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Interactions with Oxycodone

Contents
Pentobarbital, Phenobarbital, Primidone, Prochlorperazine, Secobarbital, Temazepam, Thioridazine (oral), Thiothixene, Trazodone, Triazolam, Clemastine, Tripelennamine, Brompheniramine, Promethazine (oral), Cyproheptadine, Azatadine, Phenindamine, Perphenazine, Thiethylperazine, Meclizine, Trimethobenzamide, Dronabinol, Trimipramine, Amoxapine, Protriptyline, Clomipramine, Mesoridazine, Trifluoperazine, Molindone, Loxapine, Pimozide (oral), Halazepam, Hydroxyzine, Zolpidem, Estazolam, Quazepam, Mephobarbital, Mephenytoin, Ethotoin, Paramethadione, Trimethadione, Carisoprodol, Chlorphenesin, Chlorzoxazone, Cyclobenzaprine, Metaxalone, Methocarbamol, Orphenadrine, Baclofen, Dantrolene, Apraclonidine ophthalmic, Felbamate, Risperidone (oral), Gabapentin, Lamotrigine, Divalproex sodium, Olanzapine, Topiramate (oral), Triprolidine, Promethazine (rectal), Promethazine (injection), Maprotiline, Mirtazapine, Pramipexole (oral), Ropinirole (oral), Quetiapine, Tiagabine, Tolcapone, Thalidomide, Zaleplon, Entacapone, Levetiracetam, Oxcarbazepine, Zonisamide, Nabilone, Ziprasidone, Aripiprazole, Eszopiclone, Ziconotide, Pregabalin, Rotigotine (transdermal), Paliperidone

If you are currently being treated with any of the following medications, you should not use Oxycodone without reading these interactions.

Naltrexone (oral), Naltrexone (injection)

ADJUST DOSE: Patients taking naltrexone may not benefit from opioid medications, due to opioid receptor antagonism by naltrexone.

MANAGEMENT: If an emergency situation requires that opioid analgesia be administered to a patient who has received naltrexone, the amount of opioid required may be greater than usual, and the resulting respiratory depression may be deeper and more prolonged. Patients should be closely monitored for altered efficacy and safety.

Phenelzine, Tranylcypromine, Procarbazine, Isocarboxazid

CONTRAINDICATED: The coadministration of narcotic analgesics and monoamine oxidase inhibitors (MAOIs) may rarely result in hypotension, respiratory depression, or coma. The mechanism is unknown but may be related to additive CNS and respiratory depressant effects. Rare case reports of severe hypotensive reactions have included propoxyphene (with multiple medications), morphine, and methadone, although others have reported the safe use of MAOIs with narcotic analgesics including methadone and morphine.

MANAGEMENT: Some manufacturers consider the administration of narcotics and MAOIs within 2 weeks of each other to be contraindicated. However, morphine has been safely used in MAOI patients who previously had an adverse reaction with meperidine and is generally suggested as an alternative to meperidine in anesthesia, as long as vital signs are closely monitored. Other recommendations include giving patients small initial test doses of narcotics and monitoring vital signs for adverse reactions.

Apomorphine

GENERALLY AVOID: Central nervous system (CNS) depressant effects may be additively or synergistically increased in patients using apomorphine in combination with other drugs that can also cause these effects. Apomorphine alone has been frequently associated with somnolence and dizziness. Patients may suddenly fall asleep during activities of daily living.

MANAGEMENT: The use of other sedating drugs should generally be avoided during apomorphine treatment. Patients prescribed these agents concurrently should be monitored for potentially excessive or prolonged CNS depression, especially if they are elderly or debilitated. Ambulatory patients should be made aware of the possibility of additive CNS effects (e.g., drowsiness, dizziness, lightheadedness, confusion) and counseled to avoid activities requiring mental alertness until they know how these agents affect them. If patients experience increased episodes of falling asleep during normal daily activities, they should avoid driving and other potentially hazardous activities until they have contacted their physician.

Tramadol

GENERALLY AVOID: Concomitant use of tramadol increases the seizure risk in patients taking other opioids. These agents are often individually epileptogenic and may have additive effects on seizure threshold during coadministration. CNS- and respiratory-depressant effects may also be additive. In patients who have been previously dependent on or chronically using opioids, tramadol can also reinitiate physical dependence or precipitate withdrawal symptoms.

