The plasma levels of diltiazem, isradipine and nifedipine areincreased by cimetidine and it may possibly be necessary to reduce dosages of these calcium-channel blockers. High doses ofcimetidine may increase bioavailability of lercanidipine. Although studies suggest no important interactions occur betweennicardipine or nisoldipine and cimetidine, manufacturers advise caution. Plasma felodipine,lacidipine, nimodipine, and nitrendipine levels are also increased by cimetidine, but thisseems to be clinically unimportant. Cimetidine does not interactwith amlodipine. It is uncertain whether cimetidine interacts significantly with verapamil. Ranitidine appears to interact onlyminimally with calcium-channel blockers,if at all. Famotidinedoes not interact pharmacokinetically with nifedipine.
A crossover study in 12 healthy subjects found that cimetidine 400mg twice daily for 14 days had no effect on pharmacokinetics of amlodipine 10mg (See reference number 1)
Cimetidine 300mg before meals and at bedtime for a week increased AUC of a single 60mg oral dose of diltiazem by 50 % in 6 healthy subjects and increased peak plasma levels by 57%. Ranitidine 150mg twice daily for a week increased AUC of diltiazem by 15%, but this was not statistically significant (See reference number 2). Increases in serum levels and AUC of diltiazem of 40 % and 25 to 50%, respectively, were seen in another study using ci
Cimetidine 1 g daily increased AUC of felodipine 10mg by 56%, and raised peak serum level by 54 % in 12 subjects. There was a short lasting effect on their heart rates but clinical effects were minimal (See reference number 4).
The manufacturer of isradipine(See reference number 5) notes that cimetidine increases bioavailability of isradipine by about 50%
A single 800mg dose of cimetidine increased maximum plasma level of a single 4mg dose of lacidipine by 59 % and increased AUC by 74 % in one study in healthy subjects
Cimetidine 800mg daily causes no significant alteration in plasma levels of lercanidipine but manufacturer says that bioavailability of lercanidipine and its hypotensive effects may be increased by higher doses of
No adverse interaction was seen in 22 patients given calcium-channel blockers,including nicardipine, with oral famotidine for 6 to 8 weeks (See reference number 8). No changes in pharmacokinetics or pharmacodynamics of a 12-hour intravenous infusion of nicardipine 24mg were seen in 12 healthy subjects given intravenous cimetidine 300mg every 6 hrs for 48 hrs (See reference number 9).
Cimetidine 1 g daily for a week increased AUC of nifedipine 40mg daily by about 60 % and increased maximum plasma levels by about 90%. Ranitidine 150mg twice daily for a week caused an insignificant rise of about 25 % in maximum nifedipine plasma levels and AUC (See reference number 10). Seven hypertensive patients had a fall in mean blood pressure from 127 to 109 mmHg after taking nifedipine 40mg daily for 4 weeks,and a further fall to 95 mmHg after they also took cimetidine 1 g daily for 3 weeks. When they took ranitidine 300mg instead of cimetidine,there was an insignificant fall in blood pressure (See reference number 10,11).
Other studies clearly confirm that cimetidine causes a very significant rise in plasma nifedipine levels and an increase in its effects,whereas ranitidine interacts only minimally (See reference number 12-18).
A study found no pharmacokinetic interaction between nifedipine and famotidine, but famotidine reversed effects of nifedipine on systolic time intervals and significantly reduced stroke volume and cardiac output (See reference number 19,20). No adverse interaction was seen in 22 patients given calcium-channel blockers,including nifedipine, with famotidine for 6 to 8 weeks (See reference number 8).
Cimetidine 1 g daily for 7 days increased bioavailability of nimodipine 30mg three times daily in 8 healthy subjects by 75%, but haemodynamic effects were unchanged. Ranitidine did not interact (See reference number 21).
A study in 8 healthy subjects found that taking cimetidine 1 g in divided doses on day before study and then three 200mg doses every 4 hrs on study day, increased bioavailability of a single 10mg dose of nisoldipine by about 50%, but haemodynamic effects of nisoldipine were unaltered (See reference number 22). Ranitidine does not interact with nisoldipine (See reference number 23).
Cimetidine 800mg given before, and 400mg in divided doses given after, a single 20mg dose of nitrendipine was found to increase its bioavailability by 154 % but haemodynamic effects were unchanged (See reference number 24). Another study found that ranitidine increased AUC of oral nitrendipine 20mg daily for 1 week by about 50 % and decreased its clearance, but there were no changes in haemodynamic measurements (systolic time intervals, impedance cardiography) (See reference number 25,26). A further study found that ranitidine increases AUC of nitrendipine by 89%, but this does not appear to be clinically significant (See reference number 27).
A study in 8 healthy subjects found that cimetidine 300mg every 6 hrs for 8 days did not affect pharmacokinetics of a single 10mg intravenous dose of verapamil, but bioavailability of a 120mg oral dose of verapamil was increased from 26 to 49%. A small insignificant change in clearance occurred but no change in AUC. The changes in PR interval caused by verapamil were unaltered in presence of cimetidine (See reference number 28). Another study found that cimetidine 300mg four times daily for 5 days reduced clearance of a single intravenous dose of verapamil by 21 % and increased its elimination half-life by 50 % (See reference number 29). Cimetidine 400mg twice daily for a week increased bioavailability of verapamil from 35 to 42 % and its clearance was reduced by almost 30 % in another study (See reference number 30). A further study found a small increase in bioavailability of both enantiomers of verapamil (See reference number 31). In contrast, other studies have found that pharmacokinet
It is believed that cimetidine increases nifedipine levels by inhibiting its oxidative metabolism by liver. Like ranitidine, it may also increase bioavailability of nifedipine by lowering gastric acidity (See reference number 14). The mechanisms of other interactions are probably similar.
The interactions of cimetidine with diltiazem and nifedipine are established. Concurrent use need not be avoided but increase in calcium-channel blocker effects should be taken into account. It has been suggested that dosage of diltiazem should be reduced by 30 to 50%(See reference number 34,35) and that of nifedipine by 40 to 50 % (See reference number 34,35). The interaction between verapamil and cimetidine is not well established, but monitor effects until more is known. It has been suggested that verapamil dose may need to be reduced by 50 % (See reference number 35). Monitoring is advised if isradipine is given with cimetidine and a reduction in isradipine dose may be required (See reference number 5).
Similarly, high doses of cimetidine may increase hypotensive effects of lercanidipine and caution is advised (See reference number 7). The evidence available suggests that, although cimetidine increases serum levels of felodipine, lacidipine, nimodipine, and nitrendipine, haemodynamic changes are unimportant. However,this needs confirmation. The manufacturer of nisoldipine warns that antihypertensive effect may be potentiated by cimetidine,(See reference number 23) but study available suggests that this is not significant, Although some studies indicate no interaction between nicardipine and cimetidine, manufacturer notes that cimetidine increases nicardipine plasma levels and monitoring is recommended (See reference number 36). Amlodipine and cimetidine do not interact.
Ranitidine does not interact significantly with diltiazem,nimodipine, nisoldipine or nifedipine, and is possibly a non-interacting alternative for cimetidine with other calcium-channel blockers. Note that nitrendipine AUC was increased by 50 % and 89 % by ranitidine, although this was not considered clinically relevant.
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