Percodan

Percodan is part of the drug class:

• Other agents for local oral treatment

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of oxycodone and aspirin combination in the pediatric population. Because of aspirin's toxicity, use in children is not recommended. Do not give aspirin to a child who has chickenpox or flu symptoms, unless approved by a doctor. Aspirin can cause a life-threatening reaction called Reye syndrome.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of oxycodone and aspirin combination in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or lung problems, which may require caution and an adjustment in the dose for patients receiving oxycodone and aspirin combination.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using this medicine.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Defibrotide
• Dichlorphenamide
• Influenza Virus Vaccine, Live
• Ketorolac
• Nalmefene
• Naltrexone
• Safinamide

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abiraterone
• Acarbose
• Aceclofenac
• Acemetacin
• Acepromazine
• Alfentanil
• Alipogene Tiparvovec
• Almotriptan
• Alprazolam
• Alteplase, Recombinant
• Alvimopan
• Amiloride
• Amineptine
• Amiodarone
• Amisulpride
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Amprenavir
• Amtolmetin Guacil
• Anagrelide
• Anileridine
• Anisindione
• Apixaban
• Aprepitant
• Argatroban
• Aripiprazole
• Asenapine
• Atazanavir
• Baclofen
• Bendroflumethiazide
• Benperidol
• Benzphetamine
• Benzthiazide
• Betrixaban
• Bivalirudin
• Boceprevir
• Bromazepam
• Bromfenac
• Bromopride
• Brompheniramine
• Bufexamac
• Bumetanide
• Buprenorphine
• Buspirone
• Butabarbital
• Butorphanol
• Carbamazepine
• Carbinoxamine
• Carisoprodol
• Carphenazine
• Celecoxib
• Ceritinib
• Chloral Hydrate
• Chlordiazepoxide
• Chlorothiazide
• Chlorpheniramine
• Chlorpromazine
• Chlorpropamide
• Chlorthalidone
• Chlorzoxazone
• Choline Salicylate
• Cilostazol
• Citalopram
• Clarithromycin
• Clobazam
• Clomipramine
• Clonazepam
• Clonixin
• Clopamide
• Clopidogrel
• Clorazepate
• Clozapine
• Cobicistat
• Cocaine
• Codeine
• Conivaptan
• Cyclobenzaprine
• Cyclopenthiazide
• Cyclosporine
• Dabigatran Etexilate
• Danaparoid
• Darunavir
• Desipramine
• Desirudin
• Desmopressin
• Desvenlafaxine
• Dexibuprofen
• Dexketoprofen
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Diazoxide
• Dibenzepin
• Dichloralphenazone
• Diclofenac
• Dicumarol
• Difenoxin
• Diflunisal
• Digoxin
• Dihydrocodeine
• Diphenhydramine
• Diphenoxylate
• Dipyrone
• Dolasetron
• Donepezil
• Dothiepin
• Doxepin
• Doxylamine
• Droperidol
• Droxicam
• Duloxetine
• Edoxaban
• Eletriptan
• Enflurane
• Enzalutamide
• Eplerenone
• Eptifibatide
• Erythromycin
• Escitalopram
• Estazolam
• Eszopiclone
• Ethacrynic Acid
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fentanyl
• Fepradinol
• Feprazone
• Feverfew
• Flibanserin
• Floctafenine
• Flufenamic Acid
• Fluoxetine
• Fluphenazine
• Flurazepam
• Flurbiprofen
• Fluspirilene
• Fluvoxamine
• Fondaparinux
• Fosaprepitant
• Fosphenytoin
• Fospropofol
• Frovatriptan
• Furazolidone
• Furosemide
• Ginkgo
• Glimepiride
• Glipizide
• Glyburide
• Gossypol
• Granisetron
• Halazepam
• Haloperidol
• Halothane
• Heparin
• Hexobarbital
• Hydrochlorothiazide
• Hydrocodone
• Hydroflumethiazide
• Hydromorphone
• Hydroxytryptophan
• Hydroxyzine
• Ibuprofen
• Idelalisib
• Imipramine
• Indapamide
• Indinavir
• Indomethacin