MANAGEMENT: Concomitant use of tramadol and other opioids should be avoided in general. Tramadol should not be used in opioid-dependent patients, and use in patients who are chronically on opioids is also not recommended. Tramadol is contraindicated in patients with acute opioid intoxication. Tramadol dosage should be reduced if it must be used in patients receiving opioids. Patients should be monitored for development of seizures and CNS and respiratory depression.

Iopamidol

GENERALLY AVOID: Intrathecal administration of iodinated contrast media may induce seizures. Although clinical data are generally lacking, there may be a theoretical risk of increased seizure potential when used with selective serotonin reuptake inhibitors (SSRI antidepressants or anorectics), monoamine oxidase inhibitors, neuroleptic agents, central nervous system stimulants, opioids, tricyclic antidepressants, other tricyclic compounds (e.g., cyclobenzaprine, phenothiazines), and/or any substance that can reduce the seizure threshold (e.g., carbapenems, cholinergic agents, fluoroquinolones, interferons, chloroquine, mefloquine, lindane, theophylline). These agents are often individually epileptogenic and may have additive effects when combined.

MANAGEMENT: Drugs that can lower the seizure threshold should preferably be withheld for at least 48 hours prior to and 24 hours following intrathecal administration of iodinated contrast media, provided that temporary interruption of therapy does not pose an undue risk to the patient. Otherwise, close monitoring is advised during and after contrast administration. The manufacturers typically recommend avoiding concomitant administration of phenothiazines (including those used for their antihistamine properties), monoamine oxidase inhibitors, tricyclic antidepressants, central nervous system stimulants, and psychoactive drugs.

Buprenorphine (oral), Buprenorphine (injection), Butorphanol

GENERALLY AVOID: Mixed agonist/antagonist analgesics may reduce the analgesic effect of pure opioid agonists and/or precipitate withdrawal symptoms in patients who have received or are receiving a course of therapy with a pure opioid agonist analgesic.

MANAGEMENT: Mixed agonist/antagonist analgesics such as pentazocine, nalbuphine, dezocine, butorphanol, and buprenorphine should generally be avoided or administered with caution to patients who have received or are receiving pure opioid agonists.

Sodium oxybate

GENERALLY AVOID: The central nervous system (CNS)- and respiratory-depressant effects of sodium oxybate may be potentiated by other agents with CNS-depressant effects.

MANAGEMENT: Agents with CNS depressant effects should be avoided during sodium oxybate therapy.

Sertraline, Paroxetine, Venlafaxine (oral), Fluvoxamine, Sibutramine (oral), Citalopram (oral), Escitalopram, Duloxetine

MONITOR: A case report suggests that use of serotonin reuptake inhibitors with oxycodone may potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A receptors. However, unlike other analgesics such as phenylpiperidine opioids (e.g., meperidine) and tramadol, oxycodone is not known to possess serotonergic activity and has not previously been associated with the serotonin syndrome. The report describes a bone marrow transplant patient who developed severe tremors and visual hallucinations after he dramatically increased his dosage of oxycodone while on a stable dosage of sertraline and cyclosporine. Discontinuation of cyclosporine did not completely resolve his hallucinations and had no effect on the tremors after 72 hours, which led to consideration of a possible sertraline-oxycodone interaction. The patient's symptoms resolved after sertraline was withheld and cyproheptadine (a central serotonin antagonist) administered.

MANAGEMENT: Until further data are available, caution is advised if serotonin reuptake inhibitors is coadministered with oxycodone, particularly in complicated patients such as transplant patients who are also receiving cyclosporine. Close monitoring is recommended for signs and symptoms of excessive serotonergic activity such as CNS irritability, altered consciousness, confusion, myoclonus, ataxia, abdominal cramping, hyperpyrexia, shivering, pupillary dilation, diaphoresis, hypertension, and tachycardia. Particular caution is advised when increasing the dosages of these agents.

