Medication Guide App

Hydrocodone and Ibuprofen (Systemic)


VA CLASSIFICATION
Primary: CN900

Note: Controlled substance classification—

Note: Controlled substance classification


U.S.—Schedule III
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. —

Indications

Accepted

Pain (treatment)—Hydrocodone and ibuprofen combination is indicated for the short-term (< 10 days) management of acute pain {01}.

Unaccepted
Hydrocodone and ibuprofen combination is not indicated for the treatment of osteoarthritis and rheumatoid arthritis {01}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Hydrocodone bitartrate: 494.5 {01}
    Ibuprofen: 206.29 {01}

Mechanism of action/Effect:

Hydrocodone—The exact mechanism of action of hydrocodone is unknown {01}. Hydrocodone is an opioid analgesic {01}. It has been proposed that opioid analgesics bind with specific opioid receptors at many sites in the central nervous system (CNS) to alter processes affecting pain sensation {01}.

Ibuprofen—Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic therapeutic effects {01}. The exact mechanism of action of ibuprofen has not been determined {01}. However, it has been proposed that ibuprofen, like other NSAIDs, inhibits the activity of the enzyme cyclo-oxygenase, resulting in a decreased formation of precursors of prostaglandins {01}. The resulting decrease in prostaglandin synthesis may be responsible for the therapeutic effects of ibuprofen {01}.


Other actions/effects:

Hydrocodone also has antitussive activity {01}.

Absorption:

Rapid {01}.

Protein binding:

Hydrocodone—The extent of hydrocodone protein binding in human plasma is not known {01}. However, it is expected to fall in the low-to- moderate range (19 to 45%), similar to that of other opioid agents {01}.

Ibuprofen—Very high (99%) {01}.

Biotransformation:

Hydrocodone—Hepatic {01}. Extensively metabolized by N- and O-demethylation via hepatic cytochrome P450 enzymes (CYP2D6 and CYP3A4, respectively) and 6-keto reduction to hydroxy metabolites {01}. The O-demethylation of hydrocodone forms the potent opioid analgesic hydromorphone that contributes to the total analgesic action of hydrocodone {01}.

Ibuprofen—Hepatic {01}. Ibuprofen is present as a racemate, which undergoes conversion in the plasma from an R-isomer to an S-isomer following absorption {01}. These isomers are metabolized to two primary phenyl proprionic acid metabolites, which appear in the plasma at lower concentration levels than the parent {01}.

Half-life:

Hydrocodone—4.5 hours {01}.

Ibuprofen—2.2 hours {01}.

Time to peak concentration:

Hydrocodone—1.7 hours {01}.

Ibuprofen—1.8 hours {01}.

Peak serum concentration:

Hydrocodone—27 nanograms/mL {01}.

Ibuprofen—30 mcg/mL {01}.

Elimination:
    Hydrocodone—Renal {01}.
    Ibuprofen—Renal, approximately 50 to 60% is excreted in the urine as metabolites (15% as unchanged drug and conjugate) {01}.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to ibuprofen, other nonsteroidal anti-inflammatory drugs (NSAIDs), hydrocodone, or one of the other opioid analgesics may be sensitive to hydrocodone and ibuprofen combination also {01}.

Hydrocodone and ibuprofen combination may cause bronchoconstriction or anaphylaxis in aspirin-sensitive asthmatics, especially those with aspirin-induced nasal polyps, asthma, and other allergic reactions (the “aspirin triad”) {01}.

Carcinogenicity/Mutagenicity

Studies have not been done to evaluate the carcinogenic or mutagenic potential of hydrocodone and ibuprofen combination {01}.

Pregnancy/Reproduction
Fertility—
Reproductive studies have not been done to determine the effect of hydrocodone and ibuprofen combination on fertility {01}.

Pregnancy—
Adequate and well-controlled trials in humans have not been done {01}.

In rabbits receiving doses of hydrocodone and ibuprofen combination of up to 95 mg per kilogram of body weight (mg/kg) (approximately 5.72 times and 1.9 times the maximum recommended human dose [MRHD] on a mg/kg basis and mg/m 2 basis, respectively), an increase in major and minor fetal abnormalities was observed {01}. However, no reproductive toxicity was observed in rats receiving doses of hydrocodone and ibuprofen combination of up to 166 mg/kg (approximately 10 times and 1.66 times the MRHD on a mg/kg basis and mg/m 2 basis, respectively) {01}.

