Drug Interactions between clonidine and IFE-Bimix 30/1

MONITOR: Coadministration of clonidine with other sympatholytic drugs such as alpha-adrenergic blockers may produce additive effects on the sinus and atrioventricular (AV) nodes, potentially causing sinus node dysfunction and AV block. There have been postmarketing reports of patients with conduction abnormalities and/or concomitant use of other sympatholytic drugs who developed severe bradycardia while taking clonidine. Intravenous atropine, isoproterenol, and temporary cardiac pacing were required in some cases.

MONITOR: Limited data suggest that the antihypertensive effects of clonidine may be antagonized by prazosin and possibly other alpha-adrenergic blockers. The exact mechanism of interaction is unknown, and data are conflicting. In a study of 18 patients with essential hypertension, prazosin given for 4 days at an average dosage of 11 mg three times daily decreased the hypotensive effect of a single 150 mcg intravenous dose of clonidine by nearly 50%. Animal data have also supported this finding. In contrast, several clinical studies found neither a significant additive antihypertensive effect nor reduced effects of clonidine when combined with prazosin, and a study of ten patients with hypertension not controlled by a treatment including clonidine (300 to 450 microgram/day) reported that progressive addition of prazosin 4 to 22.5 mg/day led to control of hypertension in nine cases (mean supine blood pressure decreased from 174/102 to 144/88 mmHg). Additionally, a protective effect of prazosin against clonidine withdrawal syndrome (hypertensive rebound) was observed in 13 hospitalized patients whose clonidine was abruptly interrupted while prazosin was continued.

MANAGEMENT: Close clinical monitoring of hemodynamic response and tolerance is recommended if clonidine is prescribed with an alpha-adrenergic blocker, and the dosage of one or both agents adjusted as necessary.

MONITOR: Concomitant use of multiple vasodilator drugs for the treatment of erectile dysfunction (ED) may increase the risk of additive adverse effects, including hypotension, dizziness, syncope, prolonged erection, or priapism. However, available data are conflicting. For example, approximately 4.9% and 7.1% of people in selected studies using single ingredient intracavernosal injections (ICIs) of papaverine reported experiencing painful/prolonged erections and priapism, respectively. Conversely, selected studies of people using ICIs containing papaverine and phentolamine reported an increase in the average rate of prolonged/painful erections to approximately 8.9%, but a reduction in the average rate of priapism to approximately 5.5%. Additionally, 1 case series reported an increase in dizziness and syncope when patients used both oral agents and ICIs to treat ED. Clinical data are not available for all possible combinations. The route of administration and amount of medication absorbed systemically may affect the clinical significance and severity of this interaction.

MANAGEMENT: Most clinical guidelines advise caution and closer clinical monitoring for patients on erectile dysfunction (ED) regimens that include multiple vasodilative agents due to the potential for additive adverse effects. Some drug manufacturers recommend avoiding combinations due to the potential risks and a lack of established data on safety. However, some of these medications are available as combinations (either commercially or via compounding) and some ED guidelines indicate that combination therapy may be appropriate in certain situations. Healthcare providers should refer to the product labeling and appropriate treatment guidelines for the most up to date information and recommendations; as well as, counsel patients on potential adverse effects and what to do should they occur.