Dyanavel XR

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using amphetamine and call your doctor at once if you have:

• chest pain, trouble breathing, feeling like you might pass out;
• fast heartbeats, rapid breathing;
• confusion, unusual thoughts, paranoia, hallucinations (seeing or hearing things that are not real);
• new behavior problems, aggression, anger, feeling irritable;
• numbness, pain, cold feeling, unexplained wounds, or skin color changes (pale, red, or blue appearance) in your fingers or toes;
• changes in your vision; or
• unexplained muscle pain, tenderness, or weakness (especially if you also have fever, unusual tiredness, and dark colored urine).

Amphetamine can affect growth in children. Tell your doctor if your child is not growing at a normal rate while using this medicine.

Common side effects may include:

• stomach pain, nausea, vomiting, loss of appetite;
• diarrhea, constipation;
• weight loss;
• mood changes, feeling restless or nervous, sleep problems (insomnia);
• dry mouth, unusual or unpleasant taste in the mouth;
• runny nose, nosebleeds;
• increased heart rate;
• headache, dizziness;
• itching; or
• impotence, sexual problems.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• Monoamine oxidase inhibitors such as tranylcypromine (Parnate), phenelzine (Nardil), selegiline (Eldepryl, Zelapar), isocarboxazid (Marplan), and rasagiline (Azilect)
• tricyclic antidepressants such as trimipramine (Surmontil), amitriptyline (Elavil), nortriptyline (Pamelor, Aventyl), protriptyline (Vivactil), and clomipramine (Anafranil)
• Acidifying agents such guanethidine, reserpine, glutamic acid HCl, ascorbic acid, and fruit juices 
• Urinary acidifying agents such as ammonium chloride and sodium acid phosphate 
• Gastrointestinal alkalizing agents such as sodium carbonate and urinary alkalizing agents such as acetazolamide
• medications that reduce the acid level in your stomach such as omeprazole (Prilosec)

This is not a complete list of Dyanavel XR drug interactions. Ask your doctor or pharmacist for more information.

Tell your doctor if you are breastfeeding or plan to breastfeed.

Dyanavel XR has been detected in human breast milk. Because of the possibility for adverse reactions in nursing infants from Dyanavel XR, a choice should be made whether to stop nursing or to stop use of this medication. The importance of the drug to the mother should be considered. Breastfeeding is not recommended during treatment with Dyanavel XR. 

Take Dyanavel XR exactly as prescribed. Your doctor may adjust the dose until it is right for you or your child.

This medication comes in solution form and is taken once a day, with or without food.

Take Dyanavel XR oral suspension 1 time each day in the morning.

Shake the Dyanavel XR bottle well before you use it.

Use an oral dosing syringe or other measuring device to help you measure the right amount of Dyanavel XR.

Your doctor may sometimes stop Dyanavel XR treatment for a while to check your ADHD symptoms.

Your doctor may do regular checks of your or your child’s blood, heart, and blood pressure while taking Dyanavel XR.

Children should have their height and weight checked often while taking Dyanavel XR. Dyanavel XR treatment may be stopped if a problem is found during these check-ups.

Avoid drinking alcohol while taking Dyanavel XR.

You should not use amphetamine if you are allergic to any stimulant medicine, or if you have:

• moderate to severe high blood pressure;

• overactive thyroid;

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

• a history of drug or alcohol addiction.

Do not use amphetamine 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.

Some medicines can interact with amphetamine and cause a serious condition called serotonin syndrome. Be sure your doctor knows if you also take opioid medicine, herbal products, or medicine for depression, mental illness, Parkinson's disease, migraine headaches, serious infections, or prevention of nausea and vomiting. Ask your doctor before making any changes in how or when you take your medications.

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 amphetamine 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;

• problems with drug or alcohol abuse;

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

• kidney disease;

• a thyroid disorder;

• seizures or epilepsy;

• an abnormal brain wave test (EEG);

• coronary artery disease (clogged arteries); or

• blood circulation problems in the hands or feet.

It is not known whether this medicine will harm an unborn baby. However, taking the medicine during pregnancy can cause premature birth, low birth weight, or withdrawal symptoms in the newborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Amphetamine can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

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

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 amphetamine, and may increase side effects.

