Get your patient on Hydrocodone Bitartrate And Ibuprofen - Hydrocodone Bitartrate And Ibuprofen tablet, Film Coated (Hydrocodone Bitartrate And Ibuprofen)

Hydrocodone Bitartrate and Ibuprofen Tablets are indicated for the short-term management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.
Limitations of Use
Carefully consider the potential benefits and risks of Hydrocodone Bitartrate and Ibuprofen Tablets and other treatment options before deciding to use Hydrocodone Bitartrate and Ibuprofen Tablets Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals (see WARNINGS: Cardiovascular Thrombotic Events, Gastrointestinal Bleeding, Ulceration, and Perforation ). Do not use Hydrocodone Bitartrate and Ibuprofen Tablets for the treatment of conditions such as osteoarthritis or rheumatoid arthritis.
Because of the risks of addiction, abuse, misuse, overdose and death, which can occur at any dosage or duration and persist over the course of therapy (see WARNINGS ), reserve opioid analgesics, including Hydrocodone Bitartrate and Ibuprofen Tablets for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

Hydrocodone Bitartrate and Ibuprofen Tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks.

Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see Warnings]. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of Hydrocodone Bitartrate and Ibuprofen Tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks.

Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available.

There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see Warnings].

Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with Hydrocodone Bitartrate and Ibuprofen Tablets. Consider this risk when selecting an initial dose and when making dose adjustments [see Warnings].

Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose
Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene). Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose. The presence of risk factors for overdose should not prevent the management of pain in any patient [see WARNINGS; Addiction, Abuse, and Misuse; Life-Threatening Respiratory Depression; Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants].

Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program).

There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics. Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent.


Initial Dosage

Use of Hydrocodone Bitartrate and Ibuprofen Tablets as the First Opioid Analgesic

Initiate treatment with Hydrocodone Bitartrate and Ibuprofen Tablets at a dose of one tablet every 4 to 6 hours as needed for pain, at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient’s response to their initial dose of Hydrocodone Bitartrate and Ibuprofen Tablets. Dosage should not exceed 5 tablets in a 24-hour period.

The lowest effective dose or the longest dosing interval should be sought for each patient (see WARNINGS), especially in the elderly. After observing the initial response to therapy with hydrocodone bitartrate and ibuprofen tablets, the dose and frequency of dosing should be adjusted to suit the individual patient's need, without exceeding the total daily dose recommended.

Titration and Maintenance of Therapy

Individually titrate Hydrocodone Bitartrate and Ibuprofen Tablets to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving Hydrocodone Bitartrate and Ibuprofen Tablets to assess the maintenance of pain control, signs and symptoms of opioid withdrawal and other adverse reactions, as well as reassessing 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 Hydrocodone Bitartrate and Ibuprofen Tablets dosage. If after increasing the dosage unacceptable opioid-related adverse reactions are observed (including an increase in pain after dosage increase), consider reducing the dosage [see Warnings]. Adjust the dosage to obtain an appropriate balance between management of pain and opioid- related adverse reactions.

Safe Reduction and Discontinuation of Hydrocodone Bitartrate and Ibuprofen Tablets

Do not abruptly discontinue Hydrocodone Bitartrate and Ibuprofen tablets in patients who may be physically dependent on opioids. Rapid   reduction or abrupt discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid reduction or abrupt discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances.

When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient taking Hydrocodone Bitartrate and Ibuprofen tablets there are a variety of factors that should be considered, including the total daily dose of opioid ( including Hydrocodone Bitartrate and Ibuprofen tablets) the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with co-morbid pain and substance use disorders may benefit from referral to a specialist.

There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on Hydrocodone Bitartrate and Ibuprofen tablets who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose lowering at an interval of every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper.

It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common withdrawal symptoms include 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. If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, evaluate patients for any changes in mood, emergence of suicidal thoughts, or use of other substances.

When managing patients taking opioid analgesics, particularly those who have been treated for a extended period of time and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic [see WARNINGS/ Withdrawal , DRUG ABUSE AND DEPENDENCE ].

