Notes
Distributed by Sandoz Pty Ltd
1 Name of Medicine
Diltiazem hydrochloride.
2 Qualitative and Quantitative Composition
Diltiazem Sandoz CD capsules contain a blend of beads with controlled dissolution characteristics for once-a-day administration. The capsules are available as either 180 mg, 240 mg or 360 mg diltiazem hydrochloride in sustained release form.
Diltiazem hydrochloride is a white to off-white crystalline powder with a bitter taste. It is freely soluble in water, methanol, and chloroform.
For the full list of excipients, see Section 6.1 List of Excipients.
3 Pharmaceutical Form
Modified release capsule.
Diltiazem Sandoz CD is registered in 3 strengths:
180 mg. Light turquoise blue/blue capsule.
240 mg. Blue/blue capsule.
360 mg. Light blue/white capsule.
4 Clinical Particulars
4.9 Overdose
The oral LD50 in mice and rats ranged from 415 to 740 mg/kg and from 560 to 810 mg/kg, respectively. The intravenous LD50 in these species was 60 and 38 mg/kg, respectively. The oral LD50 in dogs is considered to be in excess of 50 mg/kg, while lethality was seen in monkeys at 360 mg/kg. The toxic dose in man is not known. Due to extensive metabolism, blood levels after a standard dose of diltiazem can vary over tenfold, limiting the usefulness of blood levels in overdose cases. There have been 29 cases of diltiazem overdose in doses ranging from less than 1 g to 10.8 g. Sixteen of these reports involved multiple drug ingestions. Twenty-two reports indicated patients had recovered from diltiazem overdose ranging from less than 1 g to 10.8 g. There were seven reports with a fatal outcome; although the amount of diltiazem ingested was unknown, multiple drug ingestions were confirmed in six of the seven reports.
The clinical effects of acute overdose can involve pronounced hypotension possibly leading to collapse and acute kidney injury, sinus bradycardia with or without isorhythmic dissociation, sinus arrest, cardiac arrest, heart block, cardiac failure and atrio-ventricular conduction disturbances. Most reports of overdose described some supportive medical measure and/or drug treatment.
Bradycardia frequently responded favourably to atropine as did heart block, although cardiac pacing was also frequently utilised to treat heart block. Fluids and vasopressors were used to maintain blood pressure, and in cases of cardiac failure inotropic agents were administered. In addition, some patients received treatment with ventilatory support, gastric lavage, activated charcoal, and/or intravenous calcium. Evidence of the effectiveness of intravenous calcium administration to reverse the pharmacological effects of diltiazem overdose was conflicting.
Non-cardiogenic pulmonary oedema has rarely been reported as a consequence of diltiazem overdose that may manifest with a delayed onset (24-48 hours post-ingestion) and require ventilatory support. Early resuscitative measures (including fluid resuscitation) to maintain perfusion and cardiac output may be precipitating factors due to fluid overload.
In the event of overdose or exaggerated response, appropriate supportive measures should be employed in addition to gastrointestinal decontamination. Diltiazem does not appear to be removed by peritoneal or haemodialysis. Based on the known pharmacological effects of diltiazem and/or reported clinical experiences, the following measures may be considered.
Bradycardia. Administer atropine (0.60 to 1.0 mg). If there is no response to vagal blockade administer isoprenaline cautiously.
High degree AV block. Treat as for bradycardia above. Fixed high-degree AV block should be treated with cardiac pacing.
Cardiac failure. Administer inotropic agents (isoprenaline, dopamine, or dobutamine) and diuretics.
Hypotension. Vasopressors (e.g. dopamine or noradrenaline acid tartrate).
Actual treatment and dosage should depend on the severity of the clinical situation and the judgement and experience of the treating physician.
Symptoms and signs of overdose may be delayed due to the controlled release properties of the product, so patients should be kept under observation for at least 24 hours.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26.
5 Pharmacological Properties
5.3 Preclinical Safety Data
Genotoxicity. No data available.
Carcinogenicity. No data available.
6 Pharmaceutical Particulars
6.7 Physicochemical Properties
Chemical structure. Diltiazem hydrochloride is a calcium ion influx inhibitor (slow channel blocker or calcium antagonist). Its molecular formula is C22H26N2O4S.HCl and it has the following structure:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSDILTIA.gif Chemically diltiazem hydrochloride is the hydrochloride salt of (2S, 3S)-5-(2-dimethylaminoethyl)-2, 3, 4, 5-tetrahydro-2-(4-methoxyphenyl)-4-oxo-1, 5-benzothiazepin-3-yl acetate. It has a molecular weight of 450.98.
CAS number. CAS 33286-22-5.
7 Medicine Schedule (Poisons Standard)
Prescription Only Medicine (Schedule 4).
Summary Table of Changes
https://stagingapi.mims.com/au/public/v2/images/fulltablegif/DISACDST.gif
