Lower UTI Drugs for Women

Question 1

Do not prescribe trimethoprim in:

Answer 1

People with hypersensitivity to trimethoprim or any of the excipients.

People with severe hepatic insufficiency, or severe renal insufficiency.

People with megaloblastic anaemia or other blood dyscrasias.

Premature infants or children aged under 4 months.

Women who are pregnant.

People with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galacactose malabsorption.

Question 2

Prescribe trimethoprim with caution in people

Answer 2

With impaired renal function.
With hyperkalaemia, or taking medication that is known to cause hyperkalaemia.
With acute porphyria.
Predisposed to folate deficiency — because of the potential anti-folate effect of trimethoprim, there is a risk of further exacerbating folate deficiency in people who are folate deficient, or who are predisposed to folate deficiency (for example elderly people), or who are taking folate antagonists.

Question 3

Adverse effects trimethoprim

Answer 3

Blood disorders — leucopenia, megaloblastic anaemia, thrombocytopenia, agranulocyctosis, methaemoglobinaemia.
Gastrointestinal — diarrhoea, nausea, vomiting, glossitis.
Nervous system — aseptic meningitis (frequency unknown), headache.
Skin — Pruritus, and skin rashes (common).
Rarely: Photosensitivity, exfoliative dermatitis, fixed drug eruption, erythema multiforme, erythema nodusum, Stevens-Johnson Syndrome, toxic epidermal necrolysis, bullous dermatitis, purpura, angioedema.
Other adverse effects include:
Anaphylaxis.
Liver enzyme disturbances, cholestatic jaundice.
Myalgia.
Raised serum creatinine and electrolyte disturbance such as hyperkalaemia (particularly in the elderly and in HIV patients),

Question 4

Drug interactions of trimethoprim

Answer 4

Aciclovir — increased risk of nephrotoxicity.
Amitryptaline — increased risk of hyponatraemia.
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II receptor antagonists AIIRAs — there may be an increased risk of hyperkalaemia with the concurrent use of these drugs and trimethoprim. Monitor potassium concentrations.
Azathioprine and mercaptopurine — increased risk of haematological toxicity in people who have had a renal transplant. However, the combination is commonly used in practice. Monitor the full blood count routinely.
Carbamazepine — increased risk of hyponatraemia.
Ciclosporin — serum creatinine levels may be increased. Possible increased risk of nephrotoxicity. Increased risk of hyperkalaemia. Monitor renal function closely.
Citalopram, escitalopram, fluoxetine and sertraline — increased risk of hyponatraemia.
Coumarins (warfarin) — the anticoagulant effect of coumarins may be potentiated. Monitor international normalised ratio (INR) and adjust dose accordingly.
Dapsone — dapsone increases the exposure to trimethoprim and trimethoprim increases the exposure to dapsone.
Digoxin — digoxin levels may be increased in the elderly if taken with trimethoprim. Monitor for digoxin adverse effects, and adjust dose accordingly.
Diuretics — hyperkalaemia may be exacerbated by concomitant administration of diuretics, particularly potassium sparing diuretics and/or thiazide diuretics and eplerenone.
Mefenamic acid — increased risk of hyponatraemia, hyperkalaemia and nephrotoxicity.
Methotrexate (a folate antagonist) — there is an increased risk of haematologic adverse effects. Several cases of bone marrow suppression have been reported (some fatal). Full blood count should be monitored routinely.
NSAIDS — increased risk of hyponatraemia, hyperkalaemia and nephrotoxicity.
Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of trimethoprim. However, women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea.
For further information, see the sections on vomiting or diarrhoea in the CKS topics on Contraception - combined hormonal methods and Contraception - progestogen-only methods.
Phenytoin – phenytoin levels may be increased if taken with trimethoprim. Monitor phenytoin levels and adjust dose accordingly.

Question 5

Pregnancy and breastfeeding with trimethoprim

Answer 5

Pregnancy
There is a teratogenic risk in the first trimester of pregnancy (folate antagonist). The manufacturer advises that it should not be used in women who are pregnant.
Trimethoprim should not be administered to pregnant women, premature infants or infants during the first few weeks of life — seek specialist advice.
Breastfeeding
Trimethoprim is excreted in breastmilk, short-term use is not known to be harmful.