Hydrocodone Bitartrate and Ibuprofen Tablets are contraindicated in patients with:

• Significant respiratory depression (see WARNINGS: Life-Threatening Respiratory Depression ).
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment (see WARNINGS: Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients ).
• Known or suspected gastrointestinal obstruction, including paralytic ileus (see WARNINGS: Risks of Use in Patients with Gastrointestinal Conditions ).
• Known hypersensitivity (e.g., anaphylactic reactions, serious skin reactions) to hydrocodone, ibuprofen, or any components of the drug product (see WARNINGS: Anaphylactic Reactions, Serious Skin Reactions ). Patients known to be hypersensitive to other opioids may exhibit cross-sensitivity to hydrocodone.
• History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients (see WARNINGS: Anaphylactic Reactions, Exacerbation of Asthma Related to Aspirin Sensitivity ).
• In the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS: Cardiovascular Thrombotic Events ).
  

The following adverse reactions are described below and elsewhere in the labeling including the

WARNINGS section.

• Addiction, Abuse, and Misuse
• Life-Threatening Respiratory Depression
• Neonatal Opioid Withdrawal Syndrome
• Interactions with Cytochrome P450 3A4 Inhibitors and Inducers
• Interactions with Benzodiazepines or Other CNS Depressants
• Adrenal Insufficiency
• Severe Hypotension
• Seizures
• Withdrawal
• Cardiovascular Thrombotic Events
• Gastrointestinal Bleeding, Ulceration, and Perforation
• Hepatotoxicity
• Hypertension
• Heart Failure and Edema
• Renal Toxicity and Hyperkalemia
• Anaphylactic Reactions
• Exacerbation of Asthma Related to Aspirin Sensitivity
• Serious Skin Reactions
• Premature Closure of Fetal Ductus Arteriosus
• Hematologic Toxicity
• Aseptic Meningitis
• Opioid-Induced Hyperalgesia and Allodynia [See Warnings]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Hydrocodone bitartrate and ibuprofen tablets were administered to approximately 300 pain patients in a safety study that employed dosages and a duration of treatment sufficient to encompass the recommended usage (see DOSAGE AND ADMINISTRATION ). Adverse event rates generally increased with increasing daily dose. The event rates reported below are from approximately 150 patients who were in a group that received one tablet of hydrocodone bitartrate and ibuprofen tablets an average of three to four times daily. The overall incidence rates of adverse experiences in the trials were fairly similar for this patient group and those who received the comparison treatment, acetaminophen 600 mg with codeine 60 mg.

The following lists adverse events that occurred with an incidence of 1% or greater in clinical trials of Hydrocodone Bitartrate and Ibuprofen Tablets, without regard to the causal relationship of the events to the drug. To distinguish different rates of occurrence in clinical studies, the adverse events are listed as follows:

name of adverse event = less than 3%

adverse events marked with an asterisk • = 3% to 9%

adverse event rates over 9% are in parentheses.

Body as a Whole

Abdominal pain•; Asthenia•; Fever; Flu syndrome; Headache (27%); Infection•; Pain.

Cardiovascular

Palpitations; Vasodilation.

Central Nervous System

Anxiety•; Confusion; Dizziness (14%); Hypertonia; Insomnia•; Nervousness•; Paresthesia;

Somnolence (22%); Thinking abnormalities.

Digestive

Anorexia; Constipation (22%); Diarrhea•; Dry mouth•; Dyspepsia (12%); Flatulence•; Gastritis;

Melena; Mouth ulcers; Nausea (21%); Thirst; Vomiting•.

Metabolic and Nutritional Disorders

Edema•.

Respiratory

Dyspnea; Hiccups; Pharyngitis; Rhinitis.

Skin and Appendages

Pruritus•; Sweating•.

Special Senses

Tinnitus.

Urogenital

Urinary frequency.

Incidence less than 1%

Body as a Whole

Allergic reaction.

Cardiovascular

Arrhythmia; Hypotension; Tachycardia.

Central Nervous System

Agitation; Abnormal dreams; Decreased libido; Depression; Euphoria; Mood changes; Neuralgia; Slurred speech; Tremor, Vertigo.

Digestive

Chalky stool; "Clenching teeth"; Dysphagia; Esophageal spasm; Esophagitis; Gastroenteritis; Glossitis; Liver enzyme elevation.

