Amlodipine-Celecoxib

Amlodipine-Celecoxib is a combination medication indicated in adults for whom treatment with both amlodipine for hypertension and celecoxib for osteoarthritis are appropriate.

• Amlodipine-Celecoxib is available under the following different brand names: Consensi

Common side effects of Amlodipine-Celecoxib include:

• abdominal pain
• diarrhea
• indigestion/heartburn
• gas
• swelling of extremities
• accidental injury
• dizziness
• throat infection
• runny nose
• sinus infection
• upper respiratory tract infection
• rash
• swelling (edema)
• fatigue
• nausea
• drowsiness

Serious side effects of Amlodipine-Celecoxib include:

• swelling
• rapid weight gain
• shortness of breath
• bloody or tarry stools
• coughing up blood or vomit that looks like coffee grounds
• nausea
• upper right side stomach pain
• itching
• tiredness
• dark urine
• yellowing of the skin or eyes (jaundice)
• little or no urination
• swelling in the feet or ankles
• feeling tired
• pale skin
• lightheadedness
• cold hands and feet
• stomach and intestinal ulcer

Rare side effects of Amlodipine-Celecoxib include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, light-headedness, or passing out

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and Geriatric dosage

Tablet

• 2.5 mg/200 mg
• 5 mg/200 mg
• 10 mg/200 mg

Osteoarthritis and Hypertension

Adult dosage

• Use the lowest effective dosage of celecoxib for the shortest duration consistent with individual patient treatment goals
• Only 200 mg of celecoxib once daily is available for each dosage strength
• Initial: 5 mg/200 mg orally every day or 2.5 mg/200 mg in small, fragile, or elderly patients or patients with mild hepatic insufficiency
• Use 2.5 mg/200 mg Amlodipine-Celecoxib when adding to other antihypertensive therapy
• Adjust amlodipine component dosage according to blood pressure goals; in general, wait 7-14 days between titration steps; if more rapid titration is clinically warranted, monitor closely
• Not to exceed 10 mg/200 mg every day

Geriatric dosage

• Use the lowest effective dosage of celecoxib for the shortest duration consistent with individual patient treatment goals
• Only 200 mg of celecoxib once daily is available for each dosage strength
• Initial: 2.5 mg/200 mg orally every day in small, fragile, or elderly patients or patients with mild hepatic insufficiency

Dosage Considerations – Should be Given as Follows:

• See "Dosages"

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Amlodipine-Celecoxib has severe interactions with the following drugs:
  • dantrolene
  • fezolinetant
• Amlodipine-Celecoxib has serious interactions with at least 34 drugs.
• Amlodipine-Celecoxib has moderate interactions with at least 374 drugs.
• Amlodipine-Celecoxib has minor interactions with at least 167 drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• Known hypersensitivity (eg, anaphylactic reactions and serious skin reactions) to amlodipine, celecoxib, or any of the inactive ingredients
• History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs); severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients
• Demonstrated allergic-type reactions to sulfonamides
• In the setting of coronary artery bypass graft (CABG) surgery

Effects of drug abuse

• None

Short-Term Effects

• See "What Are Side Effects Associated with Using Amlodipine-Celecoxib?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Amlodipine-Celecoxib?"

