Medikinet® CR 40 mg: composition and pharmaceutical form
Medikinet® CR 40 mg are hard capsules with modified release. One capsule contains 40 mg of methylphenidate hydrochloride, which corresponds to 34.60 mg of methylphenidate. The range also includes capsules of 5, 10, 20 and 30 mg.
Half the dose is released at once, the other half gradually. The capsule is taken in the morning during breakfast or after it; it can be swallowed whole with liquid, or its contents can be tipped into a teaspoon of apple purée, taken immediately and washed down with water — such a mixture must not be kept. Neither the capsules nor their contents may be chewed or crushed. The composition includes sucrose, so the medicine is not suitable in hereditary fructose intolerance, glucose-galactose malabsorption syndrome and sucrase-isomaltase deficiency.
How Medikinet® CR 40 mg works
Methylphenidate is a mild stimulant of the central nervous system that influences the psyche more noticeably than motor activity. Its mechanism in humans is not fully understood: it is assumed to work through cortical stimulation and, probably, activation of the reticular formation, blocking the reuptake of noradrenaline and dopamine by the presynaptic neuron and increasing the release of monoamines into the extracellular space. The medicine is a racemic mixture of the d- and l-threo enantiomers, of which the d enantiomer is pharmacologically more active.
The plasma concentration curve has two phases. The immediate-release part of the capsule dissolves quickly and gives the first peak, and after the passage from the stomach into the small intestine the second half of the dose is released — after about 3 hours the concentration rises again. As a result a plateau of 3–4 hours is formed, during which the concentration does not fall below 75% of the maximum, and the therapeutic level holds for about 8 hours — which corresponds to a school day rather than to a whole day. The amount of methylphenidate absorbed with once-daily dosing is comparable to two doses of the conventional forms. Fatty food delays absorption by about 1.5 hours, but the bioavailability is the same with an ordinary and with a high-calorie breakfast: taking the capsule with food is obligatory, and the composition of the breakfast does not matter.
Indications
The medicine is used as part of a comprehensive programme for the treatment of attention deficit hyperactivity disorder (ADHD) in children from 6 years, when other measures have proved insufficient. Treatment is started under the supervision of a doctor specialising in behavioural disorders in children.
The diagnosis must meet the DSM criteria or the ICD-10 recommendations and rest on a full history and an assessment of the condition — the presence of one or several symptoms is not enough, and there is no single diagnostic test for ADHD. The comprehensive programme includes psychological, educational and social work alongside drug therapy, and its aim is to stabilise the condition of a child with a chronic inability to hold attention, distractibility, emotional instability, impulsivity and hyperactivity.
Method of use and dosage
Before the medicine is prescribed, the state of the cardiovascular system is assessed with measurement of blood pressure and pulse, a full history is taken — the medicines being used, past and current physical and mental disorders, cases of sudden cardiac or unexplained death in the family — and the child's baseline height and weight are recorded (in adults only the weight). The dose is built up cautiously, starting with the lowest, and the aim is the minimum daily dose that gives satisfactory control of the symptoms. Children should not take the medicine too late in the morning: this disturbs sleep.
| Group of patients | Dose titration scheme |
|---|---|
| Children from 6 years, start of treatment | One usually starts with the immediate-release form, 5 mg 1–2 times a day, increasing by 5–10 mg a week; a start with 10 mg of this medicine once a day is also possible |
| Children, maximum | 60 mg of methylphenidate hydrochloride a day |
| Adults continuing treatment from childhood | The same daily dose, with regular review |
| Adults starting treatment | 10 mg a day, an increase of 10 mg a week; the daily dose is split into two — morning and midday |
| Adults, maximum | No more than 1 mg per kg of body weight and no more than 80 mg a day |
| Children under 6 and people over 60 | The medicine is not used — safety and efficacy have not been established |
Replacing the conventional forms and the length of treatment
The 10 mg capsule delivers 5 mg of methylphenidate hydrochloride at once and gradually releases another 5 mg, so 20 mg of the medicine replaces 10 mg of the immediate-release form at breakfast plus 10 mg at lunch: a midday dose is not needed. If the effect ends too early in the evening and the behavioural disturbances return, the question of a small additional dose of the conventional form is settled by the doctor, weighing it against the risk of difficulty falling asleep. Therapy should not be open-ended: with treatment lasting more than 12 months the doctor periodically withdraws the medicine — in children better during the holidays — in order to assess the condition without it, and treatment can usually be stopped during or after puberty. If after a month on a correctly chosen dose the symptoms have not eased, treatment is stopped; with a paradoxical intensification of the symptoms or serious undesirable reactions the dose is reduced or the medicine is withdrawn.
