Vyvanse (Lisdexamfetamine Dimesylate) Capsules

Manufacturer: Shire US Inc. Lexington, MA

In which dosage forms and strengths this drug is available?

  • It is available as capsules for oral administration once daily
  • The strengths available are 10, 20, 30, 40, 50, 60 and 70 mg capsules

What should the patients know about this drug?

  • The patients should be advised to read the instruction properly on the FDA approved guide.
  • Patients should be advised about this drug related hypersensitivity/allergic reactions which can result in anaphylactic reactions, Stevens-Johnson syndrome, angioedema, and urticaria.
  • Vyvanse is a federally controlled substance (CII) because it can be abused or lead to dependence. Keep Vyvanse in a safe place to prevent misuse and abuse. Selling or giving away Vyvanse may harm others, and is against the law. The patients should be warned about the serious cardiovascular effects related to the Vyvanse use. These effects may include development of myocardial infarction, death, hypertension, tachycardia and stroke. If the patient experiences any of the above symptoms they must consult their healthcare prescriber immediately.
  • CNS stimulants cause an increase in blood pressure (mean increase about 2-4 mmHg) and heart rate (mean increase about 3-6 bpm) so all patients should be monitored for potential tachycardia and hypertension.
  • The patients should also be informed about the psychiatric risks associated with the Vyvanse therapy. The normal daily doses of the drug can cause manic or psychotic episodes.
  • Similarly, the patients on the Vyvanse therapy should also be advised that this drug may cause weight loss and reduction in the growth.
  • Vyvanse use can disturb the patient’s ability to drive and to operate the machines properly.
  • The patients should be informed about the blood circulation problems in their fingers and toes. The signs and symptoms include feeling of the numbness pain, coolness, and changes in the color. This condition is called Raynaud’s phenomenon or peripheral vasculopathy.
  • It should be used with caution in hyperthyroidism, glaucoma, mild to severe hypertension, advanced arteriosclerosis, symptomatic CVD, agitated states, history of psychosis or drug abuse.
  • Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation.
  • Particular care should be taken in using stimulants to treat ADHD patients with comorbid bipolar disorder because of the concern for possible induction of mixed/manic episode in such patients.

Under which conditions can this drug be used?

This drug Vyanse can be used for treating the following conditions

  • For treating attention deficit hyperactivity disorder (ADHD)
  • For treating binge eating disorder (BED) of moderate to severe nature
  • This drug is not recommended for reducing the body weight as its safety and efficacy for treating obesity is not well established as yet. The use of sympathomimetic drugs can result in serious cardiovascular adverse effects.

Dosing Considerations: Recommended dose for ADHD

  • The recommended initial dose for treating ADHD is 30 mg once daily administered in the morning. The dose can be increased on weekly basis by 10 to 20 mg gradually. The maximum recommended dose is 70 mg/day.

Recommended dose for BED

  • The initial recommended dose is 30 mg per day. It can be increased by 20 mg on weekly basis. The recommended target dose is 50 to 70 mg/ day.

How should you use this drug?

  • Take Vyvanse by mouth in the morning with or without food; avoid afternoon doses because of the potential for insomnia.
  • Swallow Vyvanse capsules whole or open capsules, empty and mix the entire contents with yogurt, water, or orange juice. If the contents of the capsule include any compacted powder, a spoon may be used to break apart the powder. The contents should be mixed until completely dispersed.
  • Consume the entire mixture immediately. It should not be stored. The active ingredient dissolves completely once dispersed; however, a film containing the inactive ingredients may remain in the glass or container once the mixture is consumed.
  • Do not take anything less than one capsule per day, and a single capsule should not be divided.

In which conditions this drug should not be administered?

  • It should not be administered in the patients who are allergic to Vyvanse or its ingredients. The hyper-sensitivity reactions include Stevens-Johnsons syndrome, anaphylaxis, urticarial and angioedema.
  • It is also contraindicated for the concomitant administration with the monoamine oxidase inhibitors (MAOI) because of the potential risk of developing hypertensive crisis.

What adverse drug reactions or side effects can occur?

The adverse effects of Vyvanse use include

  • Potential risk for developing drug dependence and abuse
  • Suppression in growth include
    • Slow growing rate
    • Reduction in weight
  • Development of peripheral vasculopathy and Raynaud’s phenomenon include
    • Digital ulceration
    • Numbness in the toes and fingers
  • The psychiatric adverse reactions include
    • Worsening of already existing psychosis
    • Development of bipolar disorder
    • Development of the manic episodes
    • Hallucinations
    • Delusions
    • Mania or psychotic illness
  • Serious cardiovascular reactions include
    • Sudden death
    • Stroke
    • Myocardial infarction
    • Cardiac myopathy
    • Arrhythmia
    • Coronary artery disease
    • Tachycardia (increased heart rate)
    • Hypertension (increased blood pressure)

How does Vyvanse interact with other drugs?

  • No dose adjustment of Vyvanse is necessary when Vyvanse is co-administered with guanfacine, venlafaxine, or omeprazole. In addition, no dose adjustment of guanfacine or venlafaxine is needed when Vyvanse is co-administered.
  • No dose adjustment for drugs that are substrates of CYP1A2 (e.g. theophylline, duloxetine, melatonin), CYP2D6 (e.g., atomoxetine, desipramine, venlafaxine), CYP2C19 (e.g. omeprazole, lansoprazole, clobazam), and CYP3A4 (e.g., midazolam, pimozide, simvastatin) is necessary when Vyvanse is co-administered.
  • Agents that alter urinary pH can alter blood levels of amphetamine. Acidifying agents decrease amphetamine blood levels, while alkalinizing agents increase amphetamine blood levels.so, Vyvanse dosage should be adjusted accordingly.

