Topotecan

Registered South African indications:

• Small cell lung carcinoma
• Metastatic carcinoma of the ovary
• Carcinoma of the cervix

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding
• Severe bone marrow depression prior to starting first course, as evidenced by baseline neutrophils < 1.5 x 10⁹/l and/or a platelet count of < 100 x 10⁹/l

Cautions

• Renal impairment
• Hepatic impairment
• Elderly
• History of interstitial lung disease, pulmonary fibrosis, lung cancer, thoracic exposure to radiation and use of pneumotoxic substances and/or colony stimulating factors
• Patients at increased risk of tumour bleeds 

Forms avail. in SA and covered in this monograph: cap, inj

Used for the treatment of

Palliative treatment of small cell lung carcinoma
- As a second-line chemotherapeutic agent in patients who have relapsed after an initial response to treatment with first-line chemotherapeutic agents (cap, inj)
Metastatic carcinoma of the ovary 
- After first line treatment failure (inj)
Carcinoma of the cervix (additional agent required)
- Stage IV-B, recurrent, or persistent (inj)

Consult specialist for dosages and regimens

Not established for use in children

Pregnancy

• Contraindicated

Breastfeeding

• Contraindicated

Renal Impairment

• Mild: Caution; dose adjustment recommended 
• Moderate to severe: Caution; no information available 

Hepatic Impairment

• Caution; no information available

Elderly

• Caution; no dose adjustment recommended

Central Nervous System Disorders

• Fatigue

Respiratory Disorders

• Interstitial lung disease 

Gastrointestinal Disorders

• Nausea and vomiting 
• Diarrhoea 
• Dehydration
• Abdominal pain
• Constipation
• Mucositis
• Dyspepsia
• Neutropenic colitis

Hepatobiliary Disorders

• Hyperbilirubinaemia

Endocrine and Metabolic Disorders

• Anorexia 

Skin and Subcutaneous Tissue Disorders

• Angioedema
• Urticaria
• Extravasation
• Alopecia
• Pruritis

Immune, Blood and Lymphatic System Disorders

• Pyrexia
• Hypersensitivity reaction 
• Anaphylactic reaction
• Sepsis
• Febrile neutropenia
• Neutropenia thrombocytopenia
• Anaemia
• Leucopenia
• Pancytopenia
• Severe bleeding
• Infection
• Sepsis

• ABCB1 inhibitors
• ABCG2 inhibitors
• ABCC1 [MRP-1] inhibitors
• CYP3A4 inhibitors
• Other chemotherapy agents

• Full blood count with differential
• Renal function
• Hepatic function

The anti-tumour activity of topotecan involves the inhibition of topoisomerase-I, an enzyme intimately involved in DNA replication as it relieves the torsional strain introduced ahead of the moving replication fork. Topotecan inhibits topoisomerase-I by stabilising the covalent complex of enzyme and strand-cleaved DNA which is an intermediate of the catalytic mechanism.

Capsule 0.25mg

• Hycamtin (Novartis) originator

Capsule 1mg

• Hycamtin (Novartis) originator

Injection (per 4ml) 4mg

• Hycamtin (GKS) originator