خواص دارویی و گیاهی
Domperidone, sold under the brand name Motilium among others, is a peripherally selective dopamine D2 receptor antagonist that was developed by Janssen Pharmaceutica and is used as an antiemetic, gastroprokinetic agent, and galactagogue.[1][6][7] It may be administered orally or rectally, and is available in the form of tablets, orally disintegrating tablets (based on Zydis technology),[8] suspension, and suppositories.[9] The drug is used to relieve nausea and vomiting; to increase the transit of food through the stomach (by increasing gastrointestinal peristalsis); and to promote lactation (breast milk production) by release of prolactin.[1][7]
It was reported in 2007 that domperidone is available in 58 countries, including Canada,[10] but the uses or indications of domperidone vary between nations. In Italy it is used in the treatment of gastroesophageal reflux disease and in Canada, the drug is indicated in upper gastrointestinal motility disorders and to prevent gastrointestinal symptoms associated with the use of dopamine agonist antiparkinsonian agents.[11] In the United Kingdom, domperidone is only indicated for the treatment of nausea and vomiting and the treatment duration is usually limited to 1 week.
In the United States, domperidone is not currently a legally marketed human drug and it is not approved for sale in the U.S. On 7 June 2004, FDA issued a public warning that distributing any domperidone-containing products is illegal.[12]
There is some evidence that domperidone has antiemetic activity.[13] It is recommended in the Canadian Headache Society’s guidelines for treatment of nausea associated with acute migraine.[14]
قرص motidon domperidone
Gastroparesis is a medical condition characterised by delayed emptying of the stomach when there is no mechanical gastric outlet obstruction. Its cause is most commonly idiopathic, a diabetic complication or a result of abdominal surgery. The condition causes nausea, vomiting, fullness after eating, early satiety (feeling full before the meal is finished), abdominal pain and bloating.
Domperidone may be useful in diabetic and idiopathic gastroparesis.[15][16]
However, increased rate of gastric emptying induced by drugs like domperidone does not always correlate (equate) well with relief of symptoms.[17]
Parkinson’s disease is a chronic neurological condition where a decrease in dopamine in the brain leads to rigidity (stiffness of movement), tremor and other symptoms and signs. Poor gastrointestinal function, nausea and vomiting is a major problem for people with Parkinson’s disease because most medications used to treat Parkinson’s disease are given by mouth. These medications, such as levodopa, can cause nausea as a side effect. Furthermore, anti-nausea drugs, such as metoclopramide, which do cross the blood–brain barrier may worsen the extra-pyramidal symptoms of Parkinson’s disease.
Domperidone can be used to relieve gastrointestinal symptoms in Parkinson’s disease; it blocks peripheral D2 receptors but does not cross the blood–brain barrier in normal doses (the barrier between the blood circulation of the brain and the rest of the body) so has no effect on the extrapyramidal symptoms of the disease.[18] In addition to this, domperidone may enhance the bioavailability (effect) of levodopa (one of the main treatments in Parkinson’s disease).[19]
Although these features make domperidone a useful drug in Parkinson’s disease, caution is needed due to the cardiotoxic side effects of domperidone especially when given intravenously, in elderly people and in high doses (> 30 mg per day).[20] A clinical sign of domperidone’s potential toxicity to the heart is the prolongation (lengthening) of the QT interval (a segment of the heart’s electrical pattern).[21]
Domperidone may be used in functional dyspepsia in both adults and children.[22][23]
The hormone prolactin stimulates lactation (production of breast milk). Dopamine, released by the hypothalamus stops the release of prolactin from the pituitary gland. Domperidone, by acting as an anti-dopaminergic agent, results in increased prolactin secretion, and thus promotes lactation (that is, it is a galactogogue). Domperidone moderately increases the volume of expressed breast milk in mothers of preterm babies where breast milk expression was inadequate, and appears to be safe for short-term use for this purpose.[24][25][26] In the United States, domperidone is not approved for this or any other use.[27][28]
A study called the EMPOWER trial was designed to assess the effectiveness and safety of domperidone in assisting mothers of preterm babies to supply breast milk for their infants.[29] The study randomized 90 mothers of preterm babies to receive either domperidone 10 mg orally three times daily for 28 days (Group A) or placebo 10 mg orally three times daily for 14 days followed by domperidone 10 mg orally three times daily for 14 days (Group B). Mean milk volumes at the beginning of the intervention were similar between the 2 groups. After the first 14 days, 78% of mothers receiving domperidone (Group A) achieved a 50% increase in milk volume, while 58% of mothers receiving placebo (Group B) achieved a 50% increase in milk volume.[30]
To induce lactation, domperidone is used at a dosage of 10 to 20 mg 3 or 4 times per day by mouth.[31] Effects may be seen within 24 hours or may not be seen for 3 or 4 days.[31] The maximum effect occurs after 2 or 3 weeks of treatment, and the treatment period generally lasts for 3 to 8 weeks.[31] A 2012 review shows that no studies support prophylactic use of a galactagogue medication at any gestation including Domperidone.[32]
Domperidone has been found effective in the treatment of pediatric reflux.[33] However some specialists consider its risks prohibitory of the treatment of infantile reflux.[34]
Side effects associated with domperidone include dry mouth, abdominal cramps, diarrhea, nausea, rash, itching, hives, and hyperprolactinemia (the symptoms of which may include breast enlargement, galactorrhea, breast pain/tenderness, gynecomastia, hypogonadism, and menstrual irregularities).[31] Due to blockade of D2 receptors in the central nervous system, D2 receptor antagonists like metoclopramide can also produce a variety of additional side effects including drowsiness, akathisia, restlessness, insomnia, lassitude, fatigue, extrapyramidal symptoms, dystonia, Parkinsonian symptoms, tardive dyskinesia, and depression.[1][7] However, this is not the case with domperidone, because, unlike other D2 receptor antagonists, it minimally crosses the blood-brain-barrier, and for this reason, is rarely associated with such side effects.[1][7]
Due to D2 receptor blockade, domperidone causes hyperprolactinemia.[36] Hyperprolactinemia can suppress the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus, in turn suppressing the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and resulting in hypogonadism (low sex hormone (e.g., testosterone, estradiol) levels).[37] As such, male patients may experience low libido, erectile dysfunction, and impaired spermatogenesis.[37] Also in accordance with hyperprolactinemia, 10–15% of female patients have been reported to experience mammoplasia (breast enlargement), mastodynia (breast pain/tenderness), galactorrhea (inappropriate or excessive milk production/secretion), and amenorrhea (cessation of menstrual cycles) with domperidone treatment.[36] Gynecomastia has been reported in males treated with domperidone,[38] and galactorrhea could occur in males as well.[37]
Domperidone use is associated with an increased risk of sudden cardiac death (by 70%)[39] most likely through its prolonging effect of the cardiac QT interval and ventricular arrhythmias.[40][41] The cause is thought to be blockade of hERG voltage-gated potassium channels.[42][43] The risks are dose-dependent, and appear to be greatest with high/very high doses via intravenous administration and in the elderly, as well as with drugs that interact with domperidone and increase its circulating concentrations (namely CYP3A4 inhibitors).[44][45] Conflicting reports exist, however.[46] In neonates and infants, QT prolongation is controversial and uncertain.[47][48]
UK drug regulatory authorities (MHRA) have issued the following restriction on domperidone in 2014 due to increased risk of adverse cardiac effects:
Domperidone (Motilium) is associated with a small increased risk of serious cardiac side effects. Its use is now restricted to the relief of nausea and vomiting and the dosage and duration of use have been reduced. It should no longer be used for the treatment of bloating and heartburn. Domperidone is now contraindicated in those with underlying cardiac conditions and other risk factors. Patients with these conditions and patients receiving long-term treatment with domperidone should be reassessed at a routine appointment, in light of the new advice.
However, a 2015 Australian review concluded the following:[45]
Based on the results of the two TQT (the regulatory agency gold standard for assessment of QT prolongation) domperidone does not appear to be strongly associated with QT prolongation at oral doses of 20 mg QID in healthy volunteers. Further, there are limited case reports supporting an association with cardiac dysfunction, and the frequently cited case-control studies have significant flaws. While there remains an ill-defined risk at higher systemic concentrations, especially in patients with a higher baseline risk of QT prolongation, our review does not support the view that domperidone presents intolerable risk.
