GB2158714A - Injectable metoclopramide compositions - Google Patents
Injectable metoclopramide compositions Download PDFInfo
- Publication number
- GB2158714A GB2158714A GB08510115A GB8510115A GB2158714A GB 2158714 A GB2158714 A GB 2158714A GB 08510115 A GB08510115 A GB 08510115A GB 8510115 A GB8510115 A GB 8510115A GB 2158714 A GB2158714 A GB 2158714A
- Authority
- GB
- United Kingdom
- Prior art keywords
- metoclopramide
- composition
- composition according
- pharmaceutically acceptable
- sodium metabisulphite
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 25
- 229960004503 metoclopramide Drugs 0.000 title claims abstract description 17
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 title claims abstract description 17
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical group [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims abstract description 13
- 239000004296 sodium metabisulphite Substances 0.000 claims abstract description 13
- 235000010262 sodium metabisulphite Nutrition 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 239000007788 liquid Substances 0.000 claims abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 239000002552 dosage form Substances 0.000 claims description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 1
- 206010047700 Vomiting Diseases 0.000 abstract description 6
- 238000002512 chemotherapy Methods 0.000 abstract description 5
- 206010028980 Neoplasm Diseases 0.000 abstract description 4
- 201000011510 cancer Diseases 0.000 abstract description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 7
- 229960004316 cisplatin Drugs 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000008215 water for injection Substances 0.000 description 4
- 239000003708 ampul Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000007972 injectable composition Substances 0.000 description 3
- IRQVJPHZDYMXNW-UHFFFAOYSA-N metoclopramide dihydrochloride monohydrate Chemical compound O.[Cl-].[Cl-].CC[NH+](CC)CCNC(=O)C1=CC(Cl)=C([NH3+])C=C1OC IRQVJPHZDYMXNW-UHFFFAOYSA-N 0.000 description 3
- 229960000923 metoclopramide hydrochloride Drugs 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000003474 anti-emetic effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 229940125683 antiemetic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- WBZKQQHYRPRKNJ-UHFFFAOYSA-L disulfite Chemical compound [O-]S(=O)S([O-])(=O)=O WBZKQQHYRPRKNJ-UHFFFAOYSA-L 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A parenteral pharmaceutical composition comprising metoclopramide or a pharmaceutically acceptable salt thereof, and from 0 to 0.06% by weight, preferably from 0 to 0.006% by weight, of the composition of sodium metabisulphite, together with a pharmaceutically acceptable liquid carrier. The use of this composition to alleviate nausea and vomiting, particularly in that associated with cancer chemotherapy is described.
Description
SPECIFICATION
Composition
The present invention relates to a pharmaceutical composition containing metoclopramide, and its use in medicine.
Metoclopramide is a known anti-emetic agent which is used to alleviate nausea and vomiting.
Hitherto, it has been administered by oral and injection routes, and for the latter use it has conveniently been packaged into 2ml ampoules for injection, each ampoule containing 10mg metoclopramide in saline solution. It has also been found necessary to include an effective level of the antoxidant sodium metabisulphite in the injectable composition to maintain stability.
Recently, the injectable composition has been used in association with certain types of cancer chemotheropy in which an anti-cancer agent such as Cisplatin is administered, and where a side effect of such treatment is severe nausea and vomiting. However, Cisplatin has been found to be incompatible with sodium metabisulphite, and this has limited the extent to which metoclopramide can be used in the chemotherapy treatment.
We have now found that, surprisingly, sodium metabisulphite can be omitted from the injectable composition without unduly affecting the stability of the composition, and that as a result larger ampoules, of up to 20ml in size, can be employed in combination with Cisplatin in infusion for the chemotherapy treatment. It is also possible to include small amounts of sodium metabisulphite, substantially less than the 0.15% by weight of metabisulphite hitherto employed in the 2ml ampoule size, without having compatability problems with
Cisplatin.
Accordingly, the present invention provides a parenteral pharmaceutical composition comprising metoclopram ide or a pharmaceutically acceptable salt thereof and from 0 to 0.06% by weight of the composition of sodium metabisulphite, in combination with a pharmaceutically acceptable liquid carrier.
Preferably the amount of sodium metabisulphite present is from 0% to 0.006% by weight of the composition and most preferably 0% of sodium metabisulphite is present.
Examples of a pharmaceutically acceptable salt of metoclopramide include the hydrochloride.
Preferably, the liquid carrier comprises sterile saline solution.