Question 6

Do not prescribe nitrofurantoin in infants aged less than 3 months, or people with:

Answer 6

Hypersensitivity to the active substance, other nitrofurans or to any of the excipients.
Acute porphyria.
Renal impairment — estimated glomerular filtration rate (eGFR) less than 45 mL/minute/1.73 m2.
A short course (3–7 days) may be considered with caution in certain people if the eGFR is 30–44 mL/minute/1.73 m2 and a urinary tract infection has suspected or proven multi-drug resistance, when the benefits of nitrofurantoin are considered to outweigh the risks of adverse effects.
Glucose-6-phosphate dehydrogenase deficiency.
At term in pregnancy because of the risk of neonatal haemolysis.

Question 7

Prescribe nitrofurantoin with caution in people with

Answer 7

Peripheral neuropathy or susceptibility to peripheral neuropathy — treatment should be stopped at the first signs of neural involvement (paraesthesiae).
Anaemia, diabetes mellitus, electrolyte imbalance, debilitating conditions, pulmonary disease, hepatic impairment, renal impairment and vitamin B (particularly folate) deficiency since these conditions may enhance the occurrence of peripheral neuropathy

Question 8

Adverse effects of NF

Answer 8

Blood disorders — agranulocytosis, leucopenia, granulocytopenia, haemolytic anaemia, thrombocytopenia, megaloblastic anaemia, glucose-6-phosphate dehydrogenase deficiency anaemia, and eosinophilia (rare).
Gastrointestinal — nausea and anorexia.
Vomiting, abdominal pain, and diarrhoea are less common.
Hepatobiliary disorders — chronic hepatitis, cholestatic jaundice (rarely).
Respiratory — acute pulmonary reactions may occur within the first week of treatment, and are manifested by: fever, chills, cough, chest pain, dyspnoea, and eosinophilia. Reversible on stopping treatment.
Rarely: chronic pulmonary reactions occur in people who have received continuous therapy for six months or longer. It is more common in the elderly.
Nervous system — peripheral neuropathy (infrequent).
Less frequently: depression, euphoria, confusion, psychotic reactions, nystagmus, vertigo, dizziness, asthenia, headache and drowsiness.
Cardiac — circulatory collapse.
Skin — angioneurotic oedema, maculopapular, erythematous or eczematous eruptions, urticaria, rash, and pruritus.
Rarely: lupus-like syndrome, exfoliative dermatitis and erythema multiforme (including Stevens-Johnson Syndrome).
Musculoskeletal — arthralgia.

Question 9

Drug interactions of NF

Answer 9

Alkalinizing agents (such as potassium citrate) — the antibacterial activity of nitrofurantoin is reduced when the pH of the urine is increased. It may be prudent to avoid in people taking nitrofurantoin, however there is no evidence that this possible interaction presents a problem in practice.
Magnesium trisilicate — absorption of nitrofurantoin may be reduced.
Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of nitrofurantoin. However, women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea.
For further information, see the sections on vomiting or diarrhoea in the CKS topics on Contraception - combined hormonal methods and Contraception - progestogen-only methods.
Amiodarone, isoniazid, lamivudine, metronidazole, phenytoin, stavudine — can increase risk of peripheral neuropathy.
Dapsone, topical prilocaine — predicted to increase the risk of methaemoglobinaemia.
Typhoid Vaccine (oral) — antibacterials inactivate oral typhoid vaccine.

Question 10

Pregnancy and breastfeeding for NF

Answer 10

Pregnancy
Nitrofurantoin is not known to be harmful in pregnancy, however clinical guidelines [NICE, 2018d] and the BNF recommend that nitrofurantoin should be avoided at term, because of the risk of neonatal haemolysis. This includes women with threatened pre-term labour [All Wales Medicines Strategy Group, 2018].
Breastfeeding
Nitrofurantoin is excreted in small amounts in breastmilk. Avoid breastfeeding during treatment with nitrofurantoin if the newborn is glucose-6-phosphate dehydrogenase deficient.

