When a pharmaceutical company changes an SPC or PIL, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.
Children (below 18 years of age):
There are no data available on use of diltiazem in children below the age of 18 years, and diltiazem is not recommended for use in children. In section 4.3, 3rd bullet point has changed the pulse aret to 40: · Severe bradycardia (resting pulse rate of less than 40 beats per minute) In the 7th bullet point there is an addition of a contraindication: · pulmonary congestion In section 4.4 there is the following new text: 1.) .......with impaired renal function or patients with renal or hepatic impairment..... and the following text has been added: 3. Prior to general anaesthesia, the anaesethist must be informed of ongoing diltiazem treatment. Depression of cardiac contractility, conductivity and automaticity, as well as the vascular dilatation associated with anaesthetics such as enflurane, halothane and isoflurane, may be potentiated by calcium channel blockers. 4. The risk of raised creatine kinease, myopathy and rhabdomyolisis due to statins (metabolised by CYP3A4) may be increased in case of a concomitant use of diltiazem. Closer monitoring for signs and symptoms is warranted in such case. 5. Calcium channel blocking agents, such as diltiazem, may be associated with mood changes, including depression. 6. Like other calcium channel antagonists, diltiazem has an inhibitory effect on intestinal motility. Therefore it should be used with caution in patients at risk to develop an intestinal obstruction. In section 4.5, the following text has been added: all the patients treated with calcium antagonists, the prescription of nitrate derivatives should only be carried out at gradually increasing doses. - The combination of diltiazem with an alpha-antagonist should be considered only with the strict monitoring of the blood pressure. Dantrolene (infusion) a lethal ventricular fibrillation is regularly observed in animals when intravenous verapamil and dantrolene are administered concomitantly. The combination of calcium antagonist and dantrolene is therefore potentially dangerous (see section 4.3 Contraindications). Due to the potential for additive effects, caution and careful titration are necessary in patients receiving diltiazem concomitantly with other agents known to affect cardiac contractility and/or conduction. - Since diltiazem has antiarrhythmic properties, its concomitant prescription with other antiarrhythmic agents is not recommended (additive risk of increased cardiac adverse effects). This combination should only be used under close clinical and ECG monitoring. In section 4.5, Pharmacokinetic interactions the following tetx has been added: - The patient should be carefully monitored when initiating or discontinuing rifampicin treatment. ......(cimetidine, ranitidine) ..... Patients currently receiving diltiazem therapy should be carefully monitored when initiating or discontinuing therapy with anti-H2 agents. An adjustment in diltiazem daily dose may be necessary. - When possible, a non CYP3A4‑metabolised statin should be used together with diltiazem, otherwise close monitoring for signs and symptoms of a potential statin toxicity is required. .....and after its discontinuation....... - Special care should be taken when prescribing short-acting benzodiazepines metabolized by the CYP3A4 pathway in patients using diltiazem. In section 4.6 the following has been added: .....as well as in women of child-bearing potential not using effective contraception. ....... If use of diltiazem is considered medically essential, an alternative method of infant feeding should be instituted. In section 4.7 the following has been added: However, no studies have been performed. In section 4.8 the following has been presented in a table format: The following CIOMS frequency rating is used, when applicable: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to ≤1/100); rare (≥1/10,000 to ≤1/1,000); very rare (≤1/10,000); not known (cannot be estimated from the available data). Within each frequency grouping, adverse events are presented in order of decreasing seriousness. Very Common Common Uncommon Rare Not Known Blood and lymphatic system disorders Thrombocytopenia Psychiatric disorders nervousness, insomnia Mood changes (including depression) Nervous system disorders headache, dizziness extrapyramidal syndrome Cardiac disorders atrioventricular block (may be of first, second or third degree; bundle branch block may occur), palpitations bradycardia Sinotrial block, congestive heart failure, syncope Vascular disorders flushing orthostatic hypotension Vasculitis (including leukocytoclastic vasculitis) Gastrointestinal disorders constipation, dyspepsia, gastric pain, nausea vomiting, diarrhoea dry mouth Gingival hyperplasia Hepatobiliary disorders hepatic enzymes increase (AST, ALT, LDH, ALP increase) Hepatitis Musculoskeletal and connective tissue disorders Arthralgia Skin and subcutaneous tissue disorders erythema urticaria Photosensitivity (including lichenoid keratosis at sun exposed skin areas), angioneurotic oedema, erythema multiforme (including Steven- Johnson's syndrome and toxic epidermal necrolysis), sweating, exfoliative dermatitis, acute generalized exanthematous pustulosis, occasionally desquamative erythema with or without fever Reproductive system and breast disorders Gynecomastia General disorders and administration site conditions lower limb oedema (peripheral oedema) malaise Asthenia/fatigue In section 6.5 the following text has been added: ....packed in an outer cardboard carton. In section 10, date of revision of text has changed to March 2011 In section 4.4 there is the following new text:1.) .......with impaired renal function or patients with renal or hepatic impairment..... and the following text has been added:In section 4.5, the following text has been added:In section 4.5, Pharmacokinetic interactions the following tetx has been added: ......) .................In section 4.6 the following has been added: ...........In section 4.7 the following has been added: In section 4.8 the following has been presented in a table format: In section 6.5 the following text has been added: ....
