CLIAMS:1. A compliance blister package (1) comprises a planar surface (2); the planar surface (2) comprise a matrix of blisters (3) arranged in a plurality of columns and plurality of rows for containing a fixed dosage form (4) ; the dosage form comprises a therapeutically active ingredient for once a day administration; the columns represent weeks of the dosage duration such as Week 1, Week 2, Week 3, Week 4 and Week 5; the rows represent days of the week; the blister package (1) is characterized in that the administration of dosage form (4) is for a five continuous days per week on alternate weeks; the planar surface (2) comprising the fixed dosage form (4) is identifiable by start date and calendar day of the week 1 and end date and calendar day of the week 5.
2. The compliance blister package of claim 1 wherein the dosage form (4) therapeutically active ingredient is methotrexate.
3. The compliance blister package of claim 1 wherein the dosage form (4) on alternate week 3 is identifiable by the exact day since the start date and calendar day of the week.
4. The compliance blister package of claim 1 wherein the dosage form (4) on alternate week 5 is identifiable by the exact day since the start date, calendar day of the week and the end date.
5. The compliance blister package of claim 1 wherein the dosage form (4) is filled in the blisters (3) in the first five days of the week 1, week 3 and week 5. ,TagSPECI:Field of the invention
A compliance blister package comprises a planar surface; the planar surface comprise a matrix of blisters arranged in a plurality of columns and plurality of rows for containing a fixed dosage form; the dosage form comprises a therapeutically active ingredient for once a day administration; the columns represent weeks of the dosage duration; the rows represent days of the week; the blister package is characterized in that the administration of dosage form is for a five continuous days per week on alternate weeks ; the planar surface comprising the fixed dosage form is identifiable by start date and calendar day of the week 1 and end date and calendar day of the week 5.
Background of the invention
Non-compliance is generally associated with patients having chronic illness or illnesses such as hypertension, diabetes, psychotics, hypercholesterolemia, malaria etc. The reasons for non compliance are many which include multiple medication administration, complex treatment regimens, frequent dose regimens, increasing numbers of medication prescribed and the increase in side effects and/ or drug interactions associated with multiple drug regimens.
Besides the above reasons for non compliance even wherein only two different fixed dosage forms have to be ingested/administered, each one of them once a day for two weeks sequentially, other non compliance extraneous factors such as availability of each one of the fixed dosage forms in different volumes in bottles in large quantities, difficulties in carrying them if the patient is mobile, wastage of available excess fixed dosage forms than the requisite dosages to be ingested/administered, tendency to ingest wrong dosage forms, prevention of procurement of loose dosage forms due to regulatory aspects etc prevent adherence to non compliance. In case even if loose dosage forms are
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available, finding suitable hygienic storage means for the patient at his residence would act as a deterrent for non compliance.
Medication compliance aids have been developed to enhance compliance. In medicine, compliance (also adherence, concordance, or capacitance) describes the degree to which a patient correctly follows medical advice. Most commonly, it refers to medication or drug compliance, but may also mean use of medical appliances such as compression stockings, chronic wound care, self-directed physiotherapy exercises, or attending counseling or other courses of therapy. One example is a compliance package. A compliance package may be defined as "a prepackaged unit that provides one treatment cycle of the medication to the patient in a ready-to-use package”
US Patent No. 7,328,802 provides a child resistant blister packages utilizing walled structures enclosing medicament therein.
US Application No. 20080190801 relates to pharmaceutical packaging systems or improved patience compliance.
US Application No. 20070093497 relates to methotrexate compliance package.
WO98/22072 relates to compliance package and method of improving or aiding patient compliance for complex drug regimens.
Some of the prior art compliance packages are; For example, OvconX 35 and 50 (Bristol-Meyers Squibb), Ortho-Novum Dialpak 1/35, 1/50, 10/11 and 7/7/7 (Ortho Pharmaceutical Corp.), Loestrin (D Fe 1/20 and 1.5/30 (Parke-Davis), etc. are oral contraceptives packaged in blister cards. These packages are generally a single blister card, with 21 or 28 day regimens; RheumatrexQ) Dose Packs made by Lederle Laboratories, containing four blister-pack cards each containing either 2, 3, 4, 5, or 6 tablets (for 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg per week, respectively) for l-week's therapy of methotrexate; Medrol Dosepak (Upjohn Company), is a packaging designed
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for the administration of steroids, (i.e. methylprednisolone) which require staggered dosing. For each day of drug treatment the number of tablets (and total dose) that the patient must take, decreases. For example, the Medrol Dosepak contains 21, 4mg tablets for 6 days of treatment where for each day of treatment, the total daily dose decreases by one tablet; ZithromaxX Z-Pak made by Pfizer Laboratories, contains a single medication blister card with 6, 250mg capsules. Each blister medication card is labeled with "Day 1 to Day 5" for each dose, the first dose being two, 250 mg capsules labeled "Day 1." Each subsequent capsule is labeled with "Day 2" to "Day 5.”
