Roxiprin Disease Interactions

The use of aspirin is contraindicated in patients with significant active bleeding or hemorrhagic disorders such as hemophilia, von Willebrand's disease, or telangiectasia. Aspirin interferes with coagulation by irreversibly inhibiting platelet aggregation and prolonging bleeding time. The non-aceylated salicylates (i.e. salicylate salts such as sodium or magnesium salicylate) do not demonstrate these effects and may be appropriate substitutions in these patients. However, all salicylates can interfere with the action of vitamin K and induce a dose-dependent alteration in hepatic synthesis of coagulation factors VII, IX and X. At usual recommended dosages, a slight increase in prothrombin time (PT) may occur. Therapy with salicylates, especially aspirin, should be administered with extreme caution in patients with hypoprothrombinemia, vitamin K deficiency, thrombocytopenia, thrombotic thrombocytopenic purpura, severe hepatic impairment, or anticoagulant use.

Narcotic (opioid) analgesic agents increase smooth muscle tone in the gastrointestinal tract and decrease peristalsis, which can lead to elevated intraluminal pressure, spasm, and constipation following prolonged use. In patients with severe or acute inflammatory bowel disease, the decrease in colonic motility may induce toxic megacolon. Therapy with opioids should be administered cautiously in patients with gastrointestinal obstruction, constipation, inflammatory bowel disease, or recent gastrointestinal tract surgery. Gastrointestinal effects appear to be the most pronounced with morphine.

Narcotic (opioid) analgesic agents may prolong and/or worsen diarrhea associated with organisms that invade the intestinal mucosa, such as toxigenic Escherichia coli, Salmonella, Shigella, and pseudomembranous colitis due to broad-spectrum antibiotics. These agents decrease gastrointestinal motility, which may delay the excretion of infective gastroenteric organisms and/or their toxins. Other symptoms and complications such as fever, shedding of organisms, and extraintestinal illness may also be increased or prolonged. Therapy with opioids should be avoided or administered cautiously in patients with infectious diarrhea, particularly that due to pseudomembranous enterocolitis or enterotoxin-producing bacteria or if accompanied by high fever, pus, or blood in the stool.

The use of narcotic (opioid) analgesic agents is contraindicated in premature infants. These agents may cross the immature blood-brain barrier to a greater extent than in adults, resulting in disproportionate respiratory depression.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated in patients with history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs; severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients. A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps, severe potentially fatal bronchospasm, and/or intolerance to aspirin and other NSAIDs. Since cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, therapy with any NSAID should be avoided in patients with this form of aspirin sensitivity. NSAIDs should be used with caution in patients with preexisting asthma (without known aspirin sensitivity), and these patients should be monitored for changes in the signs and symptoms of asthma.

The use of opiate agonists is contraindicated in patients with acute alcohol intoxication exhibiting depressed vital signs. The central nervous system depressant effects of opiate agonists may be additive with those of alcohol. Severe respiratory depression and death may occur. Therapy with opiate agonists should be administered cautiously in patients who might be prone to acute alcohol intake.

Opiate agonists have the potential to cause dependence and abuse. Tolerance as well as physical and psychological dependence can develop after prolonged use. Abrupt cessation, reduction in dosage, or administration of an opiate antagonist such as naloxone may precipitate withdrawal symptoms. In patients who have developed tolerance to an opiate agonist, overdosage can still produce respiratory depression and death, and cross-tolerance usually will occur with other agents in the class. Addiction-prone individuals, such as those with a history of alcohol or substance abuse, should be under careful surveillance or medical supervision when treated with opiate agonists. It may be prudent to refrain from dispensing large quantities of medication to these patients. After prolonged use or if dependency is suspected, withdrawal of opiate therapy should be undertaken gradually using a dosage-tapering schedule.

Opiate agonists can induce vasodilation and significant hypotension, particularly when given in high dosages and/or by rapid intravenous administration. Opiate analgesics cause vasodilatation that may exacerbate hypotension and hypoperfusion and, therefore, are contraindicated in circulatory shock. At therapeutic analgesic dosages, ambulatory patients are more likely to experience dizziness and hypotension than patients who are confined to bed. However, orthostatic hypotension may occur in supine patients upon rising. Therapy with opiate agonists should be administered cautiously and initiated at reduced dosages in patients with hypovolemia, or a predisposition to hypotension. When given by intramuscular or subcutaneous administration, clinicians should also be aware that impaired perfusion in these patients may prevent complete absorption of the drug. With repeated injections, an excessive amount may be absorbed suddenly if normal circulation is reestablished.

The hypoventilation associated with administration of opiate agonists, particularly by the intravenous route, can induce cerebral hypoxia and vasodilatation with resultant increase in intracranial pressure. Opiate agonists should not be used in patients with suspected or known head injury or increased intracranial pressure. Also, clinicians treating such patients should be aware that opiate agonists may interfere with the evaluation of CNS function, especially with respect to consciousness levels, respiratory status, and pupillary changes.

