Oxycodone; Aspirin Half-Strength

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Oxycodone; Aspirin Half-Strength uses

Oxycodone; Aspirin Half-Strength consists of Aspirin, Oxycodone Hydrochloride, Oxycodone Terephthalate.

Aspirin:


Pharmacological action

Oxycodone; Aspirin Half-Strength is a NSAIDs. It has anti-inflammatory, analgesic and antipyretic effect, and inhibits platelet aggregation. The mechanism of action is associated with inhibition of COX activity - the main enzyme metabolism of arachidonic acid which is a precursor of prostaglandins which play a major role in the pathogenesis of inflammation, pain and fever. Reduction of prostaglandins (mainly E1) in the thermoregulation center leads to a decrease in body temperature due to expansion of blood vessels of the skin and increase perspiration. Analgesic effect of Oxycodone; Aspirin Half-Strength (Aspirin) is due to both central and peripheral effects. Reduces aggregation, platelet adhesion and thrombus formation through suppression of synthesis of thromboxane A2 in platelets.

Reduces mortality and risk of myocardial infarction in unstable stenocardia. It is effective in primary prevention of cardio-vascular system and secondary prevention of myocardial infarction. At a daily dose of 6 g or more inhibits the synthesis of prothrombin in the liver and increases the prothrombin time. Oxycodone; Aspirin Half-Strength (Aspirin) increases fibrinolytic activity of plasma and reduces the concentration of vitamin K-dependent coagulation factors (II, VII, IX, X). Increases the rate of hemorrhagic complications in carrying out surgical procedures, increases the risk of bleeding during therapy with anticoagulants. It stimulates the excretion of uric acid (violating its reabsorption in the renal tubules) but in high doses. The blockade of COX-1 in the mucosa of the stomach leads to inhibition of gastroprotective prostaglandins, which may lead to ulceration of the mucous membrane and subsequent bleeding.

Pharmacokinetics

When administered orally Oxycodone; Aspirin Half-Strength (Aspirin) is rapidly absorbed mainly from the proximal small intestine and to a lesser extent from the stomach. The presence of food in the stomach significantly affects the absorption of Oxycodone; Aspirin Half-Strength (Aspirin).

Metabolised in the liver by hydrolysis with the formation of salicylic acid with subsequent conjugation with glycine or two drugs. The concentration of salicylates in blood plasma is variable.

About 80% of salicylic acid binds to plasma proteins. Salicylates easily penetrate into many tissues and body fluids, including the cerebrospinal, peritoneal and synovial fluid. In small quantities salicylates are found in brain tissue, traces - in bile, sweat and feces. Quickly penetrates the placental barrier in small amounts excreted in breast milk.

For newborns salicylates may displace bilirubin from its association with albumin and promote bilirubin encephalopathy.

Penetration into the joint cavity is accelerated in the presence of hyperemia and edema, and slows down in the proliferative phase of inflammation.

If you have acidosis most of salicylate becomes unionized acid, good penetration into the tissue, including in the brain.

Oxycodone; Aspirin Half-Strength (Aspirin) withdraws mainly by active secretion in the tubules of the kidneys in unchanged form (60%) and in the form of metabolites. The withdraw of unchanged salicylate is dependent on the pH of urine (for alkalinization of urine increases ionized salicylates, worsening their reabsorption and increases excretion). T1/2 of Oxycodone; Aspirin Half-Strength (Aspirin) is approximately 15 minutes. T1/2 of salicylate at a reception in low doses is 2-3 h, with an increase in dose may increase to 15-30 hours. Newborns' elimination of salicylate is much slower than in adults.

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Why is Oxycodone; Aspirin Half-Strength prescribed?

Rheumatism, rheumatoid arthritis, infectious-allergic myocarditis, fever during infectious and inflammatory diseases, pain syndrome, weak and medium intensity of various origins (including neuralgia, myalgia, headache); based prevention of thrombosis and embolism, primary and secondary prevention of myocardial infarction, prevention of violations of cerebral circulation by ischemic type.

In the clinical immunology and allergy: a gradually increasing doses for a prolonged "aspirin" desensitization and the formation of stable tolerance to NSAIDs in patients with "aspirin asthma" and "aspirin triad."

Dosage and administration

Individual. For oral administration dosing of Oxycodone; Aspirin Half-Strength regimen depends on indication for use. Usual adult dose when used as antipyretic and analgesic is 500-1000 mg / day (up to 3 g) were divided into 3 admission.

In myocardial infarction, as well as for secondary prevention in patients after myocardial infarction - 40-325 mg 1 time a day (usually 160 mg). As an inhibitor of platelet aggregation - a dose of 300-325 mg / day, for a long time. At the dynamic circulatory disorders in men, cerebral thromboembolism, including to prevent a recurrence - 325 mg / day with gradual increase to a maximum of 1 g / day. For prevention of thrombosis or occlusion of the aortic shunt - by 325 mg every 7 h after intranasal gastric tube set, and then - through the mouth to 325 mg 3 times a day (usually in combination with dipyridamole, which abolished after 1 week, continuing the long-term treatment with Oxycodone; Aspirin Half-Strength (Aspirin)).

Oxycodone; Aspirin Half-Strength (Aspirin) side effects, adverse reactions

Digestive system: nausea, vomiting, anorexia, epigastric pain, diarrhea; rarely - occurrence of erosive and ulcerative lesions, bleeding from the gastrointestinal tract, abnormal liver function.

Central nervous system: long-term use may be dizziness, headache, reversible visual disturbances, tinnitus, aseptic meningitis.

Hemopoietic system: rarely - thrombocytopenia, anemia.

Blood coagulation system: rarely - haemorrhagic syndrome, prolongation of bleeding time.

Urinary system: rarely - renal dysfunction, with prolonged use - acute kidney failure, nephrotic syndrome.

Allergic reactions: rarely - skin rash, Quincke's edema, bronchospasm, "aspirin triad" (a combination of bronchial asthma, recurrent nasal polyposis, and paranasal sinuses and intolerance of Oxycodone; Aspirin Half-Strength (Aspirin) and medicines pirazolonic series).

Other: in some cases - Reye syndrome, long-term use - increased symptoms of chronic heart failure.

