What is Oxycodone?

Oxycodone is a semi-synthetic thebaine derivative. It is a species listed in the United Nations Single Convention on Narcotic Drugs of 1961. China has included it in the control of narcotic drugs.

Chinese name: Oxycodone
English name: Oxycodone

nickname: OxyContin, Hydroxycodene
Types of: Semi-synthetic thebaine derivative

Introduction to oxycodone

Oxycodone (oxycodone) is a semi-synthetic opioid extracted from the alkaloid thebaine. It has been in clinical use as a powerful analgesic for more than 80 years. Because oxycodone has high bioavailability and multiple routes of administration, it is widely used in clinical practice. However, it was clinically found that after continuous use of high-dose oxycodone, abrupt interruption or reduction, some patients had withdrawal syndrome. This suggests that oxycodone has the same adverse reactions as other opioids. The US Food and Drug Administration (FDA) approved in 1997 that oxycodone hydrochloride controlled-release tablets are used to treat patients with moderate to severe pain who need to take opioid analgesics for several days.

Basic information of oxycodone

Chinese name: oxycodone

Chinese alias: oxycodone

English name: Oxycodone

English alias: Dihydrone; OXYCODONE; percocet; Oxycodone; Percodan; Oxicone; Oxycodon;

14-hydroxy-dihydrocodeinone; oxanest; Morphinan-6-one, 4,5-epoxy-14-hydroxy-3-methoxy-17-methyl-, (5a)-; Eucodalum; Oxicon; endone

CAS number: 76-42-6

Molecular formula: C ₁₈ H ₂₁ NO ₄

Molecular weight: 315.36400

Exact mass: 315.14700

PSA: 59.00000

LogP: 0.98610

Structural formula:

Physicochemical properties of oxycodone

Density: 1.39 g / cm ³

Boiling point: 501.6ºC at 760 mmHg

Flash point: 257.1ºC

Refractive index: 1.659

Oxycodone Safety Information

Packing level: II

Hazard category: 6.1 (a)

Dangerous Goods Transport Code: UN 1544 ^[1]

Oxycodone oxycodone-related drug instructions

Oxycodone pharmacological action

Oxycodone is a semi-synthetic pure opioid receptor agonist. Its pharmacological action and mechanism of action are similar to morphine. It mainly acts by analgesic opioid receptors in the central nervous system and has analgesic efficacy. This medicine can also have an antitussive effect by directly acting on the cough center of the medulla oblongata. In addition, this medicine also has anti-anxiety and sedative effects.

Pharmacokinetics

The drug is rapidly absorbed orally and reaches the maximum effect after 1 hour. The single-dose effect can last for 3 to 4 hours (the effect of the controlled-release preparation can last for 12 hours). The peak time of oral blood concentration of the immediate release preparation is 1.6h, and the bioavailability is 60% to 87%; the peak time of the oral blood concentration of the controlled release preparation is 2.1 to 3.2h, and the bioavailability is 50% to 87%.

The dosage was proportional to the peak blood concentration and the area under the curve (AUC). The AUC of the elderly is 15% higher than the young. On the basis of weight adjustment, the blood concentration of women is on average 25% higher than that of men. The drug can be distributed in skeletal muscle, liver, intestine, lung, spleen and brain tissues after entering the body. The total protein binding rate was 45%. The volume of distribution after intravenous administration was 2.6 L / kg.

This drug is extensively metabolized in the liver, and the metabolites are active noroxycodone and hydroxyhydromorphone. Among them, noroxycodone is the main metabolite, and the area under the curve is 60% of this drug. Hydroxymorphone is metabolized by cytochrome P450 2D6 (CYP 2D6), which has analgesic effect but low blood concentration. .

The drug is mainly excreted through the kidneys, with an overall clearance of 0.8L / min. The elimination half-life is 3.2 hours when the oral immediate-release preparation is 20 mg, and the elimination half-life is 4.5-8 hours when the oral controlled-release preparation is taken. In renal insufficiency, the peak blood concentrations of oxycodone and noroxycodone increased by approximately 50% and 20%, respectively, and the AUC of oxycodone, noroxycodone, and hydroxyhydromorphone increased by approximately 60% and 60%, respectively And 40%, the elimination half-life can be prolonged by 1 h; the peak plasma concentration can increase by 40%, the area under the curve (AUC) increases by 90%, and the elimination half-life can be prolonged by 2 h during liver insufficiency.

