Consensi

What Is Consensi?

Consensi (amlodipine and celecoxib) is a combination of a calcium channel blocker and a nonsteroidal anti-inflammatory drug (NSAID) indicated for patients for whom treatment with amlodipine for high blood pressure (hypertension) and celecoxib for osteoarthritis are appropriate. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular (CV) events, primarily strokes and heart attacks (myocardial infarctions).

What Are Side Effects of Consensi?

Side effects of Consensi are uncommon and typically short-term, and include:

• abdominal pain,
• diarrhea,
• indigestion/heartburn,
• gas (flatulence),
• swelling of extremities,
• accidental injury,
• dizziness,
• sore throat,
• runny nose,
• sinus infection (sinusitis),
• upper respiratory tract infection, and
• rash

Dosage for Consensi

The starting dose of Consensi is 5 mg/200 mg (2.5 mg/200 mg for small, elderly, or frail patients or hepatic impairment) orally once daily. Titrate to 5 mg/200 mg or 10 mg/200 mg once daily as needed for blood pressure control.

Consensi In Children

Safety and effectiveness of Consensi in pediatric patients have not been established.

What Drugs, Substances, or Supplements Interact with Consensi?

Consensi may interact with other medicines such as:

• warfarin,
• aspirin,
• selective serotonin reuptake inhibitors (SSRIs),
• serotonin–norepinephrine reuptake inhibitors (SNRIs),
• angiotensin converting enzyme (ACE) inhibitors,
• angiotensin receptor blockers (ARBs),
• beta-blockers,
• diuretics (water pills),
• digoxin,
• simvastatin,
• lithium,
• methotrexate,
• cyclosporine,
• salicylates and other nonsteroidal anti-inflammatory drugs (NSAIDs),
• pemetrexed,
• CYP2C9 inhibitors (e.g. fluconazole) or inducers (e.g. rifampin),
• CYP2D6 substrates (e.g. atomoxetine), and
• corticosteroids

Consensi During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Consensi; Use of NSAIDs, including Consensi, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including Consensi, in pregnant women starting at 30 weeks of gestation. The individual components of Consensi pass into breast milk in small amounts. Consult your doctor before breastfeeding.

Additional Information

Our Consensi (amlodipine and celecoxib) Tablets, for Oral Administration Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

 

Consensi Consumer Information

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Get emergency medical help if you have signs of a heart attack or stroke: chest pain spreading to your jaw or shoulder, sudden numbness or weakness on one side of the body, slurred speech, leg swelling, feeling short of breath.

Stop using this medicine and call your doctor at once if you have:

• nausea, weakness, tingly feeling;
• new or worsening chest pain;
• the first sign of any skin rash, no matter how mild;
• rapid weight gain, feeling short of breath;
• swelling in your arms, hands, legs, or feet;
• signs of stomach bleeding--bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;
• liver problems--stomach pain (upper right side), dark urine, jaundice (yellowing of the skin or eyes); or
• low red blood cells (anemia)--pale skin, unusual tiredness, feeling light-headed, cold hands and feet.

Common side effects may include:

• stomach pain, heartburn, gas, diarrhea, nausea;
• drowsiness, feeling tired;
• swelling;
• increased urination;
• joint pain;
• rash;
• flushing (sudden warmth or redness in your face);
• headache, dizziness; or
• cold symptoms such as stuffy nose, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Consensi (Amlodipine and Celecoxib Tablets)

 

Consensi Professional Information

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Cardiovascular Thrombotic Events [see WARNINGS AND PRECAUTIONS]
• GI Bleeding, Ulceration and Perforation [see WARNINGS AND PRECAUTIONS]
• Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
• Hypertension [see WARNINGS AND PRECAUTIONS]
• Hypotension [see WARNINGS AND PRECAUTIONS]
• Increased Angina or Myocardial Infarction [see WARNINGS AND PRECAUTIONS]
• Heart Failure and Edema [see WARNINGS AND PRECAUTIONS]
• Renal Toxicity and Hyperkalemia [see WARNINGS AND PRECAUTIONS]
• Anaphylactic Reactions [see WARNINGS AND PRECAUTIONS]
• Serious Skin Reactions [see WARNINGS AND PRECAUTIONS]
• Hematologic Toxicity [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