Contraindications
Medikinet® CR 40 mg is not prescribed in the following cases:
- hypersensitivity to methylphenidate or to any excipient;
- marked anxiety, tension or agitation — the medicine intensifies them;
- glaucoma, hyperthyroidism and thyrotoxicosis;
- severe angina pectoris, arrhythmia, severe hypertension, heart failure, myocardial infarction;
- current severe depression, psychotic symptoms, a psychopathic personality structure, aggression in the history or suicidal tendencies;
- established drug dependence or alcoholism;
- use of non-selective irreversible MAO inhibitors now or in the preceding 14 days — the risk of hypertensive crisis and hyperthermia;
- motor tics in the patient or in their siblings, Tourette's syndrome in the patient or in the family, pregnancy, and also a prolonged absence of gastric acidity with a pH above 5.5, the use of H2 receptor antagonists or of antacids.
Special warnings and precautions
Methylphenidate is not suitable for every case of ADHD: the decision depends on the doctor's assessment of the severity of the symptoms and their correspondence to the child's age, not on the presence of one or several behavioural features. Where the symptoms are linked to an acute reaction to stress the medicine is usually not indicated; nor is it prescribed to overcome ordinary tiredness. In children with psychotic disorders it can intensify disturbances of behaviour and thought, and in severe depression, with suicidal thoughts and tendencies, it is used with caution because of the risk of worsening those symptoms.
- with prolonged use of stimulants in children, slowed growth and insufficient weight gain have been described: the parameters of development are monitored, and if there is a lag the medicine is stopped temporarily;
- blood pressure is checked regularly in all patients, especially in hypertension;
- an intensification of motor and vocal tics and of Tourette's syndrome has been reported — their presence is assessed before treatment begins;
- methylphenidate reduces the appetite — caution is needed in anorexia nervosa;
- in emotionally unstable patients, including those with dependence in their history, there is a risk of them raising the dose on their own; prolonged abuse leads to tolerance and psychological dependence, and by the parenteral route to psychotic episodes;
- the medicine can lower the seizure threshold where there is a history of seizures and EEG changes, and very rarely without such a background; if fits appear, treatment is stopped;
- during prolonged therapy a full blood count with differential and a platelet count are done periodically;
- after withdrawal the patient is watched closely: depression and chronic hyperactivity may appear, and sometimes the monitoring has to be a long one.
There is no experience of use in impaired kidney or liver function. Women of childbearing age should use reliable contraception during treatment. The medicine causes dizziness and drowsiness, which significantly affects the ability to drive a car and to operate machinery. In athletes its use may give a positive result in a test for psychostimulants.
Drug interactions
Combination with non-selective irreversible MAO inhibitors is contraindicated — now and for two weeks after their withdrawal — because of the risk of a hypertensive crisis. With agents that constrict the vessels and raise blood pressure the medicine is combined cautiously. It is not known how methylphenidate affects the plasma concentrations of other medicines, so caution is needed with all medicines of narrow therapeutic range.
