Apo-Tramadol; Acetaminophen

Apo-Tramadol; Acetaminophen tablets contains Tramadol (Apo-Tramadol; Acetaminophen) HCl 37.5 mg and paracetamol 325 mg. It also contain the following excipients: Powdered cellulose, pregelatinized starch, sodium starch glycolate, starch, purified water, magnesium stearate, yellow iron oxide, carnauba wax.

Apo-Tramadol; Acetaminophen® is indicated for the short-term (five days or less) management of acute pain.

Apo-Tramadol; Acetaminophen contains a combination of Tramadol (Apo-Tramadol; Acetaminophen) and Acetaminophen (Apo-Tramadol (Apo-Tramadol; Acetaminophen); Acetaminophen). Tramadol (Apo-Tramadol; Acetaminophen) is a narcotic-like pain reliever. Acetaminophen (Apo-Tramadol (Apo-Tramadol; Acetaminophen); Acetaminophen) is a less potent pain reliever that increases the effects of Tramadol (Apo-Tramadol; Acetaminophen).

Apo-Tramadol; Acetaminophen is used to treat moderate to severe pain.

Apo-Tramadol; Acetaminophen may also be used for purposes not listed in this medication guide.

Adults and Children >16 years: 1-2 tablets every 4-6 hrs as needed for pain relief up to a maximum of 8 tablets/day.

Children: The safety and effectiveness of Apo-Tramadol; Acetaminophen has not been studied in the pediatric population (<16 years). Therefore treatment is not recommended in this population.

Elderly: Elimination of the active components may be prolonged in elderly patients >75 yrs. Therefore, if necessary the dosage interval may be extended according to the patients requirements.

Renal/Dialysis/Hepatic Insufficiency: The pharmacokinetics of the Tramadol (Apo-Tramadol; Acetaminophen)/paracetamol combination in patients with renal impairment have not been studied. Experience with Tramadol (Apo-Tramadol; Acetaminophen) suggests that impaired renal function results in a decreased rate and extent of excretion of Tramadol (Apo-Tramadol; Acetaminophen). In patients with creatinine clearance of <30 mL/min, it is recommended that the dosing interval of Apo-Tramadol; Acetaminophen be increased not to exceed 2 tablets every 12 hrs. The pharmacokinetics and tolerability of Apo-Tramadol; Acetaminophen in patients with impaired hepatic function has not been studied. Tramadol (Apo-Tramadol; Acetaminophen) and paracetamol are both extensively metabolized by the liver. The use of Apo-Tramadol; Acetaminophen in patients with severe hepatic impairment is not recommended.

The tablets should be taken whole, not divided or chewed, with sufficient liquid, without regard to food.

Apo-Tramadol; Acetaminophen should under no circumstances be administered for longer than absolutely necessary. If long-term pain treatment with Apo-Tramadol; Acetaminophen is necessary in view of the nature and severity of the illness, then careful and regular monitoring should be carried out (if necessary with breaks in treatment) to establish whether and to what extent further treatment is necessary.

See also:
What is the most important information I should know about Apo-Tramadol; Acetaminophen?

Apo-Tramadol; Acetaminophen® should not be administered to patients who have previously demonstrated hypersensitivity to Tramadol (Apo-Tramadol; Acetaminophen), Acetaminophen (Apo-Tramadol (Apo-Tramadol; Acetaminophen); Acetaminophen), any other component of this product, or opioids. Apo-Tramadol; Acetaminophen® is contraindicated in any situation where opioids are contraindicated, including acute intoxication with any of the following: alcohol, hypnotics, narcotics, centrally acting analgesics, opioids, or psychotropic drugs. Apo-Tramadol; Acetaminophen® may worsen central nervous system and respiratory depression in these patients.

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

• Take Apo-Tramadol; Acetaminophen by mouth with or without food.
• Do not take Apo-Tramadol; Acetaminophen for more than 5 days unless advised to do so by your doctor.
• Do not take more than 8 tablets per day. Do not take more than 4 tablets per day if you have kidney problems.
• If you miss a dose of Apo-Tramadol; Acetaminophen 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 Apo-Tramadol; Acetaminophen.

Use: Labeled Indications

Pain management: Short-term (≤5 days) management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Limitations of use: Reserve Apo-Tramadol; Acetaminophen 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.

See also:
What other drugs will affect Apo-Tramadol; Acetaminophen?

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

Use With Quinidine

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

Potential For Other Drugs To Affect Tramadol (Apo-Tramadol; Acetaminophen)

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

Potential For Tramadol (Apo-Tramadol; Acetaminophen) To Affect Other Drugs

In vitro studies indicate that Tramadol (Apo-Tramadol; Acetaminophen) is unlikely to inhibit the CYP3A4-mediated metabolism of other drugs when Tramadol (Apo-Tramadol; Acetaminophen) is administered concomitantly at therapeutic doses. Tramadol (Apo-Tramadol; Acetaminophen) does not appear to induce its own metabolism in humans, since observed maximal plasma concentrations after multiple oral doses are higher than expected based on single-dose data. Tramadol (Apo-Tramadol; Acetaminophen) is a mild inducer of selected drug metabolism pathways measured in animals.

Use With Cimetidine

Concomitant administration of Apo-Tramadol; Acetaminophen® and cimetidine has not been studied. Concomitant administration of Tramadol (Apo-Tramadol; Acetaminophen) and cimetidine does not result in clinically significant changes in Tramadol (Apo-Tramadol; Acetaminophen) pharmacokinetics. Therefore, no alteration of the Apo-Tramadol; Acetaminophen® dosage regimen is recommended.

Use With Digoxin

Post-marketing surveillance of Tramadol (Apo-Tramadol; Acetaminophen) has revealed rare reports of digoxin toxicity.