In Britain a legal case involved the death of two children of a mother whose three children had all had hypernatraemia. She was charged with poisoning the children with salt. One of the children, who was born at 28 weeks gestation with respiratory complications and had a fundoplication for gastroesophageal reflux and failure to thrive was prescribed domperidone. An advocate for the mother suggested the child may have suffered neuroleptic malignant syndrome as a side effect of domperidone due to the drug crossing the child’s immature blood-brain-barrier.[49]
Domperidone is almost exclusively metabolized by CYP3A4, and for this reason, inhibitors and inducers of this enzyme may alter the metabolism and concentrations of domperidone. Moreover, domperidone has been identified as a modest mechanism-based (irreversible) inhibitor of CYP3A4 (Ki = 12 μM), and it has been estimated that it may increase the serum concentrations of CYP3A4 substrates by approximately 50%.[50]
Itraconazole and ketoconazole, both used to treat fungal infections, are potent CYP3A4 inhibitors and increase the plasma concentration of domperidone.[51][52] In healthy volunteers, ketoconazole increased the Cmax and AUC concentrations of domperidone by 3- to 10-fold.[53] This was accompanied by a QT interval prolongation of about 10–20 milliseconds when domperidone 10 mg four times daily and ketoconazole 200 mg twice daily were administered, whereas domperidone by itself at the dosage assessed produced no such effect.[53] As such, domperidone with ketoconazole or other CYP3A4 inhibitors is a potentially dangerous combination.[53]
Erythromycin and certain other macrolide antibiotics are CYP3A4 inhibitors and inhibit the metabolism of domperidone (in vitro), thus increasing the concentration of domperidone and potential side effects of the drug. This is of concern as both drugs may be used to treat gastroparesis.[54]
There is evidence that domperidone should not be taken with grapefruit juice, which is a known CYP3A4 inhibitor.[55]
Domperidone is a peripherally selective dopamine D2 and D3 receptor antagonist.[7] It has no clinically significant interaction with the D1 receptor, unlike metoclopramide.[7] The medication provides relief from nausea by blocking D2 receptors in the chemoreceptor trigger zone (a location in the nervous system that mediates nausea) at the floor of the fourth ventricle (a location near the brain). It increases motility in the upper gastrointestinal tract to a moderate degree and increases[56] lower esophageal sphincter pressure by blocking dopamine receptors in the gastric antrum and the duodenum. It blocks dopamine receptors in the anterior pituitary gland increasing release of prolactin which in turn increases lactation.[57][58] Domperidone may be more useful in some patients and cause harm in others by way of the genetics of the person, such as polymorphisms in the drug transporter gene ABCB1 (which encodes P-glycoprotein), the voltage-gated potassium channel KCNH2 gene (hERG/Kv11.1), and the α1D—adrenoceptor ADRA1D gene.[59]
A single 20 mg oral dose of domperidone has been found to increase mean serum prolactin levels (measured 90 minutes post-administration) in non-lactating women from 8.1 ng/mL to 110.9 ng/mL (a 13.7-fold increase).[7][60][61][62] This was similar to the increase in prolactin levels produced by a single 20 mg oral dose of metoclopramide (7.4 ng/mL to 124.1 ng/mL; 16.7-fold increase).[61][62] After two weeks of chronic administration (30 mg/day in both cases), the increase in prolactin levels produced by domperidone was reduced (53.2 ng/mL; 6.6-fold above baseline), but the increase in prolactin levels produced by metoclopramide, conversely, was heightened (179.6 ng/mL; 24.3-fold above baseline).[7][62] This indicates that acute and chronic administration of both domperidone and metoclopramide is effective in increasing prolactin levels, but that there are differential effects on the secretion of prolactin with chronic treatment.[61][62] The mechanism of the difference is unknown.[62] The increase in prolactin levels observed with the two drugs was, as expected, much greater in women than in men.[61][62] This appears to be due to the higher estrogen levels in women, as estrogen stimulates prolactin secretion.[63]
For comparison, normal prolactin levels in women are less than 20 ng/mL, prolactin levels peak at 100 to 300 ng/mL at parturition in pregnant women, and in lactating women, prolactin levels have been found to be 90 ng/mL at 10 days postpartum and 44 ng/mL at 180 days postpartum.[64][65]
Along with prolactin, domperidone has, to a lesser extent, been found to increase the secretion of thyroid-stimulating hormone (TSH), even in patients with hypothyroidism.[61] A single 4 mg intravenous dose of domperidone produced peak TSH levels of 1.9-fold above baseline and peak prolactin levels of 23-fold above baseline (which occurred at 30 minutes post-administration) in women with hypothyroidism.[61] Levels of TSH and prolactin decreased to 1.6-fold and 17-fold above baseline, respectively, at 120 minutes post-administration.[61]
With oral administration, domperidone is extensively metabolized in the liver (almost exclusively by CYP3A4/5, though minor contributions by CYP1A2, CYP2D6, and CYP2C8 have also been reported)[66] and in the intestines.[4] Due to the marked first-pass effect via this route, the oral bioavailability of domperidone is low (13–17%);[1] conversely, its bioavailability is high via intramuscular injection (90%).[1] The terminal half-life of domperidone is 7.5 hours in healthy individuals, but can be prolonged to 20 hours in people with severe renal dysfunction.[1] All of the metabolites of domperidone are inactive as D2 receptor ligands.[1][4] The drug is a substrate for the P-glycoprotein (ABCB1) transporter, and animal studies suggest that this is the reason for the low central nervous system penetration of domperidone.[67]
Domperidone is a benzimidazole derivative and is structurally related to butyrophenone neuroleptics like haloperidol.[68][69]
Domperidone is the generic name of the drug and its INN, USAN, BAN, and JAN.[75][6][76]
In 2007, it was reported that domperidone was available in 58 countries.[1] It is available over-the-counter to treat gastroesophageal reflux and functional dyspepsia in many countries, such as Ireland, the Netherlands, Italy, South Africa, Mexico, Chile, and China.[77]
Domperidone is not generally approved for use in the United States. There is an exception for use in people with treatment-refractory gastrointestinal symptoms under an FDA Investigational New Drug application.[1]
Domperidone has been studied as a potential hormonal contraceptive to prevent pregnancy in women.[81]
Domperidone, sold under the brand name Motilium among others, is a peripherally selective dopamine D2 receptor antagonist that was developed by Janssen Pharmaceutica and is used as an antiemetic, gastroprokinetic agent, and galactagogue.[1][6][7] It may be administered orally or rectally, and is available in the form of tablets, orally disintegrating tablets (based on Zydis technology),[8] suspension, and suppositories.[9] The drug is used to relieve nausea and vomiting; to increase the transit of food through the stomach (by increasing gastrointestinal peristalsis); and to promote lactation (breast milk production) by release of prolactin.[1][7]
It was reported in 2007 that domperidone is available in 58 countries, including Canada,[10] but the uses or indications of domperidone vary between nations. In Italy it is used in the treatment of gastroesophageal reflux disease and in Canada, the drug is indicated in upper gastrointestinal motility disorders and to prevent gastrointestinal symptoms associated with the use of dopamine agonist antiparkinsonian agents.[11] In the United Kingdom, domperidone is only indicated for the treatment of nausea and vomiting and the treatment duration is usually limited to 1 week.
In the United States, domperidone is not currently a legally marketed human drug and it is not approved for sale in the U.S. On 7 June 2004, FDA issued a public warning that distributing any domperidone-containing products is illegal.[12]
There is some evidence that domperidone has antiemetic activity.[13] It is recommended in the Canadian Headache Society’s guidelines for treatment of nausea associated with acute migraine.[14]
قرص motidon domperidone
Gastroparesis is a medical condition characterised by delayed emptying of the stomach when there is no mechanical gastric outlet obstruction. Its cause is most commonly idiopathic, a diabetic complication or a result of abdominal surgery. The condition causes nausea, vomiting, fullness after eating, early satiety (feeling full before the meal is finished), abdominal pain and bloating.
Domperidone may be useful in diabetic and idiopathic gastroparesis.[15][16]
However, increased rate of gastric emptying induced by drugs like domperidone does not always correlate (equate) well with relief of symptoms.[17]
Parkinson’s disease is a chronic neurological condition where a decrease in dopamine in the brain leads to rigidity (stiffness of movement), tremor and other symptoms and signs. Poor gastrointestinal function, nausea and vomiting is a major problem for people with Parkinson’s disease because most medications used to treat Parkinson’s disease are given by mouth. These medications, such as levodopa, can cause nausea as a side effect. Furthermore, anti-nausea drugs, such as metoclopramide, which do cross the blood–brain barrier may worsen the extra-pyramidal symptoms of Parkinson’s disease.
Domperidone can be used to relieve gastrointestinal symptoms in Parkinson’s disease; it blocks peripheral D2 receptors but does not cross the blood–brain barrier in normal doses (the barrier between the blood circulation of the brain and the rest of the body) so has no effect on the extrapyramidal symptoms of the disease.[18] In addition to this, domperidone may enhance the bioavailability (effect) of levodopa (one of the main treatments in Parkinson’s disease).[19]
Although these features make domperidone a useful drug in Parkinson’s disease, caution is needed due to the cardiotoxic side effects of domperidone especially when given intravenously, in elderly people and in high doses (> 30 mg per day).[20] A clinical sign of domperidone’s potential toxicity to the heart is the prolongation (lengthening) of the QT interval (a segment of the heart’s electrical pattern).[21]
Domperidone may be used in functional dyspepsia in both adults and children.[22][23]
The hormone prolactin stimulates lactation (production of breast milk). Dopamine, released by the hypothalamus stops the release of prolactin from the pituitary gland. Domperidone, by acting as an anti-dopaminergic agent, results in increased prolactin secretion, and thus promotes lactation (that is, it is a galactogogue). Domperidone moderately increases the volume of expressed breast milk in mothers of preterm babies where breast milk expression was inadequate, and appears to be safe for short-term use for this purpose.[24][25][26] In the United States, domperidone is not approved for this or any other use.[27][28]
A study called the EMPOWER trial was designed to assess the effectiveness and safety of domperidone in assisting mothers of preterm babies to supply breast milk for their infants.[29] The study randomized 90 mothers of preterm babies to receive either domperidone 10 mg orally three times daily for 28 days (Group A) or placebo 10 mg orally three times daily for 14 days followed by domperidone 10 mg orally three times daily for 14 days (Group B). Mean milk volumes at the beginning of the intervention were similar between the 2 groups. After the first 14 days, 78% of mothers receiving domperidone (Group A) achieved a 50% increase in milk volume, while 58% of mothers receiving placebo (Group B) achieved a 50% increase in milk volume.[30]
To induce lactation, domperidone is used at a dosage of 10 to 20 mg 3 or 4 times per day by mouth.[31] Effects may be seen within 24 hours or may not be seen for 3 or 4 days.[31] The maximum effect occurs after 2 or 3 weeks of treatment, and the treatment period generally lasts for 3 to 8 weeks.[31] A 2012 review shows that no studies support prophylactic use of a galactagogue medication at any gestation including Domperidone.[32]
Domperidone has been found effective in the treatment of pediatric reflux.[33] However some specialists consider its risks prohibitory of the treatment of infantile reflux.[34]
Side effects associated with domperidone include dry mouth, abdominal cramps, diarrhea, nausea, rash, itching, hives, and hyperprolactinemia (the symptoms of which may include breast enlargement, galactorrhea, breast pain/tenderness, gynecomastia, hypogonadism, and menstrual irregularities).[31] Due to blockade of D2 receptors in the central nervous system, D2 receptor antagonists like metoclopramide can also produce a variety of additional side effects including drowsiness, akathisia, restlessness, insomnia, lassitude, fatigue, extrapyramidal symptoms, dystonia, Parkinsonian symptoms, tardive dyskinesia, and depression.[1][7] However, this is not the case with domperidone, because, unlike other D2 receptor antagonists, it minimally crosses the blood-brain-barrier, and for this reason, is rarely associated with such side effects.[1][7]
Due to D2 receptor blockade, domperidone causes hyperprolactinemia.[36] Hyperprolactinemia can suppress the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus, in turn suppressing the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and resulting in hypogonadism (low sex hormone (e.g., testosterone, estradiol) levels).[37] As such, male patients may experience low libido, erectile dysfunction, and impaired spermatogenesis.[37] Also in accordance with hyperprolactinemia, 10–15% of female patients have been reported to experience mammoplasia (breast enlargement), mastodynia (breast pain/tenderness), galactorrhea (inappropriate or excessive milk production/secretion), and amenorrhea (cessation of menstrual cycles) with domperidone treatment.[36] Gynecomastia has been reported in males treated with domperidone,[38] and galactorrhea could occur in males as well.[37]
Domperidone use is associated with an increased risk of sudden cardiac death (by 70%)[39] most likely through its prolonging effect of the cardiac QT interval and ventricular arrhythmias.[40][41] The cause is thought to be blockade of hERG voltage-gated potassium channels.[42][43] The risks are dose-dependent, and appear to be greatest with high/very high doses via intravenous administration and in the elderly, as well as with drugs that interact with domperidone and increase its circulating concentrations (namely CYP3A4 inhibitors).[44][45] Conflicting reports exist, however.[46] In neonates and infants, QT prolongation is controversial and uncertain.[47][48]
UK drug regulatory authorities (MHRA) have issued the following restriction on domperidone in 2014 due to increased risk of adverse cardiac effects:
Domperidone (Motilium) is associated with a small increased risk of serious cardiac side effects. Its use is now restricted to the relief of nausea and vomiting and the dosage and duration of use have been reduced. It should no longer be used for the treatment of bloating and heartburn. Domperidone is now contraindicated in those with underlying cardiac conditions and other risk factors. Patients with these conditions and patients receiving long-term treatment with domperidone should be reassessed at a routine appointment, in light of the new advice.
