Targretin Side Effects
Generic Name: Bexarotene
Please note - some side effects for Targretin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).
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For the consumer For the professional
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Side Effects of Targretin - for the consumer
Targretin
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Targretin:
Seek medical attention right away if any of these SEVERE side effects occur when using Targretin:Diarrhea; dizziness; dry skin; headache; loss of appetite; nausea; trouble sleeping; weakness.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloating or swelling of ankles, feet, or hands; changes in vision; chest pain; chills; confusion; dark urine or pale stools; fever; severe stomach or back pain with continuing nausea or vomiting; red, swollen, or blistered skin; sore throat; unusual fatigue; yellowing of the skin or eyes.
Targretin Gel
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Targretin Gel:
Seek medical attention right away if any of these SEVERE side effects occur when using Targretin Gel:Headache; pain or itching at the application site.
TopSevere allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); fever, chills, or sore throat; irritation at the application site; numbness or tingling of the skin; swelling.
For the professional
Targretin
The safety of Targretin® capsules has been evaluated in clinical studies of 152 patients with CTCL who received Targretin® capsules for up to 97 weeks and in 352 patients in other studies. The mean duration of therapy for the 152 patients with CTCL was 166 days. The most common adverse events reported with an incidence of at least 10% in patients with CTCL treated at an initial dose of 300 mg/m2/day of Targretin® capsules are shown in Table 1. The events at least possibly related to treatment are lipid abnormalities (elevated triglycerides, elevated total and LDL cholesterol and decreased HDL cholesterol), hypothyroidism, headache, asthenia, rash, leukopenia, anemia, nausea, infection, peripheral edema, abdominal pain, and dry skin. Most adverse events occurred at a higher incidence in patients treated at starting doses of greater than 300 mg/m2/day.
Adverse events leading to dose reduction or study drug discontinuation in at least two patients were hyperlipemia, neutropenia/leukopenia, diarrhea, fatigue/lethargy, hypothyroidism, headache, liver function test abnormalities, rash, pancreatitis, nausea, anemia, allergic reaction, muscle spasm, pneumonia, and confusion.
The moderately severe (NCI Grade 3) and severe (NCI Grade 4) adverse events reported in two or more patients with CTCL treated at an initial dose of 300 mg/m2/day of Targretin® capsules were hypertriglyceridemia, pruritus, headache, peripheral edema, leukopenia, rash, and hypercholesteremia. Most of these moderately severe or severe adverse events occurred at a higher rate in patients treated at starting doses of greater than 300 mg/m2/day than in patients treated at a starting dose of 300 mg/m2/day.
As shown in Table 3, in patients with CTCL receiving an initial dose of 300 mg/m2/day, the incidence of NCI Grade 3 or 4 elevations in triglycerides and total cholesterol was 28% and 25%, respectively. In contrast, in patients with CTCL receiving greater than 300 mg/m2/day, the incidence of NCI Grade 3 or 4 elevated triglycerides and total cholesterol was 45% and 45%, respectively. Other Grade 3 and 4 laboratory abnormalities are shown in Table 3.
In addition to the 152 patients enrolled in the two CTCL studies, 352 patients received Targretin® capsules as monotherapy for various advanced malignancies at doses from 5 mg/m2/day to 1000 mg/m2/day. The common adverse events (incidence greater than 10%) were similar to those seen in patients with CTCL.
In the 504 patients (CTCL and non-CTCL) who received Targretin® capsules as monotherapy, drug-related serious adverse events that were fatal, in one patient each, were acute pancreatitis, subdural hematoma, and liver failure.
In the patients with CTCL receiving an initial dose of 300 mg/m2/day of Targretin® capsules, adverse events reported at an incidence of less than 10% and not included in Tables 1-3 or discussed in other parts of labeling and possibly related to treatment were as follows:
Body as a Whole: chills, cellulitis, chest pain, sepsis, and monilia.
Cardiovascular: hemorrhage, hypertension, angina pectoris, right heart failure, syncope, and tachycardia.
Digestive: constipation, dry mouth, flatulence, colitis, dyspepsia, cheilitis, gastroenteritis, gingivitis, liver failure, and melena.
Hemic and Lymphatic: eosinophilia, thrombocythemia, coagulation time increased, lymphocytosis, and thrombocytopenia.
Metabolic and Nutritional: LDH increased, creatinine increased, hypoproteinemia, hyperglycemia, weight decreased, weight increased, and amylase increased.
Musculoskeletal: arthralgia, myalgia, bone pain, myasthenia, and arthrosis.
Nervous: depression, agitation, ataxia, cerebrovascular accident, confusion, dizziness, hyperesthesia, hypesthesia, and neuropathy.
Respiratory: pharyngitis, rhinitis, dyspnea, pleural effusion, bronchitis, cough increased, lung edema, hemoptysis, and hypoxia.
Skin and Appendages: skin ulcer, acne, alopecia, skin nodule, macular papular rash, pustular rash, serous drainage, and vesicular bullous rash.
Special Senses: dry eyes, conjunctivitis, ear pain, blepharitis, corneal lesion, keratitis, otitis externa, and visual field defect.
