a) SUDDEN DEATH

a) In a review of methylphenidate exposures reported to poison centers, the majority of cases resulted in minimal or minor toxicity. Of those who developed major effects, tachycardia and hypertension were the most commonly reported (Foley et al, 2000).
b) CASE REPORT: A 7-year-old girl presented with agitation, hyperactivity, talkativeness, hallucinations, tachycardia, and hypertension after ingesting 25 methylphenidate tablets (5 mg each). Treatment with multiple doses of IV midazolam (total dose: 1.5 mg/kg) provided some transient resolution of her symptoms. However, her symptoms returned 4 hours later and because of concerns for airway stability after high doses of midazolam, dexmedetomidine (initial dose: 0.5 mcg/kg/hr infusion for 4 hours; weaned by 0.1 mcg/kg every 30 minutes) was used to manage her agitation and cardiovascular symptoms. Her condition gradually improved and she was discharged after 18 hours of observation (Bagdure et al, 2013).
c) CASE REPORT: An 8-year-old girl with ADHD who was taking immediate-release methylphenidate 5 mg twice daily, developed mild hypertension and tachycardia, confusion, irritability, and agitation after ingesting 210 mg (8.74 mg/kg) of methylphenidate in a suicide attempt. Despite supportive therapy, his symptoms worsened and she developed hallucinations and delusion. Following treatment with phenobarbital, her symptoms gradually resolved and she was discharged the next day (Fettahoglu et al, 2009).
d) CASE REPORT: A 33-year-old man developed tachycardia after ingesting methylphenidate 30 mg (Bruggisser et al, 2011).
e) CASE REPORT: Agitation, tachycardia (heart rate, 170 beats/min), hypertension, and hallucinations developed in a 28-year-old man after ingesting 270 mg of methylphenidate (Bruggisser et al, 2011).
f) CASE REPORT: A 14-year-old girl with ADHD intentionally ingested 1134 mg (recommended maximum dose: 60 to 90 mg/day) of extended-release methylphenidate and presented to the emergency department approximately 2 hours later with agitation, visual hallucinations, hypertension (155/97 mmHg), and sinus tachycardia (130 to 140 beats/minute). She was treated with 30 g of activated charcoal and IV hydration. Three days after admission she had recovered fully and was transferred to a psychiatric inpatient facility for further treatment (Klampfl et al, 2010).
g) CASE REPORT: A 17-year-old girl with ADHD who intentionally ingested 270 mg (usual daily dose: 10 to 60 mg) of extended-release methylphenidate arrived at the emergency department approximately 3 hours after ingestion. Tachycardia (132 beats/minute) was noted on exam but she remained otherwise stable. After 12 hours of observation she was discharged without sequelae (Ozdemir et al, 2010).
h) NOPAINE (ETHYLPHENIDATE): Ethylphenidate (ethyl 2-phenyl-2-(piperidin-2-yl)acetate), an analogue of methylphenidate, is sold under the street name Nopaine. It is a psychostimulant that inhibits reuptake of both dopamine and norepinephrine (Bailey et al, 2015).

a) Hypertension has occurred following overdose and appears to be dose-related (Gahr & Kolle, 2014; Klein-Schwartz, 2002).
b) CASE REPORT: An 8-year-old girl with ADHD who was taking immediate-release methylphenidate 5 mg twice daily, developed mild hypertension and tachycardia, confusion, irritability, and agitation after ingesting 210 mg (8.74 mg/kg) of methylphenidate in a suicide attempt. Despite supportive therapy, his symptoms worsened and she developed hallucinations and delusion. Following treatment with phenobarbital, her symptoms gradually resolved and she was discharged the next day (Fettahoglu et al, 2009).
c) CASE REPORT: A 7-year-old girl presented with agitation, hyperactivity, talkativeness, hallucinations, tachycardia, and hypertension after ingesting 25 methylphenidate tablets (5 mg each). Treatment with multiple doses of IV midazolam (total dose: 1.5 mg/kg) provided some transient resolution of her symptoms. However, her symptoms returned 4 hours later and because of concerns for airway stability after high doses of midazolam, dexmedetomidine (initial dose: 0.5 mcg/kg/hr infusion for 4 hours; weaned by 0.1 mcg/kg every 30 minutes) was used to manage her agitation and cardiovascular symptoms. Her condition gradually improved and she was discharged after 18 hours of observation (Bagdure et al, 2013).
d) CASE REPORT: Agitation, tachycardia (heart rate, 170 beats/min), hypertension (systolic BP, 160 mm Hg), and hallucinations developed in a 28-year-old man after ingesting 270 mg of methylphenidate (Bruggisser et al, 2011).
e) In two retrospective reviews of methylphenidate exposure, hypertension was commonly reported among patients who developed significant toxicity (Foley et al, 2000; Hopkins et al, 1999).
f) CASE REPORT: A 14-year-old girl with ADHD intentionally ingested 1134 mg (recommended maximum dose: 60 to 90 mg/day) of extended-release methylphenidate and presented to the emergency department approximately 2 hours later with agitation, visual hallucinations, hypertension (155/97 mmHg), and sinus tachycardia (130 to 140 beats/minute). She was treated with 30 g of activated charcoal and IV hydration. Three days after admission she had recovered fully and was transferred to a psychiatric inpatient facility for further treatment (Klampfl et al, 2010).
g) NOPAINE (ETHYLPHENIDATE): Ethylphenidate (ethyl 2-phenyl-2-(piperidin-2-yl)acetate), an analogue of methylphenidate, is sold under the street name Nopaine. It is a psychostimulant that inhibits reuptake of both dopamine and norepinephrine (Bailey et al, 2015).

a) Pulmonary hypertension was suggested in 9 of 21 patients aged 35 to 54 years with pulmonary emphysema associated with methylphenidate injection (Stern et al, 1994).