However, a 2015 Australian review concluded the following:[45]
Based on the results of the two TQT (the regulatory agency gold standard for assessment of QT prolongation) domperidone does not appear to be strongly associated with QT prolongation at oral doses of 20 mg QID in healthy volunteers. Further, there are limited case reports supporting an association with cardiac dysfunction, and the frequently cited case-control studies have significant flaws. While there remains an ill-defined risk at higher systemic concentrations, especially in patients with a higher baseline risk of QT prolongation, our review does not support the view that domperidone presents intolerable risk.
In Britain a legal case involved the death of two children of a mother whose three children had all had hypernatraemia. She was charged with poisoning the children with salt. One of the children, who was born at 28 weeks gestation with respiratory complications and had a fundoplication for gastroesophageal reflux and failure to thrive was prescribed domperidone. An advocate for the mother suggested the child may have suffered neuroleptic malignant syndrome as a side effect of domperidone due to the drug crossing the child’s immature blood-brain-barrier.[49]
Domperidone is almost exclusively metabolized by CYP3A4, and for this reason, inhibitors and inducers of this enzyme may alter the metabolism and concentrations of domperidone. Moreover, domperidone has been identified as a modest mechanism-based (irreversible) inhibitor of CYP3A4 (Ki = 12 μM), and it has been estimated that it may increase the serum concentrations of CYP3A4 substrates by approximately 50%.[50]
Itraconazole and ketoconazole, both used to treat fungal infections, are potent CYP3A4 inhibitors and increase the plasma concentration of domperidone.[51][52] In healthy volunteers, ketoconazole increased the Cmax and AUC concentrations of domperidone by 3- to 10-fold.[53] This was accompanied by a QT interval prolongation of about 10–20 milliseconds when domperidone 10 mg four times daily and ketoconazole 200 mg twice daily were administered, whereas domperidone by itself at the dosage assessed produced no such effect.[53] As such, domperidone with ketoconazole or other CYP3A4 inhibitors is a potentially dangerous combination.[53]
Erythromycin and certain other macrolide antibiotics are CYP3A4 inhibitors and inhibit the metabolism of domperidone (in vitro), thus increasing the concentration of domperidone and potential side effects of the drug. This is of concern as both drugs may be used to treat gastroparesis.[54]
There is evidence that domperidone should not be taken with grapefruit juice, which is a known CYP3A4 inhibitor.[55]
Domperidone is a peripherally selective dopamine D2 and D3 receptor antagonist.[7] It has no clinically significant interaction with the D1 receptor, unlike metoclopramide.[7] The medication provides relief from nausea by blocking D2 receptors in the chemoreceptor trigger zone (a location in the nervous system that mediates nausea) at the floor of the fourth ventricle (a location near the brain). It increases motility in the upper gastrointestinal tract to a moderate degree and increases[56] lower esophageal sphincter pressure by blocking dopamine receptors in the gastric antrum and the duodenum. It blocks dopamine receptors in the anterior pituitary gland increasing release of prolactin which in turn increases lactation.[57][58] Domperidone may be more useful in some patients and cause harm in others by way of the genetics of the person, such as polymorphisms in the drug transporter gene ABCB1 (which encodes P-glycoprotein), the voltage-gated potassium channel KCNH2 gene (hERG/Kv11.1), and the α1D—adrenoceptor ADRA1D gene.[59]
A single 20 mg oral dose of domperidone has been found to increase mean serum prolactin levels (measured 90 minutes post-administration) in non-lactating women from 8.1 ng/mL to 110.9 ng/mL (a 13.7-fold increase).[7][60][61][62] This was similar to the increase in prolactin levels produced by a single 20 mg oral dose of metoclopramide (7.4 ng/mL to 124.1 ng/mL; 16.7-fold increase).[61][62] After two weeks of chronic administration (30 mg/day in both cases), the increase in prolactin levels produced by domperidone was reduced (53.2 ng/mL; 6.6-fold above baseline), but the increase in prolactin levels produced by metoclopramide, conversely, was heightened (179.6 ng/mL; 24.3-fold above baseline).[7][62] This indicates that acute and chronic administration of both domperidone and metoclopramide is effective in increasing prolactin levels, but that there are differential effects on the secretion of prolactin with chronic treatment.[61][62] The mechanism of the difference is unknown.[62] The increase in prolactin levels observed with the two drugs was, as expected, much greater in women than in men.[61][62] This appears to be due to the higher estrogen levels in women, as estrogen stimulates prolactin secretion.[63]
For comparison, normal prolactin levels in women are less than 20 ng/mL, prolactin levels peak at 100 to 300 ng/mL at parturition in pregnant women, and in lactating women, prolactin levels have been found to be 90 ng/mL at 10 days postpartum and 44 ng/mL at 180 days postpartum.[64][65]
Along with prolactin, domperidone has, to a lesser extent, been found to increase the secretion of thyroid-stimulating hormone (TSH), even in patients with hypothyroidism.[61] A single 4 mg intravenous dose of domperidone produced peak TSH levels of 1.9-fold above baseline and peak prolactin levels of 23-fold above baseline (which occurred at 30 minutes post-administration) in women with hypothyroidism.[61] Levels of TSH and prolactin decreased to 1.6-fold and 17-fold above baseline, respectively, at 120 minutes post-administration.[61]
With oral administration, domperidone is extensively metabolized in the liver (almost exclusively by CYP3A4/5, though minor contributions by CYP1A2, CYP2D6, and CYP2C8 have also been reported)[66] and in the intestines.[4] Due to the marked first-pass effect via this route, the oral bioavailability of domperidone is low (13–17%);[1] conversely, its bioavailability is high via intramuscular injection (90%).[1] The terminal half-life of domperidone is 7.5 hours in healthy individuals, but can be prolonged to 20 hours in people with severe renal dysfunction.[1] All of the metabolites of domperidone are inactive as D2 receptor ligands.[1][4] The drug is a substrate for the P-glycoprotein (ABCB1) transporter, and animal studies suggest that this is the reason for the low central nervous system penetration of domperidone.[67]
Domperidone is a benzimidazole derivative and is structurally related to butyrophenone neuroleptics like haloperidol.[68][69]
Domperidone is the generic name of the drug and its INN, USAN, BAN, and JAN.[75][6][76]
In 2007, it was reported that domperidone was available in 58 countries.[1] It is available over-the-counter to treat gastroesophageal reflux and functional dyspepsia in many countries, such as Ireland, the Netherlands, Italy, South Africa, Mexico, Chile, and China.[77]
Domperidone is not generally approved for use in the United States. There is an exception for use in people with treatment-refractory gastrointestinal symptoms under an FDA Investigational New Drug application.[1]
Domperidone has been studied as a potential hormonal contraceptive to prevent pregnancy in women.[81]
Domperidone, sold under the brand name Motilium among others, is a peripherally selective dopamine D2 receptor antagonist that was developed by Janssen Pharmaceutica and is used as an antiemetic, gastroprokinetic agent, and galactagogue.[1][6][7] It may be administered orally or rectally, and is available in the form of tablets, orally disintegrating tablets (based on Zydis technology),[8] suspension, and suppositories.[9] The drug is used to relieve nausea and vomiting; to increase the transit of food through the stomach (by increasing gastrointestinal peristalsis); and to promote lactation (breast milk production) by release of prolactin.[1][7]
It was reported in 2007 that domperidone is available in 58 countries, including Canada,[10] but the uses or indications of domperidone vary between nations. In Italy it is used in the treatment of gastroesophageal reflux disease and in Canada, the drug is indicated in upper gastrointestinal motility disorders and to prevent gastrointestinal symptoms associated with the use of dopamine agonist antiparkinsonian agents.[11] In the United Kingdom, domperidone is only indicated for the treatment of nausea and vomiting and the treatment duration is usually limited to 1 week.
In the United States, domperidone is not currently a legally marketed human drug and it is not approved for sale in the U.S. On 7 June 2004, FDA issued a public warning that distributing any domperidone-containing products is illegal.[12]
There is some evidence that domperidone has antiemetic activity.[13] It is recommended in the Canadian Headache Society’s guidelines for treatment of nausea associated with acute migraine.[14]
قرص motidon domperidone
Gastroparesis is a medical condition characterised by delayed emptying of the stomach when there is no mechanical gastric outlet obstruction. Its cause is most commonly idiopathic, a diabetic complication or a result of abdominal surgery. The condition causes nausea, vomiting, fullness after eating, early satiety (feeling full before the meal is finished), abdominal pain and bloating.
Domperidone may be useful in diabetic and idiopathic gastroparesis.[15][16]
However, increased rate of gastric emptying induced by drugs like domperidone does not always correlate (equate) well with relief of symptoms.[17]
Parkinson’s disease is a chronic neurological condition where a decrease in dopamine in the brain leads to rigidity (stiffness of movement), tremor and other symptoms and signs. Poor gastrointestinal function, nausea and vomiting is a major problem for people with Parkinson’s disease because most medications used to treat Parkinson’s disease are given by mouth. These medications, such as levodopa, can cause nausea as a side effect. Furthermore, anti-nausea drugs, such as metoclopramide, which do cross the blood–brain barrier may worsen the extra-pyramidal symptoms of Parkinson’s disease.
