Diclofon MR

A centrally acting central muscle relaxant with sedative properties. It is claimed to inhibit muscle spasm by exerting an effect primarily at the level of the spinal cord and subcortical areas of the brain. (From Martindale, The Extra Pharmacopoea, 30th ed, p1202)

Diclofenac (Diclofon MR) potassium is potassium-o-[(2,6-dichlorophenyl)-amino]-phenyl-acetate.

Diclofenac (Diclofon MR) resinate is [o-[(2, 6-dichlorophenyl)-amino]-phenyl-acetate resinate.

Each mL of oral drops contains Diclofenac (Diclofon MR) resinate equivalent to Diclofenac (Diclofon MR) potassium 15 mg (0.5 mg/drop).

Excipients/Inactive Ingredients: Tablet: Core: Magnesium stearate, povidone, anhydrous colloidal silica, sodium starch glycollate, maize starch, calcium phosphate. Sugar-Coat: Microcrystalline cellulose, polyethylene glycol 8000, red iron oxide (E172) and titanium dioxide (E171) (dispersed Anstead), povidone, talc, sucrose. Polish: Polyethylene glycol 8000, sucrose.

Oral Drops:

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 action on the cough center and may be given to control intractable cough associated with terminal lung cancer. Tramadol (Diclofon MR) 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)

Chlorzoxazone (Diclofon MR) is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions. The mode of action of this drug has not been clearly identified, but may be related to its sedative properties. Chlorzoxazone (Diclofon MR) does not directly relax tense skeletal muscles in man.

Intramuscular

Renal colic

Adult: As Diclofenac (Diclofon MR) Na: 75 mg, may repeat once after 30 min if needed. Max: 150 mg/day. Max period: 2 days.

Intramuscular

Bursitis, Pain and inflammation associated with musculoskeletal and joint disorders, Rheumatoid arthritis, Sprains, Strains, Tendinitis, Acute gout, Dysmenorrhoea

Adult: As Diclofenac (Diclofon MR) Na: 75 mg once daily, injected into the gluteal muscle, may increase to 75 mg bid in severe conditions. Max period: 2 days.

Intravenous

Postoperative pain

Adult: As Diclofenac (Diclofon MR) Na: 75 mg infusion in glucose 5% or NaCl 0.9% (previously buffered w/ Na bicarbonate) given over 30-120 min or as bolus inj, may repeat after 4-6 hr if necessary. Max period: 2 days.

Intravenous

Prophylaxis of postoperative pain

Adult: As Diclofenac (Diclofon MR) Na: Initially, 25-50 mg infusion given after surgery over 15-60 min followed by 5 mg/hr. Alternatively, initial dose may be given as bolus inj over 5-60 sec followed by additional inj, may repeat after 4-6 hr if necessary. Max: 150 mg/day. Max period: 2 days.

Ophthalmic

Postoperative ocular inflammation

Adult: As Diclofenac (Diclofon MR) Na (0.1% soln): Instill into the appropriate eye 4 times daily starting 24 hr after surgery for up to 28 days.

Ophthalmic

Inflammation and discomfort after strabismus surgery

Adult: As Diclofenac (Diclofon MR) Na (0.1% soln): Instill 1 drop 4 times daily for the 1st wk; then tid in the 2nd wk, bid in the 3rd wk, and as required for the 4th wk.

Ophthalmic

Pain and discomfort after radial keratotomy

Adult: As Diclofenac (Diclofon MR) Na (0.1% soln): Instill 1 drop before surgery followed by 1 drop immediately after surgery, and then 1 drop 4 times daily for up to 2 days.

Ophthalmic

Pain after accidental trauma

Adult: As Diclofenac (Diclofon MR) Na (0.1% soln): Instill 1 drop 4 times daily for up to 2 days.

Ophthalmic

Control of inflammation after argon laser trabeculoplasty

Adult: As Diclofenac (Diclofon MR) Na (0.1% soln): Instill 1 drop 4 times during the 2 hr before procedure followed by 1 drop 4 times daily, up to 7 days after procedure.

Ophthalmic

Prophylaxis of intra-operative miosis

Adult: As Diclofenac (Diclofon MR) Na (0.1% soln): Instill into appropriate eye 4 times w/in 2 hr before surgery.

