Prophylactic or preventive medications* in cyclic vomiting syndrome

Children 2 to 5 years old

Antihistamines – Cyproheptadine (first choice)

Dosing – 0.25 to 0.5 mg/kg/day orally divided into 2 or 3 daily doses, or given once daily at night to reduce daytime sedation (maximum of 12 mg per 24 hours). Available in 4 mg tablets and a 2 mg/5 mL syrup.

Side effects – Increased appetite, weight gain, sedation, dry mouth, constipation, urinary retention; may also cause paradoxical excitation in young children.

Alternatives – Pizotifen (available in United Kingdom and Canada).

Beta blockers – Propranolol (second choice)

Dosing – 0.25 to 1 mg/kg/day orally divided into 2 or 3 daily doses, most often 10 mg 2 or 3 times daily. Initiate at 0.25 mg/kg/day and increase every 1 to 4 weeks in increments of 5 or 10 mg as needed and tolerated. Maximum dose 80 mg per 24 hours. Available in tablet and liquid forms in various strengths and concentrations.

Monitoring – Monitor and maintain resting heart rate ≥60 bpm.

Side effects – Lethargy, reduced exercise tolerance, hypoglycemia, bradycardia, bronchospasm, hypotension, night terrors.

Contraindications – Asthma, diabetes, heart disease.

Discontinuation – Do not stop abruptly, must be tapered over 1 to 2 weeks.

Children older than 5 years and adults

Tricyclic antidepressants – Amitriptyline (first choice)

Dosing:

Children – Initiate at 0.2 to 0.3 mg/kg/day orally at bedtime, may gradually increase dose based on response and tolerability in weekly increments up to 1 to 1.5 mg/kg/day. For dose >1 mg/kg/day, may administer at bedtime or divide twice daily.
Adults – Initiate at 10 to 25 mg orally at night. May increase in increments of 10 mg as needed and tolerated at weekly intervals. The mean effective dose for adults is 75 to 100 mg daily^[1].

Monitoring – Check ECG QTc interval before starting, during titration and after the target dose is reached. QTc interval should be maintained <460 msec for children, <470 msec for adult women, and <450 msec in adult men^[1].

Side effects – Constipation, sedation, weight gain, dry mouth, arrhythmia, behavioral changes (especially in young children).

Discontinuation – Gradually taper dose to minimize the incidence of withdrawal.

Alternatives – Nortriptyline^¶ (available in 10 mg/5 mL liquid).

Beta blockers – Propranolol (second choice for children; not generally used for cyclic vomiting syndrome in adults) – Refer to section on younger children above for dosing.

Formulation consideration – For adolescents, may use the extended-release form of propranolol (for once-daily dosing), after titration to a minimum daily dose of 60 mg.

NK1 receptor antagonist – Aprepitant^[1,2]

Dosing for prophylaxis:^Δ

For <40 kg body weight – 40 mg orally twice weekly.
For 40 to 60 kg body weight – 80 mg orally twice weekly.
For >60 kg body weight – 125 mg orally twice weekly.

Side effects – Hiccups, lethargy/fatigue, headache.

Drug-drug interactions – Significant inhibitors and inducers of CYP3A4 increase and decrease levels of aprepitant, respectively, and should be avoided if possible.

Other agents – For children older than 5 years and adults

Antiseizure medications – Phenobarbital^◊ (used primarily for children)

Dosing – 2 mg/kg/day orally, administered at bedtime. Maximum dose 80 mg per 24 hours.

Side effects – Sedation, cognitive impairment.

Alternative antiseizure medications

Topiramate

Dosing:

Children – 2 mg/kg/day divided in 2 daily doses. Titrate weekly as tolerated from a beginning dose of 15 or 25 mg once a day. Consult a pediatric neurologist for drug selection and dose adjustment.
Adults – Initiate at 25 mg orally once a day. Titrate dose by 25 mg weekly as tolerated to a target dose of 100 mg daily.

Others – Levetiracetam and zonisamide (primarily in adults).

Supplements^◊^§ (used primarily in children, but also suggested as a consideration for adults^[1])

Coenzyme Q₁₀

Dosing:

Children – 10 mg/kg/day orally divided into 2 or 3 daily doses.
Adults – 200 mg orally 2 times daily.

Side effects: diarrhea.

L-carnitine

Dosing:

Children – 50 to 100 mg/kg/day orally divided into 2 or 3 daily doses. Usual maximum dose 1 g twice daily.
Adults – 1 g orally 2 times daily.

Side effects: diarrhea, fishy body odor.

Riboflavin

Dosing:

Children – Approximately 10 mg/kg/day orally divided in 2 daily doses (usually 100 or 200 mg twice daily).
Adults – 200 mg orally 2 times daily.

ECG: electrocardiogram; NK1: neurokinin 1.

* All medication recommendations are made for off-label use.

¶ Nortriptyline, a less sedating alternative to amitriptyline, has also been successfully used in adults and children with cyclic vomiting syndrome, based on clinical experience and very limited published evidence. Starting and target doses for nortriptyline are similar to those of amitriptyline. For both amitriptyline and nortriptyline, the effects typically take 1 to 2 months to become fully evident once the target dose is reached.

Δ Aprepitant has also been used for abortive therapy. For abortive dosing, refer to UpToDate table on supportive and abortive therapy for cyclic vomiting syndrome.

◊ Limited or no published experience regarding efficacy.

§ For children with cyclic vomiting syndrome, UpToDate authors suggest a trial of adjunctive treatment with coenzyme Q₁₀ and/or L-carnitine and riboflavin, in addition to the first- or second-line therapies described above.

References:

Venkatesan T, Levinthal DJ, Tarbell SE et al. Guidelines on Management of Cyclic Vomiting Syndrome in Adults by the American Neurogastroenterology and Motility Society and the Cyclic Vomiting Syndrome Association. Neurogastroenterol Motil 2019; Suppl 2:e13604.
Cristofori F, Thapar N, Saliakellis E, et al. Efficacy of the neurokinin-1 receptor antagonist aprepitant in children with cyclical vomiting syndrome. Aliment Pharmacol Ther 2014; 40:309.

Adapted from: Li BU, Lefevre F, Chelimsky GG, et al. North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition consensus statement on the diagnosis and management of cyclic vomiting syndrome. J Pediatr Gastroenterol Nutr 2008; 47:379.

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Prophylactic or preventive medications* in cyclic vomiting syndrome