Skip to Content

Oxycodone and Ibuprofen

Generic Name: oxycodone hydrochloride and ibuprofen
Dosage Form: tablet, film coated

CII

40-9065

Revised – March 2016

Rx Only

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; CARDIOVASCULAR THROMBOTIC EVENTS; and GASTROINTESTINAL RISK

Addiction, Abuse, and Misuse
Oxycodone hydrochloride and ibuprofen tablets expose patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing oxycodone hydrochloride and ibuprofen tablets, and monitor all patients regularly for the development of these behaviors or conditions [see WARNINGS].

Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of oxycodone hydrochloride and ibuprofen tablets. Monitor for respiratory depression, especially during initiation of oxycodone hydrochloride and ibuprofen tablets or following a dose increase [see WARNINGS].

Accidental Ingestion
Accidental ingestion of even one dose of oxycodone hydrochloride and ibuprofen tablets, especially by children, can result in a fatal overdose of oxycodone hydrochloride and ibuprofen tablets [see WARNINGS].

Neonatal Opioid Withdrawal Syndrome
Prolonged use of oxycodone hydrochloride and ibuprofen tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see WARNINGS].

Cytochrome P450 3A4 Interaction
The concomitant use of oxycodone hydrochloride and ibuprofen tablets with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone hydrochloride and ibuprofen tablets plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone hydrochloride and ibuprofen tablets plasma concentration. Monitor patients receiving oxycodone hydrochloride and ibuprofen tablets and any CYP3A4 inhibitor or inducer [see CLINICAL PHARMACOLOGY, WARNINGS, PRECAUTIONS; Drug Interactions].

Cardiovascular Thrombotic Events
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use [see WARNINGS and PRECAUTIONS].

Oxycodone hydrochloride and Ibuprofen is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see CONTRAINDICATIONS and WARNINGS].

Gastrointestinal Risk
NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events [see WARNINGS].

Oxycodone and Ibuprofen Description

Each combination tablet contains: Oxycodone hydrochloride, USP 5 mg and ibuprofen, USP 400 mg.

Oxycodone hydrochloride and ibuprofen is supplied in a fixed combination tablet form for oral administration and combines the opioid analgesic agent, oxycodone hydrochloride, with the nonsteroidal anti-inflammatory (NSAID) agent, ibuprofen.

Oxycodone hydrochloride, USP is a centrally acting semisynthetic opioid analgesic. Its chemical name is 4,5α-Epoxy-14-hydroxy-3-methoxy-methylmorphinan-6-one hydrochloride. Its molecular formula is C18H21NO4 HCl and molecular weight is 351.83. Its structural formula is:

Ibuprofen, USP is a nonsteroidal anti-inflammatory drug with analgesic and antipyretic properties. Its chemical name is (±)-2-(p-isobutylphenyl) propionic acid. Its molecular formula is C13H18O2 and molecular weight is 206.29. Its structural formula is:

Inactive ingredients in oxycodone hydrochloride and ibuprofen tablets include: calcium stearate, croscarmellose sodium, colloidal silicon dioxide, hydroxypropyl cellulose, microcrystalline cellulose, pregelatinized starch (corn), and stearic acid. The coloring agents consist of hypromellose, lactose monohydrate, polyethylene glycol, synthetic yellow iron oxide, titanium dioxide, and triacetin.

Oxycodone and Ibuprofen - Clinical Pharmacology

Oxycodone hydrochloride component:

Oxycodone hydrochloride is a semisynthetic opioid analgesic with multiple actions which involve the central nervous system and smooth muscle. The mechanism of action of oxycodone is not known but is thought to be related to its binding to opiate receptors in the central nervous system. In addition to analgesia, opioids may produce sedation and respiratory depression.

Ibuprofen component:

Ibuprofen is a nonsteroidal anti-inflammatory agent that possesses analgesic and antipyretic activities. Its mode of action, similar to other NSAIDs, is not completely understood, but is thought to be related to its inhibition of cyclooxygenase activity and prostaglandin synthesis. Ibuprofen is a peripherally acting analgesic. Ibuprofen does not have any known effects on opiate receptors.

Pharmacokinetics

Absorption:

Oxycodone is rapidly absorbed after single dose administration of oxycodone hydrochloride and ibuprofen tablets. Maximum concentrations (Cmax) of oxycodone, ranging from 9.8 ng/mL to 11.7 ng/mL, are obtained within 1.3 hr to 2.1 hr after administration of oxycodone hydrochloride and ibuprofen. Repeated administration of oxycodone hydrochloride and ibuprofen, every 6 hours, results in approximately 50% to 65% increase in Cmax. In the presence of food, the bioavailability of oxycodone is slightly (25%) increased.

Ibuprofen is rapidly absorbed after oral administration of oxycodone hydrochloride and ibuprofen tablets. Cmax values range from 18.5 mcg/mL to 34.3 mcg/mL and are reached 1.6 hr to 3.1 hr after oral administration of oxycodone hydrochloride and ibuprofen. Repeated administration of oxycodone hydrochloride and ibuprofen every 6 hours does not result in any accumulation of ibuprofen. The bioavailability of ibuprofen is not altered in the presence of food.

Distribution:

Oxycodone binding to protein in serum is approximately 45%.

Ibuprofen is extensively bound to plasma proteins (99%).

Metabolism:

Oxycodone is metabolized in the liver by means of N-demethylation and O-demethylation, 6-ketoreduction and glucuronidation. The major circulating metabolite is noroxycodone, which possesses weak analgesic activity.

Oxymorphone, the end product of O-demethylation, has analgesic activity but is present in the plasma at low concentrations. Metabolism of oxycodone to oxymorphone occurs via CYP2D6.

Ibuprofen is present 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'-(2-hydroxy-2-methyl-propyl) phenyl propionic acid and (+)-2-4'-(2-carboxypropyl) phenyl propionic acid, both of which circulate in the plasma at low levels relative to the parent.

Elimination:

Oxycodone is eliminated from the systemic circulation with half life (T1/2) values ranging from 3.1 hr to 3.7 hr after single dose administration of oxycodone hydrochloride and ibuprofen tablets. Urinary excretion of unchanged oxycodone amounts to approximately 4% of the administered oxycodone dose.

