Estimated 0.1%-1%: renal failure acute, urinary frequency increased, hematuria, renal pain
Reproductive:
Estimated 0.1%-1%: breast enlargement, menorrhagia, sexual dysfunction, gynecomastia, erectile dysfunction, menstruation irregular, nipple pain, scrotal edema
Respiratory:
Estimated 1%-10%: epistaxis
Estimated 0.1%-1%: pleural effusion
Estimated 0.01%-0.1%: interstitial pneumonitis, pulmonary fibrosis, pleuritic pain, pulmonary hypertension, pulmonary hemorrhage
Special Senses:
Estimated 1%-10%: conjunctivitis, vision blurred, eyelid edema, conjunctival hemorrhage, dry eye
Estimated 0.1%-1%: vertigo, tinnitus, eye irritation, eye pain, orbital edema, scleral hemorrhage, retinal hemorrhage, blepharitis, macular edema, hearing loss
Estimated 0.01%-0.1%: papilledema1, glaucoma, cataract
1Including some fatalities
6.13 Postmarketing Experience
The following additional adverse reactions have been identified during post approval use of Gleevec. 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.
Nervous system disorders: cerebral edema1
Eye disorders: vitreous hemorrhage
Cardiac disorders: pericarditis, cardiac tamponade1
Vascular disorders: thrombosis/embolism, anaphylactic shock
Respiratory, thoracic and mediastinal disorders: acute respiratory failure1, interstitial lung disease
Gastrointestinal disorders: ileus/intestinal obstruction, tumor hemorrhage/tumor necrosis, gastrointestinal perforation1[see Warnings and Precautions (5.6)],diverticulitis
Skin and subcutaneous tissue disorders: lichenoid keratosis, lichen planus, toxic epidermal necrolysis, palmar-plantar erythrodysesthesia syndrome
Musculoskeletal and connective tissue disorders: avascular necrosis/hip osteonecrosis, rhabdomyolysis/myopathy, growth retardation in children
Reproduction disorders: hemorrhagic corpus luteum/hemorrhagic ovarian cyst
1Including some fatalities
7DRUG INTERACTIONS
7.1 Agents Inducing CYP3A Metabolism
Pretreatment of healthy volunteers with multiple doses of rifampin followed by a single dose of Gleevec, increased Gleevec oral-dose clearance by 3.8-fold, which significantly (p<0.05) decreased mean Cmax and AUC.
Similar findings were observed in patients receiving 400-1200 mg/day Gleevec concomitantly with enzyme-inducing anti-epileptic drugs (EIAED) (e.g., carbamazepine, oxcarbamazepine, phenytoin, fosphenytoin, phenobarbital, and primidone). The mean dose normalized AUC for imatinib in the patients receiving EIAED’s decreased by 73% compared to patients not receiving EIAED.
Concomitant administration of Gleevec and St. John’s Wort led to a 30% reduction in the AUC of imatinib.
Consider alternative therapeutic agents with less enzyme induction potential in patients when rifampin or other CYP3A4 inducers are indicated. Gleevec doses up to 1200 mg/day (600 mg BID) have been given to patients receiving concomitant strong CYP3A4 inducers. [see Dosage and Administration (2.9)].
7.2 Agents Inhibiting CYP3A MetabolismThere was a significant increase in exposure to imatinib (mean Cmax and AUC increased by 26% and 40%, respectively) in heal
