CA2100777C - Pharmaceutical composition containing granisetron and dexamethasone - Google Patents
Pharmaceutical composition containing granisetron and dexamethasone Download PDFInfo
- Publication number
- CA2100777C CA2100777C CA002100777A CA2100777A CA2100777C CA 2100777 C CA2100777 C CA 2100777C CA 002100777 A CA002100777 A CA 002100777A CA 2100777 A CA2100777 A CA 2100777A CA 2100777 C CA2100777 C CA 2100777C
- Authority
- CA
- Canada
- Prior art keywords
- granisetron
- dexamethasone
- vomiting
- nausea
- cytotoxic agent
- 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.)
- Expired - Lifetime
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/243—Platinum; Compounds thereof
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
Abstract
A pharmaceutical product comprising granisetron and dexamethasone as a combined preparation far simultaneous, sepa-rate or sequential use in the treatment and/or prevention of nausea and vomiting.
Description
WO 92/12716 ~ ~ ~,~ ~f ~~ ,,~ r~ PCT/GB92/00091 Pharmaceutical composition containing granisetron and dexamethasone This invention relates to the use of a compound having 5-HT3 receptor antagonist activity and dexamethasone in the treatment of emesis, and to pharmaceutical compositions containing the two compounds.
EP-A-200449 tBeecham Group p.l.c.), Example 6 discloses granisetron, and its use as an anti-emetic, especially 1o useful in treating cytotoxic agent-induced nausea and vomiting. All references herein to granisetron include pharmaceutically acceptable salts, such as the hydrochloride, and solvates, such as hydrates.
i5 The anti-emetic properties of granisetron are potentially enhanced by administering the compound in conjunction with systemic corticosteraids, such as dexamethasone.
Dexamethasone is a systemic anti-inflammatory corticosteroid, which is known to have anti-emetic 20 properties and to be useful in the treatment of emesis resulting from chemotherapy, especially cancer chemotherapy involving the use of, for example, cisplatin.
Accordingly, the present invention provides a pharmaceutical 25 product comprising granisetron and dexamethasone as a combined preparation for simultaneous, separate or sequential use in the treatment and/or prevention of nausea and vomiting.
3o The present invention also provides a method of treatment and/or prophylaxis of nausea and vomiting, which comprises administering to a human or animal subject, granisetron and dexamethasone or a pharmaceutically acceptable salt or ester thereof.
The invention further provides the use of granisetron for the manufacture of a medicament for administration in WO 92/12716 ~~/~~~ PCT/GB92/00091 - ,-.~_ conjunction with dexame'thasone or a pharmaceutically acceptable salt or ester thereof, for the treatment and/or prevention of nausea and vomiting.
Co-administration of granisetron with dexamethasone is particularly useful for the treatment and/or prevention of nausea and vomiting associated with chemotherapy using cytotoxic drugs, especially cancer chemotheraphy involving the use of, for example, platinum complexes such as cisplatin or carboplatin, or cylcophosphamide or doxorubicin. Such co-administration may also reduce delayed or prolonged nausea and vomiting associated with this type of chemotherapy. Particular note should also be made of the use in the treatment of nausea and vomiting associated with other cytotoxic agents, such as that associated with radiation treatment.
Granisetron and dexamethasone or a pharmaceutically acceptable salt or ester thereof, may be administered as a 2o single pharmaceutical composition comprising effective amounts of the two active ingredients. Alternatively the two active ingredients may be co-administered in the form of two separate pharmaceutical compositions for simultaneous or sequential use.
Suitable pharmaceutically acceptable salts of granisetron for use according to the invention include acid addition salts formed with organic or inorganic acids for example, hydrochlorides, hydrobromides, sulphates, phosphates, 3o citrates, fumarates and maleates. The solvates may, for example, be hydrates. A preferred form of granisetron for -use according to the invention is the hydrochloride.
Dexamethasone may be administered according to the invention as dexamethasone alcohol or in the form of a pharmaceutically acceptable salt or ester. Suitable salts and esters include the acetate, isonicotinoate, WO 92/12716 ~ ~~ ( '~ PCT/GB92/00091 phenylpropionate, pivalate, t-butyl acetate, trioxaundecanoate, disodium metasulphobenzoate and disodium phosphate.
