Medications – NASPGHAN Toolbox

Steroids

5-ASA

Immunomodulators

Biologics

Anti –TNF

- Infliximab (Remicade)

- - IV, infusion over 2 hours, pre-medications (Tylenol + Benadryl)
  - Induction: 5-10mg/kg at 0,2,6 weeks
  - Maintenance: q4-8 weeks

- Adalimumab (Humira)

- - SQ, No need pre-medication
  - Moderate to severe Crohn’s disease 6 years and older
    - (6 years or older, 17 to less than 40 kg) 80 mg subQ on day 1, followed by 40 mg subQ 2 weeks later on day 15, and then 20 mg subQ every other week starting at week 4 on day 29
    - 6 years or older, 40 kg or greater) 160 mg subQ on day 1 (given in 1 day or split over 2 consecutive days), followed by 80 mg subQ 2 weeks later on day 15, and then 40 mg subQ every other week starting at week 4 on day 29
  - Moderate to severe ulcerative colitis 5 years and older
    - (5 years or older, 20 to less than 40 kg) 80 mg subQ on day 1, 40 mg on day 8, and 40 mg on day 15, followed by 40 mg subQ every other week or 20 mg subQ every week starting on day 29
    - (5 years or older, 40 kg or greater) 160 mg subQ on day 1 (given in 1 day or split over 2 consecutive days), 80 mg subQ on day 8, and 80 mg subQ on day 15 followed by 80 mg subQ every other week or 40 mg subQ every week starting on day 29. Continue the recommended pediatric dosage in patients who become 18 years old and are well-controlled

Antagonist to α4β7 Integrin

- Vedolizumab (Entyvio)

- - IV, 5-7mg/kg. Max 300mg.
  - 0, 2, 6weeks induction then q8 weeks.
  - Level: Before 3^rd dose of induction and then depending on the patient, before next dose
  - Not FDA approved for pediatrics. FDA approved for moderate to severe Crohn’s disease or ulcerative colitis for those 18 years or older.

Anti IL12/23

- Ustekinumab (Stelara)

- - First IV once (over 1 hour), then q4-8 weeks next SQ
  - Induction (IV)
    - < 56kg: 260mg, 2 vials
    - 56-85kg: 390mg, 3 vials
    - >85kg: 520mg, 4 vials
  - Maintenance
    - Starting 8 weeks after induction dose, 90mg q8 weeks
  - Used in Crohn’s > ulcerative colitis
  - Not FDA approved for pediatrics. FDA approved for moderate to severe Crohn’s disease or ulcerative colitis for those 18 years or older.

Jak Inhibitor

- Tofacitinib (Xeljanz)

- - Oral
  - Induction: XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily for 8 weeks
  - If needed, continue for a maximum of 16 weeks
  - Discontinue if after 16 weeks the therapeutic response is not achieved
  - Maintenance: XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily
  - Not FDA approved for pediatrics. FDA approved for moderate to severe ulcerative colitis for those 18 years or older.
  - Black Box Warning: Increased risk of blood clots (1.5- 3x), CHD, malignancy, and death

