Drugs List

Therapeutic Indications

Uses

Potassium-sparing diuretic and anti-hypertensive for the treatment of patients in whom potassium depletion might be expected or anticipated with the following conditions:

Hypertension
Congestive heart failure
Hepatic cirrhosis with ascites and oedema

Administration

For oral administration.

Contraindications

Hyperkalaemia (plasma potassium over 5.5mmol/litre)

Anuria

Acute renal failure

Severe progressive renal disease

Renal impairment - creatinine clearance below 30ml/minute

Severe hepatic failure

Pre-coma associated with hepatic cirrhosis

Addison's disease

Hypercalcaemia

Diabetic nephropathy

Children under 18 years

Blood urea over 10mmol/l, serum creatinine over 130 micromole/l or diabetes mellitus where serum electrolyte and blood urea levels cannot be monitored frequently and carefully.

Breastfeeding - (see Lactation section )

Pregnancy - (see Pregnancy section)

Galactosaemia

Precautions and Warnings

Elderly - particular caution is needed in the elderly because of their susceptibility to electrolyte imbalance. The dosage should be carefully adjusted to renal function and clinical response.

Hyperkalaemia has been observed in patients receiving amiloride hydrochloride, either alone or with other diuretics. Patients at risk include the elderly, hospital patients with hepatic cirrhosis or congestive heart failure with renal involvement, seriously ill, or undergoing vigorous diuretic therapy. Observe such patients carefully for clinical, laboratory, and ECG evidence of hyperkalaemia (not always associated with an abnormal ECG).
Neither potassium supplements, potassium containing salt substitutes nor a potassium-rich diet should be used with co-amilozide except under careful monitoring in severe and/or refractory cases of hypokalaemia. Advise patients to avoid an excess of potassium-rich foods.
Should hyperkalaemia develop, discontinue treatment immediately and, if necessary, take active measures to reduce the plasma potassium to normal.

Hypokalaemia may follow brisk diuresis, after prolonged therapy or when severe cirrhosis is present. Hypokalaemia can sensitise or exaggerate the response of the heart to the toxic effects of digitalis (e.g. increased ventricular irritability).

Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. See Dosage Patient with Hepatic Impairment .

Oral diuretic therapy is more frequently accompanied by adverse reactions in patients with hepatic cirrhosis and ascites because of intolerance to acute shifts in electrolyte balance and because they often have pre-existing hypokalaemia due to aldosteronism associated with the condition. Hepatic encephalopathy, manifested by confusion, tremors and coma, has been reported in patients on amiloride hydrochloride. Patients with liver disease should be observed for this complication. A deepening of jaundice has occurred in cirrhotic patients receiving amiloride hydrochloride alone, but the causative relationship is uncertain.

Hyperlipidaemia - an increase in cholesterol and triglycerides may be associated with thiazide therapy.

Diabetes mellitus - hyperkalaemia may occur and patients with pre-renal azotaemia or chronic renal disease or more at risk. Monitor renal function before prescribing co-amilozide to known or suspected diabetics. Thiazide diuretics may impair glucose tolerance. Dosage adjustment of the patient's hypoglycaemic medication may be required. Co-amilozide should be discontinued three days before giving a glucose tolerance test. Latent diabetes mellitus may become manifest during hydrochlorothiazide therapy.

Use with caution in impaired renal function and monitor renal function prior to initiating treatment. Co-amilozide treatment in patients with impaired renal function may result in the rapid development of hyperkalaemia.
Thiazide diuretics become ineffective when creatinine clearance falls below 30 ml/min.

Amiloride can block the tubular secretion of creatinine and may lead to falsely high measurements of creatinine clearance.

May activate or exacerbate systemic lupus erythematosus.

Initiate potassium-sparing therapy with caution in in severely ill patients in whom metabolic or respiratory acidosis may occur e.g. patients with decompensated diabetes or cardiopulmonary disease. Shifts in acid base balance alter the balance of extracellular/intracellular potassium. The development of acidosis may be associated with rapid increases in serum potassium.

