Dexamfetamine Sulfate

Registered South African indications:

• Attention deficit/hyperactivity disorder (ADHD) when response to previous methylphenidate treatment is considered clinically inadequate

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Known hypersensitivity to sympathomimetic amines
• Glaucoma
• Phaeochromocytoma
• Symptomatic cardiovascular disease, structural cardiac abnormalities, moderate or severe hypertension, heart failure, arterial occlusive disease, angina, haemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction, potentially life-threatening dysrhythmias, and channelopathies (disorders caused by the dysfunction of ion channels)
• Advanced arteriosclerosis
• Concomitant use of monoamine oxidase inhibitors (MAOI) or within 14 days of MAOI treatment
• Hyperthyroidism or thyrotoxicosis
• Severe depression, anorexia nervosa/anorexic disorders, suicidal ideation, hyperexcitability, psychotic symptoms, severe and episodic (type I) bipolar (affective) disorder that is not well-controlled, schizophrenia, psychopathic/borderline personality disorder
• Gilles de la Tourette syndrome or similar dystonias
• Cerebrovascular disorders (cerebral aneurysm, vascular abnormalities including vasculitis or stroke)
• Porphyria
• History of drug abuse or alcohol abuse
• Pregnancy
• Lactation

Contraindications registered in other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• Known hypersensitivity to sympathomimetic amines
• Glaucoma
• Phaeochromocytoma
• Symptomatic cardiovascular disease, structural cardiac abnormalities, moderate or severe hypertension, heart failure, arterial occlusive disease, angina, haemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction, potentially life-threatening dysrhythmias, and channelopathies (disorders caused by the dysfunction of ion channels)
• Advanced arteriosclerosis
• Concomitant use of monoamine oxidase inhibitors (MAOI) or within 14 days of MAOI treatment
• Hyperthyroidism or thyrotoxicosis
• Severe depression, anorexia nervosa/anorexic disorders, suicidal ideation, hyperexcitability, psychotic symptoms, severe and episodic (type I) bipolar (affective) disorder that is not well-controlled, schizophrenia, psychopathic/borderline personality disorder
• Gilles de la Tourette syndrome or similar dystonias
• Cerebrovascular disorders (cerebral aneurysm, vascular abnormalities including vasculitis or stroke)
• Porphyria
• History of drug abuse or alcohol abuse

Recommendations in South Africa & other jurisdictions

Use with caution in the following patient groups

• Elderly
• Women of childbearing age
• Pregnancy (Recommendations in other jurisdictions)
• Breastfeeding (Recommendations in other jurisdictions)

Use in renal or hepatic insufficiency

• There is no experience with the use of dexamfetamine sulfate in patients with renal or hepatic insufficiency, thus, special caution is required in this patient group by taking care of titration and dosage

Pre-treatment screening

• Evaluate cardiovascular health, including blood pressure and heart rate
• Review patient's medical and psychiatric history, medication use, and family history of cardiac events
• Record baseline height and weight

Ongoing monitoring

• Monitor cardiovascular health, growth, and psychiatric status continually. Check and chart blood pressure and heart rate at every dose change and every 6 months
• Record height, weight, and appetite 6 monthly
• Watch for new or worsening psychiatric symptoms at each dose adjustment and during regular visits
• Be alert to any potential misuse or abuse of dexamfetamine sulfate

Long-term use (more than 12 months) in children and adolescents

• Controlled trials have not systematically evaluated the long-term (over 12 months) use of dexamfetamine sulfate
• Treatment typically stops during or after puberty
• Ongoing monitoring for cardiovascular health, growth, appetite, and psychiatric conditions is crucial

Psychiatric monitoring

• Watch for new or worsening psychiatric disorders, including motor or vocal tics, aggressive behaviour, agitation, anxiety, depression, psychosis, mania, delusions, irritability, withdrawal, and obsessive behaviours