Patient Education

Motility

Drug Class	Drug	Oral Dose	Indication / Where It Works	Side Effects
Antibiotic	Erythromycin	3 mg/kg/dose (1-6mg/kg/dose) TID (20-30 min before meals) Max 250mg QID IV dose 3 mg/kg TID	Gastroparesis, upper GI symptoms	Tachyphylaxis, diarrhea, abdominal cramping QT prolongation Antibiotic resistance
	Azithromycin	250 mg BID * evidence unknown Max 500 mg/d IV dose same	Gastroparesis, upper GI symptoms	Tachyphylaxis, diarrhea, abdominal cramping QT prolongation Antibiotic resistance
	Augmentin	2.5-4 mg/kg/dose BID Max 250 mg per dose, 500 mg per day	Small bowel prokinetic	Antibiotic resistance, C. diff
Dopamine antagonist	Metoclopramide (Reglan)	0.1-0.2mg/kg/dose 10mg/dose (max) 15 min before meals and at BT (4x/D), Max 40 mg per day, 12 weeks duration Find lowest effective dose	Gastroparesis	Parkinsonian symptoms esp in adolescent females Higher risk of EPS if used >12weeks QT prolongation
D2 receptor antagonist	Domperidone (Motilium)	0.1-0.2 mg/kg/dose (Max10 mg/dose TID), can increase to 20 mg QID before meals and BT (in >18 years)	Gastroparesis, also increases duodenal motility	Cardiotoxicity, QT prolongation Only available in Canada and other countries or through IND in USA. Galactogogue
5-HT4 agonist/5-HT3 antagonist	Cisapride (Prepulsid)	(0.1-0.2mg/kg/dose) up to max 10mg /dose(max 20mg >18years) QID, 30 min before meals and BT MAX 1 mg/kg/day or 60-80 mg daily	Whole gut motility	Cardiotoxicity – P450 interaction, QT prolongation compassionate use or IND only – strict inclusion and exclusion criteria – refractory GERD, gastroparesis or constipation
Selective 5-HT4 agonist (no cardiac effects)	Prucalopride (Motegrity)	<30 kg: 0.5 mg daily >30 kg 1 mg daily Can go to 2 mg daily if not seeing effect	Whole gut motility but approved for refractory constipation – only one peds trial and wasn’t superior to placebo	Headaches, URI
Antagonist of multiple receptors – serotonin, H1, muscarinic, calcium channel	Cyproheptadine (Periactin)	0.25 mg/kg/day in 2-3 divided doses Max 12 mg in <6 years Max 16 mg 7-14 years	Upper GI symptoms and pain. FAP, FD, CVS, abdominal migraines	Sedation Increased appetite Dizziness (drink water)
Antidepressant, tetracyclic	Mirtazapine (Remeron)	7.5 mg, 15 mg, or 30 mg at bedtime (higher doses for psych indications)	FD, FN, FE, CVS, anxiety	Appetite stimulation at lower doses (7.5 mg, 15 mg). More sedating at lower doses (7.5 mg) because more antihistamine and alpha agonist action. Higher doses like 30-45 mg – more serotonin and norepi action.
Antidepressant, TCA	Amitriptyline (Elavil)	10-50 mg at bedtime	FAP, IBS-D, FD, CVS (>5 years), anxiety	QT prolongation, constipation
Chloride channel activator	Lubiprostone (Amitiza) (not FDA approved in children <18)	8 mcg BID, 16 mcg BID, 24 BID daily Dose with food to avoid nausea	Restores barrier function, hydrates stool. Works similarly to osmotic laxative if miralax isn’t working or pill is preferred. Does not help with motility or pain in IBS	Nausea
Guanylate cyclase-C receptor agonist	Linaclotide (Linzess) (not FDA approved in children <18)	72 mcg, 145 mcg (CIC), 290 mcg (IBS-C) daily Dose 30 min before breakfast to avoid diarrhea Take at same time every day Black box warning in <6 years because pups died from dehydration	IBS-C, Chronic idiopathic constipation. Treats both pain and increases intestinal fluid via stimulating secretion of chloride, bicarb, and water into lumen via CFTR ion channel activation	Diarrhea
Guanylate cyclase-C receptor agonist	Plecanitide (Trulance) (not FDA approved in children <18))	3 mg, 6 mg daily – seem to both be effective Unlike linaclotide, don’t have to take at same time every day or with food	IBS-C, FC	Diarrhea
Somatostatin analogue	Octreotide (Sandostatin)	1 ucg/kg SQ[KJ1] daily or 0.5 ucg/kg IV BID	Increases small bowel motility – relieves nausea and vomiting via inhibiting release of GI hormones and secretion	Delayed gastric emptying
Acetylcholinesterase inhibitors	Pyridostigmine	0.-25-2.0mg/kg/day	Increases acetylcholine at NMJ promoting intestinal contractions
Muscle relaxant	Baclofen	0.5mg/kg	Inhibitory role on the lower esophageal sphincter relaxation through its stimulation of gamma-aminobutyric acid B (GABA) receptors, improving delayed gastric emptying

