Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (www.bnf.org).

• Avoid using trimethoprim in men with blood dyscrasias.

• Because of its potential anti-folate effect, there have been reports that trimethoprim causes blood disorder. Consequently, trimethoprim is contraindicated in people with dyscrasias [Actavis, 2007; BNF 57, 2009].

Trimethoprim should be prescribed with caution in the following conditions:

• Severe renal impairment
• As the drug is predominantly excreted by the kidney, dose adjustment may be required.

[Actavis, 2007; BNF 57, 2009]

• Trimethoprim is generally well tolerated.
• Nausea, vomiting, pruritus, and skin rashes have occasionally been reported. These are generally mild and reversible when trimethoprim is withdrawn.
• Severe adverse drug reactions with trimethoprim are rare.

[Aronson, 2006; Actavis, 2007]

The following drug interactions have been reported with trimethoprim, when it is combined:

• With phenytoin
• There is a small risk of phenytoin toxicity (particularly if the serum phenytoin levels are at the top end of the range) as trimethoprim can decrease the clearance of phenytoin [Baxter, 2008]. Signs of phenytoin toxicity include blurred vision, nystagmus, ataxia, or drowsiness.
• With ciclosporin
• Increased nephrotoxicity has been reported. However, this interaction has not been firmly established.

[Baxter, 2008; BNF 57, 2009]

• Avoid prescribing nitrofurantoin for people with:
• Creatinine clearance less than 60 mL per minute, or elevated serum creatinine [Goldshield Pharmaceuticals, 2007].
• Confirmed deficiency of glucose-6-phosphate dehydrogenase — as it may cause haemolysis.
• This is found in 10% of black people and a variable percentage of ethnic groups of Mediterranean, near Eastern, and Asian origin. It is rare in white people.
• Discontinue nitrofurantoin if there is any sign of haemolysis (which ceases when the drug is withdrawn).
• Peripheral neuropathy
• Nitrofurantoin should be used with caution in people with anaemia, diabetes mellitus, electrolyte imbalance, debilitating conditions, or vitamin B (particularly folate) deficiency since these conditions may enhance the occurrence of peripheral neuropathy.
• The manufacturer of nitrofurantoin advises stopping the drug at the first signs of neural involvement (paraesthesiae).
• If the person develops unexplained pulmonary, hepatotoxic, haematological, or neurologic syndromes, discontinue treatment with nitrofurantoin.

[Goldshield Pharmaceuticals, 2002a; Goldshield Pharmaceuticals, 2002b; Goldshield Pharmaceuticals, 2007]

Adverse effects associated with nitrofurantoin

• Pulmonary: nitrofurantoin-associated pulmonary reactions are reported in less than 1% of people treated with nitrofurantoin. Common manifestations are dry cough, chest pain, dyspnoea, and hypoxemia. Skin rash, arthralgia, and elevated liver enzymes are occasionally present. Chest imaging shows patchy infiltrates and fibrosis. Treatment includes stopping the medication and prescribing a course of corticosteroids [Vahid and Wildemore, 2006].
• Gastrointestinal: nausea and anorexia have been reported. Vomiting, abdominal pain, and diarrhoea are less common gastrointestinal reactions.
• Peripheral neuropathy (including optical neuritis), with symptoms of sensory as well as motor involvement, has been reported infrequently.
• Stop treatment at the first sign of neurological involvement.

• The use of alkalinizing agents (such as potassium citrate) should be avoided in people taking nitrofurantoin. The antibacterial activity of nitrofurantoin is reduced when the pH of the urine is increased [SIGN, 2006].
• Although the manufacturer of nitrofurantoin advises against concomitant administration of magnesium trisilicate with nitrofurantoin (due to reduced absorption), the clinical significance is uncertain as only one very small study in six people has reported this effect [Baxter, 2008].