Akineton SR may be available in the countries listed below.
Biperiden hydrochloride (a derivative of Biperiden) is reported as an ingredient of Akineton SR in the following countries:
International Drug Name Search
Bromhexine-Darnitsa may be available in the countries listed below.
Bromhexine hydrochloride (a derivative of Bromhexine) is reported as an ingredient of Bromhexine-Darnitsa in the following countries:
International Drug Name Search
Arthrobic may be available in the countries listed below.
Meloxicam is reported as an ingredient of Arthrobic in the following countries:
International Drug Name Search
Michol may be available in the countries listed below.
Simvastatin is reported as an ingredient of Michol in the following countries:
International Drug Name Search
Gastropaque may be available in the countries listed below.
Barium Sulfate is reported as an ingredient of Gastropaque in the following countries:
International Drug Name Search
Amphadase is a brand name of hyaluronidase, approved by the FDA in the following formulation(s):
No. There is currently no therapeutically equivalent version of Amphadase available.
Note: Fraudulent online pharmacies may attempt to sell an illegal generic version of Amphadase. These medications may be counterfeit and potentially unsafe. If you purchase medications online, be sure you are buying from a reputable and valid online pharmacy. Ask your health care provider for advice if you are unsure about the online purchase of any medication.
See also: About generic drugs.
There are no current U.S. patents associated with Amphadase.
Dermolin may be available in the countries listed below.
Fluocinolone Acetonide is reported as an ingredient of Dermolin in the following countries:
International Drug Name Search
Antiprost may be available in the countries listed below.
Finasteride is reported as an ingredient of Antiprost in the following countries:
International Drug Name Search
Generic Name: interferon beta-1a (in ter FEAR on BAY ta)
Brand Names: Avonex, Avonex Prefilled Syringe, Rebif
Interferon beta-1a is made from human proteins. Interferons help the body fight viral infections.
Interferon beta-1a is used to treat relapsing multiple sclerosis (MS). This medication will not cure MS, it will only decrease the frequency of relapse symptoms.
Interferon beta-1a may also be used for other purposes not listed in this medication guide.
Before using interferon beta-1a, tell your doctor if you are allergic to any drugs, or if you have liver disease, a thyroid disorder, epilepsy or other seizure disorder, heart disease, chest pain (angina), congestive heart failure, a heart rhythm disorder, or a history of depression or suicidal behavior.
To be sure this medication is not causing harmful effects, your blood may need to be tested often. Your liver or thyroid function may also need to be tested. Visit your doctor regularly.
If you have any of these other conditions, you may need a dose adjustment or special tests:
liver disease;
epilepsy or other seizure disorder;
heart disease, chest pain (angina), congestive heart failure, or a heart rhythm disorder;
a thyroid disorder; or
a history of depression or suicidal behavior.
Avonex powder contains albumin, but the Avonex prefilled syringe does not. Albumin comes from human plasma (part of the blood) and may contain viruses and other infectious agents that can cause disease. Although donated human plasma is screened, tested, and treated to reduce the risk of it containing anything that could cause disease, there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.
Avonex is injected into a muscle. It is usually given once weekly at bedtime, on the same day each week (such as every Monday). Follow your doctor's instructions.
Rebif is injected under the skin. It is usually given 3 times per week (such as Monday, Wednesday, and Friday) at the same time on each dosing day. Follow your doctor's instructions.
This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.
Use a different place on your body each time you give the injection. Your care provider will show you the best places on your body to inject the medication. Do not inject into the same place two times in a row.
The powder form of Avonex must be mixed with a liquid (diluent) in the medicine vial. Gently swirl but do not shake the vial after mixing the medicine. The mixture should be clear or light yellow. Do not use the mixture if it has changed colors or has any particles in it. Mix a new dose or call your doctor for a new prescription.
Each prefilled syringe or single use vial (bottle) of this medicine is for one use only. Throw away after one use, even if there is still some medicine left after injecting your dose.
Use each disposable needle only one time. Throw away used needles in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.