Domperidone can be used to relieve gastrointestinal symptoms in Parkinson’s disease; it blocks peripheral D2 receptors but does not cross the blood–brain barrier in normal doses (the barrier between the blood circulation of the brain and the rest of the body) so has no effect on the extrapyramidal symptoms of the disease.[18] In addition to this, domperidone may enhance the bioavailability (effect) of levodopa (one of the main treatments in Parkinson’s disease).[19]
Although these features make domperidone a useful drug in Parkinson’s disease, caution is needed due to the cardiotoxic side effects of domperidone especially when given intravenously, in elderly people and in high doses (> 30 mg per day).[20] A clinical sign of domperidone’s potential toxicity to the heart is the prolongation (lengthening) of the QT interval (a segment of the heart’s electrical pattern).[21]
Domperidone may be used in functional dyspepsia in both adults and children.[22][23]
The hormone prolactin stimulates lactation (production of breast milk). Dopamine, released by the hypothalamus stops the release of prolactin from the pituitary gland. Domperidone, by acting as an anti-dopaminergic agent, results in increased prolactin secretion, and thus promotes lactation (that is, it is a galactogogue). Domperidone moderately increases the volume of expressed breast milk in mothers of preterm babies where breast milk expression was inadequate, and appears to be safe for short-term use for this purpose.[24][25][26] In the United States, domperidone is not approved for this or any other use.[27][28]
A study called the EMPOWER trial was designed to assess the effectiveness and safety of domperidone in assisting mothers of preterm babies to supply breast milk for their infants.[29] The study randomized 90 mothers of preterm babies to receive either domperidone 10 mg orally three times daily for 28 days (Group A) or placebo 10 mg orally three times daily for 14 days followed by domperidone 10 mg orally three times daily for 14 days (Group B). Mean milk volumes at the beginning of the intervention were similar between the 2 groups. After the first 14 days, 78% of mothers receiving domperidone (Group A) achieved a 50% increase in milk volume, while 58% of mothers receiving placebo (Group B) achieved a 50% increase in milk volume.[30]
To induce lactation, domperidone is used at a dosage of 10 to 20 mg 3 or 4 times per day by mouth.[31] Effects may be seen within 24 hours or may not be seen for 3 or 4 days.[31] The maximum effect occurs after 2 or 3 weeks of treatment, and the treatment period generally lasts for 3 to 8 weeks.[31] A 2012 review shows that no studies support prophylactic use of a galactagogue medication at any gestation including Domperidone.[32]
Domperidone has been found effective in the treatment of pediatric reflux.[33] However some specialists consider its risks prohibitory of the treatment of infantile reflux.[34]
Side effects associated with domperidone include dry mouth, abdominal cramps, diarrhea, nausea, rash, itching, hives, and hyperprolactinemia (the symptoms of which may include breast enlargement, galactorrhea, breast pain/tenderness, gynecomastia, hypogonadism, and menstrual irregularities).[31] Due to blockade of D2 receptors in the central nervous system, D2 receptor antagonists like metoclopramide can also produce a variety of additional side effects including drowsiness, akathisia, restlessness, insomnia, lassitude, fatigue, extrapyramidal symptoms, dystonia, Parkinsonian symptoms, tardive dyskinesia, and depression.[1][7] However, this is not the case with domperidone, because, unlike other D2 receptor antagonists, it minimally crosses the blood-brain-barrier, and for this reason, is rarely associated with such side effects.[1][7]
Due to D2 receptor blockade, domperidone causes hyperprolactinemia.[36] Hyperprolactinemia can suppress the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus, in turn suppressing the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and resulting in hypogonadism (low sex hormone (e.g., testosterone, estradiol) levels).[37] As such, male patients may experience low libido, erectile dysfunction, and impaired spermatogenesis.[37] Also in accordance with hyperprolactinemia, 10–15% of female patients have been reported to experience mammoplasia (breast enlargement), mastodynia (breast pain/tenderness), galactorrhea (inappropriate or excessive milk production/secretion), and amenorrhea (cessation of menstrual cycles) with domperidone treatment.[36] Gynecomastia has been reported in males treated with domperidone,[38] and galactorrhea could occur in males as well.[37]
Domperidone use is associated with an increased risk of sudden cardiac death (by 70%)[39] most likely through its prolonging effect of the cardiac QT interval and ventricular arrhythmias.[40][41] The cause is thought to be blockade of hERG voltage-gated potassium channels.[42][43] The risks are dose-dependent, and appear to be greatest with high/very high doses via intravenous administration and in the elderly, as well as with drugs that interact with domperidone and increase its circulating concentrations (namely CYP3A4 inhibitors).[44][45] Conflicting reports exist, however.[46] In neonates and infants, QT prolongation is controversial and uncertain.[47][48]
UK drug regulatory authorities (MHRA) have issued the following restriction on domperidone in 2014 due to increased risk of adverse cardiac effects:
Domperidone (Motilium) is associated with a small increased risk of serious cardiac side effects. Its use is now restricted to the relief of nausea and vomiting and the dosage and duration of use have been reduced. It should no longer be used for the treatment of bloating and heartburn. Domperidone is now contraindicated in those with underlying cardiac conditions and other risk factors. Patients with these conditions and patients receiving long-term treatment with domperidone should be reassessed at a routine appointment, in light of the new advice.
However, a 2015 Australian review concluded the following:[45]
Based on the results of the two TQT (the regulatory agency gold standard for assessment of QT prolongation) domperidone does not appear to be strongly associated with QT prolongation at oral doses of 20 mg QID in healthy volunteers. Further, there are limited case reports supporting an association with cardiac dysfunction, and the frequently cited case-control studies have significant flaws. While there remains an ill-defined risk at higher systemic concentrations, especially in patients with a higher baseline risk of QT prolongation, our review does not support the view that domperidone presents intolerable risk.
In Britain a legal case involved the death of two children of a mother whose three children had all had hypernatraemia. She was charged with poisoning the children with salt. One of the children, who was born at 28 weeks gestation with respiratory complications and had a fundoplication for gastroesophageal reflux and failure to thrive was prescribed domperidone. An advocate for the mother suggested the child may have suffered neuroleptic malignant syndrome as a side effect of domperidone due to the drug crossing the child’s immature blood-brain-barrier.[49]
Domperidone is almost exclusively metabolized by CYP3A4, and for this reason, inhibitors and inducers of this enzyme may alter the metabolism and concentrations of domperidone. Moreover, domperidone has been identified as a modest mechanism-based (irreversible) inhibitor of CYP3A4 (Ki = 12 μM), and it has been estimated that it may increase the serum concentrations of CYP3A4 substrates by approximately 50%.[50]
Itraconazole and ketoconazole, both used to treat fungal infections, are potent CYP3A4 inhibitors and increase the plasma concentration of domperidone.[51][52] In healthy volunteers, ketoconazole increased the Cmax and AUC concentrations of domperidone by 3- to 10-fold.[53] This was accompanied by a QT interval prolongation of about 10–20 milliseconds when domperidone 10 mg four times daily and ketoconazole 200 mg twice daily were administered, whereas domperidone by itself at the dosage assessed produced no such effect.[53] As such, domperidone with ketoconazole or other CYP3A4 inhibitors is a potentially dangerous combination.[53]
Erythromycin and certain other macrolide antibiotics are CYP3A4 inhibitors and inhibit the metabolism of domperidone (in vitro), thus increasing the concentration of domperidone and potential side effects of the drug. This is of concern as both drugs may be used to treat gastroparesis.[54]
There is evidence that domperidone should not be taken with grapefruit juice, which is a known CYP3A4 inhibitor.[55]
Domperidone is a peripherally selective dopamine D2 and D3 receptor antagonist.[7] It has no clinically significant interaction with the D1 receptor, unlike metoclopramide.[7] The medication provides relief from nausea by blocking D2 receptors in the chemoreceptor trigger zone (a location in the nervous system that mediates nausea) at the floor of the fourth ventricle (a location near the brain). It increases motility in the upper gastrointestinal tract to a moderate degree and increases[56] lower esophageal sphincter pressure by blocking dopamine receptors in the gastric antrum and the duodenum. It blocks dopamine receptors in the anterior pituitary gland increasing release of prolactin which in turn increases lactation.[57][58] Domperidone may be more useful in some patients and cause harm in others by way of the genetics of the person, such as polymorphisms in the drug transporter gene ABCB1 (which encodes P-glycoprotein), the voltage-gated potassium channel KCNH2 gene (hERG/Kv11.1), and the α1D—adrenoceptor ADRA1D gene.[59]
A single 20 mg oral dose of domperidone has been found to increase mean serum prolactin levels (measured 90 minutes post-administration) in non-lactating women from 8.1 ng/mL to 110.9 ng/mL (a 13.7-fold increase).[7][60][61][62] This was similar to the increase in prolactin levels produced by a single 20 mg oral dose of metoclopramide (7.4 ng/mL to 124.1 ng/mL; 16.7-fold increase).[61][62] After two weeks of chronic administration (30 mg/day in both cases), the increase in prolactin levels produced by domperidone was reduced (53.2 ng/mL; 6.6-fold above baseline), but the increase in prolactin levels produced by metoclopramide, conversely, was heightened (179.6 ng/mL; 24.3-fold above baseline).[7][62] This indicates that acute and chronic administration of both domperidone and metoclopramide is effective in increasing prolactin levels, but that there are differential effects on the secretion of prolactin with chronic treatment.[61][62] The mechanism of the difference is unknown.[62] The increase in prolactin levels observed with the two drugs was, as expected, much greater in women than in men.[61][62] This appears to be due to the higher estrogen levels in women, as estrogen stimulates prolactin secretion.[63]
For comparison, normal prolactin levels in women are less than 20 ng/mL, prolactin levels peak at 100 to 300 ng/mL at parturition in pregnant women, and in lactating women, prolactin levels have been found to be 90 ng/mL at 10 days postpartum and 44 ng/mL at 180 days postpartum.[64][65]
Along with prolactin, domperidone has, to a lesser extent, been found to increase the secretion of thyroid-stimulating hormone (TSH), even in patients with hypothyroidism.[61] A single 4 mg intravenous dose of domperidone produced peak TSH levels of 1.9-fold above baseline and peak prolactin levels of 23-fold above baseline (which occurred at 30 minutes post-administration) in women with hypothyroidism.[61] Levels of TSH and prolactin decreased to 1.6-fold and 17-fold above baseline, respectively, at 120 minutes post-administration.[61]
With oral administration, domperidone is extensively metabolized in the liver (almost exclusively by CYP3A4/5, though minor contributions by CYP1A2, CYP2D6, and CYP2C8 have also been reported)[66] and in the intestines.[4] Due to the marked first-pass effect via this route, the oral bioavailability of domperidone is low (13–17%);[1] conversely, its bioavailability is high via intramuscular injection (90%).[1] The terminal half-life of domperidone is 7.5 hours in healthy individuals, but can be prolonged to 20 hours in people with severe renal dysfunction.[1] All of the metabolites of domperidone are inactive as D2 receptor ligands.[1][4] The drug is a substrate for the P-glycoprotein (ABCB1) transporter, and animal studies suggest that this is the reason for the low central nervous system penetration of domperidone.[67]
Domperidone is a benzimidazole derivative and is structurally related to butyrophenone neuroleptics like haloperidol.[68][69]
Domperidone is the generic name of the drug and its INN, USAN, BAN, and JAN.[75][6][76]
In 2007, it was reported that domperidone was available in 58 countries.[1] It is available over-the-counter to treat gastroesophageal reflux and functional dyspepsia in many countries, such as Ireland, the Netherlands, Italy, South Africa, Mexico, Chile, and China.[77]
Domperidone is not generally approved for use in the United States. There is an exception for use in people with treatment-refractory gastrointestinal symptoms under an FDA Investigational New Drug application.[1]
Domperidone has been studied as a potential hormonal contraceptive to prevent pregnancy in women.[81]
Domperidone, sold under the brand name Motilium among others, is a peripherally selective dopamine D2 receptor antagonist that was developed by Janssen Pharmaceutica and is used as an antiemetic, gastroprokinetic agent, and galactagogue.[1][6][7] It may be administered orally or rectally, and is available in the form of tablets, orally disintegrating tablets (based on Zydis technology),[8] suspension, and suppositories.[9] The drug is used to relieve nausea and vomiting; to increase the transit of food through the stomach (by increasing gastrointestinal peristalsis); and to promote lactation (breast milk production) by release of prolactin.[1][7]
It was reported in 2007 that domperidone is available in 58 countries, including Canada,[10] but the uses or indications of domperidone vary between nations. In Italy it is used in the treatment of gastroesophageal reflux disease and in Canada, the drug is indicated in upper gastrointestinal motility disorders and to prevent gastrointestinal symptoms associated with the use of dopamine agonist antiparkinsonian agents.[11] In the United Kingdom, domperidone is only indicated for the treatment of nausea and vomiting and the treatment duration is usually limited to 1 week.