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Oxycodone; Aspirin Half-Strength contraindications

Exacerbation phase of erosive-ulcerative lesions in the gastrointestinal tract, gastro-intestinal bleeding, "aspirin triad", a history of indications urticaria, rhinitis, caused by taking Oxycodone; Aspirin Half-Strength (Aspirin) and other NSAIDs, hemophilia, hemorrhagic diathesis, gipoprotrombinemii, dissecting aneurysm of the aorta, portal hypertension, deficiency of vitamin K, liver and / or renal failure, deficiency of glucose-6-phosphate dehydrogenase, Reye syndrome, children's age (under 15 years - the risk of developing Reye syndrome in children with hyperthermia on a background of viral diseases), I and III trimester of pregnancy, lactation, hypersensitivity to Oxycodone; Aspirin Half-Strength (Aspirin) and other salicylates.

Using during pregnancy and breastfeeding

Oxycodone; Aspirin Half-Strength (acetylsalicylic acid) is contraindicated in I and III trimester of pregnancy. In pregnancy trimester II can a one-off reception on the strict condition.

This medication has a teratogenic effect: when used in the I trimester leads to top palatoschisis, in the III trimester - cause inhibition of labor (inhibition of prostaglandin synthesis), premature closure of the ductus arteriosus in the fetus, pulmonary vascular hyperplasia and hypertension in the pulmonary circulation.

Oxycodone; Aspirin Half-Strength (Aspirin) (acetylsalicylic acid) is excreted in breast milk, which increases the risk of bleeding in a child due to dysfunction of platelets, and therefore should not be applied Oxycodone; Aspirin Half-Strength (Aspirin) in the mother during lactation.

Special instructions

Oxycodone; Aspirin Half-Strength (Aspirin) with caution used in patients with liver diseases and kidney, bronchial asthma, erosive and ulcerative lesions, and bleeding from the digestive tract in history, with increased bleeding or while holding anticoagulant therapy, decompensated congestive heart failure.

Oxycodone; Aspirin Half-Strength (Aspirin) even in small doses reduces the excretion of uric acid from the organism that can cause an acute attack of gout in predisposed patients. When conducting long-term therapy and / or use of Oxycodone; Aspirin Half-Strength (Aspirin) in high doses required medical supervision and regular monitoring of hemoglobin levels.

The use of Oxycodone; Aspirin Half-Strength (Aspirin) as anti-inflammatory drugs in a daily dose of 5-8 g is limited due to the high probability of adverse effects from the gastrointestinal tract.

Before surgery to reduce bleeding during surgery and postoperative period should stop taking salicylates for 5-7 days.

During prolonged therapy is necessary to conduct a general analysis of blood and study of occult blood.

The use of Oxycodone; Aspirin Half-Strength (Aspirin) is contraindicated in pediatrics, as in the case of viral infection in children under the influence of Oxycodone; Aspirin Half-Strength (Aspirin) increases the risk of developing Reye syndrome. Symptoms of Reye syndrome are prolonged vomiting, acute encephalopathy, liver enlargement.

Duration of treatment (without consulting a doctor) with Oxycodone; Aspirin Half-Strength (Aspirin) should not exceed 7 days when administered as analgesic and more than 3 days as an antipyretic.

During treatment the patient should abstain from alcohol.

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Precautionary measures

Undesirable combined use with other NSAIDs and glucocorticoids. For 5-7 days before surgery should stop taking.

The probability of NSAID-gastropathy decreases in the appointment after a meal, use of tablets with buffer additives or coated with a special enteric-soluble shell. The risk of hemorrhagic complications is minimal when used in doses less than 100 mg / day.

Note that in predisposed patients Oxycodone; Aspirin Half-Strength (Aspirin) (even in small doses) reduces the excretion of uric acid from the body and can cause the development of acute attack of gout.

During prolonged therapy should regularly carry out the analysis of blood and to investigate faeces for occult blood. In connection with the observed cases hepatogenic encephalopathy is not recommended for relief of fever syndrome in children.

Oxycodone; Aspirin Half-Strength (Aspirin) drug interactions

With simultaneous use of antacids containing magnesium and / or aluminum hydroxide, slow down and reduce the absorption of Oxycodone; Aspirin Half-Strength (Aspirin).

With simultaneous use of calcium channel blockers, means limiting intake of calcium or increasing the excretion of calcium from the body, increases the risk of bleeding.

With simultaneous use with Oxycodone; Aspirin Half-Strength (Aspirin) enhances the action of heparin and indirect anticoagulants, hypoglycemic funds derived sulfonylureas, insulin, methotrexate, phenytoin, valproic acid.

With simultaneous use of Oxycodone; Aspirin Half-Strength (Aspirin) with SCS increases the risk of ulcerogenic effect and occurrence of gastrointestinal bleeding.

With simultaneous use of decreasing the effectiveness of diuretics (spironolactone, furosemide).

With simultaneous use of other NSAIDs increases the risk of side effects. Oxycodone; Aspirin Half-Strength (Aspirin) may reduce plasma concentrations indomethacin, piroxicam.

With simultaneous use of gold drugs Oxycodone; Aspirin Half-Strength (Aspirin) can induce liver damage.

With simultaneous use decreases effectiveness of uricosuric medications (including probenecid, sulfinpirazon, benzbromarone).

With simultaneous use of Oxycodone; Aspirin Half-Strength (Aspirin) and alendronate sodium may develop severe esophagitis.

With simultaneous use of griseofulvin may be in breach Absorption of Oxycodone; Aspirin Half-Strength (Aspirin).

There is one case of spontaneous hemorrhage in the iris while taking Ginkgo Biloba extract on the background of prolonged use of Oxycodone; Aspirin Half-Strength (Aspirin) in a dose of 325 mg / day. It is believed that this may be due to additive inhibitory effect on platelet aggregation.

With simultaneous use of dipyridamole may increase Cmax of salicylate in plasma and AUC.

When applied simultaneously with Oxycodone; Aspirin Half-Strength (Aspirin) increased concentration of digoxin, barbiturates and lithium salts in the blood plasma.

With simultaneous use of salicylates in high doses with carbonic anhydrase inhibitors can intoxication salicylates.