Celecoxib Clinical Trials

Of the celecoxib-treated patients in the pre-marketing controlled clinical trials, approximately 4,250 were patients with osteoarthritis, approximately 2,100 were patients with rheumatoid arthritis, and approximately 1,050 were patients with post-surgical pain. More than 8,500 patients received a total daily dose of celecoxib of 200 mg (100 mg twice daily or 200 mg once daily) or more, including more than 400 treated at 800 mg (400 mg twice daily). Approximately 3,900 patients received celecoxib at these doses for 6 months or more; approximately 2,300 of these have received it for 1 year or more and 124 of these have received it for 2 years or more.

Pre-Marketing Controlled Arthritis Trials

The table below lists all adverse events, regardless of causality, occurring in ≥2% of patients receiving celecoxib from 12 controlled studies conducted in patients with osteoarthritis or rheumatoid arthritis that included a placebo and/or a positive control group. Since these 12 trials were of different durations, and patients in the trials may not have been exposed for the same duration of time, these percentages do not capture cumulative rates of occurrence.

Adverse Events Occurring in ≥ 2% of Celecoxib Patients from Pre-Marketing Controlled Arthritis Trials

	CBX N=4146	Placebo N=1864	NAP N=1366	DCF N=387	IBU N=345
Gastrointestinal
Abdominal Pain	4.1%	2.8%	7.7%	9.0%	9.0%
Diarrhea	5.6%	3.8%	5.3%	9.3%	5.8%
Dyspepsia	8.8%	6.2%	12.2%	10.9%	12.8%
Flatulence	2.2%	1.0%	3.6%	4.1%	3.5%
Nausea	3.5%	4.2%	6.0%	3.4%	6.7%
Body as a whole
Back Pain	2.8%	3.6%	2.2%	2.6%	0.9%
Peripheral Edema	2.1%	1.1%	2.1%	1.0%	3.5%
Injury-Accidental	2.9%	2.3%	3.0%	2.6%	3.2%
Central, Peripheral Nervous System
Dizziness	2.0%	1.7%	2.6%	1.3%	2.3%
Headache	15.8%	20.2%	14.5%	15.5%	15.4%
Psychiatric
Insomnia	2.3%	2.3%	2.9%	1.3%	1.4%
Respiratory
Pharyngitis	2.3%	1.1%	1.7%	1.6%	2.6%
Rhinitis	2.0%	1.3%	2.4%	2.3%	0.6%
Sinusitis	5.0%	4.3%	4.0%	5.4%	5.8%
Upper Respiratory Infection	8.1%	6.7%	9.9%	9.8%	9.9%
Skin
Rash	2.2%	2.1%	2.1%	1.3%	1.2%
CBX = Celecoxib 100 - 200 mg twice daily or 200 mg once daily; NAP = Naproxen 500 mg twice daily; DCF = Diclofenac 75 mg twice daily; IBU = Ibuprofen 800 mg three times daily

In placebo- or active-controlled clinical trials, the discontinuation rate due to adverse events was 7.1% for patients receiving celecoxib and 6.1% for patients receiving placebo. Among the most common reasons for discontinuation due to adverse events in the celecoxib treatment groups were dyspepsia and abdominal pain (cited as reasons for discontinuation in 0.8% and 0.7% of celecoxib patients, respectively). Among patients receiving placebo, 0.6% discontinued due to dyspepsia and 0.6% withdrew due to abdominal pain.