• Iproniazid
• Isocarboxazid
• Isoflurane
• Itraconazole
• Ketamine
• Ketazolam
• Ketobemidone
• Ketoconazole
• Ketoprofen
• Lepirudin
• Levomilnacipran
• Levorphanol
• Linezolid
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lopinavir
• Lorazepam
• Lorcaserin
• Lornoxicam
• Loxapine
• Loxoprofen
• Lumacaftor
• Lumiracoxib
• Meclizine
• Meclofenamate
• Mefenamic Acid
• Melitracen
• Meloxicam
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Metformin
• Methadone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrexate
• Methotrimeprazine
• Methyclothiazide
• Methylene Blue
• Methylnaltrexone
• Metolazone
• Midazolam
• Milnacipran
• Mirtazapine
• Mitotane
• Moclobemide
• Molindone
• Moricizine
• Morniflumate
• Morphine
• Morphine Sulfate Liposome
• Nabumetone
• Nalbuphine
• Nalorphine
• Naloxone
• Naproxen
• Naratriptan
• Nateglinide
• Nefazodone
• Nelfinavir
• Nepafenac
• Nialamide
• Nicomorphine
• Nicorandil
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Nitrazepam
• Nitrous Oxide
• Nortriptyline
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxaprozin
• Oxazepam
• Oxymorphone
• Oxyphenbutazone
• Palonosetron
• Papaveretum
• Parecoxib
• Paregoric
• Paroxetine
• Pemetrexed
• Pentazocine
• Pentobarbital
• Pentosan Polysulfate Sodium
• Pentoxifylline
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenelzine
• Phenindione
• Phenobarbital
• Phenprocoumon
• Phenylbutazone
• Phenytoin
• Piketoprofen
• Pimozide
• Piperacetazine
• Pipotiazine
• Piracetam
• Piritramide
• Piroxicam
• Polythiazide
• Posaconazole
• Pralatrexate
• Pranoprofen
• Prasugrel
• Prazepam
• Primidone
• Procarbazine
• Prochlorperazine
• Proglumetacin
• Promazine
• Promethazine
• Propofol
• Propyphenazone
• Proquazone
• Protein C
• Protriptyline
• Quazepam
• Quetiapine
• Ramelteon
• Rasagiline
• Remifentanil
• Remoxipride
• Repaglinide
• Reteplase, Recombinant
• Ribociclib
• Ritonavir
• Rivaroxaban
• Rizatriptan
• Rofecoxib
• Salicylic Acid
• Salsalate
• Samidorphan
• Saquinavir
• Secobarbital
• Selegiline
• Sertindole
• Sertraline
• Sibutramine
• Sodium Oxybate
• Sodium Salicylate
• Spironolactone
• Sufentanil
• Sulindac
• Sulpiride
• Sumatriptan
• Suvorexant
• Tacrolimus
• Tapentadol
• Telaprevir
• Telithromycin
• Temazepam
• Tenoxicam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tianeptine
• Tiaprofenic Acid
• Ticagrelor
• Ticlopidine
• Tilidine
• Tirofiban
• Tizanidine
• Tolazamide
• Tolbutamide
• Tolfenamic Acid
• Tolmetin
• Tolonium Chloride
• Topiramate
• Torsemide
• Tramadol
• Tranylcypromine
• Trazodone
• Treprostinil
• Triamterene
• Triazolam
• Trichlormethiazide
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Valdecoxib
• Varicella Virus Vaccine
• Venlafaxine
• Vilazodone
• Vortioxetine
• Warfarin
• Xipamide
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acebutolol
• Atenolol
• Betamethasone
• Betaxolol
• Bisoprolol
• Captopril
• Carteolol
• Carvedilol
• Celiprolol
• Cortisone
• Delapril
• Dexamethasone
• Enalaprilat
• Enalapril Maleate
• Esmolol
• Imidapril
• Labetalol
• Levobunolol
• Lisinopril
• Methylprednisolone
• Metipranolol
• Metoprolol
• Miconazole
• Nadolol
• Nebivolol
• Nitroglycerin
• Oxprenolol
• Paramethasone
• Penbutolol
• Pindolol
• Practolol
• Prednisolone
• Prednisone
• Probenecid
• Propranolol
• Rifampin
• Sotalol
• St John's Wort
• Streptokinase
• Tamarind
• Temocapril
• Tenecteplase
• Timolol
• Triamcinolone
• Valproic Acid
• Voriconazole