A proposed dosage of granisetron for use according to the invention for administration to man (of approximately 70kg body weight), is 0.05 to 25mg., more preferably 0.05 to 20mg, and most preferably 0.1 to lOmg per unit dose, expressed as the weight of free base. A preferred dose of dexamethasone for use according to the invention is in the range of 0.5 to 20mg per dosage unit, expressed as the weight of the alcohol.
The unit doses may be administered, for example, 1 to 4 times per day. The exact dose will depend on the route of administration and the condition being treated, and it will be appreciated that it may be necessary to make routine variations to the dosage depending on the age and weight of the patient as well as the severity of the condition to be treated.
When the two active ingredients are administered as separate preparations, they are preferably given enterally, such as orally or parenterally (e. g. intramuscularly or, more particularly, intravenously).
According to a further aspect the invention provides a pharmaceutical composition, for use in human or veterinary medicine, comprising the granisetron, and dexamethasone or a 3o pharmaceutically acceptable salt or ester thereof.
Compositions according to the invention may be formulated in conventional manner using one or more physiologically acceptable carriers or excipients. Thus the compositions may, for example, be formulated for oral, buccal, parenteral ;~
EP-A-200449 tBeecham Group p.l.c.), Example 6 discloses granisetron, and its use as an anti-emetic, especially 1o useful in treating cytotoxic agent-induced nausea and vomiting. All references herein to granisetron include pharmaceutically acceptable salts, such as the hydrochloride, and solvates, such as hydrates.
i5 The anti-emetic properties of granisetron are potentially enhanced by administering the compound in conjunction with systemic corticosteraids, such as dexamethasone.
Dexamethasone is a systemic anti-inflammatory corticosteroid, which is known to have anti-emetic 20 properties and to be useful in the treatment of emesis resulting from chemotherapy, especially cancer chemotherapy involving the use of, for example, cisplatin.
Accordingly, the present invention provides a pharmaceutical 25 product comprising granisetron and dexamethasone as a combined preparation for simultaneous, separate or sequential use in the treatment and/or prevention of nausea and vomiting.
3o The present invention also provides a method of treatment and/or prophylaxis of nausea and vomiting, which comprises administering to a human or animal subject, granisetron and dexamethasone or a pharmaceutically acceptable salt or ester thereof.
The invention further provides the use of granisetron for the manufacture of a medicament for administration in WO 92/12716 ~~/~~~ PCT/GB92/00091 - ,-.~_ conjunction with dexame'thasone or a pharmaceutically acceptable salt or ester thereof, for the treatment and/or prevention of nausea and vomiting.
Co-administration of granisetron with dexamethasone is particularly useful for the treatment and/or prevention of nausea and vomiting associated with chemotherapy using cytotoxic drugs, especially cancer chemotheraphy involving the use of, for example, platinum complexes such as cisplatin or carboplatin, or cylcophosphamide or doxorubicin. Such co-administration may also reduce delayed or prolonged nausea and vomiting associated with this type of chemotherapy. Particular note should also be made of the use in the treatment of nausea and vomiting associated with other cytotoxic agents, such as that associated with radiation treatment.
Granisetron and dexamethasone or a pharmaceutically acceptable salt or ester thereof, may be administered as a 2o single pharmaceutical composition comprising effective amounts of the two active ingredients. Alternatively the two active ingredients may be co-administered in the form of two separate pharmaceutical compositions for simultaneous or sequential use.
Suitable pharmaceutically acceptable salts of granisetron for use according to the invention include acid addition salts formed with organic or inorganic acids for example, hydrochlorides, hydrobromides, sulphates, phosphates, 3o citrates, fumarates and maleates. The solvates may, for example, be hydrates. A preferred form of granisetron for -use according to the invention is the hydrochloride.
Dexamethasone may be administered according to the invention as dexamethasone alcohol or in the form of a pharmaceutically acceptable salt or ester. Suitable salts and esters include the acetate, isonicotinoate, WO 92/12716 ~ ~~ ( '~ PCT/GB92/00091 phenylpropionate, pivalate, t-butyl acetate, trioxaundecanoate, disodium metasulphobenzoate and disodium phosphate.