Metabolic and Nutritional

Weight decrease.

Musculoskeletal

Arthralgia; Myalgia.

Respiratory

Asthma; Bronchitis; Hoarseness; Increased cough; Pulmonary congestion; Pneumonia; Shallow breathing; Sinusitis.

Skin and Appendages

Rash; Urticaria.

Special Senses

Altered vision; Bad taste; Dry eyes.

Urogenital

Cystitis; Glycosuria; Impotence; Urinary incontinence; Urinary retention.

Post marketing Experience

The following adverse reactions have been identified during post approval use of hydrocodone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Serotonin syndrome : Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.

Adrenal insufficiency : Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

Anaphylaxis : Anaphylaxis has been reported with ingredients contained in Hydrocodone Bitartrate and Ibuprofen Tablets.

Androgen deficiency : Cases of androgen deficiency have occurred with chronic use of opioids for an extended period of time.
Hyperalgesia and Allodynia : Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see Warnings]
Hypoglycemia : Cases of hypoglycemia have been reported in patients taking opioids. Most reports were in patients with at least one predisposing risk factor (e.g., diabetes).
Skin and Appendages : exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE).

Opioid-induced esophageal dysfunction (OIED): Cases of OIED have been reported in patients taking opioids and may occur more frequently in patients taking higher doses of opioids, and/or in patients taking opioids longer term [see WARNINGS].

Adverse Reactions from Observational Studies

A prospective, observational cohort study estimated the risks of addiction, abuse, and misuse in patients initiating long-term use of Schedule II opioid analgesics between 2017 and 2021. Study participant included in one or more analyses had been enrolled in selected insurance plans or health systems for at least one year, were free of at least one outcome at baseline, completed a minimum number of follow-up assessments, and either: 1) filled multiple extended-release/long-acting opioid analgesic prescriptions during a 90 day period (n=978); or 2) filled any Schedule II opioid analgesic prescriptions covering at least 70 of 90 days (n=1,244). Those included also had no dispensing of the qualifying opioids in the previous 6 months.

Over 12 months:
• approximately 1% to 6% of participants across the two cohorts newly met criteria for addiction, as assessed with two validated interview-based measures of moderate-to-severe opioid use disorder based on
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, and
• approximately 9% and 22% of participants across the two cohorts newly met criteria for prescription opioid abuse and misuse [defined in DRUG ABUSE AND DEPENDENCE], respectively, as measured with a validated self-reported instrument.

A retrospective, observational cohort study estimated the risk of opioid-involved overdose or opioid overdose-related death in patients with new long-term use of Schedule II opioid analgesics from 2006 through 2016 (n=220,249). Included patients had been enrolled in either one of two commercial insurance programs, one managed care program, or one Medicaid program for at least 9 months. New long-term use was defined as having Schedule II opioid analgesic prescriptions covering at least 70 days’ supply over the 3 months prior to study entry and none during the preceding 6 months. Patients were excluded if they had an opioid-involved overdose in the 9 months prior to study entry. Overdose was measured using a validated medical code-based algorithm with linkage to the National Death Index database. The 5-year cumulative incidence estimates for opioid-involved overdose or opioid overdose-related death ranged from approximately 1.5% to 4% across study sites, counting only the first event during follow-up. Approximately 17% of first opioid overdoses observed over the entire study period (5-11 years, depending on the study site) were fatal. Higher baseline opioid dose was the strongest and most consistent predictor of opioid-involved overdose or opioid overdose-related death. Study exclusion criteria may have selected patients at lower risk of overdose, and substantial loss to follow-up (approximately 80%) also may have biased estimates.

The risk estimates from the studies described above may not be generalizable to all patients receiving opioid analgesics, such as those with exposures shorter or longer than the duration evaluated in the studies.

Inhibitors of CYP3A4 and CYP2D6

The concomitant use of hydrocodone bitartrate and ibuprofen tablets and CYP3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir), can increase the plasma concentration of hydrocodone, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of hydrocodone bitartrate and ibuprofen tablets and CYP2D6 and CYP3A4 inhibitors, particularly when an inhibitor is added after a stable dose of hydrocodone bitartrate and ibuprofen tablets are achieved (see WARNINGS: Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers ).

