The toxicity database consists of the observations made during Phase 1-4 studies. The most common adverse reactions in all patients and in patients with lymphoma are shown in Table 2 below.
Arachnoiditis is an expected and well-documented side effect of both neoplastic meningitis and of intrathecal chemotherapy. The incidence of severe and life-threatening arachnoiditis in patients receiving DepoCyt was 19% (48/257) in all patients and 30% (10/33) in patients with lymphomatous meningitis. The incidence of symptoms possibly reflecting meningeal irritation are shown in Table 3.
In the early dose-finding study, chemical arachnoiditis was observed in 100% of cycles without dexamethasone prophylaxis. When concurrent dexamethasone was administered, chemical arachnoiditis was observed in 33% of cycles. Patients receiving DepoCyt should be treated concurrently with dexamethasone to mitigate the symptoms of chemical arachnoiditis (see DOSAGE AND ADMINISTRATION).
Table 2: Incidence of adverse reactions occurring in > 10% of patients in all Phase 1-4 adult study patients and in patients with lymphomatous meningitis receiving DepoCyt 50 mg or an active comparator
| System Organ Class / Preferred Term | All DepoCyt (N=257) | Lymphoma | |
| Depo Cyt (N=33) | Ara-C (N=28) | ||
| Nervous System Disorders | |||
| Headache NOS | 144(56%) | 17(52%) | 9(32%) |
| Arachnoiditis | 108(42%) | 14(42%) | 10(36%) |
| Confusion | 86(33%) | 12(36%) | 3(11%) |
| Gait abnormal NOS | 60(23%) | 7(21%) | 8(29%) |
| Convulsions NOS | 52(20%) | 7(21%) | 1(4%) |
| Dizziness NOS | 47(18%) | 7(21%) | 6(21%) |
| Memory impairment | 36(14%) | 4(12%) | 1(4%) |
| Hypoaesthesia | 26(10%) | 4(12%) | 3(11%) |
| Tremor | 22(9%) | 5(15%) | 5(18%) |
| Peripheral neuropathy NOS | 9(4%) | 4(12%) | 1(4%) |
| Syncope | 8(3%) | 00%) | 3(11%) |
| Neuropathy NOS | 7(3%) | 3(9%) | 3(11%) |
| Peripheral sensory neuropathy | 7(3%) | 2(6%) | 3(11%) |
| Reflexes abnormal | 7(3%) | 0(0%) | 3(11%) |
| General Disorders and Administration Site Conditions | |||
| Weakness | 103(40%) | 13(39%) | 15(54%) |
| Pyrexia | 81(32%) | 15(45%) | 12(43%) |
| Fatigue | 64(25%) | 9(27%) | 13(46%) |
| Lethargy | 41(16%) | 4(12%) | 4(14%) |
| Death NOS | 35(14%) | 9(27%) | 5(18%) |
| Pain NOS | 35(14%) | 3(9%) | 5(18%) |
| Oedema peripheral | 27(11%) | 6(18%) | 7(25%) |
| Fall | 12(5%) | 0(0%) | 3(11%) |
| Mucosal inflammation NOS | 8(3%) | 4(12%) | 2(7%) |
| Oedema NOS | 6(2%) | 1(3%) | 6(21%) |
| Gastrointestinal Disorders | |||
| Nausea | 117(46%) | 11(33%) | 15(54%) |
| Vomiting NOS | 112(44%) | 11(33%) | 9(32%) |
| Constipation | 64(25%) | 8(24%) | 7(25%) |
| Diarrhoea NOS | 31(12%) | 9(27%) | 9(32%) |
| Abdominal pain NOS | 22(9%) | 5(15%) | 4(14%) |
| Dysphagia | 20(8%) | 3(9%) | 3(11%) |
| Haemorrhoids | 8(3%) | 0(0%) | 3(11%) |
| Musculoskeletal and Connective Tissue Disorders | |||
| Back pain | 61(24%) | 7(21%) | 5(18%) |
| Pain in limb | 39(15%) | 4(12%) | 8(29%) |
| Neck pain | 36(14%) | 5(15%) | 3(11%) |