a) Myocardial infarction has been reported in adults taking stimulant drugs at therapeutic doses for ADHD (Prod Info RITALIN(R) oral tablets, 2006; Prod Info FOCALIN(R) oral tablets, 2006).

a) Myocardial ischemia has been reported following elevated doses of methylphenidate.

a) CASE REPORT: A 19-year-old man suffered full cardiopulmonary arrest after inhaling crushed methylphenidate tablets. He sustained severe hypoxic brain damage and subsequently developed fever, tachycardia, and elevated CK-MB concentrations. Echocardiography revealed left ventricular segmental hypokinesis with low ejection fraction, consistent with a congestive cardiomyopathy or global myocardial ischemia. He died 16 hours later. Autopsy revealed cardiac lesions that were similar to catecholamine cardiomyopathy without the contraction bands. Concentrations of ritalinic acid (the principal metabolite of methylphenidate) were 2 to 3 times the therapeutic concentrations upon admission and postmortem (Massello & Carpenter, 1999b).

a) Angina pectoris was reported during post-marketing experience with methylphenidate hydrochloride extended-release (Prod Info CONCERTA(R) extended-release oral tablets, 2008).

a) Bradycardia was reported during post-marketing experience with methylphenidate hydrochloride extended-release (Prod Info CONCERTA(R) extended-release oral tablets, 2008).

a) Supraventricular tachycardia and ventricular extrasystoles were reported during post-marketing experience with methylphenidate hydrochloride extended-release (Prod Info CONCERTA(R) extended-release oral tablets, 2008).

a) LACK OF EFFECT: In a retrospective observational 7-year study of 23 methylphenidate overdoses (median dose ingested, 120 mg; range 40 to 1500 mg) in adults (mean age, 27.8 years; range 14 to 53 years), dysrhythmias did not develop in any patient (Hill et al, 2010).

a) Raynaud's phenomenon was reported during post-marketing experience with methylphenidate hydrochloride extended-release (Prod Info CONCERTA(R) extended-release oral tablets, 2008).

a) In a retrospective observational 7-year study of 23 methylphenidate overdoses (median dose ingested, 120 mg; range 40 to 1500 mg) in adults (mean age, 27.8 years; range 14 to 53 years), palpitations developed in 12% of patients (Hill et al, 2010).
b) NOPAINE (ETHYLPHENIDATE): Ethylphenidate (ethyl 2-phenyl-2-(piperidin-2-yl)acetate), an analogue of methylphenidate, is sold under the street name Nopaine. It is a psychostimulant that inhibits reuptake of both dopamine and norepinephrine (Bailey et al, 2015).

a) In a retrospective observational 7-year study of 23 methylphenidate overdoses (median dose ingested, 120 mg; range 40 to 1500 mg) in adults (mean age, 27.8 years; range 14 to 53 years), chest pain developed in 8% of patients (Hill et al, 2010).

a) Tachypnea has been reported after intravenous injection of methylphenidate (Stecyk et al, 1985; Anon, 1989; Chan et al, 1994).

a) Intravenous use of methylphenidate for a mean of 6.7 years was associated with severe obstructive lung disease in six patients less than 41 years of age (Sherman et al, 1987).
b) Methylphenidate injection was associated with panlobular pulmonary emphysema in a symmetric, basilar distribution in 21 patients aged 35 to 54 years (Stern et al, 1994).

a) Anxiety has occurred in 8.2% of adult patients on methylphenidate hydrochloride extended-release (n=415) compared with 2.4% of patients on placebo (n=212), in 2 double-blind, placebo-controlled clinical trials (Prod Info CONCERTA(R) extended-release oral tablets, 2008).