Although the likelihood of electrolyte imbalance is reduced by co-amilozide, a careful check should be kept for such signs of fluid and electrolyte imbalance as hyponatraemia, hypochloraemic alkalosis, hypokalaemia and hypomagnesaemia.
It is particularly important to make serum and urine electrolyte determinations when the patient is vomiting excessively or receiving parenteral fluids. Warning signs or symptoms of fluid or electrolyte imbalance include: dryness of the mouth, weakness, lethargy, drowsiness, restlessness, seizures, confusion, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastro-intestinal disturbances such as nausea and vomiting.

Diuretic-induced hyponatraemia is usually mild and asymptomatic. It may become severe and symptomatic in a few patients who will then require immediate attention and appropriate treatment.

Thiazide diuretics should be used with caution in nephrotic syndrome, hyperaldosteronism and malnourishment.

Thiazides may decrease urinary calcium excretion. Thiazides may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Therapy should be discontinued before carrying out tests for parathyroid function.

Uraemia may be precipitated or increased by hydrochlorothiazide. Cumulative effects of the drug may develop in patients with impaired renal function. If increasing uraemia and oliguria develop during treatment of renal disease, co-amilozide should be discontinued.

This medication contains lactose and should used with caution in patients with glucose-galactose malabsorption syndrome, or in those who are lactose intolerant.

Use with caution in patients with gout. Hyperuricaemia or gout may be precipitated or aggravated by this medication.

Advise patient not to consume NSAIDs concurrently with this medication unless under the guidance of a physician.

Advise patient that concurrent alcohol may potentiate orthostatic hypotension.

Advise patient that this medication may cause weakness, fatigue, dizziness, stupor and vertigo. If affected the patient should not drive or operate machinery.

Acute porphyria - (see Porphyria section)

There is an increased risk of hypercalcaemia with calcium salts and vitamin D. Patients taking large amounts of calcium or vitamin D in combination with thiazides have an increased risk of developing milk-alkali syndrome. Advise patients not to consume calcium or vitamin D supplements unless under the guidance of a physician.

Dose dependent increased risk of non-melanoma skin cancer with exposure to increasing cumulative doses of hydrochlorothiazide.

Use with caution in patients who have had previous skin cancer.

Advise patient to monitor for and report any skin changes.

Advise patient to minimise exposure to sunlight and avoid sunlamps during therapy.

Use in Porphyria

One manufacturer of this medication considers hydrochlorothiazide to be unsafe for use in patients with acute porphyria. However, The Norwegian Porphyria Centre considers hydrochlorothiazide to be probably not porphyrinogenic. The European Porphyria Initiative and the Welsh Medicine Information Centre both consider hydrochlorothiazide to be safe for use in patients with acute porphyria. Amiloride is considered safe in porphyria.

Pregnancy and Lactation

Pregnancy

This product should not be used during pregnancy. As this product contains two medically active ingredients these are discussed separately below.

No reports of amiloride passing to the foetus in humans have been found. However, due to its low molecular weight and the fact that it crosses the placenta in mice and rabbits, amiloride is expected to pass through the placenta in humans. There is a lack of human data for amiloride use during pregnancy. However, in one study where 28 newborns had been exposed to amiloride in the first trimester two major birth defects where seen (one expected), one of these was a hypospadias. No anomalies where seen in the other five categories (cardiovascular, oral clefts, spina bifida, polydactyly and limb reduction defects) for which specific data were available. Briggs (2011) states that there is limited human data, but animal data indicate that there is a low risk to the foetus. Schaefer (2007) concludes that amiloride should not be used during pregnancy. However, use with any of the diuretics is not an indication for termination of the pregnancy.

Hydrochlorothiazide is contraindicated during pregnancy for hypertension. Animal studies on mice, rats and rabbits reported no external malformations, however no internal examination was undertaken. Hydrochlorothiazide is known to cross the placenta. Diuretics are contraindicated for their possible affects on the mother and therefore the foetus. The hypovolaemia characteristic of gestational hypertension would be adversely affected by hydrochlorothiazide. This could lead to a decrease in placental perfusion. Other risks to the foetus or newborn include bone marrow depression, hypoglycaemia, thrombocytopenia, hyponatraemia, hypokalaemia, jaundice and death from maternal complications. Prolonged labour has also been described as the result of inhibition of smooth muscle action caused by hydrochlorothiazide.