In the United States, domperidone is not currently a legally marketed human drug and it is not approved for sale in the U.S. On 7 June 2004, FDA issued a public warning that distributing any domperidone-containing products is illegal.[12]
There is some evidence that domperidone has antiemetic activity.[13] It is recommended in the Canadian Headache Society’s guidelines for treatment of nausea associated with acute migraine.[14]
قرص motidon domperidone
Gastroparesis is a medical condition characterised by delayed emptying of the stomach when there is no mechanical gastric outlet obstruction. Its cause is most commonly idiopathic, a diabetic complication or a result of abdominal surgery. The condition causes nausea, vomiting, fullness after eating, early satiety (feeling full before the meal is finished), abdominal pain and bloating.
Domperidone may be useful in diabetic and idiopathic gastroparesis.[15][16]
However, increased rate of gastric emptying induced by drugs like domperidone does not always correlate (equate) well with relief of symptoms.[17]
Parkinson’s disease is a chronic neurological condition where a decrease in dopamine in the brain leads to rigidity (stiffness of movement), tremor and other symptoms and signs. Poor gastrointestinal function, nausea and vomiting is a major problem for people with Parkinson’s disease because most medications used to treat Parkinson’s disease are given by mouth. These medications, such as levodopa, can cause nausea as a side effect. Furthermore, anti-nausea drugs, such as metoclopramide, which do cross the blood–brain barrier may worsen the extra-pyramidal symptoms of Parkinson’s disease.
Domperidone can be used to relieve gastrointestinal symptoms in Parkinson’s disease; it blocks peripheral D2 receptors but does not cross the blood–brain barrier in normal doses (the barrier between the blood circulation of the brain and the rest of the body) so has no effect on the extrapyramidal symptoms of the disease.[18] In addition to this, domperidone may enhance the bioavailability (effect) of levodopa (one of the main treatments in Parkinson’s disease).[19]
Although these features make domperidone a useful drug in Parkinson’s disease, caution is needed due to the cardiotoxic side effects of domperidone especially when given intravenously, in elderly people and in high doses (> 30 mg per day).[20] A clinical sign of domperidone’s potential toxicity to the heart is the prolongation (lengthening) of the QT interval (a segment of the heart’s electrical pattern).[21]
Domperidone may be used in functional dyspepsia in both adults and children.[22][23]
The hormone prolactin stimulates lactation (production of breast milk). Dopamine, released by the hypothalamus stops the release of prolactin from the pituitary gland. Domperidone, by acting as an anti-dopaminergic agent, results in increased prolactin secretion, and thus promotes lactation (that is, it is a galactogogue). Domperidone moderately increases the volume of expressed breast milk in mothers of preterm babies where breast milk expression was inadequate, and appears to be safe for short-term use for this purpose.[24][25][26] In the United States, domperidone is not approved for this or any other use.[27][28]
A study called the EMPOWER trial was designed to assess the effectiveness and safety of domperidone in assisting mothers of preterm babies to supply breast milk for their infants.[29] The study randomized 90 mothers of preterm babies to receive either domperidone 10 mg orally three times daily for 28 days (Group A) or placebo 10 mg orally three times daily for 14 days followed by domperidone 10 mg orally three times daily for 14 days (Group B). Mean milk volumes at the beginning of the intervention were similar between the 2 groups. After the first 14 days, 78% of mothers receiving domperidone (Group A) achieved a 50% increase in milk volume, while 58% of mothers receiving placebo (Group B) achieved a 50% increase in milk volume.[30]
To induce lactation, domperidone is used at a dosage of 10 to 20 mg 3 or 4 times per day by mouth.[31] Effects may be seen within 24 hours or may not be seen for 3 or 4 days.[31] The maximum effect occurs after 2 or 3 weeks of treatment, and the treatment period generally lasts for 3 to 8 weeks.[31] A 2012 review shows that no studies support prophylactic use of a galactagogue medication at any gestation including Domperidone.[32]
Domperidone has been found effective in the treatment of pediatric reflux.[33] However some specialists consider its risks prohibitory of the treatment of infantile reflux.[34]
Side effects associated with domperidone include dry mouth, abdominal cramps, diarrhea, nausea, rash, itching, hives, and hyperprolactinemia (the symptoms of which may include breast enlargement, galactorrhea, breast pain/tenderness, gynecomastia, hypogonadism, and menstrual irregularities).[31] Due to blockade of D2 receptors in the central nervous system, D2 receptor antagonists like metoclopramide can also produce a variety of additional side effects including drowsiness, akathisia, restlessness, insomnia, lassitude, fatigue, extrapyramidal symptoms, dystonia, Parkinsonian symptoms, tardive dyskinesia, and depression.[1][7] However, this is not the case with domperidone, because, unlike other D2 receptor antagonists, it minimally crosses the blood-brain-barrier, and for this reason, is rarely associated with such side effects.[1][7]
Due to D2 receptor blockade, domperidone causes hyperprolactinemia.[36] Hyperprolactinemia can suppress the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus, in turn suppressing the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and resulting in hypogonadism (low sex hormone (e.g., testosterone, estradiol) levels).[37] As such, male patients may experience low libido, erectile dysfunction, and impaired spermatogenesis.[37] Also in accordance with hyperprolactinemia, 10–15% of female patients have been reported to experience mammoplasia (breast enlargement), mastodynia (breast pain/tenderness), galactorrhea (inappropriate or excessive milk production/secretion), and amenorrhea (cessation of menstrual cycles) with domperidone treatment.[36] Gynecomastia has been reported in males treated with domperidone,[38] and galactorrhea could occur in males as well.[37]
Domperidone use is associated with an increased risk of sudden cardiac death (by 70%)[39] most likely through its prolonging effect of the cardiac QT interval and ventricular arrhythmias.[40][41] The cause is thought to be blockade of hERG voltage-gated potassium channels.[42][43] The risks are dose-dependent, and appear to be greatest with high/very high doses via intravenous administration and in the elderly, as well as with drugs that interact with domperidone and increase its circulating concentrations (namely CYP3A4 inhibitors).[44][45] Conflicting reports exist, however.[46] In neonates and infants, QT prolongation is controversial and uncertain.[47][48]
UK drug regulatory authorities (MHRA) have issued the following restriction on domperidone in 2014 due to increased risk of adverse cardiac effects:
Domperidone (Motilium) is associated with a small increased risk of serious cardiac side effects. Its use is now restricted to the relief of nausea and vomiting and the dosage and duration of use have been reduced. It should no longer be used for the treatment of bloating and heartburn. Domperidone is now contraindicated in those with underlying cardiac conditions and other risk factors. Patients with these conditions and patients receiving long-term treatment with domperidone should be reassessed at a routine appointment, in light of the new advice.
However, a 2015 Australian review concluded the following:[45]
Based on the results of the two TQT (the regulatory agency gold standard for assessment of QT prolongation) domperidone does not appear to be strongly associated with QT prolongation at oral doses of 20 mg QID in healthy volunteers. Further, there are limited case reports supporting an association with cardiac dysfunction, and the frequently cited case-control studies have significant flaws. While there remains an ill-defined risk at higher systemic concentrations, especially in patients with a higher baseline risk of QT prolongation, our review does not support the view that domperidone presents intolerable risk.