Many drugs can interact with amphetamine. 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.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Seeing, hearing, or feeling things that are not there
• severe mental changes

• Agitation
• blurred vision
• confusion
• diarrhea
• dizziness
• false or unusual sense of well-being
• fast, irregular, pounding, or racing heartbeat or pulse
• fever
• headache
• nervousness
• overactive reflexes
• pounding in the ears
• restlessness
• shakiness in the legs, arms, hands, or feet
• shivering
• slow or fast heartbeat
• sweating
• talking or acting with excitement you cannot control
• trouble sleeping
• twitching, twisting, or uncontrolled repetitive movements of the tongue, lips, face, arms, or legs
• uncontrolled vocal outbursts or tics (uncontrolled repeated body movements)

Get emergency help immediately if any of the following symptoms of overdose occur:

• Abdominal or stomach cramps
• dark-colored urine
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fainting
• muscle cramps or spasms
• muscle pain or stiffness
• nausea
• seizures
• sweating
• unusual tiredness or weakness
• vomiting

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Decreased interest in sexual intercourse
• difficulty having a bowel movement (stool)
• dry mouth
• hives or welts, itching, or skin rash
• inability to have or keep an erection
• loss in sexual ability, desire, drive, or performance
• loss of appetite
• redness of the skin
• unpleasant taste
• weight loss

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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

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

• Drug Dependence [see Boxed Warning, Warnings and Precautions (5.1), and Drug Abuse and Dependence (9.2, 9.3)]
• Hypersensitivity to amphetamine, or other components of Dyanavel XR [see Contraindications (4)]
• Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors [see Contraindications (4) and Drug Interactions (7.1)]
• Serious Cardiovascular Reactions [see Warnings and Precautions (5.2)]
• Blood Pressure and Heart Rate Increases [see Warnings and Precautions (5.3)]
• Psychiatric Adverse Reactions [see Warnings and Precautions (5.4)]
• Long-Term Suppression of Growth [see Warnings and Precautions (5.5)]
• Peripheral Vasculopathy, including Raynaud's phenomenon [see Warnings and Precautions (5.6)]
• Serotonin Syndrome [see Warnings and Precautions (5.7)]

6.1       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.

Clinical Trials Experience with Other Amphetamine Products in Pediatric Patients and Adults with ADHD

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.

Clinical Trials Experience with Dyanavel XR in Pediatric Patients with ADHD

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.

6.2       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.

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.

13.1       Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

No evidence of carcinogenicity was found in studies in which d, l-amphetamine (enantiomer ratio of 1:1) was administered to mice and rats in the diet for 2 years at doses of up to 30 mg/kg/day in male mice, 19 mg/kg/day in female mice, and 5 mg/kg/day in male and female rats. These doses are approximately 2.4, 1.5, and 0.8 times, respectively, the maximum recommended human dose of 20 mg/day (as base) on a mg/m2 body surface area basis for a child.

Mutagenesis

Amphetamine, in the enantiomer ratio present in Dyanavel XR (d- to l- ratio of 3.2 to 1), was not clastogenic in the mouse bone marrow micronucleus test in vivo and was negative when tested in the E. coli component of the Ames test in vitro. d, l-Amphetamine (1:1 enantiomer ratio) has been reported to produce a positive response in the mouse bone marrow micronucleus test, an equivocal response in the Ames test, and negative responses in the in vitro sister chromatid exchange and chromosomal aberration assays.

Impairment of Fertility

Amphetamine, in the enantiomer ratio present in Dyanavel XR (d- to l- ratio of approximately 3.2 to 1), did not adversely affect fertility or early embryonic development in the rat at doses of up to 20 mg/kg/day [approximately 5 times the maximum recommended human dose of 20 mg/day (as base) on a mg/m2 body surface area basis for an adolescent].

13.2       Animal Toxicology and/or Pharmacology

Acute administration of high doses of amphetamine (d- or d, l-) has been shown to produce long-lasting neurotoxic effects, including irreversible nerve fiber damage, in rodents. The significance of these findings to humans is unknown.

Applies to amphetamine: oral suspension extended release, oral tablet, oral tablet disintegrating extended release

Cardiovascular

Frequency not reported: Palpitations, tachycardia, elevated blood pressure, cardiomyopathy
Postmarketing reports: Peripheral vasculopathy[Ref]

Psychiatric

Rare (less than 0.1%): Psychotic episodes
Frequency not reported: Euphoria, dysphoria, insomnia, restlessness[Ref]

Nervous system

Frequency not reported: Overstimulation, dizziness, dyskinesia, tremor, headache, exacerbation of motor/phonic tics and Tourette's syndrome[Ref]

Musculoskeletal

Postmarketing reports: Rhabdomyolysis[Ref]

Gastrointestinal

Common (1% to 10%): Upper abdominal pain
Frequency not reported: Dry mouth, unpleasant taste, diarrhea, constipation, other GI disturbances[Ref]

Endocrine

Frequency not reported: Impotence, libido changes, frequent or prolonged erections[Ref]

Immunologic

Frequency not reported: Urticaria[Ref]

Metabolic

Frequency not reported: Anorexia, weight loss[Ref]

Respiratory

Common (1% to 10%): Epistaxis, allergic rhinitis[Ref]

Some side effects of Dyanavel XR may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.