Ibuprofen is eliminated from the systemic circulation with half life (T1/2) values ranging from 1.8 hr to 2.6 hr after single dose administration of oxycodone hydrochloride and ibuprofen tablets. Urinary excretion of unchanged ibuprofen is minimal (less than 0.2% of administered ibuprofen dose).

Special Populations:

Gender: There are no gender effects on the pharmacokinetics of oxycodone or ibuprofen after administration of oxycodone hydrochloride and ibuprofen tablets.

Age: The effects of age on the pharmacokinetics of Oxycodone and Ibuprofen after administration of oxycodone hydrochloride and ibuprofen tablets have not been evaluated.

When either drug was administered alone, the pharmacokinetics of Oxycodone and Ibuprofen were similar in elderly subjects, compared to young healthy subjects.

Pediatrics: The pharmacokinetics of Oxycodone and Ibuprofen after administration of oxycodone hydrochloride and ibuprofen tablets has not been evaluated in a pediatric population.

Renal Impairment: The effects of renal impairment on the pharmacokinetics of Oxycodone and Ibuprofen after administration of oxycodone hydrochloride and ibuprofen tablets have not been evaluated.

Hepatic Impairment: The effects of hepatic impairment on the pharmacokinetics of Oxycodone and Ibuprofen after administration of oxycodone hydrochloride and ibuprofen tablets have not been evaluated [see PRECAUTIONS; Hepatic Effects].

Clinical Studies

Oxycodone hydrochloride and ibuprofen combination product was investigated in three clinical studies. Two studies involving a total of 949 patients following dental surgery (removal of ipsilateral molars) and a third study of 456 patients following abdominal/pelvic surgery were conducted. In the three studies patients were administered a single dose of the oxycodone hydrochloride and ibuprofen tablets, ibuprofen alone, oxycodone hydrochloride alone or placebo for acute, moderate to severe pain.

In these single dose studies, oxycodone hydrochloride and ibuprofen combination product produced greater efficacy than placebo and each of oxycodone hydrochloride and ibuprofen tablets individual components as measured by the magnitude of pain relief and the reduction in pain intensity through six hours. No multiple dose efficacy studies have been performed with oxycodone hydrochloride and ibuprofen.

Indications and Usage for Oxycodone and Ibuprofen

Oxycodone hydrochloride and ibuprofen tablets are indicated for the management of short term (no more than 7 days)  acute to moderate pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate

Limitations of Use

Because of the risks of addiction, abuse, and misuse, with opioids, even at recommended doses [see WARNINGS], reserve oxycodone hydrochloride and ibuprofen tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics]:

  •  Have not been tolerated, or are not expected to be tolerated,
  • Have not provided adequate analgesia, or are not expected to provide adequate analgesia

Carefully consider the potential benefits and risks of oxycodone hydrochloride and ibuprofen tablets and other treatment options before deciding to use oxycodone hydrochloride and ibuprofen tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals [see WARNINGS].

 

Contraindications

Oxycodone hydrochloride and ibuprofen tablets are contraindicated in patients with:

  •  Significant respiratory depression [see WARNINGS]
  • Acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in the absence of resuscitative equipment [see WARNINGS]

  • Previously exhibiting hypersensitivity to oxycodone , ibuprofen, or any components in oxycodone hydrochloride and ibuprofen tablets  

  • Known hypersensitivity to other opioids

  • Known or suspected paralytic ileus.

  • Experiencing asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe anaphylactoid reactions to NSAIDs, some of which were fatal, have been reported in such patients [see WARNINGS; Anaphylactoid Reactions, and PRECAUTIONS; Pre-existing Asthma].

  • The setting of coronary artery bypass graft (CABG) surgery [see WARNINGS].

Warnings

Addiction, Abuse, and Misuse

Oxycodone hydrochloride and ibuprofen tablets contain oxycodone hydrochloride, a Schedule II controlled substance. As an opioid, oxycodone hydrochloride and ibuprofen tablets exposes users to the risks of addiction, abuse, and misuse [see DRUG ABUSE AND DEPENDENCE].

Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed oxycodone hydrochloride and ibuprofen tablets. Addiction can occur at recommended dosages and if the drug is misused or abused.

Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing oxycodone hydrochloride and ibuprofen tablets, and monitor all patients receiving oxycodone hydrochloride and ibuprofen tablets for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as oxycodone hydrochloride and ibuprofen tablets, but use in such patients necessitates intensive counseling about the risks and proper use of oxycodone hydrochloride and ibuprofen tablets along with intensive monitoring for signs of addiction, abuse, and misuse.

Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing oxycodone hydrochloride and ibuprofen tablets. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see PRECAUTIONS; Information for Patients]. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see OVERDOSAGE]. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of oxycodone hydrochloride and ibuprofen tablets, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with and following dosage increases of oxycodone hydrochloride and ibuprofen tablets.

To reduce the risk of respiratory depression, proper dosing and titration of oxycodone hydrochloride and ibuprofen tablets are essential [see DOSAGE AND ADMINISTRATION].  Overestimating the oxycodone hydrochloride and ibuprofen tablets dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.

Accidental ingestion of even one dose of oxycodone hydrochloride and ibuprofen tablets, especially by children, can result in respiratory depression and death due to an overdose of oxycodone hydrochloride.

Neonatal Opioid Withdrawal Syndrome

Prolonged use of oxycodone hydrochloride and ibuprofen tablets during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see PRECAUTIONS; Information for Patients, Pregnancy].

Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers

Concomitant use of oxycodone hydrochloride and ibuprofen tablets with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of oxycodone hydrochloride and ibuprofen and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression [see WARNINGS], particularly when an inhibitor is added after a stable dose of oxycodone hydrochloride and ibuprofen tablets is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in oxycodone hydrochloride and ibuprofen tablets-treated patients may increase oxycodone hydrochloride and ibuprofen plasma concentrations and prolong opioid adverse reactions. When using oxycodone hydrochloride and ibuprofen tablets with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in oxycodone hydrochloride and ibuprofen tablets-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of oxycodone hydrochloride and ibuprofen tablets until stable drug effects are achieved. [see PRECAUTIONS; Drug Interactions].

