Clonidine extended-release

The following have been reported with other oral immediate release formulations of clonidine: Table 6: Clinically Important Drug Interactions Concomitant Drug Name or Drug Class Clinical Rationale Clinical Recommendation Tricyclic antidepressants Increase blood pressure and may counteract clonidine’s hypotensive effects Monitor blood pressure and adjust as needed Antihypertensive drugs Potentiate clonidine’s hypotensive effects Monitor blood pressure and adjust as needed CNS depressants Potentiate sedating effects Avoid use Drugs that affect sinus node function or AV node conduction (e.g., digitalis, calcium channel blockers, beta blockers) Potentiate bradycardia and risk of AV block Avoid use Sedating Drugs: Clonidine may potentiate the CNS-depressive effects of alcohol, barbiturates or other sedating drugs. ( 7 ) Tricyclic Antidepressants: May reduce the hypotensive effect of clonidine. ( 7 ) 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. ( 7 ) Antihypertensive drugs: Use caution when coadministered with clonidine hydrochloride extended-release tablets. ( 7 )

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including clonidine hydrochloride extended-release tablets, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388 or visiting https://womensmentalhealth.org/adhd-medications/ .

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, and 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 10 and 5 times, respectively, the maximum recommended human dose (MRHD) given to adolescents on a mg/m 2 basis.

No developmental effects were seen in rabbits administered oral clonidine hydrochloride during organogenesis at doses up to 3 times the 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 80 mcg/kg/day (approximately 3 times the oral maximum recommended daily dose [MRHD] of 0.4 mg/day given to adolescents on a mg/m 2 basis) produced no developmental effects. In pregnant rats, however, doses as low as 15 mcg/kg/day (1/3 the MRHD given to adolescents on a mg/m 2 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 (up to 3 times the MRHD) when treatment of the dams was restricted to gestation days 6 to 15. Increases in resorptions were observed in both rats and mice at 500 mcg/kg/day (10 and 5 times the MRHD in rats and mice, respectively) or higher when the animals were treated on gestation days 1 to 14; 500 mcg/kg/day was the lowest dose employed in this study.

8.3 Females and Males of Reproductive Potential Infertility Based on findings in Animal studies revealed that clonidine hydrochloride extended-release tablets may impair fertility in females and males of reproductive potential [see Nonclinical Toxicology ( 13.1 )].