Interferon beta-1 can lower blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood may need to be tested often. Your liver or thyroid function may also need to be tested. Visit your doctor regularly.
Throw away any interferon beta-1a that has become frozen or has been exposed to light or high heat.
Call your doctor for instructions if you miss a dose of this medication. Your injections should be at least 48 hours apart. Do not use interferon beta-1a injections 2 days in a row.
Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.
depressed mood, anxiety, trouble sleeping, restlessness, or thoughts of suicide or hurting yourself;
easy bruising or bleeding, weakness;
seizure (convulsions);
numbness or tingling in your hands or feet;
pain or burning when you urinate;
pain, swelling, or skin changes where the injection was given;
fever, chills, body aches, flu symptoms; or
nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).
Less serious side effects may include:
headache, dizziness;
stomach pain; or
runny or stuffy nose.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Interferon beta-1a can harm your liver. This effect is increased when you also use other medicines harmful to the liver. Many other drugs (including some over-the-counter medicines) can be harmful to the liver, such as:
acetaminophen (Tylenol);
cancer medications;
tuberculosis medications;
birth control pills or hormone replacement therapy;
methotrexate (Rheumatrex, Trexall);
arthritis medications such as auranofin (Ridaura);
an antibiotic;
HIV/AIDS medications;
cholesterol medications such atorvastatin (Lipitor), simvastatin (Zocor), and others;
an ACE inhibitor such as benazepril (Lotensin), captopril (Capoten), lisinopril (Prinivil, Zestril), and others;
an NSAID (non-steroidal anti-inflammatory drug) such as ibuprofen (Motrin, Advil), naproxen (Aleve, Naprosyn), indomethacin (Indocin), and others; or
seizure medications such as carbamazepine (Carbatrol, Tegretol), phenytoin (Dilantin), or valproic acid (Depakene).
This list is not complete and other drugs may interact with interferon beta-1a. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.
See also: Rebif side effects (in more detail)
CII
40-9065
Revised – August 2011
Rx Only
Cardiovascular Risk
Gastrointestinal Risk
Each combination tablet contains: Oxycodone hydrochloride, USP 5 mg and ibuprofen, USP 400 mg
Oxycodone hydrochloride and ibuprofen is supplied in a fixed combination tablet form for oral administration and combines the opioid analgesic agent, oxycodone hydrochloride, with the nonsteroidal anti-inflammatory (NSAID) agent, ibuprofen.
Oxycodone hydrochloride is a centrally acting semisynthetic opioid analgesic. Its chemical name is 4,5(-Epoxy-14-hydroxy-3-methoxy-methylmorphinan-6-one hydrochloride. Its molecular formula is C18H21NO4 •HCl and molecular weight is 351.83. Its structural formula is:
Ibuprofen is a nonsteroidal anti-inflammatory drug with analgesic and antipyretic properties. Its chemical name is (±)-2-(p-isobutylphenyl) propionic acid. Its molecular formula is C13H18O2 and molecular weight is 206.29. Its structural formula is:
Inactive ingredients in oxycodone hydrochloride and ibuprofen tablets include: calcium stearate, croscarmellose sodium, colloidal silicon dioxide, hydroxypropyl cellulose, microcrystalline cellulose, pregelatinized starch, and stearic acid. The coloring agents consist of hypromellose, lactose monohydrate, polyethylene glycol, synthetic yellow iron oxide, titanium dioxide, and triacetin.
Oxycodone hydrochloride component:
Oxycodone hydrochloride is a semisynthetic opioid analgesic with multiple actions which involve the central nervous system and smooth muscle. The mechanism of action of oxycodone is not known but is thought to be related to its binding to opiate receptors in the central nervous system. In addition to analgesia, opioids may produce sedation and respiratory depression.
Ibuprofen component:
Ibuprofen is a nonsteroidal anti-inflammatory agent that possesses analgesic and antipyretic activities. Its mode of action, similar to other NSAIDs, is not completely understood, but is thought to be related to its inhibition of cyclooxygenase activity and prostaglandin synthesis. Ibuprofen is a peripherally acting analgesic. Ibuprofen does not have any known effects on opiate receptors.
