Clonipress

Clonidine HCl.

Pharmacology: Pharmacodynamics: Clonidine, an imidazoline derivative, is a central α-adrenergic stimulant that inhibits sympathetic cardio-accelerator and vasoconstrictor centers. Clonidine stimulates peripheral α-adrenergic receptors producing transient vasoconstriction. Stimulation of α-adrenergic receptors in the brain stem results in reduced sympathetic outflow from the central nervous system (CNS) and a decrease in peripheral resistance, renal vascular resistance, heart rate and blood pressure. Renal blood flow and glomerular filtration rate remain essentially unchanged.
Orthostatic effects are mild and infrequent. The drug does not alter normal hemodynamic responses to exercise. Acute studies have demonstrated a moderate reduction (15-20%) of cardiac output and a decrease of peripheral resistance. During long-term therapy, cardiac output tends to return to control values while peripheral resistance remains decreased. The co-administration of a diuretic enhances antihypertensive efficacy of clonidine.
Blood pressure declines within 30-60 min after an oral clonidine dose.
Pharmacokinetics: The peak plasma clonidine level occurs approximately 3-5 hrs after oral dosing, the plasma half-life (t_½) is 12-16 hrs and the elimination t_½ is 6-24 hrs. About 50% of the absorbed dose is metabolized in the liver. The t_½ increases up to 41 hrs in patients with impaired renal function. About 40-60% of the absorbed dose is recovered in the urine as unchanged drug in 24 hrs.

Treatment of hypertension; may be used alone or concomitantly with other antihypertensives.

Individualize and adjust dose according to patient’s blood pressure response and tolerance.
Mild to Moderate Hypertension: Initial Dose: 75-150 mcg oral twice daily, in the morning and at bedtime. Dose may be increased in increments of 150 mcg/day until optimum response is achieved. Maintenance Dose: Most common range is 200-600 mcg/day given in 2 divided doses. Maximum Dose: 2,400 mcg/day in 2-3 divided doses. Sedative effects may be minimized by giving bulk of the daily dose at bedtime.
Severe Hypertension: Initial Dose: Increase to 300 mcg 3 times daily (900 mcg/day total loading dose).

Symptoms: In a patient who ingested clonidine 100 mg, plasma levels were 60 ng/mL (1 hr), 100 ng/mL (1.5 hrs), 370 ng/mL (2 hrs) and 120 ng/mL (5.5 and 6.5 hrs). The patient developed hypertension followed by hypotension, bradycardia, apnea, hallucinations, semicoma and premature ventricular contractions. The patient fully recovered after intensive treatment.
Other symptoms of clonidine overdosage are bradycardia, hypotension, CNS depression, respiratory depression, apnea, hypothermia, miosis, coma, seizures, lethargy, agitation, irritability, vomiting, hypoventilation, reversible cardiac conduction defects, arrhythmias, transient hypotension, profound hypotension, weakness, somnolence and diminished or absent reflexes.
Treatment: Naloxone may be a useful adjunct for the management of clonidine-induced respiratory depression.
Induction of emesis is usually not recommended because of rapid onset of CNS depression. Establish respiration if necessary, perform gastric lavage and administer activated charcoal. A saline cathartic (magnesium sulfate) will increase the rate of transport through the gastrointestinal tract. Routine hemodialysis is of limited benefit because a maximum of 5% of circulating clonidine is removed.
Supportive care may include atropine sulfate for the treatment of persistent bradycardia, and dopamine infusion and IV fluids for hypotension.
Hypertension can be treated with IV furosemide or diazoxide or α-blocking agents eg, phentolamine. Tolazoline, an α-blocker, in IV doses of 10 mg at 30-min intervals may reverse clonidine's effects if other efforts fail. Naloxone may be a useful adjunct for the management of clonidine-induced respiratory depression, hypotension or coma.

Hypersensitivity to clonidine or to any of the components of Clonipress.

