Magnacet

Misuse, Abuse and Diversion of Opioids

Oxycodone is an opioid agonist of the morphine-type. Such drugs are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.

Oxycodone can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing oxycodone and acetaminophen tablets, USP in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion. Concerns about misuse, addiction and diversion should not prevent the proper management of pain.

Healthcare professionals should contact their State Professional Licensing Board or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product.

Administration of oxycodone and acetaminophen tablets, USP should be closely monitored for the following potentially serious adverse reactions and complications:

Respiratory Depression

Respiratory depression is a hazard with the use of oxycodone, one of the active ingredients in oxycodone and acetaminophen tablets, USP , as with all opioid agonists. Elderly and debilitated patients are at particular risk for respiratory depression as are non-tolerant patients given large initial doses of oxycodone or when oxycodone is given in conjunction with other agents that depress respiration. Oxycodone should be used with extreme caution in patients with acute asthma, chronic obstructive pulmonary disorder (COPD), cor pulmonale, or preexisting respiratory impairment. In such patients, even usual therapeutic doses of oxycodone may decrease respiratory drive to the point of apnea. In these patients alternative non-opioid analgesics should be considered, and opioids should be employed only under careful medical supervision at the lowest effective dose.

In case of respiratory depression, a reversal agent such as naloxone hydrochloride may be utilized (see OVERDOSAGE).

Head Injury and Increased Intracranial Pressure

The respiratory depressant effects of opioids include carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure, and may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure. Oxycodone produces effects on pupillary response and consciousness which may obscure neurologic signs of worsening in patients with head injuries.

Hypotensive Effect

Oxycodone may cause severe hypotension particularly in individuals whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs which compromise vasomotor tone such as phenothiazines. Oxycodone, like all opioid analgesics of the morphine-type, should be administered with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure. Oxycodone may produce orthostatic hypotension in ambulatory patients.

Hepatotoxicity

Precaution should be taken in patients with liver disease. Hepatotoxicity and severe hepatic failure occurred in chronic alcoholics following therapeutic doses.

Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 milligrams per day, and often involve more than one acetaminophen-containing product. The excessive intake of acetaminophen may be intentional to cause self-harm or unintentional as patients attempt to obtain more pain relief or unknowingly take other acetaminophen-containing products.

The risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest alcohol while taking acetaminophen.

Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one product that contains acetaminophen. Instruct patients to seek medical attention immediately upon ingestion of more than 4000 milligrams of acetaminophen per day, even if they feel well.

Serious Skin Reactions

Rarely, acetaminophen can cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Patients should be informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

Hypersensitivity/anaphylaxis

There have been post-marketing reports of hypersensitivity and anaphylaxis associated with use of acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, pruritus, and vomiting. There were infrequent reports of life-threatening anaphylaxis requiring emergency medical attention. Instruct patients to discontinue oxycodone and acetaminophen tablets, USP immediately and seek medical care if they experience these symptoms. Do not prescribe oxycodone and acetaminophen tablets, USP for patients with acetaminophen allergy.

Oxycodone and acetaminophen tablets, USP are a Schedule II controlled substance. Oxycodone is a mu-agonist opioid with an abuse liability similar to morphine. Oxycodone, like morphine and other opioids used in analgesia, can be abused and is subject to criminal diversion.

Drug addiction is defined as an abnormal, compulsive use, use for non-medical purposes of a substance despite physical, psychological, occupational or interpersonal difficulties resulting from such use, and continued use despite harm or risk of harm. Drug addiction is a treatable disease, utilizing a multi-disciplinary approach, but relapse is common. Opioid addiction is relatively rare in patients with chronic pain but may be more common in individuals who have a past history of alcohol or substance abuse or dependence. Pseudoaddiction refers to pain relief seeking behavior of patients whose pain is poorly managed. It is considered an iatrogenic effect in ineffective pain management. The health care provider must assess continuously the psychological and clinical condition of a pain patient in order to distinguish addiction from pseudoaddiction and thus, be able to treat the pain adequately.