Concomitant use of oxycodone hydrochloride and ibuprofen tablets with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease oxycodone hydrochloride and ibuprofen plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to oxycodone hydrochloride and ibuprofen tablets. When using oxycodone hydrochloride and ibuprofen tablets with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur [see PRECAUTIONSDrug Interactions]

Risks due to Interactions with Central Nervous System Depressants

Hypotension, profound sedation, respiratory depression, coma, and death may result if oxycodone hydrochloride and ibuprofen tablets is used concomitantly with alcohol or other central nervous system (CNS) depressants (e.g., benzodiazepines and other sedatives/hypnotics, anxiolytics, and tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids).

When considering the use of oxycodone hydrochloride and ibuprofen tablets in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient’s response, including the degree of tolerance that has developed to CNS depression. Additionally, evaluate the patient’s use of alcohol or illicit drugs that can cause CNS depression. If the decision to begin oxycodone hydrochloride and ibuprofen tablets is made, start with a lower dosage of oxycodone hydrochloride and ibuprofen tablets, monitor patients for signs of respiratory depression, sedation, and hypotension, and consider using a lower dose of the concomitant CNS depressant [see PRECAUTIONS; Drug Interactions].

Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients

The use of oxycodone hydrochloride and ibuprofen tablets in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

Patients with Chronic Pulmonary Disease: Oxycodone hydrochloride and ibuprofen tablets-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of oxycodone hydrochloride and ibuprofen tablets [see WARNINGS].

Elderly, Cachetic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients [see WARNINGS].

Monitor such patients closely, particularly when initiating and titrating oxycodone hydrochloride and ibuprofen tablets and when oxycodone hydrochloride and ibuprofen tablets are given concomitantly with other drugs that depress respiration [see WARNINGS].  Alternatively, consider the use of non-opioid analgesics in these patients.

Adrenal Insufficiency

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than 1 month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure.  If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

Hypotensive Effect

Oxycodone hydrochloride and ibuprofen tablets, like all opioid analgesics, may cause severe hypotension in an individual whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs such as phenothiazines or other agents which compromise vasomotor tone. Oxycodone hydrochloride and ibuprofen tablets may produce orthostatic hypotension in ambulatory patients. Oxycodone hydrochloride and ibuprofen tablets, like all opioid analgesics, should be administered with caution to patients in circulatory shock, since vasodilatation produced by the drug may further reduce cardiac output and blood pressure.

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 that may obscure the clinical course of patients with head injuries.

 

Cardiovascular Effects

Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.

To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.

There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as Oxycodone and Ibuprofen tablets, increases the risk of serious gastrointestinal (GI) events [see Warnings].

Status Post Coronary Artery Bypass Graft (CABG) Surgery

Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG [see Contraindications].

Post-MI Patients

Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up.

Avoid the use of Oxycodone and Ibuprofen tablets in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If Oxycodone and Ibuprofen tablets are used in patients with a recent MI, monitor patients for signs of cardiac ischemia.

Hypertension

NSAIDs, including oxycodone hydrochloride and ibuprofen tablets, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events.

Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including oxycodone hydrochloride and ibuprofen tablets, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.

Heart Failure and Edema

The Coxib and traditional NSAID Trialists’ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.

Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of Oxycodone and Ibuprofen may blunt the CV effects of several therapeutic agents used to treat these medical conditions [e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers (ARBs)] [see Drug Interactions].

Avoid the use of Oxycodone and Ibuprofen tablets in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If Oxycodone and Ibuprofen tablets are used in patients with severe heart failure, monitor patients for signs of worsening heart failure.

Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation

NSAIDs, including oxycodone hydrochloride and ibuprofen tablets, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3 to 6 months, and in about 2% to 4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, 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. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. 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 in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.

Acute Abdominal Conditions

The administration of opioids may obscure the diagnosis or clinical course of patients with acute abdominal conditions.

Anaphylactoid Reactions

Anaphylactoid reactions may occur in patients without known prior exposure to oxycodone hydrochloride and ibuprofen. Oxycodone hydrochloride and ibuprofen tablets should not be given to patients with the aspirin triad or a history of angioedema. 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.

Renal Effects

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom 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 NSAID therapy is usually followed by recovery to the pretreatment state.

Advanced Renal Disease

In patients with advanced kidney disease, treatment with oxycodone hydrochloride and ibuprofen tablets is not recommended. No information is available from controlled clinical studies regarding the use of oxycodone hydrochloride and ibuprofen tablets in patients with advanced renal disease. However, if oxycodone hydrochloride and ibuprofen tablets therapy must be initiated, due to the NSAID component, close monitoring of the patient’s kidney function is advisable [see WARNINGS; Renal Effects].

Skin Reactions

NSAIDs, including oxycodone hydrochloride and ibuprofen tablets, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

Pregnancy

Starting at 30 weeks gestation, oxycodone hydrochloride and ibuprofen tablets, and other NSAIDs, should be avoided by pregnant women as premature closure of the ductus arteriosus may occur.

Precautions

General

Oxycodone hydrochloride and ibuprofen cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.

The pharmacological activity of oxycodone hydrochloride and ibuprofen in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

Special Risk Patients

As with any opioid analgesic agent, oxycodone hydrochloride and ibuprofen tablets should be used with caution in elderly or debilitated patients, and those with severe impairment of hepatic, pulmonary or renal function, hypothyroidism, Addison's disease, acute alcoholism, convulsive disorders, CNS depression or coma, delirium tremens, kyphoscoliosis associated with respiratory depression, toxic psychosis, prostatic hypertrophy or urethral stricture. The usual precautions should be observed and the possibility of respiratory depression, postural hypotension, and altered mental states should be kept in mind.

Use in Pancreatic/Biliary Tract Disease

Oxycodone hydrochloride and ibuprofen may cause spasm of the sphincter of Oddi and should be used with caution in patients with biliary tract disease, including acute pancreatitis. Opioids like oxycodone hydrochloride and ibuprofen may cause increases in the serum amylase level.