Diuretics are no longer used as part of the standard therapy for hypertension and oedema during pregnancy, due to the maternal, hypovolaemic character of the disease. Many sources contraindicate the use of diuretics during pregnancy, except for patients with heart disease, mainly because they do not prevent or alter the course of toxaemia and they may decrease placental perfusion. If long term treatment is necessary the mother's electrolytes and haematocrit should be measured and the development of oligohydramnios should be ruled out. Hypoglycaemia in the newborn should also be monitored.

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 14-17 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 ).

Licensed in pregnancy? - No, contraindicated

Recommended for use in pregnancy? - No

Known human teratogen? - Unknown

Crosses placenta? - Hydrochlorothiazide - Yes, Amiloride - Unknown but is expected to.

Effects on foetus - Hydrochlorothiazide will exacerbate the hypovolaemia characteristic to hypertension in pregnancy and could therefore reduce placental perfusion, adversely affecting the foetus .

Lactation

This product is contraindicated while breastfeeding. As this product contains two medically active ingredients these are discussed separately below.

It is not known whether amiloride is excreted in human milk. Due to its low molecular weight and the fact that amiloride is excreted in the milk of lactating rats at concentrations higher than that measured in blood, passage into human milk is expected. There is a lack of human data with amiloride during breastfeeding and the effects on the nursing infant are unknown. Schaefer (2007) concludes that due to insufficient information amiloride should not be used during breastfeeding. However, single doses do not require limitation of breastfeeding, but therapy should be changed.

Hydrochlorothiazide is excreted in small quantities into breast milk. There have been reports of thrombocytopenia in the nursing infants of mothers receiving a thiazide diuretic, however, the risk is considered low by Hale (2010) and Briggs (2011). Thiazide diuretics have been used in large quantities to suppress lactation. Overall, hydrochlorothiazide is considered safe while breastfeeding (Briggs (2011), Schaefer (2007), and Hale (2010)).

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

Drug excreted in breast milk? - Amiloride - Unknown, but is expected to be found in human milk, Hydrochlorothiazide - Yes

Considered suitable or recommended by manufacturer? - No

UK Drugs in Lactation Advisory Service Classification - Hydrochlorothiazide is classified safe except in large quantities, diuretics may suppress lactation.

Drug substance licensed in infants? - No

Drug known to affect lactation? - High doses may theoretically suppress lactation.

Side Effects

Headache
Weakness
Fatigue
Malaise
Chest pain
Back pain
Syncope
Arrhythmias
Tachycardia
Orthostatic hypotension
Angina pectoris
Nausea
Vomiting
Diarrhoea
Constipation
Abdominal pain
Gastrointestinal bleeding
Disturbances of appetite
Abdominal discomfort
Flatulence
Thirst
Hiccups
Hyperkalaemia
Hyponatraemia
Gout
Dehydration
Rash
Pruritus
Flushing
Diaphoresis
Muscle cramps
Joint pain
Vertigo
Dizziness
Paraesthesia
Stupor
Insomnia
Nervousness
Confusion
Depression
Sleepiness
Dyspnoea
Unpleasant taste
Visual disturbances
Nasal congestion
Impotence
Dysuria
Nocturia
Incontinence
Renal impairment
Renal failure
Neck pain
Painful extremities
Abnormal liver function tests
Aggravation of peptic ulcer
Dyspepsia
Cholestatic jaundice
Dry mouth
Alopecia
Tremor
Encephalopathy
Aplastic anaemia
Neutropenia
Heart block
Palpitations
Reduced libido
Cough
Tinnitus
Increased intra-ocular pressure
Polyuria
Urinary frequency
Bladder spasm
Anaphylactoid reaction
Fever
Necrotising angiitis
Pancreatitis
Gastric irritation
Glycosuria
Hyperglycaemia
Hyperuricaemia
Hypokalaemia
Photosensitivity
Sialadenitis
Urticaria
Toxic epidermal necrolysis
Agranulocytosis
Anaemia
Leucopenia
Purpura
Thrombocytopenia
Restlessness
Respiratory difficulties
Interstitial nephritis
Pneumonitis
Pulmonary oedema
Altered serum lipid profile
Anorexia
Worsening of lupus erythematosus
Somnolence

