Ibudone contains Hydrocodone and Ibuprofen, a combination of an opioid analgesic and a non-steroidal anti-inflammatory drug that is used to treat patients with mild to moderate pain when alternative treatment modalities are ineffective.

Hydrocodone and Ibuprofen (Ibudone) Uses:

• Pain management:

  • It is recommended for the short-term (often less than 10 days) treatment of acute pain. When other treatments are not effective, this one should be utilised.
  • Restrictions on use: For the relief of pain associated with rheumatoid arthritis or osteoarthritis, this combination should not be utilised. It is possible to utilise hydrocodone and ibuprofen when other therapy choices (such as nonopioid analgesics) are ineffective, poorly tolerated, or insufficient.

Hydrocodone and Ibuprofen (Ibudone) dose in Adults

Hydrocodone and Ibuprofen (Ibudone) dose in the management of Pain:

• Orally: Take one tablet containing 200 mg of ibuprofen and 2.5–10 mg of hydrocodone every 4–6 hours as needed.
• Maximum: five pills (hydrocodone 12.5–50 mg/ibuprofen 1,000 mg) in a day.

Note: Use for no more than ten days total of therapy is advised.

• Discontinuation of therapy:

  • After prolonged use of opioids, gradually reduce the dose by 25% – 50% every 2 – 4 days; monitor for signs/symptoms of withdrawal.
  • In case of the development of withdrawal symptoms, increase the dose to the prior level and then reduce the dose more slowly at prolonged intervals

Use in Children:

Refer to adults dosing.

Ibudone Pregnancy Risk Category: X

• Studies on animal reproduction have shown that this combination can cause adverse events in animals.
• [US Boxed Warning]: Neonatal withdrawal syndrome can develop after prolonged opioid use by the mother. 
• This can be fatal if it is not treated as per the protocols of neonatology experts.

Use of hydrocodone or ibuprofen while breastfeeding

• Breast milk contains hydrocodone, ibuprofen, and other drugs.
• After considering the risks to infants and the benefits to mother, therapy should be offered to lactating mothers.

Dose in Kidney Disease:

The manufacturer has not provided any dose adjustment in labeling. Start with a lower dose. Do not use in advanced renal disease.

Dose in Liver disease:

• The manufacturer has not provided any dose adjustment in labeling
• Use cautiously and start with a lower dose and monitor liver function if the patient has a severe impairment.

Common Side Effects of Hydrocodone and Ibuprofen (Ibudone):

• Central Nervous System:

  • Headache
  • Drowsiness
  • Dizziness

• Gastrointestinal:

  • Constipation
  • Nausea
  • Dyspepsia

Less Common Side Effects Of Hydrocodone and Ibuprofen (Ibudone):

• Cardiovascular:

  • Edema
  • Palpitations
  • Vasodilatation

• Central Nervous System:

  • Anxiety
  • Insomnia
  • Nervousness
  • Abnormality In Thinking
  • Confusion
  • Hypertonia
  • Pain
  • Paresthesia

• Dermatologic:

  • Diaphoresis
  • Pruritus

• Endocrine & Metabolic:

  • Increased Thirst

• Gastrointestinal:

  • Abdominal Pain
  • Diarrhea
  • Flatulence
  • Hiccups
  • Vomiting
  • Xerostomia
  • Anorexia
  • Gastritis
  • Melena
  • Oral Mucosa Ulcer

• Infection:

  • Infection

• Neuromuscular & Skeletal:

  • Weakness

• Otic:

  • Tinnitus

• Renal:

  • Polyuria

• Respiratory:

  • Flu-Like Symptoms
  • Dyspnea
  • Pharyngitis
  • Rhinitis

• Miscellaneous:

  • Fever

Contraindications to Hydrocodone and Ibuprofen (Ibudone):

• Hypersensitivity to any ingredient of the formulation
• Respiratory depression is a serious problem
• Acute or severe bronchial asthma in an unmonitored setting, or without resuscitative devices
• Paralytic ileus, GI obstruction (known or suspected).
• History of asthma, urticaria or allergic-type reactions to aspirin and other NSAIDs
• In the setting coronary artery bypass surgery (CABG).
• There is a small chance that opioids may cause allergic cross-reactivity.
• However, this cannot be excluded because of similar chemical structures and/or pharmacologic effects.

Warnings and precautions

• Anaphylactoid reactions

  • Anaphylactoid reactions may occur without or with prior exposure.
  • Patients with the "aspirin trifecta" (bronchial asthma and aspirin intolerance, rhinitis, and "aspirin triad") are more at risk
  • Contraindicated if the patient has a history bronchospasm or asthma or rhinitis.