Ophthalmic

Post-photorefractive keratectomy pain

Adult: As Diclofenac (Diclofon MR) Na (0.1% soln): Instill into the affected eye twice, an hr before surgery, then 1 drop twice at 5-min intervals immediately after surgery, then every 2-5 hr while awake for up to 24 hr.

Ophthalmic

Seasonal allergic conjunctivitis

Adult: As Diclofenac (Diclofon MR) Na (0.1% soln): Instill 1 drop before surgery followed by 1 drop immediately after surgery, and then 1 drop 4 times daily for up to 2 days.

Oral

Bursitis, Pain and inflammation associated with musculoskeletal and joint disorders, Rheumatoid arthritis, Sprains, Strains, Tendinitis, Acute gout, Dysmenorrhoea

Adult: As Diclofenac (Diclofon MR) Na: 75-150 mg/day in divided doses. Max: 150 mg/day.

Oral

Migraine

Adult: As Diclofenac (Diclofon MR) K: Initially, 50 mg taken at the 1st sign of an attack, an additional dose of 50 mg may be taken after 2 hr if symptoms persist. If needed, further doses of 50 mg may be taken 4-6 hrly. Max: 200 mg/day.

Rectal

Acute gout, Bursitis, Dysmenorrhoea, Pain and inflammation associated with musculoskeletal and joint disorders, Rheumatoid arthritis, Sprains, Strains, Tendinitis

Adult: As Diclofenac (Diclofon MR) Na: 100 mg once daily.

Topical/Cutaneous

Actinic keratoses

Adult: As Diclofenac (Diclofon MR) Na (3% gel): Apply bid for 60-90 days.

Topical/Cutaneous

Osteoarthritis

Adult: As Diclofenac (Diclofon MR) Na (1.6% soln): Apply in small amounts (20 or 40 drops) onto affected area 4 times daily. As Na: (1% gel): Apply to the affected area 4 times daily. Max: 32 g/day over the affected area.

Topical/Cutaneous

Local symptomatic relief of pain and inflammation

Adult: As Diclofenac (Diclofon MR) Na (1% gel): Apply onto affected area 3 or 4 times daily.

Transdermal

Acute pain

Adult: Sprains, strains, contusions: 1 patch bid.

Adults

Tramadol (Diclofon MR)® (Tramadol (Diclofon MR) 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 (Diclofon MR) have plasma concentrations and elimination half-lives comparable to those observed in healthy subjects less than 65 years of age. Tramadol (Diclofon MR)® 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 (Diclofon MR)® have not been studied in the pediatric population. Therefore, use of Tramadol (Diclofon MR)® tablets is not recommended in patients under 18 years of age.

Chlorzoxazone (Diclofon MR) is used to relax certain muscles in your body and relieve the discomfort caused by acute (short-term), painful muscle or bone conditions. However, Chlorzoxazone (Diclofon MR) does not take the place of rest, exercise, physical therapy, or other treatments that your doctor may recommend for your medical condition.

Chlorzoxazone (Diclofon MR) is a skeletal muscle relaxant. It acts on the central nervous system (CNS) to relax muscles.

Chlorzoxazone (Diclofon MR) is available only with your doctor's prescription.

Diclofenac (Diclofon MR) is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and other symptoms of arthritis of the joints (eg, osteoarthritis), such as inflammation, swelling, stiffness, and joint pain. However, Diclofenac (Diclofon MR) does not cure osteoarthritis and will help you only as long as you continue to use it.

Diclofenac (Diclofon MR) topical 3% gel is also used to treat actinic keratosis, a skin problem that may become cancerous if not treated. The exact way that topical Diclofenac (Diclofon MR) helps this condition is unknown.

Diclofenac (Diclofon MR) topical solution is used to treat pain and swelling caused by osteoarthritis of the knees.

Diclofenac (Diclofon MR) topical patch is used to treat acute pain caused by minor strains, sprains, and contusions (bruises).

Diclofenac (Diclofon MR) is available only with your doctor's prescription.

Tramadol (Diclofon MR) is a narcotic-like pain reliever.

Tramadol (Diclofon MR) is used to treat moderate to severe pain.