After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the hydrocodone plasma concentration will decrease (see CLINICAL PHARMACOLOGY: Pharmacokinetics ), resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to Hydrocodone Bitartrate and Ibuprofen Tablets.

If concomitant use is necessary, consider dosage reduction of hydrocodone bitartrate and ibuprofen tablets until stable drug effects are achieved. Evaluate patients at frequent intervals for respiratory depression and sedation. If a CYP3A4 inhibitor is discontinued, consider a dosage increase of hydrocodone bitartrate and ibuprofen tablets until stable drug effects are achieved. Evaluate for signs of opioid withdrawal.

CYP3A4 Inducers

The concomitant use of hydrocodone bitartrate and ibuprofen tablets and CYP3A4 inducers, such as rifampin, carbamazepine, and phenytoin, can decrease the plasma concentration of hydrocodone (see CLINICAL PHARMACOLOGY: Pharmacokinetics ), resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to hydrocodone (see WARNINGS: Withdrawal ).

After stopping a CYP3A4 inducer, as the effects of the inducer decline, the hydrocodone plasma concentration will increase (see CLINICAL PHARMACOLOGY: Pharmacokinetics ), which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression.

If concomitant use is necessary, consider a dosage increase of hydrocodone bitartrate and ibuprofen tablets until stable drug effects are achieved. Evaluate for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider hydrocodone bitartrate and ibuprofen tablets dosage reduction and evaluate patients at frequent intervals for signs of respiratory depression and sedation.

Benzodiazepines and Other Central Nervous System (CNS) Depressants

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

Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Inform patients and caregivers of this potential interaction, educate them on the signs and symptoms of respiratory depression (including sedation). If concomitant use is warranted, consider recommending or prescribing an opioid overdose reversal agent [see WARNINGS, DOSAGE AND ADMINISTRATION].

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), certain muscle relaxants (i.e., cyclobenzaprine,metaxalone), 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, frequently evaluate the patient, particularly during treatment initiation and dose adjustment. Discontinue hydrocodone bitartrate and ibuprofen tablets if serotonin syndrome is suspected.

Monoamine Oxidase Inhibitors (MAOIs)

MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma).

If urgent use of an opioid is necessary with MAOIs such as phenelzine, tranylcypromine, linezolid, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

The use of hydrocodone bitartrate and ibuprofen tablets are not recommended for patients taking MAOIs or within 14 days of stopping such treatment.

Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics

Agonist/antagonist analgesics such as pentazocine, nalbuphine, butorphanol and buprenorphine may reduce the analgesic effect of hydrocodone bitartrate and ibuprofen tablets and/or precipitate withdrawal symptoms in these patients.

Avoid concomitant use of these drugs.

Muscle Relaxants

Hydrocodone Bitartrate and Ibuprofen Tablets may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.

Because respiratory depression may be greater than otherwise expected, decrease the dosage of hydrocodone bitartrate and ibuprofen tablets and/or the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider recommending or prescribing an opioid overdose reversal agent (see WARNINGS, DOSAGE AND ADMINISTRATION). Examples: Cyclobenzaprine, metaxalone.

Anticholinergics

The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

Evaluate patients for signs of urinary retention or reduced gastric motility when hydrocodone bitartrate and ibuprofen tablets are used concomitantly with anticholinergic drugs.

Drugs That Interfere With Hemostasis

Ibuprofen and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of ibuprofen and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone.

Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone.

Monitor patients with concomitant use of hydrocodone bitartrate and ibuprofen tablets with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), SSRIs, and SNRIs for signs of bleeding (see WARNINGS: Hematologic Toxicity ).

Aspirin

Pharmacodynamic studies have demonstrated interference with the antiplatelet activity of aspirin when ibuprofen 400 mg, given three times daily, is administered with enteric coated low-dose aspirin. The interaction exists even following a once-daily regimen of ibuprofen 400 mg, particularly when ibuprofen is dosed prior to aspirin. The interaction is alleviated if immediate-release low-dose aspirin is dosed at least 2 hours prior to a once daily regimen of ibuprofen; however, this finding cannot be extended to enteric-coated low-dose aspirin [see Clinical Pharmacology/Pharmacodynamics ].

