Get your patient on Hydrocodone Bitartrate And Ibuprofen - Hydrocodone Bitartrate And Ibuprofen tablet (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.

Important Dosage and Administration Instructions

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 in a dosing range 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 or Discontinuation of Hydrocodone Bitartrate and Ibuprofen Tablets

Do not rapidly reduce or 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, there are a variety of factors that should be considered, including the dose of hydrocodone bitartrate and ibuprofen 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 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 an 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 )

Each hydrocodone bitartrate and ibuprofen tablet contains either:

Hydrocodone Bitartrate, USP 2.5 mg, 5 mg, 7.5 mg, or 10 mg and 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 combine the opioid agonist, hydrocodone bitartrate, USP, with the nonsteroidal anti-inflammatory (NSAID) agent, ibuprofen, USP.

Hydrocodone bitartrate, USP 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, USP is a nonsteroidal 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: C ₁₃ H ₁₈ O ₂ , and the molecular weight is: 206.29. Its structural formula is:

Inactive ingredients in hydrocodone bitartrate and ibuprofen 2.5 mg/200 mg, 5 mg/200 mg and 7.5 mg/200 mg tablets include: carnauba wax, colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polydextrose, pregelatinized starch and titanium dioxide.

Inactive ingredients in hydrocodone bitartrate and ibuprofen 10 mg/200 mg tablets include: colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polydextrose, pregelatinized starch, titanium dioxide, triacetin and D&C Yellow #10 Aluminum Lake.

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

Hydrocodone

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, 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: Postmarketing 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: Postmarketing 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  opioid agonists. 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 ) .

Ibuprofen

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 B2 (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 B2 (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 tablet, a peak hydrocodone plasma level of 27 ng/mL is achieved at 1.7 hours, and a peak ibuprofen plasma level of 30 mcg/mL is achieved at 1.8 hours. The effect of food on the absorption of either component from the hydrocodone bitartrate and ibuprofen 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 has not been evaluated in children.

Renal Impairment

The effect of renal insufficiency on the pharmacokinetics of the hydrocodone bitartrate and ibuprofen 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 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, 2.5 mg/200 mg , are supplied as white, capsule-shaped, film-coated tablets, debossed “IP 116” on obverse and plain on reverse.

They are available as follows:

Bottles of 100:             NDC 53746-116-01

Hydrocodone bitartrate and ibuprofen tablets, 5 mg/200 mg , are supplied as white, oval-shaped, film-coated tablets, debossed “IP 146” on obverse and plain on reverse.

They are available as follows:

Bottles of 100:             NDC 53746-146-01

Hydrocodone bitartrate and ibuprofen tablets, 7.5 mg/200 mg , are supplied as white, round, film-coated, biconvex tablets, debossed with “IP” over “145” on one side and plain on the other side.

They are available as follows:

Bottles of 100:             NDC 53746-145-01

Bottles of 500:             NDC 53746-145-05

Hydrocodone bitartrate and ibuprofen tablets, 10 mg/200 mg , are supplied as yellow, round-shaped, film-coated tablets, debossed “IP 117” on obverse and plain on reverse.

They are available as follows:

Bottles of 100:             NDC 53746-117-01

Storage

Store at room temperature 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Dispense in a tight, light-resistant container.

Store hydrocodone bitartrate and ibuprofen tablets securely and dispose of properly (see PRECAUTIONS: Information for Patients ) .

Manufactured by:
Amneal Pharmaceuticals of NY, LLC
Brookhaven, NY 11719

Rev. 11-2025-15