zoledronic acid Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
calcium metabolism regulator, pharmaceutical aid 2868 118072-93-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • zoledronic acid
  • zoledronate
  • zoledronic acid monohydrate
  • zometa
  • zoledronic acid hydrate
An imidobisphosphonate inhibitor of BONE RESORPTION that is used for the treatment of malignancy-related HYPERCALCEMIA; OSTEITIS DEFORMANS; and OSTEOPOROSIS.
  • Molecular weight: 272.09
  • Formula: C5H10N2O7P2
  • CLOGP: -3.07
  • LIPINSKI: 0
  • HAC: 9
  • HDO: 5
  • TPSA: 153.11
  • ALOGS: -1.92
  • ROTB: 4

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
4 mg P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 39 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.01 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution) 0.60 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 2.20 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.78 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 11 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
March 20, 2001 EMA
Aug. 20, 2001 FDA NOVARTIS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Osteonecrosis of jaw 15279.62 33.43 2930 11116 5066 2338973
Osteonecrosis 14755.63 33.43 2809 11237 4533 2339506
Tooth extraction 5037.68 33.43 983 13063 1737 2342302
Bone disorder 4946.14 33.43 999 13047 2293 2341746
Pain in jaw 3528.46 33.43 854 13192 5518 2338521
Exposed bone in jaw 3314.47 33.43 575 13471 251 2343788
Pain 3133.65 33.43 1333 12713 60524 2283515
Osteomyelitis 3080.60 33.43 689 13357 2944 2341095
Impaired healing 2405.09 33.43 609 13437 4802 2339237
Bone pain 2228.25 33.43 638 13408 8358 2335681
Arthralgia 2024.40 33.43 948 13098 53337 2290702
Pyrexia 1793.13 33.43 870 13176 52838 2291201
Bone sequestrum 1764.84 33.43 304 13742 111 2343928
Myalgia 1702.77 33.43 658 13388 22675 2321364
Malignant neoplasm progression 1600.07 33.43 531 13515 11597 2332442
Metastases to bone 1514.97 33.43 355 13691 1914 2342125
Purulent discharge 1449.08 33.43 288 13758 565 2343474
Influenza like illness 1359.54 33.43 470 13576 11644 2332395
Debridement 1303.42 33.43 232 13814 149 2343890
Gingivitis 1280.47 33.43 284 13762 1137 2342902
Bone lesion 1260.80 33.43 247 13799 432 2343607
Sequestrectomy 1255.15 33.43 219 13827 102 2343937
Jaw disorder 1183.06 33.43 262 13784 1039 2343000
Toothache 1144.37 33.43 292 13754 2352 2341687
Swelling 1129.43 33.43 444 13602 15906 2328133
Fistula 1090.25 33.43 257 13789 1422 2342617
Pain in extremity 1049.81 33.43 564 13482 41976 2302063
Osteitis 1048.01 33.43 212 13834 472 2343567
Gingival swelling 971.43 33.43 205 13841 607 2343432
Nausea 958.47 33.43 763 13283 111426 2232613
Death 921.03 33.43 656 13390 80812 2263227
Tooth loss 898.99 33.43 211 13835 1140 2342899
Tooth disorder 883.13 33.43 262 13784 3861 2340178
Osteolysis 873.32 33.43 170 13876 281 2343758
Back pain 868.36 33.43 451 13595 31208 2312831
Hypocalcaemia 850.18 33.43 251 13795 3632 2340407
Bone debridement 840.93 33.43 143 13903 37 2344002
Chills 812.26 33.43 346 13700 15206 2328833
Femur fracture 772.04 33.43 266 13780 6473 2337566
Metastases to liver 745.12 33.43 213 13833 2728 2341311
Fatigue 736.65 33.43 584 13462 84289 2259750
Periodontitis 714.16 33.43 154 13892 520 2343519
Vomiting 702.11 33.43 530 13516 71072 2272967
Blood creatinine increased 694.42 33.43 277 13769 10256 2333783
Jaw operation 683.63 33.43 127 13919 136 2343903
Headache 678.81 33.43 544 13502 79635 2264404
Actinomycosis 674.24 33.43 125 13921 131 2343908
Asthenia 673.32 33.43 439 13607 46487 2297552
Tooth abscess 624.09 33.43 172 13874 1907 2342132
Dyspnoea 621.40 33.43 513 13533 78220 2265819
Neoplasm malignant 618.08 33.43 210 13836 4883 2339156
Infection 599.21 33.43 293 13753 17736 2326303
Atypical femur fracture 562.34 33.43 139 13907 963 2343076
Malaise 560.53 33.43 419 13627 55166 2288873
Pathological fracture 538.51 33.43 138 13908 1126 2342913
Fall 538.04 33.43 383 13663 46716 2297323
Inflammation 536.49 33.43 199 13847 6014 2338025
Dental operation 534.10 33.43 109 13937 257 2343782
Dental care 529.73 33.43 109 13937 272 2343767
Oral cavity fistula 528.85 33.43 98 13948 102 2343937
Oral pain 528.33 33.43 169 13877 3228 2340811
Erythema 523.40 33.43 299 13747 24860 2319179
Acute kidney injury 515.86 33.43 308 13738 27814 2316225
Oral surgery 509.34 33.43 104 13942 246 2343793
Loose tooth 509.03 33.43 117 13929 565 2343474
Oral disorder 498.66 33.43 133 13913 1288 2342751
Metastases to lung 495.50 33.43 138 13908 1593 2342446
Chest pain 487.20 33.43 297 13749 27840 2316199
Gait disturbance 485.15 33.43 274 13772 22271 2321768
Osteosclerosis 480.83 33.43 99 13947 248 2343791
Surgery 476.77 33.43 177 13869 5358 2338681
Neoplasm progression 475.65 33.43 169 13877 4499 2339540
Dental caries 454.27 33.43 131 13915 1729 2342310
Diarrhoea 451.15 33.43 440 13606 83124 2260915
Gingival pain 431.70 33.43 113 13933 1010 2343029
Abscess jaw 423.55 33.43 89 13957 255 2343784
Breast cancer metastatic 422.97 33.43 128 13918 2016 2342023
Musculoskeletal pain 420.31 33.43 196 13850 10634 2333405
General physical health deterioration 419.73 33.43 213 13833 13926 2330113
Breast cancer 409.72 33.43 185 13861 9310 2334729
Hypoaesthesia 408.74 33.43 236 13810 19979 2324060
Blood calcium decreased 396.56 33.43 122 13924 2036 2342003
Decreased appetite 395.43 33.43 263 13783 28628 2315411
Purulence 391.29 33.43 85 13961 299 2343740
Oedema peripheral 373.44 33.43 236 13810 23527 2320512
Anaemia 369.33 33.43 271 13775 34521 2309518
Renal failure 362.52 33.43 207 13839 17142 2326897
Dizziness 356.00 33.43 330 13716 58335 2285704
Dental fistula 350.56 33.43 67 13979 94 2343945
Neuropathy peripheral 350.23 33.43 176 13870 11256 2332783
Eye pain 344.12 33.43 135 13911 4756 2339283
Jaw fracture 341.16 33.43 79 13967 396 2343643
Paraesthesia 338.60 33.43 216 13830 21872 2322167
Mouth ulceration 336.39 33.43 125 13921 3787 2340252
Soft tissue infection 325.14 33.43 72 13974 283 2343756
Gingival erythema 324.98 33.43 63 13983 100 2343939
Periodontal disease 321.26 33.43 73 13973 331 2343708
Joint swelling 320.36 33.43 189 13857 16630 2327409
Blood urea increased 309.25 33.43 115 13931 3490 2340549
Bone swelling 306.71 33.43 63 13983 155 2343884
Pleural effusion 306.49 33.43 162 13884 11506 2332533
Metastases to central nervous system 305.86 33.43 100 13946 2048 2341991
Osteoarthritis 304.80 33.43 137 13909 6809 2337230
Tenderness 300.45 33.43 96 13950 1822 2342217
Abscess 297.64 33.43 101 13945 2330 2341709
Neck pain 297.53 33.43 139 13907 7558 2336481
Weight decreased 294.11 33.43 218 13828 28153 2315886
Osteotomy 293.92 33.43 53 13993 40 2343999