WO2013030697 discloses a compliance blister package comprising a matrix of blisters arranged in a plurality of columns and plurality of rows which comprises a combination of one of the fixed dose combination dosage form comprising two or more therapeutically active ingredients loaded into blisters of one of the columns and the other dosage form which comprises one or more of therapeutically active ingredient form loaded into the successive column blisters for once a day administration or concurrent administration; and the compliance blister package is identifiable by the product name, the product strength, the lot number, the expiry date and order time for patient compliance.
US 5,788,974 discloses a pharmaceutical dispensing container which holds multiple dosage units for aiding in the compliance in the eradication/treatment for Helicobater pylori and subsequent/related gastric maladies in relation to said bacterial infection using a repetitive dosage regimen for a treatment period of sufficient duration to mitigate said bacterial infection formatted in such a way to gain optimal ease of compliance resulting in improved outcome of treatment. Dosage units may be antibiotic, anti microbial or symptomatic relief agents in any combination. However, this container is capable of dispensing multiple doses of discrete doses of medicines 4 times a day for about a week;
US4039080 discloses a tray having individual compartments for holding pills, capsules, or similar solid medication, each compartment being rectangular in plan view and arranged in a rectangular format or seven columns and a plurality of rows. The tray may
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be loaded with a week's medication for an individual patient with indicia adjacent each column indicating the day of the week
In FR2705886 each column represents a week identifiable by different colors for once a day administration;
DE29913195 discloses nn each blister pack is below the medication in the left lower field of the brand name (eg. B.Heli-Set®) and in the right lower field below the medication is on the one blister pack in red "morning", on the second in blue "evening" for precise treatment instructions. On the back of each blister pack Is Open the foil printed directly on the appropriate medications ranks of the corresponding drug names
All prior art compliance packs discussed above disclose either repetitive or concurrent administration of medicines under any one of the following conditions; once a day administration or concurrent administration of fixed doses over a month or 4 times a day. These prior art compliance packs cater to multiple medicament doses to be administered simultaneously or concurrently.
Summary of the invention
The present inventors while working on a compliance blister package have surprisingly designed a simple, cost effective, and simple to use design which may cater to administration of fixed dosage form of methotrexate for treating neoplastic diseases.
Methotrexate is indicated in the management of selected adults with severe, active, rheumatoid arthritis (ACR criteria), or children with active polyarticularcourse juvenile rheumatoid arthritis, who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first line therapy including full dose nonsteroidal anti-inflammatory agents (NSAIDs). Oral administration in tablet form is often preferred when low doses are being administered since absorption is rapid and effective serum
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levels are obtained. 2.5 mg methotrexate tablets are supplied in bottles of 100 and bottles of 36. 5mg, 7.5 mg, 10 mg and 15 mg are supplied in bottles of 30.
USFDA label references neoplastic diseases to comprise choriocarcinoma and similar trophoblastic diseases. Methotrexate is administered orally or intramuscularly in doses of 15 to 30 mg daily for a five day course. Such courses are usually repeated for 3 to 5 times as required, with rest periods of one or more weeks interposed between courses, until any manifesting toxic symptoms subside.
Since the methotrexate tablets are supplied in various strengths, non availability of 15 mg tablets in pharmacies may pose the problem of compliance. Suppose if the lower strengths tablets may be available, the patient may have to purchase not only more tablet bottles but also needs to calculate the correct dosage posing the problem of non compliance. The non compliance may also result as a consequence of the need to remember the days of the week, the calendar days, the start date and the end date.
The present inventors have found a need for a compliance blister package which may comprise a fixed dosage form for once a day administration for five days a week on alternate weeks for a duration of five weeks.
The present inventors while working on a compliance blister package have surprisingly designed a simple, cost effective, and simple to use design which may cater to administration of fixed dosage form comprising a therapeutically active ingredient for five days a week on alternate weeks for duration of five weeks. The therapeutically active ingredient may be methotrexate.
