PERCOCET 10

Percocet PIL – final 06.2019

File Name

Percocet-PIL-ENG-D14

Product

Percocet

Job No.

13649

Language

English

Artwork

Patient Leaflet

Document History

Ver.

Date

Change description

By

18-Feb-20 10:26

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Percocet PIL – final 06.2019

Patient package insert in accordance with the Pharmacists' Regulations (Preparations) -

1986

This medicine is dispensed with a doctor’s prescription only

Percocet

®

5

Tablets

Percocet

®

10

Tablets

Name and quantity of active ingredients:

Name and quantity of active ingredients:

Each tablet contains:

Each tablet contains:

oxycodone HCl 5 mg

oxycodone HCl 10 mg

paracetamol 325 mg

paracetamol 325 mg

Please see Section 6 for a list of the inactive ingredients.

Read the entire leaflet carefully before using this medicine. This leaflet contains concise

information about this medicine. If you have further questions, refer to your doctor or

pharmacist; this medicine has been prescribed to treat you. Do not pass it on to others. It may

harm them, even if it seems to you that their medical condition is similar to yours; this medicine

is usually not recommended for children and babies; this medicine may cause addiction and

substance abuse; this medicine may cause life-threatening respiratory depression; keep out of

children’s reach. Unintentional exposure can be life-threatening; prolonged use during

pregnancy may cause withdrawal symptoms in your newborn baby; this medicine contains

paracetamol which may cause liver toxicity; using this medicine at the same time with other

medicines may change the concentration of Percocet in your blood and cause side effects (see

additional information in Section 2: 'Before using this medicine').

Taking this medicine with benzodiazepines, other medicines which suppress the central nervous

system (including narcotic drugs), or alcohol may cause deep drowsiness, breathing difficulty

(respiratory depression), coma and death.

Opioid medicines may cause addiction, especially with prolonged use. It is also possible to

abuse these medicines or overdose on them. An opioid overdose is often marked by slowed

breathing and can cause death.

Make sure you know the name of the medicine you are taking, your dosage, how often you take

it, how long you are taking it, its side effects and potential risks.

To find out more about the risk of dependence and addiction follow this link:

https://www.health.gov.il/UnitsOffice/HD/MTI/Drugs/risk/DocLib/opioids_en.pdf

1. What is this medicine intended for?

This medicine is intended to relieve medium to acute pain.

Therapeutic group:

Oxycodone is an opioid pain reliever.

Paracetamol is a pain reliever and fever reducer.

2. Before using this medicine

X Do not use this medicine if:

Percocet PIL – final 06.2019

You are sensitive (allergic) to the active ingredients (oxycodone hydrochloride or paracetamol)

or to any of the other ingredients that this medicine contains (listed in Section 6).

Using opioid medicines is contraindicated.

There is severe respiratory depression, difficulty breathing or other lung-related problems.

You have severe or acute bronchial asthma in an uncontrolled environment or if there is no

resuscitation equipment available.

You have a bowel blockage or suspected blockage or you have a narrowed stomach or

bowel.

You are pregnant or breastfeeding (unless you have received other instructions from your

doctor).

! Special warnings regarding the use of this medicine:

Using Percocet, even at the recommended doses, can result in addiction and substance

abuse that can lead to overdose and death. The risk of these effects is higher when

Percocet is used at the same time as alcohol or other depressors of the central nervous

system. Prolonged use may cause dependence! Do not give this medicine to anyone

else. Protect from theft and misuse. To avoid withdrawal symptoms, do not stop using

this medicine abruptly (see section 'If you stop taking this medicine').

Using Percocet may cause life-threatening respiratory depression even when it is used

at the recommended doses. The risk of respiratory depression is greater at the

beginning of your treatment or after increasing the dose. Patients who have a severe

chronic obstructive lung disease (COPD), cor pulmonale (enlarged and failing right

ventricle of the heart, usually due to a chronic lung disease), significantly low lung

capacity, hypoxia (lack of oxygen), hypercapnia (excess carbon dioxide) or respiratory

depression since before starting treatment are at an increased risk of reduced

respiratory drive, including respiratory arrest, even at the recommended doses of

Percocet. Respiratory depression that is not identified and treated on time may lead to

apnea and death. In addition, respiratory depression caused by using opioids may cause

excess carbon dioxide in your blood and may make their sedative effect worse. If you

notice respiratory depression or if you develop difficulty breathing, you must get medical

help.

Taking Percocet unintentionally, particularly by children, may cause respiratory

depression and death. Store this medicine safely, out of children’s reach. If taken

unintentionally, go immediately to an emergency room.

Prolonged use during pregnancy for any reason (medical or otherwise) may cause

physical dependence in your newborn baby and withdrawal symptoms in your newborn

baby shortly after birth. Unlike withdrawal symptoms in adults, this can be life-

threatening if not identified and treated on time.

Using Percocet at the same time with benzodiazepines or other central nervous system

depressors, including alcohol, may cause low blood pressure, deep sedation, respiratory

depression, coma and death. Do not use these medicines together unless supervised by

a doctor. (See section: 'Other medicines and Percocet').

Using Percocet with inhibitors of cytochrome P450 3A4 and P450 2D6 in the liver (such

as erythromycin, ketoconazole, ritonavir and others) may increase the concentration of

oxycodone in your blood and make the side effects become worse or last longer. This

may lead to life-threatening respiratory depression. This is particularly true when the

inhibitor medicine is added after a stable dose of Percocet has been reached. In the

same way, stopping a medicine that increases cytochrome P450 3A4 activity in your

Percocet PIL – final 06.2019

liver (such as rifampin, carbamazepine and phenytoin) may increase the concentration

of Percocet in your blood and make the side effects become worse or last longer.

Alternatively, using this medicine together with medicines that increase the activity of

cytochrome P450 3A4 in your liver or stopping a medicine that inhibits the activity of

cytochrome P450 3A4 in your liver, may reduce the concentration of Percocet in your

blood making the medicine less effective or causing withdrawal symptoms in a patient

who has developed a dependence on Percocet.

Percocet may cause adrenal insufficiency which may be a life-threatening condition. The

following may be signs of this: nausea, vomiting, lack of appetite, tiredness, weakness,

dizziness and low blood pressure. If you have these symptoms, you must get medical

help as soon as possible.

Opioid medicines tend to cause an increase in carbon dioxide concentration and the

pressure inside your skull may increase as a result. Previous pressure in the skull or

brain tumors may make the condition worse.

This medicine may make it difficult to diagnose worsening conditions or it may mask

worsening conditions in patients with head injuries. Do not use in patients in a stupor or

in a coma.

Paracetamol may cause liver damage and acute liver insufficiency; in some cases it may

cause the need for a liver transplant and death, when: given at a higher than the

recommended dose - when the maximum daily dose (4000 mg a day) is exceeded

and/or you take additional medicines that contain paracetamol. Do not use more than

one paracetamol product at the same time; given to patients with an undiagnosed liver

disease; drinking alcoholic beverages during the course of treatment; taking other

medicines that affect your liver function; the risk of acute liver insufficiency is higher in

patients with an existing liver disease.

To avoid a paracetamol overdose or poisoning, do not take additional fever and pain

relief medicines or cold medicines without consulting your doctor or pharmacist.

Do not take additional paracetamol medicines and/or additional products that contain

paracetamol.

Avoid taking other opioid pain relievers (such as: pentazocine, nalbuphine, butorphanol,

and buprenorphine) together with Percocet. Using these medicines together with

Percocet may reduce the pain-relief effect of Percocet and/or cause withdrawal

syndrome.

This medicine may cause a sharp drop in your blood pressure and you may

experience dizziness or fainting particularly when standing (orthostatic) and

when getting up suddenly from a reclining or sitting position. You are advised

to get up slowly to keep this effect to a minimum. This risk is higher in patients

who are less able to regulate their blood pressure, for example patients with a

low blood volume or after taking certain medicines that depress the central

nervous system, such as phenothiazines and anesthetics.

Use with caution in elderly, emaciated, or weak patients, because these

populations are at a greater risk of life-threatening respiratory depression.

This medicine may make it more difficult to make a diagnosis or it may mask

the clinical condition in patients with acute abdominal disorders.

This medicine may make spasms or seizures worse.

If you ever developed skin-related side effects as a result of taking medicines

that contain paracetamol, do not take medicines that contain paracetamol so

that you do not get severe skin effects again. In rare cases, paracetamol may

cause severe skin side effects such as exanthemous pustulosis (AGEP),

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)

Percocet PIL – final 06.2019

which can cause death. Stop using this medicine on the first appearance of a

rash or other sign of hypersensitivity.

