Oxycodone Hydrochloride Tablets - Pharmacological Aspects

Overview:

Oxycodone hydrochloride tablets with abuse-deterrent technology is an extended-release pain medication designed for moderate to severe pain when ongoing, long-lasting relief is needed. Approved in 2010, it uses a slow-release system to provide continuous pain control. When it was originally released in 1995, the United States Food and Drug Administration believed this slow-release formula would have a lower risk of abuse compared to fast-acting Oxycodone. However, reports showed that people were finding ways to abuse Oxycodone by breaking, chewing, or altering the pill to release more of the drug quickly. In response, the drug was reformulated to incorporate a special coating and a plastic-like tablet structure that is harder to crush or grind. When tampered with, the pill forms a thick gel that is much harder to crush or grind. Manufacture of the original version was stopped in August 2010. Since then, the FDA has required studies to monitor how well this new version reduces misuse and to understand its impact on public health.

Drug Group: Opioid Analgesics

Available Doses and Dosage Forms:

Extended-release tablets come in various strengths, and each strength has a unique color and marking for easy identification:

• 10 mg (milligrams): White, round tablet marked with "OP" on one side and "10" on the other.

• 15 mg: Gray, round tablet marked with "OP" on one side and "15" on the other.

• 20 mg: Pink, round tablet marked with "OP" on one side and "20" on the other.

• 30 mg: Brown, round tablet marked with "OP" on one side and "30" on the other.

• 40 mg: Yellow, round tablet marked with "OP" on one side and "40" on the other.

• 60 mg: Red, round tablet marked with "OP" on one side and "60" on the other.

• 80 mg: Green, round tablet marked with "OP" on one side and "80" on the other.

For Patients:

How Do Oxycodone Hydrochloride Tablets Work in the Management of Pain?

Oxycodone hydrochloride tablets are used to relieve severe pain that requires opioid treatment and also when other pain medications do not work well enough or cannot be tolerated. Oxycodone usually acts on the CNS (central nervous system) to relieve the pain.

What Are the Things to Inform the Doctor Before Taking Oxycodone Hydrochloride?

Before using Oxycodone, inform the healthcare provider if having any history of:

• Head injuries.

• Seizures.

• Liver, kidney, or thyroid issues.

• Trouble urinating.

• Pancreas or gallbladder issues.

• Past drug or alcohol addiction or mental health issues.

Also, let them know if:

• Pregnant or planning to be, as long-term use during pregnancy can cause withdrawal symptoms in the baby, which could be life-threatening if untreated.

• Breastfeeding, since Oxycodone passes into breast milk and may harm the baby.

• Taking any other medicines, vitamins, or herbal supplements, as combining them with Oxycodone may lead to serious, possibly fatal, side effects.

How Is Oxycodone Hydrochloride Administered?

• Always take Oxycodone hydrochloride exactly as the doctor suggested. Use the lowest dose for the shortest time possible.

• Take it every 12 hours, at the same time each day. Do not take more than the prescribed dose.

• Swallow the tablet whole. Do not crush, break, chew, or dissolve it, as this can lead to an overdose and could be fatal.

• Only take one tablet at a time, and do not wet or lick it before swallowing to avoid choking.

• If the medication does not control the pain, contact the doctor.

• Do not stop taking Oxycodone hydrochloride without talking to the doctor.

• If Oxycodone hydrochloride is unused or expired, dispose of it by flushing it down the toilet.

• Do not drive or use heavy machinery, as it may feel sleepy or dizzy.

• Avoid drinking alcohol or using any medicines that contain alcohol. Mixing alcohol with Oxycodone hydrochloride can lead to a dangerous event or even death.

What Are the Side Effects of Oxycodone Hydrochloride?

• Addiction, abuse, and misuse of the drug.

• Life-threatening breathing problems.

• Dangerous interactions with other medications.

• Newborn withdrawal.

• Increased sensitivity to pain.

• Low blood pressure.

• Digestive issues.

• Withdrawal symptoms.

Missed Dose: If a dose of Oxycodone hydrochloride is missed, just take the next dose at the usual time.

Overdose:

• Signs of Overdose: Oxycodone overdose can cause severe breathing problems, extreme drowsiness leading to coma, limp muscles, cold skin, tiny pupils (or widened if oxygen is low), fluid in lungs, slow heart rate, low blood pressure, and potentially death.

