Oxycodone

Oxycodone is an Opioid receptor agonist belonging to the analgesic class.

Oxycodone is an opioid used in the management of moderate to severe pain.

Oxycodone is well Absorbed from the GI tract. Its Bioavailability is Approximately 60-87%. The volume of distribution of Oxycodone is 2.6L/kg. It is 45% protein bound Oxycodone is primarily bound to serum albumin and to a lesser degree alpha1-acid glycoprotein. Oxycodone is mainly metabolized via glucuronidation to nor oxycodone by CYP3A isoenzymes and to a lesser extent, to oxymorphone by CYP2D6.It is primarily excreted Via urine as unchanged drug.

Oxycodone shows side effects like Dry mouth, stomach pain, drowsiness, flushing, headache, mood changes.

Oxycodone is available in the form of Oral solution, Oral tablet, oral capsule, compounding powder.

Oxycodone is available in India, US, UK, Malaysia, Germany, Singapore, France.

Oxycodone is an Analgesic belonging to the class Opioid agonist.

Oxycodone and its active metabolites, noroxycodone, oxymorphone, and noroxymorphone are opioid agonists. These compounds passively diffuse across the blood brain barrier or may be actively transported across by an unknown mechanism. Oxycodone and its active metabolites can selectively bind to the mu opioid receptor, but also the kappa and delta opioid receptors in the central nervous system and periphery and induce a G protein coupled receptor signaling pathway. The activation of mu opioid receptors inhibits N-type voltage operated calcium channels, inhibiting responses to pain.

The onset of action of Oxycodone is approximately 10-15 min (immediate release).

The duration of the action of Oxycodone is about 3-6 hours (immediate-release); ≤12 hours (extended-release).

Oxycodone is available in the form of Oral solution, Oral tablet, oral capsule, compounding powder.

Oxycodone is an opioid pain medication sometimes called a narcotic. Oxycodone is used to treat moderate to severe pain.

Oxycodone is an Opioid receptor agonist belonging to the analgesic class.

Oxycodone is a synthetic phenanthrene-derivative opiate agonist. It binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain. It produces generalised CNS depression.

Oxycodone is approved for use in the following clinical indications

• Acute pain in opioid-naive patients
• Acute pain in patients on chronic opioid therapy
• Acute postoperative pain, postoperative recovery/postanesthesia care unit
• Chronic pain, including chronic cancer pain

• Acute pain in opioid-naive patients

Oral Dose: Initial: 5 mg every 4 to 6 hours as needed; adjust dose according to patient response. Usual dosage range: 5 to 15 mg every 4 to 6 hours as needed. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies. For outpatient use, usually up to 20 mg/day for moderate pain or up to 30 mg/day for severe pain will suffice. Dosing is based on severity of pain and patient-specific factors; reduced dosing may be indicated in patients with comorbidities.

Rectal Usual dosage range: One (10 or 20 mg) suppository up to 3 to 4 times daily as needed. If the usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies.

• Acute pain in patients on chronic opioid therapy

Immediate release: Oral: Usual dose: In conjunction with the scheduled opioid, administer 5% to 15% (rarely up to 20%) of the 24-hour oxycodone requirement (or MME) as needed using an IR formulation every 4 to 6 hours with subsequent dosage adjustments based upon response.

• Acute postoperative pain, postoperative recovery/postanesthesia care unit

Oral Dose: Usual dosage range: 5 to 10 mg every 4 to 6 hours as needed. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies. Some experts use 5 to 10 mg every 3 to 4 hours as needed.

• Chronic pain, including chronic cancer pain

Oral Dose: Initial: 2.5 to 10 mg every 4 to 6 hours as needed or scheduled around the clock (eg, cancer pain); adjust dose according to patient response (see "Titration" below). Usual maintenance dosage range: 5 to 15 mg every 4 to 6 hours as needed or scheduled around the clock. If the usual dose and frequency is insufficient, reassess the patient and reconsider pain management strategies. Dosing is based on severity of pain and patient-specific factors; start at the lower end of dosing range.