Sildenafil (oral)

MONITOR: Acute intake of opiates during sildenafil use may result in prolonged erections. The proposed mechanism is an opiate-induced acute increase in cyclic guanosine monophosphate concentrations in peripheral nerve endings, which can be additive with that produced by sildenafil. The interaction has been reported specifically with dihydrocodeine but could conceivably occur with other opiates. In two patients who had been using sildenafil for erectile dysfunction, prolonged erections lasting 2 to 5 hours occurred on several occasions of sildenafil use within the first week after initiation of treatment with dihydrocodeine. One patient discontinued the dihydrocodeine, whereupon his erections from sildenafil returned to normal. The other patient continued taking dihydrocodeine for an additional 2 weeks but had no further problems.

MANAGEMENT: Patients using sildenafil should be advised of the potential for prolonged erections during acute intake of opiates, and to contact their physician if problems occur. The interaction may not occur during chronic use of opiates.

Procyclidine, Trihexyphenidyl, Biperiden

MONITOR: Central anticholinergic agents may have additive central nervous system (CNS) effects with cannabinoids, barbiturates, opiates, and alcohol. These agents individually can cause cognitive and psychomotor impairment, drowsiness, and dizziness, thus concomitant use may result in more potent effects. In addition, the potential for abuse may be increased when central anticholinergic agents are combined with these drugs.

MANAGEMENT: Patients taking central anticholinergic agents in combination with other CNS depressants should be monitored for potentially excessive or prolonged CNS depression, especially if they are elderly or debilitated. Ambulatory patients should be made aware of the possibility of additive CNS effects (e.g., drowsiness, dizziness, lightheadedness, confusion) and counseled to avoid activities requiring mental alertness until they know how these agents affect them. Patients should also be advised to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Pentobarbital, Phenobarbital, Primidone, Prochlorperazine, Secobarbital, Temazepam, Thioridazine (oral), Thiothixene, Trazodone, Triazolam, Clemastine, Tripelennamine, Brompheniramine, Promethazine (oral), Cyproheptadine, Azatadine, Phenindamine, Perphenazine, Thiethylperazine, Meclizine, Trimethobenzamide, Dronabinol, Trimipramine, Amoxapine, Protriptyline, Clomipramine, Mesoridazine, Trifluoperazine, Molindone, Loxapine, Pimozide (oral), Halazepam, Hydroxyzine, Zolpidem, Estazolam, Quazepam, Mephobarbital, Mephenytoin, Ethotoin, Paramethadione, Trimethadione, Carisoprodol, Chlorphenesin, Chlorzoxazone, Cyclobenzaprine, Metaxalone, Methocarbamol, Orphenadrine, Baclofen, Dantrolene, Apraclonidine ophthalmic, Felbamate, Risperidone (oral), Gabapentin, Lamotrigine, Divalproex sodium, Olanzapine, Topiramate (oral), Triprolidine, Promethazine (rectal), Promethazine (injection), Maprotiline, Mirtazapine, Pramipexole (oral), Ropinirole (oral), Quetiapine, Tiagabine, Tolcapone, Thalidomide, Zaleplon, Entacapone, Levetiracetam, Oxcarbazepine, Zonisamide, Nabilone, Ziprasidone, Aripiprazole, Eszopiclone, Ziconotide, Pregabalin, Rotigotine (transdermal), Paliperidone

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Brimonidine ophthalmic

MONITOR: Central nervous system (CNS) depressant effects may be additively or synergistically increased in patients using brimonidine ophthalmic solution in combination with other drugs that can also cause these effects, especially in elderly or debilitated patients.

MANAGEMENT: Patients prescribed brimonidine ophthalmic drops with other agents that can cause CNS depression should be made aware of the possibility of additive CNS effects (e.g., drowsiness, dizziness, lightheadedness, confusion) and counseled to avoid activities requiring mental alertness until they know how these agents affect them. Patients should be advised to contact their physician if they experience excessive or prolonged CNS depression.

