Ritalin/Ritalin LA

Ritalin/Ritalin LA Special Precautions

methylphenidate

Manufacturer:

Novartis

Distributor:

Zuellig
/
Four Star
Full Prescribing Info
Special Precautions
General: Treatment with methylphenidate is not indicated in all cases of ADHD and should be considered only after detailed  history taking and evaluation of the patient. The decision to prescribe methylphenidate should depend on the physician's assessment of the chronicity and severity of the symptoms and in paediatric patients, the appropriateness to the child's age. Prescription should not depend solely on the presence of isolated behavioural characteristics. When the symptoms are associated with acute stress reactions, treatment with methylphenidate is usually not indicated.
Sudden Death and Pre-exisiting Structural Cardiac Abnormalities or Other Serious Heart Problems: It is essential that patients with pre-existing structural cardiac abnormalities or other serious heart problems being considered for treatment are assessed by a cardiologist before initiating treatment. On-going cardiological supervision should be maintained throughout treatment in these patients.
Children and Adolescents: Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems.
Stimulant products, including methylphenidate, generally should not be used in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may increase the risk of sudden death due to the sympathomimetic effects of a stimulant drug. Before initiating methylphenidate treatment, patients should be assessed for pre-existing cardiovascular disorders and a family history of sudden death and ventricular arrhythmia (see Dosage & Administartion).
Adults: Sudden death, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs.
Cardiovascular Conditions: Ritalin is contraindicated in patients with severe hypertension. Ritalin increases heart rate and systolic and diastolic blood pressure. Therefore, caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, e.g., those with pre-existing hypertension. Severe cardiovascular disorders are contraindicated (see Contraindications).
Methylphenidate should be used cautiously in patients with hypertension. Blood pressure should be monitored at appropriate intervals in all patients taking methylphenidate, especially in those with hypertension. Patients who develop symptoms suggestive of cardiac disease during methylphenidate treatment should undergo a prompt cardiac evaluation.
Children, adolescents, or adults who are being considered for treatment with stimulant medicine should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further cardiac evaluation if findings suggest such disease. 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.
Misuse and Cardiovascular Events: Misuse of stimulants of the central nervous system, including methylphenidate may be associated with sudden death and other serious cardiovascular adverse events.
Cerebrovascular: Cerebrovascular Conditions: Patients with pre-existing central nervous system (CNS) abnormalities, e.g., cerebral aneurysm and/or other vascular abnormalities such as vasculitis or pre-existing stroke should not be treated with Ritalin. Patients with additional risk factors (history of cardiovascular disease, concomitant medicine that elevates blood pressure) should be assessed regularly for neurological/psychiatric signs and symptoms after initiating treatment with Ritalin (see Cardiovascular Conditions and Interactions).
Psychiatric Conditions: Ritalin should not be used to treat severe depression or for the prevention or treatment of normal fatigue states. In psychotic patients, administration of methylphenidate may exacerbate symptoms of behaviour disturbance and thought disorder. Co-morbidity of psychiatric disorders in ADHD is common and should be taken into account when prescribing stimulant products. Prior to initiating treatment with methylphenidate, patients should be assessed for pre-existing psychiatric disorders and a family history of psychiatric disorders (see Dosage & Administration).
Treatment of ADHD with stimulant products including Ritalin should not be initiated in patients with acute psychosis, acute mania, or acute suicidality. These acute conditions should be treated and controlled before ADHD treatment is considered. Methylphenidate should not be used as treatment for severe depression of either exogenous or endogenous origin.
In the case of emergent psychiatric symptoms or exacerbation of pre-existing psychiatric symptoms, Ritalin should not be given to patients unless the benefit outweighs the potential risk.
Psychotic Symptoms: Psychotic symptoms, including visual and tactile hallucinations or mania have been reported in patients administered usual prescribed doses of stimulant products, including Ritalin (see Adverse Reactions). Physicians should consider treatment discontinuation if psychotic symptoms occur.
Bipolar Illness: Particular care should be taken in using stimulants to treat ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in such patients.
Aggressive Behaviour: Emergent aggressive behaviour or an exacerbation of baseline aggressive behaviour has been reported during stimulant therapy, including Ritalin. However patients with ADHD may experience aggression as part of their medical condition. Therefore, causal association with treatment is difficult to assess. Physicians should evaluate the need for adjustment of treatment regimen in patients experiencing these behavioural changes, bearing in mind that upwards or downwards titration may be appropriate. Treatment interruption can be considered.
Suicidal Tendency: Patients with emergent suicidal ideation and behaviour during treatment for ADHD should be evaluated immediately by their physician. The physician should initiate appropriate treatment of the underlying psychiatric condition and consider a possible change in the ADHD treatment regimen.
Motor and Verbal Tics: CNS stimulants, including methylphenidate, have been associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourette's syndrome has also been reported (see Adverse Reactions). Therefore, clinical evaluation for tics in patients should precede use of stimulant medicine. Family history should be assessed and clinical evaluation for tics or Tourette's syndrome in patients should precede use of methylphenidate for ADHD treatment. Ritalin is contraindicated in case of diagnosis or family history of Tourette's syndrome (see Contraindications). Patients should be regularly monitored for the emergence or worsening of tics during treatment with methylphenidate.
Growth Retardation: Moderately reduced weight gain and slight growth retardation have been reported with the long term use of stimulants, including methylphenidate, in children (see Adverse Reactions). Growth should be monitored as clinically necessary during treatment with methylphenidate, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.
