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PHARMACOLOGICAL COMPATIBILITY*

Carvedilol Metabolization

Carvedilol is a non-selective vasodilator β-blocker drug with antioxidant properties (which also selectively blocks alpha-1 adrenoreceptors). It has no intrinsic sympathomimetic activity and does have membrane stabilizing properties.

CONTRAINDICATIONS

Carvedilol is contraindicated in the following cases: Hypersensitivity, NYHA class IV heart failure requiring treatment with type IV inotropic agents; COPD with bronchial obstruction, liver dysfunction, bronchial asthma; A-V blockade of 2nd and 3rd grade; severe bradycardia (<50 bpm), cardiogenic shock, sinus disease (including sinoatrial node block), severe hypotension (systolic pressure <85 mm Hg), metabolic acidosis, Prinzmetal’s angina, untreated pheochromocytoma; severe peripheral arterial circulatory disturbances; concomitant IV treatment with verapamil or diltiazem.

CAUTIONS

Precautions should be taken when carvedilol is prescribed in the cases listed below.

Congestive heart failure controlled with digitalis, diuretics and/or ACE inhibitors, diabetes mellitus (since carvedilol masks symptoms of hypoglycemia), peripheral vascular disease, peripheral circulatory disorders (Raynaud’s disease), general surgery, first degree heart blockade, history of severe hypersensitivity reactions as well as subjected to desensitization therapy, labile or secondary hypertension, if pheochromocytoma or vasospastic angina of Prinzmetal is suspected, if it is necessary to treat NYHA class IV congestive heart failure.

It is mandatory to assess risk-benefit in patients with: history of psoriasis associated with therapy with β-blockers and COPD with bronchospastic component and without receiving pharmacological treatment.

Renal function should be controlled by increasing the dose, and discontinuing treatment or reducing the dose if it worsens in patients with congestive heart failure and patients with low blood pressure (systolic BP<100 mm Hg), ischemic heart disease and diffuse vascular disease and/or underlying renal failure.

It is advisable to carry out a gradual withdrawal of the treatment

Carvedilol is not a recommended drug in children and adolescents under 18 years old.

SIDE EFFECTS

Headaches, dizziness, fatigue and asthenia; depressed mood, depression; heart failure, bradycardia, edema, hypervolaemia, fluid overload; hypotension, postural hypotension, peripheral circulation disorders (cold extremities), exacerbation of symptoms in patients with intermittent claudication or Raynaud’s phenomenon, peripheral edema; asthma and dyspnea in predisposed patients, pulmonary edema; gastrointestinal discomfort (nausea, diarrhea, abdominal pain, dyspepsia, vomiting); anemia; decreased lacrimation, eye irritation, vision disturbances; abnormalities of renal function in patients with diffuse vascular disease or underlying kidney disease, acute renal failure, urination disorders; pain in the extremities; weight gain, hypercholesterolemia, worsening of blood glucose control (hyperglycaemia, hypoglycaemia) in patients with pre-existing diabetes; asthenia (fatigue), pain.

PHARMACOLOGICAL INTERACTIONS

  • Treatment with carvedilol increases the risk of changes in AV conduction with: verapamil, diltiazem, class I antiarrhythmics; contraindicated intravenously.
  • Risk of prolongation of atrioventricular conduction time in concomitancy of carvedilol with digoxin.
  • Carvedilol increases blood pressure and decreases the heart rate in concomitance with clonidine.
  • Carvedilol potentiates the effect of insulin and oral antidiabetics.
  • Carvedylol increases the risk of hypotension and/or severe bradycardia if taken in combination with reserpine or MAOIs.
  • Carvedilol increases the plasma concentration of ciclosporin.
  • Synergy of negative inotropic and hypotensive effects with anesthetics.
  • Plasma levels of carvedilol may be decreased by rifampicin.
  • The plasma levels of carvedilol can be increased by: SSRI, fluoxetine, paroxetine, quinidine, propafenone, cimetidine.
  • Carvedilol increases blood pressure if taken together with NSAIDs

BRAND NAMES

  • Coropres ®
  • Normotride ®
  • Palacimol ®

GENE OR REGION STUDIED


  • CYP2D6

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