Bulk-Forming Laxatives

Osmotic Laxatives

Stimulant Laxatives

Lubricant Laxative

Prosecretory Agents

Nausea & Vomiting

IBS

Drug Class	Drug	Oral Dose	Indication / Where It Works	Side Effects
Laxative	Polyethylene glycol (Miralax)	0.2 to 1 g/kg/day, titrate to effect	Constipation/IBS-C - Osmotic laxative leading to water retention in gut lumen	Diarrhea, electrolyte disturbances, metabolic acidosis, unclear association with neuropsychiatric events
	Linaclotide (Linzess)	72mcg-290mcg in 72mcg increments	Use in IBS-C. Guanylate cyclase C agonist increases chloride and bicarbonate secretion into intestinal lumen via CFTR channel.	Diarrhea. Black box warning in children <6yo. Warning for children 6-18 due to single dose causing lethal diarrhea in neonatal mouse model.
	Lubiprostone (Amitiza)	8mcg BID for IBS (higher dosing for constipation. No pediatric dosing available)	Use in IBS-C. Chloride channel activator	Diarrhea. Recommended negative pregnancy test and contraception during use in women of childbearing potential. No safety data established in children.
Antispasmodic	Dicyclomine (Bentyl)	6 months to <2 years: Oral: 5 to 10 mg 3 to 4 times daily ≥2 years Oral: 10 mg 3 to 4 times daily Adolescents 10-20mg 3-4x/day	Inhibit parasympathetic acetylcholine signaling	CNS effects: drowsiness, blurry vision. Diarrhea. Anhidrosis. Psychosis/delirium.
Antispasmodic	Hyoscyamine (Hyocyne, Levsin	Infants: drops 0.125mg/mL - <5kg: 4 drops; 5-7kg: 5 drops; 7-10kg: 6 drops; >10kg: 8 drops. Q4hr prn. Multiple formulations available for older children. Sublingual tablets 0.125-0.25mg q4hr PRN Multiple formulations and routes exist.	Inhibit parasympathetic acetylcholine signaling	Contraindicated with myasthenia, obstructive GI diseases, ileus. CNS effects: drowsiness/blurry vision. Diarrhea. Anhidrosis. Psychosis
Herbal remedy	Peppermint oil	Adult dosing max dose 1200mg/day. Typically 180-200mg up to 3x/day.	Reduce pain, bloating in patients with IBS-C or IBS-D. More useful for lower GI symptoms. May attenuate visceral hypersensitivity. Anti-spasmodic properties of L-menthol. Possible analgesic effects via TRPM8 agonism.	Refer to specific formulations. Allergic reaction, heartburn, contact sensitivity/burns/skin necrosis/dermatitis
Herbal mixture	Iberogast	>12 – 20 drops TID premeals or with meals 6-12 15 drops TID <6 10 drops TID	Functional dyspepsia, IBS	Hepatotoxicity—extremely rare but would avoid in patient with liver disease
Tri-cyclic anti-depressants	Amitriptyline (Elavil)	No pediatric dosing specifically for IBS. Adults 10-25mg qhs with max 75mg. Pediatric 0.1mg/kg-2mg/kg titrate up slowly over several weeks	Inhibit reuptake of synaptic serotonin/norepinephrine	Anticholinergic effects, QTc prolongation, CNS depression, Mania in bipolar disorder, Suicidal thinking. Should not be discontinued abruptly.
Tri-cyclic anti-depressants	Nortriptyline (Pamelor)	Neuropathic pain dosing 0.05-1mg/kg qhs. Max 3mg/kg/d (150mg/d) can titrate up as often as every 3 days.	- inhibit histamine/5-HT/acetylcholine activity, increase post-synaptic serotonin/norepinephrine	Suicidal thinking/behavior, Anticholinergic effects, CNS depression, QTc prolongation, Mania in bipolar disorder. Should not be discontinued abruptly.
