34/20. Oliceridne -(OLINVYK)- (Aug 2020)- Management of Pain
Drug Name:34/20. Oliceridne -(OLINVYK)- (Aug 2020)- Management of Pain
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
DRUG INTERACTIONS-summary
Moderate and Strong CYP2D6 and CYP3A4 Inhibitors: Patients may require less frequent dosing. Monitor closely and administer subsequent doses based on severity of pain and patient response.
Serotonergic Drugs: Concomitant use may result in serotonin syndrome. Discontinue OLINVYK if serotonin syndrome is suspected.
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics: Avoid use with OLINVYK because they may reduce analgesic effect of OLINVYK or precipitate withdrawal symptoms.
Indication:
U.S. FDA APPROVED DRUGS DURING 2020
Sr.No- 34
Adverse Reaction:
ADVERSE REACTIONS
The most common (incidence =10%) adverse reactions in controlled clinical trials (Studies 1 and 2) were nausea, vomiting, dizziness, headache, constipation, pruritus, and hypoxia.
Contra-Indications:
CONTRAINDICATIONS
• Significant respiratory depression • Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment • Known or suspected gastrointestinal obstruction, including paralytic ileus • Known hypersensitivity to oliceridine
WARNINGS AND PRECAUTIONS
Potential for QT Prolongation with Daily Doses Exceeding 27 mg: May increase risk for QT interval prolongation. Do not exceed a cumulative daily dose of 27 mg.
Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients: Monitor closely, particularly during initiation and titration.
Adrenal Insufficiency: If diagnosed, treat with physiologic replacement corticosteroids and wean the patient off the opioid.
Severe Hypotension: Monitor patients during initiation or titration. Avoid use of OLINVYK in patients with circulatory shock.
Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness: Monitor for signs of sedation and respiratory depression. Avoid the use of OLINVYK in patients with impaired consciousness or coma.
Dosages/ Overdosage Etc:
Patient Information:
PATIENT COUNSELING INFORMATION
Serotonin Syndrome- Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs.
Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop.
Instruct patients to inform their health care provider if they are taking or plan to take serotonergic medications
Constipation- Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention
Distributed by: Trevena, Inc. Chesterbrook, PA 19087 USA OLINVYK™ is a trademark of Trevena, Inc. © 2020 Trevena, Inc. All rights reserved. OLI-001 08/2020
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action Oliceridine is a full opioid agonist and is relatively selective for the mu-opioid receptor. The principal therapeutic action of oliceridine is analgesia.
Like all full opioid agonists, there is no ceiling effect to analgesia for oliceridine. Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory, and CNS depression.
The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.
2 Pharmacodynamics In nonclinical models, the antinociceptive effect of oliceridine can be antagonized by the opioid antagonist naloxone.
Effects on the Central Nervous System- Opioids produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation.
Opioids causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings).
Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations.
Effects on the Gastrointestinal Tract and Other Smooth Muscle- Opioids causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum.
Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm, resulting in constipation.
Other opioidinduced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase.
Effects on the Cardiovascular System- Opioids produces peripheral vasodilation, which may result in orthostatic hypotension or syncope. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension.
Effects on the Endocrine System- Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon.
Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date
Effects on the Immune System - Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown.
Overall, the effects of opioids appear to be modestly immunosuppressive.
3. Pharmacokinetics - Distribution - The mean steady-state volume of distribution of oliceridine ranges between 90-120 L indicating extensive tissue distribution. The plasma protein binding of oliceridine is 77%.
Elimination- Metabolism- In vitro studies suggest that oliceridine is metabolized primarily by CYP3A4 and CYP2D6 P450 hepatic enzymes, with minor contributions from CYP2C9 and CYP2C19 into inactive metabolites.
The mean clearance of oliceridine decreases slightly with increasing dose, resulting in greaterthan-proportional exposure, particularly at doses greater than 2 mg. The percent of unchanged oliceridine excreted in the urine is low (0.97-6.75% of dose), reflecting its low renal clearance.
Excretion- Metabolic clearance is the major route of elimination of oliceridine, primarily by oxidation with subsequent glucuronidation. Additional biotransformation pathways included N-dealkylation, glucuronidation, and dehydrogenation. The majority of the metabolites (approximately 70%) are eliminated in the urine, with the remainder eliminated in the feces. Only a small amount of unchanged drug (0.97-6.75% of a dose) is found in the urine.
