FDA Okays First ADHD Drug for Use With Stimulant
By Cole Petrochko, Staff Writer, MedPage Today
Published: October 05, 2010
WASHINGTON -- The FDA has approved clonidine hydrochloride (Kapvay) as the first attention deficit hyperactivity disorder (ADHD) drug concomitantly used with a stimulant.
The drug -- manufactured by Shionogi -- is an alpha2-adrenergic receptor agonist indicated for children and teens ages 6 to 17. It is also approved for use as a monotherapy in ADHD.
The drug's formulation "minimizes peaks and troughs in blood levels," Donald C. Manning, MD, the chief medical officer at Shionogi, said in a statement.
Approval was based on two phase III trials of 6-to-17-year-olds, one of which tested the drug as a stand-alone ADHD treatment, while the other tested efficacy and safety as an add-on to therapy with a stimulant.
The eight-week monotherapy trial randomized 236 patients with ADHD or combined inattentive/hyperactive subtype to either clonidine 0.4 mg/day, clonidine 0.2 mg/day, or placebo. Patients in either clonidine group were started on 0.1 mg/day and received a dosage increased weekly by 0.1 mg to the respective dose, and then treated on that final dose for at least two weeks before then gradually decreasing dosage down to 0.1 mg/day during the final treatment week.
The second eight-week study included 198 patients ages 6 to 17 who had been treated with a psychostimulant (methylphenidate or amphetamine) for four weeks and had an inadequate response. Patients were randomized to a clonidine 0.4 mg/day and psychostimulant group or to a psychostimulant-only group. Those in the clonidine group were started at 0.1 mg/day and had dosage increased weekly by 0.1 mg as divided doses over three weeks based on tolerability and clinical response, before gradually decreasing dosage to 0.1 mg/day for the final week of treatment.
ADHD symptom scores showed significant improvement in each clonidine group over placebo, and in the clonidine and psychostimulant group over psychostimulant-alone group at five weeks of treatment.
In the monotherapy trial, adverse events included somnolence, headache, upper abdominal pain, fatigue, and upper respiratory tract infection.
In the stimulant trial, adverse events included somnolence, fatigue, abdominal pain, nasal congestion, throat pain, decreased appetite, increased body temperature, dizziness, insomnia, epistaxis, rhinorrhea, anxiety, and pain in extremities.
Patients taking tricyclic antidepressants may experience reduced efficacy of clonidine.
Clonidine may have increased risk for bradycardia and AV block in patients taking drugs that affect sinus node function or AV nodal conduction.
Patients taking hypertension drugs should avoid taking clonidine due to risk of hypotension and other overlapping side effects.