Drug Appendix

A weak diuretic and carbonic anhydrase inhibitor.

Hyponatremia, hypokalemia, hyperchloremic acidosis, adrenocortical insufficiency, a history of allergy to sulfa drugs (a sulfonamide derivative), and significant renal, or hepatic dysfunction.

Increases the serum levels of primidone, pseudoephedrine, quinidine, and lithium. Increased risk of nephrolithiasis, especially when used in combination with topiramate.

Drowsiness, dizziness, fatigue, paresthesias of extremities and face, tinnitus, taste changes, polyuria, muscle weakness, delirium, anorexia, nausea, vomiting, and diarrhea. Less common but potentially serious side effects include metabolic acidosis, electrolyte imbalance, nephrolithiasis, hepatotoxicity, Stevens–Johnson syndrome, bone marrow suppression, and hypersensitivity reactions.

Successful in controlling paroxysmal conditions such as periodic paralysis, episodic ataxia and vertigo in episodic ataxia types 1 and 2, and in spinocerebellar ataxia type 6 with episodic features. Treatment of paroxysmal dyskinesias has been less beneficial and only a few case reports suggest that it may help action myoclonus. Obtaining a renal ultrasound has been suggested when patients take acetazolamide for longer than 6 months. Monitor CBC and electrolyte levels.

Initial dose of 125–250 mg/day, with gradual titration as tolerated. Daily doses may range from 1000 to 2000 mg/day divided into two to four daily doses.

Antiviral agent that modestly increases dopamine release, inhibits dopamine reuptake, has N-methyl- d -aspartate receptor antagonist properties, and possibly central anticholinergic effects.

Hypersensitivity. Use with caution in patients with congestive heart failure. Since cleared by the kidneys, renal insufficiency will increase the risk of side effects. Relative contraindications include dementia, psychosis, enlarged prostate, neurogenic bladder, and glaucoma.

Concurrent use with anticholinergic medications may augment their side effects. Caution is advised when coadministered with CNS stimulants. Renal clearance of amantadine is reduced with the coadministration of quinine or quinidine.

Primarily anticholinergic-type side effects, including dry mouth, nose, and throat, blurred vision, nausea, lightheadedness, urinary frequency or retention, constipation, hypotension, headaches, sedation, disturbed sleep, myoclonus, hair loss, memory difficulties, confusion, anxiety, psychosis, pedal edema, and livedo reticularis. Abrupt withdrawal can lead to delirium.

Effective in treating symptoms of early stages of Parkinson's disease but is mainly used off label to treat levodopa-induced dyskinesias. Long-acting preparation of amantadine, given nightly has been approved for the treatment of levodopa-induced dyskinesia and motor fluctuations. Refractoriness to therapy may develop but can be restored after a brief drug holiday. The dose should be tapered over weeks to avoid inducing a neuroleptic malignant syndrome, seen with abrupt withdrawal. Limited studies exist assessing its efficacy in the treatment of movement disorders (chorea) in the pediatric population.

Children should receive about half the adult dose and increase more slowly, for example, starting with 50 mg/day and increasing to 50 mg twice a day after 1–2 weeks, then 50 mg 2–3 times/day. Dosages in small double-blind, placebo-controlled trials in adults ranged from 200 to 400 mg/day typically administered in 100-mg increments. A liquid formulation (50 mg/5 mL) is available.

4-Aminopyridine (4-AP) selectively blocks voltage-gated potassium channels, prolongs the action potential, increases calcium influx, and subsequently, enhances interneuronal and neuromuscular synaptic transmission.

Common side effects include dizziness, nervousness, and nausea. Toxicity combines cholinergic features including diaphoresis, altered mental status, and seizures with dopamine-related movement abnormalities including tremor, choreoathetosis, and dystonia.

Primarily used in patients with multiple sclerosis for improving visual function, fatigue, cognition, and walking speed. 4-AP has also had a beneficial effect in patients with episodic ataxia type 2 (EA2), cerebellar downbeat nystagmus, cerebellar gait ataxia, and hereditary spastic paraplegia.

Only limited studies in children.

Amphetamines bind to dopamine and norepinephrine transporter molecules preventing transmitter uptake and substitute for monoamines at the level of the vesicular monoamine transporter (VMAT).

Avoid concurrent use with monoamine oxidase inhibitors due to risk of potentiating life-threatening hypertensive crisis. Structural heart defects, advanced heart disease, hyperthyroidism, or history of drug abuse.

Amphetamines may increase the activity of tricyclic antidepressants or sympathomimetic agents. Increases risk for serotonin syndrome.

