Cambia Information
Cambia (Diclofenac) Dosage And Administration
Administer one packet (50 mg) of Cambia (Diclofenac) for the acute treatment of migraine. Empty the contents of one packet into a cup containing 1 to 2 ounces (30 to 60 mL) of water, mix well and drink immediately. Do not use liquids other than water.
Taking Cambia (Diclofenac) with food may cause a reduction in effectiveness compared to taking Cambia (Diclofenac) on an empty stomach .
Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals. The safety and effectiveness of a second dose have not been established.
Different formulations of oral diclofenac (e.g., Cambia (Diclofenac) , diclofenac sodium enteric-coated tablets, diclofenac sodium extended-release tablets, or diclofenac potassium immediate-release tablets) may not be bioequivalent even if the milligram strength is the same. Therefore, it is not possible to convert dosing from any other formulation of diclofenac to Cambia (Diclofenac) .
Cambia (Diclofenac) Dosage Forms And Strengths
Cambia (Diclofenac) is available in individual packets each designed to deliver a 50 mg dose when mixed in water.
Cambia (Diclofenac) Warnings And Precautions
Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years’ duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Inform patients about the signs and symptoms of serious CV events and the steps to take if they occur.
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 increases the risk of serious GI events .
Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following coronary artery bypass graft (CABG) surgery found an increased incidence of myocardial infarction and stroke .
NSAIDs, including Cambia (Diclofenac) , can cause serious gastrointestinal (GI) adverse events such as inflammation, bleeding, ulceration, and perforation of the stomach, small intestine or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months, and in about 2%-4% of patients treated for one year. These trends continue with longer duration of use, thus increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term NSAID therapy is not without risk.
Prescribe NSAIDs, including Cambia (Diclofenac) , with extreme caution in patients with a prior history of ulcer disease or GI bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleedingwho use NSAIDs have a greater than 10-fold risk for developing a GI bleed than patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients, and therefore special care should be taken in treating this population.
To minimize the potential risk for an adverse GI event in patients treated with an NSAID, use the lowest effective dose for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during Cambia (Diclofenac) therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the Cambia (Diclofenac) until a serious GI adverse event is ruled out. For high risk patients, alternative therapies that do not include NSAIDs should be considered.
Elevations of one or more liver tests may occur during therapy with Cambia (Diclofenac) . These laboratory abnormalities may progress, may persist, or may only be transient with continued therapy. Borderline elevations (less than 3 times the upper limit of the normal [ULN] range) or greater elevations of transaminases occurred in about 15% of diclofenac-treated patients. Of the markers of hepatic function, ALT (SGPT) is recommended for the monitoring of liver injury.
In clinical trials, meaningful elevations (i.e., more than 3 times the ULN) of AST (SGOT) occurred in about 2% of approximately 5,700 patients at some time during treatment (ALT was not measured in all studies). In an open-label, controlled trial of 3,700 patients treated for 2–6 months, patients were monitored at 8 weeks and 1,200 patients were monitored again at 24 weeks. Meaningful elevations of ALT and/or AST occurred in about 4% of the 3,700 patients and included marked elevations (>8 times the ULN) in about 1% of the 3,700 patients. In this open-label study, a higher incidence of borderline (less than 3 times the ULN), moderate (3–8 times the ULN), and marked (>8 times the ULN) elevations of ALT or AST was observed in patients receiving diclofenac when compared to other NSAIDs.. Almost all meaningful elevations in transaminases were detected before patients became symptomatic.
Abnormal tests occurred during the first 2 months of therapy with diclofenac in 42 of the 51 patients in all trials who developed marked transaminase elevations. In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first month, and in some cases, the first 2 months of NSAID therapy, but can occur at any time during treatment with diclofenac.
Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases resulted in fatalities or liver transplantation.
Measure transaminases (ALT and AST) periodically in patients receiving long-term therapy with diclofenac because severe hepatotoxicity may develop without a prodrome of distinguishing symptoms. The optimum times for making the first and subsequent transaminase measurements are not known. Based on clinical trial data and postmarketing experiences, transaminases should be monitored within 4 to 8 weeks after initiating treatment with diclofenac. However, severe hepatic reactions can occur at any time during treatment with diclofenac. If abnormal liver tests persist or worsen, if clinical signs and/or symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, abdominal pain, diarrhea, dark urine, etc.), discontinue Cambia (Diclofenac) immediately.
To minimize the possibility that hepatic injury will become severe between transaminase measurements, 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), and the appropriate action patients should take if these signs and symptoms appear.
To minimize the potential risk for an adverse liver-related event in patients treated with Cambia (Diclofenac) , use the lowest effective dose for the shortest duration possible. Exercise caution when prescribing Cambia (Diclofenac) with concomitant drugs that are known to be potentially hepatotoxic (e.g., acetaminophen, certain antibiotics, antiepileptics). Caution patients to avoid taking nonprescription acetaminophen-containing products while using Cambia (Diclofenac) .