The amount of metoclopramide administered to a patient should be sufficient to exert an antiemetic effect. An anti-emetically effective amount of metoclopramide will depend on a number of factors such as the severity of the emesis being treated and the body weight of the patient. However in general a dosage of from 0.014 mg/kg to 10 mg/kg per day will be administered to a human,
Suitably the composition is in a unit dosage form, such as an ampoule, preferably containing an anti-emetically effective amount of metoclopramide. A unit dose in excess of 1mg, in particular in excess of 10mg, for a 70kg adult will have an anti-emetic effect. For the severe emesis caused by cancer chemotherapy, such as by Cisplatin therapy, however, a unit dose of 50 to 200 mg, in particular about 100mg, is preferred.The volume of the unit dose may be from 1ml to 40 ml, in particular from 2ml to 20ml, the smaller volumes correlating with the smaller dosage units and the larger volumes with the larger dosage units. The larger volumes are thus most suitable for use in cancer chemotherapy such as Cisplatin therapy.
The unit dose may be administered from once a day to as many times as is necessary to give a dosage in 24 hours of from 0.014 to 10 mgikg bodyweight. Thus for example in the aforementioned
Cisplatin therapy, a 100mg unit dose of metoclopramide may suitably be administered from 1 to 7 times in a 24 hour period to a 70kg adult.
The composition of the invention may be prepared by admixing the components in conventional manner.
Further according to the present invention there is provided a method of treating nausea and vomiting which comprises administering to a patient in need thereof an anti-emetically amount of a composition of the invention.
The invention is now illustrated by means of the following Example
Example
The following formulations were made up as follows:
Formulation 1
Metoclopramide hydrochloride BP 0.526
Sodium chloride BP 0.800
Water for injection BP to 100.000
Formulation 2
Metoclopramide hydrochloride BP 0.526
Sodium chloride BP 0.800
Sodium metabisulphite 0.006
Water for injection BP to 100.000
Preparation 1
The sodium chloride, sodium metabisulphite where present and the metoclopramide hydrochloride were dissolved in that order in boiled water for injection BP (about 80% final volume) at below 30"C under stirring and with nitrogen bubbled through the water. The solution was made up to the final volume with water for injection at below 30"C. The solution was filtered under nitrogen pressure through a 511m filter, collected and filled into 20ml glass ampoules under nitrogen. The product was sterilised by heat treatment of the sealed ampoules in an autoclave.
Preparation 2
The above procedure was repeated except that the final solution was filtered through a sterilising filter, and the filling was effected in a sterile area.
Claims (11)
1. A parenteral pharmaceutial composition comprising metoclopramide or a pharmaceutically acceptable salt thereof, and from 0 to 0.6% by weight of the composition of sodium metabisulphite, in combination with a pharmaceutically acceptable liquid carrier.
2. A composition according to claim 1 which contains from 0.to 0.006% by weight of the composition of sodium metabisulphite.
3. A composition according to claim 1 or 2 which contains 0% of sodium metabisulphite.
4. A composition according to any one of claims 1 to 3 wherein the metoclopramide is in the form of the hydrochloride salt.
5. A composition according to any one of the preceding claims in unit dosage form.
6. A composition according to claim 5 wherein the unit dosage form contains at least 1 mg of metoclopramide or a pharmaceutically acceptable salt thereof.
7. A composition according to claim 6 wherein the unit dosage contains from 50 to 200 mg of metoclopramide or a pharmaceutically acceptable salt thereof.
8. A composition according to claim 7 wherein the unit dosage contains 100 mg of metoclopramide or a pharmaceutically acceptable salt thereof.
