Pentoxifylline

Registered South African indications:

• Symptomatic relief of intermittent claudication
  - Associated with chronic occlusive arterial disorders of the limbs and trophic ulcers. Pentoxifylline may improve function as well as provide symptomatic relief
• Raynaud’s syndrome

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to other methyl xanthines
• Cerebral haemorrhage
• Extensive retinal haemorrhage
• Severe cardiac arrhythmias
• Acute myocardial infarction
• Porphyria
• Pregnancy
• Breastfeeding

South African recommendations

Caution in the following patient groups:

• Renal impairment
• Hepatic impairment
• Elderly

Anaphylactic/ anaphylactoid reactions

• Discontinue pentoxifylline immediately and inform a physician at the first sign of an anaphylactic or anaphylactoid reaction

Cardiovascular conditions

• Use pentoxifylline with caution in patients with severe cardiac dysrhythmias, myocardial infarction, ischaemic heart disease, or in those who are hypotensive

Antihypertensive medicines

• Pentoxifylline may increase the effect of antihypertensive medicines

Hypotension and unstable circulation

• In hypotensive patients, those with unstable circulation, or those at particular risk from reduced blood pressure (e.g., severe coronary heart disease or relevant cerebral vessel stenosis), treatment with pentoxifylline must be started at low doses and increased gradually

Renal and hepatic impairment

• Use pentoxifylline with caution in patients with cirrhosis
• Careful monitoring and possible dose adjustment of pentoxifylline are required in patients with severely impaired renal function (CrCl<30ml/min) and in those with hepatic impairment

Increased bleeding tendency

• Use pentoxifylline with caution in patients with an increased bleeding tendency, such as those taking anticoagulant medicines or having coagulant disorders, as bleeding events (e.g., skin, mucosa, gastrointestinal) have been reported, and thrombocytopenia may occur

Aseptic meningitis

• Reports of aseptic meningitis with pentoxifylline were predominantly in patients with underlying connective tissue disorders

Hypoglycaemic action of insulin

• High parenteral doses of pentoxifylline may increase the hypoglycaemic action of insulin in patients with diabetes

Concomitant use with ketorolac

• Pentoxifylline should not be given with ketorolac due to an increased risk of bleeding and/or prolongation of the prothrombin time

Concomitant use with ciprofloxacin and theophylline

• Careful monitoring is required when pentoxifylline is used at the same time as ciprofloxacin or theophylline

Excipient (lactose) precautions

• Due to the presence of lactose, pentoxifylline is contraindicated in patients with rare hereditary conditions such as lactose or galactose intolerance, galactosaemia, Lapp lactase deficiency, or glucose-galactose malabsorption
• The lactose content may also affect the glycaemic control of patients with diabetes mellitus

Ability to drive and use machines

• Pentoxifylline can cause side effects such as dizziness. During pentoxifylline administration, patients should be cautioned about engaging in activities requiring rapid and precise responses such as driving a vehicle or operating machinery

Forms avail. in SA and covered in this monograph: Slow release tab (SR tab)

South African registered indications and dosages

Symptomatic relief of intermittent claudication
- Associated with chronic occlusive arterial disorders of the limbs and trophic ulcers
Raynaud's syndrome

• Oral (SR tab): 400mg, 2-3 times daily

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Should be taken after meals, swallowed whole with sufficient amounts of liquid (approximately half a glass)

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Missed dose
Doctors should advise patients who forget to take pentoxifylline to take a dose as soon as possible and then continue with the normal dose. Patients should not take a double dose to compensate for the missed dose

Not established for use in children

Pregnancy

South African recommendations

• Contraindicated
• Safety has not been established

Breastfeeding

South African recommendations

• Contraindicated
• Pentoxifylline passes into breast milk. Safety has not been established

Fertility

South African recommendations

• No information available

South African recommendations

• CrCl≥30ml/min: Caution; no dose adjustment recommended
• CrCl<30ml/min: Caution; dose adjustment recommended
  In patients with impairment of renal function (CrCl<30ml/min) a dose reduction of approximately 30% to 50% may be necessary
  Careful monitoring is recommended

South African recommendations

• Mild to moderate: Caution; no dose adjustment recommended
• Severe: Caution; dose adjustment recommended
  A dose reduction is necessary in patients with severely impaired liver function
  Use pentoxifylline with caution in patients with cirrhosis
  Careful monitoring is required

South African recommendations

• Caution; no dose adjustment recommended
  Elimination of pentoxifylline is decreased in elderly patients, with resulting increased potential for toxicity
  In addition, elderly patients are more likely to have age-related renal function impairment, which may require caution in patients receiving pentoxifylline

Central Nervous System Disorders

• Dizziness
• Headache
• Aseptic meningitis
• Agitation
• Sleep disorder

Cardiovascular Disorders

• Arrhythmia
• Tachycardia
• Angina pectoris
• Haemorrhage
• Hypotension

Respiratory Disorders

• Bronchospasm

Gastrointestinal Disorders

• Epigastric discomfort
• Abdominal distension
• Nausea and vomiting
• Diarrhoea
• Constipation
• Hypersalivation

Hepatobiliary Disorders

• Cholestasis
• Increased transaminases

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Erythema
• Urticaria
• Hot flush
• Rash

Immune, Blood and Lymphatic System Disorders

• Thrombocytopenia
• Leukopenia
• Neutropenia
• Anaphylactic reactions
• Angioedema

• Antidiabetic agents
• Vitamin K antagonists
• Antihypertensives
• Ketorolac 
• Theophylline 
• Ciprofloxacin
• Platelet aggregation inhibitors 
• Cimetidine 
• Non-steroidal anti-inflammatories

• Renal function

Specific cases may require

• Blood glucose
• International normalised ratio
• Full blood count

Pentoxifylline improves erythrocyte flexibility, microcirculatory flow, tissue oxygen concentrations and reduces viscosity.

Tablet SR 400mg

• Aspen Pentoxifylline 400 SR (Pharmacare)
• Dyna Pentoxifylline SR (Pharma Dynamics)