Table 2.

Comparison of the field of application and the safety of STW 5 vs. metoclopramide and domperidone (oral dosage forms), as documented in summaries of product characteristics (SPCs, shortened) for Germany

Safety related sections from the SPC	STW 5	Metoclopramide	Domperidone
Field of application	For the treatment of functional and motility related gastrointestinal diseases such as functional dyspepsia and irritable bowel syndrome as well as for the supportive treatment of gastritis. These diseases manifest predominantly in complaints of stomach pain, feeling of fullness, bloating, gastro-intestinal cramps, nausea and heartburn	Prevention of delayed chemotherapy induced nausea and vomiting Prevention of radiotherapy induced nausea and vomiting Symptomatic treatment of nausea and vomiting, including acute migraine induced nausea and vomiting Metoclopramide can be used in combination with oral analgesics to improve the absorption of analgesics in acute migraine	For the treatment of the symptoms nausea and vomiting in adults and adolescents with an age of more than 12 years and a body weight of 35 kg at minimum
Duration of use	Basically, there is no restriction of the duration of use. The duration of use is determined by the form, severity and course of the disease	The maximum recommended duration of use is 5 days	As a rule, the maximum duration of use should not exceed one week
Contraindication	Hypersensitivity against the active substances Children below 3 years, due to the lack of sufficient data	Hypersensitivity against one of the constituents – Gastrointestinal bleeding, mechanical obstruction or gastrointestinal perforation, where a stimulation of motility is a risk – Phaeochromocytoma – Neuroleptic or metoclopramide triggered tardive dyskinesia – Epilepsy – Parkinson disease – Combination with levodopa or dopaminergic agonists – Known history of methamoglobinamia – Use in children below 1 year due to the enhanced risk of extrapyramidal diseases	– Hypersensitivity against one of the constituents – Prolactinoma – Disturbance of hepatic function – Prolonged QTc interval, electrolyte disturbances or congestive cardiac insufficiency – Concomitant use with drugs leading to prolonged QT, or with strong CYP3A4 inhibitors – Gastrointestinal bleedings, mechanical obstruction or gastrointestinal perforation where a stimulation of motility is a risk
Special warnings and safety measures	In case that symptoms persist or in case of lack of success of treatment for more than a week or in case symptoms worsen, a medical doctor should be consulted for excluding organic causes Generally, in children below 6 years, in case of abdominal pain a medical doctor should be consulted	Neurological diseases: Extrapyramidal diseases (usually reversible) Tardive dyskinesia (especially after prolonged use) Malign neuroleptic syndrome Symptoms of Parkinson disease can worsen. Methemoglobinemia Cardiac diseases: Care is needed in prolonged QTc interval, electrolyte disturbances (hypokalemia, hyperkalemia, hypomagnesemia) or congestive cardiac insufficiency, as well as with concomitant use with drugs leading to prolonged QT time Functional disturbances of liver and kidney: Reduction of dose needed	Functional disturbances of kidney: Reduce dosing frequency and dose Cardiovascular effects: Very rarely: Prolongation of QT interval and torsade de pointes in predisposed patients Enhanced risk of severe ventricular arrhythmias or sudden cardiac death, predominantly in high doses and predisposed patients with prolonged QTc interval, electrolyte disturbances (hypokalemia, hyperkalemia, hypomagnesemia) or congestive cardiac insufficiency, as well as with concomitant use of drugs leading to prolonged QT time Concomitant use with Levodopa can lead to increased plasma concentrations of levodopa