Tachycardia, hypertension, palpitations, sweating, anorexia, weight loss, tremor, seizures, and increased anxiety. At high dose, amphetamines may precipitate psychosis.

Schedule II medication effective and FDA-approved for the treatment of hypersomnia in narcolepsy. Tailor to the timing of hypersomnia. These drugs are primarily used in the treatment of attention deficit hyperactivity disorders.

Typical dosing range for amphetamine and methamphetamine is between 5 and 60 mg given once or twice daily. For hypersomnia, adjust dosage to its timing with usual starting dose of 10 mg twice daily upon waking up and at noon. An extended-release formulation of Adderall exists.

Functions as a partial agonist at D2 and 5-HT1A receptors, and as an antagonist at the 5-HT2A receptor.

Hypersensitivity.

Benzodiazepines increase risk for orthostatic hypertension and sedation. Drugs that induce CYP3A4 (e.g., carbamazepine) can cause an increase in aripiprazole clearance and lower blood levels. Inhibitors of CYP3A4 (e.g., ketoconazole) or CYP2D6 (e.g., quinidine, fluoxetine, or paroxetine) can inhibit aripiprazole elimination and cause increased blood levels.

Suicidal ideation and behavior, worsening depression, hypotension, hyperglycemia, weight gain, dizziness, prolonged Q-T interval, gastrointestinal issues, akathisia, tremor, tardive dyskinesia, headache, insomnia, sedation, fatigue, anxiety, and restlessness.

Approved as a tic suppressing medication. Also used as an antipsychotic and antidepressant.

10 years and older: start 2 mg every day for 3 days, then if needed 5 mg once a day. Titrate in 5 mg intervals with typical dose of 10–30 mg/day.

Selective norepinephrine reuptake inhibitor. Increases norepinephrine and dopamine levels in the prefrontal cortex and striatum.

Hypersensitivity, cardiac or vascular disorders, MAO inhibitor use, narrow angle glaucoma, and pheochromocytoma.

Concurrent use of albuterol may increase heart rate and blood pressure. Tricyclic antidepressants and SSRIs can increase plasma concentrations of atomoxetine.

Nausea, reduced appetite, constipation, weight loss, xerostomia, urinary retention, insomnia, psychosis, mania, and suicide. Increased risk of suicidality in children/adolescents with major depression especially during the first month of treatment.

Approved for the treatment of attention deficit hyperactivity disorder in children (≥6 years of age), adolescents, and adults.

For hypersomnia varies from 10 to 60 mg given in two divided doses. For attention deficit hyperactivity disorders (ADHD) 1–1.8 mg/kg/day in children.

Acts at gamma-aminobutyric acid (GABA) type B receptors in the spinal cord.

Children under 2 years. Medication may exacerbate absence seizures. Use with caution in patients with diabetes, renal insufficiency, seizure disorders, stroke, severe psychiatric disturbances, or confusional states.

Synergistic effect with other CNS depressants.

Sedation, dizziness, weakness, hallucinations, confusion, headache, nausea, constipation, hypotonia, paresthesias, ataxia, may increase serum glucose.

Sudden cessation can cause seizures and psychosis. Used mainly in the treatment of spasticity and may be helpful in some forms of dystonia.

Start with 5–10 mg at bedtime. Titrate slowly until desired therapeutic response or side effects. Usual maintenance dose is 10–60 mg/day in three divided doses, lower dose in children ages 2–7 years. Occasionally, a maximum dose of 180 mg/day may be optimal for some children.

Administered via continuous infusion via a catheter placed within the spinal dura. Treatment requires surgery for catheter placement, implantation of a small pump and reservoir in the abdomen.

Infusion system should not be implanted in a child whose weight is less than 14 kg or in the presence of infection.

Synergistic effect with other CNS depressants.

(see Baclofen). Abrupt drug withdrawal is associated with hallucinations, seizures, and status epilepticus. Infusion system-related side effects include infection, catheter breakage, or persistent fistula.

Mainly used in the treatment of spasticity and spastic dystonia. Safety and effectiveness in children less than age 4 years has not been established. Surgery is costly and use as a treatment for generalized dystonia is controversial.

Variable; dose starts at about 100 μg/day; but some individuals may require as much as 1000 μg/day.

Centrally acting anticholinergic also increases dopamine effect by inhibiting presynaptic reuptake.

Use with caution in patients taking other drugs with anticholinergic activity, such as antihistamines, tricyclic antidepressants, or amantadine, since these medications may cause increased confusion or side effects. Benztropine can reduce plasma levels of antipsychotic medications.