The extended-release form of Tramadol (Diclofon MR) is for around-the-clock treatment of pain. This form of Tramadol (Diclofon MR) is not for use on an as-needed basis for pain.

Tramadol (Diclofon MR) may also be used for purposes not listed in this medication guide.

Usual Adult Dosage

Chlorzoxazone (Diclofon MR)® Tablets (Chlorzoxazone (Diclofon MR) USP) 375 mg

One tablet three or four times daily. If adequate response is not obtained with this dose, the 375 mg tablets may be increased to two tablets (750 mg) three or four times daily. As improvement occurs dosage can usually be reduced.

Chlorzoxazone (Diclofon MR)® Tablets (Chlorzoxazone (Diclofon MR) USP) 750 mg

1/3 tablet (250 mg) three or four times daily. Initial dosage for painful musculoskeletal condition should be 2/3 tablet (500 mg) three to four times daily. If adequate response is not obtained with this dose, it may be increased to one tablet (750 mg) three or four times daily. As improvement occurs dosage can usually be reduced.

How supplied

Chlorzoxazone (Diclofon MR)® Tablets (Chlorzoxazone (Diclofon MR) USP) are supplied as follows:

375 mg

A white capsule shaped tablet, debossed “ADG” on one side and “375” on the other side, in bottles of 100 tablets, NDC 68025-046-10.

750 mg

A white capsule shaped tablet, debossed “ADG” on the trisected side and “750” on the bisected side, in bottles of 100 tablets, NDC 68025-047-10.

Dispense in a tight container as defined in the official compendium.

Store at 20° to 25° C (68° to 77° F).

Manufactured for: Vertical Pharmaceuticals, LLC, Sayreville, NJ 08872. Revised: 2014

General Dosing Instructions

Carefully consider the potential benefits and risks of Diclofenac (Diclofon MR) and other treatment options before deciding to use Diclofenac (Diclofon MR). Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.

The effectiveness of Diclofenac (Diclofon MR) when taken with food has not been studied in clinical studies. Taking Diclofenac (Diclofon MR) with food may cause a reduction in effectiveness compared to taking Diclofenac (Diclofon MR) on an empty stomach.

Acute Pain

For management of mild to moderate acute pain, the dosage is 18 mg or 35 mg orally three times daily.

Osteoarthritis Pain

For management of osteoarthritis pain, the dosage is 35 mg orally three times daily.

Dosage Adjustments In Patients With Hepatic Impairment

Patients with hepatic disease may require reduced doses of Diclofenac (Diclofon MR) compared to patients with normal hepatic function. As with other Diclofenac (Diclofon MR) products, start treatment at the lowest dose. If efficacy is not achieved with the lowest dose, discontinue use.

Non-Interchangeability With Other Formulations Of Diclofenac (Diclofon MR)

Diclofenac (Diclofon MR) capsules are not interchangeable with other formulations of oral Diclofenac (Diclofon MR) even if the milligram strength is the same. Diclofenac (Diclofon MR) capsules contain Diclofenac (Diclofon MR) free acid whereas other Diclofenac (Diclofon MR) products contain a salt of Diclofenac (Diclofon MR), i.e., Diclofenac (Diclofon MR) potassium or sodium. A 35 mg dose of Diclofenac (Diclofon MR) is approximately equal to 37.6 mg of sodium Diclofenac (Diclofon MR) or 39.5 mg of potassium Diclofenac (Diclofon MR). Therefore, do not substitute similar dosing strengths of other Diclofenac (Diclofon MR) products without taking this into consideration.

How supplied

Dosage Forms And Strengths

Diclofenac (Diclofon MR) (Diclofenac (Diclofon MR)) capsules: 18 mg - blue body and light green cap (imprinted IP-203 on the body and 18 mg on the cap in white ink).

Diclofenac (Diclofon MR) (Diclofenac (Diclofon MR)) capsules: 35 mg - blue body and green cap (imprinted IP-204 on the body and 35 mg on the cap in white ink).