Cases have been described in which methylphenidate inhibited the metabolism of coumarin anticoagulants, of anticonvulsants — phenobarbital, phenytoin, primidone — and of some antidepressants; their doses sometimes have to be reduced, and at the start and on stopping the combined use the plasma concentrations or the clotting parameters should be monitored. Serious adverse events, including cases of sudden death, have been reported with the concomitant use of clonidine, although a causal relationship has not been established; the safety of such a combination has not been studied systematically. Interactions with antipsychotics — haloperidol and thioridazine — are possible, and methylphenidate can weaken the hypotensive action of guanethidine. Combination with H2 receptor antagonists and antacids is prohibited: they speed up the release of the whole dose of the active substance. Alcohol intensifies the undesirable effects of psychoactive agents, so it is excluded during treatment. Before a planned operation with halogenated anaesthetics the medicine is not taken on the day of the procedure, because of the risk of a sharp rise in blood pressure.
Pregnancy and breastfeeding
Data on the use of methylphenidate in pregnancy are scarce, and animal studies showed a toxic effect on reproductive function; the potential risk to humans is unknown. Use of the medicine during pregnancy is contraindicated, and women of childbearing age are advised to use reliable contraception for the duration of treatment.
Whether methylphenidate and its metabolites pass into breast milk is unknown. For safety reasons the decision on whether to stop breastfeeding or the medicine is taken with the importance of the treatment for the mother in mind.
Adverse effects
Nervousness and insomnia are very common reactions at the start of treatment, and they can usually be reduced by lowering the dose. Reduced appetite is also common but as a rule passes.
- very common — insomnia and nervousness;
- common — unusual behaviour, aggression, agitation, restlessness, depression, irritability, loss of appetite;
- common — dizziness, drowsiness, dyskinesia, headache, excessive activity;
- common — arrhythmia, palpitations, tachycardia, changes in blood pressure and pulse rate, usually upwards;
- common — abdominal pain, nausea and vomiting, more often at the start of treatment and milder when taken with food, dry mouth, joint pain;
- common — hair loss, itching, rash, urticaria, fever;
- rare — angina pectoris, disturbances of accommodation and vision, delayed development with prolonged use in children;
- very rare — seizures, choreoathetoid movements, hallucinations, psychotic disorders, suicidal behaviour, tics or their intensification, anaemia, leucopenia, thrombocytopenia, impaired liver function up to hepatic coma, erythema multiforme, exfoliative dermatitis, inflammation or blockage of a cerebral artery, cardiac arrest and sudden death.
Very rarely, poorly documented reports of neuroleptic malignant syndrome were received; in most of those cases the patients were also receiving other medicines, so the role of methylphenidate remains unclear.
Overdose
In treating an overdose it is taken into account that methylphenidate from this form is released over a long period. Acute poisoning is linked mainly to excessive stimulation of the central and sympathetic nervous system: vomiting, agitation, tremor, hyperreflexia, muscle twitching, seizures followed by coma, euphoria, confusion, hallucinations, delusions, profuse sweating, flushes, headache, very high fever, tachycardia, palpitations, rhythm disturbances, raised blood pressure, dilated pupils and dry mucous membranes are possible.
There is no specific antidote. Treatment comes down to supportive measures and to protecting the patient from self-injury and from external stimuli that would intensify the overexcitation. If the symptoms are not too severe and the patient is conscious, removal of the stomach contents may be considered — inducing vomiting or lavage; in severe poisoning a carefully chosen dose of a short-acting barbiturate is given before the lavage. Intensive care may be needed to support the circulation and breathing and, with a very high temperature, external cooling. The efficacy of peritoneal dialysis and haemodialysis in methylphenidate overdose has not been established.
How to get a prescription for Medikinet® CR 40 mg online
Methylphenidate is dispensed on prescription, and prescribing it calls for an established diagnosis of ADHD, an assessment of the state of the heart and the psyche and correct dose selection by a specialist.
During the online consultation the doctor will go through the medical history, the previous regimens and the results of investigations and, if there are indications and no contraindications, will issue an electronic prescription — the medicine can be collected from a pharmacy using its code.
