Oxycodone

Dosage for oxycodone must be highly individualized based on the patient's pain severity, prior opioid exposure, and individual response. Healthcare providers follow the principle of "start low and go slow" to minimize side effects.

• Opioid-Naive Patients (Immediate Release): For patients not currently taking opioids, the typical starting dose is 5 mg to 15 mg every 4 to 6 hours as needed for pain.
• Opioid-Tolerant Patients: Patients who have been taking other opioids may require higher starting doses. The provider will use an equianalgesic conversion table to calculate a safe starting point.
• Extended-Release (ER) Dosing: ER tablets are usually started at 10 mg every 12 hours. These are NOT for "as needed" (PRN) use. They are intended for patients who require continuous, around-the-clock pain control.
• Maximum Dose: There is no formal ceiling dose for pure oxycodone; however, the dose is limited by side effects, particularly respiratory depression. If using combination products (e.g., with acetaminophen), the dose is strictly limited by the maximum daily allowance of the non-opioid component (usually 4,000 mg of acetaminophen).

Oxycodone use in children is generally restricted. The immediate-release formulations are sometimes used off-label in pediatric populations for severe post-operative pain under strict hospital supervision, often calculated by weight (e.g., 0.05 mg/kg to 0.15 mg/kg). The extended-release formulation (OxyContin) is FDA-approved only for opioid-tolerant children aged 11 years and older who have a condition requiring daily, long-term opioid treatment. Use in children younger than 11 for chronic pain is not recommended and has not been established as safe.

Renal Impairment

Because oxycodone is excreted by the kidneys, patients with reduced renal function (CrCl < 60 mL/min) may experience drug accumulation. Healthcare providers typically start these patients at 50% to 75% of the standard dose and monitor closely for signs of sedation or respiratory depression.

Hepatic Impairment

Since the liver metabolizes oxycodone, patients with hepatic insufficiency (liver failure) will have higher plasma concentrations. For patients with mild to moderate liver impairment, the starting dose should be reduced, and the interval between doses may be lengthened.

Elderly Patients

Older adults are more sensitive to the effects of opioids. Providers often start with the lowest possible dose (e.g., 2.5 mg to 5 mg) due to the increased risk of confusion, falls, and slowed breathing in this population.

1. 1Consistency: Immediate-release forms can be taken with or without food. If the medication causes nausea, taking it with a meal may help.
2. 2Swallow Whole: Extended-release tablets (ER) must be swallowed whole. Never crush, chew, break, or dissolve them. Doing so releases the entire 12-hour dose at once, which can be fatal.
3. 3Liquid Measurement: If using the oral solution, always use a calibrated medication measuring device (oral syringe or dose cup). A household teaspoon is not accurate.
4. 4Storage: Store oxycodone at room temperature in a secure, locked location. This is critical to prevent accidental ingestion by children or theft/misuse by others.
5. 5Disposal: Unused oxycodone should be taken to a drug take-back site or, if unavailable, flushed down the toilet (as per FDA "flush list" guidelines for high-risk medications).

If you miss a dose of immediate-release oxycodone, take it as soon as you remember, unless it is almost time for your next dose. For extended-release forms, if you miss a dose, skip it and return to your regular schedule. Never double the dose to make up for a missed one, as this significantly increases the risk of overdose.

An oxycodone overdose is a medical emergency. Signs include pinpoint pupils, extreme drowsiness, cold/clammy skin, limp muscles, and dangerously slow or stopped breathing. If an overdose is suspected, call 911 immediately. If available, administer Naloxone (Narcan) according to the package instructions. Naloxone is an opioid antagonist that can temporarily reverse the effects of the overdose while waiting for emergency responders.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose without medical guidance.

Most patients taking oxycodone will experience at least one side effect. These are generally manageable but should be monitored:

• Constipation: This is the most common side effect and, unlike others, does not go away with time. Opioids slow down the movement of the digestive tract. Patients are often advised to start a bowel regimen (stimulant laxative and stool softener) proactively.
• Nausea and Vomiting: This often occurs during the first few days of treatment as the body adjusts. It may be worse when standing up (orthostatic hypotension).
• Somnolence (Drowsiness): Many patients feel sleepy or "foggy." This typically improves after a few days of consistent dosing.
• Dizziness: A feeling of lightheadedness, especially when moving from a sitting to a standing position.
• Pruritus (Itching): This is caused by histamine release and is not necessarily an allergic reaction. It often affects the nose and face.