Because there may be an increased risk of cardiovascular events due to the interference of ibuprofen with the antiplatelet effect of aspirin, for patients taking low-dose aspirin for cardioprotection who require analgesics, consider use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or non-NSAID analgesics, where appropriate.

Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone (see WARNINGS: Gastrointestinal Bleeding, Ulceration, and Perforation ).

Concomitant use of hydrocodone bitartrate and ibuprofen tablets and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding (see WARNINGS: Hematologic Toxicity ).

ACE-Inhibitors, Angiotensin Receptor Blockers, and Beta-blockers

NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers (including propranolol).

During concomitant use of hydrocodone bitartrate and ibuprofen tablets and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained.

In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure. Evaluate for signs of worsening renal function (see WARNINGS: Renal Toxicity and Hyperkalemia ). These effects are usually reversible.

When these drugs are administered concomitantly, patients should be adequately hydrated. Assess renal function at the beginning of the concomitant treatment and periodically thereafter.

Diuretics

Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis.

During concomitant use of hydrocodone bitartrate and ibuprofen tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects (see WARNINGS: Renal Toxicity and Hyperkalemia ).

Digoxin

The concomitant use of ibuprofen with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin.

During concomitant use of hydrocodone bitartrate and ibuprofen tablets and digoxin, monitor serum digoxin levels.

Lithium

NSAIDs have produced elevations in plasma lithium concentration and reductions in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 20%. This effect has been attributed to NSAID inhibition of renal prostaglandin synthesis.

During concomitant use of hydrocodone bitartrate and ibuprofen tablets and lithium, evaluate patients for signs of lithium toxicity.

Methotrexate

Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction).

During concomitant use of hydrocodone bitartrate and ibuprofen tablets and methotrexate, evaluate patients for methotrexate toxicity.

Cyclosporine

Concomitant use of hydrocodone bitartrate and ibuprofen tablets and cyclosporine may increase cyclosporine’s nephrotoxicity.

During concomitant use of hydrocodone bitartrate and ibuprofen tablets and cyclosporine, evaluate patients for signs of worsening renal function.

NSAIDs and Salicylates

Concomitant use of ibuprofen with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy (see WARNINGS: Gastrointestinal Bleeding, Ulceration, and Perforation).

The concomitant use of ibuprofen with other NSAIDs or salicylates is not recommended.

Pemetrexed
Concomitant use of hydrocodone bitartrate and ibuprofen tablets and Pemetrexed may increase the risk of Pemetrexed associated myelosuppression, renal, and GI toxicity (see the Pemetrexed prescribing information).

During concomitant use of hydrocodone bitartrate and ibuprofen tablets and Pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal and GI toxicity.

NSAIDs with short elimination half-lives (e.g., diclofenac, indomethacin) should be avoided for a period of two days before, the day of, and two days following administration of Pemetrexed.

In the absence of data regarding potential interaction between Pemetrexed and NSAIDs with longer half-lives (e.g., meloxicam, nabumetone), patients taking these NSAIDs should interrupt dosing for at least five days before, the day of, and two days following Pemetrexed administration.

Each hydrocodone bitartrate and ibuprofen tablet contains:
Hydrocodone Bitartrate, USP  7.5 mg
Ibuprofen, USP    200 mg

Hydrocodone Bitartrate and Ibuprofen Tablets are supplied in a fixed combination tablet form for oral administration. Hydrocodone Bitartrate and Ibuprofen Tablets combines the opioid agonist agent, hydrocodone bitartrate, with the nonsteroidal anti-inflammatory (NSAID) agent, ibuprofen.