Caution in patients with cerebrovascular disease, ischemic heart disease including myocardial infarction, renal impairment, occlusive peripheral vascular disorders eg, Raynaud's disease or those with a history of depression.
Clonidine Discontinuation: Instruct patients not to discontinue clonidine therapy without consulting a physician. Abrupt withdrawal of clonidine treatment may result in symptoms eg, nervousness, agitation, headache and tremor followed by a rapid rise in blood pressure, and increase in plasma catecholamine concentration. Such occurrences have usually been associated with previous administration of high oral doses (exceeding 1,200 mcg/day) or with continuation of concomitant α-blocker therapy. Rare cases of hypertensive encephalopathy, cerebrovascular accidents and death have been reported after clonidine withdrawal. When discontinuing therapy, clonidine dose should be reduced gradually over 2-4 days to avoid withdrawal symptoms.
Use with caution in patients with severe coronary insufficiency, conduction disturbances, recent myocardial infarction or cerebrovascular disease and chronic renal failure.
Use in pregnancy & lactation: Pregnancy Category C: There are no adequate and well controlled studies in pregnant women. Use in pregnancy only if clearly needed.
Exercise caution when clonidine is administered to a breastfeeding woman as it can be excreted in human milk.
Use in children: Safety and effectiveness in pediatric patients <12 years have not been established.

Pregnancy Category C: There are no adequate and well controlled studies in pregnant women. Use in pregnancy only if clearly needed.
Exercise caution when clonidine is administered to a breastfeeding woman as it can be excreted in human milk.

Most Common: Dry mouth, drowsiness, dizziness, sedation, constipation.
Cardiovascular: Syncope, congestive heart failure, orthostatic symptoms, palpitations, tachycardia, bradycardia, Raynaud's phenomenon, electrocardiogram (ECG) abnormalities (eg, sinus node arrest) manifested as Wenckebach period or ventricular trigeminy, conduction disturbances, arrhythmias, sinus bradycardia and atrioventricular block (rare).
Central Nervous System: Dreams or nightmares, insomnia, hallucinations, delirium, nervousness, agitation, restlessness, anxiety, depression, headache.
Dermatologic: Rash, angioneurotic edema, hives, urticaria, alopecia, pruritus.
Gastrointestinal: Abdominal pain, anorexia, malaise, nausea, vomiting, mild transient abnormalities in liver function tests, hepatitis, parotitis (rare).
Genitourinary: Impotence, decreased sexual activity, loss of libido, nocturia, difficulty in micturition and urinary retention.
Hematologic: Thrombocytopenia (rare).
Metabolic: Weight gain, transient elevation of blood glucose or serum creatinine phosphokinase (rare), gynecomastia.
Musculoskeletal: Weakness, fatigue, muscle or joint pain, cramps of the lower limbs.
Miscellaneous: Increased sensitivity to alcohol, dryness and itching or burning of the eyes, dryness of the nasal mucosa, pallor, fear, weakly positive Coombs' test, blurred vision.

Concomitant administration of substances with a negative chronotropic or dromotropic effect eg, nonsteroidal and anti-inflammatory agents can reduce the therapeutic effect of clonidine.
Central Nervous System Depressants: Clonidine may be additive with or may potentiate the action of other CNS depressants eg, opiates or other analgesics, barbiturates, or other sedatives, anesthetics or alcohol. Concomitant administration of opiate analgesics with clonidine may also potentiate the hypotensive effects of clonidine.
Psychotherapeutic Agents: Tricyclic antidepressants (eg, imipramine, desipramine) may block the antihypertensive effects of clonidine and possibly life-threatening elevations in blood pressure may occur.
Beta-Adrenergic Blocking Agents: Concomitant administration with clonidine may result in attenuation or reversal of antihypertensive effect and potentially life-threatening increases in blood pressure.

Store at temperatures not exceeding 30°C.

Other Antihypertensives

C02AC01 - clonidine ; Belongs to the class of imidazoline receptor agonists, centrally-acting antiadrenergic agents. Used in the treatment of hypertension.

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