Storage And Handling

Diclofenac (Diclofon MR) (Diclofenac (Diclofon MR)) capsules are supplied as:

• 18 mg - blue body and light green cap (imprinted IP-203 on the body and 18 mg on the cap in white ink)

NDC (42211-203-23), Bottles of 30 capsules

NDC (42211-203-29), Bottles of 90 capsules

• 35 mg - blue body and green cap (imprinted IP-204 on the body and 35 mg on the cap in white ink)

NDC (42211-204-23), Bottles of 30 capsules

NDC (42211-204-29), Bottles of 90 capsules

Storage

Store at room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).

Store in the original container and keep the bottle tightly closed to protect from moisture. Dispense in a tight container if package is subdivided.

Manufactured (under license from iCeutica Pty Ltd) for and Distributed by: Iroko Pharmaceuticals, LLC, One Kew Place, 150 Rouse Boulevard, Philadelphia, PA 19112. Revised: May 2016

General Dosing Considerations

Tramadol (Diclofon MR)® is an extended-release formulation intended for once a day dosing in adults aged 18 years and older. The capsules must be swallowed whole with liquid and must not be split, chewed, dissolved or crushed. Chewing, crushing or splitting the capsule could result in the uncontrolled delivery of Tramadol (Diclofon MR), in overdose and death.

Do not administer Tramadol (Diclofon MR)® at a dose exceeding 300 mg per day. Do not use Tramadol (Diclofon MR)® more than once daily or concomitantly with other Tramadol (Diclofon MR) products.

Patients Not Currently on Tramadol (Diclofon MR) Immediate-Release Products

Initiate treatment with Tramadol (Diclofon MR)® at a dose of 100 mg once daily and titrated up as necessary by 100 mg increments every five days to achieve a balance between relief of pain and tolerability.

Patients Currently on Tramadol (Diclofon MR) Immediate-Release Products

Calculate the 24-hour Tramadol (Diclofon MR) IR dose and initiate a total daily dose of Tramadol (Diclofon MR)® 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 (Diclofon MR)®, some patients maintained on Tramadol (Diclofon MR) IR products may not be able to convert to Tramadol (Diclofon MR)®.

Patients 65 Years of Age and Older

Initiate 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 (Diclofon MR)® should be administered with even greater caution in patients over 75 years, due to the greater frequency of adverse events seen in this population.

Patients with Renal Impairment

The limited availability of dose strengths and once daily dosing of Tramadol (Diclofon MR)® do not permit the dosing flexibility required for safe use in patients with severe renal impairment. Do not use Tramadol (Diclofon MR)® in patients with creatinine clearance less than 30 mL/min.

Patients with Hepatic Impairment

The limited availability of dose strengths and once daily dosing of Tramadol (Diclofon MR) hydrochloride extended-release capsules do not permit the dosing flexibility required for safe use in patients with severe hepatic impairment. Do not use Tramadol (Diclofon MR)® in patients with severe hepatic impairment (Child-Pugh Class C).

Discontinuation of Treatment

Withdrawal symptoms may occur if Tramadol (Diclofon MR)® is discontinued abruptly. Clinical experience with Tramadol (Diclofon MR) suggests that withdrawal symptoms may be reduced by tapering Tramadol (Diclofon MR)®.

Food Effects

Tramadol (Diclofon MR)® may be taken without regard to food.

See also:
What is the most important information I should know about Chlorzoxazone (Diclofon MR)?

Chlorzoxazone (Diclofon MR) Chlorzoxazone (Diclofon MR) is contraindicated in patients with known intolerance to the drug.

See also:
What is the most important information I should know about Diclofenac (Diclofon MR)?

Hypersensitivity to Diclofenac (Diclofon MR) sodium or to any of the excipients of Diclofenac (Diclofon MR).

Active gastric or intestinal ulcer, bleeding or perforation.

Last trimester of pregnancy.

Hepatic, renal and severe cardiac failure.

Patients in whom attacks of asthma, urticaria or acute rhinitis are precipitated by acetylsalicylic acid and/or other drugs with prostaglandin-synthetase inhibitory activity.

Treatment of peri-operative pain in setting of coronary artery bypass graft (CABG) surgery.

The use of high dose Diclofenac (Diclofon MR) (150 mg/day) for >4 weeks is contraindicated in patients with established cardiovascular disease (congestive heart failure, established ischemic heart disease, peripheral arterial disease) or uncontrolled hypertension.

