Cambia

Cardiovascular Thrombotic Events

• Clinical trials of several COX-2 selective and nonselective NSAIDs of up to 3 years duration have shown an increased risk of serious CV thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. The increase in CV thrombotic risk has been observed most consistently at higher doses. 

• Use the lowest effective dose for the shortest duration possible to minimize the potential risk for an adverse CV event in NSAID-treated patients. Remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. 

• There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as naproxen, increases the risk of serious gastrointestinal (GI) events.

• Status Post Coronary Artery Bypass Graft (CABG) Surgery: NSAIDs are contraindicated in the setting of CABG.

• Post-MI Patients: Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. 

• Avoid use in patients with a recent MI unless benefits are expected to outweigh the risk of recurrent CV thrombotic events. If Cambia is used in patients with a recent MI, monitor patients for signs of cardiac ischemia.

Gastrointestinal (GI) Bleeding, Ulceration, and Perforation

• Serious GI adverse events, including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, may occur with the use of NSAIDS, including naproxen, a component of Cambia. These serious adverse events can be fatal and can occur at any time, with or without warning symptoms, in patients treated with NSAIDs.

• Risk Factors for GI Bleeding, Ulceration, and Perforation: 

• Patients with a prior history of peptic ulcer disease and/or GI bleeding who use NSAIDs have a greater than 10-fold increased risk for developing GI bleeding compared with patients with neither of these risk factors.

• Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or SSRIs; smoking; use of alcohol; older age; and poor general health status. 

• Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients, and therefore special care should be taken in treating this population. Patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding.

• Strategies to Minimize the GI Risks in NSAID-treated patients: Use the lowest effective dosage for the shortest possible duration. • Avoid administration of more than one NSAID at a time. • Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding. For high risk patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs. •Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy. • If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue Cambia until a serious GI adverse event is ruled out. • In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding.

Hepatotoxicity

• Discontinue immediately and perform a clinical evaluation if clinical signs and symptoms consistent with liver disease develop or if systemic manifestations occur (e.g., eosinophilia, rash). 

• Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). 

• Use lowest effective dose for the shortest duration possible to minimize the risk for an adverse liver-related event.

• Exercise caution when using Cambia with concomitant drugs known to be potentially hepatotoxic (eg, acetaminophen, certain antibiotics, antiepileptics).

• Exercise caution to avoid patients taking nonprescription acetaminophen-containing products while using Cambia.

Hypertension

• May lead to new onset of hypertension or worsening of pre-existing hypertension.

• Monitor blood pressure closely at initiation of therapy and during treatment.

• Concomitant use with ACE inhibitors, thiazides, or loop diuretics may have impaired response to these therapies when taking NSAIDs.

Heart Failure and Edema

• May blunt the CV effects of several therapeutic agents used to treat these medical conditions (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs])

• Avoid use in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. 

• Monitor for signs of worsening heart failure if used in patients with severe heart failure.  

Renal Toxicity and Hyperkalemia

• Long-term administration of NSAIDs has increased risk of renal toxicity in patients with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, salt depletion, those taking diuretics and angiotensin-converting enzyme (ACE) inhibitors or ARBs, and the elderly.

• Correct volume status in dehydrated or hypovolemic patients prior to initiating Cambia. 

• Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during treatment.

• Avoid use in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function. If Cambia is used in patients with advanced renal disease, monitor patients for signs of worsening renal function.

• Increases in serum potassium concentration, including hyperkalemia, have been reported with the use of NSAIDs, even in some patients without renal impairment.

Anaphylactic Reactions

• Seek emergency help if an anaphylactic reaction occurs.

Exacerbation of Asthma Related to Aspirin Sensitivity

• Monitor for changes in the signs and symptoms of asthma in patients with pre-existing asthma (without known aspirin sensitivity).

Serious Skin Reactions

• May cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal.

• Discontinue at the first appearance of skin rash or any other sign of hypersensitivity. Cambia is contraindicated in patients with previous serious skin reactions to NSAIDs.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

• Discontinue and evaluate immediately if signs or symptoms of DRESS are present.

Medication Overuse Headache

• Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, or a combination of these drugs for 10 or more days per month) may lead to exacerbation of headache (medication overuse headache). 

• Medication overuse headache may present as migraine-like daily headaches, or as a marked increase in frequency of migraine attacks. 

• May be necessary to detoxify patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache). 

Fetal Toxicity 

• Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs, including Cambia, in pregnant women at about 30 weeks gestation and later. NSAIDs, including Cambia, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age. 

• Oligohydramnios/Neonatal Renal Impairment: Use of NSAIDs, including Cambia, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. 

• If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit Cambia use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if Cambia treatment extends beyond 48 hours. Discontinue Cambia if oligohydramnios occurs and follow up according to clinical practice. 

Hematologic Toxicity

• Monitor hemoglobin or hematocrit if signs or symptoms of anemia develop.  

• May increase risk of bleeding events with concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs). Monitor for signs of bleeding.

Masking of Inflammation and Fever

• May diminish the utility of diagnostic signs in detecting infections. 

Laboratory Monitoring

• Consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile periodically due to serious GI bleeding, hepatotoxicity, and renal injury which may occur without warning symptoms or signs. 

• Discontinue if abnormal liver tests or renal tests persist or worsen.