• Dry Mouth (Xerostomia): Reduced saliva production can lead to dental issues if prolonged.
• Hyperhidrosis (Excessive Sweating): Patients may experience sudden bouts of sweating or "cold sweats."
• Headache: Some patients report dull, persistent headaches.
• Anxiety or Euphoria: Mood changes ranging from intense happiness to nervousness.
• Abdominal Pain: Cramping or discomfort related to slowed gastric motility.

• Urinary Retention: Difficulty starting or completing urination, more common in older men with enlarged prostates.
• Miosis: Extreme constriction of the pupils (pinpoint pupils).
• Hiccups: Persistent, involuntary contractions of the diaphragm.
• Hypotension: Low blood pressure that can lead to fainting.

> Warning: Stop taking Oxycodone and call your doctor immediately if you experience any of these.

• Respiratory Depression: Breathing that is too slow, shallow, or stops entirely. This is the most dangerous side effect and can be fatal.
• Anaphylaxis: Severe allergic reactions including swelling of the face, tongue, or throat, hives, and difficulty breathing.
• Serotonin Syndrome: If taken with certain antidepressants, you may experience agitation, hallucinations, rapid heart rate, muscle stiffness, and loss of coordination.
• Adrenal Insufficiency: Long-term use can cause the adrenal glands to stop producing enough cortisol. Symptoms include nausea, vomiting, loss of appetite, worsening tiredness, or dizziness.
• Severe Hypotension: A drastic drop in blood pressure, especially when combined with other medications or alcohol.

With prolonged use (months to years), oxycodone can cause lasting physiological changes:

• Tolerance: The body becomes used to the drug, requiring higher doses to achieve the same pain relief.
• Physical Dependence: The body requires the drug to function normally; stopping it abruptly causes withdrawal symptoms.
• Hypogonadism: Opioids can suppress sex hormones, leading to low libido, erectile dysfunction, or irregular menstrual cycles.
• Immunosuppression: Some evidence suggests chronic opioid use may weaken the immune system.
• Opioid-Induced Hyperalgesia: Paradoxically, long-term use can make a person more sensitive to pain.

The FDA has issued several "Black Box" warnings for oxycodone, the highest level of caution for prescription drugs:

1. 1Addiction, Abuse, and Misuse: Oxycodone exposes users to the risks of opioid addiction, which can lead to overdose and death.
2. 2Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression may occur, particularly during initiation or following a dose increase.
3. 3Accidental Ingestion: Accidental ingestion of even one dose, especially by children, can result in a fatal overdose.
4. 4Neonatal Opioid Withdrawal Syndrome (NOWS): Prolonged use during pregnancy can result in withdrawal in the newborn, which may be life-threatening.
5. 5Cytochrome P450 3A4 Interaction: Using oxycodone with drugs that inhibit or induce the CYP3A4 enzyme can result in fatal levels of oxycodone in the blood.
6. 6Risks from Concomitant Use with Benzodiazepines: Using opioids with benzodiazepines (like Xanax or Valium) or other CNS depressants may result in profound sedation, respiratory depression, coma, and death.

Report any unusual symptoms to your healthcare provider.

Oxycodone is a high-alert medication. It must only be used by the person for whom it was prescribed. Sharing this medication with others is illegal and dangerous. Patients should be screened for a personal or family history of substance abuse before starting treatment. It is also essential to inform your doctor if you have a history of depression or other mental health conditions, as opioids can exacerbate these issues.

As detailed in the side effects section, the FDA mandates a Black Box Warning for oxycodone regarding its potential for addiction, fatal respiratory depression, and dangerous interactions with benzodiazepines and alcohol. These warnings emphasize that oxycodone should only be used when other non-opioid treatments are insufficient. The warning also highlights the risk of Neonatal Opioid Withdrawal Syndrome (NOWS) if used during pregnancy.

• Allergic Reactions: While rare, anaphylaxis can occur. If you have a known allergy to codeine or other opioids, you may be cross-sensitive to oxycodone.
• Respiratory Conditions: Patients with COPD, severe asthma, or sleep apnea are at a significantly higher risk for fatal respiratory depression. Oxycodone should be used with extreme caution in these populations.
• Head Injury: Opioids can increase intracranial pressure (pressure inside the skull) and may mask the clinical signs of a worsening head injury.
• Gastrointestinal Issues: Oxycodone should not be used in patients with known or suspected gastrointestinal obstruction, including paralytic ileus (where the bowel stops moving).
• Seizure Disorders: Oxycodone may aggravate convulsions in patients with convulsive disorders.