Cautions

• Celecoxib may cause premature closure of the ductus arteriosus; avoid
• NSAIDs in pregnant women starting at 30 weeks of gestation
• Celecoxib may increase the risk for bleeding events; anemia reported
• Because celecoxib reduces inflammation and possibly fever, diagnostic signs for detecting infection may be diminished
• Because serious gastrointestinal (GI) bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider periodically monitoring patients on long-term NSAIDs with a complete CBC and a chemistry profile
• Cardiovascular events
  • Clinical trials of several cyclooxygenase-2 (COX-2) selective and nonselective NSAIDs have shown an increased risk for serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal
  • Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of MI and stroke; NSAIDs are contraindicated in the setting of CABG
  • Observational studies conducted in the Danish National Registry reported that patients treated with NSAIDs post-MI were at an increased risk for reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment; avoid NSAIDs in patients following recent MI
  • Randomized controlled trials demonstrated an approximately doubling in hospitalizations for heart failure (HF) in COX-2 selective-treated patients and nonselective NSAID-treated patients; avoid use with severe HF
  • NSAIDs may lead to new-onset hypertension or worsening of preexisting hypertension
  • Amlodipine may worsen angina, and acute MI can develop after starting or increasing the dose, particularly in patients with severe obstructive coronary artery disease
  • Amlodipine may cause symptomatic hypotension, particularly in patients with severe aortic stenosis
• GI bleeding, ulceration, and perforation
  • NSAIDs, including celecoxib, cause serious GI adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal
  • Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic
  • Patients with a history of peptic ulcer disease and/or GI bleeding who use NSAIDs have a greater than 10-fold increased risk of developing a GI bleed than patients without these risk factors
• Hepatotoxicity and patients with hepatic impairment
  • Elevated alanine transaminase or aspartate aminotransferase (3 × ULN and more) reported in approximately 1% of NSAID-treated patients in clinical trials
  • Rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure, have also been reported with NSAIDs
  • Amlodipine is extensively metabolized by the liver, and the plasma elimination half-life is 56 hours in patients with impaired hepatic function
• Renal toxicity and hyperkalemia
  • Long-term NSAID use 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
  • Patients at greatest risk are those with impaired renal function, dehydration, hypovolemia, HF, and liver dysfunction; those taking diuretics, Angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers (ARBs); and elderly individuals
  • Increased serum potassium, including hyperkalemia, reported with NSAIDs, even without renal impairment; this is attributed to a hyporeninemic-hypoaldosteronism state
• Anaphylactic, asthma exacerbation, and serious skin reactions
  • Celecoxib is a sulfonamide and has been associated with anaphylactic reactions, including in patients with aspirin-sensitive asthma
  • A subpopulation of patients with asthma may have aspirin-sensitive asthma, which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs
  • Serious skin reactions have occurred following treatment with celecoxib, including erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis; these serious events may occur without warning and can be fatal
• DRESS
  • Drug reaction reported in patients taking NSAIDs; some of these events have been fatal or life-threatening; DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling
  • Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis; sometimes, symptoms of DRESS may resemble an acute viral infection
  • Eosinophilia is often present; because this disorder is variable in its presentation, other organ systems not noted here may be involved
  • Early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident; if such signs or symptoms are present, discontinue therapy and evaluate the patient immediately
• Drug interaction overview
• Celecoxib
  • Coadministration with anticoagulants or antiplatelets (eg, acetylsalicylic acid, selective serotonin reuptake inhibitors) has a synergistic effect on bleeding
  • NSAIDs may decrease the antihypertensive effects of ACE inhibitors, ARBs, or beta-blockers
  • NSAIDs may reduce natriuretic effect of loop diuretics and thiazide diuretics
  • Celecoxib may prolong digoxin elimination half-life
  • NSAIDs may elevate plasma lithium levels and reduce renal lithium clearance
  • Coadministration with methotrexate may increase the risk for methotrexate toxicity (eg, neutropenia, thrombocytopenia, renal dysfunction)
  • Coadministration with cyclosporine may increase cyclosporine’s risk for nephrotoxicity
  • Coadministration with other NSAIDs or salicylates increases the risk for GI toxicity, with little or no increase in analgesic efficacy
  • Coadministration with corticosteroids may increase the risk for GI ulceration or bleeding
  • Coadministration with pemetrexed may increase the risk for pemetrexed-associated myelosuppression, renal, and GI toxicity
  • Celecoxib metabolism is primarily via CYP2C9 in the liver; coadministration with CYP2C9 inhibitors or inducers may increase toxicity or reduce efficacy, respectively
  • Celecoxib may inhibit CYP2D6; may increase systemic exposure of CYP2D6 substrates
• Amlodipine
  • Coadministration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction
  • If coadministered with CYP3A inducers, monitor blood pressure to assure efficacy
  • Amlodipine may increase systemic exposure to simvastatin; limit simvastatin dose to 20 mg/day if coadministered
  • Amlodipine may increase systemic exposure to cyclosporine or tacrolimus; monitor trough cyclosporine or tacrolimus levels and adjust the dose when appropriate

Pregnancy and Lactation

• There are no adequate and well-controlled studies in pregnant women; data from observational studies regarding potential embryofetal risks for NSAID use in women in the first or second trimesters of pregnancy are inconclusive
• Clinical considerations
• In animal studies, NSAIDs, including ibuprofen, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth
• Fetal toxicity
  • Use of NSAIDs can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment
  • Because of these risks, limit dose and duration of use between about 20 and 30 weeks of gestation and avoid use at about 30 weeks of gestation and later in pregnancy
  • Use of NSAIDs at about 30 weeks gestation or later in pregnancy increases the risk for premature closure of fetal ductus arteriosus
  • Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment
  • There are no available data on use in pregnant women to inform a drug-associated risk for major birth defects and miscarriage; however, there are published studies with each individual component of the drug combination
  • Data from observational studies regarding potential embryofetal risks for NSAID use in women in the first or second trimesters of pregnancy are inconclusive
  • In animal reproduction studies, there were no clear developmental effects at doses up to 0.4-times the maximum recommended human dose (MRHD) in the rabbit and 0.5-times in the MRHD rat when dosed throughout gestation
  • By contrast, an increase in membranous ventricular septal defects was reported in rats treated on gestation days 9 and 10 with 0.8-times the MRHD
  • Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as ibuprofen, resulted in increased pre- and post-implantation loss
  • Prostaglandins also have been shown to have an important role in fetal kidney development; in published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses
  • Avoid the use of NSAIDs in women at about 30 weeks gestation and later in pregnancy because NSAIDs can cause premature closure of fetal ductus arteriosus
  • If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit use to the lowest effective dose and shortest duration possible
  • If treatment is needed for a pregnant woman, consider monitoring with ultrasound for oligohydramnios; if oligohydramnios occurs, discontinue therapy and follow-up according to clinical practice
• Labor or delivery
  • There are no studies on the effects of celecoxib during labor or delivery
  • In animal studies, NSAIDs inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth
• Infertility
  • Published animal studies have shown that the administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation
  • Consider withdrawal of NSAIDs in women who have difficulties conceiving or who are undergoing investigation of infertility
• Amlodipine
  • Available data from postmarketing reports and a small study with amlodipine use in pregnant women with mild-to-moderate chronic hypertension did not identify a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes
  • There are risks to the mother and fetus associated with poorly controlled hypertension in pregnancy
• Lactation
  • The development and health benefits of breastfeeding should be considered along with the mother's clinical need for the drug and any potential adverse effects on the breastfed child or from the underlying maternal condition
  • Celecoxib
    • Limited data from 12 breastfeeding women showed low levels of celecoxib in breast milk
    • Calculated average daily infant dose was 10-40 mcg/kg/day, less than 1% of the weight-based therapeutic dose for a 2-year-old child
    • There is no information available regarding the effects of the drug on milk production; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed infant from the drug or from underlying maternal conditions
  • Amlodipine
    • Estimated median infant dose 4.17 mcg/kg/day, which is approximately 1.7%-3.3% of the recommended dose for an average 6-year-old (20 kg)