• Overdose Treatment: For overdose, ensure an open airway and support breathing. Use Naloxone to reverse breathing issues, but monitor closely as effects can last 24 to 48 hours. For opioid-dependent individuals, start with small doses of Naloxone to avoid intense withdrawal symptoms.

Storage:

Store at 77°F (degrees Fahrenheit) (25°C (degrees Celsius)), but short-term temperature changes between 59°F and 86°F (15°C to 30°C) are allowed. Keep Oxycodone hydrochloride in a secure place and dispose of it safely.

For Doctors:

Indication: Oxycodone hydrochloride is a long-term strong pain relief medication, specifically for severe pain when other treatments do not work well enough. Since Oxycodone has risks like addiction, abuse, and misuse, even at regular doses, it should only be prescribed to people who:

• Cannot tolerate other pain relievers (like non-opioid painkillers or medications that combine opioids with other drugs).

• Have not received adequate pain relief from other treatments or are not likely to get adequate pain relief from previous medications.

• Adults.

• For pain management in opioid-tolerant patients aged 11 and older who need at least 20 mg of Oxycodone daily.

Dosing Consideration:

• Oxycodone hydrochloride should only be prescribed by healthcare professionals who are experienced in its use for long-acting opioids and are aware of the potential risks.

• Dosing for Opioid-Tolerant Patients Only:

  • High doses (60 mg and 80 mg tablets): These doses are for patients who are already tolerant to opioids of similar strength. Opioid tolerance is defined as taking at least 20 mg of opioids daily for a week or more.

  • Initial Dosage: For the non-tolerant opioid patients, start Oxycodone hydrochloride 10 mg every 12 hours. Using higher doses may be necessary to initiate adequate analgesia, and such high doses may lead to severe respiratory depression.

• When switching from other opioids to Oxycodone hydrochloride, employ the lowest effective dose and observe patients for signs and symptoms of overdosage and accordingly adjust as needed.

• Tablets should not be crushed, chipped, or dissolved in an attempt to avoid overdose dangers. Patients should swallow tablets whole with water immediately.

• Patients should have access to Naloxone for emergency treatment of overdose. This is especially important if there are risk factors like concurrent CNS depressant use or prior incidence of overdose.

Adjust Dosing Gradually: Increase by 25 to 50 percent when necessary, but carefully monitor for respiratory depression and other adverse reactions.

• Assess pain relief, withdrawal symptoms, and adverse effects periodically.

• For elderly and severely impaired patients, administer a lower dose, often one-third to one-half of a standard dosing.

• For hepatic impairment, start with lower doses to begin with, and further adjustments will be made with caution since patients are more sensitive to side effects.

Discontinuation: Avoid abrupt discontinuation to prevent withdrawal. Taper by 10 to 25 percent every two to four weeks, based on the patient’s situation and response.

What Are the Pharmacological Aspects of Oxycodone Hydrochloride?

• Pharmacodynamics:

  • Central Nervous System: Oxycodone can slow down breathing by acting on the brain’s breathing control centers. It may also lead to pinpoint pupils. In dire situations, there may be dilation of large pupils if there is a significant inadequacy in the oxygen supply.

  • Digestive System: Its movements retard the functioning of the stomach and intestines, which causes a delayed process of digestion and even constipation. It causes spasms of the gall bladder and also affects the secretion of bile.

  • Heart and Blood Pressure: Oxycodone may interfere with the blood pressure and cause dizziness or fainting while standing up. Skin flushing, sweating, and itchy skin may also occur.

  • Hormones: Since this drug might impair the production of hormones, its use for an extended period can bring about such complications as low libido, infertility, and irregular periods, although this is still currently under research because other factors are involved.

  • Immune System: It may weakly depress the immune system, but it is not known if it strongly does so.

• Mechanism of Action: It acts centrally by stimulation of specific receptors in the brain, though other receptors may be stimulated at full doses. It does not have a maximal dose for pain relief, as the dosage will be adjusted based on how well it manages pain and the body's reaction to it. The specific mechanism through which it relieves pain is unknown, but it has its reaction with certain brain receptors for natural compounds similar to opioids.