In one of the aspects of the invention a compliance blister package may comprise a planar surface; the planar surface may comprise a matrix of blisters arranged in a plurality of columns and plurality of rows for containing a fixed dosage form; the dosage form may comprise a therapeutically active ingredient for once a day administration; the columns represent weeks of the dosage duration such as Week 1, Week 2, Week 3, Week 4 and 6
Week 5; the rows represent days of the week; the blister package is characterized in that the administration of dosage form is for a five continuous days per week on alternate weeks; the planar surface comprising the fixed dosage form may be identifiable by start date, calendar day of the week 1, end date and calendar day of the week 5.
In one of the embodiment of the invention the compliance blister package of the invention may comprise 15 mg of methotrexate.
In another embodiment of the invention the compliance blister package of the invention may comprise 30 mg of methotrexate.
In yet another embodiment of the invention for treatment of neoplastic disease for five days on every alternate day for 5 weeks, two compliance blister packages may be provided; the fixed dosages in each of them may be 15 mg or 30 mg as the case may be.
Detailed description of the drawings
Figure 1 Illustrate an embodiment of compliance blister package comprising a fixed dosage form for once a day administration for five days a week on alternate weeks for duration of five weeks.
Detailed description of the invention
The following terminologies will have the meanings as defined below. The compliance blister pack may refer to planar sheets with one or more blisters or wells, inside which may be contained an active ingredient, which may be sealed within the well by a second sheet. The construction of the foldable compliance blister pack may be such that the sealing sheet or backing strip may be independently accessible, removable or breakable. The blister pack and the sealing sheet or backing strip may be made of known material of construction in the prior art such as polyvinyl chloride, polyvinylidene chloride, polypropylene, polyethylene, polychlorotrifluoroethylene and combinations thereof.
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The term "active ingredient" may refer to a therapeutically active compound, as well as any prodrugs thereof and pharmaceutically acceptable salts, hydrates and solvates of the compound and the prodrugs.
The term “blister” or “well” as used herein may refer to a reservoir or pocket or cell of the compliance package which may accommodate the active ingredient in any of the dosage form as defined under “dosage form”.
The “dosage form” as defined here may be in the form of a tablet or capsule of any geometrical shape. The dosage form may comprise methotrexate as a therapeutically active ingredient.
“Administration” or “Ingestion” as used herein may refer to once a day administration of a dosage form.
Figure 1 shows a planar compliance blister package (1) comprising a planar surface (2); the planar surface (2) may comprise a matrix of blisters (3) arranged in a plurality of vertical columns and plurality of horizontal rows for containing a fixed dosage form (4) on the continuous five days starting from the beginning of the week 1, week 3 and week 5; however, the blisters of last 2 days of the week 1, week 3 and week 5 and the alternate week 2 and week 4 may be kept empty; the dosage form may comprise a therapeutically active ingredient for once a day administration; the columns represent weeks of the dosage duration such as Week 1, Week 2, Week 3, Week 4 and Week 5; the rows represent days of the week; on one side of the blister (3) column days are notified and on the other side calendar days are notified. Day 1, Day 2, Day 3, Day 4 and Day 5 of the week 1, Day 15, Day 16, Day 17, Day 18, Day 19 of the week 3 and Day 22, Day 23, Day 24, Day 25, Day 26 of the week 5 may be filled with 15 mg Methotrexate. In Figure 1, calendar days have been shown against Day 1, Day 15 and Day 22. All the days of alternate week 2 and week 4 may be identifiable by the calendar day.
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A compliance blister package (1) of the invention may comprise a planar surface (2); the planar surface (2) may comprise a matrix of blisters (3) arranged in a plurality of columns and plurality of rows for containing a fixed dosage form (4); the dosage form may comprise a therapeutically active ingredient for once a day administration; the columns represent weeks of the dosage duration such as Week 1, Week 2, Week 3, Week 4 and Week 5; the rows represent days of the week; the blister package (1) may be characterized in that the administration of dosage form (4) may be for a five continuous days per week on alternate weeks; the planar surface (2) may comprise a fixed dosage form (4) identifiable by start date and calendar day of the week 1 and end date and calendar day of the week 5.
The blister package may be any known child resistant or non child resistant one. The blister package may be provided in a carton cover or carton box.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the invention.