Depade (naltrexone HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Naltrexone is an opioid antagonist.
Naltrexone is an opioid antagonist and generally has little or no agonist activity. Naltrexone acts as a competitive antagonist at mc, kappa, and delta receptors in the CNS; the drug appears to have the highest affinity for the micro receptor. The major metabolite of naltrexone, 6beta-naltrexol, is also an opioid antagonist and may contribute to the antagonist activity of the drug.
Naltrexone does not produce physical or psychologic dependence, and tolerance to the drug's opioid antagonist activity reportedly does not develop.
In patients who have received single or repeated large doses of opioid agonists, naltrexone attenuates or produces a complete but reversible block of the pharmacologic effects (e.g., physical dependence, analgesia, euphoria, tolerance) of the opiate. Naltrexone may precipitate mild to potentially severe withdrawal in individuals physically dependent on opiates. By blocking the effects of opioids by competitive binding at opioid receptors, it makes the blockade produced potentially surmountable, but overcoming full naltrexone blockade by administration of opioids may result in non-opioid receptor-mediated symptoms such as histamine release.
However, in usual doses in patients who have not recently received opiates, naloxone exerts little or no pharmacologic effect, but may produce pupillary constriction by an unknown mechanism. Naltrexone does not produce physical or psychologic dependence, and tolerance to the drug's opioid antagonist activity reportedly does not develop.
The mechanism of action of naltrexone in alcohol dependence is not entirely known, but is thought to involve the endogenous opioid system. Evidence from studies in animals suggests that alcohol ingestion stimulates release of endogenous opioid agonists, which may increase some of the rewarding effects associated with alcohol ingestion through agonist activity at opiate (e.g., micro) receptors. In animals and humans, opiate antagonists (e.g., naltrexone) that competitively bind to opiate receptors may reduce alcohol consumption by blocking the effects of endogenous opiates and thus making alcohol ingestion less pleasurable.
Naltrexone also has been found in humans to augment plasma cortisol and adrenocorticotropic hormone (ACTH) levels through activation of the hypothalamic-pituitary-adrenal (HPA)-axis, which is found to be related to reduced urge and amount of alcohol drinking. In addition, naltrexone appears to decrease substantially the subjective alcohol ''high'' and this may reduce alcohol drinking behaviors. Naltrexone does not cause disulfiram-like reactions following ingestion of alcohol.
Naltrexone is rapidly and almost completely (about 96%) absorbed following oral administration with peak plasma concentrations of both naltrexone and the primary metabolite, 6beta-naltrexol, occurring within 1 hour of oral dosing. After IM administration of extended-release injection, plasma concentration time profile characterized by a transient initial peak approximately 2 hours after injection, followed by a second peak observed approximately 2-3 days later. Then, beginning approximately 14 days after dosing, concentrations slowly decline, with measurable levels beyond 1 month.
Less 6beta-naltrexol is generated following IM administration compared with oral administration due to a reduction in first-pass hepatic metabolism.
Plasma protein binding is low (21%) over the therapeutic range of naltrexone. The cytochrome P-450 (CYP) system is not involved in naltrexone metabolism. Naltrexone and its metabolites are excreted primarily in the urine, with minimal unchanged drug.
The elimination half- life of extended-release injectable suspension is 5-10 days and is dependent on the erosion of the polymer. Elimination half-life of 6beta-naltrexol following extended-release injectable suspension administration is 5-10 days. The mean elimination half-life after oral administration for naltrexone and 6beta-naltrexol are 4 hours and 13 hours, respectively.
USES: This medication is used to prevent people who have been addicted to certain drugs (opiates) from taking them again. It is used as part of a complete treatment program for drug abuse (such as compliance monitoring, counseling, behavioral contract, lifestyle changes). This medication must not be used in people currently taking opiates, including methadone.
Doing so can cause sudden withdrawal symptoms. Naltrexone belongs to a class of drugs known as opiate antagonists. It works in the brain to prevent opiate effects (such as feelings of well-being, pain relief).
It also decreases the desire to take opiates. Ask your doctor or pharmacist if you should have medication available to treat opioid overdose (such as naloxone, nalmefene). Teach your family or household members about the signs of an opioid overdose and how to treat it.