• Pharmacokinetics:

  • Absorption: The human body absorbs between 60 to 87 percent of the administered dose shortly after using Oxycodone. The extended-release formulation of the drug lasts for 12 hours.

  • Metabolism: The liver breaks Oxycodone down into other compounds, some of which are still active but do not cross the brain barrier much. It is mostly eliminated through urine.

  • Excretion: Oxycodone stays in the body longer in people with liver or kidney problems. Older adults may also experience slightly higher drug levels.

Toxicity: Long-term studies have not been done on animals to check if Oxycodone can cause cancer. Oxycodone showed the potential to cause genetic mutations in one lab test using mouse cells with certain conditions. However, other tests, including bacterial mutation tests and a study with mouse bone marrow, showed no evidence that Oxycodone causes genetic damage. No studies have been done in animals to see if Oxycodone affects fertility.

Clinical Studies:

In trials, Oxycodone hydrochloride was tested in 713 adults for moderate to severe pain, including cancer patients. Common side effects (more than five percent) included constipation (23 percent), nausea (23 percent), drowsiness (23 percent), dizziness, itching, vomiting, headache, dry mouth, fatigue, and sweating. Rare side effects (less than one percent) included swollen lymph nodes, ringing in the ears, blurry vision, appetite changes, and mental symptoms like depression and memory issues.

• Pediatric Trial Findings (Ages 11 to 16): A study with 140 patients aged 11 to 16 showed that 51 percent had at least one side effect, with vomiting, nausea, headache, fever, and constipation among the most common. Other reported side effects included decreased appetite, dizziness, and skin itching.

• Post-market Observations (After Oxycodone Hydrochloride Was on the Market): Additional side effects reported include drug addiction, aggression, liver issues, dental problems, muscle rigidity, hormone imbalances, depression, and suicidal thoughts. In some cases, users experienced tablets sticking in their throats, leading to gagging or choking.

What Are the Contraindications of Oxycodone Hydrochloride?

Oxycodone hydrochloride should not be used in people who:

• Have serious breathing problems.

• Have severe asthma in situations where they cannot be closely monitored or do not have emergency equipment nearby.

• Have a known or suspected blockage in the intestines, including a condition where the bowel is paralyzed.

• Are allergic to Oxycodone hydrochloride or have had severe allergic reactions, such as anaphylaxis.

Warnings and Precautions:

• Risk of Addiction and Abuse: Oxycodone is a controlled opioid prescription drug and can lead to addiction even at the recommended doses. Patients with a history of abuse of alcohol or drugs or any mental illness should be kept under close scrutiny. To minimize abuse, the lowest effective dose should be prescribed, along with a discussion of plans for the disposal of unused tablets.

• Respiratory Depression: Such medication causes severe breathing disorders, especially at the onset of treatment and when a patient's dose is increased. Keep such patients under observation for these symptoms, especially during the first few days. One accidental dosage could be fatal for children.

• Combined Use with CNS Depressants: Because of the risks of severe sedation, respiratory depression, or even death, reserve such combinations for situations in which alternative treatment is ineffective or not tolerated. Advise patients to recognize and report sedation and respiratory depression.

• Neonatal Withdrawal Syndrome: Chronic use during pregnancy can result in withdrawal in neonates with potentially lethal symptoms. Counseling should include reference to these risks and the availability of appropriate care for infants if withdrawal does occur. Drugs that are inhibitors or inducers of CYP3A4 enzymes may decrease plasma concentrations of Oxycodone or lead to increased levels, causing adverse effects. Use Oxycodone with caution because interactions may lead to a dangerous increase in plasma concentrations of Oxycodone because of its CYP3A4 inhibitory actions and possibly significant drug interactions with chronic cannabis use. Monitor patients for evidence of sedation and respiratory depression when initiating CYP3A4 inhibitors or discontinuing CYP3A4 inducers.

• Opioid-Induced Hyperalgesia (OIH): OIH in which opioids increase sensitivity to pain rather than decreasing it may occur and is the converse of tolerance. In the case of OIH consider reducing the dose or changing to another opioid.

• Risks in Chronic Pulmonary Disease and the Elderly, Cachectic, or Debilitated Patients: Respiratory impairment and significant chronic obstructive pulmonary disease; patients with a history of opioid misuse are at increased risk of opioid abuse and dependence. Monitor respiratory status in elderly and physically debridement patients. Alternative analgesics in non-opioid analgesics may be preferred for the treatment of chronic pain in patients with these conditions.