In Britain a legal case involved the death of two children of a mother whose three children had all had hypernatraemia. She was charged with poisoning the children with salt. One of the children, who was born at 28 weeks gestation with respiratory complications and had a fundoplication for gastroesophageal reflux and failure to thrive was prescribed domperidone. An advocate for the mother suggested the child may have suffered neuroleptic malignant syndrome as a side effect of domperidone due to the drug crossing the child’s immature blood-brain-barrier.[49]
Domperidone is almost exclusively metabolized by CYP3A4, and for this reason, inhibitors and inducers of this enzyme may alter the metabolism and concentrations of domperidone. Moreover, domperidone has been identified as a modest mechanism-based (irreversible) inhibitor of CYP3A4 (Ki = 12 μM), and it has been estimated that it may increase the serum concentrations of CYP3A4 substrates by approximately 50%.[50]
Itraconazole and ketoconazole, both used to treat fungal infections, are potent CYP3A4 inhibitors and increase the plasma concentration of domperidone.[51][52] In healthy volunteers, ketoconazole increased the Cmax and AUC concentrations of domperidone by 3- to 10-fold.[53] This was accompanied by a QT interval prolongation of about 10–20 milliseconds when domperidone 10 mg four times daily and ketoconazole 200 mg twice daily were administered, whereas domperidone by itself at the dosage assessed produced no such effect.[53] As such, domperidone with ketoconazole or other CYP3A4 inhibitors is a potentially dangerous combination.[53]
Erythromycin and certain other macrolide antibiotics are CYP3A4 inhibitors and inhibit the metabolism of domperidone (in vitro), thus increasing the concentration of domperidone and potential side effects of the drug. This is of concern as both drugs may be used to treat gastroparesis.[54]
There is evidence that domperidone should not be taken with grapefruit juice, which is a known CYP3A4 inhibitor.[55]
Domperidone is a peripherally selective dopamine D2 and D3 receptor antagonist.[7] It has no clinically significant interaction with the D1 receptor, unlike metoclopramide.[7] The medication provides relief from nausea by blocking D2 receptors in the chemoreceptor trigger zone (a location in the nervous system that mediates nausea) at the floor of the fourth ventricle (a location near the brain). It increases motility in the upper gastrointestinal tract to a moderate degree and increases[56] lower esophageal sphincter pressure by blocking dopamine receptors in the gastric antrum and the duodenum. It blocks dopamine receptors in the anterior pituitary gland increasing release of prolactin which in turn increases lactation.[57][58] Domperidone may be more useful in some patients and cause harm in others by way of the genetics of the person, such as polymorphisms in the drug transporter gene ABCB1 (which encodes P-glycoprotein), the voltage-gated potassium channel KCNH2 gene (hERG/Kv11.1), and the α1D—adrenoceptor ADRA1D gene.[59]
A single 20 mg oral dose of domperidone has been found to increase mean serum prolactin levels (measured 90 minutes post-administration) in non-lactating women from 8.1 ng/mL to 110.9 ng/mL (a 13.7-fold increase).[7][60][61][62] This was similar to the increase in prolactin levels produced by a single 20 mg oral dose of metoclopramide (7.4 ng/mL to 124.1 ng/mL; 16.7-fold increase).[61][62] After two weeks of chronic administration (30 mg/day in both cases), the increase in prolactin levels produced by domperidone was reduced (53.2 ng/mL; 6.6-fold above baseline), but the increase in prolactin levels produced by metoclopramide, conversely, was heightened (179.6 ng/mL; 24.3-fold above baseline).[7][62] This indicates that acute and chronic administration of both domperidone and metoclopramide is effective in increasing prolactin levels, but that there are differential effects on the secretion of prolactin with chronic treatment.[61][62] The mechanism of the difference is unknown.[62] The increase in prolactin levels observed with the two drugs was, as expected, much greater in women than in men.[61][62] This appears to be due to the higher estrogen levels in women, as estrogen stimulates prolactin secretion.[63]
For comparison, normal prolactin levels in women are less than 20 ng/mL, prolactin levels peak at 100 to 300 ng/mL at parturition in pregnant women, and in lactating women, prolactin levels have been found to be 90 ng/mL at 10 days postpartum and 44 ng/mL at 180 days postpartum.[64][65]
Along with prolactin, domperidone has, to a lesser extent, been found to increase the secretion of thyroid-stimulating hormone (TSH), even in patients with hypothyroidism.[61] A single 4 mg intravenous dose of domperidone produced peak TSH levels of 1.9-fold above baseline and peak prolactin levels of 23-fold above baseline (which occurred at 30 minutes post-administration) in women with hypothyroidism.[61] Levels of TSH and prolactin decreased to 1.6-fold and 17-fold above baseline, respectively, at 120 minutes post-administration.[61]
With oral administration, domperidone is extensively metabolized in the liver (almost exclusively by CYP3A4/5, though minor contributions by CYP1A2, CYP2D6, and CYP2C8 have also been reported)[66] and in the intestines.[4] Due to the marked first-pass effect via this route, the oral bioavailability of domperidone is low (13–17%);[1] conversely, its bioavailability is high via intramuscular injection (90%).[1] The terminal half-life of domperidone is 7.5 hours in healthy individuals, but can be prolonged to 20 hours in people with severe renal dysfunction.[1] All of the metabolites of domperidone are inactive as D2 receptor ligands.[1][4] The drug is a substrate for the P-glycoprotein (ABCB1) transporter, and animal studies suggest that this is the reason for the low central nervous system penetration of domperidone.[67]
Domperidone is a benzimidazole derivative and is structurally related to butyrophenone neuroleptics like haloperidol.[68][69]
Domperidone is the generic name of the drug and its INN, USAN, BAN, and JAN.[75][6][76]
In 2007, it was reported that domperidone was available in 58 countries.[1] It is available over-the-counter to treat gastroesophageal reflux and functional dyspepsia in many countries, such as Ireland, the Netherlands, Italy, South Africa, Mexico, Chile, and China.[77]
Domperidone is not generally approved for use in the United States. There is an exception for use in people with treatment-refractory gastrointestinal symptoms under an FDA Investigational New Drug application.[1]
Domperidone has been studied as a potential hormonal contraceptive to prevent pregnancy in women.[81]
Domperidone, sold under the brand name Motilium among others, is a peripherally selective dopamine D2 receptor antagonist that was developed by Janssen Pharmaceutica and is used as an antiemetic, gastroprokinetic agent, and galactagogue.[1][6][7] It may be administered orally or rectally, and is available in the form of tablets, orally disintegrating tablets (based on Zydis technology),[8] suspension, and suppositories.[9] The drug is used to relieve nausea and vomiting; to increase the transit of food through the stomach (by increasing gastrointestinal peristalsis); and to promote lactation (breast milk production) by release of prolactin.[1][7]
It was reported in 2007 that domperidone is available in 58 countries, including Canada,[10] but the uses or indications of domperidone vary between nations. In Italy it is used in the treatment of gastroesophageal reflux disease and in Canada, the drug is indicated in upper gastrointestinal motility disorders and to prevent gastrointestinal symptoms associated with the use of dopamine agonist antiparkinsonian agents.[11] In the United Kingdom, domperidone is only indicated for the treatment of nausea and vomiting and the treatment duration is usually limited to 1 week.
In the United States, domperidone is not currently a legally marketed human drug and it is not approved for sale in the U.S. On 7 June 2004, FDA issued a public warning that distributing any domperidone-containing products is illegal.[12]
There is some evidence that domperidone has antiemetic activity.[13] It is recommended in the Canadian Headache Society’s guidelines for treatment of nausea associated with acute migraine.[14]
قرص motidon domperidone
Gastroparesis is a medical condition characterised by delayed emptying of the stomach when there is no mechanical gastric outlet obstruction. Its cause is most commonly idiopathic, a diabetic complication or a result of abdominal surgery. The condition causes nausea, vomiting, fullness after eating, early satiety (feeling full before the meal is finished), abdominal pain and bloating.
Domperidone may be useful in diabetic and idiopathic gastroparesis.[15][16]
However, increased rate of gastric emptying induced by drugs like domperidone does not always correlate (equate) well with relief of symptoms.[17]
Parkinson’s disease is a chronic neurological condition where a decrease in dopamine in the brain leads to rigidity (stiffness of movement), tremor and other symptoms and signs. Poor gastrointestinal function, nausea and vomiting is a major problem for people with Parkinson’s disease because most medications used to treat Parkinson’s disease are given by mouth. These medications, such as levodopa, can cause nausea as a side effect. Furthermore, anti-nausea drugs, such as metoclopramide, which do cross the blood–brain barrier may worsen the extra-pyramidal symptoms of Parkinson’s disease.
Domperidone can be used to relieve gastrointestinal symptoms in Parkinson’s disease; it blocks peripheral D2 receptors but does not cross the blood–brain barrier in normal doses (the barrier between the blood circulation of the brain and the rest of the body) so has no effect on the extrapyramidal symptoms of the disease.[18] In addition to this, domperidone may enhance the bioavailability (effect) of levodopa (one of the main treatments in Parkinson’s disease).[19]
Although these features make domperidone a useful drug in Parkinson’s disease, caution is needed due to the cardiotoxic side effects of domperidone especially when given intravenously, in elderly people and in high doses (> 30 mg per day).[20] A clinical sign of domperidone’s potential toxicity to the heart is the prolongation (lengthening) of the QT interval (a segment of the heart’s electrical pattern).[21]
Domperidone may be used in functional dyspepsia in both adults and children.[22][23]
The hormone prolactin stimulates lactation (production of breast milk). Dopamine, released by the hypothalamus stops the release of prolactin from the pituitary gland. Domperidone, by acting as an anti-dopaminergic agent, results in increased prolactin secretion, and thus promotes lactation (that is, it is a galactogogue). Domperidone moderately increases the volume of expressed breast milk in mothers of preterm babies where breast milk expression was inadequate, and appears to be safe for short-term use for this purpose.[24][25][26] In the United States, domperidone is not approved for this or any other use.[27][28]
A study called the EMPOWER trial was designed to assess the effectiveness and safety of domperidone in assisting mothers of preterm babies to supply breast milk for their infants.[29] The study randomized 90 mothers of preterm babies to receive either domperidone 10 mg orally three times daily for 28 days (Group A) or placebo 10 mg orally three times daily for 14 days followed by domperidone 10 mg orally three times daily for 14 days (Group B). Mean milk volumes at the beginning of the intervention were similar between the 2 groups. After the first 14 days, 78% of mothers receiving domperidone (Group A) achieved a 50% increase in milk volume, while 58% of mothers receiving placebo (Group B) achieved a 50% increase in milk volume.[30]
To induce lactation, domperidone is used at a dosage of 10 to 20 mg 3 or 4 times per day by mouth.[31] Effects may be seen within 24 hours or may not be seen for 3 or 4 days.[31] The maximum effect occurs after 2 or 3 weeks of treatment, and the treatment period generally lasts for 3 to 8 weeks.[31] A 2012 review shows that no studies support prophylactic use of a galactagogue medication at any gestation including Domperidone.[32]
Domperidone has been found effective in the treatment of pediatric reflux.[33] However some specialists consider its risks prohibitory of the treatment of infantile reflux.[34]
Side effects associated with domperidone include dry mouth, abdominal cramps, diarrhea, nausea, rash, itching, hives, and hyperprolactinemia (the symptoms of which may include breast enlargement, galactorrhea, breast pain/tenderness, gynecomastia, hypogonadism, and menstrual irregularities).[31] Due to blockade of D2 receptors in the central nervous system, D2 receptor antagonists like metoclopramide can also produce a variety of additional side effects including drowsiness, akathisia, restlessness, insomnia, lassitude, fatigue, extrapyramidal symptoms, dystonia, Parkinsonian symptoms, tardive dyskinesia, and depression.[1][7] However, this is not the case with domperidone, because, unlike other D2 receptor antagonists, it minimally crosses the blood-brain-barrier, and for this reason, is rarely associated with such side effects.[1][7]
Due to D2 receptor blockade, domperidone causes hyperprolactinemia.[36] Hyperprolactinemia can suppress the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus, in turn suppressing the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and resulting in hypogonadism (low sex hormone (e.g., testosterone, estradiol) levels).[37] As such, male patients may experience low libido, erectile dysfunction, and impaired spermatogenesis.[37] Also in accordance with hyperprolactinemia, 10–15% of female patients have been reported to experience mammoplasia (breast enlargement), mastodynia (breast pain/tenderness), galactorrhea (inappropriate or excessive milk production/secretion), and amenorrhea (cessation of menstrual cycles) with domperidone treatment.[36] Gynecomastia has been reported in males treated with domperidone,[38] and galactorrhea could occur in males as well.[37]
Domperidone use is associated with an increased risk of sudden cardiac death (by 70%)[39] most likely through its prolonging effect of the cardiac QT interval and ventricular arrhythmias.[40][41] The cause is thought to be blockade of hERG voltage-gated potassium channels.[42][43] The risks are dose-dependent, and appear to be greatest with high/very high doses via intravenous administration and in the elderly, as well as with drugs that interact with domperidone and increase its circulating concentrations (namely CYP3A4 inhibitors).[44][45] Conflicting reports exist, however.[46] In neonates and infants, QT prolongation is controversial and uncertain.[47][48]
UK drug regulatory authorities (MHRA) have issued the following restriction on domperidone in 2014 due to increased risk of adverse cardiac effects:
Domperidone (Motilium) is associated with a small increased risk of serious cardiac side effects. Its use is now restricted to the relief of nausea and vomiting and the dosage and duration of use have been reduced. It should no longer be used for the treatment of bloating and heartburn. Domperidone is now contraindicated in those with underlying cardiac conditions and other risk factors. Patients with these conditions and patients receiving long-term treatment with domperidone should be reassessed at a routine appointment, in light of the new advice.