Rectal Usual dosage range: One (10 or 20 mg) suppository up to 3 to 4 times daily as needed. If the usual dose and frequency is insufficient, reassess the patient and reconsider pain management strategies.

Oxycodone is available in various strengths as 5 mg/5 mL; 20 mg/mL; 5 mg; 15 mg; 30 mg; 10 mg; 20 mg; 40 mg; 80 mg; 60 mg; 9 mg; 13.5 mg; 18 mg; 27 mg; 36 mg; 160 mg; 7.5 mg.

Oxycodone is available in the form of Oral solution, Oral tablet, oral capsule, compounding powder.

Oxycodone is contraindicated in patients with

• Significant respiratory depression
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
• Known or suspected paralytic ileus and gastrointestinal obstruction
• Hypersensitivity (e.g., anaphylaxis) to oxycodone

• CNS depression

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).

• Constipation

May cause constipation, which may be problematic in patients with unstable angina and patients post-myocardial infarction (MI). Consider preventive measures (eg, stool softener, increased fiber) to reduce the potential for constipation.

• Hypotension

May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs that may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration. Avoid use in patients with circulatory shock.

• Phenanthrene hypersensitivity

Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (codeine, hydrocodone, hydromorphone, levorphanol, oxymorphone).

• Respiratory depression

Fatal respiratory depression may occur. Swallow ER tablets whole; crushing, chewing, or dissolving can cause rapid release and a potentially fatal dose. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. Patients and caregivers should be educated on how to recognize respiratory depression and the importance of getting emergency assistance immediately in the event of a known or suspected overdose.

• Abdominal conditions

May obscure diagnosis or clinical course of patients with acute abdominal conditions.

• Adrenocortical insufficiency

Use with caution in patients with adrenocortical insufficiency, including Addison disease; dose adjustment may be required. Long-term opioid use may cause secondary hypogonadism, which may lead to mood disorders and osteoporosis.

• Biliary tract impairment

Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; may cause constriction of sphincter of Oddi.

• CNS depression/coma

Avoid use in patients with impaired consciousness or coma as these patients are susceptible to intracranial effects of CO₂ retention.

• Delirium tremens

Use with caution in patients with delirium tremens.

• Head trauma

Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur.

• Hepatic impairment

Use with caution in patients with hepatic impairment; oxycodone clearance may decrease.

• Mental health conditions

Use opioids with caution for chronic pain in patients with mental health conditions (eg, depression, anxiety disorders, post-traumatic stress disorder) due to potential increased risk for opioid use disorder and overdose; more frequent monitoring is recommended.

• Obesity

Use with caution in patients who are morbidly obese.

• Prostatic hyperplasia/urinary stricture

Use with caution in patients with prostatic hyperplasia and/or urinary stricture; dose adjustment may be required.

• Psychosis

Use with caution in patients with toxic psychosis.

• Renal impairment

Use with caution in patients with renal impairment; oxycodone clearance may decrease.

• Respiratory disease

Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression, particularly when initiating and titrating therapy; critical respiratory depression may occur, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.

• Seizures

Use with caution in patients with a history of seizure disorders; may cause or exacerbate preexisting seizures.

• Sleep-related disorders

Use with caution in patients with sleep-related disorders, including sleep apnea, due to increased risk for respiratory and CNS depression. Monitor carefully and titrate dosage cautiously in patients with mild sleep-disordered breathing. Avoid opioids in patients with moderate to severe sleep-disordered breathing.

• Thyroid dysfunction

Use with caution in patients with thyroid dysfunction.

• Benzodiazepines or other CNS depressants

Concomitant use may result in respiratory depression and sedation, which may be fatal. Consider prescribing naloxone for emergency treatment of opioid overdose in patients taking benzodiazepines or other CNS depressants concomitantly with opioids.

• CYP 3A4 interactions

Oxycodone has been detected in breast milk. Instruct patients not to undertake nursing while receiving Oxycodone. Do not initiate Oxycodone therapy while nursing because of the possibility of sedation or respiratory depression in the infant. Withdrawal signs can occur in breast-fed infants when maternal administration of an opioid analgesic or when breastfeeding is stopped.