Patients on long-term oxycodone therapy require regular monitoring:

• Pain Assessment: Regular evaluation to see if the drug is still effective.
• Respiratory Status: Monitoring for slowed breathing, especially when starting or increasing doses.
• Liver and Kidney Function: Periodic blood tests (CMP - Complete Metabolic Panel) to ensure the organs can still process the drug.
• Prescription Drug Monitoring Programs (PDMP): Doctors will check state databases to ensure the patient is not receiving multiple opioid prescriptions from different providers.

Oxycodone causes significant impairment of mental and physical abilities. Do not drive a car, operate heavy machinery, or engage in potentially hazardous activities until you know how the medication affects you. Dizziness and sleepiness are most common during the first week of treatment.

Do not drink alcohol while taking oxycodone. Alcohol significantly increases the risk of life-threatening respiratory depression. Combining alcohol with extended-release oxycodone can cause "dose dumping," where the entire dose is released into the bloodstream at once, often leading to a fatal overdose.

Do not stop taking oxycodone suddenly if you have been using it for more than a few days. Abrupt discontinuation can lead to severe withdrawal symptoms, including anxiety, sweating, muscle aches, insomnia, diarrhea, and tremors. Your healthcare provider will provide a tapering schedule to slowly reduce the dose over time.

> Important: Discuss all your medical conditions with your healthcare provider before starting Oxycodone.

• MAO Inhibitors (MAOIs): Do not use oxycodone if you have taken an MAOI (such as linezolid, phenelzine, or selegiline) in the last 14 days. This combination can lead to unpredictable and severe reactions, including respiratory depression or extreme changes in blood pressure.
• Alcohol: As noted, the combination is potentially fatal due to additive CNS depression.

• Benzodiazepines and CNS Depressants: Drugs like alprazolam (Xanax), diazepam (Valium), or sleep medications (Zolpidem) increase the risk of profound sedation and respiratory failure.
• CYP3A4 Inhibitors: Medications like ketoconazole, erythromycin, and ritonavir can slow the metabolism of oxycodone, leading to toxic levels in the blood.
• CYP3A4 Inducers: Drugs like rifampin, carbamazepine, and phenytoin can speed up metabolism, making the oxycodone less effective and potentially causing withdrawal in dependent patients.

• Serotonergic Drugs: SSRIs (Prozac, Zoloft) and SNRIs (Cymbalta) can increase the risk of serotonin syndrome, a life-threatening condition caused by too much serotonin in the nervous system.
• Anticholinergic Drugs: Medications for overactive bladder or certain antihistamines can increase the risk of severe constipation and urinary retention when taken with oxycodone.
• Diuretics: Oxycodone can reduce the efficacy of diuretics (water pills) by stimulating the release of antidiuretic hormone.

• Grapefruit and Grapefruit Juice: Grapefruit inhibits the CYP3A4 enzyme in the gut. Consuming grapefruit while taking oxycodone can increase the concentration of the drug in your blood, raising the risk of side effects and overdose.
• High-Fat Meals: For certain extended-release formulations, a high-fat meal can increase the peak concentration (Cmax) of the drug by up to 25%, potentially leading to increased sedation.

• St. John's Wort: This herbal supplement is a potent CYP3A4 inducer. It can significantly lower the levels of oxycodone in your blood, reducing its pain-relieving effects.
• Kava, Valerian, and Melatonin: These supplements have sedative properties and can increase the drowsiness caused by oxycodone.

Oxycodone does not typically interfere with standard blood chemistry or hematology tests. However, it will show up on a standard 5-panel or 10-panel urine drug screen as an opiate. Specific "expanded" panels are often required to distinguish oxycodone from other opioids like morphine or codeine.

For each major interaction, the management strategy usually involves dose adjustment or increased monitoring by the healthcare provider.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking.

Oxycodone must NEVER be used in the following circumstances:

• Significant Respiratory Depression: If a patient has pre-existing respiratory failure or significantly slowed breathing, oxycodone can be fatal.
• Acute or Severe Bronchial Asthma: In an unmonitored setting or in the absence of resuscitative equipment, opioids can cause fatal airway constriction and respiratory arrest.
• Gastrointestinal Obstruction: This includes known or suspected paralytic ileus. Opioids slow gastric motility, which can lead to bowel perforation or toxic megacolon in these patients.
• Hypersensitivity: Any known severe allergy to oxycodone hydrochloride or any of the inactive ingredients in the formulation.