Cough Reflex

Oxycodone suppresses the cough reflex; as with other opioid containing products, caution should be exercised when oxycodone hydrochloride and ibuprofen is used postoperatively and in patients with pulmonary disease.

Hepatic Effects

Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including ibuprofen as found in oxycodone hydrochloride and ibuprofen tablets. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.

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 a more severe hepatic reaction while on therapy with oxycodone hydrochloride and ibuprofen. If clinical signs and symptoms consistent with liver disease develop, or if systematic manifestations occur (e.g., eosinophilia, rash, etc.), oxycodone hydrochloride and ibuprofen should be discontinued.

Hematological Effects

Anemia is sometimes seen in patients receiving NSAIDs, including ibuprofen as found in oxycodone hydrochloride and ibuprofen tablets. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including ibuprofen, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.

NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving oxycodone hydrochloride and ibuprofen who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored. Patients previously treated with NSAIDs and currently using oxycodone hydrochloride and ibuprofen should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.

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 can be fatal. Since cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, oxycodone hydrochloride and ibuprofen tablets 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 as found in oxycodone hydrochloride and ibuprofen tablets. 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 oxycodone hydrochloride and ibuprofen tablets, the possibility of its being related to ibuprofen should be considered.

Information for Patients

Patients should be informed of the following information before initiating therapy with oxycodone hydrochloride and ibuprofen tablets and periodically during the course of ongoing therapy. Patients should also be encouraged to read the Medication Guide that accompanies each prescription dispensed.

Addiction, Abuse, and Misuse

Inform patients that the use of oxycodone hydrochloride and ibuprofen tablets, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see WARNINGS]. Instruct patients not to share oxycodone hydrochloride and ibuprofen tablets with others and to take steps to protect oxycodone hydrochloride and ibuprofen tablets from theft or misuse.

Life-Threatening Respiratory Depression

Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting oxycodone hydrochloride and ibuprofen tablets or when the dosage is increased, and that it can occur even at recommended dosages [see WARNINGS]. Advise patients how to recognize respiratory depression and to seek medical attention if breathing difficulties develop.

Accidental Ingestion

Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see WARNINGS].  Instruct patients to take steps to store oxycodone hydrochloride and ibuprofen tablets securely and to dispose of unused oxycodone hydrochloride and ibuprofen tablets by flushing the unused tablets down the toilet when they are no longer needed.

Interactions with Alcohol and Other CNS Depressants

Inform patients that potentially serious additive effects may occur if oxycodone hydrochloride and ibuprofen tablets are used with alcohol or other CNS depressants and not to use such drugs unless supervised by a health care provider [see WARNINGS, PRECAUTIONS; Drug Interactions].

Serotonin Syndrome

Inform patients that oxycodone hydrochloride and ibuprofen tablets could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their physicians if they are taking, or plan to take serotonergic medications [see PRECAUTIONSDrug Interactions].

Adrenal Insufficiency

Inform patients that oxycodone hydrochloride and ibuprofen tablets could cause adrenal insufficiency, a potentially life- threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients to seek medical attention if they experience a constellation of these symptoms [see WARNINGS].

Pregnancy

Neonatal Opioid Withdrawal Syndrome

Inform patients that prolonged use of oxycodone hydrochloride and ibuprofen tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated [see WARNINGS, PRECAUTIONS; Pregnancy].

Embryo-Fetal Toxicity

Inform female patients of reproductive potential that oxycodone hydrochloride and ibuprofen tablets can cause fetal harm and to inform the prescriber of a known or suspected pregnancy [see PRECAUTIONS; Pregnancy].

Lactation

Advise nursing mothers to monitor infants for increased sleepiness (more than usual), breathing

difficulties, or limpness. Instruct nursing mothers to seek immediate medical care if they notice these signs [see PRECAUTIONS; Nursing Mothers].

Driving and/or Operating Heavy Machinery

Oxycodone hydrochloride and ibuprofen tablets, similar to 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.

Cardiovascular Thrombotic Events

Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately [see WARNINGS].

Gastrointestinal Conditions

Oxycodone hydrochloride and ibuprofen like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up [see WARNINGS; Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation].

Skin Reactions

Oxycodone hydrochloride and ibuprofen, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever or other signs of hypersensitivity, and should ask medical advice when observing any indicative signs or symptoms. Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physician as soon as possible.

Heart Failure and Edema

Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur [see WARNINGS].

Hepatic Effects

Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritius, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If these occur, patients should be instructed to seek immediate medical therapy.

Anaphylactoid Reactions

Patients should be informed of the signs and symptoms of an anaphylactoid reaction (e.g. difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help [see WARNINGS].

Laboratory Tests

Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs should have their CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g. eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, oxycodone hydrochloride and ibuprofen should be discontinued.

Disposal of Unused Oxycodone Hydrochloride and Ibuprofen Tablets

Advise patients to flush the unused oxycodone hydrochloride and ibuprofen tablets down the toilet when no longer needed.

Drug Interactions

Drugs Affecting Cytochrome P450 Isoenzymes

Inhibitors of CYP3A4 and CYP2D6

The concomitant use of oxycodone hydrochloride and ibuprofen tablets and CYP3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), and protease inhibitors (e.g., ritonavir), can increase the plasma concentration of oxycodone hydrochloride and ibuprofen, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of oxycodone hydrochloride and ibuprofen tablets and CYP3A4 inhibitors, particularly when an inhibitor is added after a stable dose of oxycodone hydrochloride and ibuprofen tablets is achieved [see WARNINGS].

After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the oxycodone hydrochloride and ibuprofen plasma concentration will decrease [see CLINICAL PHARMACOLOGY], resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to oxycodone hydrochloride and ibuprofen tablets.

If concomitant use is necessary, consider dosage reduction of oxycodone hydrochloride and ibuprofen tablets until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the oxycodone hydrochloride and ibuprofen tablets dosage until stable drug effects are achieved [see DOSAGE AND ADMINISTRATION]. Monitor for signs of opioid withdrawal.