Hydrocodone bitartrate is a semisynthetic opioid agonist. Its chemical name is: 4,5 α-epoxy-3-methoxy-17-methylmorphinan-6-one tartrate (1:1) hydrate (2:5). Its chemical formula is: C ₁₈ H ₂₁ NO ₃ •C ₄ H ₆ O ₆ •2½H ₂ O, and the molecular weight is 494.50. Its structural formula is:

Ibuprofen is a non-steroidal anti-inflammatory agent [non-selective COX inhibitor] with analgesic and antipyretic properties. Its chemical name is: (±)-2-(p-isobutylphenyl) propionic acid. Its chemical formula is: C13H18O2, and the molecular weight is: 206.29. Its structural formula is:

Inactive ingredients in Hydrocodone Bitartrate and Ibuprofen tablets include: anhydrous lactose, colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, sodium starch glycolate, sodium lauryl sulfate, polysorbate 80, hypromellose, titanium dioxide and polyethylene glycol.

Mechanism of Action
Hydrocodone Component
Hydrocodone  is  a  full  opioid  agonist  with  relative  selectivity  for  the  mu-opioid  receptor, although it can interact with other opioid receptors at higher doses. The principal therapeutic action of hydrocodone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with hydrocodone. Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression.
The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.
Ibuprofen Component
Ibuprofen has analgesic, anti-inflammatory, and antipyretic properties.
The mechanism of action, like that of other NSAIDs, is not completely understood, but involves inhibition of cyclooxygenase (COX-1 and COX-2).
Ibuprofen is a potent inhibitor of prostaglandin synthesis in vitro. Ibuprofen concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because ibuprofen is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.

Pharmacodynamics
Effects on the Central Nervous System
Hydrocodone produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation.
Hydrocodone causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings). Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations.
Effects on the Gastrointestinal Tract and Other Smooth Muscle
Hydrocodone causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm, resulting in constipation. Other opioid- induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase, and opioid-induced esophageal dysfunction (OIED).
Effects on the Cardiovascular System
Hydrocodone produces peripheral vasodilation, which may result in orthostatic hypotension or syncope. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension.
Effects on the Endocrine System
Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans (see ADVERSE REACTIONS: Post marketing Experience). They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon.
Use of opioids for an extended period of time may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical 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 (see ADVERSE REACTIONS: Post marketing Experience ).
Effects on the Immune System
Opioids have been shown to have a variety of effects on components of the immune system in both in vitro and animal models. The clinical significance of these findings is unknown. Overall, the effects of opioids appear to be modestly immunosuppressive.

Concentration-Efficacy Relationships
The minimum effective analgesic concentration will vary widely among patients, especially among patients who have been previously treated with extended-release agonist opioids. The minimum effective analgesic concentration of hydrocodone for any individual patient may increase over time due to an increase in pain, the development of a new pain syndrome, and/or the development of analgesic tolerance (see DOSAGE AND ADMINISTRATION ).
Concentration-Adverse Reaction Relationships
There is a relationship between increasing hydrocodone plasma concentration and increasing frequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression. In opioid-tolerant patients, the situation may be altered by the development of tolerance to opioid-related adverse reactions (see DOSAGE AND ADMINISTRATION ).

In a healthy volunteer study, ibuprofen 400 mg given once daily, administered 2 hours prior to immediate-release aspirin (81 mg) for 6 days, showed an interaction with the antiplatelet activity of aspirin as measured by % serum thromboxane 82 (TxB2) inhibition at 24 hours following the day-6 aspirin dose [53%]. An interaction was still observed, but minimized, when ibuprofen 400 mg given once-daily was administered as early as 8 hours prior to the immediate-release aspirin dose [90.7%]. However, there was no interaction with the antiplatelet activity of aspirin when ibuprofen 400 mg, given once daily, was administered 2 hours after (but not concomitantly, 15 min, or 30 min after) the immediate-release aspirin dose [99.2%].

In another study, where immediate-release aspirin 81 mg was administered once daily with ibuprofen 400 mg given three times daily (1 , 7, and 13 hours post-aspirin dose) for 10 consecutive days, the mean % serum thromboxane 82 (TxB2) inhibition suggested no interaction with the antiplatelet activity of aspirin [98.3%]. However, there were individual subjects with serum TxB2 inhibition below 95%, with the lowest being 90.2%.

When a similarly designed study was conducted with enteric-coated aspirin, where healthy subjects were administered enteric-coated aspirin 81 mg once daily for 6 days and ibuprofen 400 mg three times daily (2, 7 and 12 h post-aspirin dose) for 6 days, there was an interaction with the antiplatelet activity at 24 hours following the day-6 aspirin dose [67%]. [See Precautions/Drug Interactions ].

