Diltiazem 24 hour modified release preparations
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
24 hour modified release formulations of diltiazem hydrochloride.
Drugs List
Therapeutic Indications
Uses
Hypertension - mild to moderate
Prophylaxis of angina pectoris
Treatment of angina pectoris
Dosage
Dosage requirements may differ between patients with angina and patients with hypertension.
Careful titration should be considered where appropriate, as individual response may vary. Dosage requirements can differ significantly between individuals.
Different modified release preparations may not have the same clinical effect. Prescribers should specify the brand to be supplied.
Different modified release preparations may have different recommended initial and maximum doses. Consult specific brand literature.
Adults
Hypertension
The usual starting dose is 180 mg to 240 mg once daily depending on formulation used.
The dose may be increased after 2 to 4 weeks according to the patient's response and the usual maintenance dose is 240 to 360 mg once daily. The maximum dose is 500 mg.
However, the single doses of 300 mg and 360 mg should only be administered to patients when no satisfactory response has been seen with lower doses and after the benefit risk ratio has been carefully assessed by the doctor.
Angina
Care should be taken when titrating patients with stable angina in order to establish the optimal dose. The usual starting dose is 180 mg to 240 mg once daily depending on formulation used.
The dose may be increased after 2 to 4 weeks according to the patient's response. The maximum daily dose is 500 mg.
How ever, the single daily dose of 300 mg and 360 mg should only be administered to patients when no satisfactory therapeutic effect has been effected with lower doses and after the benefit risk ratio has been carefully assessed by the doctor.
Elderly
The initial dose for the elderly varies between brands.
Use with caution. Increased plasma concentrations of diltiazem may be seen in these patients.
The usual starting dose 120 mg once daily. The dose may be increased slowly if necessary but careful monitoring of the patient is advised. Do not increase the dose if the pulse rate falls below 50 beats per minute.
Elderly patients transferring to once daily diltiazem capsules should receive the same total daily dose of diltiazem, titrating upwards as required.
Patients with Renal Impairment
Use with caution. Increased plasma concentrations of diltiazem may be seen in these patients.
The usual starting dose 120 mg once daily. The dose may be increased slowly if necessary but careful monitoring of the patient is advised. Do not increase the dose if the pulse rate falls below 50 beats per minute.
Patients with Hepatic Impairment
Use with caution. Increased plasma concentrations of diltiazem may be seen in these patients.
The usual starting dose 120 mg once daily. The dose may be increased slowly if necessary but careful monitoring of the patient is advised. Do not increase the dose if the pulse rate falls below 50 beats per minute.
Contraindications
Children under 18 years
Systolic blood pressure < 90mmHg
Bradycardia - if treating myocardial infarction
Bradycardia with pulse rate at rest < 50 beats per minute
Cardiogenic shock
Cerebrovascular accident
Decompensated cardiac failure
Hypotension - if treating myocardial infarction
Left ventricular dysfunction - if treating myocardial infarction
Left ventricular failure with stasis
Lown-Ganong-Levine syndrome
Non paced second/third degree AV block
Non-paced sinus node dysfunction
Porphyria
Pregnancy
Pulmonary oedema
Wolff-Parkinson-White syndrome
Precautions and Warnings
Elderly
Females of childbearing potential
Predisposition to gastrointestinal obstruction
Bradycardia
Breastfeeding
Bronchial hyperreactivity
Crohn's disease
Diabetes mellitus
First degree atrioventricular block
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hereditary fructose intolerance
Myasthenia gravis
Reduced left ventricular function
Renal impairment
Severe hypotension
Ulcerative colitis
Anaesthetist should be made aware patient is taking this medication
Avoid concurrent use of beta blockers in patients with conduction defects
May exacerbate asthma
Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Some formulations contain sucrose
Some products may contain soya or soya derivative
Prescribing by brand recommended to ensure consistent bioavailability
The release profile of some brands may be affected by short GI transit time
Exclude pregnancy prior to initiation of treatment
Monitor antidiabetic drug treatment
Monitor patients with existing or tendency towards diabetes mellitus
Monitor respiratory function
Advise patient to report any new or worsening respiratory symptoms
May cause bronchospasm
Patient should be made aware of possible adverse effects on mood/behaviour
Abrupt withdrawal may be associated with exacerbation of angina
Discontinue treatment if angina appears or worsens
Reduce dose in elderly
The release profile of some brands may be affected by alcohol
Advise patient grapefruit products may increase plasma level
Female: Ensure adequate contraception during treatment
Advise patients that empty tablet/capsule may be observed in stools
Calcium channel blockers do not reduce the risk of myocardial infarction in unstable angina. The use of diltiazem should be reversed for patients resistant to treatment with beta-blockers. However, because of the risk of bradycardia diltiazem should be used with caution in association with beta-blockers. Avoid concurrent use of beta blockers with diltiazem in patients with pre-existing conduction defects.
