Clonidine: uses, appearance and warnings

QLONILIK TM (clonidine hydrochloride) oral solution is indicated for the treatment of hypertension, to lower blood pressure in adults. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including this drug. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the American College of Cardiology/American Heart Association (ACC/AHA). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. QLONILIK may be employed alone or concomitantly with other antihypertensive agents. QLONILIK is a central alpha-2 adrenergic agonist indicated for the treatment of hypertension, to lower blood pressure in adults. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. It may be employed alone or concomitantly with other antihypertensive agents. ( 1 )

Oral Solution: 0.05 mg/mL clonidine hydrochloride; clear colorless solution with a raspberry flavor. Oral Solution: 0.05 mg/mL ( 3 )

QLONILIK (clonidine hydrochloride) Oral Solution, 0.05 mg/mL is a clear, colorless solution with a raspberry flavor filled in a white, opaque HDPE bottle with a child-resistant closure containing 120 mL of the oral solution. NDC 46287-085-04 Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] . Store and dispense in the original container. Discard unused portion 60 days after first opening.

QLONILIK is contraindicated in patients with known hypersensitivity to clonidine. QLONILIK should not be used in patients with known hypersensitivity to clonidine. ( 4 )

QLONILIK can cause bradycardia, cardiac conduction abnormalities, and symptomatic hypotension. ( 5.1 ) Abrupt discontinuation of QLONILIK can cause rebound hypertension with elevated plasma catecholamines, especially with higher doses or concomitant beta-blocker use. Symptoms of abrupt discontinuation include tachycardia, rapid blood pressure elevation, headache, nervousness, and agitation. ( 5.2 ) QLONILIK may cause sedation. Advise patients who engage in potentially hazardous activities, such as operating machinery or driving, of possible sedative effects. Avoid use with other central nervous system (CNS) depressants ( 5.3 ) 5.1 Bradycardia, Cardiac Conduction Abnormalities, and Symptomatic Hypotension Treatment with QLONILIK can cause bradycardia, cardiac conduction abnormalities, and symptomatic hypotension [see Adverse Reactions (6.1) ]. The sympatholytic action of clonidine may worsen sinus node dysfunction and atrioventricular (AV) block, especially in patients taking other sympatholytic drugs. There have been post-marketing reports of patients with conduction abnormalities and/or taking other sympatholytic drugs who developed severe bradycardia requiring intravenous (IV) atropine, IV isoproterenol, and temporary cardiac pacing while taking clonidine. Titrate QLONILIK slowly in patients with a history of syncope, cardiac conduction abnormalities, and those with underlying conditions that may be worsened by hypotension and bradycardia; e.g., heart block, bradycardia, cardiovascular disease, vascular disease, cerebrovascular disease, or chronic renal failure. Monitor blood pressure and heart rate and adjust dosages accordingly in patients treated concomitantly with antihypertensives or other drugs that can reduce blood pressure or heart rate or increase the risk of syncope. Avoid the use of drugs that can affect the sinus node function or AV node conduction [see Drug Interactions (7) ]. In patients who have a history of syncope or may have a condition that predisposes them to syncope, such as symptomatic hypotension, bradycardia, or dehydration, advise patients to avoid becoming dehydrated or overheated. 5.2 Rebound Hypertension Abrupt discontinuation of QLONILIK can cause rebound hypertension with elevated plasma catecholamines, especially with higher doses or concomitant beta-blocker use. Symptoms of abrupt discontinuation include tachycardia, rapid blood pressure elevation, headache, nervousness, and agitation. Serious cases of hypertensive encephalopathy, stroke, and death have been reported after abrupt clonidine discontinuation. To reduce the risk of rebound hypertension, taper clonidine gradually over 2-4 days. If rebound hypertension occurs, reverse hypertensive crisis with oral clonidine or IV phentolamine. When discontinuing concurrent beta-blocker therapy, withdraw the beta-blocker several days before beginning clonidine taper. Administration of QLONILIK should be continued up to 4 hours before surgery and resumed as soon as possible thereafter. Blood pressure should be carefully monitored during surgery and additional measures to control blood pressure should be available if required. 5.3 Sedation and Somnolence QLONILIK may cause sedation. Patients who engage in potentially hazardous activities, such as operating machinery or driving, should be advised of possible sedative effects of clonidine. Avoid use with other central nervous system (CNS) depressants, as this combination may cause excessive drowsiness or sedation [see Drug Interactions (7) ].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Most adverse effects are mild and tend to diminish with continued therapy. The most frequent (which appear to be dose-related) are dry mouth (40%), drowsiness (33%); dizziness (16%); constipation and sedation (10%, respectively). The following less frequent adverse experiences have also been reported in patients receiving clonidine hydrochloride tablets, but in many cases patients were receiving concomitant medication and a causal relationship has not been established. Body as a Whole: Fatigue, headache, pallor, malaise, weakness, and withdrawal syndrome. …

The interactions of QLONILIK with co-administration of other drugs have not been studied. The drug interaction data provided in this section is based on oral immediate-release clonidine formulations. Table 1 displays clinically important drug interactions with QLONILIK. Table 1: Clinically Important Drug Interactions with QLONILIK. Antihypertensive drugs Clinical Implication Concomitant use of antihypertensive drugs with clonidine potentiates the hypotensive effects of clonidine [see Warnings and Precautions (5.1) ]. Intervention Monitor blood pressure and heart rate, and adjust dosage of QLONILIK accordingly in patients treated concomitantly with antihypertensives CNS depressants Clinical Implication Concomitant use of CNS depressants with clonidine potentiates the sedating effects [see Warnings and Precautions (5.3) ]. …