However, a 2015 Australian review concluded the following:[45]
Based on the results of the two TQT (the regulatory agency gold standard for assessment of QT prolongation) domperidone does not appear to be strongly associated with QT prolongation at oral doses of 20 mg QID in healthy volunteers. Further, there are limited case reports supporting an association with cardiac dysfunction, and the frequently cited case-control studies have significant flaws. While there remains an ill-defined risk at higher systemic concentrations, especially in patients with a higher baseline risk of QT prolongation, our review does not support the view that domperidone presents intolerable risk.
In Britain a legal case involved the death of two children of a mother whose three children had all had hypernatraemia. She was charged with poisoning the children with salt. One of the children, who was born at 28 weeks gestation with respiratory complications and had a fundoplication for gastroesophageal reflux and failure to thrive was prescribed domperidone. An advocate for the mother suggested the child may have suffered neuroleptic malignant syndrome as a side effect of domperidone due to the drug crossing the child’s immature blood-brain-barrier.[49]
Domperidone is almost exclusively metabolized by CYP3A4, and for this reason, inhibitors and inducers of this enzyme may alter the metabolism and concentrations of domperidone. Moreover, domperidone has been identified as a modest mechanism-based (irreversible) inhibitor of CYP3A4 (Ki = 12 μM), and it has been estimated that it may increase the serum concentrations of CYP3A4 substrates by approximately 50%.[50]
Itraconazole and ketoconazole, both used to treat fungal infections, are potent CYP3A4 inhibitors and increase the plasma concentration of domperidone.[51][52] In healthy volunteers, ketoconazole increased the Cmax and AUC concentrations of domperidone by 3- to 10-fold.[53] This was accompanied by a QT interval prolongation of about 10–20 milliseconds when domperidone 10 mg four times daily and ketoconazole 200 mg twice daily were administered, whereas domperidone by itself at the dosage assessed produced no such effect.[53] As such, domperidone with ketoconazole or other CYP3A4 inhibitors is a potentially dangerous combination.[53]
Erythromycin and certain other macrolide antibiotics are CYP3A4 inhibitors and inhibit the metabolism of domperidone (in vitro), thus increasing the concentration of domperidone and potential side effects of the drug. This is of concern as both drugs may be used to treat gastroparesis.[54]
There is evidence that domperidone should not be taken with grapefruit juice, which is a known CYP3A4 inhibitor.[55]
Domperidone is a peripherally selective dopamine D2 and D3 receptor antagonist.[7] It has no clinically significant interaction with the D1 receptor, unlike metoclopramide.[7] The medication provides relief from nausea by blocking D2 receptors in the chemoreceptor trigger zone (a location in the nervous system that mediates nausea) at the floor of the fourth ventricle (a location near the brain). It increases motility in the upper gastrointestinal tract to a moderate degree and increases[56] lower esophageal sphincter pressure by blocking dopamine receptors in the gastric antrum and the duodenum. It blocks dopamine receptors in the anterior pituitary gland increasing release of prolactin which in turn increases lactation.[57][58] Domperidone may be more useful in some patients and cause harm in others by way of the genetics of the person, such as polymorphisms in the drug transporter gene ABCB1 (which encodes P-glycoprotein), the voltage-gated potassium channel KCNH2 gene (hERG/Kv11.1), and the α1D—adrenoceptor ADRA1D gene.[59]
A single 20 mg oral dose of domperidone has been found to increase mean serum prolactin levels (measured 90 minutes post-administration) in non-lactating women from 8.1 ng/mL to 110.9 ng/mL (a 13.7-fold increase).[7][60][61][62] This was similar to the increase in prolactin levels produced by a single 20 mg oral dose of metoclopramide (7.4 ng/mL to 124.1 ng/mL; 16.7-fold increase).[61][62] After two weeks of chronic administration (30 mg/day in both cases), the increase in prolactin levels produced by domperidone was reduced (53.2 ng/mL; 6.6-fold above baseline), but the increase in prolactin levels produced by metoclopramide, conversely, was heightened (179.6 ng/mL; 24.3-fold above baseline).[7][62] This indicates that acute and chronic administration of both domperidone and metoclopramide is effective in increasing prolactin levels, but that there are differential effects on the secretion of prolactin with chronic treatment.[61][62] The mechanism of the difference is unknown.[62] The increase in prolactin levels observed with the two drugs was, as expected, much greater in women than in men.[61][62] This appears to be due to the higher estrogen levels in women, as estrogen stimulates prolactin secretion.[63]
For comparison, normal prolactin levels in women are less than 20 ng/mL, prolactin levels peak at 100 to 300 ng/mL at parturition in pregnant women, and in lactating women, prolactin levels have been found to be 90 ng/mL at 10 days postpartum and 44 ng/mL at 180 days postpartum.[64][65]
Along with prolactin, domperidone has, to a lesser extent, been found to increase the secretion of thyroid-stimulating hormone (TSH), even in patients with hypothyroidism.[61] A single 4 mg intravenous dose of domperidone produced peak TSH levels of 1.9-fold above baseline and peak prolactin levels of 23-fold above baseline (which occurred at 30 minutes post-administration) in women with hypothyroidism.[61] Levels of TSH and prolactin decreased to 1.6-fold and 17-fold above baseline, respectively, at 120 minutes post-administration.[61]
With oral administration, domperidone is extensively metabolized in the liver (almost exclusively by CYP3A4/5, though minor contributions by CYP1A2, CYP2D6, and CYP2C8 have also been reported)[66] and in the intestines.[4] Due to the marked first-pass effect via this route, the oral bioavailability of domperidone is low (13–17%);[1] conversely, its bioavailability is high via intramuscular injection (90%).[1] The terminal half-life of domperidone is 7.5 hours in healthy individuals, but can be prolonged to 20 hours in people with severe renal dysfunction.[1] All of the metabolites of domperidone are inactive as D2 receptor ligands.[1][4] The drug is a substrate for the P-glycoprotein (ABCB1) transporter, and animal studies suggest that this is the reason for the low central nervous system penetration of domperidone.[67]
Domperidone is a benzimidazole derivative and is structurally related to butyrophenone neuroleptics like haloperidol.[68][69]
Domperidone is the generic name of the drug and its INN, USAN, BAN, and JAN.[75][6][76]
In 2007, it was reported that domperidone was available in 58 countries.[1] It is available over-the-counter to treat gastroesophageal reflux and functional dyspepsia in many countries, such as Ireland, the Netherlands, Italy, South Africa, Mexico, Chile, and China.[77]
Domperidone is not generally approved for use in the United States. There is an exception for use in people with treatment-refractory gastrointestinal symptoms under an FDA Investigational New Drug application.[1]
Domperidone has been studied as a potential hormonal contraceptive to prevent pregnancy in women.[81]
دومپریدون
دومپریدون داروی پرکاربردی است که جهت برطرف کردن حالت تهوع یا استفراغ مصرف می شود.
احساس تهوع اگرچه یک علامت شایع می باشد اما می تواند ناشی از عوامل مختلفی باشد. داروهای ضدتهوع مانند دومپریدون را تنها زمانی می توانید مصرف کنید که علت تهوع شما مشخص شده باشد.
دومپریدون با کمک به تسریع حرکت غذا در دستگاه گوارش ، تهوع را مهار می نماید.
پیش از مصرف دومپریدون
– در صورت بارداری یا شیردهی به پزشک اطلاع دهید .
– در صورت سابقه ی مشکلات کبدی ، ضربان قلب نامنظم ، گوارشی (انسداد یا خونریزی دستگاه گوارشی)و حساسیت دارویی پزشک خود را مطلع نمایید .
-از آنجا که این دارو می تواند در عملکرد داروهای دیگر در بدن اختلال ایجاد کند لازم است پیش از شروع مصرف لیستی از کلیه ی داروهای مصرفی خود در اختیار پزشک یا داروسازتان قرار دهید.
