Mayonaise
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- Dec 8, 2023
- 335
Many people are concerned about Metoclopramide side effects or interactions with other medications they're on.
This concern has been addressed many times and while I have nothing relevant to add to this topic, I found myself researching other dopamine-blocking antiemetics for personal reasons.
In my opinion, Metopimazine may be an effective substitute for Metoclopramide/Domperidone for 3 reasons:
Metopimazine (the most common brand name is Vogalib) is apparently only used in France and it's OTC there. It can be purchased without prescription from online pharmacies as well (some ship internationally). It is sold in tablets which dissolve rapidly under the tongue.
I researched this drug as much as I could, here's my report:
What it is and how it works
Metopimazine is an antiemetic of the phenothiazine group.
It is a highly potent and selective dopamine D2/D3 receptor antagonist and has dual mechanisms of action: central antagonism of D2/D3 receptors in the chemoreceptor trigger zone in the area postrema, resulting in the antiemetic and antinauseant properties, and antagonism of D2 receptors in the gut resulting in increased motility.
It has also shown alpha 1 and Histamine H1 receptors antagonism.
It seems to be widely used as an AE drug against chemotherapy-induced nausea and vomiting, often combined with serotonin 5-HT3 receptor antagonists such as Ondansetron.
Sources: 1 | 2
It crosses the blood–brain barrier less than domperidone and metoclopramide, and hence has peripheral selectivity.
Unlike domperidone, metopimazine is expected to have less cardiovascular side-effects.
Unlike metoclopramide, metopimazine does not interact with serotonin 5-HT3 and 5-HT4 receptors.
The maximum plasma concentration of metopimazine is reached approximately 45 minutes after oral administration.
Sources: 1 | 2 | 3
Dosage and side-effects
Metopimazine is generally well tolerated, and the approved dose is 30 mg per day (4 tablets per day - see leaflet for dosage information).
However, it was determined to be safe at a dose of 30 mg administered orally 6 times daily (180 mg/day).
At higher doses, the primary side effects were dizziness and orthostatic hypotension.
The rare neurologic side effects are sedation, drowsiness and extrapyramidal syndrome which are reversible once the drug is stopped.
This possible extrapyramidal adverse event was reported by Herrstedt et al. (1997) in a single patient with a very high dose of 360 mg per day.
Source: https://pubmed.ncbi.nlm.nih.gov/9010988
Interactions with other drugs
- antihypertensive drugs and beta-blockers: the antihypertensive and vasodilator effect may be increased
- morphine derivatives, antipsychotics, barbiturates, benzodiazepines, other anxiolytics, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedative H1 antihistamines, baclofen, pizotifen, thalidomide: central nervous system depression may be increased
Bioavailability
Bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the circulatory system. When a medication is administered intravenously, its bioavailability is 100%. However, when a medication is administered via routes other than intravenous, its bioavailability is lower.
The bioavailability of Metopimazine in humans is low. A 10 mg dose was reported to have an absolute bioavailability of about 20%.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8929364
A drug with relatively low bioavailability requires a larger dose to reach the minimum effective concentration threshold.
https://www.ncbi.nlm.nih.gov/books/NBK557852
Luckily, Metopimazine was determined to be safe at higher doses..
Note on bioavailability: I still haven't found out whether low bioavailability is necessarily a bad thing.
For example, Domperidone's bioavailability is even lower (about 15%) and it's one of the recommended AE anyway.
Metoclopramide's bioavailability seems to be very variable (32 to 100%) - I haven't been able to find a definitive info for that.
But even if all these drugs had the same 100% oral bioavailability, potency would have to be considered.
1g of Metopimazine may be more potent than 1g of Domperidone, thus less quantity of the former would be required to equal the same effect of the latter.
To sum it up (and this is just my personal opinion), comparing bioavailability of different drugs without considering their respective potency is not very useful. What surely is useful is comparing bioavailability of the same drug when given in different ROAs.
If someone is more knowledgeable than me, please correct me if I'm wrong.
Last, here's the medication leaflet.
This concern has been addressed many times and while I have nothing relevant to add to this topic, I found myself researching other dopamine-blocking antiemetics for personal reasons.
In my opinion, Metopimazine may be an effective substitute for Metoclopramide/Domperidone for 3 reasons:
- it seems to be an effective dopamine blocker
- it doesn't seem to interact badly with other commonly prescribed drugs
- even if taken in higher doses, it seems to be pretty safe and the side-effects appear neglectable
Metopimazine (the most common brand name is Vogalib) is apparently only used in France and it's OTC there. It can be purchased without prescription from online pharmacies as well (some ship internationally). It is sold in tablets which dissolve rapidly under the tongue.
