What Are the Signs of an Oxycodone Overdose?

Oxycodone hydrochloride injection, this product is a powerful analgesic. It is used to treat moderate to severe acute pain, including moderate to severe pain caused by surgery, and severe pain requiring treatment with strong opioids. ^[1] .

Drug Name: Oxycodone hydrochloride injection

Hanyu Pinyin: YinSuan Qiang Kao Tong Zhu She Ye
Drug type: Doping

Composition of oxycodone hydrochloride injection

The main ingredient of this product is oxycodone hydrochloride.
Chemical name: 4,5a-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one hydrochloride Chemical structural formula:
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Molecular formula: C ₁₈ H ₂₂ C1N0 ₄ (C ₁₈ H ₂₁ N0 ₄ HCl)
Molecular weight: 351.83
Excipients: sodium citrate, citric acid, sodium chloride, hydrochloric acid, sodium hydroxide, water for injection.

Characters of oxycodone hydrochloride injection

This product is a colorless clear solution.

Indications of oxycodone hydrochloride injection

This product is a powerful analgesic. It is used to treat moderate to severe acute pain, including moderate to severe pain caused by surgery, and severe pain requiring treatment with strong opioids.

Specification of oxycodone hydrochloride injection

(1) lml: 10mg (2) 2ml: 20mg

Dosage and Administration of Oxycodone Hydrochloride Injection

Route of administration: subcutaneous injection or infusion; intravenous injection or infusion. Adjust the dose according to the severity of the patient's pain, the patient's overall condition, and the medications that have been and are being used.
Adults over 18 years of age: The following are the recommended starting doses. If the analgesic effect is insufficient or the pain is aggravated, the dose should be gradually increased.
Intravenous bolus injection: Dilute the drug solution to 1 mg / ml with 0.9% physiological saline, 5% glucose or water. A slow bolus dose of 1 to 10 mg is administered within 1 to 2 minutes. Dosing frequency should not be shorter than every 4 hours.
Intravenous infusion: Dilute the drug solution to 1 mg / ml with 0.9% physiological saline, 5% glucose or water. The recommended initial dose is 2 mg per hour.
Intravenous (PCA pump): Dilute the medicinal solution to 1 mg / ml with 0.9% physiological saline, 5% glucose or water. Each dose is 0.03mg / kg body weight, and the dosing interval should not be shorter than 5 minutes.
Subcutaneous bolus: use a solution with a concentration of 10mg / ml, the recommended starting dose is 5mg, if necessary, repeat administration every .4 hours.
Subcutaneous infusion: Dilute with 0.9% saline, 5% glucose or water if necessary. The recommended starting dose for patients who have not used opioids is 7.5 mg per day. Gradually titrate according to the symptoms. Patients who have previously taken oral oxycodone may require higher doses if they switch to this drug (see below).
Conversion of oral oxycodone and injection of oxycodone The dose conversion ratio is as follows: 2mg of oral oxycodone is equivalent to 1mg of oxycodone for injection. It is important to emphasize that this is only a basic principle. There are individual differences between different patients, and each patient should be carefully titrated to reach the appropriate dose.
Elderly patients Be careful when treating. Care should be taken to start the titration from the lowest starting dose.
For patients with renal dysfunction and liver dysfunction Patients with mild to moderate renal dysfunction and / or mild liver dysfunction should be cautious, and titration should be started carefully from the lowest dose until pain relief .
Children under 18 years of age There are no data on the use of oxycodone hydrochloride injections in children under 18 years of age.
Opioids for non-cancerous pain are not a first-line treatment for chronic non-cancerous pain, and it is not recommended to use only opioids for chronic non-cancerous pain. Some chronic pains, such as osteoarthritis pain and disc disease, can be relieved after treatment with strong opioids. The need for continued use of opioids for non-cancer pain requires periodic evaluation.
Stop treatment When patients no longer need oxycodone treatment, the dose of the drug should be gradually reduced to prevent withdrawal symptoms.