Oxycodone; Aspirin Half-Strength (Aspirin) in doses of less than 300 mg have little effect on the effectiveness of captopril and enalapril. When Oxycodone; Aspirin Half-Strength (Aspirin) (acetylsalicylic acid) is admistered in high doses may decrease the effectiveness of captopril and enalapril.

With simultaneous application of caffeine increases the rate of absorption, plasma concentrations and bioavailability of Oxycodone; Aspirin Half-Strength (Aspirin).

With simultaneous use of Oxycodone; Aspirin Half-Strength (Aspirin) with metoprolol may increase Cmax of salicylate in blood plasma.

In the application of pentazocine on the background of long-term use of Oxycodone; Aspirin Half-Strength (Aspirin) in high doses there is a risk of severe adverse reactions in the kidneys.

With simultaneous application phenylbutazone reduces uricosuria caused by Oxycodone; Aspirin Half-Strength (Aspirin).

With simultaneous application of ethanol may exacerbate the effects of Oxycodone; Aspirin Half-Strength (Aspirin) on the gastrointestinal tract.

Oxycodone; Aspirin Half-Strength in case of emergency / overdose

May occur after receiving a single large dose or prolonged use. If a single dose of less than 150 mg / kg, acute poisoning feel light, 150-300 mg / kg - moderate, when using higher doses - heavy.

Symptoms: salicylism syndrome (nausea, vomiting, tinnitus, blurred vision, dizziness, severe headache, malaise, fever - a poor prognostic sign in adults). More severe poisoning - stupor, convulsions and coma, noncardiogenic pulmonary edema, abrupt dehydration, violations ABE (initially - respiratory alkalosis, then - metabolic acidosis), renal failure and shock.

In chronic overdose concentration determined in plasma are poorly correlated with the severity of intoxication. The greatest risk of chronic intoxication is found among elderly people at reception for a few days more than 100 mg / kg / day. In children and elderly patients the initial signs of salicylism are not always visible, and therefore desirable to periodically determine the concentration of salicylates in the blood. Level above 70 mg% indicates moderate or severe poisoning; above 100 mg% - on extremely heavy, a poor prognosis. If poisoning moderate require hospitalization for at least 24 hours.

Treatment: the provocation of vomiting, the appointment of activated charcoal and laxatives, monitoring ABE and electrolyte balance, depending on the state of metabolism - the introduction of sodium bicarbonate, solution of sodium citrate or sodium lactate. Raising reserve alkalinity increases the excretion of Oxycodone; Aspirin Half-Strength (Aspirin) by alkalinization of urine. Alkalinization of urine is shown at the level of salicylates above 40 mg%, is provided in / by infusion of sodium bicarbonate - 88 mEq in 1 liter of 5% glucose solution, the rate of 10-15 ml / kg / h. Restoring BCC and induction of diuresis (achieved by introducing a bicarbonate in the same dose and dilution, repeat 2-3 times); should be aware that intense infusion fluid elderly patients may lead to pulmonary edema. Not recommended the use of acetazolamide for alkalinization of urine (may cause acidemia and enhance the toxic effect of salicylates). Hemodialysis is shown at the level of salicylates over 100-130 mg%, and in patients with chronic poisoning - 40 mg% or lower in the presence of witnesses (refractory acidosis, progressive deterioration, severe damage of the CNS, pulmonary edema and renal failure). When pulmonary edema - a mixture of artificial ventilation, oxygen enriched, in the mode of positive end-expiratory pressure, to treat cerebral edema apply hyperventilation and osmotic diuresis.

Oxycodone Hydrochloride:


1 INDICATIONS AND USAGE

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) capsule is an opioid analgesic, indicated for the management of moderate to severe acute and chronic pain where use of an opioid analgesic is appropriate.

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) is an opioid agonist indicated for the management of moderate to severe acute and chronic pain where the use of an opioid analgesic is appropriate. (1)

2 DOSAGE AND ADMINISTRATION

Selection of patients for treatment with Oxycodone; Aspirin Half-Strength should be governed by the same principles that apply to the use of similar opioid analgesics. Individualize treatment in every case, using non-opioid analgesics, opioids on an as needed basis and/or combination products, and chronic opioid therapy in a progressive plan of pain management such as outlined by the World Health Organization, the Agency for Healthcare Research and Quality, and the American Pain Society.

  • Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) Capsule, 5 mg: 5 mg to 15 mg every 4 to 6 hours as needed. (2.2).

2.1 Individualization of Dosage

As with any opioid drug product, adjust the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience. In the selection of the initial dose of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride), give attention to the following:

  • the total daily dose, potency and specific characteristics of the opioid the patient has been taking previously;
  • the reliability of the relative potency estimate used to calculate the equivalent Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) dose needed;
  • the patient's degree of opioid tolerance;
  • the general condition and medical status of the patient;
  • concurrent medications;
  • the type and severity of the patient's pain;
  • risk factors for abuse, addiction or diversion, including a prior history of abuse, addiction or diversion.

The following dosing recommendations, therefore, can only be considered suggested approaches to what is actually a series of clinical decisions over time in the management of the pain of each individual patient.

Continual re-evaluation of the patient receiving Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) is important, with special attention to the maintenance of pain control and the relative incidence of side effects associated with therapy. During chronic therapy, especially for non-cancer-related pain, periodically re-assess the continued need for the use of opioid analgesics.

During periods of changing analgesic requirements, including initial titration, frequent contact is recommended between physician, other members of the healthcare team, the patient, and the caregiver/family.

2.2 Initiation of Therapy in Opioid-Naïve Patients

Start patients who have not been receiving opioid analgesics on Oxycodone; Aspirin Half-Strength in the following dosing range using Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) Capsules, 5 mg strength:

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) Capsules: 5 to 15 mg every 4 to 6 hours as needed for pain.

Titrate the dose based upon the individual patient's response to their initial dose of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride). Adjust the dose to an acceptable level of analgesia taking into account the improvement in pain intensity and the tolerability of the oxycodone by the patient.

2.3 Conversion to Oral Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride)

There is inter-patient variability in the potency of opioid drugs and opioid formulations. Therefore, a conservative approach is advised when determining the total daily dose of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride). It is better to underestimate a patient's 24-hour oral Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) dose and make available rescue medication than to overestimate the 24-hour oral Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) dose and manage an adverse experience of overdose.

Consider the following general points regarding opioid conversions.

Conversion From other Non-Oxycodone Opioids to Oral Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride).

In converting patients from other opioids to Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride), close observation and adjustment of dosage based upon the patient's response to Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) is imperative. Physicians and other healthcare professionals are advised to refer to published relative potency information, keeping in mind that conversion ratios are only approximate.

Conversion From Controlled-Release Oral Oxycodone to Oral Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride).

The relative bioavailability of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) Capsule compared to controlled-release oxycodone is unknown. The extended duration of release of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) from controlled-release tablets results in reduced maximum and increased minimum plasma Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) concentrations than with shorter acting Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) products. Conversion from controlled-release tablets could lead to excessive sedation at peak serum levels. Therefore, dose adjustment with close observation is necessary.

Conversion From Oral Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) to Controlled-Release Oral Oxycodone

The relative bioavailability of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) Capsules compared to controlled-release oxycodone is unknown, so conversion to controlled-release tablets must be accompanied by close observation for signs of excessive sedation.

2.4 Maintenance of Therapy

Continual re-evaluation of the patient receiving Oxycodone; Aspirin Half-Strength is important, with special attention to the maintenance of pain management and the relative incidence of side effects associated with therapy. If the level of pain increases, effort should be made to identify the source of increased pain, while adjusting the dose as described above to decrease the level of pain. During chronic therapy, especially for non-cancer-related pain (or pain associated with other terminal illnesses), periodically reassess the continued need for the use of opioid analgesics.

2.5 Cessation of Therapy

When a patient no longer requires therapy with Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) gradually taper the dose to prevent signs and symptoms of withdrawal in the physically dependent patient.

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3 DOSAGE FORMS AND STRENGTHS

Each Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) capsule has an opaque yellow cap imprinted in black ink with "LV" and an opaque white body imprinted in black ink with "901" containing 5 mg of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride), USP.

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) capsules are available in one strength. Each hard gelatin capsule contains 5 mg Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride). (3)

4 CONTRAINDICATIONS

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) is contraindicated in patients with respiratory depression in the absence of resuscitative equipment.

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) is contraindicated in any patient who has or is suspected of having paralytic ileus.

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) is contraindicated in patients with acute or severe bronchial asthma or hypercarbia.

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) is contraindicated in patients with known hypersensitivity to oxycodone, oxycodone salts, or any components of the product.

  • Respiratory depression in the absence of resuscitative equipment. (4)
  • Paralytic ileus. (4)
  • Acute or severe bronchial asthma or hypercarbia. (4)
  • Known hypersensitivity to oxycodone. (4)

5 WARNINGS AND PRECAUTIONS

  • Respiratory depression: Increased risk in elderly, debilitated patients, those suffering from conditions accompanied by hypoxia, hypercapnia, or upper airway obstruction.
  • Misuse, Abuse and Diversion: Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) is a Schedule II controlled substance with an abuse liability similar to other opioids. (5.2)
  • CNS effects: Additive CNS depressive effects when used in conjunction with alcohol, other opioids, or illicit drugs. (5.3)
  • Elevation of intracranial pressure: May be markedly exaggerated in the presence of head injury, other intracranial lesions. (5.4)
  • Hypotensive effect: Increased risk with compromised ability to maintain blood pressure. (5.5)
  • Prolonged gastric obstruction: In patients with gastrointestinal obstruction, especially paralytic ileus. (5.6)
  • Sphincter of Oddi spasm and diminished biliary/pancreatic secretions. Increased risk with biliary tract disease. (5.7)
  • Special Risk Groups: Use with caution and in reduced dosages in patients with severe renal or hepatic impairment, Addison's disease, hypothyroidism, prostatic hypertrophy, or urethral stricture, elderly, CNS depression, toxic psychosis, acute alcoholism and delirium tremens, may aggravate or induce seizures. (5.8)
  • Impaired mental/physical abilities: Caution must be used with potentially hazardous activities. (5.9)
  • Concomitant use of CYP3A4 inhibitors may increase opioid effects. (5.10)

5.1 Respiratory Depression

Respiratory depression is the primary risk of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride). Respiratory depression occurs more frequently in elderly or debilitated patients and in those suffering from conditions accompanied by hypoxia, hypercapnia, or upper airway obstruction, in whom even moderate therapeutic doses may significantly decrease pulmonary ventilation.

Use Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) with extreme caution in patients with chronic obstructive pulmonary disease or cor pulmonale and in patients having a substantially decreased respiratory reserve (e.g., severe kyphoscoliosis), hypoxia, hypercapnia, or preexisting respiratory depression. In such patients, even usual therapeutic doses of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) may increase airway resistance and decrease respiratory drive to the point of apnea. Consider alternative non-opioid analgesics, and use Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) only under careful medical supervision at the lowest effective dose in such patients.

5.2 Misuse, Abuse and Diversion of Opioids

Oxycodone; Aspirin Half-Strength is an opioid agonist and a Schedule II controlled substance. Such drugs are sought by drug abusers and people with addiction disorders. Diversion of Schedule II products is an act subject to criminal penalty.

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) may be abused by crushing, chewing, snorting or injecting the product. These practices pose a significant risk to the abuser that could result in overdose and death.

Concerns about abuse, addiction, and diversion should not prevent the proper management of pain. Healthcare professionals should contact their State Professional Licensing Board or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product.

5.3 Interactions with Alcohol and Drugs of Abuse

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression because respiratory depression, hypotension, profound sedation, coma or death may result.

5.4 Use In Head Injury and Increased Intracranial Pressure

In the presence of head injury, intracranial lesions or a preexisting increase in intracranial pressure, the possible respiratory depressant effects of Oxycodone; Aspirin Half-Strength and its potential to elevate cerebrospinal fluid pressure (resulting from vasodilation following CO2 retention) may be markedly exaggerated. Furthermore, Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) can produce effects on pupillary response and consciousness, which may obscure neurologic signs of further increases in intracranial pressure in patients with head injuries.

5.5 Hypotensive Effect

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) may cause severe hypotension in an individual whose ability to maintain blood pressure has already been compromised by a depleted blood volume or concurrent administration of drugs such as phenothiazines or general anesthetics. Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) may produce orthostatic hypotension and syncope in ambulatory patients.

Administer Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) with caution to patients in circulatory shock, as vasodilation produced by the drug may further reduce cardiac output and blood pressure.

5.6 Gastrointestinal Effects

Do not administer Oxycodone; Aspirin Half-Strength to patients with gastrointestinal obstruction, especially paralytic ileus because Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) diminishes propulsive peristaltic waves in the gastrointestinal tract and may prolong the obstruction.

The administration of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) may obscure the diagnosis or clinical course in patients with acute abdominal condition.

5.7 Use In Pancreatic/Biliary Tract Disease:

Use Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) with caution in patients with biliary tract disease, including acute pancreatitis, as Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) may cause spasm of the sphincter of Oddi and diminish biliary and pancreatic secretions.

5.8 Special Risk Groups

Use Oxycodone; Aspirin Half-Strength with caution and in reduced dosages in patients with severe renal or hepatic impairment, Addison's disease, hypothyroidism, prostatic hypertrophy, or urethral stricture, and in elderly or debilitated patients. Exercise caution in the administration of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) to patients with CNS depression, toxic psychosis, acute alcoholism and delirium tremens. All opioids may aggravate convulsions in patients with convulsive disorders, and all opioids may induce or aggravate seizures in some clinical settings.

Keep Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) capsules out of the reach of children. In case of accidental ingestion, seek emergency medical help immediately.

5.9 Driving and Operating Machinery

Caution patients that Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) could impair the mental and/or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Caution patients about the potential combined effects of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) with other CNS depressants, including other opioids, phenothiazines, sedative/hypnotics and alcohol.

5.10 Cytochrome P450 3A4 Inhibitors and Inducers

Since the CYP3A4 isoenzyme plays a major role in the metabolism of oxycodone, drugs that alter CYP3A4 activity may cause changes in clearance of oxycodone which could lead to changes in oxycodone plasma concentrations. The expected clinical results with CYP3A4 inhibitors would be an increase in oxycodone plasma concentrations and possibly increased or prolonged opioid effects. The expected clinical results with CYP3A4 inducers would be a decrease in oxycodone plasma concentrations, lack of efficacy or, possibly, development of an abstinence syndrome in a patient who had developed physical dependence to oxycodone.

If co-administration is necessary, caution is advised when initiating oxycodone treatment in patients currently taking, or discontinuing, CYP3A4 inhibitors or inducers. Evaluate these patients at frequent intervals and consider dose adjustments until stable drug effects are achieved.

6 ADVERSE REACTIONS

Serious adverse reactions that may be associated with oxycodone therapy in clinical use are those observed with other opioid analgesics and include: respiratory depression, respiratory arrest, circulatory depression, cardiac arrest, hypotension, and/or shock.

The common adverse events seen on initiation of therapy with oxycodone are also typical opioid side effects. These events are dose dependent, and their frequency depends on the clinical setting, the patient's level of opioid tolerance, and host factors specific to the individual. They should be expected and managed as a part of opioid therapy. The most frequent of adverse events include nausea, constipation, vomiting, headache, and pruritus.

The frequency of adverse events during initiation of opioid therapy may be minimized by careful individualization of starting dosage, slow titration and the avoidance of large rapid swings in plasma concentration of the opioid. Many of these common adverse events may abate as therapy is continued and some degree of tolerance is developed, but others may be expected to remain throughout therapy.

In all patients for whom dosing information was available (n=191) from the open-label and double-blind studies involving immediate-release oxycodone, the following adverse events were recorded in oxycodone treated patients with an incidence 3%. In descending order of frequency they were: nausea, constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, and somnolence.

The following adverse experiences occurred in less than 3% of patients involved in clinical trials with oxycodone:

Body as a Whole: abdominal pain, accidental injury, allergic reaction, back pain, chills and fever, fever, flu syndrome, infection, neck pain, pain, photosensitivity reaction, and sepsis.

Cardiovascular: deep thrombophlebitis, heart failure, hemorrhage, hypotension, migraine, palpitation, and tachycardia.

Digestive: anorexia, diarrhea, dyspepsia, dysphagia, gingivitis, glossitis, and nausea and vomiting.

Hemic and Lymphatic: anemia and leukopenia.

Metabolic and Nutritional: edema, gout, hyperglycemia, iron deficiency anemia and peripheral edema.

Musculoskeletal: arthralgia, arthritis, bone pain, myalgia and pathological fracture.

Nervous: agitation, anxiety, confusion, dry mouth, hypertonia, hypesthesia, nervousness, neuralgia, personality disorder, tremor, and vasodilation.

Respiratory: bronchitis, cough increased, dyspnea, epistaxis, laryngismus, lung disorder, pharyngitis, rhinitis, and sinusitis.

Skin and Appendages: herpes simplex, rash, sweating, and urticaria.

Special Senses: amblyopia.

Urogenital: urinary tract infection

Most common adverse reactions are nausea, constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, and somnolence. (6)

To report SUSPECTED ADVERSE REACTIONS, contact Pharm-Olam at 1-866-511-6754 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

7 DRUG INTERACTIONS

  • CNS depressants: Increased risk of respiratory depression, hypotension, profound sedation, or coma. Use with caution in reduced dosages.
  • Muscle relaxants: Enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. (7.2)
  • Mixed agonist/antagonist opioid analgesics (i.e. pentazocine, nalbuphine, and butorphanol): May reduce the analgesic effect and/or may precipitate withdrawal symptoms. (7.3)
  • The CYP3A4 enzyme plays a major role in the metabolism of oxycodone, drugs that inhibit CYP3A4 activity may cause decreased clearance of oxycodone which could lead to an increase in oxycodone plasma concentrations. (7.4)
  • Monoamine oxidase inhibitors (MAOIs): No specific interaction has been observed but caution in the use of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) in patients taking this class of drugs is appropriate. (7.5)

7.1 CNS Depressants

Other central nervous system (CNS) depressants including sedatives, hypnotics, general anesthetics, antiemetics, phenothiazines, or other tranquilizers or alcohol increases the risk of respiratory depression, hypotension, profound sedation, or coma. Use Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) with caution and in reduced dosages in patients taking these agents.

7.2 Muscle Relaxants

Oxycodone; Aspirin Half-Strength may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.

7.3 Mixed Agonist/Antagonist Opioid Analgesics

Do not administer mixed agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, butorphanol and buprenorphine) to patients who have received or are receiving a course of therapy with a pure opioid agonist analgesic such as Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride). In these patients, mixed agonist/antagonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms.

7.4 Agents Affecting Cytochrome P450 Enzymes

CYP3A4 Inhibitors

A published study showed that the co-administration with voriconazole, a CYP3A4 inhibitor, significantly increased the plasma concentrations of oxycodone. Inhibition of CYP3A4 activity by its inhibitors, such as macrolide antibiotics, azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may prolong opioid effects. If co-administration is necessary, caution is advised when initiating therapy with, currently taking, or discontinuing CYP3A4 inhibitors. Evaluate these patients at frequent intervals and consider dose adjustments until stable drug effects are achieved. [see Clinical Pharmacology (12.3) ]

CYP3A4 Inducers

A published study showed that the co-administration of rifampin, a drug metabolizing enzyme inducer, significantly decreased plasma oxycodone concentrations. Induction of CYP3A4 activity by its inducers, such as rifampin, carbamazepine, and phenytoin, may lead to a lack of efficacy or, possibly, development of an abstinence syndrome in a patient who had developed physical dependence to oxycodone. If co-administration is necessary, caution is advised when initiating therapy with, currently taking, or discontinuing CYP3A4 inducers. Evaluate these patients at frequent intervals and consider dose adjustments until stable drug effects are achieved. [see Clinical Pharmacology (12.3)]

CYP2D6 Inhibitors

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.

7.5 Monoamine Oxidase Inhibitors (MAOIs)

No specific interaction between oxycodone and monoamine oxidase inhibitors has been observed, but caution in the use of any opioid in patients taking this class of drugs is appropriate.

7.6 Anticholinergics

Anticholinergics or other medications with anticholinergic activity when used concurrently with opioid analgesics may result in increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

8 USE IN SPECIFIC POPULATIONS

  • Geriatric patients , Renal impairment (8.7): Use caution during dose selection, starting at the low end of the dosing range while carefully monitoring for side effects.
  • Hepatic impairment (8.6): initiate therapy at 1/3 to 1/2 the usual doses and titrate carefully.

8.1 Pregnancy

Pregnancy Category B: There are no adequate and well-controlled studies of oxycodone use during pregnancy. Based on limited human data in the literature, oxycodone does not appear to increase the risk of congenital malformations. Because animal reproduction studies are not always predictive of human response, oxycodone should be used during pregnancy only if clearly needed.

Teratogenic Effects

Reproduction studies in Sprague-Dawley rats and New Zealand rabbits revealed that when oxycodone was administered orally at doses up to 16 mg/kg (approximately 2 times the daily oral dose of 90 mg for adults on a mg/m2 basis) and 25 mg/kg (approximately 5 times the daily oral dose of 90 mg on a mg/m2 basis), respectively was not teratogenic or embryo-fetal toxic.

Nonteratogenic effects

Neonates whose mothers have taken oxycodone chronically may exhibit respiratory depression and/or withdrawal symptoms, either at birth and/or in the nursery.

8.2 Labor and Delivery

Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. Oxycodone; Aspirin Half-Strength is not recommended for use in women during and immediately prior to labor. Occasionally, opioid analgesics may prolong labor through actions which temporarily reduce the strength, duration and frequency of uterine contractions. However this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor. Closely observe neonates whose mothers received opioid analgesics during labor for signs of respiratory depression. Have a specific opioid antagonist, such as naloxone or nalmefene, available for reversal of opioid-induced respiratory depression in the neonate.

8.3 Nursing Mothers

Low levels of oxycodone have been detected in maternal milk. The amount of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) delivered to the infant depends on the plasma concentration of the mother, the amount of milk ingested by the infant, and the extent of first-pass metabolism. Because of the potential for serious adverse reactions in nursing infants from Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) including respiratory depression, sedation and possibly withdrawal symptoms, upon cessation of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) administration to the mother, decide whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

8.4 Pediatric Use

The safety and effectiveness and the pharmacokinetics of Oxycodone; Aspirin Half-Strength Capsule in pediatric patients below the age of 18 have not been established.

8.5 Geriatric Use

Elderly patients (aged 65 years or older) may have increased sensitivity to Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride). In general, use caution when selecting a dose for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

8.6 Hepatic Impairment

Since oxycodone is extensively metabolized, its clearance may be decreased in patients with hepatic impairment. Follow a conservative approach to dose initiation in patients with hepatic impairment, monitor patients closely and adjust the dose based on clinical response.

8.7 Renal Impairment

Information from oxycodone tablets indicate that patients with renal impairment (defined as a creatinine clearance <60 mL/min) had higher plasma concentrations of oxycodone than subjects with normal renal function. Use a conservative approach to dose initiation in patients with renal impairment, monitor patients closely and adjust the dose based on clinical response.

9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

Oxycodone; Aspirin Half-Strength is a mu-agonist opioid and is a Schedule II controlled substance. Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride), like other opioids used in analgesia, can be abused and is subject to criminal diversion.

9.2 Abuse

Drug addiction is characterized by compulsive use, use for non-medical purposes, and continued use despite harm or risk of harm. Drug addiction is a treatable disease, utilizing a multi-disciplinary 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. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence. The converse is also true. In addition, abuse of opioids can occur in the absence of true addiction and is characterized by misuse for nonmedical purposes, often in combination with other psychoactive substances. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised.

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) is intended for oral use only. Abuse of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) poses a risk of overdose and death. The risk is increased with concurrent abuse of alcohol and other substances. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

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.

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms. [See USE IN SPECIFIC POPULATIONS (8.2) ]

9.3 Dependence

Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Physical dependence is manifested by withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an antagonist. Physical dependence and tolerance are not unusual during chronic opioid therapy.

The opioid abstinence or withdrawal syndrome is characterized by some or all of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other 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.

In general, taper opioids rather than abruptly discontinue.

10 OVERDOSAGE

10.1 Symptoms

Acute overdosage with Oxycodone; Aspirin Half-Strength is manifested by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, cardiac arrest and death.

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) may cause 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 origin may produce similar findings). Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.

10.2 Treatment

Give primary attention to re-establishment of a patent airway and institution of assisted or controlled ventilation. Employ supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema accompanying overdose as indicated. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation.

