Cambia

Cambia information, interactions and side effects, CAMBIA (Diclofenac Potassium for Oral Solution) is a benzeneacetic acid derivative NSAID. CAMBIA (diclofenac potassium for oral solution) is available as a buffered soluble powder, designed to be mixed with water prior to oral administration.

CAMBIA (diclofenac potassium for oral solution) is a white to off-white, buffered, flavored, powder for oral solution packaged in individual unit dose packets [see HOW SUPPLIED].

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 C14H10Cl2NKO2, and it has the following structural formula:

cambia1

The inactive ingredients in CAMBIA (diclofenac potassium for oral solution) include: aspartame (equivalent to 25 mg phenylalanine), flavoring agents (anise and mint), glycerol behenate, mannitol, potassium bicarbonate, and saccharin sodium.

INDICATIONS

Acute Treatment of Migraine

CAMBIA (diclofenac potassium for oral solution) ™ (Diclofenac Potassium for Oral Solution) is indicated for the acute treatment of migraine attacks with or without aura in adults (18 years of age or older).

Important Limitations

  • CAMBIA (diclofenac potassium for oral solution) is not indicated for the prophylactic therapy of migraine.
  • The safety and effectiveness of CAMBIA (diclofenac potassium for oral solution) have not been established for cluster headache, which is present in an older, predominantly male population.

DOSAGE AND ADMINISTRATION

Acute Treatment of Migraine

Administer one packet (50 mg) of CAMBIA (diclofenac potassium for oral solution) ™ 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 potassium for oral solution) with food may cause a reduction in effectiveness compared to taking CAMBIA (diclofenac potassium for oral solution) on an empty stomach [see CLINICAL PHARMACOLOGY].

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.

Interchangeability with Other Formulations of Diclofenac

Different formulations of oral diclofenac (e.g., CAMBIA (diclofenac potassium for oral solution) , 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 potassium for oral solution).

HOW SUPPLIED

Dosage Forms And Strengths

CAMBIA (diclofenac potassium for oral solution) is available in individual packets each designed to deliver a 50 mg dose when mixed in water.

CAMBIA™ 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 potassium for oral solution) is a white to off-white, buffered, flavored, powder for oral solution packaged in individual unit dose packets.

Individual CAMBIA (diclofenac potassium for oral solution) ™ Packets – NDC 66869-513-01

Boxes of nine (9) CAMBIA (diclofenac potassium for oral solution) ™ Packets – NDC 66869-513-09

Store at 25°C (77°F) Excursions permitted from 15°C-30°C (59°F-86°F). [See USP Controlled Room Temperature]

SIDE EFFECTS

The following serious adverse reactions are discussed elsewhere in the labeling:

  • Cardiovascular thrombotic events [see Boxed Warning and WARNINGS AND PRECAUTIONS]
  • Gastrointestinal effects [see Boxed Warning and WARNINGS AND PRECAUTIONS]
  • Hepatic effects [see WARNINGS AND PRECAUTIONS]
  • Hypertension [see WARNINGS AND PRECAUTIONS]
  • Congestive Heart Failure and Edema [see WARNINGS AND PRECAUTIONS]
  • Renal Effects [see WARNINGS AND PRECAUTIONS]
  • Anaphylactoid Reactions [see WARNINGS AND PRECAUTIONS]
  • Serious Skin Reactions [see WARNINGS AND PRECAUTIONS]

The most common adverse reactions reported with CAMBIA (diclofenac potassium for oral solution) are nausea and dizziness.

The most common adverse events resulting in discontinuation of patients following CAMBIA (diclofenac potassium for oral solution) dosing in controlled clinical trials were urticaria (0.2%) and flushing (0.2%).

Clinical Studies Experience with CAMBIA (diclofenac potassium for oral solution)

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of a single dose of CAMBIA (diclofenac potassium for oral solution) was evaluated in 2 placebo-controlled trials with a total of 634 migraine patients treated with CAMBIA (diclofenac potassium for oral solution) for a single migraine headache. Following treatment with diclofenac potassium (either CAMBIA or diclofenac potassium immediate-release tablets [as a control]), 5 subjects (0.8%) withdrew from the studies; following placebo exposure, 1 subject (0.2%) withdrew. No withdrawals were due to a serious reaction.

The most common adverse reactions (i.e., that occurred in 1% or more of CAMBIA (diclofenac potassium for oral solution) -treated patients) and more frequent with CAMBIA (diclofenac potassium for oral solution) than with placebo were nausea and dizziness (see Table 1).