Absorption:
Oxycodone is rapidly absorbed after single dose administration of oxycodone hydrochloride and ibuprofen tablets. Maximum concentrations (Cmax) of oxycodone, ranging from 9.8 ng/mL to 11.7 ng/mL, are obtained within 1.3 hr to 2.1 hr after administration of oxycodone hydrochloride and ibuprofen. Repeated administration of oxycodone hydrochloride and ibuprofen, every 6 hours, results in approximately 50 to 65% increase in Cmax. In the presence of food, the bioavailability of oxycodone is slightly (25%) increased.
Ibuprofen is rapidly absorbed after oral administration of oxycodone hydrochloride and ibuprofen. Cmax values range from 18.5 mcg/mL to 34.3 mcg/mL and are reached 1.6 hr to 3.1 hr after oral administration of oxycodone hydrochloride and ibuprofen. Repeated administration of oxycodone hydrochloride and ibuprofen every 6 hours does not result in any accumulation of ibuprofen. The bioavailability of ibuprofen is not altered in the presence of food.
Distribution:
Oxycodone binding to protein in serum is approximately 45%.
Ibuprofen is extensively bound to plasma proteins (99%).
Metabolism:
Oxycodone is metabolized in the liver by means of N-demethylation and O-demethylation, 6-ketoreduction and glucuronidation. The major circulating metabolite is noroxycodone, which possesses weak analgesic activity.
Oxymorphone, the end product of O-demethylation, has analgesic activity but is present in the plasma at low concentrations. Metabolism of oxycodone to oxymorphone occurs via CYP2D6.
Ibuprofen is present 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'-(2-hydroxy-2-methyl-propyl) phenyl propionic acid and (+)-2-4'-(2-carboxypropyl) phenyl propionic acid, both of which circulate in the plasma at low levels relative to the parent.
Elimination:
Oxycodone is eliminated from the systemic circulation with half life (T1/2) values ranging from 3.1 hr to 3.7 hr after single dose administration of oxycodone hydrochloride and ibuprofen tablets. Urinary excretion of unchanged oxycodone amounts to approximately 4% of the administered oxycodone dose.
Ibuprofen is eliminated from the systemic circulation with half life (T1/2) values ranging from 1.8 hr to 2.6 hr after single dose administration of oxycodone hydrochloride and ibuprofen tablets. Urinary excretion of unchanged ibuprofen is minimal (less than 0.2% of administered ibuprofen dose).
Special Populations:
Gender: There are no gender effects on the pharmacokinetics of oxycodone or ibuprofen after administration of oxycodone hydrochloride and ibuprofen tablets.
Age: The effects of age on the pharmacokinetics of Oxycodone and Ibuprofen after administration of oxycodone hydrochloride and ibuprofen tablets have not been evaluated.
When either drug was administered alone, the pharmacokinetics of Oxycodone and Ibuprofen were similar in elderly subjects, compared to young healthy subjects.
Pediatrics: The pharmacokinetics of Oxycodone and Ibuprofen after administration of oxycodone hydrochloride and ibuprofen tablets has not been evaluated in a pediatric population.
Renal Impairment: The effects of renal impairment on the pharmacokinetics of Oxycodone and Ibuprofen after administration of oxycodone hydrochloride and ibuprofen tablets have not been evaluated.
Hepatic Impairment: The effects of hepatic impairment on the pharmacokinetics of Oxycodone and Ibuprofen after administration of oxycodone hydrochloride and ibuprofen tablets have not been evaluated. (See PRECAUTIONS; Hepatic Effects)
Oxycodone hydrochloride and ibuprofen was investigated in three clinical studies. Two studies involving a total of 949 patients following dental surgery (removal of ipsilateral molars) and a third study of 456 patients following abdominal/pelvic surgery were conducted. In the three studies patients were administered a single dose of the oxycodone hydrochloride and ibuprofen tablets, ibuprofen alone, oxycodone hydrochloride alone or placebo for acute, moderate to severe pain.
