amlodipine/celecoxib

General

Genetic Implications: Genetic Implications

Pronunciation:
am-loe-di-peen/sel-e-kox-ib

Trade Name(s)

  • Consensi

Ther. Class.
antihypertensives
nonopioid analgesics

Pharm. Class.
calcium channel blockers
cox 2 inhibitors

Indications

Management of hypertension in patients with osteoarthritis.

Action

Amlodipine–Inhibits the transport of calcium into myocardial and vascular smooth muscle cells, resulting in inhibition of excitation-contraction coupling and subsequent contractionCelecoxib–Inhibits COX-2, an enzyme required for the synthesis of prostaglandins.

Therapeutic Effect(s):

  • Systemic vasodilation resulting in decreased blood pressure.
  • Reduction in inflammation and pain.

Pharmacokinetics

Absorption: Amlodipine–Well absorbed after oral administration (64–90%); Celecoxib–Extent of absorption unknown.

Distribution: Amlodipine and celecoxib–Extensively distributed to tissues.

Protein Binding: Amlodipine–95–98%; Celecoxib–97%.

Metabolism and Excretion: Amlodipine–Mostly metabolized by the CYP3A4 isoenzyme in the liver; Celecoxib–Mostly metabolized by the CYP2C9 isoenzyme in the liver; Genetic implication the CYP2C9 enzyme system exhibits genetic polymorphism; poor metabolizers may have significantly ↑ celecoxib concentrations and an ↑ risk of adverse effects; <3% excreted unchanged in urine and feces.

Half-life: Amlodipine–30–50 hr (↑ in older adults and patients with hepatic impairment); Celecoxib–11 hr.

TIME/ACTION PROFILE (plasma concentrations)

ROUTEONSETPEAKDURATION
POunknown2.8 hr24 hr

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity;
  • History of asthma, urticaria, or allergic-type reactions to aspirin or other NSAIDs;
  • History of allergic-type reactions to sulfonamides;
  • Coronary artery bypass graft (CABG) surgery;
  • HF;
  • Severe renal or hepatic impairment;
  • Genetic implicationPatients who are known or suspected to be poor CYP2C9 metabolizers;;
  • OB: Celecoxib should not be used during 3rd trimester of pregnancy (may cause premature closure of the ductus arteriosus).

Use Cautiously in:

  • Cardiovascular disease or risk factors for cardiovascular disease (may ↑ risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, especially with prolonged use or use of higher doses); avoid use in patients with recent MI;
  • Pre-existing asthma;
  • Pre-existing renal disease, HF, hepatic impairment, dehydration, concurrent diuretic, ACE inhibitor, or angiotensin receptor blocker therapy, or older adults (↑ risk of renal impairment);
  • Moderate hepatic impairment (↓ dose);
  • Pedi: Safety and effectiveness not established;
  • Geri: ↑ risk of cardiovascular, renal and GI toxicity; start with lowest dose.

Exercise Extreme Caution in:

History of ulcer disease or GI bleeding.

Adverse Reactions/Side Effects

CNS: headache, dizziness, fatigue, insomnia

CV: HF, MYOCARDIAL INFARCTION, STROKE, edema, angina, hypertension, hypotension, palpitations

Derm: ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS, EXFOLIATIVE DERMATITIS, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, flushing, rash

F and E: hyperkalemia

GI: GI BLEEDING, HEPATOTOXICITY, ↑ liver enzymes, abdominal pain, diarrhea, dyspepsia, flatulence, gingival hyperplasia, nausea, vomiting

GU: renal impairment

Hemat: anemia

Misc: ANAPHYLAXIS, fever

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

Route/Dosage

PO (Adults) Amlodipine 5 mg/celecoxib 200 mg once daily (start with amlodipine 2.5 mg/celecoxib 200 mg once daily in older adults or when adding to other antihypertensive therapy); may ↑ dose every 1–2 wk based on blood pressure response (max dose = amlodipine 10 mg/celecoxib 200 mg once daily).