Table 1: Treatment-Related Adverse Reactions with Incidence > 1% and Greater than Placebo in Studies 1 and 2 Combined

 

Disorder Event CAMBIA
N=634
Placebo
N=646
Gastrointestinal
  Nausea 3% 2%
Nervous System
  Dizziness 1% 0.5%

 

Adverse reactions reported with diclofenac and other NSAIDs

In patients taking diclofenac or other NSAIDs, the most frequently reported adverse reactions occurring in approximately 1%-10% of patients are: GI reactions (including abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers [gastric/duodenal], and vomiting), abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritus, rashes, and tinnitus.

Additional adverse reactions reported in patients taking NSAIDs include occasionally:

Body as a Whole: Fever, infection, sepsis

Cardiovascular System: Congestive heart failure, hypertension, tachycardia, syncope

Digestive System: Dry mouth, esophagitis, gastric/peptic ulcers, gastritis, gastrointestinal bleeding, glossitis, hematemesis, hepatitis, jaundice

Hemic and Lymphatic System: Ecchymosis, eosinophilia, leukopenia, melena, purpura, rectal bleeding, stomatitis, thrombocytopenia

Metabolic and Nutritional: Weight changes

Nervous System: Anxiety, asthenia, confusion, depression, dream abnormalities, drowsiness, insomnia, malaise, nervousness, paresthesia, somnolence, tremors, vertigo

Respiratory System: Asthma, dyspnea

Skin and Appendages: Alopecia, photosensitivity, sweating increased

Special Senses: Blurred vision

Urogenital System: Cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, proteinuria, renal failure

Other adverse reactions in patients taking NSAIDs, which occur rarely , are:

Body as a Whole: Anaphylactic reactions, appetite changes, death

Cardiovascular System: Arrhythmia, hypotension, myocardial infarction, palpitations, vasculitis

Digestive System: Colitis, eructation, liver failure, pancreatitis

Hemic and Lymphatic System: Agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy, pancytopenia

Metabolic and Nutritional: Hyperglycemia

Nervous System: Convulsions, coma, hallucinations, meningitis

Respiratory System: Respiratory depression, pneumonia

Skin and Appendages: Angioedema, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, urticaria

Special Senses: Conjunctivitis, hearing impairment.

DRUG INTERACTIONS

Aspirin

When administered with aspirin, diclofenac potassium’s protein binding is reduced. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of CAMBIA (diclofenac potassium for oral solution) and aspirin is not generally recommended because of the potential of increased adverse effects.

Anticoagulants

The effects of anticoagulants such as warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than that with use of either drug alone.

ACE Inhibitors

NSAIDs may diminish the antihypertensive effect of ACE inhibitors. This interaction should be given consideration in patients taking CAMBIA (diclofenac potassium for oral solution) concomitantly with ACE inhibitors.

Diuretics

Clinical studies, as well as post-marketing observations, have shown that diclofenac potassium can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, observe patients closely for signs of renal failure as well as to assure diuretic efficacy [see WARNINGS AND PRECAUTIONS].

Lithium

NSAIDs have produced elevations of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. When CAMBIA (diclofenac potassium for oral solution) and lithium are administered concurrently, observe patients carefully for signs of lithium toxicity.

Methotrexate

NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This indicates that NSAIDs may enhance the toxicity of methotrexate. Use caution when NSAIDs are administered concomitantly with methotrexate.

Cyclosporine

CAMBIA (diclofenac potassium for oral solution) , like other NSAIDs, may affect renal prostaglandins and increase the toxicity of certain drugs. Therefore, concomitant therapy with CAMBIA (diclofenac potassium for oral solution) may increase cyclosporine’s nephrotoxicity. Use caution when CAMBIA (diclofenac potassium for oral solution) is administered concomitantly with cyclosporine.

Inhibitors of Cytochrome P450 2C9

Diclofenac is metabolized predominantly by Cytochrome P-450 CYP2C9. Co-administration of medications that inhibit CYP2C9 may affect the pharmacokinetics of diclofenac [see CLINICAL PHARMACOLOGY].

PRECAUTIONS

Cardiovascular Thrombotic Events

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 [see WARNINGS AND PRECAUTIONS].

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 [see CONTRAINDICATIONS].

