Oxycodone Hydrochloride and Acetaminophen For Pain Relief

Overview

The combination of Oxycodone hydrochloride and Acetaminophen is employed for the management of severe pain that necessitates opioid treatment, especially when alternative pain medications have proven ineffective or are not well-tolerated. Acetaminophen is employed to alleviate pain and reduce fever in patients. It does not tend to lead to dependency when used over an extended period. Nevertheless, consuming Acetaminophen in large quantities can result in adverse effects, such as liver damage.

How Does Oxycodone Hydrochloride and Acetaminophen Work?

Oxycodone hydrochloride falls under the category of narcotic analgesics, commonly known as pain medications. Nevertheless, individuals with ongoing pain should not let concerns about dependence deter them from utilizing narcotics to alleviate their pain. The likelihood of developing mental dependence or addiction when narcotics are used for pain relief purposes is low. Physical dependence may lead to withdrawal symptoms if treatment is abruptly discontinued. However, gradually tapering the dosage over time before discontinuation can typically prevent severe withdrawal effects.

Dosage and Strength Forms:

Oxycodone hydrochloride and Acetaminophen are available at the following strengths:

1. Oxycodone hydrochloride, USP (United States Pharmacopeia) 2.5 mg (milligram) with Acetaminophen, USP (United States Pharmacopeia) 325 mg (equivalent to 2.2409 mg of Oxycodone hydrochloride).

2. Oxycodone hydrochloride, USP (United States Pharmacopeia) 5 mg with Acetaminophen, USP (United States Pharmacopeia) 325 mg (equivalent to 4.4815 mg of Oxycodone hydrochloride).

3. Oxycodone hydrochloride, USP (United States Pharmacopeia) 7.5 mg with Acetaminophen, USP (United States Pharmacopeia) 325 mg (equivalent to 6.7228 mg of Oxycodone hydrochloride).

4. Oxycodone hydrochloride, USP (United States Pharmacopeia) 7.5 mg with Acetaminophen, USP (United States Pharmacopeia) 500 mg (equivalent to 6.7228 mg of Oxycodone hydrochloride).

5. Oxycodone hydrochloride, USP (United States Pharmacopeia) 10 mg with Acetaminophen, USP (United States Pharmacopeia) 325 mg (equivalent to 8.9637 mg of Oxycodone hydrochloride).

6. Oxycodone hydrochloride, USP (United States Pharmacopeia) 10 mg with Acetaminophen, USP (United States Pharmacopeia) 650 mg (equivalent to 8.9637 mg of Oxycodone hydrochloride).

Warning:

• Hepatotoxicity: Special care should be exercised when treating patients with liver disease. Hepatotoxicity and severe hepatic failure have been reported in chronic alcoholics following therapeutic doses of Oxycodone hydrochloride.

• Misuse, Abuse, and Diversion of Opioids: Oxycodone hydrochloride is classified as an opioid agonist, sharing similarities with morphine-type drugs. These substances are actively sought by individuals with substance abuse issues and addiction disorders and are susceptible to being unlawfully diverted. Oxycodone hydrochloride can be misused in a manner akin to other opioid agonists, whether legally prescribed or illicit. This consideration should be taken into account when prescribing or dispensing tablets, especially in situations where there is a concern about an elevated risk of misuse, abuse, or diversion. It is essential to recognize that concerns about misuse, addiction, and diversion should not hinder the appropriate management of pain.

• Hypotensive Effect: Oxycodone hydrochloride has the potential to induce severe hypotension, especially in individuals whose ability to maintain blood pressure is compromised due to reduced blood volume or concurrent administration with medications that affect vasomotor tone, such as phenothiazines. Oxycodone hydrochloride, like all morphine-type opioid analgesics, should be administered cautiously to patients in circulatory shock, as the drug's vasodilatory effects may further reduce cardiac output and blood pressure. Ambulatory patients may experience orthostatic hypotension.