Drug effect

1. This medicine can strengthen the central inhibitory effect when combined with central nervous system inhibitors [such as sedatives (such as diazepam), hypnotics, general anesthetics, phenothiazines, central antiemetics] The initial dosage should be 1/3 to 1/2 of the conventional dosage. 2. When this drug is used in combination with central muscle relaxant, the respiratory inhibitory effect is enhanced, and the direct effect on the brain stem respiratory center is part of the reason. 3. This medicine has an additive effect when used in combination with antidepressants and antihypertensive drugs. 4. Monoamine oxidase inhibitors can enhance the effect of this drug, leading to increased likelihood of disturbance of consciousness, anxiety, respiratory depression and coma. The combination of the two is not recommended, and the monoamine oxidase inhibitor should be discontinued for at least 14 days before the drug can be started. 5. Rifampicin is a cytochrome P450-inducing drug, which can increase the metabolism of the drug through the liver, reduce the blood concentration, and reduce the efficacy. The structure of rifabutin is similar to that of rifampin, so it is theoretically believed that the above-mentioned interaction exists between rifabutin and this drug. 6. This medicine is partially metabolized to hydroxyhydromorphone by cytochrome P450-2D6 enzyme. Certain drugs (such as cardiovascular drugs such as amiodarone and quinidine) may block this metabolic pathway. However, the combination of this drug with quinidine, which has the effect of inhibiting the cytochrome P450-2D6 enzyme, did not affect the efficacy. In addition, cytochrome P450-3A enzyme inhibitors such as cimetidine, ketoconazole, and erythromycin may also inhibit the metabolism of this drug. 7. When naltrexone is used in combination with this drug, it can compete with the binding of opioid receptors and trigger acute withdrawal syndrome. The combination of both should be prohibited. 8. When opioid receptor antagonists (except naltrexone) are used in combination with this drug, they can reduce the analgesic effect of this drug and / or induce withdrawal symptoms. Caution should be exercised when the two are combined. 9. Case reports of serotonin syndrome when combined with sertraline. 10. When combined with levofloxacin, it will not cause significant decrease in AUC, peak plasma concentration (Cmax) and peak time. 11. When combined with ethanol, this drug can cause additive or synergistic central inhibitory effects. Avoid alcohol during medication. 12. Ingestion of high-fat foods does not affect the absorption of the drug controlled release tablets. However, it has been reported that patients with high-fat diets who take the controlled-release tablets of this drug at 160 mg have a Cmax that is 25% higher than those taken on an empty stomach. It is speculated that when oral fast-release tablets are taken by patients on a high-fat diet, the AUC of this drug may increase, but the absorption rate will not be affected.

Dosage form and specifications

Tablet: 5mg. Controlled-release tablets: 5mg; 10mg; 20mg; 40mg.

Oxycodone indication

Suitable for relieving moderate to severe pain, such as joint pain, back pain, cancerous pain, toothache, post-operative pain, etc. (foreign data).

Oxycodone contraindications

People who are allergic to this medicine. 2. Suspicious or confirmed patients with paralytic intestinal obstruction. 3. Chronic bronchial asthma or chronic obstructive respiratory disease. 4. Patients with hypercapnia. 5. Patients with significant respiratory depression (including hypoxic respiratory depression). 6. Head injury. 7. Patients with acute abdomen. 8. Delayed gastric emptying. 9. Patients with pulmonary heart disease. 10. People with moderate to severe liver dysfunction. 11. Patients with severe renal dysfunction. 12. Chronic constipation. 13. Pregnant women. 14. Lactating women.

Oxycodone adverse reactions

1. Cardiovascular system: Occasionally vasodilation, hypotension (including orthostatic hypotension) may occur. Rare flush, palpitations, supraventricular tachycardia. 2. Mental nervous system: common dizziness, headache, drowsiness, and fatigue. Occasionally nervousness, insomnia, blurred consciousness, paresthesia, anxiety, euphoria, depression, nightmares, abnormal thinking. Rare vertigo, convulsions, disorientation, mood changes, hallucinations, agitation, forgetfulness, hypersensitivity, discomfort, speech disorders, tremors, syncope. 3. Metabolic / endocrine system: Dry mouth and sweating are common. Occasionally fever and chills. Rare dehydration and edema (such as peripheral edema). 4. Respiratory system: occasional dyspnea. Rarely bronchospasm. 5. Musculoskeletal system: rare abnormalities of tension (too high or too low), involuntary contraction of muscles. 6. Urogenital system: Difficult urination and ureteric spasm can be seen. Rare amenorrhea, loss of libido, impotence. 7. Digestive system: common constipation (preventable by laxatives), nausea (can be treated with antiemetics), and vomiting (can be treated with antiemetics). Visible biliary spasm, transient increase in serum amylase. Occasionally fear of eating, diarrhea, abdominal pain, indigestion, hiccups. Rare gastritis, difficulty swallowing, belching, intestinal obstruction, abnormal taste, and thirst. 8. Skin: Occasionally rash. Rare dry skin and hives. 9. Eye: Rare visual abnormalities, dilated pupils, and colic. Others: rare allergic reactions, withdrawal syndrome. In addition, the drug can develop tolerance and dependence. 11. References of adverse reactions abroad: Cardiovascular system: Studies have shown that less than 3% of patients can develop deep thrombophlebitis, heart failure, bleeding, hypotension, palpitations, and tachycardia during medication. In addition, opioid analgesics can cause circulation inhibition, cardiac arrest and shock, and the above-mentioned adverse reactions may also occur when using this drug. Central nervous system: Studies have shown that more than 3% of patients may experience headache (including migraine), insomnia, dizziness, and drowsiness during medication; less than 3% of patients may experience excitement, anxiety, disturbance of consciousness, neuroticism, and neuralgia. Personality disorders and tremors. Digestive system: constipation, nausea, vomiting, dry mouth, Oddi sphincter spasm, and decreased gastric juice, bile, and pancreas secretion, etc., among which nausea, vomiting, and constipation during the initial treatment period are dose-dependent. Respiratory system: This medicine can cause serious adverse reactions, such as respiratory depression, apnea and apnea. Oral controlled-release tablets of 80 mg or 160 mg in patients who have not used opioids may cause fatal respiratory depression. Urogenital system: can cause sexual dysfunction. eyes: can cause pupils to shrink. Needle-like pupils appear, suggesting overdose. skin: itching and sweating can occur, itching usually occurs early in the medication. Others: a. Weakness may occur. b. Long-term use can cause physical dependence and tolerance. c. Withdrawal syndrome caused by opioids includes: restlessness, tearing, runny nose, yawning, sweating, chills, myalgia, and dilated pupils. Other possible symptoms include: irritability, anxiety, back pain, joint pain, weakness, abdominal cramps, insomnia, nausea, lack of appetite, vomiting, diarrhea, increased blood pressure, increased breathing frequency or heart rate.