Metastases to spine 292.85 33.43 67 13979 315 2343724
Dehydration 290.47 33.43 197 13849 22098 2321941
Gingival ulceration 287.38 33.43 58 13988 126 2343913
Hyperbaric oxygen therapy 284.13 33.43 47 13999 3 2344036
Mastication disorder 283.13 33.43 67 13979 375 2343664
Haemoglobin decreased 279.29 33.43 178 13868 17973 2326066
Breath odour 277.05 33.43 60 13986 207 2343832
Tooth infection 273.67 33.43 90 13956 1878 2342161
C-reactive protein increased 270.06 33.43 122 13924 6133 2337906
Feeling abnormal 266.56 33.43 191 13855 23390 2320649
Muscle spasms 265.39 33.43 184 13862 21382 2322657
Mucosal inflammation 261.34 33.43 113 13933 5111 2338928
Atrial fibrillation 260.20 33.43 154 13892 13614 2330425
Muscular weakness 259.21 33.43 158 13888 14739 2329300
Tooth fracture 258.41 33.43 84 13962 1687 2342352
Disease progression 249.02 33.43 162 13884 16933 2327106
Excessive granulation tissue 248.98 33.43 51 13995 123 2343916
Musculoskeletal chest pain 241.78 33.43 86 13960 2290 2341749
Hypertension 236.94 33.43 189 13857 27172 2316867
Bone fistula 236.90 33.43 42 14004 25 2344014
Gingival disorder 231.15 33.43 62 13984 613 2343426
Wound treatment 230.52 33.43 42 14004 36 2344003
Alopecia 229.96 33.43 170 13876 21831 2322208
Stomatitis 227.47 33.43 125 13921 9585 2334454
Cough 225.29 33.43 199 13847 32918 2311121
Hypercalcaemia 219.75 33.43 82 13964 2510 2341529
Wound closure 217.34 33.43 38 14008 18 2344021
Hypokalaemia 216.64 33.43 125 13921 10529 2333510
Haematocrit decreased 214.63 33.43 93 13953 4225 2339814
Dysphagia 212.98 33.43 132 13914 12673 2331366
Plastic surgery 210.18 33.43 39 14007 41 2343998
Swelling face 208.12 33.43 117 13929 9376 2334663
Confusional state 206.11 33.43 166 13880 24178 2319861
Movement disorder 205.68 33.43 80 13966 2748 2341291
Gait inability 203.98 33.43 99 13947 5856 2338183
Anxiety 200.79 33.43 177 13869 29182 2314857
Osteoporosis 199.75 33.43 89 13957 4325 2339714
Palmar-plantar erythrodysaesthesia syndrome 197.49 33.43 87 13959 4114 2339925
Lymphadenopathy 195.98 33.43 95 13951 5603 2338436
Metastases to lymph nodes 195.31 33.43 59 13987 921 2343118
Blood alkaline phosphatase increased 195.10 33.43 99 13947 6446 2337593
Bone operation 193.85 33.43 38 14008 66 2343973
Renal impairment 193.52 33.43 114 13932 9978 2334061
Osteomyelitis chronic 190.99 33.43 39 14007 92 2343947
Hypophosphataemia 190.20 33.43 59 13987 1011 2343028
Osteopenia 189.17 33.43 68 13978 1867 2342172
Spinal osteoarthritis 187.90 33.43 66 13980 1691 2342348
Acute phase reaction 187.41 33.43 37 14009 68 2343971
Neutropenia 184.63 33.43 148 13898 21400 2322639
Exostosis 183.47 33.43 61 13985 1317 2342722
Abscess oral 182.85 33.43 43 14003 233 2343806
Sinusitis 182.34 33.43 132 13914 16394 2327645
Arthritis 179.14 33.43 108 13938 9860 2334179
Hypoaesthesia oral 177.45 33.43 67 13979 2119 2341920
Rib fracture 176.98 33.43 70 13976 2515 2341524
Oedema 174.26 33.43 107 13939 10096 2333943
Radioisotope scan 170.82 33.43 29 14017 7 2344032
Thrombocytopenia 169.43 33.43 134 13912 18997 2325042
Iridocyclitis 168.56 33.43 45 14001 436 2343603
Gingival bleeding 166.87 33.43 63 13983 1992 2342047
Urinary tract infection 166.78 33.43 161 13885 29781 2314258
Bone trimming 166.36 33.43 29 14017 13 2344026
Cellulitis 166.14 33.43 100 13946 9101 2334938
Injury 165.70 33.43 86 13960 5868 2338171
Deformity 162.41 33.43 44 14002 453 2343586
Vision blurred 161.43 33.43 117 13929 14551 2329488
Hypophagia 159.95 33.43 74 13972 3926 2340113
Oral infection 158.64 33.43 49 13997 827 2343212
Biopsy bone abnormal 157.87 33.43 27 14019 8 2344031
Abscess drainage 157.48 33.43 34 14012 115 2343924
Blood pressure increased 156.93 33.43 122 13924 16864 2327175
Red blood cell count decreased 155.40 33.43 74 13972 4192 2339847
Chest discomfort 155.13 33.43 114 13932 14481 2329558
Constipation 155.02 33.43 134 13912 21495 2322544
Trismus 154.10 33.43 48 13998 834 2343205
Polyneuropathy 153.91 33.43 57 13989 1706 2342333
Bone loss 153.81 33.43 43 14003 502 2343537
Iritis 153.34 33.43 43 14003 508 2343531
Biopsy site unspecified abnormal 151.70 33.43 27 14019 17 2344022
Wound dehiscence 151.66 33.43 45 14001 658 2343381
Musculoskeletal stiffness 151.66 33.43 105 13941 12142 2331897
Stress fracture 151.65 33.43 52 13994 1237 2342802
Tumour marker increased 149.15 33.43 45 14001 699 2343340
Renal tubular necrosis 148.40 33.43 54 13992 1536 2342503
Pneumonia 148.16 33.43 192 13854 49104 2294935
Parophthalmia 146.99 33.43 29 14017 53 2343986
Aspartate aminotransferase increased 146.56 33.43 104 13942 12508 2331531
Facial pain 146.39 33.43 51 13995 1274 2342765
Exostosis of jaw 145.01 33.43 37 14009 295 2343744
Endodontic procedure 144.67 33.43 40 14006 447 2343592
Insomnia 144.20 33.43 139 13907 25648 2318391
Red blood cell sedimentation rate increased 143.25 33.43 57 13989 2080 2341959
Plasma cell myeloma 140.66 33.43 86 13960 8047 2335992
Foot fracture 140.60 33.43 61 13985 2777 2341262
Ocular hyperaemia 140.58 33.43 68 13978 3988 2340051
Syncope 140.44 33.43 114 13932 16761 2327278
Rash 138.54 33.43 205 13841 59353 2284686
Fracture 136.27 33.43 59 13987 2672 2341367
Bacterial infection 134.27 33.43 55 13991 2166 2341873
Incisional drainage 134.11 33.43 29 14017 99 2343940
Mass 130.71 33.43 51 13995 1765 2342274
Bone density decreased 129.61 33.43 47 13999 1323 2342716
Atypical fracture 129.53 33.43 29 14017 121 2343918
Abdominal pain 129.29 33.43 150 13896 34224 2309815
Paraesthesia oral 129.18 33.43 54 13992 2240 2341799
Lethargy 127.64 33.43 83 13963 8647 2335392
Atelectasis 126.81 33.43 51 13995 1914 2342125
Tremor 126.23 33.43 117 13929 20544 2323495
Intervertebral disc degeneration 125.84 33.43 48 13998 1561 2342478
Glomerular filtration rate decreased 125.67 33.43 47 13999 1446 2342593
Gastrooesophageal reflux disease 124.54 33.43 83 13963 9012 2335027
Blood calcium increased 122.41 33.43 44 14002 1207 2342832
X-ray abnormal 122.11 33.43 28 14018 133 2343906
Terminal state 121.73 33.43 38 14008 665 2343374
Intervertebral disc protrusion 120.76 33.43 56 13990 2985 2341054
Computerised tomogram abnormal 120.22 33.43 34 14012 415 2343624
Depression 119.83 33.43 131 13915 28001 2316038
Hypotension 119.39 33.43 140 13906 32296 2311743
Dysgeusia 117.76 33.43 78 13968 8381 2335658
Urine output decreased 117.66 33.43 45 14001 1474 2342565
Hip fracture 116.76 33.43 63 13983 4649 2339390
Body temperature increased 115.46 33.43 55 13991 3116 2340923
White blood cell count increased 115.16 33.43 72 13974 7006 2337033
Oral mucosal erythema 113.34 33.43 29 14017 234 2343805
Skin toxicity 113.31 33.43 37 14009 753 2343286
Gingival abscess 113.13 33.43 26 14020 125 2343914
Blood glucose increased 112.87 33.43 88 13958 12202 2331837