The use of NSAIDs, such as ibuprofen, is not recommended in the last trimester due to the possible adverse effects on the fetus, such as premature closure of the ductus arteriosus {01}. In addition, regular use of an opioid during pregnancy will cause physical dependence in the fetus, leading to withdrawal symptoms, such as convulsions, irritability, excessive crying, tremors, hyperactive reflexes, fever, vomiting, diarrhea, sneezing, and yawning in the neonate {01}. The dose and duration of maternal use of opioids is not necessarily reflective of the intensity of the withdrawal symptoms in the neonate {01}.

FDA Pregnancy Category C {01}.


Labor and delivery—

The use of hydrocodone and ibuprofen combination is not recommended during labor and delivery {01}.

In rats receiving hydrocodone and ibuprofen combination, an increased incidence of dystocia and delayed parturition was observed {01}.

Breast-feeding

It is not known whether hydrocodone and ibuprofen combination is distributed into breast milk. However, use of hydrocodone and ibuprofen combination is not recommended in nursing mothers due to the potential adverse effects of the ibuprofen, a prostaglandin-inhibiting drug, on neonates {01}.

Hydrocodone—It is not known whether hydrocodone is distributed into human breast milk {01}.

Ibuprofen—In studies using a 1 mg/mL assay to determine the concentration of ibuprofen in nursing mothers, no measurable quantity of ibuprofen was detected {01}.

Pediatrics

No information is available on the relationship of age to the effects of hydrocodone and ibuprofen combination in pediatric patients. Safety and efficacy in children up to 16 years of age have not been established {01}.


Geriatrics


Studies performed to date have demonstrated an increase in the incidence of constipation in geriatric patients to be the only difference in the tolerability of hydrocodone and ibuprofen combination compared with younger adults {01}. However, elderly patients may be more likely to be more sensitive to nonsteroidal anti-inflammatory drug–induced renal and gastrointestinal effects and opioid-induced respiratory depression {01}. Therefore, caution and dosage adjustment are recommended in geriatric patients receiving hydrocodone and ibuprofen combination {01}.


Dental

Hydrocodone and ibuprofen combination may cause soreness of the oral mucosa {01}. Also, hydrocodone and ibuprofen combination may decrease or inhibit salivary flow, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Alcohol or
» Central nervous system (CNS) depression-producing medications, other (see Appendix II )    (concurrent use with hydrocodone and ibuprofen combination may result in increased CNS depressant effects; caution is recommended and dosage of one or both agents should be reduced {01})


» Angiotensin-converting enzyme (ACE) inhibitors    (concurrent use with hydrocodone and ibuprofen combination may reduce the effects of the ACE inhibitor; concurrent use may also result in an increased risk of renal failure {01})


Anticholinergics    (concurrent use with hydrocodone and ibuprofen combination may result in paralytic ileus {01})


» Anticoagulants, coumarin- or indandione-derivative    (concurrent use with hydrocodone and ibuprofen combination may increase the risk of gastrointestinal bleeding {01})


» Antidepressants, tricyclic (TCAs)    (concurrent use with hydrocodone and ibuprofen combination may result in increased adverse effects of hydrocodone or increased antidepressant effects of the TCAs {01})


Aspirin or
Corticosteroids, glucocorticoid or
Nonsteroidal anti-inflammatory drugs (NSAIDs)    (concurrent use is not recommended due to the increased risk of gastrointestinal effects, including ulceration and hemorrhage {01})


» Diuretics    (ibuprofen has been shown to reduce the effects of antihypertensive agents, possibly by inhibiting renal prostaglandin synthesis; increased monitoring of the response to the diuretic agent is recommended when it is used concurrently with hydrocodone and ibuprofen combination {01})

    (concurrent use of diuretics with hydrocodone and ibuprofen also may increase the risk of renal failure secondary to a decrease in renal blood flow caused by the inhibition of the renal prostaglandin synthesis by ibuprofen {01})


» Lithium    (inhibition of renal prostaglandin activity by ibuprofen has been reported to result in an increase in the plasma concentration of lithium and a decrease in its renal clearance; increased monitoring for lithium toxicity is recommended during concurrent use with hydrocodone and ibuprofen combination {01})


» Methotrexate    (ibuprofen may decrease renal elimination of methotrexate, thereby resulting in increased and prolonged methotrexate plasma concentration and an increased risk of toxicity; caution is recommended with the concurrent use of hydrocodone and ibuprofen combination and methotrexate {01})


