Amlodipine toxicity

DellaGreca, M., Iesce, M.R., Isidori, M., Montanaro, S., Previtera, L. and Rubino, M. (2007) Phototransformation of amlodipine in aqueous solution toxicity of the drug and its photoproduct on aquatic organisms, bit. J. Photoenergy, article ID 63459. 

CALCIUM CHANNEL BLOCKERS CICLOSPORIN 1. Plasma concentrations of ciclosporin are t when co-administered with diltiazem, nicardipine, verapamil and possibly amlodipine and nisoldipine. However, calcium channel blockers seem to protect renal function 2. Ciclosporin t nifedipine levels 1. Uncertain presumed to be due to impaired hepatic metabolism. Also, diltiazem and verapamil inhibit intestinal P-gp, which may t the bioavailability of ciclosporin. Uncertain mechanism of renal protection 2. Uncertain effect of ciclosporin on nifedipine 1. Monitor ciclosporin levels and i dose accordingly (possibly by up to 25-50% with nicardipine) 2. Monitor BP closely and warn patients to watch for signs of nifedipine toxicity... 

Adams BD, Browne WT. Amlodipine overdose causes prolonged calcium channel blocker toxicity. Am J Emerg Med 1998 16 527-528. 

Both diltiazem and verapamil can increase serum carbamazepine levels causing toxicity. Limited evidence suggests that amlodipine and nifedipine do not affect carbamazepine levels. A single case report describes neurological toxicity in a patient taking phenytoin and carbamazepine with isradipine. 

Nifedipine 20 mg twice daily for 2 weeks did not affect the steady-state carbamazepine levels in 12 epileptic patients. Similarly, a retrospective study of 5 patients suggested that nifedipine does not usually raise carbamazepine levels or cause toxicity.A man had a marked rise in serum carbamazepine levels when nifedipine was replaced by diltiazem. When diltiazem was replaced by amlodipine, his carbamazepine levels returned to normal, suggesting that neither nifedipine nor amlodipine interact with carbamazepine. " Another patient had no change in carbamazepine levels when also given nifedipine. ... 

Information about the effects of calcium-channel bloekers on ear-bamazepine is limited, but what is known indicates that if carbamazepine is given with verapamil or diltiazem, the carbamazepine dosage may possibly need to be reduced to avoid toxicity. A 50% reduction in the dose of carbamazepine has been suggested if diltiazem is to be used. Nifedipine and amlodipine normally appear to be non-interaeting alternatives. Oxear-bazepine appears to be a non-interaeting alternative for carbamazepine. 

Drug-drug interactions Imatinib Peripheral neuropathy is uncommon in imatinib-treated patients and has previously been reported only during combination therapy with cytotoxic agents that affect microtubule function, such as vinca alkaloids and taxanes. A suspected adverse interaction with amlodipine has been reported, with a temporal association between amlodipine and symptoms of imatinib toxicity [21 ]. 

A 74-year-old man with chronic myeloid leukemia took imatinib mesylate 400 mg bd. His other medications were perindopril and ator-vastatin. After 2 months he developed angio-edema, probably related to perindopril, which was withdrawn and replaced by amlodipine 10 mg/day. After 2 weeks he developed typical symptoms of imatinib toxicity nausea, marked periorbital, and ankle edema. Diuretics improved the edema, but after 10 days he complained of numbness of the chin and bilateral pain and numbness in the soles of the feet. Light touch and vibration sense were reduced, but power and reflexes were intact. Imatinib was reduced to 400 mg/day and amlodipine was withdrawn. The edema, numbness and neuropathic pain resolved. Despite residual plantar numbness he was able to increase the dose of imatinib to 600 mg/day without worsening symptoms. About 1 month later he took two doses of amlodipine in error and developed nausea and palpitation, which resolved when the amlodipine was withdrawn. Nerve conduction testing 1 month later showed a mild sensorimotor axonal neuropathy. After 9 months the neuropathy had resolved despite continuing imatinib therapy. 

A 63-year-old female was on treatment with double antiplatelet medication, bisoprolol, amlodipine, atorvastatin and ranolazine due to a previous medical history of hypertension and unstable angina with no signs of myocardial damage. At 3 months, she began to experience malaise and insomnia. A biochemical study showed an increase in liver function parameters. The most common viral and autoimmune causes were ruled out. Laboratory results pointed towards a hepatocellular toxic-medication source. After cessation of ranolazine the patient was asymptomatic and normalisation of liver function tests was achieved [35]. 

Drug-drug interactions Amlodipine markedly inhibits tacrolimus clearance with renal toxicity. 

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