THALOMID SIDE EFFECTS
- Generic Name: thalidomide
- Brand Name: Thalomid
- Drug Class: Antineoplastics, Angiogenesis Inhibitor
SIDE EFFECTS
The following clinically significant adverse reactions are described in detail in other labeling sections:
- Teratogenicity
- Venous and Arterial Thromboembolism
- Increased Mortality in Patients with MM When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone
- Drowsiness and Somnolence
- Peripheral Neuropathy
- Dizziness and Orthostatic Hypotension
- Neutropenia
- Thrombocytopenia
- Increased HIV Viral Load
- Bradycardia
- Severe Cutaneous Reactions
- Seizures
- Tumor Lysis Syndrome
- Hypersensitivity
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Most patients taking THALOMID can be expected to experience adverse reactions.
Adverse Reactions In Multiple Myeloma Controlled Clinical Trials
The safety analyses were conducted in two controlled clinical studies (Study 1 and Study 2). The safety analysis in Study 1 was conducted on 204 patients who received treatment. Table 1 lists the most common adverse reactions (≥ 10%). The most frequently reported adverse reactions were fatigue, hypocalcemia, edema, constipation, sensory neuropathy, dyspnea, muscle weakness, leukopenia, neutropenia, rash/desquamation, confusion, anorexia, nausea, anxiety/agitation, tremor, fever, weight loss, thrombosis/embolism, neuropathy-motor, weight gain, dizziness, and dry skin.
Twenty-three percent of patients (47/204) discontinued due to adverse reactions; 30% (31/102) from the THALOMID/dexamethasone arm and 16% (16/102) from the dexamethasone alone arm.
Table 1: Adverse Reactions Reported in ≥10% of Patients in the THALOMID/Dexamethasone Arm (Study 1 – Safety Population; N=204)
| Body System Adverse Reaction |
Thal + Dex* (N=102) |
Dex Alone* (N=102) |
||
| All Grades n (%) |
Grade 3/4 n (%) |
All Grades n (%) |
Grade 3/4 n (%) |
|
| Metabolic/Laboratory | 97 (95) | 33 (32) | 96 (94) | 30 (29) |
| Hypocalcemia | 73 (72) | 11 (11) | 60 (59) | 5 (5) |
| Neurology | 92 (90) | 30 (29) | 76 (74) | 18 (18) |
| Neuropathy-sensory | 55 (54) | 4 (4) | 28 (28) | 1 (1) |
| Confusion | 29 (28) | 9 (9) | 12 (12) | 3 (3) |
| Anxiety/agitation | 26 (26) | 1 (1) | 14 (14) | 3 (3) |
| Tremor | 26 (26) | 1 (1) | 6 (6) | 0 (0) |
| Neuropathy-motor | 22 (22) | 8 (8) | 16 (16) | 5 (5) |
| Dizziness/ lightheadedness | 20 (20) | 1 (1) | 14 (14) | 0 (0) |
| Depressed level of consciousness | 16 (16) | 3 (3) | 3 (3) | 3 (3) |
| Constitutional Symptoms | 91 (89) | 19 (19) | 84 (82) | 16 (16) |
| Fatigue | 81 (79) | 17 (17) | 72 (71) | 13 (13) |
| Fever | 24 (24) | 1 (1) | 20 (20) | 3 (3) |
| Weight loss | 23 (23) | 1 (1) | 21 (21) | 2 (2) |
| Weight gain | 22 (22) | 1 (1) | 13 (13) | 0 (0) |
| Blood/Bone Marrow | 88 (86) | 29 (29) | 96 (94) | 19 (19) |
| Leukocytes (decreased) | 36 (35) | 6 (6) | 30 (29) | 3 (3) |
| Neutrophils (decreased) | 32 (31) | 10 (10) | 24 (24) | 10 (10) |
| Gastrointestinal | 83 (81) | 22 (22) | 70 (69) | 8 (8) |
| Constipation | 56 (55) | 8 (8) | 29 (28) | 1 (1) |
| Anorexia | 29 (28) | 4 (4) | 25 (24) | 2 (2) |
| Nausea | 29 (28) | 5 (5) | 23 (22) | 1 (1) |
| Mouth dryness | 12 (12) | 1 (1) | 6 (6) | 0 (0) |
| Cardiovascular | 70 (69) | 37 (36) | 60 (59) | 21 (21) |
| Edema | 58 (56) | 6 (6) | 47 (46) | 4 (4) |