In these single dose studies, oxycodone hydrochloride and ibuprofen combination product produced greater efficacy than placebo and each of oxycodone hydrochloride and ibuprofen tablets individual components as measured by the magnitude of pain relief and the reduction in pain intensity through six hours. No multiple dose efficacy studies have been performed with oxycodone hydrochloride and ibuprofen.
Carefully consider the potential benefits and risks of oxycodone hydrochloride and ibuprofen and other treatment options before deciding to use oxycodone hydrochloride and ibuprofen tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).
Oxycodone hydrochloride and ibuprofen tablets are indicated for the short term (no more than 7 days) management of acute, moderate to severe pain.
Oxycodone hydrochloride and ibuprofen tablets should not be administered to patients who have previously exhibited hypersensitivity to oxycodone hydrochloride, ibuprofen, or any of oxycodone hydrochloride and ibuprofen tablets components.
Oxycodone hydrochloride and ibuprofen tablets should not be administered in any situation where opioids are contraindicated. This includes patients with significant respiratory depression (in unmonitored settings or the absence of resuscitative equipment) and patients with acute or severe bronchial asthma or hypercarbia. Patients known to be hypersensitive to other opioids may exhibit cross-sensitivity to oxycodone. Oxycodone hydrochloride and ibuprofen tablets are contraindicated in any patient who has or is suspected of having paralytic ileus.
Oxycodone hydrochloride and ibuprofen tablets should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe anaphylactoid reactions to NSAIDs, some of which were fatal, have been reported in such patients (see WARNINGS; Anaphylactoid Reactions, and PRECAUTIONS; Pre-existing Asthma).
Oxycodone hydrochloride and ibuprofen tablets are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).
Cardiovascular Thrombotic Events
Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events (see WARNINGS; Gastrointestinal
Effects - Risk of Ulceration, Bleeding, and Perforation).
Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS).
NSAIDs, including oxycodone hydrochloride and ibuprofen, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events.
Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including oxycodone hydrochloride and ibuprofen, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.
Fluid retention and edema have been observed in some patients taking NSAIDs. Oxycodone hydrochloride and ibuprofen should be used with caution in patients with fluid retention or heart failure.
NSAIDs, including oxycodone hydrochloride and ibuprofen, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3 to 6 months, and in about 2 to 4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk.
NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population.
To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.
Oxycodone hydrochloride and ibuprofen tablets contain oxycodone, which is an opioid agonist, and a Schedule II controlled substance. Opioid agonists have the potential for being abused and are sought by abusers and people with addiction disorders, and are subject to diversion.
Oxycodone hydrochloride and ibuprofen can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing oxycodone hydrochloride and ibuprofen tablets in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion (see DRUG ABUSE AND DEPENDENCE).
Oxycodone may produce dose-related respiratory depression by acting directly on the brain stem respiratory centers. Oxycodone hydrochloride also affects the center that controls respiratory rhythm, and may produce irregular and periodic breathing. Respiratory depression occurs most frequently in elderly or debilitated patients, usually following large initial doses in non-tolerant patients, or when opioids are given in conjunction with other agents that depress respiration. Oxycodone hydrochloride and ibuprofen should be used with extreme caution in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and in patients having substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression. In such patients, even usual therapeutic doses of oxycodone hydrochloride and ibuprofen may decrease respiratory drive to the point of apnea.
Oxycodone hydrochloride and ibuprofen, like all opioid analgesics, may cause severe hypotension in an individual whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs such as phenothiazines or other agents which compromise vasomotor tone. Oxycodone hydrochloride and ibuprofen may produce orthostatic hypotension in ambulatory patients. Oxycodone hydrochloride and ibuprofen, like all opioid analgesics, should be administered with caution to patients in circulatory shock, since vasodilatation produced by the drug may further reduce cardiac output and blood pressure.
The respiratory depressant effects of opioids and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, intracranial lesions or a pre-existing increase in intracranial pressure. Furthermore, opioids produce adverse reactions that may obscure the clinical course of patients with head injuries.
The administration of opioids may obscure the diagnosis or clinical course of patients with acute abdominal conditions.
Anaphylactoid reactions may occur in patients without known prior exposure to oxycodone hydrochloride and ibuprofen. Oxycodone hydrochloride and ibuprofen should not be given to patients with the aspirin triad or a history of angioedema. The triad typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs. Fatal reactions to NSAIDs have been reported in such patients (see CONTRAINDICATIONS and PRECAUTIONS; Pre-existing Asthma). Emergency help should be sought when anaphylactoid reaction occurs.
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
In patients with advanced kidney disease, treatment with oxycodone hydrochloride and ibuprofen is not recommended. No information is available from controlled clinical studies regarding the use of oxycodone hydrochloride and ibuprofen in patients with advanced renal disease. However, if oxycodone hydrochloride and ibuprofen tablets therapy must be initiated, due to the NSAID component, close monitoring of the patient’s kidney function is advisable (see WARNINGS; Renal Effects).
NSAIDs, including oxycodone hydrochloride and ibuprofen, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
Starting at 30 weeks gestation, oxycodone hydrochloride and ibuprofen, and other NSAIDs, should be avoided by pregnant women as premature closure of the ductus arteriosus may occur.
Oxycodone may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression.
Oxycodone hydrochloride and ibuprofen cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.
The pharmacological activity of oxycodone hydrochloride and ibuprofen in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.
As with any opioid analgesic agent, oxycodone hydrochloride and ibuprofen tablets should be used with caution in elderly or debilitated patients, and those with severe impairment of hepatic, pulmonary or renal function, hypothyroidism, Addison's disease, acute alcoholism, convulsive disorders, CNS depression or coma, delirium tremens, kyphoscoliosis associated with respiratory depression, toxic psychosis, prostatic hypertrophy or urethral stricture. The usual precautions should be observed and the possibility of respiratory depression, postural hypotension, and altered mental states should be kept in mind.
Oxycodone hydrochloride and ibuprofen may cause spasm of the sphincter of Oddi and should be used with caution in patients with biliary tract disease, including acute pancreatitis. Opioids like oxycodone hydrochloride and ibuprofen may cause increases in the serum amylase level.
Oxycodone suppresses the cough reflex; as with other opioid containing products, caution should be exercised when oxycodone hydrochloride and ibuprofen is used postoperatively and in patients with pulmonary disease.
Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including ibuprofen as found in oxycodone hydrochloride and ibuprofen tablets. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.
A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with oxycodone hydrochloride and ibuprofen. If clinical signs and symptoms consistent with liver disease develop, or if systematic manifestations occur (e.g., eosinophilia, rash, etc.), oxycodone hydrochloride and ibuprofen should be discontinued.
Anemia is sometimes seen in patients receiving NSAIDs, including ibuprofen as found in oxycodone hydrochloride and ibuprofen tablets. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including ibuprofen, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.
NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving oxycodone hydrochloride and ibuprofen who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored. Patients previously treated with NSAIDs and currently using oxycodone hydrochloride and ibuprofen should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.
Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which can be fatal. Since cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, oxycodone hydrochloride and ibuprofen should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with pre-existing asthma.
Aseptic meningitis with fever and coma has been observed on rare occasions in patients on ibuprofen as found in oxycodone hydrochloride and ibuprofen tablets. Although it is probably more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease. If signs or symptoms of meningitis develop in a patient on oxycodone hydrochloride and ibuprofen tablets, the possibility of its being related to ibuprofen should be considered.
Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs should have their CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g. eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, oxycodone hydrochloride and ibuprofen should be discontinued.
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.
Anticholinergics: The concurrent use of anticholinergics with oxycodone preparations may produce paralytic ileus.
CNS Depressants: 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.
ACE-Inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking oxycodone hydrochloride and ibuprofen concomitantly with ACE-inhibitors.