Periodic evaluation

• Reassess the need for dexamfetamine sulfate regularly, considering trial periods off medication to evaluate the patient’s function without pharmacotherapy
• It is recommended that dexamfetamine sulfate is de-challenged at least once yearly to assess the child’s condition (preferably during times of school holidays). Improvement may be sustained when treatment is either temporarily or permanently discontinued

Cardiovascular considerations

• Careful screening for cardiac disease is necessary before starting treatment, including family history of of sudden cardiac or unexplained death or malignant dysrhythmia
• Prompt cardiac evaluation is advised if symptoms like palpitations, chest pain, fainting, shortness of breath, or other cardiac symptoms occur during treatment
• Regularly monitor blood pressure and heart rate
• Be cautious with patients having conditions that could worsen with increased blood pressure or heart rate
• Dexamfetamine sulfate is contraindicated in some pre-existing cardiovascular conditions, requiring specialist advice before use

Sudden death and cardiac disorders

• Sudden death reported in children using CNS stimulants, including some with cardiac abnormalities
• Stimulants not recommended for children/adolescents with cardiac structural abnormalities, cardiomyopathy, serious rhythm abnormalities, or other serious cardiac problems

Cardiovascular events

• Misuse of CNS stimulants linked to sudden death and serious cardiovascular events
• Chronic use of amfetamine may lead to cardiomyopathy

Cerebrovascular disorders

• Patients with additional risk factors  (beyond those listed in contraindications) should be monitored for neurological signs after starting dexamfetamine sulfate
• Cerebral vasculitis, though very rare, can occur. Symptoms such as severe headache, numbness, weakness, or paralysis should prompt consideration of this diagnosis
• Dexamfetamine sulfate is not contraindicated in patients with hemiplegic cerebral palsy

Psychiatric disorders

• ADHD often coexists with psychiatric disorders. Assess risks and benefits of stimulant use in these cases
• Monitor for emergent or worsening psychiatric symptoms at each dose change, every 6 months, and each visit. Treatment discontinuation may be necessary
• In psychotic patients, dexamfetamine sulfate may worsen behavioural disturbances and thought disorder

Emergence of new psychotic or manic symptoms

• Usual doses of dexamfetamine sulfate can cause psychotic symptoms (visual/tactile/auditory hallucinations and delusions) or mania, even without a prior history of these conditions
• Occurrence is about 0.1% in treated patients, based on a pooled analysis of short-term studies
• If such symptoms arise, consider the role of dexamfetamine sulfate and possibly discontinue treatment

Aggressive or hostile behaviour

• Treatment with stimulants like dexamfetamine sulfate can lead to new or worsening aggression or hostility
• Monitor closely at treatment start, each dose change, every 6 months, and at each visit
• Treatment regimen may need adjustment if behavioural changes occur

Suicidal ideation

• Immediate evaluation is necessary for patients showing suicidal ideation or behaviour during ADHD treatment
• Assess the exacerbation of underlying psychiatric conditions and dexamfetamine sulfate's potential causal role
• Treating the underlying psychiatric condition and considering discontinuation of dexamfetamine sulfate may be necessary

Tics and Tourette’s Syndrome

• Dexamfetamine sulfate may trigger or worsen motor and verbal tics or Tourette’s syndrome
• Evaluate family history and screen for tics or Tourette’s before starting dexamfetamine sulfate
• Regularly monitor for tics during treatment, at every dose adjustment, and then at least every 6 months or at every visit

Anxiety, agitation, or tension

• Dexamfetamine sulfate can exacerbate pre-existing anxiety, agitation, or tension
• Perform clinical evaluations for these conditions before using dexamfetamine sulfate and monitor regularly during treatment, at every dose adjustment, and then at least every 6 months or at every visit

