Drugs List

Therapeutic Indications

Uses

Depressive illness

Contraindications

Acute alcohol intoxication
Children under 18 years
Drug intoxication
Risk of paralytic ileus
Within 2 weeks of discontinuing MAOIs
Within 2 weeks of discontinuing selegiline
Acute porphyria
Atrioventricular block
Cardiac arrhythmias
Delirium tremens
Long QT syndrome
Mania
Recent myocardial infarction
Severe hepatic impairment
Torsade de pointes
Uncontrolled narrow angle glaucoma

Precautions and Warnings

Anaesthesia
Debilitation
Elderly
Electroconvulsive therapy
Family history of long QT syndrome
Recent seizure
Suicidal ideation
Alcohol withdrawal syndrome
Benign prostatic hyperplasia
Breastfeeding
Cardiac disorder
Cardiovascular disorder
Chronic constipation
Congenital long QT syndrome
Diabetes mellitus
Electrolyte imbalance
Epileptic disorder
Galactosaemia
Glucose-galactose malabsorption syndrome
Haematological disorder
Hepatic impairment
Hereditary fructose intolerance
History of mania
History of torsade de pointes
Hypertension
Hyperthyroidism
Lactose intolerance
Narrow angle glaucoma
Neuroblastoma
Phaeochromocytoma
Pregnancy
Psychosis
Renal impairment
Urinary retention

Correct electrolyte disorders before treatment
Patients at risk of suicide should be closely supervised
Advise impaired alertness may affect ability to drive or operate machinery
May reduce seizure threshold
Oral solution with maltitol unsuitable in hereditary fructose intolerance
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain hydroxybenzoate
Some formulations contain lactose
Some formulations may contain alcohol
Monitor blood pressure before starting treatment
Perform full blood count before treatment
Consider monitoring ECG in patients at risk of QT prolongation
Monitor blood pressure in hypertensive patients
Monitor full blood count regularly
Monitor serum electrolytes
Advise patients/carers to seek medical advice if suicidal intent develops
Consider hyponatraemia in all patients with drowsiness/confusion/seizures
Increased risk of fractures in patients over 50 years
Life threatening arrhythmias may occur during anaesthesia and surgery
May cause activation of latent psychosis
Do not withdraw this drug suddenly
Dosage reduction should be done gradually over about 4 weeks
Discontinue if patient enters a manic phase
Discontinue if Torsade de Pointes should occur during treatment
Consider reducing initial dose in the elderly
Advise patient not to take St John's wort concurrently
Advise patient that the effects of alcohol may be potentiated
Advise patient to avoid alcohol during treatment

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of self harm is highest shortly after presentation and the risk of suicide may increase again in the early stages of recovery. Furthermore, there is evidence that antidepressants may increase the risk of suicidal thoughts and self harm in children and adolescents.

Patients with a history of suicide-related events, those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, and young adults, are at a greater risk of suicidal thought or suicide attempt, and should receive careful monitoring during treatment.

Patients, (and caregivers of patients) should be alerted about the need to monitor for the emergence of suicidal thoughts and behaviour, and to seek medical advice immediately if these symptoms present.

Pregnancy and Lactation

Pregnancy

Use lofepramine with caution in pregnancy.

The manufacturers advise that lofepramine should not be used during pregnancy unless there are compelling medical reasons to do so.

At the time of writing, there are no or very limited data available on the use of lofepramine guidance has been derived from the general knowledge on tricyclic antidepressants:

Maternal exposure to tricyclic antidepressants may be associated with risks for spontaneous abortions, preterm births and low birth weights. Also, gestational orthostatic hypotension may be exacerbated.

Schaefer recommends monitoring of maternal serum levels, due to altered pharmacokinetics during pregnancy, especially in the second and third trimesters.

Tricyclic antidepressants used during pregnancy may also elicit adverse reactions in the neonate: withdrawal symptoms, respiratory depression, irritability, myoclonus and convulsions have been reported.

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

Use lofepramine with caution in breastfeeding.

Lofepramine is excreted into breast milk. The manufacturers advise against using lofepramine during breastfeeding.

At the time of writing, there is highly limited data describing the use of lofepramine during breastfeeding.

