Javadin Drug Information

Recommended Dosage Dosage should be individualized based on response.

The recommended initial dosage is 0.1 mg orally twice daily (morning and bedtime). Dosage can be titrated in increments of 0.1 mg per day at weekly intervals as necessary. Doses should be taken twice a day, with either an equal or higher split dosage being given at bedtime. The therapeutic doses most commonly employed have ranged from 0.2 mg to 0.6 mg per day, given in divided doses.

Maximum recommended daily dose is 2.4 mg, but doses as high as this have rarely been employed.

Administration Instructions

A calibrated measuring device, such as an oral dosing syringe or oral dosing cup, is recommended to measure and deliver the prescribed dose accurately. A household teaspoon or tablespoon is not an adequate measuring device. Administer JAVADIN (clonidine hydrochloride) oral solution with or without food.

JAVADIN may be administered up to 4 hours before surgery and resume as soon as possible post-operatively.

Clinical Trial Experience

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. Cardiovascular: Bradycardia, congestive heart failure, electrocardiographic abnormalities (i.e., sinus node arrest, junctional bradycardia, high degree AV block and arrhythmias), orthostatic symptoms, palpitations, syncope, and tachycardia. Central Nervous System: Agitation, anxiety, delirium, hallucinations (including visual and auditory), insomnia, mental depression, behavioral changes, paresthesia, sleep disorder, and vivid dreams or nightmares.

Gastrointestinal: Anorexia, constipation, nausea, and vomiting. Hematologic: Thrombocytopenia. Hepatobiliary: Hepatitis and transaminitis.

Hypersensitivity: Angioedema, hives, pruritus, rash, and urticaria. Metabolic: Transient elevation of blood glucose or serum creatine phosphokinase, and weight gain. Musculoskeletal: Leg cramps and muscle or joint pain.

Ophthalmological: Accommodation disorder, blurred vision, burning of the eyes, decreased lacrimation, and dryness of eyes. Renal and Urinary: Difficulty in micturition, nocturia, and urinary retention. Reproductive System and Breast Disorders: Gynecomastia. erectile dysfunction, and loss of libido.

Vascular: Raynaud's phenomenon.

The interactions of JAVADIN 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 JAVADIN. Table 1: Clinically Important Drug Interactions with JAVADIN. Antihypertensive drugs Clinical Implication Concomitant use of antihypertensive drugs with clonidine potentiates the hypotensive effects of clonidine.

Intervention Monitor blood pressure and heart rate, and adjust dosage of JAVADIN accordingly in patients treated concomitantly with antihypertensives CNS depressants Clinical Implication Concomitant use of CNS depressants with clonidine potentiates the sedating effects. Intervention Avoid concomitant use of CNS depressants with JAVADIN. Drugs that affect sinus node function or AV node conduction (e.g., digitalis, calcium channel blockers, beta blockers) Clinical Implication Concomitant use of drugs that affect sinus node function or AV node conduction with clonidine potentiate bradycardia and risk of AV block. Intervention Avoid concomitant use of drugs that affect sinus node function or AV node conduction with JAVADIN. Tricyclic antidepressants Clinical Implication Concomitant use of tricyclic antidepressants with clonidine can increase blood pressure and may counteract the hypotensive effects of clonidine.

Intervention Monitor blood pressure and adjust dosage of JAVADIN as needed. Sedating Drugs : Clonidine may potentiate the CNS-depressive effects of alcohol, barbiturates or other sedating drugs. Tricyclic Antidepressants: May reduce the hypotensive effect of clonidine.

Neuroleptics: May induce or exacerbate the orthostatic regulation disturbances (e.g., orthostatic hypotension, dizziness, fatigue). Drugs Known to Affect Sinus Node Function or AV Nodal Conduction: Caution is warranted in patients receiving clonidine concomitantly with agents known to affect sinus node function or AV nodal conduction (e.g., digitalis, calcium channel blockers and beta-blockers) due to a potential for additive effects such as bradycardia and AV block.

Pregnancy Risk Summary Prolonged experience with clonidine in pregnant women over several decades, based on published literature, including controlled trials, a retrospective cohort study and case reports, have not identified a drug associated risk of major birth defects, miscarriage, adverse maternal or fetal outcomes. In animal embryofetal studies, increased resorptions were seen in rats and mice administered oral clonidine hydrochloride from implantation through organogenesis at approximately 2 times the maximum recommended human dose (MRHD) (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Oral administration of clonidine hydrochloride to pregnant rabbits during the period of embryo/fetal organogenesis at doses of up to 0.08 mg/kg/day (approximately 0.6 times the oral maximum recommended human dose of 2.4 mg/day) produced no developmental effects. In pregnant rats, however, doses as low as 0.015 mg/kg/day (~1/16 the oral MRHD on a mg/kg basis) were associated with increased resorptions in a study in which dams were treated continuously from 2 months prior to mating and throughout gestation.

Increased resorptions were not associated with treatment at the same or at higher dose levels when treatment of the dams was restricted to gestation days 6-15. Increases in resorptions were observed in both rats and mice at 0.5 mg/kg/day (2 and 1 times the MRHD in rats and mice, respectively) or higher when the animals were treated on gestation days 1-14; 0.5 mg/kg/day was the lowest dose employed in this study.

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

• is contraindicated in patients with known hypersensitivity to clonidine. [see Adverse Reactions ( 6 )].
• JAVADIN is contraindicated in patients with known hypersensitivity to clonidine ( 4 )

Hypertension may develop early and may be followed by hypotension, bradycardia, respiratory depression, hypothermia, drowsiness, decreased or absent reflexes, weakness, irritability and miosis. The frequency of CNS depression may be higher in pediatric patients than adults. Large overdoses may result in reversible cardiac conduction defects or dysrhythmias, apnea, coma and seizures.

Signs and symptoms of overdose generally occur within 30 minutes to two hours after exposure. Dialysis is not likely to significantly enhance the elimination of clonidine.