Consensi (amlodipine and celecoxib)

WARNING

RISK OF SERIOUS CARDIOVASCULAR and GASTROINTESTINAL EVENTS

Cardiovascular Thrombotic Events

• Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI), and stroke, which can be fatal. This risk may occur early in the treatment and may increase with duration of use.
• Consensi is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

Gastrointestinal Bleeding, Ulceration, and Perforation

• NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.

Consensi can cause serious side effects, including:

• liver problems, including liver failure
• worsening chest pain (angina) or heart attack, particularly in people with severe obstructive coronary artery disease
• heart failure
• swelling of your arms, legs, hands and feet (peripheral edema) is common with Consensi but can sometimes be serious.
• kidney problems, including kidney failure
• increased potassium levels (hyperkalemia)
• life-threatening allergic reactions
• life-threatening skin reactions
• low red blood cells (anemia)

Your healthcare provider will monitor your blood pressure and do blood tests to check you for side effects during treatment with Consensi.

Consensi may cause fertility problems in females that is reversible when treatment with Consensi is stopped. Talk to your healthcare provider if this is a concern for you.

The most common side effects of Consensi include:

• swelling of the arms, legs, hands, and feet
• joint swelling
• dizziness
• stomach pain
• diarrhea
• heartburn
• headache
• frequent urination
• hot or warm feeling in your face (flushing)
• gas
• tiredness
• extreme sleepiness

Get emergency help right away if you get any of the following symptoms:

• shortness of breath or trouble breathing
• chest pain
• weakness in one part or side of your body
• slurred speech
• swelling of the face or throat

Stop taking Consensi and call your healthcare provider right away if you get any of the following symptoms:

• nausea
• more tired or weaker than usual
• diarrhea
• itching
• indigestion or stomach pain
• flu-like symptoms
• vomit blood
• there is blood in your bowel movement or it is black and sticky like tar
• unusual weight gain
• your skin or eyes look yellow
• skin rash or blisters with fever
• swelling of the arms, legs, hands and feet

These are not all the possible side effects of Consensi.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Recommended 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 with Consensi.
• Start Consensi in adults at (amlodipine/celecoxib) 5 mg/200 mg orally once daily or 2.5 mg/200 mg in small, fragile, or elderly patients, or patients with mild hepatic insufficiency. Use 2.5 mg/200 mg when adding Consensi to other antihypertensive therapy.
• Adjust amlodipine component dosage according to blood pressure goals. In general, wait 7 to 14 days between titration steps. If more rapid titration is clinically warranted, monitor closely. The maximum dose is 10 mg/200 mg once daily.

Discontinuation

• If analgesic therapy is no longer indicated, discontinue Consensi and initiate patient on alternative antihypertensive therapy, such as amlodipine monotherapy. If Consensi is stopped and replaced with an equal dose of amlodipine, monitor blood pressure carefully.

Replacement Therapy

• For patients receiving celecoxib and amlodipine from separate capsules and tablets, respectively, substitute Consensi containing the same component doses. Monitor blood pressure carefully.

Celecoxib

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

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.

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.

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.

• Use of NSAIDs, including Consensi, 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 Consensi use between about 20 and 30 weeks of gestation and avoid Consensi use at about 30 weeks of gestation and later in pregnancy.
• The available published literature report the individual components of Consensi (celecoxib, amlodipine) are present in human breast milk at low levels.
• No adverse effects of amlodipine were observed in the breastfed infants.
• There is no available information on the effects of celecoxib or amlodipine on milk production.