Hydrocodone and Aspirin


(hye droe KOE done & AS pir in)

U.S. Brand Names



Aspirin and Hydrocodone

Generic Available



Relief of moderate to moderately severe pain

Use - Dental

Treatment of postoperative pain



Pregnancy Risk Factor



Enters breast milk/contraindicated


Based on hydrocodone component: Hypersensitivity to hydrocodone or any component of the formulation

Based on aspirin component: Hypersensitivity to salicylates, other NSAIDs, or any component of the formulation; asthma; rhinitis; nasal polyps; inherited or acquired bleeding disorders (including factor VII and factor IX deficiency); pregnancy (in 3rd trimester especially); do not use in children (<16 years) for viral infections (chickenpox or flu symptoms), with or without fever, due to a potential association with Reye's syndrome


Use with caution in patients with impaired renal function, erosive gastritis, or peptic ulcer disease; children and teenagers should not use for chickenpox or flu symptoms before a physician is consulted about Reye's syndrome; tolerance or drug dependence may result from extended use

Based on hydrocodone component: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (morphine, codeine, hydromorphone, levorphanol, oxycodone, oxymorphone); should be used with caution in elderly or debilitated patients, and those with severe impairment of hepatic or renal function, prostatic hyperplasia, or urethral stricture. Also use caution in patients with head injury, increased intracranial pressure, acute abdomen, or impaired thyroid function. Hydrocodone suppresses the cough reflex; caution should be exercised when this agent is used postoperatively and in patients with pulmonary diseases (including asthma, emphysema, COPD)

Based on aspirin component: Use with caution in patients with platelet and bleeding disorders, renal dysfunction, dehydration, erosive gastritis, or peptic ulcer disease. Heavy ethanol use (>3 drinks/day) can increase bleeding risks. Avoid use in severe renal failure or in severe hepatic failure. Discontinue use if tinnitus or impaired hearing occurs. Caution in mild-moderate renal failure (only at high dosages). Patients with sensitivity to tartrazine dyes, nasal polyps and asthma may have an increased risk of salicylate sensitivity. Surgical patients should avoid ASA if possible, for 1-2 weeks prior to surgery, to reduce the risk of excessive bleeding.

Adverse Reactions


Cardiovascular: Hypotension

Central nervous system: Lightheadedness, dizziness, sedation, drowsiness, fatigue

Gastrointestinal: Nausea, heartburn, stomach pain, dyspepsia, epigastric discomfort

Neuromuscular & skeletal: Weakness

1% to 10%:

Cardiovascular: Bradycardia

Central nervous system: Confusion

Dermatologic: Rash

Gastrointestinal: Vomiting, gastrointestinal ulceration

Genitourinary: Decreased urination

Hematologic: Hemolytic anemia

Respiratory: Dyspnea

Miscellaneous: Anaphylactic shock

<1%: Hypertension, hallucinations, insomnia, nervousness, jitters, xerostomia, anorexia, biliary tract spasm, urinary tract spasm, occult bleeding, prolongated bleeding time, leukopenia, thrombocytopenia, iron-deficiency anemia, hepatotoxicity, diplopia, miosis, impaired renal function, bronchospasm, histamine release, physical and psychological dependence with prolonged use


Naloxone is the antidote for hydrocodone. Naloxone, 2 mg I.V. with repeat administration as necessary up to a total of 10 mg, can also be used to reverse toxic effects of the opiate. Nomograms, such as the "Done" nomogram, can be very helpful for estimating the severity of aspirin poisoning and for directing treatment using serum salicylate levels. Treatment can also be based upon symptomatology; symptoms of aspirin overdose include tinnitus, headache, dizziness, confusion, metabolic acidosis, hyperpyrexia, hypoglycemia, and coma.

Drug Interactions

Based on hydrocodone component: Substrate of CYP2D6 (major)

CNS depressants, MAO inhibitors, general anesthetics, and tricyclic antidepressants: May potentiate the effects of opiate agonists; dextroamphetamine may enhance the analgesic effect of opiate agonists.

CYP2D6 inhibitors: May decrease the effects of hydrocodone. Example inhibitors include chlorpromazine, delavirdine, fluoxetine, miconazole, paroxetine, pergolide, quinidine, quinine, ritonavir, and ropinirole.

Based on aspirin component: Substrate of CYP2C8/9 (minor)

ACE inhibitors: The effects of ACE inhibitors may be blunted by aspirin administration, particularly at higher dosages.

Buspirone increases aspirin's free % in vitro.

Carbonic anhydrase inhibitors and corticosteroids have been associated with alteration in salicylate serum concentrations.

Heparin and low molecular weight heparins: Concurrent use may increase the risk of bleeding

Methotrexate serum levels may be increased; consider discontinuing aspirin 2-3 days before high-dose methotrexate treatment or avoid concurrent use.

NSAIDs may increase the risk of gastrointestinal adverse effects and bleeding. Serum concentrations of some NSAIDs may be decreased by aspirin.

Platelet inhibitors (IIb/IIIa antagonists): Risk of bleeding may be increased.

Probenecid effects may be antagonized by aspirin.