a) CASE REPORT: A 7-year-old girl presented with agitation, hyperactivity, talkativeness, hallucinations, tachycardia, and hypertension after ingesting 25 methylphenidate tablets (5 mg each). Treatment with multiple doses of IV midazolam (total dose: 1.5 mg/kg) provided some transient resolution of her symptoms. However, her symptoms returned 4 hours later and because of concerns for airway stability after high doses of midazolam, dexmedetomidine (initial dose: 0.5 mcg/kg/hr infusion for 4 hours; weaned by 0.1 mcg/kg every 30 minutes) was used to manage her agitation and cardiovascular symptoms. Her condition gradually improved and she was discharged after 18 hours of observation (Bagdure et al, 2013).
b) CASE REPORT: An 8-year-old girl with ADHD who was taking immediate-release methylphenidate 5 mg twice daily, developed mild hypertension and tachycardia, confusion, irritability, and agitation after ingesting 210 mg (8.74 mg/kg) of methylphenidate in a suicide attempt. Despite supportive therapy, his symptoms worsened and she developed hallucinations and delusion. Following treatment with phenobarbital, her symptoms gradually resolved and she was discharged the next day (Fettahoglu et al, 2009).
c) ORAL: In a retrospective study of 14 methylphenidate abuse cases, agitation (n=1), tachycardia (n=1), headache (n=1), tremor (n=1), and dizziness (n=1) developed after ingestions of up to 100 mg of methylphenidate. Two of these patients also ingested alcohol. A 33-year-old woman developed disorientation and agitation after ingesting 300 to 400 mg of methylphenidate. Agitation, tachycardia, hypertension, and hallucinations developed in a 28-year-old man after ingesting 270 mg of methylphenidate(Bruggisser et al, 2011).
d) INTRANASAL: A 29-year-old woman developed anxiety after the intranasal use of methylphenidate 80 mg (Bruggisser et al, 2011).
e) INTRAARTERIAL: A 39-year-old woman developed anxiety after an accidental inguinal intra-arterial injection of methylphenidate (unknown dose) (Bruggisser et al, 2011).
f) In a retrospective observational 7-year study of 23 methylphenidate overdoses (median dose ingested, 120 mg; range 40 to 1500 mg) in adults (mean age, 27.8 years; range 14 to 53 years), anxiety developed in 32% of patients (Hill et al, 2010).
g) In a retrospective review of 113 methylphenidate exposures, agitation and confusion were reported among adolescents and young adults following significant exposure (Foley et al, 2000).
h) In one study, agitation/irritability was noted in 35% (17/149) of children following inadvertent methylphenidate exposure (Bailey et al, 2005).
i) CASE REPORT: A 14-year-old girl with ADHD developed agitation and restlessness 2 hours after intentionally ingesting 1134 mg (recommended maximum dose: 60 to 90 mg/day) of extended-release methylphenidate. She was treated with 30 g of activated charcoal and IV hydration, and was fully recovered within 3 days (Klampfl et al, 2010).
j) CASE REPORT: A 23-month-old boy presented to the ED after ingestion of unknown quantity of methylphenidate (10 mg, immediate release). He developed agitation, slurred speech, and hyperactive behaviors 2 hours after ingestion and subsequently developed repetitive tongue thrusting to the left 4 hours after ingestion. The boy presented to the ED with dilated pupils and dyskinesias and was treated with diphenhydramine (1.1 mg/kg), which slowed the frequency of dyskinesias. Diphenhydramine was repeated 15 hours after ingestion with complete resolution of all movements. At 14 months, his development continued normally post-discharge with no further complications (Waugh, 2013).
k) CASE REPORT: A 31-year-old man injected 120 mg of methylphenidate intravenously daily for 8 weeks. He reported a 45-minute "up" period consisting of euphoria, anxiolysis, and feelings of increased focus and intellectual abilities, followed by a 4-hour "down" period comprised of anxiety and dysphoria. He used flunitrazepam and zolpidem to limit these effects. Doses increased rapidly, which was linked to the appearance of verboacoustic delusions and paranoia after 4 weeks of use (Imbert et al, 2013).
l) CASE REPORT: A 42-year-old man injected a daily dose of 80 mg of methylphenidate intravenously for 9 months. He had lost 20% of his initial weight. Following his referral to a hospital unit for weaning and after discontinuing methylphenidate, he developed a withdrawal syndrome that included anxiety, cravings, sleeping disruption, and dysphoria. Benzodiazepine therapy did not relieve his symptoms. He continued to have withdrawal symptoms (ie, abdominal and lumbar pains, sweating, shivering, nausea, and vomiting) for about a week (Imbert et al, 2013).
m) CASE REPORT: After self-injecting methylphenidate 300 to 500 mg daily intravenously for 4 months, a 27-year-old man described an "up" period occurring 30 minutes after injection, consisting of moderate euphoria, psychic healing, better concentration, and the ability to speak more easily, followed by a "down" period lasting 4 to 5 hours. He also lost 15% of his initial weight during methylphenidate use. He subsequently self-medicated with clonazepam and flunitrazepam to limit cravings and anxiety (Imbert et al, 2013).
n) CASE REPORT: A 26-year-old man with a previous suicidal ideation who was using methylphenidate 160 mg daily, presented with somnolence, disorganized and accelerated thinking, marked psychomotor agitation when awake and hypertension. On admission, several blisters of methylphenidate 40 mg tablets and a prescription for methylphenidate were found in his belongings. All laboratory results, including a CT scan of the brain and cerebrospinal fluid puncture, were normal. Although his methylphenidate serum concentration obtained about 8 hours after presentation was subnormal (3 mcg/L; reference range, 8 to 30 mcg/L), a marked elevation in serum ritalinic acid was observed (821 mcg/L; reference range, 80 to 300 mcg/L). Inpatient detoxification was recommended, but the patient refused further therapy and was discharged 3 days after presentation (Gahr & Kolle, 2014).
o) NOPAINE (ETHYLPHENIDATE): Ethylphenidate (ethyl 2-phenyl-2-(piperidin-2-yl)acetate), an analogue of methylphenidate, is sold under the street name Nopaine. It is a psychostimulant that inhibits reuptake of both dopamine and norepinephrine (Bailey et al, 2015).

a) In patients with a prior history of seizures or EEG abnormalities with no history of seizures, methylphenidate may lower the convulsive threshold (Prod Info CONCERTA(R) extended-release oral tablets, 2007).

a) Seizures have been reported in overdose (Prod Info CONCERTA(R) extended-release oral tablets, 2007).
b) ORAL: A 25-year-old woman developed multiple absence seizures after ingesting methylphenidate 320 mg with a benzodiazepine and alcohol (Bruggisser et al, 2011).
c) INTRAVENOUS: In a study of 22 adults with a history of chronic methylphenidate abuse, the mean daily dose during a binge was 200 mg, with a range of 40 to 700 mg. Clinical symptoms included grand mal seizures which occurred during a peak binge period, and were a late finding of methylphenidate abuse (Parran & Jasinski, 1991).

a) Cerebral infarction was associated with chronic oral therapeutic use of methylphenidate in a 12-year-old boy (Trugman, 1988).
b) CASE REPORT: A 53-year-old woman who was treated with 10 mg of methylphenidate daily for one year, suffered multiple ischemic strokes thought to be secondary to drug-induced cerebral vasculitis (Thomalla et al, 2006).
c) Stroke has ben reported in adults taking stimulant drugs at therapeutic doses prescribed for ADHD(Prod Info DAYTRANA(TM) transdermal system, 2006)
d) CASE REPORT: A case of cerebral vasculitis was reported in an 8-year-old boy who was taking methylphenidate 20 milligrams per day for hyperactivity and behavioral problems. A year and a half after he started the methylphenidate treatment, he suddenly had 3 episodes of paresthesias with increasing intensity over a 4-month period. At the third episode, the paresthesias resulted in ataxia, dysmetria in the left hemibody, and dystonic movements of the left upper limb. Cerebral angiogram revealed bilateral complete occlusion of the posterior cerebral arteries distal to the origin of choroidal arteries, indicating localized vasculitis. After discontinuing the methylphenidate treatment, he was free of symptoms (Schteinschnaider et al, 2000).

