"Nov. 2, 2012 -- Safety steps taken in the wake of the fungal meningitis outbreak have worsened drug shortages, raising questions about whether the U.S. must choose between the safety and the availability of crucial medicines.
Listed below are the adverse event incidence rates from single dose analgesia trials in which a total of 2437 patients received either Combunox (oxycodone hcl and ibuprofen) , ibuprofen (400 mg), oxycodone HCl (5 mg), or placebo. Adverse event information is also provided from an additional 334 patients who were exposed to Combunox (oxycodone hcl and ibuprofen) 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
HCl (n = 286)
|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|
|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 Combunox (oxycodone hcl 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 Combunox (oxycodone hcl 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 Combunox (oxycodone hcl 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 Combunox (oxycodone hcl 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.
Drug Abuse And Dependence
Combunox (oxycodone hcl and ibuprofen) contains oxycodone, which is a mu-opioid agonist with an abuse liability similar to other opioid agonists and is a Schedule II controlled substance. Combunox (oxycodone hcl and ibuprofen) , and other opioids used in analgesia, can be abused and are subject to criminal diversion.
Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a treatable disease utilizing a multidisciplinary approach, but relapse is common.
“Drug seeking” behavior is very common in addicts and drug abusers. 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 physician(s). “Doctor shopping” to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction.
Abuse and addiction are separate and distinct from physical dependence and tolerance. Physical dependence usually assumes clinically significant dimensions only after several weeks of continued opioid use, although a mild degree of physical dependence may develop after a few days of opioid therapy. Tolerance, in which increasingly large doses are required in order to produce the same degree of analgesia, is manifested initially by a shortened duration of analgesic effect, and subsequently by decreases in the intensity of analgesia. The rate of development of tolerance varies among patients. Physicians should be aware that abuse of opioids can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. Combunox (oxycodone hcl and ibuprofen) , like other opioids, may be diverted for non-medical use. Record-keeping of prescribing information, including quantity, frequency, and renewal requests 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.
Read the Combunox (oxycodone hcl and ibuprofen) Side Effects Center for a complete guide to possible side effects
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.
The concurrent use of anticholinergics with oxycodone preparations may produce paralytic ileus.
Patients receiving narcotic analgesics, general anesthetics, phenothiazines, other tranquilizers, sedative-hypnotics or other CNS depressants (including alcohol) concomitantly with oxycodone may exhibit an additive CNS depression. Interactive effects resulting in respiratory depression, hypotension, profound sedation, or coma may result if these drugs are taken in combination with the usual dosage of oxycodone. When such combined therapy is contemplated, the dose of one or both agents should be reduced.
Mixed Agonist/Antagonist Opioid Analgesics
Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, butorphanol and buprenorphine) should be administered with caution to patients who have received or are receiving a course of therapy with a pure opioid agonist analgesic such as oxycodone. In this situation, mixed agonist/antagonist analgesics may reduce the analgesic effect of oxycodone and/or may precipitate withdrawal symptoms in these patients.
Monoamine Oxidase Inhibitors (MAOIs)
MAOIs have been reported to intensify the effects of at least one opioid drug causing anxiety, confusion and significant depression of respiration or coma. The use of oxycodone is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.
Neuromuscular Blocking Agents
Oxycodone, as well as other opioid analgesics, may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking Combunox (oxycodone hcl and ibuprofen) concomitantly with ACE-inhibitors.
When Combunox (oxycodone hcl and ibuprofen) is administered with aspirin, its protein binding is reduced, although the clearance of free Combunox (oxycodone hcl and ibuprofen) is not altered. The clinical significance of this interaction is not known; however as with other products containing NSAIDs, concomitant administration of Combunox (oxycodone hcl and ibuprofen) and aspirin is not generally recommended because of the potential of increased adverse effects.
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 Combunox (oxycodone hcl and ibuprofen) the patient should be observed closely for signs of renal failure (see WARNINGS; Renal Effects), as well as diuretic efficacy.
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 Combunox (oxycodone hcl and ibuprofen) and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.
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 Combunox (oxycodone hcl and ibuprofen) is administered concomitantly with methotrexate.
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.
Read the Combunox Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 9/23/2010
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