FDA Safety Changes: Toradol and Minocin

[Admin]

March 28, 2007 — The US Food and Drug Administration (FDA) has approved safety labeling revisions to advise of multiple risks associated with use of oral ketorolac tromethamine and the potential for development of Clostridium difficile–associated diarrhea more than 2 months after completion of minocycline HCl therapy.

Oral Ketorolac Tromethamine (Toradol) Linked to Risk for Gastrointestinal Bleed
On January 19, the FDA approved safety labeling revisions for ketorolac tromethamine tablets (Toradol; Roche Pharmaceuticals) to warn of the potential risks for gastrointestinal (GI) bleeding, cardiovascular (CV) events, allergic reactions, and hepatic dysfunction.

Oral ketorolac is a potent nonsteroidal anti-inflammatory drug (NSAID) that is only indicated for the short-term management of moderately severe acute pain requiring analgesia at the opioid level, following intravenous or intramuscular administration. The total duration of therapy should not exceed 5 days.

The FDA notes that ketorolac oral therapy is not indicated for use in children or for the management of minor or chronic painful conditions. Dose increases beyond 40 mg/day do not provide better efficacy and increase the risk for serious adverse events.

As with other NSAIDs, ketorolac is linked to an increased risk for serious and potentially fatal GI events in patients. Inflammation, bleeding, ulceration, and perforation of the stomach or small and/or large intestines may occur at any time and are symptomatic in only 20% of patients.

Factors that exacerbate this risk include increased dose, concomitant use of corticosteroids or anticoagulants, longer duration of therapy, smoking, alcohol consumption, advanced age, and poor general health status. Use of ketorolac is contraindicated in patients with a history of peptic ulcer and/or GI bleeding and should be used with particular caution in the elderly because of the increased rate of spontaneous GI fatalities in this population. Concomitant use of pentoxifylline is linked to an increased risk of bleeding and therefore contraindicated.

Healthcare professionals are advised to limit therapy to the lowest dose for the shortest possible time consistent with therapeutic goals and to remain alert for symptoms of ulceration and bleeding. These should be evaluated promptly and ketorolac discontinued until serious GI events have been ruled out.

The FDA also warned of the risks for cardiovascular thrombotic events and hypertension associated with NSAID therapy, including ketorolac. Clinical trials of up to 3 years' duration have linked several cyclooxgenase-2 selective and nonselective NSAIDs to an increased risk for serious and potentially fatal CV thrombotic events, myocardial infarction, and stroke. According to the FDA, all NSAIDs may have similar risks that increase with duration of use and in the presence of existing CV disease and/or related risk factors.

Clinicians are advised to remain alert for the development of CV events, even in the absence of previous symptoms. The FDA notes that there is no consistent evidence that concurrent use of low-dose aspirin mitigates the risk for thrombotic events, and concomitant use of both drugs does increase the risk for serious GI events.

An increased incidence of myocardial infarction and stroke also has been observed in 2 large controlled clinical trials of cyclooxgenase-2 selective NSAIDs for pain relief after coronary artery bypass graft surgery; use of NSAIDs is therefore contraindicated in this setting.

The FDA notes that all NSAIDs, including ketorolac, can lead to the onset of new hypertension or worsening of preexisting disease of which either may contribute to an increased incidence of CV events. Because the effects of furosemide and thiazides may be diminished, close monitoring of blood pressure is recommended prior to and during therapy. In addition, reports suggest that NSAIDs may reduce the effects of angiotensin-converting enzyme inhibitor therapy. All 3 classes of antihypertensive agents are linked to an increased risk for renal impairment when administered with ketorolac.

Ketorolac therapy also has been associated with fluid retention, edema, sodium retention, oliguria, and elevations of serum urea nitrogen and creatinine during clinical trials and should therefore be used with caution in patients with cardiac decompensation, hypertension, or similar conditions.

Although ketorolac often is used in a perioperative setting, it is contraindicated in patients having undergone coronary artery bypass graft surgery. Data from 2 large controlled trials have revealed an increased risk for myocardial infarction and stroke in patients receiving cyclooxygenase-2 selective NSAIDs for pain relief in this setting.

Serious and potentially fatal dermatologic adverse events (eg, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis) can occur without warning in patients receiving ketorolac or other NSAIDs. Patients should be advised to discontinue treatment and seek immediate medical attention for symptoms such as hives, facial swelling, asthma, shock, skin reddening, rash, and blisters.

Patients with asthma may have aspirin sensitivity that has been associated with severe and potentially fatal bronchospasm. Because of the risk for cross-sensitivity, ketorolac should be used with caution in patients with asthma and is contraindicated in those who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin.

Caution also should be exercised when treating patients with impaired hepatic function or a history of liver disease. Up to 15% of patients receiving treatment with NSAIDs develop borderline elevations of 1 or more liver tests; these may progress, remain unchanged, or remain transient with continued therapy. Notable elevations of alanine aminotransferase or aspartate aminotransferase have been observed in approximately 1% of clinical study patients and have progressed rarely to jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure.

Patients with signs suggestive of hepatic dysfunction or having abnormal liver tests should therefore be evaluated for evidence of more severe reactions while taking ketorolac. Treatment should be discontinued in those patients with clinical signs of liver disease or systemic manifestations thereof (eg, eosinophilia and rash).

Minocycline Intravenous Injection and Oral Suspension (Minocin) Linked to Risk for CDAD
On January 23, the FDA approved safety labeling revisions for minocycline HCl intravenous injection and oral suspension (Minocin; Triax Pharmaceuticals, LLC) to warn of the risk for Clostridium difficile–associated diarrhea (CDAD).