Wound 110.71 33.43 51 13995 2677 2341362
Pulpitis dental 109.76 33.43 26 14020 146 2343893
Eating disorder 109.64 33.43 48 13998 2233 2341806
Blood pressure decreased 109.21 33.43 77 13969 9159 2334880
Dialysis 108.72 33.43 47 13999 2120 2341919
Oedema mouth 108.70 33.43 36 14010 767 2343272
Hypokinesia 107.95 33.43 44 14002 1710 2342329
Respiratory failure 107.51 33.43 89 13957 13439 2330600
Carbohydrate antigen 15-3 increased 107.22 33.43 24 14022 100 2343939
Bone fragmentation 107.22 33.43 24 14022 100 2343939
Fistula discharge 107.08 33.43 27 14019 204 2343835
Maxillofacial operation 106.12 33.43 19 14027 13 2344026
Palpitations 104.01 33.43 95 13951 16361 2327678
Alveolar osteitis 103.16 33.43 22 14024 69 2343970
Bone scan abnormal 103.16 33.43 22 14024 69 2343970
Chronic obstructive pulmonary disease 102.74 33.43 67 13979 7010 2337029
Gingival recession 102.32 33.43 28 14018 300 2343739
Bedridden 102.30 33.43 40 14006 1392 2342647
Pruritus 101.83 33.43 150 13896 43190 2300849
Tubulointerstitial nephritis 100.25 33.43 46 14000 2392 2341647
Vitamin D deficiency 100.14 33.43 40 14006 1474 2342565
Joint effusion 99.54 33.43 38 14008 1238 2342801
Blood phosphorus decreased 98.80 33.43 31 14015 552 2343487
Peripheral swelling 98.57 33.43 95 13951 17502 2326537
Osteomyelitis acute 97.11 33.43 20 14026 50 2343989
Alanine aminotransferase increased 96.56 33.43 85 13961 13947 2330092
Creatinine renal clearance decreased 96.36 33.43 34 14012 882 2343157
Blood lactate dehydrogenase increased 95.98 33.43 50 13996 3434 2340605
Osteoradionecrosis 95.85 33.43 19 14027 36 2344003
Soft tissue inflammation 95.73 33.43 20 14026 55 2343984
Bone erosion 95.51 33.43 30 14016 536 2343503
Denture wearer 95.51 33.43 19 14027 37 2344002
Conjunctivitis 94.80 33.43 44 14002 2349 2341690
Groin pain 93.94 33.43 37 14009 1313 2342726
Oroantral fistula 93.89 33.43 19 14027 42 2343997
Concomitant disease progression 93.88 33.43 28 14018 417 2343622
Lymph node pain 92.92 33.43 25 14021 250 2343789
Discomfort 92.90 33.43 56 13990 5103 2338936
Tachycardia 92.68 33.43 89 13957 16320 2327719
Blood sodium decreased 92.65 33.43 47 13999 3053 2340986
Spinal compression fracture 92.37 33.43 40 14006 1811 2342228
Arthropathy 88.83 33.43 62 13984 7254 2336785
Tooth avulsion 88.45 33.43 17 14029 25 2344014
Wound drainage 88.22 33.43 22 14024 158 2343881
Uveitis 87.75 33.43 37 14009 1568 2342471
Physical disability 87.39 33.43 22 14024 165 2343874
Musculoskeletal discomfort 86.84 33.43 40 14006 2098 2341941
Blood potassium decreased 86.37 33.43 54 13992 5251 2338788
Loss of consciousness 86.20 33.43 91 13955 18676 2325363
Necrosis 85.97 33.43 32 14014 971 2343068
Soft tissue disorder 85.84 33.43 23 14023 226 2343813
Sepsis 85.54 33.43 90 13956 18398 2325641
Scleritis 85.54 33.43 24 14022 284 2343755
Hepatic lesion 85.09 33.43 28 14018 584 2343455
Metastasis 84.73 33.43 31 14015 895 2343144
Lung infiltration 84.66 33.43 40 14006 2224 2341815
Pulmonary mass 84.43 33.43 38 14008 1888 2342151
Oedema mucosal 82.97 33.43 22 14024 207 2343832
Scoliosis 82.90 33.43 31 14015 953 2343086
Tetany 82.59 33.43 26 14020 468 2343571
Flank pain 82.41 33.43 35 14011 1510 2342529
Dry mouth 82.12 33.43 62 13984 8191 2335848
Tibia fracture 81.41 33.43 29 14017 774 2343265
Lymphocyte count decreased 80.62 33.43 44 14002 3319 2340720
Hepatic failure 80.47 33.43 53 13993 5636 2338403
Dysstasia 80.44 33.43 42 14004 2897 2341142
Bone density increased 80.28 33.43 17 14029 51 2343988
Bone lesion excision 80.24 33.43 15 14031 17 2344022
Dyspnoea exertional 80.21 33.43 53 13993 5667 2338372
Dental discomfort 79.66 33.43 18 14028 79 2343960
Polymyalgia rheumatica 79.06 33.43 25 14021 457 2343582
Internal fixation of fracture 78.78 33.43 21 14025 202 2343837
Renal cyst 78.41 33.43 31 14015 1111 2342928
Onycholysis 78.05 33.43 22 14024 265 2343774
Compression fracture 78.00 33.43 29 14017 877 2343162
Chondrocalcinosis pyrophosphate 77.87 33.43 20 14026 164 2343875
Tooth erosion 77.51 33.43 19 14027 126 2343913
Idiopathic orbital inflammation 77.37 33.43 14 14032 11 2344028
Eye swelling 77.35 33.43 47 13999 4343 2339696
Dental prosthesis placement 77.13 33.43 16 14030 42 2343997
Palatal disorder 76.76 33.43 18 14028 96 2343943
Renal disorder 76.40 33.43 47 13999 4441 2339598
Spinal fracture 76.34 33.43 40 14006 2779 2341260
Ulcer 75.82 33.43 35 14011 1845 2342194
Sinus disorder 75.39 33.43 39 14007 2639 2341400
Chronic sinusitis 75.15 33.43 25 14021 540 2343499
Feeling cold 74.92 33.43 41 14005 3109 2340930
Dysaesthesia 74.85 33.43 26 14020 643 2343396
Leukopenia 74.65 33.43 64 13982 10132 2333907
Somnolence 74.37 33.43 94 13952 23391 2320648
Mitral valve incompetence 74.28 33.43 38 14008 2512 2341527
Blood albumin decreased 74.21 33.43 34 14012 1761 2342278
Urinary incontinence 73.77 33.43 45 14001 4188 2339851
Spinal cord compression 73.68 33.43 25 14021 575 2343464
Cardiomegaly 73.57 33.43 37 14009 2359 2341680
Eye inflammation 73.55 33.43 27 14019 787 2343252
Neuralgia 73.46 33.43 39 14007 2783 2341256
Lacrimation increased 73.36 33.43 39 14007 2791 2341248
Nephrolithiasis 73.34 33.43 46 14000 4497 2339542
Pulmonary oedema 72.56 33.43 55 13991 7308 2336731
Aortic arteriosclerosis 72.48 33.43 25 14021 605 2343434
Resorption bone increased 72.44 33.43 20 14026 222 2343817
Abdominal pain upper 72.43 33.43 90 13956 22010 2322029
Bursitis 72.23 33.43 34 14012 1874 2342165
Heart rate increased 71.88 33.43 65 13981 11040 2332999
Burning sensation 71.73 33.43 56 13990 7772 2336267
Metastases to meninges 71.17 33.43 22 14024 372 2343667
Oral discomfort 71.10 33.43 30 14016 1273 2342766
Alveolar bone resorption 70.89 33.43 13 14033 12 2344027
Acute sinusitis 70.75 33.43 23 14023 461 2343578
Joint stiffness 70.70 33.43 43 14003 3980 2340059
Emotional distress 70.62 33.43 44 14002 4251 2339788
Poor personal hygiene 70.48 33.43 16 14030 72 2343967
Spinal pain 70.18 33.43 30 14016 1315 2342724
Oral pustule 70.13 33.43 14 14032 28 2344011
Decubitus ulcer 69.63 33.43 30 14016 1341 2342698
Liver function test abnormal 69.54 33.43 54 13992 7436 2336603
Rhinorrhoea 69.47 33.43 54 13992 7446 2336593
Face and mouth X-ray abnormal 69.09 33.43 12 14034 5 2344034
Balance disorder 68.96 33.43 60 13986 9687 2334352
Dysuria 68.94 33.43 42 14004 3899 2340140
Visual impairment 68.72 33.43 65 13981 11690 2332349
Fracture nonunion 68.45 33.43 23 14023 513 2343526
Fanconi syndrome acquired 68.33 33.43 19 14027 217 2343822
Oropharyngeal pain 67.92 33.43 64 13982 11454 2332585
Platelet count decreased 67.89 33.43 74 13972 15739 2328300
Magnetic resonance imaging abnormal 67.55 33.43 25 14021 746 2343293