Presentation

Tablets containing 5mg amiloride hydrochloride and 50mg hydrochlorothiazide.
Tablets containing 2.5mg amiloride hydrochloride and 25mg hydrochlorothiazide.

Drugs List

Therapeutic Indications

Uses

Potassium-sparing diuretic and anti-hypertensive for the treatment of patients in whom potassium depletion might be expected or anticipated with the following conditions:

Hypertension
Congestive heart failure
Hepatic cirrhosis with ascites and oedema

Dosage

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Administration

For oral administration.

Contraindications

Hyperkalaemia (plasma potassium over 5.5mmol/litre)

Anuria

Acute renal failure

Severe progressive renal disease

Renal impairment - creatinine clearance below 30ml/minute

Severe hepatic failure

Pre-coma associated with hepatic cirrhosis

Addison's disease

Hypercalcaemia

Diabetic nephropathy

Children under 18 years

Blood urea over 10mmol/l, serum creatinine over 130 micromole/l or diabetes mellitus where serum electrolyte and blood urea levels cannot be monitored frequently and carefully.

Breastfeeding - (see Lactation section )

Pregnancy - (see Pregnancy section)

Galactosaemia

Precautions and Warnings

Elderly - particular caution is needed in the elderly because of their susceptibility to electrolyte imbalance. The dosage should be carefully adjusted to renal function and clinical response.

Hyperkalaemia has been observed in patients receiving amiloride hydrochloride, either alone or with other diuretics. Patients at risk include the elderly, hospital patients with hepatic cirrhosis or congestive heart failure with renal involvement, seriously ill, or undergoing vigorous diuretic therapy. Observe such patients carefully for clinical, laboratory, and ECG evidence of hyperkalaemia (not always associated with an abnormal ECG).
Neither potassium supplements, potassium containing salt substitutes nor a potassium-rich diet should be used with co-amilozide except under careful monitoring in severe and/or refractory cases of hypokalaemia. Advise patients to avoid an excess of potassium-rich foods.
Should hyperkalaemia develop, discontinue treatment immediately and, if necessary, take active measures to reduce the plasma potassium to normal.

Hypokalaemia may follow brisk diuresis, after prolonged therapy or when severe cirrhosis is present. Hypokalaemia can sensitise or exaggerate the response of the heart to the toxic effects of digitalis (e.g. increased ventricular irritability).

Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. See Dosage Patient with Hepatic Impairment .

Oral diuretic therapy is more frequently accompanied by adverse reactions in patients with hepatic cirrhosis and ascites because of intolerance to acute shifts in electrolyte balance and because they often have pre-existing hypokalaemia due to aldosteronism associated with the condition. Hepatic encephalopathy, manifested by confusion, tremors and coma, has been reported in patients on amiloride hydrochloride. Patients with liver disease should be observed for this complication. A deepening of jaundice has occurred in cirrhotic patients receiving amiloride hydrochloride alone, but the causative relationship is uncertain.

Hyperlipidaemia - an increase in cholesterol and triglycerides may be associated with thiazide therapy.

Diabetes mellitus - hyperkalaemia may occur and patients with pre-renal azotaemia or chronic renal disease or more at risk. Monitor renal function before prescribing co-amilozide to known or suspected diabetics. Thiazide diuretics may impair glucose tolerance. Dosage adjustment of the patient's hypoglycaemic medication may be required. Co-amilozide should be discontinued three days before giving a glucose tolerance test. Latent diabetes mellitus may become manifest during hydrochlorothiazide therapy.

