Rozlytrek Special Precautions

General: Congestive Heart Failure: Congestive heart failure (CHF) has been reported across clinical trials with ROZLYTREK (see Table 13 under Adverse Reactions). These reactions were observed in patients with or without a history of cardiac disease and resolved upon treatment with diuretics and/or dose reduction/interruption of ROZLYTREK.
For patients with symptoms or known risk factors of CHF, left ventricular ejection fraction (LVEF) should be assessed prior to initiation of Rozlytrek treatment. Patients receiving ROZLYTREK should be carefully monitored and those with clinical signs and symptoms of CHF, including shortness of breath or edema, should be evaluated and treated as clinically appropriate.
Based on the severity of CHF, ROZLYTREK treatment should be modified as described in Table 12 in Dosage & Administration.
Cognitive Disorders: Cognitive disorders, including confusion, mental status changes, memory impairment, and hallucinations, were reported in clinical trials with ROZLYTREK, (see Adverse Reactions for description of events). Patients should be monitored for signs of cognitive changes.
Based on the severity of the cognitive disorder, ROZLYTREK treatment should be modified as described in Table 12 in Dosage & Administration.
Patients should be counseled on the potential for cognitive changes with ROZLYTREK treatment. Patients should be instructed not to drive or use machines until symptoms resolve, if they experience symptoms of cognitive disorders. (See Effects on ability to drive and use machine as follows.)
Fractures: Rozlytrek increases the risk of fractures (see Description of selected adverse drug reactions under Adverse Reactions). Patients with signs or symptoms (e.g., pain, changes in mobility, deformity) of fractures should be evaluated promptly. In adult patients, some fractures occurred in the setting of a fall or other trauma to the affected area, while in pediatric patients fractures occurred in patients with minimal or no trauma. There are no data on the effects of Rozlytrek on healing of known fractures and the risk of occurrence of future fractures. In the majority of pediatric patients treatment was continued with Rozlytrek and the fracture healed.
QTc Interval Prolongation: QT interval prolongation has been observed in patients treated with ROZLYTREK in clinical trials (see Adverse Reactions).
Use of ROZLYTREK should be avoided in patients with congenital long QT syndrome and in patients taking medications that are known to prolong QT interval. Assessment of ECG at baseline and periodic monitoring of ECGs and electrolytes are recommended.
Based on the severity of QTc prolongation, ROZLYTREK treatment should be modified as described in Table 12 in Dosage & Administration.
Central Nervous System Effects: A broad spectrum of central nervous system (CNS) adverse reactions occurred in patients receiving ROZLYTREK, including cognitive impairment, mood disorders, dizziness, and sleep disturbances.
Advise patients and caregivers of these risks with ROZLYTREK. Advise patients not to drive or operate hazardous machinery if they are experiencing CNS adverse reactions. Withhold and then resume at same or reduced dose upon improvement, or permanently discontinue ROZLYTREK based on severity.
Hepatotoxicity: Increased AST or ALT has been reported across clinical trials with ROZLYTREK (see Adverse Reactions).
Monitor liver tests, including ALT and AST, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated. Withhold or permanently discontinue ROZLYTREK based on the severity. If withheld, resume ROZLYTREK at the same or reduced dose.
Hyperuricemia: Hyperuricemia has been reported across clinical trials with ROZLYTREK (see Adverse Reactions).
Assess serum uric acid levels prior to initiating ROZLYTREK and periodically during treatment. Monitor patients for signs and symptoms of hyperuricemia. Initiate treatment with urate-lowering medications as clinically indicated and withhold ROZLYTREK for signs and symptoms of hyperuricemia. Resume ROZLYTREK at same or reduced dose upon improvement of signs or symptoms based on severity.
Vision Disorders: Vision disorders has been observed in patients treated with ROZLYTREK in clinical trials (see Adverse Reactions).
For patients with new visual changes or changes that interfere with activities of daily living, withhold ROZLYTREK until improvement or stabilization and conduct an ophthalmological evaluation as clinically appropriate. Upon improvement or stabilization, resume ROZLYTREK at same or reduced dose.
Drug Abuse and Dependence: Not applicable.
Renal Impairment: No dose adjustment is required in patients with mild or moderate renal impairment based on population pharmacokinetic analysis. The safety and efficacy of ROZLYTREK in patients with severe renal impairment have not been studied. See Special Dosage Instructions: Renal Impairment under Dosage & Administration and PHARMACOLOGY: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.
Hepatic Impairment: See Special Dosage Instructions under Dosage & Administration and PHARMACOLOGY: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.
Effects on ability to drive and use machine: ROZLYTREK may influence the ability to drive and use machines. Patients should be instructed not to drive or use machines until the symptoms resolve, if they experience cognitive adverse reactions, syncope, blurred vision, or dizziness, during treatment with ROZLYTREK. (See previous text and Adverse Reactions).
Use in Pregnancy: Embryo-fetal toxicity: Based on the findings in animal studies, ROZLYTREK may cause fetal harm when administered to a pregnant woman. When administrated to pregnant rats, ROZLYTREK caused maternal toxicity and developmental toxicities at exposures 2.3-fold the human exposure by AUC at the recommended dose. (See PHARMACOLOGY: Toxicology: Preclinical safety data: Reproductive toxicity under Actions.)
Female patients receiving ROZLYTREK should be advised of the potential harm to the fetus. Female patients of reproductive potential, must use highly effective contraceptive methods during treatment and for 5 weeks following the last dose of ROZLYTREK. (See Females and Males of Reproductive Potential under Use in Pregnancy & Lactation.)
Use in Children: The safety and efficacy of ROZLYTREK have been studied in pediatric patients. See previous text, Clinical Trials under Adverse Reactions and PHARMACOLOGY: Pharmacodynamics: Clinical/Efficacy Studies under Actions. In addition, use of ROZLYTREK in pediatric patients is supported by extrapolation of evidence from clinical trials in adults to pediatric population, based on population pharmacokinetic data demonstrating similar drug exposure in adults and pediatric patients. See Special Dosage Instructions under Dosage & Administration, and PHARMACOLOGY: Pharmacodynamics: Clinical/Efficacy Studies and Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.
Rozlytrek was associated with a higher incidence of skeletal fractures in the pediatric patients compared to adult patients. See previous text and Clinical Trials under Adverse Reactions.
Use in the Elderly: No differences in safety or efficacy were observed between patients ≥ 65 years of age and younger patients. No dose adjustment is required in patients ≥ 65 years of age. See Special Dosage Instructions under Dosage & Administration and PHARMACOLOGY: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.