There are reports of hypersensitivity, anaphylaxis, when using paracetamol.

Signs of this include: swelling of the face, mouth, throat, respiratory distress,

urticaria (hives), rash, itch and vomiting. There are rare reports of anaphylaxis

that required emergency treatment. If you experience any of these signs, stop

taking the medicine immediately and get medical attention.

Oxycodone and other opioid medicines cause reduced motility of the bowels

which may cause severe constipation.

Use this medicine with caution in patients who have pancreas or gall bladder

problems. Opioids may cause a rise in blood levels of the enzyme amylase.

Percocet may cause serotonin syndrome, which is a rare but life-threatening

syndrome, that happens as a result of using opioids together with serotonergic

medicines such as SNRI/SSRI (increase serotonin levels), TCAs, triptans, 5-

HT3 blockers, medicines that affect serotonin transmission in the nerves (such

as mirtazapine, trazodone, tramadol), monoamine oxidase inhibitors (MAOI)

(used to treat psychiatric disorders) and other substances such as linezolid

and methylene blue for infusion. Tell your doctor if you are using or plan to

use serotonergic medicines. If you develop signs of the syndrome, get medical

help immediately.

Using opioids and monoamine oxidase inhibitors (MAOI) such as phenelzine,

tranylcypromine and linezolid may cause serotonin syndrome or opioid toxicity

(such as respiratory depression or coma). Using Percocet is not

recommended in people using MAOI medicines or patients who have stopped

using MAOI medicines within the last 14 days.

Avoid taking high doses (within recommended limits) of this medicine while

fasting.

! Before using Percocet, tell your doctor if:

You have or have had in the past impaired function of your respiratory system or lungs

[such as asthma, hypoxia (lack of oxygen), hypercapnia (excess carbon dioxide),

respiratory depression, chronic obstructive pulmonary disease, cor pulmonale (enlarged

and failing right ventricle of the heart, usually as a result of a chronic lung disease)]

; you

have circulatory shock; you have or have had in the past impaired function of the heart

and/or blood vessels; you have or have had in the past impaired function of the liver or

kidney/urinary system or if you have problems passing urine; you have or have had in

the past impaired function of the thyroid (hypothyroidism)

; you have or have had in the

past a head injury, increased pressure in the skull or brain tumors; you have or have

ever had spasms; you have a biliary tract disease including acute inflammation of the

pancreas (pancreatitis)

; you have a depressed central nervous system; you have acute

alcoholism; you have or have ever had jaundice; you or a member of your family, are

experiencing or have experienced chemical substance abuse (including drug or alcohol

addiction)

; you or a member of your family, have or have had in the past a mental

disease (such as depression)

; you have acute abdominal problems; you are sensitive to

any food or medicine; you are pregnant or breastfeeding.

!

Tests and follow-up

Paracetamol may cause false results in home glucose (sugar) tests.

Other medicines and Percocet

If you are taking or have recently taken other medicines, including nonprescription

medications and dietary supplements, tell your doctor or pharmacist. Particularly if you are

taking:

Percocet PIL – final 06.2019

Medicines that inhibit the liver enzyme cytochrome P450 3A4 and P450 2D6, such as:

erythromycin, ketoconazole and ritonavir (see section 'Special warnings regarding the use of

this medicine'); medicines that increase the activity of cytochrome P450 3A4 in the liver (for

example rifampicin, carbamazepine, phenytoin); nonsteroidal anti-inflammatory drugs (NSAIDs);

medicines that affect or depress the central nervous system [such as: other opioid pain

relievers, general anesthesia medicines, phenothiazines, sedatives, benzodiazepines, alcohol,

hypnotic medicines, anti-anxiety medicines, muscle relaxants, medicines for treating psychiatric

or mental disorders (see section 'Special warnings regarding the use of the medicine')];

medicines that affect serotonin levels, such as: SSRIs, SNRIs, tricyclic anti-depressants,

triptans, 5-HT3 receptor antagonists, other medicines that affect the serotonin system (such as:

mirtazapine, trazodone, tramadol), monoamine oxidase inhibitors (MAOI) intended for treating

psychiatric disorders and other monoamine oxidase inhibitors (such as: linezolid, intravenous

methylene blue, phenelzine, tranylcypromine). Using these medicines with opioids may cause

serotonin syndrome; tell your doctor if you have used MAOIs in the last 14 days. Using these

medicines with opioids may cause serotonin syndrome or opioid toxicity (respiratory depression,

coma); skeletal muscle relaxants. Using Percocet may increase the activity of skeletal muscle

relaxant medicines and make the respiratory depression worse; metoclopramide or

domperidone (for treating nausea, vomiting and other digestion problems), beta-blockers

(propranolol). Propranolol may increase the effect of the paracetamol; diuretics - opioids may

reduce the effectiveness of diuretic medicines; loop diuretics - paracetamol may reduce their

effect; cough and cold medicines; other opioids: pentazocine, nalbuphine and butorphanol - may

reduce the pain-relieving effect of Percocet or cause withdrawal symptoms; anticholinergic

medicines - using this medicine together with anticholinergic medicines may increase urinary

retention and/or severe constipation (may result in a blocked bowel); contraceptive pills - reduce

the half-life of paracetamol and assist with fast removal from the plasma; activated carbon -

reduces the absorption of paracetamol when taken immediately after an overdose; lamotrigine-

using Percocet may reduce the therapeutic effects of lamotrigine because its concentration in

the blood is reduced; probenecid (for treating gout) - may slightly increase the therapeutic

effectiveness of paracetamol; zidovudine - using Percocet may reduce the therapeutic effects of

zidovudine; anticoagulants, particularly warfarin; chloramphenicol (an antibiotic); cholestyramine

(for reducing excess fat in the blood).

Each of the components of Percocet (oxycodone and paracetamol) may affect the results of

early detection tests of cocaine or marijuana in the urine. More specific tests must be used to

confirm the presence of these substances in the body.

! Using this medicine and alcohol consumption:

Do not consume alcohol. Drinking alcohol while on this medicine may increase the risk of

damage to the liver. In addition, using this medicine together with alcohol may increase the

depressing effect on the central nervous system, sedation, respiratory depression and risk of

death.

! Pregnancy, breastfeeding and fertility:

Percocet may harm your unborn baby. If you are pregnant or are planning to become pregnant,

consult your doctor before using this medicine.

Opioids can pass to your unborn baby and may cause respiratory depression in your unborn

baby. In addition, opioids may cause dependence in your unborn baby. After birth, your

newborn may experience severe withdrawal symptoms which can be life-threatening. Signs of

withdrawal symptoms in newborns include irritability, hyperactivity and irregular sleeping

patterns, shrill crying, chills, vomiting, diarrhea and not gaining weight. The emergence, duration

and severity of withdrawal symptoms in your newborn depend on the type of opioid used, how

long it was used, at what times, what amounts the mother used lately, and how fast the newborn

is able to break down the substance.

Percocet PIL – final 06.2019

Babies born to mothers who are opioid-dependent will also develop dependence and may

experience difficulty breathing and signs of withdrawal.

Percocet is not recommended to women during labor and just before they deliver the baby

because of possible respiratory depression in the newborn. Opioid pain-relievers, including

Percocet, may extend the duration of labor because the strength, duration and frequency of

contractions are reduced. However, this is not a consistent effect, and Percocet may also

shorten labor.

Usually, you are not allowed to breastfeed while using this medicine because of its sedative

effect and its depressive effect on breathing in your newborn.

Your doctor will weigh the benefits of breastfeeding, such as your baby’s development and

health, against the mother's needs and the drawbacks of side effects in babies who are

breastfed by mothers on Percocet. Oxycodone, one of the active ingredients in this medicine,

passes into breastmilk in small amounts and there have been rare reports of sleepiness,

tiredness and difficulty breathing in babies who were breastfed by women taking this medicine.

In addition, breastfed babies may experience withdrawal symptoms when their mother stops the

medicine or when their mother stops breastfeeding. Also paracetamol passes into breastmilk in

low concentrations.

Fertility - Chronic use of opioids may impair fertility. It is unknown if this impairment is reversible

or not.

! Driving and using machines:

Using this medicine may impair your alertness and the physical and mental abilities you need to

perform dangerous actions. So, exercise caution when driving a car, operating dangerous

machines and performing any other activity that requires alertness. When using Percocet

together with other benzodiazepines or with other central nervous system depressants, you are

advised to avoid driving and operating dangerous machines until the effects of taking these

medicines together have become clear.