9. A composition according to any one of claims 5 to 8 wherein the volume of the unit dosage is from 1 ml to 40 ml.
10. A composition according to claim 9 wherein the volume of the unit dosages is from 2 ml to 20 ml.
11. A parenteral pharmaceutical composition substantially as hereinbefore described with reference to the examples.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB848412585A GB8412585D0 (en) | 1984-05-17 | 1984-05-17 | Composition |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB8510115D0 GB8510115D0 (en) | 1985-05-30 |
| GB2158714A true GB2158714A (en) | 1985-11-20 |
| GB2158714B GB2158714B (en) | 1989-01-05 |
Family
ID=10561084
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB848412585A Pending GB8412585D0 (en) | 1984-05-17 | 1984-05-17 | Composition |
| GB08510115A Expired GB2158714B (en) | 1984-05-17 | 1985-04-19 | Composition |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB848412585A Pending GB8412585D0 (en) | 1984-05-17 | 1984-05-17 | Composition |
Country Status (5)
| Country | Link |
|---|---|
| AU (1) | AU623694B2 (en) |
| CA (1) | CA1262686A (en) |
| GB (2) | GB8412585D0 (en) |
| NZ (1) | NZ212097A (en) |
| ZA (1) | ZA853671B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0241837A3 (en) * | 1986-04-07 | 1989-05-10 | Bristol-Myers Company | Stable injectable antiemetic compositions |
| US5561161A (en) * | 1994-03-25 | 1996-10-01 | Oxigene, Inc. | Methods of administering and pharmaceutical formulations containing n-substituted benzamides and/or acid addition salts thereof |
| AT404796B (en) * | 1990-09-28 | 1999-02-25 | Solvay Pharm Gmbh | METOCLOPRAMIDE HYDROCHLORIDE SOLUTIONS TO BE APPLIED PERORALLY |
| RU2181588C2 (en) * | 1996-03-14 | 2002-04-27 | Райбоджин, Инк. | Method to prevent delayed vomiting |
| DE4131276B4 (en) * | 1990-09-28 | 2007-07-19 | Solvay Pharmaceuticals Gmbh | Perorally administrable metoclopramide solutions |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2205633C1 (en) * | 2002-05-07 | 2003-06-10 | Закрытое акционерное общество "Брынцалов-А" | Agent "tserulan" eliciting antiemetic effect and regulating digestive tract functions |
| RU2344813C1 (en) * | 2007-04-26 | 2009-01-27 | Федеральное государственное учреждение "Межотраслевой научно-технический комплекс "Микрохирургия глаза" имени академика С.Н. Федорова Федерального агентства по здравоохранению и социальному развитию | Method of post-operation nausea and vomiting prevention for children |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU528310B2 (en) * | 1978-11-16 | 1983-04-21 | Beecham Group Plc | Composition of paracetamol and metoclopramide |
| FR2492661A1 (en) * | 1980-10-28 | 1982-04-30 | Laruelle Claude | NOVEL GALENIC FORM OF ADMINISTRATION OF METOCLOPRAMIDE, ITS PREPARATION METHOD AND MEDICINAL PRODUCT COMPRISING THIS NOVEL FORM |
-
1984
- 1984-05-17 GB GB848412585A patent/GB8412585D0/en active Pending
-
1985
- 1985-04-19 GB GB08510115A patent/GB2158714B/en not_active Expired
- 1985-05-15 ZA ZA853671A patent/ZA853671B/en unknown
- 1985-05-15 NZ NZ212097A patent/NZ212097A/en unknown
- 1985-05-16 CA CA000481696A patent/CA1262686A/en not_active Expired
-
1989
- 1989-10-20 AU AU43624/89A patent/AU623694B2/en not_active Expired
Non-Patent Citations (3)
| Title |
|---|
| JOURNAL OF AMERICAN MEDICAL ASSOCIATION ON VOL 250 NO.19 (ADVERTISEMENT FOR REGLON) * |
| THE EXTRA PHARMACOPOEIA (MARTINDALE) 1982 THE PHARMACEUTICAL PRESS, SEE PAGES 965 TO 966 * |
| THE PHARMACEUTICAL CODEX, 1979 THE PHARMACEUTICAL PRESS PAGES 566-567 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0241837A3 (en) * | 1986-04-07 | 1989-05-10 | Bristol-Myers Company | Stable injectable antiemetic compositions |
| AU597955B2 (en) * | 1986-04-07 | 1990-06-14 | Bristol-Myers Squibb Company | Stable injectable antiemetic compositions |
| AT404796B (en) * | 1990-09-28 | 1999-02-25 | Solvay Pharm Gmbh | METOCLOPRAMIDE HYDROCHLORIDE SOLUTIONS TO BE APPLIED PERORALLY |
| DE4131276B4 (en) * | 1990-09-28 | 2007-07-19 | Solvay Pharmaceuticals Gmbh | Perorally administrable metoclopramide solutions |
| US5561161A (en) * | 1994-03-25 | 1996-10-01 | Oxigene, Inc. | Methods of administering and pharmaceutical formulations containing n-substituted benzamides and/or acid addition salts thereof |
| AU702675B2 (en) * | 1994-03-25 | 1999-03-04 | Oxigene, Inc. | Methods of administering N-substituted benzamides or phenothiazines |
| EP0754037A4 (en) * | 1994-03-25 | 2002-10-23 | Oxigene Inc | Methods of administering n-substituted benzamides or phenothiazines |
| RU2181588C2 (en) * | 1996-03-14 | 2002-04-27 | Райбоджин, Инк. | Method to prevent delayed vomiting |
Also Published As
| Publication number | Publication date |
|---|---|
| NZ212097A (en) | 1988-11-29 |
| AU623694B2 (en) | 1992-05-21 |
| AU591631B2 (en) | 1989-12-14 |
| GB8510115D0 (en) | 1985-05-30 |
| AU4260785A (en) | 1985-11-21 |
| GB8412585D0 (en) | 1984-06-20 |
| CA1262686A (en) | 1989-11-07 |
| AU4362489A (en) | 1990-03-01 |
| GB2158714B (en) | 1989-01-05 |
| ZA853671B (en) | 1986-04-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PE20 | Patent expired after termination of 20 years |
Effective date: 20050418 |