Quillivant XR

• Pfizer Laboratories

Tell your doctor about all of the medicines that you or your child take including prescription and nonprescription medicines, vitamins, and herbal supplements. Quillivant XR and some medicines may interact with each other and cause serious side effects. Sometimes the doses of other medicines will need to be adjusted while taking Quillivant XR.

Your doctor will decide whether Quillivant XR can be taken with other medicines.

Especially tell your doctor if you or your child takes:

• anti-depression medicines including MAOIs
• seizure medicines
• blood thinner medicines
• blood pressure medicines
• cold or allergy medicines that contain decongestants

Know the medicines that you or your child takes. Keep a list of your medicines with you to show your doctor and pharmacist.

Do not start any new medicine while taking Quillivant XR without talking to your doctor first.

Quillivant XR is a federally controlled substance (CII) because it can be abused or lead to dependence. Keep Quillivant XR in a safe place to prevent misuse and abuse. Selling or giving away Quillivant XR may harm others, and is against the law.

Tell your doctor if you or your child have (or have a family history of) ever abused or been dependent on alcohol, prescription medicines or street drugs.

Drug Dependence

Quillivant XR should be given cautiously to patients with a history of drug dependence or alcoholism. Chronic abusive use can lead to marked tolerance and psychological dependence with varying degrees of abnormal behavior. Frank psychotic episodes can occur, especially with parenteral abuse. Careful supervision is required during withdrawal from abusive use, since severe depression may occur. Withdrawal following chronic therapeutic use may unmask symptoms of the underlying disorder that may require follow-up.

Methylphenidate is a prescription medication used to treat Attention-Deficit Hyperactivity Disorder (ADHD). Methylphenidate belongs to a group of drugs called central nervous system (CNS) stimulants, which works by changing the amount of natural substances in the brain to decrease impulsiveness and hyperactivity.

This medication comes in tablet, extended release (long acting) tablet, extended release (long acting) capsule, patch, solution, and suspension forms. It is usually taken 1, 2, or 3 times a day (depending on form of medication prescribed). The tablets and oral solution should be taken 30 to 45 minutes before a meal. The capsule and suspension forms may be taken with or without food.

Do not crush, chew, or divide extended release tablets and capsules. Swallow the extended release tablets and capsules whole.

Common side effects of methylphenidate are headache, decreased appetite, and stomach ache.

Serious side effects have been reported with methylphenidate. See “Methylphenidate Precautions” section.

Methylphenidate may cause serious side effects, including:

• seizures, mainly in patients with a history of seizures
• slowing of growth (weight and height)
• eyesight changes or blurred vision
• allergic skin rash (patch form) Stop using methylphenidate patch and see your doctor right away if you have swelling or blisters at or around the application site. You may have a skin allergy to the patch. People who have skin allergies to methylphenidate patch may develop an allergy to all medicines that contain methylphenidate, even those methylphenidate medicines that are taken by mouth.

The most common side effects of methylphenidate include:

• poor appetite
• nausea
• vomiting
• stomach pain
• weight loss
• tics
• trouble sleeping
• mood swings
• dizziness
• redness, small bumps, itching where you apply methylphenidate patch

This is not a complete list of methylphenidate side effects. Ask your doctor or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Keep this and all medicines out of the reach of children.

Methylphenidate is a federally controlled substance (CII) because it can be abused or lead to dependence. Keep methylphenidate in a safe place to prevent misuse and abuse. Selling or giving away methylphenidate may harm others, and is against the law.

Tell your doctor if you or your child have (or have a family history of) ever abused or been dependent on alcohol, prescription medicines or street drugs.

Drug Dependence

Methylphenidate should be given cautiously to patients with a history of drug dependence or alcoholism. Chronic abusive use can lead to marked tolerance and psychological dependence with varying degrees of abnormal behavior. Frank psychotic episodes can occur, especially with parenteral abuse. Careful supervision is required during withdrawal from abusive use, since severe depression may occur. Withdrawal following chronic therapeutic use may unmask symptoms of the underlying disorder that may require follow-up.

Do not use methylphenidate if you have used an MAO inhibitor in the past 14 days. A dangerous drug interaction could occur. MAO inhibitors include isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, tranylcypromine, and others.

You should not use methylphenidate if you are allergic to it, or if you have:

• glaucoma;

• a personal or family history of tics (muscle twitches) or Tourette's syndrome; or

• severe anxiety, tension, or agitation (stimulant medicine can make these symptoms worse).