Adverse reactions of oxycodone hydrochloride injection

Has the typical adverse effects of full opioid receptor agonists. Tolerance and dependence develop (see section Drug tolerance and dependence below). Appropriate laxatives can be applied to prevent the occurrence of constipation. If nausea and vomiting occur, antiemetics can be used simultaneously.
The common (incidence rate> = 1%) and uncommon (incidence rate <= 1%) adverse reactions are shown in the table below:
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Drug tolerance and drug dependence Patients who use this product for a long time may develop tolerance and need to gradually increase the dosage to maintain pain control. Long-term use of oxycodone hydrochloride injection may cause physical dependence, and withdrawal symptoms may occur if the drug is abruptly stopped. If oxycodone treatment is no longer needed, a gradual reduction until discontinuation should be used to prevent withdrawal symptoms. Opioid withdrawal symptoms include some or all of the following manifestations: restlessness, tearing, runny nose, yawning, sweating, chills, myalgia, dilated pupils, and palpitations. Other symptoms can also occur, including: sensitivity, anxiety, back pain, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, increased blood pressure, and increased breathing and heart rate.

Contraindications of oxycodone hydrochloride injection

Oxycodone hydrochloride injection is contraindicated in patients who are known to be allergic to oxycodone or any other component of the drug; respiratory depression; head injury; paralytic intestinal obstruction; acute abdomen; chronic obstructive airway Disease; Pulmonary heart disease; Chronic bronchial asthma; Hypercapnia; Moderate to severe impaired liver function; Severe renal impairment (inosine clearance <10ml / min); Chronic constipation; Simultaneously taking monoamine oxidase inhibitor Within 2 weeks of administration or discontinuation; pregnancy; and any other situation where opioid use is prohibited.

Precautions for oxycodone hydrochloride injection

1. The major danger of opioid overdose is respiratory depression.
2. As with all other opioids, the dose should be reduced for patients with hypothyroidism.
3. This medicine should be used with caution in the following cases: increased intracranial pressure, low blood pressure, decreased blood volume, toxic psychosis, biliary disorders, pancreatitis, inflammatory bowel disease, prostatic hypertrophy, insufficient adrenal function, acute alcohol Poisoning, tremor, delirium, chronic kidney and liver disease, severe lung disease, excessive fatigue, elderly and frail patients.
4. Oxycodone hydrochloride injection should not be used in patients who may have paralytic intestinal obstruction. During use, if paralytic intestinal obstruction occurs or is suspected, the drug should be discontinued immediately.
5. Patients who continuously use this product for a long time may develop tolerance, and need to gradually increase the dose to maintain the control of pain.
6. Long-term use may lead to the occurrence of physical dependence, and withdrawal symptoms may occur if the drug is abruptly stopped. If patients no longer require oxycodone treatment, a gradual reduction until discontinuation should be used to prevent withdrawal symptoms.
7. For some patients with chronic non-cancerous pain, opioid therapy should be part of a comprehensive treatment plan that includes other medications and non-drug therapies. An important part of the assessment of these patients with chronic non-cancerous pain is the patient's addiction and history of drug abuse. Opioid analgesics (including oxycodone) have a potential tendency for psychological dependence (addiction). Therefore, when applying opioids such as oxycodone hydrochloride injection, special attention should be paid to patients with a history of alcohol and drug abuse.
8. If the doctor believes that the patient is suitable for opioid therapy, the main purpose of treatment is not to minimize the dose of opioids, but to minimize the adverse effects of the drugs while fully analgesic. Patients and doctors often need to communicate multiple times to adjust the amount of medication administered. It is recommended that doctors judge the effectiveness of patients based on guidelines for pain management. If this is not achieved, treatment can be terminated when the doctor and patient agree.
9. Oxycodone has the potential for abuse similar to other strong opioids, and should be used with caution in patients who are dependent on other opioids. Oxycodone may be sought and abused by potential or apparent external addicts.
10. Like other opioids, if pregnant women are drug dependent, they may cause withdrawal symptoms and respiratory depression at birth.
11. Oxycodone may change the patient's ability to respond to varying degrees, and this change is related to the dosage and the sensitivity of the individual. If affected, patients should not drive and operate machines.
12. No special notice before opening.
Each ampoule can only be used once by one patient. Use immediately after opening the ampoule and discard unused solutions. Studies have shown that the physical and chemical properties of the solution are stable when stored at room temperature for 24 hours after unsealing.
From a microbiological point of view, the solution should be used immediately after opening. If it cannot be used immediately, it should not be stored for more than 24 hours at 2 ~ 8 ° C, unless all configuration, dilution and other processes are completely completed under controlled and verified aseptic conditions.
Oxycodone hydrochloride injection is compatible with the following: butyl scopolamine, scopolamine hydrobromide, dexamethasone sodium phosphate, haloperidol, imidazolidine hydrochloride, metoclopramide hydrochloride, and levmepromazine hydrochloride.
Oxycodone hydrochloride injection undiluted and diluted to a concentration of 1 mg / ml in 0.9% w / v saline or 5% glucose or water, with a reliable polyethylene or polycarbonate syringe, PVC tube, PVC or The EVA infusion bag is physically and chemically stable within 24 hours at room temperature.
Studies have shown that in various containers, whether it is an undiluted injection or an infusion diluted to 1 mg / ml, there is no need to protect from light.
After opening the ampoule, improper handling of undiluted injections poses the risk of contamination.
13. This product cannot be mixed with other pharmaceutical products except the drugs mentioned in the above (Note 12 section).
When the benzoxazine concentration is 3mg / ml or lower, whether it is mixed with oxycodone hydrochloride injection or oxycodone hydrochloride injection diluted with water, it is stored at room temperature for 24 hours without precipitation Signs. Precipitation occurs when oxycodone hydrochloride injection is mixed with a benzophenazine solution with a concentration greater than 3 mg / ml or diluted with physiological saline. When benzophenazine and oxycodone hydrochloride are administered simultaneously by intravenous or subcutaneous infusion, they should be diluted with water.
Clopyrazine is chemically incompatible with oxycodone hydrochloride injection.
14. According to the Anti-Doping Regulations, oxycodone is a banned substance listed in the stimulant list, so athletes should use this product with caution.