A proposed dosage of granisetron for use according to the invention for administration to man (of approximately 70kg body weight), is 0.05 to 25mg., more preferably 0.05 to 20mg, and most preferably 0.1 to lOmg per unit dose, expressed as the weight of free base. A preferred dose of dexamethasone for use according to the invention is in the range of 0.5 to 20mg per dosage unit, expressed as the weight of the alcohol.
The unit doses may be administered, for example, 1 to 4 times per day. The exact dose will depend on the route of administration and the condition being treated, and it will be appreciated that it may be necessary to make routine variations to the dosage depending on the age and weight of the patient as well as the severity of the condition to be treated.
When the two active ingredients are administered as separate preparations, they are preferably given enterally, such as orally or parenterally (e. g. intramuscularly or, more particularly, intravenously).
According to a further aspect the invention provides a pharmaceutical composition, for use in human or veterinary medicine, comprising the granisetron, and dexamethasone or a 3o pharmaceutically acceptable salt or ester thereof.
Compositions according to the invention may be formulated in conventional manner using one or more physiologically acceptable carriers or excipients. Thus the compositions may, for example, be formulated for oral, buccal, parenteral ;~
2~.~fl'~7'~
or rectal administration. Compositions for administration by the oral route, in the form of for example tablets or capsules, are preferred.
Compositions for oral use such as tablets and capsules may be prepared by conventional means. with pharmaceutically acceptable excipients such as binding agents (e. g.
pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose): fillers (e. g. lactose, to microcrystalline cellulose or calcium hydrogen phosphate) lubricant (e. g. magnesium stearate, talc or silica);
disintegrants (e. g. potato starch or sodium starch glycollate); or wetting agent (e. g. sodium lauryl sulphate).
Tablets may be coated by methods well known in the art.
Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or they may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations may be prepared by conventional means with 2o pharmaceutically acceptable additives such as suspending agents (e.g. sorbitol syrup, cellulose derivatives or hydrogenated edible fats): emulsifying agents (e. g. lecithin or acacia); non-aqueous vehzcles (e. g. almond oil, oily esters, ethyl alcohol or fractionated vegetable oils) and preservatives (e.g. methyl or propyl-~-hydroxybenzoates or sorbic acid). The preparations may also contain buffer salts, flavouring, colouring and sweetening agents as appropriate.
Preparations for oral administration may be suitably formulated to give controlled release of one or both active ingredients.
For parenteral administration the compositions may be.
presented in a form suitable for bolus injection or continuous infusion. Formulations for injection may be WO 92/12716 ~ ~ ~ ~ ~ ~ ~ PCf/GB92/00091 presented in unit dosage form e.g. in syringes, ampoules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilising and/or dispersing agents. Alternatively, the active ingredients may be in powder form for constitution with a suitable vehicle, e.g. sterile pyrogen-free Water, before use.
E'or rectal administration the compositions may be formulated as suppositories or retention enemas, e.g. containing conventional suppository bases such as cocoa butter or other glycerides.
The pharmaceutical compositions of the invention may be prepared according to conventional techniques well known in the pharmaceutical industry. Thus, for example, the granisetron and the dexamethasone or dexamethasone salt or ester may be admixed together, if desired, with suitable excipients. Tablets may be prepared, for example, by direct compression of such a mixture. Capsules may be prepared by filling the blend along with suitable excipients into gelatin capsules, using a suitable filling machine.
Controlled release forms for oral or rectal administration may be formulated in a conventional manner associated with controlled release forms.
The compositions for use according to the invention may, if desired, be presented in a pack or dispenser device which may contain one or more unit dosage forms containing the active ingredients. The pack may for example comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. Where the granisetron and the dexamethasone are intended fox administration as two separate compositions these may be presented in the form of, for example, a twin pack.
- 6- ,, .
2~.0~"~7'~ ._ , Clinical Studies FIRST STUDY
A randomised, double blind, parallel group study comparing the use of granisetron and/or dexamethasone for prophylactic control of cisplatin (>_ 50 mglm2) induced nausea and vomiting is carried out for a period of seven days.
