Oxycodone + Naloxone

Oxycodone + Naloxone is used for: Chronic Pain

Chronic Pain Indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate Use as first opioid analgesic or in non-opioid tolerant patients Starting dose: 10 mg/5 mg PO q12hr Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression Titration and maintenance May be up-titrated from current dose by increasing by 10 mg/5 mg q12hr q1-2 days as needed based on efficacy, safety, and tolerability Not to exceed daily dose of 80 mg/40 mg (ie, 40 mg/20 mg q12hr) If breakthrough pain experienced, assess need for a dosage increase or a rescue dose of an immediate-release analgesic Opioid tolerant patients Patients who are opioid tolerant are those receiving the following for ?1 week: ->60 mg/day PO morphine ->25 mcg/hr transdermal fentanyl ->30 mg/day PO oxycodone ->8 mg/day PO hydromorphone ->25 mg/day PO oxymorphone, OR -Equianalgesic dose of another opioid Hepatic impairment Mild: Reduce dose by one-third to one-half of the usual starting dose followed by careful titration Moderate-to-severe: Contraindicated

<18 years: Safety and efficacy not established

Renal impairment Reduce dose by one-half of the usual starting dose followed by careful dose titration

May take with or without food Tablets must be swallowed intact and are not to be cut, broken, chewed, crushed, or dissolved (risk of rapid release and absorption of potentially fatal overdose) Do not abruptly discontinue in a physically dependent patient; use a gradual downward titration to prevent withdrawa

Significant respiratory depression Acute or severe bronchial asthma Known or suspected paralytic ileus and GI obstruction Known hypersensitivity to oxycodone or naloxone Moderate-to-severe hepatic impairment

Exposes users to risks of addiction, abuse and misuse, which can lead to overdose and death; assess each patient’s risk before prescribing and monitor regularly for development of these behaviors and conditions Instruct patients to swallow extended-release tablets whole to avoid exposure to a potentially fatal dose of oxycodone Accidental ingestion, especially in children, can result in a fatal overdose of oxycodone Cases of serotonin syndrome, a potentially life-threatening condition, reported with concomitant use of serotonergic drugs; this may occur within the recommended dosage range; the onset of symptoms generally occur within several hours to a few days of concomitant use, but may occur later than that; discontinue therapy immediately if serotonin syndrome is suspected While serious, life-threatening, or fatal respiratory depression can occur at any time during therapy, risk is greatest during initiation of therapy or following dosage increase; monitor patients closely for respiratory depression, especially within first 24 to 72 hr of initiating therapy with and following dosage increases; accidental ingestion of even one dose, especially by children, can result in respiratory depression and death due to overdose of opioid Deaths have occurred in nursing infants exposed to high levels of opioid in breast milk because mothers were ultra-rapid metabolizers of opioid Profound sedation, respiratory depression, coma, and death may result from concomitant administration with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol); because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate Use in patients with acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment is contraindicated; patients with significant chronic obstructive pulmonary disease or cor pulmonale, and with substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages Use caution when selecting dosage for an elderly patient, usually starting at low end of dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy; because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and may be useful to monitor renal function Elderly, cachectic, debilitated patients, and those with chronic pulmonary disease: Monitor closely because of increased risk for life-threatening respiratory depression May cause severe hypotension, including orthostatic hypotension and syncope; this risk is increased in patients whose ability to maintain blood pressure has been compromised by reduced blood volume or coadministration with certain CNS depressants (eg, phenothiazines, general anesthetics) Patients with head injury or increased intracranial pressure: Monitor for sedation and respiratory depression; avoid use in patients with impaired consciousness or coma susceptible to intracranial effects of carbon dioxoide retention May aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings May impair the mental or physical abilities needed to perform potentially hazardous activities Avoid the use of mixed agonist/antagonist (ie, pentazocine, nalbuphine, butorphanol) or partial agonist (buprenorphine) analgesics in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic; mixed agonist/antagonists may reduce the analgesic effect and/or may precipitate withdrawal symptoms

Pregnancy Prolonged use of opioid analgesics during pregnancy can cause neonatal opioid withdrawal syndrome; there are no available data in pregnant women to inform a drug associated risk for major birth defects and miscarriage; published studies with morphine use during pregnancy have not reported a clear association with morphine and major birth defects Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth; the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of drug by newborn; observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly Severe fetal bradycardia reported when administered during labor; naloxone may reverse these effects; although there are no reports of fetal bradycardia earlier in pregnancy, it is possible it may occur; drug should be used in pregnancy only if clearly needed, if potential benefit outweighs risk to fetus, and if appropriate measures such as fetal monitoring are taken to detect and manage potential adverse effect on fetus Labor or delivery Opioids cross placenta and may produce respiratory depression and psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid induced respiratory depression in neonate; drug is not recommended for use in women during and immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate; opioid analgesics can prolong labor through actions that temporarily reduce strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor; monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression Fertility Due to effects of androgen deficiency, chronic use of opioids may cause reduced fertility in females and males of reproductive potential; it is not known whether effects on fertility are reversible Lactation Drug is present in breast milk; published lactation studies report variable concentrations of drug in breast milk with administration of immediate-release formulation to nursing mothers in early postpartum period The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy; capsules and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition Monitor infants exposed to drug through breast milk for excess sedation and respiratory depression; withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast- feeding is stopped Do not initiate oxycodone/naloxone in breastfeeding women because of the possibility of sedation or respiratory depression in an infant Withdrawal signs can occur in breast-fed infants when maternal administration of an opioid analgesic is stopped or when breastfeeding is stopped; naloxone may precipitate opioid withdrawal in a breast-fed infant whose mother received opioid analgesics

Side effects of Oxycodone + Naloxone : -10% Nausea (7-8%) Vomiting (2-5%) Headache (3-4%) Constipation (3%) Abdominal pain (3%) Back pain (3%) Anxiety (1-3%) Pruritus (2%) Insomnia (1-2%)

Oxycodone: Opioid agonist; relatively selective for the mu receptor, but it can bind to other opioid receptors at higher doses; inhibits ascending pain pathways, thus altering response to pain; produces analgesia, respiratory depression, and sedation Naloxone: Antagonist of mu, kappa, and delta opioid receptors, with greatest affinity for the mu receptor; produces opioid withdrawal signs and symptoms in individuals physically dependent on full opioid agonists when administered parenterally