Established Cardiovascular Disease or Significant Cardiovascular Risk Factors: The use of high dose Diclofenac (Diclofon MR) (150mg/day) for >4 weeks is contraindicated in patients with established cardiovascular disease (congestive heart failure, established ischemic heart disease, peripheral arterial disease) or uncontrolled hypertension. If Diclofenac (Diclofon MR) treatment is needed, patients with established cardiovascular disease, uncontrolled hypertension or significant cardiovascular risk factors (eg, hypertension, hyperlipidaemia, diabetes mellitus and smoking) should be treated only after careful consideration and at doses ≤100 mg daily if the treatment is for >4 weeks. As the cardiovascular risks of Diclofenac (Diclofon MR) may increase with dose and duration of exposure, Diclofenac (Diclofon MR) should always be prescribed at the lowest effective daily dose and for the shortest duration possible.

Renal Impairment: Diclofenac (Diclofon MR) is contraindicated in patients with renal failure. No specific studies have been carried out in patients with renal impairment, therefore, no specific dose adjustment recommendations can be made. Caution is advised when administering Diclofenac (Diclofon MR) to patients with mild to moderate renal impairment.

Hepatic Impairment: Diclofenac (Diclofon MR) is contraindicated in patients with hepatic failure. No specific studies have been carried out in patients with hepatic impairment, therefore, no specific dose adjustment recommendations can be made. Caution is advised when administering Diclofenac (Diclofon MR) to patients with mild to moderate hepatic impairment.

See also:
What is the most important information I should know about Tramadol (Diclofon MR)?

You should not take Tramadol (Diclofon MR) 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 (Diclofon MR) 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 (Diclofon MR). Tramadol (Diclofon MR) 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 (Diclofon MR) overdose can be fatal.

Tramadol (Diclofon MR) 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 (Diclofon MR) 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.

Use Chlorzoxazone (Diclofon MR) as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Chlorzoxazone (Diclofon MR) by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation.
• If you miss a dose of Chlorzoxazone (Diclofon MR), 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 Chlorzoxazone (Diclofon MR).

Use Diclofenac (Diclofon MR) solution as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Diclofenac (Diclofon MR) solution comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Diclofenac (Diclofon MR) solution refilled.
• Do not apply Diclofenac (Diclofon MR) solution to infected skin; open wounds; or red, swollen, or peeling skin.
• Wash your hands immediately before and after using Diclofenac (Diclofon MR) solution.
• Wash the affected area and dry completely before using Diclofenac (Diclofon MR) solution.
• To apply Diclofenac (Diclofon MR) solution, dispense 10 drops at a time onto the knee or into your hand. Spread Diclofenac (Diclofon MR) solution evenly around the front, back, and sides of the knee. Repeat until you have used the whole dose.
• Be sure that you cover your entire knee with your dose of Diclofenac (Diclofon MR) solution. Do not use more than the recommended amount.
• Do not apply sunscreens, cosmetics, insect repellants, other topical medicines, or any other substance to the treated area until it is completely dry.
• Do not put on clothes over the treated area until it is completely dry.
• Do not wrap, bandage, or apply heat to the treated area.
• Let the treated skin dry before touching it or letting it touch anyone else's skin.
• Do not shower, bathe, or wash the treated area for at least 30 minutes after you use Diclofenac (Diclofon MR) solution.
• If you miss a dose of Diclofenac (Diclofon MR) solution, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Diclofenac (Diclofon MR) solution.

Use Tramadol (Diclofon MR) orally disintegrating tablets as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Tramadol (Diclofon MR) orally disintegrating tablets 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 (Diclofon MR) orally disintegrating tablets, place the tablet in your mouth. Let it dissolve, and then swallow it with saliva. Tramadol (Diclofon MR) orally disintegrating tablets may be taken with or without water.
• If you miss a dose of Tramadol (Diclofon MR) orally disintegrating tablets 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 (Diclofon MR) orally disintegrating tablets.

Chlorzoxazone (Diclofon MR) is used to treat muscle spasms/pain. It is usually used along with rest, physical therapy, and other treatment. It works by helping to relax the muscles.

How to use Chlorzoxazone (Diclofon MR)

Take this medication by mouth with or without food as directed by your doctor, usually 3 or 4 times a day.