Stimulants have caused stroke, heart attack, and sudden death in certain people. Tell your doctor if you have:

• heart problems or a congenital heart defect;

• high blood pressure; or

• a family history of heart disease or sudden death.

To make sure this medicine is safe for you, tell your doctor if you or anyone in your family has ever had:

• depression, mental illness, bipolar disorder, psychosis, or suicidal thoughts or actions;

• motor tics (muscle twitches) or Tourette's syndrome;

• blood circulation problems in the hands or feet;

• seizures or epilepsy;

• problems with the esophagus, stomach, or intestines;

• an abnormal brain wave test (EEG); or

• a history of drug or alcohol addiction.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether methylphenidate passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Methylphenidate is not approved for use by anyone younger than 6 years old.

Take the missed dose as soon as you remember. Skip the missed dose if it is later than 6:00 p.m. Do not take extra medicine to make up the missed dose.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of methylphenidate could be fatal.

Avoid drinking alcohol, especially if you take extended-release methylphenidate. Alcohol may cause the medicine to be released into the bloodstream too fast.

Methylphenidate may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Ask your doctor before using a stomach acid medicine (including Alka-Seltzer or sodium bicarbonate). Some of these medicines can change the way your body absorbs methylphenidate, and may increase side effects.

Many drugs can interact with methylphenidate. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide. Tell your doctor about all your current medicines and any medicine you start or stop using.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Extended-release oral suspension (after reconstitution with water): 25 mg per 5 mL (5 mg per mL).

Consult with a Certified Poison Control Center (1-800-222-1222) for up-to-date guidance and advice on the management of overdosage with methylphenidate. Signs and symptoms of acute methylphenidate overdosage, resulting principally from overstimulation of the CNS and from excessive sympathomimetic effects, may include the following: nausea, vomiting, diarrhea, restlessness, anxiety, agitation, tremors, hyperreflexia, muscle twitching, convulsions (may be followed by coma), euphoria, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, tachycardia, palpitations, cardiac arrhythmias, hypertension, hypotension, tachypnea, mydriasis, dryness of mucous membranes, and rhabdomyolysis.

The efficacy of Quillivant XR was evaluated in a laboratory classroom study conducted in 45 pediatric patients (ages 6 to 12 years) with ADHD. Patients in the trial met Diagnostic and Statistical Manual of Mental Diseases, 4th edition (DSM-IV®) criteria for ADHD. The study began with an open-label dose optimization period (4 to 6 weeks) with an initial Quillivant XR dose of 20 mg once daily in the morning. The dose could be titrated weekly in increments of 10 or 20 mg until a therapeutic dose or the maximum dose of 60 mg/day was reached. At the end of the dose optimization period, approximately 5% of subjects were receiving 20 mg/day; 39%, 30 mg/day; 31%, 40 mg/day; 10%, 50 mg/day; and 15%, 60 mg/day. Subjects then entered a 2-week randomized, double-blind, crossover treatment with the individually optimized dose of Quillivant XR or placebo. At the end of each week, school teachers and raters evaluated the attention and behavior of the subjects in a laboratory classroom using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) rating scale. The primary efficacy endpoint was the SKAMP-Combined score at 4 hours post-dosing. The key secondary efficacy endpoints were the SKAMP-Combined scores at 0.75, 2, 8, 10, and 12 hours post-dosing.

Results from the first double-blind, placebo-controlled week of the study are summarized in Figure 3. SKAMP-Combined scores were statistically significantly lower (improved) at all time points (0.75, 2, 4, 8, 10, 12 hours) post-dosing with Quillivant XR compared to placebo.

Figure 3. Absolute SKAMP-Combined Score after treatment with Quillivant XR or Placebo during Period 1.

How Supplied

Quillivant XR is supplied as powder that, after reconstitution with water, forms an extended-release oral suspension. The product is supplied in a carton. Each carton also contains one bottle, one oral dosing dispenser, and one bottle adapter.

The product must be reconstituted only by the pharmacist and not by the patient or caregiver. After reconstitution, the product is a light beige to tan viscous suspension containing 25 mg per 5 mL (5 mg per mL) of methylphenidate hydrochloride.

Storage and Handling

Store at 25ºC (77ºF); excursions permitted from 15ºC to 30ºC (59ºF to 86ºF). [See USP Controlled Room Temperature.]

Dispense in original container.