| Thrombosis/embolism | 23 (22) | 21 (21) | 5 (5) | 5 (5) |
| Pain | 64 (63) | 10 (10) | 66 (65) | 15 (15) |
| Myalgia | 17 (17) | 0 (0) | 14 (14) | 1 (1) |
| Arthralgia | 13 (13) | 0 (0) | 10 (10) | 2 (2) |
| Pulmonary | 52 (51) | 19 (19) | 51 (50) | 20 (20) |
| Dyspnea | 43 (42) | 13 (13) | 32 (31) | 15 (15) |
| Dermatology/Skin | 48 (47) | 5 (5) | 35 (34) | 2 (2) |
| Rash/desquamation | 31 (30) | 4 (4) | 18 (18) | 2 (2) |
| Dry skin | 21 (21) | 0 (0) | 11 (11) | 0 (0) |
| Hepatic | 47 (46) | 7 (7) | 45 (44) | 4 (4) |
| Bilirubin | 14 (14) | 2 (2) | 10 (10) | 2 (2) |
| Musculoskeletal | 42 (41) | 9 (9) | 41 (40) | 14 (14) |
| Muscle weakness | 41 (40) | 6 (6) | 38 (37) | 13 (13) |
| * Treatment-emergent adverse reactions reported in ≥10% of patients in THALOMID/dexamethasone arm and with a ≥1% difference in the THALOMID/dexamethasone arm compared to the dexamethasone alone arm. | ||||
The safety analysis in Study 2 was conducted on 466 patients who received treatment. Table 2 lists the most common adverse reactions (≥10%) that were observed. Table 3 lists the most common Grade 3/4 adverse reactions (occurring at >2%) that were observed. The adverse reactions most often reported by patients treated with THALOMID/dexamethasone were constipation, peripheral edema, tremor, asthenia, dizziness and fatigue. Adverse reactions with a frequency at least 2-fold higher in the THALOMID/dexamethasone group than in the placebo/dexamethasone group include constipation, tremor, deep vein thrombosis and peripheral sensory neuropathy.
Twenty-six percent of patients (121/466) discontinued due to adverse reactions; 37% (86/234) from the THALOMID/dexamethasone arm and 15% (35/232) from the placebo/dexamethasone arm.
Table 2: Adverse Reactions Reported in ≥10% of Patients in the THALOMID/Dexamethasone Arm (Study 2 – Safety Population; N=466)
| Body System Adverse Reaction |
Thal/Dex (N=234)* n (%) |
Placebo/Dex (N=232)* n (%) |
| Patients with at least 1 Adverse Reaction | 233 (99) | 230 (99) |
| General Disorders and Administration Site Conditions | 176 (75) | 149 (64) |
| Edema peripheral | 80 (34) | 57 (25) |
| Asthenia | 56 (24) | 47 (20) |
| Fatigue | 50 (21) | 36 (16) |
| Edema NOS | 31 (13) | 19 (8) |
| Gastrointestinal Disorders | 162 (69) | 149 (64) |
| Constipation | 116 (50) | 49 (21) |
| Nausea | 30 (13) | 27 (12) |
| Dyspepsia | 27 (11) | 21 (9) |
| Nervous System Disorders | 161 (69) | 138 (60) |
| Tremor | 62 (26) | 29 (12) |
| Dizziness | 51 (23) | 32 (14) |
| Paresthesia | 27 (12) | 15 (6) |
| Peripheral sensory neuropathy | 24 (10) | 12 (5) |
| Infections and Infestations | 139 (59) | 138 (60) |
| Pneumonia NOS | 35 (15) | 28 (12) |
| Psychiatric Disorders | 90 (38) | 97 (42) |
| Anxiety | 27 (12) | 22 (10) |
| Depression | 24 (10) | 19 (8) |
| Metabolism and Nutrition Disorders | 96 (41) | 89 (38) |
| Hyperglycemia NOS | 36 (15) | 32 (14) |
| Vascular Disorders | 92 (39) | 53 (23) |
| Deep vein thrombosis | 30 (13) | 4 (2) |
| NOS = not otherwise specified. * All adverse reactions reported in ≥10% of patients in THALOMID/dexamethasone arm and with a ≥1% difference in proportion of patients between the THALOMID/dexamethasone arm compared to the placebo/dexamethasone arm. |
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Table 3: Grade 3/4 Adverse Reactions Reported in >2% of Patients in the THALOMID/Dexamethasone Arm (Study 2 – Safety Population; N=466)