Opiate agonists may produce significant central nervous system and respiratory depression of varying duration, particularly when given in high dosages and/or by rapid intravenous administration. Apnea may result from decreased respiratory drive as well as increased airway resistance, and rigidity of respiratory muscles may occur during rapid IV administration or when these agents are used in the induction of anesthesia. At therapeutic analgesic dosages, the respiratory effects are usually not clinically important except in patients with preexisting pulmonary impairment. Therapy with opiate agonists should be avoided or administered with extreme caution and initiated at reduced dosages in patients with severe CNS depression; sleep apnea; hypoxia, anoxia, or hypercapnia; upper airway obstruction; chronic pulmonary insufficiency; a limited ventilatory reserve; or other respiratory disorders. In the presence of excessive respiratory secretions, the use of opiate agonists may also be problematic because they decrease ciliary activity and reduce the cough reflex. Caution is also advised in patients who may be at increased risk for respiratory depression, such as comatose patients or those with head injury, intracranial lesions, or intracranial hypertension. Clinical monitoring of pulmonary function is recommended, and equipment for resuscitation should be immediately available if parenteral or neuraxial routes are used. Naloxone may be administered to reverse clinically significant respiratory depression, which may be prolonged depending on the opioid agent, cumulative dose, and route of administration.

Opioid analgesics are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

Salicylates, particularly aspirin, can cause dose-related gastrointestinal bleeding and mucosal damage, which may occur independently of each other. Occult, often asymptomatic GI blood loss is quite common with usual dosages of aspirin and stems from the drug's local effect on the GI mucosa. During chronic therapy, this type of bleeding may occasionally produce iron deficiency anemia. In contrast, major upper GI bleeding rarely occurs except in patients with active peptic ulcers or recent GI bleeding. However, these patients generally do not experience greater occult blood loss than healthy patients following small doses of aspirin. Mucosal damage associated with the use of salicylates may lead to development of peptic ulcers with or without bleeding, reactivation of latent ulcers, and ulcer perforation. Therapy with salicylates and related agents such as salicylamide should be considered and administered cautiously in patients with a history of GI disease or alcoholism, particularly if they are elderly and/or debilitated, since such patients may be more susceptible to the GI toxicity of these drugs and seem to tolerate ulceration and bleeding less well than other individuals. Extreme caution and thorough assessment of risks and benefits are warranted in patients with active or recent GI bleeding or lesions. Whenever possible, especially if prolonged use is anticipated, treatment with non-ulcerogenic agents should be attempted first. If salicylates are used, close monitoring for toxicity is recommended. Some adverse GI effects may be minimized by administration with high dosages of antacids, use of enteric-coated or extended-release formulations, and/or concurrent use of a histamine H2-receptor antagonist or a cytoprotective agent such as misoprostol. Patients with active peptic ulceration or GI bleeding treated with salicylates should generally be administered a concomitant anti-ulcer regimen.

Salicylate and its metabolites are eliminated almost entirely by the kidney. Therapy with salicylate drugs should be administered cautiously in patients with renal impairment, especially if it is severe. Reduced dosages may be necessary to avoid drug accumulation. Clinical monitoring of renal function is recommended during prolonged therapy, since the use of salicylate drugs has rarely been associated with renal toxicities, including elevations in serum creatinine, renal papillary necrosis, and acute tubular necrosis with renal failure. Most of the data have been derived from experience with aspirin but may apply to other salicylates as well. In patients with impaired renal function, aspirin has caused reversible and sometimes marked decreases in renal blood flow and glomerular filtration rate. Adverse renal effects have usually reversed rapidly following withdrawal of aspirin therapy.

The use of salicylates, primarily aspirin, in children with varicella infections or influenza-like illnesses has been associated with an increased risk of Reye's syndrome. Although a causal relationship has not been established, the majority of evidence to date seems to support the association. Most authorities, including the American Academy of Pediatrics Committee on Infectious Diseases, recommend avoiding the use of salicylates in children and teenagers with known or suspected varicella or influenza and during presumed outbreaks of influenza. If antipyretic or analgesic therapy is indicated under these circumstances, acetaminophen may be an appropriate alternative. The same precautions should also be observed with related agents such as salicylamide or diflunisal because of their structural and pharmacological similarities to salicylate.

Patients with Addison's disease may have increased risk of respiratory depression and prolonged CNS depression associated with the use of narcotic (opioid) analgesic agents. Conversely, these agents may cause or potentiate adrenal insufficiency. Therapy with opioids should be administered cautiously and initiated at reduced dosages in patients with adrenocortical insufficiency. Subsequent doses should be titrated based on individual response rather than a fixed dosing schedule.