Hepatic Impairment
PO (Adults) Mild hepatic impairment–Amlodipine 2.5 mg/celecoxib 200 mg once daily; may ↑ dose every 1–2 wk based on blood pressure response (max dose = amlodipine 10 mg/celecoxib 200 mg once daily).

Availability

Tablets: amlodipine 2.5 mg/celecoxib 200 mg, amlodipine 5 mg/celecoxib 200 mg, amlodipine 10 mg/celecoxib 200 mg

Assessment

  • Monitor BP and pulse before therapy, during dose titration, and periodically during therapy. Monitor ECG periodically during prolonged therapy.
    • Monitor intake and output ratios and daily weight. Assess for signs of HF (peripheral edema, rales/crackles, dyspnea, weight gain, jugular venous distention).
  • Monitor frequency of prescription refills to determine adherence.
  • Assess range of motion, degree of swelling, and pain in affected joints before and periodically throughout therapy.
  • Assess patient for allergy to sulfonamides, aspirin, or NSAIDs. Patients with these allergies should not receive celecoxib.
  • Assess patient for skin rash frequently during therapy. Discontinue at first sign of rash; may be life-threatening. Stevens-Johnson syndrome may develop. Treat symptomatically; may recur once treatment is stopped.

Lab Test Considerations: Total serum calcium concentrations are not affected by calcium channel blockers.

  • Monitor CBC periodically during therapy.
  • May cause ↑ AST and ALT levels.
  • May cause hypophosphatemia, hyperkalemia, and ↑ BUN.

Potential Diagnoses

Implementation

  • Use lowest effective dose for shortest period of time. Wait 7–14 days before titration.
  • May be administered without regard to meals.

Patient/Family Teaching

Advise patient to take medication as directed, even if feeling well. Increasing doses does not appear to increase effectiveness. Do not stop medication without consulting health care professional; may need to be discontinued gradually and an alternative antihypertensive agent started. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.

  • Encourage patient to comply with other interventions for hypertension (weight reduction, low-sodium diet, smoking cessation, moderation of alcohol consumption, regular exercise, and stress management). Medication controls but does not cure hypertension.
  • Instruct patient and family in proper technique for monitoring BP and pulse. Advise patient to take BP weekly and to report significant changes and heart rate is <50 bpm to health care professional.
  • Caution patient to change positions slowly to minimize orthostatic hypotension.
  • Advise patient to notify health care professional promptly if signs or symptoms of GI toxicity (abdominal pain, black stools), skin rash, unexplained weight gain, edema, shortness of breath, slurred speech, weakness, chest pain, irregular heartbeats, swelling of hands and feet, pronounced dizziness, nausea, constipation, or hypotension occurs or if headache is severe or persistent. Patients should discontinue medication and notify health care professional if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.
  • May cause drowsiness or dizziness. Advise patient to avoid driving or other activities requiring alertness until response to the medication is known.
  • Instruct patient on importance of maintaining good dental hygiene and seeing dentist frequently for teeth cleaning to prevent tenderness, bleeding, and gingival hyperplasia (gum enlargement).
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken, to avoid alcohol and other NSAIDs, and to consult health care professional before taking any new medications, especially cold preparations.
  • Advise patient to notify health care professional if irregular heartbeats, dyspnea, swelling of hands and feet, pronounced dizziness, nausea, constipation, or hypotension occurs or if headache is severe or persistent.
  • Caution patient to wear protective clothing and use sunscreen to prevent photosensitivity reactions.
  • Advise patient to inform health care professional of medication regimen before treatment or surgery.
  • Rep: Instruct female patient to notify health care professional if pregnancy is planned or suspected or if breast feeding. Advise women to avoid NSAIDs in the 3rd trimester of pregnancy. May cause reversible infertility in women attempting to conceive; may consider discontinuing NSAIDs.

Evaluation/Desired Outcomes

  • Decrease in BP and reduction in joint pain in patients with osteoarthritis.
  • If analgesic therapy no longer indicated, discontinue amlodipine/celecoxib and initiate alternative antihypertensive, such as amlodipine monotherapy. If amlodipine/celecoxib is stopped and replaced with an equal dose of amlodipine, monitor blood pressure carefully.
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