CARVEDILOL (carvedilol)

There are 1 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction

Drug Names

Colchicine (for Cardioprotection)/P-glycoprotein (P-gp) Inhibitors SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: P-glycoprotein (P-gp) inhibitors may affect the transport of colchicine, a P-gp substrate.(1,2) CLINICAL EFFECTS: Concurrent use of a P-gp inhibitor may result in elevated levels of and toxicity from colchicine. Symptoms of colchicine toxicity include abdominal pain; nausea or vomiting; severe diarrhea; muscle weakness or pain; numbness or tingling in the fingers or toes; myelosuppression; feeling weak or tired; increased infections; and pale or gray color of the lips, tongue, or palms of hands.(1,2) PREDISPOSING FACTORS: This interaction is expected to be more severe in patients with renal or hepatic impairment.(1,2) PATIENT MANAGEMENT: The manufacturer of colchicine used for cardiovascular risk reduction states that concurrent use of colchicine with P-gp inhibitors is contraindicated.(1) DISCUSSION: There are several reports of colchicine toxicity(3-5) and death(6,7) following the addition of clarithromycin to therapy. In a retrospective review of 116 patients who received clarithromycin and colchicine during the same hospitalization, 10.2% (9/88) of patients who received simultaneous therapy died, compared to 3.6% (1/28) of patients who received sequential therapy.(8) An FDA review of 117 colchicine-related deaths that were not attributable to overdose found that 60 deaths (51%) involved concurrent use of clarithromycin.(2) There is one case report of colchicine toxicity with concurrent erythromycin.(9) In a study in 20 subjects, pretreatment with diltiazem (240 mg daily for 7 days) increased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of colchicine (0.6 mg) by 44.2% (range -46.6% to 318.3%) and by 93.4% (range -30.2% to 338.6%), respectively.(1) In a study in 24 subjects, pretreatment with verapamil (240 mg twice daily for 7 days) increased the Cmax and AUC of a single dose of colchicine (0.6 mg) by 40.1% (range -47.1% to 149.5%) and by 103.3% (range -9.8% to 217.2%), respectively.(1) Colchicine toxicity has been reported with concurrent use of CYP3A4 and P-gp inhibitors such as clarithromycin, cyclosporine, diltiazem, erythromycin, and verapamil.(1,2) P-gp inhibitors include abrocitinib, amiodarone, asciminib, asunaprevir, azithromycin, belumosudil, capmatinib, carvedilol, cimetidine, cyclosporine, danicopan, daridorexant, diltiazem, diosmin, dronedarone, erythromycin, flibanserin, fluvoxamine, fostamatinib, glecaprevir/pibrentasvir, lapatinib, ledipasvir, mavorixafor, neratinib, osimertinib, pirtobrutinib, propafenone, quinidine, ranolazine, schisandra, selpercatinib, sotorasib, tepotinib, tezacaftor, valbenazine, velpatasvir, vemurafenib, verapamil, vimseltinib, and voclosporin.(1,10,11)

LODOCO

Drug contraindication overview.

Bronchial asthma or related bronchospastic conditions. Second or third degree AV block. Sick sinus syndrome or severe bradycardia (unless permanent pacemaker is in place).

Cardiogenic shock or decompensated heart failure requiring IV inotropic therapy; initiate carvedilol only after the patient is weaned from IV therapy. Clinically apparent or otherwise severe hepatic impairment. History of serious hypersensitivity reaction (e.g., Stevens-Johnson syndrome, anaphylactic reaction, angioedema) to carvedilol or any ingredient in the formulation.

Adverse reaction overview.

Adverse effects reported in 5% or more of patients with heart failure receiving immediate-release carvedilol tablets include dizziness, headache, fatigue, asthenia, arthralgia, hypotension, bradycardia, generalized edema, diarrhea, nausea, vomiting, hyperglycemia, weight gain, increased BUN, increased nonprotein nitrogen (NPN), increased cough, and abnormal vision. Adverse effects reported in patients with left ventricular dysfunction following MI receiving immediate-release carvedilol tablets generally were similar to those in patients receiving the drug for the treatment of heart failure. Additional adverse effects reported in 3% or more of such patients include anemia, dyspnea, and pulmonary edema.

Adverse effects reported in 2% or more of patients receiving immediate-release carvedilol tablets for the treatment of hypertension include dizziness, bradycardia, diarrhea, insomnia, and postural hypotension. Adverse effects reported in 2% or more of patients receiving extended-release carvedilol phosphate capsules for the treatment of hypertension include nasopharyngitis, dizziness, nausea, and peripheral edema.

Safety and efficacy not established in children younger than 18 years of age. In a clinical trial in pediatric patients (mean age 6 years, range 2 months to 17 years) with chronic heart failure (NYHA class II-IV), carvedilol resulted in beta-blockade activity as demonstrated by a placebo-corrected heart rate reduction of 4-6 beats/minute; however, no clinically important effect on treatment outcome was observed after 8 months of follow-up. Common adverse effects included chest pain, dizziness, and dyspnea.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None