• Adrenal Insufficiency: Prolonged administration of opioids leads to a state of adrenal insufficiency. Prolonged administration may result in symptoms like fatigue, low blood pressure, and nausea. Use corticosteroids with or without tapering the opioids as needed to restore adrenal function.

• Extreme Hypotension: An extreme decrease in blood pressure can also occur with Oxycodone, particularly in volume-depleted patients as well as ones on CNS depressants. Monitor BP closely for those in circulatory shock or poor perfusion.

• Increased Intracranial Pressure or Head Injury: In case of brain injury or tumors, increased intracranial pressure due to retention from Oxycodone use can make the patient's condition worse. Always closely monitor for signs of respiratory depression and avoid using it in head injury if possible.

What Are the Drug Interactions of Oxycodone Hydrochloride?

• CYP3A4 or CYP2D6 inhibitors: Increased Oxycodone increases risk and adverse effects. Example-Erythromycin will decrease the dosage of Oxycodone and closely monitor.

• For Induction of CYP3A4: Lower concentrations of Oxycodone with a high risk of causing withdrawal syndrome or failure to be therapeutic. Example-Rifampin may increase the dosage of Oxycodone if combined with Benzodiazepines or central nervous system depressants to cause grave sedation. There could be severe, fatal problems in the airways due to respiration. Example-alcohol use is rarely required unless necessary- consider close monitoring for administering Naloxone.

• Serotonin Modulators: Increased risk of serotonin syndrome. Example: SSRIs. Monitor for signs and symptoms; if there is suspicion of serotonin syndrome, discontinue Oxycodone.

• MAOIs: Severe reactions to opioids or potential for serotonin syndrome. Example: Phenelzine. Avoid administering Oxycodone within 14 days following an MAOI.

• Mixed Agonist or Anti-opioid and Partial Opioids: Reduced analgesic effect; may increase the incidence of withdrawal. Example: Buprenorphine. Hence, concomitant administration is not recommended.

• Muscle Relaxants: Potential increased risk of respiratory depression. Example: Cyclobenzaprine. Monitor within the clinically appropriate range for dose adjustments with Oxycodone.

• Diuretics: May reduce the effects of diuretics, monitor urine output and blood pressure

• Anticholinergics: There is a higher risk of developing constipation and urinary problems, so observe for signs and symptoms in the digestive and urinary systems.

Specific Considerations:

• Pregnancy: Long-term opioid use during pregnancy can lead to withdrawal symptoms in newborns. There is not enough research on Oxycodone’s risks for birth defects or miscarriage, but animal studies show no birth defects, though some behavioral effects were seen in baby rats. Pregnant women should be aware of the potential risks to the baby since opioids can cause withdrawal symptoms in newborns and affect labor by causing breathing issues. Babies exposed to opioids should be monitored.

• Breastfeeding: Oxycodone is excreted in human milk. Infants exposed to Oxycodone through breast milk should be monitored for signs of somnolence or respiratory depression. Oxycodone may cause withdrawal syndrome in a neonate if it is abruptly withdrawn from the mother or child.

• Reproductive Health: Chronic opioid use may decrease fertility in both women and men, but it is not known if this effect is reversible.

• Pediatric Use: Safety and effectiveness in pediatric patients below 18 years of age have not been established. The most frequently reported adverse events in children were nausea, vomiting, fever, headache, and constipation.

• Geriatric Use: Patients over 65 years of age may be more sensitive to the effect of Oxycodone because of the potential for significant respiratory problems. Reduce the dose if signs of overdose appear. Titrate the dose to achieve appropriate response in elderly patients. Increase the dosing interval as kidney function decreases with old age. For patients with impaired kidney function with expected long-term treatment, kidney function should be monitored.

• Liver Damage: For patients with damage to the liver, the metabolic absorption of Oxycodone is slower. In such cases, it must be started with a smaller dose and increased gradually. Monitor for symptoms of low blood pressure and respiratory problems, along with drowsiness.

• Kidney Impairment: Oxycodone levels may be higher in people with kidney problems. Start with a lower dose and increase carefully, watching for side effects like breathing issues, drowsiness, and low blood pressure.