Skip to main content

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