Specific Populations- Renal Impairment- In a study comparing subjects with end stage renal disease (N=8) to healthy age and sex-matched healthy subjects (N=8), no significant difference in oliceridine clearance was observed. OLINVYK doses do not need to be adjusted in patients with renal impairment.
Hepatic Impairment- In a study of mild (N=8), moderate (N=8), or severe hepatic impairment (N=6), both clearance and total exposure were similar to age and sex-matched healthy controls (N=8).
The mean halflife of oliceridine was increased in subjects with moderate (4.3 hours) or severe (5.8 hours) hepatic impairment, as compared with healthy subjects (2.1 hours), or patients with mild hepatic impairment (2.6 hours).
The estimated volume of distribution of oliceridine was significantly higher in subjects with moderate or severe hepatic impairment (212 and 348 L, respectively), as compared to healthy subjects (126 L) or patients with mild hepatic impairment (167 L).
Based on these data, the initial dose of OLINVYK does not need to be reduced in patients with mild or moderate hepatic impairment, but these patients may require less frequent dosing.
Use caution when dosing OLINVYK in patients with severe hepatic impairment. Consider reducing the initial dose, and administer subsequent doses only after a careful review of the patient’s severity of pain and overall clinical status.
Drug Interaction Studies- In vitro studies suggest that oliceridine is metabolized primarily by the CYP3A4 and CYP2D6 P450 hepatic enzymes, with minor contributions from CYP2C9 and CYP2C19.
Inhibition studies using selective inhibitors of all the major CYP enzymes show that only the inhibition of CYP3A4 and CYP2D6 significantly affects the metabolism of oliceridine in these assays, suggesting that the contribution of CYP2C9 and CYP2C19 to the metabolism of oliceridine is minor.
The effect of concomitant administration of a CYP2D6 inhibitor on the pharmacokinetics of OLINVYK, although not studied, may be similar to that noted in subjects who are CYP2D6 poor metabolizers.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy Risk Summary- Prolonged use of opioid analgesics during pregnancy may result in neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.3) and Clinical Considerations].
There are no available data on OLINVYK use in pregnant women to evaluate for a drug-associated risk of major birth defects and miscarriage.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
2. Lactation Risk Summary It is not known whether oliceridine is present in human milk. The effects of oliceridine on a breastfeeding infant and on milk production have not been evaluated.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for OLINVYK and any potential adverse effects on the breastfed infant from OLINVYK or from the underlying maternal condition.
3. Females and Males of Reproductive Potential- Infertility - Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible.
4. Pediatric Use- The safety and effectiveness of OLINVYK in pediatric patients has not been established.
5. Geriatric Use- Controlled clinical studies of OLINVYK did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Elderly patients (aged 65 years or older) may have increased sensitivity to OLINVYK. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.
Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration.
Titrate the dosage of OLINVYK slowly in geriatric patients and monitor for signs of central nervous system and respiratory depression
6. Renal Impairment- In patients with end-stage renal disease, there was no clinically significant change in oliceridine clearance. Therefore, dosage adjustment of OLINVYK in patients with renal impairment is not required
7 Hepatic Impairment- In patients with mild or moderate hepatic impairment, no adjustment of the initial dose is needed; however, these patients may require less frequent dosing.
When using OLINVYK in patients with severe hepatic impairment, consider reducing the initial dose, and administer subsequent doses only after a careful review of the patient’s severity of pain and overall clinical status
8. Poor Metabolizers of CYP2D6 Substrates In patients who are known or suspected to be poor CYP2D6 metabolizers, based on genotype or previous history/experience with other CYP2D6 substrates, less frequent dosing of OLINVYK may be required.
These patients should be closely monitored
DRUG ABUSE AND DEPENDENCE
1 Controlled Substance OLINVYK contains oliceridine. [This section cannot be completed until the Drug Enforcement Administration completes a scheduling action under the Controlled Substances Act.]
2. Abuse OLINVYK contains oliceridine, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and tapentadol. OLINVYK can be abused and is subject to misuse, abuse, addiction, and criminal diversion
10 OVERDOSAGE
10.1 Clinical Presentation Acute overdose with OLINVYK can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen due to severe hypoxia in overdose situations
10.2Treatment of Overdose- In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed.
Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated.
Cardiac arrest or arrhythmias will require advanced life-support techniques. The opioid antagonist, naloxone, is a specific antidote for respiratory depression resulting from opioid overdose.