Bipolar disorder comorbidity

• Exercise caution when treating ADHD with dexamfetamine sulfate in patients with bipolar disorder due to the risk of triggering mixed/manic episodes
• Screen for bipolar risk, including a detailed psychiatric history and family history of suicide, bipolar disorder, and depression, before starting dexamfetamine sulfate
• Monitor closely for psychiatric symptoms at each dose adjustment, every 6 months, and at every visit

Growth concerns

• Long-term use of dexamfetamine sulfate may cause reduced weight gain and growth retardation in children
• The impact on final height and weight is still under study
• Regularly monitor growth: record height, weight, and appetite every 6 months and maintain a growth chart
• Consider interrupting treatment if expected growth or weight gain is not observed

Patients with anorexia nervosa

• Dexamfetamine sulfate should be administered with special caution in patients with anorexia nervosa due to potential appetite reduction

Use in patients with seizures

• Use dexamfetamine sulfate cautiously in patients with epilepsy
• Dexamfetamine sulfate may decrease the seizure threshold in patients with a history of seizures, prior EEG abnormalities, or even in those without such a history
• Discontinue dexamfetamine sulfate if seizure frequency increases or new-onset seizures occur

Monitoring for abuse and misuse

• Carefully monitor for risks of diversion, misuse, and abuse
• Should not be used in patients with known drug or alcohol dependency because of a potential for abuse, misuse, or diversion
• Risk is generally higher with short-acting stimulants compared to long-acting forms

Effects of chronic abuse

• Can lead to tolerance, psychological dependence, and abnormal behaviour
• Severe cases might involve psychosis, similar to schizophrenia, predominantly with parenteral abuse
• Chronic intoxication signs include severe skin issues, sleeplessness, confusion, hyperactivity, and personality changes
• Intracerebral bleeding and serious cardiovascular events like sudden death, cardiomyopathy, and myocardial infarction have been associated with misuse

Patient selection for treatment

• Consider patient age and history of substance use disorders, oppositional-defiant or conduct disorders, and bipolar disorder
• Use caution in emotionally unstable patients, particularly those with a history of substance dependence
• Non-stimulant treatments should be considered for high-risk substance abuse patients

Withdrawal considerations

• Supervise closely during withdrawal to monitor for depression and chronic overactivity (may require long-term follow up)
• Severe depression may occur upon withdrawal from abusive use
• Sudden cessation after prolonged high-dose use may result in extreme fatigue and EEG sleep changes

Misuse for fatigue prevention

• Dexamfetamine sulfate should not be used for preventing or treating normal fatigue states

Drug screening implications

• Dexamfetamine sulfate can cause a positive result for amphetamines in drug tests, especially with immunoassay screening

Haematological effects

• The long-term safety of dexamfetamine sulfate, especially regarding blood disorders, is not fully established
• In cases of leukopenia, thrombocytopenia, anaemia, or other significant blood changes, consider discontinuing treatment

Presence of isomalt

• Dexamfetamine sulfate contains isomalt
• Patients with rare hereditary fructose intolerance should not take dexamfetamine sulfate due to the presence of isomalt

Impact of dexamfetamine sulfate on driving and machinery operation

• Dexamfetamine sulfate may lead to dizziness, drowsiness, and visual disturbances like problems with accommodation, diplopia and blurred vision
• Patients should be informed about these potential effects. If experiencing these symptoms, patients should refrain from engaging in potentially hazardous activities, including driving or operating machinery

Not registered for use in adults. Safety and efficacy of dexamfetamine sulfate has not been established

Forms avail. in SA and covered in this monograph: tab

Registered indications and dosages in South Africa & other jurisdictions

Treatment should be under the supervision of a specialist in childhood and/or adolescent behavioural disorders

Attention deficit/hyperactivity disorder (ADHD) when response to previous methylphenidate treatment is considered clinically inadequate
- As part of a comprehensive treatment programme in children and adolescents aged 6-17 years, which typically includes psychological, educational and social measures