• Respiratory Depression: Respiratory depression is a significant risk associated with Oxycodone hydrochloride, one of the active components in Oxycodone hydrochloride and Acetaminophen tablets, as with all opioid agonists. Elderly and debilitated patients, as well as non-tolerant patients receiving high initial doses of Oxycodone hydrochloride or using it in conjunction with other respiratory-depressing agents, are particularly susceptible to respiratory depression. Extreme caution should be exercised when using Oxycodone hydrochloride in patients with chronic obstructive pulmonary disorder (COPD), acute asthma, cor pulmonale, or preexisting respiratory issues. Even typical therapeutic doses of Oxycodone hydrochloride can lead to a decrease in respiratory drive to the point of apnea in such patients. In such situations, it is advisable to explore alternative non-opioid pain relievers, and the use of opioids should be managed with utmost medical supervision, commencing at the smallest effective dosage. In instances of respiratory depression, a reversal agent like Naloxone hydrochloride may be necessary.

• Head Injury and Increased Intracranial Pressure: The respiratory-depressant effects of opioids encompass carbon dioxide retention and a subsequent rise in cerebrospinal fluid pressure. These effects can be significantly amplified in the presence of head injury, other intracranial abnormalities, or a preexisting elevation in intracranial pressure. Oxycodone hydrochloride's impact on pupillary response and consciousness may obscure neurological signs of deterioration in patients with head injuries.

For Patients

Learn About Pain Relief

What Are Pain Relievers?

Pain relievers are medications designed to alleviate or reduce various discomforts such as headaches, muscle soreness, arthritis (joint inflammation), and other forms of bodily pain. There exists a diverse array of pain medications, each carrying its own set of advantages and potential risks. The effectiveness of a particular pain reliever can vary based on the type of pain being addressed, and individual responses to these medications may also differ.

For many types of pain, over-the-counter (OTC) medications prove to be effective. These OTC pain relievers primarily fall into two categories: Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs). Some examples of OTC NSAIDs include Aspirin, Naproxen, and Ibuprofen.

If OTC medications fail to provide relief, a healthcare provider may prescribe stronger alternatives. Many NSAIDs are available in higher prescription doses to address more severe pain. The most potent pain relievers are opioids, known for their exceptional efficacy. However, it is important to note that opioids can carry the potential for serious side effects and the risk of addiction. Due to these risks, opioids should only be used under the careful supervision of a medical professional.

Learn More About Oxycodone Hydrochloride and Acetaminophen

Before Starting Oxycodone Hydrochloride and Acetaminophen

1. Patients should be informed that Oxycodone hydrochloride and Acetaminophen tablets contain Oxycodone hydrochloride, which is a substance with properties similar to morphine.

2. Patients should be instructed to store Oxycodone hydrochloride and Acetaminophen tablets securely, out of reach of children.

3. When patients no longer require Oxycodone hydrochloride and Acetaminophen tablets, any unused tablets should be disposed of by flushing them down the toilet.

4. Patients should be advised against adjusting their medication dosage independently and should consult their prescribing physician for any dosage changes.

5. Patients should be made aware that Oxycodone hydrochloride and Acetaminophen tablets may impair their mental or physical abilities necessary for tasks like driving or operating heavy machinery.

6. Patients should avoid combining Oxycodone hydrochloride and Acetaminophen tablets with alcohol, other opioid analgesics, tranquilizers, sedatives, or other central nervous system depressants unless recommended and supervised by a physician. Combining these substances can result in hazardous synergistic effects on the central nervous system or respiratory depression, which may lead to serious harm or even death.

7. The safety of Oxycodone hydrochloride and Acetaminophen tablets during pregnancy has not been determined. Therefore, women who are planning to become pregnant or are already pregnant should consult their physician before taking Oxycodone hydrochloride and Acetaminophen tablets.

8. Nursing mothers should consult their physicians to decide whether to stop breastfeeding or cease taking Oxycodone hydrochloride and Acetaminophen tablets due to the potential for serious adverse reactions in nursing infants.

