Drugs List

Therapeutic Indications

Uses

Hypertension
Oedema

Contraindications

Children under 18 years
Breastfeeding
Hypercalcaemia
Hypovolaemia
Long QT syndrome
Pre-coma associated with hepatic cirrhosis
Pregnancy
Severe electrolyte imbalance
Severe hepatic impairment
Severe renal impairment
Symptomatic hyperuricaemia
Torsade de pointes
Uncontrolled Addison's disease

Precautions and Warnings

Ascites
Diarrhoea
Elderly
Family history of long QT syndrome
Oedema
Vomiting
Benign prostatic hyperplasia
Cerebral arteriosclerosis
Coronary arteriosclerosis
Diabetes mellitus
Electrolyte imbalance
Hepatic cirrhosis
History of torsade de pointes
Hyperaldosteronism
Hyperuricaemia
Ischaemic heart disease
Malnutrition
Mild hepatic impairment
Nephrotic syndrome
Systemic lupus erythematosus

Advise patient to protect skin if restarting following photosensitivity
Correct electrolyte disorders before treatment
May decrease glucose tolerance in patients with diabetes mellitus
Advise ability to drive/operate machinery may be affected by side effects
Consider monitoring ECG in patients at risk of QT prolongation
Monitor blood glucose closely in patients with diabetes mellitus
Monitor elderly receiving therapeutic doses
Monitor fluid and electrolyte status
Monitor serum urate levels in patients with gout
Discontinue if acute cholecystitis occurs
Discontinue if central nervous disturbances occur
Discontinue if distinct gastrointestinal symptoms occur
Discontinue if existing myopia is aggravated
Discontinue if orthostatic regulatory disorders occur
Discontinue if vasculitis occurs
Excess consumption of liquorice may increase the risk of hypokalaemia
Potassium supplements may be required
Prolonged use may cause fluid/electrolyte imbalance and hypokalaemia
Discontinue before parathyroid function tests
Discontinue at once if hepatic encephalopathy occurs
Discontinue if blood dyscrasia develops
Discontinue if hypersensitivity reactions occur
Discontinue if pancreatitis occurs
Discontinue if photosensitivity occurs
Discontinue if signs of fluid or electrolyte imbalance occur
Advise patient that photosensitivity possible

In cases of diuretic abuse, pseudo Bartter's may occur.

In patients with prostatic hypertrophy, there is an increased risk of developing urinary retention.

A decrease in sodium plasma level is a serious complication of diuretic therapy and may initially be asymptomatic. Therefore, regular control is advisable, especially in elderly patients and patients with liver cirrhosis.

During therapy with thiazide diuretics, calcium plasma level may increase and its excretion via urine is temporarily decreased. Hypercalcaemia may occur due to a previous undiagnosed hyperparathyroidism.

Thiazide diuretics are only fully effective in patients with normal or only mildly impaired renal function (creatinine serum level less than 25 mg/litre). In elderly patients, the serum creatinine value has to be adjusted according to age, weight and sex of the patient.

Pregnancy and Lactation

Pregnancy

Xipamide is contraindicated in pregnancy.

Diuretics pass the placenta and can reduce the plasma volume, lead to electrolyte disturbances and cause hypoglycaemia, haemolytic anaemia and thrombocytopenia in the unborn or newborn infant. Diuretics are not to be used under any circumstances for the treatment if pregnancy-related oedemas or physiological oedemas. This is because diuretics may cause foetoplacental ischaemia and foetal growth disturbances. Thiazides should also not be used to treat hypertension as they may cause neonatal thrombocytopenia, bone marrow suppression, jaundice, electrolyte disturbances and hypoglycaemia. Stimulation of labour, uterine inertia and meconium staining has also been reported.

Hydrochlorothiazide is the thiazide diuretic of choice during pregnancy as it is the best studied. Use of xipamide, however, does not require a risk-based termination of the pregnancy, nor invasive diagnostic interventions (Schaefer, 2015).

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Xipamide is contraindicated during breastfeeding.

It is not known if xipamide is expressed in breast milk.

If a diuretic is urgently needed whilst breastfeeding, hydrochlorothiazide may be considered in moderate doses. Due to limited experience, xipamide should not be used, but single doses will not require limitation of breastfeeding (Schaefer, 2015).

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal discomfort
Aggravation of pre-existing myopia
Agitation
Agranulocytosis
Anaphylactoid reaction
Anxiety
Aplastic anaemia
Arrhythmias
Cholecystitis
Constipation
Dehydration
Diabetes mellitus
Diarrhoea
Dizziness
Dry mouth
ECG changes
Embolism
Fatigue
Fluid and electrolyte disturbances
Gout
Headache
Hyperlipidaemia
Hyperuricaemia
Hypochloraemic alkalosis
Hypokalaemia
Hypomagnesaemia
Hyponatraemia
Increase in serum glucose
Interstitial nephritis
Jaundice
Lethargy
Leucopenia
Muscle hypotonia
Muscle spasm
Muscular cramps
Nausea
Orthostatic hypotension
Palpitations
Pancreatitis
Photosensitivity
Pseudo Barrter's syndrome
Serum uric acid disturbances
Skin reactions
Sweating
Thrombocytopenia
Thrombosis
Visual disturbances
Vomiting