Younger than 6 years

• Not established for use

Between 6-17 years

• Oral (tab): Initial: 5mg, once or twice daily (e.g at breakfast and lunch); Titrate at weekly intervals by 5mg in the daily dose according to tolerability and the degree of efficacy observed; Max: 20mg/24hrs (doses of 40mg may in rare cases be necessary for optimum titration)

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Diagnosis should be made according to DSM-5 criteria or the guidelines in ICD-10 and should be based on a comprehensive multidisciplinary evaluation of the patient

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Careful dose titration is necessary at the start of treatment with dexamfetamine sulfate. Dose titration should be started at the lowest possible dose. The regimen that achieves satisfactory symptom control with the lowest total daily dose should be employed

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Tablets may be swallowed whole with the aid of liquids, or alternatively, in cases of swallowing problems the tablets can be divided. See Additional Prescribing Points for method of administration

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In the treatment of hyperkinetic disorders/ADHD, the times at which the doses of dexamfetamine sulfate are administered should be selected to provide the best effect when it is most needed to combat school and social behavioural difficulties. Normally the first increasing dose is given in the morning. Tablets should not be taken too late after lunch time to avoid disturbances of sleep

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Dexamfetamine sulfate is not indicated in all children with ADHD and the decision to use dexamfetamine sulfate must be based on a very thorough assessment of the severity and chronicity of the child’s symptoms in relation to the child’s age and potential for abuse, misuse or diversion

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Dose reduction and discontinuation
Treatment must be stopped if the symptoms do not improve after appropriate dosage adjustment over a one-month period. If paradoxical aggravation of symptoms or other serious adverse events occur, the dosage should be reduced or discontinued

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The decision to give dexamfetamine sulfate once or twice daily should be based on the course of symptoms at different times of the day

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For long-term use see Additional Prescribing Points

Pregnancy

South African recommendations

• Contraindicated
• Dexamfetamine sulfate is contraindicated during pregnancy
• Children of mothers who are dependent on amfetamine have been shown to be at an increased risk of premature birth and reduced birth weight
• Moreover, these children may develop withdrawal symptoms like dysphoria, including hyperexcitability and pronounced exhaustion
• Results of studies in animals suggest that high doses of dexamfetamine sulfate may elicit reproductive toxicity
• Women of childbearing age should discontinue the use of dexamfetamine sulfate when intending to become pregnant and should use reliable contraception when not planning to become pregnant

Recommendations in other jurisdictions

• Caution; not recommended
• There is a limited amount of data from the use of dexamfetamine in pregnant women
• Children of mothers who are dependent on amfetamine have been shown to be at an increased risk of premature birth and reduced birth weight
• Moreover, these children may develop withdrawal symptoms like dysphoria, including hyperexcitability and pronounced exhaustion
• Results of studies in animals suggest that high doses of dexamfetamine may elicit reproductive toxicity
• The use of dexamfetamine sulfate during pregnancy is not recommended
• Women of childbearing age should discontinue use when intending to become pregnant

Breastfeeding

South African recommendations

• Contraindicated
• Mothers who are breastfeeding their infants should not take dexamfetamine sulfate
• Dexamfetamine sulphate is excreted in human milk. A risk to the newborns/infants cannot be excluded
• A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from dexamfetamine sulfate therapy

Recommendations in other jurisdictions

• Caution; not recommended
• Dexamfetamine is excreted in human milk. A risk to the newborns/infants cannot be excluded
• A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from dexamfetamine sulfate therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman

Fertility

Recommendations below are applicable to South Africa and other jurisdictions

• No information available

Recommendations below are applicable to South Africa and other jurisdictions

• Caution; no information available
  There is no experience with the use of dexamfetamine sulfate in patients with renal insufficiency. Thus, dexamfetamine sulfate should be used with special caution in this patient group by taking care of titration and dosage

