Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Lorviqua

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HOS-140218 · Präparat HOS-098468

10 therapeutic indices (e.g. digoxin, dabigatran etexilate) should be used with caution in combination with lorlatinib due to the likelihood of reduced plasma concentrations of these substrates.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): digoxin (HOS-086172) dabigatran etexilate (HOS-086233)

Wechselwirkungen · Lorviqua

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HOS-140219 · Präparat HOS-098468

In vitro inhibition and induction studies of other CYP enzymes

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Wechselwirkungen · Lorviqua

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HOS-140220 · Präparat HOS-098468

In vitro, lorlatinib has a low potential to cause drug-drug interactions by induction of CYP1A2.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Lorviqua

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HOS-140221 · Präparat HOS-098468

In vitro studies with drug transporters other than P-gp

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Lorviqua

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HOS-140222 · Präparat HOS-098468

In vitro studies indicated that lorlatinib may have the potential to inhibit BCRP (gastrointestinal tract), OATP1B1, OATP1B3, OCT1, MATE1 and OAT3 at clinically relevant concentrations. Lorlatinib should be used with caution in combination with substrates of BCRP, OATP1B1, OATP1B3, OCT1, MATE1 and OAT3 as clinically relevant changes in the plasma exposure of these substrates cannot be ruled out.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Lorviqua

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HOS-140223 · Präparat HOS-098468

Summary of the safety profile

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Nebenwirkungen · Lorviqua

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HOS-140224 · Präparat HOS-098468

The most frequently reported adverse reactions were hypercholesterolaemia (79.0%), hypertriglyceridaemia (67.5%), oedema (55.4%), peripheral neuropathy (44.2%), fatigue (30.7%), weight increased (29.8%), arthralgia (27.8%), cognitive effects (27.4%), diarrhoea (22.7%) and mood effects (21.4%).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Lorviqua

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HOS-140225 · Präparat HOS-098468

Serious adverse reactions were reported in 9.1% of patients receiving lorlatinib. The most frequent serious adverse drug reactions were cognitive effects, and pneumonitis.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Lorviqua

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HOS-140226 · Präparat HOS-098468

Dose reductions due to adverse reactions occurred in 20.1% of patients receiving lorlatinib. The most common adverse reactions that led to dose reductions were oedema, cognitive effects and peripheral neuropathy. Permanent treatment discontinuation associated with adverse reactions occurred in 4.0% of patients receiving lorlatinib. The most frequent adverse reactions that led to permanent discontinuations were cognitive effects, peripheral neuropathy, pneumonitis and psychotic effects.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Lorviqua

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HOS-140227 · Präparat HOS-098468

Tabulated list of adverse reactions

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Nebenwirkungen · Lorviqua

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HOS-140228 · Präparat HOS-098468

Table 2 presents adverse reactions occurring in 547 adult patients treated with lorlatinib 100 mg once daily with advanced NSCLC from Study A (N=327), CROWN study (N=149) and Study B (N=71).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Lorviqua

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HOS-140229 · Präparat HOS-098468

The adverse reactions listed in Table 2 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.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Lorviqua

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HOS-140230 · Präparat HOS-098468

Table 2. Adverse reactions System organ class and adverse Frequency category All Grades Grades 3-4 reaction % % Blood and lymphatic system disorders Anaemia Very common 19.6 4.4 Metabolism and nutrition disorders Hypercholesterolaemiaa Very common 79.0 19.2 Hypertriglyceridaemiab Very common 67.5 20.3 Hyperglycaemia Common 9.7 3.7 Psychiatric disorders Mood effectsc Very common 21.4 1.3 Psychotic effectsd Common 6.9 0.9 Mental status changes Common 1.1 0.9 Nervous system disorders Cognitive effectse Very common 27.4 3.5 Peripheral neuropathyf Very common 44.2 2.6 Headache Very common 18.6 0.7 Speech effectsg Common 8.2 0.7 Eye disorders Vision disorderh Very common 16.1 0.2 Vascular disorders Hypertension Very common 14.8 6.0

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Lorviqua

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HOS-140231 · Präparat HOS-098468

