Side Effects of Oxycontin (oxycodone)

Oxycontin (oxycodone) is a strong narcotic pain-reliever and cough suppressant used to manage pain severe enough to require daily, around-the-clock, long-term treatment with a narcotic, and for which alternative treatment options are inadequate for the relief of moderate to severe pain.

The precise mechanism of action of Oxycontin is not known, but it may involve stimulation of opioid receptors in the brain. Oxycontin does not eliminate the sensation of pain but decreases discomfort by increasing the tolerance to pain. In addition to tolerance to pain, Oxycontin also causes sedation and depression of respiration.

Common side effects of Oxycontin include

• lightheadedness,
• dizziness,
• sedation,
• nausea,
• vomiting,
• headache,
• rash,
• constipation,
• dry mouth,
• sweating,
• faintness, and
• itching.

Serious side effects of Oxycontin include

• heart attack,
• depression,
• abnormal heartbeats,
• agitation,
• seizures,
• urinary retention,
• depressed breathing and
• impaired thinking and physical abilities required for driving or operating machinery.

Oxycontin is habit forming. Mental and physical dependence can occur but are unlikely when used for short-term pain relief. Withdrawal symptoms may occur if you suddenly stop taking Oxycontin.

Drug interactions of Oxycontin include drugs that slow brain function, such as alcohol, barbiturates, skeletal muscle relaxants, and benzodiazepines, because combined use with Oxycontin may lead to increased respiratory depression.

Oxycontin should not be taken with monoamine oxidase inhibitors (MAOIs) or other drugs that inhibit monoamine oxidase such as linezolid, because it may lead to

• confusion,
• high blood pressure,
• tremor,
• hyperactivity,
• coma, and
• death.

Since Oxycontin causes constipation, the use of antidiarrheals in persons taking Oxycontin can lead to severe constipation.

Drugs that stimulate and block opioid receptors such as pentazocine, nalbuphine, butorphanol, and buprenorphine may reduce the effect of Oxycontin and may precipitate withdrawal symptoms.

Combining Oxycontin with drugs that affect activity of certain liver enzymes or discontinuing such drugs may result in fatal Oxycontin overdose.

A fatty meal may increase the absorption of Oxycontin by 27%. Safety of Oxycontin during pregnancy has not been established. Children born to mothers who were taking Oxycontin for a prolonged period may exhibit respiratory depression or withdrawal symptoms.

Small amounts of Oxycontin are secreted in breast milk, which may cause side effects in the newborn. Consult your doctor before breastfeeding. 

The most frequent side effects of oxycodone include:

• Lightheadedness
• Dizziness
• Sedation
• Nausea
• Vomiting
• Headache
• Rash
• Constipation
• Dry mouth
• Sweating

Other side effects of oxycodone include:

• Faintness
• Heart attack
• Rash
• Itching
• Depression
• Abnormal heartbeats
• Agitation
• Seizures
• Urinary retention

Oxycodone is used with caution in the elderly, debilitated patients, and in patients with serious lung disease because it can depress breathing.

Oxycodone can impair thinking and the physical abilities required for driving or operating machinery.

Oxycodone is habit forming. Mental and physical dependence can occur but are unlikely when used for short-term pain relief. If oxycodone is suddenly withdrawn after prolonged use, symptoms of withdrawal may develop. The dose of oxycodone should be gradually reduced in order to avoid withdrawal symptoms.

The following serious adverse reactions are described elsewhere in the labeling:

• Addiction, Abuse, and Misuse
• Life-Threatening Respiratory Depression
• Neonatal Opioid Withdrawal Syndrome
• Interactions With Benzodiazepines and Other CNS Depressants
• Adrenal Insufficiency
• Severe Hypotension
• Gastrointestinal Adverse Reactions
• Seizures
• Withdrawal

Clinical Trial Experience

Adult 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 practice.

The safety of Oxycontin was evaluated in double-blind clinical trials involving 713 patients with moderate to severe pain of various etiologies. In open-label studies of cancer pain, 187 patients received Oxycontin in total daily doses ranging from 20 mg to 640 mg per day. The average total daily dose was approximately 105 mg per day.

Oxycontin may increase the risk of serious adverse reactions such as those observed with other opioid analgesics, including

• respiratory depression,
• apnea,
• respiratory arrest,
• circulatory depression,
• hypotension, or
• shock.

The most common adverse reactions (>5%) reported by patients in clinical trials comparing Oxycontin with placebo are shown in Table 2 below:

TABLE 2: Common Adverse Reactions (>5%)

In clinical trials, the following adverse reactions were reported in patients treated with Oxycontin with an incidence between 1% and 5%:

Gastrointestinal disorders: abdominal pain, diarrhea, dyspepsia, gastritis

General disorders and administration site conditions: chills, fever

Metabolism and nutrition disorders: anorexia

Musculoskeletal and connective tissue disorders: twitching

Psychiatric disorders: abnormal dreams, anxiety, confusion, dysphoria, euphoria, insomnia, nervousness, thought abnormalities

Respiratory, thoracic and mediastinal disorders: dyspnea, hiccups

Skin and subcutaneous tissue disorders: rash

Vascular disorders: postural hypotension

The following adverse reactions occurred in less than 1% of patients involved in clinical trials:

Blood and lymphatic system disorders: lymphadenopathy

Ear and labyrinth disorders: tinnitus

Eye disorders: abnormal vision

Gastrointestinal disorders: dysphagia, eructation, flatulence, gastrointestinal disorder, increased appetite, stomatitis

General disorders and administration site conditions: withdrawal syndrome (with and without seizures), edema, peripheral edema, thirst, malaise, chest pain, facial edema

Injury, poisoning and procedural complications: accidental injury

Investigations: ST depression

Metabolism and nutrition disorders: dehydration

Nervous system disorders: syncope, migraine, abnormal gait, amnesia, hyperkinesia, hypoesthesia, hypotonia, paresthesia, speech disorder, stupor, tremor, vertigo, taste perversion

Psychiatric disorders: depression, agitation, depersonalization, emotional lability, hallucination

Renal and urinary disorders: dysuria, hematuria, polyuria, urinary retention

Reproductive system and breast disorders: impotence

Respiratory, thoracic and mediastinal disorders: cough increased, voice alteration

Skin and subcutaneous tissue disorders: dry skin, exfoliative dermatitis

Clinical Trial Experience In Pediatric Patients 11 Years And Older

The safety of Oxycontin has been evaluated in one clinical trial with 140 patients 11 to 16 years of age. The median duration of treatment was approximately three weeks.

The most frequently reported adverse events were

• vomiting,
• nausea,
• headache,
• pyrexia, and
• constipation.

Table 3 includes a summary of the incidence of treatment emergent adverse events reported in ≥5% of patients.

Table 3: Incidence of Adverse Reactions Reported in ≥ 5.0% Patients 11 to 16 Years

The following adverse reactions occurred in a clinical trial of Oxycontin in patients 11 to 16 years of age with an incidence between ≥1.0% and < 5.0%. Events are listed within each System/Organ Class.

Blood and lymphatic system disorders: febrile neutropenia, neutropenia

Cardiac disorders: tachycardia

Gastrointestinal disorders: abdominal pain, gastroesophageal reflux disease

General disorders and administration site conditions: fatigue, pain, chills, asthenia

Injury, poisoning, and procedural complications: procedural pain, seroma

Investigations: oxygen saturation decreased, alanine aminotransferase increased, hemoglobin decreased, platelet count decreased, neutrophil count decreased, red blood cell count decreased, weight decreased

Metabolic and nutrition disorders: hypochloremia, hyponatremia

Musculoskeletal and connective tissue disorders: pain in extremity, musculoskeletal pain

Nervous system disorders: somnolence, hypoesthesia, lethargy, paresthesia

Psychiatric disorders: insomnia, anxiety, depression, agitation

Renal and urinary disorders: dysuria, urinary retention

Respiratory, thoracic, and mediastinal disorders: oropharyngeal pain

Skin and subcutaneous tissue disorders: hyperhidrosis, rash

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of extended-release oxycodone. 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.

Abuse, addiction, aggression, amenorrhea, cholestasis, completed suicide, death, dental caries, increased hepatic enzymes, hyperalgesia, hypogonadism, hyponatremia, ileus, intentional overdose, mood altered, muscular hypertonia, overdose, palpitations (in the context of withdrawal), seizures, suicidal attempt, suicidal ideation, syndrome of inappropriate antidiuretic hormone secretion, and urticaria.

In addition to the events listed above, the following have also been reported, potentially due to the swelling and hydrogelling property of the tablet: choking, gagging, regurgitation, tablets stuck in the throat and difficulty swallowing the tablet.

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 Oxycontin.

Androgen Deficiency

Cases of androgen deficiency have occurred with chronic use of opioids.

Table 4 includes clinically significant drug interactions with Oxycontin.

Table 4: Clinically Significant Drug Interactions with Oxycontin

Drug Abuse And Dependence

Controlled Substance

Oxycontin contains oxycodone, a Schedule II controlled substance.

Abuse

Oxycontin contains oxycodone, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxymorphone, and tapentadol. Oxycontin can be abused and is subject to misuse, addiction, and criminal diversion.

The high drug content in extended-release formulations adds to the risk of adverse outcomes from abuse and misuse.

• 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.
• Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: 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 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 healthcare provider(s).
• “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate 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. Healthcare providers 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.
• Oxycontin, 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 reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific to Abuse of Oxycontin

Oxycontin is for oral use only. Abuse of Oxycontin poses a risk of overdose and death. The risk is increased with concurrent use of Oxycontin with alcohol and other central nervous system depressants. Taking cut, broken, chewed, crushed, or dissolved Oxycontin enhances drug release and increases the risk of overdose and death.

With parenteral abuse, the inactive ingredients in Oxycontin can be expected to result in local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis, valvular heart injury, embolism, and death. Cases of thrombotic microangiopathy (a condition characterized clinically by thrombocytopenia and microangiopathic hemolytic anemia) associated with parenteral abuse have been reported.

Parenteral drug abuse is commonly associated with transmission of infectious diseases, such as hepatitis and HIV.

Abuse Deterrence Studies

Oxycontin is formulated with inactive ingredients intended to make the tablet more difficult to manipulate for misuse and abuse. For the purposes of describing the results of studies of the abuse-deterrent characteristics of Oxycontin resulting from a change in formulation, in this section, the original formulation of Oxycontin, which is no longer marketed, will be referred to as “original Oxycontin” and the reformulated, currently marketed product will be referred to as “Oxycontin".

In Vitro Testing

In vitro physical and chemical tablet manipulation studies were performed to evaluate the success of different extraction methods in defeating the extended-release formulation. Results support that, relative to original Oxycontin, there is an increase in the ability of Oxycontin to resist crushing, breaking, and dissolution using a variety of tools and solvents.

The results of these studies also support this finding for Oxycontin relative to an immediate-release oxycodone. When subjected to an aqueous environment, Oxycontin gradually forms a viscous hydrogel (i.e., a gelatinous mass) that resists passage through a needle.

Clinical Studies

In a randomized, double-blind, placebo-controlled 5-period crossover pharmacodynamic study, 30 recreational opioid users with a history of intranasal drug abuse received intranasally administered active and placebo drug treatments.

The five treatment arms were finely crushed Oxycontin 30 mg tablets, coarsely crushed Oxycontin 30 mg tablets, finely crushed original Oxycontin 30 mg tablets, powdered oxycodone HCl 30 mg, and placebo. Data for finely crushed Oxycontin, finely crushed original Oxycontin, and powdered oxycodone HCl are described below.

• Drug liking was measured on a bipolar drug liking scale of 0 to 100 where 50 represents a neutral response of neither liking nor disliking, 0 represents maximum disliking and 100 represents maximum liking.
• Response to whether the subject would take the study drug again was also measured on a bipolar scale of 0 to 100 where 50 represents a neutral response, 0 represents the strongest negative response (“definitely would not take drug again”) and 100 represents the strongest positive response (“definitely would take drug again”).
• Twenty-seven of the subjects completed the study. Incomplete dosing due to granules falling from the subjects’ nostrils occurred in 34% (n = 10) of subjects with finely crushed Oxycontin, compared with 7% (n = 2) of subjects with finely crushed original Oxycontin and no subjects with powdered oxycodone HCl.
• The intranasal administration of finely crushed Oxycontin was associated with a numerically lower mean and median drug liking score and a lower mean and median score for take drug again, compared to finely crushed original Oxycontin or powdered oxycodone HCl as summarized in Table 5.

Table 5: Summary of Maximum Drug Liking (Emax) Data Following Intranasal Administration

Figure 1 demonstrates a comparison of drug liking for finely crushed Oxycontin compared to powdered oxycodone HCl in subjects who received both treatments. The Y-axis represents the percent of subjects attaining a percent reduction in drug liking for Oxycontin vs. oxycodone HCl powder greater than or equal to the value on the X-axis. Approximately 44% (n = 12) had no reduction in liking with Oxycontin relative to oxycodone HCl.

Approximately 56% (n = 15) of subjects had some reduction in drug liking with Oxycontin relative to oxycodone HCl. Thirty-three percent (n = 9) of subjects had a reduction of at least 30% in drug liking with Oxycontin compared to oxycodone HCl, and approximately 22% (n = 6) of subjects had a reduction of at least 50% in drug liking with Oxycontin compared to oxycodone HCl.

Figure 1: Percent Reduction Profiles for Emax of Drug Liking VAS for Oxycontin vs. oxycodone HCl, N=27 Following Intranasal Administration

Percent Reduction Profiles for Emax of Drug Liking VAS for OXYCONTIN vs. oxycodone HCl.

The results of a similar analysis of drug liking for finely crushed Oxycontin relative to finely crushed original Oxycontin were comparable to the results of finely crushed Oxycontin relative to powdered oxycodone HCl.

• Approximately 43% (n = 12) of subjects had no reduction in liking with Oxycontin relative to original Oxycontin.
• Approximately 57% (n = 16) of subjects had some reduction in drug liking,
• 36% (n = 10) of subjects had a reduction of at least 30% in drug liking, and
• approximately 29% (n = 8) of subjects had a reduction of at least 50% in drug liking with Oxycontin compared to original Oxycontin.

Summary

The in vitro data demonstrate that Oxycontin has physicochemical properties expected to make abuse via injection difficult. The data from the clinical study, along with support from the in vitro data, also indicate that Oxycontin has physicochemical properties that are expected to reduce abuse via the intranasal route. However, abuse of Oxycontin by these routes, as well as by the oral route, is still possible.

• Additional data, including epidemiological data, when available, may provide further information on the impact of the current formulation of Oxycontin on the abuse liability of the drug. Accordingly, this section may be updated in the future as appropriate.
• Oxycontin contains oxycodone, an opioid agonist and Schedule II controlled substance with an abuse liability similar to other opioid agonists, legal or illicit, including fentanyl, hydromorphone, methadone, morphine, and oxymorphone. Oxycontin can be abused and is subject to misuse, addiction, and criminal diversion.

Dependence

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 dosage 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 (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 opioid usage.
• Oxycontin should not be abruptly discontinued. If Oxycontin is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and 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.
• Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs.