is supplied in a fixed combination tablet form for oral administration. VICOPROFEN
combines the opioid analgesic agent, hydrocodone bitartrate, with the nonsteroidal
anti-inflammatory (NSAID) agent, ibuprofen.
bitartrate is a semisynthetic and centrally acting opioid analgesic. Its
chemical name is: 4,5 α-epoxy-3-methoxy-17-methylmorphinan-6-one tartrate
(1:1) hydrate (2:5). Its chemical formula is: C18H21NO3•C4H6O6•2½H2O, and the molecular
weight is 494.50. Its structural formula is:
Ibuprofen is a nonsteroidal anti-inflammatory
drug with analgesic and antipyretic properties. Its chemical name is: (±)-2-(p-isobutylphenyl) propionic acid. Its chemical
formula is: C13H18O2, and the molecular
weight is: 206.29. Its structural formula is:
Hydrocodone is a semisynthetic opioid analgesic
and antitussive with multiple actions qualitatively similar to those of codeine.
Most of these involve the central nervous system and smooth muscle. The
precise mechanism of action of hydrocodone and other opioids is not known,
although it is believed to relate to the existence of opiate receptors in
the central nervous system. In addition to analgesia, opioids may produce
drowsiness, changes in mood, and mental clouding.
Ibuprofen is a non-steroidal anti-inflammatory agent
that possesses analgesic and antipyretic activities. Its mode action, like
that of other NSAIDs, is not completely understood, but may be related to
inhibition of cyclooxygenase activity and prostaglandin synthesis. Ibuprofen
is a peripherally acting analgesic. Ibuprofen does not have any known effects
on opiate receptors.
After oral dosing with the VICOPROFEN tablet,
a peak hydrocodone plasma level of 27 ng/mL is achieved at 1.7 hours,
and a peak ibuprofen plasma level of 30 mcg/mL is achieved at 1.8 hours.
The effect of food on the absorption of either component from the VICOPROFEN
tablet has not been established.
Ibuprofen is highly protein-bound (99%) like most
other non-steroidal anti-inflammatory agents. Although the extent of protein
binding of hydrocodone in human plasma has not been definitely determined,
structural similarities to related opioid analgesics suggest that hydrocodone
is not extensively protein bound. As most agents in the 5-ring morphinan
group of semi-synthetic opioids bind plasma protein to a similar degree (range 19% [hydromorphone]
to 45% [oxycodone]), hydrocodone is expected to fall within this range.
Hydrocodone exhibits a complex pattern of metabolism,
including O-demethylation, N-demethylation, and 6-keto reduction to the
corresponding 6-α-and 6-β-hydroxy metabolites. Hydromorphone,
a potent opioid, is formed from the O-demethylation
of hydrocodone and contributes to the total analgesic effect of hydrocodone.
The O- and N-demethylation processes are mediated by separate P-450 isoenzymes:
CYP2D6 and CYP3A4, respectively.
is present in this product as a racemate, and following absorption it undergoes
interconversion in the plasma from the R-isomer to the S-isomer. Both the
R- and S- isomers are metabolized to two primary metabolites: (+)-2-4'-(2hydroxy-2-methyl-propyl)
phenyl propionic acid and (+)-2-4'-(2carboxypropyl) phenyl propionic
acid, both of which circulate in the plasma at low levels relative to the
Hydrocodone and its metabolites are eliminated
primarily in the kidneys, with a mean plasma half-life of 4.5 hours. Ibuprofen
is excreted in the urine, 50% to 60% as metabolites and approximately 15%
as unchanged drug and conjugate. The plasma half-life is 2.2 hours.
No significant pharmacokinetic differences based
on age or gender have been demonstrated. The pharmacokinetics of hydrocodone
and ibuprofen from VICOPROFEN has not been evaluated in children.
The effect of renal insufficiency on the pharmacokinetics
of the VICOPROFEN dosage form has not been determined.