Tricuspid valve incompetence 67.31 33.43 31 14015 1625 2342414
Cardiac failure congestive 66.79 33.43 74 13972 16027 2328012
Epistaxis 66.78 33.43 59 13987 9720 2334319
Hyperkeratosis 66.26 33.43 25 14021 788 2343251
Haemorrhoids 66.24 33.43 34 14012 2263 2341776
Hyperparathyroidism 66.10 33.43 22 14024 476 2343563
Gingival operation 65.86 33.43 14 14032 43 2343996
Red cell distribution width increased 65.79 33.43 23 14023 580 2343459
Pollakiuria 65.63 33.43 40 14006 3716 2340323
Hyperaesthesia teeth 65.35 33.43 21 14025 405 2343634
Bone formation increased 65.15 33.43 14 14032 46 2343993
Kyphosis 64.93 33.43 20 14026 334 2343705
Gingival erosion 64.92 33.43 14 14032 47 2343992
Leukocytosis 64.84 33.43 39 14007 3537 2340502
Mental status changes 64.72 33.43 46 14000 5536 2338503
Feeding disorder 64.65 33.43 29 14017 1429 2342610
Aminoaciduria 64.47 33.43 13 14033 28 2344011
Feeling hot 64.43 33.43 50 13996 6878 2337161
Biopsy 64.39 33.43 16 14030 113 2343926
Exophthalmos 63.45 33.43 19 14027 287 2343752
Pneumonitis 62.96 33.43 40 14006 3999 2340040
White blood cell count decreased 62.64 33.43 76 13970 18132 2325907
Cataract 62.38 33.43 46 14000 5862 2338177
Prosthesis implantation 62.16 33.43 13 14033 36 2344003
Ascites 62.15 33.43 45 14001 5575 2338464
Cellulitis orbital 61.38 33.43 15 14031 98 2343941
Lip pain 61.36 33.43 19 14027 323 2343716
Lymphoedema 61.27 33.43 26 14020 1119 2342920
Blood parathyroid hormone increased 60.83 33.43 22 14024 614 2343425
Upper limb fracture 60.80 33.43 34 14012 2689 2341350
Seizure 60.75 33.43 87 13959 24379 2319660
Haemorrhage 60.66 33.43 59 13987 10980 2333059
Breast cancer recurrent 60.63 33.43 23 14023 736 2343303
Metastases to skin 59.92 33.43 17 14029 210 2343829
Chronic kidney disease 59.79 33.43 39 14007 4079 2339960
Dental cleaning 59.78 33.43 12 14034 25 2344014
Influenza 59.69 33.43 63 13983 12915 2331124
Proteinuria 59.36 33.43 34 14012 2816 2341223
Metastases to the mediastinum 59.34 33.43 14 14032 77 2343962
Diverticulum intestinal 59.33 33.43 22 14024 660 2343379
Secretion discharge 59.18 33.43 26 14020 1219 2342820
Lumbar spinal stenosis 58.86 33.43 22 14024 675 2343364
Migraine 58.66 33.43 57 13989 10596 2333443
Spondylolisthesis 58.58 33.43 20 14026 469 2343570
Paralysis 58.16 33.43 29 14017 1815 2342224
Metastatic neoplasm 58.14 33.43 22 14024 699 2343340
Product use in unapproved indication 58.08 33.43 58 13988 11142 2332897
Mouth swelling 57.83 33.43 21 14025 593 2343446
Radiculopathy 57.82 33.43 22 14024 710 2343329
Vein disorder 57.76 33.43 21 14025 595 2343444
Ostectomy 57.71 33.43 11 14035 15 2344024
Radius fracture 57.50 33.43 21 14025 603 2343436
Hyperhidrosis 57.38 33.43 67 13979 15355 2328684
Hypothyroidism 56.98 33.43 39 14007 4418 2339621
Vertigo 56.97 33.43 53 13993 9331 2334708
Pelvic fracture 56.70 33.43 26 14020 1349 2342690
Localised infection 56.42 33.43 33 14013 2843 2341196
Cardiac failure 56.14 33.43 59 13987 12035 2332004
Hyperlipidaemia 55.96 33.43 32 14014 2642 2341397
Conjunctival oedema 55.86 33.43 16 14030 205 2343834
Febrile neutropenia 55.78 33.43 56 13990 10826 2333213
Pallor 55.70 33.43 36 14010 3706 2340333
Loss of personal independence in daily activities 55.28 33.43 41 14005 5270 2338769
Vertebral foraminal stenosis 54.70 33.43 14 14032 113 2343926
Deep vein thrombosis 54.60 33.43 60 13986 12872 2331167
Bone graft 54.55 33.43 16 14030 224 2343815
Amnesia 54.04 33.43 46 14000 7207 2336832
X-ray dental 54.00 33.43 9 14037 1 2344038
Single photon emission computerised tomogram abnormal 54.00 33.43 9 14037 1 2344038
Walking aid user 53.96 33.43 21 14025 721 2343318
Candida infection 53.82 33.43 32 14014 2841 2341198
Mucosal ulceration 53.66 33.43 16 14030 238 2343801
Gamma-glutamyltransferase increased 53.59 33.43 41 14005 5521 2338518
Metastases to soft tissue 53.55 33.43 11 14035 27 2344012
Heart rate irregular 53.36 33.43 30 14016 2397 2341642
Contusion 53.33 33.43 59 13987 12751 2331288
Abscess management 53.15 33.43 9 14037 2 2344037
Deafness 53.00 33.43 31 14015 2670 2341369
Dental alveolar anomaly 52.45 33.43 11 14035 31 2344008
Dental prosthesis user 52.45 33.43 11 14035 31 2344008
Thrombosis 52.36 33.43 50 13996 9094 2334945
Chronic inflammatory demyelinating polyradiculoneuropathy 52.30 33.43 13 14033 92 2343947
Abdominal discomfort 52.29 33.43 68 13978 17388 2326651
Hiatus hernia 51.99 33.43 28 14018 2056 2341983
Nail toxicity 51.99 33.43 12 14034 59 2343980
Fanconi syndrome 51.82 33.43 15 14031 200 2343839
Cachexia 51.65 33.43 21 14025 810 2343229
Limb discomfort 51.51 33.43 33 14013 3346 2340693
Wrist fracture 51.12 33.43 26 14020 1697 2342342
Pericardial effusion 51.06 33.43 35 14011 3974 2340065
Device failure 50.53 33.43 26 14020 1739 2342300
Anhedonia 50.33 33.43 23 14023 1184 2342855
Mobility decreased 50.12 33.43 48 13998 8762 2335277
Cancer pain 50.01 33.43 16 14030 304 2343735
Upper respiratory tract infection 49.93 33.43 48 13998 8803 2335236
Ear pain 49.89 33.43 30 14016 2719 2341320
Ankle fracture 49.81 33.43 28 14018 2237 2341802
Condition aggravated 49.75 33.43 92 13954 31887 2312152
Bone cancer 49.29 33.43 15 14031 240 2343799
Multiple fractures 49.27 33.43 19 14027 636 2343403
Hydronephrosis 49.26 33.43 23 14023 1244 2342795
Nasal disorder 49.01 33.43 16 14030 325 2343714
Metaphyseal corner fracture 48.85 33.43 8 14038 0 2344039
Visual acuity reduced 48.74 33.43 38 14008 5260 2338779
Femoral neck fracture 48.71 33.43 23 14023 1276 2342763
Disorientation 48.68 33.43 41 14005 6331 2337708
Dental implantation 48.50 33.43 15 14031 254 2343785
Humerus fracture 48.50 33.43 22 14024 1113 2342926
Eyelid ptosis 48.44 33.43 22 14024 1116 2342923
Multiple organ dysfunction syndrome 48.02 33.43 44 14002 7597 2336442
Post procedural complication 47.90 33.43 30 14016 2924 2341115
Cholelithiasis 47.79 33.43 39 14007 5764 2338275
Left ventricular hypertrophy 47.76 33.43 19 14027 692 2343347
Breast pain 47.53 33.43 23 14023 1348 2342691
Platelet count increased 47.42 33.43 27 14019 2210 2341829
Thoracic vertebral fracture 47.18 33.43 18 14028 585 2343454
Lymphocytic infiltration 47.03 33.43 14 14032 207 2343832
Ejection fraction decreased 46.82 33.43 29 14017 2772 2341267
Spinal stenosis 46.79 33.43 23 14023 1395 2342644
Transient ischaemic attack 46.77 33.43 39 14007 5939 2338100
Bronchitis 46.76 33.43 57 13989 13657 2330382
Osteitis deformans 46.70 33.43 11 14035 60 2343979
Metabolic acidosis 46.66 33.43 39 14007 5959 2338080
Lower limb fracture 46.51 33.43 26 14020 2055 2341984
Peri-implantitis 46.30 33.43 8 14038 3 2344036
Hyperparathyroidism secondary 46.16 33.43 13 14033 156 2343883
Speech disorder 46.13 33.43 40 14006 6424 2337615
Hypouricaemia 46.05 33.43 10 14036 35 2344004