Propoxyphene

MONITOR CLOSELY: Sedatives, tranquilizers, muscle relaxants, antidepressants, and other central nervous system (CNS) depressants may have additive CNS- and/or respiratory-depressant effects with propoxyphene. Misuse of propoxyphene, either alone or in combination with other CNS depressants, has been a major cause of drug-related deaths, particularly in patients with a history of emotional disturbances, suicidal ideation, or alcohol and drug abuse. In a large Canadian study, propoxyphene use was also associated with a 60% increased risk of hip fracture in the elderly, and the risk was further increased by concomitant use of psychotropic agents (sedatives, antidepressants, neuroleptics), presumably due to additive psychomotor impairment. Therefore, these drugs may constitute a dangerous combination in certain susceptible populations. Pharmacokinetically, propoxyphene is an inhibitor of CYP450 2D6 and may increase the plasma concentrations of many psychotropic agents that are metabolized by the isoenzyme such as phenothiazines, haloperidol, risperidone, phenobarbital, and some tricyclic antidepressants and serotonin reuptake inhibitors.

MANAGEMENT: Caution is advised if propoxyphene is used with sedatives, tranquilizers, muscle relaxants, antidepressants, and other CNS depressants, particularly in the elderly and in patients with a history of emotional disturbances, suicidal ideation, or alcohol and drug abuse. Dosage reductions may be appropriate. Patients should be monitored for potentially excessive or prolonged CNS and respiratory depression and other CNS adverse effects. Patients should be warned not to exceed recommended dosages, to avoid alcohol, and to avoid activities requiring mental alertness until they know how these agents affect them.

Propantheline, Hyoscyamine, Belladonna, Methscopolamine, Clidinium, Dicyclomine, Flavoxate, Tolterodine, Trospium

MONITOR: Coadministration of narcotic analgesics with anticholinergic agents may have additive central nervous system (CNS) and gastrointestinal (GI) system effects, and increase the risk of severe constipation or paralytic ileus and CNS depression.

MANAGEMENT: If concomitant use cannot be avoided, patients should be monitored for potentially excessive or prolonged CNS depression and constipation. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

Loperamide (oral)

MONITOR: Coadministration of narcotic analgesics with antidiarrheal agents may have additive central nervous system (CNS) and gastrointestinal (GI) system effects, and increase the risk of severe constipation or paralytic ileus and CNS depression.

MANAGEMENT: If concomitant use cannot be avoided, patients should be monitored for potentially excessive or prolonged CNS depression and constipation. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

Celecoxib (oral)

MONITOR: Coadministration with celecoxib may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by celecoxib.

MANAGEMENT: Caution is advised if celecoxib must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever celecoxib is added to or withdrawn from therapy.

Cinacalcet

MONITOR: Coadministration with cinacalcet may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by cinacalcet, which is expected to occur in patients who are CYP450 2D6 extensive metabolizers (approximately 93% of Caucasians and more than 98% of Asians and individuals of African descent). Concurrent administration of cinacalcet (25 or 100 mg) increased the systemic exposure of amitriptyline (50 mg) and its active metabolite, nortriptyline, by approximately 20% in CYP450 2D6 extensive metabolizers. However, because amitriptyline is metabolized by multiple CYP450 isoenzymes in addition to 2D6, the degree of interaction with cinacalcet may be less than that expected for other drugs that are primarily metabolized by 2D6.

MANAGEMENT: Caution is advised if cinacalcet must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range (e.g., class IC antiarrhythmic agents, phenothiazines, certain beta blockers, and most tricyclic antidepressants). Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever cinacalcet is added to or withdrawn from therapy.

Imatinib (oral)

MONITOR: Coadministration with imatinib may increase the plasma concentrations of drugs that are substrates of CYP450 2C9, 2D6 and/or 3A4. The mechanism is decreased clearance due to inhibition of these isoenzymes by imatinib. According to the manufacturer, imatinib increased the mean peak plasma concentration and area under the concentration-time curve of simvastatin (a CYP450 3A4 substrate) by 2- and 3.5-fold, respectively. Data for other substrates are not currently available, although human liver microsome studies indicate that imatinib is a potent competitive inhibitor of all three isoenzymes.

MANAGEMENT: Caution is advised if imatinib must be used concomitantly with medications that undergo metabolism by CYP450 2C9, 2D6 and/or 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever imatinib is added to or withdrawn from therapy.

Terbinafine

MONITOR: Coadministration with terbinafine may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by terbinafine, which is expected to occur in patients who are CYP450 2D6 extensive metabolizers (approximately 93% of Caucasians and more than 98% of Asians and individuals of African descent). A case of nortriptyline (a CYP450 2D6 substrate) intoxication corresponding to significantly increased serum drug concentrations was reported in a patient shortly after the addition of terbinafine. Rechallenge in the patient produced similar results.