The dosage is based on your medical condition and response to treatment. Do not increase your dose or take it more often than prescribed. Your condition will not improve any faster, and your risk of side effects will increase.

Tell your doctor if your condition does not improve or if it worsens.

Diclofenac (Diclofon MR) is used to relieve pain from various conditions. This form of Diclofenac (Diclofon MR) is used to treat migraine headaches. Diclofenac (Diclofon MR) is a nonsteroidal anti-inflammatory drug (NSAID). It works by blocking your body's production of certain natural substances that cause inflammation. This effect helps to decrease swelling, pain, or fever.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This medication may also be used to treat gout attacks.

How to use Diclofenac (Diclofon MR)

Read the Medication Guide provided by your pharmacist before you start taking Diclofenac (Diclofon MR) and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth as directed by your doctor. Empty the contents of one packet into a cup containing 1 to 2 ounces (30 to 60 milliliters) of water. Mix well and drink all of it right away. Do not mix with any liquid other than water. If stomach upset occurs while taking this medication, take it with food, milk, or an antacid. However, if you take this medication with a meal high in fat, it may not work as well.

There are different brands and forms of this medication available. Because different forms do not have the same effects at equal strengths, do not switch forms of Diclofenac (Diclofon MR) unless your doctor tells you to.

To reduce your risk of stomach bleeding and other side effects, take this medication at the lowest effective dose. Do not increase your dose or take it more often than prescribed.

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

Tell your doctor if your condition persists or worsens.

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 (Diclofon MR) 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 (Diclofon MR) ER is not indicated as an as-needed analgesic.

Off Label Uses

Premature ejaculation

Data from mostly placebo-controlled clinical trials suggest that Tramadol (Diclofon MR) may be beneficial for the treatment of premature ejaculation.

See also:
What other drugs will affect Chlorzoxazone (Diclofon MR)?

Alcohol (Ethyl): May enhance the CNS depressant effect of Chlorzoxazone (Diclofon MR). Alcohol (Ethyl) may decrease the serum concentration of Chlorzoxazone (Diclofon MR). Specifically, chronic alcohol ingestion may decrease serum concentrations of Chlorzoxazone (Diclofon MR). Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Botulinum Toxin-Containing Products: Muscle Relaxants (Centrally Acting) may enhance the adverse/toxic effect of Botulinum Toxin-Containing Products. Specifically, the risk for increased muscle weakness may be enhanced. Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of Chlorzoxazone (Diclofon MR). Chlormethiazole may increase the serum concentration of Chlorzoxazone (Diclofon MR). Management: Consider reduced doses of Chlorzoxazone (Diclofon MR) when combined with chlormethiazole. Monitor patients for increased Chlorzoxazone (Diclofon MR) effects/toxicities (ie, CNS depression, sedation) if these agents are combined. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

CYP2E1 Inhibitors (Strong): May increase the serum concentration of Chlorzoxazone (Diclofon MR). Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Consider therapy modification

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Isoniazid: May increase the serum concentration of Chlorzoxazone (Diclofon MR). Isoniazid may decrease the serum concentration of Chlorzoxazone (Diclofon MR). Specifically, it may decrease Chlorzoxazone (Diclofon MR) concentrations below baseline after isoniazid discontinuation. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Consider therapy modification

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Consider therapy modification

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Tolperisone: May enhance the adverse/toxic effect of Muscle Relaxants (Centrally Acting). Management: Monitor for increased sedation or CNS effects if tolperisone is combined with other centrally acting muscle relaxants. Consider decreasing the tolperisone dose if these agents are combined. Consider therapy modification

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant weak CYP3A4 inhibitors. Consider therapy modification

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (if needed) of ubrogepant should be limited to 50 mg. Consider therapy modification

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

See also:
What other drugs will affect Diclofenac (Diclofon MR)?

Aspirin: Concomitant administration of Diclofenac (Diclofon MR) and aspirin is not recommended because Diclofenac (Diclofon MR) is displaced from its binding sites during the concomitant administration of aspirin, resulting in lower plasma concentrations, peak plasma levels and AUC values.