Randomisation is stratified by cisplatin dose (50-79 mg/m2 and >_ 75 mg/m2). Patients receive either granisetron for seven days, granisetron and dexamethasone for seven days, or granisetron and dexamethasone for one day followed by dexamethasone for six days.
The following are evaluated:
o The improvement by dexamethasone of the efficacy of granisetron when both medications are given over a period of 24 hours and seven days.
o The efficacy improvement of dexamethasone in preventing delayed onset nausea and/or vomiting when granisetron is administered from day 2-7.
Patients receiving cisplatin (>_50 mg/m2) therapy for malignant disease are randomised in a double blind fashion, stratified according to cisplatin dosage, to receive the study medication.
The study design consists of 3 treatment arms:
1. Placebo (saline) 15 minutes infusion to be completed 20 minutes prior to cisplatin infusion (TIME 0) and granisetron 3 mg I.V. 15 minute infusion to be completed 5 min prior to TIME 0 followed by granisetron 1 mg p.o. at 6 and 12h. Granisetron 1 mg p.o. B.I.D. begins at 24h for 6 consecutive days.
2. Dexamethasone 10 mg I.V. 15 minute infusion to be completed 20 munutes prior to cisplatin infusion (TIME
0) and granisetron 3 mg I.V. 15 minute infusion to be completed 5 min prior to TIME ) followed by granisetron 1 mg p.o. at 6 and 12h.
Granisetron 1 mg p.o. B.I.D. and dexamethasone 8 mg p.o. B.I.D. begins at 24h for 6 consecutive days.
io 3. Dexamethasone lOmg I.V. 15 minute infusion to be completed 20 minutes prior to cisplatin infusion (TIME
0) and granisetron 3 mg I.V. 15 minute infusion to be completed 5 min prior to TIME 0 followed by granisetron 1 mg p.o. at 6 and 12. Dexamethasone 8 mg p.o. B.I.D. begins at 24h for 6 consecutive days.
Patients disease state is assessed using the WHO
classification and they must have a score of 2 or less. All 2o patients are naive to cytotoxic therapy to avoid anticipatory emesis.
Patients who develop nausea and vomiting after their cisplatin therapy may be given up to four doses of prochlorperazine (10 mg suppositories) per day. If nausea and vomiting continue after this such that other anti-emetics have to be given, the physician decides whether or not to stop the study medication and/or treat with standard anti-emetics. As far as is medically safe, 3o patients remain on the study medication for as much of the 7 day treatment period as possible.
The primary efficacy assessments in the study are the percentage of Complete Responders, the time to first vomiting, and the use of other anti-emetics over the seven day period.
Secondary efficacy assessments of nausea and vomiting during s the first 24 hours determine the increase in efficacy of granisetron by dexamethasone. As well, nausea and vomiting assessments after the first 29 hours determine the increase in efficacy of dexamethasone by granisetron in the maintenance phase of treatment.
SECOND STUDY
A randomised, double blind, parallel group study is carried out, comparing oral granisetron (1.0 mg bd) with oral granisetron in combination with dexamethasone (12 mg iv) on the first day only and a conventional anti-emetic therapy, (metoclopramide 7mg/kg iv plus dexamethasone 12 mg iv on the first day, followed by metoclopramide 10 mg tds po) over a 7 day period in controlling cisplatin induced nausea and 2o vomiting.
The following are primary efficacy assessments:
o The percentage of complete responders over the seven 2s day period.
o The time to less than complete response and use of other antiemetics using survival methods over the seven day period.
The following are secondary efficacy assessments:
o The percentage of complete responders over the crtical 24 hour period.
o Subjective symptom scoring for nausea and vomiting.
or rectal administration. Compositions for administration by the oral route, in the form of for example tablets or capsules, are preferred.
Compositions for oral use such as tablets and capsules may be prepared by conventional means. with pharmaceutically acceptable excipients such as binding agents (e. g.
pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose): fillers (e. g. lactose, to microcrystalline cellulose or calcium hydrogen phosphate) lubricant (e. g. magnesium stearate, talc or silica);
disintegrants (e. g. potato starch or sodium starch glycollate); or wetting agent (e. g. sodium lauryl sulphate).