The following adverse reactions occurred in 0.1 - 1.9% of patients treated with celecoxib (100 - 200 mg twice daily or 200 mg once daily):

Gastrointestinal: Constipation, diverticulitis, dysphagia, eructation, esophagitis, gastritis, gastroenteritis, gastroesophageal reflux, hemorrhoids, hiatal hernia, melena, dry mouth, stomatitis, tenesmus, vomiting

Cardiovascular: Aggravated hypertension, angina pectoris, coronary artery disorder, myocardial infarction

General: Hypersensitivity, allergic reaction, chest pain, cyst not otherwise specified (NOS), edema generalized, face edema, fatigue, fever, hot flushes, influenza- like symptoms, pain, peripheral pain

Central, peripheral nervous system: Leg cramps, hypertonia, hypoesthesia, migraine, paresthesia, vertigo

Hearing and vestibular: Deafness, tinnitus

Heart rate and rhythm: Palpitation, tachycardia

Liver and biliary: Hepatic enzyme increased [including serum glutamic oxaloacetic transaminase (SGOT) increased, serum glutamic pyruvic transaminase (SGPT) increased]

Metabolic and nutritional: BUN increased, creatine phosphokinase (CPK) increased, hypercholesterolemia, hyperglycemia, hypokalemia, non-protein nitrogen (NPN) increased, creatinine increased, alkaline phosphatase increased, weight increased

Musculoskeletal: Arthralgia, arthrosis, myalgia, synovitis, tendinitis

Platelets (bleeding or clotting): Ecchymosis, epistaxis, thrombocythemia

Psychiatric: Anorexia, anxiety, appetite increased, depression, nervousness, somnolence

Hemic: Anemia

Respiratory: Bronchitis, bronchospasm, bronchospasm aggravated, coughing, dyspnea, laryngitis, pneumonia

Skin and appendages: Alopecia, dermatitis, photosensitivity reaction, pruritus, rash erythematous, rash maculopapular, skin disorder, skin dry, sweating increased, urticaria

Application site disorders: Cellulitis, dermatitis contact

Urinary: Albuminuria, cystitis, dysuria, hematuria, micturition frequency, renal calculus

The following serious adverse events (causality not evaluated) occurred in <0.1% of patients:

Cardiovascular: Syncope, congestive heart failure, ventricular fibrillation, pulmonary embolism, cerebrovascular accident, peripheral gangrene, thrombophlebitis

Gastrointestinal: Intestinal obstruction, intestinal perforation, GI bleeding, colitis with bleeding, esophageal perforation, pancreatitis, ileus

General: Sepsis, sudden death

Liver and biliary: Cholelithiasis

Hemic and lymphatic: Thrombocytopenia

Nervous: Ataxia, suicide [see DRUG INTERACTIONS]

Renal: Acute renal failure

The Celecoxib Long-Term Arthritis Safety Study

[see Clinical Studies]

Hematological Events

The incidence of clinically significant decreases in hemoglobin (>2 g/dL) was lower in patients on celecoxib 400 mg twice daily (0.5%) compared to patients on either diclofenac 75 mg twice daily (1.3%) or ibuprofen 800 mg three times daily 1.9%. The lower incidence of events with celecoxib was maintained with or without ASA use [see CLINICAL PHARMACOLOGY].

Withdrawals/Serious Adverse Events

Kaplan-Meier cumulative rates at 9 months for withdrawals due to adverse events for celecoxib, diclofenac and ibuprofen were 24%, 29%, and 26%, respectively. Rates for serious adverse events (i.e., causing hospitalization or felt to be life-threatening or otherwise medically significant), regardless of causality, were not different across treatment groups (8%, 7%, and 8%, respectively).

Juvenile Rheumatoid Arthritis Study

In a 12-week, double-blind, active-controlled study, 242 juvenile rheumatoid arthritis patients 2 years to 17 years of age were treated with celecoxib or naproxen; 77 juvenile rheumatoid arthritis patients were treated with celecoxib 3 mg/kg twice daily, 82 patients were treated with celecoxib 6 mg/kg twice daily, and 83 patients were treated with naproxen 7.5 mg/kg twice daily. The most commonly occurring (≥5%) adverse events in celecoxib treated patients were headache, fever (pyrexia), upper abdominal pain, cough, nasopharyngitis, abdominal pain, nausea, arthralgia, diarrhea and vomiting. The most commonly occurring (≥5%) adverse experiences for naproxen-treated patients were headache, nausea, vomiting, fever, upper abdominal pain, diarrhea, cough, abdominal pain, and dizziness. Compared with naproxen, celecoxib at doses of 3 and 6 mg/kg twice daily had no observable deleterious effect on growth and development during the course of the 12 week double-blind study. There was no substantial difference in the number of clinical exacerbations of uveitis or systemic features of juvenile rheumatoid arthritis among treatment groups.