· Severe bradycardia (resting pulse rate of less than 40 beats per minute) In the 7th bullet point there is an addition of a contraindication: · pulmonary congestion In section 4.4 there is the following new text: 1.) .......with impaired renal function or patients with renal or hepatic impairment..... and the following text has been added: 3. Prior to general anaesthesia, the anaesethist must be informed of ongoing diltiazem treatment. Depression of cardiac contractility, conductivity and automaticity, as well as the vascular dilatation associated with anaesthetics such as enflurane, halothane and isoflurane, may be potentiated by calcium channel blockers. 4. The risk of raised creatine kinease, myopathy and rhabdomyolisis due to statins (metabolised by CYP3A4) may be increased in case of a concomitant use of diltiazem. Closer monitoring for signs and symptoms is warranted in such case. 5. Calcium channel blocking agents, such as diltiazem, may be associated with mood changes, including depression. 6. Like other calcium channel antagonists, diltiazem has an inhibitory effect on intestinal motility. Therefore it should be used with caution in patients at risk to develop an intestinal obstruction. In section 4.5, the following text has been added: all the patients treated with calcium antagonists, the prescription of nitrate derivatives should only be carried out at gradually increasing doses. - The combination of diltiazem with an alpha-antagonist should be considered only with the strict monitoring of the blood pressure. Dantrolene (infusion) a lethal ventricular fibrillation is regularly observed in animals when intravenous verapamil and dantrolene are administered concomitantly. The combination of calcium antagonist and dantrolene is therefore potentially dangerous (see section 4.3 Contraindications). Due to the potential for additive effects, caution and careful titration are necessary in patients receiving diltiazem concomitantly with other agents known to affect cardiac contractility and/or conduction. - Since diltiazem has antiarrhythmic properties, its concomitant prescription with other antiarrhythmic agents is not recommended (additive risk of increased cardiac adverse effects). This combination should only be used under close clinical and ECG monitoring. In section 4.5, Pharmacokinetic interactions the following tetx has been added: - The patient should be carefully monitored when initiating or discontinuing rifampicin treatment. ......(cimetidine, ranitidine) ..... Patients currently receiving diltiazem therapy should be carefully monitored when initiating or discontinuing therapy with anti-H2 agents. An adjustment in diltiazem daily dose may be necessary. - When possible, a non CYP3A4‑metabolised statin should be used together with diltiazem, otherwise close monitoring for signs and symptoms of a potential statin toxicity is required. .....and after its discontinuation....... - Special care should be taken when prescribing short-acting benzodiazepines metabolized by the CYP3A4 pathway in patients using diltiazem. In section 4.6 the following has been added: .....as well as in women of child-bearing potential not using effective contraception. ....... If use of diltiazem is considered medically essential, an alternative method of infant feeding should be instituted. In section 4.7 the following has been added: However, no studies have been performed. In section 4.8 the following has been presented in a table format: The following CIOMS frequency rating is used, when applicable: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to ≤1/100); rare (≥1/10,000 to ≤1/1,000); very rare (≤1/10,000); not known (cannot be estimated from the available data). Within each frequency grouping, adverse events are presented in order of decreasing seriousness. Very Common Common Uncommon Rare Not Known Blood and lymphatic system disorders Thrombocytopenia Psychiatric disorders nervousness, insomnia Mood changes (including depression) Nervous system disorders headache, dizziness extrapyramidal syndrome Cardiac disorders atrioventricular block (may be of first, second or third degree; bundle branch block may occur), palpitations bradycardia Sinotrial block, congestive heart failure, syncope Vascular disorders flushing orthostatic hypotension Vasculitis (including leukocytoclastic vasculitis) Gastrointestinal disorders constipation, dyspepsia, gastric pain, nausea vomiting, diarrhoea dry mouth Gingival hyperplasia Hepatobiliary disorders hepatic enzymes increase (AST, ALT, LDH, ALP increase) Hepatitis Musculoskeletal and connective tissue disorders Arthralgia Skin and subcutaneous tissue disorders erythema urticaria Photosensitivity (including lichenoid keratosis at sun exposed skin areas), angioneurotic oedema, erythema multiforme (including Steven- Johnson's syndrome and toxic epidermal necrolysis), sweating, exfoliative dermatitis, acute generalized exanthematous pustulosis, occasionally desquamative erythema with or without fever Reproductive system and breast disorders Gynecomastia General disorders and administration site conditions lower limb oedema (peripheral oedema) malaise Asthenia/fatigue In section 6.5 the following text has been added: ....packed in an outer cardboard carton. In section 10, date of revision of text has changed to March 2011
· pulmonary congestion
3. Prior to general anaesthesia, the anaesethist must be informed of ongoing diltiazem treatment. Depression of cardiac contractility, conductivity and automaticity, as well as the vascular dilatation associated with anaesthetics such as enflurane, halothane and isoflurane, may be potentiated by calcium channel blockers.