Oxycodone is metabolized in part to oxymorphone via the cytochrome P450 isoenzyme CYP2D6. While this pathway may be blocked by a variety of drugs (e.g., certain cardiovascular drugs and antidepressants), such blockade has not yet been shown to be of clinical significance with this agent. However, clinicians should be aware of this possible interaction [see CLINICAL PHARMACOLOGY].

Inducers of CYP3A4

The concomitant use of oxycodone hydrochloride and ibuprofen tablets and CYP3A4 inducers, such as rifampin, carbamazepine, and phenytoin, can decrease the plasma concentration of oxycodone hydrochloride and ibuprofen [see CLINICAL PHARMACOLOGY], resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to oxycodone hydrochloride and ibuprofen tablets [see WARNINGS].

After stopping a CYP3A4 inducer, as the effects of the inducer decline, the oxycodone hydrochloride and ibuprofen plasma concentration will increase [see CLINICAL PHARMACOLOGY], which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression.

If concomitant use is necessary, consider increasing the oxycodone hydrochloride and ibuprofen tablets dosage until stable drug effects are achieved [see DOSAGE AND ADMINISTRATION]. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider oxycodone hydrochloride and ibuprofen tablets dosage reduction and monitor for signs of respiratory depression.

Central Nervous System Depressants

Due to additive pharmacologic effect, the concomitant use of CNS depressants such as alcohol, benzodiazepines and other sedative hypnotics, anxiolytics, and tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.

Consider dose reduction of one or both drugs. Monitor patients for signs of respiratory depression, sedation, and hypotension [see WARNINGS].

Serotonergic Drugs

The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue), has resulted in serotonin syndrome [see PRECAUTIONS; Information for Patients].

If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue oxycodone hydrochloride and ibuprofen tablets if serotonin syndrome is suspected.

Anticholinergics

The concurrent use of anticholinergics with oxycodone preparations may produce paralytic ileus.

ACE-Inhibitors

Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking oxycodone hydrochloride and ibuprofen concomitantly with ACE-inhibitors.

Aspirin

When oxycodone hydrochloride and ibuprofen is administered with aspirin, its protein binding is reduced, although the clearance of free oxycodone hydrochloride and ibuprofen is not altered. The clinical significance of this interaction is not known; however as with other products containing NSAIDs, concomitant administration of oxycodone hydrochloride and ibuprofen and aspirin is not generally recommended because of the potential of increased adverse effects.

Diuretics

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 oxycodone hydrochloride and ibuprofen the patient should be observed closely for signs of renal failure [see WARNINGS ; Renal Effects], as well as diuretic efficacy.

Lithium

Ibuprofen has been shown to produce an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when oxycodone hydrochloride and ibuprofen and lithium are administered concurrently, subjects should be observed carefully 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 oxycodone hydrochloride and ibuprofen 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 greater risk of serious GI bleeding than users of either drug alone.

 

Carcinogenesis, Mutagenesis and Impairment of Fertility

Infertility

Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see ADVERSE REACTIONS].

Studies to evaluate the potential effects of the combination of Oxycodone and Ibuprofen on carcinogenicity and mutagenicity have not been conducted.

Oxycodone hydrochloride was not genotoxic in the following assays: Ames bacterial mutuation assay, chromosomal aberrations in cultured human lymphocytes, and in vivo mouse micronucleus assay in mice.

There was no evidence of impairment of fertility in either male or female Sprague-Dawley rats administered oxycodone hydrochloride; ibuprofen up to (1:80 mg/kg/day) which is equivalent to 0.5-times the maximum recommended human daily dose (MRHD) (20:1600 mg/day) on a body surface area (mg/m2 ) basis.

Pregnancy

Teratogenic Effects

Pregnancy Category C prior to 30 weeks gestation; Category D starting at 30 weeks gestation

Starting at 30 weeks gestation, oxycodone hydrochloride and ibuprofen, and other NSAIDS, should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur. Oxycodone hydrochloride and ibuprofen can cause fetal harm when administered to a pregnant woman starting at 30 weeks gestation. If oxycodone hydrochloride and ibuprofen, and other NSAIDS, are used during this time period in pregnancy, the patient should be apprised of the potential hazard to a fetus. There are no adequate and well-controlled studies in pregnant women. Prior to 30 weeks gestation, oxycodone hydrochloride and ibuprofen should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

Animal studies to assess the potential effects of the combination of Oxycodone and Ibuprofen on embryo-fetal development were conducted in the rat and rabbit model.

Pregnant rats were treated by oral gavage with combination doses of oxycodone:ibuprofen mg/kg/day (0.25:20, 0.5:40, 1:80, or 2:160) on days 7 to16 of gestation. There was no evidence for developmental toxicity or teratogenicity at any dose, although maternal toxicity was noted at doses of 0.5:40 and above. The highest dose tested in the rat (2:160 mg/kg/day) is equivalent to the maximum recommended human daily dose (20:1600 mg/day) on a body surface area (mg/m2) basis. This dose was associated with maternal toxicity (death, clinical signs, decreased BW).

Pregnant rabbits were treated by oral gavage with combination doses of oxycodone/ibuprofen (0.38:30, 0.75:60, 1.5:120 or 3:240 mg/kg/day) on gestation days 7 to19. Oxycodone/ibuprofen treatment was not teratogenic under the conditions of the assay. Maternal toxicity was noted at doses of 1.5:120 (reduced body weight and food consumption) and 3:240 mg/kg/day (mortality). The NOAEL for maternal toxicity, 0.75:60 mg/kg/day, is 0.75 fold the proposed maximum daily human dose based upon the body surface area. Developmental toxicity, as evidenced by delayed ossification and reduced fetal body weights, was noted at the highest dose, which is approximately 3 times the MRHD on a mg/m2 basis, and is likely due to maternal toxicity. The fetal no adverse effect level (NOAEL) of 1.5:120 mg/kg/day is approximately 1.5 times the MRHD on a mg/m2 basis.

