1: Clin Calcium. 2005 Oct;15(10):1709-16.


[Clinically significant drug-drug and drug-food interactions associated with calcium channel blockers]

[Article in Japanese]

Imaura M, Ohno Y, Nakajima K, Suzuki H.

Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, University of Tokyo.

Calcium channel blockers have been widely used for treatment of hypertension, angina pectoris, arrhythmia, and other heart diseases. Nowadays, combination therapy is widely common for these diseases. However, combination therapy is associated with increasing risks of pharmacokinetic or pharmacodynamic drug-drug interaction, and therefore clinicians should pay attention to prevent it. Furthermore, in addition to drug-drug interactions, we need to be cautions for drug interaction with food and drink including health-food and supplement.

Publication Types:
English Abstract
Review

PMID: 16199918 [PubMed - indexed for MEDLINE]

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2: Clin Pharmacokinet. 1991 Dec;21(6):448-60.


Pharmacokinetic interactions with calcium channel antagonists (Part II).

Schlanz KD, Myre SA, Bottorff MB.

Division of Clinical and Hospital Pharmacy, College of Pharmacy, University of Cincinnati Medical Center, Ohio.

Since calcium channel antagonists are a diverse class of drugs frequently administered in combination with other agents, the potential for clinically significant pharmacokinetic drug interactions exists. These interactions occur most frequently via altered hepatic blood flow and impaired hepatic enzyme activity. Part I of the article, which appeared in the previous issue of the Journal, dealt with interactions between calcium antagonists and marker compounds, theophylline, midazolam, lithium, doxorubicin, oral hypoglycaemics and cardiac drugs. Part II examines interactions with cyclosporin, anaesthetics, carbamazepine and cardiovascular agents.

Publication Types:
Review

PMID: 1782739 [PubMed - indexed for MEDLINE]

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3: Clin Pharmacokinet. 1991 Nov;21(5):344-56.


Pharmacokinetic interactions with calcium channel antagonists (Part I).

Schlanz KD, Myre SA, Bottorff MB.

Division of Clinical and Hospital Pharmacy, College of Pharmacy, University of Cincinnati Medical Center, Ohio.

Calcium channel antagonists are a diverse class of drugs widely used in combination with other therapeutic agents. The potential exists for many clinically significant pharmacokinetic interactions between these and other concurrently administered drugs. The mechanisms of calcium channel antagonist-induced changes in drug metabolism include altered hepatic blood flow and impaired hepatic enzyme metabolising activity. Increases in serum concentrations and/or reductions in clearance have been reported for several drugs used with a number of calcium channel antagonists. A number of reports and studies of calcium channel antagonist interactions have yielded contradictory results and the clinical significance of pharmacokinetic changes seen with these agents is ill-defined. The first part of this article deals with interactions between calcium antagonists and marker compounds, theophylline, midazolam, lithium, doxorubicin, oral hypoglycaemics and cardiac drugs.

Publication Types:
Review

PMID: 1773549 [PubMed - indexed for MEDLINE]

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4: Gen Pharmacol. 1990;21(2):171-4.


Interactions between analgesics and calcium channel blockers.

Miranda HF, Paeile C.

Department of Pharmacology, Faculty of Medicine, Universidad de Chile, Santiago.

1. The findings, derived from different experimental models, examined in this review, provide evidence that the calcium channel blockers and related drugs possess analgesic effects. 2. The antinociceptive action that some analgesic drugs exhibit may be related to calcium channel blockade. 3. Evidence from a variety of biochemical and pharmacological experimental approaches, support the existence of an interelation between the calcium modulators and the opioid drugs. 4. This idea agrees with the novel neuropharmacological hypothesis that a common very high affinity binding site for multiple neurotransmitters could exist, as has been proposed by Pasternak and Wood (1986). 5. This hypothesis could be extended to the neuromodulators or other neuromediators.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 2185118 [PubMed - indexed for MEDLINE]

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5: Cardiovasc Drugs Ther. 1988 Jul;2(2):177-89.


Calcium channel antagonists. Part IV: Side effects and contraindications drug interactions and combinations.

Opie LH.

Department of Medicine, University of Cape Town, Medical School, Observatory, Republic of South Africa.

With the correct selection of drug and patient, the calcium antagonists as a group can be remarkably effective at relatively low cost of serious side effects. Almost all side effects are dose related. Minor side effects include those caused by vasodilation (flushing and headaches), constipation (verapamil), and ankle edema. Serious side effects are rare and result from improper use of these agents, as when intravenous verapamil (or diltiazem) is given to patients with sinus or atrioventricular nodal depression from drugs or disease, or nifedipine to patients with aortic stenosis. The potential of a marked negative inotropic effect is usually offset by afterload reduction, especially in the case of nifedipine which actually has the most marked negative inotropic effect. Yet caution is required when even calcium antagonists, especially verapamil, are given to patients with myocardial failure unless caused by hypertensive heart disease. Drug interactions of calcium antagonists occur with other cardiovascular agents such as alpha-adrenergic blockers, beta-adrenergic blockers, digoxin, quinidine, and disopyramide. The most marked interaction with digoxin is that with verapamil, which may raise digoxin levels by over 50%. Combination therapy of calcium antagonists with beta-blockers is increasingly common, and is probably safest in the case of dihydropyridines. Other combinations being explored are those with angiotensin-converting enzyme inhibitors and diuretics.