| Body System Adverse Reaction |
THALOMID/Dex (N=234)* n (%) |
Placebo/Dex (N=232)* n (%) |
| Infections and Infestations | 50 (21) | 36 (16) |
| Pneumonia NOS | 17 (7) | 14 (6) |
| Bronchopneumonia NOS | 7 (3) | 3 (1) |
| General Disorders and Administration Site Conditions | 44 (19) | 26 (11) |
| Asthenia | 11 (5) | 4 (2) |
| Metabolism and Nutrition Disorders | 33 (14) | 34 (15) |
| Hypokalemia | 7 (3) | 3 (1) |
| Nervous System Disorders | 47 (20) | 20 (9) |
| Syncope | 8 (3) | 1 (<1) |
| Peripheral neuropathy NOS | 8 (3) | 0 (0) |
| Cerebrovascular accident | 6 (3) | 1 (<1) |
| Cardiac Disorders | 35 (15) | 27 (11) |
| Atrial fibrillation | 11 (5) | 8 (3) |
| Myocardial ischemia | 6 (3) | 2 (1) |
| Vascular Disorders | 42 (18) | 14 (6) |
| Deep vein thrombosis | 27 (12) | 4 (2) |
| Gastrointestinal Disorders | 26 (11) | 22 (10) |
| Constipation | 7 (3) | 2 (1) |
| Investigations | 21 (9) | 21 (9) |
| Weight increased | 8 (3) | 4 (2) |
| Blood and Lymphatic System Disorders | 24 (10) | 17 (7) |
| Neutropenia | 8 (3) | 6 (3) |
| Respiratory, Thoracic, and Mediastinal Disorders | 27 (12) | 13 (6) |
| Pulmonary embolism | 16 (7) | 4 (2) |
| Psychiatric Disorders | 19 (8) | 8 (3) |
| Anxiety | 5 (2) | 3 (1) |
| Confusional state | 5 (2) | 2 (1) |
| Ear and Labyrinth Disorders | 6 (3) | 0 (0) |
| Vertigo | 5 (2) | 0 (0) |
| NOS = not otherwise specified. * All Grade 3/4 adverse reactions with >2% of patients in THALOMID/dexamethasone arm and with a higher frequency in the THALOMID/dexamethasone arm compared to the placebo/dexamethasone arm. |
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Less Common Adverse Reactions In Multiple Myeloma Controlled Clinical Trials
In Study 2, THALOMID in combination with dexamethasone in patients with multiple myeloma, the following adverse reactions not described above were reported1:
Gastrointestinal disorders: Vomiting NOS, dry mouth, peritonitis, diverticular perforation
Nervous system disorders: Somnolence, hypoesthesia, polyneuropathy NOS, transient ischemic attack
Respiratory, thoracic, and mediastinal disorders: Bronchitis NOS
Psychiatric disorders: Mood alteration NOS
Vascular disorders: Hypotension NOS, orthostatic hypotension
Cardiac disorders: Bradycardia NOS
Eye disorders: Blurred vision
1All adverse reactions with ≥3% of patients in THALOMID/dexamethasone arm and with a ≥1% difference in proportion of patients between the THALOMID/dexamethasone arm compared to the placebo/dexamethasone arm. All grade 3/4 and serious adverse reactions reported >2 patients in THALOMID/dexamethasone arm and with a percentage higher in the THALOMID/dexamethasone arm compared to the placebo/dexamethasone arm have been considered for possible inclusion. In any cases medical judgment has been applied for consideration of causality assessment.
Adverse Reactions In Erythema Nodosum Leprosum (ENL) Clinical Trials
Table 4 lists treatment-emergent signs and symptoms that occurred in THALOMID-treated patients in clinical trials in ENL. The most common adverse reactions (≥10%) reported in patients with ENL were somnolence, rash, headache. Doses ranged from 50 to 300 mg/day. All adverse reactions were mild to moderate in severity, and none resulted in discontinuation.