There are no adequate and well-controlled studies in pregnant women. Oxycodone should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

• Common

Drowsiness, headache, dizziness, Pruritus, Nausea , constipation, vomiting, Fever Flushing, hypertension, orthostatic hypotension, oxygen saturation decreased, edema, tachycardia, cardiac failure, deep vein thrombosis, hypotension, palpitations, peripheral edema, thrombophlebitis, vasodilation, Abnormality in thinking, dysphoria, insomnia, irritability, twitching, abnormal dreams, anxiety , chills , confusion , euphoria, fatigue, hypoesthesia , migraine , nervousness , withdrawal syndrome, agitation, pain, depression, lethargy, paresthesia, procedural pain, hypertonia, neuralgia, personality disorder Excoriation, diaphoresis , hyperhidrosis , skin rash , skin photosensitivity, urticaria, Hypochloremia, hyponatremia, weight loss, hyperglycemia , gout, Diarrhea , xerostomia, gastritis, hiccups, upper abdominal pain, abdominal pain , anorexia , decreased appetite , dyspepsia , gastroesophageal reflux disease, dysphagia, gingivitis, glossitis, Dysuria, urinary retention, urinary tract infection, Decreased hemoglobin, decreased platelet count, decreased red blood cells, febrile neutropenia, neutropenia, anemia, hemorrhage, iron deficiency anemia, leukopenia, Increased serum alanine aminotransferase Hypersensitivity reaction, Herpes simplex infection, infection, sepsis, Asthenia, limb pain, arthralgia , back pain , musculoskeletal pain, myalgia , tremor , arthritis, laryngospasm, neck pain, ostealgia, pathological fracture, Blurred vision, amblyopia , Cough, dyspnea, oropharyngeal pain, bronchitis, epistaxis, flu-like symptoms, laryngismus, pharyngitis, pulmonary disease, rhinitis , sinusitis, Seroma, accidental injury, Circulatory depression, shock, Depersonalization, Respiratory depression.

• Rare

Abnormal gait, aggressive behavior, amenorrhea, amnesia, chest pain, choking sensation, cholestasis, dehydration, dental caries, depression of ST segment on ECG, diverticulitis of the gastrointestinal tract (exacerbation), drug abuse, drug dependence, drug overdose (may be intentional), dysgeusia, emotional lability, eructation, exfoliative dermatitis, facial edema, flatulence, gag reflex, gastrointestinal disease, hallucination, hematuria, hyperalgesia, hyperkinesia, hypogonadism, hypotonia, impotence, increased appetite, increased gamma-glutamyl transferase, increased heart rate, increased liver enzymes, increased thirst, intestinal obstruction, lymphadenopathy, malaise, memory impairment, mood changes, neonatal withdrawal, night sweats, pharyngeal edema, polyuria, restlessness, seizure, SIADH, sleep disturbance, speech disturbance, stomatitis, stupor, suicidal ideation, suicidal tendencies, syncope, tinnitus, vertigo, visual disturbance, voice disorder, xeroderma.

• Alizapride

May enhance the CNS depressant effect of CNS Depressants.

• Alvimopan

Opioid Agonists may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation.

• Amphetamines

May enhance the analgesic effect of Opioid Agonists.

• Anticholinergic Agents

May enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination.

• Azelastine (Nasal)

May enhance the CNS depressant effect of CNS Depressants.

• Blonanserin

CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin.

• Brimonidine (Topical)

May enhance the CNS depressant effect of CNS Depressants.

• Bromopride

May enhance the CNS depressant effect of CNS Depressants.

• Bromperidol

May enhance the CNS depressant effect of CNS Depressants.

• Cannabinoid-Containing Products

CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products.

• Chlormethiazole

May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.

• Chlorphenesin Carbamate

May enhance the adverse/toxic effect of CNS Depressants.

• Clofazimine

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

• CNS Depressants

May enhance the CNS depressant effect of Oxycodone. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.

• CYP3A4 Inducers (Moderate)

May decrease the serum concentration of oxycodone.

