Knee Problem? Assess your knee pain and find relief.

Opioid (Narcotic Analgesics and Aspirin Systemic )

This monograph includes information on the following:

1) Aspirin and Codeine
2) Aspirin and Codeine, Buffered
3) Aspirin and Dihydrocodeine 
4) Hydrocodone and Aspirin 
5) Oxycodone and Aspirin
6) Pentazocine and Aspirin 
7) Propoxyphene and Aspirin

Pharmacy Equivalent Name (PEN):
Aspirin and Codeine
Co-codaprin

INN:
Propoxyphene— Dextropropoxyphene

VA CLASSIFICATION
Primary: CN101

Note: Controlled substance classification—

Note: Controlled substances in the U.S. and Canada as follows:



Drug
U.S.
Canada
Aspirin and Codeine
III
N
Aspirin and Codeine, Buffered
III
N
Aspirin and Dihydrocodeine
III
**
 
Hydrocodone and Aspirin
III
**
 
Oxycodone and Aspirin
II
N
Pentazocine and Aspirin
IV
**
 
Propoxyphene and Aspirin
IV
N
** Not available in Canada.
Commonly used brand name(s): 2221; 2821; 2921; 6927; Anacin with Codeine1; C2 Buffered with Codeine2; C2 with Codeine1; Damason-P4; Darvon Compound-657; Darvon-N Compound7; Darvon-N with A.S.A.7; Empirin with Codeine No.31; Empirin with Codeine No.41; Endodan5; Lortab ASA4; Novo-AC and C1; Oxycodan5; PC-Cap7; Panasal 5/5004; Percodan5; Percodan-Demi5; Propoxyphene Compound-657; Roxiprin5; Synalgos-DC3; Talwin Compound6.

Other commonly used names are:
A.C.&C —ASA, Codeine, and Caffeine
AC and C — ASA, Codeine, and Caffeine
Dihydrocodeine Compound — Aspirin and Dihydrocodeine
Drocode and aspirin —Aspirin and Dihydrocodeine
Propoxyphene Hydrochloride Compound — Propoxyphene, Aspirin, and Caffeine

  Aspirin is a brand name in Canada; acetylsalicylic acid is the generic name. ASA, a commonly used designation for aspirin (or acetylsalicylic acid) in both the U.S. and Canada, is the term used in Canadian product labeling.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.



Category:


Analgesic—
Note: Opioid agonist analgesics—Codeine, dihydrocodeine, hydrocodone, oxycodone, and propoxyphene.
Opioid agonist/antagonist analgesic—Pentazocine.



Indications

Accepted

Pain (treatment)—Indicated for symptomatic relief of
Mild to severe pain (depending on the dose of codeine)—Aspirin and codeine; buffered aspirin and codeine.

Mild to moderate pain—Propoxyphene and aspirin.

Moderate pain—Pentazocine and aspirin.

Moderate to moderately severe pain—Aspirin and dihydrocodeine; oxycodone and aspirin.

Moderate to severe pain—Hydrocodone and aspirin.


Pharmacology/Pharmacokinetics

Aspirin—See Salicylates (Systemic) .

Caffeine—See Caffeine (Systemic) .

Codeine—See Opioid (Narcotic) Analgesics (Systemic) .

Dihydrocodeine—Although dihydrocodeine is not specifically referenced, see Opioid (Narcotic) Analgesics (Systemic) for the proposed mechanism of action for opioid agonist analgesics.

Hydrocodone—See Opioid (Narcotic) Analgesics (Systemic) .

Oxycodone—See Opioid (Narcotic) Analgesics (Systemic) .

Pentazocine—See Opioid (Narcotic) Analgesics (Systemic) .

Propoxyphene—See Opioid (Narcotic) Analgesics (Systemic) .


Precautions to Consider

Aspirin—See Salicylates (Systemic) .

Caffeine—See Caffeine (Systemic) .

Codeine—See Opioid (Narcotic) Analgesics (Systemic) .

Dihydrocodeine—Although dihydrocodeine is not specifically referenced, see Opioid (Narcotic) Analgesics (Systemic) for precautions that may apply to all opioid agonist analgesics.

Hydrocodone—See Opioid (Narcotic) Analgesics (Systemic) .

Oxycodone—See Opioid (Narcotic) Analgesics (Systemic) .

Pentazocine—See Opioid (Narcotic) Analgesics (Systemic) .

Propoxyphene—See Opioid (Narcotic) Analgesics (Systemic) .


Side/Adverse Effects
Aspirin—See Salicylates (Systemic) .
Caffeine—See Caffeine (Systemic) .
Codeine—See Opioid (Narcotic) Analgesics (Systemic) .
Dihydrocodeine—Although dihydrocodeine is not specifically referenced, see Opioid (Narcotic) Analgesics (Systemic) for side/adverse effects that may occur with opioid agonist analgesics.
Hydrocodone—See Opioid (Narcotic) Analgesics (Systemic) .
Oxycodone—See Opioid (Narcotic) Analgesics (Systemic) .
Pentazocine—See Opioid (Narcotic) Analgesics (Systemic) .
Propoxyphene—See Opioid (Narcotic) Analgesics (Systemic) .



Overdose
For specific information on the agents used in the management of opioid (narcotic) analgesics and aspirin overdose, see:    • Naloxone (Systemic) monograph; and/or
   • Vitamin K (Systemic) monograph.


For more information on the managment of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Treatment of overdose


For aspirin:
To decrease absorption—Emptying the stomach via induction of emesis or gastric lavage.

Administering activated charcoal.

Specific treatment—Administering blood or Vitamin K 1 if necessary to treat hemorrhaging. See the package insert or Vitamin K (Systemic) for specific dosing guidelines for use of this product.

Monitoring—Monitoring serum salicylate concentration until it is apparent that the concentration is decreasing to the nontoxic range. Salicylate concentrations of 50 mg per 100 mL 2 hours after ingestion indicate serious toxicity; salicylate concentrations above 80 mg per 100 mL 2 hours after ingestion indicate possible fatality. In addition, prolonged monitoring may be necessary in massive overdosage because absorption may be delayed; if a determination performed prior to 6 hours after ingestion fails to show a toxic salicylate concentration, the determination should be repeated. Salicylate concentrations of 45 to 65 mg per 100 mL 6 hours after ingestion or 35 to 55 mg per 100 mL 12 hours after ingestion indicate a mild degree of toxicity; salicylate concentrations of 65 to 90 mg per 100 mL 6 hours after ingestion or 55 to 75 mg per 100 mL 12 hours after ingestion indicate a moderate degree of toxicity; and salicylate concentrations of 90 mg (or more) per 100 mL 6 hours after ingestion or 75 mg (or more) per 100 mL 12 hours after ingestion indicate a severe degree of toxicity.

Monitoring for pulmonary edema and instituting appropriate therapy if required.

To enhance elimination—Inducing forced alkaline diuresis to increase salicylate excretion. However, bicarbonate should not be administered orally for this purpose because salicylate absorption may be increased. Also, if acetazolamide is used, the increased risk of severe metabolic acidosis and salicylate toxicity (caused by increased penetration of salicylate into the brain because of metabolic acidosis) must be considered. Some emergency care practitioners recommend that acetazolamide not be used at all in the treatment of salicylate overdose. Others state that acetazolamide may be used, provided that precautions are taken to prevent systemic metabolic acidosis, such as concurrent administration of an alkaline intravenous solution, e.g., one that contains sodium bicarbonate or sodium lactate.

Institution of exchange transfusion, hemodialysis, peritoneal dialysis, or hemoperfusion as needed in severe overdose.

Supportive care—Correcting hyperthermia; fluid, electrolyte, and acid-base imbalances; ketosis; and plasma glucose concentration as needed. Monitoring and supporting vital functions. Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.



For opioid analgesics:
To decrease absorption—Emptying the stomach by induction of emesis or gastric lavage. However, treatment of respiratory depression or other potentially life-threatening adverse effects must take precedence.

Specific treatment—Administering the opioid antagonist naloxone. Larger doses of naloxone may be required to reverse the effects of pentazocine or propoxyphene than are required to antagonize the effects of other opioids. See the package insert or Naloxone (Systemic) for specific dosing guidelines for use of this product.

Monitoring—Continuing to monitor the patient (mandatory because the duration of action of the opioid analgesic may exceed that of naloxone) so that additional antagonist may be administered as needed. Alternatively, initial treatment may be followed by continuous intravenous infusion of naloxone, with the rate of infusion being adjusted according to patient response. The fact that naloxone may also antagonize the analgesic actions of opioid analgesics and may precipitate withdrawal symptoms in physically dependent patients must be kept in mind.

Supportive care—Establishing adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled respiration.

Administering intravenous fluids, vasopressors, and other supportive measures as needed. Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Narcotic Analgesics and Aspirin (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to the opioid considered for use, to aspirin, or to nonsteroidal anti-inflammatory drugs (NSAIDs), history of

Pregnancy—Aspirin and opioid analgesics cross the placenta; high-dose chronic use or abuse of aspirin in the third trimester may be hazardous to the mother as well as the fetus and/or neonate, causing heart problems in fetus or neonate and/or bleeding in mother, fetus, or neonate; high-dose chronic use or abuse may also prolong and complicate labor and delivery; also, regular use of opioids by pregnant women may cause physical dependence in the fetus and withdrawal symptoms in the neonate; not taking aspirin during the third trimester unless prescribed by physician





Breast-feeding—Aspirin, codeine, and propoxyphene are distributed into breast milk




Use in children and in teenagers——Checking with physician before giving to children or teenagers with symptoms of acute febrile illness, especially influenza or varicella, because of the risk of Reye's syndrome; also, increased susceptibility to aspirin toxicity in children, especially with fever and dehydration; also, children up to 2 years of age are more susceptible to the effects of opioids, especially respiratory depression; in addition, children may be more likely to experience opioid-induced paradoxical CNS excitation during therapy






Use in the elderly—Increased risk of aspirin toxicity and of opioid-induced adverse effects, especially respiratory depression
Other medications, especially alcohol or other CNS depressants, anticoagulants, antidiabetic agents (oral), those cephalosporins that may cause hypoprothrombinemia, methotrexate, monoamine oxidase inhibitors, naltrexone, nonsteroidal anti-inflammatory drugs (NSAIDs), platelet aggregation inhibitors, plicamycin, probenecid, sulfinpyrazone, urinary alkalizers, valproic acid, vancomycin, and zidovudine
Other medical problems, especially coagulation or platelet function disorders, diarrhea caused by antibiotics or poisoning, asthma or other respiratory problems, and gastrointestinal problems such as ulceration or erosive gastritis (especially a bleeding ulcer) or other severe inflammatory bowel disease

Proper use of this medication
» Taking with food or a full glass (240 mL) of water to minimize stomach irritation

» Not taking medication if it has a strong vinegar-like odor

» Importance of not taking more medication than the amount prescribed because of danger of overdose of aspirin or opioid analgesics and habit-forming potential of opioid analgesics

» Not increasing dose if medication seems less effective after a few weeks; checking with physician instead

» Proper dosing
Missed dose (if on scheduled dosing): Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
Regular visits to physician to check progress during long-term therapy

» Caution if other medications containing aspirin or other salicylates or opioid analgesics are used

» Avoiding use of alcohol or other central nervous system (CNS) depressants during therapy unless prescribed or otherwise approved by physician; also, alcohol consumption may increase risk of aspirin-induced stomach problems

Not taking acetaminophen or ibuprofen or other NSAIDs concurrently for more than a few days unless directed by physician or dentist

» Caution if dizziness, drowsiness, lightheadedness, or false sense of well-being occurs

Caution when getting up suddenly from a lying or sitting position

Lying down if nausea or vomiting, or dizziness or lightheadedness occurs

Need to inform physician or dentist of use of medication if any kind of surgery (including dental surgery) or emergency treatment is required

Caution if any kind of surgery is required; aspirin should be discontinued 5 days prior to surgery unless otherwise directed by physician or dentist

Checking with pharmacist before using the buffered formulation (available in Canada) with any other oral medication; antacids in the formulation may interfere with absorption of many oral medications

Diabetics: Aspirin may cause false urine sugar test results with prolonged use of 8 or more 325-mg (5-grain), or 4 or more 650-mg (10-grain), doses per day

Possible dryness of mouth; using sugarless gum or candy, ice, or saliva substitute for relief; checking with dentist if dry mouth continues for more than 2 weeks

» Checking with physician before discontinuing medication after prolonged use of high doses; gradual dosage reduction may be necessary to avoid withdrawal symptoms

» Suspected overdose: Getting emergency help at once


Side/adverse effects
Signs of potential side effects, especially respiratory depression or impairment; allergic reactions; confusion, convulsions, hallucinations, mental depression, or other signs of CNS toxicity; gastrointestinal toxicity; hepatotoxicity; hypertension, and paradoxical CNS excitation, especially in children


General Dosing Information
Medications containing aspirin should be administered with food or a full glass (240 mL) of water to lessen gastric irritation.

Opioid analgesics may depress respiration, especially in very young, elderly, very ill, or debilitated patients and those with respiratory problems. Lower doses may be required for these patients. However, elderly patients may also be more sensitive to the analgesic effects of these medications so that lower doses and/or a longer dosing interval may be sufficient to provide adequate analgesia.

Dosage of opioid analgesics should be individualized on the basis of the potency and duration of action of the specific agent used, the severity of pain, the condition of the patient, other medications given concurrently, and patient response.

Administration of aspirin concurrently with opioid analgesics provides additive analgesia and may permit lower doses of the opioid analgesic to be utilized.

Some clinicians recommend that patients in chronic severe pain receive opioid analgesics on a fixed dosage schedule in order that they remain free of pain rather than on an as needed basis after pain recurs.

Tolerance to many of the effects of opioid analgesics may develop with repeated administration. The first sign of tolerance is usually a decrease in the duration of effective analgesia. Patients who become tolerant to one of these agents may be partially cross-tolerant to the others.

If tolerance to the effects of the opioid analgesic should develop, an increase in dosage or decrease in dosing interval may be necessary. However, the analgesic efficacy of aspirin is subject to a ceiling effect; single doses larger than 1 gram may not provide additional therapeutic benefit (if the pain is not associated with severe inflammation), but chronic use of such doses will increase the risk of adverse effects, including gastrointestinal bleeding or ulceration. Therefore, administration of supplemental opioid analgesic, or administration of an opioid analgesic and aspirin separately, may be necessary to achieve adequate analgesia in opioid-tolerant patients.

Psychological and physical dependence may occur with chronic administration of opioid analgesics; an abstinence syndrome may occur when these medications are discontinued. Gradual withdrawal may minimize the development of withdrawal symptoms following prolonged use.

ASPIRIN AND CODEINE

Summary of Differences


Category:
Codeine is an opioid agonist analgesic.



Indications:
Indicated for relief of mild to severe pain, depending on the dose of codeine.



Pharmacology/pharmacokinetics: For orally administered codeine:
Mechanism of action/effect: An opioid agonist analgesic; exerts agonist activity primarily at the mu receptor, but with usual doses is relatively weak.

Equivalence: 200 mg therapeutically equivalent to 10 mg of intramuscular morphine.

Protein binding: Very low.

Half-life: 2.5–4 hours.

Biotransformation: Hepatic; about 10% demethylated to morphine.

Onset of action: 30–45 minutes.

Time to peak effect: 1–2 hours.

Duration of action (nontolerant patients only; decreases as tolerance develops during chronic therapy): 4 hours.

Elimination: Renal, 5–15% as unchanged codeine and 10% as unchanged or conjugated morphine.



Precautions:
Pregnancy—Codeine has been shown to cause delayed ossification in mice and increased resorptions in rats.

Breast-feeding—Codeine is distributed into breast milk.



Side/adverse effects:
Codeine is more likely than most other opioids to cause constipation, especially during chronic therapy.

Codeine has lower dependence liability and potential for abuse than most other opioid agonists with usual doses.

Withdrawal symptoms produced by codeine are less severe than those produced by stronger opioid agonist analgesics.



Oral Dosage Forms

ASPIRIN AND CODEINE PHOSPHATE TABLETS USP

Usual adult dose
Oral, 1 or 2 tablets every four hours as needed.

Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


325 mg of aspirin and 15 mg of codeine phosphate (Rx)[Generic]{01}


325 mg of aspirin and 30 mg of codeine phosphate (Rx) [Empirin with Codeine No.3{02}][Generic]{01}


325 mg of aspirin and 60 mg of codeine phosphate (Rx) [Empirin with Codeine No.4{02}][Generic]{01}

Canada—
Not commercially available.

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed, light-resistant container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Take with food or with a full glass of water.
   • May be habit-forming.

Note: Controlled substance in the U.S.



ASPIRIN, CODEINE PHOSPHATE, AND CAFFEINE TABLETS USP

Usual adult dose
Analgesic
Oral, 1 or 2 tablets every four hours as needed.


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


325 mg of ASA, 8 mg of codeine phosphate, and 15 mg of caffeine (OTC) [C2 with Codeine{04}][Generic]


325 mg of ASA, 8 mg of codeine phosphate, and 32 mg of caffeine (OTC) [Anacin with Codeine{05}]


375 mg of ASA, 8 mg of codeine phosphate, and 30 mg of caffeine (OTC)[Generic]{05}


375 mg of ASA, 8 mg of codeine phosphate, and 30 mg of caffeine citrate (OTC) [222{06} (double-scored)]


375 mg of ASA, 15 mg of codeine phosphate, and 30 mg of caffeine citrate (Rx) [282{06} (scored)]


375 mg of ASA, 30 mg of codeine phosphate, and 30 mg of caffeine citrate (Rx) [292{06} (scored)]


400 mg of ASA, 8 mg of codeine phosphate, and 15 mg of caffeine (OTC) [Novo-AC and C{05}]


500 mg of ASA, 8 mg of codeine phosphate, and 15 mg of caffeine (OTC)[Generic]{05}

Note: 30 mg of caffeine citrate are equivalent to 15 mg of caffeine base.


Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed, light-resistant container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Take with food or with a full glass of water.
   • May be habit-forming.

Note: Controlled substance in Canada.



ASPIRIN AND CODEINE, BUFFERED

Summary of Differences


Category:
Codeine is an opioid agonist analgesic.



Indications:
Indicated for relief of mild to severe pain, depending on the dose of codeine.



Pharmacology/pharmacokinetics: For orally administered codeine:
Mechanism of action/effect: An opioid agonist analgesic; exerts agonist activity primarily at the mu receptor, but with usual doses is relatively weak.

Equivalence: 200 mg therapeutically equivalent to 10 mg of intramuscular morphine.

Protein binding: Very low.

Half-life: 2.5–4 hours.

Biotransformation: Hepatic; about 10% demethylated to morphine.

Onset of action: 30–45 minutes.

Time to peak effect: 1–2 hours.

Duration of action (nontolerant patients only; decreases as tolerance develops during chronic therapy): 4 hours.

Elimination: Renal, 5–15% as unchanged codeine and 10% as unchanged or conjugated morphine.



Precautions:
Pregnancy—Codeine has been shown to cause delayed ossification in mice and increased resorptions in rats.

Breast-feeding—Codeine is distributed into breast milk.

Drug interactions and/or related problems—Antacids present as buffering agents may decrease absorption of many orally administered medications; antacids generally should be taken 1 to 2 hours before or after other orally administered medications, although intervals of 3 to 8 hours between antacid ingestion and administration of specific agents (i.e., fluoroquinolone antibiotics, ketoconazole, and oral tetracyclines) have been recommended.



Side/adverse effects:
Codeine is more likely than most other opioids to cause constipation, especially during chronic therapy.

Codeine has lower dependence liability and potential for abuse than most other opioid agonists with usual doses.

Withdrawal symptoms produced by codeine are less severe than those produced by stronger opioid agonist analgesics.



Oral Dosage Forms

ASPIRIN, CODEINE PHOSPHATE, CAFFEINE, ALUMINA, AND MAGNESIA TABLETS

Usual adult dose
Analgesic
Oral, 1 or 2 tablets every four hours as needed.


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


325 mg of ASA, 8 mg of codeine phosphate, and 15 mg of caffeine, with 35 mg of aluminum hydroxide and 70 mg of magnesium hydroxide (OTC) [C2 Buffered with Codeine{04}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Take with food or with a full glass of water.
   • May be habit-forming.

Note: Controlled substance in Canada.



ASPIRIN AND DIHYDROCODEINE

Summary of Differences


Category:
Dihydrocodeine is an opioid agonist analgesic.



Indications:
Indicated for relief of moderate to moderately severe pain.



Oral Dosage Forms

ASPIRIN, CAFFEINE, AND DIHYDROCODEINE BITARTRATE CAPSULES USP

Usual adult dose
Analgesic
Oral, 2 capsules every four hours as needed.


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


356.4 mg of aspirin, 30 mg of caffeine, and 16 mg of dihydrocodeine bitartrate (Rx) [Synalgos-DC{07}]

Canada—
Not commercially available.

Packaging and storage:
Store below 25 °C (77 °F), in a light-resistant container, unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Take with food or with a full glass of water.
   • May be habit-forming.

Note: Controlled substance in the U.S.



HYDROCODONE AND ASPIRIN

Summary of Differences


Category:
Hydrocodone is an opioid agonist analgesic.



Indications:
Indicated for relief of moderate to severe pain.



Pharmacology/pharmacokinetics: For orally administered hydrocodone:
Mechanism of action/effect: An opioid agonist analgesic; exerts agonist activity primarily at the mu receptor.

Half-life: 3.8 hours.

Onset of action: 10–30 minutes.

Time to peak effect: 30–60 minutes.

Duration of action (nontolerant patients only; decreases as tolerance develops during chronic therapy): 4–6 hours.



Precautions:
Pregnancy—Hydrocodone teratogenic in animals in very high doses.

Breast-feeding—Not known whether hydrocodone is distributed into breast milk.



Side/adverse effects:
Hydrocodone is more likely than most other opioids to cause side effects associated with histamine release.



Oral Dosage Forms

HYDROCODONE BITARTRATE AND ASPIRIN TABLETS

Usual adult dose
Analgesic
Oral, 1 or 2 tablets every four to six hours as needed.


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


5 mg of hydrocodone bitartrate and 500 mg of aspirin (Rx) [Damason-P{08}] [Lortab ASA{10}] [Panasal 5/500{01}]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Take with food or with a full glass of water.
   • May be habit-forming.

Note: Controlled substance in the U.S.



OXYCODONE AND ASPIRIN

Summary of Differences


Category:
Oxycodone is an opioid agonist analgesic.



Indications:
Indicated for relief of moderate to moderately severe pain.



Pharmacology/pharmacokinetics: For orally administered oxycodone:
Mechanism of action/effect: An opioid agonist analgesic; has agonist activity primarily at the mu receptor.

Equivalence: 30 mg via oral administration therapeutically equivalent to 10 mg of intramuscular morphine.

Half-life: 2–3 hours.

Time to peak effect: 1 hour.

Duration of action (nontolerant patients only; duration decreases as tolerance develops during chronic therapy): 3–4 hours.

Elimination: Renal.



Precautions:
Breast-feeding—Not known whether oxycodone is distributed into breast milk.



Oral Dosage Forms

OXYCODONE AND ASPIRIN TABLETS USP

Usual adult dose
Analgesic
Oral, 1 or 2 half-strength tablets or 1 full-strength tablet, every four to six hours as needed. Dosage may be increased if necessary for severe pain.


Usual pediatric dose
Analgesic
Children up to 6 years of age—Use is not recommended.

Children 6 to 12 years of age—Oral, 1/4 half-strength tablet every six hours as needed.

Children 12 years of age and over—Oral, 1/2 half-strength tablet every six hours as needed.


Strength(s) usually available
U.S.—


Half-strength: 2.25 mg of oxycodone hydrochloride and 190 mcg (0.19 mg) of oxycodone terephthalate, with 325 mg of aspirin (Rx) [Percodan-Demi{11} (scored)]


Full-strength: 4.5 mg of oxycodone hydrochloride and 380 mcg (0.38 mg) of oxycodone terephthalate, with 325 mg of aspirin (Rx) [Endodan{01}] [Percodan{12} (scored)] [Roxiprin{01}][Generic]{01}

Canada—


Half-strength: 2.5 mg of oxycodone hydrochloride and 325 mg of ASA (Rx) [Percodan-Demi{13} (scored)]


Full-strength: 5 mg of oxycodone hydrochloride and 325 mg of ASA (Rx) [Endodan{14} (scored)] [Oxycodan{15} ( scored)] [Percodan{13} (scored)]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Take with food or with a full glass of water.
   • May be habit-forming.

Note: Controlled substance in both the U.S. and Canada.



PENTAZOCINE AND ASPIRIN

Summary of Differences


Category:
Pentazocine is an opioid agonist/antagonist analgesic.



Indications:
Indicated for relief of moderate pain.



Pharmacology/pharmacokinetics: For orally administered pentazocine:
Mechanism of action/effect: An opioid agonist/antagonist analgesic.

Agonist—Has agonist activity at the kappa and sigma receptors.

Antagonist—Has antagonist activity at the mu receptor; may precipitate withdrawal symptoms in patients who are physically dependent on mu-receptor agonists.

Equivalence: 180 mg therapeutically equivalent to 10 mg of intramuscular morphine.

Protein binding: Moderate.

Half-life: 2–3 hours

Onset of action: 15–30 minutes.

Time to peak effect: 60–90 minutes.

Duration of action (nontolerant patients only; decreases as tolerance develops during chronic therapy): 3 hours.

Elimination: Renal, 5–23% as unchanged pentazocine, and biliary.



Precautions:
Pregnancy— Studies in animals have not shown that pentazocine causes adverse effects in the fetus.

Breast-feeding— Not known whether pentazocine is distributed into breast milk.

Drug interactions and/or related problems—

May partially antagonize effects of opioid agonist analgesics.

May cause withdrawal symptoms if given to a patient physically dependent on an opioid agonist.

Medical considerations/contraindications—

Precaution in patients who are physically dependent on an opioid agonist.

Precaution in patients with acute myocardial infarction.



Side/adverse effects:
Although effects occur rarely, pentazocine more likely than butorphanol or nalbuphine to cause subjective and psychotomimetic effects characteristic of sigma receptor agonists.

Respiratory depression subject to a ``ceiling effect"", after which the depth of respiratory depression does not increase with dose.