! Use in children:

Efficacy and safety of use in children has not been tested.

! Use in the elderly:

Elderly patients (over 65) may be more sensitive to Percocet and its side effects; the greatest

risk is respiratory depression. Use with caution and according to the dose prescribed by your

doctor (you may need a lower dose). Your doctor will consider the concomitant effect of a

disease or medical treatment and the higher incidence of reduced liver, kidney, or heart function

in this population.

! Use in patients with impaired liver function:

Patients with impaired liver function will have their dose adjusted by their doctor (they may need

a lower dose) and will be monitored for side effects such as respiratory depression, sedation

and low blood pressure.

! Use in patients with impaired kidney function:

Patients with impaired kidney function will have their dose adjusted by their doctor (they may

need a lower dose) and will be monitored for side effects such as respiratory depression,

sedation and low blood pressure.

3. How to use this medicine?

Always use according to your doctor's instructions. Check with your doctor or pharmacist if you

are not sure about the dose and how to take this medicine. Only your doctor will determine

your dose and how you should take this medicine. The recommended dose is usually:

One tablet every six hours, as needed. Do not exceed 4 grams of paracetamol a day.

Maximum dose: Percocet 5: 12 tablets a day. Percocet 10: 6 tablets a day.

Patients with impaired liver or kidney function will have their dose adjusted by their doctor (they

may need a lower dose).

Percocet PIL – final 06.2019

Do not stop using Percocet abruptly after having used it for several weeks. Consult

your doctor about stopping this medicine gradually. Do not change your dose without

consulting your doctor.

Do not exceed the recommended dose.

Do not chew! To make it easier to swallow, you may, if necessary, split the tablet immediately

before you use it. Swallow both halves together, immediately after you have split the tablet.

Swallow the medicine with a large amount of water. Do not keep the medicine in your mouth

longer than the time it takes to swallow it.

If you have taken an overdose, or if a child has accidentally swallowed some medicine, go

immediately to a doctor or proceed to a hospital emergency room, even if you feel well. Bring

the medicine package with you. Signs of oxycodone overdose are: narrowed pupils, respiratory

depression, losing consciousness, extreme sleepiness which progresses to stupor or coma,

relaxed skeletal muscles, cold and moist skin, occasionally lung edema, slow heart rate

(bradycardia), low blood pressure, partial or complete blockage of the respiratory tract, unusual

snoring, and death. Other signs are widened pupils together with hypoxia (lack of oxygen).

Paracetamol overdose may lead to dose-dependent liver necrosis that may be life-threatening.

Kidney necrosis, coma due to low blood-sugar level, and coagulation problems may also occur.

Early signs of toxic injury in the liver are: nausea, vomiting, excessive sweating, and feeling

generally unwell. Clinical and laboratory signs of liver necrosis may appear only 48-72 hours

after taking the medicine.

If you forget to take this medicine at the scheduled time, take a dose as soon as you

remember, but never take two doses together!

Adhere to the treatment as recommended by the doctor.

Even if your health improves, do not stop taking this medicine without consulting your doctor or

pharmacist.

If you stop taking this medicine

Consult your doctor before you stop a long-duration high-dose treatment. Patients who have

been treated for several days to several weeks and do not need treatment any more must stop

taking this medicine gradually. Stopping this medicine abruptly or greatly reducing the dose may

cause withdrawal symptoms, including: restlessness, watering eyes, runny nose, yawning,

excessive sweating, chills, muscle pain and widened pupils, irritability, anxiety, back pain, joint

pain, weakness, stomach cramps, insomnia, nausea, anorexia, vomiting, diarrhea, increased

blood pressure, breathing rate, or heart rate. Withdrawal syndrome may also occur as a result of

using medicines that suppress opioid activity (such as naloxone, nalmefene) or other opioid pain

relievers that work differently (pentazocine, butorphanol, nalbuphine, buprenorphine).

Do not take medicines in the dark! Check the label and the dose each time you take a

medicine. Wear glasses if you need them. If you have any further questions about using

this medicine, consult your doctor or the pharmacist.

4. Side effects

Like all medicines, taking Percocet may cause side effects in some people. Do not be alarmed

by this list of side effects. You may not experience any of them.

Serious side effects:

Stop using this medicine and consult a doctor immediately if:

you experience temporary disruption of breathing (apnea)

; you experience respiratory arrest;

you experience circulatory depression; you develop serotonin syndrome while using this

medicine together with medicines that affect serotonin release (a condition that results from a

dangerous increase in serotonin levels in the body and which has the following signs: rise in

body temperature, fast heartbeat, chest pain, headache, altered mental state such as confusion,

involuntary movements, hallucinations, tremor, chills, feeling faint, sweating, nausea, diarrhea,

stiff muscles and difficulty walking)

; you have allergic reactions (such as: swelling of the face,

Percocet PIL – final 06.2019

lips, tongue, throat and/or limbs, respiratory distress or difficulty swallowing, hives, rash, itch

and vomiting), shortness of breath (anaphylactic reaction)

; in rare cases, paracetamol can

cause acute skin diseases. Signs of these may include: redness, rash, blisters, wide-spread

skin damage. Acute skin side effects may occur even if you have previously taken without issue

medicines that contain the active ingredient paracetamol. If you experience skin side effects,

stop the treatment and consult a doctor immediately; you experience signs of changes in your

circulatory blood system such as: bleeding, bruises, getting inflammations more easily because

you have fewer red blood cells, reduced number of neutrophils, reduced number of platelets and

reduced number of all blood cells. Rare cases have been reported of a sharp and dangerous

drop in leucocytes (agranulocytosis) when using paracetamol; you experience respiratory

depression; you experience reduced blood pressure; you experience shock; you have liver or

kidney necrosis or diabetes-related coma; you experience overdose side effects.

Additional side effects:

the most common reactions: dizziness, dozing or feeling calm, nausea and vomiting,

feeling euphoric or dysphoric, constipation and itch; endocrine reactions: lack of male

hormone

(androgen)

which

expressed

reduced

libido,

impotence,

absence

menstruation or infertility; general body reactions: anaphylactic reaction, allergic reaction,

feel unwell, exhaustion, tiredness, chest pain, fever, low body temperature (hypothermia),

thirst,

headache,

excessive

sweating,

overdose;

cardiovascular

reactions:

blood

pressure, high blood pressure, fast heart rate (tachycardia), orthostatic hypotension, slow

heart rate (bradycardia), palpitations, heart rhythm disorders (dysrhythmia

; nervous system

reactions: stupor, tremor, prickling (paresthesia), reduced sensitivity to touch, lethargy,

seizures, anxiety, mental disorder, agitation, brain edema, confusion, dizziness; reactions

related to fluids and electrolytes: dehydration, excess potassium in the blood, metabolic

ketoacidosis, respiratory alkalosis; digestive system reactions: indigestion, taste disorders,

stomachache,

swollen

stomach,

excessive

sweating,

diarrhea,

mouth,

flatulence,

digestive tract disorders, nausea, vomiting, inflammation of the pancreas, blocked bowel;

liver reactions: temporary increase in liver enzymes, increased bilirubin, liver inflammation,

liver failure, jaundice, liver toxicity, liver disorders; hearing and balance reactions: hearing

loss,

ringing

your

ears;

blood

vessel

reactions:

reduced

number

platelets

(thrombocytopenia), reduced number of white blood cells, red blood cells and platelets at

the same time (pancytopenia), reduced number of neutrophils (a type of white blood cells),

and hemolytic anemia. Rare cases of agranulocytosis (severe deficiency in white blood

cells) have been reported with paracetamol use; hypersensitivity reactions: acute allergic

reaction

(anaphylaxis),

fast

swelling

(edema)

skin

(angioedema),

asthma,

bronchospasm, throat edema, hives (urticaria), allergic reaction (anaphylactoid)

; metabolic

reactions: low blood sugar, high blood sugar, acidosis, alkalosis; skeleton and muscle

reactions:

muscle

pain,

muscle

cells

break

down

(rhabdomyolysis)

reactions:

contracted pupils, vision disorders, redness of the eye; psychiatrist reactions: medicine

dependence, medicine abuse, medicine tolerance, insomnia, confusion, anxiety, agitation,

reduced

consciousness,

irritability,

hallucinations,

sleepiness,

depression,

suicide;

respiratory system reactions: bronchospasm, shortness of breath, increased frequency and

depth of breathing, lung edema, rapid breathing, aspiration (inhaling) of foreign substances

(food, saliva, acids) into the respiratory tract, inadequate ventilation (hypoventilation),

throat edema; skin reactions: redness, hives, rash, flushing; urinary and genital reactions:

inflammation of the interstitial tissue (the tissue between the cells) in the kidneys, papillary

necrosis, protein in the urine, kidney insufficiency and kidney failure, urinary retention;

adrenal insufficiency; at high doses, dose-dependent liver necrosis may occur which can

be life-threatening. Necrosis of the kidney tubules and hypoglycemic coma may also occur.

If any side effect gets worse, or if you experience a side effect not mentioned in this

leaflet, consult your doctor.

Percocet PIL – final 06.2019

Reporting side effects

You can report side effects to the Ministry of Health by following the link ‘Reporting Side Effects

of Medication’ on the Ministry of Health home page (www.health.gov.il) which links to an online

form for reporting side effects or by following this link:

https://sideeffects.health.gov.il

5. How to store the medicine?

Prevent poisoning! To prevent poisoning, keep this and all other medicines, in a closed place

out of reach and sight of children and/or infants. Do not induce vomiting unless explicitly

instructed to do so by a doctor! Do not use the medicine after the expiry date (exp. date) stated

on the package. The expiry date refers to the last day of that month; store below 25˚C; when

you no longer need these tablets consult your pharmacist about how to dispose of them.

6. Additional information

In addition to the active ingredients this medicine also contains:

microcrystalline cellulose, pregelatinized starch, stearic acid, magnesium stearate, povidone.

Percocet 10 tablets also contain: color D&C yellow # 10.

What the medicine looks like and what are the contents of the package:

Percocet 5: Flat, round, white tablets with a score line on one side; packaged in blisters in a

carton. Each package contains 10, 20, or 1000 tablets.

Percocet 10: Flat, round, yellow tablets with a score line on one side; packaged in blisters in a

carton. Each package contains 10 or 20 tablets.

Not all package sizes are available.

Manufacturer and registration holder's name and address: Taro Pharmaceutical Industries

Ltd., 14 Hakitor St., Haifa Bay 2624761

Registration number of the medicine in the Ministry of Health National Drug Registry:

Percocet 5: 023 99 21468 Percocet 10: 139 21 31414

This leaflet was reviewed and approved by the Ministry of Health in November 2013 and revised

in June 2019 in accordance with Ministry of Health guidelines.

Percocet 5mg and 10 mg

Percocet Physician Leaflet final 06.2019

PERCOCET

®

Tablets

Rx only

Prescribing Information

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY

DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME,

CYTOCHROME P450 3A4 INTERACTION; HEPATOTOXICITY and RISKS FROM

CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS

Addiction, Abuse, and Misuse

PERCOCET exposes patients and other users to the risks of opioid addiction, abuse, and misuse,

which can lead to overdose and death. Assess each patient's risk prior to prescribing PERCOCET,

and monitor all patients regularly for the development of these behaviors and conditions [see

WARNINGS].

Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression may occur with use of PERCOCET. Monitor

for respiratory depression, especially during initiation of PERCOCET or following a dose increase

[see WARNINGS].

Accidental Ingestion

Accidental ingestion of PERCOCET, especially by children, can result in a fatal overdose of

PERCOCET [see WARNINGS].

Neonatal Opioid Withdrawal Syndrome

Prolonged use of PERCOCET during pregnancy can result in neonatal opioid withdrawal syndrome,

which may be life-threatening if not recognized and treated, and requires management according to

protocols developed by neonatology experts. If opioid use is required for a prolonged period in a

pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure

that appropriate treatment will be available [see WARNINGS].

Cytochrome P450 3A4 Interaction

The concomitant use of PERCOCET with all cytochrome P450 3A4 inhibitors may result in an

increase in oxycodone plasma concentrations, which could increase or prolong adverse reactions and

may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly

used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration.

Monitor patients receiving PERCOCET and any CYP3A4 inhibitor or inducer [see CLINICAL

PHARMACOLOGY, WARNINGS, PRECAUTIONS; Drug Interactions].

Hepatotoxicity

Paracetamol has been associated with cases of acute liver failure, at times resulting in liver transplant

and death. Most of the cases of liver injury are associated with the use of paracetamol at doses that

exceed 4000 mg per day, and often involve more than one paracetamol-containing product.

RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS

DEPRESSANTS

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants,

including alcohol, may result in profound sedation, respiratory depression, coma, and death [see

WARNINGS, PRECAUTIONS; Drug Interactions].

Reserve concomitant prescribing of PERCOCET and benzodiazepines or other CNS

depressants for use in patients for whom alternative treatment options are inadequate.

Limit dosages and durations to the minimum required.

Follow patients for signs and symptoms of respiratory depression and sedation.

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DESCRIPTION

Oxycodone hydrochloride and Paracetamol is available in tablets for oral administration.

Each tablet for oral administration, contains oxycodone hydrochloride and paracetamol in the following strengths:

PERCOCET-5

Oxycodone Hydrochloride

5 mg*

(*5 mg oxycodone hydrochloride is equivalent to 4.4815 mg of oxycodone.)

Paracetamol

325 mg

PERCOCET-10

Oxycodone Hydrochloride

10 mg*

(*10 mg oxycodone hydrochloride is equivalent to 8.9637 mg of oxycodone.)

Paracetamol

325 mg

All strengths of PERCOCET also contain the following inactive ingredients: microcrystalline cellulose, pregelatinized

starch, stearic acid, magnesium stearate, povidone. In addition, the 10 mg/325 mg strength contains D&C yellow No.

10 lake.

Oxycodone hydrochloride and Paracetamol tablets contain oxycodone, 14-hydroxydihydrocodeinone, a semisynthetic

opioid analgesic which occurs as a white to off-white fine crystalline powder. The molecular formula for oxycodone

hydrochloride is C

HCl and the molecular weight is 351.82. It is derived from the opium alkaloid, thebaine,

and may be represented by the following structural formula:

Oxycodone hydrochloride and Paracetamol tablets contain Paracetamol, 4’-hydroxyacetanilide, is a non-opiate, non-

salicylate analgesic and antipyretic which occurs as a white, odorless, crystalline powder. The molecular formula for

paracetamol is C

and the molecular weight is 151.17. It may be represented by the following structural

formula:

CLINICAL PHARMACOLOGY

Mechanism of Action

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Oxycodone is a full opioid agonist with relative selectivity for the mu-opioid receptor, although it can interact with

other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Like all full opioid

agonists, there is no ceiling effect for analgesia with oxycodone.

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.

The precise mechanism of the analgesic properties of paracetamol is not established but is thought to involve central

actions

Pharmacodynamics

Effects on the Central Nervous System

Oxycodone 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. Oxycodone 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. Therapeutic

doses of paracetamol have negligible effects on the cardiovascular or respiratory systems; however, toxic doses may

cause circulatory failure and rapid, shallow breathing.

Effects on the Gastrointestinal Tract and Other Smooth Muscle

Oxycodone causes a reduction in motility associated with an increase in smooth muscle tone in the antrum 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 opioid 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

Oxycodone 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 [see

ADVERSE REACTIONS

]. 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 symptoms as low libido, impotence, erectile dysfunction,

amenorrhea, or infertility. The causal role of opioids in the 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 [see

ADVERSE REACTIONS

Effects on the Immune System

Opioids have been shown to have a variety of effects on components of the immune system. The clinical significance

of these findings is unknown. Overall, the effects of opioids appear to be modestly immunosuppressive.

Concentration–Efficacy Relationships

The minimum effective analgesic concentration will vary widely among patients, especially among patients who have

been previously treated with potent agonist opioids. The minimum effective analgesic concentration of oxycodone for

any individual patient may increase over time due to an increase in pain, the development of a new pain syndrome,

and/or the development of analgesic tolerance [see

DOSAGE AND ADMINISTRATION

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Concentration–Adverse Reaction Relationships

There is a relationship between increasing oxycodone plasma concentration and increasing frequency of dose-related

opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression. In opioid-tolerant patients,

the situation may be altered by the development of tolerance to opioid-related adverse reactions [see

DOSAGE AND

ADMINISTRATION

Pharmacokinetics

Absorption and Distribution

The mean absolute oral bioavailability of oxycodone in cancer patients was reported to be about 87%. Oxycodone has

been shown to be 45% bound to human plasma proteins in vitro. The volume of distribution after intravenous

administration is 211.9 ±186.6 L.