Diplopia 45.91 33.43 31 14015 3434 2340605
Pulmonary fibrosis 45.82 33.43 28 14018 2612 2341427
Arteriosclerosis 45.74 33.43 23 14023 1465 2342574
Lung neoplasm 45.65 33.43 20 14026 931 2343108
BRAF gene mutation 45.61 33.43 8 14038 4 2344035
Tinnitus 45.45 33.43 36 14010 5099 2338940
Temporomandibular joint syndrome 44.70 33.43 18 14028 677 2343362
Sinus tachycardia 44.66 33.43 30 14016 3295 2340744
Cerebrovascular accident 44.65 33.43 68 13978 20118 2323921
Pulmonary embolism 44.43 33.43 64 13982 18019 2326020
Blood chloride decreased 44.43 33.43 18 14028 688 2343351
Herpes zoster 44.34 33.43 47 13999 9678 2334361
Haematuria 44.19 33.43 33 14013 4285 2339754
Synovial cyst 44.06 33.43 19 14027 851 2343188
Hypercholesterolaemia 43.92 33.43 23 14023 1595 2342444
Aphthous ulcer 43.83 33.43 22 14024 1396 2342643
Sciatica 43.31 33.43 25 14021 2100 2341939
Diabetes mellitus 42.94 33.43 41 14005 7454 2336585
Oral discharge 42.70 33.43 10 14036 53 2343986
Blood potassium increased 42.55 33.43 25 14021 2171 2341868
Blood magnesium decreased 42.46 33.43 21 14025 1291 2342748
Renal tubular disorder 42.32 33.43 16 14030 507 2343532
Malignant pleural effusion 42.19 33.43 15 14031 398 2343641
Blood creatinine decreased 42.05 33.43 16 14030 516 2343523
Hepatic cyst 42.05 33.43 17 14029 646 2343393
Uterine leiomyoma 42.05 33.43 22 14024 1523 2342516
Asthma 41.82 33.43 49 13997 11265 2332774
Monocyte count increased 41.77 33.43 16 14030 526 2343513
Hyponatraemia 41.62 33.43 53 13993 13272 2330767
Photophobia 41.59 33.43 25 14021 2264 2341775
Lung disorder 41.45 33.43 37 14009 6175 2337864
Anuria 41.34 33.43 23 14023 1801 2342238
Rotator cuff syndrome 41.32 33.43 23 14023 1802 2342237
Seborrhoeic keratosis 41.30 33.43 14 14032 321 2343718
Concomitant disease aggravated 41.23 33.43 19 14027 997 2343042
Bone development abnormal 41.12 33.43 9 14037 33 2344006
Eyelid oedema 40.90 33.43 26 14020 2600 2341439
Tooth deposit 40.70 33.43 10 14036 67 2343972
Hyperglycaemia 40.58 33.43 33 14013 4852 2339187
Lymphadenopathy mediastinal 40.42 33.43 14 14032 343 2343696
Aortic valve incompetence 40.31 33.43 18 14028 877 2343162
Low turnover osteopathy 40.10 33.43 19 14027 1062 2342977
Synovitis 40.01 33.43 26 14020 2700 2341339
Breath sounds abnormal 39.98 33.43 17 14029 735 2343304
Quality of life decreased 39.96 33.43 17 14029 736 2343303
Oral candidiasis 39.74 33.43 23 14023 1942 2342097
Fibrosis 39.68 33.43 15 14031 475 2343564
Decreased interest 39.65 33.43 15 14031 476 2343563
Tendonitis 39.63 33.43 24 14022 2203 2341836
Alveoloplasty 39.58 33.43 7 14039 4 2344035
Local anaesthesia 39.58 33.43 7 14039 4 2344035
Mitral valve calcification 39.37 33.43 11 14035 128 2343911
Dry skin 39.28 33.43 37 14009 6615 2337424
Skin ulcer 39.27 33.43 30 14016 4029 2340010
Metastases to pelvis 39.20 33.43 9 14037 43 2343996
Neoplasm 39.10 33.43 19 14027 1124 2342915
Oliguria 38.87 33.43 20 14026 1337 2342702
Anaesthesia 38.86 33.43 9 14037 45 2343994
Dyspepsia 38.68 33.43 44 14002 9800 2334239
Cyst 38.61 33.43 21 14025 1572 2342467
Eye disorder 38.40 33.43 27 14019 3192 2340847
General physical condition abnormal 38.34 33.43 16 14030 660 2343379
Tonsillar disorder 38.27 33.43 12 14034 213 2343826
Mouth haemorrhage 38.23 33.43 18 14028 992 2343047
Hypovolaemia 38.17 33.43 19 14027 1184 2342855
Corneal endotheliitis 37.89 33.43 7 14039 7 2344032
Life expectancy shortened 37.78 33.43 8 14038 24 2344015
Vitamin D decreased 37.39 33.43 18 14028 1043 2342996
Pelvic pain 37.27 33.43 22 14024 1927 2342112
Haematoma 37.17 33.43 32 14014 5089 2338950
Jaundice 37.13 33.43 33 14013 5475 2338564
Vascular calcification 37.11 33.43 11 14035 160 2343879
Urinary tract inflammation 37.06 33.43 8 14038 27 2344012
Hand fracture 37.03 33.43 16 14030 720 2343319
Emphysema 37.00 33.43 18 14028 1067 2342972
Gastrointestinal disorder 36.99 33.43 41 14005 8876 2335163
Depressed level of consciousness 36.90 33.43 38 14008 7566 2336473
Neutrophil count increased 36.69 33.43 22 14024 1983 2342056
Azotaemia 36.62 33.43 15 14031 590 2343449
Intervertebral disc space narrowing 36.55 33.43 10 14036 107 2343932
Pancytopenia 36.47 33.43 46 14000 11406 2332633
Hyperplasia 36.32 33.43 11 14035 173 2343866
Rales 36.26 33.43 18 14028 1115 2342924
Tooth resorption 36.20 33.43 8 14038 31 2344008
Malnutrition 36.19 33.43 21 14025 1782 2342257
Open reduction of fracture 36.14 33.43 13 14033 357 2343682
Pubis fracture 35.90 33.43 13 14033 364 2343675
Intervertebral disc disorder 35.78 33.43 15 14031 626 2343413
Polyuria 35.54 33.43 18 14028 1164 2342875
Fibromyalgia 35.52 33.43 26 14020 3274 2340765
Pleural fibrosis 35.36 33.43 11 14035 190 2343849
Cerebral atrophy 35.35 33.43 16 14030 805 2343234
Protein total decreased 35.18 33.43 16 14030 814 2343225
Cataract nuclear 35.13 33.43 10 14036 125 2343914
Cranial nerve disorder 35.13 33.43 10 14036 125 2343914
Edentulous 35.13 33.43 9 14037 73 2343966
Lung neoplasm malignant 35.10 33.43 25 14021 3017 2341022
Blood creatine phosphokinase increased 35.08 33.43 31 14015 5105 2338934
Biopsy kidney abnormal 35.06 33.43 8 14038 37 2344002
Abdominal distension 35.05 33.43 43 14003 10368 2333671
Blood urine present 35.04 33.43 21 14025 1891 2342148
Coronary artery disease 35.00 33.43 33 14013 5906 2338133
Tooth discolouration 34.88 33.43 12 14034 288 2343751
Rheumatoid arthritis 34.82 33.43 59 13987 19081 2324958
Radiation injury 34.77 33.43 10 14036 130 2343909
Prosthesis user 34.74 33.43 7 14039 15 2344024
Thirst 34.71 33.43 20 14026 1674 2342365
Phlebitis 34.60 33.43 17 14029 1030 2343009
Poor venous access 34.52 33.43 16 14030 851 2343188
Bone neoplasm 34.50 33.43 10 14036 134 2343905
Oesophagitis 34.11 33.43 21 14025 1985 2342054
Skin discolouration 33.64 33.43 31 14015 5389 2338650
Pyogenic granuloma 33.63 33.43 9 14037 88 2343951
Blood pressure systolic increased 33.58 33.43 22 14024 2317 2341722
Device related infection 33.55 33.43 25 14021 3234 2340805
Recurrent cancer 33.55 33.43 12 14034 324 2343715
General anaesthesia 33.54 33.43 9 14037 89 2343950
Road traffic accident 33.48 33.43 28 14018 4280 2339759
Dental plaque 33.46 33.43 8 14038 47 2343992
Dry eye 33.44 33.43 27 14019 3929 2340110

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Osteonecrosis of jaw 11788.79 43.30 2095 5655 2208 1736823
Osteonecrosis 10337.85 43.30 1856 5894 2106 1736925
Bone disorder 3493.27 43.30 639 7111 746 1738285
Tooth extraction 3147.52 43.30 575 7175 657 1738374
Exposed bone in jaw 2371.44 43.30 395 7355 97 1738934
Osteomyelitis 2285.66 43.30 488 7262 1807 1737224
Pain in jaw 2279.42 43.30 477 7273 1561 1737470
Impaired healing 1432.51 43.30 341 7409 2238 1736793
Pain 1191.50 43.30 514 7236 26143 1712888