Disposal

Comply with local laws and regulations on drug disposal of CNS stimulants. Dispose of remaining, unused, or expired Quillivant XR by a medicine take-back program or by an authorized collector registered with the Drug Enforcement Administration. If no take-back program or authorized collector is available, mix Quillivant XR with an undesirable, nontoxic substance to make it less appealing to children and pets. Place the mixture in a container such as a sealed plastic bag and discard Quillivant XR in the household trash.

Advise patients to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Controlled Substance Status/Potential for Abuse and Dependence

Advise patients and their caregivers that Quillivant XR is a federally controlled substance, and it can be abused and lead to dependence [see Drug Abuse and Dependence (9.1, 9.2, 9.3)]. Instruct patients that they should not give Quillivant XR to anyone else. Advise patients to store Quillivant XR in a safe place, preferably locked, to prevent abuse. Advise patients to comply with laws and regulations on drug disposal. Advise patients to dispose of remaining, unused, or expired Quillivant XR through a medicine take-back program if available [see Warnings and Precautions (5.1), Abuse and Dependence (9.2, 9.3)].

Instructions for Using the Enclosed Oral Dosing Dispenser

Provide the following instructions on administration to the patient or caregiver:

• The pharmacist should provide this medicine in its original packaging (bottle within carton) with the bottle adapter fully inserted and the accompanying oral dosing dispenser. Use only with the oral dosing dispenser provided with this product.
• Check and make sure that the Quillivant XR bottle contains liquid medicine. If Quillivant XR is in powder form, do not use it. Return it to your pharmacist.
• VIGOROUSLY SHAKE the bottle of Quillivant XR for at least 10 seconds before each dose, to ensure that the proper dose is administered.
• Remove the bottle cap. Confirm that the bottle adapter has been inserted into top of the bottle.
• Insert the tip of the oral dosing dispenser provided with this product into the bottle adapter.
• Turn bottle upside down and withdraw prescribed amount of Quillivant XR into the oral dosing dispenser.
• Remove filled oral dosing dispenser from bottle and dispense Quillivant XR directly into mouth.
• Replace bottle cap and store bottle as directed.
• Wash oral dosing dispenser after each use (components are dishwasher-safe).

Serious Cardiovascular Risks

Advise patients, caregivers, and family members that there is a potential for serious cardiovascular risks including sudden death, myocardial infarction, and stroke with Quillivant XR use. Instruct patients to contact a health care provider immediately if they develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease [see Warnings and Precautions (5.2)].

Blood Pressure and Heart Rate Increases

Advise patients that Quillivant XR can elevate blood pressure and heart rate [see Warnings and Precautions (5.3)].

Psychiatric Risks

Advise patients that Quillivant XR, at recommended doses, can cause psychotic or manic symptoms, even in patients without a prior history of psychotic symptoms or mania [see Warnings and Precautions (5.4)].

Priapism

Advise patients, caregivers, and family members of the possibility of painful or prolonged penile erections (priapism). Instruct the patient to seek immediate medical attention in the event of priapism [see Warnings and Precautions (5.5)].

Circulation Problems in Fingers and Toes [Peripheral Vasculopathy, including Raynaud's Phenomenon]

• Instruct patients beginning treatment with Quillivant XR about the risk of peripheral vasculopathy, including Raynaud's phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red.
• Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes.
• Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking Quillivant XR.
• Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Suppression of Growth

Advise patients, families, and caregivers that Quillivant XR can cause slowing of growth and weight loss [see Warnings and Precautions (5.7)].

Alcohol Effect

Patients should be advised to avoid alcohol while taking Quillivant XR Oral Suspension. Consumption of alcohol while taking Quillivant XR may result in a more rapid release of the dose of methylphenidate [see Clinical Pharmacology (12.3)].

This product's label may have been updated. For current full prescribing information, please visit www.pfizer.com.

Manufactured by:
Tris Pharma, Inc., Monmouth Junction, NJ 08852

LAB-0656-12.0

LAB-0657-8.0
June 2017

LAB-0658-5.0
June 2017

NDC 24478-190-10

Pfizer

Pharmacist: Dispense the enclosed
Medication Guide to each patient.

Quillivant XR®
methylphenidate HCl
for extended-release oral suspension

300 mg
(60 mL when reconstituted)

25 mg/5 mL
(5 mg/mL) when reconstituted
CII

LiquiXR™
TECHNOLOGY
Rx only