In a 12-week, open-label extension of the double-blind study described above, 202 juvenile rheumatoid arthritis patients were treated with celecoxib 6 mg/kg twice daily. The incidence of adverse events was similar to that observed during the double-blind study; no unexpected adverse events of clinical importance emerged.

Adverse Events Occurring in ≥5% of Juvenile Rheumatoid Arthritis Patients in Any Treatment Group, by System Organ Class (% of patients with events)

System Organ Class Preferred Term	All Doses Twice Daily
	Celecoxib 3 mg/kg N=77	Celecoxib 6 mg/kg N=82	Naproxen 7.5 mg/kg N=83
Any Event	64	70	72
Eye Disorders	5	5	5
Gastrointestinal	26	24	36
Abdominal pain NOS	4	7	7
Abdominal pain upper	8	6	10
Vomiting NOS	3	6	11
Diarrhea NOS	5	4	8
Nausea	7	4	11
General	13	11	18
Pyrexia	8	9	11
Infection	25	20	27
Nasopharyngitis	5	6	5
Injury and Poisoning	4	6	5
Investigations *	3	11	7
Musculoskeletal	8	10	17
Arthralgia	3	7	4
Nervous System	17	11	21
Headache NOS	13	10	16
Dizziness (excl vertigo)	1	1	7
Respiratory	8	15	15
Cough	7	7	8
Skin & Subcutaneous	10	7	18
*Abnormal laboratory tests, which include: Prolonged activated partial thromboplastin time, Bacteriuria NOS present, Blood creatine phosphokinase increased, Blood culture positive, Blood glucose increased, Blood pressure increased, Blood uric acid increased, Hematocrit decreased, Hematuria present, Hemoglobin decreased, Liver function tests NOS abnormal, Proteinuria present, Transaminase NOS increased, Urine analysis abnormal NOS

Other Pre-Approval Studies

Adverse Events From Ankylosing Spondylitis Studies

A total of 378 patients were treated with celecoxib in placebo- and active-controlled ankylosing spondylitis studies. Doses up to 400 mg once daily were studied. The types of adverse events reported in the ankylosing spondylitis studies were similar to those reported in the osteoarthritis/rheumatoid arthritis studies.

Adverse Events From Analgesia And Dysmenorrhea Studies

Approximately 1,700 patients were treated with celecoxib in analgesia and dysmenorrhea studies. All patients in post-oral surgery pain studies received a single dose of study medication. Doses up to 600 mg/day of celecoxib were studied in primary dysmenorrheal and post-orthopedic surgery pain studies. The types of adverse events in the analgesia and dysmenorrhea studies were similar to those reported in arthritis studies. The only additional adverse event reported was post-dental extraction alveolar osteitis (dry socket) in the post-oral surgery pain studies.

The APC And PreSAP Trials

Adverse Reactions From Long-Term, Placebo-Controlled Polyp Prevention Studies

Exposure to celecoxib in the Adenoma Prevention with Celecoxib (APC) and Prevention of Spontaneous Adenomatous Polyps (PreSAP) trials was 400 to 800 mg daily for up to 3 years [see Clinical Studies] . Some adverse reactions occurred in higher percentages of patients than in the arthritis pre-marketing trials (treatment durations up to 12 weeks; see Adverse Events from celecoxib pre-marketing controlled arthritis trials, above). The adverse reactions for which these differences in patients treated with celecoxib were greater as compared to the arthritis pre-marketing trials were as follows:

	Celecoxib (400 to 800 mg daily) N=2285	Placebo N=1303
Diarrhea	10.5%	7.0%
Gastroesophageal reflux disease	4.7%	3.1%
Nausea	6.8%	5.3%
Vomiting	3.2%	2.1%
Dyspnea	2.8%	1.6%
Hypertension	12.5%	9.8%
Nephrolithiasis	2.1%	0.8%

The following additional adverse reactions occurred in ≥0.1% and <1% of patients taking celecoxib, at an incidence greater than placebo in the long-term polyp prevention studies, and were either not reported during the controlled arthritis pre-marketing trials or occurred with greater frequency in the long-term, placebo-controlled polyp prevention studies:

Nervous system disorders: Cerebral infarction

Eye disorders: Vitreous floaters, conjunctival hemorrhage

Ear and labyrinth: Labyrinthitis

Cardiac disorders: Angina unstable, aortic valve incompetence, coronary artery atherosclerosis, sinus bradycardia, ventricular hypertrophy

Vascular disorders: Deep vein thrombosis

Reproductive system and breast disorders: Ovarian cyst

Investigations: Blood potassium increased, blood sodium increased, blood testosterone decreased

Injury, poisoning and procedural complications: Epicondylitis, tendon rupture

Amlodipine Clinical Trials

Amlodipine has been evaluated for safety in more than 11,000 patients in U.S. and foreign clinical trials. In general, treatment with amlodipine was well-tolerated at doses up to 10 mg daily. Most adverse reactions reported during therapy with amlodipine were of mild or moderate severity. In controlled clinical trials directly comparing amlodipine (N=1730) at doses up to 10 mg to placebo (N=1250), discontinuation of amlodipine because of adverse reactions was required in only about 1.5% of patients and was not significantly different from placebo (about 1%). The most commonly reported side effects more frequent than placebo are reflected in the table below. The incidence (%) of side effects that occurred in a dose related manner are as follows:

	Amlodipine			Placebo N=520
	2.5 mg N=275	5 mg N=296	10 mg N=268
Edema	1.8	3.0	10.8	0.6
Dizziness	1.1	3.4	3.4	1.5
Flushing	0.7	1.4	2.6	0.0
Palpitation	0.7	1.4	4.5	0.6

Other adverse reactions that were not clearly dose related but were reported with an incidence greater than 1.0% in placebocontrolled clinical trials include the following:

	Amlodipine (%) (N=1730)	Placebo (%) (N=1250)
Fatigue	4.5	2.8
Nausea	2.9	1.9
Abdominal Pain	1.6	0.3
Somnolence	1.4	0.6

For several adverse experiences that appear to be drug and dose related, there was a greater incidence in women than men associated with amlodipine treatment as shown in the following table:

	Amlodipine		Placebo
	Male=% (N=1218)	Female=% (N=512)	Male=% (N=914)	Female=% (N=336)
Edema	5.6	14.6	1.4	5.1
Flushing	1.5	4.5	0.3	0.9
Palpitations	1.4	3.3	0.9	0.9
Somnolence	1.3	1.6	0.8	0.3

The following events occurred in <1% but >0.1% of patients in controlled clinical trials or under conditions of open trials or marketing experience where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship:

Cardiovascular: arrhythmia (including ventricular tachycardia and atrial fibrillation), bradycardia, chest pain, peripheral ischemia, syncope, tachycardia, vasculitis.

Central and Peripheral Nervous System: hypoesthesia, neuropathy peripheral, paresthesia, tremor, vertigo.

Gastrointestinal: anorexia, constipation, dysphagia, diarrhea, flatulence, pancreatitis, vomiting, gingival hyperplasia.

General: allergic reaction, asthenia,¹ back pain, hot flushes, malaise, pain, rigors, weight gain, weight decrease.

Musculoskeletal System: arthralgia, arthrosis, muscle cramps, ¹ myalgia.

Psychiatric: sexual dysfunction (male¹ and female), insomnia, nervousness, depression, abnormal dreams, anxiety, depersonalization.

Respiratory System: dyspnea, ¹ epistaxis.