Table 4: Summary of Adverse Reactions (ARs) Reported in Celgene-sponsored Controlled Clinical Trials
| All ARs Reported in Patients with ENL | ARs Reported in ≥3 HIV-seropositive Patients | |||
| Body System/Adverse Reaction | THALOMID 50 to 300 mg/day (N=24) n (%) |
THALOMID 100 mg/day (N=36) n (%) |
THALOMID 200 mg/day (N=32) n (%) |
Placebo (N=35) n (%) |
| Blood and Lymphatic | 0 | 8 (22) | 13 (41) | 10 (29) |
| Anemia | 0 | 2 (6) | 4 (13) | 3 (9) |
| Leukopenia | 0 | 6 (17) | 8 (25) | 3 (9) |
| Lymphadenopathy | 0 | 2 (6) | 4 (13) | 3 (9) |
| Body as a Whole | 16 (67) | 18 (50) | 19 (59) | 13 (37) |
| Abdominal pain | 1 (4) | 1 (3) | 1 (3) | 4 (11) |
| Accidental injury | 1 (4) | 2 (6) | 0 | 1 (3) |
| Asthenia | 2 (8) | 2 (6) | 7 (22) | 1 (3) |
| Back pain | 1 (4) | 2 (6) | 0 | 0 |
| Chills | 1 (4) | 0 | 3 (9) | 4 (11) |
| Facial edema | 1 (4) | 0 | 0 | 0 |
| Fever | 0 | 7 (19) | 7 (22) | 6 (17) |
| Headache | 3 (13) | 6 (17) | 6 (19) | 4 (11) |
| Infection | 0 | 3 (8) | 2 (6) | 1 (3) |
| Malaise | 2 (8) | 0 | 0 | 0 |
| Neck pain | 1 (4) | 0 | 0 | 0 |
| Neck rigidity | 1 (4) | 0 | 0 | 0 |
| Pain | 2 (8) | 0 | 1 (3) | 2 (6) |
| Digestive System | 5 (21) | 16 (44) | 16 (50) | 15 (43) |
| Anorexia | 0 | 1 (3) | 3 (9) | 2 (6) |
| Constipation | 1 (4) | 1 (3) | 3 (9) | 0 |
| Diarrhea | 1 (4) | 4 (11) | 6 (19) | 6 (17) |
| Dry mouth | 0 | 3 (8) | 3 (9) | 2 (6) |
| Flatulence | 0 | 3 (8) | 0 | 2 (6) |
| Liver function tests multiple abnormalities | 0 | 0 | 3 (9) | 0 |
| Nausea | 1 (4) | 0 | 4 (13) | 1 (3) |
| Oral moniliasis | 1 (4) | 4 (11) | 2 (6) | 0 |
| Tooth pain | 1 (4) | 0 | 0 | 0 |
| Metabolic and Endocrine Disorders | 1 (4) | 8 (22) | 12 (38) | 8 (23) |
| Edema peripheral | 1 (4) | 3 (8) | 1 (3) | 0 |
| Hyperlipidemia | 0 | 2 (6) | 3 (9) | 1 (3) |
| SGOT increased | 0 | 1 (3) | 4 (13) | 2 (6) |
| Nervous System | 13 (54) | 19 (53) | 18 (56) | 12 (34) |
| Agitation | 0 | 0 | 3 (9) | 0 |
| Dizziness | 1 (4) | 7 (19) | 6 (19) | 0 |
| Insomnia | 0 | 0 | 3 (9) | 2 (6) |
| Nervousness | 0 | 1 (3) | 3 (9) | 0 |
| Neuropathy | 0 | 3 (8) | 0 | 0 |
| Paresthesia | 0 | 2 (6) | 5 (16) | 4 (11) |
| Somnolence | 9 (38) | 13 (36) | 12 (38) | 4 (11) |
| Tremor | 1 (4) | 0 | 0 | 0 |
| Vertigo | 2 (8) | 0 | 0 | 0 |
| Respiratory System | 3 (13) | 9 (25) | 6 (19) | 9 (26) |
| Pharyngitis | 1 (4) | 3 (8) | 2 (6) | 2 (6) |
| Rhinitis | 1 (4) | 0 | 0 | 4 (11) |
| Sinusitis | 1 (4) | 3 (8) | 1 (3) | 2 (6) |
| Skin and Appendages | 10 (42) | 17 (47) | 18 (56) | 19 (54) |
| Acne | 0 | 4 (11) | 1 (3) | 0 |
| Dermatitis fungal | 1 (4) | 2 (6) | 3 (9) | 0 |
| Nail disorder | 1 (4) | 0 | 1 (3) | 0 |
| Pruritus | 2 (8) | 1 (3) | 2 (6) | 2 (6) |
| Rash | 5 (21) | 9 (25) | 8 (25) | 11 (31) |
| Rash maculopapular | 1 (4) | 6 (17) | 6 (19) | 2 (6) |
| Sweating | 0 | 0 | 4 (13) | 4 (11) |
| Urogenital System | 2 (8) | 6 (17) | 2 (6) | 4 (11) |
| Albuminuria | 0 | 3 (8) | 1 (3) | 2 (6) |
| Hematuria | 0 | 4 (11) | 0 | 1 (3) |
| Impotence | 2 (8) | 1 (3) | 0 | 0 |
Other Adverse Reactions Observed In ENL Patients