a) Lacunar infarctions occurred in a 24-year-old man ingesting 60 mg of methylphenidate orally for 6 months (Sadeghian, 2004).

a) Lethargy was commonly reported among children exposed to methylphenidate (Klein-Schwartz, 2002).
b) In a retrospective review of 113 methylphenidate exposures, drowsiness was reported among adolescents and adults following significant exposure (Foley et al, 2000).
c) CASE REPORT: A 26-year-old man with a previous suicidal ideation who was using methylphenidate 160 mg daily, presented with somnolence, disorganized and accelerated thinking, marked psychomotor agitation when awake and hypertension. On admission, several blisters of methylphenidate 40 mg tablets and a prescription for methylphenidate were found in his belongings. All laboratory results, including a CT scan of the brain and cerebrospinal fluid puncture, were normal. Although his methylphenidate serum concentration obtained about 8 hours after presentation was subnormal (3 mcg/L; reference range, 8 to 30 mcg/L), a marked elevation in serum ritalinic acid was observed (821 mcg/L; reference range, 80 to 300 mcg/L). Inpatient detoxification was recommended, but the patient refused further therapy and was discharged 3 days after presentation (Gahr & Kolle, 2014).

a) A 15-year-old boy with ADHD was inhaling his Ritalin(R) (3 20 mg-methylphenidate tablets {crushed} per dose) over a 2-week period for its euphoric effects and developed symptoms of clinical depression with drug withdrawal (Garland, 1998).
b) INTRAVENOUS: In a study of 22 adults with a chronic history of intravenous methylphenidate abuse, the mean daily dose during a binge was 200 mg, with a range of 40 to 700 mg. Clinical symptoms included depression as a common finding following a binge period (Parran & Jasinski, 1991).

a) Chronic methylphenidate abuse has been associated with chorea (Extein, 1978).

a) In 3 children aged 9 to 13 years with ADHD and either a bipolar disorder or Tourette's disorder receiving methylphenidate and an antipsychotic, acute dystonia occurred after methylphenidate was discontinued. Symptoms resolved with the administration of either benztropine or the reinstitution of methylphenidate (Benjamin & Salek, 2005).
b) In a retrospective review of 113 methylphenidate exposures, uncontrolled movement was reported in adolescent and adults following significant intentional misuse. Symptoms resolved with minimal clinical intervention (Foley et al, 2000).
c) CASE REPORT: A 14-year-old girl with ADHD experienced uncontrolled movements after intentionally ingesting 1134 mg (recommended maximum dose: 60 to 90 mg/day) of extended-release methylphenidate. She recovered fully within 3 days (Klampfl et al, 2010).

a) Insomnia has been reported with therapeutic use (Prod Info CONCERTA(R) extended-release oral tablets, 2007).

a) CASE REPORT: A 14-year-old girl with ADHD reported an inability to sleep or keep her eyes closed the first night after intentionally ingesting 1134 mg (recommended maximum dose: 60 to 90 mg/day) of extended-release methylphenidate (Klampfl et al, 2010).

a) CASE REPORT: Symptoms of akathisia occurred in a 46-year-old Caucasian female following initiation of methylphenidate. The woman, who had a history of recurrent type major depressive disorder, alcohol dependence in full sustained remission, nicotine dependence, COPD, multiple sclerosis, and multiple pulmonary eosinophilic granulomas, was prescribed oral methylphenidate 10 mg twice daily for the treatment of apathy. The patient was additionally receiving a complex regimen of medications, which included quetiapine. Although she experienced restlessness following the third dose of methylphenidate, she continued treatment. By the fifth day, she was restless, pacing, and felt like she wanted to crawl out of her skin. Taking clonazepam and diazepam (part of her regular regimen of medications) did not resolve the symptoms, and by day 6 her left leg stiffened and she began experiencing tremors in her left arm. She presented to the emergency room where she was administered intramuscular benztropine, which led to a prompt relief of symptoms. She was advised to discontinue methylphenidate and following discharge with a week's supply of oral benztropine, her symptoms did not recur. It was proposed that the addition of methylphenidate may have unmasked latent extrapyramidal symptoms, a potential side effect of quetiapine (Almeida et al, 2006).

a) ADULTS: Headache occurred in 22.2% of adult patients on methylphenidate hydrochloride extended-release (n=415) compared with 15.6% of patients on placebo (n=212), in 2 double-blind, placebo-controlled clinical trials (Prod Info CONCERTA(R) extended-release oral tablets, 2008).
b) CHILDREN: In unpublished study data provided by the manufacturer involving children 6 to 12 years of age treated with long-acting methylphenidate (Ritalin(R) LA) for up to 4 weeks, insomnia and headache reportedly occurred in greater than 5% of patients (Prod Info Ritalin(R) LA, 2002).

a) Dyskinesia was reported during post-marketing experience with methylphenidate hydrochloride extended-release (Prod Info CONCERTA(R) extended-release oral tablets, 2008).

a) CASE REPORT: A 23-month-old boy presented to the ED after ingestion of unknown quantity of methylphenidate (10 mg, immediate release). He developed agitation, slurred speech, and hyperactive behaviors 2 hours after ingestion and subsequently developed repetitive tongue thrusting to the left 4 hours after ingestion. The boy presented to the ED with dilated pupils and dyskinesias and was treated with diphenhydramine (1.1 mg/kg), which slowed the frequency of dyskinesias. Diphenhydramine was repeated 15 hours after ingestion with complete resolution of all movements. At 14 months, his development continued normally post-discharge with no further complications (Waugh, 2013).