Use with caution in impaired renal function and monitor renal function prior to initiating treatment. Co-amilozide treatment in patients with impaired renal function may result in the rapid development of hyperkalaemia.
Thiazide diuretics become ineffective when creatinine clearance falls below 30 ml/min.

Amiloride can block the tubular secretion of creatinine and may lead to falsely high measurements of creatinine clearance.

May activate or exacerbate systemic lupus erythematosus.

Initiate potassium-sparing therapy with caution in in severely ill patients in whom metabolic or respiratory acidosis may occur e.g. patients with decompensated diabetes or cardiopulmonary disease. Shifts in acid base balance alter the balance of extracellular/intracellular potassium. The development of acidosis may be associated with rapid increases in serum potassium.

Although the likelihood of electrolyte imbalance is reduced by co-amilozide, a careful check should be kept for such signs of fluid and electrolyte imbalance as hyponatraemia, hypochloraemic alkalosis, hypokalaemia and hypomagnesaemia.
It is particularly important to make serum and urine electrolyte determinations when the patient is vomiting excessively or receiving parenteral fluids. Warning signs or symptoms of fluid or electrolyte imbalance include: dryness of the mouth, weakness, lethargy, drowsiness, restlessness, seizures, confusion, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastro-intestinal disturbances such as nausea and vomiting.

Diuretic-induced hyponatraemia is usually mild and asymptomatic. It may become severe and symptomatic in a few patients who will then require immediate attention and appropriate treatment.

Thiazide diuretics should be used with caution in nephrotic syndrome, hyperaldosteronism and malnourishment.

Thiazides may decrease urinary calcium excretion. Thiazides may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Therapy should be discontinued before carrying out tests for parathyroid function.

Uraemia may be precipitated or increased by hydrochlorothiazide. Cumulative effects of the drug may develop in patients with impaired renal function. If increasing uraemia and oliguria develop during treatment of renal disease, co-amilozide should be discontinued.

This medication contains lactose and should used with caution in patients with glucose-galactose malabsorption syndrome, or in those who are lactose intolerant.

Use with caution in patients with gout. Hyperuricaemia or gout may be precipitated or aggravated by this medication.

Advise patient not to consume NSAIDs concurrently with this medication unless under the guidance of a physician.

Advise patient that concurrent alcohol may potentiate orthostatic hypotension.

Advise patient that this medication may cause weakness, fatigue, dizziness, stupor and vertigo. If affected the patient should not drive or operate machinery.

Acute porphyria - (see Porphyria section)

There is an increased risk of hypercalcaemia with calcium salts and vitamin D. Patients taking large amounts of calcium or vitamin D in combination with thiazides have an increased risk of developing milk-alkali syndrome. Advise patients not to consume calcium or vitamin D supplements unless under the guidance of a physician.

Dose dependent increased risk of non-melanoma skin cancer with exposure to increasing cumulative doses of hydrochlorothiazide.

Use with caution in patients who have had previous skin cancer.

Advise patient to monitor for and report any skin changes.

Advise patient to minimise exposure to sunlight and avoid sunlamps during therapy.

Use in Porphyria

One manufacturer of this medication considers hydrochlorothiazide to be unsafe for use in patients with acute porphyria. However, The Norwegian Porphyria Centre considers hydrochlorothiazide to be probably not porphyrinogenic. The European Porphyria Initiative and the Welsh Medicine Information Centre both consider hydrochlorothiazide to be safe for use in patients with acute porphyria. Amiloride is considered safe in porphyria.

Pregnancy and Lactation

Pregnancy

This product should not be used during pregnancy. As this product contains two medically active ingredients these are discussed separately below.

No reports of amiloride passing to the foetus in humans have been found. However, due to its low molecular weight and the fact that it crosses the placenta in mice and rabbits, amiloride is expected to pass through the placenta in humans. There is a lack of human data for amiloride use during pregnancy. However, in one study where 28 newborns had been exposed to amiloride in the first trimester two major birth defects where seen (one expected), one of these was a hypospadias. No anomalies where seen in the other five categories (cardiovascular, oral clefts, spina bifida, polydactyly and limb reduction defects) for which specific data were available. Briggs (2011) states that there is limited human data, but animal data indicate that there is a low risk to the foetus. Schaefer (2007) concludes that amiloride should not be used during pregnancy. However, use with any of the diuretics is not an indication for termination of the pregnancy.

