Table VII.
Non-consistency in the literature regarding repositioning and reformulations illustrated by cases found in our results
| Drug (s) | Original indication | New indication | Original formulation | New formulation | Type (Ref./Rep./Ref.-Rep.)a | Description of the reformulation or repositioning | Definition or classification | Reference |
|---|---|---|---|---|---|---|---|---|
| Azelastine hcl | Use in patients with seasonal allergic rhinitis (SAR) and non-allergic vasomotor rhinitis (VMR) | – | Astepro® 0.1% twice daily | Astepro® 0.15% once daily | Ref. | Higher dose, different dosing regimen | Dose change being considered as a reformulation | (10) |
| Azelastine (Astelin® 0.1%) Bitter taste (Side effect) Saline (Excipient) | Astepro® 0.1% sucralose and sorbitol (Excipient) | Ref. | Change of sweetener agent | Change of ingredient considered as reformulation | (10) | |||
| Dabigatran etexilate (Pradaxa®) | Thromboprophylaxis in adults following a hip or knee joint replacement | Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) | – | – | Rep. | New indication, Similar therapeutic area | New use in similar indication considered as repositioning | (30) |
| Bevacizumab | Treatment of metastatic colorectal cancer | Multiple cancers (approved) Gastric Cancer (failed) | – | – | Rep. | Repositioning within similar therapeutic area (oncology) | New use in similar indication considered as repositioning | (1) |
| Treatment of choroidal neovascularization in age-related macular degeneration (Off label) | – | – | Rep. | Repositioned but Off label use for the new indication (Not approved) | Approval status for the new use | (18) | ||
| Bromocriptine (Parlodel®-Cycloset®) | Parkinson's disease, hyperprolactinaemia and galactorrhoea | Diabetes mellitus (T2DM) | Standard release (Parlodel®) | Quick release (QR) (Cycloset®) | Rep. | New indication | Repositioning case, regardless the formulation change by release modification | (7) |
| Ref.-Rep. | New formulation and indications for existing product | Modified release formulation for a new use considered as repositioning and reformulation | (8) | |||||
| Bupropion hcl | Major depressive disorder (MDD) | Major depressive disorder (MDD) | Wellbutrin® | Wellbutrin® (once a day dosing) | Rep. | New formulation (modified release) | Reformulation as a repositioning strategy | (5) |
| Smoking cessation | Wellbutrin®, Wellbutrin SR® | Wellbutrin SR® 150 mg | Rep. | New indication | Repositioning case, regardless the change of pharmaceutical form and dosage | (7) | ||
| Ref.-Rep. | Change of dose Modified release with a new indication | Change of dose with release modification for a new use | (5) | |||||
| Buproprion + naltrexone | Opioid addiction | Obesity | – | – | Rep. | Combination for synergistic effects in a new indication | Repositioning via combination for a new indication | (1) |
| Crizotinib | Anaplastic large-cell lymphoma | Non-small-cell lung cancer (NSCLC) | – | – | Rep. | Repositioning within similar therapeutic area (oncology) | New use in similar indication considered as repositioning | (1) |
| Desloratadine | Allergies | – | Loratadine (Lorastine® or Claritin®) | Desloratadine (Clarinex®, NeoClarityn® or Aerius®) Active metabolite of loratadine | Ref. | Active metabolite | Active metabolite considered as a reformulation strategy | (9) |
| Doxep in (Sinequan®-Silenor®) | Major depressive disorder(MDD) and/or anxiety | Insomnia | 10, 25, 50, 75, 100 mg capsules | Low dosage 3 and 6 mg tablets | Ref.-Rep. | New formulation (lower dose) and indications for existing product | Dose change being considered as a reformulation | (5) |
| Duloxetine | Major depressive disorder (MDD) | Stress urinary incontinence (SUI), Fibromyalgia, Chronic Musculoskeletal pain | – | – | Rep. | Repositioning in different therapeutic area | New use in a different therapeutic area considered as repositioning | (1, 5) |
| Maintenance treatment of MDD; general anxiety disorder (GAD); maintenance treatment of GAD | – | – | Rep. | Repositioning in similar therapeutic area (psychiatry) | New use in similar indication considered as repositioning | (5) | ||
| Efavirenz, emtricitabine and tenofovir diprovoxil fumarate (Atripla®) | HIV | – | Efavirenz, emtricitabine (available individually or in combination with tenofovir diprovoxil fumarate) and tenofovir diprovoxil fumarate (available individually as or in combination with emtricitabine) | Efavirenz/emtricitabine/tenofovir | Ref. | Combination for the same indications as the mixed compounds | Fixed Dose Combination considered as reformulation | (14) |