a) Diarrhea has developed with therapeutic methylphenidate use (Prod Info CONCERTA(R) extended-release oral tablets, 2007).

a) Dry mouth has been reported in 14% of adult patients on methylphenidate hydrochloride extended-release (n=415) compared with 3.8% of patients on placebo (n=212), in 2 double-blind, placebo-controlled clinical trials (Prod Info CONCERTA(R) extended-release oral tablets, 2008).

a) Nausea and vomiting have developed with therapeutic methylphenidate use (Prod Info CONCERTA(R) extended-release oral tablets, 2007; Karapinar et al, 2014).
b) Nausea has been reported in 12.8% of adult patients on methylphenidate hydrochloride extended-release (n=415) compared with 3.3% of patients on placebo (n=212), in 2 double-blind, placebo-controlled clinical trials (Prod Info CONCERTA(R) extended-release oral tablets, 2008).

a) Nausea and vomiting have been reported following overdose (Klein-Schwartz, 2002; White et al, 2000).
b) In a retrospective observational 7-year study of 23 methylphenidate overdoses (median dose ingested, 120 mg; range 40 to 1500 mg) in adults (mean age, 27.8 years; range 14 to 53 years), vomiting developed in 12% of patients (Hill et al, 2010).

a) Decreased appetite has been reported in 25.3% of adult patients on methylphenidate hydrochloride extended-release (n=415) compared with 6.6% of patients on placebo (n=212), in 2 double-blind, placebo-controlled clinical trials (Prod Info CONCERTA(R) extended-release oral tablets, 2008).

a) Anorexia has been reported following overdose (Klein-Schwartz, 2002; White et al, 2000).

a) Abdominal pain has been reported following overdose (Klein-Schwartz, 2002; White et al, 2000).
b) In a retrospective observational 7-year study of 23 methylphenidate overdoses (median dose ingested, 120 mg; range 40 to 1500 mg) in adults (mean age, 27.8 years; range 14 to 53 years), abdominal pain developed in 16% of patients (Hill et al, 2010).

a) Abnormal liver enzymes (aminotransferase elevation) have been reported rarely during postmarketing experience with methylphenidate (Prod Info CONCERTA(R) extended-release oral tablets, 2007).

a) CASE REPORT: Hepatic injury was reported in a 19-year-old woman who regularly abused IV methylphenidate. Liver enzyme changes were reproducible on rechallenge after receiving 20 mg of IV methylphenidate twice daily for 2 days (Mehta et al, 1984).
b) Oral administration of methylphenidate, 10 mg 3 times daily, resulted in elevated SGOT values in a 67-year-old woman (Goodman, 1974).

a) CASE REPORT: Autoimmune hepatitis occurred in a 57-year-old, asymptomatic man one month following initiation of methylphenidate. The patient, who had a history of orthotopic liver transplantation secondary to chronic hepatitis C infection 4 years prior, was found to have sudden-onset liver elevation of liver chemistries during a routine scheduled follow-up. Baseline liver chemistries had been stable in the months prior to presentation. His current values for AST, ALT, and total bilirubin were 572 U/L, 338 U/L, and 2.7 mg/dL, respectively. Medications taken over the previous year were cyclosporine, venlafaxine, omeprazole, hydrochlorothiazide, fosinopril, and a multivitamin. Long-acting methylphenidate had been initiated 1 month prior to current presentation for impaired concentration and depressive symptoms. The patient denied alcohol abuse and use of herbal or complementary medicines, and did not have any fever, chills, abdominal pain, or urine discoloration. Physical examination revealed a flat, nondistended abdomen, with no ascites or hepatosplenomegaly evident. No change in mental status or asterixis was found on neurological examination. Laboratory exam showed positive titers for anti-smooth muscle antibody (1:40) and antinuclear antibody (1:80), with a nucleolar pattern, and an elevated IgG of 1950 mg/dL, all of which had been normal at baseline. A liver biopsy showed severe lobular and periportal necroinflammatory infiltrate with predominant lymphocytes, plasma cells, and eosinophils, but lacking endothelialitis and bile duct damage. Subsequently, methylphenidate therapy was discontinued and liver chemistries began to normalize. Besides methylphenidate, other prior medications were continued and prednisone 10 mg/day was added approximately 1 month later. Liver chemistries returned to patient's approximate baseline values over the next few months, and a liver biopsy 1 year following this episode showed marked improvement. Later, the patient was started on combination amphetamine/dextroamphetamine with no further elevation of liver enzymes (Lewis et al, 2007).

a) Cases of painful and prolonged penile erections (ie, more than 4 hours) and priapism have been reported with methylphenidate use following dose increases, with longer than usual dosing intervals, and after temporary or permanent drug withdrawal. Some cases required surgical intervention (Prod Info Ritalin-SR(R) oral sustained-release tablets, 2013).
b) In an FDA analysis, 15 cases of priapism associated with methylphenidate were reported over a 15-year period, with the majority of affected patients under age 18 (median age, 12.5 years; range, 8 to 33 years). Some cases required inpatient care, including surgical treatment in 2 patients (ie, shunt placement, needle aspiration of the corpus cavernosum). Priapism developed following methylphenidate withdrawal in 4 cases. Priapism resolved after the drug was restarted in some patients (U.S. Food and Drug Administration (FDA), 2013).

a) NOPAINE (ETHYLPHENIDATE): Elevated BUN (7.9 mmol/L; normal range: 3.3 to 6.7 mmol/L) developed in a 37-year-old woman after using 1 g of ethylphenidate IV injection (Bailey et al, 2015).

