Herbesser 30/Herbesser 60合心爽

Herbesser 30/Herbesser 60

diltiazem

Manufacturer:

Mitsubishi Tanabe Pharma

Distributor:

Primal
Full Prescribing Info
Contents
Diltiazem HCl.
Description
Herbesser 30: Tablet Size: Diameter 8 mm, thickness 3.5 mm, weight 0.19 g. Code: TA120.
Herbesser 60: Tablet Size: Diameter 8 mm, thickness 3.5 mm, weight 0.185 g. Code: TA125.
Diltiazem HCl is (2S,3S)-3-acetoxy-2,3-dihydro-2-(4-methoxyphenyl)-5-(2-dimethyl)-1-5-benzothiazepine-4(5H)-one monohydrochloride. Molecular Formula: C22H26N2O4S·HCl. Molecular Weight: 450.99. It occurs as white crystals or crystalline powder and odorless. It is very soluble in formic acid, freely soluble in water, in methanol and in chloroform, sparingly soluble in acetonitrile, slightly soluble in dehydrated ethanol and in acetic anhydride and practically insoluble in ether. Melting Point: 210-215°C (decomposition).
Action
Herbesser 30/Herbesser 60 are benzothiazepine-type calcium-antagonist products originally developed by Tanabe Seiyaku Co., Ltd. They are useful for the treatment of angina pectoris, variant angina and essential hypertension, which are due to the dilation of coronary blood vessels, relief of coronary spasms and dilation of peripheral blood vessels, etc, which are attributable to the calcium-antagonistic action of diltiazem HCl.
Pharmacology: The therapeutic benefits achieved with diltiazem HCl eg, improvement of myocardial ischemia and hypotensive effect are related to the ability to dilate blood vessels by inhibiting the influx of calcium ions into blood vessel smooth muscle cells eg, the coronary and peripheral blood vessels.
1. Effects on Myocardial Ischemia:
a. Effects of Improving the Balance of Myocardial Oxygen Demand and Supply:
1) To increase coronary blood flow into myocardial ischemic region by dilating the collateral channels and large coronary artery (dogs).
2) To suppress coronary artery spasms (monkeys, humans).
3) To decrease myocardial oxygen-consumption, without decreasing cardiac output, by decreasing afterload due to peripheral vasodilating effect and the heart rate (dogs).
b. Effect of Myocardial Protection: To retain cardiac function and myocardial energy metabolism and reduce the infarct size by inhibiting excess calcium ion influx into cells under myocardial ischemia (rats).
2. Action on Blood Pressure:
a. To lower elevated blood pressure gradually although they hardly affect normal blood pressure (rats, humans).
To suppress the elevation of blood pressure induced by exercise load (humans).
b. To lower blood pressure without decreasing cerebral and renal blood flow (dogs, humans).
c. To suppress myocardial and vascular hypertrophy together while lowering blood pressure (rats).
3. Action on Sinus Rhythms and the Cardiac Conduction System: To prolong slightly spontaneous sinus rhythm intervals and AV node conduction times. Not to affect the His-Purkinje conduction time (dogs, humans).
Pharmacokinetics: Plasma Level: When 2 tabs of Herbesser 30 (60 mg as diltiazem HCl) were orally administered to healthy adult men, its plasma level reached the peak 3-5 hrs after administration. The elimination half-life was about 4.5 hrs. In the long-term repeated oral administration of 90 mg (30 mg x 3)/day of diltiazem HCl to patients, plasma level at 2-4 hrs after administration was about 40 ng/mL.
Metabolism: When Herbesser 30 was orally administered to healthy adult men, diltiazem HCl was mainly metabolized by oxidative deamination, oxidative demethylation, deacetylation and conjugation.
Clinical Studies:
Angina Pectoris and Variant Angina: The usefulness of Herbesser 30 and Herbesser 60 in the treatment of angina pectoris was demonstrated by double-blind comparative studies, single-blind comparative studies and open studies. Their usefulness in the treatment of variant angina was demonstrated by open studies, including investigation with the Holter ECG.
Hypertension: The usefulness of Herbesser 30 and Herbesser 60 in the treatment of essential hypertension was demonstrated by 4 double-blind comparative studies with a placebo, reserpine and propranolol as control drugs.
Adverse Reactions: 442 cases (4.6%) of adverse reactions were reported out of total 9630 cases. The most common occurrences as well as their frequency were:
Gastrointestinal System: 1.4% (stomach discomfort 0.2%, constipation 0.2%, abdominal pain 0.1%, etc).
Cardiovascular System: 1.4% (dizziness 0.5%, bradycardia 0.4%, flush 0.2%, AV block 0.2%, etc).
Hypersensitivity: 1.2%.
Headache: 0.2%, etc.
Toxicology: Preclinical Studies:
Single-Dose Toxicity (LD50 mg/kg): See table.
Click on icon to see table/diagram/image
Repeated-Dose Toxicity: When 2, 10, 25 and 125 mg/kg/day and 10, 20 and 40 mg/kg/day of diltiazem HCl were orally given respectively to SD-strain rats and beagle dogs for 6 successive months, the mortal cases in the 125 mg/kg/day group and hepatic and renal impediments in the 25 and 12.5 mg/kg/day groups were observed in rats, but no influences were observed in the 2 and 10 mg/kg/day group. The mortal cases and abnormalities in ECG in the 40 mg/kg group were observed in beagle dogs and the transient increase in GOT and GPT in the 20 mg/kg/day group was observed.
Reproductive and Developmental Toxicity:
Administration Before Mating and During Pregnancy and Lactation: 12.5, 25, 50 and 100 mg/kg/day of diltiazem HCl were orally given to CFY strain rats. Adverse effects on reproductive function in parents and lethality, teratogenicity and growth retardation in fetuses and pups were not observed.
Administration during the period of fetal organogenesis 10, 25, 50, 100, 200 and 400 mg/kg/day and 10, 50, 100, 200 and 400 mg/kg/day of diltiazem HCl were orally given respectively to ICR-JCL strain mice and Wistar strain rats. The feticidal effects were observed in all groups of mice and in the 200 and 400 mg/kg/day groups of rats. Teratogenicity was observed in the 50, 100, 200 and 400 mg/kg/day groups of mice, but it was not observed even in the 400 mg/kg/day group of rats.
Administration During the Peri- and Postnatal Periods: 10, 50, 100, 200 and 400 mg/kg/day of diltiazem HCl were orally given to Wistar strain rats. As general conditions in dams changed for the worse, decreases in the birth rate and nursing rate and decreases in the viability rate and body weight gain of pups were observed in the 200 and 400 mg/kg/day group, but no remarkable change was observed in the 10, 50 and 100 mg/kg/day groups.
Antigenicity: The antigenicity of diltiazem HCl was not observed in guinea pigs, mice and rats.
Mutagenicity: The mutagenicity of diltiazem HCl was not observed either by the repair and reverse mutation test with bacteria, the chromosomal aberration test with cultured cells of mammalia or the micronucleus test with mice.
Carcinogenicity: The carcinogenicity of diltiazem HCl was not observed by the test with mice.
Indications/Uses
Angina pectoris, variant angina. Essential hypertension (mild to moderate case).
Dosage/Direction for Use
Angina Pectoris, Variant Angina: Usually for adults, 30 mg as diltiazem HCl 3 times/day orally. If needed, 30 mg may be increased to 60 mg.
Essential Hypertension (Mild to Moderate Cases): Usually for adults, 30-60 mg as diltiazem HCl 3 times/day orally.
The dose may be adjusted according to the age of the patients and the severity of the symptoms.
Swallow the tablets without chewing.
Contraindications
Patients having 2nd- or 3rd-degree atrioventricular block or sinoatrial block. Pregnant women and women suspected of being pregnant.
Special Precautions
General Precautions: Since it was reported that symptoms were aggravated after the sudden withdrawal of calcium-antagonist medication, the dose should be reduced gradually and the symptoms should be carefully observed if Herbesser 30/Herbesser 60 are to be withdrawn. Patients should be given precautions not to discontinue Herbesser 30/Herbesser 60 medication without a physician's direction.
Herbesser 30/Herbesser 60 are to be carefully administered to patients with severe bradycardia (<50 bpm) or with 1st-degree atrioventricular block.
Use in pregnancy & lactation: Since animal experiments have proven the teratogenic and feticidal effects of diltiazem HCl, the administration of Herbesser 30/Herbesser 60 is contraindicated to pregnant women and women suspected of being pregnant.
It is not recommended to administer Herbesser 30/Herbesser 60 to nursing mothers since it was reported that diltiazem HCl was excreted in human milk. If administration is necessitated, nursing should be avoided.
Use in children: The safety of Herbesser 30/Herbesser 60 in children has not been established.
Use in the elderly: Since excessive lowering of blood pressure is undesirable for the elderly, it is advisable to start with a low dose, and Herbesser 30/Herbesser 60 should be administered under careful supervision.
Adverse Reactions