Physical dependence on a prescribed medication does not signify addiction. Physical dependence involves the occurrence of a withdrawal syndrome when there is a sudden reduction or cessation in drug use or if an opiate antagonist is administered. Physical dependence can be detected after a few days of opioid therapy. However, clinically significant physical dependence is only seen after several weeks of relatively high dosage therapy. In this case, abrupt discontinuation of opioid may result in a withdrawal syndrome. If the discontinuation of opioids is therapeutically indicated, gradual tapering of the drug over a 2-week period will prevent withdrawal symptoms. The severity of the withdrawal syndrome depends primarily on the daily dosage of the opioid, the duration of therapy and medical status of the individual.

The withdrawal syndrome of oxycodone is similar to that of morphine. This syndrome is characterized by yawning, anxiety, increased heart rate and blood pressure, restlessness, nervousness, muscle aches, tremor, irritability, chills alternating with hot flashes, salivation, anorexia, severe sneezing, lacrimation, rhinorrhea, dilated pupils, diaphoresis, piloerection, nausea, vomiting, abdominal cramps, diarrhea and insomnia, and pronounced weakness and depression.

"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 infection.

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

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

Like other opioid medications, oxycodone and acetaminophen tablets, USP are subject to the Federal Controlled Substances Act. After chronic use, oxycodone and acetaminophen tablets, USP should not be discontinued abruptly when it is thought that the patient has become physically dependent on oxycodone.

Interactions with Alcohol and Drugs of Abuse

Oxycodone may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression.

Signs and Symptoms

Toxicity from oxycodone poisoning includes the opioid triad of: pinpoint pupils, depression of respiration, and loss of consciousness. Serious overdosage with oxycodone is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest, and death may occur.

In acetaminophen overdosage: dose-dependent potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and coagulation defects may also occur. Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis, and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion.

Treatment

A single or multiple drug overdose with oxycodone and acetaminophen is a potentially lethal polydrug overdose, and consultation with a regional poison control center is recommended. Immediate treatment includes support of cardiorespiratory function and measures to reduce drug absorption. Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. Assisted or controlled ventilation should also be considered.

Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation. The narcotic antagonist naloxone hydrochloride is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to narcotics, including oxycodone. Since the duration of action of oxycodone may exceed that of the antagonist, the patient should be kept under continued surveillance, and repeated doses of the antagonist should be administered as needed to maintain adequate respiration. A narcotic antagonist should not be administered in the absence of clinically significant respiratory or cardiovascular depression.

Gastric decontamination with activated charcoal should be administered just prior to N-acetylcysteine (NAC) to decrease systemic absorption if acetaminophen ingestion is known or suspected to have occurred within a few hours of presentation. Serum acetaminophen levels should be obtained immediately if the patient presents 4 hours or more after ingestion to assess potential risk of hepatotoxicity; acetaminophen levels drawn less than 4 hours post-ingestion may be misleading. To obtain the best possible outcome, NAC should be administered as soon as possible where impending or evolving liver injury is suspected. Intravenous NAC may be administered when circumstances preclude oral administration.

Vigorous supportive therapy is required in severe intoxication. Procedures to limit the continuing absorption of the drug must be readily performed since the hepatic injury is dose dependent and occurs early in the course of intoxication.

Dosage should be adjusted according to the severity of the pain and the response of the patient. It may occasionally be necessary to exceed the usual dosage recommended below in cases of more severe pain or in those patients who have become tolerant to the analgesic effects of opioids. If pain is constant, the opioid analgesic should be given at regular intervals on an around-the-clock schedule. Oxycodone and acetaminophen tablets, USP are given orally.

The usual adult dosage of  oxycodone and acetaminophen tablets, USP are as follows. The total daily dosage of acetaminophen should not exceed 4 grams.

Cessation of Therapy

In patients treated with oxycodone and acetaminophen tablets, USP for more than a few weeks who no longer require therapy, doses should be tapered gradually to prevent signs and symptoms of withdrawal in the physically dependent patient.