a) Thrombocytopenia was reported during post-marketing experience with methylphenidate hydrochloride extended-release (Prod Info CONCERTA(R) extended-release oral tablets, 2008).
b) CASE REPORT: Thrombocytopenia was reported in a 10-year-old boy who received methylphenidate for attention deficit hyperactivity disorder. The patient had been treated with methylphenidate for 10 months when a routine blood count revealed thrombocytopenia. Blood counts returned to normal within 2 weeks of drug discontinuation (Kuperman et al, 2003).

a) Pancytopenia was reported during post-marketing experience with methylphenidate hydrochloride extended-release (Prod Info CONCERTA(R) extended-release oral tablets, 2008).

a) Thrombocytopenic purpura was reported during post-marketing experience with methylphenidate hydrochloride extended-release (Prod Info CONCERTA(R) extended-release oral tablets, 2008).

a) INTRAVENOUS: In a study of 22 adults with a chronic history of intravenous methylphenidate abuse, 20 patients developed peripheral venous sclerosis and 19 had an abscess or cellulitis which required surgical intervention (Parran & Jasinski, 1991).
b) INTRAVENOUS: A 41-year-old woman developed inguinal erythema and abscess with fever after using methylphenidate IV (unknown dose) (Bruggisser et al, 2011).

a) INTRAARTERIAL: A 28-year-old woman used 6 mg of crushed methylphenidate intra-arterially and developed pain and necrosis of forearm, requiring the amputation of the forearm. Pain and necrosis of finger tips developed in a 37-year-old man after using methylphenidate (unknown amount) intra-arterially. Amputation of finger tips was required (Bruggisser et al, 2011).

a) TRANSDERMAL: Skin depigmentation or hypopigmentation consistent with chemical leukoderma has been reported during postmarketing surveillance with transdermal methylphenidate. All of the 51 reported cases were permanent. Although most cases occurred only around where the patch was applied, some cases also occurred in areas the patch was never applied. Time to onset ranged from 2 months to 4 years, and occurred after treatment discontinuation in some patients. Of the 13 patients prescribed medicine to reverse the loss of skin color, 3 of those patients reported a slight improvement (U.S. Food and Drug Administration (FDA), 2015).

a) As a consequence of seizure, hypothermia, psychomotor agitation, or excess muscular activity from sympathomimetic toxicity, rhabdomyolysis may occur (Hadad et al, 2003).

a) NOPAINE (ETHYLPHENIDATE): Elevated creatine kinase (290 International Units [IU]/L; normal range: 0 to 229 IU/L) developed in a 21-year-old man 3 hours after using 500 mg of ethylphenidate by nasal insufflation and smoking (in incremental doses over several hours) and drinking 7 cans of beer. Another patient, a 23-year-old man, developed an elevated creatine kinase level (579 International Units/L) after using 2 g of ethylphenidate over 3 days by nasal insufflation (Bailey et al, 2015).

a) Arthralgia has been reported in post-marketing experience with methylphenidate extended-release (Prod Info CONCERTA(R) extended-release oral tablets, 2008).

a) Myalgia has been reported in post-marketing experience with methylphenidate extended-release (Prod Info CONCERTA(R) extended-release oral tablets, 2008).

a) Hypersensitivity reactions such as angioedema, anaphylactic reactions, exfoliative conditions, and auricular swelling have been reported in post-marketing experience with methylphenidate hydrochloride extended-release (Prod Info CONCERTA(R) extended-release oral tablets, 2008).

a) No congenital malformations were reported in an infant exposed to methylphenidate in utero. The infant was born at 38 weeks of gestation to a 20-year-old woman with a history of ADHD, recurrent depression, and borderline personality disorder. Extended-release methylphenidate 72 mg/day was administered from conception to gestation week 13, at which point the dosage was titrated down to 54 mg/day. The methylphenidate dosage was reduced to 18 mg/day 6 weeks prior to delivery and discontinued completely 1 week before delivery to avoid infant withdrawal symptoms. The infant spent 6 hours in the neonatal intensive care unit for ventilation and observation. No developmental problems were observed at follow-up visits performed at 6 months, 1 year, and 2 years after delivery. Due to mental deterioration of the mother, treatment with methylphenidate was reinitiated along with sertraline 50 mg/day (Bolea-Alamanac et al, 2014).
b) Increased rates of prematurity (21%) and growth retardation (31%) were observed in a case series of 38 mothers abusing methylphenidate and IV pentazocine during pregnancy. Withdrawal symptoms were reported in approximately one-third (28%) of the exposed infants. Congenital anomalies, including polydactyly and heart septal defects, were reported in 2 of the exposed infants (Bolea-Alamanac et al, 2014).

a) In a systematic review of a case report (n=1) and a case series (n=3), no adverse effects were observed in children exposed to methylphenidate through breastfeeding. In one case report, a woman with a history of ADHD, recurrent depression, and borderline personality disorder, chose to breastfeed while taking methylphenidate HCl 72 mg/day. A pediatric examination 14 weeks after delivery revealed that the infant had a good temperament and no feeding difficulties were reported. No methylphenidate was detected in samples of the maternal milk or the infant's blood (Bolea-Alamanac et al, 2014).

a) Monitor vital signs.

a) Obtain an ECG and institute continuous cardiac monitoring in patients with moderate to severe toxicity.
b) Obtain cardiac enzymes if patient has chest pain.

a) Monitor mental status.
b) Consider a head CT and lumbar puncture to rule out intracranial mass, bleeding, or infection.

