per day.

Patients Currently on Tramadol Immediate-Release Products

For patients maintained on tramadol IR products, calculate the 24-hour tramadol IR dose and initiate a total daily dose of Tramadol rounded down to the next lowest 100 mg increment. The dose may subsequently be individualized according to patient need. Due to limitations in flexibility of dose selection with Tramadol, some patients maintained on tramadol IR products may not be able to convert to Tramadol. Tramadol should not be administered at a dose exceeding 300 mg per day. The concomitant use of Tramadol with other tramadol products is not recommended.

Individualization of Dose

Good pain management practice dictates that the dose be individualized according to patient need using the lowest beneficial dose. Start at the lowest possible dose and titrate upward as tolerated to achieve an adequate effect. Clinical studies of Tramadol have not demonstrated a clinical benefit at a total daily dose exceeding 300 mg.

In general, dosing of an elderly patient (over 65 years of age) should be initiated cautiously, 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. Tramadol should be administered with even greater caution in patients over 75 years, due to the greater frequency of adverse events seen in this population.

Tramadol interactions

See also:
What other drugs will affect Tramadol?

CYP2D6 and CYP3A4 Inhibitors: Concomitant administration of CYP2D6 and/or CYP3A4 inhibitors, 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 Tramadol 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 Tramadol 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.

Triptans

Based on the mechanism of Tramadol of tramadol and the potential for serotonin syndrome, caution is advised when Tramadol is coadministered with a triptan. If concomitant treatment of Tramadol with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.

Use With Carbamazepine

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

Use With Quinidine

Coadministration of quinidine with Tramadol resulted in a 50-60% increase in tramadol exposure and a 50-60% decrease in M1 exposure. The clinical consequences of these findings are unknown.

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.

Potential for 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.

Administration of CYP3A4 inhibitors, such as ketoconazole and erythromycin, or inducers, such as rifampin and St. John's Wort, with Tramadol may affect the metabolism of tramadol leading to altered tramadol exposure.

Potential for Tramadol to Affect Other Drugs

In vitro drug interaction studies in human liver microsomes indicate that tramadol has no effect on quinidine metabolism. 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.

Tramadol side effects

See also:
What are the possible side effects of Tramadol?

Adverse Drug Reaction Overview

The most commonly reported adverse reactions are dizziness, nausea, constipation, headache, somnolence and vomiting as presented in Table 1.1.

Clinical Trial Adverse Drug Reactions

Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.

Incidence of Adverse Reactions for Tramadol® in Chronic Trials of Non-Malignant Pain (Non-titration Trials)

Tramadol® was administered to 550 patients during the double-blind or open-label extension periods in studies of chronic non-malignant pain. Of these patients, 375 were 65 years old or older. Table 1.1 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. The overall incidence rates of adverse experiences in these trials were similar for Tramadol® and the active control groups, acetaminophen with codeine, and aspirin with codeine; however, the rates of withdrawals due to adverse events appeared to be higher in the Tramadol® group. In the tramadol treatment groups, 16.8-24.5% of patients withdrew due to an AE, compared to 9.6-11.6% for acetaminophen with codeine and 18.5% for aspirin with codeine.

Table 1.1: Cumulative Incidence of Adverse Reactions for Tramadol® in Chronic Trials of Non-Malignant Pain

Incidence 1% to less than 5% possibly causally related: the following lists 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 lists 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® during clinical trials and/or reported in post-marketing experience. A causal relationship between Tramadol® and these events has not been determined. However, the most significant events are listed 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 Adverse Experiences Previously Reported in Clinical Trials or Post-Marketing Reports with Tramadol Hydrochloride

Adverse events which have been reported with the use of tramadol products include: allergic reactions (including anaphylaxis, angioneurotic edema and urticaria), bradycardia, convulsions, drug dependence, drug withdrawal (including agitation, anxiety, gastrointestinal symptoms, hyperkinesia, insomnia, nervousness, tremors), hyperactivity, hypoactivity, hypotension, worsening of asthma and respiratory depression. Other adverse events which have been reported with the use of tramadol products and for which a causal association has not been determined include: difficulty concentrating, hepatitis, liver failure, pulmonary edema, Stevens-Johnson syndrome and suicidal tendency.

Serotonin syndrome (whose symptoms may include mental status change, hyperreflexia, fever, shivering, tremor, agitation, diaphoresis, seizures and coma) has been reported with tramadol when used concomitantly with other serotonergic agents such as SSRIs and MAOIs. Post-marketing experience with the use of tramadol-containing products included rare reports of delirium, miosis, mydriasis, and speech disorder, and very rare reports of movement disorder including dyskinesia and dystonia.

Cases of hypoglycemia have been reported in patients taking tramadol, mostly in patients with pre-disposing risk factors, including diabetes, elderly and renal insufficiency. Caution should be exercised when prescribing tramadol to diabetic patients. More frequent monitoring of blood glucose levels may be appropriate, including at initiation or dose increase.

Drug Abuse, Addiction And Dependence

Tramadol may induce psychic and physical dependence of the morphine-type (μ-opioid). Dependence and abuse, including drug-seeking behaviour and taking illicit actions to obtain the drug are not limited to those patients with a prior history of opioid dependence. The risk in patients with substance abuse has been observed to be higher. Tramadol is associated with craving and tolerance development.

A Risk Management program to support the safe and effective use of Tramadol® has been established. The following are considered to be the essential components of the Risk Management program:

1. Commitment to not emphasize or highlight the scheduling status of Tramadol® (i.e., not listed under a schedule to the CDSA) in its advertising or promotional activities.
2. Inclusion of a PAAB-approved fair balance statement in all Tramadol® advertising and promotional materials.
3. Assurance that health-care education activities on pain management with Tramadol® include balanced, evidence-based and current information. Commitment to take reasonable actions to inform health-care professionals that there is Health Canada-approved patient information on benefits and risks, and to ensure that this information can be readily accessed through electronic and/or hard copy sources.

Withdrawal Symptoms

Withdrawal symptoms may occur if Tramadol® is discontinued abruptly. These symptoms may include: anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, and rarely, hallucinations. Other symptoms that have been seen less frequently with Tramadol® discontinuation include: panic attacks, severe anxiety, and paresthesias. Clinical experience suggests that withdrawal symptoms may be relieved by reinstitution of opioid therapy followed by a gradual, tapered dose reduction of the medication combined with symptomatic support.

Tramadol contraindications

See also:
What is the most important information I should know about Tramadol?

You should not take tramadol if you are allergic to it, 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 tramadol. 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 and should be used only by the person it was prescribed for. Keep the medication in a secure 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.

Active ingredient matches for Aceclofenac/paracetamol/tramadol:

Aceclofenac/paracetamol/tramadol

References

1. PubChem. "Aceclofenac". https://pubchem.ncbi.nlm.nih.gov/com... (accessed September 17, 2018).
2. PubChem. "Tramadol". https://pubchem.ncbi.nlm.nih.gov/com... (accessed September 17, 2018).
3. DrugBank. "Aceclofenac". http://www.drugbank.ca/drugs/DB06736 (accessed September 17, 2018).

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Information checked by Dr. Sachin Kumar, MD Pharmacology