Dibol

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

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

Each mL of oral drops contains Diclofenac (Dibol) resinate equivalent to Diclofenac (Dibol) 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 (Dibol) 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)

Intramuscular

Renal colic

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

Ophthalmic

Post-photorefractive keratectomy pain

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

Oral

Migraine

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

Topical/Cutaneous

Actinic keratoses

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

Topical/Cutaneous

Osteoarthritis

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

Transdermal

Acute pain

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

Adults

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

Diclofenac (Dibol) 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 (Dibol) does not cure osteoarthritis and will help you only as long as you continue to use it.

Diclofenac (Dibol) 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 (Dibol) helps this condition is unknown.

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

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

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

Tramadol (Dibol) is a narcotic-like pain reliever.

Tramadol (Dibol) is used to treat moderate to severe pain.

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

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

General Dosing Instructions

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

The effectiveness of Diclofenac (Dibol) when taken with food has not been studied in clinical studies. Taking Diclofenac (Dibol) with food may cause a reduction in effectiveness compared to taking Diclofenac (Dibol) 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 (Dibol) compared to patients with normal hepatic function. As with other Diclofenac (Dibol) 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 (Dibol)

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

How supplied

Dosage Forms And Strengths

Diclofenac (Dibol) (Diclofenac (Dibol)) 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 (Dibol) (Diclofenac (Dibol)) 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 (Dibol) (Diclofenac (Dibol)) 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 (Dibol)® 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 (Dibol), in overdose and death.

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

Patients Not Currently on Tramadol (Dibol) Immediate-Release Products

Initiate treatment with Tramadol (Dibol)® 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 (Dibol) Immediate-Release Products

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

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 (Dibol)® 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 (Dibol)® do not permit the dosing flexibility required for safe use in patients with severe renal impairment. Do not use Tramadol (Dibol)® 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 (Dibol) hydrochloride extended-release capsules do not permit the dosing flexibility required for safe use in patients with severe hepatic impairment. Do not use Tramadol (Dibol)® in patients with severe hepatic impairment (Child-Pugh Class C).

Discontinuation of Treatment

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

Food Effects

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

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

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

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 (Dibol) (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 (Dibol) (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 (Dibol) 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 (Dibol) may increase with dose and duration of exposure, Diclofenac (Dibol) should always be prescribed at the lowest effective daily dose and for the shortest duration possible.

Renal Impairment: Diclofenac (Dibol) 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 (Dibol) to patients with mild to moderate renal impairment.

Hepatic Impairment: Diclofenac (Dibol) 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 (Dibol) to patients with mild to moderate hepatic impairment.

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

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

Tramadol (Dibol) 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 (Dibol) 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 Diclofenac (Dibol) solution as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Diclofenac (Dibol) solution comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Diclofenac (Dibol) solution refilled.
• Do not apply Diclofenac (Dibol) solution to infected skin; open wounds; or red, swollen, or peeling skin.
• Wash your hands immediately before and after using Diclofenac (Dibol) solution.
• Wash the affected area and dry completely before using Diclofenac (Dibol) solution.
• To apply Diclofenac (Dibol) solution, dispense 10 drops at a time onto the knee or into your hand. Spread Diclofenac (Dibol) 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 (Dibol) 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 (Dibol) solution.
• If you miss a dose of Diclofenac (Dibol) 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 (Dibol) solution.

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

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

Diclofenac (Dibol) is used to relieve pain from various conditions. This form of Diclofenac (Dibol) is used to treat migraine headaches. Diclofenac (Dibol) 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 (Dibol)

Read the Medication Guide provided by your pharmacist before you start taking Diclofenac (Dibol) 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 (Dibol) 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 (Dibol) 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 (Dibol) ER is not indicated as an as-needed analgesic.

Off Label Uses

Premature ejaculation

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

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

Aspirin: Concomitant administration of Diclofenac (Dibol) and aspirin is not recommended because Diclofenac (Dibol) 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 (Dibol) 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 (Dibol) and warfarin, requires close monitoring of patients to be certain that no change in their anticoagulant dosage is required.

Digoxin, Methotrexate, Cyclosporine: Diclofenac (Dibol), like other NSAIDs, may affect renal prostaglandins and increase the toxicity of certain drugs. Ingestion of Diclofenac (Dibol) may increase serum concentrations of digoxin and methotrexate and increase cyclosporine's nephrotoxicity. Patients who begin taking Diclofenac (Dibol) or who increase their Diclofenac (Dibol) 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 (Dibol) decreases lithium renal clearance and increases lithium plasma levels. In patients taking Diclofenac (Dibol) and lithium concomitantly, lithium toxicity may develop.

Oral Hypoglycemics:

Diuretics: Diclofenac (Dibol) 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 (Dibol). Phenobarbital toxicity has been reported to have occurred in a patient on chronic phenobarbital treatment following the initiation of Diclofenac (Dibol) therapy.

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

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

Use With Quinidine

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

Potential for Other Drugs to Affect Tramadol (Dibol)

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 (Dibol).

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

Potential for Tramadol (Dibol) to Affect Other Drugs

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

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

Fluid Retention and Edema: Fluid retention and edema have been observed in some patients taking Diclofenac (Dibol). Therefore, as with other NSAIDs, Diclofenac (Dibol) 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 (Dibol) 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 (Dibol), 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 (Dibol) 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 (Dibol) 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 (Dibol), the possibility of it being related to Diclofenac (Dibol) 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 (Dibol)?

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

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

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

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