Ritalin (methylphenidate/dexmethylphenidate)
FDA ALERT [02/2006] Sudden Unexplained Death, Cardiac/Cardiovascular, and Psychiatric Adverse Events Associated with Stimulant Therapy for ADHD.
In February of 2006, FDA warned of serious cardiac and cardiovascular risks including sudden unexplained death (SUD) associated with the use of methylphenidate or dexmethylphenidate in children, adolescents and adults. Individuals with structural heart abnormalities are at a greater risk for these adverse cardiac/cardiovascular effects although those without structural cardiac abnormalities are also at risk. In addition, psychiatric adverse events including hallucinations, increased aggression, and mania have been reported in individuals taking methylphenidate or dexmethylphenidate. The risk of these effects is greater in those with existing psychiatric illness.
Rarely, sudden unexplained death has been associated with stimulant use. Tell your prescriber about any history of heart disease in yourself or family member as it could increase the risk. These drugs also increase blood pressure and heart rate. Stimulants have a high potential for abuse and long term use may lead to dependence. Use of misuse may cause sudden death and serious cardiovascular events or stroke.
Stimulant have been associated with serious psychiatric adverse reactions including worsening psychosis, mania, panic and severe anxiety.
Available as:
- Ritalin®, Methylin® (methylphenidate) – Immediate release
- Tablets: 5 mg, 10 mg, 20 mg
- Duration of effect: 3-4 hours
- 2.5 mg, 5mg, 10 mg chewable tablets
- 5 mg/5 ml and 10 mg/5 ml liquid
- Metadate ER®, Ritalin SR® (methylphenidate, extended release, wax matrix)
- Tablets: 10 mg, 20 mg
- Variable absorption
- Duration of effect: 3-8 hours
- Methylin ER® (methylphenidate, extended release, methylcellulose base)
- 10 mg, 20 mg tablets
- Duration of effect: 3-8 hours
- Ritalin LA® (methylphenidate long-acting)
- 10mg, 20 mg, 30 mg, 40 mg capsules
- Can be opened and sprinkled on food
- Duration of effect: 8-12 hours
- Metadate CD® (methylphenidate controlled delivery)
- 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg capsules
- Can be opened and sprinkled on food
- Duration of effect: 8-12 hours
- Concerta® (methylphenidate once daily)
- 18 mg, 27 mg, 36 mg, 54 mg bullet shaped caplet
- Cannot be opened or crushed and tablet shell may appear in stool
- Duration of effect: 12 hours
- Daytrana® (Methylphenidate patch)
- 10 mg, 15 mg, 20 mg, 30 mg patch strengths
- Apply to clean hairless area in the morning and remove after 9 hours
- Duration of effect coincides with the duration the patch is worn
- Focalin® (Dexmethylphenidate) – Immediate release
- 2.5 mg, 5 mg, and 10 mg tablet
- Duration of effect:3 – 5 hours
- Focalin XR® (Dexmethylphenidate extended release)
- 5 mg , 10 mg, 15 mg and 20 mg capsule
- Can be opened and sprinkled on food
- Duration of effect: 12 hours
Note: Even though methylphenidate and dexmethylphenidate are available as different brand names and formulations, all of these formulations result in the same active medicine when they are absorbed in the blood stream. For example, upon swallowing Ritalin LA, Metadate CD, or Concerta, a person will have the active ingredient, methylphenidate in their blood stream. Upon swallowing Focalin or Focalin XR, a person will have dexmethylphenidate in their blood stream.
What is methylphenidate/dexmethylphenidate and what does each medication treat?
Methylphenidate and dexmethylphenidate are prescription medications that have been proven effective in the treatment of attention-deficit hyperactivity disorder (ADHD) in children, adolescents and adults. ADHD is associated with severe inattention, hyperactivity and impulsivity that interfere with an individual’s ability to function in school, at work or in social settings. Examples of functionally impairing ADHD symptoms include making careless mistakes, losing things necessary for tasks, the inability to sit still and focus, and interrupting or intruding on others. Adults have similar symptoms but display less hyperactivity compared to children. Adults with ADHD may be more prone to procrastination, becoming easily frustrated and taking on many tasks at once while accomplishing none of them. A person may have severe inattention without hyperactivity or impulsivity and still meet criteria for a diagnosis of ADHD. A person with inattentive symptoms only can respond equally well to methylphenidate or dexmethylphenidate as someone who has inattentive and/or hyperactive and impulsive symptoms. Methylphenidate immediate release tablets may also be used in treating elderly patients who are very withdrawn and disinterested in their activities.