Dry mouth, sedation, pupil dilatation, blurred vision, constipation, urinary hesitancy or retention, fatigue, confusion, hallucinations, weakness, tachycardia, increased intraocular pressure, precipitation of narrow angle glaucoma, impaired concentration and memory, delirium, anhidrosis, and susceptibility to hyperthermia. Other side effects include dizziness, nausea, vomiting, and anxiety. Patients may develop tolerance to some of these effects with continued low-dose treatment.

May be helpful in the treatment of dystonia. No substantial evidence that one drug in this medication class (benztropine, trihexyphenidyl) is superior to another. Increase dosage very slowly to avoid side effects; relatively low doses may be helpful. Anticholinergics can exacerbate tardive dyskinesia and chorea but may be helpful for tardive dystonia. Rapid taper can cause malignant hyperthermia, worsening dystonia, or cholinergic symptoms.

Usual dosage is 0.5–2 mg twice daily.

Botulinum toxin is a neurotoxin produced by the anerobic bacteria Clostridium botulinum . The toxin exerts its effect by inhibiting the release of acetylcholine from the presynaptic site at the muscle-nerve junction. Two serotypes, botulinum toxin type A and B are available.

Hypersensitivity to any form of botulinum toxin. Preexisting weakness due to myasthenia gravis or other neuromuscular conditions. Infection at the proposed injection site(s). Patients receiving high doses of aminoglycosides or with bleeding risks should be treated with caution.

Botox may be potentiated by aminoglycoside antibiotics or other drugs that interfere with neuromuscular transmission.

Transient weakness of injected or neighboring muscles. Local side effects at the injection site include pain and ecchymosis. Generalized side effects can include transient malaise, dysphagia, dry mouth/sore throat, and flu-like symptoms.

The onset of benefit generally takes several days; symptomatic improvement may last for as long as 2–4 months. Rarely, patients may develop antibodies to botulinum toxin, resulting in lack of efficacy of future injections. To minimize the risk of antibody formation, at least 3 months should elapse before injections are repeated. Botulinum toxin injections have been used in the treatment of dystonia, blepharospasm, tremors, spasticity, tics, and a large variety of other neurologic and nonneurologic disorders.

Intramuscular dose is highly dependent on the muscle group injected and botulinum toxin serotype. Botulinum toxin A is given in dosages of 50–400 units per injection session. Botulinum toxin B is given in dosages of 5000–25,000 units per injection session. Dosage guidance is available for individual brands.

Anticonvulsant; slows the rate of recovery of inactivated sodium channels.

Hypersensitivity to carbamazepine, history of bone marrow suppression or known sensitivity to tricyclic antidepressants and use in patients who have taken an MAO inhibitor in the past 14 days.

Carbamazepine is a CYP-450-3A4 inducer. Phenytoin and phenobarbital may decrease its effect and valproic acid and erythromycin may increase its effect.

Dizziness, nausea, drowsiness, fatigue, unsteadiness, blurred vision, double vision, weight gain, rash, hepatotoxicity, pancreatitis, and hyponatremia. Serious side effects include bone marrow suppression and skin reactions (erythema multiforme, Stevens–Johnson syndrome, toxic epidermal necrolysis).

Paroxysmal kinesigenic dyskinesias typically respond to doses that are less than those necessary to control seizures. Carbamazepine may be as effective as valproic acid in managing chorea. Need to monitor sodium levels, complete blood count, and liver function tests.

Typical pediatric dose is 10–30 mg/kg/day, divided 3 times per day. To improve tolerance, a dose of 7–10 mg/kg divided twice per day should be initiated for the first week.

Levodopa is converted to dopamine by dopa decarboxylase; Carbidopa is a peripheral dopa decarboxylase inhibitor which blocks the peripheral conversion of levodopa to dopamine and mitigates against levodopa-induced nausea.

Hypersensitivity, the use of monoamine oxidase inhibitors, narrow angle glaucoma, and melanoma. Use with caution in patients with orthostatic hypotension, psychosis, and asthma.

Use with caution with antihypertensive agents. Beneficial effect is reduced with simultaneous use of dopamine receptor blockers (e.g., antipsychotic agents and metoclopramide). Pyridoxine increases the peripheral metabolism of l -dopa, if it is administered in absence of carbidopa. Oral iron salts, multivitamins/minerals (with ADEK, folate, iron) and large doses of methionine may diminish the therapeutic effect of levodopa.

Nausea/vomiting, confusion, dizziness, somnolence, orthostatic hypotension, hallucinations, depression, impulse control, headache, dry mouth, insomnia, fatigue, muscle cramps, and constipation. Motor complications include dyskinesia, dystonia, myoclonus, and the end-of-dose wearing-off effect.