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Addison disease (adrenal gland problem) or
• Alcohol abuse, or history of or
• Bleeding problems or
• Brain tumor, history of or
• Chronic obstructive pulmonary disease (COPD) or
• Cor pulmonale (serious heart condition) or
• Drug dependence, especially with narcotics, or history of or
• Gallbladder disease or gallstones or
• Head injury, history of or
• Hypothyroidism (an underactive thyroid) or
• Hypovolemia (low blood volume) or
• Kyphoscoliosis (curvature of the spine with breathing problems) or
• Peptic ulcer disease, active or history of or
• Problems with passing urine or
• Prostatic hypertrophy (enlarged prostate, BPH) or
• Vitamin K deficiency—Use with caution. May increase risk for more serious side effects.

• Hemophilia or
• Lung disease or breathing problems (eg, respiratory depression), severe or
• Stomach or bowel blockage (eg, paralytic ileus) or
• Viral infection—Should not be used in patients with these conditions.

• Hypotension (low blood pressure) or
• Pancreatitis (inflammation of the pancreas) or
• Seizures, history of—Use with caution. May make these conditions worse.

• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• It is used to ease pain.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how Percodan affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• Do not take this medicine with other strong pain drugs or if you are using a pain patch without talking to your doctor first.
• You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
• If you are taking aspirin to help prevent a heart attack, talk with your doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take Percodan.
• Long-term use of an opioid drug like this medicine may lead to lower sex hormone levels. This may lead to signs like change in sex ability in men, no menstrual period in women, lowered interest in sex, or fertility problems. Call your doctor if you have any of these signs.
• This medicine may raise the chance of seizures in some people, including people who have had seizures in the past. Talk to your doctor to see if you have a greater chance of seizures while taking Percodan.
• Very bad stomach ulcers or bleeding can happen with this medicine. Taking it in high doses or for a long time, smoking, or drinking alcohol raises the chance of these side effects. Taking Percodan with food will not lower the chance of these effects. Call your doctor or get medical help right away if you get very bad stomach or back pain; black, tarry, or bloody stools; throwing up blood or throw up that looks like coffee grounds; or weight gain or swelling that is not normal.
• Taking an opioid drug like this medicine may lead to a rare but very bad adrenal gland problem. Call your doctor right away if you have very bad dizziness or passing out, very bad upset stomach or throwing up, or if you feel less hungry, very tired, or very weak.
• If you are 65 or older, use Percodan with care. You could have more side effects.
• Do not give to children and teenagers who have or are getting better from flu signs, chickenpox, or other viral infections due to the chance of Reye's syndrome. Reye's syndrome causes very bad problems to the brain and liver.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking this medicine, call your doctor right away.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

General

Opioid analgesics should be used with caution when combined with CNS depressant drugs, and should be reserved for cases where the benefits of opioid analgesia outweigh the known risks of respiratory depression, altered mental state, and postural hypotension.

Percodan tablets should be given with caution to patients with CNS depression, elderly or debilitated patients, patients with severe impairment of hepatic, pulmonary, or renal function, hypothyroidism, Addison's disease, prostatic hypertrophy, urethral stricture, acute alcoholism, delirium tremens, kyphoscoliosis with respiratory depression, myxedema, and toxic psychosis.

Percodan tablets may obscure the diagnosis or clinical course in patients with acute abdominal conditions. Oxycodone may aggravate convulsions in patients with convulsive disorders, and all opioids may induce or aggravate seizures in some clinical settings.

Following administration of Percodan tablets, anaphylactic reactions have been reported in patients with a known hypersensitivity to codeine, a compound with a structure similar to morphine and oxycodone. The frequency of this possible cross-sensitivity is unknown.