Bone sequestrum 1190.12 43.30 196 7554 29 1739002
Purulent discharge 892.53 43.30 177 7573 392 1738639
Debridement 781.31 43.30 138 7612 100 1738931
Gingivitis 779.35 43.30 161 7589 472 1738559
Sequestrectomy 737.09 43.30 124 7626 37 1738994
Swelling 729.25 43.30 251 7499 6745 1732286
Jaw disorder 728.75 43.30 145 7605 328 1738703
Malignant neoplasm progression 698.52 43.30 294 7456 13864 1725167
Hypocalcaemia 692.44 43.30 200 7550 2956 1736075
Bone lesion 678.53 43.30 136 7614 324 1738707
Bone debridement 656.24 43.30 109 7641 22 1739009
Toothache 648.14 43.30 150 7600 843 1738188
Fistula 642.20 43.30 153 7597 994 1738037
Pyrexia 640.70 43.30 408 7342 45992 1693039
Bone pain 640.56 43.30 191 7559 3171 1735860
Metastases to bone 607.89 43.30 159 7591 1579 1737452
Osteitis 597.92 43.30 117 7633 233 1738798
Death 538.53 43.30 473 7277 86970 1652061
Neoplasm malignant 515.69 43.30 172 7578 4167 1734864
Tooth disorder 495.33 43.30 130 7620 1307 1737724
Gingival swelling 460.35 43.30 95 7655 275 1738756
General physical health deterioration 445.42 43.30 210 7540 12908 1726123
Periodontitis 437.21 43.30 88 7662 215 1738816
Tooth loss 416.68 43.30 96 7654 525 1738506
Osteolysis 413.14 43.30 84 7666 220 1738811
Dental care 405.25 43.30 74 7676 79 1738952
Actinomycosis 403.35 43.30 74 7676 83 1738948
Oral disorder 391.90 43.30 93 7657 590 1738441
Dental operation 385.41 43.30 71 7679 83 1738948
Oral surgery 370.38 43.30 69 7681 90 1738941
Jaw operation 367.76 43.30 65 7685 47 1738984
Neoplasm progression 358.25 43.30 122 7628 3145 1735886
Blood creatinine increased 344.68 43.30 180 7570 13766 1725265
Oral cavity fistula 334.84 43.30 58 7692 31 1739000
Erythema 316.33 43.30 171 7579 14017 1725014
Prostatic specific antigen increased 306.43 43.30 102 7648 2444 1736587
Terminal state 306.26 43.30 79 7671 735 1738296
Soft tissue infection 301.52 43.30 63 7687 197 1738834
Infection 300.91 43.30 158 7592 12202 1726829
Loose tooth 293.41 43.30 60 7690 163 1738868
Surgery 286.96 43.30 100 7650 2763 1736268
Osteosclerosis 279.87 43.30 52 7698 66 1738965
Tooth abscess 278.70 43.30 74 7676 778 1738253
Pathological fracture 275.63 43.30 68 7682 518 1738513
Gingival pain 270.24 43.30 63 7687 365 1738666
Haemoglobin decreased 265.72 43.30 163 7587 16951 1722080
Abscess jaw 251.63 43.30 50 7700 111 1738920
Malaise 248.86 43.30 193 7557 29372 1709659
Blood calcium decreased 247.85 43.30 75 7675 1302 1737729
Oral pain 245.06 43.30 75 7675 1355 1737676
Jaw fracture 238.88 43.30 51 7699 182 1738849
Purulence 238.19 43.30 53 7697 240 1738791
Dental caries 237.08 43.30 62 7688 611 1738420
Inflammation 232.59 43.30 90 7660 3360 1735671
Osteotomy 230.58 43.30 39 7711 13 1739018
Asthenia 227.96 43.30 196 7554 34474 1704557
Arthralgia 221.32 43.30 164 7586 23280 1715751
Back pain 209.89 43.30 139 7611 16474 1722557
Dyspnoea 203.49 43.30 221 7529 51838 1687193
Fatigue 200.95 43.30 217 7533 50564 1688467
Hypophosphataemia 200.52 43.30 63 7687 1245 1737786
Prostate cancer metastatic 199.31 43.30 58 7692 873 1738158
Prostate cancer 197.31 43.30 87 7663 4539 1734492
Wound closure 195.85 43.30 33 7717 10 1739021
Anaemia 194.40 43.30 167 7583 29290 1709741
Abscess 191.59 43.30 67 7683 1867 1737164
Periodontal disease 190.12 43.30 39 7711 108 1738923
Influenza like illness 186.93 43.30 91 7659 5962 1733069
Gingival erythema 185.77 43.30 34 7716 37 1738994
Haematocrit decreased 181.05 43.30 80 7670 4193 1734838
Vomiting 180.64 43.30 180 7570 38135 1700896
Blood urea increased 179.86 43.30 82 7668 4629 1734402
Dental fistula 177.37 43.30 31 7719 19 1739012
Myalgia 171.51 43.30 120 7630 15538 1723493
Hyperbaric oxygen therapy 169.84 43.30 28 7722 4 1739027
Bone swelling 168.30 43.30 32 7718 50 1738981
Red blood cell count decreased 165.85 43.30 72 7678 3614 1735417
Tooth infection 158.23 43.30 47 7703 762 1738269
Wound treatment 157.92 43.30 28 7722 21 1739010
Acute kidney injury 156.96 43.30 160 7590 34784 1704247
Mouth ulceration 155.60 43.30 56 7694 1699 1737332
Renal impairment 155.30 43.30 103 7647 12211 1726820
Decreased appetite 154.62 43.30 134 7616 23737 1715294
Chills 150.39 43.30 99 7651 11588 1727443
Oral infection 147.77 43.30 35 7715 219 1738812
Wound dehiscence 147.36 43.30 42 7708 584 1738447
Breath odour 145.06 43.30 34 7716 202 1738829
Nausea 137.94 43.30 180 7570 51016 1688015
Dehydration 136.81 43.30 110 7640 17548 1721483
Blood alkaline phosphatase increased 136.44 43.30 70 7680 5125 1733906
Neuropathy peripheral 135.37 43.30 85 7665 9168 1729863
C-reactive protein increased 133.80 43.30 72 7678 5813 1733218
Bone lesion excision 133.59 43.30 23 7727 11 1739020
Cellulitis 130.14 43.30 73 7677 6395 1732636
Bone trimming 129.19 43.30 21 7729 1 1739030
Gingival disorder 127.63 43.30 31 7719 219 1738812
Renal failure 126.78 43.30 111 7639 19906 1719125
Disease progression 126.26 43.30 104 7646 17159 1721872
Excessive granulation tissue 123.73 43.30 26 7724 84 1738947
Tenderness 122.95 43.30 41 7709 984 1738047
Oroantral fistula 122.69 43.30 21 7729 9 1739022
Wound 122.16 43.30 46 7704 1588 1737443
Lymphadenopathy 121.41 43.30 60 7690 4054 1734977
Dysphagia 120.82 43.30 82 7668 10086 1728945
Metastases to lung 117.62 43.30 44 7706 1491 1737540
Bone operation 117.05 43.30 22 7728 31 1739000
Osteomyelitis chronic 115.42 43.30 23 7727 52 1738979
Injury 114.42 43.30 52 7698 2908 1736123
Bone fistula 113.33 43.30 19 7731 5 1739026
Gingival ulceration 113.25 43.30 22 7728 41 1738990
Wound drainage 111.65 43.30 24 7726 89 1738942
Mastication disorder 111.00 43.30 27 7723 192 1738839
Biopsy site unspecified abnormal 110.12 43.30 20 7730 20 1739011
Stomatitis 108.72 43.30 61 7689 5343 1733688
Pain in extremity 108.12 43.30 98 7652 18374 1720657
Hypercalcaemia 105.39 43.30 43 7707 1843 1737188
Metastases to lymph nodes 105.30 43.30 35 7715 831 1738200
Hypoaesthesia 104.36 43.30 74 7676 9761 1729270
Pneumonia 102.53 43.30 148 7602 46034 1692997
Sinusitis 102.47 43.30 58 7692 5165 1733866
Plastic surgery 100.24 43.30 17 7733 6 1739025
Trismus 98.41 43.30 30 7720 533 1738498
Bacterial infection 98.26 43.30 41 7709 1861 1737170
Osteoarthritis 97.23 43.30 43 7707 2253 1736778
Blood sodium decreased 97.09 43.30 43 7707 2261 1736770
Chest pain 96.19 43.30 95 7655 19819 1719212
Blood lactate dehydrogenase increased 94.96 43.30 49 7701 3626 1735405
Diarrhoea 94.81 43.30 155 7595 53697 1685334
Tooth fracture 94.12 43.30 28 7722 456 1738575
Plasma cell myeloma 94.08 43.30 70 7680 9944 1729087
Platelet count decreased 93.42 43.30 86 7664 16437 1722594
Confusional state 92.71 43.30 96 7654 21182 1717849
Biopsy bone abnormal 92.04 43.30 16 7734 9 1739022
Abdominal pain 90.13 43.30 95 7655 21395 1717636