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

Agitation
Agranulocytosis
Allergic skin reactions
Alopecia
Angioedema
Anorexia
Anxiety
Arrhythmias
Ataxia
Behavioural disturbances
Blood sugar changes
Blurred vision
Bone marrow depression
Cardiac conduction disturbances
Cardiac insufficiency
Confusion
Constipation
Convulsions
Cutaneous bleeding disorders
Delirium
Delusions
Dermatological and photosensitivity reactions
Diarrhoea
Disturbances in accommodation
Dizziness
Drowsiness
Dry mouth
Dysarthria
Dysgeusia
ECG changes
Eosinophilia
Exacerbation of psychoses
Extrapyramidal effects
Facial oedema
Galactorrhoea
Glaucoma
Granulocytopenia
Gynaecomastia
Hallucinations
Headache
Hepatic impairment
Hepatitis
Hypomania
Hyponatraemia
Hypotension
Impaired co-ordination
Inappropriate secretion of antidiuretic hormone
Increased appetite
Increased risk of fractures
Increases in hepatic enzymes
Jaundice
Leucopenia
Malaise
Mania
Mucosal inflammation
Mydriasis
Nausea
Neuroleptic malignant syndrome
Nightmares
Oedema
Pancytopenia
Paraesthesia
Paralytic ileus
Peripheral neuropathy
Postural hypotension
Prolongation of QT interval
Pruritus
Purpura
Rash
Sexual dysfunction
Sleep disturbances
Stomatitis
Suicidal tendencies
Sweating
Syncope
Tachycardia
Testicular disorders
Thrombocytopenia
Tinnitus
Tremor
Urinary hesitancy
Urinary retention
Urticaria
Visual disturbances
Vomiting
Weight gain
Weight loss
Withdrawal symptoms

Presentation

Oral formulations containing lofepramine

Drugs List

Therapeutic Indications

Uses

Depressive illness

Dosage

Adults

Elderly

Patients with Renal Impairment

Contraindications

Acute alcohol intoxication
Children under 18 years
Drug intoxication
Risk of paralytic ileus
Within 2 weeks of discontinuing MAOIs
Within 2 weeks of discontinuing selegiline
Acute porphyria
Atrioventricular block
Cardiac arrhythmias
Delirium tremens
Long QT syndrome
Mania
Recent myocardial infarction
Severe hepatic impairment
Torsade de pointes
Uncontrolled narrow angle glaucoma

Precautions and Warnings

Anaesthesia
Debilitation
Elderly
Electroconvulsive therapy
Family history of long QT syndrome
Recent seizure
Suicidal ideation
Alcohol withdrawal syndrome
Benign prostatic hyperplasia
Breastfeeding
Cardiac disorder
Cardiovascular disorder
Chronic constipation
Congenital long QT syndrome
Diabetes mellitus
Electrolyte imbalance
Epileptic disorder
Galactosaemia
Glucose-galactose malabsorption syndrome
Haematological disorder
Hepatic impairment
Hereditary fructose intolerance
History of mania
History of torsade de pointes
Hypertension
Hyperthyroidism
Lactose intolerance
Narrow angle glaucoma
Neuroblastoma
Phaeochromocytoma
Pregnancy
Psychosis
Renal impairment
Urinary retention

Correct electrolyte disorders before treatment
Patients at risk of suicide should be closely supervised
Advise impaired alertness may affect ability to drive or operate machinery
May reduce seizure threshold
Oral solution with maltitol unsuitable in hereditary fructose intolerance
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain hydroxybenzoate
Some formulations contain lactose
Some formulations may contain alcohol
Monitor blood pressure before starting treatment
Perform full blood count before treatment
Consider monitoring ECG in patients at risk of QT prolongation
Monitor blood pressure in hypertensive patients
Monitor full blood count regularly
Monitor serum electrolytes
Advise patients/carers to seek medical advice if suicidal intent develops
Consider hyponatraemia in all patients with drowsiness/confusion/seizures
Increased risk of fractures in patients over 50 years
Life threatening arrhythmias may occur during anaesthesia and surgery
May cause activation of latent psychosis
Do not withdraw this drug suddenly
Dosage reduction should be done gradually over about 4 weeks
Discontinue if patient enters a manic phase
Discontinue if Torsade de Pointes should occur during treatment
Consider reducing initial dose in the elderly
Advise patient not to take St John's wort concurrently
Advise patient that the effects of alcohol may be potentiated
Advise patient to avoid alcohol during treatment

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of self harm is highest shortly after presentation and the risk of suicide may increase again in the early stages of recovery. Furthermore, there is evidence that antidepressants may increase the risk of suicidal thoughts and self harm in children and adolescents.