Sulfonylureas: The effects of older sulfonylurea agents (tolazamide, tolbutamide) may be potentiated due to displacement from plasma proteins. This effect does not appear to be clinically significant for newer sulfonylurea agents (glyburide, glipizide, glimepiride).

Valproic acid may be displaced from its binding sites which can result in toxicity.

Verapamil may potentiate the prolongation of bleeding time associated with aspirin.

Warfarin and oral anticoagulants may increase the risk of bleeding.

Ethanol/Nutrition/Herb Interactions

Based on hydrocodone component: Ethanol: Avoid or limit ethanol (may increase CNS depression). Watch for sedation.

Based on aspirin component:

Ethanol: Avoid ethanol (may enhance gastric mucosal damage).

Food: Food may decrease the rate but not the extent of oral absorption. Take with food or or large volume of water or milk to minimize GI upset.

Herb/Nutraceutical: Avoid cat's claw, dong quai, evening primrose, feverfew, garlic, ginger, ginkgo, red clover, horse chestnut, green tea, ginseng (all have additional antiplatelet activity).

Mechanism of Action

Based on hydrocodone component: Binds to opiate receptors in the CNS, altering the perception of and response to pain; suppresses cough in medullary center; produces generalized CNS depression

Based on aspirin component: Inhibits prostaglandin synthesis, acts on the hypothalamus heat-regulating center to reduce fever, blocks prostaglandin synthetase action which prevents formation of the platelet-aggregating substance thromboxane A2


Aspirin: See Aspirin monograph.


Onset of action: Narcotic analgesic: 10-20 minutes

Duration: 4-8 hours

Distribution: Crosses placenta

Metabolism: Hepatic; O-demethylation; N-demethylation and 6-ketosteroid reduction

Half-life elimination: 3.3-4.4 hours

Excretion: Urine


Adults: Oral: 1-2 tablets every 4-6 hours as needed for pain


Administer with food or a full glass of water to minimize GI distress

Monitoring Parameters

Observe patient for excessive sedation, respiratory depression

Test Interactions

Urine glucose, urinary 5-HIAA, serum uric acid

Patient Education

If self-administered, use exactly as directed; do not increase dose or frequency. Drug may cause physical and/or psychological dependence. Take with food or milk. While using this medication, do not use alcohol, excessive amounts of vitamin C, or salicylate-containing foods (curry powder, prunes, raisins, tea, or licorice), other aspirin- or salicylate-containing medications, and other prescription or OTC medications (especially sedatives, tranquilizers, antihistamines, or pain medications) without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. May cause hypotension, dizziness, drowsiness, impaired coordination, or blurred vision (use caution when driving, climbing stairs, or changing position - rising from sitting or lying to standing, or when engaging in tasks requiring alertness until response to drug is known); nausea, vomiting, or dry mouth (frequent mouth care, small, frequent meals, chewing gum, or sucking lozenges may help); or constipation (increased exercise, fluids, fruit, or fiber may help; if unresolved, consult prescriber about use of stool softeners). Report ringing in ears; persistent stomach pain; unresolved nausea or vomiting; respiratory difficulty or shortness of breath; yellowing of skin or eyes; changes in color of stool or urine; or unusual bruising or bleeding. Use appropriate contraceptive measures; do not get pregnant while taking this drug. Do not breast-feed.

Pregnancy/breast-feeding precautions:

Nursing Implications

May cause drowsiness; avoid alcohol; watch for bleeding gums or any signs of GI bleeding; notify healthcare provider if ringing in ears or persistent GI pain occurs

Dental Health: Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Nausea is the most common adverse effect seen after use in dental patients. Sedation and constipation are second. Aspirin component affects bleeding times and could influence wound-healing time. Elderly are a high-risk population for adverse effects from NSAIDs. As many as 60% of elderly patients with GI complications from NSAIDs can develop peptic ulceration and/or hemorrhage asymptomatically. Concomitant disease and drug use contribute to the risk of GI adverse effects.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Dental Comment

Because of addiction liability of opiate analgesics, the use of hydrocodone should be limited to 2-3 days postoperatively for treatment of dental pain; nausea is the most common adverse effect seen after use in dental patients; sedation and constipation are second; aspirin component affects bleeding times and could influence time of wound healing

Mental Health: Effects on Mental Status

Sedation is common; may cause confusion or dizziness; may rarely cause hallucinations

Mental Health: Effects on Psychiatric Treatment

May result in loss of pain control when used in combination with SSRIs (especially paroxetine and fluoxetine); concurrent use with psychotropics may produce additive sedation

Dosage Forms

Tablet: Hydrocodone bitartrate 5 mg and aspirin 500 mg


Dionne RA, "New Approaches to Preventing and Treating Postoperative Pain,"J Am Dent Assoc, 1992, 123(6):26-34.

Gobetti JP, "Controlling Dental Pain,"J Am Dent Assoc, 1992, 123(6):47-52.

Mokhlesi B, Leikin JB, Murray P, et al, "Adult Toxicology in Critical Care: Part II: Specific Poisonings,"Chest, 2003, 123(3):897-922.

Review Date: 1969-12-31 Reviewed By: Keywords: ,
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