The pure opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose. Since the duration of reversal is expected to be less than the duration of action of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride), carefully monitor the patient until spontaneous respiration is reliably re-established. If the response to opioid antagonists is suboptimal or only brief in nature, administer additional antagonist as directed by the manufacturer of the product.

Do not administer opioid antagonists in the absence of clinically significant respiratory or circulatory depression secondary to oxycodone overdose. Administer such agents cautiously to persons who are known, or suspected to be physically dependent on oxycodone. In such cases, an abrupt or complete reversal of opioid effects may precipitate an acute abstinence syndrome. In an individual physically dependent on opioids, administration of the usual dose of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. Reserve use of an opioid antagonist for cases where such treatment is clearly needed. If it is necessary to treat serious respiratory depression in the physically dependent patient, initiate administration of the antagonist with care and titrate with smaller than usual doses.

11 DESCRIPTION

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) is a white, odorless crystalline powder derived from the opium alkaloid, thebaine. It is soluble in water and slightly soluble in alcohol.

Chemically, Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) is (5R,9R,13S,14S)-4, 5α-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one, hydrochloride (salt) with a molecular mass of 351.82.

Each hard gelatin capsule contains 5 mg of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride), USP and the following inactive ingredients: colloidal silicon dioxide, FD&C Yellow #6, gelatin, lactose anhydrous, magnesium stearate, microcrystalline cellulose, pregelatinized starch, sodium lauryl sulfate, sodium starch glycolate, titanium dioxide and yellow iron oxide.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Oxycodone; Aspirin Half-Strength, a pure opioid agonist, is relatively selective for the mu receptor, although it can interact with other opioid receptors at higher doses. In addition to analgesia, the widely diverse effects of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) include drowsiness, changes in mood, respiratory depression, decreased gastrointestinal motility, nausea, vomiting, and alterations of the endocrine and autonomic nervous system.

Effects of the Central Nervous System (CNS)

The principal therapeutic action of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) is analgesia. Although the precise mechanism of the analgesic action is unknown, specific CNS opioid receptors for endogenous compounds with oxycodone hydrochloride-like activity have been identified throughout the brain and spinal cord and are likely to play a role in the expression and perception of analgesic effects. In common with other opioids, Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) causes respiratory depression, in part by a direct effect on the brainstem respiratory centers. Oxycodone and related opioids depress the cough reflex by direct effect on the cough center in the medulla. Oxycodone causes miosis, even in total darkness.

Effects on the Gastrointestinal Tract And Other Smooth Muscle

Gastric, biliary and pancreatic secretions are decreased by Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride). Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride), like other opioid analgesics, produces some degree of nausea and vomiting which is caused by direct stimulation of the chemoreceptor trigger zone (CTZ) located in the medulla. The frequency and severity of emesis gradually diminishes with time. Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) may cause a decrease in the secretion of hydrochloric acid in the stomach, may reduce motility, while increasing the 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. The end result may be constipation. Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) may also cause spasm of the sphincter of Oddi and transient elevations in serum amylase.

Effects on the Cardiovascular System

In therapeutic doses, Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride), produces peripheral vasodilatation (arteriolar and venous), decreased peripheral resistance, and inhibits baroreceptor reflexes. Manifestations of histamine release and/or peripheral vasodilatation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension. Caution should be used in hypovolemic patients, such as those suffering acute myocardial infarction, because oxycodone may cause or further aggravate their hypotension. Caution should also be used in patients with corpulmonale who have received therapeutic doses of opioids.

Endocrine System

Opioid agonists have been shown to have a variety of effects on the secretion of hormones. Opioids inhibit the secretion of ACTH, cortisol, and luteinizing hormone (LH) in humans. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon in humans and other species, rats and dogs. Thyroid stimulating hormone (TSH) has been shown to be both inhibited and stimulated by opioids.

Immune System

Opioids have been shown to have a variety of effects on components of the immune system in in-vitro and animal models. The clinical significance of these findings is unknown.

12.3 Pharmacokinetics

The activity of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) capsules is primarily due to the parent drug oxycodone.

The oral bioavailability of oxycodone is 60% to 87%. Oxycodone is extensively metabolized and eliminated primarily in the urine as both conjugated and unconjugated parent and its metabolites. The apparent elimination half-life of oxycodone is approximately 4 hours.

Absorption

About 60 to 87% of an oral dose reaches the systemic circulation in comparison to a parenteral dose. This high oral bioavailability (compared to other opioids) is due to lower pre-systemic and/or first-pass metabolism of oxycodone.

Food Effects

When administered with a high-fat meal mean AUC values are increased by 23% and peak concentrations are decreased by 14%. Food caused a delay in Tmax (1.00 to 3.00 hours).

Distribution

Following intravenous administration, the volume of distribution (Vss) for oxycodone was 2.6 L/kg. Plasma protein binding of oxycodone at 37°C and a pH of 7.4 was about 45%.

Oxycodone has been found in breast milk.

Metabolism

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) is extensively metabolized by multiple metabolic pathways to noroxycodone, oxymorphone, and noroxymorphone, which are subsequently glucuronidated. CYP3A4 mediated N-demethylation to noroxycodone is the primary metabolic pathway of oxycodone with less contribution from CYP2D6 mediated O-demethylation to oxymorphone. Therefore, the formation of these and related metabolites can, in theory, be affected by other drugs. The major circulating metabolite is noroxycodone with an AUC ratio of 0.6 relative to that of oxycodone. Noroxycodone is reported to be a considerably weaker analgesic than oxycodone. Oxymorphone, although possessing analgesic activity, is present in the plasma only in low concentrations. The correlation between oxymorphone concentrations and opioid effects was much less than that seen with oxycodone plasma concentrations. The analgesic activity profile of other metabolites is not known.

Excretion

Oxycodone and its metabolites are excreted primarily via the kidney. The amounts measured in the urine have been reported as follows: free oxycodone up to 19%; conjugated oxycodone up to 50%; free oxymorphone 0%; conjugated oxymorphone < 14%; both free and conjugated noroxycodone have been found in the urine but not quantified. The total plasma clearance was 0.8 L/min for adults.

Apparent elimination half-life of oxycodone following the administration of oxycodone is approximately 4 hours.