» Monoamine oxidase (MAO) inhibitors, including furazolidone, pargyline, and procarbazine    (concurrent use with hydrocodone and ibuprofen combination may result in increased adverse effects of hydrocodone or of the antidepressant effects of the MAO inhibitor {01})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Bleeding time    (may be prolonged by ibuprofen because of suppressed platelet aggregation {01})


Hemoglobin    (values may be decreased {01})


Liver function tests, including
Alkaline phosphatase, serum and
Lactate dehydrogenase (LDH), serum and
Transaminases    (values may be increased; liver function test abnormalities may return to normal despite continued use; however, if significant abnormalities occur, clinical signs and symptoms consistent with liver disease develop, or systemic manifestations such as eosinophilia or skin rash occur, hydrocodone and ibuprofen combination should be discontinued; routine monitoring is recommended in patients with severe hepatic or renal function impairment {01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Allergic reaction, severe, such as anaphylaxis or angioedema, induced by aspirin, other NSAIDs, history of, or other opioids, history of or
» Nasal polyps associated with bronchospasm, aspirin-induced     (high risk of severe allergic reactions because of cross-sensitivity {01})


» Peptic ulcer disease, active    (may be exacerbated; increased risk of perforation and/or bleeding {01})


» Renal disease, severe    (adverse renal effects may be increased in the presence of pre-existing renal disease {01})


» Respiratory depression    (may be exacerbated, especially in patients sensitive to opioids {01})


Risk-benefit should be considered when the following medical problems exist
Abdominal conditions, acute    (diagnosis or clinical course may be obscured {01})


Addison's disease or
Hepatic function impairment, severe or
Hypothyroidism or
Prostatic hypertrophy or
Urethral stricture    (increased risk of respiratory depression {01})


Allergic reaction, mild, induced by aspirin, other NSAIDs, or opioids, history of {01}    (possibility of cross-sensitivity)


Anemia or
» Respiratory impairment or disease, including
Asthma, pre-existing    (may be exacerbated; caution is recommended {01})


» Coagulation or platelet function disorders    (increased risk of bleeding; caution is recommended {01})


Conditions predisposing to and/or exacerbated by fluid retention, such as:
Compromised cardiac function
Congestive heart disease
Hypertension    (ibuprofen has been reported to cause fluid retention and edema; therefore, hydrocodone and ibuprofen combination should be used with caution in patients with these conditions {01})


Conditions predisposing to gastrointestinal toxicity, such as:
Alcoholism, active
Peptic ulcer disease, active or history of
Tobacco use, or recent history of    (nonsteroidal anti-inflammatory drugs (NSAIDs) should be used with extreme caution in patients with peptic ulcer disease or gastrointestinal bleeding; dosage adjustment of NSAIDs is recommended to minimize potential risk of gastrointestinal bleeding {01})


Congestive heart failure or
Extracellular volume depletion or
Hepatic function impairment    (increased risk of renal failure; patients who are dehydrated should be rehydrated before receiving hydrocodone and ibuprofen combination {01})


Drug abuse or dependence, current or history of    (patient predisposition to drug abuse)


Head injury or
Increased intracranial pressure, pre-existing or
Intracranial lesions    (risk of respiratory depression and further elevation of cerebrospinal fluid pressure is increased; also, hydrocodone and ibuprofen combination may cause sedation and pupillary changes that may obscure clinical course of head injury {01})


» Renal function impairment    (increased risk of adverse renal effects and respiratory depressant effects; careful monitoring of the patient is recommended, especially for patients with severe renal function impairment {01})

    (ibuprofen and its metabolites are excreted primarily via the kidneys; a reduction in dosage of hydrocodone and ibuprofen combination may be required to prevent accumulation {01})


Sensitivity to hydrocodone and ibuprofen combination {01}
» Caution is also advised in administration to very elderly, very ill, debilitated, or postoperative patients, who may be more sensitive to the effects, especially the respiratory depressant effects, of hydrocodone and ibuprofen combination {01}
» Caution is also recommended in geriatric patients, who may be more likely to develop adverse hepatic or renal effects with hydrocodone and ibuprofen combination and in whom gastrointestinal ulceration or bleeding is more likely to cause serious consequences {01}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Liver function tests or
» Renal function tests    (routine monitoring may be required during hydrocodone and ibuprofen combination therapy in patients with severe hepatic or renal function impairment {01})