Anticoagulants: While studies have not shown Diclofenac (Diclofon MR) to interact with anticoagulants of the warfarin type, caution should be exercised, nonetheless, since interactions have been seen with other NSAIDs. Because prostaglandins play an important role in hemostasis and NSAIDs affect platelet function as well, concurrent therapy with all NSAIDs, including Diclofenac (Diclofon MR) and warfarin, requires close monitoring of patients to be certain that no change in their anticoagulant dosage is required.

Digoxin, Methotrexate, Cyclosporine: Diclofenac (Diclofon MR), like other NSAIDs, may affect renal prostaglandins and increase the toxicity of certain drugs. Ingestion of Diclofenac (Diclofon MR) may increase serum concentrations of digoxin and methotrexate and increase cyclosporine's nephrotoxicity. Patients who begin taking Diclofenac (Diclofon MR) or who increase their Diclofenac (Diclofon MR) dose or any other NSAID while taking digoxin, methotrexate or cyclosporine may develop toxicity characteristics for these drugs. They should be observed closely, particularly if renal function is impaired. In the case of digoxin, serum levels should be monitored.

Lithium: Diclofenac (Diclofon MR) decreases lithium renal clearance and increases lithium plasma levels. In patients taking Diclofenac (Diclofon MR) and lithium concomitantly, lithium toxicity may develop.

Oral Hypoglycemics:

Diuretics: Diclofenac (Diclofon MR) and other NSAIDs can inhibit the activity of diuretics. Concomitant treatment with potassium-sparing diuretics may be associated with increased serum potassium levels.

Other Drugs: In small groups of patients (7-10/interaction study), the concomitant administration of azathioprine, gold, chloroquine, D-penicillamine, prednisolone, doxycycline or digitoxin did not significantly affect the peak levels and AUC values of Diclofenac (Diclofon MR). Phenobarbital toxicity has been reported to have occurred in a patient on chronic phenobarbital treatment following the initiation of Diclofenac (Diclofon MR) therapy.

See also:
What other drugs will affect Tramadol (Diclofon MR)?

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 (Diclofon MR) 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 (Diclofon MR) and SSRIs/SNRIs or MAOIs and α2-adrenergic blockers. Caution is advised when Tramadol (Diclofon MR) 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 (Diclofon MR) 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 action of Tramadol (Diclofon MR) and the potential for serotonin syndrome, caution is advised when Tramadol (Diclofon MR) is coadministered with a triptan. If concomitant treatment of Tramadol (Diclofon MR) 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 (Diclofon MR). Because carbamazepine increases Tramadol (Diclofon MR) metabolism and because of the seizure risk associated with Tramadol (Diclofon MR), concomitant administration of Tramadol (Diclofon MR) and carbamazepine is not recommended.

Use With Quinidine

Coadministration of quinidine with Tramadol (Diclofon MR) resulted in a 50-60% increase in Tramadol (Diclofon MR) 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 (Diclofon MR) has revealed rare reports of digoxin toxicity and alteration of warfarin effect, including elevation of prothrombin times.

Potential for Other Drugs to Affect Tramadol (Diclofon MR)

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 (Diclofon MR).

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

Potential for Tramadol (Diclofon MR) to Affect Other Drugs

In vitro drug interaction studies in human liver microsomes indicate that Tramadol (Diclofon MR) has no effect on quinidine metabolism. In vitro studies indicate that Tramadol (Diclofon MR) is unlikely to inhibit the CYP3A4-mediated metabolism of other drugs when administered concomitantly at therapeutic doses. Tramadol (Diclofon MR) is a mild inducer of selected drug metabolism pathways measured in animals.

See also:
What are the possible side effects of Chlorzoxazone (Diclofon MR)?

Applies to Chlorzoxazone (Diclofon MR): oral capsule, oral tablet

In addition to its needed effects, some unwanted effects may be caused by Chlorzoxazone (Diclofon MR) (the active ingredient contained in Chlorzoxazone (Diclofon MR)). In the event that any of these side effects do occur, they may require medical attention.