In a pre- and postnatal development study conducted in rats, there was increased mortality of pups born to dams dose with 0.5:40 mg/kg/day oxycodone:ibuprofen and above which is equivalent to 0.25-times of the MRHD (20:1600 mg/day) on a body surface area (mg/m2) basis. There was an increase in stillborn F1 pups and decrease in mean pup weight in dams dosed with 1:80 mg/kg/day oxycodone:ibuprofen, which is 0.5-times the MRHD (20:1600 mg/day) on a body surface area (mg/m2) basis.

 

Non-teratogenic Effects

Fetal/Neonatal Adverse Reactions

Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.

Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see WARNINGS].

Labor and Delivery

Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. Oxycodone hydrochloride and ibuprofen tablets are not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including oxycodone hydrochloride and ibuprofen tablets, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.

Oxycodone hydrochloride and ibuprofen tablets should not be used during the third trimester of pregnancy due to the potential for ibuprofen to inhibit prostaglandin synthetase which may prolong pregnancy and inhibit labor.

In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred.

Nursing Mothers

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for oxycodone hydrochloride and ibuprofen tablets and any potential adverse effects on the breastfed infant from oxycodone hydrochloride and ibuprofen tablets or from the underlying maternal condition.

Infants exposed to oxycodone hydrochloride and ibuprofen through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breastfeeding is stopped.

Pediatric Use

In the placebo-controlled, clinical studies of pain following dental surgery, 109 patients between the ages of 14 and 17 years were administered a single dose of oxycodone hydrochloride and ibuprofen tablets. No apparent differences were noted in the safety of oxycodone hydrochloride and ibuprofen in patients below and above 17 years of age. Oxycodone hydrochloride and ibuprofen has not been studied in patients under 14 years of age. Safety and effectiveness in pediatric patients below the age of 14 have not been established.

Geriatric Use

Elderly patients (aged 65 years or older) may have increased sensitivity to oxycodone hydrochloride and ibuprofen tablets. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were coadministered with other agents that depress respiration. Titrate the dosage of oxycodone hydrochloride and ibuprofen tablets slowly in geriatric patients [see WARNINGS].

Of the total number of subjects in clinical studies of oxycodone hydrochloride and ibuprofen, 89 patients were 65 and over, while 37 patients were 75 and over. No overall differences in safety were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

However, because the elderly may be more sensitive to the renal and gastrointestinal effects of nonsteroidal anti-inflammatory agents  extra caution should be used when treating the elderly with oxycodone hydrochloride and ibuprofen [see WARNINGS].

Adverse Reactions

Listed below are the adverse event incidence rates from single dose analgesia trials in which a total of 2437 patients received either oxycodone hydrochloride and ibuprofen combination product, ibuprofen (400 mg), oxycodone hydrochloride (5 mg), or placebo. Adverse event information is also provided from an additional 334 patients who were exposed to oxycodone hydrochloride and ibuprofen combination product in a multiple dose analgesia trial, without placebo or active component comparison arms, given up to four times daily for up to 7 days.

Adverse Events Which Occurred at a Frequency of ≥1% and at a Higher Incidence than in the Placebo Group in Single Dose Studies
       5 mg  
     400 mg  Oxycodone  
   5/400 mg  Ibuprofen  Hydrochloride  Placebo
   (n=923)  (n=913)  (n = 286)  (n=315)
 Digestive        
 Nausea  81 (8.8%)  44 (4.8%)  46 (16.1%)  21( 6.7%)
 Vomiting  49 (5.3%)  16 (1.8%)  30 (10.5%)  10 (3.2%)
 Flatulence  9 (1.0%)  7 (0.8%)  3 (1.0%)  0
 Nervous System        
 Somnolence  67 (7.3%)  38 (4.2%)  12 (4.2%)  7 (2.2%)
 Dizziness  47 (5.1%)  21 (2.3%)  17 (5.9%)  8 (2.5%)
 Skin and Appendages        
 Sweat  15 (1.6%)  7 (0.8%)  4 (1.4%)  1 (0.3%)

Adverse events that were reported by at least 1% of patients taking oxycodone hydrochloride and ibuprofen but were observed at a greater incidence in the placebo treated patients were fever, headache and pruritus.

Adverse events that occurred in less than 1% and in at least two oxycodone hydrochloride and ibuprofen treated patients in Single Dose studies not listed above include the following: Body as Whole: abdominal pain, asthenia, chest pain, enlarged abdomen. Cardiovascular System: hypotension, syncope, tachycardia, vasodilation. Digestive System: constipation, dry mouth, dyspepsia, eructation, ileus. Hemic and Lymphatic System: anemia. Metabolic and Nutritional Disorders: edema. Nervous System: euphoria, insomnia, nervousness. Respiratory System: hypoxia, lung disorder, pharyngitis. Urogenital System: urinary retention.

Adverse events that occurred in the Multiple Dose study in at least 2% of patients treated with oxycodone hydrochloride and ibuprofen include the following: Body as Whole: asthenia (3.3%), fever (3.0%), headache (10.2%). Cardiovascular System: vasodilation (3.0%). Digestive System: constipation (4.5%), diarrhea (2.1%), dyspepsia (2.1%), nausea (25.4%), vomiting (4.5%). Nervous System: dizziness (19.2%), somnolence (17.4%).

Adverse events that occurred in less than 2% of and at least two oxycodone hydrochloride and ibuprofen treated patients in the Multiple Dose study not listed previously include the following: Body as Whole: back pain, chills, infection. Cardiovascular System: thrombophlebitis. Hemic and Lymphatic System: ecchymosis. Metabolic and Nutritional Disorders: hypokalemia. Musculoskeletal System: arthritis. Nervous System: abnormal thinking, anxiety, hyperkinesia, hypertonia. Skin and Appendages: rash. Special Senses: amblyopia, taste perversion. Urogenital System: urinary frequency.

 

Postmarketing Experience

  • serotonin syndrome
  • adrenal insufficiency

Androgen deficiency

Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as symptoms of hypogonadism, such as impotence, erectile dysfunction, or amenorrhea. The causal role of opioids in the syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date. Patients presenting with symptoms of androgen deficiency should undergo laboratory evaluation.

