Oxycodone is an opioid agonist prescription medication. The oxycodone immediate-release formulation is FDA-approved for the management of acute or chronic moderate to severe pain for which other treatments do not suffice, and for which the use of opioid medication is appropriate. The extended-release formulation is FDA-approved for the management of pain severe enough to require continuous (24 hours per day), long-term opioid treatment and for which there are no alternative options to treat the pain. The oxycodone to morphine dose equivalent ratio is approximately 1:1.5 for immediate-release and 1:2 for extended-release formulations.
Oxycodone is a semisynthetic opioid which has agonistic properties on mu, kappa, and delta-type opioid receptors, with the strongest affinity being for mu-type receptors. Upon binding to these G-protein coupled receptors, oxycodone stimulates the exchange of GDP on the G-alpha subunit for GTP, resulting in the inhibition of adenylate cyclase and thus a decrease in intracellular cAMP. This signal cascade leads to a consequent inhibition of the nociceptive neurotransmitters acetylcholine, dopamine, GABA, noradrenaline, and substance P, as well as the hormones glucagon, insulin, somatostatin, and vasopressin.
As with other opioids, oxycodone causes hyperpolarization and reduced excitability of neurons in the central nervous system (CNS). This generalized CNS depression is a result of the agonistic effect on kappa-type receptors which lead to a closure of N-type voltage-gated calcium channels, while stimulation of the mu and delta-type receptors open calcium-dependent inward-rectifying potassium channels.
Oxycodone is metabolized by the hepatic enzymes CYP3A4 and CYP2D6, producing the metabolites noroxycodone and oxymorphone, respectively. These metabolites are excreted from the body via the kidneys.
Oxycodone is widely available in tablet, capsule, and oral solutions. It is currently available in 10-mg, 20-mg, 40-mg, or 80-mg pills. The 160-mg dose was discontinued in May 2001 due to the high abuse potential. Oxycodone is available in combination with other analgesics, including acetaminophen, aspirin, or ibuprofen. In select countries, oxycodone may be available in intramuscular and/or intravenous forms as well.
Initial doses of oxycodone are recommended in the 5 to 15 mg range, every 4 to 6 hours as needed for adequate analgesia of acute pain. Further dosing should titrate upwards as required for pain control, with attention and monitoring for potential side effects.
For patients with chronic pain, it is recommended to titrate dosage, in the same manner. However, the medication should be taken at regularly scheduled intervals to prevent the reoccurrence of pain as opposed to treating the pain after it has started.
Tablets are intended to be taken the whole and must not be broken, chewed, crushed, or dissolved in liquid.
Dose reduction may be necessary for the elderly and patients with hepatic or renal failure. Initiating a starting dose at one-third to one half the usual doses and close monitoring is recommended. Titration upwards should be done at a careful rate.
The onset of action is 10 to 30 minutes for immediate-release and about 1 hour for controlled-release.
Duration range is from 3 to 6 hours for immediate-release or 12 hours in controlled-release formulations.
Plasma half-life is 3 to 5 hours, and stable plasma levels are reached within 24 to 36 hours.
The side effect profile of oxycodone is similar to that of the other opioid medications. Constipation is the most common overall side effect. The intensity of these side effects tends to decrease over time.
Most Common (more than 5%)
Other Reported Side Effects
Oxycodone therapy is contraindicated in patients with:
While there is limited information involving studies of allergenic cross-reactivity in opioid medications, the possibility of a cross-sensitivity cannot be fully excluded. For patients with an opioid allergy, a clear description of the allergic reaction should be explored and properly documented before considering oxycodone. Patients who are found to have a true allergic reaction to other opioid medications should avoid oxycodone therapy when possible.
Pregnancy is not an absolute contraindication to oxycodone therapy; however, it is listed as a US Boxed Warning. Maternal oxycodone use during pregnancy may result in serious and sometimes fatal events, as opioids can cross the placental barrier. These events may include preterm delivery, birth defects, and poor fetal growth. With prolonged exposure, babies born to opioid-dependent mothers may suffer from potentially life-threatening neonatal withdrawal syndrome. Neonatal risks of oxycodone therapy should be discussed in women who are pregnant or plan to become pregnant and alternative treatments should considered.
Patients taking oxycodone should be monitored for the presence of constipation, pain relief, other side effects and appropriate usage. Their blood pressure, heart rate, and respiratory rate should also be monitored, especially for the first 24 to 72 hours after initiating therapy or increasing dosage. If pain continues to increase after stabilization of dosage, alternative causes of pain should be investigated before increasing medication dosage or frequency. If adverse effects develop, consider decreasing the dosage to find an appropriate therapeutic level without unacceptable adverse effects. Patients who are taking oxycodone should be monitored or cautioned when starting a new medication that is a known cytochrome P450 inhibitor. Inhibition of these enzymes can lead to potentially fatal increases of oxycodone concentration in the blood. This medication should not be abruptly discontinued in patients who may be opioid dependent as this could precipitate withdrawal symptoms. If oxycodone therapy is to be terminated, consider decreasing in increments of 25% to 50%, while monitoring for withdrawal symptoms.
Due to the high abuse potential and possibly fatal results of an oxycodone overdose, prescriptions should be written for the lowest therapeutic dose and only for the period the patient is expected to be in pain. Close follow-up should be arranged. Many hospital systems, states, and government agencies in the United States have published guidelines to help physicians with pain management and opioid prescriptions. The legislation is evolving in the United States, and in some states, state law will require signed informed consent to prescribe opioid medications to a patient. In opioid naïve patients with acute pain, long-acting opioids are not advised. For patients who require long-term opioid therapy for pain management, regularly scheduled visits should be conducted to reassess their level of pain and monitor for possible indications of opioid abuse.
Signs and symptoms of oxycodone overdose include bradycardia, hypotension, miosis, respiratory depression, somnolence, muscle flaccidity, cold and clammy skin, and death. When a person overdoses on oxycodone, an opioid antagonist such as naloxone should be administered. Opioid antagonists should not be given in the absence of clinically significant respiratory or circulatory depression. Repeat dosing may be required as the duration of action of these drugs can vary from 30 to 120 minutes.
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