THALOMID in doses up to 400 mg/day has been administered investigationally in the United States over a 19-year period in 1465 patients with ENL. The published literature describes the treatment of an additional 1678 patients. To provide a meaningful estimate of the proportion of the individuals having adverse reactions, similar types of events were grouped into a smaller number of standardized categories using a modified COSTART dictionary/terminology. These categories are used in the listing below. All reported events are included except those already listed in the previous table. Due to the fact that these data were collected from uncontrolled studies, the incidence rate cannot be determined. No causal relationship between THALOMID and these events can be conclusively determined at this time. These are reports of all adverse events noted by investigators in patients to whom they had administered THALOMID.
Blood and Lymphatic: ESR decrease, eosinophilia, granulocytopenia, hypochromic anemia, leukemia, leukocytosis, leukopenia, MCV elevated, RBC abnormal, spleen palpable, thrombocytopenia.
Body as a Whole: Abdomen enlarged, fever, photosensitivity, upper extremity pain.
Cardiovascular System: Bradycardia, hypertension, hypotension, peripheral vascular disorder, tachycardia, vasodilation.
Digestive System: Anorexia, appetite increase/weight gain, dry mouth, dyspepsia, enlarged liver, eructation, flatulence, increased liver function tests, intestinal obstruction, vomiting.
Metabolic and Endocrine: ADH inappropriate, amyloidosis, bilirubinemia, BUN increased, creatinine increased, cyanosis, diabetes, edema, electrolyte abnormalities, hyperglycemia, hyperkalemia, hyperuricemia, hypocalcemia, hypoproteinemia, LDH increased, phosphorus decreased, SGPT increased.
Muscular Skeletal: Arthritis, bone tenderness, hypertonia, joint disorder, leg cramps, myalgia, myasthenia, periosteal disorder.
Nervous System: Abnormal thinking, agitation, amnesia, anxiety, causalgia, circumoral paresthesia, confusion, depression, euphoria, hyperesthesia, insomnia, nervousness, neuralgia, neuritis, neuropathy, paresthesia, peripheral neuritis, psychosis.
Respiratory System: Cough, emphysema, epistaxis, pulmonary embolus, rales, upper respiratory infection, voice alteration.
Skin and Appendages: Acne, alopecia, dry skin, eczematous rash, exfoliative dermatitis, ichthyosis, perifollicular thickening, skin necrosis, seborrhea, sweating, urticaria, vesiculobullous rash.
Special Senses: Amblyopia, deafness, dry eye, eye pain, tinnitus.
Urogenital: Decreased creatinine clearance, hematuria, orchitis, proteinuria, pyuria, urinary frequency.
Other Adverse Reactions Observed In HIV-Seropositive Patients
In addition to controlled clinical trials, THALOMID has been used in uncontrolled studies in 145 patients. Less frequent adverse reactions that have been reported in these HIV-seropositive patients treated with THALOMID were grouped into a smaller number of standardized categories using modified COSTART dictionary/terminology and these categories are used in the listing below. Adverse reactions that have already been included in the tables and narrative above, or that are too general to be informative are not listed.