Aspirin has been associated with elevated hepatic enzymes, blood urea nitrogen and serum creatinine, hyperkalemia, proteinuria, and prolonged bleeding time.

Hemorrhage

Aspirin may increase the likelihood of hemorrhage due to its effect on the gastric mucosa and platelet function (prolongation of bleeding time). Salicylates should be used with caution in the presence of peptic ulcer or coagulation abnormalities.

Pregnancy

Aspirin can cause fetal harm when administered to a pregnant woman. Salicylates readily cross the placenta and by inhibiting prostaglandin synthesis, may cause constriction of ductus arteriosus, resulting in pulmonary hypertension and increased fetal mortality and, possibly other untoward fetal effects. Aspirin use in pregnancy can also result in alteration in maternal and neonatal hemostasis mechanisms. Maternal aspirin use during later stages of pregnancy may cause low birth weight, increased incidence of intracranial hemorrhage in premature infants, stillbirths and neonatal death. The use of aspirin during pregnancy especially in the third trimester should be avoided. If Percodan tablets are used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Renal Failure

Avoid aspirin in patients with severe renal failure (glomerular filtration rate less than 10 mL/minute).

Hepatic Insufficiency

Avoid aspirin in patients with severe hepatic insufficiency.

Interactions with Other CNS Depressants

Patients receiving other opioid analgesics, general anesthetics, phenothiazines, other tranquilizers, centrally-acting anti-emetics, sedative-hypnotics or other CNS depressants (including alcohol) concomitantly with Percodan tablets may exhibit an additive CNS depression. When such combined therapy is contemplated, the dose of one or both agents should be reduced.

Interactions with Mixed Agonist/Antagonist Opioid Analgesics

Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and butorphanol) should be administered with caution to a patient who has received or is receiving a course of therapy with a pure opioid agonist analgesic such as oxycodone. In this situation, mixed agonist/antagonist analgesics may reduce the analgesic effect of oxycodone and/or may precipitate withdrawal symptoms in these patients.

Ambulatory Surgery and Postoperative Use

Oxycodone and other morphine-like opioids have been shown to decrease bowel motility. Ileus is a common postoperative complication, especially after intra-abdominal surgery with use of opioid analgesia. Caution should be taken to monitor for decreased bowel motility in postoperative patients receiving opioids. Standard supportive therapy should be implemented.

Use in Pancreatic/Biliary Tract Disease

Oxycodone may cause spasm of the sphincter of Oddi and should be used with caution in patients with biliary tract disease, including acute pancreatitis. Opioids like oxycodone may cause increases in the serum amylase level.

Tolerance and Physical Dependence

Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Physical dependence is manifested by withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an antagonist. Physical dependence and tolerance are not unusual during chronic opioid therapy.

The opioid abstinence or withdrawal syndrome is characterized by some or all of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate or heart rate.

In general, opioids should not be abruptly discontinued (see DOSAGE AND ADMINISTRATION: Cessation of Therapy).

Information for Patients/Caregivers

The following information should be provided to patients receiving Percodan tablets by their physician, nurse, pharmacist, or caregiver:

1. Patients should be aware that Percodan tablets contain oxycodone, which is a morphine-like substance.
2. Patients should be instructed to keep Percodan tablets in a secure place out of the reach of children. In the case of accidental ingestions, emergency medical care should be sought immediately.
3. When Percodan tablets are no longer needed, the unused tablets should be destroyed by flushing down the toilet.
4. Patients should be advised not to adjust the medication dose themselves. Instead, they must consult with their prescribing physician.
5. Patients should be advised that Percodan tablets may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating heavy machinery).
6. Patients should not combine Percodan tablets with alcohol, opioid analgesics, tranquilizers, sedatives, or other CNS depressants unless under the recommendation and guidance of a physician. When co-administered with another CNS depressant, Percodan tablets can cause dangerous additive central nervous system or respiratory depression, which can result in serious injury or death.
7. The safe use of Percodan tablets during pregnancy has not been established; thus, women who are planning to become pregnant or are pregnant should consult with their physician before taking Percodan tablets.
8. Nursing mothers should consult with their physicians about whether to discontinue nursing or discontinue Percodan tablets because of the potential for serious adverse reactions to nursing infants.
9. Patients who are treated with Percodan tablets for more than a few weeks should be advised not to abruptly discontinue the medication. Patients should consult with their physician for a gradual discontinuation dose schedule to taper off the medication.
10. Patients should be advised that Percodan tablets are a potential drug of abuse. They should protect it from theft, and it should never be given to anyone other than the individual for whom it was prescribed.
11. Patients should be advised that Percodan tablets may cause or worsen constipation, as generally occurs with all opioids. They should discuss any past history of constipation with their prescribing physician so a management plan may be initiated.

