Adverse reactions : תופעות לוואי

ADVERSE REACTIONS

The following adverse reactions have been identified during post approval use of PERCOCET.
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.
Serious adverse reactions that may be associated with oxycodone and paracetamol use include respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension and shock (see OVERDOSAGE).
The most frequently observed non-serious adverse reactions include lightheadedness, dizziness, drowsiness or sedation, nausea, and vomiting. These effects seem to be more prominent in ambulatory than in nonambulatory patients, and some of these adverse reactions may be alleviated if the patient lies down. Other adverse reactions include euphoria, dysphoria, constipation and pruritus.
Hypersensitivity reactions may include: Skin eruptions, urticarial, erythematous skin reactions.
Hematologic reactions may include: thrombocytopenia, neutropenia, pancytopenia, hemolytic anemia. Rare cases of agranulocytosis have likewise been associated with paracetamol use. In high doses, the most serious adverse effect is a dose-dependent, potentially fatal hepatic necrosis. Renal tubular necrosis and hypoglycemic coma also may occur.
Other adverse reactions obtained from postmarketing experiences with oxycodone and paracetamol are listed by organ system and in decreasing order of severity and/or frequency as follows: 
Body as a Whole
Anaphylactoid reaction, allergic reaction, malaise, asthenia, fatigue, chest pain, fever, hypothermia, thirst, headache, increased sweating, accidental overdose, non-accidental overdose

Cardiovascular
Hypotension, hypertension, tachycardia, orthostatic hypotension, bradycardia, palpitations, dysrhythmias 
Central and Peripheral Nervous System
Stupor, tremor, paraesthesia, hypoaesthesia, lethargy, seizures, anxiety, mental impairment, agitation, cerebral edema, confusion, dizziness

Fluid and Electrolyte
Dehydration, hyperkalemia, metabolic acidosis, respiratory alkalosis

Gastrointestinal
Dyspepsia, taste disturbances, abdominal pain, abdominal distention, sweating increased, diarrhea, dry mouth, flatulence, gastrointestinal disorder, nausea, vomiting, pancreatitis, intestinal obstruction, ileus Hepatic
Transient elevations of hepatic enzymes, increase in bilirubin, hepatitis, hepatic failure, jaundice, hepatotoxicity, hepatic disorder

Hearing and Vestibular
Hearing loss, tinnitus

Hematologic
Thrombocytopenia
Hypersensitivity
Acute anaphylaxis, angioedema, asthma, bronchospasm, laryngeal edema, urticaria, anaphylactoid reaction 
Metabolic and Nutritional
Hypoglycemia, hyperglycemia, acidosis, alkalosis

Musculoskeletal
Myalgia, rhabdomyolysis
Ocular
Miosis, visual disturbances, red eye

Psychiatric
Drug dependence, drug abuse, insomnia, confusion, anxiety, agitation, depressed level of consciousness, nervousness, hallucination, somnolence, depression, suicide

Respiratory System
Bronchospasm, dyspnea, hyperpnea, pulmonary edema, tachypnea, aspiration, hypoventilation, laryngeal edema 
Skin and Appendages
Erythema, urticaria, rash, flushing

Urogenital
Interstitial nephritis, papillary necrosis, proteinuria, renal insufficiency and failure, urinary retention 

•   Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.
•   Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.
•   Anaphylaxis: Anaphylaxis has been reported with ingredients contained in PERCOCET.
•   Androgen deficiency: Cases of androgen deficiency have occurred with use of opioids for an extended period of time [see CLINICAL PHARMACOLOGY].
•   Hyperalgesia and Allodynia: Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see WARNINGS].
•   Hypoglycemia: Cases of hypoglycemia have been reported in patients taking opioids.
Most reports were in patients with at least one predisposing risk factor (e.g., diabetes).


DRUG ABUSE AND DEPENDENCE
Controlled Substance
PERCOCET contains oxycodone, a Schedule II controlled substance.

Abuse
PERCOCET contains oxycodone, a substance with a high potential for misuse and abuse , which can lead to the development of substance use disorder, including addiction (see WARNINGS).
Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed.
Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects.
Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence.
Misuse and abuse of PERCOCET increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. The risk is increased with concurrent abuse of PERCOCET with alcohol and other CNS depressants. Abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. In addition, abuse of opioids can occur in the absence of addiction.
All patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Patients at high risk of PERCOCET abuse include those with a history of prolonged use of any opioid, including products containing oxycodone, those with a history of drug or alcohol abuse, or those who use PERCOCET in combination with other abused drugs.


“Drug-seeking” behavior is very common in persons with substance use disorders. 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 health care provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder.
Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control.
PERCOCET 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 state and federal 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 PERCOCET
Abuse of PERCOCET poses a risk of overdose and death. The risk is increased with concurrent use of PERCOCET with alcohol and/or other central nervous system depressants.
Paracetamol has been associated with cases of acute liver failure, at times resulting in liver transplant and death.
Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

Dependence
Both tolerance and physical dependence can develop during use of opioid therapy.
Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).
Physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.

Withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use.
Do not abruptly discontinue PERCOCET in a patient physically dependent on opioids. Rapid tapering of PERCOCET in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide.
Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse.

When discontinuing PERCOCET, gradually taper the dosage using a patient-specific plan that considers the following: the dose of PERCOCET the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. To improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. In patients taking opioids for an extended period of time at high doses, ensure that a multimodal approach to pain management, including mental health support
(if needed), is in place prior to initiating an opioid analgesic taper [see DOSAGE AND ADMINISTRATION and WARNINGS].
Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs (see PRECAUTIONS; Pregnancy).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il