Oxycodone hydrochloride injection for pregnant and lactating women

There are no sufficient studies to understand the effects of oxycodone on human reproduction. Nor have they studied the effects of exposure to drugs during pregnancy on childbirth and postpartum birth. However, oxycodone equivalent to 3 times and 47 times the adult dose (160 mg / day) was orally administered to rats and rabbits, and no toxicity to fetuses was found. Oxycodone hydrochloride injection is not recommended for pregnancy and childbirth. If pregnant women have used opioids during pregnancy, the baby should be monitored for respiratory depression after birth.
Oxycodone is excreted through breast milk and may cause respiratory depression in newborn babies. Therefore, oxycodone hydrochloride injection should not be used in nursing women.

Oxycodone hydrochloride injection for children

There are no data on the use of oxycodone hydrochloride injections in children under 18 years of age.

Oxycodone hydrochloride injection for the elderly

Use caution when treating. Care should be taken to start the titration from the lowest starting dose.

Drug interactions of oxycodone hydrochloride injection

Oxycodone enhances the central sedative effect of drugs including sedatives, anesthetics, sleeping pills, antidepressants, sedatives, phenothiazines, tranquilizers, alcohol, other opioids, muscle relaxants and antihypertensives . Monoamine oxidase inhibitors are known to interact with narcotic analgesics and cause excitement or inhibition of the central nervous system with hypertension or hypotension crisis.
Oxycodone is partially metabolized through the CYP2D6 and CYP3A4 pathways. These pathways can be blocked by a variety of drugs, but the blocking effect of these drugs has not been clinically significant.

Oxycodone hydrochloride injection overdose

Symptoms of overdose:
Signs of oxycodone poisoning and overdose are: needle-like pupils, respiratory depression, hypotension, and hallucinations. Nausea and vomiting usually occur in a few severe cases. Noncardiogenic pulmonary edema and rhabdomyolysis are common after intravenous opioid analgesics. In some more severe cases, circulatory failure and drowsiness or coma or deep coma, skeletal muscle weakness, bradycardia, and even death may occur.
Concomitant use of alcohol or other psychotropic substances can increase the effects of overdose.
Rescue treatment for drug overdose:
First, the airway should be ensured to be unobstructed. A special ventilation catheter should be established and provided with auxiliary or controllable breathing facilities.
In the case of a large overdose, naloxone should be administered intravenously (0.4 to 2 mg for adults and 0.1 mg per kg of body weight) if the patient is unconscious or has respiratory depression. If there is still no response, the administration is repeated after a 2-minute interval. If repeated dosing is required, naloxone can be given intravenously at an initial dose of 60% of the initial dose / hour. The liquid was prepared by dissolving 10 mg of naloxone in 50 ml of glucose solution to make a 200 mg / ml solution and infusion using an intravenous infusion pump (adjusting the dosage according to the clinical response of the patient). Periodic examination of the patient's clinical signs is also required during infusion.
If intravenous fluids are not appropriate for the patient, intramuscular injections can be performed. Because the naloxone effect lasts for a relatively short period of time, it must be closely observed until the patient's spontaneous breathing is re-established. Naloxone is a competitive antagonist and may require a larger dose (4 mg) for severely toxic patients.
If the poisoning is not serious, 0.2 mg naloxone can be injected intravenously, and then if necessary, 0.1 mg is given every 2 minutes. After the last dose of naloxone, the patient must continue to observe for 6 hours.
After taking oxycodone overdose, naloxone should not be used in the absence of clinically significant respiratory depression or secondary circulation suppression. People who know or suspect that they have a physical dependence on morphine should give it cautiously. In this case, a sudden and complete reversal of opioid effects may accelerate the appearance of acute withdrawal symptoms.