Side/Adverse Effects

Note: Physical dependence, with or without psychological dependence, and tolerance may occur with long-term administration of opioid analgesics {01}. However, the manufacturer states that psychological dependence is not likely to develop with the short-term use of hydrocodone and ibuprofen combination {01}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent or rare
    
Allergic reaction {01} (changes in facial skin color; skin rash, hives, and/or itching; fast or irregular breathing; puffiness or swelling of the eyelids or around the eyes; shortness of breath, troubled breathing, tightness in chest and/or wheezing )
    
arrythmia {01} (irregular heartbeat)
    
bronchitis {01} (congestion in chest; cough)
    
dyspnea {01} (shortness of breath)
    
fever {01}
    
frequent urge to urinate {01}
    
gastrointestinal effects, including esophagitis {01} (difficulty in swallowing), gastritis {01} (burning feeling in chest or stomach; tenderness in the stomach area), gastroenteritis {01} (diarrhea; nausea; stomach pain)
    
hypotension {01} (lightheadedness or dizziness)
    
melena {01} (bloody stools)
    
tachycardia {01} ( increased heart rate)
    
tinnitus {01} (ringing or buzzing in the ears)
    
urinary incontinence {01} ( loss of bladder control)
    
urinary retention {01} (inability to urinate)

Note: Meningitis has been reported to occur in patients taking ibuprofen {01}. Signs and symptoms of meningitis, including severe headache, drowsiness, confusion, stiff neck and/or back, or general feeling of illness or nausea, may be related to the ibuprofen in the hydrocodone and ibuprofen combination {01}.




Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Anxiety {01}
    
asthenia {01} (unusual tiredness or weakness)
    
constipation {01}
    
dry mouth {01}
    
edema {01} (swelling of feet or lower legs)
    
flatulence {01} (gas)
    
headache {01}
    
increased sweating {01}
    
insomnia (trouble in sleeping)
    
nausea and vomiting {01}
    
nervousness {01}
    
palpitations {01} (pounding heart beat)
    
pruritus {01} (itching of the skin)
    
somnolence {01} (sleepiness)

Incidence less frequent or rare
    
Anorexia {01} (decreased appetite)
    
central nervous system (CNS) effects, including confusion {01}
dizziness
depression {01}
euphoria {01} (unusual feeling of well-being), irritability {01}
mood or mental changes {01}
paresthesias (sensation of burning, warmth, heat, numbness, tightness, or tingling), slurred speech {01}
thinking abnormalities {01}
tremor {01} (trembling or shaking of hands or feet)
    
dyspepsia {01} (stomach upset )
    
dysphagia {01} (difficulty swallowing)
    
impotence {01} (decrease in sexual ability)
    
increased thirst {01}
    
mouth ulcers {01}
    
pharyngitis {01} (pain or burning in throat)
    
rhinitis {01} (runny nose)
    
sinusitis {01} (runny nose; headache)
    
visual disturbances {01}
    
weight loss, unexplained {01}





Overdose
For specific information on the agents used in the management of hydrocodone and ibuprofen combination overdose, see:    • Charcoal, Activated (Oral-Local) monograph; and/or
   • Naloxone (Systemic) monograph.

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

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute and/or chronic
Hydrocodone
    
Cold, clammy skin{01}
    
drowsiness, severe{01}
    
slow heartbeat{01}
    
slow or troubled breathing{01}

Ibuprofen
    
Blurred vision{01}
    
difficulty hearing or ringing or buzzing in ears{01}
    
dizziness{01}
    
headache{01}
    
meningitis{01} (severe headache; drowsiness; confusion; stiff neck and/or back; general feeling of illness or nausea)
    
mood or mental changes{01}
    
nausea and/or vomiting{01}
    
skin rash{01}
    
stomach pain, severe{01}
    
swelling of the face, fingers, feet, or lower legs{01}



Treatment of overdose
To decrease absorption—Emptying the stomach via emesis or gastric lavage {01}. However, if gastric lavage is performed more than an hour after ingestion, the effectiveness of recovering the drug decreases {01}. Activated charcoal may also be used to reduce the absorption and reabsorption of ibuprofen {01}.

To enhance elimination—Administering urinary alkalizers may increase ibuprofen excretion {01}.

Dialysis is not likely to be of value because of ibuprofen's high degree of protein binding {01}.

Specific treatment—Administering the opioid antagonist naloxone. See the package insert or the Naloxone (Systemic) monograph for specific dosing guidelines for this product {01}.