Patients with a history of suicide-related events, those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, and young adults, are at a greater risk of suicidal thought or suicide attempt, and should receive careful monitoring during treatment.

Patients, (and caregivers of patients) should be alerted about the need to monitor for the emergence of suicidal thoughts and behaviour, and to seek medical advice immediately if these symptoms present.

Pregnancy and Lactation

Pregnancy

Use lofepramine with caution in pregnancy.

The manufacturers advise that lofepramine should not be used during pregnancy unless there are compelling medical reasons to do so.

At the time of writing, there are no or very limited data available on the use of lofepramine guidance has been derived from the general knowledge on tricyclic antidepressants:

Maternal exposure to tricyclic antidepressants may be associated with risks for spontaneous abortions, preterm births and low birth weights. Also, gestational orthostatic hypotension may be exacerbated.

Schaefer recommends monitoring of maternal serum levels, due to altered pharmacokinetics during pregnancy, especially in the second and third trimesters.

Tricyclic antidepressants used during pregnancy may also elicit adverse reactions in the neonate: withdrawal symptoms, respiratory depression, irritability, myoclonus and convulsions have been reported.

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

Use lofepramine with caution in breastfeeding.

Lofepramine is excreted into breast milk. The manufacturers advise against using lofepramine during breastfeeding.

At the time of writing, there is highly limited data describing the use of lofepramine during breastfeeding.

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

Agitation
Agranulocytosis
Allergic skin reactions
Alopecia
Angioedema
Anorexia
Anxiety
Arrhythmias
Ataxia
Behavioural disturbances
Blood sugar changes
Blurred vision
Bone marrow depression
Cardiac conduction disturbances
Cardiac insufficiency
Confusion
Constipation
Convulsions
Cutaneous bleeding disorders
Delirium
Delusions
Dermatological and photosensitivity reactions
Diarrhoea
Disturbances in accommodation
Dizziness
Drowsiness
Dry mouth
Dysarthria
Dysgeusia
ECG changes
Eosinophilia
Exacerbation of psychoses
Extrapyramidal effects
Facial oedema
Galactorrhoea
Glaucoma
Granulocytopenia
Gynaecomastia
Hallucinations
Headache
Hepatic impairment
Hepatitis
Hypomania
Hyponatraemia
Hypotension
Impaired co-ordination
Inappropriate secretion of antidiuretic hormone
Increased appetite
Increased risk of fractures
Increases in hepatic enzymes
Jaundice
Leucopenia
Malaise
Mania
Mucosal inflammation
Mydriasis
Nausea
Neuroleptic malignant syndrome
Nightmares
Oedema
Pancytopenia
Paraesthesia
Paralytic ileus
Peripheral neuropathy
Postural hypotension
Prolongation of QT interval
Pruritus
Purpura
Rash
Sexual dysfunction
Sleep disturbances
Stomatitis
Suicidal tendencies
Sweating
Syncope
Tachycardia
Testicular disorders
Thrombocytopenia
Tinnitus
Tremor
Urinary hesitancy
Urinary retention
Urticaria
Visual disturbances
Vomiting
Weight gain
Weight loss
Withdrawal symptoms

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: November 2016

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.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press Accessed on 09 November 2016.

Martindale: The Complete Drug Reference, 36th edition (2009) ed. Sweetman, S. Pharmaceutical Press, London.

Summary of Product Characteristics: Lofepramine Oral Suspension 70mg/5ml. Rosemont Pharmaceuticals Ltd. Revised January 2016.

Summary of Product Characteristics: Lofepramine 70 mg tablets. Merck Sorono. Revised November 2010.

The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.

MHRA 4th February 2008
https://www.mhra.gov.uk/NewsCentre/Pressreleases/CON2033960
Accessed 11th February 2008

MHRA Drug Safety Update May 2010
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON081863
Last accessed: 14th July 2010

Antenatal and postnatal mental health. Clinical management and service guidance (Dated April 2007, review of new evidence: 2 years after this date).
Available at
https://www.nice.org.uk/guidance/cg192
Accessed 09 November 2016