Endocet 2.5/325
Endocet 2.5/325 Uses, Dosage, Side Effects, Food Interaction and all others data.
Oxycodone is a semisynthetic opioid analgesic derived from thebaine in Germany in 1917. It is currently indicated as an immediate release product for moderate to severe pain and as an extended release product for chronic moderate to severe pain requiring continuous opioid analgesics for an extended period. The first oxycodone containing product, Percodan, was approved by the FDA on April 12, 1950.
Oxycodone acts directly on a number of tissues not related to its analgesic effect. These tissues include the respiratory centre in the brain stem, the cough centre in the medulla, muscles of the pupils, gastrointestinal tract, cardiovascular system, endocrine system, and immune system. Oxycodone's effect on the respiratory centre is dose dependant respiratory depression. The action on the cough centre is suppression of the cough reflex. Pupils become miopic or decrease in size, peristalsis of the gastrointestinal tract slows, and muscle tone in the colon may increase causing constipation. In the cardiovascular system histamine may be released leading to pruritis, red eyes, flushing, sweating, and decreased blood pressure. Endocrine effects may include increased prolactin, decreased cortisol, and decreased testosterone. It is not yet known if the effects of opioids on the immune system are clinically significant.
Paracetamol exhibits analgesic action by peripheral blockage of pain impulse generation. It produces antipyresis by inhibiting the hypothalamic heat-regulating centre. Its weak anti-inflammatory activity is related to inhibition of prostaglandin synthesis in the CNS.
Paracetamol (Acetaminophen) is thought to act primarily in the CNS, increasing the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin (PG) synthesis. Unlike NSAIDs, acetaminophen does not inhibit cyclooxygenase in peripheral tissues and, thus, has no peripheral anti-inflammatory affects. While aspirin acts as an irreversible inhibitor of COX and directly blocks the enzyme's active site, studies have found that acetaminophen indirectly blocks COX, and that this blockade is ineffective in the presence of peroxides. This might explain why acetaminophen is effective in the central nervous system and in endothelial cells but not in platelets and immune cells which have high levels of peroxides. Studies also report data suggesting that acetaminophen selectively blocks a variant of the COX enzyme that is different from the known variants COX-1 and COX-2. This enzyme is now referred to as COX-3. Its exact mechanism of action is still poorly understood, but future research may provide further insight into how it works. The antipyretic properties of acetaminophen are likely due to direct effects on the heat-regulating centres of the hypothalamus resulting in peripheral vasodilation, sweating and hence heat dissipation.
| Trade Name | Endocet 2.5/325 |
| Generic | Paracetamol + oxycodone |
| Type | |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Oxycodone is an opioid used in the management of moderate to severe pain.
Oxycodone is indicated for the treatment of moderate to severe pain. There is also an extended release formulation indicated for chronic moderate to severe pain requiring continuous opioid analgesics for an extended period.
Paracetamol IV is used for the management of mild to moderate pain, the management of moderate to severe pain with adjunctive opioid analgesics, the reduction of fever.
Paracetamol is a non-salicylate antipyretic and non-opioid analgesic agent. Paracetamol IV injection is a sterile, clear, colorless, non pyrogenic, isotonic formulation of Paracetamol intended for intravenous infusion.