To report SUSPECTED ADVERSE EVENTS, contact Actavis at 1-800-432-8534 or FDA at 1-800-FDA-1088 or http://www.fda.gov/ for voluntary reporting of adverse reactions.

Drug Abuse and Dependence

Controlled Substance

Oxycodone hydrochloride and ibuprofen tablets contain oxycodone, a Schedule II controlled substance.

Abuse

Oxycodone hydrochloride and ibuprofen tablets contain oxycodone, a substance with a high potential for abuse similar to other opioids including codeine, hydromorphone, and morphine.  Oxycodone hydrochloride and ibuprofen tablets can be abused and are subject to misuse, addiction, and criminal diversion [see WARNINGS].

All patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use.

Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.

“Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating health care provider(s). “Doctor shopping” (visiting multiple prescribers) to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Health care providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.

Oxycodone hydrochloride and ibuprofen tablets, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific to Abuse of Oxycodone hydrochloride and Ibuprofen Tablets

Oxycodone hydrochloride and ibuprofen tablets contain oxycodone. The abuse of oxycodone poses a risk of overdose and death. The risk is increased with concurrent abuse of alcohol and other substances.

Dependence

Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.

Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug.  Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (pentazocine, butorphanol, nalbuphine), or partial agonists (buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.

Oxycodone hydrochloride and ibuprofen tablets should not be abruptly discontinued [see DOSAGE AND ADMINISTRATION].  If oxycodone hydrochloride and ibuprofen tablets are abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see PRECAUTIONS; Pregnancy].

 

Overdosage

Clinical Presentation

Acute overdose with oxycodone hydrochloride and ibuprofen tablets can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.

The toxicity of ibuprofen overdose is dependent on the amount of drug ingested and the time elapsed since ingestion, although individual response may vary, necessitating individual evaluation of each case. Although uncommon, serious toxicity and death have been reported in the medical literature with ibuprofen overdosage. The most frequently reported symptoms of ibuprofen overdose include abdominal pain, nausea, vomiting, lethargy, and drowsiness. Other central nervous system symptoms include headache, tinnitus, CNS depression, and seizures. Cardiovascular toxicity, including hypotension, bradycardia, tachycardia, and atrial fibrillation, have also been reported.

Treatment of Overdose

In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques.

The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to oxycodone hydrochloride and ibuprofen tablets overdose, administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to oxycodone hydrochloride and ibuprofen tablets overdose.

Because the duration of opioid reversal is expected to be less than the duration of action of oxycodone in oxycodone hydrochloride and ibuprofen tablets, carefully monitor the patient until spontaneous respiration is reliably re-established. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s prescribing information.

In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist.

Orally administered activated charcoal may help in reducing the absorption and reabsorption of ibuprofen. Emesis is most effective if initiated within 30 minutes of ingestion. Induced emesis is not recommended in patients with impaired consciousness or overdoses greater than 400 mg/kg of the ibuprofen component in children because of the risk for convulsions and the potential for aspiration of gastric contents.

 

Oxycodone and Ibuprofen Dosage and Administration

Important Dosage and Administration Instructions

Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see WARNINGS].

Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and following dosage increases with oxycodone hydrochloride and ibuprofen tablets and adjust the dosage accordingly [see WARNINGS].

Initial Dosage

Initiating Treatment with Oxycodone hydrochloride and Ibuprofen Tablets

Initiate treatment with oxycodone hydrochloride and ibuprofen tablets in a dosing range of one 5 mg/400 mg tablet every 6 hours as needed for pain.

Dosage should not exceed four 5 mg/400 mg tablets in a 24-hour period and should not exceed 7 days.

Titration and Maintenance of Therapy

Individually titrate oxycodone hydrochloride and ibuprofen tablets to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving oxycodone hydrochloride and ibuprofen tablets to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse [see WARNINGS].  Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration.

If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the oxycodone hydrochloride and ibuprofen tablets dosage. If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

Discontinuation of Oxycodone Hydrochloride and Ibuprofen Tablets

When a patient who has been taking oxycodone hydrochloride and ibuprofen tablets regularly and may be physically dependent no longer requires therapy with oxycodone hydrochloride and ibuprofen tablets, use a gradual downward titration of the dosage to prevent signs and symptoms of withdrawal. Do not stop oxycodone hydrochloride and ibuprofen tablets abruptly [see WARNINGS, DRUG ABUSE AND DEPENDENCE].

How is Oxycodone and Ibuprofen Supplied

Oxycodone hydrochloride and Ibuprofen tablets, 5 mg/400 mg are available as follows:

Each yellow, capsule-shaped, film-coated tablet imprinted with 29 on one side and bisect on both sides contains 5 mg of Oxycodone hydrochloride, USP and 400 mg of Ibuprofen, USP.  Tablets are supplied in bottles of 30 (NDC 0228-4029-03) and 100 (NDC 0228-4029-11) with a child-resistant closure, and 500 (NDC 0228-4029-50) without a child-resistant closure.

Dispense in a tight, light-resistant container as defined in the USP.

Store at 25ºC (77ºF); excursions permitted to 15º to 30ºC (59º to 86ºF) [see USP Controlled Room Temperature].

Manufactured by:
Actavis Elizabeth LLC
Elizabeth, NJ 07207 USA

Distributed by:
Actavis Pharma, Inc.
Parsippany, NJ 07054 USA

40-9065

Revised – March 2016

Medication Guide

Oxycodone Hydrochloride (ox"  i koe'  done  hye" droe klor' ide) and Ibuprofen (eye" bue proe' fen) Tablets    CII

Oxycodone hydrochloride and ibuprofen tablets are:

  • A strong prescription pain medicine that contains an opioid (narcotic) that is used to manage acute moderate to severe pain, when other pain treatments such as non-opioid pain medicines do not treat your pain well enough or you cannot tolerate them.

  • An opioid pain medicine that can put you at risk for overdose and death. Even if you take your dose correctly as prescribed you are at risk for opioid addiction, abuse, and misuse that can lead to death.