• Cardiovascular events: [US Boxed Warn]

  • Negative cardiovascular events have been linked to NSAIDs, including stroke, myocardial injury, and heart failure.
  • Patients with underlying or preexisting cardiac disease are at greater risk for developing adverse cardiac events.
  • Before treatment can be initiated, patients must be assessed for any underlying heart disease, especially elderly patients.
  • Patients with heart disease should avoid NSAIDs as they can cause fluid retention.
  • Aspirin can be affected by NSAIDs administered in combination with it. Therefore, they should not be taken for longer than necessary.
  • If necessary, patients may be prescribed alternative pain medication.

• CNS depression:

  • It can cause CNS depression and impair mental/physical abilities.
  • Be aware of the possible impairment to mental alertness. Driving or operating machinery

• GI events: [US Boxed Warning]

  • NSAIDs, including ibuprofen, can increase the risk of gastrointestinal bleeding. 
  • Patients over 60 years old or with a history of peptic or gastrointestinal bleeding should not use the drug.
  • Patients taking anticoagulants such as warfarin, aspirin, and corticosteroids with their medications are at greater risk for gastrointestinal bleeding.
  • People who consume ethanol (three or more alcoholic drinks per week) could also experience gastrointestinal bleeding. 
  • To reduce the risk of GI hemorhage, it is important to use the lowest effective dose and for the shortest time.
  • If patients develop symptoms such as melena or hematemesis, stomach cramps, hypotension, or stomach pain, they should stop receiving treatment immediately.
  • Patients with a history or lower gastrointestinal bleeding should not take non-aspirin anti-inflammatory drugs if they have had telangiectasias or diverticulosis. 
  • It is recommended to use gastroprotective therapy, such as proton pump inhibitors, in conjunction with the treatment.

• Hematologic effects

  • It can impair platelet function and cause bleeding to be prolonged.
  • If the patient is taking anticoagulants, or has a coagulation disorder, be sure to monitor closely
  • Anemia can occur. Monitor your NSAIDs to prolong use
  • Rarely, NSAIDs can cause blood disorders.

• Hepatic effects

  • Elevated liver enzymes, especially transaminase, can lead to elevated levels. Patients with abnormal LFT should be closely monitored.
  • Very rarely, NSAIDs can cause severe hepatic reactions (e.g. severe hepatic reactions, such as hepatic failure or fulminant liver disease. In such cases, discontinue

• Hyperkalemia:

  • Particularly among the elderly, diabetics, people with pre-existing renal impairment, and when used with other medications that also cause hyperkalemia, NSAIDs can increase the risk of hyperkalemia (eg, angiotensin-converting enzyme [ACE] inhibitors).
  • Keep an eye on potassium levels.

• Hypotension

  • Serious hypotension, such as orthostatic hypotension or syncope, may result from it.
  • Patients at high risk of hypotension should be treated with caution Hypovolemia, cardiovascular disease (including acute MI), and drugs that can exaggerate hypotensive effect (including phenothiazines and general anesthetics) are some of the risks.
  • After starting dose adjustment or dose titration, monitor your symptoms and blood pressure.
  • If the patient is experiencing a circulatory crisis, do not use it.

• Ophthalmic events

  • Ibuprofen may cause blurred/diminished color vision, scotomata, or worsen your color vision.
  • Refer to an ophthalmologist and discontinue.

• Phenanthrene hypersensitivity:

  • If the patient is allergic to codeine, hydromorphone or levorphanol, use caution.

• Effects on the renal system:

  • Use of NSAIDs can cause deranged renal function.
  • There is decrease in prostaglandin synthesis (dose-dependent), which reduces renal blood flow and leads to renal decompensation.
  • Risk factors include:
    • dehydration, hypovolemia
    • heart failure
    • Hepatic impairment
    • People who are taking diuretics, ACE inhibitors, or ARBs
    • Elderly are at risk 
  • Before starting treatment, hydrate the patient and closely monitor their renal function.
  • Renal papillary necrosis can be caused by long-term NSAIDs.

• Respiratory depression [US Boxed Warning]

  • Opioids can cause serious respiratory depression.
  • Monitor carefully at the beginning of therapy or any dose increase.
  • Respiratory depression can increase CO2 retention, which may further exacerbate the sedative effects of opioids.

• Reactions to skin:

  • NSAIDs can cause serious skin reactions (including SJS and TEN). If a skin rash develops, the treatment should be stopped immediately.

• Conditions abdominales:

  • It can mask acute abdominal symptoms and obscure the diagnosis.

• Adrenocortical Insufficiency

  • Patients with Addison disease, adrenocortical impairment or other conditions should be cautious.
  • Dose adjustment may be necessary. Opioid use for long periods can lead to secondary hypogonadism. This could cause mood disorders or osteoporosis.