Laboratory Tests

Although oxycodone may cross-react with some drug urine tests, no available studies were found which determined the duration of detectability of oxycodone in urine drug screens. However, based on pharmacokinetic data, the approximate duration of detectability for a single dose of oxycodone is roughly estimated to be one to two days following drug exposure.

Urine testing for opiates may be performed to determine illicit drug use and for medical reasons such as evaluation of patients with altered states of consciousness or monitoring efficacy of drug rehabilitation efforts. The preliminary identification of opiates in urine involves the use of an immunoassay screening and thin-layer chromatography (TLC). Gas chromatography/mass spectrometry (GC/MS) may be utilized as a third-stage identification step in the medical investigational sequence for opiate testing after immunoassay and TLC. The identities of 6-keto opiates (e.g., oxycodone) can further be differentiated by the analysis of their methoxime-trimethylsilyl (MO-TMS) derivative.

Drug/Drug Interactions with Oxycodone

CYP3A4 Inhibitors and CYP450 Inducers:
Oxycodone is extensively metabolized by multiple metabolic pathways. CYP3A4 is the major enzyme involved in noroxycodone formation followed by CYP2B6, CYP2C9/19 and CYP2D6. Drugs that inhibit CYP3A4 activity, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may cause decreased clearance of oxycodone which could lead to an increase in oxycodone plasma concentrations and prolonged opioid effects. Similarly, CYP450 inducers, such as rifampin, carbamazepine, and phenytoin, may induce the metabolism of oxycodone and, therefore, may cause increased clearance of the drug which could lead to a decrease in oxycodone plasma concentrations, lack of efficacy or, possibly, development of an abstinence syndrome in a patient who had developed physical dependence to oxycodone.

If co-administration with Percodan is necessary, caution is advised when initiating therapy with, currently taking, or discontinuing CYP3A4 inhibitors or CYP450 inducers. Evaluate these patients at frequent intervals and consider dose adjustments until stable drug effects are achieved.

Skeletal Muscle Relaxants:
Opioid analgesics may enhance the neuromuscular-blocking action of skeletal muscle relaxants and produce an increase in the degree of respiratory depression.

CNS Depressants:
Patients receiving CNS depressants such as other opioid analgesics, general anesthetics, phenothiazines, other tranquilizers, centrally-acting anti-emetics, sedative-hypnotics or other CNS depressants (including alcohol) concomitantly with Percodan tablets may exhibit an additive CNS depression. When such combined therapy is contemplated, the dose of one or both agents should be reduced.

Analgesics:
Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, naltrexone, and butorphanol) should be administered with caution to a patient who has received or is receiving a pure opioid agonist such as oxycodone. These agonist/antagonist analgesics may reduce the analgesic effect of oxycodone or may precipitate withdrawal symptoms.

Drug/Drug Interactions with Aspirin

Angiotensin Converting Enzyme (ACE) Inhibitors: The hyponatremic and hypotensive effects of ACE inhibitors may be diminished by the concomitant administration of aspirin due to its indirect effect on the renin-angiotensin conversion pathway.

Acetazolamide: Concurrent use of aspirin and acetazolamide can lead to high serum concentrations of acetazolamide (and toxicity) due to competition at the renal tubule for secretion.