Methylphenidate and dexmethylphenidate increase effective utilization of dopamine and norepinephrine in parts of the brain that regulate attention and behavior in order to control symptoms associated with ADHD and improve functioning. Scientific literature shows stimulant medications including methylphenidate and dexmethylphenidate are the most effective treatment options for ADHD. The American Academy of Pediatrics and the American Academy of Child and Adolescent Psychiatry consider these medicines to be the best treatment options, however behavioral interventions like positive rewards for good behavior and lifestyle modifications like breaking down homework into manageable 15-minute blocks are useful interventions to implement with medication. Scientific studies show adults with ADHD respond well to methylphenidate and dexmethylphenidate but lifestyle modifications may be different. For example, adults may use an electronic organizer or select a career that keeps them stimulated like traveling sales or real estate.
What is the most important information I should know about methylphenidate and dexmethylphenidate?
Methylphenidate and dexmethylphenidate should not be taken together with or within 14 days of taking a drug used to treat depression, called a Monoamine Oxidase Inhibitor (MAOI). MAOIs include Nardil (phenelzine), Parnate (tranylcypromine), Emsam (selegiline), Zyvox (linezolid), and other brands. Coadministering methylphenidate or dexmethylphenidate within 2 weeks of taking a MAOI can result in dangerously high blood pressure that can be fatal.
Are there any special concerns about methylphenidate or dexmethylphenidate use in pregnancy?
The safety of methylphenidate or dexmethylphenidate has not been established in pregnant women. It should not be used in pregnancy unless the potential benefits clearly outweigh the risks as determined by an individual woman’s healthcare professional. The effects of methylphenidate or dexmethylphenidate on an unborn baby are unknown.
What should I discuss with my healthcare provider before taking methylphenidate/dexmethylphenidate?
- Symptoms that are most bothersome about ADHD
- Medications taken in the past to treat ADHD
- All other medications you are currently taking (including herbal products and dietary supplements)
- Any medication allergies you have
- Any medication side effects you may have experienced in the past or are currently experiencing
- If you have or have had: liver problems, high blood pressure, heart problems, irregular heartbeat, low blood pressure, depression, bipolar disorder or other psychiatric disorders
- If a seizure disorder is present
- If you are trying to become pregnant, are already pregnant or are breast-feeding
- If you use any illegal drugs or alcohol
How should I take methylphenidate or dexmethylphenidate?
- Methylphenidate and dexmethylphenidate should be taken as prescribed on an empty stomach (except for Concerta), usually early in the day to minimize the risk of insomnia.
- Immediate release formulations should be given 2 or three times a day to provide symptom coverage throughout the day.
- Extended release and long-acting medications that last for 8 to 12 hours should be taken once a day in the morning. The capsules with beads may be opened if a person has trouble swallowing, however, the beads should be swallowed whole without chewing. If the beads are chewed, too much medicine is absorbed at once and the duration of action is no longer extended.
- The tablet shell from the Concerta tablet is not changed in the intestines and may appear in the stool intact. It should not be given to individuals with narrowing of the intestines or in those who have undergone stomach bypass surgery.
- The methylphenidate patch should be applied to a clean, hair-free area in the morning before school and removed approximately nine hours later.
What happens if I miss a dose?
If you miss a dose of methylphenidate, take it as soon as you remember if it is still before noon. If it is late in the day, consult your health care provider. They may recommend that you resume dosing the next morning so that your sleep is not disrupted by taking the stimulant too late in the day.
What should I avoid while taking methylphenidate or dexmethylphenidate?
You should not drink alcohol or take illegal drugs while taking methylphenidate or dexmethylphenidate.
Avoid taking other stimulant medications such as mixed amphetamine salts, dextroamphetamine, diet pills (eg. sibutramine, phentermine), stimulant herbal supplements (eg. guarana, bitter orange), and monoamine oxidase inhibitors (eg. phenelzine, tranylcypromine).
The absorption of methylphenidate and dexmethylphenidate can be reduced if strong organic acids are present in the gut. The following foods should be avoided for 1 hour before and for two hours after taking methylphenidate or dexmethylphenidate medication: citrus fruit, citrus juices, sodas/carbonated beverages, lemonade, Gatorade, vitamins/food and food supplements containing vitamin C.
What happens if I overdose?
If an overdose occurs, whether intentional or accidental, immediate medical attention is necessary. Call your doctor or emergency medical service (911). You may also contact the national poison control center (1-800-222-1222).
Overdosing with methylphenidate or dextmethylphenidate may lead to high body temperature, tremors or muscle twitching, large pupils, extreme agitation, abnormal heart rhythms, seizures, excessively high blood pressure, and in some cases, death.
What are the possible side effects of methylphenidate and dexmethylphenidate?
Common:
- Upset stomach, loss of appetite and insomnia are the most common side effects associated with the use of methylphenidate or dexmethylphenidate. Upset stomach can be managed by taking the medicine on a full stomach or lowering the dose.