| Arthralgia | 29(11%) | 3(9%) | 4(14%) |
| Neck stiffness | 28(11%) | 2(6%) | 4(14%) |
| Muscle weakness NOS | 25(10%) | 5(15%) | 2(7%) |
| Psychiatric Disorders | |||
| Insomnia | 35(14%) | 6(18%) | 7(25%) |
| Agitation | 26(10%) | 5(15%) | 2(7%) |
| Depression | 21(8%) | 6(18%) | 4(14%) |
| Anxiety | 17(7%) | 1(3%) | 3(11%) |
| Infections and Infestations | |||
| Urinary tract infection NOS | 35(14%) | 6(18%) | 5(18%) |
| Pneumonia NOS | 16(6%) | 2(6%) | 3(11%) |
| Metabolism and Nutrition Disorders | |||
| Dehydration | 33(13%) | 6(18%) | 3(11%) |
| Appetite decreased NOS | 29(11%) | 4(12%) | 3(11%) |
| Hyponatraemia | 18(7%) | 4(12%) | 1(4%) |
| Hypokalaemia | 17(7%) | 5(15%) | 2(7%) |
| Hyperglycaemia | 15(6%) | 4(12%) | 2(7%) |
| Anorexia | 14(5%) | 1(3%) | 5(18%) |
| Investigations | |||
| Platelet count decreased | 8(3%) | 00%) | 3(11%) |
| Renal and Urinary Disorders | |||
| Incontinence NOS | 19(7%) | 3(9%) | 5(18%) |
| Urinary retention | 14(5%) | 00%) | 3(11%) |
| Respiratory, Thoracic and Mediastinal Disorders | |||
| Dyspnoea NOS | 25(10%) | 4(12%) | 6(21%) |
| Cough | 17(7%) | 3(9%) | 6(21%) |
| Eye Disorders | |||
| Vision blurred | 29(11%) | 4(12%) | 4(14%) |
| Blood and Lymphatic Disorders | |||
| Anaemia NOS | 31(12%) | 6(18%) | 5(18%) |
| Thrombocytopenia | 27(11%) | 8(24%) | 9(32%) |
| Neutropenia | 26(10%) | 12(36%) | 7(25%) |
| Skin and Subcutaneous Tissue Disorders | |||
| Contusion | 6(2%) | 1(3%) | 3(11%) |
| Pruritus NOS | 6(2%) | 00%) | 4(14%) |
| Sweating increased | 6(2%) | 1(3%) | 3(11%) |
| Vascular Disorders | |||
| Hypotension NOS | 21(8%) | 6(18%) | 2(7%) |
| Hypertension NOS | 15(6%) | 5(15%) | 1(4%) |
| Ear and Labyrinth Disorders | |||
| Hypoacusis | 15(6%) | 6(18%) | 3(11%) |
| Cardiac Disorders | |||
| Tachycardia NOS | 22(9%) | 00%) | 5(18%) |
| Neoplasms Benign, Malignant and Unspecified (Incl Cysts and Polyps) | |||
| Diffuse Large B-Cell Lymphoma NOS | 10%) | 1(3%) | 3(11%) |
Table 3: Incidence of adverse reactions possibly reflecting meningeal irritation occurring in > 10% of all studied adult patients receiving DepoCyt 50 mg or an active comparator*
| System Organ Class / Preferred Term | DepoCyt (N=257) |
MTX (N=78) |
Ara-C (N=28) |
||
| Nervous System Disorders | |||||
| Headache NOS | 145 (56%) | 33(42%) | 9(32%) | ||
| Arachnoiditis | 108 (42%) | 15(19%) | 10(36%) | ||
| Convulsions NOS | 56 (22%) | 11(14%) | 1(4%) | ||
| Gastrointestinal Disorders | |||||
| Nausea | 117 (46%) | 24(31%) | 15(54%) | ||
| Vomiting NOS | 112 (44%) | 22(28%) | 9(32%) | ||
| Musculoskeltal and Connective Tissue Disorders | |||||
| Back pain | 61 (24%) | 15(19%) | 5(18%) | ||
| Neck pain | 36 (14%) | 6(8%) | 3(11%) | ||
| Neck stiffness | 28 (11%) | 1(1%) | 4(14%) | ||
| General Disorders and Administration Site Conditions | |||||
| Pyrexia | 81 (32%) | 15(19%) | 12(43%) | ||
| * Hydrocephalus acquired, CSF pleocytosis and meningism occurred in ≤ 10% of all studied adult patients receiving DepoCyt or an active comparator | |||||