Presentation

Oral formulations containing xipamide

Drugs List

Therapeutic Indications

Uses

Hypertension
Oedema

Dosage

Adults

Contraindications

Children under 18 years
Breastfeeding
Hypercalcaemia
Hypovolaemia
Long QT syndrome
Pre-coma associated with hepatic cirrhosis
Pregnancy
Severe electrolyte imbalance
Severe hepatic impairment
Severe renal impairment
Symptomatic hyperuricaemia
Torsade de pointes
Uncontrolled Addison's disease

Precautions and Warnings

Ascites
Diarrhoea
Elderly
Family history of long QT syndrome
Oedema
Vomiting
Benign prostatic hyperplasia
Cerebral arteriosclerosis
Coronary arteriosclerosis
Diabetes mellitus
Electrolyte imbalance
Hepatic cirrhosis
History of torsade de pointes
Hyperaldosteronism
Hyperuricaemia
Ischaemic heart disease
Malnutrition
Mild hepatic impairment
Nephrotic syndrome
Systemic lupus erythematosus

Advise patient to protect skin if restarting following photosensitivity
Correct electrolyte disorders before treatment
May decrease glucose tolerance in patients with diabetes mellitus
Advise ability to drive/operate machinery may be affected by side effects
Consider monitoring ECG in patients at risk of QT prolongation
Monitor blood glucose closely in patients with diabetes mellitus
Monitor elderly receiving therapeutic doses
Monitor fluid and electrolyte status
Monitor serum urate levels in patients with gout
Discontinue if acute cholecystitis occurs
Discontinue if central nervous disturbances occur
Discontinue if distinct gastrointestinal symptoms occur
Discontinue if existing myopia is aggravated
Discontinue if orthostatic regulatory disorders occur
Discontinue if vasculitis occurs
Excess consumption of liquorice may increase the risk of hypokalaemia
Potassium supplements may be required
Prolonged use may cause fluid/electrolyte imbalance and hypokalaemia
Discontinue before parathyroid function tests
Discontinue at once if hepatic encephalopathy occurs
Discontinue if blood dyscrasia develops
Discontinue if hypersensitivity reactions occur
Discontinue if pancreatitis occurs
Discontinue if photosensitivity occurs
Discontinue if signs of fluid or electrolyte imbalance occur
Advise patient that photosensitivity possible

In cases of diuretic abuse, pseudo Bartter's may occur.

In patients with prostatic hypertrophy, there is an increased risk of developing urinary retention.

A decrease in sodium plasma level is a serious complication of diuretic therapy and may initially be asymptomatic. Therefore, regular control is advisable, especially in elderly patients and patients with liver cirrhosis.

During therapy with thiazide diuretics, calcium plasma level may increase and its excretion via urine is temporarily decreased. Hypercalcaemia may occur due to a previous undiagnosed hyperparathyroidism.

Thiazide diuretics are only fully effective in patients with normal or only mildly impaired renal function (creatinine serum level less than 25 mg/litre). In elderly patients, the serum creatinine value has to be adjusted according to age, weight and sex of the patient.

Pregnancy and Lactation

Pregnancy

Xipamide is contraindicated in pregnancy.

Diuretics pass the placenta and can reduce the plasma volume, lead to electrolyte disturbances and cause hypoglycaemia, haemolytic anaemia and thrombocytopenia in the unborn or newborn infant. Diuretics are not to be used under any circumstances for the treatment if pregnancy-related oedemas or physiological oedemas. This is because diuretics may cause foetoplacental ischaemia and foetal growth disturbances. Thiazides should also not be used to treat hypertension as they may cause neonatal thrombocytopenia, bone marrow suppression, jaundice, electrolyte disturbances and hypoglycaemia. Stimulation of labour, uterine inertia and meconium staining has also been reported.

Hydrochlorothiazide is the thiazide diuretic of choice during pregnancy as it is the best studied. Use of xipamide, however, does not require a risk-based termination of the pregnancy, nor invasive diagnostic interventions (Schaefer, 2015).

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Xipamide is contraindicated during breastfeeding.

It is not known if xipamide is expressed in breast milk.

If a diuretic is urgently needed whilst breastfeeding, hydrochlorothiazide may be considered in moderate doses. Due to limited experience, xipamide should not be used, but single doses will not require limitation of breastfeeding (Schaefer, 2015).

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal discomfort
Aggravation of pre-existing myopia
Agitation
Agranulocytosis
Anaphylactoid reaction
Anxiety
Aplastic anaemia
Arrhythmias
Cholecystitis
Constipation
Dehydration
Diabetes mellitus
Diarrhoea
Dizziness
Dry mouth
ECG changes
Embolism
Fatigue
Fluid and electrolyte disturbances
Gout
Headache
Hyperlipidaemia
Hyperuricaemia
Hypochloraemic alkalosis
Hypokalaemia
Hypomagnesaemia
Hyponatraemia
Increase in serum glucose
Interstitial nephritis
Jaundice
Lethargy
Leucopenia
Muscle hypotonia
Muscle spasm
Muscular cramps
Nausea
Orthostatic hypotension
Palpitations
Pancreatitis
Photosensitivity
Pseudo Barrter's syndrome
Serum uric acid disturbances
Skin reactions
Sweating
Thrombocytopenia
Thrombosis
Visual disturbances
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: June 2017

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Summary of Product Characteristics: Diurexan Tablets. Meda Pharmaceuticals. Revised December 2016.