Pharmacokinetics

Absorption
After oral dosing with the Hydrocodone Bitartrate and Ibuprofen Tablets, a peak hydrocodone plasma level of 27 ng/mL is achieved at 1.7 hours, and a peak ibuprofen plasma level of 30 mcg/mL is achieved at 1.8 hours. The effect of food on the absorption of either component from the Hydrocodone Bitartrate and Ibuprofen Tablets tablet has not been established.
Distribution
Ibuprofen is highly protein-bound (99%) like most other non-steroidal anti-inflammatory agents. Although the extent of protein binding of hydrocodone in human plasma has not been definitely determined, structural similarities to related opioid analgesics suggest that hydrocodone is not extensively protein bound. As most agents in the 5-ring morphinan group of semi-synthetic opioids bind plasma protein to a similar degree (range 19% [hydromorphone] to 45% [oxycodone]), hydrocodone is expected to fall within this range.
Elimination
Metabolism
Hydrocodone exhibits a complex pattern of metabolism, including O-demethylation, N­ demethylation, and 6-keto reduction to the corresponding 6-α-and 6-β-hydroxy metabolites. Hydromorphone, a potent opioid, is formed from the O-demethylation of hydrocodone and contributes to the total analgesic effect of hydrocodone. The O- and N- demethylation processes are mediated by separate P-450 isoenzymes: CYP2D6 and CYP3A4, respectively.
Ibuprofen is present in this product as a racemate, and following absorption it undergoes interconversion in the plasma from the R-isomer to the S-isomer. Both the R- and S- isomers are metabolized to two primary metabolites: (+)-2-4'-(2hydroxy-2-methyl-propyl) phenyl propionic acid and (+)-2-4'-(2carboxypropyl) phenyl propionic acid, both of which circulate in the plasma at low levels relative to the parent.
Excretion
Hydrocodone and its metabolites are eliminated primarily in the kidneys, with a mean plasma half-life of 4.5 hours. Ibuprofen is excreted in the urine, 50% to 60% as metabolites and approximately 15% as unchanged drug and conjugate. The plasma half-life is 2.2 hours.

Specific Populations
No significant pharmacokinetic differences based on age or gender have been demonstrated. The pharmacokinetics of hydrocodone and ibuprofen from Hydrocodone Bitartrate and Ibuprofen Tablets have not been evaluated in children.
Renal Impairment
The effect of renal insufficiency on the pharmacokinetics of the Hydrocodone Bitartrate and Ibuprofen Tablets dosage form has not been determined.
Drug Interaction Studies
Aspirin
When NSAIDs were administered with aspirin, the protein binding of NSAIDs were reduced, although the clearance of free NSAID was not altered. The clinical significance of this interaction is not known (see PRECAUTIONS: Drug Interactions ).

In single-dose studies of post-surgical pain (abdominal, gynecological, orthopedic), 940 patients were studied at doses of one or two tablets. Hydrocodone Bitartrate and Ibuprofen Tablets produced greater efficacy than placebo and each of its individual components given at the same dose. No advantage was demonstrated for the two-tablet dose.

Hydrocodone Bitartrate and Ibuprofen Tablets, 7.5 mg/200 mg are white to off-white, round, film coated tablets, debossed with “U13” on one side and plain on the other side.

Bottles of 10                  NDC 13107-004-11
Bottles of 100                NDC 13107-004-01
Bottles of 500                NDC 13107-004-05
Bottles of 1,000             NDC 13107-004-99

Storage

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].


Dispense in a tight, light-resistant container. Keep this and all medication out of the reach of children.

A Schedule II Controlled Drug Substance.


Store Hydrocodone Bitartrate and Ibuprofen Tablets securely and dispose of properly [see PRECAUTIONS/ Information for Patients ].

Dispense with Medication Guide available at https://www.aurobindousa.com/medication-guides/

Distributed by:
Aurobindo Pharma USA, Inc.
279 Princeton-Hightstown Road
East Windsor, NJ 08520

Revised: 11/2025