Tablets may be coated by methods well known in the art.
Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or they may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations may be prepared by conventional means with 2o pharmaceutically acceptable additives such as suspending agents (e.g. sorbitol syrup, cellulose derivatives or hydrogenated edible fats): emulsifying agents (e. g. lecithin or acacia); non-aqueous vehzcles (e. g. almond oil, oily esters, ethyl alcohol or fractionated vegetable oils) and preservatives (e.g. methyl or propyl-~-hydroxybenzoates or sorbic acid). The preparations may also contain buffer salts, flavouring, colouring and sweetening agents as appropriate.
Preparations for oral administration may be suitably formulated to give controlled release of one or both active ingredients.
For parenteral administration the compositions may be.
presented in a form suitable for bolus injection or continuous infusion. Formulations for injection may be WO 92/12716 ~ ~ ~ ~ ~ ~ ~ PCf/GB92/00091 presented in unit dosage form e.g. in syringes, ampoules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilising and/or dispersing agents. Alternatively, the active ingredients may be in powder form for constitution with a suitable vehicle, e.g. sterile pyrogen-free Water, before use.
E'or rectal administration the compositions may be formulated as suppositories or retention enemas, e.g. containing conventional suppository bases such as cocoa butter or other glycerides.
The pharmaceutical compositions of the invention may be prepared according to conventional techniques well known in the pharmaceutical industry. Thus, for example, the granisetron and the dexamethasone or dexamethasone salt or ester may be admixed together, if desired, with suitable excipients. Tablets may be prepared, for example, by direct compression of such a mixture. Capsules may be prepared by filling the blend along with suitable excipients into gelatin capsules, using a suitable filling machine.
Controlled release forms for oral or rectal administration may be formulated in a conventional manner associated with controlled release forms.
The compositions for use according to the invention may, if desired, be presented in a pack or dispenser device which may contain one or more unit dosage forms containing the active ingredients. The pack may for example comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. Where the granisetron and the dexamethasone are intended fox administration as two separate compositions these may be presented in the form of, for example, a twin pack.
- 6- ,, .
2~.0~"~7'~ ._ , Clinical Studies FIRST STUDY
A randomised, double blind, parallel group study comparing the use of granisetron and/or dexamethasone for prophylactic control of cisplatin (>_ 50 mglm2) induced nausea and vomiting is carried out for a period of seven days.
Randomisation is stratified by cisplatin dose (50-79 mg/m2 and >_ 75 mg/m2). Patients receive either granisetron for seven days, granisetron and dexamethasone for seven days, or granisetron and dexamethasone for one day followed by dexamethasone for six days.
The following are evaluated:
o The improvement by dexamethasone of the efficacy of granisetron when both medications are given over a period of 24 hours and seven days.
o The efficacy improvement of dexamethasone in preventing delayed onset nausea and/or vomiting when granisetron is administered from day 2-7.
Patients receiving cisplatin (>_50 mg/m2) therapy for malignant disease are randomised in a double blind fashion, stratified according to cisplatin dosage, to receive the study medication.
The study design consists of 3 treatment arms:
1. Placebo (saline) 15 minutes infusion to be completed 20 minutes prior to cisplatin infusion (TIME 0) and granisetron 3 mg I.V. 15 minute infusion to be completed 5 min prior to TIME 0 followed by granisetron 1 mg p.o. at 6 and 12h. Granisetron 1 mg p.o. B.I.D. begins at 24h for 6 consecutive days.
2. Dexamethasone 10 mg I.V. 15 minute infusion to be completed 20 munutes prior to cisplatin infusion (TIME
0) and granisetron 3 mg I.V. 15 minute infusion to be completed 5 min prior to TIME ) followed by granisetron 1 mg p.o. at 6 and 12h.
Granisetron 1 mg p.o. B.I.D. and dexamethasone 8 mg p.o. B.I.D. begins at 24h for 6 consecutive days.
io 3. Dexamethasone lOmg I.V. 15 minute infusion to be completed 20 minutes prior to cisplatin infusion (TIME
0) and granisetron 3 mg I.V. 15 minute infusion to be completed 5 min prior to TIME 0 followed by granisetron 1 mg p.o. at 6 and 12. Dexamethasone 8 mg p.o. B.I.D. begins at 24h for 6 consecutive days.