Absorption of paracetamol is rapid and almost complete from the GI tract after oral administration. With overdosage,

absorption is complete in 4 hours. Paracetamol is relatively uniformly distributed throughout most body fluids.

Binding of the drug to plasma proteins is variable; only 20% to 50% may be bound at the concentrations encountered

during acute intoxication.

Metabolism and Elimination

Oxycodone

In humans, oxycodone is extensively metabolized to noroxycodone by means of CYP3A-mediated N-demethylation,

oxymorphone by means of CYP2D6-mediated O-demethylation, and their glucuronides [see

PRECAUTIONS; Drug

Interactions].

Paracetamol

Paracetamol is rapidly absorbed from the gastrointestinal tract and is distributed throughout most body tissues. A

small fraction (10-25%) of paracetamol is bound to plasma proteins. The plasma half-life is 1.25 to 3 hours, but may

be increased by liver damage and following over dosage. Elimination of paracetamol is principally by liver

metabolism (conjugation) and subsequent renal excretion of metabolites. Paracetamol is primarily metabolized in the

liver by first-order kinetics and involves three principal separate pathways: conjugation with glucuronide; conjugation

with sulfate; and oxidation via the cytochrome, P450-dependent, mixed-function oxidase enzyme pathway to form a

reactive

intermediate metabolite, which conjugates with glutathione and is then further metabolized to form cysteine

and mercapturic acid conjugates. The principal cytochrome P450 isoenzyme involved appears to be CYP2E1, with

CYP1A2 and CYP3A4 as additional pathways. Approximately 85% of an oral dose appears in the urine within 24

hours of administration, most as the glucuronide conjugate, with small amounts of other conjugates and unchanged

drug [see

OVERDOSAGE

] for toxicity information.

INDICATIONS AND USAGE

PERCOCET is indicated for the management of moderate to moderately severe pain.

CONTRAINDICATIONS

PERCOCET is contraindicated in patients with:

Significant respiratory depression (see

WARNINGS

Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment (see

WARNINGS

Known or suspected gastrointestinal obstruction, including paralytic ileus (see

WARNINGS

Hypersensitivity to oxycodone, paracetamol, or any other component of the product listed in section 'Description'

(e.g., anaphylaxis) [see

WARNINGS

WARNINGS

Addiction, Abuse, and Misuse

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PERCOCET contains Oxycodone, a schedule II controlled substance. As an opioid, PERCOCET exposes users to the

risks of addiction, abuse, and misuse (see

DRUG ABUSE AND DEPENDENCE

Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed

PERCOCET. Addiction can occur at recommended dosages and if the drug is misused or abused.

Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing PERCOCET, and monitor all

patients receiving PERCOCET for the development of these behaviors and conditions. Risks are increased in patients

with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness

(e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in

any given patient. Patients at increased risk may be prescribed opioids such as PERCOCET, but use in such patients

necessitates intensive counseling about the risks and proper use of PERCOCET along with intensive monitoring for

signs of addiction, abuse, and misuse.

Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.

Consider these risks when prescribing or dispensing PERCOCET. Strategies to reduce these risks include prescribing

the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see

PRECAUTIONS; Information for Patients/Caregivers

Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as

recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and

death. Management of respiratory depression may include close observation, supportive measures, and use of opioid

antagonists, depending on the patient’s clinical status (see

OVERDOSAGE

). Carbon dioxide (CO

) retention from

opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of PERCOCET, the

risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory

depression, especially within the first 24 to 72 hours of initiating therapy with and following dosage increases of

PERCOCET.

To reduce the risk of respiratory depression, proper dosing and titration of PERCOCET are essential (see

DOSAGE

AND ADMINISTRATION

). Overestimating the PERCOCET dosage when converting patients from another opioid

product can result in a fatal overdose with the first dose.

Accidental ingestion of PERCOCET, especially by children, can result in respiratory depression and death due to an

overdose of PERCOCET.

Neonatal Opioid Withdrawal Syndrome

Prolonged use of PERCOCET during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal

syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and

requires management according to protocols developed by neonatology experts.

Observe newborns for signs of

neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a

prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be

available (see

PRECAUTIONS; Information for Patients/Caregivers , Pregnancy

Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers

Concomitant use of PERCOCET with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-

antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of

oxycodone hydrochloride and prolong opioid adverse reactions, which may cause potentially fatal respiratory

depression (see

WARNINGS

), particularly when an inhibitor is added after a stable dose of PERCOCET is achieved.

Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in PERCOCET-

treated patients may increase oxycodone plasma concentrations and prolong opioid adverse reactions. When using

PERCOCET with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in PERCOCET-treated patients, monitor

patients closely at frequent intervals and consider dosage reduction of PERCOCET until stable drug effects are

achieved (see

PRECAUTIONS; Drug Interactions

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Concomitant use of PERCOCET with CYP3A4 inducers or discontinuation of an CYP3A4 inhibitor could decrease

oxycodone hydrochloride plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome

in a patient who had developed physical dependence to oxycodone hydrochloride. When using PERCOCET with

CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider

increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur (see

PRECAUTIONS; Drug Interactions

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of PERCOCET 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.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the

risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological

properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid

analgesics (see

PRECAUTIONS; Drug Interactions

If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic,

prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an

opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the

absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already

taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate

based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.

Advise both patients and caregivers about the risks of respiratory depression and sedation when PERCOCET is used

with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or

operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have

been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn

them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and

illicit drugs.

Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic,

or Debilitated Patients

The use of PERCOCET in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence

of resuscitative equipment is contraindicated.

Patients with Chronic Pulmonary Disease:

PERCOCET-treated patients with significant chronic obstructive

pulmonary disease or cor pulmonale, and those with a 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 of PERCOCET (see

WARNINGS; Life Threatening Respiratory

Depression

Elderly, Cachetic, or Debilitated Patients:

Life-threatening respiratory depression is more likely to occur in elderly,

cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to

younger, healthier patients (see

WARNINGS; Life Threatening Respiratory Depression

Monitor such patients closely, particularly when initiating and titrating PERCOCET and when PERCOCET is given

concomitantly with other drugs that depress respiration (see

WARNINGS; Life Threatening Respiratory

Depression

). Alternatively, consider the use of non-opioid analgesics in these patients.

Adrenal Insufficiency

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of

use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting,

anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the

diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic

replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and

continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported

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use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any

particular opioids as being more likely to be associated with adrenal insufficiency.

Severe Hypotension

PERCOCET may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients

There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a

reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g. phenothiazines or general

anesthetics) [see

PRECAUTIONS;

Drug Interactions

]. Monitor these patients for signs of hypotension after

initiating or titrating the dosage of PERCOCET.

In patients with circulatory shock PERCOCET may cause

vasodilatation that can further reduce cardiac output and blood pressure. Avoid the use of PERCOCET with

circulatory shock.

Hepatotoxicity

Paracetamol has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most

of the cases of liver injury are associated with the use of paracetamol at doses that exceed 4000 milligrams per day,

and often involve more than one paracetamol-containing product. The excessive intake of paracetamol may be

intentional to cause self-harm or unintentional as patients attempt to obtain more pain relief or unknowingly take other

paracetamol-containing products.

The risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest

alcohol or additional medications which affect hepatic function while taking paracetamol.

Instruct patients to look for paracetamol or APAP on package labels and not to use more than one product that

contains paracetamol. Instruct patients to seek medical attention immediately upon ingestion of more than 4000

milligrams of paracetamol per day, even if they feel well.

Serious Skin Reactions

Rarely, paracetamol may cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP),

Stevens Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Patients should be

informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance

of skin rash or any other sign of hypersensitivity.

Hypersensitivity / Anaphylaxis

There have been post-marketing reports of hypersensitivity and anaphylaxis associated with use of paracetamol.

Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, pruritus, and

vomiting. There were infrequent reports of life-threatening anaphylaxis requiring emergency medical attention.

Instruct patients to discontinue PERCOCET immediately and seek medical care if they experience these symptoms.

Do not prescribe PERCOCET for patients with paracetamol allergy [see

PRECAUTIONS; Information for Patients

/Caregivers

Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired

Consciousness

In patients who may be susceptible to the intracranial effects of CO

retention (e.g., those with evidence of increased

intracranial pressure or brain tumors), PERCOCET may reduce respiratory drive, and the resultant CO

retention can

further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression,

particularly when initiating therapy with PERCOCET.

Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of PERCOCET in patients

with impaired consciousness or coma.

Risks of Use in Patients with Gastrointestinal Conditions

PERCOCET is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic

ileus.

