Carivalan Special Precautions

Stopping treatment: Ivabradine intake can be interrupted if necessary, however an abrupt cessation of therapy with a beta-blocker should be avoided, especially in patients with ischemic heart disease. The cessation of Carvedilol + Ivabradine (Carivalan) therapy should immediately be followed by the intake of carvedilol individual tablet ensuring the patient is maintained at an optimal dose of carvedilol. Posology of individual carvedilol should be decreased gradually; for example by reducing the daily dose by half every three days. If necessary, replacement therapy to prevent the exacerbation of angina pectoris should be initiated simultaneously. If the patient develops any symptoms, the dose should be reduced more slowly.
Renal function in congestive heart failure: Reversible deterioration of renal function has been observed with carvedilol therapy in chronic heart failure patients with low arterial blood pressure (SBP < 100 mmHg), ischemic heart disease and diffuse vascular disease, and/or underlying renal insufficiency.
Patients with hypotension: Limited data are available in patients with mild to moderate hypotension, and ivabradine should therefore be used with caution in these patients. Carvedilol + Ivabradine (Carivalan) is contra-indicated in patients with severe hypotension (systolic arterial blood pressure <90 mmHg, diastolic arterial blood pressure <50 mmHg).
Atrial fibrillation - Cardiac arrhythmias: There is no evidence of risk of (excessive) bradycardia on return to sinus rhythm when pharmacological cardioversion is initiated in patients treated with ivabradine. However, in the absence of extensive data, non-urgent DC-cardioversion should be considered 24 hours after the last dose of Carvedilol + Ivabradine (Carivalan).
Use in patients with congenital QT syndrome or treated with QT prolonging medicinal products: The use of Carvedilol + Ivabradine (Carivalan) in patients with congenital QT syndrome or treated with QT prolonging medicinal products should be avoided. If the combination appears necessary, close cardiac monitoring is needed. Heart rate reduction, as caused by ivabradine, may exacerbate QT prolongation, which may give rise to severe arrhythmias, in particular Torsade de pointes.
Hypertensive patients requiring blood pressure treatment modifications: In the SHIFT trial, more patients experienced episodes of increased blood pressure while treated with ivabradine (7.1%) compared to patients treated with placebo (6.1%). These episodes occurred most frequently shortly after blood pressure treatment was modified, were transient, and did not affect the treatment effect of ivabradine. When treatment modifications are made in chronic heart failure patients treated with ivabradine blood pressure should be monitored at an appropriate interval.
Diabetic patients: Carvedilol + Ivabradine (Carivalan) may mask symptoms and signs of acute hypoglycemia. Impaired blood glucose control may occasionally occur in patients with diabetes mellitus and heart failure in connection with the use of carvedilol. Therefore, close monitoring of diabetic patients receiving Carvedilol + Ivabradine (Carivalan) is required by means of regular blood glucose measurements and adjustment of anti-diabetic medication as necessary.
Peripheral vascular disease: Carvedilol + Ivabradine (Carivalan) should be used with caution in patients with peripheral vascular diseases, as beta-blockers may precipitate or aggravate symptoms of the disease. The same also applies to those with Raynaud's syndrome, as there may be exacerbation or aggravation of symptoms. Carvedilol + Ivabradine (Carivalan) is contraindicated in case of severe peripheral vascular disease.
Anesthesia and major surgery: Beta-blockers reduce the risk of arrhythmias under anesthesia, but the risk of hypotension may be increased. Caution should therefore be applied when using certain anesthetics due to the negative synergic, inotropic effects of carvedilol and anesthetic products.
Thyrotoxicosis/hyperthyroidism: Beta-blockers, such as carvedilol, may mask the signs of hyperthyroidism and the symptoms of thyrotoxicosis.
Contact lenses: Patients who wear contact lenses and are treated with Carvedilol + Ivabradine (Carivalan) should be advised of the possible reduction of lachrymal secretion due to the carvedilol component.
Hypersensitivity: Carvedilol + Ivabradine (Carivalan) should be used with caution in patients with a history of serious hypersensitivity reactions and in those undergoing desensitization therapy as beta-blockers, such as carvedilol, may increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions.
Psoriasis: In patients with a personal or family history of psoriasis associated with beta-blocker therapy, Carvedilol + Ivabradine (Carivalan) should only be prescribed after a careful weighing of risks and benefits as beta-blockers may worsen the skin reactions.
Pheochromocytoma: In patients with pheochromocytoma, a treatment with alpha-blocking agent should be initiated prior to the use of any beta-blocking agent. Although carvedilol has both alpha- and beta- blocking pharmacological activity, there is no data regarding the use of carvedilol in this condition. Therefore, caution should be considered when in the administration of Carvedilol + Ivabradine (Carivalan) to patients suspected of having pheochromocytoma.
Further precautions: Due to insufficient clinical data, carvedilol should not be administered to patients with labile or secondary hypertension, orthostatic hypotension, acute myocarditis, a hemodynamically relevant stenosis of the heart valves or ventricular outflow tract, end-stage peripheral arterial disease or who are concomitantly receiving an α1-receptor antagonist or α2-receptor agonist.
Excipients: Since tablets contain lactose, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Effects on ability to drive and use machines: Based on existing data with the individual components, the use of Carvedilol + Ivabradine (Carivalan) may affect the ability to drive or use machinery.
Due to variability of individual reactions on carvedilol (such as dizziness, fatigue or decreased alertness), the ability to drive or operate machinery may be impaired. This is particularly true at the start of treatment, when the dose is increased, during the switch to a new preparation, or when taken together with alcohol.
Ivabradine may affect the patient's ability to drive. Patients should be warned that ivabradine may cause transient luminous phenomena (consisting mainly of phosphenes). Luminous phenomena may occur in situations when there are sudden variations in light intensity, especially when driving at night. Ivabradine has no influence on the ability to use machines. However, in post-marketing experience, cases of impaired driving ability due to visual symptoms have been reported.