Monitoring—Continuing to monitor the patient and administering additional naloxone as needed {01}.

Supportive care—Establishing adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled respiration {01}. Administering supportive measures as needed {01}. Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation {01}.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Hydrocodone and Ibuprofen (Systemic) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to hydrocodone or ibuprofen

Allergies to aspirin or any other nonsteroidal anti-inflammatory drugs (NSAIDs), or other opioid analgesics

Pregnancy—Regular use of opioids by pregnant women may cause physical dependence in the fetus and withdrawal symptoms in the neonate; use of NSAIDs are not recommended during the last trimester of pregnancy due to the potential adverse effects on renal blood flow





Breast-feeding—Use of hydrocodone and ibuprofen combination is not recommended for nursing mothers due to the potential adverse effects of ibuprofen on the neonate





Use in the elderly—Increased risk of toxicity, especially respiratory depression and gastrointestinal effects
Other medications, especially alcohol or other central nervous system (CNS) depressants; angiotensin-converting enzyme (ACE) inhibitors; anticoagulants, coumarin- or indandione-derivative; diuretics; lithium; methotrexate; monoamine oxidase (MAO) inhibitors; and tricyclic antidepressants
Other medical problems, especially allergic reaction; aspirin-induced nasal polyps associated with bronchospasm; coagulation disorders or platelet function disorders; peptic ulcer disease (active); renal disease (severe); renal function impairment; respiratory disease or impairment

Proper use of this medication
» Not taking more medication than prescribed

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

» Proper storage

Precautions while using this medication
» Avoiding use of alcoholic beverages or other CNS depressants during therapy, unless prescribed or otherwise approved by physician

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

» Caution when getting up from a lying or sitting position

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

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


Side/adverse effects
Signs of potential side effects, especially allergic reaction; arrhythmia; bronchitis; dyspnea; fever; frequent urge to urinate; gastrointestinal effects, including esophagitis; gastritis; gastroenteritis; hypotension; melena; tachycardia; tinnitus; urinary incontinence; urinary retention


General Dosing Information
Hydrocodone and ibuprofen combination may suppress respiration, especially in very young, elderly, very ill, or debilitated patients and those with respiratory problems {01}. Lower doses may be required for these patients {01}. Elderly patients also may be more sensitive to the analgesic effect of this medication so that lower doses or an increased dosing interval may be sufficient to provide effective analgesia {01}.

Dosage and dosing intervals should be individualized on the basis of the severity of pain, the condition of the patient, other medications given concurrently, and patient response {01}.

Concurrent use of other analgesics provides additive analgesia and may permit lower doses of the hydrocodone and ibuprofen combination to be utilized {01}.

Tolerance to many of the effects of hydrocodone and ibuprofen combination may develop with repeated administration {01}.

Psychological and physical dependence may occur with repeated administration of opioid analgesics {01}. However, the manufacturer states that physical dependence is not likely to develop with the short-term use of hydrocodone and ibuprofen combination {01}.

A reduction of the dosage may be required to prevent accumulation of hydrocodone and ibuprofen and/or their metabolites in patients with renal function impairment {01}.


Oral Dosage Forms

HYDROCODONE AND IBUPROFEN TABLETS

Usual adult dose
Analgesic
Oral, 1 tablet containing 7.5 mg of hydrocodone and 200 mg of ibuprofen every four to six hours as needed {01}.


Usual adult prescribing limits
5 tablets containing 7.5 mg of hydrocodone and 200 mg of ibuprofen in twenty-four hours {01}.

Usual pediatric dose
Safety and efficacy have not been established {01}.

Usual geriatric dose
See Usual adult dose .

Note: Dosage adjustment may be required {01}.


Strength(s) usually available
U.S.—


7.5 mg of hydrocodone and 200 mg of ibuprofen (Rx) [Vicoprofen{01} (colloidal silicon dioxide) (corn starch) (croscarmellose sodium) (hydroxypropyl methylcellulose) (magnesium stearate) (microcrystalline cellulose) (polyethylene glycol) (polysorbate 80) (titanium dioxide)]

Packaging and storage:
Store at 20 to 25 ºC (68 to 77 ºF) {01}.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • May be habit-forming

Note: Controlled substance in the U.S.




Developed: 07/13/1998
Revised: 07/13/1998



References
  1. Vicoprofen package insert (Knoll—US), Rev 8/97, Rec 5/98.
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