Pentazocine has less dependence liability and potential for abuse than opioid agonists.

Pentazocine produces withdrawal symptoms that are less severe than those produced by opioid agonist analgesics.



Oral Dosage Forms

PENTAZOCINE HYDROCHLORIDE AND ASPIRIN TABLETS USP

Usual adult dose
Analgesic
Oral, 2 tablets three or four times a day as needed.


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


12.5 mg of pentazocine (base) and 325 mg of aspirin (Rx) [Talwin Compound{16}]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Take with food or with a full glass of water.
   • May be habit-forming.

Note: Controlled substance in the U.S.



PROPOXYPHENE AND ASPIRIN

Summary of Differences


Category:
Propoxyphene is an opioid agonist analgesic.



Indications:
Indicated for relief of mild to moderate pain.



Pharmacology/pharmacokinetics: For orally administered propoxyphene :
Mechanism of action/effect: An opioid agonist analgesic; has agonist activity primarily at the mu receptor.

Equivalence: Dose therapeutically equivalent to 10 mg of intramuscular morphine too toxic to administer.

Protein binding: High.

Biotransformation: Metabolite norpropoxyphene is toxic.

Half-life:

Propoxyphene—6–12 hours.

Norpropoxyphene—30–36 hours.

Onset of action: 15–60 minutes.

Time to peak concentration: 2–2.5 hours.

Peak plasma concentration: 0.05–0.1 mcg per mL.

Time to peak effect: 2 hours.

Duration of action (nontolerant patients only; decreases as tolerance develops during chronic therapy): 4–6 hours.

Elimination: Renal, <10% as unchanged propoxyphene; biliary.



Precautions:
Pregnancy—Studies in animals have not shown that propoxyphene causes adverse effects in the fetus.

Breast-feeding—Propoxyphene is distributed into breast milk.

Drug interactions and/or related problems—

Risk of convulsions if overdose of propoxyphene administered to amphetamine-treated patients.

May increase effects of coumarin- or indandione-derivative anticoagulants.

Concurrent use with carbamazepine not recommended because may decrease carbamazepine metabolism, leading to increased risk of toxicity.

Laboratory value alterations— May cause liver function test abnormalities.



Side/adverse effects:
Propoxyphene may be more likely than most opioid analgesics to cause convulsions.

Hepatotoxicity has been reported with propoxyphene.

Propoxyphene has less dependence liability and potential for abuse than other opioid agonists with usual doses.

Propoxyphene produces withdrawal symptoms that are less severe than those produced by stronger opioid agonist analgesics.



Oral Dosage Forms

PROPOXYPHENE HYDROCHLORIDE, ASPIRIN, AND CAFFEINE CAPSULES USP

Usual adult dose
Oral, 1 capsule every four hours, as needed.

Usual adult prescribing limits
Up to 390 mg of propoxyphene hydrochloride a day.

Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


65 mg of propoxyphene hydrochloride, 389 mg of aspirin, and 32.4 mg of caffeine (Rx) [Darvon Compound-65{17}] [PC-Cap{18}] [Propoxyphene Compound-65{01}][Generic]{01}

Canada—
Not commercially available.

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Take with food or with a full glass of water.
   • May be habit-forming.

Note: Controlled substance in the U.S.



PROPOXYPHENE HYDROCHLORIDE, ASPIRIN, AND CAFFEINE TABLETS

Usual adult dose
Analgesic
Oral, 1 tablet every four hours, as needed.


Usual adult prescribing limits
Up to 390 mg of propoxyphene hydrochloride a day.

Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


65 mg of propoxyphene hydrochloride, 375 mg of ASA, and 30 mg of caffeine (Rx) [692{19} (scored)]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Take with food or with a full glass of water.
   • May be habit-forming.

Note: Controlled substance in Canada.



PROPOXYPHENE NAPSYLATE AND ASPIRIN CAPSULES

Usual adult dose
Analgesic
Oral, 1 capsule every four hours, as needed.


Usual adult prescribing limits
Up to 600 mg of propoxyphene napsylate a day.

Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


100 mg of propoxyphene napsylate and 325 mg of ASA (Rx) [Darvon-N with A.S.A.{20}]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Take with food or with a full glass of water.
   • May be habit-forming.

Note: Controlled substance in Canada.



PROPOXYPHENE NAPSYLATE, ASPIRIN, AND CAFFEINE CAPSULES

Usual adult dose
Analgesic
Oral, 1 capsule every four hours, as needed.


Usual adult prescribing limits
Up to 600 mg of propoxyphene napsylate a day.

Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


100 mg of propoxyphene napsylate, 375 mg of ASA, and 30 mg of caffeine (Rx) [Darvon-N Compound{20}]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Take with food or with a full glass of water.
   • May be habit-forming.

Note: Controlled substance in Canada.




Revised: 6/14/2000



References

Note: All references used in the development and earlier revisions of this monograph have not yet been incorporated into the computer database and, therefore, are not listed below. Citations for information not yet referenced in the monograph will be provided upon request.

  1. Red book 1995. Montvale, NJ. Medical Economics Company, 1995: 134, 135, 228, 360, 394, 406.
  1. Aspirin and Codeine (Empirin with Codeine, BW). In: PDR Physicians' desk reference. 49th ed. 1995. Montvale, NJ: Medical Economics Data Production Company, 1995: 757-8.
  1. Aspirin, Codeine, and Caffeine (A.C.&C., Wampole, WestCan). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 29th ed. Ottawa: Canadian Pharmaceutical Association, 1994: 11.
  1. Aspirin, Codeine, and Caffeine formulations (C2 Buffered with Codeine, C2 with Codeine, Wampole). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 29th ed. Ottawa: Canadian Pharmaceutical Association, 1994: 303-4.
  1. Internal Analgesics and Antipyretics Table. In: Krogh CME, editor. Self-Medication Product Information. Volume 2, 4th edition. Canadian Pharmaceutical Association, 1993: 205, 207, 208, 211.
  1. Aspirin, Codeine, and Caffeine (222, 282, 292, Frosst). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 29th ed. Ottawa: Canadian Pharmaceutical Association, 1994: 1375-6.
  1. Aspirin, Caffeine, and Dihydrocodeine (Synalgos DC, Wyeth Ayerst). In: PDR Physicians' desk reference. 49th ed. 1995. Montvale, NJ: Medical Economics Data Production Company, 1995: 2742.
  1. Hydrocodone and Aspirin (Azdone, Central). In: PDR Physicians' desk reference. 49th ed. 1995. Montvale, NJ: Medical Economics Data Production Company, 1995: 851.
  1. Hydrocodone and Aspirin (Damason P, Mason). In: PDR Physicians' desk reference. 49th ed. 1995. Montvale, NJ: Medical Economics Data Production Company, 1995: 1434.
  1. Hydrocodone and Aspirin (Lortab ASA, Whitby). In: PDR Physicians' desk reference. 49th ed. 1995. Montvale, NJ: Medical Economics Data Production Company, 1995: 2633-4.
  1. Oxycodone and Aspirin (Percodan-Demi, DuPont). In: PDR Physicians' desk reference. 49th ed. 1995. Montvale, NJ: Medical Economics Data Production Company, 1995: 958-9.
  1. Oxycodone and Aspirin (Percodan, DuPont). In: PDR Physicians' desk reference. 49th ed. 1995. Montvale, NJ: Medical Economics Data Production Company, 1995: 958.
  1. Oxycodone and Aspirin (Percodan, Percodan-Demi, DuPont). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 29th ed. Ottawa: Canadian Pharmaceutical Association, 1994: 1005-6.
  1. Oxycodone and Aspirin (Endodan, Endo). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 29th ed. Ottawa: Canadian Pharmaceutical Association, 1994: 439.
  1. Oxycodone and Aspirin (Oxycodan, Technilab). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 29th ed. Ottawa: Canadian Pharmaceutical Association, 1994: 974.
  1. Pentazocine and Aspirin (Talwin Compound, Sanofi Winthrop). In: PDR Physicians' desk reference. 49th ed. 1995. Montvale, NJ: Medical Economics Data Production Company, 1995: 2233.
  1. Propoxyphene, Aspirin, and Caffeine (Darvon Compound-65, Lilly). In: PDR Physicians' desk reference. 49th ed. 1995. Montvale, NJ: Medical Economics Data Production Company, 1995: 1322-4.
  1. Propoxyphene, Aspirin, and Caffeine (PC-Cap, Alra). In: PDR Physicians' desk reference. 49th ed. 1995. Montvale, NJ: Medical Economics Data Production Company, 1995: 499.
  1. Propoxyphene, Aspirin, and Caffeine (692, Frosst). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 29th ed. Ottawa: Canadian Pharmaceutical Association, 1994: 1210-1.
  1. Propoxyphene and Aspirin formulations (Darvon-N Compound, Darvon-N with A.S.A, Lilly). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 29th ed. Ottawa: Canadian Pharmaceutical Association, 1994: 334-5.
Hide
(web1)