Hydrochlorothiazide is contraindicated during pregnancy for hypertension. Animal studies on mice, rats and rabbits reported no external malformations, however no internal examination was undertaken. Hydrochlorothiazide is known to cross the placenta. Diuretics are contraindicated for their possible affects on the mother and therefore the foetus. The hypovolaemia characteristic of gestational hypertension would be adversely affected by hydrochlorothiazide. This could lead to a decrease in placental perfusion. Other risks to the foetus or newborn include bone marrow depression, hypoglycaemia, thrombocytopenia, hyponatraemia, hypokalaemia, jaundice and death from maternal complications. Prolonged labour has also been described as the result of inhibition of smooth muscle action caused by hydrochlorothiazide.

Diuretics are no longer used as part of the standard therapy for hypertension and oedema during pregnancy, due to the maternal, hypovolaemic character of the disease. Many sources contraindicate the use of diuretics during pregnancy, except for patients with heart disease, mainly because they do not prevent or alter the course of toxaemia and they may decrease placental perfusion. If long term treatment is necessary the mother's electrolytes and haematocrit should be measured and the development of oligohydramnios should be ruled out. Hypoglycaemia in the newborn should also be monitored.

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 14-17 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 ).

Licensed in pregnancy? - No, contraindicated

Recommended for use in pregnancy? - No

Known human teratogen? - Unknown

Crosses placenta? - Hydrochlorothiazide - Yes, Amiloride - Unknown but is expected to.

Effects on foetus - Hydrochlorothiazide will exacerbate the hypovolaemia characteristic to hypertension in pregnancy and could therefore reduce placental perfusion, adversely affecting the foetus .

Lactation

This product is contraindicated while breastfeeding. As this product contains two medically active ingredients these are discussed separately below.

It is not known whether amiloride is excreted in human milk. Due to its low molecular weight and the fact that amiloride is excreted in the milk of lactating rats at concentrations higher than that measured in blood, passage into human milk is expected. There is a lack of human data with amiloride during breastfeeding and the effects on the nursing infant are unknown. Schaefer (2007) concludes that due to insufficient information amiloride should not be used during breastfeeding. However, single doses do not require limitation of breastfeeding, but therapy should be changed.

Hydrochlorothiazide is excreted in small quantities into breast milk. There have been reports of thrombocytopenia in the nursing infants of mothers receiving a thiazide diuretic, however, the risk is considered low by Hale (2010) and Briggs (2011). Thiazide diuretics have been used in large quantities to suppress lactation. Overall, hydrochlorothiazide is considered safe while breastfeeding (Briggs (2011), Schaefer (2007), and Hale (2010)).

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

Drug excreted in breast milk? - Amiloride - Unknown, but is expected to be found in human milk, Hydrochlorothiazide - Yes

Considered suitable or recommended by manufacturer? - No

UK Drugs in Lactation Advisory Service Classification - Hydrochlorothiazide is classified safe except in large quantities, diuretics may suppress lactation.

Drug substance licensed in infants? - No

Drug known to affect lactation? - High doses may theoretically suppress lactation.

Effects on Ability to Drive and Operate Machinery

May cause weakness, fatigue, dizziness, stupor and vertigo. If affected the patient should be cautioned not to drive or operate machinery.

Counselling

Advise patients that the use of potassium containing salt substitutes or a high intake of potassium rich foods may lead to significant increases in serum potassium.

Advise patient not to consume calcium of vitamin D supplements unless under the guidance of a physician.

Advise patient not to consume NSAIDs concurrently with this medication unless under the guidance of a physician.

Advise patient that concurrent alcohol may potentiate orthostatic hypotension.

Advise patient that co-amilozide may cause weakness, fatigue, dizziness, stupor and vertigo. If affected the patient should be cautioned not to drive or operate machinery

Advise patient to monitor for and report any skin changes.