نحوه ی مصرف دومپریدون
-اگرچه باید دومپریدون را دقیقاً طبق دستور پزشک مصرف نمایید، اما معمولاً مقدار مصرف روزانه ی آن برای بزرگسالان و افراد بالای ۱۶سال، یک قرص، سه مرتبه در روز می باشد.
-از مصرف بیش از سه قرص در ۲۴ساعت خودداری نمایید .
-در صورتی که این دارو برای کودک شما تجویز شده است، مقدار مصرف آن باید توسط پزشک محاسبه گردد.
-بهتر است دومپریدون را نیم ساعت پیش از غذا مصرف کنید.با این حال مصرف پس از غذا نیز موثر می باشد اما زمان بیشتری طول می کشد تا اثر نماید.
-درمان با این دارو عموماً کوتاه مدت می باشد و بیشتر از هفت روز طول نمی کشد.
عوارض شایع دومپریدون
_خشکی دهان نیز از علائم مربوط به مصرف این دارو میباشد که با آدامس یا آبنبات فاقد شکر می توان آن را برطرف نمود .
-ضربان قلب بالا و از هوش رفتن در برخی افراد مصرف کننده ی این دارو مشاهده می شود. در صورت وقوع این علائم به پزشک خود مراجعه نمایید.
-در صورت احساس اضطراب، خواب آلودگی، ضعف، سردرد و اسهال با پزشک خود مشورت نمایید تا راهکار مناسب را دریافت نمایید.
-در صورت ورم و دردناکی سینه ها، قاعدگی نامنظم، ترشح شیر غیر معمول از سینه ها، لکه های قرمز و خارش پوستی پزشک خود را مطلع سازید.
چنانچه در خصوص “دومپریدون” سوالی دارید، عارضه خاصی مشاهده نموده اید و یا مطلب ویژه ای به نظرتان می رسد با دیگران به اشتراک بگذارید
Domperidone
دومپریدون جهت درمان تهوع ، استفراغ ، سوء هاضمه و رفلاکس معده به مری استفاده می شود. دومپریدون در گروه ترکیبات آلی بنزیمیدازول قرار دارد.
دومپریدون مسدد گیرنده های محیطی دوپامین می باشد و موجب افزایش فشار اسفنگتر تحتانی مری می شود. دومپریدون باعث افزایش حرکات دستگاه گوارش شده و متعاقبا سبب تسهیل تخلیه معده و کاهش زمان عبور موادغذایی از روده می شود .
دمپریدون یک مسدد اختصاصی گیرنده های دوپامین می باشد . دومپریدون حرکات دودی دستگاه گوارش را سرعت می بخشد و موجب رهاسازی پرولاکتین نیز می شود. دومپریدون بعنوان ضد تهوع بکار می رود.
دومپریدون بسرعت جذب می شود. دومپریدون به مقدارکم در شیر ترشح می شود. به سادگی از سد مغزی-خونی عبور نمی کند. اتصال به پروتئینهای پلاسما دومپریدون بسیار بالا، 91-93% می باشد.
دومپریدون تحت عبور اول کبدی قرار گرفته و در دیواره روده تحت متابولیسم قرار می گیرد. نیمه عمر دومپریدون 7 ساعت می باشد.
دومپریدون هم از طریق ادرار (تقریبا 31% مقدار مصرفی) و هم از طریق مدفوع ( تقریبا 66% مقدار مصرفی ) دفع می گردد.
قرص motidon domperidone
مقدار معمول برای اختلالات حرکتی قسمت فوقانی دستگاه گوارش :
بزرگسالان : 10 mg خوراکی ، سه تا چهار بار در روز ، در موارد شدید یا مقاوم ممکن است تا حداکثر مقدار مجاز 20 mg ، سه تا چهار بار در روز افزایش یابد.
مقدار معمول برای تهوع و استفراغ :
بزرگسالان : 20 mg خوراکی 3-4 بار در روز.
1-دومپریدون را در موارد زیر با احتیاط فراوان مصرف کنید: کودکان،سنین بالای 60 سال ،بیمارانی که در روز بیش از mg 30 دومپریدون مصرف می کنند، نارسایی عملکرد کلیه ، عدم تعادل الکترولیت های خون . 2-در حین مصرف دومپریدون در صورت بروز غش ،گیجی ،ضربان قلب نامنظم و یا هر گونه علائم غیرطبیعی پزشک خود را مطلع کنید .
1-اگر مصرف دومپریدون علائم بیماری شما را کنترل نکرد،پزشک خود را مطلع کنید و از مصرف بیش از حد مقدار تجویز شده خودداری کنید. 2-درحین مصرف داروی دمپریدون در صورت بروز غش، افزایش ضربان قلب یا نا منظم بودن ضربان قلب سریعا پزشک خود را مطلع کنید. 3-قرص دومپریدون را 15 تا 30 دقیقه قبل از غذا وهمراه یک لیوان آب میل کنید.
دارو
رفلاکس معده
تهوع
سوء هاضمه
موسسه خدمات دارویی رضوی با هدف ایجاد بانک مرجع در زمینه اطلاعات دارویی و پزشکی و همچنین ایجاد بستر مناسب جهت مشاوره دارویی و خرید آسان دارو و تحویل در محل ایجاد شده است. ادامه …
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قرص motidon domperidone
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قرص دومپریدون اغلب برای درمان ناراحتی های گوارشی و میگرن مورد استفاده قرار می گیرد. در این مطلب به طور کامل و جامع موارد مصرف، منع مصرف و عوارض جانبی این قرص را مورد بررسی قرار داه ایم. این دارو همچنین ممکن است با برخی داروها تداخلات دارویی داشته باشد.
قرص دومپریدون 10 میلی گرم ضد تهوع و استفراغ می باشد که مصرف آن باعث می شود احساس ناراحتی و مریضی شما متوقف گردد. ماده فعال موجود در این قرص دومپریدون مالیت است. در این مطلب اطلاعاتی جامع در مورد این قرص در اختیار شما عزیزان قرار گرفته است. در صورت داشتن سوالات بیشتر لطفا با پزشک متخصص خود مشورت کنید.
قبل از شروع مصرف هر دارو بهتر است اطلاعاتی جامع و کامل در مورد نحوه مصرف آن و احتیاطی که در هنگام مصرف آن باید کرد اطلاعاتی داشته باشیم. یکی از قرص هایی که اغلب برای تهوع و استفراغ، سوء هاضمه و گاستروپارزی دیابتی و میگرن مورد استفاده قرار می گیرد دومپریدون می باشد. در این مطلب اطلاعات دارویی این قرص را با هم مطالعه خواهیم کرد. تا پایان مطلب همراه ما باشید.
این دارو اغلب برای حالت تهوع و استفراغ و شکایت از ناراحتی های معده که اغلب در اثر تخلیه دیر هنگام شکم صورت می گیرد مورد استفاده قرار می گیرد. ناراحتی معده ممکن است همچنین عواملی مثل احساس پر بودن شکم در طول خوردن غذا یا بلافاصله پس از آن، نفخ، آروغ، تهوع، سوزش معده و دل درد را به همراه داشته باشد.
قرص motidon domperidone
این دارو را پزشک شما تجویز کرده است پس مطابق دستور پزشک آن را مصرف کنید. دوز مصرفی قرص دومپریدون در افراد بزرگسال و کودکان متفاوت می باشد. قرص را باید به یکباره و همراه مقدار کافی مایعات( یک لیوان آب) بخورید. افراد با ناراحتی های کلیوی باید از دوزهای کمتری استفاده کنند. اگر احساس کردید قدرت داروی دومپریدون زیاد یا کم می باشد با دکتر یا پزشک متخصص خود مشورت کنید. دوز معمول آن به سن، جنس، شرایط پزشکی، واکنش به درمان و استفاده از داروهایی معینی که با این دارو تداخل دارند وابسته می باشد. افراد بزرگسال نباید بیش از سه قرص در روز مصرف کنند. اگر بعد از 28 روز پس از گذشت مصرف این قرص همچنان از ناراحتی و بیماری خود رنج می برید با پزشک خود در مورد ادامه طول درمان مشورت کنید. اگر بیش از دوز معمول از این دارو استفاده کردید فورا پزشک خود را در جریان قرار دهید یا به نزدیک ترین بیمارستان مراجعه کنید. علایم مصرف بیشتر از دوز معمول خواب آلودگی، گیجی، حرکات چشم نامنظم و حرکات عجیب بدن بویژه در کودکان است. و اگر استفاده از دوز معمول خود را فراموش کردید اگر تقریبا به زمان بعدی مصرف نزدیک می باشد منتظر باشید تا زمان بعدی مصرف فرا برسد و به استفاده دوزها به طور معمول ادامه دهید. برای جبران دوز فراموش شده هرگز دو وعده را با هم مصرف نکنید. حداکثر دوره درمان نباید به طور معمول از یک هفته بیشتر باشد.
این قرص ها حاوی لاکتوز مونوهیدرات هستند. اگر به دومپریدون یا هر یک از عناصر موجود در این دارو حساسیت دارید یا مشکلات جدی روده ای مثل خونریزی معده داخلی دارید یا مانعی در شکم یا روده شما وجود دارد یا از تومور غده هیپوفیز رنج می برید نباید از این قرص استفاده کنید. و اگر مبتلا به اختلالات کبد، کلیه می باشید یا اگر حامله هستید و یا قصد بارداری دارید و یا در دوران شیردهی می باشید. اگر از ناراحتی های قلبی رنج می برید قبل از مصرف دارو حتما با پزشک خود مشورت کنید. زیرا این دارو ضربان قلب شما را تحت تاثیر قرار می دهد به ویژه در افرادی که بیش از شصت سال سن دارند و بیش از 30 میلی گیرم روزانه استفاده می کنند.
اگر هر یک از داروهای زیر را مصرف می کنید یا قبلا از آن ها استفاده کرده اید قبل از مصرف قرص دومپریدون با پزشک خود مشورت کنید.
مصرف این دارو را بلافاصله پس از مشاهده این علایم متوقف کنید و با پزشک خود تماس بگیرید.
امیدواریم هنگام مصرف قرص دومپریدون به عوارض و موارد احتیاط در مصرف آن توجه نمایید. به یاد داشته باشید این مقاله صرفا جهت افزایش آگاهی شما ترجمه و گردآوری شده است و لازم است مصرف داروی دومپریدون تحت نظر پزشک صورت گیرد.
منبع : آرگا
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Active substance(s): DOMPERIDONE MALEATE
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قرص motidon domperidone
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