Publication Types:
Review

PMID: 3154704 [PubMed - indexed for MEDLINE]

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6: Pharmacol Toxicol. 1988 Jul;63(1):1-7.


Interactions between calcium channel blockers and non-cardiovascular drugs: interactions with anticancer drugs.

Baeyens JM.

Department of Pharmacology, University of Granada Medical School, Spain.

Publication Types:
Review

PMID: 3041398 [PubMed - indexed for MEDLINE]

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7: Pharmacol Toxicol. 1988 Feb;62(2):59-63.


Interactions between calcium channel blockers and non-cardiovascular drugs: interactions with drugs acting at the neuromuscular or the CNS level.

Baeyens JM, Del Pozo E.

Department of Pharmacology, University of Granada Medical School, Spain.

Publication Types:
Review

PMID: 3281158 [PubMed - indexed for MEDLINE]

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8: Cardiovasc Drugs Ther. 1987 Aug;1(2):183-9.


Pharmacokinetic drug interactions between digoxin and antiarrhythmic agents and calcium channel blocking agents: an appraisal of study methodology.

Antman EM, Arnold JM, Friedman PL, Smith TW.

Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.

While preliminary screening for interactions between new cardiovascular pharmacotherapeutic agents and digoxin can be efficiently and safely conducted in normal healthy volunteers, it is particularly important to detect and quantify drug interactions in patients with varying degrees of cardiac, hepatic and/or renal dysfunction. Much of the previously published literature provides only minimal data to guide clinical practice because of limitations of study design including sample size and measurement techniques. Important factors that determine the ability of a particular study design to detect a drug interaction with digoxin include the accuracy and precision of the assay method for serum digoxin concentrations, intrasubject and intersubject variability in serum digoxin concentration, and sample size. The format of the trial (chronic versus single digoxin dosing in cardiac patients; chronic versus single digoxin dosing in normal subjects) and the method of assessment of alterations in digoxin handling (formal determination of digoxin clearance, comparison of multiple or single digoxin measurements during various phases of trial) also impact greatly on the clinical relevance of such investigations. Guidelines for future studies of drug interactions with digoxin in cardiac patients are proposed with particular emphasis on laboratory methods; measurement techniques during baseline, placebo, and active drug phases; calculation of the statistical power of the study; time course of the trial; and assessment of the clinical significance of the findings.

Publication Types:
Clinical Trial
Controlled Clinical Trial
Review

PMID: 3154322 [PubMed - indexed for MEDLINE]

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9: Acta Pharmacol Toxicol (Copenh). 1986;58 Suppl 2:119-30.


Calcium channel blockers: spectrum of side effects and drug interactions.

Hedner T.

Calcium antagonists are a chemically heterogenous group of agents with potent cardiovascular effects which are beneficial in the treatment of angina pectoris, arterial hypertension and cardiac arrhythmias. The main side effects for the group are dose-dependent and the result of the main action or actions of the calcium antagonists, i.e. vasodilatation, negative inotropic effects and antiarrhythmic effects. Pronounced hypotension is reported for the main calcium antagonist drugs; verapamil, diltiazem and nifedipine. While conduction disturbances and bradycardia are seen more often after verapamil and diltiazem, tachycardia, headache and flush are more frequent after nifedipine. Constipation is relatively frequent after verapamil while nifedipine is reported to induce diarrhea in som patients. Idiosyncratic side effects are rare but have been reported from the skin, mouth, musculoskeletal system, the liver and the central nervous system. These side effects include urticarial rashes, gingival hyperplasia, arthralgia, hepathotoxicity and transistory mental confusion or akathisia. Verapamil, diltiazem and possibly also nifedipine have been reported to increase serum digoxin concentrations but the clinical relevance of these drug interactions are not clear. Furthermore, verapamil and diltiazem may potentiate the effects of beta-adrenergic blocking drugs and verapamil may also potentiate the effects of neuromuscular blocking drugs. It is concluded that side effects after calcium antagonist drugs are mostly trivial and transient although they may sometimes be relatively common. Clinically relevant drug interactions are few. Judged from the point of efficacy and safety, calcium antagonists will have a major place in the future pharmacotherapy of several cardiovascular disorders.

Publication Types:
Review

PMID: 2872768 [PubMed - indexed for MEDLINE]