Urogenital: albuminuria, hematuria, urinary incontinence, urinary tract infection, urinary urgency, dysuria, kidney function abnormal, and breast pain.
| Initial Assigned Dose
Group (mg/m2/day) |
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|---|---|---|---|
| 300 | >300 | ||
| Body
System Adverse Event1,2 |
N=84 N (%) |
N=53 N (%) |
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1 Preferred English term coded according to Ligand-modified COSTART 5 Dictionary. 2 Patients are counted at most once in each AE category. | |||
METABOLIC AND NUTRITIONAL DISORDERS |
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Hyperlipemia |
66 (78.6) |
42 (79.2) |
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BODY AS A
WHOLE |
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ENDOCRINE |
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SKIN AND
APPENDAGES |
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HEMIC AND LYMPHATIC SYSTEM |
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Leukopenia |
14 (16.7) |
25 (47.2) |
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DIGESTIVE
SYSTEM |
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CARDIOVASCULAR
SYSTEM |
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NERVOUS
SYSTEM |
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| Initial Assigned Dose Group (mg/m2/day) | |||||
|---|---|---|---|---|---|
| 300 (N=84) | >300 (N=53) | ||||
| Mod Sev | Severe | Mod Sev | Severe | ||
| Body
System Adverse Event1,2 |
N (%) |
N (%) |
N (%) |
N (%) |
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1 Preferred English term coded according to Ligand-modified COSTART 5 Dictionary. 2 Patients are counted at most once in each AE category. Patients are classified by the highest severity within each row. | |||||
BODY AS A
WHOLE |
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CARDIOVASCULAR
SYS. |
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DIGESTIVE
SYSTEM |
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ENDOCRINE |
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HEM. & LYMPH.
SYS. |
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META. AND NUTR.
DIS. |
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RESPIRATORY
SYSTEM |
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SKIN AND
APPENDAGES |
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| Initial Assigned Dose (mg/m2/day) | |||||
|---|---|---|---|---|---|
| 300 | >300 | ||||
| N=831 | N=531 | ||||
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Analyte |
Grade 32 (%) |
Grade 42 (%) |
Grade 3 (%) |
Grade 4 (%) |
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1 Number of patients with at least one analyte value post-baseline. 2Adapted from NCI Common Toxicity Criteria, Grade 3 and 4, Version 2.0. Patients are considered to have had a Grade 3 or 4 value if either of the following occurred: a) Value becomes Grade 3 or 4 during the study; b) Value is abnormal at baseline and worsens to Grade 3 or 4 on study, including all values beyond study drug discontinuation, as defined in data handling conventions. 3The denominator used to calculate the incidence rates for fasting Total Cholesterol and Triglycerides were N=75 for the 300 mg/m2/day initial dose group and N=44 for the >300 mg/m2/day initial dose group. | |||||
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Targretin Gel
The safety of Targretin® gel has been assessed in clinical studies of 117 patients with CTCL who received Targretin® gel for up to 172 weeks. In the multicenter open label study, 50 patients with CTCL received Targretin® gel for up to 98 weeks. The mean duration of therapy for these 50 patients was 199 days. The most common adverse events reported with an incidence at the application site of at least 10% in patients with CTCL were rash, pruritus, skin disorder, and pain.
Adverse events leading to dose reduction or study drug discontinuation in at least two patients were rash, contact dermatitis, and pruritus.
Of the 49 patients (98%) who experienced any adverse event, most experienced events categorized as mild (9 patients, 18%) or moderate (27 patients, 54%). There were 12 patients (24%) who experienced at least one moderately severe adverse event. The most common moderately severe events were rash (7 patients, 14%) and pruritus (3 patients, 6%). Only one patient (2%) experienced a severe adverse event (rash).
In the patients with CTCL receiving Targretin® gel, adverse events reported regardless of relationship to study drug at an incidence of ≥5% are presented in Table 1.
A similar safety profile for Targretin® gel was demonstrated in the Phase I-II program. For the 67 patients enrolled in the Phase I-II program, the mean duration of treatment was 436 days (range 12-1203 days). As in the multicenter study, the most common adverse events regardless of relationship to study drug in the Phase I-II program were rash (78%), pain (40%), and pruritus (40%).
| All Adverse Events | Application Site Adverse Events | |
|---|---|---|
| COSTART 5 Body System/Preferred Term |
N = 50 n (%) |
N = 50 n (%) |
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* Regardless of association with treatment Includes Investigator terms such as: 1 Contact dermatitis, irritant contact dermatitis, irritant dermatitis 2 Pruritus, itching, itching of lesion 3 Erythema, scaling, irritation, redness, rash, dermatitis 4 Skin inflammation, excoriation, sticky or tacky sensation of skin; NOS = Not Otherwise Specified | ||
Skin and Appendages |
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Contact Dermatitis1 |
7 (14) |
4 (8) |
Exfoliative Dermatitis |
3 (6) |
0 |
Pruritus2 |
18 (36) |
9 (18) |
Rash3 |
36 (72) |
28 (56) |
Maculopapular Rash |
3 (6) |
0 |
Skin Disorder (NOS)4 |
13 (26) |
9 (18) |
Sweating |
3 (6) |
0 |
Body as a Whole |
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Asthenia |
3 (6) |
0 |
Headache |
7 (14) |
0 |
Infection |
9 (18) |
0 |
Pain |
15 (30) |
9 (18) |
Cardiovascular |
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Edema |
5 (10) |
0 |
Peripheral Edema |
3 (6) |
0 |
Hemic and Lymphatic |
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Leukopenia |
3 (6) |
0 |
Lymphadenopathy |
3 (6) |
0 |
WBC Abnormal |
3 (6) |
0 |
Metabolic and Nutritional |
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Hyperlipemia |
5 (10) |
0 |
Nervous |
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Paresthesia |
3 (6) |
3 (6) |
Respiratory |
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Cough Increased |
3 (6) |
0 |
Pharyngitis |
3 (6) |
0 |
More resources:
Targretin - Includes detailed dosage instructions.
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