These conditions require a careful risk-benefit analysis by a physician:

• Chronic Obstructive Pulmonary Disease (COPD): The risk of CO2 retention and respiratory drive suppression is high.
• Biliary Tract Disease: Oxycodone can cause spasms of the Sphincter of Oddi, potentially worsening biliary colic or pancreatitis.
• Severe Renal or Hepatic Impairment: The drug will not be cleared efficiently, leading to rapid toxicity unless doses are extremely low.
• Hypothyroidism and Addison's Disease: These patients are often more sensitive to the CNS depressant effects of opioids.
• Prostatic Hypertrophy: Increased risk of acute urinary retention.

Patients with a true anaphylactic allergy to codeine, morphine, or hydrocodone may experience a cross-allergic reaction to oxycodone, as they share a similar phenanthrene chemical structure. However, many "allergies" reported to codeine (like nausea) are side effects rather than true allergies. A specialist should evaluate true hypersensitivity.

> Important: Your healthcare provider will evaluate your complete medical history before prescribing Oxycodone.

Oxycodone is traditionally classified as FDA Pregnancy Category C (under the old system). There are no adequate and well-controlled studies in pregnant women. However, prolonged use of oxycodone during pregnancy can result in Neonatal Opioid Withdrawal Syndrome (NOWS). This is a life-threatening condition for the newborn, characterized by irritability, hyperactivity, abnormal sleep patterns, high-pitched cry, tremors, vomiting, diarrhea, and failure to gain weight. Use during labor can also cause respiratory depression in the newborn. Oxycodone should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.

Oxycodone is excreted in human milk. Low levels of oxycodone have been detected in the plasma of breastfed infants. There is a risk of sedation and respiratory depression in the nursing infant. If a breastfeeding mother must take oxycodone, the infant should be closely monitored for excessive sleepiness, difficulty breastfeeding, or limpness. Withdrawal symptoms can also occur in the infant when the mother stops taking the medication or stops breastfeeding.

Safety and effectiveness in pediatric patients below the age of 18 have not been established for immediate-release oxycodone. For extended-release oxycodone (OxyContin), approval is limited to opioid-tolerant children aged 11 and older with severe chronic pain. Pediatric patients may be more susceptible to the respiratory depressant effects of opioids compared to adults.

In patients over 65, the clearance of oxycodone is reduced by approximately 15% to 20%. Older adults are at a much higher risk for confusion, delirium, and falls while taking oxycodone. Furthermore, the risk of respiratory depression is higher in the elderly, especially those with underlying lung disease. Starting doses should be conservative, usually 1/2 of the normal adult dose.

In patients with end-stage renal disease or significant impairment (GFR < 30 mL/min), the peak plasma concentration of oxycodone increases by about 50%. These patients require careful titration and frequent monitoring for signs of CNS toxicity.

In patients with hepatic cirrhosis, the half-life of oxycodone can increase to 14 hours or more (compared to the normal 3-4 hours). For patients with any degree of liver failure, the starting dose should be reduced by 50-66%, and the frequency of dosing should be decreased.

> Important: Special populations require individualized medical assessment.

Oxycodone is a semi-synthetic pure opioid agonist. Its primary therapeutic action is analgesia. It interacts predominantly with the mu-opioid receptors, which are coupled with G-protein receptors. By activating these receptors, oxycodone inhibits the release of neurotransmitters such as substance P, glutamate, and acetylcholine. This inhibition occurs at both the pre-synaptic and post-synaptic levels in the spinal cord and brain, effectively blocking the transmission of pain impulses to the cerebral cortex.

Oxycodone exerts its effects mainly on the central nervous system (CNS) and the smooth muscles. In addition to analgesia, it causes respiratory depression by direct action on brainstem respiratory centers. It also suppresses the cough reflex and causes miosis (pupillary constriction). In the digestive system, it decreases the motility of the stomach and intestines, leading to increased smooth muscle tone and constipation.

| Parameter | Value |

|---|---|

| Bioavailability | 60% - 87% (Oral) |

| Protein Binding | 38% - 45% |

| Half-life | 3.2 hours (IR), 4.5 hours (ER) |

| Tmax | 1 - 2 hours (IR) |

| Metabolism | Hepatic (CYP3A4, CYP2D6) |

| Excretion | Renal (8% - 14% unchanged) |

The molecular formula for oxycodone hydrochloride is C18H21NO4•HCl. It has a molecular weight of 351.82 g/mol. It is a white, odorless crystalline powder that is soluble in water and slightly soluble in alcohol. Its structure is closely related to morphine and codeine but contains an additional hydroxyl group at the C14 position.

Oxycodone is classified as an Opioid Agonist. It belongs to the phenanthrene chemical class of opioids, which also includes morphine, codeine, and hydrocodone.