Applies to acetaminophen / oxycodone: oral capsule, oral solution, oral tablet, oral tablet extended release

General

The most commonly reported adverse events have included lightheadedness, dizziness, drowsiness, sedation, nausea, and vomiting.[Ref]

Respiratory

Common (1% to 10%): Cough
Frequency not reported: Apnea, respiratory arrest, respiratory depression, hiccups
Postmarketing reports: Bronchospasm, dyspnea, hyperpnea, pulmonary edema, tachypnea, hypoventilation, laryngeal edema[Ref]

Hepatic

Oxycodone-acetaminophen:
Postmarketing reports: Transient elevations of hepatic enzymes, increased bilirubin, hepatic failure, jaundice, hepatotoxicity, hepatic disorder, hepatitis

Acetaminophen:
Frequency not reported: Hepatic necrosis[Ref]

At high doses, the most serious acetaminophen related adverse event is a dose-dependent, potentially fatal hepatic necrosis.[Ref]

Hypersensitivity

Frequency not reported: Skin eruptions, urticaria, erythematous skin reactions
Postmarketing reports: Anaphylaxis, allergic reaction, angioedema[Ref]

Dermatologic

Common (1% to 10%): Rash, blister, excoriation, pruritus, erythema
Frequency not reported: Dermatitis, ecchymosis, hyperhidrosis
Postmarketing reports: Urticaria, flushing, increased sweating[Ref]

Nervous system

Very common (10% or more): Dizziness (up to 13%)
Common (1% to 10%): Headache, somnolence
Frequency not reported: Lightheadedness, dizziness, drowsiness, sedation, migraine, myoclonus, paresthesia, tremor
Postmarketing reports: Stupor, cerebral edema, coma, subdural or intracranial hemorrhage, seizures

Opioids:
Postmarketing reports: Serotonin syndrome[Ref]

Psychiatric

Frequency not reported: Euphoria, dysphoria, insomnia, altered mood, sleep disorder, withdrawal syndrome
Postmarketing reports: Agitation, confusion, anxiety, mental impairment, drug dependence, drug abuse, depression, nervousness, hallucination, suicide[Ref]

Gastrointestinal

Very common (10% or more): Nausea (up to 31%)
Common (1% to 10%): Vomiting, constipation, dry mouth, dyspepsia, diarrhea
Frequency not reported: Esophageal spasm, oropharyngeal pain, throat irritation
Postmarketing reports: Abdominal pain, abdominal distention, flatulence, gastrointestinal disorder, pancreatitis, intestinal obstruction, ileus, thirst[Ref]

Hematologic

Oxycodone-acetaminophen:
Frequency not reported: Thrombocytopenia, neutropenia, pancytopenia, hemolytic anemia

Acetaminophen:
Rare (0.01% to 0.1%): Agranulocytosis[Ref]

Renal

Postmarketing reports: Renal insufficiency and failure[Ref]

Cardiovascular

Common (1% to 10%): Edema
Frequency not reported: Hypotension, chest discomfort
Postmarketing reports: Tachycardia, dysrhythmias, orthostatic hypotension, bradycardia, palpitations, hypertension[Ref]

Metabolic

Frequency not reported: Decreased appetite
Postmarketing reports: Hypoglycemia, hyperglycemia, acidosis, alkalosis, hyperkalemia, dehydration

Musculoskeletal

Postmarketing reports: Rhabdomyolysis, myalgia

Ocular

Postmarketing reports: Miosis, visual disturbances, red eye

Genitourinary

Common (1% to 10%): Dysuria
Frequency not reported: Urinary retention, interstitial nephritis, proteinuria, decreased urine flow

Other

Postmarketing reports: Malaise, asthenia, fatigue, fever, hypothermia, accidental overdose, non-accidental overdose, hearing loss, tinnitus[Ref]

Endocrine

Adrenal insufficiency and androgen deficiency have been reported with opioid use, most often with chronic use.

Opioids:
Postmarketing reports: Adrenal insufficiency, androgen deficiency

Some side effects of Magnacet may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.