I researched this drug as much as I could, here's my report:
What it is and how it works
Metopimazine is an antiemetic of the phenothiazine group.
It is a highly potent and selective dopamine D2/D3 receptor antagonist and has dual mechanisms of action: central antagonism of D2/D3 receptors in the chemoreceptor trigger zone in the area postrema, resulting in the antiemetic and antinauseant properties, and antagonism of D2 receptors in the gut resulting in increased motility.
It has also shown alpha 1 and Histamine H1 receptors antagonism.
It seems to be widely used as an AE drug against chemotherapy-induced nausea and vomiting, often combined with serotonin 5-HT3 receptor antagonists such as Ondansetron.
Sources: 1 | 2
It crosses the blood–brain barrier less than domperidone and metoclopramide, and hence has peripheral selectivity.
Unlike domperidone, metopimazine is expected to have less cardiovascular side-effects.
Unlike metoclopramide, metopimazine does not interact with serotonin 5-HT3 and 5-HT4 receptors.
The maximum plasma concentration of metopimazine is reached approximately 45 minutes after oral administration.
Sources: 1 | 2 | 3
Dosage and side-effects
Metopimazine is generally well tolerated, and the approved dose is 30 mg per day (4 tablets per day - see leaflet for dosage information).
However, it was determined to be safe at a dose of 30 mg administered orally 6 times daily (180 mg/day).
At higher doses, the primary side effects were dizziness and orthostatic hypotension.
The rare neurologic side effects are sedation, drowsiness and extrapyramidal syndrome which are reversible once the drug is stopped.
This possible extrapyramidal adverse event was reported by Herrstedt et al. (1997) in a single patient with a very high dose of 360 mg per day.
Source: https://pubmed.ncbi.nlm.nih.gov/9010988
Interactions with other drugs
- antihypertensive drugs and beta-blockers: the antihypertensive and vasodilator effect may be increased
- morphine derivatives, antipsychotics, barbiturates, benzodiazepines, other anxiolytics, sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine), sedative H1 antihistamines, baclofen, pizotifen, thalidomide: central nervous system depression may be increased
Bioavailability
Bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the circulatory system. When a medication is administered intravenously, its bioavailability is 100%. However, when a medication is administered via routes other than intravenous, its bioavailability is lower.
The bioavailability of Metopimazine in humans is low. A 10 mg dose was reported to have an absolute bioavailability of about 20%.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8929364
A drug with relatively low bioavailability requires a larger dose to reach the minimum effective concentration threshold.
https://www.ncbi.nlm.nih.gov/books/NBK557852
Luckily, Metopimazine was determined to be safe at higher doses..
Note on bioavailability: I still haven't found out whether low bioavailability is necessarily a bad thing.
For example, Domperidone's bioavailability is even lower (about 15%) and it's one of the recommended AE anyway.
Metoclopramide's bioavailability seems to be very variable (32 to 100%) - I haven't been able to find a definitive info for that.
But even if all these drugs had the same 100% oral bioavailability, potency would have to be considered.
1g of Metopimazine may be more potent than 1g of Domperidone, thus less quantity of the former would be required to equal the same effect of the latter.
To sum it up (and this is just my personal opinion), comparing bioavailability of different drugs without considering their respective potency is not very useful. What surely is useful is comparing bioavailability of the same drug when given in different ROAs.
If someone is more knowledgeable than me, please correct me if I'm wrong.
Last, here's the medication leaflet.
WHAT IS VOGALIB 7.5 mg SUGAR-FREE, oral lyophilisate sweetened with aspartame AND WHAT IS IT USED FOR?
Pharmacotherapeutic class
This medicine is an anti-emetic.
Therapeutic indications
VOGALIB is indicated for the short-term treatment of nausea and vomiting not accompanied by fever in adults and children over 6 years of age.
Contraindications
In elderly people, or in cases of serious liver or kidney disease, the appearance of drowsiness or dizziness may indicate an overdose: stop taking the medicine and consult your doctor.
Interactions with other drugs
TO AVOID POSSIBLE INTERACTIONS BETWEEN MEDICATIONS, IT IS NECESSARY TO REPORT ANY OTHER CURRENT TREATMENT TO YOUR DOCTOR OR PHARMACIST: in particular, avoid association with dopaminergic drugs (used in particular in the treatment of the symptoms of Parkinson's disease), or even alcohol because of the increased sedative effect of their association.
Use during pregnancy and lactation
This medicine should be used with caution by pregnant or breastfeeding women. In general, it is advisable to ask your doctor or pharmacist for advice before taking any medicine.
Effects on ability to drive and use machines
The attention of patients is drawn, particularly in drivers of vehicles and users of machines, to the risk of drowsiness.