Use With Warfarin-Like Compounds

Post-marketing surveillance of both Tramadol (Apo-Tramadol; Acetaminophen) and Acetaminophen (Apo-Tramadol (Apo-Tramadol; Acetaminophen); Acetaminophen) individual products have revealed rare alterations of warfarin effect, including elevation of prothrombin times.

While such changes have been generally of limited clinical significance for the individual products, periodic evaluation of prothrombin time should be performed when Apo-Tramadol; Acetaminophen® and warfarin-like compounds are administered concurrently.

See also:
What are the possible side effects of Apo-Tramadol; Acetaminophen?

Table 2 reports the incidence rate of treatment-emergent adverse events over five days of Apo-Tramadol; Acetaminophen® use in clinical trials (subjects took an average of at least 6 tablets per day).

Table 2: Incidence of Treatment-Emergent Adverse Events ( ≥ 2.0%)

Incidence at least 1%, causal relationship at least possible or greater: the following lists adverse reactions that occurred with an incidence of at least 1% in single-dose or repeated-dose clinical trials of Apo-Tramadol; Acetaminophen®.

Body as a Whole – Asthenia, fatigue, hot flushes

Central and Peripheral Nervous System – Dizziness, headache, tremor

Gastrointestinal System – Abdominal pain, constipation, diarrhea, dyspepsia, flatulence, dry mouth, nausea, vomiting

Psychiatric Disorders – Anorexia, anxiety, confusion, euphoria, insomnia, nervousness, somnolence

Skin and Appendages – Pruritus, rash, increased sweating

Selected Adverse events occurring at less than 1%: the following lists clinically relevant adverse reactions that occurred with an incidence of less than 1% in Apo-Tramadol; Acetaminophen clinical trials.

Body as a Whole – Chest pain, rigors, syncope, withdrawal syndrome

Cardiovascular Disorders – Hypertension, aggravated hypertension, hypotension

Central and Peripheral Nervous System – Ataxia, convulsions, hypertonia, migraine, aggravated migraine, involuntary muscle contractions, paresthesias, stupor, vertigo

Gastrointestinal System – Dysphagia, melena, tongue edema

Hearing and Vestibular Disorders – Tinnitus

Heart Rate and Rhythm Disorders – Arrhythmia, palpitation, tachycardia

Liver and Biliary System – Hepatic function abnormal

Metabolic and Nutritional Disorders – Weight decrease

Psychiatric Disorders – Amnesia, depersonalization, depression, drug abuse, emotional lability, hallucination, impotence, paroniria, abnormal thinking

Red Blood Cell Disorders – Anemia

Respiratory System – Dyspnea

Urinary System – Albuminuria, micturition disorder, oliguria, urinary retention

Vision Disorders – Abnormal vision

Postmarketing Experience

The following adverse reactions, not noted above, have been identified during post approval use of Tramadol (Apo-Tramadol; Acetaminophen)-containing products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Eye disorders – miosis, mydriasis

Nervous system disorders – movement disorder, speech disorder

Psychiatric disorders – delirium

Other clinically significant adverse experiences previously reported with Tramadol (Apo-Tramadol; Acetaminophen) hydrochloride:

Other events which have been reported with the use of Tramadol (Apo-Tramadol; Acetaminophen) products and for which a causal association has not been determined include: vasodilation, orthostatic hypotension, myocardial ischemia, pulmonary edema, allergic reactions (including anaphylaxis and urticaria, Stevens-Johnson syndrome/TENS), cognitive dysfunction, difficulty concentrating, depression, suicidal tendency, hepatitis, liver failure, and gastrointestinal bleeding. Reported laboratory abnormalities included elevated creatinine and liver function tests. Serotonin syndrome (whose symptoms may include mental status change, hyperreflexia, fever, shivering, tremor, agitation, diaphoresis, seizures, and coma) has been reported with Tramadol (Apo-Tramadol; Acetaminophen) when used concomitantly with other serotonergic agents such as SSRIs and MAOIs. Cases of hypoglycemia have been reported very rarely in patients taking Tramadol (Apo-Tramadol; Acetaminophen). Most reports were in patients with predisposing risk factors, including diabetes or renal insufficiency, or in elderly patients.

Other clinically significant adverse experiences previously reported with Acetaminophen (Apo-Tramadol (Apo-Tramadol; Acetaminophen); Acetaminophen):

Allergic reactions (primarily skin rash) or reports of hypersensitivity secondary to Acetaminophen (Apo-Tramadol (Apo-Tramadol; Acetaminophen); Acetaminophen) are rare and generally controlled by discontinuation of the drug and, when necessary, symptomatic treatment.

Drug Abuse And Dependence

Controlled Substance

Apo-Tramadol; Acetaminophen® (Tramadol (Apo-Tramadol; Acetaminophen) hydrochloride/Acetaminophen (Apo-Tramadol (Apo-Tramadol; Acetaminophen); Acetaminophen)) Tablets are classified as a Schedule IV controlled substance.

Abuse

Tramadol (Apo-Tramadol; Acetaminophen) has mu-opioid agonist activity. Apo-Tramadol; Acetaminophen®, a Tramadol (Apo-Tramadol; Acetaminophen)-containing product, can be abused and may be subject to criminal diversion.

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

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

Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of Apo-Tramadol; Acetaminophen® can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances.

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

Proper assessment of the patient and periodic re-evaluation of therapy are appropriate measures that help to limit the potential abuse of this product.

Apo-Tramadol; Acetaminophen® is intended for oral use only.

Dependence

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

The opioid abstinence or withdrawal syndrome is characterized by some or all of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.

Generally, tolerance and/or withdrawal are more likely to occur the longer a patient is on continuous therapy with Apo-Tramadol; Acetaminophen®.