Patients with dopa-responsive dystonia (DRD) show a marked response at relatively low doses of carbidopa/levodopa compared with doses used in Parkinson's disease. If dyskinesia occurs with the initiation of therapy for DRD, dose should be reduced and then gradually increased. Neuroleptic malignant syndrome has been reported upon abrupt withdrawal of levodopa, especially after long-term use. Additional carbidopa can be prescribed if nausea occurs with combined carbidopa/levodopa tablets.

Levodopa is commonly available in the United States as a combination of carbidopa plus levodopa (10/100, 25/100, and 25/250 mg). Initial dosage of levodopa in children is 1 mg/kg/day, divided into three doses. Dose is determined by the levodopa component and the use of 25/100 tablets are recommended in children. Medication should be gradual titrated based on efficacy or adverse effects. The target dosage of levodopa is usually 4–5 mg/kg/day, though some have suggested doses up to 10 mg/kg/day. When peripheral side effects are disturbing (nausea, vomiting, hypotension), additional carbidopa can be administered 30 min before the levodopa. Levodopa/carbidopa should be taken at least 30 min before or 60 min after meals to avoid competition with other amino acids for gastrointestinal absorption. Tablets can be crushed and dissolved in an ascorbic acid solution or in orange juice and used within 24 h.

Long-acting benzodiazepine with mechanism of action through enhancement of GABAergic transmission (primarily at the GABA _A receptor) in the CNS.

Contraindicated in patients with significant hepatic dysfunction, respiratory depression, or acute narrow-angle glaucoma.

Central nervous system depressant action may be potentiated by other sedative hypnotic drugs (e.g., alcohol, narcotics, barbiturates, monoamine oxidase inhibitors, anxiolytic, antipsychotic, anticonvulsant, or antidepressant drugs).

Sedation, somnolence, fatigue, confusion, cognitive impairments, dizziness, hyperactivity, and ataxia. Serious side effects include hypotension and respiratory depression. Medication may cause a paradoxical change in behavior with increased aggression, hyperexcitability, and irritability.

Clonazepam is a controlled substance with the potential for psychological and physical dependence. Abrupt discontinuation of clonazepam may precipitate withdrawal symptoms including seizures. Tolerance is common, and dose escalation with prolonged use may be needed. Useful in treating most types of myoclonus and helpful in parasomnias of NREM and REM sleep, such as REM behavioral disorder (RBD).

Start with 0.25–0.5 mg at bedtime and titrate slowly as tolerated. An amount of 0.05 mg/kg per dose has been advocated (0.01 mg/kg/day in children less than age 10). Usual maintenance dose is 1–4 mg/day divided 3 times daily, although some patients require considerably more. Weekly dose escalation is recommended to allow for patients to become tolerant to the sedating effects of this medication.

Alpha-adrenergic agonist.

Documented hypersensitivity, pregnant, and breastfeeding individuals. Use with caution if there is impaired liver or renal function.

Sedation is increased when clonidine is used in combination with CNS depressing agents. The hypotensive effects of clonidine are enhanced by narcotic analgesics and inhibited by tricyclic antidepressants. Beta-blockers may potentiate bradycardia and enhance rebound hypertension associated with abrupt withdrawal. Clonidine may enhance the CNS-depressive effects of alcohol, barbiturates, or other sedating drugs.

Sedation is the most common adverse effect. Other side effects include orthostatic hypotension, headache, dizziness, fatigue, bradycardia, insomnia, irritability, dysphoria, dry mouth, and nightmares. Do not discontinue suddenly because of risk of rebound hypertension and symptoms of sympathetic hyperactivity. Local dermatitis is common with the transdermal patch.

Considered by some as first-line therapy for tics and ADHD symptoms. Combination with methylphenidate has been shown to be more effective than monotherapy for children with tics and ADHD. Tolerance can develop.

Start with 0.05 mg orally at bedtime. Increase the dosage as needed, every 3–7 days by 0.05 mg/day. Use in divided doses. Twice a day dosing is often adequate for treating tics, but 3–4 times per day is required for other usages (half-life is approximately 6 h). The usual maximum dosage is 0.3–0.4 mg/day. Clonidine is also available as a transdermal patch that can be used as a once weekly patch. Patches are formulated to deliver 0.1, 0.2, or 0.3 mg/day. The usual patch dose is 0.2 mg.

An atypical neuroleptic that affects D4, 5-HT ₂ , muscarinic, and α-1 antagonist receptors and is a relatively weak blocker of D2 receptors.

Myeloproliferative disorder, previous bone marrow suppression, paralytic ileus, and uncontrolled seizure disorder.