HOW TO TAKE VOGALIB 7.5 mg SUGAR-FREE, oral lyophilisate sweetened with aspartam
Dosage
Oral administration.
In adults and children, the duration of treatment without medical advice should not exceed 2 days.
POSSIBLE SIDE EFFECTS/ADVERSE REACTIONS
Conditions of storage
No special storage precautions
Complete list of active ingredients and excipients
The active substance is:
Metopimazine: 7.5 mg for an oral lyophilisate.
The other components are: xanthan gum (Rhodigel 23), aspartam, docusate sodium, dextran 70, mannitol.
This medicinal product comes in the form of an oral lyophilisate in a box of 8.
Name and address of the marketing authorisation holder and of the manufacturing authorisation holder responsible for batch release, if different
Holder
TEVA SANTE
110, ESPLANADE DU GENERAL DE GAULLE
92931 PARIS LA DEFENSE CEDEX
Pharmacotherapeutic class
This medicine is an anti-emetic.
Therapeutic indications
VOGALIB is indicated for the short-term treatment of nausea and vomiting not accompanied by fever in adults and children over 6 years of age.
Contraindications
Do not take VOGALIB 7.5 mg SUGAR-FREE, oral lyophilisate sweetened with aspartame in the following cases:
- glaucoma (eye disease characterized by an increase in pressure in the eye),
- difficulty in urinating due to prostate problems,
- hypersensitivity to metopimazine or to any of the excipients,
- phenylketonuria (a rare disease detected at birth), due to the presence of aspartame.
In elderly people, or in cases of serious liver or kidney disease, the appearance of drowsiness or dizziness may indicate an overdose: stop taking the medicine and consult your doctor.
Precautions for use
- The intake of alcoholic beverages during treatment is not recommended.
- For children under 6 years of age, use the drop form.
Interactions with other drugs
TO AVOID POSSIBLE INTERACTIONS BETWEEN MEDICATIONS, IT IS NECESSARY TO REPORT ANY OTHER CURRENT TREATMENT TO YOUR DOCTOR OR PHARMACIST: in particular, avoid association with dopaminergic drugs (used in particular in the treatment of the symptoms of Parkinson's disease), or even alcohol because of the increased sedative effect of their association.
Use during pregnancy and lactation
This medicine should be used with caution by pregnant or breastfeeding women. In general, it is advisable to ask your doctor or pharmacist for advice before taking any medicine.
Effects on ability to drive and use machines
The attention of patients is drawn, particularly in drivers of vehicles and users of machines, to the risk of drowsiness.
HOW TO TAKE VOGALIB 7.5 mg SUGAR-FREE, oral lyophilisate sweetened with aspartam
Dosage
- In adults:
1 oral lyophilisate (7.5 mg) at the time of symptoms, to be repeated if necessary if symptoms persist or reappear, without exceeding 4 lyophilisates per day (30 mg of metopimazine). - In children over 6 years of age:
1 oral lyophilisate at the time of symptoms, to be repeated if necessary if symptoms persist or reappear, without exceeding 2 lyophilisates per day (i.e. 15 mg of metopimazine).
Oral administration.
The oral lyophilisate is taken
- either after depositing on the tongue where it disintegrates almost immediately (do not chew),
- or after dissolution in half a glass of water, where its dispersion is instantaneous.
In adults and children, the duration of treatment without medical advice should not exceed 2 days.
POSSIBLE SIDE EFFECTS/ADVERSE REACTIONS
Like all medicines, VOGALIB 7.5 mg SUGAR-FREE, oral lyophilisate sweetened with aspartame is likely to have undesirable effects, although not everyone is subject to them:
- drowsiness,
- Muscle contractures, which may lead to difficulties in performing certain movements (walking, writing, speaking..), or abnormal movements.
- Discomfort such as hypotension, when changing position (lying down/standing up) observed in particular with the injectable form,
- dry mouth,
- constipation,
- visual accommodation disorders,
- difficulty in urination,
- impotence, frigidity,
- cessation of menstruation, abnormal milk flow, breast development in men, excess of prolactin (hormone causing lactation),
- rash, redness of the skin.
Conditions of storage
No special storage precautions
Complete list of active ingredients and excipients
The active substance is:
Metopimazine: 7.5 mg for an oral lyophilisate.
The other components are: xanthan gum (Rhodigel 23), aspartam, docusate sodium, dextran 70, mannitol.
This medicinal product comes in the form of an oral lyophilisate in a box of 8.
Name and address of the marketing authorisation holder and of the manufacturing authorisation holder responsible for batch release, if different
Holder
TEVA SANTE
110, ESPLANADE DU GENERAL DE GAULLE
92931 PARIS LA DEFENSE CEDEX