Question 11

Do not prescribe pivmecillinam to children under the age of 3 months or in people with:

Answer 11

Hypersensitivity to penicillins or cephalosporins. Allergic reactions to penicillins occur in 1–10% of exposed individuals. Anaphylactic reactions occur in fewer than 0.05% of treated patients.
Gastrointestinal adverse effects alone (for example nausea, vomiting, or diarrhoea) do not constitute an allergy to penicillin. See the CKS topic on Angio-oedema and anaphylaxis for more information.
Acute porphyrias.
Carnitine deficiency.
Gastrointestinal obstruction.
Oesophageal strictures

Question 12

Prescribe pivmecillinam with caution to people

Answer 12

With hypersensitivity to cephalosporins.
Taking valproic acid, or valproate concurrently, or any other medication liberating pivalic due to increased risk of carnitine depletion.

Question 13

Adverse effects of pivmecillinam

Answer 13

Common adverse effects include:
Diarrhoea.
Nausea.
Vulvovaginal fungal infection.
Uncommon adverse effect include:
Dizziness.
Fatigue.
Gastrointestinal discomfort/disorders including Clostridium difficile colitis.
Headache.
Oral ulceration.
Skin reactions.
Thrombocytopenia.
Vertigo.

Question 14

Drug interactions of pivmecillinam

Answer 14

Methotrexate — pivmecillinam may reduce methotrexate clearance, causing an increased risk of toxicity.
Monitor methotrexate levels more closely. Consider twice-weekly platelet and white cell counts for two weeks initially, with the measurement of methotrexate levels if toxicity is suspected.
Oral anticoagulants (warfarin, phenindione) — INR may be increased. Monitor the international normalized ratio (INR) closely during concomitant use. Dosage adjustments may be necessary.
Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of amoxicillin. However, women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea.
For further information, see the sections on vomiting or diarrhoea in the CKS topics on Contraception - combined hormonal methods and Contraception - progestogen-only methods.
Valproate — concurrent treatment with valproic acid, valproate or other medication liberating pivalic acid increase the risk of carnitine depletion. Avoid concurrent use. If this is not possible, monitor closely.

Question 15

Pregnancy and breastfeeding for pivmecillinam

Answer 15

Pregnancy
Pivmecillinam is not known to be harmful in pregnancy — manufacturer advises can be used during pregnancy if clinically needed.
Breastfeeding
Pivmecillinam is excreted in breastmilk, but in small amounts not thought to adversely affect infants.

Question 16

Do not prescribe fosfomycin in people with

Answer 16

Hypersensitivity to the active substance or to any of the excipients
Severe renal insufficiency — eGFR less than 10 mL/minute/1.73 m2 or those undergoing haemodialasis.

Question 17

Prescribe fosfomycin with caution to people

Answer 17

Who are older.

With renal impairment.

Question 18

Adverse effects of fosfomycin

Answer 18

Common adverse effects include:
Abdominal pain; diarrhoea; headache; nausea; vomiting; dizziness; vulvovaginal infection
Uncommon adverse effect include:
Skin reactions
Frequency unknown
Antibiotic associated colitis

Question 19

Drug interactions of fosfomycin

Answer 19

Metoclopramide — concomitant administration with metoclopramide has been shown to lower serum and urinary concentrations — manufacturer recommends avoid.
Oral contraceptives
Women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea. For further information, see the sections on vomiting or diarrhoea in the CKS topics on Contraception - combined hormonal methods and Contraception - progestogen-only methods.