Acute renal failure secondary to decreased renal perfusion has been reported in patients with reduced left ventricular function, severe bradycardia or severe hypotension.
In elderly patients or those with renal or hepatic insufficiency monitor closely, particularly heart rate, at the beginning of treatment.
Pregnancy and Lactation
Pregnancy
Diltiazem is contraindicated in pregnancy.
Animal studies in rats, rabbits and mice revealed an increase in embryonic and foetal mortality. Skeletal abnormalities and digital defects were reported. Schaefer (2007) comments, that for antiarrhythmic therapy, although animal data indicate teratogenic developmental disturbances of distal phalanges, similar effects have not been seen in human pregnancies and in the class IV antiarrhythmic drugs diltiazem is acceptable.
There is little experience with the use of diltiazem in the first trimester of pregnancy. Early embryonic differentiation may be disturbed with results including digital defects. Diltiazem may suppress the contractility of the uterus, however comprehensive evidence that this will prolong the partus in full-term pregnancy is lacking. A risk of hypoxia in the foetus may arise in the event of hypotension in the mother and reduced perfusion of the uterus. One study reported there may be a association with cardiovascular defects in newborns and the use of diltiazem in the first trimester of pregnancy, but maternal disease, concurrent drug use and chance can not be ruled out.
Schaefer (2007) comments that in the first trimester, calcium antagonists are considered to be second line therapy and suggests that following exposure during the first trimester a detailed ultrasound examination should be undertaken, but neither invasive diagnostic procedures or termination of pregnancy are required.
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 diltiazem with caution in breastfeeding.
Diltiazem is excreted in human breast milk with approximately equal concentration in maternal serum and the breast milk. The quantities ingested by the infant are likely to be small and Hale (2010) considers the quantity unlikely to be problematic. Use of diltiazem should be avoided unless there is no safer alternative. Schaefer (2007) considers diltiazem to be one of the calcium channel blockers of choice for hypertension while breastfeeding. Possible effects on the infant include hypotension and bradycardia.
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 pain
Acute generalised exanthematous pustulosis
Acute renal failure
Aggravation of existing asthma
Allergic skin reactions
Amblyopia
Amnesia
Angina
Angioneurotic oedema
Anorexia
Arrhythmias
Asthenia
Atrioventricular block
Bradycardia
Bronchospasm
Bundle branch block
Congestive cardiac failure
Constipation
Creatine kinase increased
Depression
Desquamative erythema
Diarrhoea
Dizziness
Drowsiness
Dry mouth
Dyspepsia
Dyspnoea
Eosinophilia
Epistaxis
Erythema
Erythema multiforme
Exfoliative dermatitis
Extrapyramidal effects
Eye irritation
Fatigue
Fever
Flushing
Gait abnormality
Gastric pain
Gastro-intestinal symptoms
Gingival hyperplasia
Gingivitis
Gynaecomastia
Hallucinations
Headache
Hepatitis
Hyperglycaemia
Hyperpigmentation
Hypotension
Impotence
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Increase in serum ALT/AST
Insomnia
Leukocytoclastic vasculitis
Lichenoid keratosis
Lower limb oedema
Lymphadenopathy
Malaise
Mood changes
Muscle pain
Muscle weakness
Nasal congestion
Nausea
Nervousness
Nocturia
Oedema
Orthostatic hypotension
Osteoarticular pain
Palpitations
Paraesthesia
Parkinsonism
Personality change
Petechiae
Photosensitivity
Polyuria
Pruritus
Rash
Sexual dysfunction
Sino-atrial block
Somnolence
Stevens-Johnson syndrome
Sweating
Syncope
Taste disturbances
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Tremor
Urticaria
Vasculitis
Vomiting
Weight gain
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: September 2014
Reference Sources
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, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press Accessed on 24 September, 2014.
Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.
Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.
Summary of Product Characteristics: Adizem-XL capsules. Napp Pharmaceuticals Ltd. Revised November 2011.
Summary of Product Characteristics: Angitil SR/XL 90,120,180, 240 and 300 mg Prolonged Release capsules. Chiesi Ltd. Revised October 2013.
Summary of Product Characteristics: Dilzem XL 120mg hard-capsules. Cephalon (UK) Ltd. Revised March 2012.
Summary of Product Characteristics: Dilzem XL 180mg hard-capsules. Cephalon (UK) Ltd. Revised March 2012.
Summary of Product Characteristics: Dilzem XL 240mg hard-capsules. Cephalon (UK) Ltd. Revised March 2012.
Summary of Product Characteristics: Slozem 120mg, 180mg, 240mg, 300mg capsules. Zentiva. Revised July 2020.
Summary of Product Characteristics: Tildiem LA 200 prolonged release capsules. Sanofi-Aventis. Revised May 2020.
Summary of Product Characteristics: Tildiem LA 300 prolonged release capsules. Sanofi-Aventis. Revised May 2020.
Summary of Product Characteristics: Uard XL 120mg. Ennogen Healthcare Ltd. Revised November 2011.
Summary of Product Characteristics: Uard XL 180mg. Ennogen Healthcare Ltd. Revised November 2011.
Summary of Product Characteristics: Uard XL 240mg. Ennogen Healthcare Ltd. Revised November 2011.
Summary of Product Characteristics: Uard XL 300mg. Ennogen Healthcare Ltd. Revised November 2011.
Summary of Product Characteristics: Viazem XL 120mg. Genus Pharmaceuticals. Revised November 2011.
Summary of Product Characteristics: Viazem XL 180mg. Genus Pharmaceuticals. Revised November 2011.
Summary of Product Characteristics: Viazem XL 240mg. Genus Pharmaceuticals. Revised November 2011.
Summary of Product Characteristics: Viazem XL 300mg. Genus Pharmaceuticals. Revised November 2011.
Summary of Product Characteristics: Viazem XL 360mg. Genus Pharmaceuticals. Revised November 2011.
Summary of Product Characteristics: Zemtard 120XL. Galen Limited. Revised November 2012.
Summary of Product Characteristics: Zemtard 180XL. Galen Limited. Revised November 2012.
Summary of Product Characteristics: Zemtard 240XL. Galen Limited. Revised November 2012.
Summary of Product Characteristics: Zemtard 300XL. Galen Limited. Revised November 2012.
National Institute for Health and Clinical excellence (NICE) clinical guidance 107: Hypertension in pregnancy. Issue date August 2010
Available at: https://guidance.nice.org.uk/CG107
Last accessed: 24 September, 2014.
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
Diltiazem Last revised: 7 September, 2013
Last accessed: 24 September, 2014
The Norwegian Porphyria Centre (NAPOS).
Available at: https://www.drugs-porphyria.com/languages/UnitedKingdom/s1.php?l=gbr
Last revised: 1 October, 2004
Last accessed: 24 September, 2014
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.