• CYP3A4 Inducers (Strong)

May decrease the serum concentration of Oxycodone.

• CYP3A4 Inhibitors (Moderate)

May increase the serum concentration of Oxycodone. Serum concentrations of the active metabolite Oxymorphone may also be increased.

• CYP3A4 Inhibitors (Strong)

May enhance the adverse/toxic effect of Oxycodone. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Oxycodone. Serum concentrations of the active metabolite oxymorphone may also be increased.

• Daridorexant

May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended.

• Desmopressin

Opioid Agonists may enhance the hyponatremic effect of Desmopressin.

• Dexmedetomidine

CNS Depressants may enhance the CNS depressant effect of dexmedetomidine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants and consider dose reductions of either agent to avoid excessive CNS depression.

• Difelikefalin

May enhance the CNS depressant effect of CNS Depressants.

• Dimethindene (Topical)

May enhance the CNS depressant effect of CNS Depressants.

• Diuretics

Opioid Agonists may enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics.

• DroPERidol

May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use.

• Eluxadoline

Opioid Agonists may enhance the constipating effect of Eluxadoline.

• Fexinidazole

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

• Flunarizine

CNS Depressants may enhance the CNS depressant effect of Flunarizine.

• Flunitrazepam

CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available.

• Fusidic Acid (Systemic)

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

• Gastrointestinal Agents (Prokinetic)

Opioid Agonists may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).

• Hydroxyzine

May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant.

• Ixabepilone:

May enhance the CNS depressant effect of CNS Depressants.

• Kava Kava

May enhance the CNS depressant effect of CNS Depressants.

• Kratom

May enhance the CNS depressant effect of CNS Depressants.

• Lemborexant

May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary.

• Lisuride

May enhance the CNS depressant effect of CNS Depressants.

• Lofexidine:

May enhance the CNS depressant effect of CNS Depressants.

• Magnesium Sulfate

May enhance the CNS depressant effect of CNS Depressants.

• Methotrimeprazine

May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patients closely for evidence of CNS depression.

• Metoclopramide

May enhance the CNS depressant effect of CNS Depressants.

• Metyrosine

CNS Depressants may enhance the sedative effect of Metyrosine.

• Minocycline (Systemic)

May enhance the CNS depressant effect of CNS Depressants.

• Monoamine Oxidase Inhibitors

Oxycodone may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: Use of oxycodone is not recommended for patients taking MAOIs or within 14 days of MAOI discontinuation. If combined, use test doses and frequent titration of small doses while monitoring blood pressure, CNS depression, and signs of serotonin syndrome.

• Nalmefene

May diminish the therapeutic effect of Opioid Agonists. Management: Avoid the concomitant use of oral nalmefene and opioid agonists. Discontinue oral nalmefene 1 week prior to any anticipated use of opioid agonists. If combined, larger doses of opioid agonists will likely be required.

• Naltrexone

May diminish the therapeutic effect of Opioid Agonists. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations.

• Nefazodone

Opioid Agonists (metabolized by CYP3A4) may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Opioid Agonists (metabolized by CYP3A4). Management: If concomitant use of opioid agonists that are metabolized by CYP3A4 and nefazodone is necessary, consider dose reduction of the opioid until stable drug effects are achieved. Monitor for increased opioid effects and serotonin syndrome/serotonin toxicity.

• Olopatadine (Nasal)

May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

• Opioids (Mixed Agonist / Antagonist)

May diminish the analgesic effect of Opioid Agonists. Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations.

• Orphenadrine

CNS Depressants may enhance the CNS depressant effect of Orphenadrine.

• Oxomemazine

May enhance the CNS depressant effect of CNS Depressants.

• Paraldehyde

CNS Depressants may enhance the CNS depressant effect of Paraldehyde.

• Pegvisomant

Opioid Agonists may diminish the therapeutic effect of Pegvisomant.

• Phenobarbital

May enhance the CNS depressant effect of Oxycodone. Phenobarbital may decrease the serum concentration of Oxycodone. Management: Avoid use of oxycodone and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined.