Antidiarrheal	Loperamide (Imodium)	2-5yo: 1mg/dose; 6-8yo: 2mg/dose (max 4/day); 9-11yo: 2mg/dose (max 6mg/day); >12yo: 4mg/dose (max 8mg/day). Higher doses utilized with other causes of chronic diarrhea (SBS, intestinal failure).	Diarrhea Inhibit peristalsis and prolong transit time by action on circular/longitudinal muscles via opioid receptors.	Constipaiton, abdominal pain/distention, ileus. Black Box warning: Torsades de pointes. Avoid in patients with risk for prolonged QT.
Antidiarrheal	Fiber Supplementation	Various formulations. Dose: (Age + 5g)/day	Soluble fiber absorbs water in intestine and promotes peristalsis to reduce transit time. Insoluble fiber creates stool bulk.	Cramps, constipation or diarrhea
Analgesic	Pregabalin (Lyrica)	Fibromyalgia dosing: adolescents – 37.5mg BID x1 week then titrate up weekly (150mg-max450mg/day divided BID)	Pain/bloating. Alpha-2-delta subunit of voltage-gated Calcium channels in CNS. Inhibit excitatory neurotransmitter release.	Agioedema, weight gain, Xerostermia, CNS/ophthalmic complaints. Need gradual withdrawal.
Analgesic	Gabapentin (Neurontin)	Neuropathic pain dosing: 5mg/kg/dose (increase from qhs à BID à TID over 3 days). Titrate dose typically 8-35mg/kg/day divided TID)	Pain/bloating. Modulation of excitatory neurotransmitter release via alpha-2-delta subunit binding in voltage-gated calcium channels.	Viral infection, Drowsiness, dizziness. Need gradual withdrawal.
Antibiotic	Rifaxamin (Xifaxin)	Adult IBS dosing: 550mg TID x14 days. Pediatric SIBO dosing - 3-8yo: 200mg TID, >8yo: 200-550mg TID 7-14 days	Bloating, diarrhea Inhibit bacterial RNA synthesis by binding to bacterial DNA-dependent RNA polymerase. Minimally absorbed.	Nausea, elevated ALT, peripheral edema, dizziness, fatigue.
SSRI	Fluoxetine (Prozac)	Starting 5-10mg daily. Titrate to 10-20mg daily. Slow increase q3 weeks. Adolescents max 60mg/d. No IBS dosing	Inhibit CNS neuron presynaptic serotonin reuptake.	Increasing suicidality. QT prolongation, CNS depression, nausea/diarrhea
	Sertraline (Zoloft)	25-50mg/d. Max 200mg/d. Slow titration q3-4 weeks	Inhibit CNS neuron presynaptic serotonin reuptake.	Increasing suicidality, QTc prolongation, CNS depression, restlessness, hyperkinesis, hyperactivity, agitation.
	Citalopram (Celexa)	Children >7yo: 10mg daily. Increase by 10mg every 1-2 weeks. Typically, 20-40mg/day	Inhibit CNS neuron presynaptic serotonin reuptake.	Increasing suicidality, QTc prolongation, Somnolence, insomnia, nausea, diarrhea. Should not stop abruptly.
Opioid receptor agonist/antagonist	Eluxadoline (Viberzi)	Adult dosing 100mg BID.	IBS-D, Mixed mu-opiate agonist and delta-opiate antagonist	Acute pancreatitis. Constipation. Contraindicated in patients without gallbladder or with hepatic impairment.
Other classes of medications that have shown varying degrees of success in treating symptoms of IBS include prokinetics (e.g., domperidone), acid suppressing agents (e.g., PPIs), antihistamines (e.g., cyproheptadine) and probiotics. Also consider psychological interventions including cognitive behavioral therapy when appropriate.

Liver Transplant

Pancreatic Enzyme Replacement Therapy

IBD

Motility

Motility

Constipation

Nausea & Vomiting

IBS

IBS

Liver Transplant

Pancreatic Enzyme Replacement Therapy

Types

Dosing