Aspirin: When oxycodone hydrochloride and ibuprofen is administered with aspirin, its protein binding is reduced, although the clearance of free oxycodone hydrochloride and ibuprofen is not altered. The clinical significance of this interaction is not known; however as with other products containing NSAIDs, concomitant administration of oxycodone hydrochloride and ibuprofen and aspirin is not generally recommended because of the potential of increased adverse effects.
Diuretics: 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 oxycodone hydrochloride and ibuprofen the patient should be observed closely for signs of renal failure (see WARNINGS; Renal Effects), as well as diuretic efficacy.
Lithium: 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 oxycodone hydrochloride and ibuprofen and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.
Methotrexate: 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 oxycodone hydrochloride and ibuprofen is administered concomitantly with methotrexate.
Warfarin: 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.
Studies to evaluate the potential effects of the combination of Oxycodone and Ibuprofen on carcinogenicity and mutagenicity have not been conducted.
Oxycodone hydrochloride was not genotoxic in the following assays: Ames bacterial mutuation assay, chromosomal aberrations in cultured human lymphocytes, and in vivo mouse micronucleus assay in mice.
There was no evidence of impairment of fertility in either male or female Sprague-Dawley rats administered oxycodone hydrochloride; ibuprofen up to (1:80 mg/kg/day) which is equivalent to 0.5-times the maximum recommended human daily dose (MRHD) (20:1600 mg/day) on a body surface area (mg/m2 ) basis.
Pregnancy Category C prior to 30 weeks gestation; Category D starting at 30 weeks gestation
Starting at 30 weeks gestation, oxycodone hydrochloride and ibuprofen, and other NSAIDS, should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur. Oxycodone hydrochloride and ibuprofen can cause fetal harm when administered to a pregnant woman starting at 30 weeks gestation. If oxycodone hydrochloride and ibuprofen, and other NSAIDS, are used during this time period in pregnancy, the patient should be apprised of the potential hazard to a fetus. There are no adequate and well-controlled studies in pregnant women. Prior to 30 weeks gestation, oxycodone hydrochloride and ibuprofen should be used during pregnancy only if the potential benefit justifies the risk to the fetus.
Animal studies to assess the potential effects of the combination of Oxycodone and Ibuprofen on embryo-fetal development were conducted in the rat and rabbit model.
Pregnant rats were treated by oral gavage with combination doses of oxycodone:ibuprofen mg/kg/day (0.25:20, 0.5:40, 1:80, or 2:160) on days 7 to16 of gestation. There was no evidence for developmental toxicity or teratogenicity at any dose, although maternal toxicity was noted at doses of 0.5:40 and above. The highest dose tested in the rat (2:160 mg/kg/day) is equivalent to the maximum recommended human daily dose (20:1600 mg/day) on a body surface area (mg/m2) basis. This dose was associated with maternal toxicity (death, clinical signs, decreased BW).
Pregnant rabbits were treated by oral gavage with combination doses of oxycodone/ibuprofen (0.38:30, 0.75:60, 1.5:120 or 3:240 mg/kg/day) on gestation days 7 to19. Oxycodone/ibuprofen treatment was not teratogenic under the conditions of the assay. Maternal toxicity was noted at doses of 1.5:120 (reduced body weight and food consumption) and 3:240 mg/kg/day (mortality). The NOAEL for maternal toxicity, 0.75:60 mg/kg/day, is 0.75 fold the proposed maximum daily human dose based upon the body surface area. Developmental toxicity, as evidenced by delayed ossification and reduced fetal body weights, was noted at the highest dose, which is approximately 3 times the MRHD on a mg/m2 basis, and is likely due to maternal toxicity. The fetal no adverse effect level (NOAEL) of 1.5:120 mg/kg/day is approximately 1.5 times the MRHD on a mg/m2 basis.