Anticoagulant Therapy (Heparin and Warfarin): Patients on anticoagulation therapy are at increased risk for bleeding because of drug-drug interactions and the effect on platelets. Aspirin can displace warfarin from protein binding sites, leading to prolongation of both the prothrombin time and the bleeding time. Aspirin can increase the anticoagulant activity of heparin, increasing bleeding risk.

Anticonvulsants: Salicylate can displace protein-bound phenytoin and valproic acid, leading to a decrease in the total concentration of phenytoin and an increase in serum valproic acid levels.

Beta Blockers: The hypotensive effects of beta blockers may be diminished by the concomitant administration of aspirin due to inhibition of renal prostaglandins, leading to decreased renal blood flow, and salt and fluid retention.

Diuretics: The effectiveness of diuretics in patients with underlying renal or cardiovascular disease may be diminished by the concomitant administration of aspirin due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.

Methotrexate: Aspirin may enhance the serious side and toxicity of methotrexate due to displacement from its plasma protein binding sites and/or reduced renal clearance.

Nonsteroidal Anti-inflammatory Drugs (NSAID's): The concurrent use of aspirin with other NSAID's should be avoided because this may increase bleeding or lead to decreased renal function. Aspirin may enhance the serious side effects and toxicity of ketorolac, due to displacement from its plasma protein binding sites and/or reduced renal clearance.

Oral Hypoglycemics Agents: Aspirin may increase the serum glucose-lowering action of insulin and sulfonylureas leading to hypoglycemia.

Uricosuric Agents: Salicylates antagonize the uricosuric action of probenecid or sulfinpyrazone.

Drug/Laboratory Test Interactions

Depending on the sensitivity/specificity and the test methodology, the individual components of Percodan tablets may cross-react with assays used in the preliminary detection of cocaine (primary urinary metabolite, benzoylecgonine) or marijuana (cannabinoids) in human urine. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. The preferred confirmatory method is gas chromatography/mass spectrometry (GC/MS). Moreover, clinical considerations and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.

Salicylates may increase the protein bound iodine (PBI) result by competing for the protein binding sites on pre-albumin and possibly thyroid-binding globulins.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Animal studies to evaluate the carcinogenic potential of oxycodone and aspirin have not been performed.

Mutagenesis

The combination of oxycodone and aspirin has not been evaluated for mutagenicity. Oxycodone alone was negative in a bacterial reverse mutation assay (Ames), an in vitro chromosome aberration assay with human lymphocytes without metabolic activation and an in vivo mouse micronucleus assay. Oxycodone was clastogenic in the human lymphocyte chromosomal assay in the presence of metabolic activation and in the mouse lymphoma assay with or without metabolic activation. Aspirin induced chromosome aberrations in cultured human fibroblasts.

Fertility

Animal studies to evaluate the effects of oxycodone on fertility have not been performed. Aspirin has been shown to inhibit ovulation in rats.

Pregnancy

Oxycodone: Pregnancy Category B

Reproduction studies in rats and rabbits demonstrated that oral administration of oxycodone was not teratogenic or embryo-fetal toxic.

Aspirin: Pregnancy Category D (see PRECAUTIONS)

Salicylates readily cross the placenta and by inhibiting prostaglandin synthesis, may cause constriction of ductus arteriosus resulting in pulmonary hypertension and increased fetal mortality and, possibly other untoward fetal effects. Aspirin use in pregnancy can also result in alteration in maternal and neonatal hemostasis mechanisms. Maternal aspirin use during later stages of pregnancy may cause low birth weight, increased incidence of intracranial hemorrhage in premature infants, stillbirths and neonatal death. Use during pregnancy, especially in the third trimester, should be avoided.

Safe use of Percodan (Oxycodone and Aspirin Tablets, USP) in pregnancy has not been established relative to possible adverse effects on fetal development. Therefore, Percodan tablets should not be used in pregnant women unless, in the judgment of the physician, the potential benefits outweigh the possible hazards.

Opioids can cross the placental barrier and have the potential to cause neonatal respiratory depression. Opioid use during pregnancy may result in a physically drug-dependent fetus. After birth, the neonate may suffer severe withdrawal symptoms. Aspirin may produce anemia, ante- or postpartum hemorrhage, prolonged gestation and labor, and oligohydramnios.

