Diltiazem interactions

Important differences between the available calcium channel blockers arise from the details of their interactions with cardiac ion channels and, as noted above, differences in their relative smooth muscle versus cardiac effects. Sodium channel block is modest with verapamil, and still less marked with diltiazem. It is negligible with nifedipine and other dihydropyridines. Verapamil and diltiazem interact kinetically with the calcium channel receptor in a different manner than the dihydropyridines they block tachycardias in calcium-dependent cells, eg, the atrioventricular node, more selectively than do the dihydropyridines. (See Chapter 14 for additional details.) On the other hand, the dihydropyridines appear to block smooth muscle calcium channels at concentrations below those required for significant cardiac effects they are therefore less depressant on the heart than verapamil or diltiazem. 

Diltiazem interacts with lovastatin but not with pravastatin (96). In 10 healthy volunteers given lovastatin orally with or without intravenous diltiazem in a randomized, two-way, crossover design, the interaction of diltiazem with lovastatin was primarily a first-pass effect, due to inhibition of CYP3A4 (97). Thus, drug interactions with diltiazem may become evident when a patient is switched from intravenous to oral dosing. 

However, diltiazem interacts with lovastatin although not with pravastatin (SEDA-24, 511). 

Oyama Y, Fuji S, Kanda K, Akino E, Kawasaki H, Nagata M, Goto K. Digoxin-diltiazem interaction. Am J Cardiol 1984 53(10) 1480-1. 

Smith CL, Hampton EM, Pederson JA, Pennington LR, Bourne DW. Clinical and medicoeconomic impact of the cyclosporine-diltiazem interaction in renal transplant recipients. Pharmacotherapy 1994 14(4) 471-81. 

Thomas AR, Chan LN, Bauman JL, Olopade CO. Prolongation of the QT interval related to cisapride-diltiazem interaction. Pharmacotherapy 1998 18(2) 381-5. 

However, diltiazem interacts with lovastatin although not with pravastatin (SEDA-24, 511), and an interaction has also been observed with simvastatin in a 75-year-old... 

The specific Ca channel antagoni.sts verapamil, nifedipine, and diltiazem interact at specific sites on the calcium channel protein. These blockers do not occlude the channel physically but bind to sites in the channel, as they can promote both channel activation and antagonism. AITiniiy fix binding sites on the channel varies, depending un the status of the channel. The channel can exist in either an open (0. re.sting (R). or inactivated (I) state, and the equilibrium lx-, tween them is determined by stimulus frequency and mem-... 

Yust I, Hoffman M, Aronson RJ, Life-threatening bradycardic reactions due to beta blocker-diltiazem interactions, IsrJMedSci (1992) 28, 292-4,... 

Jones WN, Kem KB, Rindone JP, Mayerschn M, Bliss M, Goldman S. Di xin-diltiazem interaction a phannacokinetic evaluation. EurJ Clin Pharmacol (19Z6) 31,351—3. 

LarmanRC. A pharmacokinetic evahiationofthe digoxin-diltiazem interaction. JPho/m/Sbi (1987) 76, S79. 

Pochet JM, Pirson Y. Cyclosporin-diltiazem interaction. Lancet (1986) i, 979. 

Sabate I, Grind JM, Castelao AM, Huguet J, Seron D, Blanco A. Cyclosporin-diltiazem interaction comparison of cyclosporin levels measured with two monoclonal antibodies. Transplant Proc (1989) 21,1460-1. 

The clinical relevance of the diltiazem interaction was demonstrated in a 53-year-old man, who developed rhabdomyolysis 3 months after diltiazem 30 mg four times daily was added to established treatment with simvastatin 40 mg daily. Both drugs were discontinued and he recovered over the following 10 days. Other similar cases have also been report-ed.3- 3... 

Fig. 20.13. Potential H-bonding energy, released upon interaction with the transmembrane domains of P-gp (in arbitrary energy units, EU) for progesterone (1), propranolol (2), amitriptyline (3), diltiazem (4), amiodarone (5), colchicine (7), gramicidin S (8), daunorubicin (9), vinblastine (10), cyclosporin A, in comparison with verapamil...