Patients disease state is assessed using the WHO
classification and they must have a score of 2 or less. All 2o patients are naive to cytotoxic therapy to avoid anticipatory emesis.
Patients who develop nausea and vomiting after their cisplatin therapy may be given up to four doses of prochlorperazine (10 mg suppositories) per day. If nausea and vomiting continue after this such that other anti-emetics have to be given, the physician decides whether or not to stop the study medication and/or treat with standard anti-emetics. As far as is medically safe, 3o patients remain on the study medication for as much of the 7 day treatment period as possible.
The primary efficacy assessments in the study are the percentage of Complete Responders, the time to first vomiting, and the use of other anti-emetics over the seven day period.
Secondary efficacy assessments of nausea and vomiting during s the first 24 hours determine the increase in efficacy of granisetron by dexamethasone. As well, nausea and vomiting assessments after the first 29 hours determine the increase in efficacy of dexamethasone by granisetron in the maintenance phase of treatment.
SECOND STUDY
A randomised, double blind, parallel group study is carried out, comparing oral granisetron (1.0 mg bd) with oral granisetron in combination with dexamethasone (12 mg iv) on the first day only and a conventional anti-emetic therapy, (metoclopramide 7mg/kg iv plus dexamethasone 12 mg iv on the first day, followed by metoclopramide 10 mg tds po) over a 7 day period in controlling cisplatin induced nausea and 2o vomiting.
The following are primary efficacy assessments:
o The percentage of complete responders over the seven 2s day period.
o The time to less than complete response and use of other antiemetics using survival methods over the seven day period.
The following are secondary efficacy assessments:
o The percentage of complete responders over the crtical 24 hour period.
o Subjective symptom scoring for nausea and vomiting.
Claims (16)
1. A pharmaceutical product comprising granisetron and dexamethasone for simultaneous, separate or sequential use in the treatment and/or prevention of nausea and vomiting.
2. Use of granisetron and dexamethasone or a pharmaceutically acceptable salt or ester thereof for treatment and/or prophylaxis of nausea and vomiting in a human or animal subject.
3. The use of granisetron for the manufacture of a medicament for administration in conjunction with dexamethasone or a pharmaceutically acceptable salt or ester thereof, for the treatment and/or prevention of nausea and vomiting.
4. A pharmaceutical composition, for use in human or veterinary medicine, comprising granisetron, and dexamethasone or a pharmaceutically acceptable salt or ester thereof.
5. A product according to claim 1, wherein the nausea and vomiting is cytotoxic agent-induced.
6. A product according to claim 5, wherein the cytotoxic agent is cisplatin.
7. A product according to any one of claims 1, 5-6, wherein the granisetron is in the form of the hydrochloride salt.
8. The use according to claim 2, wherein the nausea and vomiting is cytotoxic agent-induced.
9. The use according to claim 8, wherein the cytotoxic agent is cisplatin.
10. The use according to any one of claims 2 and 8-9, wherein the granisetron is in the form of the hydrochloride salt.
11. The use according to claim 3, wherein the nausea and vomiting is cytotoxic agent-induced.
12. The use according to claim 11, wherein the cytotoxic agent is cisplatin.
13 The use according to any one of claims 3 and 11-12, wherein the granisetron is in the form of the hydrochloride salt.
14. The composition according to claim 4 for use in the treatment and/or prevention of nausea and vomiting, wherein the nausea and vomiting is cytotoxic agent-induced.