• Piribedil

CNS Depressants may enhance the CNS depressant effect of Piribedil.

• Pramipexole

CNS Depressants may enhance the sedative effect of Pramipexole.

• Primidone

May enhance the CNS depressant effect of Oxycodone. Primidone may decrease the serum concentration of Oxycodone. Management: Avoid use of oxycodone and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitors decrease oxycodone efficacy and withdrawal if combined.

• Procarbazine

May enhance the CNS depressant effect of CNS Depressants.

• Rufinamide

May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.

• Samidorphan

May diminish the therapeutic effect of Opioid Agonists.

• Serotonergic Agents (High Risk)

Opioid Agonists (metabolized by CYP3A4) may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

• Sincalide

Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction.

• Somatostatin Analogs

Opioid Agonists may diminish the analgesic effect of Somatostatin Analogs. Opioid Agonists may enhance the analgesic effect of Somatostatin Analogs.

• Succinylcholine

May enhance the bradycardic effect of Opioid Agonists.

• Suvorexant

CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended.

• Thalidomide

CNS Depressants may enhance the CNS depressant effect of Thalidomide.

• Valerian

May enhance the CNS depressant effect of CNS Depressants.

• Zolpidem

• Alizapride

May enhance the CNS depressant effect of CNS Depressants.

• Alvimopan

Opioid Agonists may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation.

• Amphetamines

May enhance the analgesic effect of Opioid Agonists.

• Anticholinergic Agents

May enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination.

• Azelastine (Nasal)

May enhance the CNS depressant effect of CNS Depressants.

• Blonanserin

CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin.

• Brimonidine (Topical)

May enhance the CNS depressant effect of CNS Depressants.

• Bromopride

May enhance the CNS depressant effect of CNS Depressants.

• Bromperidol

May enhance the CNS depressant effect of CNS Depressants.

• Cannabinoid-Containing Products

CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products.

• Chlormethiazole

May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.

• Chlorphenesin Carbamate

May enhance the adverse/toxic effect of CNS Depressants.

• Clofazimine

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

• CNS Depressants

May enhance the CNS depressant effect of Oxycodone. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.

• CYP3A4 Inducers (Moderate)

May decrease the serum concentration of oxycodone.

• CYP3A4 Inducers (Strong)

May decrease the serum concentration of Oxycodone.

• CYP3A4 Inhibitors (Moderate)

May increase the serum concentration of Oxycodone. Serum concentrations of the active metabolite Oxymorphone may also be increased.

• CYP3A4 Inhibitors (Strong)

May enhance the adverse/toxic effect of Oxycodone. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Oxycodone. Serum concentrations of the active metabolite oxymorphone may also be increased.

• Daridorexant

May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended.

• Desmopressin

Opioid Agonists may enhance the hyponatremic effect of Desmopressin.

• Dexmedetomidine

CNS Depressants may enhance the CNS depressant effect of dexmedetomidine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants and consider dose reductions of either agent to avoid excessive CNS depression.

• Difelikefalin

May enhance the CNS depressant effect of CNS Depressants.

• Dimethindene (Topical)

May enhance the CNS depressant effect of CNS Depressants.

• Diuretics

Opioid Agonists may enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics.

• DroPERidol

May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use.

• Eluxadoline

Opioid Agonists may enhance the constipating effect of Eluxadoline.

• Fexinidazole

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

• Flunarizine

CNS Depressants may enhance the CNS depressant effect of Flunarizine.

• Flunitrazepam

CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available.

• Fusidic Acid (Systemic)

May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

• Gastrointestinal Agents (Prokinetic)

Opioid Agonists may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).

• Hydroxyzine

May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant.

• Ixabepilone:

May enhance the CNS depressant effect of CNS Depressants.

• Kava Kava

May enhance the CNS depressant effect of CNS Depressants.

• Kratom

May enhance the CNS depressant effect of CNS Depressants.

• Lemborexant

May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary.

• Lisuride

May enhance the CNS depressant effect of CNS Depressants.