MANAGEMENT: Caution is advised if terbinafine must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever terbinafine is added to or withdrawn from therapy. Due to the long elimination half-life of terbinafine, especially following prolonged use, such interactions may be observed for several months after discontinuation of terbinafine therapy.

Cetirizine

MONITOR: Concurrent use of cetirizine or levocetirizine with alcohol or other central nervous system (CNS) depressants may result in additive impairment of mental alertness and performance. Several studies have shown no effect of racemic cetirizine on cognitive function, motor performance, or sleep latency as indicated by objective measurements. However, there have been reports of somnolence, fatigue, and asthenia in some patients treated with cetirizine or levocetirizine in clinical trials.

MANAGEMENT: Concomitant use of cetirizine or levocetirizine with alcohol or other CNS depressants should generally be avoided if possible. In the event that they are used together, patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Pegvisomant

MONITOR: In clinical trials, patients on opioids often required higher serum pegvisomant concentrations to achieve appropriate IGF-I (insulin-like growth factor-I) suppression compared with patients not receiving opioids. The mechanism of interaction is unknown.

MANAGEMENT: Clinicians should be aware of this potential interaction and adjust the dosage of pegvisomant appropriately in patients treated with opioids.

Lindane topical

MONITOR: Lindane penetrates human skin and has the potential to cause central nervous system toxicity. Seizures have been reported after excessive use or oral ingestion of lindane. There may be a theoretical risk of increased seizure potential when lindane is used with selective serotonin reuptake inhibitors (SSRI antidepressants or anorectics), monoamine oxidase inhibitors, neuroleptic agents, central nervous system stimulants, opioids, tricyclic antidepressants, other tricyclic compounds (e.g., cyclobenzaprine, phenothiazines), and/or any substance that can reduce the seizure threshold (e.g., carbapenems, cholinergic agents, fluoroquinolones, interferons, chloroquine, mefloquine, theophylline). These agents are often individually epileptogenic and may have additive effects when combined.

MANAGEMENT: Caution is advised if lindane is used with any substance that can reduce the seizure threshold, particularly in the very young or the elderly and in patients with epilepsy, a history of seizures, or other risk factors for seizures (e.g., head trauma, brain tumor, metabolic disorders, alcohol and drug withdrawal, CNS infections). Lindane should be used according to recommended dosage and directions for application.

Tizanidine

MONITOR: Sedation is a major side effect of tizanidine and may be potentiated by coadministration with other substances that have central nervous system-depressant effects or that may commonly cause drowsiness.

MANAGEMENT: Use of tizanidine with other substances that commonly cause sedation should be approached with caution, particularly in elderly or debilitated patients. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Quinapril, Spironolactone, Terazosin, Triamterene, Amlodipine, Bisoprolol, Doxazosin, Ramipril, Lisinopril, Phenoxybenzamine, Torsemide, Losartan, Moexipril, Carvedilol, Trandolapril, Valsartan, Sotalol, Sotalol AF, Nisoldipine (oral), Irbesartan, Eprosartan, Candesartan, Telmisartan, Perindopril, Alfuzosin, Olmesartan

MONITOR: The concomitant administration of agents with hypotensive effects and psychotherapeutic agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics), narcotic analgesics, alcohol, or muscle relaxants may additively increase hypotensive and/or central nervous system depressant effects.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for hypotension and excessive or prolonged CNS depression. Ambulatory patients should be made aware of the possibility of additive effects (e.g., drowsiness, dizziness, lightheadedness, confusion, orthostasis, fainting) and be cautioned about driving, operating machinery, or performing other hazardous tasks, and to arise slowly from a sitting or lying position. Patients should also be advised to notify their doctor if they experience excessive side effects that interfere with their normal activities, or dizziness and fainting.

Tacrine

Tacrine antagonizes the respiratory-depressant and sedative effects of morphine without altering its analgesic effects. The mechanism may be related both to the cholinergic effects of tacrine and to alterations in the metabolic fate of morphine. Other narcotic analgesics may participate in this interaction as well.

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