Conditions required for the storage of Vyvanse

  • Store in the light resistant and air-tight containers
  • The drug should be stored at the room temperature, 20-25° C or 15-30°C.
  • The disposal of the unused or the expired drug should be as per the laws regarding the disposal of CNS stimulants.

How this drug acts pharmacologically?

This drug is a pro-drug of dextroamphetamine. A pro-drug is the inactive form of the drug that is converted into its therapeutically active metabolites inside the body. All the amphetamines show the central nervous system stimulant activities. They belong to a class of drugs known as non-catecholamine based sympathomimetic amines. Their mechanism of action is blocking the reuptake of the neurotransmitters like norepinephrine and dopamine into a pre-synaptic neuron. As a result, the release of these monoamine neurotransmitters is increased within the extra-neuronal space. The parent compound lisdexamfetamine possesses no therapeutic activity and does not bind to any receptors responsible for norepinephrine and dopamine reuptake.

Pharmacokinetics of Vyvanse

The pharmacokinetic studies for dextroamphetamine have been performed in the patients of attention deficit hyperactivity syndrome (ADHD) and healthy volunteers. The ages of all these individuals ranged from 6 to 12 years

The Tmax. i.e. maximum time to reach the maximum plasma drug concentration (Cmax.) for dextroamphetamine was found to be 3.5 hours after the administration of the single oral dose. Linear pharmacokinetics was observed both in children and adults within the dose ranges of 30 to 70mg and 50 to 250 mg respectively. The pharmacokinetic parameters of dextroamphetamine demonstrated less inter-subject and intra-subject variabilities. No accumulation after once daily oral administration for 7 continuous days of lisdexamfetamine was observed. Similarly, no accumulation at the steady state AUC of dextroamphetamine in the healthy human subjects was noted.

The AUC and Cmax. for the dextroamphetamine remain unaffected by food and juice. However, the food can prolong the Tmax. by 1 hour approx.

How is it metabolized and eliminated?

The absorption of the drug lisdexamfetamine mostly occurs from the gastrointestinal (GI) tract. Due to the hydrolytic activity of the red blood cells the inactive lisdexamfetamine is converted into two metabolites i.e. dextroamphetamine and L- lysine in the blood. The drug lisdexamfetamine is not metabolized readily in the liver by the P450 enzyme system. After the administration of 70 mg of radiolabelled lisdexamfetamine 0.3% of the drug was recovered through feces and almost 96% was recovered through urine after 120 hours. The elimination half-life through plasma was observed to be less than 1 hour.

Pharmacokinetics in some special populations

  • The average renal clearance in the patients with any type of renal impairment was reduced to in comparison with the normal patients i.e. 0.4L/hr/kg from 0.7L/hr/kg
  • The evidence of development of carcinogenesis by using lisdexamfetamine dimesylate is not established yet. It was also observed that it does not cause carcinogenesis in rats.
  • This drug is not mutagenic i.e. does not cause any type of mutations and is not clastogenic. Similarly, this drug does not show any harmful effects on the fertility and development of the embryo.

 Can this drug be used in the specific populations?

  • During Pregnancy: it is a pregnancy category C There are no adequate and well-controlled studies with Vyvanse in pregnant women. Adverse pregnancy outcomes, including premature delivery and low birth weight, have been seen in infants born to mothers dependent on amphetamines. Amphetamines, such as Vyvanse, cause vasoconstriction and thereby may decrease placental perfusion. Infants born to amphetamine-dependent mothers have an increased risk of premature delivery and low birth weight. Monitor infants born to mothers taking amphetamines for symptoms of withdrawal such as feeding difficulties, irritability, agitation, and excessive drowsiness.
  • In nursing mothers: Amphetamines are excreted into human milk. Long-term neurodevelopmental effects on infants from amphetamine exposure are unknown. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
  • In pediatrics: Safety and efficacy in pediatric patients below the age of 6 years have not been established.
  • In geriatrics: dose selection for an elderly patient should start at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
  • On gender basis: No dosage adjustment of Vyvanse is necessary on the basis of gender.
  • In renal impairment: Due to reduced clearance in patients with severe renal impairment (GFR 15 to < 30 mL/min/1.73 m2), the maximum dose should not exceed 50 mg/day. The maximum recommended dose in ESRD (GFR < 15 mL/min/1.73 m2) patients is 30 mg/day. Lisdexamfetamine and d-amphetamine are not dialyzable.

Toxicology of Vyvanse:

  • This drug was not found to be carcinogenic or clastogenic during animal testing.
  • No adverse effects on fertility or initial embryonic growth were seen in the rats at doses of up to 20 mg/kg/day.
  • Acute administration of high doses of amphetamine 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.

What should you tell your doctor before taking this medication?

Before you take Vyvanse, tell your doctor if you have or if there is a family history of:

  • heart problems, heart defects, high blood pressure
  • mental problems including psychosis, mania, bipolar illness, or depression
  • circulation problems in fingers and toes
  • any kidney problems. Your doctor may lower your dose.
  • you are pregnant or plan to become pregnant. It is not known if Vyvanse will harm your unborn baby.
  • you are breastfeeding or plan to breastfeed. Vyvanse passes into breast milk. Discuss with your doctor before you breastfeed while you are taking this drug.
  • Tell your doctor about all of the medicines that you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

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