Amphetamine Extended-Release Oral Suspension

DYANAVEL XR (amphetamine) extended release oral suspension, a CNS stimulant, is an extended-release liquid formulation containing a 3.2 to1 ratio of d- to l-amphetamine.

Each 1 mL of DYANAVEL XR contains 2.5 mg of amphetamine which is the same as the amount of amphetamine (base equivalent) found in a 4 mg strength amphetamine mixed salts product.

Structural Formula:

DYANAVEL XR utilizes an ion exchange resin where the drug is bound to the resin (sodium polystyrene sulfonate) through an ionic binding reaction. DYANAVEL XR contains immediate release and extended-release components. The extended-release component is coated with an aqueous, pH-independent polymer. After drug release the ion-exchange resin is excreted in the feces.

Inactive Ingredients: anhydrous citric acid, bubblegum flavor, glycerin, methylparaben, modified food starch, polysorbate 80, povidone, polyvinyl acetate, propylparaben, sodium lauryl sulfate, sodium polystyrene sulfonate, sucralose, triacetin and xanthan gum.

DYANAVEL XR is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) [see Clinical Studies].

Dosage Forms And Strengths

Extended-release oral suspension contains 2.5 mg amphetamine base per mL.

DYANAVEL XR (amphetamine) extended-release oral suspension, the concentration is 2.5 mg/mL amphetamine base and is supplied as light beige to tan viscous suspension with bubblegum flavor in bottles of 464 mL (NDC 27808-102-01).

Storage And Handling

Dispense in a tight container with child-resistant closure.

Store at 20° to 25°C (68° to 77°F); excursions permitted from 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. The pharmacist should provide an oral dosing syringe or other suitable measuring device.

Comply with local laws and regulations on drug disposal of CNS stimulants. Dispose of remaining, unused, or expired DYANAVEL XR at authorized collection sites such as retail pharmacies, hospital or clinic pharmacies, and law enforcement locations. If no take-back program or authorized collector is available, mix DYANAVEL 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 DYANAVEL XR in the household trash.

Manufactured by: Tris Pharma, Inc. Monmouth Junction, NJ 08852. Revised: Jan 2017

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Drug Dependence [see BOXED WARNING, WARNINGS AND PRECAUTIONS, and Drug Abuse and Dependence]
• Hypersensitivity to amphetamine, or other components of DYANAVEL XR [see CONTRAINDICATIONS]
• Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors [see CONTRAINDICATIONS and DRUG INTERACTIONS]
• Serious Cardiovascular Reactions [see WARNINGS AND PRECAUTIONS]
• Blood Pressure and Heart Rate Increases [see WARNINGS AND PRECAUTIONS]
• Psychiatric Adverse Reactions [see WARNINGS AND PRECAUTIONS]
• Long-Term Suppression of Growth [see WARNINGS AND PRECAUTIONS]
• Peripheral Vasculopathy, including Raynaud's phenomenon [see WARNINGS AND PRECAUTIONS]
• Serotonin Syndrome [see WARNINGS AND PRECAUTIONS]

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Cardiovascular: Palpitations, tachycardia, elevation of blood pressure, sudden death, myocardial infarction. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use.

Central Nervous System: Psychotic episodes at recommended doses, overstimulation, restlessness, irritability, euphoria, dyskinesia, dysphoria, depression, tremor, tics, aggression, anger, logorrhea.

Eye Disorders: Vision blurred, mydriasis.

Gastrointestinal: Dryness of the mouth, unpleasant taste, diarrhea, constipation, other gastrointestinal disturbances. Anorexia and weight loss may occur as undesirable effects.

Allergic: Urticaria, rash, hypersensitivity reactions including angioedema and anaphylaxis. Serious skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported.

Endocrine: Impotence, changes in libido.

Skin: Alopecia.

There is limited experience with DYANAVEL XR in controlled trials. Based on this limited experience, the adverse reaction profile of DYANAVEL XR appears similar to other amphetamine extended-release products. The most common ( ≥ 2% in the DYANAVEL XR group and greater than placebo) adverse reactions reported in the Phase 3 controlled study conducted in 108 patients with ADHD (aged 6-12 years) were: epistaxis, allergic rhinitis and upper abdominal pain.

Table 1: Common adverse reactions occurring in ≥ 2% of Subjects on DYANAVEL XR and greater than Placebo during the double blind phase

Postmarketing Experience

The following adverse reactions have been identified during post approval use of other amphetamine products. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Endocrine: frequent or prolonged erections.

Musculoskeletal, Connective Tissue, and Bone Disorders: rhabdomyolysis. Psychiatric Disorders: dermatillomania.

Included as part of the PRECAUTIONS section.

Consult with a Certified Poison Control Center (1-800-222-1222) for up-to-date guidance and advice for treatment of overdosage. Individual patient response to amphetamines varies widely. Toxic symptoms may occur idiosyncratically at low doses.

Manifestations of amphetamine overdose include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia, and rhabdomyolysis. Fatigue and depression usually follow the central nervous system stimulation. Other reactions include arrhythmias, hypertension or hypotension, circulatory collapse, nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning is usually preceded by convulsions and coma.