• Aseptic meningitis

  • In patients with mixed connective tissue illnesses and systemic lupus erythematosus (SLE), use of it may increase their risk of developing aseptic meningitis (MCTD).

• Asthma

  • Patients with aspirin-sensitive asthma should not be treated; serious and fatal bronchospasm may occur.

• Insufficiency of the biliary tract:

  • The sphincter Oddi may become constricted as a result of opioid usage.
  • Be mindful that patients with pancreatitis or biliary dysfunction require close monitoring.

• CNS depression/coma:

  • CNS depression may be caused by opioids.
  • Carbon dioxide retention could also occur. Patients with impaired consciousness or coma should not take Opioids.
• Coronary bypass surgery for coronary artery bypass: [US Boxed Warn]
  • Contraindicated for the placement of coronary bypass graft surgery (CABG).
  • With head injuries, brain lesions, or high intracranial pressure, extreme caution is advised (ICP).
  • It's possible for intracranial pressure to increase.

• Delirium tremens:

  • Avoid delirium tremens.

• Head trauma

  • If you use it within the first 10 to 14 days following CABG surgery, you run the risk of having a stroke or MI.

• Hepatic impairment

  • If the patient has severe hepatic impairment, proceed with caution.
  • Monitor closely liver functions

• Obesity:

  • Be cautious with patients who are morbidly obese

• Prostatic hyperplasia/urinary restriction:

  • If the patient is suffering from prostatic hyperplasia or urinary stricture, be cautious.

• Psychosis:

  • Avoid toxic psychosis.

• Renal impairment

  • Use of NSAIDs may impair renal function already present.
  • Advanced renal disease patients should not be treated.

• Respiratory disease

  • If the patient has COPD, corpulmonale or any other underlying lung disease, such as COPD, corpulmonale, hypoxia, hypercarbia, or any other condition that reduces respiratory reserve, hypoxia, and/or hypoxia, be cautious. These patients are at increased risk for respiratory depression, especially at the beginning of therapy and dose escalation.
  • You might consider using non-opioid analgesics for these patients.

• Seizures:

  • If the patient has had seizure disordered in the past, be cautious.
  • Use of it may result in seizures or aggravate current seizures.

• Thyroid dysfunction:

  • If the patient has thyroid dysfunction, be cautious.

Monitoring parameters:

• Pain relief
• Respiratory status
• Mental status
• Blood pressure
• Signs of misuse, abuse, and addiction
• Signs/symptoms of bleeding
• Signs or symptoms of hypogonadism or hypoadrenalism

How to administer Hydrocodone and Ibuprofen (Ibudone)?

• It is administered orally after meals every four to six hours as and when required.
• It is best to use the lowest effective dose for the shortest possible time.
• Avoid taking it with other CNS-depressant drugs such as alcohol.

Mechanism of action of Hydrocodone and Ibuprofen (Ibudone):

Hydrocodone

• It is an opioid receptor agonist in Mu, it binds to it in CNS, alters perception and response to pain, suppresses coughing in the medullary centre; causes generalized CNS depression.

Ibuprofen

• Ibuprofen is a reversible inhibitor of the enzyme cyclooxygenase I and II. It relieves pain and inflammation and helps with fever.

Ibuprofen: See Ibuprofen monograph.

Hydrocodone:

The onset of action:

• Opioid analgesic: 10 to 20 minutes

Duration:

• 4 - 8 hours

Protein binding:

• Hydrocodone: 19% - 45%

Metabolism:

• Hydrocodone: hepatic by the following mechanism
  • CYP2D6: Via O-demethylation and produces hydromorphone (major, active metabolite with higher binding affinity for the mu-opioid receptor than hydrocodone)
  • CYP3A4: Via N-demethylation  and produces norhydrocodone (major metabolite)
  • Non-CYP pathways, 40% clearance occurs through these pathways which includes 6-ketosteroid reduction to 6-alpha-hydrocol and 6-betahydrocol, and other elimination pathways (eg, fecal, biliary, intestinal, renal).

Half-life elimination:

• Hydrocodone: 4.5 hours

Time to peak:

• Hydrocodone: 1.7 hours

Excretion:

• Hydrocodone: Urine (26% of the single dose is excreted in 72 hours, with ~12% as unchanged drug, 5% as norhydrocodone, 4% as conjugated hydrocodone, 3% as 6-hydrocodol, and 0.21% as conjugated 6-hydromorphol).

International Brand Names of Hydrocodone and Ibuprofen:

• Ibudone
• Reprexain
• Vicoprofen
• Xylon
• Dovir

Hydrocodone and Ibuprofen Brand Names in Pakistan:

No Brands Available in Pakistan