9. Patients who have been on Oxycodone hydrochloride and Acetaminophen tablets for an extended period should be advised not to suddenly stop the medication. Instead, they should consult their physician for a gradual discontinuation plan to taper off the medication safely.

10. Patients should be informed that Oxycodone hydrochloride and Acetaminophen tablets have the potential for abuse. They should take precautions to prevent theft and should never share the medication with anyone other than the individual for whom it was prescribed.

Things to Inform Before Starting Oxycodone Hydrochloride and Acetaminophen

Prior to initiating treatment with Oxycodone hydrochloride and Acetaminophen tablets, it is imperative to inform the healthcare provider about the following medical history:

• Any history of head injury or seizures.

• Preexisting conditions related to the liver, kidneys, or thyroid.

• Any difficulties with urination.

• Previous issues with the pancreas or gallbladder.

• A history of substance abuse, whether involving street drugs or prescription medications, as well as alcohol addiction or mental health disorders.

In addition, the patient should also communicate the following to their healthcare provider:

• If they are currently pregnant or planning to become pregnant. Extended use of Oxycodone hydrochloride and Acetaminophen tablets during pregnancy may lead to withdrawal symptoms in newborns, which, if not promptly identified and managed, could pose life-threatening risks.

• If a patient is breastfeeding. Oxycodone hydrochloride and Acetaminophen tablets have the potential to pass into breast milk and may pose risks to their infant.

• If the patient is taking any prescription or over-the-counter medications, dietary supplements like vitamins, or herbal products. Combining Oxycodone hydrochloride and Acetaminophen tablets with certain other substances can result in severe side effects that may have serious consequences, including the possibility of fatal outcomes.

How to Take Oxycodone Hydrochloride and Acetaminophen?

• Please adhere to the prescribed dosage and do not make any adjustments.

• It is advisable to utilize the lowest effective dose for the shortest necessary duration.

• Take the dosage prescribed every six hours as required for pain relief. Avoid exceeding the recommended dose. In case a patient misses a dose, take the next scheduled dose at the usual time.

• If the currently prescribed dose fails to adequately manage the pain, promptly contact the healthcare provider.

• If the patient has been on a regular regimen of Oxycodone hydrochloride and Acetaminophen tablets, refrain from discontinuing them without consulting their healthcare provider.

• For the disposal of expired, unwanted, or unused Oxycodone hydrochloride and Acetaminophen tablets, it is recommended to dispose of them by flushing them down the toilet, especially if a drug take-back option is not readily accessible.

Look Out for the Side Effects:

Oxycodone hydrochloride and Acetaminophen tablets can lead to a spectrum of adverse reactions, including serious ones like apnea (cessation of breathing), respiratory arrest, respiratory depression (shallow breathing), circulatory depression (blood circulation becomes slow), hypotension (reduced blood pressure), and shock (circulatory collapse). These severe reactions can pose significant health risks. Among the more commonly observed non-serious adverse reactions are dizziness, lightheadedness, drowsiness or sedation, nausea, and vomiting. These effects are more prominent in ambulatory patients and may be mitigated by resting in a reclined position.

In rare cases, Acetaminophen use has been linked to agranulocytosis. Elevated doses of this medication have the potential to cause dose-dependent, potentially lethal hepatic necrosis (destruction of liver cells), along with increased risks of renal tubular necrosis (cell death of kidney cells) and hypoglycemic coma (loss of consciousness due to lower blood sugar levels). Other adverse reactions have been reported across various organ systems, including the central cardiovascular and peripheral nervous system, fluid and electrolyte, hepatic, gastrointestinal, hearing and vestibular, metabolic and nutritional, musculoskeletal, ocular, psychiatric, respiratory system, skin and appendages, and urogenital, each presenting its own set of potential complications.

For Doctors

Indication:

Oxycodone hydrochloride and Acetaminophen tablets are used to treat moderate to severe pain.