Pharmacotoxicology of oxycodone hydrochloride injection

Pharmacological effects:
Oxycodone hydrochloride is an opioid analgesic, a pure opioid receptor agonist, whose main therapeutic effect is analgesia. The pharmacological effects of opioid agonists include anti-anxiety, euphoria, respiratory depression, constipation, antitussive and analgesic. Pure n receptor agonists increase the analgesic effect with increasing dose. Like all pure opioid agonist analgesics, oxycodone has no established maximum dose; the maximum analgesic effect can only be determined by side effects, and more serious side effects may include lethargy and respiratory depression.
The exact mechanism of oxycodone analgesic effect is unknown. Some specific central nervous system opioid receptors with opioid endogenous substances have been found in the brain and spinal cord, which may be related to the analgesic effect of oxycodone.
Toxicology research:
Genotoxicity The results of the oxycodone Ames test and the micronucleus test in mice were negative. In human lymphocyte chromosome aberration test, the result was negative when the dose was 1500 g / ml in the absence of metabolic activation and 5000 g / ml in the case of metabolic activation, but the result was negative when treated with a metabolic activation dose 1250 pg / ml for 24 hours The result was positive; in the mouse lymphoma test, the result was positive when there was a metabolic activation dose 50 pg / m and when there was no metabolic activation dose 400 ng / ml.
Reproductive toxicity In the rat fertility test, rats were given intragastric administration of oxycodone hydrochloride 0.5, 2, 8 mg / kg once a day. Male rats were administered 28 days before mating until necropsy (mating). After 2 to 3 weeks), the female rats were administered 14 days before mating to the 6th day of pregnancy, and there was no effect on the fertility of male or female rats. Rats and rabbits were given orally doses of 8 mg / kg and 125 mg / kg (calculated as mg / m ^[2] , equivalent to 0.5 and 15 times the adult dose of 160 mg / day, respectively), No fetal toxicity due to oxycodone was seen. There was no long-term effect on the development and reproduction of pups in the perinatal toxicity test in rats. The high dose (6 mg / kg, calculated as mg / m ^[2] is equivalent to 0.4 times the adult dose of 160 mg / day) group Weight loss can be seen in pups during lactation and early weaning, but this weight loss is recoverable.
Carcinogenicity An animal test for oxycodone carcinogenicity has not been performed.

Pharmacokinetics of oxycodone hydrochloride injection

Subcutaneous or intravenous injection of oxycodone injection into healthy subjects, regardless of whether it is a single injection or continuous infusion over 8 hours, the subcutaneous injection and intravenous injection are bioequivalent .
After absorption, oxycodone is distributed throughout the body. About 45% bind to plasma proteins. It is metabolized by the liver into noroxycodone, oxymorphone and its combination with uronic acid. The analgesic effect of metabolites has no clinical significance.
Active drugs and metabolites can be excreted through urine and feces.
Oxycodone plasma concentrations are less affected by age, with elderly patients 15% higher than younger patients.
For female subjects, in general, blood concentrations were up to 25% higher than males on a weight-adjusted basis.
The drug penetrates the placenta and is excreted in breast milk.
Compared with normal subjects, patients with mild to severe liver dysfunction may have increased levels of oxycodone and noroxycodone in plasma and decreased levels of oxymorphone. The elimination half-life of oxycodone may increase, which may be accompanied by enhanced drug action.
Compared with healthy subjects, patients with mild to severe renal dysfunction may have increased concentrations of oxycodone and noroxycodone in plasma, and the elimination half-life of oxycodone may increase. May be accompanied by increased drug action.

Storage of oxycodone hydrochloride injection

Store at 10 ~ 30 ° C.

Packaging of oxycodone hydrochloride injection

Clear glass ampoules, 5 per box.

Validity of oxycodone hydrochloride injection

36 months.

Oxycodone hydrochloride injection standard

Import Drug Registration Standard JM20080005