Dosage of oxycodone

1. Routine dosage for adults: Oral administration: (1) General analgesia: Use this drug controlled release tablet once every 12 hours, the dosage depends on the patient's pain severity and previous analgesic medicinal history. When adjusting the dosage, only the dosage of each medication is adjusted without changing the number of medications, and the adjustment range is an increase or decrease of 25% to 50% from the previous dosage.

For patients with severe pain taking opioids for the first time or weak opioids, the initial dose is usually 5mg, once every 12 hours. Then adjust the dose according to the condition until the desired effect. The highest dose for most patients is 200 mg every 12 hours, and a few patients may require higher doses (the highest reported clinically is 520 mg every 12 hours).

For patients who have received oral morphine treatment, the daily dose conversion ratio of this drug is: 10 mg of this drug is equivalent to 20 mg of oral morphine.

(2) Postoperative pain: use this medicine compound capsule, 1 to 2 capsules at a time (each capsule contains oxycodone hydrochloride 5mg, acetaminophen 500mg), and the medication can be repeated once every 4 to 6 hours. (3) Cancer, chronic pain: Use this medicine compound capsule, 1 to 2 capsules at a time, 3 times a day. Elderly dose: The clearance rate of elderly patients (greater than 65 years) is only slightly lower than that of adults. Adult doses and medication intervals are also applicable to elderly patients. 2. Children's regular dose: oral administration: The usual dose is 0.05 ~ 0.15mg / kg once, once every 4 ~ 6 hours. It can be used up to 5mg at a time. ^[2]

Oxycodone regulations

Oxycodone is a semi-synthetic thebaine derivative. It is a species listed in the United Nations Single Convention on Narcotic Drugs of 1961. China has included it in the control of narcotic drugs. Oxycodone was first used clinically in 1917 and has a history of nearly a century. Oxycodone hydrochloride controlled-release tablets (patented products) have been widely used in many countries for the treatment of moderate and severe pain since they were launched in 1995. Beijing Mengdi Pharmaceutical Co., Ltd. applied for the import of oxycodone hydrochloride controlled-release tablets from the United Kingdom in 1998. After review, our office has approved the drug for clinical use. The management regulations for controlled release tablets of oxycodone hydrochloride are hereby notified as follows:

1. Beijing Mengdi Pharmaceutical Co., Ltd. is responsible for the import and packaging of oxycodone hydrochloride controlled-release tablets (trade name: OxyContin). All imported packaged drugs are delivered to Sinopharm Group Pharmaceuticals Co., Ltd. to operate according to the narcotic drug business channel.

2. Medical institutions at all levels can purchase controlled release tablets of oxycodone hydrochloride for medical use at the local narcotic drug operating unit with the narcotic drug seal card. Oxycodone hydrochloride controlled-release tablets are used in medical institutions to treat pain. The amount of each prescription should not exceed 15 days. The prescription is kept for 3 years for reference.

3. When oxycodone hydrochloride controlled-release tablets are used for cancer analgesia, they should follow the WHO "Guidelines for Three-Step Cancer Analgesia". When used for the treatment of non-cancer chronic pain, the "Notice on Increasing Indications of Fentanyl Transdermal Patch (Dorigi)" issued by the State Drug Administration and the Ministry of Health should be followed (Sinopec Jian'an [2002 ] No. 194) Article 4 of Annex 1, "Guiding Principles of Strong Opioids in the Treatment of Chronic Non-Cancer Pain". ^[3]