Dexamphetamine Tentin 5 mg

Clinical Monograph: Tentin 5 mg (Dexamfetamine Sulfate)

Tentin 5 mg tablets packaging. Source: Oladoctor

1. Classification and Chemical Overview

Dexamfetamine (dextroamphetamine) is the dextrorotatory $(S)$-enantiomer of amphetamine, exhibiting significantly higher central nervous system potency than its levorotatory counterpart ($(R)$-amphetamine). It belongs to the phenethylamine and amphetamine chemical classes. Under the Anatomical Therapeutic Chemical (ATC) classification system, dexamfetamine is indexed under N06BA02.

Tentin 5 mg is presented as oral tablets containing 5 mg of dexamfetamine sulfate (equivalent to 3.67 mg of free dexamfetamine base). In the UK, European Union, and international jurisdictions, dexamfetamine is strictly regulated as a Controlled Substance (Schedule 2 Controlled Drug under the UK Misuse of Drugs Regulations 2001) and is available exclusively as a Prescription Only Medicine (POM).

2. Mechanism of Action and Pharmacodynamics

Dexamfetamine functions as a potent sympathomimetic amine and non-catecholamine CNS stimulant that increases monoaminergic neurotransmission in the brain, particularly in the prefrontal cortex and basal ganglia:

• Inhibition of Reuptake Transporters: Binds to and blocks the dopamine transporter (DAT) and norepinephrine transporter (NET), preventing synaptic clearance of dopamine and norepinephrine.

• TAAR1 Activation & Reversal of Transport: Enters presynaptic axon terminals via DAT/NET and activates Trace Amine-Associated Receptor 1 (TAAR1). This triggers protein kinase signaling that leads to competitive inhibition and structural reversal of DAT and NET, pumping intracellular dopamine and norepinephrine directly into the synaptic cleft.

• VMAT2 Inhibition: Inhibits Vesicular Monoamine Transporter 2 (VMAT2), disrupting vesicular storage and elevating cytosolic concentrations of monoamines available for efflux.

• Monoamine Oxidase (MAO) Inhibition: At higher therapeutic concentrations, weakly inhibits MAO enzymes, slowing monoamine degradation.

These combined mechanisms increase synaptic concentrations of dopamine and norepinephrine, enhancing impulse control, executive function, working memory, and vigilance while reducing hyperactive and impulsive behaviors.

3. Approved Clinical Indications and Therapeutic Scope

Licensing for Tentin 5 mg includes:

• Attention Deficit Hyperactivity Disorder (ADHD): Indicated as part of a comprehensive treatment strategy for ADHD in children and adolescents aged 6 to 17 years when response to previous methylphenidate treatment is considered clinically inadequate. (Treatment must be initiated under the supervision of a specialist in childhood behavioral disorders).

• Narcolepsy: Management of excessive daytime sleepiness and cataplexy in adults (off-label or licensed depending on specific regional marketing authorizations).

Dosing & Administration Regimen:

• For ADHD in paediatric populations, the typical initial dose is 5 mg once or twice daily, titrated in weekly increments of 5 mg based on clinical efficacy and tolerability. The total daily dose is divided across 2 to 3 doses per day (e.g., morning, midday, and late afternoon).

• The maximum recommended daily dose for ADHD in children aged 6–17 years is generally 20 mg to 40 mg per day. The last dose should not be administered too close to bedtime to prevent insomnia.

4. Pharmacokinetic Profile and Metabolic Fate

• Absorption: Dexamfetamine sulfate is rapidly and completely absorbed from the gastrointestinal tract. Peak plasma concentration (Cmax​) occurs within 1.5 to 2.5 hours (Tmax​) post-dose for immediate-release tablets. Onset of clinical action occurs within 30 to 60 minutes.

• Distribution: Highly lipophilic, rapidly distributing across the blood-brain barrier. Volume of distribution (Vd​) is approximately 3.5 to 5.0 L/kg. Plasma protein binding is relatively low (15% to 30%).