Advise patient to minimise exposure to sunlight and avoid sunlamps during therapy.

Side Effects

Headache
Weakness
Fatigue
Malaise
Chest pain
Back pain
Syncope
Arrhythmias
Tachycardia
Orthostatic hypotension
Angina pectoris
Nausea
Vomiting
Diarrhoea
Constipation
Abdominal pain
Gastrointestinal bleeding
Disturbances of appetite
Abdominal discomfort
Flatulence
Thirst
Hiccups
Hyperkalaemia
Hyponatraemia
Gout
Dehydration
Rash
Pruritus
Flushing
Diaphoresis
Muscle cramps
Joint pain
Vertigo
Dizziness
Paraesthesia
Stupor
Insomnia
Nervousness
Confusion
Depression
Sleepiness
Dyspnoea
Unpleasant taste
Visual disturbances
Nasal congestion
Impotence
Dysuria
Nocturia
Incontinence
Renal impairment
Renal failure
Neck pain
Painful extremities
Abnormal liver function tests
Aggravation of peptic ulcer
Dyspepsia
Cholestatic jaundice
Dry mouth
Alopecia
Tremor
Encephalopathy
Aplastic anaemia
Neutropenia
Heart block
Palpitations
Reduced libido
Cough
Tinnitus
Increased intra-ocular pressure
Polyuria
Urinary frequency
Bladder spasm
Anaphylactoid reaction
Fever
Necrotising angiitis
Pancreatitis
Gastric irritation
Glycosuria
Hyperglycaemia
Hyperuricaemia
Hypokalaemia
Photosensitivity
Sialadenitis
Urticaria
Toxic epidermal necrolysis
Agranulocytosis
Anaemia
Leucopenia
Purpura
Thrombocytopenia
Restlessness
Respiratory difficulties
Interstitial nephritis
Pneumonitis
Pulmonary oedema
Altered serum lipid profile
Anorexia
Worsening of lupus erythematosus
Somnolence

Effects on Laboratory Tests

Amiloride can block the tubular secretion of creatinine and may lead to falsely high measurements of creatinine clearance.

Thiazides may interfere with tests for parathyroid function. This medication should be discontinued before such tests are carried out.

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 ).

Shelf Life and Storage

Store in a dry place below 25 degrees C
Protect from light

Further Information

Last Full Review Date: January 2012

Reference Sources

British National Formulary, 62nd Edition (2011) Pharmaceutical Press, London.

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 8th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Medications and Mother's Milk, 13th edition (2010) Hale, T.W. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Moduret 25. Merck, Sharp & Dohme Ltd. Revised December 2009.

Summary of Product Characteristics: Moduretic. Merck, Sharp & Dohme. Revised December 2009.

Summary of Product Characteristics: Co-amilozide 2.5/25 Tablets. Wockhardt UK Ltd. Revised February 2008.

Summary of Product Characteristics: Co-amilozide 5/50 Tablets. Wockhardt UK Ltd. Revised February 2008.

Summary of Product Characteristics: Co-amilozide Tablets BP 5/50mg. Actavis UK Ltd. Revised October 2011.

European Porphyria Network.
Available at: https://www.porphyria-europe.com/03-drugs/warning.asp?strPageRub=selecting-drugs.asp
Last accessed: January 9, 2012.

NAPOS The Drug Database For Acute Porphyria.
Available at: https://www.drugs-porphyria.com/languages/UnitedKingdom/s1.php?l=gbr
Last accessed: January 9, 2012.

MHRA Drug Safety Update November 2018
Available at: https://www.mhra.gov.uk
Last accessed: 08 January 2019

The Welsh Medicines Porphyria Information Service.
Available at: https://www.wmic.wales.nhs.uk/porphyria_info.php
Last accessed: January 9, 2012.

UK Drugs in Lactation Advisory Service.
Available at: https://www.ukmicentral.nhs.uk/drugpreg/guide.htm
Last accessed: January 9, 2012.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Hydrochlorothiazide. Last revised: January 4, 2011.
Last accessed: January 9, 2012.