Baclofen/flurbiprofen/lidocaine topical Disease Interactions

Antiarrhythmic agents can induce severe hypotension (particularly with IV administration) or induce or worsen congestive heart failure (CHF). Patients with primary cardiomyopathy or inadequately compensated CHF are at increased risk. Antiarrhythmic agents should be administered cautiously and dosage and/or frequency of administration modified in patients with hypotension or adequately compensated CHF. Alternative therapy should be considered unless these conditions are secondary to cardiac arrhythmia.

Baclofen is primarily eliminated by the kidney. Patients with impaired renal function may be at greater risk for adverse effects from baclofen due to decreased drug clearance. Therapy with baclofen should be administered cautiously in such patients. Dosage adjustments may be necessary.

Lidocaine is rapidly and extensively metabolized by the liver. Less than 10% is eliminated unchanged in the urine. Several inactive and two active forms (MEGX and GX) have been identified. MEGX and GX exhibit antiarrhythmic and convulsant properties. GX accumulates during prolonged intravenous lidocaine infusion. The pharmacokinetic disposition of lidocaine is altered by changes in hepatic function, including hepatic blood flow. Therapy with lidocaine should be administered cautiously and dosing modifications for repeated or loading and maintenance doses may be necessary. Clinical monitoring of cardiac (continuous ECG) is required and serum metabolite concentrations and monitoring hepatic function are recommended.

Lidocaine is primarily eliminated by the kidney. Less than 10% is eliminated unchanged in the urine. Two active metabolites (MEGX and GX) have been identified that exhibit antiarrhythmic and convulsant properties. GX accumulates during prolonged intravenous lidocaine infusion. Serum concentrations of lidocaine and the active metabolites are increased and the half-life prolonged in patients with renal impairment. Therapy with lidocaine should be administered cautiously and dosing modified for repeated or maintenance doses in patients with compromised renal function. Clinical monitoring of cardiac function (continual ECG) is required and serum metabolite concentrations and monitoring renal function are recommended.

Seizures have occurred during lidocaine therapy and have been associated with the rapid administration of a large intravenous doses or accumulation of active metabolites with maintenance therapy. Therapy with lidocaine should be administered cautiously to patients with or predisposed to seizure disorders. Clinical monitoring of cardiac (continuous ECG) is required, and serum metabolite concentrations are recommended.

The use of lidocaine is contraindicated in patients with Stokes-Adam syndrome, Wolff-Parkinson White syndrome, or second- or third-degree AV block in the absence of a functional artificial pacemaker, or congenital QT prolongation.

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.

Fluid retention and edema have been reported in association with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Therapy with NSAIDs should be administered cautiously in patients with preexisting fluid retention, hypertension, or a history of heart failure. Blood pressure and cardiovascular status should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.

Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can develop at any time, with or without warning symptoms. NSAIDs should be used with caution in patients with history of peptic ulcer disease and/or GI bleeding, as these patients had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Caution is also advised if NSAIDs are prescribed to patients with other factors that increase risk of GI bleeding, such as: prolonged NSAID therapy; concomitant use of oral corticosteroids, antiplatelet agents (e.g., aspirin), anticoagulants, selective serotonin reuptake inhibitors; alcohol use; smoking; history of gastrointestinal surgery or anastomosis, older age; poor general health status; and advanced liver disease and/or coagulopathy. Particular vigilance is necessary when treating elderly or debilitated patients since most postmarketing reports of fatal GI events occurred in these patients.

Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious skin adverse reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, and exfoliative dermatitis), which can be fatal. These serious events may occur without warning. Patients should be advised to discontinue the NSAID and seek medical attention promptly at the first sign of skin rash or any other sign of hypersensitivity. NSAIDs are contraindicated in patients with previous serious skin reactions to these drugs.

Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) has resulted in renal papillary necrosis and other renal injury. Renal toxicity has been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion: in such patients, NSAIDs may cause a dose-dependent reduction in prostaglandin synthesis and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk for this reaction include the elderly, those with impaired renal function, dehydration, hypovolemia, heart failure, or liver dysfunction, and those taking diuretics, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers; discontinuation of NSAID therapy will usually lead to recovery to the pretreatment state. No information is available regarding use NSAIDs in patients with advanced renal disease; the renal effects of NSAIDs may hasten the progression of renal dysfunction in patients with preexisting renal disease. Volume status should be corrected in dehydrated or hypovolemic patients prior to initiating treatment. Renal function should be monitored during therapy in patients with renal or liver dysfunction, heart failure, dehydration, or hypovolemia. NSAIDs should be avoided in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function; if an NSAID is used in such patients, they should be monitored for signs of worsening renal function.

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. Clinical trials of several cyclooxygenase-2 (COX-2) selective and nonselective NSAIDs of up to 3 years duration have supported this increased risk. It is unclear from available data if the risk for cardiovascular thrombotic events is similar for all NSAIDs. Therapy with NSAIDs should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease. Patients should be treated with the lowest effective dosage for the shortest duration necessary. Appropriate antiplatelet therapy should be administered to patients requiring cardioprotection; however, there is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious cardiovascular thrombotic events associated with NSAID use, while the risk of serious gastrointestinal events is increased. Physicians and patients should remain alert for the development of adverse cardiovascular events throughout the entire duration of therapy, even without prior cardiovascular symptoms. Patients should be advised to promptly seek medical attention if they experience symptoms of cardiovascular thrombotic events (including chest pain, shortness of breath, weakness, or slurring of speech).

