Lorviqua Adverse Reactions

Summary of the safety profile: The most frequently reported adverse reactions were hypercholesterolaemia (81.1%), hypertriglyceridaemia (67.2%), oedema (55.7%), peripheral neuropathy (43.7%), weight increased (30.9%), cognitive effects (27.7%), fatigue (27.3%), arthralgia (23.5%), diarrhoea (22.9%) and mood effects (21.0%).
Serious adverse reactions were reported in 7.4% of patients receiving lorlatinib. The most frequent serious adverse drug reactions were cognitive effects and pneumonitis.
Dose reductions due to adverse reactions occurred in 20.0% of patients receiving lorlatinib. The most common adverse reactions that led to dose reductions were oedema and peripheral neuropathy. Permanent treatment discontinuation associated with adverse reactions occurred in 3.2% of patients receiving lorlatinib. The most frequent adverse reactions that led to permanent discontinuations were cognitive effects peripheral neuropathy, pneumonitis and psychotic effects.
Tabulated list of adverse reactions: Table 5 presents adverse reactions occurring in 476 adult patients treated with lorlatinib 100 mg once daily with advanced NSCLC from Study A (N=327) and CROWN study (N=149).
The adverse reactions listed in Table 5 are presented by system organ class and frequency categories, defined using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000). Within each frequency grouping, undesirable effects are presented in order of decreasing medical seriousness. (See Table 5.)

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Description of selected adverse reactions: Hypercholesterolaemia/hypertriglyceridaemia: Adverse reactions of increase in serum cholesterol or triglycerides were reported in 81.1% and 67.2% of patients, respectively. Of those, mild or moderate adverse reactions of hypercholesterolaemia or hypertriglyceridaemia occurred in 62.8% and 47.9% of patients, respectively (see Precautions). The median time to onset for both hypercholesterolaemia and hypertriglyceridaemia was 15 days (hypercholesterolaemia range: 1 to 784 days; hypertriglyceridaemia range: 1 to 796 days). The median duration of hypercholesterolaemia and hypertriglyceridaemia was 451 and 427 days, respectively.
Central nervous system effects: CNS adverse reactions were primarily cognitive effects (27.7%), mood effects (21.0%), and speech effects (8.2%), and psychotic effects (6.5%), and were generally mild, transient, and reversible spontaneously upon dose delay and/or dose reduction (see Dosage & Administration and Precautions). The most frequent cognitive effect of any grade was memory impairment (11.3%), and the most frequent Grade 3 or 4 reactions were confusional state and cognitive disorder (1.7% and 0.8% respectively). The most frequent mood effect of any grade was anxiety (6.5%), and the most frequent Grade 3 and 4 reactions were irritability and depression (0.8% and 0.4%, respectively).The most frequent speech effect of any grade was dysarthria (4.0%), and the Grade 3 or 4 reactions were dysarthria, slow speech and speech disorder (0.2% each). The most frequent psychotic effect of any grade was hallucination (3.7%) and the most frequent Grade 3 or 4 reactions were hallucination, hallucination auditory and hallucination visual (0.3% each). Median time to onset for cognitive, mood, and speech and psychotic effects was 109, 43, 49 and 23 days, respectively. Median duration of cognitive, mood, speech and psychotic effects was 223, 143, 147 and 74 days, respectively.
Hypertension: Adverse reactions of hypertension were reported in 13% of patients from Study A and CROWN (B7461006). Of those, mild or moderate adverse reactions of hypertension occurred in 6.9% of patients (see Precautions). The median time to onset of hypertension was 208 days (range: 1 to 1028 days). The median duration of hypertension was 219 days.
Hyperglycaemia: Adverse reactions of hyperglycaemia were reported in 9.2% of patients from Study A and CROWN (B7461006). Of those, mild or moderate adverse reactions of hyperglycaemia occurred in 6.1% of patients (see Precautions). The median time to onset of hyperglycaemia was 145 days (range: 1 to 1058 days). The median duration of hyperglycaemia was 113 days.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.