Skin and Appendages: angioedema, erythema multiforme, pruritus, ¹ rash,¹ rash erythematous, rash maculopapular.

Special Senses: abnormal vision, conjunctivitis, diplopia, eye pain, tinnitus.

Urinary System: micturition frequency, micturition disorder, nocturia.

Autonomic Nervous System: dry mouth, sweating increased.

Metabolic and Nutritional: hyperglycemia, thirst.

Hemopoietic: leukopenia, purpura, thrombocytopenia.

Amlodipine therapy has not been associated with clinically significant changes in routine laboratory tests. No clinically relevant changes were noted in serum potassium, serum glucose, total triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, uric acid, BUN, or creatinine.

In patients with angiographically documented coronary artery disease [PREVENT study: 825 patients randomized to amlodipine (5- 10 mg once daily) or placebo and followed for 3 years; CAMELOT study: 1318 patients randomized to amlodipine (5-10 mg once daily) or placebo in addition to standard care and followed for mean duration of 19 months], the adverse event profile was similar to that reported previously (see above), with the most common adverse event being peripheral edema.

¹These events occurred in less than 1% in placebo-controlled trials, but the incidence of these side effects was between 1% and 2% in all multiple dose studies

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of either celecoxib or amlodipine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Celecoxib

Cardiovascular: Vasculitis, deep venous thrombosis

General: Anaphylactoid reaction, angioedema

Liver and biliary: Liver necrosis, hepatitis, jaundice, hepatic failure

Hemic and lymphatic: Agranulocytosis, aplastic anemia, pancytopenia, leucopenia

Metabolic: Hypoglycemia, hyponatremia

Nervous: Aseptic meningitis, ageusia, anosmia, fatal intracranial hemorrhage

Renal: Interstitial nephritis

Amlodipine

The following postmarketing event has been reported infrequently where a causal relationship is uncertain: gynecomastia. In postmarketing experience, jaundice and hepatic enzyme elevations (mostly consistent with cholestasis or hepatitis), in some cases severe enough to require hospitalization, have been reported in association with use of amlodipine.

Postmarketing reporting has also revealed a possible association between extrapyramidal disorder and amlodipine.

Amlodipine has been used safely in patients with chronic obstructive pulmonary disease, well-compensated congestive heart failure, coronary artery disease, peripheral vascular disease, diabetes mellitus, and abnormal lipid profiles.

DRUG INTERACTIONS

Celecoxib

Clinically significant drug interactions with celecoxib are shown in the following table:

Drugs That Interfere with Hemostasis
Clinical Impact:	Celecoxib and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of celecoxib and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone. Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone.
Intervention:	Monitor patients with concomitant use of celecoxib with anticoagulants (e.g., warfarin), antiplatelet drugs (e.g., aspirin), SSRIs, and SNRIs for signs of bleeding [see WARNINGS AND PRECAUTIONS].
Aspirin
Clinical Impact:	Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone [see WARNINGS AND PRECAUTIONS] . In two studies in healthy volunteers, and in patients with osteoarthritis and established heart disease respectively, celecoxib (200-400 mg daily) has demonstrated a lack of interference with the cardioprotective antiplatelet effect of aspirin (100-325 mg).
Intervention:	Concomitant use of celecoxib and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [see WARNINGS AND PRECAUTIONS]. Celecoxib is not a substitute for low dose aspirin for CV protection.
ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers
Clinical Impact:	NSAIDs may diminish the antihypertensive effect of ACE inhibitors, ARBs, orbeta-blockers (including propranolol). In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible.
Intervention:	During concomitant use of celecoxib and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. During concomitant use of celecoxib and ACE-inhibitors or ARBs in patients who are elderly, volume-depleted, or have impaired renal function, monitor for signs of worsening renal function [see WARNINGS AND PRECAUTIONS] . When these drugs are administered concomitantly, patients should be adequately hydrated. Assess renal function at the beginning of the concomitant treatment and periodically thereafter.
Diuretics
Clinical Impact:	Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis.
Intervention:	During concomitant use of celecoxib with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see WARNINGS AND PRECAUTIONS] .
Digoxin
Clinical Impact:	The concomitant use of celecoxib with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin.
Intervention:	During concomitant use of celecoxib and digoxin, monitor serum digoxin levels.
Lithium
Clinical Impact:	NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 20%. This effect has been attributed to NSAID inhibition of renal prostaglandin synthesis.
Intervention:	During concomitant use of celecoxib and lithium, monitor patients for signs of lithium toxicity.
Methotrexate
Clinical Impact:	Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). Celecoxib has no effect on methotrexate pharmacokinetics.
Intervention:	During concomitant use of celecoxib and methotrexate, monitor patients for methotrexate toxicity.
Cyclosporine
Clinical Impact:	Concomitant use of celecoxib and cyclosporine may increase cyclosporine's nephrotoxicity.
Intervention:	During concomitant use of celecoxib and cyclosporine, monitor patients for signs of worsening renal function.
NSAIDs and Salicylates
Clinical Impact:	Concomitant use of celecoxib with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy [see WARNINGS AND PRECAUTIONS].
Intervention:	The concomitant use of celecoxib with other NSAIDs or salicylates is not recommended.
Pemetrexed
Clinical Impact:	Concomitant use of celecoxib and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing information).
Intervention:	During concomitant use of celecoxib and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal and GI toxicity. NSAIDs with short elimination half-lives (e.g., diclofenac, indomethacin) should be avoided for a period of two days before, the day of, and two days following administration of pemetrexed. In the absence of data regarding potential interaction between pemetrexed and NSAIDs with longer half-lives (e.g., meloxicam, nabumetone), patients taking these NSAIDs should interrupt dosing for at least five days before, the day of, and two days following pemetrexed administration.
CYP2C9 Inhibitors or Inducers
Clinical Impact:	Celecoxib metabolism is predominantly mediated via CYP2C9 in the liver. Coadministration of celecoxib with drugs that are known to inhibit CYP2C9 (e.g. fluconazole) may enhance the exposure and toxicity of celecoxib whereas co-administration with CYP2C9 inducers (e.g. rifampin) may lead to compromised efficacy of celecoxib.
Intervention:	Evaluate each patient's medical history when consideration is given to prescribing celecoxib. A dosage adjustment may be warranted when celecoxib is administered with CYP2C9 inhibitors or inducers [see CLINICAL PHARMACOLOGY] .
CYP2D6 Substrates
Clinical Impact:	In vitro studies indicate that celecoxib, although not a substrate, is an inhibitor of CYP2D6. Therefore, there is a potential for an in vivo drug interaction with drugs that are metabolized by CYP2D6 (e.g. atomoxetine), and celecoxib may enhance the exposure and toxicity of these drugs.
Intervention:	Evaluate each patient's medical history when consideration is given to prescribing celecoxib. A dosage adjustment may be warranted when celecoxib is administered with CYP2D6 substrates [see CLINICAL PHARMACOLOGY] .
Corticosteroids
Clinical Impact:	Concomitant use of corticosteroids with celecoxib may increase the risk of GI ulceration or bleeding.
Intervention:	Monitor patients with concomitant use of celecoxib with corticosteroids for signs of bleeding [see WARNINGS AND PRECAUTIONS] .

Amlodipine

Impact Of Other Drugs On Amlodipine

CYP3A Inhibitors

Co-administration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is co-administered with CYP3A inhibitors to determine the need for dose adjustment [see CLINICAL PHARMACOLOGY] .

CYP3A Inducers

No information is available on the quantitative effects of CYP3A inducers on amlodipine. Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers.

Impact Of Amlodipine On Other Drugs

Simvastatin

Co-administration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily [see CLINICAL PHARMACOLOGY] .

Immunosuppressants

Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. Frequent monitoring of trough blood levels of cyclosporine and tacrolimus is recommended and adjust the dose when appropriate [see CLINICAL PHARMACOLOGY] .

Read the entire FDA prescribing information for Consensi (Amlodipine and Celecoxib Tablets)