Endocet 2.5/325 is also used to associated treatment for these conditions: Severe Pain, Severe, Chronic Pain, Acute, moderate Pain, Acute, severe Pain, Chronic, moderate PainAcute Gouty Arthritis, Acute Musculoskeletal Pain, Allergies, Ankylosing Spondylitis (AS), Arthritis, Chills, Cold, Cold Symptoms, Common Cold, Common Cold/Flu, Cough, Cough caused by Common Cold, Coughing caused by Flu caused by Influenza, Dyskinesia of the Biliary Tract, Dyskinesia of the Urinary Tract, Febrile Convulsions, Febrile Illness Acute, Fever, Fibromyalgia Syndrome, Flu caused by Influenza, Headache, Joint dislocations, Menstrual Distress (Dysmenorrhea), Mild pain, Muscle Inflammation, Muscle Injuries, Muscle Spasms, Musculoskeletal Pain, Nasal Congestion, Neuralgia, Osteoarthritis (OA), Pain, Pollen Allergy, Postoperative pain, Premenstrual cramps, Rheumatoid Arthritis, Rhinopharyngitis, Rhinorrhoea, Severe Pain, Sinusitis, Soreness, Muscle, Spasms, Spastic Pain of the Gastrointestinal Tract, Sprains, Tension Headache, Toothache, Upper Respiratory Tract Infection, Whiplash Syndrome, Acute Torticollis, Mild to moderate pain, Minor aches and pains, Minor pain, Moderate Pain, Airway secretion clearance therapy, Antispasmodic, Bronchodilation
How Endocet 2.5/325 works
The full mechanism of oxycodone is not known. Under conditions of inflammation or hyperalgesia, opioid receptors in the heart, lungs, liver, gastrointestinal tract, and reproductive system are upregulated and transported to nerve terminals. Oxycodone and its active metabolites, noroxycodone, oxymorphone, and noroxymorphone are opioid agonists. These compounds passively diffuse across the blood brain barrier or may be actively transported across by an unknown mechanism. Oxycodone and its active metabolites can selectively bind to the mu opioid receptor, but also the kappa and delta opioid receptors in the central nervous system and periphery, and induce a G protein coupled receptor signalling pathway. Activation of mu opioid receptors inhibits N-type voltage operated calcium channels, inhibiting responses to pain.
Dosage
Endocet 2.5/325 dosage
Adults and adolescents weighing 50 kg and over: the recommended dosage of Paracetamol IV is 1000 mg every 6 hours or 650 mg every 4 hours, with a maximum single dose of Paracetamol IV of 1000 mg, a minimum dosing interval of 4 hours, and a maximum daily dose of Paracetamol of 4000 mg per day.
Adults and adolescents weighing under 50 kg: the recommended dosage of Paracetamol IV is 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours, with a maximum single dose of Paracetamol IV of 15 mg/kg, a minimum dosing interval of 4 hours, and a maximum daily dose of Paracetamol of 75 mg/kg per day.
Children >2 to 12 years of age: the recommended dosage of Paracetamol IV is 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours, with a maximum single dose of Paracetamol IV of 15 mg/kg, a minimum dosing interval of 4 hours, and a maximum daily dose of Paracetamol of 75 mg/kg per day.
Side Effects
As all paracetamol products, adverse drug reactions are rare (>1/10000, <1/1000) or very rare (<1/10000). Frequent adverse reactions at injection site have been reported during clinical trials (pain and burning sensation). Very rare cases of hypersensitivity reactions ranging from simple skin rash or urticaria to anaphylactic shock have been reported and require discontinuation of treatment. Cases of erythema, flushing, pruritus and tachycardia have been reported.
Toxicity
Patients experiencing an overdose may present with respiratory depression, sleepiness, stupor, coma, skeletal muscle flaccidity, cold sweat, constricted pupils, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Overdose should be treated by maintaining airway, ventilation, and oxygenation. Oxygen and vasopressor treatment may be necessary to treat circulatory shock and pulmonary edema and defibrillation may be required for cardiac arrest of arrhythmia. Naloxone, nalmefene, or naltrexone may be used to counteract the effects of opioids but patients should be monitored in case further doses are required.
The intraperitoneal LD50 in mice is 320mg/kg, the oral LD50 is 426mg/kg. The oral lowest dose causing toxic effects in humans is 0.14mg/kg and subcutaneously in rats it is 1.53mg/kg.
Oxycodone is pregnancy category B according to the FDA. There is a paucity of data regarding oxycodone use in pregnancy, though animal studies show no teratogenic effects. Rats given oxycodone during lactation showed smaller offspring, though after lactation, they recovered to normal size. Oxycodone is excreted in breast milk and so patients should not breastfeed while taking oxycodone due to risk of sedation and respiratory depression in infants.
No studies on the carcinogenicity of oxycodone have been performed. Oxycodone was genotoxic at 50mcg/mL with metabolic activation and at 400mcg/mL without. It was also clastogenic with metabolic activation at ≥1250mcg/mL. Oxycodone was not found to be genotoxic in other tests. Oxycodone does not affect reproduction and fertility in rats at doses of up to 8mg/kg/day.