This medication is also used to treat alcohol abuse. It can help people drink less alcohol or stop drinking altogether. It also decreases the desire to drink alcohol when used with a treatment program that includes counseling, support, and lifestyle changes.
Generic name: naltrexone HCl
Pronunciation: (nal-TREX-one)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Depade
Indications
The following indications are listed for Depade:
- Alcohol Use Disorder
- Prevention Of Relapse To Opioid Dependence
Also known as: Alcohol Addiction, Alcohol Dependence, Alcoholism.
Dosing
Dosage of oral naltrexone is expressed in terms of the hydrochloride salt; dosage of the extended-release IM injection is expressed in terms of naltrexone. The following dosage recommendations are usual dosages recommended by the manufacturer; alternative flexible dosing schedules in which the dose and/or frequency of administration of the drug are altered in an attempt to improve compliance have also been suggested.
Administer naltrexone orally or by IM injection. Do not administer the parenteral preparation by IV or subcutaneous injection.
Therapy may be initiated with the parenteral preparation; it is not necessary to initiate therapy with oral naltrexone and then switch to parenteral preparation.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
The manufacturer states that concomitant administration of naltrexone with drugs other than opioid agonists has not been studied; therefore, naltrexone should be used with caution in patients receiving other drugs.
Naltrexone is not metabolized by the cytochrome P-450 (CYP) isoenzyme system.
Naltrexone does not inhibit or induce major CYP enzymes.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Patients receiving opioid analgesics.
*Patients with current physiologic opioid dependence, including those currently maintained on opiate agonists (e.g., methadone) or partial agonists (e.g., buprenorphine).
*Patients in acute opioid withdrawal.
*Patients who have failed the naloxone challenge test or who have a positive urine screen for opioids.
*Patients with known hypersensitivity to naltrexone or any components of the products. I
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effects in patients with opioid use disorder receiving naltrexone extended-release injectable suspension (incidence >=2% and at least twice as frequent as with placebo) include hepatic enzyme abnormalities, injection site pain, nasopharyngitis, insomnia, and toothache.
The most common adverse effects in patients with opioid use disorder receiving naltrexone oral tablets (incidence >=10%) include difficulty sleeping, anxiety, nervousness, abdominal pain/cramps, nausea and/or vomiting, low energy, joint and muscle pain, and headache.
The most common adverse effects in patients with alcohol use disorder receiving naltrexone extended-release injectable suspension (incidence >=5% and at least twice as frequent as with placebo) include nausea, vomiting, injection site reactions (including induration, pruritus, nodules and swelling), muscle cramps, dizziness or syncope, somnolence or sedation, anorexia, and decreased appetite or other appetite disorders.
The most common adverse effects in patients with alcohol use disorder receiving naltrexone oral tablets (incidence >=2%) include depression, nausea, headache, dizziness, nervousness, fatigue, insomnia, vomiting, anxiety, and somnolence.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
The safety and efficacy of naltrexone have not been established in pediatric patients younger than 18 years of age.
In reproduction studies in rats and rabbits, oral naltrexone increased the incidence of early fetal loss. There are no adequate and well-controlled studies of oral naltrexone use in pregnant women. Available data from published case series of naltrexone extended-release injectable suspension are insufficient to identify a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Naltrexone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes, such as low birth weight, preterm birth, and fetal death, and often results in continued or relapsing illicit opioid use. Published studies have demonstrated that alcohol is associated with fetal harm, including growth restriction, facial abnormalities, CNS abnormalities, behavioral disorders, and impaired intellectual development.
Naltrexone and its major metabolite, 6beta-naltrexol, are present in human milk. There are no data on the effects of the drug on the breastfed infant or on milk production. Consider the developmental health benefits of breastfeeding along with the mother's clinical need for naltrexone and any potential adverse effects on the breastfed infant from naltrexone or the underlying maternal condition.
Clinical studies of naltrexone extended-release injectable suspension did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger patients. In trials of alcohol-dependent patients, 2.6% of patients were over 65 years of age, and one patient was over 75 years of age. No individuals older than 65 years of age were included in studies of opioid dependency.
The pharmacokinetics of naltrexone have not been evaluated in the geriatric population. This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function in this population.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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