Special Populations

Elderly: Information obtained from oxycodone tablets indicate that the plasma concentrations of oxycodone did not appear to be increased in patients over the age of 65.

Gender: Information obtained from oxycodone tablets support the lack of gender effect on the pharmacokinetics of oxycodone.

Renal Impairment: Information obtained from oxycodone tablets indicate that patients with renal impairment (defined as creatinine clearance <60 mL/min) had higher plasma concentrations of oxycodone than subjects with normal renal function.

Hepatic Impairment: Since oxycodone is extensively metabolized, its clearance may decrease in patients with hepatic impairment.

Drug-Drug Interactions

CYP3A4 Inhibitors

CYP3A4 is the major enzyme involved in noroxycodone formation. A published study showed that the co-administration of voriconazole, a CYP3A4 inhibitor, increased oxycodone AUC and Cmax by 3.6 and 1.7 fold, respectively.

CYP3A4 Inducers

A published study showed that the co-administration of rifampin, a drug metabolizing enzyme inducer, decreased oxycodone AUC and Cmax values by 86% and 63%, respectively.

CYP2D6 Inhibitors

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.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Studies of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) to evaluate its carcinogenic potential have not been conducted.

Mutagenesis

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) was genotoxic in an in vitro mouse lymphoma assay in the presence of metabolic activation. There was no evidence of genotoxic potential in an in vitro bacterial reverse mutation assay (Salmonella typhimurium and Escherichia coli) and in an assay for chromosomal aberrations (in vivo mouse bone marrow micronucleus assay).

Impairment of Fertility

The potential effects of oxycodone on male and female fertility have not been evaluated.

16 HOW SUPPLIED/STORAGE AND HANDLING

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) Capsule

Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) Capsule 5 mg is a hard gelatin capsule with an opaque yellow cap imprinted in black ink with "LV" and an opaque white body imprinted in black ink with "901" available in one strength as follows:

5 mg capsule

NDC# 68462-204-01: Bottle of 100 Capsules

Storage

Store at Controlled Room Temperature, 25°C (77°F); excursions are permitted to 15° - 30°C (59° - 86°F).

PROTECT from MOISTURE and LIGHT.

Handling

All opioids, including Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride), are liable to diversion and misuse both by the general public and healthcare workers and should be handled accordingly.

DEA Order Form Required

Dispense in a tight, light-resistant container.

Protect from moisture.

17 PATIENT COUNSELING INFORMATION

Provide the following information to patients receiving Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) or their caregivers:

  • Advise patients that Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) is a narcotic pain reliever, and should be taken only as directed.
  • Advise patients that Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) capsule is available in one strength: 5 mg.
  • Advise patients not to adjust the dose of Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) without consulting with a physician or other healthcare professional.
  • Advise patients that Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) may cause drowsiness, dizziness, or lightheadedness and may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating machinery). Advise patients started on Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) or patients whose dose has been adjusted to refrain from any potentially dangerous activity until it is established that they are not adversely affected.
  • Advise patients that Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) will add to the effect of alcohol and other CNS depressants (such as antihistamines, sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and monoamine oxidase [MAO] inhibitors).
  • Instruct patients not to combine Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) with central nervous system depressants (sleep aids, tranquilizers) except by the orders of the prescribing physician, and not to combine with alcohol because dangerous additive effects may occur, resulting in serious injury or death.
  • Instruct women of childbearing potential who become or are planning to become pregnant to consult a physician prior to initiating or continuing therapy with Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride).
  • Advise patients that safe use in pregnancy has not been established and that prolonged use of opioid analgesics during pregnancy may cause fetal-neonatal physical dependence, and neonatal withdrawal may occur.
  • If patients have been receiving treatment with Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) for more than a few weeks and cessation of therapy is indicated, counsel them on the importance of safely tapering the dose and that abruptly discontinuing the medication could precipitate withdrawal symptoms. Provide a dose schedule to accomplish a gradual discontinuation of the medication.
  • Advise patients that sharing this oxycodone can result in fatal overdose and death.
  • Advise patients that Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) is a potential drug of abuse. They must protect it from theft. It should never be given to anyone other than the individual for whom it was prescribed.
  • Instruct patients to keep Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) in a secure place out of the reach of children. When Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) is no longer needed, the unused capsules should be destroyed by flushing down the toilet.
  • Advise patients taking Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride) of the potential for severe constipation; appropriate laxatives and/or stool softeners as well as other appropriate treatments should be initiated from the onset of opioid therapy.
  • Advise patients of the most common adverse events that may occur while taking Oxycodone; Aspirin Half-Strength (Oxycodone Hydrochloride): constipation, nausea, somnolence, lightheadedness, dizziness, sedation, vomiting, and sweating.
  • Advise patients to call 911 or the local Poison Control center, and get emergency help immediately if they take more oxycodone than prescribed, or overdose.
  • Advise patients, that if they miss a dose, to take the missed dose as soon as possible. If it is almost time for the next dose, skip the missed dose and go back to their regular dosing schedule. Do not take two doses at once unless instructed by their doctor.

Revision: November 2010

Manufactured by:

Lehigh Valley Technologies, Inc.

Allentown, PA 18102

Distributed by:

Glenmark Generics Inc., USA

Mahwah, NJ 07430

Oxycodone Hcl 5mg (CII) Tablet

Chemical Structure

Oxycodone; Aspirin Half-Strength pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Oxycodone; Aspirin Half-Strength available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Oxycodone; Aspirin Half-Strength destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Oxycodone; Aspirin Half-Strength Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Oxycodone; Aspirin Half-Strength pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."OXYCODONE HYDROCHLORIDE CAPSULE [BRYANT RANCH PREPACK]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."BUFFERIN LOW DOSE BUFFERED ASPIRIN (ASPIRIN) TABLET [NOVARTIS CONSUMER HEALTH, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."OXYCODONE HYDROCHLORIDE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Oxycodone; Aspirin Half-Strength?

Depending on the reaction of the Oxycodone; Aspirin Half-Strength after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Oxycodone; Aspirin Half-Strength not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Oxycodone; Aspirin Half-Strength addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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sdrugs.com conducted a study on Oxycodone; Aspirin Half-Strength, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Oxycodone; Aspirin Half-Strength consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Rachana Salvi, MD Pharmacology

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