NSAIDs are contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Two large 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.

The use of NSAIDs should be avoided in patients with a recent myocardial infarction unless the benefits are expected to outweigh the risk of recurrent cardiovascular thrombotic events. If an NSAID is used in patients with a recent myocardial infarction, they should be monitored for signs of cardiac ischemia.

Electrolyte imbalance can alter the therapeutic effectiveness of antiarrhythmic agents. Hypokalemia and hypomagnesemia can reduce the effectiveness of antiarrhythmic agents. In some cases, these disorders can exaggerate the degree of QTc prolongation and increase the potential for torsade de pointes. Hyperkalemia can potentiate the toxic effects of antiarrhythmic agents. Electrolyte imbalance should be corrected prior to initiating antiarrhythmic therapy. Clinical monitoring of cardiac function and electrolyte concentrations is recommended.

Therapy with intrathecal baclofen should be administered cautiously in patients with a history of autonomic dysreflexia, since the presence of nociceptive stimuli or abrupt withdrawal of the medication may trigger an episode of dysreflexia.

Baclofen may precipitate or exacerbate psychotic symptoms, both during therapy and following abrupt withdrawal of the drug. Therapy with baclofen should be administered cautiously in patients with a history of psychiatric disorders.

Deterioration in seizure control and electroencephalographic (EEG) changes have been reported occasionally in epileptic patients treated with baclofen. Therapy with baclofen should be administered cautiously in patients with a history of seizures. Clinical status and EEG should be monitored at regular intervals during treatment. Except in cases of overdose or severe adverse reactions, cessation of baclofen therapy, whenever necessary, should occur gradually with incrementally reduced dosages. Abrupt withdrawal has been associated with central nervous system effects including seizures, hallucinations, and psychosis.

Anemia has been reported in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs). This may be due to fluid retention, occult/gross blood loss, or an incompletely described effect on erythropoiesis. Hemoglobin or hematocrit should be monitored in patients with any signs/symptoms of anemia or blood loss, especially during long-term therapy. NSAIDs may increase risk of bleeding events; comorbid conditions (e.g., coagulation disorders; concomitant use of warfarin/other anticoagulants, antiplatelet agents, serotonin/serotonin norepinephrine reuptake inhibitors) may increase this risk, and patients with these conditions should be monitored for signs of bleeding. Therapy with NSAIDs should be administered cautiously in patients with or predisposed to anemia. Clinical monitoring of hematopoietic function may be appropriate, particularly during chronic therapy.

Fluid retention and edema have been observed in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs), including some topical formulations. These drugs should be avoided in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If an NSAID is used in patients with severe heart failure, they should be monitored for signs of worsening heart failure.

Borderline elevations of 1 or more liver tests may occur in up to 15% of patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs). These laboratory abnormalities may progress, remain unchanged, or regress with continuing therapy. Elevations of ALT or AST (at least 3 times the upper limit of normal) have been reported in about 1% of patients in clinical trials. In addition, rare (sometimes fatal) cases of severe hepatotoxicity, including liver necrosis, hepatic failure, jaundice, and fulminant hepatitis have been reported. Therapy with NSAIDs should be administered cautiously in patients with preexisting liver disease. Periodic monitoring of liver function is recommended during prolonged therapy. NSAIDs are also highly protein-bound and some are extensively metabolized by the liver. Metabolic activity and/or plasma protein binding may be altered in patients with hepatic impairment. A dosage reduction may be required in some cases.

Increases in serum potassium concentration (including hyperkalemia) have been reported with use of nonsteroidal anti-inflammatory drugs (NSAIDs), even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state. Caution is advised in patients with hyperkalemia.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including topicals, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which can contribute to the increased incidence of cardiovascular events. NSAIDs should be used with caution in patients with hypertension. Blood pressure should be monitored closely during the initiation of NSAID therapy and throughout the course of therapy.

Nonsteroidal anti-inflammatory drugs (NSAIDs) reversibly inhibit platelet adhesion and aggregation and may prolong bleeding time in some patients. With the exception of aspirin, the platelet effects seen with most NSAIDs at usual recommended dosages are generally slight and of relatively short duration but may be more pronounced in patients with underlying hemostatic abnormalities. Thrombocytopenia has also been reported rarely during NSAID use. Therapy with NSAIDs should be administered cautiously in patients with significant active bleeding or a hemorrhagic diathesis, including hemostatic and/or coagulation defects associated with hemophilia, vitamin K deficiency, hypoprothrombinemia, thrombocytopenia, thrombocytopathy, or severe hepatic impairment. NSAIDs that selectively inhibit cyclooxygenase-2 (i.e., COX-2 inhibitors) do not appear to affect platelet function or bleeding time at indicated dosages and may be preferable if risk of bleeding is a concern.