- Loss of appetite and weight loss can be improved by serving the child small frequent meals or his or her favorite foods when stimulant effects are low (for example, in the morning before medication, or at night when the medication effects are less)
- Insomnia can be improved by giving the medication as early in the day as possible. Some clinicians will prescribe sedating medications like clonidine, guanfacine, or trazodone at night. Melatonin has also been found effective to manage insomnia associated with ADHD medication use in children.
- Mild anxiety or restlessness can be managed with dosage reduction or changing medication.
- Rebound effects or symptoms of ADHD that come back late in the day when medication effects wear off can be managed by adjusting the timing of medication. Discuss with prescriber.
- The methylphenidate patch can cause irritation and discomfort at the patch site. It may also cause a rash. Rotating the patch site each day may be helpful, however, some individuals cannot tolerate skin irritation associated with the patch and it must be discontinued.
Uncommon or rare:
-
Abnormal involuntary movements or muscle twitches called tics (for example, excessive eye-blinking, nose scrunching, or shoulder shrugging) can be associated with methylphenidate and dexmethylphenidate. If this occurs, the dose of medication should be lowered or the medication should be changed.
-
Severe anxiety, panic attacks, mania, hallucinations, paranoia, and delusions are all possible. If they occur, the medication should be discontinued and the individual should be evaluated by their health care provider.
-
Methylphenidate and dexmethylphenidate are rarely associated with clinically significant increases in blood pressure or heart rate. All have been associated with small increases in blood pressure and heart rate deemed clinically insignificant during clinical trials. Blood pressure and heart rate should be monitored before starting medication, and then weekly while adjusting the dose and then every month to three months or when side effects emerge like “racing heart”, shortness of breath, or exercise fatigue.
Talk with your healthcare provider if you experience side effects that are bothersome to you.
Go to an emergency room if you experience chest pain, shortness of breath, fainting or suicidal behavior.
Are there any risks for taking methylphenidate or dexmethylphenidate for long periods of time?
Growth Effects
Although treatment with methylphenidate or dexmethylphenidate can lead to mild growth suppression, many studies have shown that this deficit in growth is small, may attenuate with time, and should not be a clinical concern for most children treated with these medications. Height, weight, and eating habits should be assessed before starting medication and regularly thereafter. If a child’s growth is thought to be affected, the risk versus benefit of taking time off medication (drug holiday) to allow for growth acceleration should be considered.
What other medications interact with methylphenidate and dexmethylphenidate?
- Methylphenidate and dexmethylphenidate should not be taken together with or within 14 days of taking a monoamine oxidase inhibitor (MAOI). MAOIs include: phenelzine (Nardil®), tranylcypromine (Parnate®), selegiline (Emsam®), linezolid (Zyvox) and other brands. Coadministering methylphenidate or dexmethylphenidate within 2 weeks of taking a MAOI can result in dangerously high blood pressure that can be fatal.
- Medications that may increase the effects and adverse effects of methylphenidate and dexmethylphenidate when coadministered include:
- amphetamine, dextroamphetamine (Dexedrine®), mixed amphetamine salts (Adderall®), atomoxetine (Strattera®), sibutramine (Meridia®) phenylephrine, guarana, and caffeine.
- Methylphenidate and dexmethylphenidate may increase the medication levels of several other medicines by slowing down their breakdown and elimination from the body. Examples of these medications include:
- Tricyclic antidepressants (TCAs) (older)- amitriptyline (Elavil), nortriptyline (Pamelor), imipramine (Tofranil), desipramine (Norpramin), clomipramine (Anafranil)
- Newer antidepressants: venlafaxine (Effexor), bupropion (Wellbutrin), fluoxetine (Prozac), paroxetine (Paxil)
- Anticonvulsant medications such as phenobarbital, phenytoin, carbamazepine
- Warfarin
- Some medications may increase the metabolism of methylphenidate and dexmethylphenidate resulting in a lower therapeutic response. One example of this medicine is:
- Methylphenidate and dexmethylphenidate may inhibit antihypertensive response to some blood pressure medications such as clonidine, guanethidine and guanadrel.
- Urinary alkalinizers (bicarbonate) may increase the effects of methylphenidate, while urinary acidifiers (citrus beverages) may decrease the effects of methylphenidate/dexmethylphenidate. Consult with your healthcare provider before starting any medications/food/food supplements that can alkalinize or acidify the urine. The interaction may or may not be clinically significant, however, it should be discussed with a health care provider.
How long does it take for methylphenidate or dexmethylphenidate to work?
Immediate-release methylphenidate or dexmethylphenidate works within an hour of an effective dose. The once-daily preparations (e.g. Concerta, Ritalin LA, Metadate CD, Focalin XR) may take 1-2 hours for the onset of therapeutic benefit.
Updated by Julie A. Dopheide, Pharm.D., BCPP
March 2008
|