Caution is needed to avoid potential drug interactions. Tamsulosin decreases metabolism of cimetidine and diltiazem. Carbamazepine and phenytoin increase catabolism of a-adrenergic antagonists. 

Aprepitant (Emend) [Centrally Acting Antiemetic] Uses Pre-vents N/V assoc w/ emetogenic CA chemo (eg, cisplatin) (use in combo w/ other antiemetics) Action Substance P/neurokinin l(NKi) receptor antagonist Dose 125 mg PO day 1, 1 h before chemo, then 80 mg PO qAM days 2 3 Caution [B, /-] Contra Use w/ pimozide, Disp Caps SE Fatigue, asthenia, hiccups Interactions T Effects W/ clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin T effects OF alprazolam, astem-izole, cisapride, dexamethasone, methylprednisolone, midazolam, pimozide, terfe-nadine, triazolam, chemo agents, eg, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, paclitaxel, vinblastine, vincristine, vinorelbine i effects W/ paroxetine,... 

Buspirone (BuSpar) [Anxiolytic] WARNING Closely monitor for worsening depression or emergence of suicidality Uses Short-term relief of anxiety Action Antianxiety antagonizes CNS serotonin receptors Dose Initial 7.5 mg PO bid T by 5 mg q2-3d to effect usual 20-30 mg/d max 60 mg/d Contra w/ MAOI Caution [B, /-] Avoid w/ severe hepatic/renal insuff Disp Tabs SE Drowsiness, dizziness, HA, N, EPS, serotonin synd, hostility, depression Notes No abuse potential or physical/psychologic d endence Interactions T Effects W/ erythromycin, clarithromycin, itraconazole, ketoconazole, diltiazem, verapamil, grapefruit juice effects W/ carbamazepine, rifampin, phenytoin, dexamethasone, phenobarbital, fluoxetine EMS T Sedation w/ concurrent EtOH use grapefruit juice may T risk of adverse effects OD May cause dizziness, miosis, N/V symptomatic and supportive... 

Imipramine (Tofranil) [Antidepressant/TCA] WARNING Close observation for suicidal thinking or unusual changes in behavior Uses Depres-sion, enuresis, panic attack, chronic pain Action TCA t CNS synaptic serotonin or norepinephrine Dose Adults. Hospitalized Initial 100 mg/24 h PO in doses T over several wk 300 mg/d max Output Maint 50-150 mg PO hs, 300 mg/24 h max Peds. Antidepressant 1.5-5 mg/kg/24 h daUy-qid Enuresis >6 y 10-25 mg PO qhs T by 10-25 mg at 1-2-wk int vals (max 50 mg for 6-12 y, 75 mg for >12 y) Rx for 2-3 mo, then tap Caution [D, /-] Contra Use w/ MAOIs, NAG, acute recovery from MI, PRG, CHF, angina, CVD, arrhythmias Disp Tabs, caps SE CV Sxs, dizziness, xerostomia, discolored urine Interactions t Effects W/ amiodarone, anticholinergics, BBs, cimetidine, diltiazem, Li, OCPs, quinidine, phenothiazines, ritonavir, verapamil, EtOH, evening primrose oil t effects OF CNS depressants, hypoglycemics, warfarin T risk of serotonin synd W/MAOIs 4-... 

Lovastatin (Mevacor/ Altocor) [Antilipemic/HMG-CoA Reductase Inhibitor] Uses Hypercholesterolemia Action HMG-CoA reductase inhibitor Dose 20 mg/d PO w/ PM meal may T at 4-wk intervals to 80 mg/d max or 60 mg ER tab take w/ meals Caution [X, -] Avoid w/ grapefruit juice, gemfibrozil. Contra Active liver Dz Disp Tabs SE HA GI intolerance common promptly report any unexplained muscle pain, tenderness, or weakness (myopathy) Interactions T Effects W/ grapefruit juice T risk of severe myopathy W/ azole antifungals, cyclosporine, erythromycin, gemfibrozil, HMG-CoA inhibitors, niacin T effects OF warfarin >1 effects W/ isradipine, pectin EMS t Risk of photosensitivity Rxns T effects of warfarin concurrent EtOH use t risk of liver tox diltiazem and verapamil can T risk of lovastatin tox OD Unlikely to cause life-threatening Sxs... 

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