WARNINGS
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 AND DEPENDENCE).
Respiratory Depression
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 Perforation
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 health status.
Anaphylactoid Reactions
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 reaction occurs.
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 Effects).
Pregnancy
As with other NSAID-containing products, VICOPROFEN should be avoided in late pregnancy because it may cause premature closure of the ductus arteriosus.
PRECAUTIONS
General Precautions
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.
Cough Reflex
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.
Hepatic Effects
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.
Renal Effects
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 Disease).
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.
Hematological Effects
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 therapy.
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 failure.
Pre-existing Asthma
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 asthma.
Aseptic Meningitis
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 accordingly.
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 edema.
Laboratory Tests
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).
In patients with severe hepatic or renal disease, effects of therapy should be monitored with liver and/or renal function tests.
Drug Interactions
ACE-inhibitors
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.
Anticholinergics
The concurrent use of anticholinergics with hydrocodone preparations may produce paralytic ileus.
Antidepressants
The use of MAO inhibitors or tricyclic antidepressants with VICOPROFEN may increase the effect of either the antidepressant or hydrocodone.
Aspirin
As with other products containing NSAIDs, concomitant administration of VICOPROFEN and aspirin is not generally recommended because of the potential of increased adverse effects.
CNS Depressants
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 reduced.
Furosemide
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.
Lithium
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.
Methotrexate
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 methotrexate.
Warfarin
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
Pregnancy Category C.
Teratogenic Effects
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.
Nonteratogenic Effects
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 delivery.
Nursing Mothers
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.
Pediatric Use
The safety and effectiveness of VICOPROFEN in pediatric patients below the age of 16 have not been established.
Geriatric Use
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.
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