The administration of PERCOCET, or other opioids may obscure the diagnosis or clinical course in patients with

acute abdominal conditions.

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The oxycodone in PERCOCET may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum

amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

Increased Risk of Seizures in Patients with Seizure Disorders

The oxycodone in PERCOCET may increase the frequency of seizures in patients with seizure disorders, and may

increase the risk of seizures occuring in other clinical settings associated with seizures. Monitor patients with a history

of seizure disorders for worsened seizure control during PERCOCET therapy.

Withdrawal

Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g.,

buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including PERCOCET. In

these patients, mixed agonist/antagonist and partial analgesics may reduce the analgesic effect and/or precipitate

withdrawal symptoms.

When discontinuing PERCOCET, gradually taper the dosage [see

DOSAGE AND ADMINISTRATION

]. Do not

abruptly discontinue PERCOCET [see

DRUG ABUSE AND DEPENDENCE

Risks of Driving and Operating Machinery

PERCOCET may impair the mental or physical abilities needed to perform potentially hazardous activities such as

driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are

tolerant to the effects of PERCOCET and know how they will react to the medication [see

PRECAUTIONS;

Information for Patients /Caregivers

.

PRECAUTIONS

Information for Patients/Caregivers

Advise the patient to read the patient labeling (Patient Information Leaflet).

Addiction, Abuse, and Misuse

Inform patients that the use of PERCOCET, even when taken as recommended, can result in addiction, abuse, and

misuse, which can lead to overdose and death (see

WARNINGS

). Instruct patients not to share PERCOCET with

others and to take steps to protect PERCOCET from theft or misuse.

Life-Threatening Respiratory Depression

Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest

when starting PERCOCET or when the dosage is increased, and that it can occur even at recommended dosages (see

WARNINGS

). Advise patients how to recognize respiratory depression and to seek medical attention if breathing

difficulties develop.

Accidental Ingestion

Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death (see

WARNINGS

). Instruct patients to take steps to store PERCOCET securely. In the case of accidental ingestions,

emergency medical care should be sought immediately.

Interactions with Benzodiazepines and Other CNS Depressants

Inform patients and caregivers that potentially fatal additive effects may occur if PERCOCET are used with

benzodiazepines and other CNS depressants, including alcohol, and not to use these concomitantly unless supervised

by a health care provider (see

WARNINGS and PRECAUTIONS; Drug Interactions

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

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attention right away if symptoms develop. Instruct patients to inform their healthcare providers if they are taking, or

plan to take serotonergic medications (see

PRECAUTIONS; Drug Interactions

Monoamine Oxidase Inhibitor (MAOI) Interaction

Inform patients to avoid taking PERCOCET while using any drugs that inhibit monoamine oxidase. Patients should

not start MAOIs while taking PERCOCET Tablets [see

PRECAUTIONS; Drug Interactions

Adrenal Insufficiency

Inform patients that opioids could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal

insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue,

weakness, dizziness, and low blood pressure. Advise patients to seek medical attention if they experience a

constellation of these symptoms (see

WARNINGS

Important Administration Instructions

Instruct patients how to properly take PERCOCET [see

DOSAGE AND ADMINISTRATION, WARNINGS

Advise patients not to adjust the medication dose themselves and to consult with their healthcare provider prior to any

dosage adjustment. Advise patients who are treated with PERCOCET for more than a few weeks not to abruptly

discontinue the medication. Advise patients to consult with their physician for a gradual discontinuation dose schedule

to taper off the medication.

Maximum Daily Dose of Paracetamol

Inform patients to not take more than 4000 milligrams of paracetamol per day. Advise patients to call their prescriber

if they take more than the recommended dose.

Inform patients not to take high doses (in the recommended dose range) of paracetamol while fasting.

Hypotension

Inform patients that PERCOCET may cause orthostatic hypotension and syncope. Instruct patients how to recognize

symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g.,

sit or lie down, carefully rise from a sitting or lying position) [see

WARNINGS

Anaphylaxis

Inform patients that anaphylaxis have been reported with ingredients contained in PERCOCET. Advise patients how

to recognize such a reaction and when to seek medical attention [see

CONTRAINDICATIONS, ADVERSE

REACTIONS

Pregnancy

Neonatal Opioid Withdrawal Syndrome

Inform female patients of reproductive potential that prolonged use of PERCOCET during pregnancy can result in

neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated (see

WARNINGS,

PRECAUTIONS; Pregnancy

Embryo-Fetal Toxicity

Inform female patients of reproductive potential that PERCOCET can cause fetal harm and to inform the healthcare

provider of a known or suspected pregnancy (see

PRECAUTIONS; Pregnancy

Lactation

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Advise nursing mothers to monitor infants for increased sleepiness (more than usual), breathing difficulties, or

limpness. Instruct nursing mothers to seek immediate medical care if they notice these signs (see

PRECAUTIONS;

Nursing Mothers

Infertility

Inform patients that chronic use of opioids may cause reduced fertility. It is not known whether these effects on

fertility are reversible [see

ADVERSE REACTIONS

Driving or Operating Heavy Machinery

Inform patients that PERCOCET may impair the ability to perform potentially hazardous activities such as driving a

car or operating heavy machinery. Advise patients not to perform such tasks until they know how they will react to the

medication [see

PRECAUTIONS

Constipation

Advise patients of the potential for severe constipation, including management instructions and when to seek medical

attention [see

ADVERSE REACTIONS, CLINICAL PHARMACOLOGY

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 methoximetrimethylsilyl (MO-TMS) derivative.

Drug Interactions

Inhibitors of CYP3A4 and CYP2D6

The concomitant use of PERCOCET and CYP3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin),

azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), can increase the plasma

concentration of oxycodone, resulting in increased or prolonged opioid effects. These effects could be more

pronounced with concomitant use of PERCOCET and CYP3A4 and CYP2D6 inhibitors, particularly when an

inhibitor is added after a stable dose of PERCOCET is achieved (see

WARNINGS

After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the oxycodone plasma concentration will

decrease (see

CLINICAL PHARMACOLOGY

), resulting in decreased opioid efficacy or a withdrawal syndrome in

patients who had developed physical dependence to PERCOCET.

If concomitant use is necessary, consider dosage reduction of PERCOCET until stable drug effects are achieved.

Monitor patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued,

consider increasing the PERCOCET dosage until stable drug effects are achieved. Monitor for signs of opioid

withdrawal.

Inducer of CYP3A4

The concomitant use of PERCOCET and CYP3A4 inducers, such as rifampin, carbamazepine, and phenytoin, can

decrease the plasma concentration of oxycodone (see

CLINICAL PHARMACOLOGY

), resulting in decreased

efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to PERCOCET (see

WARNINGS

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After stopping a CYP3A4 inducer, as the effects of the inducer decline, the oxycodone plasma concentration will

increase (see

CLINICAL PHARMACOLOGY

), which could increase or prolong both the therapeutic effects and

adverse reactions, and may cause serious respiratory depression.

If concomitant use is necessary, consider increasing the PERCOCET dosage until stable drug effects are achieved.

Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider PERCOCET dosage reduction

and monitor for signs of respiratory depression.

Benzodiazepines and Other CNS Depressants

Due to additive pharmacologic effect, the concomitant use of benzodiazepines and other CNS depressants such as

benzodiazepines and other sedative hypnotics, anxiolytics, and tranquilizers, muscle relaxants, general anesthetics,

antipsychotics, and other opioids, including alcohol, can increase the risk of hypotension, respiratory depression,

profound sedation, coma, and death.

Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are

inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory

depression and sedation (see

WARNINGS

Serotonergic Drugs

The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system, such as selective

serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic

antidepressants (TCAs), tryptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system

(e.g., mirtazapine, trazodone, tramadol), and monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric

disorders and also others, such as linezolid and intravenous methylene blue), has resulted in serotonin syndrome (see

PRECAUTIONS; Information for Patients/ Caregivers

If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose

adjustment. Discontinue PERCOCET if serotonin syndrome is suspected.

Monoamine Oxidase Inhibitors (MAOIs)

The concomitant use of opioids and MAOIs, such as phenelzine, tranylcypromine, linezolid, may manifest as

serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see

WARNINGS

The use of PERCOCET is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.

If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely

monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics

The concomitant use of opioids with other opioid analgesics, such as butorphanol, nalbuphine, pentazocine, may

reduce the analgesic effect of PERCOCET and/or precipitate withdrawal symptoms.

Advise patient to avoid concomitant use of these drugs.

Muscle Relaxants

PERCOCET may enhance the neuromuscular-blocking action of skeletal muscle relaxants and produce an increase in

the degree of respiratory depression.

If concomitant use is warranted, monitor patients for signs of respiratory depression that may be greater than

otherwise expected and decrease the dosage of PERCOCET and/or the muscle relaxant as necessary.

Diuretics

Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.

If concomitant use is warranted, monitor patients for signs of diminished diuresis and/or effects on blood pressure and

increase the dosage of the diuretic as needed.

Anticholinergic Drugs

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The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which

may lead to paralytic ileus.

If concomitant use is warranted, monitor patients for signs of urinary retention or reduced gastric motility when

PERCOCET is used concomitantly with anticholinergic drugs.

Alcohol, ethyl

Hepatotoxicity has occurred in chronic alcoholics following various dose levels (moderate to excessive) of

paracetamol.

Oral Contraceptives

Increase in glucuronidation resulting in increased plasma clearance and a decreased half-life of paracetamol.

Charcoal (activated)

Reduces paracetamol absorption when administered as soon as possible after overdose.

Beta Blockers (Propranolol)

Propranolol appears to inhibit the enzyme systems responsible for the glucuronidation and oxidation of paracetamol.

Therefore, the pharmacologic effects of paracetamol may be increased.

Loop Diuretics

The effects of the loop diuretic may be decreased because paracetamol may decrease renal prostaglandin excretion and

decrease plasma renin activity.

Lamotrigine

Serum lamotrigine concentrations may be reduced, producing a decrease in therapeutic effects.

Probenecid

Probenecid may increase the therapeutic effectiveness of paracetamol slightly.

Zidovudine

The pharmacologic effects of zidovudine may be decreased because of enhanced non-hepatic or renal clearance of

zidovudine.

Additional interactions: NSAIDs, anticoagulants (especially warfarin), chloramphenicol, cholestyramine

Drug/Laboratory Test Interactions

Depending on the sensitivity/specificity and the test methodology, the individual components of PERCOCET 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.

Paracetamol may interfere with home blood glucose measurement systems; decreases of >20% in mean glucose values

may be noted. This effect appears to be drug, concentration and system dependent.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

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Long-term studies to evaluate the carcinogenic potential of the combination of Oxycodone Hydrochloride and

Paracetamol have not been conducted.

Long-term studies in mice and rats have been completed by the National Toxicology Program to evaluate the

carcinogenic potential of paracetamol. In 2-year feeding studies, F344/N rats and B6C3F1 mice were fed a diet

containing paracetamol up to 6000 ppm. Female rats demonstrated equivocal evidence of carcinogenic activity based

on increased incidences of mononuclear cell leukemia at 0.8 times the maximum human daily dose (MHDD) of 4

grams/day, based on a body surface area comparison. In contrast, there was no evidence of carcinogenic activity in

male rats that received up to 0.7 times or mice at up to 1.2-1.4 times the MHDD, based on a body surface area

comparison.

Mutagenesis

The combination of Oxycodone Hydrochloride and Paracetamol 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.

In the published literature, paracetamol has been reported to be clastogenic when administered at 1500 mg/kg/day to

the rat model (3.6-times the MHDD, based on a body surface area comparison). In contrast, no clastogenicity was

noted at a dose of 750 mg/kg/day (1.8-times the MHDD, based on a body surface area comparison), suggesting a

threshold effect.

Impairment of Fertility

In studies conducted by the National Toxicology Program, fertility assessments with paracetamol have been

completed in Swiss CD-1 mice via a continuous breeding study. There were no effects on fertility parameters in mice

consuming up to 1.7 times the MHDD of paracetamol, based on a body surface area comparison. Although there was

no effect on sperm motility or sperm density in the epididymis, there was a significant increase in the percentage of

abnormal sperm in mice consuming 1.78 times the MHDD (based on a body surface comparison) and there was a

reduction in the number of mating pairs producing a fifth litter at this dose, suggesting the potential for cumulative

toxicity with chronic administration of paracetamol near the upper limit of daily dosing.

Published studies in rodents report that oral paracetamol treatment of male animals at doses that are 1.2 times the

MHDD and greater (based on a body surface comparison) result in decreased testicular weights, reduced

spermatogenesis, reduced fertility, and reduced implantation sites in females given the same doses. These effects

appear to increase with the duration of treatment. The clinical significance of these findings is not known.

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 (see

ADVERSE REACTIONS

Pregnancy

Teratogenic Effects

Pregnancy Category C

Animal reproductive studies have not been conducted with PERCOCET. It is also not known whether PERCOCET

can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. PERCOCET should

not be given to a pregnant woman unless in the judgment of the physician, the potential benefits outweigh the possible

hazards.

Nonteratogenic Effects

Fetal/Neonatal Adverse Reactions

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.

Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched

cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid

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withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use,

and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal

syndrome and manage accordingly (see

WARNINGS

Labor or Delivery

Opioids cross the 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 the

neonate. PERCOCET is not recommended for use in pregnant women during or immediately prior to labor, when

other analgesic techniques are more appropriate. Opioid analgesics, including PERCOCET, can prolong labor through

actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is

not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor

neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.

Nursing Mothers

Ordinarily, nursing should not be undertaken while a patient is receiving PERCOCET 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/paracetamol product. Paracetamol is also excreted in breast milk in low concentrations.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for

PERCOCET and any potential adverse effects on the breastfed infant from PERCOCET or from the underlying

maternal condition.

Infants exposed to PERCOCET through breast milk should be monitored 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.

Pediatric Use

Safety and effectiveness of PERCOCET in pediatric patients have not been established.

Geriatric Use

Elderly patients (aged 65 years or older) may have increased sensitivity PERCOCET. 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 PERCOCET slowly in geriatric patients and monitor closely for

signs of central nervous system and respiratory depression (see

WARNINGS

These drugs are known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be

greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal

function, care should be taken in dose selection, and it may be useful to monitor renal function.

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.

Because oxycodone is extensively metabolized in the liver, its clearance may decrease in patients with hepatic

impairment. Initiate therapy in these patients with a lower than usual dosage of PERCOCET and titrate carefully.

Monitor closely for adverse events such as respiratory depression, sedation, and hypotension [see

CLINICAL

PHARMACOLOGY

Renal Impairment

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In a study of patients with end stage renal impairment, mean elimination half-life 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.

Because oxycodone is known to be substantially excreted by the kidney, its clearance may decrease in patients with

renal impairment. Initiate therapy with a lower than usual dosage of PERCOCET and titrate carefully. Monitor closely

for adverse events such as respiratory depression, sedation, and hypotension [see

CLINICAL PHARMACOLOGY

ADVERSE REACTIONS

The following adverse reactions have been identified during post approval use of PERCOCET.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to

reliably estimate their frequency or establish a causal relationship to drug exposure.

Serious adverse reactions that may be associated with oxycodone and paracetamol use include respiratory depression,

apnea, respiratory arrest, circulatory depression, hypotension and shock (see

OVERDOSAGE

The most frequently observed non-serious adverse reactions include lightheadedness, dizziness, drowsiness or

sedation, nausea, and vomiting. These effects seem to be more prominent in ambulatory than in nonambulatory

patients, and some of these adverse reactions may be alleviated if the patient lies down. Other adverse reactions

include euphoria, dysphoria, constipation and pruritus.

Hypersensitivity reactions may include: Skin eruptions, urticarial, erythematous skin reactions.

Hematologic reactions may include: thrombocytopenia, neutropenia, pancytopenia, hemolytic anemia. Rare cases of

agranulocytosis have likewise been associated with paracetamol use. In high doses, the most serious adverse effect is a

dose-dependent, potentially fatal hepatic necrosis. Renal tubular necrosis and hypoglycemic coma also may occur.