Recommendations below are applicable to South Africa and other jurisdictions

• Caution; no information available
  There is no experience with the use of dexamfetamine sulfate in patients with hepatic insufficiency. Thus, dexamfetamine sulfate should be used with special caution in this patient group by taking care of titration and dosage

Recommendations below are applicable to South Africa and other jurisdictions

• Not indicated for use in geriatrics
  Dexamfetamine sulfate should not be used in the elderly. Safety and efficacy have not been established in this age group

Blood and Lymphatic System Disorders

Very rare

• Anaemia
• Leukopenia
• Thrombocytopenia
• Thrombocytopenic purpura

Cardiac Disorders

Common

• Arrhythmia
• Palpitations
• Tachycardia

Rare

• Angina pectoris

Very rare

• Cardiac arrest

Not known

• Cardiomyopathy
• Myocardial infarction

Congenital, Familial and Genetic Disorders

Very rare

• Tourette's syndrome

Eye Disorders

Rare

• Difficulties in visual accommodation
• Blurred vision
• Mydriasis

Gastrointestinal Disorders

Common

• Abdominal pain and cramps
• Nausea and vomiting
• Dry mouth

Not known

• Ischaemic colitis
• Diarrhoea

General Disorders and Administration Site Conditions

Not known

• Chest pain
• Hyperpyrexia
• Fatigue
• Sudden death

Hepatobiliary Disorders

Very rare

• Abnormal liver ranging from hepatic enzyme elevations to hepatic coma

Immune System Disorders

Not known

• Hypersensitivity including angioedema and anaphylaxis

Investigations

Common

• Changes in blood pressure and heart rate (usually increases)

Metabolism and Nutrition Disorders

Very common

• Decreased appetite, reduced weight gain and weight loss (during prolonged use in children)

Not known

• Acidosis
• Toxic hypermetabolic state, characterised by
  - Transient hyperactivity
  - Hyperpyrexia
  - Acidosis
• - Death due to cardiovascular collapse

Musculoskeletal and Connective Tissue Disorders

Common

• Arthralgia

Rare

• Growth retardation (during prolonged use in children) 

Very rare

• Muscle cramps

Not known

• Rhabdomyolysis

Nervous System Disorders

Common

• Vertigo
• Dyskinesia
• Headache
• Hyperactivity

Rare

• Fatigue

Very rare

• Convulsions
• Choreoathetoid movements
• Intracranial haemorrhage

Not known

• Ataxia
• Dizziness
• Dysgeusia
• Concentration difficulties
• Hyperreflexia
• Stroke
• Tremor
• Withdrawal symptoms. Symptoms include
  - Dysphoric mood
  - Fatigue
  - Vivid and unpleasant dreams
  - Insomnia or hypersomnia
  - Increased appetite
  - Psychomotor retardation or agitation
  - Anhedonia
  - Drug craving

Very rarely

• Neuroleptic malignant syndrome (NMS)

Psychiatric Disorders

Very common

• Insomnia
• Nervousness

Common

• Abnormal behaviour
• Aggression
• Excitation
• Anorexia
• Anxiety
• Depression
• Irritability

Very rare

• Hallucinations
• Psychosis/ psychotic reactions
• Suicidal behaviour (including completed suicide)
• Tics, worsening of pre-existing tics

Not known

• Confusion
• Dependence
• Dysphoria
• Emotional lability
• Euphoria
• Impaired cognitive test performance
• Altered libido
• Night terrors
• Obsessive-compulsive behaviour
• Panic states
• Paranoia
• Restlessness

