A new drug is in town, and even though the newbies are usually not touched upon until they have more information available or more use in clinical practice, we are going to mix things up this time around. In the recent past, we discussed the medication immediate-release clonidine, so for the sake of keeping things in the family, we are going to be covering its close relative and the new to the market medication, Kapvay (extended-release clonidine).

Clonidine was actually synthesized in the early 1960’s for use as a nasal decongestant, and then by chance, researchers discovered it decreased blood pressure and heart rate and produced sedation at very low doses. Clonidine has been used in the United States since it was given approval from the FDA in 1974. It wasn’t until September 2010 that the FDA approved extended-release clonidine for the treatment of ADHD in pediatric patients.

Indications

Extended-release clonidine is indicated as monotherapy or as adjunctive therapy to stimulant medications for the treatment of ADHD. It would be used as an add-on to a child’s drug therapy when they have not reached an optimal response to a stable regimen of a stimulant medication. 

Because extended-release clonidine is so new, it has not been systematically evaluated in clinical trials for effectiveness of long-term use. Based on studies, we know the medication is effective for the short-term, but beyond 5 weeks, we have no proof of how well it will work!

Interestingly enough, this extended-release clonidine formulation also exists in the world under the name Jenloga, which is approved for the treatment of hypertension in adults.

How the drug works

Extended-release clonidine is a central alpha-2-adrenergic agonist just like the immediate-release clonidine, so its mechanism of action is the same.  It decreases the release of norepinephrine from nerve cells in the brain leading to a lower firing rate of nerve cells that are responsible for arousal.  The result, a decrease in excessive stimulation found in patients with ADHD.

The controlled-release nature is what makes extended-release clonidine different from its predecessor. It is designed to produce slow, constant absorption for at least 8 hours, unlike the immediate-release formulation. Potential advantages of extended-release preparations are a decrease in frequency of administration, which may lead to improved patient compliance and a therapeutic effect that can be maintained overnight. Also, the peaks in drug concentration that occur after taking an immediate-release dosage form are eliminated, thereby decreasing the occurrence and/or intensity of side effects.    

Side effects and precautions

Extended-release clonidine comes with the same side effects as the immediate-release formulation, but side effects appear to be less intense because the medication’s peak concentration in the bloodstream does not get as high. Side effects to look out for are decreased heart rate and blood pressure, sedation, depression, irritability, constipation, dry mouth and eyes, headache, upper respiratory tract infection, sore throat, ear pain, nightmares, and nasal congestion.

Precautions are similar too! Abrupt discontinuation should be avoided due to the risk of withdrawal effects like increased heart rate, palpitations, tremors, anxiety, insomnia, sweating, and agitation. Parents will still have to follow the advice of the American Heart Association and have their child be carefully screened and monitored for any cardiovascular abnormalities as extended-release clonidine has the potential to cause toxic cardiac effects too. Also, children with kidney insufficiency will need their dose adjusted based on the degree of kidney impairment.

Extended-release clonidine has not been studied in children younger than 6 years old, so it may be best to avoid using this medication in children 5 years of age or younger. 

Similar medications

We’ve already determined that extended-release clonidine is very much like immediate-release clonidine. Guanfacine and extended-release guanfacine (Intuniv) are also central alpha-2-adrenergic agonists commonly used as alternative or add-on treatments for ADHD. They may actually be better options compared to the clonidine alternatives because they have a lower incidence of side effects and appear to stay in the body longer.

Administration guidelines  

Extended-release clonidine is available as 0.1mg and 0.2mg tablets. It should not be crushed, chewed, or broken, but it can be taken with or without food. When starting this medication, it should be initiated at 0.1mg at bedtime. Until the desired response is achieved, dosages should be adjusted in increments of 0.1mg per day at weekly intervals. Doses should be given twice a day, in the morning and at bedtime, with the equal or higher split dosage being given at bedtime. For example, if your child’s total daily dose is 0.3mg, your child would take a 0.1mg tablet in the morning and a 0.2mg tablet at bedtime.

Extended-release clonidine is not to be used interchangeably with the immediate-release clonidine formulation due to lack of clinical data from studies and because they absorb at different rates in the body. 

Recommendations

Extended-release clonidine may sound like a great idea because it’s part of some cutting edge happenings taking place in the pharmaceutical industry nowadays, but it’s also one of the most expensive options for the treatment of ADHD.  Extended-release preparations come with a price! Since it is not first-line treatment for ADHD and because data on its long-term use does not exist yet, I would hold off on giving your child this medication unless you have exhausted all other options.

Up against cheaper, safer, and more effective medications for the treatment of ADHD, extended-release clonidine is going to have an uphill battle in making a difference in the world of pharmacy.  Will the drug make a name for itself?  Only time will tell!