In single-dose studies of post surgical pain (abdominal,
gynecological, orthopedic), 940 patients were studied at doses of one
or two tablets. VICOPROFEN produced greater efficacy than placebo and each
of its individual components given at the same dose. No advantage was demonstrated
for the two-tablet dose.
INDICATIONS AND USAGE
VICOPROFEN tablets are indicated for the short-term
(generally less than 10 days) management of acute pain. VICOPROFEN is not
indicated for the treatment of such conditions as osteoarthritis or rheumatoid
VICOPROFEN should not be administered to patients
who previously have exhibited hypersensitivity to hydrocodone or ibuprofen.
VICOPROFEN should not be given to patients who have experienced asthma, urticaria,
or allergic-type reactions after taking aspirin or other NSAIDs. Severe,
rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in
such patients (see WARNINGS - Anaphylactoid Reactions, and PRECAUTIONS - Pre-existing Asthma).
to be hypersensitive to other opioids may exhibit cross-sensitivity to hydrocodone.
Abuse and Dependence
Hydrocodone can produce drug dependence of the morphine
type and therefore has the potential for being abused. Psychic and physical
dependence as well as tolerance may develop upon repeated administration of
this drug and it should be prescribed and administered with the same degree
of caution as other narcotic drugs (see DRUG ABUSE
At high doses or in opioid-sensitive patients, hydrocodone
may produce dose-related respiratory depression by acting directly on the
brain stem respiratory centers. Hydrocodone also affects the center that
controls respiratory rhythm, and may produce irregular and periodic breathing.
Head Injury and Increased Intracranial Pressure
The respiratory depressant effects of opioids and
their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated
in the presence of head injury, intracranial lesions or a pre-existing increase
in intracranial pressure. Furthermore, opioids produce adverse reactions
which may obscure the clinical course of patients with head injuries.
Acute Abdominal Conditions
The administration of opioids may obscure the diagnosis
or clinical course of patients with acute abdominal conditions.
Gastrointestinal (GI) Effects - Risk of GI Ulceration, Bleeding and
Serious gastrointestinal toxicity, such as inflammation,
bleeding, ulceration, and perforation of the stomach, small intestine or large
intestine, can occur at any time, with or without warning symptoms, in patients
treated with nonsteroidal anti-inflammatory drugs (NSAIDs). Minor upper GI
problems, such as dyspepsia, are common and may also occur at any time during
NSAID therapy. Therefore, physicians and patients should remain alert for
ulceration and bleeding even in the absence of previous GI tract symptoms.
Patients should be informed about the signs and/or symptoms of serious GI
toxicity and what steps to take if they occur. The utility of periodic laboratory
monitoring has not been demonstrated, nor has it been adequately assessed.
Only one in five patients, who develop a serious upper GI adverse event of
NSAID therapy, is symptomatic. Even short-term therapy is not without risk.
NSAIDs should be prescribed with extreme caution in those
with a prior history of ulcer disease or gastrointestinal bleeding. Most
spontaneous reports of fatal GI events are in elderly or debilitated patients
and therefore special care should be taken in treating this population. To
minimize the potential risk for an adverse GI event, the lowest effective
dose should be used for the shortest possible duration. For high risk patients,
alternate therapies that do not involve NSAIDs should be considered.