4. The risk of raised creatine kinease, myopathy and rhabdomyolisis due to statins (metabolised by CYP3A4) may be increased in case of a concomitant use of diltiazem. Closer monitoring for signs and symptoms is warranted in such case.
5. Calcium channel blocking agents, such as diltiazem, may be associated with mood changes, including depression.
6. Like other calcium channel antagonists, diltiazem has an inhibitory effect on intestinal motility. Therefore it should be used with caution in patients at risk to develop an intestinal obstruction.
- The combination of diltiazem with an alpha-antagonist should be considered only with the strict monitoring of the blood pressure.
Dantrolene (infusion) a lethal ventricular fibrillation is regularly observed in animals when intravenous verapamil and dantrolene are administered concomitantly. The combination of calcium antagonist and dantrolene is therefore potentially dangerous
(see section 4.3 Contraindications).
- Since diltiazem has antiarrhythmic properties, its concomitant prescription with other antiarrhythmic agents is not recommended (additive risk of increased cardiac adverse effects). This combination should only be used under close clinical and ECG monitoring.
- The patient should be carefully monitored when initiating or discontinuing rifampicin treatment.
Patients currently receiving diltiazem therapy should be carefully monitored when initiating or discontinuing therapy with anti-H2 agents. An adjustment in diltiazem daily dose may be necessary.
- When possible, a non CYP3A4‑metabolised statin should be used together with diltiazem, otherwise close monitoring for signs and symptoms of a potential statin toxicity is required.
- Special care should be taken when prescribing short-acting benzodiazepines metabolized by the CYP3A4 pathway in patients using diltiazem.
However, no studies have been performed.
The following CIOMS frequency rating is used, when applicable: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to ≤1/100); rare (≥1/10,000 to ≤1/1,000); very rare (≤1/10,000); not known (cannot be estimated from the available data). Within each frequency grouping, adverse events are presented in order of decreasing seriousness.
Very Common
Common
Uncommon
Rare
Not Known
Blood and
lymphatic system
disorders
Thrombocytopenia
Psychiatric
nervousness,
insomnia
Mood changes
(including
depression)
Nervous system
headache,
dizziness
extrapyramidal
syndrome
Cardiac
atrioventricular
block (may be
of first, second
or third degree;
bundle branch
block may
occur),
palpitations
bradycardia
Sinotrial block,
congestive heart
failure, syncope
Vascular
flushing
orthostatic
hypotension
Vasculitis
leukocytoclastic
vasculitis)
Gastrointestinal
constipation,
dyspepsia,
gastric pain,
nausea
vomiting,
diarrhoea
dry mouth
Gingival
hyperplasia
Hepatobiliary
hepatic
enzymes
increase (AST,
ALT, LDH,
ALP increase)
Hepatitis
Musculoskeletal
and connective
tissue disorders
Arthralgia
Skin and
subcutaneous
erythema
urticaria
Photosensitivity
lichenoid keratosis
at sun exposed skin
areas),
angioneurotic
oedema, erythema
multiforme
(including Steven-
Johnson's
syndrome and toxic
epidermal
necrolysis),
sweating,
exfoliative
dermatitis, acute
generalized
exanthematous
pustulosis,
occasionally
desquamative
erythema with or
without fever
Reproductive
system and
breast disorders
Gynecomastia
General
disorders and
administration
site conditions
lower limb
oedema (peripheral oedema)
malaise
Asthenia/fatigue
Amended MA number and change to date of partial revision of text