Careful follow up of weight and height in children aged 7 to 10 years who were randomised to either methylphenidate or non-medicine treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medicine treated children over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated children (i.e. treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development.
Published data are inadequate to determine whether chronic use of amphetamines may cause similar suppression of growth, however, it is anticipated that they likely have this effect as well. Therefore, growth should be monitored during treatment with stimulants, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.
The retardation of growth referred to under Adverse Reactions is usually followed by catch-up growth when the medicine is discontinued. In order to minimise such complications, drug-free periods over weekends, school holidays and long vacations are advocated by some specialists.
Fatigue: Methylphenidate should not be employed for the prevention or treatment of normal fatigue states.
Seizures: There is some clinical evidence that methylphenidate may lower the convulsion threshold in patients with a history of seizures, with prior EEG abnormalities in the absence of seizures and, rarely, in the absence of a history of seizures and no prior EEG evidence of seizures. Safe concomitant use of anticonvulsants and methylphenidate has not been established.  In the presence of seizures, the drug should be discontinued.
Priapism: Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate products in both pediatric and adult patients. Priapism was not reported with drug initiation but developed after some time on the drug, often subsequent to an increase in dose. Priapism has also appeared during a period of drug withdrawal (drug holidays or discontinuation). Patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.
Drug Abuse and Dependence: Caution  is called for in emotionally unstable patients, such as those with a history of drug or alcohol dependence, because they may increase the dosage on their own initiative. Chronic abuse can lead to marked tolerance and psychological dependence with varying degrees of abnormal behaviour. Frank psychotic episodes may occur, especially in response to parenteral abuse.
Clinical data indicate that children given Ritalin are not more likely to abuse drugs as adolescents or adults. Methylphenidate abuse or dependence does not appear to be a problem in adolescents or adults who were treated with methylphenidate for ADHD as children.
Use with Alcohol: Alcohol may exacerbate the CNS adverse reactions of psychoactive drugs, including methylphenidate. Therefore, it is advisable for patients to abstain from alcohol during treatment.
Withdrawal: Careful supervision is required during drug withdrawal, since this may unmask depression as well as the effects of chronic over-activity. Some patients may require long-term follow-up.
Haematological Effects: Data on safety and efficacy of long-term use of methylphenidate are not complete. Patients requiring long-term therapy should be carefully monitored and periodic complete blood counts, differential and platelet counts are advisable during prolonged therapy. In the event of haematological disorders appropriate medical intervention should be considered (see Adverse Reactions).
Carcinogenicity: In a lifetime carcinogenicity study carried out in B6C3F1 mice, methylphenidate caused an increase in hepatocellular adenomas and, in males only, an increase in hepatoblastomas at a daily dose of approximately 60 mg/kg/day. This dose is approximately 4 times the maximum recommended human dose of methylphenidate on a mg/m2 basis.  Hepatoblastoma is a relatively rare rodent malignant tumour type. The mouse strain used is sensitive to the development of hepatic tumours, and the significance of these results to humans is unknown. Methylphenidate did not cause any increases in tumours in a lifetime carcinogenicity study carried out in F344 rats; the highest dose used was approximately 50 mg/kg/day, which is approximately 7 times the maximum recommended human dose of methylphenidate on a mg/m2 basis.
In a 24-week carcinogenicity study in the transgenic mouse strain p53+/-, there was no evidence of carcinogenicity. Male and female mice were fed diets containing the same concentration of methylphenidate as in the lifetime carcinogenicity study; approximately 60 and 74 mg/kg/day of methylphenidate, respectively, which is approximately 4 and 5 times the maximum recommended human dose of methylphenidate on a mg/m2 basis, respectively.
Comment: The US Food and Drug Administration examined data from the Surveillance, Epidemiology and End Results (SEER) database for the years 1973 to 1991 and found that the estimated incidence of hepatoblastoma in the general population was not greater than 1 in 10 million person-years.
A total of 174 cases of hepatoblastoma were reported by the SEER for the period 1973 to 1995. The age-adjusted incidence rate is very low (IR=0.0382 per 100,000 person-years). The majority of cases (149 out of 174) were diagnosed among the age group 0 to 4 years old, which is in accordance with the natural history of the disease.  For the age group 5 to 24 years old the rates of hepatoblastoma are very low with 14 cases reported.  For the 0 to 4 years old age group, incidence rates of hepatoblastoma have risen slowly, ranging from 0.3032 per 100,000 in 1973 to 0.4889 per 100,000 in 1995. On the basis of experience since marketing Ritalin, there is no evidence that the incidence is higher in patients receiving Ritalin.
Genotoxicity: Methylphenidate was not mutagenic in assays in vitro (Ames reverse mutation assay and the mouse lymphoma cell forward mutation assay). Methylphenidate showed evidence of a weak clastogenic response in vitro (Chinese Hamster Ovary cells) but was negative in vivo (mouse bone marrow micronucleus assay).
Effects on Fertility: Methylphenidate did not impair fertility in male or female mice that were fed diets containing the drug in an 18-week Continuous Breeding study. The study was conducted at doses up to 160 mg/kg/day, approximately 11-fold the highest recommended human dose of methylphenidate on a mg/m2 basis.
Women of Child-bearing Potential: There is no special recommendation in women of child-bearing potential. For women planning to become pregnant, see Use in Pregnancy.
Effects on Ability to Drive or Operate Machinery: Ritalin may cause dizziness, drowsiness, blurred vision, hallucinations or other CNS side effects (see Adverse Reactions). Patients experiencing such side effects should refrain from driving, operating machinery, or engaging in other potentially hazardous activities.
Use in Children: Methylphenidate should not be used in children under 6 years of age, since safety and efficacy in this age group have not been established. Medicines should be kept out of the reach of children.
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