15. The composition according to claim 14, wherein the cytotoxic agent is cisplatin.
16. The composition according to any one of claims 4 and 14-15, wherein the granisetron is in the form of the hydrochloride salt.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9101221.1 | 1991-01-19 | ||
| GB919101221A GB9101221D0 (en) | 1991-01-19 | 1991-01-19 | Pharmaceuticals |
| PCT/GB1992/000091 WO1992012716A1 (en) | 1991-01-19 | 1992-01-16 | Pharmaceutical composition containing granisetron and dexamethasone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2100777A1 CA2100777A1 (en) | 1992-07-20 |
| CA2100777C true CA2100777C (en) | 2003-08-19 |
Family
ID=10688722
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002100777A Expired - Lifetime CA2100777C (en) | 1991-01-19 | 1992-01-16 | Pharmaceutical composition containing granisetron and dexamethasone |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP0567498A1 (en) |
| JP (1) | JP3521143B2 (en) |
| KR (1) | KR930702991A (en) |
| AU (1) | AU658169B2 (en) |
| CA (1) | CA2100777C (en) |
| GB (1) | GB9101221D0 (en) |
| IE (1) | IE920148A1 (en) |
| MX (1) | MX9200214A (en) |
| NZ (1) | NZ241337A (en) |
| PT (1) | PT100033B (en) |
| WO (1) | WO1992012716A1 (en) |
| ZA (1) | ZA92343B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY164077A (en) * | 1999-05-13 | 2017-11-30 | Pharma Mar Sa | Compositions and uses of et743 for treating cancer |
| US20060263421A1 (en) * | 2005-05-18 | 2006-11-23 | Abeille Pharmaceuticals Inc | Transdermal Method and Patch for Nausea |
| WO2008103852A1 (en) * | 2007-02-21 | 2008-08-28 | Victory Pharma, Inc. | Transdermal delivery of dexamethasone and promethazine |
| JP5537104B2 (en) * | 2009-09-16 | 2014-07-02 | テルモ株式会社 | Antiemetic |
| KR101368587B1 (en) | 2010-12-27 | 2014-03-05 | 주식회사 삼양바이오팜 | Composition for prevention of nausea or vomiting |
| CN103222977A (en) * | 2013-05-22 | 2013-07-31 | 南京工业大学 | Granisetron and dexamethasone compound percutaneous controlled release patch and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0498466B1 (en) * | 1985-04-27 | 2002-07-24 | F. Hoffmann-La Roche Ag | Indazole-3-carboxamide and -3-carboxylic acid derivatives |
| GB8805269D0 (en) * | 1988-03-04 | 1988-04-07 | Glaxo Group Ltd | Medicaments |
-
1991
- 1991-01-19 GB GB919101221A patent/GB9101221D0/en active Pending
-
1992
- 1992-01-16 EP EP92902664A patent/EP0567498A1/en not_active Ceased
- 1992-01-16 CA CA002100777A patent/CA2100777C/en not_active Expired - Lifetime
- 1992-01-16 WO PCT/GB1992/000091 patent/WO1992012716A1/en not_active Application Discontinuation
- 1992-01-16 JP JP50278692A patent/JP3521143B2/en not_active Expired - Lifetime
- 1992-01-16 AU AU11641/92A patent/AU658169B2/en not_active Expired
- 1992-01-17 IE IE014892A patent/IE920148A1/en unknown
- 1992-01-17 PT PT100033A patent/PT100033B/en not_active IP Right Cessation
- 1992-01-17 NZ NZ24133792A patent/NZ241337A/en not_active IP Right Cessation
- 1992-01-17 ZA ZA92343A patent/ZA92343B/en unknown
- 1992-01-17 MX MX9200214A patent/MX9200214A/en unknown
-
1993
- 1993-07-16 KR KR1019930702140A patent/KR930702991A/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AU658169B2 (en) | 1995-04-06 |
| NZ241337A (en) | 1994-07-26 |
| KR930702991A (en) | 1993-11-29 |
| MX9200214A (en) | 1992-08-01 |
| JP3521143B2 (en) | 2004-04-19 |
| JPH06507152A (en) | 1994-08-11 |
| PT100033B (en) | 1999-09-30 |
| PT100033A (en) | 1993-02-26 |
| CA2100777A1 (en) | 1992-07-20 |
| AU1164192A (en) | 1992-08-27 |
| GB9101221D0 (en) | 1991-02-27 |
| ZA92343B (en) | 1992-12-30 |
| IE920148A1 (en) | 1992-07-29 |
| EP0567498A1 (en) | 1993-11-03 |
| WO1992012716A1 (en) | 1992-08-06 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |