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Results from the 12-week, multicenter, double-blind, placebo-controlled trial conducted i"...
The following serious adverse reactions are discussed elsewhere in the labeling:
- Addiction, Abuse, and Misuse [see WARNINGS AND PRECAUTIONS]
- Life Threatening Respiratory Depression [see WARNINGS AND PRECAUTIONS]
- Neonatal Opioid W ithdrawal Syndrome [see WARNINGS AND PRECAUTIONS]
- Interactions with Other CNS Depressants [see WARNINGS AND PRECAUTIONS]
- Hypotensive Effect [see WARNINGS AND PRECAUTIONS]
- Gastrointestinal Effects [see WARNINGS AND PRECAUTIONS]
- Seizures [see WARNINGS AND PRECAUTIONS]
Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
EXALGO was administered to a total of 2,524 patients in 15 controlled and uncontrolled clinical studies. Of these, 423 patients were exposed to EXALGO for greater than 6 months and 141 exposed for greater than one year.
The most common adverse reactions leading to study discontinuation were nausea, vomiting, constipation, somnolence, and dizziness. The most common treatment-related serious adverse reactions from controlled and uncontrolled chronic pain studies were drug withdrawal syndrome, overdose, confusional state, and constipation.
The overall incidence of adverse reactions in patients greater than 65 years of age was higher, with a greater than 5% difference in rates for constipation and nausea when compared with younger patients. The overall incidence of adverse reactions in female patients was higher, with a greater than 5% difference in rates for nausea, vomiting, constipation and somnolence when compared with male patients.
A 12-week double-blind, placebo-controlled, randomized withdrawal study was conducted in opioid tolerant patients with moderate to severe low back pain [see Clinical Studies]. A total of 447 patients were enrolled into the open-label titration phase with 268 patients randomized into the double-blind treatment phase. The adverse reactions that were reported in at least 2% of the patients are contained in Table 2.
Table 2: Number (%) of Patients with Adverse Reactions
Reported in ≥ 2% of Patients with Moderate to Severe Low Back Pain During
the Open-Label Titration Phase or Double-Blind Treatment Phase by Preferred
|Preferred Term||Open-Label Titration Phase EXALGO
|Double-Blind Treatment Phase|
|Constipation||69 (15)||10 (7)||5 (4)|
|Nausea||53 (12)||12 (9)||10 (7)|
|Somnolence||39 (9)||1 (1)||0 (0)|
|Headache||35 (8)||7 (5)||10 (7)|
|Vomiting||29 (6)||8 (6)||6 (4)|
|Pruritus||21 (5)||1 (1)||0 (0)|
|Dizziness||17 (4)||3 (2)||2 (1)|
|Insomnia||13 (3)||7 (5)||5 (4)|
|Dry Mouth||13 (3)||2 (1)||0 (0)|
|Edema Peripheral||13 (3)||3 (2)||1 (1)|
|Hyperhidrosis||13 (3)||2 (1)||2 (1)|
|Anorexia/Decreased Appetite||10 (2)||2 (1)||0 (0)|
|Arthralgia||9 (2)||8 (6)||3 (2)|
|Abdominal Pain||9 (2)||4 (3)||3 (2)|
|Muscle Spasms||5 (1)||3 (2)||1 (1)|
|Weight Decreased||3 (1)||4 (3)||3 (2)|
The adverse reactions that were reported in at least 2% of the total treated patients (N=2,474) in the 14 chronic clinical trials are contained in Table 3.
Table 3: Number (%) of Patients with Adverse Reactions
Reported in ≥ 2% of Patients with Chronic Pain Receiving EXALGO in 14
Clinical Studies by Preferred Term
|Preferred Term||All Patients
|Edema Peripheral||135 (5)|
|Anorexia/Decreased Appetite||139 (6)|
|Dry Mouth||121 (5)|
|Abdominal Pain||115 (5)|
|Back Pain||95 (4)|
|Muscle Spasms||74 (3)|
|Pain in Extremity||63 (3)|
|Drug Withdrawal Syndrome||55 (2)|
|Chest pain||51 (2)|
|* Reflux esophagitis, gastroesophageal reflux disease and Barrett's esophagus were grouped and reported with dyspepsia|
The following Adverse Reactions occurred in patients with an overall frequency of < 2% and are listed in descending order within each System Organ Class:
Endocrine disorders: hypogonadism
Gastrointestinal disorders: flatulence, dysphagia, hematochezia, abdominal distension, hemorrhoids, abnormal feces, intestinal obstruction, eructation, diverticulum, gastrointestinal motility disorder, large intestine perforation, anal fissure, bezoar, duodenitis, ileus, impaired gastric emptying, painful defecation
General disorders and administration site conditions: chills, malaise, feeling abnormal, feeling of body temperature change, feeling jittery, hangover, gait disturbance, feeling drunk, body temperature decreased
Injury, poisoning and procedural complications: contusion, overdose
Metabolism and nutrition disorders: dehydration, fluid retention, increased appetite, hyperuricemia
Musculoskeletal and connective tissue disorders: myalgia
Nervous system disorders: tremor, sedation, hypoesthesia, paresthesia, disturbance in attention, memory impairment, dysarthria, syncope, balance disorder, dysgeusia, depressed level of consciousness, coordination abnormal, hyperesthesia, myoclonus, dyskinesia, crying, hyperreflexia, encephalopathy, cognitive disorder, convulsion, psychomotor hyperactivity
Psychiatric disorders: confusional state, nervousness, restlessness, abnormal dreams, mood altered, hallucination, panic attack, euphoric mood, paranoia, dysphoria, listless, suicide ideation, libido decreased, aggression
Reproductive system and breast disorders: erectile dysfunction, sexual dysfunction Respiratory, thoracic and mediastinal disorders: rhinorrhea, respiratory distress, hypoxia, bronchospasm, sneezing, hyperventilation, respiratory depression
Skin and subcutaneous tissue disorders: erythema
The following adverse reactions have been identified during post-approval use of EXALGO:
Immune system disorders: hypersensitivity
Read the Exalgo (hydromorphone hydrochloride extended release tablets) Side Effects Center for a complete guide to possible side effects
The concomitant use of EXALGO with other CNS depressants including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol can increase the risk of respiratory depression, profound sedation, coma and death. Monitor patients receiving CNS depressants and EXALGO for signs of respiratory depression, sedation and hypotension.
Mixed Agonist/Antagonist And Partial Agonist Opioid Analgesics
Mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) and partial agonist (buprenorphine) analgesics may reduce the analgesic effect of EXALGO or precipitate withdrawal symptoms. Avoid the use of mixed agonist/antagonist and partial agonist analgesics in patients receiving EXALGO.
Monoamine Oxidase Inhibitors (MAOI)
The effects of opioid analgesics may be potentiated by MAOIs. EXALGO is not recommended for use in patients who have received MAOIs within 14 days. If concurrent therapy with an MAOI and EXALGO is unavoidable, monitor patients for increased respiratory and central nervous system depression.
Anticholinergics or other medications with anticholinergic activity when used concurrently with EXALGO may result in increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor patients for signs of urinary retention or reduced gastric motility when EXALGO is used concurrently with anticholinergic drugs.
Drug Abuse And Dependence
EXALGO contains hydromorphone, a Schedule II controlled substance with a high potential for abuse similar to fentanyl, methadone, morphine, oxycodone, and oxymorphone. EXALGO can be abused and is subject to misuse, abuse, addiction, and criminal diversion [see WARNINGS AND PRECAUTIONS].
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.
Drug abuse is the intentional non-therapeutic use of an over-the-counter or prescription drug, even once, for its rewarding psychological or physiological effects. Drug abuse includes, but is not limited to the following examples: the use of a prescription or over-the-counter drug to get “high”, or the use of steroids for performance enhancement and muscle build up.
Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and include: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.
“Drug-seeking” behavior is very common to 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 claims of loss of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” (visiting multiple prescribers) to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving pain relief can be appropriate behavior in a patient with poor pain control.
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.
EXALGO, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by law, is strongly advised.
Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.
Risks Specific to Abuse of EXALGO
EXALGO is intended for oral use only. Abuse of EXALGO poses a risk of overdose and death. This risk is increased with concurrent abuse of EXALGO with alcohol and other substances.
Taking cut, broken, chewed, crushed, or dissolved EXALGO poses a hazard of overdose and death.
With intravenous abuse, the tablet excipients, especially polyethylene oxide, can be expected to result in necrosis and inflammation of cardiac tissues. In addition, parenteral drug abuse is commonly associated with transmission of infectious disease such as hepatitis and HIV.
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.
Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.
Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dose reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity, e.g., naloxone, nalmefene, mixed agonist/antagonist analgesics (pentazocine, butorphanol, nalbuphine), or partial agonists (buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.
EXALGO should not be abruptly discontinued [see DOSAGE AND ADMINISTRATION]. If EXALGO is abruptly discontinued in a physically-dependent patient, an abstinence syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, piloerection, myalgia, mydriasis, irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, increased blood pressure, respiratory rate, or heart rate.
Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms [see WARNINGS AND PRECAUTIONS].
Read the Exalgo Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 6/19/2015
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