Other adverse reactions obtained from postmarketing experiences with oxycodone and paracetamol are listed by organ

system and in decreasing order of severity and/or frequency as follows:

Body as a Whole

Anaphylactoid reaction, allergic reaction, malaise, asthenia, fatigue, chest pain, fever, hypothermia, thirst, headache,

increased sweating, accidental overdose, non-accidental overdose

Cardiovascular

Hypotension, hypertension, tachycardia, orthostatic hypotension, bradycardia, palpitations, dysrhythmias

Central and Peripheral Nervous System

Stupor, tremor, paraesthesia, hypoaesthesia, lethargy, seizures, anxiety, mental impairment, agitation, cerebral edema,

confusion, dizziness

Fluid and Electrolyte

Dehydration, hyperkalemia, metabolic acidosis, respiratory alkalosis

Gastrointestinal

Dyspepsia, taste disturbances, abdominal pain, abdominal distention, sweating increased, diarrhea, dry mouth,

flatulence, gastrointestinal disorder, nausea, vomiting, pancreatitis, intestinal obstruction, ileus

Hepatic

Transient elevations of hepatic enzymes, increase in bilirubin, hepatitis, hepatic failure, jaundice, hepatotoxicity,

hepatic disorder

Hearing and Vestibular

Hearing loss, tinnitus

Hematologic

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Thrombocytopenia

Hypersensitivity

Acute anaphylaxis, angioedema, asthma, bronchospasm, laryngeal edema, urticaria, anaphylactoid reaction

Metabolic and Nutritional

Hypoglycemia, hyperglycemia, acidosis, alkalosis

Musculoskeletal

Myalgia, rhabdomyolysis

Ocular

Miosis, visual disturbances, red eye

Psychiatric

Drug dependence, drug abuse, insomnia, confusion, anxiety, agitation, depressed level of consciousness, nervousness,

hallucination, somnolence, depression, suicide

Respiratory System

Bronchospasm, dyspnea, hyperpnea, pulmonary edema, tachypnea, aspiration, hypoventilation, laryngeal edema

Skin and Appendages

Erythema, urticaria, rash, flushing

Urogenital

Interstitial nephritis, papillary necrosis, proteinuria, renal insufficiency and failure, urinary retention

Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported

during concomitant use of opioids with serotonergic drugs.

Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often

following greater than one month of use.

Anaphylaxis: Anaphylaxis has been reported with ingredients contained in PERCOCET.

Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see

CLINICAL PHARMACOLOGY

DRUG ABUSE AND DEPENDENCE

Abuse

PERCOCET contains oxycodone, a substance with a high potential for abuse similar to other opioids including

fentanyl, hydrocodone, hydromorphone, methadone, morphine oxymorphone, and tapentadol. PERCOCET can be

abused and is subject to misuse, addiction, and criminal diversion (see

WARNINGS

All patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid

analgesic products carries the risk of addiction even under appropriate medical use.

Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding

psychological or physiological effects.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated

substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use

despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased

tolerance, and sometimes a physical withdrawal.

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“Drug-seeking” behavior is very common in persons with substance use disorders. 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 health care provider(s). “Doctor shopping” (visiting multiple prescribers to

obtain additional prescriptions) to obtain additional prescriptions is common among drug abusers and people suffering

from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient

with poor pain control.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Health care providers 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.

PERCOCET like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful

record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state

and federal law, 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.

Risks Specific to Abuse of PERCOCET

PERCOCET is for oral use only. Abuse of PERCOCET poses a risk of overdose and death.

The risk is increased with

concurrent abuse of PERCOCET with alcohol and other central nervous system depressants.

Paracetamol has been associated with cases of acute liver failure, at times resulting in liver transplant and death.

Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

Dependence

Both tolerance and physical dependence can develop during chronic opioid therapy. 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). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at

different rates for different effects.

Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of

a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g.,

naloxone, nalmefene), mixed agonist/antagonist analgesics (pentazocine, butorphanol, nalbuphine), or partial agonists

(buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks

of continued opioid usage.

PERCOCET should not be abruptly discontinued in a physically-dependent patient (see

DOSAGE AND

ADMINISTRATION

). If PERCOCET is abruptly discontinued in a physically-dependent patient, a withdrawal

syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation,

rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and 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.

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory

difficulties and withdrawal signs (see

PRECAUTIONS; Pregnancy

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued

monitoring of the benefit/risk balance of the medicinal product.

Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by

using an online form:

https://sideeffects.health.gov.il

OVERDOSAGE

Following an acute overdosage, toxicity may result from the oxycodone or the paracetamol.

Clinical Presentation

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Acute overdosage with oxycodone can be manifested by respiratory depression, somnolence progressing to stupor or

coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema,

bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather

than miosis may be seen with hypoxia in overdose situations.

Paracetamol

Dose-dependent potentially fatal hepatic necrosis is the most serious adverse effect of paracetamol overdosage. Renal

tubular necrosis, hypoglycemic coma, and coagulation defects may also occur.

Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis, and general

malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion.

Treatment of Overdose

Oxycodone

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 antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid

overdose. For clinically significant respiratory or circulatory depression secondary to oxycodone overdose, administer

an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory

or circulatory depression secondary to oxycodone overdose.

Because the duration of opioid reversal is expected to be less than the duration of action of oxycodone in PERCOCET,

carefully monitor the patient until spontaneous respiration is reliably re-established. If the response to an opioid

antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s

prescribing information.

In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist

will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on

the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious

respiratory depression in the physically dependent patient, administration of the antagonist should be initiated with

care and by titration with smaller than usual doses of the antagonist.

Paracetamol

Gastric decontamination with activated charcoal should be administered just prior to N-acetylcysteine (NAC) to

decrease systemic absorption if paracetamol ingestion is known or suspected to have occurred within a few hours of

presentation. Serum paracetamol levels should be obtained immediately if the patient presents 4 hours or more after

ingestion to assess potential risk of hepatotoxicity; paracetamol levels drawn less than 4 hours post-ingestion may be

misleading. To obtain the best possible outcome, NAC should be administered as soon as possible where impending

or evolving liver injury is suspected. Intravenous NAC may be administered when circumstances preclude oral

administration.

Vigorous supportive therapy is required in severe intoxication. Procedures to limit the continuing absorption of the

drug must be readily performed since the hepatic injury is dose dependent and occurs early in the course of

intoxication.

DOSAGE AND ADMINISTRATION

Important Dosage and Administration Instructions

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see

WARNINGS

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Initiate the dosing regimen for each patient individually; taking into account the patient's severity of pain, patient

response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse (see

WARNINGS

Monitor patients closely for respiratory depression, especially within the first 24- to 72 hours of initiating therapy and

following dosage increases with PERCOCET and adjust the dosage accordingly (see

WARNINGS

PERCOCET 5; PERCOCET 10

The usual adult dosage is one tablet every 6 hours as needed for pain. The total daily dose of paracetamol should not

exceed 4 grams.

Strength

Usual Adult Dosage

Maximal Daily Dose

Percocet 5 mg

1 tablet every 6 hours as needed for

pain

12 Tablets

Percocet 10 mg

1 tablet every 6 hours as needed for

pain

6 Tablets

Conversion from Oxycodone Hydrochloride and Paracetamol to Extended-Release Oxycodone

The relative bioavailability of Oxycodone Hydrochloride and Paracetamol Tablets or Oral Solution compared to

extended-release oxycodone is unknown, so conversion to extended-release oxycodone must be accompanied by close

observation for signs of excessive sedation and respiratory depression.

Titration and Maintenance of Therapy

Individually titrate PERCOCET to a dose that provides adequate analgesia and minimizes adverse reactions.

Continually reevaluate patients receiving PERCOCET to assess the maintenance of pain control and the relative

incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse (see

WARNINGS

). Frequent communication is important among the prescriber, other members of the healthcare team, the

patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration.

If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before

increasing the PERCOCET dosage. If unacceptable opioid-related adverse reactions are observed, consider reducing

the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related

adverse reactions.

Discontinuation of Oxycodone Hydrochloride and Paracetamol Tablets and Oral Solution

When a patient who has been taking Oxycodone Hydrochloride and Paracetamol Tablets or Oral Solution regularly

and may be physically dependent no longer requires therapy with Oxycodone Hydrochloride and Paracetamol Tablets

or Oral Solution, use a gradual downward titration of the dosage to prevent signs and symptoms of withdrawal. Do not

stop Oxycodone Hydrochloride and Paracetamol Tablets or Oral Solution abruptly (see

WARNINGS, DRUG

ABUSE AND DEPENDENCE

HOW SUPPLIED

PERCOCET (Oxycodone and Paracetamol Tablets) are supplied as follows:

Percocet-5:

White, round, flat tablets scored on one side.

Blisters of 10 & 20 tablets

Percocet-10:

Yellow, round, flat tablets scored on one side.

Blisters of 10, 20, 1000 tablets

Not all packs may be marketed

STORAGE:

Store below 25°C.

MANUFACTURER:

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Taro Pharmaceutical Industries Ltd., 14 Hakitor St., Haifa Bay 2624761

The content of this leaflet was approved by the Ministry of Health in November 2013 and updated according to the

guidelines of the Ministry of Health in June 2019.