Gastrointestinal Effects – Risk of Ulceration, Bleeding, and Perforation

NSAIDs, including CAMBIA (diclofenac potassium for oral solution) , 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 potassium for oral solution) , 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 bleeding who 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 potassium for oral solution) therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the CAMBIA (diclofenac potassium for oral solution) until a serious GI adverse event is ruled out. For high risk patients, alternative therapies that do not include NSAIDs should be considered.

Hepatic Effects

Elevations of one or more liver tests may occur during therapy with CAMBIA (diclofenac potassium for oral solution) . 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 potassium for oral solution) 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 potassium for oral solution) , use the lowest effective dose for the shortest duration possible. Exercise caution when prescribing CAMBIA (diclofenac potassium for oral solution) 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 potassium for oral solution) .

Hypertension

NSAIDs, including CAMBIA (diclofenac potassium for oral solution) , can lead to new onset or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Use NSAIDs, including CAMBIA (diclofenac potassium for oral solution) , 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.

Congestive Heart Failure and Edema

Fluid retention and edema have been observed in some patients taking NSAIDs. Use CAMBIA (diclofenac potassium for oral solution) with caution in patients with fluid retention or heart failure.

Renal Effects

Use caution when initiating treatment with CAMBIA (diclofenac potassium for oral solution) 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 potassium for oral solution) in patients with advanced renal disease. Therefore, treatment with CAMBIA (diclofenac potassium for oral solution) is not recommended in patients with advanced renal disease. If CAMBIA (diclofenac potassium for oral solution) therapy must be initiated, close monitoring of the patient’s renal function is advisable.

Anaphylactoid Reactions

As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to CAMBIA (diclofenac potassium for oral solution) . CAMBIA (diclofenac potassium for oral solution) is contraindicated in patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs. [see CONTRAINDICATIONS].

Serious Skin Reactions

NSAIDs, including CAMBIA (diclofenac potassium for oral solution) , can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin manifestations and to discontinue CAMBIA (diclofenac potassium for oral solution) at the first appearance of skin rash or any other sign of hypersensitivity.

Pregnancy

CAMBIA (diclofenac potassium for oral solution) can cause fetal harm when administered to a pregnant woman. Starting at 30 weeks gestation, CAMBIA (diclofenac potassium for oral solution) and other NSAIDs, should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur. If this drug is used during this time period in pregnancy, the patient should be apprised of the potential hazard to a fetus [See Use in Special Populations].

Masking of Inflammation and Fever

The pharmacological activity of NSAIDs in reducing inflammation and possibly fever may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

Hematologic Effects

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 potassium for oral solution) , 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 potassium for oral solution) who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants.

Use in Patients with Pre-existing Asthma

Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm which can be fatal. Since cross-reactivity, including bronchospasm, between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, CAMBIA (diclofenac potassium for oral solution) is contraindicated in patients with this form of aspirin sensitivity and should be used with caution in all patients with preexisting asthma.

Monitoring

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 potassium for oral solution) , periodically perform a CBC and chemistry profile. Discontinue CAMBIA (diclofenac potassium for oral solution) if abnormal liver tests or renal tests persist or worsen.

Phenylketonurics

CAMBIA (diclofenac potassium for oral solution) contains aspartame equivalent to phenylalanine 25 mg per packet.

Patient Counseling Information

Inform patients of the availability of a Medication Guide for NSAIDs that accompanies each prescription dispensed, and instruct them to read the Medication Guide prior to using CAMBIA [see Medication Guide].

Cardiovascular Effects

CAMBIA (diclofenac potassium for oral solution) , like other NSAIDS, may cause serious CV events, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, advise patients to be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and to ask for medical advice when observing any indicative sign or symptoms. Inform patients of the importance of this follow-up [see WARNINGS AND PRECAUTIONS].

Gastrointestinal Effects

CAMBIA (diclofenac potassium for oral solution) , like other NSAIDS, can cause GI discomfort and more serious GI adverse events such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, advise patients to be alert for the signs and symptoms of ulcerations and bleeding, and to ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Inform patients of the importance of this follow-up [see WARNINGS AND PRECAUTIONS].

Hepatotoxicity

Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and “flulike” symptoms). Instruct patients to stop therapy with CAMBIA (diclofenac potassium for oral solution) and seek immediate medical therapy if any of these occur [see WARNINGS AND PRECAUTIONS].

Weight Gain and Edema

Advise patients to promptly report to their physicians signs or symptoms of unexplained weight gain or edema during treatment with CAMBIA (diclofenac potassium for oral solution) [see WARNINGS AND PRECAUTIONS].