Narcotic (opioid) analgesic agents are extensively metabolized by the liver, and several of them (e.g., codeine, hydrocodone, meperidine, methadone, morphine, propoxyphene) have active metabolites that are further converted to inactive substances. The serum concentrations of these agents and their metabolites may be increased and the half-lives prolonged in patients with impaired hepatic function. Therapy with opioids should be administered cautiously and initiated at reduced dosages in patients with liver disease. Subsequent doses should be titrated based on individual response rather than a fixed dosing schedule.

Although narcotic (opioid) analgesic agents are generally metabolized by the liver, renal impairment can alter the elimination of these agents and their metabolites (some of which are pharmacologically active), resulting in drug accumulation and increased risk of toxicity. Therapy with opioids should be administered cautiously and initiated at reduced dosages in patients with significantly impaired renal function. Subsequent doses should be titrated based on individual response rather than a fixed dosing schedule.

Narcotic (opioid) analgesic agents may increase the frequency of seizures in patients with seizure disorders, may increase the risk of seizures occurring in other clinical settings associated with seizures, and, at higher dosages, have been reported to induce seizures in patients without history of seizures. Patients with history of seizure disorders should be regularly evaluated for worsened seizure control during therapy. Prolonged meperidine use may increase the risk of toxicity (e.g., seizures) from the accumulation of the active metabolite (normeperidine).

Narcotic (opioid) analgesic agents may inhibit the urinary voiding reflex and increase the tone of the vesical sphincter in the bladder. Acute urinary retention requiring catheterization may occur, particularly in patients with prostatic hypertrophy or urethral stricture and in older adult patients. These agents may also decrease urine production via direct effects on the kidney and central stimulation of the release of vasopressin. Therapy with opioids should be administered cautiously in patients with or predisposed to urinary retention and/or oliguria. The effects on smooth muscle tone appear to be the most pronounced with morphine.

Opiate agonists have cholinergic activity. Large doses and/or rapid intravenous administration may produce bradycardia and arrhythmias via stimulation of medullary vagal nuclei. Therapy with opiate agonists should be administered cautiously in patients with a history of arrhythmias. Clinical monitoring of cardiovascular status is recommended during therapy.

Opioid agonists may cause spasm of the sphincter of Oddi, which may increase biliary tract pressure. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions and transient elevations in serum amylase. Patients with biliary tract disease (including acute pancreatitis) should be regularly evaluated for worsening symptoms. Therapy with opioids should be administered cautiously in patients with biliary tract disease, gallbladder disease, or acute pancreatitis.

Occult, often asymptomatic GI blood loss occurs quite frequently with the use of normal dosages of aspirin and stems from the drug's local effect on the GI mucosa. During chronic therapy, this type of bleeding may occasionally produce iron deficiency anemia. Other salicylates reportedly cause little or no GI blood loss at usual dosages, but may do so at high dosages. Prolonged therapy with salicylates, particularly aspirin, should be administered cautiously in patients with or predisposed to anemia. Periodic monitoring of hematocrit is recommended. The same precautions should also be observed with the use of related agents such as salicylamide because of their structural and pharmacological similarities to salicylate.

Salicylate and its metabolites are readily removed by hemodialysis and, to a lesser extent, by peritoneal dialysis. Doses should either be scheduled for administration after dialysis or supplemental doses be given after dialysis.

Salicylates, particularly aspirin, may cause or aggravate hemolysis in patients with pyruvate kinase or glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. However, this effect has not been clearly established. Until more data are available, therapy with salicylates should be administered cautiously in patients with G-6-PD deficiency. The same precaution should also be observed with the use of related agents such as salicylamide because of their structural and pharmacological similarities to salicylate.

The use of salicylates has occasionally been associated with acute, reversible hepatotoxicity, primarily manifested as elevations of serum transaminases, alkaline phosphatase and/or, rarely, bilirubin. Hepatic injury consistent with chronic active hepatitis has also been reported in a few patients, which resulted rarely in encephalopathy or death. Salicylate-induced hepatotoxicity appears to be dependent on serum salicylate concentration (> 25 mg/dL) and has occurred most frequently in patients with juvenile arthritis, active systemic lupus erythematosus, rheumatic fever, or preexisting hepatic impairment. Therapy with salicylates, particularly when given in high dosages, should be administered cautiously in these patients, and periodic monitoring of liver function is recommended. The same precautions should also be observed with the use of related agents such as salicylamide because of their structural and pharmacological similarities to salicylate. A dosage reduction may be necessary if liver function abnormalities develop and serum salicylate concentration exceeds 25 mg/dL, although serum transaminase elevations may sometimes be transient and return to pretreatment values despite continued therapy without dosage adjustment.