Question 20

Do not prescribe amoxicillin in people with

Answer 20

A true penicillin hypersensitivity — allergic reactions to penicillins occur in 1–10% of exposed individuals. Anaphylactic reactions occur in fewer than 0.05% of treated patients.
Gastrointestinal adverse effects alone (for example nausea, vomiting, or diarrhoea) do not constitute an allergy to penicillin. See the CKS topic on Angio-oedema and anaphylaxis for more information

Question 21

Prescribe amoxicillin with caution to people with

Answer 21

Hypersensitivity to cephalosporins.
Renal impairment — reduce the dose of amoxicillin in severe renal impairment.
Glandular fever (infective mononucleosis) — these people are especially susceptible to amoxicillin-induced skin rashes.
Acute lymphocytic leukaemia and chronic lymphocytic leukaemia — increased risk of erythematous rashes

Question 22

Adverse effects of amoxicillin

Answer 22

Gastrointestinal — nausea, diarrhoea and vomiting.
Very rarely: antibiotic associated colitis.
Skin — skin rash (common), urticaria and pruritus (uncommon).
Very rarely: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis and acute generalised exanthematous pustulosis.
Other very rare adverse effects include:
Hepatitis, cholestatic jaundice.
Hyperkinesia, dizziness, convulsions.
Interstitial nephritis.
Leucopenia, thrombocytopenia, haemolytic anaemia.
Severe allergic reactions.

Question 23

Drug interaction of amoxicillin

Answer 23

Allopurinol — increased risk of rash when allopurinol is given with amoxicillin.
Methotrexate — amoxicillin may reduce methotrexate clearance, causing an increased risk of toxicity.
Monitor methotrexate levels more closely. One recommendation is to carry out twice weekly platelet and white cell counts for 2 weeks initially, with the measurement of methotrexate levels if toxicity is suspected.
Oral anticoagulants (warfarin, phenindione) — INR may be increased. Monitor the international normalized ratio (INR) closely during concomitant use. Dosage adjustments may be necessary.
Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of amoxicillin.
However, women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea. For further information, see the sections on vomiting or diarrhoea in the CKS topics on Contraception - combined hormonal methods and Contraception - progestogen-only methods.
Probenecid — may cause increased and prolonged blood levels of amoxicillin. Manufacturer recommends avoiding concurrent use.
Tetracyclines — the antibacterial effects of amoxicillin may be antagonised.

Question 24

Do not prescribe cefalexin in people with

Answer 24

A known allergy to the cephalosporin group of antibiotics or a history of immediate hypersensitivity to penicillin and other beta-lactams.

Question 25

Prescribe cefalexin with caution in people with

Answer 25

Sensitivity to penicillin and other beta lactams. About 0.5–6.5% of penicillin-sensitive people will also be allergic to cephalosporins

Question 26

Adverse effects of cefalexin

Answer 26

Gastrointestinal — diarrhoea (most common), nausea, vomiting, abdominal discomfort.
Nervous system — headache, dizziness.
Psychiatric — hallucinations, confusion, agitation.
Skin — rash urticaria, angioedema.
Rarely: erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis (exanthematic necrolysis)
Other adverse effects include:
Anaphylaxis.
Arthralgia and myalgia.
Eosinophilia, neutropenia, thrombocytopenia, haemolytic anaemia.
Genital and anal pruritus.
Hepatitis, cholestatic jaundice.
Interstitial nephritis (rarely).
Pseudomembranous colitis (for more information, see the CKS topic on Diarrhoea - antibiotic associated.

Question 27

Drug interactions of cefalexin

Answer 27

Aciclovir — can increase the risk of nephrotoxicity.
Aminoglycosides (for example, gentamicin) — possible increased risk of nephrotoxicity. Routine renal monitoring for the aminoglycoside is usually adequate.
Ciclosporin — can increase the risk of nephrotoxicity.
Methotrexate — can increase the risk of nephrotoxicity.
NSAIDs — can increase the risk of nephrotoxicity.
Oral anticoagulants (warfarin and phenindione) — cefalexin may enhance the anticoagulant effect. Monitor the international normalized ratio (INR) closely during concomitant use.
Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of cefalexin.
However, women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea. For further information, see the sections on vomiting or diarrhoea in the CKS topics on Contraception - combined hormonal methods and Contraception - progestogen-only methods.
Probenecid — renal excretion of cefalexin is inhibited