1) Patients with no symptoms, in whom the ingestion was more than 3 hours before the call to the poison center.
2) Patients who chewed a patch briefly and the patch remained intact; significant toxicity is unlikely in these patients.
3) Patients with acute or acute-on-chronic ingestions of less than a toxic dose (for immediate release formulations or sustained release formulations that have been chewed: less than 2 mg/kg or 60 mg whichever is less; for sustained release formulations that have been swallowed intact: less than 4 mg/kg or 120 mg, whichever is less) or chronic exposures to methylphenidate with no or mild symptoms; the caller should be instructed to call the poison center back if symptoms develop or worsen. Instruct the caller to avoid taking or administering additional methylphenidate for the next 24 hours. A follow-up call by the poison center is recommended at approximately 3 hours after ingestion.

1) This prospective follow-up study identified 364 methylphenidate intoxications (median age: 18 years; range 1 to 74 years; median dose: 2.3 mg/kg; range 0.1 mg/kg to 33.9 mg/kg; 95% oral exposure) reported to the Dutch Poison Information Center, with 145 unintentional cases (median dose: 1.6 mg/kg; range, 0.1 mg/kg to 7.6 mg/kg; 34% immediate-release formulations) and 213 intentional cases (median dose: 3.1 mg/kg; range 0.3 mg/kg to 33.9 mg/kg; 62% immediate-release formulations). The reason for exposure was not reported in 6 patients (2%) and 71% of patients in the intentional group used other drugs as compared with 17% of patient in the unintentional group. Severe symptoms (eg, seizures, coma, cerebral hemorrhage, cardiac arrest) developed only in patients with concomitant exposures. Patients developed hallucinations, psychosis, and dysrhythmias only after ingesting doses above 3 mg/kg. Dry mucosa, headache, agitation, sleepiness, and tachycardia were the most commonly observed symptoms in patients taking methylphenidate alone (Hondebrink et al, 2015).

1) Patients with intentional misuse (eg; suicide, child abuse or neglect).
2) Patients who are chronically taking a monoamine oxidase inhibitor and who have ingested any amount of methylphenidate.
3) Patients experiencing any symptoms other than mild stimulation or mild agitation (eg, moderate to severe stimulation or agitation, seizures, chest pain, hallucinations, abnormal movements, loss of consciousness).
4) Patients who ingested more than 2 mg/kg or 60 mg, whichever is less, of an immediate-release formulation (or the equivalent amount of a modified-release formulation that has been chewed).
5) Patients who ingested more than 2 mg/kg or 60 mg, whichever is less, of a patch that has been swallowed (consider the entire contents of the patch, not just the labeled dose of the patch, to have been ingested). If it is known that the patch was chewed only briefly and it remains intact, toxicity is unlikely and ED referral is unnecessary.
6) Patients who ingested more than 4 mg/kg or 120 mg, whichever is less, of an intact modified-release formulation.

a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2010; Chin et al, 2008).

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

a) If seizures are not controlled by the above measures, patients will require endotracheal intubation, mechanical ventilation, continuous EEG monitoring, a continuous infusion of an anticonvulsant, and may require neuromuscular paralysis and vasopressor support. Consider continuous infusions of the following agents:
b) Endotracheal intubation, mechanical ventilation, and vasopressors will be required (Brophy et al, 2012) and consultation with a neurologist is strongly advised.
c) Neuromuscular paralysis (eg, rocuronium bromide, a short-acting nondepolarizing agent) may be required to avoid hyperthermia, severe acidosis, and rhabdomyolysis. If rhabdomyolysis is possible, avoid succinylcholine chloride, because of the risk of hyperkalemic-induced cardiac dysrhythmias. Continuous EEG monitoring is mandatory if neuromuscular paralysis is used (Manno, 2003).

a) Useful for emergent treatment of severe hypertension secondary to poisonings. Sodium nitroprusside has a rapid onset of action, a short duration of action and a half-life of about 2 minutes (Prod Info NITROPRESS(R) injection for IV infusion, 2007) that can allow accurate titration of blood pressure, as the hypertensive effects of drug overdoses are often short lived.

a) ADULT: Begin intravenous infusion at 0.1 microgram/kilogram/minute and titrate to desired effect; up to 10 micrograms/kilogram/minute may be required (American Heart Association, 2005). Frequent hemodynamic monitoring and administration by an infusion pump that ensures a precise flow rate is mandatory (Prod Info NITROPRESS(R) injection for IV infusion, 2007). PEDIATRIC: Initial: 0.5 to 1 microgram/kilogram/minute; titrate to effect up to 8 micrograms/kilogram/minute (Kleinman et al, 2010).

a) The reconstituted 50 mg solution must be further diluted in 250 to 1000 mL D5W to desired concentration (recommended 50 to 200 mcg/mL) (Prod Info NITROPRESS(R) injection, 2004). Prepare fresh every 24 hours; wrap in aluminum foil. Discard discolored solution (Prod Info NITROPRESS(R) injection for IV infusion, 2007).

a) Severe hypotension; headaches, nausea, vomiting, abdominal cramps; thiocyanate or cyanide toxicity (generally from prolonged, high dose infusion); methemoglobinemia; lactic acidosis; chest pain or dysrhythmias (high doses) (Prod Info NITROPRESS(R) injection for IV infusion, 2007). The addition of 1 gram of sodium thiosulfate to each 100 milligrams of sodium nitroprusside for infusion may help to prevent cyanide toxicity in patients receiving prolonged or high dose infusions (Prod Info NITROPRESS(R) injection for IV infusion, 2007).

a) Monitor blood pressure every 30 to 60 seconds at onset of infusion; once stabilized, monitor every 5 minutes. Continuous blood pressure monitoring with an intra-arterial catheter is advised (Prod Info NITROPRESS(R) injection for IV infusion, 2007).

a) Useful for severe hypertension, particularly if caused by agents with alpha adrenergic agonist effects usually induced by catecholamine excess (Rhoney & Peacock, 2009).