Labor and Delivery

Percodan tablets are not recommended for use in women during and immediately prior to labor and delivery due to its potential effects on respiratory function in the newborn. Aspirin should be avoided one week prior to and during labor and delivery because it can result in excessive blood loss at delivery. Prolonged gestation and prolonged labor due to prostaglandin inhibition have been reported.

Nursing Mothers

Ordinarily, nursing should not be undertaken while a patient is receiving Percodan tablets because of the possibility of sedation and/or respiratory depression in the infant. Oxycodone is excreted in breast milk in low concentrations, and there have been rare reports of somnolence and lethargy in babies of nursing mothers taking an oxycodone/acetaminophen product. Salicylic acid has also been detected in breast milk. Adverse effects on platelet function in the nursing infant exposed to aspirin in breast milk may be a potential risk. Furthermore, the risk of Reye Syndrome caused by salicylate in breast milk is unknown. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the potential benefits to the woman and the possible hazards to the nursing infant.

Pediatric Use

Percodan tablets should not be administered to pediatric patients. Reye Syndrome is a rare but serious disease which can follow flu or chicken pox in children and teenagers. While the cause of Reye Syndrome is unknown, some reports claim aspirin (or salicylates) may increase the risk of developing this disease.

Geriatric Use

Special precaution should be given when determining the dosing amount and frequency of Percodan tablets for geriatric patients, since clearance of oxycodone may be slightly reduced in this patient population when compared to younger patients.

Hepatic Impairment

In a pharmacokinetic study of oxycodone in patients with end-stage liver disease, oxycodone plasma clearance decreased and the elimination half-life increased. Care should be exercised when oxycodone is used in patients with hepatic impairment.

Avoid aspirin in patients with severe hepatic impairment.

Renal Impairment

In a study of patients with end stage renal impairment, mean elimination half-life of oxycodone was prolonged in uremic patients due to increased volume of distribution and reduced clearance. Oxycodone should be used with caution in patients with renal impairment.

Avoid aspirin in patients with severe renal impairment (glomerular filtration rate less than 10 mL/minute).

Signs and Symptoms

Serious overdose with Percodan (Oxycodone and Aspirin Tablets, USP) is characterized by signs and symptoms of opioid and salicylate overdose. Oxycodone overdosage can be manifested by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, pupillary constriction (pupils may be dilated in the setting of hypoxia), and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur. Early signs of acute aspirin (salicylate) overdose including tinnitus occur at plasma concentrations approaching 200 mcg/mL. Plasma concentrations of aspirin above 300 mcg/mL are toxic. Severe toxic effects are associated with levels above 400 mcg/mL. A single lethal dose of aspirin in adults is not known with certainty but death may be expected at 30 g. For real or suspected overdose, a Poison Control Center should be contacted immediately.

In acute salicylate overdose, severe acid-base and electrolyte disturbances may occur and are complicated by hyperthermia and dehydration, and coma. Respiratory alkalosis occurs early while hyperventilation is present, but is quickly followed by metabolic acidosis. Serious symptoms such as depression, coma, and respiratory failure progress rapidly.

Salicylism (chronic salicylate toxicity) may be noted by symptoms such as dizziness, tinnitus, difficulty hearing, nausea, vomiting, diarrhea, and mental confusion. More severe salicylism may result in respiratory alkalosis.

Treatment

Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation. Supportive measures (including oxygen, intravenous fluids, and vasopressors) should be employed in the management of circulatory shock and pulmonary edema accompanying overdose as indicated. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation. Treatment of acid-base disturbances and electrolyte disorders is also important. Because of the concern over salicylate toxicity, acid-base status should be followed closely with serial blood gas and serum pH determinations.

The opioid antagonist naloxone hydrochloride is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to opioids including oxycodone. Therefore, an appropriate dose of naloxone hydrochloride should be administered (usual initial adult dose 0.4 mg-2 mg) preferably by the intravenous route, simultaneously with efforts at respiratory resuscitation. Since the duration of action of oxycodone may exceed that of the antagonist, the patient should be kept under continued surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to oxycodone overdose. In patients who are physically dependent on any opioid agonist including oxycodone, an abrupt or complete reversal of opioid effects may precipitate an acute abstinence syndrome. The severity of the withdrawal syndrome produced will depend on the degree of physical dependence and the dose of the antagonist administered. Please see the prescribing information for the specific opioid antagonist for details of their proper use.