Blood and Lymphatic: Aplastic anemia, macrocytic anemia, megaloblastic anemia, microcytic anemia.
Body as a Whole: Ascites, AIDS, allergic reaction, cellulitis, chest pain, chills and fever, cyst, decreased CD4 count, facial edema, flu syndrome, hernia, thyroid hormone level altered, moniliasis, photosensitivity reaction, sarcoma, sepsis, viral infection.
Cardiovascular System: Angina pectoris, arrhythmia, atrial fibrillation, bradycardia, cerebral ischemia, cerebrovascular accident, congestive heart failure, deep thrombophlebitis, heart arrest, heart failure, hypertension, hypotension, murmur, myocardial infarct, palpitation, pericarditis, peripheral vascular disorder, postural hypotension, syncope, tachycardia, thrombophlebitis, thrombosis.
Digestive System: Cholangitis, cholestatic jaundice, colitis, dyspepsia, dysphagia, esophagitis, gastroenteritis, gastrointestinal disorder, gastrointestinal hemorrhage, gum disorder, hepatitis, pancreatitis, parotid gland enlargement, periodontitis, stomatitis, tongue discoloration, tooth disorder.
Metabolic and Endocrine: Avitaminosis, bilirubinemia, dehydration, hypercholesterolemia, hypoglycemia, increased alkaline phosphatase, increased lipase, increased serum creatinine, peripheral edema.
Muscular Skeletal: Myalgia, myasthenia.
Nervous System: Abnormal gait, ataxia, decreased libido, decreased reflexes, dementia, dysesthesia, dyskinesia, emotional lability, hostility, hypalgesia, hyperkinesia, incoordination, meningitis, neurologic disorder, tremor, vertigo.
Respiratory System: Apnea, bronchitis, lung disorder, lung edema, pneumonia (including Pneumocystis carinii pneumonia), rhinitis.
Skin and Appendages: Angioedema, benign skin neoplasm, eczema, herpes simplex, incomplete Stevens-Johnson syndrome, nail disorder, pruritus, psoriasis, skin discoloration, skin disorder.
Special Senses: Conjunctivitis, eye disorder, lacrimation disorder, retinitis, taste perversion.
Postmarketing Experience
The following additional adverse reactions have been identified during post approval use of THALOMID and are not already included in Clinical Trials Experience. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatic: Decreased white blood cell counts including febrile neutropenia, changes in prothrombin time, pancytopenia, chronic myelogenous leukemia, nodular sclerosing Hodgkin’s disease, erythroleukemia, lymphedema, lymphopenia.
Body as a Whole: Hangover effect
Cardiovascular System: Sick sinus syndrome, EKG abnormalities, pulmonary hypertension.
Digestive System: Intestinal perforation, gastrointestinal perforations, bile duct obstruction, stomach ulcer, aphthous, stomatitis.
Ear and Labyrinthine Disorders: Hearing impairment.
Immune System Disorders: Hypersensitivity including anaphylaxis, solid organ transplant rejection.
Infections and infestations: Severe infections (e.g., fatal sepsis including septic shock), viral infections (including varicella zoster virus, cytomegalovirus, and hepatitis B virus reactivation) and progressive multifocal leukoencephalopathy (PML).
Metabolic and Endocrine: Electrolyte imbalance including hypercalcemia, hyponatremia and hypomagnesemia, hypothyroidism, increased alkaline phosphatase, tumor lysis syndrome, myxedema.
Nervous System: Changes in mental status or mood including suicide attempts, disturbances in consciousness including lethargy, loss of consciousness or stupor, seizures including grand mal convulsions and status epilepticus, Parkinson’s disease, stroke, carpal tunnel, Raynaud’s syndrome, migraine, foot drop.
Renal and Urinary Disorders: Renal failure, acute renal failure, oliguria, enuresis.
Reproductive System and Breast Disorders: amenorrhea, sexual dysfunction, galactorrhea, gynecomastia, metrorrhagia.
Respiratory System: Pleural effusion, interstitial lung disease.
Skin and Appendages: Erythema multiforme, erythema nodosum, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), purpura, petechiae.
Special Senses: Diplopia, nystagmus.
SRC: NLM .