12  Respiratory, thoracic and mediastinal disorders Pneumonitisi Common 2.4 0.7 Gastrointestinal disorders Diarrhoea Very common 22.7 1.8 Nausea Very common 17.6 0.9 Constipation Very common 16.8 0.2 Hepatobiliary disorders Alanine aminotransferase increased Very common 14.8 2.0 Aspartate aminotransferase increased Very common 13.9 1.5 Skin and subcutaneous tissue disorders Rashj Very common 14.6 0.2 Renal and urinary disorders Proteinuria Common 3.7 0.4 Musculoskeletal and connective tissue disorders Arthralgia Very common 27.8 0.7 Myalgiak Very common 15.0 0 General disorders and administration site conditions Oedemal Very common 55.4 2.9 Fatiguem Very common 30.7 1.1 Investigations Weight increased Very common 29.8 11 Lipase increased Very common 12.8 6.8 Amylase increased Very common 11.3 2.7 Electrocardiogram PR prolongation Uncommon 0.7 0 Adverse reactions that represent the same medical concept or condition were grouped together and reported as a single adverse reaction in the table above. Terms actually reported in the studies and contributing to the relevant adverse reaction are indicated in parentheses, as listed below. a Hypercholesterolaemia (including blood cholesterol increased, hypercholesterolaemia). b Hypertriglyceridaemia (including blood triglycerides increased, hypertriglyceridaemia). c Mood effects (including affective disorder, affect lability, aggression, agitation, anger, anxiety, bipolar I disorder, depressed mood, depression, depressive symptom, euphoric mood, irritability, mania, mood altered, mood swings, panic attack, personality change, stress). d Psychotic effects (including auditory hallucination, hallucination, visual hallucination). e Cognitive effects (including events from SOC Nervous system disorders: amnesia, cognitive disorder, dementia, disturbance in attention, memory impairment, mental impairment; and also including events from SOC Psychiatric disorders: attention deficit/hyperactivity disorder, confusional state, delirium, disorientation, reading disorder). Within these effects, terms from SOC Nervous system disorders were more frequently reported than terms from SOC Psychiatric disorder. f Peripheral neuropathy (including burning sensation, dysaesthesia, formication, gait disturbance, hypoaesthesia, motor dysfunction, muscular weakness, neuralgia, neuropathy peripheral, neurotoxicity, paraesthesia, peripheral motor neuropathy, peripheral sensory neuropathy, peroneal nerve palsy, sensory disturbance). g Speech effects (dysarthria, slow speech, speech disorder). h Vision disorder (including diplopia, photophobia, photopsia, vision blurred, visual acuity reduced, visual impairment, vitreous floaters). i Pneumonitis (including interstitial lung disease, lung opacity, pneumonitis). j Rash (including dermatitis acneiform, maculopapular rash, pruritic rash, rash). k Myalgia (including musculoskeletal pain, myalgia). l Oedema (including generalised oedema, oedema, oedema peripheral, peripheral swelling, swelling). m Fatigue (including asthenia, fatigue).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Lorviqua

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HOS-140232 · Präparat HOS-098468

Description of selected adverse reactions

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Nebenwirkungen · Lorviqua

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HOS-140233 · Präparat HOS-098468

Hypercholesterolaemia/hypertriglyceridaemia Adverse reactions of increase in serum cholesterol or triglycerides were reported in 79.0% and 67.5% of patients, respectively. Of those, mild or moderate adverse reactions of hypercholesterolaemia or

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Lorviqua

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HOS-140234 · Präparat HOS-098468

13 hypertriglyceridaemia occurred in 59.8% and 47.2% of patients, respectively (see section 4.4). The median time to onset for hypercholesterolaemia and hypertriglyceridaemia was 15 days (range: 1 to 1921 days) and 16 days (range: 1 to 1921 days), respectively. The median duration of hypercholesterolaemia and hypertriglyceridaemia was 526 and 519 days, respectively.

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Nebenwirkungen · Lorviqua

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HOS-140235 · Präparat HOS-098468

Central nervous system effects CNS adverse reactions were primarily cognitive effects (27.4%), mood effects (21.4%), speech effects (8.2%) and psychotic effects (6.9%), and were generally mild, transient, and reversible spontaneously upon dose delay and/or dose reduction (see sections 4.2 and 4.4). The most frequent cognitive effect of any grade was memory impairment (10.8%), and the most frequent Grade 3 or 4 reactions were confusional state and cognitive disorder (1.6% and 0.7%, respectively). The most frequent mood effect of any grade was anxiety (7.3%), and the most frequent Grade 3 and 4 reactions were irritability (0.7%), depression (0.4%), anxiety, agitation and bipolar I disorder (0.2% each). The most frequent speech effect of any grade was dysarthria (3.8%), and the Grade 3 or 4 reactions were dysarthria (0.4%), slow speech and speech disorder (0.2% each). The most frequent psychotic effect of any grade was hallucination (2.7%), and the most frequent Grade 3 or 4 reactions were hallucination auditory, hallucination visual, delusion, acute psychosis and schizophrenic disorder (0.2% each). Median time to onset for cognitive, mood, speech and psychotic effects was 129, 57, 58 and 27 days, respectively. Median duration of cognitive, mood, speech and psychotic effects was 270, 145, 147 and 84 days, respectively.

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Nebenwirkungen · Lorviqua

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HOS-140236 · Präparat HOS-098468

Hypertension Adverse reactions of hypertension were reported in 14.8% of patients from Study A, CROWN (B7461006) and Study B (B7461027). Of those, mild or moderate adverse reactions of hypertension occurred in 8.8% of patients (see section 4.4). The median time to onset of hypertension was 295 days (range: 1 to 1990 days). The median duration of hypertension was 505 days.

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Nebenwirkungen · Lorviqua

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HOS-140237 · Präparat HOS-098468

Hyperglycaemia Adverse reactions of hyperglycaemia were reported in 9.7% of patients from Study A, CROWN (B7461006) and Study B (B7461027). Of those, mild or moderate adverse reactions of hyperglycaemia occurred in 6.0% of patients (see section 4.4). The median time to onset of hyperglycaemia was 148 days (range: 1 to 1637 days). The median duration of hyperglycaemia was 118 days.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.