Product use in unapproved indication 88.81 43.30 66 7684 9356 1729675
Oral mucosal erythema 88.38 43.30 20 7730 99 1738932
Pleural effusion 87.62 43.30 70 7680 11040 1727991
Tetany 87.32 43.30 23 7727 233 1738798
Bone erosion 85.18 43.30 22 7728 205 1738826
Metastases to liver 85.01 43.30 39 7711 2228 1736803
Constipation 84.64 43.30 78 7672 14922 1724109
Deformity 82.86 43.30 20 7730 137 1738894
Myoglobinuria 82.56 43.30 21 7729 183 1738848
Exostosis 81.96 43.30 25 7725 445 1738586
Fall 81.42 43.30 101 7649 27113 1711918
Femur fracture 81.07 43.30 31 7719 1116 1737915
Endodontic procedure 81.03 43.30 19 7731 113 1738918
Eye pain 80.87 43.30 38 7712 2293 1736738
Oedema peripheral 80.34 43.30 77 7673 15473 1723558
Lymph node pain 79.65 43.30 19 7731 123 1738908
Thrombocytopenia 78.71 43.30 88 7662 21161 1717870
Hypokalaemia 77.08 43.30 52 7698 6322 1732709
Mucosal inflammation 75.62 43.30 44 7706 4125 1734906
Metastases to central nervous system 75.44 43.30 32 7718 1513 1737518
Gingival abscess 75.37 43.30 16 7734 55 1738976
X-ray abnormal 74.81 43.30 17 7733 86 1738945
Anxiety 74.80 43.30 74 7676 15453 1723578
Metastases to spine 74.13 43.30 22 7728 355 1738676
Proteinuria 73.69 43.30 38 7712 2806 1736225
Gait disturbance 73.63 43.30 67 7683 12603 1726428
Facial pain 73.28 43.30 22 7728 370 1738661
Red cell distribution width increased 72.31 43.30 22 7728 388 1738643
Tachycardia 71.87 43.30 66 7684 12562 1726469
Rib fracture 71.36 43.30 32 7718 1732 1737299
Lymphocyte count decreased 70.65 43.30 34 7716 2164 1736867
Weight decreased 70.53 43.30 86 7664 22667 1716364
Parophthalmia 68.88 43.30 13 7737 19 1739012
Sepsis 67.72 43.30 78 7672 19360 1719671
Systemic inflammatory response syndrome 67.54 43.30 25 7725 821 1738210
Denture wearer 66.58 43.30 12 7738 11 1739020
Radioisotope scan 65.53 43.30 11 7739 3 1739028
Osteoporosis 65.44 43.30 29 7721 1526 1737505
Bone fragmentation 64.75 43.30 13 7737 31 1739000
Headache 64.52 43.30 102 7648 34274 1704757
Hypertension 64.34 43.30 76 7674 19372 1719659
Hypoaesthesia oral 64.30 43.30 24 7726 807 1738224
Acute phase reaction 64.22 43.30 12 7738 16 1739015
Blood albumin decreased 63.82 43.30 29 7721 1619 1737412
Aspartate aminotransferase increased 62.72 43.30 57 7693 10699 1728332
Swelling face 62.54 43.30 40 7710 4443 1734588
Anhedonia 60.94 43.30 23 7727 798 1738233
Alveolar osteitis 60.88 43.30 12 7738 25 1739006
Musculoskeletal pain 60.39 43.30 41 7709 5033 1733998
Gamma-glutamyltransferase increased 60.22 43.30 41 7709 5057 1733974
Musculoskeletal chest pain 59.47 43.30 26 7724 1324 1737707
Intervertebral disc degeneration 58.84 43.30 21 7729 620 1738411
Urinary retention 58.12 43.30 41 7709 5354 1733677
Urinary tract infection 57.62 43.30 53 7697 10100 1728931
Fistula discharge 57.61 43.30 14 7736 99 1738932
Rhabdomyolysis 57.40 43.30 55 7695 11035 1727996
Stem cell transplant 57.27 43.30 19 7731 448 1738583
Abscess drainage 57.13 43.30 14 7736 103 1738928
Oedema mucosal 56.85 43.30 15 7735 153 1738878
Dental discomfort 56.81 43.30 12 7738 40 1738991
Soft tissue inflammation 56.45 43.30 11 7739 21 1739010
Paraesthesia 56.31 43.30 53 7697 10398 1728633
Decubitus ulcer 55.39 43.30 23 7727 1030 1738001
Muscular weakness 55.27 43.30 52 7698 10197 1728834
Edentulous 55.05 43.30 10 7740 10 1739021
Blood phosphorus decreased 54.91 43.30 19 7731 511 1738520
Fracture 54.87 43.30 23 7727 1055 1737976
Concomitant disease progression 54.84 43.30 19 7731 513 1738518
Abscess oral 54.64 43.30 13 7737 83 1738948
Gingival recession 54.25 43.30 13 7737 86 1738945
Metastasis 53.36 43.30 21 7729 817 1738214
Mouth swelling 53.29 43.30 16 7734 269 1738762
Neuralgia 52.18 43.30 24 7726 1378 1737653
Blood glucose increased 51.97 43.30 51 7699 10533 1728498
Spinal osteoarthritis 51.14 43.30 20 7730 765 1738266
Pancytopenia 50.76 43.30 52 7698 11305 1727726
Atelectasis 50.55 43.30 26 7724 1908 1737123
Speech disorder 50.00 43.30 35 7715 4513 1734518
Radiotherapy 49.06 43.30 13 7737 135 1738896
Discomfort 48.26 43.30 28 7722 2608 1736423
Atrial fibrillation 48.22 43.30 58 7692 15053 1723978
Oral discomfort 47.60 43.30 17 7733 503 1738528
Computerised tomogram abnormal 47.34 43.30 16 7734 400 1738631
Mass 47.16 43.30 21 7729 1117 1737914
Localised infection 47.02 43.30 24 7726 1733 1737298
Gastrooesophageal reflux disease 47.02 43.30 34 7716 4613 1734418
Hydronephrosis 46.87 43.30 22 7728 1323 1737708
Internal fixation of fracture 46.74 43.30 10 7740 36 1738995
Pulmonary embolism 46.45 43.30 53 7697 13006 1726025
Exophthalmos 46.18 43.30 13 7737 172 1738859
Bone loss 46.06 43.30 12 7738 116 1738915
Chronic obstructive pulmonary disease 45.81 43.30 37 7713 5916 1733115
Creatinine renal clearance decreased 44.89 43.30 18 7732 736 1738295
Oedema mouth 44.88 43.30 15 7735 362 1738669
Prostatic specific antigen abnormal 44.87 43.30 11 7739 81 1738950
Chronic kidney disease 44.63 43.30 32 7718 4285 1734746
White blood cell count decreased 44.47 43.30 52 7698 13097 1725934
Pulpitis dental 44.44 43.30 10 7740 48 1738983
Condition aggravated 44.17 43.30 66 7684 21084 1717947
Exostosis of jaw 43.58 43.30 9 7741 26 1739005
Oral discharge 43.32 43.30 9 7741 27 1739004

Pharmacologic Action:

SourceCodeDescription
ATC M05BA08 MUSCULO-SKELETAL SYSTEM
DRUGS FOR TREATMENT OF BONE DISEASES
DRUGS AFFECTING BONE STRUCTURE AND MINERALIZATION
Bisphosphonates
ATC M05BB08 MUSCULO-SKELETAL SYSTEM
DRUGS FOR TREATMENT OF BONE DISEASES
DRUGS AFFECTING BONE STRUCTURE AND MINERALIZATION
Bisphosphonates, combinations
CHEBI has role CHEBI:50646 bone density conservation agent
MeSH PA D050071 Bone Density Conservation Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Osteitis deformans indication 2089002 DOID:5408
Humoral hypercalcemia of malignancy indication 47709007
Osteoporosis indication 64859006 DOID:11476
Postmenopausal osteoporosis indication 102447009
Bone Metastases of Solid Tumors indication
Glucocorticoid Induced Osteoporosis indication
Osteolytic Lesions of Multiple Myeloma indication
Hypogonadal Osteoporosis in Males indication
Prevention of Glucocorticoid-Induced Osteoporosis indication
Drug-induced osteoporosis off-label use 14651005
Intracranial hemorrhage contraindication 1386000
Anuria contraindication 2472002 DOID:2983
Hypophosphatemia contraindication 4996001
Hypocalcemia contraindication 5291005
Bone pain contraindication 12584003
Hyperkalemia contraindication 14140009
Hypovolemia contraindication 28560003
Dehydration contraindication 34095006
Hypoparathyroidism contraindication 36976004 DOID:11199
Hypernatremia contraindication 39355002
Chronic heart failure contraindication 48447003
Joint pain contraindication 57676002