• Lofexidine:

May enhance the CNS depressant effect of CNS Depressants.

• Magnesium Sulfate

May enhance the CNS depressant effect of CNS Depressants.

• Methotrimeprazine

May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patients closely for evidence of CNS depression.

• Metoclopramide

May enhance the CNS depressant effect of CNS Depressants.

• Metyrosine

CNS Depressants may enhance the sedative effect of Metyrosine.

• Minocycline (Systemic)

May enhance the CNS depressant effect of CNS Depressants.

• Monoamine Oxidase Inhibitors

Oxycodone may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: Use of oxycodone is not recommended for patients taking MAOIs or within 14 days of MAOI discontinuation. If combined, use test doses and frequent titration of small doses while monitoring blood pressure, CNS depression, and signs of serotonin syndrome.

• Nalmefene

May diminish the therapeutic effect of Opioid Agonists. Management: Avoid the concomitant use of oral nalmefene and opioid agonists. Discontinue oral nalmefene 1 week prior to any anticipated use of opioid agonists. If combined, larger doses of opioid agonists will likely be required.

• Naltrexone

May diminish the therapeutic effect of Opioid Agonists. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations.

• Nefazodone

Opioid Agonists (metabolized by CYP3A4) may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Opioid Agonists (metabolized by CYP3A4). Management: If concomitant use of opioid agonists that are metabolized by CYP3A4 and nefazodone is necessary, consider dose reduction of the opioid until stable drug effects are achieved. Monitor for increased opioid effects and serotonin syndrome/serotonin toxicity.

• Olopatadine (Nasal)

May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

• Opioids (Mixed Agonist / Antagonist)

May diminish the analgesic effect of Opioid Agonists. Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations.

• Orphenadrine

CNS Depressants may enhance the CNS depressant effect of Orphenadrine.

• Oxomemazine

May enhance the CNS depressant effect of CNS Depressants.

• Paraldehyde

CNS Depressants may enhance the CNS depressant effect of Paraldehyde.

• Pegvisomant

Opioid Agonists may diminish the therapeutic effect of Pegvisomant.

• Phenobarbital

May enhance the CNS depressant effect of Oxycodone. Phenobarbital may decrease the serum concentration of Oxycodone. Management: Avoid use of oxycodone and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined.

• Piribedil

CNS Depressants may enhance the CNS depressant effect of Piribedil.

• Pramipexole

CNS Depressants may enhance the sedative effect of Pramipexole.

• Primidone

May enhance the CNS depressant effect of Oxycodone. Primidone may decrease the serum concentration of Oxycodone. Management: Avoid use of oxycodone and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitors decrease oxycodone efficacy and withdrawal if combined.

• Procarbazine

May enhance the CNS depressant effect of CNS Depressants.

• Rufinamide

May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.

• Samidorphan

May diminish the therapeutic effect of Opioid Agonists.

• Serotonergic Agents (High Risk)

Opioid Agonists (metabolized by CYP3A4) may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined.

• Sincalide

Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction.

• Somatostatin Analogs

Opioid Agonists may diminish the analgesic effect of Somatostatin Analogs. Opioid Agonists may enhance the analgesic effect of Somatostatin Analogs.

• Succinylcholine

May enhance the bradycardic effect of Opioid Agonists.

• Suvorexant

CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended.

• Thalidomide

CNS Depressants may enhance the CNS depressant effect of Thalidomide.

• Valerian

May enhance the CNS depressant effect of CNS Depressants.

• Zolpidem

The common side effects of Oxycodone include the following

• Common side effects

Dry mouth, stomach pain, drowsiness, flushing, headache, mood changes.

• Rare side effects

Changes in heartbeat, agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination, nausea, vomiting, or diarrhea, nausea, vomiting, loss of appetite, weakness, or dizziness, inability to get or keep an erection, irregular menstruation, decreased sexual desire, chest pain, hives, itching, rash, swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs, hoarseness, difficulty breathing or swallowing, seizures, extreme drowsiness, lightheadedness when changing positions.

• Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Oxycodone should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

• Nursing Mothers

Oxycodone has been detected in breast milk. Instruct patients not to undertake nursing while receiving Oxycodone. Do not initiate Oxycodone therapy while nursing because of the possibility of sedation or respiratory depression in the infant. Withdrawal signs can occur in breast-fed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.

• Pediatric Use

The safety and efficacy of Oxycodone has been established in pediatric patients ages 11 to 16 years. Use of Oxycodone is supported by evidence from adequate and well-controlled trials with Oxycodone in adults as well as an open-label study in pediatric patients ages 6 to 16 years. However, there were insufficient numbers of patients less than 11 years of age enrolled in this study to establish the safety of the product in this age group.The safety of Oxycodone in pediatric patients was evaluated in 155 patients previously receiving and tolerating opioids for at least 5 consecutive days with a minimum of 20 mg per day of oxycodone or its equivalent on the two days immediately preceding dosing with Oxycodone. Patients were started on a total daily dose ranging between 20 mg and 100 mg depending on prior opioid dose. The most frequent adverse events observed in pediatric patients were vomiting, nausea, headache, pyrexia, and constipation.

• Geriatric Use

In controlled pharmacokinetic studies in elderly subjects (greater than 65 years) the clearance of oxycodone was slightly reduced. Compared to young adults, the plasma concentrations of oxycodone increased approximately 15%. Of the total number of subjects (445) in clinical studies of oxycodone hydrochloride controlled-release tablets, 148 (33.3%) were aged 65 and older (including those age 75 and older) while 40 (9.0%) were age 75 and older. In clinical trials with appropriate initiation of therapy and dose titration, no untoward or unexpected adverse reactions were seen in the elderly patients who received oxycodone hydrochloride controlled-release tablets. Thus, the usual doses and dosing intervals may be appropriate for elderly patients. However, a dosage reduction in debilitated, non-opioid ­tolerant patients is recommended Respiratory depression is the chief risk for elderly patients treated with opioids and has occurred after large initial doses were administered to patients who are not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Oxycodone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Symptoms: Pin-point pupils, resp depression, hypotension. Circulatory failure and somnolence progressing to stupor or deepening coma, skeletal muscle flaccidity, bradycardia and death may occur in more severe cases.

Management: Maintain adequate respiration and employ supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation. Naloxone may be used as an antidote.

• Pharmacodynamic

Oxycodone acts directly on a number of tissues not related to its analgesic effect. These tissues include the respiratory centre in the brain stem, the cough centre in the medulla, muscles of the pupils, gastrointestinal tract, cardiovascular system, endocrine system, and immune system. Oxycodone's effect on the respiratory centre is dose dependant respiratory depression. The action on the cough centre is suppression of the cough reflex. Pupils become miopic or decrease in size, peristalsis of the gastrointestinal tract slows, and muscle tone in the colon may increase causing constipation. In the cardiovascular system histamine may be released leading to pruritis, red eyes, flushing, sweating, and decreased blood pressure. Endocrine effects may include increased prolactin, decreased cortisol, and decreased testosterone.

• Pharmacokinetics

Absorption

Oxycodone is well Absorbed from the GI tract. Its Bioavailability is Approximately 60-87%.

Distribution

The volume of distribution of Oxycodone is 2.6L/kg. It is 45% protein bound Oxycodone is primarily bound to serum albumin and to a lesser degree alpha1-acid glycoprotein.

Metabolism and Excretion

Oxycodone is mainly metabolized via glucuronidation to nor oxycodone by CYP3A isoenzymes and to a lesser extent, to oxymorphone by CYP2D6.It is primarily excreted Via urine as unchanged drug.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022272s027lbl.pdf
• https://go.drugbank.com/drugs/DB00497
• https://www.uptodate.com/contents/oxycodone-drug-information?search=oxycodone&source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&display_rank=1
• https://medlineplus.gov/druginfo/meds/a682132.html
• https://www.drugs.com/oxycodone.html
• https://www.mims.com/india/drug/info/oxycodone?type=full&mtype=generic
• https://www.rxlist.com/oxycontin-drug.htm#description