NSAIDs, including Cambia (Diclofenac) , can lead to new onset or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Use NSAIDs, including Cambia (Diclofenac) , with caution in patients with hypertension. Monitor blood pressure closely during the initiation of NSAID treatment and throughout the course of therapy.
Patients taking ACE inhibitors, thiazides, or loop diuretics may have impaired response to these therapies when taking NSAIDs.
Use caution when initiating treatment with Cambia (Diclofenac) in patients with considerable dehydration.
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics or ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
No information is available from controlled clinical studies regarding the use of Cambia (Diclofenac) in patients with advanced renal disease. Therefore, treatment with Cambia (Diclofenac) is not recommended in patients with advanced renal disease. If Cambia (Diclofenac) therapy must be initiated, close monitoring of the patient's renal function is advisable.
Anemia may occur in patients receiving NSAIDs. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. In patients on long-term therapy with NSAIDs, including Cambia (Diclofenac) , check hemoglobin or hematocrit if they exhibit any signs or symptoms of anemia or blood loss.
NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, the NSAID effect on platelet function is quantitatively less, of shorter duration, and reversible. Carefully monitor patients treated with Cambia (Diclofenac) who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants.
Because serious GI ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding.
For patients on long-term treatment with NSAIDs, including Cambia (Diclofenac) , periodically perform a CBC and chemistry profile. Discontinue Cambia (Diclofenac) if abnormal liver tests or renal tests persist or worsen.
Cambia (Diclofenac) adverse Reactions
The following serious adverse reactions are discussed elsewhere in the labeling:
The most common adverse reactions reported with Cambia (Diclofenac) are nausea and dizziness.
The most common adverse events resulting in discontinuation of patients following Cambia (Diclofenac) dosing in controlled clinical trials were urticaria (0.2%) and flushing (0.2%).
Cambia (Diclofenac) use In Specific Populations
Pregnancy Category C prior to 30 weeks gestation; Category D starting at 30 weeks gestation.
Starting at 30 weeks gestation, Cambia (Diclofenac) , and other NSAIDS, should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur . There are no adequate and well controlled studies in pregnant women.
Prior to 30 weeks gestation, Cambia (Diclofenac) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Reproductive studies have been performed in mice given diclofenac sodium (up to 20 mg/kg/day, 2 times the recommended human dose [RHD] of 50 mg/day on a body surface area [mg/m basis), and in rats and rabbits given diclofenac sodium (up to 10 mg/kg/day; 2 [rats] and 4 [rabbits] times the RHD on a mg/m basis) and have revealed no evidence of teratogenicity despite the induction of maternal toxicity and fetal toxicity. In rats, maternally toxic doses were associated with dystocia, prolonged gestation, reduced fetal weights and growth, and reduced fetal survival.
Clinical studies of Cambia (Diclofenac) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Elderly patients are at increased risk for serious GI adverse events.
Diclofenac is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken when using Cambia (Diclofenac) in the elderly.
Cambia (Diclofenac) overdosage
Symptoms following acute NSAID overdoses are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression and coma may occur, but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose.
Patients should be managed by symptomatic and supportive care following an NSAID overdose. There are no specific antidotes. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose (5 to 10 times the usual dose). Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.
Cambia (Diclofenac) description
Cambia (Diclofenac) (Diclofenac Potassium for Oral Solution) is a benzeneacetic acid derivative NSAID. Cambia (Diclofenac) is available as a buffered soluble powder, designed to be mixed with water prior to oral administration.
Cambia (Diclofenac) is a white to off-white, buffered, flavored powder for oral solution packaged in individual unit dose packets .
The chemical name for diclofenac potassium is 2-[(2,6-dichlorophenyl)amino] benzeneacetic acid monopotassium salt. The molecular weight of diclofenac potassium is 334.25. Its molecular formula is CHClNKOand it has the following structural formula:
The inactive ingredients in Cambia (Diclofenac) include: aspartame (equivalent to 25 mg phenylalanine), flavoring agents (anise and mint), glycerol behenate, mannitol, potassium bicarbonate, and saccharin sodium.
Cambia (Diclofenac) clinical Pharmacology
: Diclofenac is 100% absorbed after oral administration compared to intravenous administration as measured by urine recovery. However, due to first-pass metabolism, only about 50% of the absorbed dose is systemically available. In fasting volunteers, measurable plasma levels were observed within 5 minutes of dosing with Cambia (Diclofenac) . Peak plasma levels were achieved at approximately 0.25 hour in fasting normal volunteers, with a range of 0.17 to 0.67 hours. High fat food had no significant effect on the extent of diclofenac absorption, but there was a reduction in peak plasma levels of approximately 70% after a high fat meal. Decreased Cmax may be associated to decreased effectiveness.