Anaphylactoid Reactions

Inform patients of the signs of an anaphylactoid reaction (e.g., difficulty breathing, swelling of the face or throat). Instruct patients to seek immediate emergency help if these occur [see WARNINGS AND PRECAUTIONS].

Adverse Skin Reactions

CAMBIA (diclofenac potassium for oral solution) , like other NSAIDS, can cause serious skin reactions such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrosis (TEN), which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, advise patients to be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and to ask for medical advice when observing any indicative signs or symptoms. Advise patients to stop CAMBIA (diclofenac potassium for oral solution) immediately if they develop any type of rash and to contact their physicians as soon as possible [see WARNINGS AND PRECAUTIONS].

Effects During Pregnancy

Starting at 30 weeks gestation, CAMBIA (diclofenac potassium for oral solution) and other NSAIDs should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur [see Use in Specific Populations].

Phenylketonurics

CAMBIA (diclofenac potassium for oral solution) packets contain aspartame equivalent to phenylalanine 25 mg per packet.

Non-clinical Studies

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term carcinogenicity studies in rats given diclofenac sodium up to 2 mg/kg/day (less than the recommended human dose [RHD] of 50 mg/day on a body surface area [mg/m2] basis) have revealed no significant increases in tumor incidence. There was a slight increase in benign mammary fibroadenomas in mid-dose treated (0.5 mg/kg/day or 3 mg/m2/day ) female rats (high-dose females had excessive mortality), but the increase was not significant for this common rat tumor. A 2-year carcinogenicity study conducted in mice employing diclofenac sodium at doses up to 0.3 mg/kg/day (less than the RHD on a mg/m2 basis) in males and 1 m/kg/day (less than the RHD on a mg/m2 basis) in females did not reveal any oncogenic potential.

Diclofenac sodium was not genotoxic in in vitro (reverse mutation in bacteria [Ames], mouse lymphoma tk) or in in vivo (including dominant lethal and male germinal epithelial chromosomal aberration in Chinese hamster) assays.

Diclofenac sodium administered to male and female rats at 4 mg/kg/day (less than the RHD on a mg/m2 basis) did not affect fertility.

Use In Specific Populations

Pregnancy

Pregnancy Category C prior to 30 weeks gestation; Category D starting at 30 weeks gestation.

Starting at 30 weeks gestation, CAMBIA (diclofenac potassium for oral solution) , and other NSAIDS, should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur [see WARNINGS AND PRECAUTIONS]. There are no adequate and well controlled studies in pregnant women.

Prior to 30 weeks gestation, CAMBIA (diclofenac potassium for oral solution) 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/m2 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/m2 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.

Labor and Delivery

The effects of CAMBIA (diclofenac potassium for oral solution) on labor and delivery in pregnant women are unknown. In rat studies, maternal exposure to NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, increased the incidence of dystocia, delayed parturition, and decreased pup survival.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from CAMBIA (diclofenac potassium for oral solution) , a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of CAMBIA (diclofenac potassium for oral solution) 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 potassium for oral solution) in the elderly.

Hepatic Impairment

Because hepatic metabolism accounts for almost 100% of diclofenac elimination, patients with hepatic impairment should be considered for treatment with CAMBIA (diclofenac potassium for oral solution) only if the benefits outweigh the risks. There is insufficient information available to support dosing recommendations for CAMBIA in patients with hepatic insufficiency. [see CLINICAL PHARMACOLOGY].

Renal Impairment

No information is available from controlled clinical studies regarding the use of CAMBIA (diclofenac potassium for oral solution) in patients with advanced renal disease. Therefore, treatment with CAMBIA (diclofenac potassium for oral solution) is not recommended in patients with advanced renal disease. If CAMBIA (diclofenac potassium for oral solution) therapy must be initiated, close monitoring of the patient’s renal function is advisable.

OVERDOSE

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.

CONTRAINDICATIONS

  • CAMBIA (diclofenac potassium for oral solution) is contraindicated in patients with known hypersensitivity (e.g., anaphylactoid reactions and serious skin reactions) to diclofenac [see WARNINGS AND PRECAUTIONS].
  • CAMBIA (diclofenac potassium for oral solution) is contraindicated in patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients [see WARNINGS AND PRECAUTIONS].
  • CAMBIA (diclofenac potassium for oral solution) is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery [see WARNINGS AND PRECAUTIONS].
693 read