Acute nephropathy contraindication 58574008
Pulmonary congestion contraindication 67599009
Muscle pain contraindication 68962001
Fracture of femur contraindication 71620000
Oliguria contraindication 83128009
Hyponatremia contraindication 89627008
Small intestine excision contraindication 107938000
Hypomagnesemia contraindication 190855004
Impaired renal function disorder contraindication 197663003
Tooth disorder contraindication 234947003 DOID:1091
Fragile capillaries contraindication 248726001
Pregnancy, function contraindication 289908002
Breastfeeding (mother) contraindication 413712001
Aseptic necrosis of bone of jaw contraindication 441809006
Severe dehydration contraindication 450316000
Invasive Dental Procedure contraindication
Thyroid Surgery contraindication
Malabsorption States contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 1.38 acidic
pKa2 5.45 acidic
pKa3 6.59 acidic
pKa4 10.35 acidic
pKa5 11.04 acidic
pKa6 5.92 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 5MG BASE/100ML RECLAST NOVARTIS N021817 April 16, 2007 RX INJECTABLE INTRAVENOUS 8052987 Oct. 27, 2023 TREATMENT AND PREVENTION OF POSTMENOPAUSAL OR GLUCOCORTICOID-INDUCED OSTEOPOROSIS AND TREATMENT TO INCREASE BONE MASS IN MEN WITH OSTEOPOROSIS
EQ 4MG BASE/100ML ZOMETA NOVARTIS N021223 June 17, 2011 RX INJECTABLE INTRAVENOUS 8324189 May 29, 2025 BONE METASTASES
EQ 4MG BASE/100ML ZOMETA NOVARTIS N021223 June 17, 2011 RX INJECTABLE INTRAVENOUS 8324189 May 29, 2025 HYPERCALCEMIA OF MALIGNANCY
EQ 4MG BASE/100ML ZOMETA NOVARTIS N021223 June 17, 2011 RX INJECTABLE INTRAVENOUS 8324189 May 29, 2025 MULTIPLE MYELOMA
EQ 4MG BASE/5ML ZOMETA NOVARTIS N021223 March 7, 2003 RX INJECTABLE INTRAVENOUS 8324189 May 29, 2025 BONE METASTASES
EQ 4MG BASE/5ML ZOMETA NOVARTIS N021223 March 7, 2003 RX INJECTABLE INTRAVENOUS 8324189 May 29, 2025 HYPERCALCEMIA OF MALIGNANCY
EQ 4MG BASE/5ML ZOMETA NOVARTIS N021223 March 7, 2003 RX INJECTABLE INTRAVENOUS 8324189 May 29, 2025 MULTIPLE MYELOMA

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Farnesyl pyrophosphate synthase Enzyme INHIBITOR Ki 10.15 CHEMBL CHEMBL
72 kDa type IV collagenase Enzyme IC50 5.15 CHEMBL
Neutrophil collagenase Enzyme IC50 4.75 CHEMBL
Geranylgeranyl pyrophosphate synthase Enzyme Ki 5.57 CHEMBL
Carbonic anhydrase 2 Enzyme IC50 7.21 CHEMBL
Carbonic anhydrase 14 Enzyme IC50 7.04 CHEMBL
Carbonic anhydrase 12 Enzyme IC50 6.50 CHEMBL
Carbonic anhydrase 9 Enzyme IC50 5.27 CHEMBL
Matrix metalloproteinase-14 Enzyme IC50 4.90 CHEMBL
Matrix metalloproteinase-9 Enzyme IC50 4.28 CHEMBL
Geranylgeranyl pyrophosphate synthase Enzyme Ki 6.59 CHEMBL
Farnesyl pyrophosphate synthase Enzyme Ki 7.96 CHEMBL
Farnesyl diphosphate synthase Enzyme IC50 5.96 CHEMBL
Farnesyl pyrophosphate synthase Unclassified INHIBITOR IC50 6.30 IUPHAR

External reference:

IDSource
D000077211 MESH_DESCRIPTOR_UI
4021276 VUID
N0000179387 NUI
C0257685 UMLSCUI
D01968 KEGG_DRUG
6XC1PAD3KF UNII
165800-06-6 SECONDARY_CAS_RN
134600006 SNOMEDCT_US
008997 NDDF
199263 MMSL
d04708 MMSL
15839 MMSL
77655 RXNORM
4021276 VANDF
395926009 SNOMEDCT_US
CHEBI:46557 CHEBI
CHEMBL924 ChEMBL_ID
DB00399 DRUGBANK_ID
ZOL PDB_CHEM_ID
68740 PUBCHEM_CID
3177 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Zometa HUMAN PRESCRIPTION DRUG LABEL 1 0078-0387 INJECTION, SOLUTION, CONCENTRATE 4 mg INTRAVENOUS NDA 17 sections
Reclast HUMAN PRESCRIPTION DRUG LABEL 1 0078-0435 INJECTION, SOLUTION 5 mg INTRAVENOUS NDA 17 sections
Zometa HUMAN PRESCRIPTION DRUG LABEL 1 0078-0590 INJECTION, SOLUTION, CONCENTRATE 4 mg INTRAVENOUS NDA 17 sections
Zoledronic Acid HUMAN PRESCRIPTION DRUG LABEL 1 0143-9642 INJECTION, SOLUTION, CONCENTRATE 4 mg INTRAVENOUS ANDA 17 sections
ZOLEDRONIC ACID HUMAN PRESCRIPTION DRUG LABEL 1 0409-4215 INJECTION, SOLUTION, CONCENTRATE 4 mg INTRAVENOUS ANDA 18 sections
ZOLEDRONIC ACID HUMAN PRESCRIPTION DRUG LABEL 1 0409-4228 INJECTION, SOLUTION 5 mg INTRAVENOUS ANDA 17 sections
Zoledronic Acid HUMAN PRESCRIPTION DRUG LABEL 1 0409-4229 INJECTION, SOLUTION 4 mg INTRAVENOUS NDA 18 sections
Zoledronic acid HUMAN PRESCRIPTION DRUG LABEL 1 16714-815 INJECTION 4 mg INTRAVENOUS ANDA 17 sections
Zoledronic acid HUMAN PRESCRIPTION DRUG LABEL 1 16729-242 INJECTION 4 mg INTRAVENOUS ANDA 17 sections
Zoledronic Acid HUMAN PRESCRIPTION DRUG LABEL 1 17478-324 SOLUTION 5 mg INTRAVENOUS ANDA 17 sections
Zoledronic Acid HUMAN PRESCRIPTION DRUG LABEL 1 17478-327 INJECTION, SOLUTION, CONCENTRATE 4 mg INTRAVENOUS ANDA 16 sections
Zoledronic acid HUMAN PRESCRIPTION DRUG LABEL 1 23155-170 INJECTION, SOLUTION, CONCENTRATE 4 mg INTRAVENOUS ANDA 16 sections
Zoledronic acid HUMAN PRESCRIPTION DRUG LABEL 1 23155-186 INJECTION, SOLUTION 5 mg INTRAVENOUS ANDA 17 sections
zoledronic acid HUMAN PRESCRIPTION DRUG LABEL 1 25021-801 INJECTION, SOLUTION, CONCENTRATE 0.80 mg INTRAVENOUS ANDA 17 sections
zoledronic acid HUMAN PRESCRIPTION DRUG LABEL 1 25021-826 INJECTION, SOLUTION 0.04 mg INTRAVENOUS NDA 16 sections
zoledronic acid HUMAN PRESCRIPTION DRUG LABEL 1 25021-830 INJECTION, SOLUTION 0.05 mg INTRAVENOUS ANDA 17 sections
Zoledronic acid HUMAN PRESCRIPTION DRUG LABEL 1 43598-255 INJECTION, SOLUTION 4 mg INTRAVENOUS ANDA 16 sections
Zoledronic Acid HUMAN PRESCRIPTION DRUG LABEL 1 43598-330 INJECTION, SOLUTION, CONCENTRATE 4 mg INTRAVENOUS ANDA 16 sections
Zoledronic Acid HUMAN PRESCRIPTION DRUG LABEL 1 43598-331 INJECTION, SOLUTION 5 mg INTRAVENOUS ANDA 18 sections
zoledronic acid HUMAN PRESCRIPTION DRUG LABEL 1 50742-416 INJECTION, SOLUTION, CONCENTRATE 4 mg INTRAVENOUS ANDA 17 sections
Zoledronic Acid HUMAN PRESCRIPTION DRUG LABEL 1 51991-064 INJECTION 5 mg INTRAVENOUS ANDA 17 sections
Zoledronic Acid HUMAN PRESCRIPTION DRUG LABEL 1 51991-065 INJECTION, SOLUTION, CONCENTRATE 4 mg INTRAVENOUS ANDA 18 sections
ZOLEDRONIC ACID HUMAN PRESCRIPTION DRUG LABEL 1 54288-100 INJECTION, SOLUTION, CONCENTRATE 4 mg INTRAVENOUS ANDA 17 sections
Zoledronic Acid HUMAN PRESCRIPTION DRUG LABEL 1 55111-685 INJECTION, SOLUTION, CONCENTRATE 4 mg INTRAVENOUS ANDA 16 sections
Zoledronic Acid HUMAN PRESCRIPTION DRUG LABEL 1 55111-688 INJECTION, SOLUTION 5 mg INTRAVENOUS ANDA 18 sections
Zoledronic Acid HUMAN PRESCRIPTION DRUG LABEL 1 55150-266 INJECTION, SOLUTION, CONCENTRATE 4 mg INTRAVENOUS ANDA 17 sections
Zoledronic Acid HUMAN PRESCRIPTION DRUG LABEL 1 55150-283 INJECTION, SOLUTION 5 mg INTRAVENOUS ANDA 17 sections
Zoledronic Acid HUMAN PRESCRIPTION DRUG LABEL 1 60505-6110 INJECTION, SOLUTION, CONCENTRATE 4 mg INTRAVENOUS ANDA 16 sections
Zoledronic Acid HUMAN PRESCRIPTION DRUG LABEL 1 63323-961 INJECTION 4 mg INTRAVENOUS ANDA 17 sections
Zoledronic Acid HUMAN PRESCRIPTION DRUG LABEL 1 63323-966 INJECTION, SOLUTION 5 mg INTRAVENOUS ANDA 17 sections