Not to be used concomitantly with other drugs that suppress bone marrow function. May potentiate the hypotensive effect of antihypertensive drugs and enhance the atropine effect of anticholinergic drugs. Use with caution together with other drugs that prolong the QTc interval. Clozapine in combination with lithium has been reported to cause severe encephalopathy.

Orthostatic hypotension, sedation, dizziness, vertigo, salivation, sweating, dry mouth, constipation, tachycardia, syncope, seizures, nausea, constipation, hyperglycemia, fever, and weight gain. Rare but serious side effects of clozapine include the agranulocytosis, eosinophilia, respiratory insufficiency, cardiac arrest, myocarditis, cardiomyopathy, hyperglycemia, neuroleptic malignant syndrome, pulmonary embolism, and hepatitis. Tardive dyskinesia has been reported in clozapine-treated patients.

Because of the risk of agranulocytosis, weekly blood counts are required. Drug is available through a distribution system to assure compliance with the required leukocyte monitoring. Clozapine is generally used to treat levodopa-induced hallucinations when other drugs such as pimavanserin, a novel agent approved for the treatment of Parkinson's disease psychosis, and quetiapine are not effective.

In adults, start with 25 mg/day and increase by 25 mg/day every several days according to clinical response and as tolerated. Typical dose is 50–75 mg/day.

Integral component of the mitochondrial electron transport chain.

Hypersensitivity to CoQ10 or product component.

May reduce anticoagulant effectiveness.

Wakefulness, sleep disruption, gastrointestinal problems, appetite suppression, and irritability.

Ubiquinone is less potent and less well absorbed than ubiquinol. Monitor CoQ10 level in plasma and leukocytes. Idebenone has been shown to improve recovery of visual loss in Leber's hereditary optic neuropathy. It has demonstrated modest efficacy in cardiac complications of Friedreich's ataxia.

Ubiquinol (a solubilized bioavailable form of CoQ10): 2–8 mg/kg/day in two divided doses (preferred); Ubiquinone : 5–30 mg/kg/day in two divided doses daily with meals; Idebenone (an analog of CoQ): 90–900 mg/day in divided doses with meals.

Cyclophosphamide is an alkylating agent with powerful and varied immunosuppressant properties. It is widely used as a chemotherapeutic agent to treat a variety of autoimmune and inflammatory diseases and cancers.

Hypersensitivity, severe bone marrow suppression. Cyclophosphamide is contraindicated in pregnant patients. Vaccinations should be updated prior to initiation when possible. The risks and benefits of cyclophosphamide should be discussed with all patients and their parents or legal guardians.

Enhances the adverse effects of other immunosuppressive agents and live vaccines. Allopurinol may enhance side effects.

Nausea, vomiting, anorexia, diarrhea, susceptibility to infection, stomatitis and mucositis, alopecia, leukopenia, anemia, thrombocytopenia, amenorrhea, and hemorrhagic cystitis. Long-term risk for bladder cancer may be mitigated using mesna, vigorous hydration, and limiting the lifetime dose of cyclophosphamide to less than 100 g. Follow-up complete blood count (with differential) and urinalysis should be performed yearly, even after cessation of treatment, to monitor for hematologic or bladder malignancies.

Cyclophosphamide is a potent immunosuppressant with potentially serious adverse effects. Pregnancy screening in women of childbearing age should be done before initiation of cyclophosphamide.

600–1000 mg/m ² intravenously, administered monthly with the minimum dose required to decrease white blood cell counts to less than 3000/mm ³ (measured at days 7, 14, and 28 postinfusion). Dosages should be modified based on CBC nadir, hemoglobin, and serum creatinine. Prophylaxis for nausea and vomiting should be used. Oral dosing is 50–100 mg daily.

Dantrolene, a ryanodine receptor antagonist, acts directly on muscle by inhibiting calcium release from sarcoplasmic reticulum causing the uncoupling of electrical excitation from contraction.

Active hepatic disease.

Drugs with probable interaction include codeine, fentanyl, meperidine, morphine, and verapamil.

Liver failure, seizures, fatigue, weakness, and ataxia.

Dantrolene has been used to treat malignant hyperthermia, neuroleptic malignant syndrome, spasticity, heatstroke, and ecstasy intoxication. Liver function tests should be checked before starting and periodically while on treatment. Treatment may facilitate conversion of muscles to a type 2 fiber predominance, which can adversely affect weight-bearing. It may be prudent to use only in children who are expected to remain wheelchair dependent.

Start at 0.5 mg/kg once/day and increase gradually over 3–4 weeks to a target dose of 2 mg/kg 3 times/day.