1. Cardiovascular System: Dizziness, bradycardia, flush and A-V block (infrequently), palpitation (rarely), etc may occur. In such cases, the dose should be reduced or the medication should be discontinued.
2. Psychoneurologic System: Lassitude, headache and heaviness of head (infrequently), weakness (rarely), etc may occur.
3. Liver: Jaundice and hepatomegaly may rarely occur. Herbesser and Herbesser 60 should be withdrawn in such cases. GOT and GPT may be increased infrequently.
4. Hypersensitivity: Hypersensitive symptoms eg, eruptions (infrequently) and multiform erythematous eruptions (rarely) may occur. In such cases, the medication should be discontinued.
5. Gastrointestinal System: Stomach discomfort, constipation, abdominal pain, heartburn and anorexia (infrequently), soft stool, nausea, diarrhea and thirst (rarely), etc may occur.
Drug Interactions
Herbesser 30 and Herbesser 60 should be carefully administered in case of their concomitant use with the following drugs:
Antihypertensive Agents: The antihypertensive effect is enhanced.
Beta-Blocking Agents or Rauwolfia Preparations: Bradycardia may occur.
Carbamazepine: The plasma level of carbamazepine may be increased and it may cause carbamazepine-induced toxic symptoms eg, sleepiness, nausea, vomiting and vertigo, etc.
Digoxin Preparations: Plasma level of digoxin is increased.
Storage
Store in a tight and light-resistant container below 30°C.
ATC Classification
C08DB01 - diltiazem ; Belongs to the class of benzothiazepine derivative selective calcium-channel blockers with direct cardiac effects. Used in the treatment of cardiovascular diseases.
Presentation/Packing
Herbesser 30: Tab 30 mg x 1000's.
Herbesser 60: Tab 60 mg x 1000's.
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