In a pre- and postnatal development study conducted in rats, there was increased mortality of pups born to dams dose with 0.5:40 mg/kg/day oxycodone:ibuprofen and above which is equivalent to 0.25-times of the MRHD (20:1600 mg/day) on a body surface area (mg/m2) basis. There was an increase in stillborn F1 pups and decrease in mean pup weight in dams dosed with 1:80 mg/kg/day oxycodone:ibuprofen, which is 0.5-times the MRHD (20:1600 mg/day) on a body surface area (mg/m2) basis.
Babies born to mothers who have been taking opioids regularly prior to delivery will be physical dependent. The withdrawal signs include irritability and excessive crying, tremors, hyperactive reflexes, increased respiratory rate, increased stools, sneezing, yawning, vomiting, and fever. The intensity of the syndrome does not always correlate with the duration of maternal opioid use or dose. There is no consensus on the best method of managing withdrawal.
Oxycodone hydrochloride and ibuprofen should not be used during the third trimester of pregnancy due to the potential for ibuprofen to inhibit prostaglandin synthetase which may prolong pregnancy and inhibit labor. Oxycodone is not recommended for use in women during and immediately prior to labor and delivery because oral opioids may cause respiratory depression in the newborn.
In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. The effects of oxycodone hydrochloride and ibuprofen on labor and delivery in pregnant women are unknown.
It is not known whether oxycodone hydrochloride and ibuprofen is excreted in human milk. Oxycodone is excreted in human milk. Withdrawal symptoms and/or respiratory depression have been observed in neonates whose mothers were taking narcotic analgesics during pregnancy. Although adverse effects in the nursing infant have not been documented, withdrawal can occur in breast-feeding infants when maternal administration of an opioid analgesic is discontinued. Because many drugs are excreted in human-milk and because of the potential for serious adverse reactions in nursing infants from oxycodone hydrochloride and ibuprofen, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
In the placebo-controlled, clinical studies of pain following dental surgery, 109 patients between the ages of 14 and 17 years were administered a single dose of oxycodone hydrochloride and ibuprofen tablets. No apparent differences were noted in the safety of oxycodone hydrochloride and ibuprofen in patients below and above 17 years of age. Oxycodone hydrochloride and Ibuprofen has not been studied in patients under 14 years of age. Safety and effectiveness in pediatric patients below the age of 14 have not been established.
Of the total number of subjects in clinical studies of oxycodone hydrochloride and ibuprofen, 89 patients were 65 and over, while 37 patients were 75 and over. No overall differences in safety were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
However, because the elderly may be more sensitive to the renal and gastrointestinal effects of nonsteroidal anti-inflammatory agents as well as possible increased risk of respiratory depression with opioids, extra caution should be used when treating the elderly with oxycodone hydrochloride and ibuprofen.
Listed below are the adverse event incidence rates from single dose analgesia trials in which a total of 2437 patients received either oxycodone hydrochloride and ibuprofen combination product, ibuprofen (400 mg), oxycodone hydrochloride (5 mg), or placebo. Adverse event information is also provided from an additional 334 patients who were exposed to oxycodone hydrochloride and ibuprofen combination product in a multiple dose analgesia trial, without placebo or active component comparison arms, given up to four times daily for up to 7 days.
| 5 mg | ||||
| 400 mg | Oxycodone | |||
| 5/400 mg | Ibuprofen | Hydrochloride | Placebo | |
| (n=923) | (n=913) | (n = 286) | (n=315) | |
| Digestive | ||||
| 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 |
| Nervous System | ||||
| 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 oxycodone hydrochloride 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 oxycodone hydrochloride 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 oxycodone hydrochloride 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 oxycodone hydrochloride 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.
Oxycodone hydrochloride and ibuprofen tablets contain oxycodone, which is a mu-opioid agonist with an abuse liability similar to other opioid agonists and is a Schedule II controlled substance. Oxycodone hydrochloride and ibuprofen tablets, and other opioids used in analgesia, can be abused and are
Hysetin P may be available in the countries listed below.
Chloramphenicol is reported as an ingredient of Hysetin P in the following countries:
Neomycin sulfate (a derivative of Neomycin) is reported as an ingredient of Hysetin P in the following countries:
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