| Enoxaparin | Prevention of venous thromboembolism (VTE) after total hip replacement | Prevention of deep venous thrombosis (DVT) following knee replacement surgery | – | – | Rep. | New indication in same therapeutic area | New use in similar indication considered as repositioning | (31) |
| Etanercept (Enbrel®) | Indicated to reduce the signs and symptoms, inhibit the progression of structural damage of active arthritis (Nov 1998) | - Improve physical function in patients with psoriatic arthritis; - Moderately to severely active polyarticular-course juvenile rheumatoid arthritis - Active ankylosing spondylitis - Moderate-to-severe plaque psoriasis |
– | – | Rep. | Repositioning within relatively similar therapeutic area | New use in similar indication considered as repositioning | (3) |
| Sciatica | – | Epidural delivery | Ref.-Rep. | New administration route for the new indication | New delivery route for a new use considered as repositioning and reformulation | (3) | ||
| Finasteride | Benign Prostatic Hyperplasia (BPH) | Male Pattern Baldness (MPB) | Proscar® 5 mg tabs | Propecia® 1 mg tabs | Rep. | New indication for existing product | Repositioning (not associated with reformulation) | (17) |
| Ref.-Rep. | New formulation (lower dose) and indications for existing product | Lower dose considered as a reformulation | (5, 18) | |||||
| Hydralazine & Isosorbide dinitrate | Hypertension/vasodilator | Heart failure | 25, 50 mg tab (Hypertension)/20 mg tab (vasodilator) | 37.5/20 mg tab | Ref.-Rep. | Repositioning and reformulation | Combination for a different therapeutic area considered as repositioning and reformulation | (5) |
| Naltrexone (Revia®-Vivitrol®) | Opioid addiction and alcohol dependence | Prevent opioid dependence relapse and alcohol dependence | 50 mg tab | Once per month extended release injectable | Rep. | New formulation of an existing product | Reformulation considered as a type of repositioning | (5) |
| Paclitaxel | Cancer chemotherapeutic agent | Prevention of restenosis of coronary stents | – | A unique form of delivery (stent elution) | Rep. | New formulation (new form) and indications for existing product | Repositioning case, regardless the change of form | (18) |
| Treatment of metastatic breast cancer | – | – | Rep. | Repositioning within similar therapeutic area (oncology) | New use in similar indication considered as repositioning | (18) | ||
| Paliperidone | Schizophrenia | – | Risperidone (Risperdal®) | Paliperidone (Invega®) contains risperidone's known active metabolite | Ref. | Active metabolite | Active metabolite as a reformulation strategy | (9) |
| Sildenafil | Angina | Erectile dysfunction | – | – | Rep. | Side effect during clinical trial, compound that failed in its lead indication | New use for a compound that failed in clinical trials, considered as repositioning | (1, 4, 7, 19–21) |
| Erectile dysfunction | Pulmonary arterial hypertension | 50–100 mg tabs | 20 mg tabs | Rep. | New indication, On target, Informed insight | Repositioning case, regardless the change of dose | (1, 19) | |
| Ref.-Rep. | New formulation and indications for existing product | Dose change being considered as a reformulation | (5) | |||||
| Sunitinib | GIST, renal cell carcinoma | Pancreatic neuroendocrine tumors Multiple cancers |
– | – | Rep. | Similar therapeutic area (oncology) | New use in similar indication considered as repositioning | (1) |
| Trastuzumab | HER2-positive breast cancer | HER2-positive metastatic gastric cancer | – | – | Rep. | Similar therapeutic area (oncology) | New use in similar indication considered as repositioning | (1) |
| Travoprost | Reduction and subsequent control of intraocular pressure (IOP) in primary open angle glaucoma (POAG) | – | Benzalkonium chloride (BAC) as preservative system | BAC-free formulation | Ref. | Reformulation by change of preservative system | Excipient change considered as reformulation | (32) |
| Warfarin | Thrombosis prevention | Secondary prophylaxis following myocardial infarction | – | – | Rep. | New indication, Similar therapeutic area | New use in similar indication considered as repositioning | (31) |
A list of all cases found in the literature search for which incoherent classification was attributed is presented in this table. Details such as original indication and formulation were provided along with the new indication and/or formulation and the classification as attributed in the literature by their respective authors.
a
Ref.: Reformulation; Rep.: Repositioning; Ref.-Rep.: Reformulation mid Repositioning.