Important information about oxycodone hydrochloride and ibuprofen tablets:

  • Get emergency help right away if you take too many oxycodone hydrochloride and ibuprofen tablets (overdose). When you first start taking oxycodone hydrochloride and ibuprofen tablets, when your dose is changed, or if you take too many (overdose), serious or life-threatening breathing problems that can lead to death may occur.

  • Never give anyone else your oxycodone hydrochloride and ibuprofen tablets. They could die from taking them. Store oxycodone hydrochloride and ibuprofen tablets away from children and in a safe place to prevent stealing or abuse. Selling or giving away oxycodone hydrochloride and ibuprofen tablets is against the law.

Do not take oxycodone hydrochloride and ibuprofen tablets:

  • if you have severe asthma, trouble breathing, or other lung problems

    • if you have a bowel blockage or have narrowing of the stomach or intestines

    • right before or after heart bypass surgery

    • if you have had an asthma attack, hives, or other allergic reaction with aspirin or any other nonsteroidal anti-inflammatory drugs (NSAIDs)

Before taking oxycodone hydrochloride and ibuprofen tablets, tell your healthcare provider if you have a history of:

  • head injury, seizures
  • liver, kidney, thyroid problems
  • problems urinating
  • pancreas or gallbladder problems
  • abuse of street or prescription drugs, alcohol addiction, or mental health problems
  • asthma
  • high blood pressure

Tell your healthcare provider if you are:

  • pregnant or planning to become pregnant. Prolonged use of oxycodone hydrochloride and ibuprofen tablets during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated.  Starting at 30 weeks gestation, use of oxycodone hydrochloride and ibuprofen tablets, should be avoided as premature closure of the ductus arteriosus may occur.

  • breastfeeding. Oxycodone hydrochloride and ibuprofen passes into breast milk and may harm your baby.

  • taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking oxycodone hydrochloride and ibuprofen tablets with certain other medicines can cause serious side effects that could lead to death.

When taking oxycodone hydrochloride and ibuprofen tablets:

  • Do not change your dose. Take oxycodone hydrochloride and ibuprofen exactly as prescribed by your healthcare provider.

  • Take your prescribed dose at the same time every day. Do not take more than your prescribed dose. If you miss a dose, take your next dose at your usual time.

  • Call your healthcare provider if the dose you are taking does not control your pain.

  • If you have been taking oxycodone hydrochloride and ibuprofen tablets regularly, do not stop taking oxycodone hydrochloride and ibuprofen tablets without talking to your healthcare provider.

  • After you stop taking oxycodone hydrochloride and ibuprofen tablets, flush any unused tablets down the toilet.

While taking oxycodone hydrochloride and ibuprofen tablets DO NOT:

  • Drive or operate heavy machinery, until you know how oxycodone hydrochloride and ibuprofen tablets affect you. Oxycodone hydrochloride and ibuprofen tablets can make you sleepy, dizzy, or lightheaded.

  • Drink alcohol or use prescription or over-the-counter medicines that contain alcohol. Using products containing alcohol during treatment with oxycodone hydrochloride and ibuprofen  tablets may cause you to overdose and die.

The possible side effects of oxycodone hydrochloride and ibuprofen tablets:

  • constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness, abdominal pain, gas, heartburn, diarrhea, new or worse high blood pressure, heart failure, liver problems including liver failure, low red blood cells (anemia), life-threatening skin reactions, life-threatening allergic reactions. Call your healthcare provider if you have any of these symptoms and they are severe.

Get emergency medical help if you have:

  • trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue, or throat, extreme drowsiness, light-headedness when changing positions, feeling faint, agitation, high body temperature, trouble walking, stiff muscles, slurred speech, weakness in one side of your body or mental changes such as confusion.

    These are not all the possible side effects of oxycodone hydrochloride and ibuprofen tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information go to dailymed.nlm.nih.gov.

For more information about oxycodone hydrochloride and ibuprofen tablets, call Actavis at
1-800-432-8534.

 

This Medication Guide has been approved by the U.S. Food and Drug Administration.                 Issued: March 2016

Manufactured by:
Actavis Elizabeth LLC
Elizabeth, NJ 07207 USA

Distributed by:
Actavis Pharma, Inc.
Parsippany, NJ 07054 USA

40-9065

(MG 41-1223/0316)

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

 

OXYCODONE HYDROCHLORIDE AND IBUPROFEN 
oxycodone hydrochloride and ibuprofen tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0228-4029
Route of Administration ORAL DEA Schedule CII    
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
OXYCODONE HYDROCHLORIDE (OXYCODONE) OXYCODONE HYDROCHLORIDE 5 mg
IBUPROFEN (IBUPROFEN) IBUPROFEN 400 mg
Inactive Ingredients
Ingredient Name Strength
CALCIUM STEARATE  
CROSCARMELLOSE SODIUM  
SILICON DIOXIDE  
HYDROXYPROPYL CELLULOSE (TYPE L)  
CELLULOSE, MICROCRYSTALLINE  
STARCH, CORN  
STEARIC ACID  
HYPROMELLOSES  
LACTOSE MONOHYDRATE  
POLYETHYLENE GLYCOLS  
FERRIC OXIDE YELLOW  
TITANIUM DIOXIDE  
TRIACETIN  
Product Characteristics
Color YELLOW Score 2 pieces
Shape OVAL (capsule-shaped) Size 17mm
Flavor Imprint Code 29
Contains         
Packaging
# Item Code Package Description
1 NDC:0228-4029-03 30 TABLET, FILM COATED in 1 BOTTLE
2 NDC:0228-4029-11 100 TABLET, FILM COATED in 1 BOTTLE
3 NDC:0228-4029-50 500 TABLET, FILM COATED in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA078769 11/04/2008
Labeler - Actavis Pharma, Inc. (119723554)
Establishment
Name Address ID/FEI Operations
Actavis Elizabeth LLC 623114928 ANALYSIS(0228-4029), LABEL(0228-4029), MANUFACTURE(0228-4029), PACK(0228-4029)
Establishment
Name Address ID/FEI Operations
Actavis LLC 017665256 LABEL(0228-4029), PACK(0228-4029)
Revised: 03/2016
 
Actavis Pharma, Inc.
Hide