Dosing and uses of Ibudone, Reprexain (hydrocodone/ibuprofen)
Adult dosage forms and strengths
hydrocodone/ibuprofen
tablet: Schedule II
- 2.5mg/200mg
- 5mg/200mg
- 7.5mg/200mg
- 10mg/200mg
Analgesia
Short-term (generally less than 10 days) management of acute pain
Lowest effective dose for the shortest duration consistent with individual patient treatment goals
Usual dose: 5-7.5 mg/200 mg PO q4-6 hr PRN; not to exceed 5 tabs/24hr
Renal Impairment
Not recommended in patients with advanced renal disease
Renal disease or impairment; increased risk of renal toxicity and injury may occur
Administration
Not indicated for the treatment of chronic conditions such as osteoarthritis or rheumatoid arthritis
Extra caution and reduced dosages should be used when treating the elderly
Elderly or debilitated patients may experience increased risk of gastrointestinal injury, including fatal events; increased risk of renal toxicity and injury; respiratory depression
Pediatric dosage forms and strengths
hydrocodone/ibuprofen
tablet: Schedule II
- 2.5mg/200mg
- 5mg/200mg
- 7.5mg/200mg
- 10mg/200mg
Analgesia
<16 years: Safety and efficacy not established
≥16 years
- Short-term (generally <10 days) management of acute pain
- Lowest effective dose for the shortest duration consistent with individual patient treatment goals
- Usual dose: 5-7.5 mg/200 mg PO q4-6 hr PRN; not to exceed 5 tabs/24hr
Ibudone, Reprexain (hydrocodone/ibuprofen) adverse (side) effects
>10%
Dizziness
Drowsiness
Constipation
Nausea
Vomiting
Diarrhea
Dyspepsia
Flatulence
Hypotension
1-10%
Syncope
Agitation, depression, dizziness, dysphoria, euphoria
Faintness, mental clouding, restlessness, sedation, weakness
Cholinergic effects
Flushing, sweating, urticaria
Respiratory depression
Headache, fatigue, lightheadedness, tinnitus
Erythematous macular rashes
Erythema multiforme, exfoliative dermatitis, toxic epidermal necrolysis, photosensitivity
GI bleeding, GI ulceration
Neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia
Jaundice
Acute renal failure, decreased creatinine clearance, elevations in BUn
<1%
Bronchitis
Asthma
Cystitis
Cough
Dysphagia
Abnormal dreams
Decreased libido
Myalgia
Neuralgia
Pulmonary congestion
Warnings
Black box warnings
Cardiovascular Risk
- NSAIDs may increase risk of serious cardiovascular thrombotic events, myocardial infarction (MI), and stroke, which can be fatal
- Risk may increase with duration of use
- Patients with risk factors for or existing cardiovascular disease may be at greater risk
- NSAIDs are contraindicated for perioperative pain in the setting of coronary artery bypass graft (CABG) surgery (increased risk of MI & stroke)
Gastrointestinal Risk
- NSAIDs increase risk of serious GI adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal
- GI adverse events may occur at any time during use and without warning symptoms
- Elderly patients are at greater risk for serious GI events
Contraindications
Coronary artery bypass graft (CABG) surgery, treatment of peri-operative pain; increased incidence of myocardial infarction and stroke
Hypersensitivity to ibuprofen, hydrocodone
Hypersensitivity to other opioids; cross-sensitivity reaction possible
ASA allergy
Relative: bleeding disorder, duodenal/gastric/peptic ulcer, stomatitis, SLE, ulcerative colitis, upper GI disease, late pregnancy (may cause premature closure of ductus), asthma, urticaria, or allergic-type reactions following aspirin or other nonsteroidal anti-inflammatory agents; severe, even fatal, anaphylactic-like reactions
Cautions
Cardiovascular event risk may increase w/ duration of use
Gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal may occur
Abuse, misuse, diversion, and dependence potentiaL
Addison's disease; respiratory depression may occur
Alcohol use or smoking; increased risk of gastrointestinal injury
Asthma, especially with history of aspirin-sensitive asthma; severe bronchospasm and fatalities may occur
Coagulation disorder; bleeding time may be prolonged
Long-term use; increased risk of gastrointestinal or renal injury; anemia may occur
Pregnancy, third trimester use; premature close of ductus arteriosus may occur
Skin reactions; serious adverse events including exfoliative dermatitis, Stevens Johnson syndrome, toxic epidermal necrolysis
Pregnancy and lactation
Pregnancy category: C; D in 3rd trimester
Lactation: Excreted in breast milk; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Ibudone, Reprexain (hydrocodone/ibuprofen)
Mechanism of action
Hydrocodone: Binds to opiate receptors in the CNS, which in turn produces generalized CNS depression and alters perception and response to pain
Ibuprofen: Inhibits synthesis of prostaglandins in body tissues by inhibiting cyclooxygenase; at least 2 isoenzymes, cyclooxygenase-1 (COX-1) & -2 (COX-2); has antipyretic, anti-inflammatory, and analgesic properties
Metabolism
Hydrocodone: by liver (O-demethylation, N-demethylation, 6-keto reduction); hepatic P450 enzyme CYP2D6
Ibuprofen: rapid hepatic oxidation to inactive metabolites: (+)-2-[4'-(2-hydroxy-2-methylpropyl) phenyl] propionic acid (metabolite A), (+)-2-[4'-(2-carboxypropyl) phenyl] propionic acid (metabolite B)
Elimination
Excretion
- Hydrocodone: Mainly urine
- Ibuprofen: Urine 50-60% (<10% unchanged)
Half-Life
- Hydrocodone: 3.3-4.4 hr
- Ibuprofen: 2-4 hr
Absorption
Onset: 0.5 hr (ibuprofen)
Bioavailability 80-90% (ibuprofen)
Vd: 0.12 L/kg (ibuprofen)
Protein Bound: 90-99% (ibuprofen)
Peak Plasma Time
- Hydrocodone: 1.3 hr
- Ibuprofen: 2 hr
Duration
- Hydrocodone: 4-8 hr
- Ibuprofen: 4-6 hr
Pharmacogenomics
Hydrocodone is metabolized to Hydromorphone via CYP2D6; CYP2D6 poor metabolizers may not achieve adequate analgesia
Ultra-rapid metabolizers (up to 7% of Caucasians and up to 30% of Asian and African populations) may have increased toxicity due to rapid conversion