Treatment with antibacterial agents such as minocycline can alter the colon's normal flora, leading to overgrowth of C difficile and subsequent release of toxins A and B that contribute to the development of CDAD. Nearly all antibiotics have been implicated in CDAD, which may range in severity from mild diarrhea to fatal colitis.

Because hypertoxin-producing strains of C difficile can be refractory to antimicrobial therapy, they are associated with increased morbidity and mortality and may require colectomy. The FDA advises that CDAD be considered in all patients who present with diarrhea following antibiotic use. Careful examination of medical history is required because of the potential for late-onset disease; cases of CDAD have been reported more than 2 months after completion of an antimicrobial course of therapy.

The FDA notes that current antibiotic therapy for the primary infection may need to be discontinued in patients with known or suspected CDAD. Appropriate fluid and electrolyte management, protein supplementation, antibiotic therapy for C difficile, and surgical evaluation also may be required.

Minocycline is a tetracycline-derived antibiotic indicated for the treatment of Gram-positive and Gram-negative infections resulting from susceptible strains of designated microorganisms. It also may be used as adjunctive therapy for acute intestinal amebiasis and severe acne.

http://www.fda.gov/medwatch/SAFETY/2007/Jan_PI/Toradol_PI.pdf

http://www.fda.gov/medwatch/SAFETY/2007/Jan_PI/MinocinIV_PI.pdf

Source: http://www.medscape.com/viewarticle/554224?src=mp

[smith11]

It's a fact- curing acne can never be achieved by tackling one of the many factors responsible for acne. If you've ever tried to cure your acne using one-dimensional treatments like antibiotics or even detox diets and failed it's probably because you tackled only one aspect of the disease. Not only will this system teach you the only way to prevent your acne from being formed, you will also learn the only way to acne treatments for good - the holistic way.

[Jessiblack]

The US Food and Drug Administration (FDA) has approved safety labeling revisions to advise of multiple risks associated with use of oral ketorolac tromethamine and the potential for development of Clostridium difficile–associated diarrhea more than 2 months after completion of minocycline HCl therapy.

Oral Ketorolac Tromethamine (Toradol) Linked to Risk for Gastrointestinal Bleed
On January 19, the FDA approved safety labeling revisions for ketorolac tromethamine tablets (Toradol; Roche Pharmaceuticals) to warn of the potential risks for gastrointestinal (GI) bleeding, cardiovascular (CV) events, allergic reactions, and hepatic dysfunction.

Oral ketorolac is a potent nonsteroidal anti-inflammatory drug (NSAID) that is only indicated for the short-term management of moderately severe acute pain requiring analgesia at the opioid level, following intravenous or intramuscular administration. The total duration of therapy should not exceed 5 days.

The FDA notes that ketorolac oral therapy is not indicated for use in children or for the management of minor or chronic painful conditions. Dose increases beyond 40 mg/day do not provide better efficacy and increase the risk for serious adverse events.

As with other NSAIDs, ketorolac is linked to an increased risk for serious and potentially fatal GI events in patients. Inflammation, bleeding, ulceration, and perforation of the stomach or small and/or large intestines may occur at any time and are symptomatic in only 20% of patients.

Factors that exacerbate this risk include increased dose, concomitant use of corticosteroids or anticoagulants, longer duration of therapy, smoking, alcohol consumption, advanced age, and poor general health status. Use of ketorolac is contraindicated in patients with a history of peptic ulcer and/or GI bleeding and should be used with particular caution in the elderly because of the increased rate of spontaneous GI fatalities in this population. Concomitant use of pentoxifylline is linked to an increased risk of bleeding and therefore contraindicated.

Healthcare professionals are advised to limit therapy to the lowest dose for the shortest possible time consistent with therapeutic goals and to remain alert for symptoms of ulceration and bleeding. These should be evaluated promptly and ketorolac discontinued until serious GI events have been ruled out.

The FDA also warned of the risks for cardiovascular thrombotic events and hypertension associated with NSAID therapy, including ketorolac. Clinical trials of up to 3 years' duration have linked several cyclooxgenase-2 selective and nonselective NSAIDs to an increased risk for serious and potentially fatal CV thrombotic events, myocardial infarction, and stroke. According to the FDA, all NSAIDs may have similar risks that increase with duration of use and in the presence of existing CV disease and/or related risk factors.

Clinicians are advised to remain alert for the development of CV events, even in the absence of previous symptoms. The FDA notes that there is no consistent evidence that concurrent use of low-dose aspirin mitigates the risk for thrombotic events, and concomitant use of both drugs does increase the risk for serious GI events.

An increased incidence of myocardial infarction and stroke also has been observed in 2 large controlled clinical trials of cyclooxgenase-2 selective NSAIDs for pain relief after coronary artery bypass graft surgery; use of NSAIDs is therefore contraindicated in this setting.

The FDA notes that all NSAIDs, including ketorolac, can lead to the onset of new hypertension or worsening of preexisting disease of which either may contribute to an increased incidence of CV events. Because the effects of furosemide and thiazides may be diminished, close monitoring of blood pressure is recommended prior to and during therapy. In addition, reports suggest that NSAIDs may reduce the effects of angiotensin-converting enzyme inhibitor therapy. All 3 classes of antihypertensive agents are linked to an increased risk fo

[amanda]

jessiblack just repost the topic. is this about acne? isn't about gastrointestinal bleeding? how do this being diagnose?

[jennart]

Acne can't be cured with antibiotics, but it can definitely be treated. It's important to treat severe acne to prevent scarring later on.

[alexjoan]

Toradol every now and then works great on me for the pain and stiffness in my muscles. The bad thing is that you can't have them very often due to intestinal issues.