Major Side Effects

You should check with your doctor immediately if any of these side effects occur when taking Chlorzoxazone (Diclofon MR):

Rare

• Bloody or black, tarry stools
• clay-colored stools
• constipation
• cough
• dark urine
• decreased appetite
• difficulty swallowing
• dizziness
• fast heartbeat
• fever
• headache
• hives
• itching
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of appetite
• nausea and vomiting
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• severe stomach pain
• shortness of breath
• skin rash
• swelling of the feet or lower legs
• tightness in the chest
• unusual tiredness or weakness
• vomiting of blood or material that looks like coffee grounds
• wheezing
• yellow eyes or skin

If any of the following symptoms of overdose occur while taking Chlorzoxazone (Diclofon MR), get emergency help immediately:

Symptoms of overdose:

• Diarrhea
• difficult or troubled breathing
• drowsiness
• general feeling of discomfort or illness
• headache
• irregular, fast or slow, or shallow breathing
• lightheadedness
• nausea
• pale or blue lips, fingernails, or skin
• sluggishness
• vomiting

Minor Side Effects

Some of the side effects that can occur with Chlorzoxazone (Diclofon MR) may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

Rare

• Bruising
• large, flat, blue, or purplish patches in the skin
• small red or purple spots on the skin

See also:
What are the possible side effects of Diclofenac (Diclofon MR)?

Fluid Retention and Edema: Fluid retention and edema have been observed in some patients taking Diclofenac (Diclofon MR). Therefore, as with other NSAIDs, Diclofenac (Diclofon MR) should be used with caution in patients with history of cardiac decompensation, hypertension or other conditions predisposing to fluid retention.

Hematological Effects: Anemia is sometimes seen in patients receiving Diclofenac (Diclofon MR) or other NSAIDs. This may be due to fluid retention, GI blood loss or an incompletely described effect upon erythropoiesis.

Renal Effects: As a class, NSAIDs have been associated with renal papillary necrosis and other abnormal renal pathology in long-term administration to animals. In patients treated with Diclofenac (Diclofon MR), rare cases of interstitial nephritis and papillary necrosis have been reported. A second form of renal toxicity, generally associated with NSAIDs, is seen in patients with conditions leading to a reduction in renal blood flow or blood volume, where renal prostaglandins have a supported role in the maintenance of renal perfusion. In these patients, administration of an NSAID results in a dose-dependent decrease in prostaglandin synthesis and secondarily, in a reduction of renal blood flow, which may precipitate over the renal failure. Patients at greater risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and the elderly.

Porphyria: The use of Diclofenac (Diclofon MR) in patients with hepatic porphyria should be avoided.

Aseptic Meningitis: As with other NSAIDs, aseptic meningitis with fever and coma has been observed in rare occasions in patients on Diclofenac (Diclofon MR) therapy. Although it is probably more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease. If signs or symptoms of meningitis develop in a patient on Diclofenac (Diclofon MR), the possibility of it being related to Diclofenac (Diclofon MR) should be considered.

There may be pain and occasionally tissue damage at the site of injection when given IM.

See also:
What are the possible side effects of Tramadol (Diclofon MR)?

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 (Diclofon MR)® in Chronic Trials of Non-Malignant Pain (Non-titration Trials)

Tramadol (Diclofon MR)® 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 (Diclofon MR)® 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 (Diclofon MR)® group. In the Tramadol (Diclofon MR) 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 (Diclofon MR)® 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 (Diclofon MR)® 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 (Diclofon MR)® during clinical trials and/or reported in post-marketing experience. A causal relationship between Tramadol (Diclofon MR)® 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 (Diclofon MR) Hydrochloride

Adverse events which have been reported with the use of Tramadol (Diclofon MR) 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 (Diclofon MR) 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 (Diclofon MR) when used concomitantly with other serotonergic agents such as SSRIs and MAOIs. Post-marketing experience with the use of Tramadol (Diclofon MR)-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 (Diclofon MR), mostly in patients with pre-disposing risk factors, including diabetes, elderly and renal insufficiency. Caution should be exercised when prescribing Tramadol (Diclofon MR) 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 (Diclofon MR) 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 (Diclofon MR) is associated with craving and tolerance development.

A Risk Management program to support the safe and effective use of Tramadol (Diclofon MR)® 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 (Diclofon MR)® (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 (Diclofon MR)® advertising and promotional materials.
3. Assurance that health-care education activities on pain management with Tramadol (Diclofon MR)® 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 (Diclofon MR)® 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 (Diclofon MR)® 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.