Studies have shown that patients with a prior history of
peptic ulcer disease and/or gastrointestinal bleeding and who use NSAIDs,
have a greater than 10-fold risk for developing a GI bleed than patients with
neither of these risk factors. In addition to a past history of ulcer disease,
pharmaco-epidemiological studies have identified several other co-therapies
or co-morbid conditions that may increase the risk for GI bleeding such as:
treatment with oral corticosteroids, treatment with anticoagulants, longer
duration of NSAID therapy, smoking, alcoholism, older age, and poor general
Anaphylactoid reactions may occur in patients without
known prior exposure to VICOPROFEN. VICOPROFEN should not be given to patients
with the aspirin triad. The triad typically occurs in asthmatic patients
who experience rhinitis with or without nasal polyps, or who exhibit severe,
potentially fatal bronchospasm after taking aspirin or other NSAIDs. Fatal
reactions to NSAIDs have been reported in such patients (see CONTRAINDICATIONS and PRECAUTIONS - Pre-existing Asthma). Emergency help should be sought when anaphylactoid
Advanced Renal Disease
In cases with advanced kidney disease, treatment
with VICOPROFEN is not recommended. If NSAID therapy, however, must
be initiated, close monitoring of the patient's kidney function
is advisable (see PRECAUTIONS - Renal
As with other NSAID-containing products, VICOPROFEN
should be avoided in late pregnancy because it may cause premature closure
of the ductus arteriosus.
Special Risk Patients
As with any opioid analgesic agent, VICOPROFEN
tablets should be used with caution in elderly or debilitated patients, and
those with severe impairment of hepatic or renal function, hypothyroidism,
Addison's disease, prostatic hypertrophy or urethral stricture. The
usual precautions should be observed and the possibility of respiratory depression
should be kept in mind.
Hydrocodone suppresses the cough reflex; as with
opioids, caution should be exercised when VICOPROFEN is used postoperatively
and in patients with pulmonary disease.
Effect on Diagnostic Signs
The antipyretic and anti-inflammatory activity
of ibuprofen may reduce fever and inflammation, thus diminishing their utility
as diagnostic signs in detecting complications of presumed noninfectious,
noninflammatory painful conditions.
As with other NSAIDs, ibuprofen has been reported
to cause borderline elevations of one or more liver enzymes; this may occur
in up to 15% of patients. These abnormalities may progress, may remain essentially
unchanged, or may be transient with continued therapy. Notable (3 times the
upper limit of normal) elevations of SGPT (ALT) or SGOT (AST) occurred in
controlled clinical trials in less than 1% of patients. A patient with symptoms
and/or signs suggesting liver dysfunction, or in whom an abnormal liver test
has occurred, should be evaluated for evidence of the development of more
severe hepatic reactions while on therapy with VICOPROFEN. Severe hepatic
reactions, including jaundice and cases of fatal hepatitis, have been reported
with ibuprofen as with other NSAIDs. Although such reactions are rare, if
abnormal liver tests persist or worsen, if clinical signs and symptoms consistent
with liver disease develop, or if systemic manifestations occur (e.g. eosinophilia,
rash, etc.), VICOPROFEN should be discontinued.
Caution should be used when initiating treatment
with VICOPROFEN in patients with considerable dehydration. It is advisable
to rehydrate patients first and then start therapy with VICOPROFEN. Caution
is also recommended in patients with pre-existing kidney disease (see WARNINGS - Advanced Renal
As with other NSAIDs,
long-term administration of ibuprofen has resulted in renal papillary necrosis
and other renal pathologic changes. Renal toxicity has also been seen in
patients in which renal prostaglandins have a compensatory role in the maintenance
of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory
drug may cause a dose-dependent reduction in prostaglandin formation and,
secondarily, in renal blood flow, which may precipitate overt renal decompensation.
Patients at greatest risk of this reaction are those with impaired renal
function, heart failure, liver dysfunction, those taking diuretics and ACE
inhibitors, and the elderly. Discontinuation of nonsteroidal anti-inflammatory
drug therapy is usually followed by recovery to the pretreatment state.
Ibuprofen metabolites are eliminated primarily by the
kidneys. The extent to which the metabolites may accumulate in patients with
renal failure has not been studied. Patients with significantly impaired
renal function should be more closely monitored.
Ibuprofen, like other NSAIDs, can inhibit platelet
aggregation but the effect is quantitatively less and of shorter duration
than that seen with aspirin. Ibuprofen has been shown to prolong bleeding
time in normal subjects. Because this prolonged bleeding effect may be exaggerated
in patients with underlying hemostatic defects, VICOPROFEN should be used
with caution in persons with intrinsic coagulation defects and those on anticoagulant
Anemia is sometimes seen in patients
receiving NSAIDs, including ibuprofen. This may be due to fluid retention,
GI loss, or an incompletely described effect upon erythropoiesis.
Fluid Retention and Edema
Fluid retention and edema have been reported in
association with ibuprofen; therefore, the drug should be used with caution
in patients with a history of cardiac decompensation, hypertension or heart
Patients with asthma may have aspirin-sensitive
asthma. The use of aspirin in patients with aspirin-sensitive asthma has
been associated with severe bronchospasm, which may be fatal. Since cross-reactivity
between aspirin and other NSAIDs has been reported in such aspirin-sensitive
patients, VICOPROFEN should not be administered to patients with this form
of aspirin sensitivity and should be used with caution in patients with pre-existing
Aseptic meningitis with fever and coma has been
observed on rare occasions in patients on ibuprofen therapy. Although it
is probably more likely to occur in patients with systemic lupus erythematosus
and related connective tissue diseases, it has been reported in patients who
do not have an underlying chronic disease. If signs or symptoms of meningitis
develop in a patient on VICOPROFEN, the possibility of its being related to
ibuprofen should be considered.
Information for Patients
VICOPROFEN (hydrocodone bitartrate 7.5 mg and ibuprofen
200 mg), like other opioid-containing analgesics, may impair mental and/or
physical abilities required for the performance of potentially hazardous tasks
such as driving a car or operating machinery; patients should be cautioned
Alcohol and other CNS depressants
may produce an additive CNS depression, when taken with this combination product,
and should be avoided.
VICOPROFEN may be habit-forming.
Patients should take the drug only for as long as it is prescribed, in the
amounts prescribed, and no more frequently than prescribed.
VICOPROFEN, like other drugs containing ibuprofen, is not
free of side effects. The side effects of these drugs can cause discomfort
and, rarely, there are more serious side effects, such as gastrointestinal
bleeding, which may result in hospitalization and even fatal outcomes. Patients
should be instructed to report any signs and symptoms of gastrointestinal
bleeding, blurred vision or other eye symptoms, skin rash, weight gain, or
A decrease in hemoglobin may occur during VICOPROFEN
therapy, and elevations of liver enzymes may be seen in a small percentage
of patients during VICOPROFEN therapy (see PRECAUTIONS - Hematological Effects and PRECAUTIONS - Hepatic Effects).
with severe hepatic or renal disease, effects of therapy should be monitored
with liver and/or renal function tests.
Reports suggest that NSAIDs may diminish the antihypertensive
effect of ACE-inhibitors. This interaction should be given consideration
in patients taking VICOPROFEN concomitantly with ACE-inhibitors.
The concurrent use of anticholinergics with hydrocodone
preparations may produce paralytic ileus.
The use of MAO inhibitors or tricyclic antidepressants
with VICOPROFEN may increase the effect of either the antidepressant or hydrocodone.
As with other products containing NSAIDs, concomitant
administration of VICOPROFEN and aspirin is not generally recommended because
of the potential of increased adverse effects.
Patients receiving other opioids, antihistamines,
antipsychotics, antianxiety agents, or other CNS depressants (including alcohol)
concomitantly with VICOPROFEN may exhibit an additive CNS depression. When
combined therapy is contemplated, the dose of one or both agents should be
Ibuprofen has been shown to reduce the natriuretic
effect of furosemide and thiazides in some patients. This response has been
attributed to inhibition of renal prostaglandin synthesis. During concomitant
therapy with VICOPROFEN the patient should be observed closely for signs of
renal failure (see PRECAUTIONS - Renal
Effects), as well as diuretic efficacy.
Ibuprofen has been shown to elevate plasma lithium
concentration and reduce renal lithium clearance. This effect has been attributed
to inhibition of renal prostaglandin synthesis by ibuprofen. Thus, when VICOPROFEN
and lithium are administered concurrently, patients should be observed for
signs of lithium toxicity.
Ibuprofen, as well as other NSAIDs, has been reported
to competitively inhibit methotrexate accumulation in rabbit kidney slices.
This may indicate that ibuprofen could enhance the toxicity of methotrexate.
Caution should be used when VICOPROFEN is administered concomitantly with
The effects of warfarin and NSAIDs on GI bleeding
are synergistic, such that users of both drugs together have a risk of serious
GI bleeding higher than users of either drug alone.
Carcinogenicity, Mutagenicity, and Impairment of Fertility
The carcinogenic and mutagenic potential of VICOPROFEN
has not been investigated. The ability of VICOPROFEN to impair fertility
has not been assessed.
Pregnancy Category C.
VICOPROFEN, administered to rabbits at 95 mg/kg
(5.72 and 1.9 times the maximum clinical dose based on body weight and
surface area, respectively), a maternally toxic dose, resulted in an increase
in the percentage of litters and fetuses with any major abnormality and
an increase in the number of litters and fetuses with one or more nonossified
metacarpals (a minor abnormality). VICOPROFEN, administered to rats at 166
mg/kg (10.0 and 1.66 times the maximum clinical dose based on body weight
and surface area, respectively), a maternally toxic dose, did not result in
any reproductive toxicity. There are no adequate and well-controlled studies
in pregnant women. VICOPROFEN should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus.
Because of the known effects of nonsteroidal anti-inflammatory
drugs on the fetal cardiovascular system (closure of the ductus arteriosus),
use during pregnancy (particularly late pregnancy) should be avoided. Babies
born to mothers who have been taking opioids regularly prior to delivery will
be physically dependent. The withdrawal signs include irritability and excessive
crying, tremors, hyperactive reflexes, increased respiratory rate, increased
stools, sneezing, yawning, vomiting, and fever. The intensity of the syndrome
does not always correlate with the duration of maternal opioid use or dose.
There is no consensus on the best method of managing withdrawal.
Labor and Delivery
As with other drugs known to inhibit prostaglandin
synthesis, an increased incidence of dystocia and delayed parturition occurred
in rats. Administration of VICOPROFEN is not recommended during labor and
It is not known whether hydrocodone is excreted
in human milk. In limited studies, an assay capable of detecting 1 mcg/mL
did not demonstrate ibuprofen in the milk of lactating mothers. However,
because of the limited nature of the studies, and the possible adverse effects
of prostaglandin-inhibiting drugs on neonates, VICOPROFEN is not recommended
for use in nursing mothers.
The safety and effectiveness of VICOPROFEN in pediatric
patients below the age of 16 have not been established.
In controlled clinical trials there was no difference
in tolerability between patients < 65 years of age and those≥ 65, apart from an increased tendency of the elderly to develop constipation.
However, because the elderly may be more sensitive to the renal and gastrointestinal
effects of nonsteroidal anti-inflammatory agents as well as possible increased
risk of respiratory depression with opioids, extra caution and reduced dosages
should be used when treating the elderly with VICOPROFEN.
VICOPROFEN was administered to approximately 300 pain
patients in a safety study that employed dosages and a duration of treatment
sufficient to encompass the recommended usage (see DOSAGE
AND ADMINISTRATION). Adverse event rates generally increased with
increasing daily dose. The event rates reported below are from approximately
150 patients who were in a group that received one tablet of VICOPROFEN an
average of three to four times daily. The overall incidence rates of adverse
experiences in the trials were fairly similar for this patient group and those
who received the comparison treatment, acetaminophen 600 mg with codeine 60
The following lists adverse events that occurred
with an incidence of 1% or greater in clinical trials of VICOPROFEN, without
regard to the causal relationship of the events to the drug. To distinguish
different rates of occurrence in clinical studies, the adverse events are
listed as follows:
of adverse event = less than 3%
adverse events marked with an asterisk
* = 3% to 9%
VICOPROFEN Tablets are a Schedule III controlled
Psychic dependence, physical dependence, and tolerance
may develop upon repeated administration of opioids; therefore, VICOPROFEN
Tablets should be prescribed and administered with the same degree of caution
appropriate to use of other oral narcotic medications.
Physical dependence, the condition in which continued
administration of the drug is required to prevent the appearance of a withdrawal
syndrome, assumes clinically significant proportions only after several weeks
of continued opioid use, although a mild degree of physical dependence may
develop after a few days of opioid therapy. Tolerance, in which increasingly
large doses are required in order to produce the same degree of analgesia,
is manifested initially by a shortened duration of analgesic effect, and subsequently
by decreases in the intensity of analgesia. The rate of development of tolerance
varies among patients. However, psychic dependence is unlikely to develop
when VICOPROFEN Tablets are used for a short time for the treatment of acute
Following an acute overdosage, toxicity may result
from hydrocodone and/or ibuprofen.
Signs and Symptoms
Serious overdose with hydrocodone is characterized
by respiratory depression (a decrease in respiratory rate and/or tidal volume,
Cheyne-Stokes respiration, cyanosis) extreme somnolence progressing to stupor
or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia
and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac
arrest and death may occur.
Symptoms include gastrointestinal irritation with
erosion and hemorrhage or perforation, kidney damage, liver damage, heart
damage, hemolytic anemia, agranulocytosis, thrombocytopenia, aplastic anemia,
and meningitis. Other symptoms may include headache, dizziness, tinnitus,
confusion, blurred vision, mental disturbances, skin rash, stomatitis, edema,
reduced retinal sensitivity, corneal deposits, and hyperkalemia.
Primary attention should be given to the re-establishment
of adequate respiratory exchange through provision of a patent airway and
the institution of assisted or controlled ventilation. Naloxone, a narcotic
antagonist, can reverse respiratory depression and coma associated with opioid
overdose or unusual sensitivity to opioids, including hydrocodone. Therefore,
an appropriate dose of naloxone hydrochloride should be administered intravenously
with simultaneous efforts at respiratory resuscitation. Since the duration
of action of hydrocodone may exceed that of the naloxone, the patient should
be kept under continuous surveillance and repeated doses of the antagonist
should be administered as needed to maintain adequate respiration. Supportive
measures should be employed as indicated. Gastric emptying may be useful
in removing unabsorbed drug. In cases where consciousness is impaired it
may be inadvisable to perform gastric lavage. If gastric lavage is performed,
little drug will likely be recovered if more than an hour has elapsed sinceingestion. Ibuprofen is acidic and is excreted in the urine; therefore, it
may be beneficial to administer alkali and induce diuresis. In addition to
supportive measures the use of oral activated charcoal may help to reduce
the absorption and reabsorption of ibuprofen. Dialysis is not likely to be
effective for removal of ibuprofen because it is very highly bound to plasma
DOSAGE AND ADMINISTRATION
For the short-term (generally less than 10 days) management
of acute pain, the recommended dose of VICOPROFEN is one tablet every 4 to
6 hours, as necessary. Dosage should not exceed 5 tablets in a 24-hour period.
It should be kept in mind that tolerance to hydrocodone can develop with
continued use and that the incidence of untoward effects is dose related.
The lowest effective dose or the longest dosing interval should
be sought for each patient, especially in the elderly. After observing the
initial response to therapy with VICOPROFEN, the dose and frequency of dosing
should be adjusted to suit the individual patient's need, without exceeding
the total daily dose recommended.
VICOPROFEN tablets are available as: White film-coated
round convex tablets, engraved with "VP" over Abbott
"A" logo on one side and plain on the other side.
Bottles of 100-NDC 0074-2277-14 Bottles of 500-NDC
0074-2277-54 Hospital Unit Dosage Package-100 tablets (4 × 25
Store at 25°C (77°F); excursions permitted
to 15°-30°C (59°-86°F). [See USP Controlled Room Temperature].