Pharmacology-

• Mechanism of Action: Oxycodone hydrochloride is a semisynthetic pure opioid agonist primarily known for its analgesic properties. It also exerts additional pharmacological effects such as anxiolysis, euphoria, and relaxation. These effects result from the activation of receptors, particularly µ and κ receptors, within the central nervous system, similar to the way endorphins and enkephalins operate as endogenous opioid-like compounds. Oxycodone hydrochloride induces respiratory depression by directly affecting the respiratory centers in the brainstem and suppresses the cough reflex by directly influencing the medulla's center.

While the exact site and mechanism responsible for its analgesic effect remain undetermined, its antipyretic effect stems from its ability to inhibit endogenous pyrogens' action on the hypothalamic heat-regulating centers.

• Pharmacokinetics: In cancer patients, Oxycodone hydrochloride exhibits a mean absolute oral bioavailability of approximately 87 percent. In vitro studies have shown that about 45 percent of Oxycodone hydrochloride binds to human plasma proteins. Following intravenous administration, the volume of distribution is approximately 211.9 ± 186.6 liters. The absorption of Acetaminophen is rapid and nearly complete when taken orally, with full absorption achieved within four hours in cases of overdosage. Acetaminophen tends to be evenly distributed across various body fluids. However, its binding to plasma proteins can vary, with only 20 to 50 percent of the drug being bound at the concentrations typically encountered during episodes of acute intoxication.

• Metabolism and Elimination: Oxycodone hydrochloride undergoes metabolic transformations involving N-dealkylation, yielding Noroxycodone hydrochloride, and O-demethylation, producing oxymorphone. These conversions are mediated by the enzyme CYP2D6. After oral administration of Oxycodone hydrochloride, both free and conjugated forms of Noroxycodone hydrochloride, Oxycodone hydrochloride, and oxymorphone are excreted in the urine, with approximately eight to 14 percent of the dose appearing as free Oxycodone hydrochloride within 24 hours. The average elimination half-life of Oxycodone hydrochloride is about 3.51 ± 1.43 hours. In contrast, Acetaminophen undergoes primary metabolic processes in the liver through cytochrome P450 microsomal enzymes. Approximately 80 to 85 percent of Acetaminophen is conjugated, primarily with glucuronic acid and, to a lesser extent, with sulfuric acid and cysteine. Most of the drug is excreted in urine within the first day after conjugation. At the same time, a small portion (around four percent) is metabolized by cytochrome P450 oxidase to create a potentially toxic metabolite called NAPQI (N acetyl-p-benzoquinoneimine, N-acety limidoquinone). NAPQI is detoxified through conjugation with glutathione, but high Acetaminophen doses can deplete glutathione stores, increasing the risk of liver damage, including necrosis. In such situations, Acetaminophen metabolism may follow alternative pathways.

Precautions:

• Opioid pain relievers should be employed with caution when taken alongside central nervous system depressant medications. Their use should be limited to scenarios where the advantages of opioid-based pain management outweigh recognized risks, including altered mental state, respiratory depression, and postural hypotension.

• In instances involving acute abdominal conditions, the use of Oxycodone hydrochloride and Acetaminophen, or other opioids, might mask the diagnosis or the patient's clinical progression, necessitating careful consideration.

• Special consideration is needed for patients with CNS depression, elderly or debilitated individuals, those with significant hepatic, pulmonary, or renal impairment, and certain medical conditions such as Addison's disease, hypothyroidism, prostatic hypertrophy, and urethral stricture.

• Oxycodone hydrochloride may exacerbate convulsions in patients with seizure disorders, and opioids, in general, may induce or worsen seizures in specific clinical contexts.

Dosage and Administration:

The dosage of Oxycodone hydrochloride and Acetaminophen should be tailored to the individual patient's pain severity and response. In situations involving more intense pain or when patients have developed tolerance to opioid analgesics, it may be necessary to exceed the standard recommended dosage. For continuous pain, the opioid analgesic should be administered at regular intervals following a scheduled around-the-clock regimen. Oxycodone hydrochloride and Acetaminophen tablets are intended for oral administration.