Precaution
Administration of Paracetamol in doses higher than recommended may result in hepatic injury, including the risk of severe hepatotoxicity and death. Do not exceed the maximum recommended daily dose of Paracetamol. Use caution when administering Paracetamol in patients with the following conditions: hepatic impairment or active hepatic disease, alcoholism, chronic malnutrition, severe hypovolemia (e.g., due to dehydration or blood loss), or severe renal impairment (creatinine clearance < 30 ml/min). There were infrequent reports of life-threatening anaphylaxis requiring emergent medical attention. Discontinue Paracetamol IV immediately if symptoms associated with allergy or hypersensitivity occurs. Do not use Paracetamol IV in patients with Paracetamol allergy.
Volume of Distribution
2.6L/kg.
Volume of distribution is about 0.9L/kg. 10 to 20% of the drug is bound to red blood cells. Acetaminophen appears to be widely distributed throughout most body tissues except in fat.
Elimination Route
Oxycodone has an oral bioavailability of 60% to 87% that is unaffected by food.
The area under the curve is 135ng/mL*hr, maximum plasma concentration is 11.5ng/mL, and time to maximum concentration is 5.11hr in patients given a 10mg oral immediate release dose of oxycodone.
Half Life
The apparent elimination half life of oxycodone is 3.2 hours for immediate release formulations and 4.5 hours for extended release formulations. Noroxycodone has a half life of 5.8 hours, oxymorphone has a half life of 8.8 hours, noroxymorphone has a half life of 9 hours.
The half-life for adults is 2.5 h after an intravenous dose of 15 mg/kg. After an overdose, the half-life can range from 4 to 8 hours depending on the severity of injury to the liver, as it heavily metabolizes acetaminophen.
Clearance
Total plasma clearance is 1.4L/min in adults.
Adults: 0.27 L/h/kg following a 15 mg/kg intravenous (IV) dose. Children: 0.34 L/h/kg following a 15 mg/kg intravenous (IV dose).
Elimination Route
Oxycodone and its metabolites are eliminated in the urine. Unbound noroxycodone makes up 23% of the dose recovered in urine and oxymorphone makes up Label Conjugated oxymorphone makes up 10% of the recovered dose. Free and conjugated oxycodone makes up 8.9% of the recovered dose, noroxymorphone makes up 14%, and reduced metabolites make up 18%.
Pregnancy & Breastfeeding use
Pregnancy Category C. There are no studies of intravenous Paracetamol in pregnant women; however, epidemiological data on oral Paracetamol use in pregnant women show no increased risk of major congenital malformations. Animal reproduction studies have not been conducted with IV Paracetamol and it is not known whether Paracetamol IV can cause fetal harm when administered to a pregnant woman. Paracetamol IV should be given to a pregnant woman only if clearly needed. There are no adequate and well-controlled studies with Paracetamol IV during labor and delivery; therefore, it should be used in such settings only after a careful benefit-risk assessment. While studies with Paracetamol IV have not been conducted, Paracetamol is secreted in human milk in small quantities after oral administration.
Contraindication
Paracetamol is contraindicated in patients with known hypersensitivity to its active ingredient or to any of the excipients in the intravenous formulation. Also contraindicated in patients with severe hepatic impairment or severe active liver disease
Special Warning
Pediatric Use: The safety and effectiveness of Paracetamol IV for the treatment of acute pain and fever in pediatric patients ages 2 years and older is supported by evidence from adequate and well-controlled studies of Paracetamol IV in adults.
Geriatric use: No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients.
Patients with Hepatic Impairment: Paracetamol is contraindicated in patients with severe hepatic impairment or severe active liver disease and should be used with caution in patients with hepatic impairment or active liver disease. A reduced total daily dose of Paracetamol may be warranted.
Patients with Renal Impairment: In cases of severe renal impairment (creatinine clearance < 30 ml/min), longer dosing intervals and a reduced total daily dose of Paracetamol may be warranted.
Storage Condition
Store in a cool & dry place & away from children. For single use only. The product should be used within 6 hours after opening. Do not refrigerate or freeze.
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