Interactions with other drugs and other interactions	None known	Contraindicated combinations: Concomitant use of levodopa or dopaminergic agonists Combination to be avoided Ethanol Take care when combining with Anticholinergic drugs, morphine derivatives, anxiolytics, sedative H1 antihistaminics, antidepressants, barbiturates, clonidine, neuroleptics, serotonergic drugs, digoxin, ciclosporin, mivacurium and suxamethonium, strong CYP2D6 inhibitors	Combinations to be avoided: Concomitant use of antacids or antisecretory drugs Concomitant use with drugs which are metabolized via CYP3A4 (e. g., ketoconazole, erythromycine) leads to enhanced plasma levels of domperidone Contraindicated combinations: Drugs leading to prolonged QT times – Antiarrhythmics class IA (e. g., disopyramid, hydrochinidine, chinidine) – Antiarrhythmics class III (e. g. amiodarone, dofetilide, dronedaron, ibutilide, sotalo). – Certain antipsychotics (e. g., haloperidol, pimozide, sertindole) – Certain antidepressants (e. g., citalopram, escitalopram) – Certain antibiotics (e. g., erythromycine, levofloxacine, moxifloxacine, spiramycine) – Certain antimycotics (e. g., pentamidine) – Certain antimalaria drugs (especially halofantrine, lumefantrine) – Certain gastrointestinal drugs (e. g., cisapride, dolasetrone, prucalopride) – Certain antihistaminics (e. g., mequitazine, mizolastine) – Certain anticancer drugs (e. g., toremifen, vandetanib, vincamin) – Certain other drugs (e. g., pepridil, diphemanil, methadone) Strong CYP3A4 inhibitors, e. g., – Protease inhibitors – Systemic azole antimycotics – Some macrolides (erythromycine, clarithromycine, telithromycine) Combinations not recommended Moderate CYP3A4 inhibitors (e. g. diltiazem, verapamil, makrolides) Take care when combining with – Drugs inducing bradycardia or hypopotassemia as well as the following macrolides: azithromycine, roxithromycine – Ketoconazole (prolongation of QTc, interactions) – Levodopa (interaction)
Impairment of the ability to drive and to use machines	None	Somnolence, drowsiness, dizziness, dyskinesias and dystonias impairing the ability to drive and to use machines	None or only negligible influence
Adverse events
Very frequent	–	– Somnolence	–
Frequent	–	– Diarrhea – Asthenia – Extrapyramidal diseases (especially in children and young adults and in case of overdose), parkinsonism, akathisia – Depression – Hypertension	– Dryness of mouth
Occasionally	–	– Bradycardia – Amenorrhea, hyperprolactinemia – Hypersensitivity – Dystonia, dyskinesia, impaired consciousness – Hallucination – Confusion	– Anxiety, loss of libido – Somnolence, headache – Diarrhea – Exanthema, pruritus – Galactorrhea, breast pain and -tension – Asthenia
Rare	–	– Galactorrhea – Cramps	–
Very rare	– Hypersensitivity reactions (as e. g., exanthema, pruritus, dyspnea)	–	–
Unknown	–	– Methemoglobinemia, sulfhemoglobinemia – Cardiac arrest, atrioventricular blockage, QT prolongation, torsade de pointes – Gynecomastia – Anaphylactic reaction (including anaphylactic shock) – Tardive dyskinesia, which may be irreversible, malign neuroleptic syndrome – Acute hypertension in patients with phaeochromocytoma	– Allergic hypersensitivity (including anaphylactic shock) – Agitation, nervousness – Oculogyric crisis – Ventricular arrhythmias, prolongation of QTc time, torsade de pointes, sudden cardiac death – Urticaria, angioedema – Urine retention – Gynecomastia, amenorrhea – Abnormal liver function tests, hyperprolactinemia – Acathisia – Depression, – Extrapyramidal side effects, cramps, agitation (mainly in children)
Overdose	The acute oral toxicity studies in different animal species and long standing therapeutic experience in patients did not give hints on intoxications	Extrapyramidal diseases, somnolence, confusion, hallucination, cardiac and respiratory arrest	Symptoms of overdose were mainly observed in children: Agitation, change of consciousness, cramps, disorientation, somnolence, extrapyramidal reactions

Up to 2014 the fields of application of MCP included in addition motility disturbances of the upper gastrointestinal tract (e. g., in functional dyspepsia, heartburn, reflux esophagitis, functional pyloric stenosis), those of domperidone epigastic feeling of fullness and upper abdominal discomfort

Frequency of adverse events is classified as follows: Very frequent ≥1/10; Frequent ≥1/100 to <1/10; Occasionally ≥1/1000 to <1/100; Rare ≥1/10,000 to <1/1000; Very rare <1/10,000; Unknown: can not be estimated based on the data available