: The apparent volume of distribution (V/F) of diclofenac potassium is 1.3 L/kg.
Diclofenac is more than 99% bound to human serum proteins, primarily to albumin. Serum protein binding is constant over the concentration range (0.15-105 µg/mL) achieved with recommended doses.
: Five diclofenac metabolites have been identified in human plasma and urine. The metabolites include 4'-hydroxy-, 5-hydroxy-, 3'-hydroxy-, 4',5-dihydroxy- and 3'-hydroxy-4'-methoxy diclofenac. The major diclofenac metabolite, 4’-hydroxydiclofenac, has very weak pharmacologic activity. The formation of 4’-hydroxy diclofenac is primarily mediated by CPY2C9. Both diclofenac and its oxidative metabolites undergo glucuronidation or sulfation followed by biliary excretion. Acylglucuronidation mediated by UGT2B7 and oxidation mediated by CPY2C8 may also play a role in diclofenac metabolism. CYP3A4 is responsible for the formation of minor metabolites, 5-hydroxy and 3’-hydroxy- diclofenac. In patients with renal impairment, peak concentrations of metabolites 4'-hydroxy-and 5- hydroxydiclofenac were approximately 50% and 4% of the parent compound after single oral dosing compared to 27% and 1% in normal healthy subjects.
: Diclofenac is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites. Little or no free unchanged diclofenac is excreted in the urine. Approximately 65% of the dose is excreted in the urine and approximately 35% in the bile as conjugates of unchanged diclofenac plus metabolites. Because renal elimination is not a significant pathway of elimination for unchanged diclofenac, dosing adjustment in patients with mild to moderate renal dysfunction is not necessary. The terminal half-life of unchanged diclofenac is approximately 2 hours.
:
Race
Hepatic Impairment
Cambia (Diclofenac) clinical Studies
The efficacy of Cambia (Diclofenac) in the acute treatment of migraine headache was demonstrated in two randomized, double-blind, placebo-controlled trials.
Patients enrolled in these two trials were predominantly female (85%) and white (86%), with a mean age of 40 years (range: 18 to 65). Patients were instructed to treat a migraine of moderate to severe pain with 1 dose of study medication. Patients evaluated their headache pain 2 hours later. Associated symptoms of nausea, photophobia, and phonophobia were also evaluated. In addition, the proportion of patients who were “sustained pain free”, defined as a reduction in headache severity from moderate or severe pain to no pain at 2 hours post-dose without a return of mild, moderate, or severe pain and no use of rescue medication for 24 hours post-dose, was also evaluated. In these studies, the percentage of patients achieving pain freedom 2 hours after treatment and sustained pain freedom from 2 to 24 hours post-dose was significantly greater in patients who received Cambia (Diclofenac) compared with those who received placebo (see ). The percentage of patients achieving pain relief 2 hours after treatment (defined as a reduction in headache severity from moderate or severe pain to mild or no pain) was also significantly greater in patients who received Cambia (Diclofenac) compared with those who received placebo (see ).
The estimated probability of achieving migraine headache pain freedom within 2 hours following treatment with Cambia (Diclofenac) is shown in Figure 1.
There was a decreased incidence of nausea, photophobia and phonophobia following administration of Cambia (Diclofenac) , compared to placebo. The efficacy and safety of Cambia (Diclofenac) was unaffected by age or gender of the patient.
Cambia (Diclofenac) how Supplied/storage And Handling
Cambia (Diclofenac) 50 mg (Diclofenac Potassium for Oral Solution) is supplied as one or more sets of three perforated co-joined individual dose packets. Each individual packet is designed to deliver a dose of 50 mg diclofenac potassium when mixed in water.
Cambia (Diclofenac) is a white to off-white, buffered, flavored powder for oral solution packaged in individual unit dose packets.
Individual Cambia (Diclofenac) Packets - NDC 50192-113-01
Boxes of three (3) Cambia (Diclofenac) Packets – NDC 50192-113-03
Boxes of nine (9) Cambia (Diclofenac) Packets - NDC 50192-113-09
Store at 25°C (77°F) Excursions permitted from 15°C-30°C (59°F-86°F). [See USP Controlled Room Temperature]
Manufactured by: MIPHARM S.p.A.Via Bernardo Quaranta, 12 20141 Milan, Italy
Manufactured for:Nautilus Neurosciences, Inc.135 Rte. 202/206 Bedminster, NJ 08921United States of America
Manufactured and Distributed Under License from APR Applied Pharma Research SA, Balerna Switzerland
Cambia (Diclofenac)
Cambia (Diclofenac)
Cambia (Diclofenac)