a) BOLUS DOSE: 5 to 15 mg IV bolus repeated as needed (U.S. Departement of Health and Human Services, National Institutes of Health, and National Heart, Lung, and Blood Institute, 2004). Onset of action is 1 to 2 minutes with a duration of 10 to 30 minutes (Rhoney & Peacock, 2009).
b) CONTINUOUS INFUSION: 1 mg/hr, adjusted hourly to stabilize blood pressure. Prepared by adding 60 mg of phentolamine mesylate to 100 mL of 0.9% sodium chloride injection; continuous infusion ranging from 12 to 52 mg/hr over 4 days has been used in case reports (McMillian et al, 2011).

a) 0.05 to 0.1 mg/kg/dose (maximum of 5 mg per dose) intravenously every 5 minutes until hypertension is controlled, then every 2 to 4 hours as needed (Singh et al, 2012; Koch-Weser, 1974).

a) Adverse events can include orthostatic or prolonged hypotension, tachycardia, dysrhythmias, angina, flushing, headache, nasal congestion, nausea, vomiting, abdominal pain and diarrhea (Rhoney & Peacock, 2009; Prod Info Phentolamine Mesylate IM, IV injection Sandoz Standard, 2005).

a) Phentolamine should be used with caution in patients with coronary artery disease because it may induce angina or myocardial infarction (Rhoney & Peacock, 2009).

a) May be used to control hypertension, and is particularly useful in patients with acute coronary syndromes or acute pulmonary edema (Rhoney & Peacock, 2009).

a) Begin infusion at 10 to 20 mcg/min and increase by 5 or 10 mcg/min every 5 to 10 minutes until the desired hemodynamic response is achieved (American Heart Association, 2005). Maximum rate 200 mcg/min (Rhoney & Peacock, 2009).

a) Usual Dose: 29 days or Older: 1 to 5 mcg/kg/min continuous IV infusion. Maximum 60 mcg/kg/min (Laitinen et al, 1997; Nam et al, 1989; Rasch & Lancaster, 1987; Ilbawi et al, 1985; Friedman & George, 1985).

a) If patient is severely agitated, sedate with IV benzodiazepines.

a) ADULT: 5 to 10 mg IV initially, repeat every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).

a) ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed (Manno, 2003).
b) CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).

a) CASE REPORT: A 7-year-old girl presented with agitation, hyperactivity, talkativeness, hallucinations, tachycardia, and hypertension after ingesting 25 methylphenidate tablets (5 mg each). Treatment with multiple doses of IV midazolam (total dose: 1.5 mg/kg) provided some transient resolution of her symptoms. However, her symptoms returned 4 hours later and because of concerns for airway stability after high doses of midazolam, dexmedetomidine (initial dose: 0.5 mcg/kg/hr infusion for 4 hours; weaned by 0.1 mcg/kg every 30 minutes) was used to manage her agitation and cardiovascular symptoms. Her condition gradually improved and she was discharged after 18 hours of observation (Bagdure et al, 2013).

a) Obtain an ECG, institute continuous cardiac monitoring and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders (particularly hypokalemia, hypocalcemia, and hypomagnesemia). Lidocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Amiodarone should be used with caution if a substance that prolongs the QT interval and/or causes torsades de pointes is involved in the overdose. Unstable rhythms require immediate cardioversion.

a) LIDOCAINE/INDICATIONS
b) LIDOCAINE/DOSE
c) LIDOCAINE/MAJOR ADVERSE REACTIONS
d) LIDOCAINE/MONITORING PARAMETERS

a) AMIODARONE/INDICATIONS
b) AMIODARONE/ADULT DOSE
c) AMIODARONE/PEDIATRIC DOSE
d) ADVERSE EFFECTS

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

a) The following American Urological Association Guideline has been developed to evaluate and treat priapism (Montague et al, 2003):

a) Extended release capsules should be swallowed whole and should not be crushed, chewed or divided; the entire contents of the capsule may be sprinkled on a small amount of chilled applesauce and consumed immediately in its entirety (Prod Info FOCALIN XR oral extended-release capsules, 2013).

a) Sustained-release tablets should be swallowed whole and should not be chewed or crushed (Prod Info RITALIN-SR(R) sustained release oral tablets, 2007).

a) Extended release capsules may be swallowed whole or sprinkled onto applesauce (Prod Info APTENSIO XR(TM) oral extended-release capsules, 2015).

a) Extended release capsules should be swallowed whole and should not be crushed, chewed or divided; the entire contents of the capsule may be sprinkled on a small amount of chilled applesauce and consumed immediately in its entirety (Prod Info FOCALIN XR oral extended-release capsules, 2013).

a) Sustained-release tablets should be swallowed whole and should not be chewed or crushed (Prod Info RITALIN-SR(R) sustained release oral tablets, 2007).

a) Extended release capsules may be swallowed whole or sprinkled onto applesauce (Prod Info APTENSIO XR(TM) oral extended-release capsules, 2015).

a) SERUM RITALINIC ACID: A 26-year-old man with a previous suicidal ideation who was using methylphenidate 160 mg daily, presented with somnolence, disorganized and accelerated thinking, marked psychomotor agitation when awake and hypertension. On admission, several blisters of methylphenidate 40 mg tablets and a prescription for methylphenidate were found in his belongings. All laboratory results, including a CT scan of the brain and cerebrospinal fluid puncture, were normal. Although his methylphenidate serum concentration obtained about 8 hours after presentation was subnormal (3 mcg/L; reference range, 8 to 30 mcg/L), a marked elevation in serum ritalinic acid was observed (821 mcg/L; reference range, 80 to 300 mcg/L). Inpatient detoxification was recommended, but the patient refused further therapy and was discharged 3 days after presentation (Gahr & Kolle, 2014).
b) FATALITIES

a) SURVIVAL