• Biotransformation: Metabolised in the liver via multiple pathways. Primary Phase I metabolism involves aromatic hydroxylation to 4-hydroxyamphetamine via Cytochrome P450 2D6 (CYP2D6), as well as deamination by oxidative pathways to phenylacetone and subsequent benzoic acid formation.

• Elimination: Urinary excretion is highly pH-dependent. At normal urinary pH (6.0), approximately 30% to 50% is excreted unchanged in the urine within 48 hours. Urinary acidification (pH < 5.5) increases ion trapping and significantly shortens the elimination half-life, whereas alkalinisation increases tubular reabsorption and prolongs elimination.

• Half-life (t1/2​): Elimination half-life ranges from 8 to 12 hours in adults (and approximately 6 to 9 hours in children), yielding a total duration of clinical action of 4 to 8 hours for immediate-release Tentin.

5. Physiological Effects and Adverse Event Spectrum

Dexamfetamine stimulates the central and peripheral sympathetic nervous systems, causing increased alertness, reduced fatigue, mild elevation of blood pressure, tachycardia, and appetite suppression.

Adverse Drug Reaction Spectrum

• Very Common ($\ge 1/10$): Decreased appetite, weight loss, insomnia, restlessness, irritability, dry mouth, abdominal pain, nausea, tachycardia, palpitations.

• Common ($\ge 1/100$ to $<1/10$): Dizziness, dyskinesia, tremor, headache, mood swings, anxiety, aggression, blood pressure fluctuations, Raynaud’s phenomenon, gastrointestinal disturbances (vomiting, diarrhoea).

• Uncommon ($\ge 1/1,000$ to $<1/100$): Tourette’s syndrome exacerbation, tics, depression, hallucinations, psychosis, visual disturbances, chest pain.

• Rare / Very Rare (<1/1,000): Neuroleptic Malignant Syndrome-like reactions, cerebrovascular accidents, myocardial infarction, sudden cardiac death, hepatic dysfunction, blood dyscrasias.

6. Contraindications, Drug Interactions, and Clinical Precautions

Contraindicaciones

• Known hypersensitivity to dexamfetamine, other amphetamines, or excipients.

• Concomitant use or use within 14 days of Monoamine Oxidase Inhibitors (MAOIs) (risk of fatal hypertensive crisis).

• Moderate to severe hypertension, advanced arteriosclerosis, or structural cardiovascular disease (e.g., cardiomyopathy, severe arrhythmia).

• Hyperthyroidism or thyrotoxicosis.

• Glaucoma.

• History of severe psychiatric disorders (e.g., severe anorexia nervosa, psychotic disorders, active bipolar disorder, suicidal ideation).

• History of drug or alcohol dependence.

Key Drug Interactions

• MAO Inhibitors: Absolutely contraindicated; co-administration triggers massive synaptic accumulation of monoamines, leading to severe hyperpyrexia, malignant hypertension, and cardiovascular collapse.

• Serotonergic Agents (SSRIs, SNRIs, Triptans, Tramadol): Co-administration increases the risk of Serotonin Syndrome.

• Urinary Acidifiers (e.g., Ascorbic Acid, Ammonium Chloride): Lower urinary pH, accelerating dexamfetamine excretion and reducing clinical efficacy.

• Urinary Alkalinisers (e.g., Sodium Bicarbonate, Antacids): Raise urinary pH, reducing renal clearance and significantly elevating systemic exposure and toxicity risk.

• Antihypertensives: Dexamfetamine opposes the therapeutic actions of guanethidine, alpha-blockers, and beta-blockers.

Clinical Precautions and Monitoring

• Cardiovascular Monitoring: Baseline blood pressure and heart rate must be recorded prior to initiation and monitored at every dose adjustment and at least every 6 months.

• Growth Tracking in Children: Height, weight, and appetite must be systematically plotted on growth charts every 6 months. Dosage adjustment or treatment breaks (“drug holidays”) may be required if growth velocity slows.

• Psychiatric Screening: Patients must be monitored for the emergence or worsening of aggressive behavior, tics, psychosis, or manic symptoms.

• Abuse and Dependence Risk: Dexamfetamine carries significant potential for tolerance, psychological dependence, and diversion. Prescribers should regularly evaluate the risk of misuse.