Gastric emptying and/or lavage may be useful in removing unabsorbed drug. This procedure is recommended as soon as possible after ingestion, even if the patient has vomited spontaneously. After lavage and/or emesis, administration of activated charcoal, as a slurry, is beneficial, if less than three hours have passed since ingestion. Charcoal adsorption should not be employed prior to lavage and emesis.

In severe cases of salicylate overdose, hyperthermia and hypovolemia are the major immediate threats to life. Children should be sponged with tepid water. Replacement fluid should be administered intravenously and augmented with correction of acidosis. Plasma electrolytes and pH should be monitored to promote alkaline diuresis of salicylate if renal function is normal. Infusion of glucose may be required to control hypoglycemia. With more severe acute toxicity respiratory alkalosis may occur.

Hemodialysis and peritoneal dialysis can be performed to reduce the body content of aspirin. In patients with renal insufficiency or in cases of life-threatening salicylate intoxication dialysis is usually required. Exchange transfusion may be indicated in infants and young children.

In case of real or suspected overdose, a poison control center should be consulted for the treatment of salicylism.

The toxicity of oxycodone and aspirin in combination is unknown.

Percodan tablets are a Schedule II controlled substance. Oxycodone is a mu-agonist opioid with an abuse liability similar to morphine. Oxycodone, like morphine and other opioids used in analgesia, can be abused and is subject to criminal diversion.

Drug addiction is defined as an abnormal, compulsive use, use for non-medical purposes of a substance despite physical, psychological, occupational or interpersonal difficulties resulting from such use, and continued use despite harm or risk of harm. Drug addiction is a treatable disease, utilizing a multi-disciplinary approach, but relapse is common. Opioid addiction is relatively rare in patients with chronic pain but may be more common in individuals who have a past history of alcohol or substance abuse or dependence. Pseudoaddiction refers to pain relief seeking behavior of patients whose pain is poorly managed. It is considered an iatrogenic effect of ineffective pain management. The health care provider must assess continuously the psychological and clinical condition of a pain patient in order to distinguish addiction from pseudoaddiction and thus, be able to treat the pain adequately.

Physical dependence on a prescribed medication does not signify addiction. Physical dependence involves the occurrence of a withdrawal syndrome when there is sudden reduction or cessation in drug use or if an opiate antagonist is administered. Physical dependence can be detected after a few days of opioid therapy. However, clinically significant physical dependence is only seen after several weeks of relatively high dosage therapy. In this case, abrupt discontinuation of the opioid may result in a withdrawal syndrome. If the discontinuation of opioids is therapeutically indicated, gradual tapering of the drug over a 2-week period will prevent withdrawal symptoms. The severity of the withdrawal syndrome depends primarily on the daily dosage of the opioid, the duration of therapy and medical status of the individual.

The withdrawal syndrome of oxycodone is similar to that of morphine. This syndrome is characterized by yawning, anxiety, increased heart rate and blood pressure, restlessness, nervousness, muscle aches, tremor, irritability, chills alternating with hot flashes, salivation, anorexia, severe sneezing, lacrimation, rhinorrhea, dilated pupils, diaphoresis, piloerection, nausea, vomiting, abdominal cramps, diarrhea and insomnia, and pronounced weakness and depression.

“Drug-seeking” behavior is very common in addicts and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. Oxycodone, like other opioids, has been diverted for non-medical use. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Like other opioid medications, Percodan tablets are subject to the Federal Controlled Substances Act. After chronic use, Percodan tablets should not be discontinued abruptly when it is thought that the patient has become physically dependent on oxycodone.

Interactions with Alcohol and Drugs of Abuse

Oxycodone may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression.

Since Percodan is used for pain, you are not likely to miss a dose. Skip any missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.