Renal and Urinary Disorders

Not known

• Renal damage

Reproductive System and Breast Disorders

Not known

• Impotence

Skin and Subcutaneous Tissue Disorders

Rare

• Rash
• Urticaria

Very rare

• Erythema multiforme
• Exfoliative dermatitis
• Fixed drug eruption

Not known

• Sweating
• Alopecia

Vascular Disorders

Very rare

• Cerebral vasculitis and/or occlusion

Not known

• Cardiovascular collapse
• Raynaud's phenomenon

• Monoamine oxidase inhibitors
• Cytochrome P450 (CYP) substrates (with narrow therapeutic index)
• Potent inhibitors or inducers of CYP enzymes
• Agents lowering blood levels of amfetamines
• Gastrointestinal acidifying agents
• Guanethidine
• Reserpine
• Glutamic acid HCl
• Ascorbic acid
• Agents that increase blood levels of amfetamines
• Urinary acidifying agents
• Ammonium chloride
• Sodium acid phosphate
• Gastrointestinal alkalinizing agents
• Sodium bicarbonate
• Urinary alkalinizing agents
• Acetazolamide
• Some thiazides
• Clonidine
• Agents whose effects may be reduced by amfetamines
• Antihistamines
• Beta-blockers
• Opiates
• Agents whose effects may be increased by amfetamines
• Halogenated narcotics
• Tricyclic antidepressants
• Vasopressors
• Noradrenaline
• Meperidine
• Morphine
• Agents that may increase the effects of amfetamines
• Coumarin anticoagulants
• Anticonvulsants
• Phenobarbital
• Phenytoin
• Primidone
• Some antidepressants (tricyclics and selective serotonin reuptake inhibitors)
• Disulfiram
• Agents that may reduce the effects of amfetamines
• Adrenergic blockers
• Propranolol
• Lithium
• α-Methyltyrosine
• Haloperidol
• Ethosuximide
• Phenothiazines
• Chlorpromazine

Other interactions

• Alcohol
• Fruit juices

• Cardiovascular status
  - At baseline
  - Any patient who develops exertional chest pain, unexplained syncope, and any symptom of cardiac disease during treatment with stimulants
• Blood pressure
• Heart rate
• Growth rate
  - Height
  - Weight

Additional observations

• Psychiatric status
  - Pre-existing psychiatric disorders, including depression and aggressive behaviour
• Appetite
• Assess for risk of diversion, misuse and abuse of dexamfetamine before prescribing
• Assess family history and evaluate for tics or Tourette syndrome prior to initiation of therapy
• Assess for emergence or worsening of tics
• Signs of peripheral vasculopathy (eg, digital changes)
• Sleep and behavioural changes

Long-term use

• Long-term usefulness of dexamfetamine sulfate for extended periods (over 12 months) in children and adolescents with ADHD should be periodically re-evaluated for the individual patient with trial periods off medication to assess the patient’s functioning without pharmacotherapy
• It is recommended that dexamfetamine sulfate is de-challenged at least once yearly to assess the child’s condition (preferably during times of school holidays)
• Improvement may be sustained when the medicine is either temporarily or permanently discontinued

Method of administration

• The tablet score lines enable division of the tablet into four parts
• For division, the tablet is placed onto a hard surface with its cross-scored, convex side downwards and is then pushed carefully with the index finger at the centre of its top side. The tablet then breaks into four parts
• Drinking some fluids, e.g. water, should follow the intake of the divided tablets
• The effect of food on the absorption of dexamfetamine sulfate has not been studied; therefore, a possible effect of food on absorption cannot be excluded
• Therefore, it is recommended that dexamfetamine sulfate tablets should be taken in a standardised manner in relation to the timing of meals, i.e. that doses should be given at the same times, relative to the time of meals, on each day, preferably with or immediately after meals
• Therefore, it is recommended that dexamfetamine sulfate should be taken in a standardised manner in relation to the timing of meals, i.e. that doses should be given at the same times, relative to the time of meals, on each day, preferably with or immediately after meals

Dexamfetamine sulfate is a sympathomimetic amine with a central stimulant and anorectic activity.

Tablet 5mg

• Amfexa 5mg (Adcock Ingram) originator

Tablet 10mg

• Amfexa 10mg (Adcock Ingram) originator

Tablet 20mg

• Amfexa 20mg (Adcock Ingram) originator