Myloxifin
Myloxifin Uses, Dosage, Side Effects, Food Interaction and all others data.
Naloxone is a pure opioid antagonist that acts competitively at opioid receptors. While the mechanism of action of naloxone is not fully understood, the preponderance of evidence suggests that naloxone antagonizes the opioid effects by competing for the same receptor sites, especially the opioid mu receptor. Recently, naloxone has been shown to bind all three opioid receptors (mu, kappa and gamma) but the strongest binding is to the mu receptor.
Naloxone is an opioid receptor antagonist indicated in the reversal of opioid overdoses. Naloxone has a shorter duration of action than opioids and multiple doses may be required. The therapeutic window of naloxone is wide, as it has no effect if a patient has not taken opioids. Patients treated with naloxone may experience opioid withdrawal and a person administering naloxone should be aware that reversal of opioid overdoses may not resolve all the symptoms a patient is experiencing if other drugs are involved.
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.
| Trade Name | Myloxifin |
| Generic | oxycodone + naloxone |
| Type | Tablet |
| Therapeutic Class | |
| Manufacturer | Zentiva |
| Available Country | United Kingdom |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Naloxone is used for the complete or partial reversal of opioid depression, including respiratory depression, induced by natural and synthetic opioids, including propoxyphene, methadone and certain mixed agonist-antagonist analgesics: nalbuphine, pentazocine, butorphanol, and cyclazocine. Naloxone is also used for diagnosis of suspected or known acute opioid overdosage. Naloxone may be useful as an adjunctive agent to increase blood pressure in the management of septic shock
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.
Myloxifin is also used to associated treatment for these conditions: Opioid Dependence, Opioid Overdose, Pruritus, Respiratory Depression, Septic Shock, Severe Pain, Moderate Pain, Suspected Opioid OverdoseSevere Pain, Severe, Chronic Pain, Acute, moderate Pain, Acute, severe Pain, Chronic, moderate Pain
How Myloxifin works
Naloxone is a competitive inhibitor of the µ-opioid receptor. Naloxone antagonizes the action of opioids, reversing their effects. If a patient has not taken opioids, naloxone does not have a significant effect on patients.
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
Myloxifin dosage
Reversal of central depression from opioid use during surgery:
- Adult:100-200 mcg at intervals of 2-3 minute, titrate dose according to response while maintaining analgesia.
- Child:5-10 mcg IV at 2-3 min intervals.
Opioid overdosage:
- Adult:0.4-2 mg repeated if necessary at 2-3 min intervals. If there is no response after a total of 10 mg has been given, consider the possibility of overdosage with other drugs. Reduce dose for opioid-dependent patients: 0.1-0.2 mg. IM/SC routes may be used (at IV doses) if IV admin is not feasible.
- Child:Initially 10 mcg/kg IV followed by 100 mcg/kg IV if necessary. Alternatively, 0.4-0.8 mg IM or SC, repeated as necessary, if IV admin is not feasible.
Opioid-induced depression in neonates due to obstetric analgesia:
- Child:10 mcg/kg IV, IM or SC repeated at 2-3 min intervals if necessary or 60 mcg/kg as a single IM dose.
Intravenous:
- Reversal of central depression from opioid: Stable in 0.9% sodium chloride and 5% dextrose inj at 4 mcg/ml for 24 hr.
- Opioid overdosage: Stable in 0.9% sodium chloride and 5% dextrose ing at 4 mcg/ml for 24 hr.
Parenteral: Stable in 0.9% sodium chloride and 5% dextrose inj at 4 mcg/ml for 24 hr.
Side Effects
Occur secondarily to reversal (withdrawal) of narcotic analgesia and sedation. Mental depression, apathy, inability to concentrate, sleepiness, irritability, anorexia, nausea, and vomiting in high oral doses during initial treatment of opiate addiction.
Toxicity
If a patient has not taken opioids, naloxone does not have a significant effect on patients.
The oral LD50 in mice and rats is >1 g/kg. The intraperitoneal LD50 is 80 mg/kg in mice and 239 mg/kg in rats. The subcutaneous LD50 is 286 mg/kg in mice and 500 mg/kg in rats.
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
Patients physically dependent on opioids, or who have received large doses of opioids (acute withdrawal syndrome may be precipitated). Pregnancy and lactation.
Interaction
Decreased effect of opioid analgesics.
Volume of Distribution
The volume of distribution of naloxone is 200 L. Naloxone distributes into tissues rapidly. It can also cross the placenta and blood-brain barrier.
2.6L/kg.
Elimination Route
An intranasal dose of naloxone is 42-47% bioavailable. An 8 mg dose of nasal naloxone reaches a Cmax of 12.3-12.8 ng/mL, with a Tmax of 0.25 hours, and an AUC of 16.7-19.0 h*ng/mL. A 0.4 mg intramuscular dose reaches a Cmax of 0.876-0.910 ng/mL, with a Tmax of 0.25 hours, and an AUC of 1.94-1.95 h*ng/mL. A 2 mg intravenous dose reaches a Cmax of 26.2 ng/mL with an AUC of 12.8 h*ng/mL.
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 mean half life of naloxone hydrochloride is 1.8-2.7 hours intranasally, 1.4 hours intramuscularly, and 1.2 hours intravenously. In neonates, the mean half life is 3.1 ± 0.5 hours.
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.
Clearance
The clearance of naloxone is 2500 L/day.
Total plasma clearance is 1.4L/min in adults.
Elimination Route
After oral or intravenous administration, naloxone is 25-40% eliminated in the urine within 6 hours, 50% in 24 hours, and 60-70% in 72 hours. The metabolites naloxone-3-glucuronide, noroxymorphone, and naloxol are all detected in the urine.
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. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.
Storage Condition
Store at 25° C. Protect from light.
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