Contraindications:

Oxycodone hydrochloride and Acetaminophen tablets must not be given to individuals with established hypersensitivity to Oxycodone hydrochloride, Acetaminophen, or any other ingredient in this medication. Oxycodone hydrochloride should not be used in circumstances where opioids are contraindicated, such as in patients with substantial respiratory depression (particularly in unmonitored environments or without access to resuscitation equipment) and those with acute or severe bronchial asthma or hypercarbia. Furthermore, Oxycodone hydrochloride is contraindicated when there is suspicion or confirmation of paralytic ileus.

Drug Interactions:

Drug interactions involving Oxycodone hydrochloride include potential enhancement of the neuromuscular-blocking effect of skeletal muscle relaxants and increased respiratory depression. When oxycodone is administered in combination with other central nervous system (CNS) depressants, such as general anesthetics, opioid analgesics, phenothiazines, tranquilizers, sedative-hypnotics, antiemetics, or alcohol, there is a potential for additive CNS depression. In such cases, it may be necessary to decrease the dosage of one or both substances. Combining anticholinergics with opioids may lead to paralytic ileus. Caution should be exercised when administering agonist/ or antagonist analgesics (for example, Pentazocine, Nalbuphine, Naltrexone, and Butorphanol) to patients concurrently receiving pure opioid agonists like Oxycodone hydrochloride, as it may diminish the analgesic effect or induce withdrawal symptoms.

As for Acetaminophen, chronic alcoholics may experience hepatotoxicity when exposed to various Acetaminophen doses, even within moderate to excessive ranges. Anticholinergics may slightly delay or decrease the onset of Acetaminophen's effects, but the overall pharmacological impact remains largely unaffected. Oral contraceptives may increase Acetaminophen's plasma clearance and reduce its half-life due to enhanced glucuronidation. Activated charcoal, when administered promptly after an overdose, can reduce Acetaminophen absorption. Beta-blockers, like Propranolol, may inhibit the enzyme systems responsible for Acetaminophen's glucuronidation and oxidation, potentially increasing its pharmacological effects.

Other Specifications:

Oxycodone Hydrochloride and Acetaminophen During Pregnancy:

Teratogenic Effects:

Pregnancy Category C: No animal studies on the reproductive effects of Oxycodone hydrochloride and Acetaminophen have been conducted. It is also uncertain whether Oxycodone hydrochloride and Acetaminophen can harm a developing fetus when administered to a pregnant woman or affect reproductive capability. The use of Oxycodone hydrochloride and Acetaminophen during pregnancy should only occur if the physician believes that the potential benefits outweigh the possible risks.

Nonteratogenic Effects: Opioids have the ability to pass through the placental barrier and may lead to respiratory depression in newborns. The use of opioids during pregnancy can result in a newborn with physical drug dependence, and after birth, the neonate may experience severe withdrawal symptoms.

Breastfeeding and Oxycodone Hydrochloride and Acetaminophen:

In general, breastfeeding is not recommended when a patient is using Oxycodone hydrochloride and Acetaminophen tablets due to the potential risk of sedation and respiratory depression in the nursing infant. Oxycodone hydrochloride is excreted into breast milk in small quantities. Although uncommon, there have been occasional reports of infants experiencing drowsiness and lethargy when their mothers were taking a combination product containing Oxycodone hydrochloride and Acetaminophen while nursing.

Oxycodone Hydrochloride and Acetaminophen in Geriatric Patients:

Extra care should be exercised when establishing the appropriate dosage and dosing frequency of Oxycodone hydrochloride and Acetaminophen tablets for elderly patients. This is because the clearance of Oxycodone hydrochloride may be slightly diminished in geriatric patients when compared to younger individuals.