justment may thus be required.
CYP3A4 inducers:
There is no data available regarding the effect of CYP3A4 inducers on amlodipine. The concomitant use of CYP3A4 inducers (i.e. rifampicin, hypericum perforatum) may give a lower plasma concentration of amlodipine. Amlodipine should be used with caution together with CYP3A4 inducers.
Administration of amlodipine with grapefruit or grapefruit juice is not recommended as bioavailability may be increased in some patients resulting in increased blood pressure lowering effects.
Dantrolene (infusion): In animals, lethal ventricular fibrillation and cardiovascular collapse are observed in association with hyperkalaemia after administration of verapamil and intravenous dantrolene. Due to risk of hyperkalaemia, it is recommended that the co-administration of calcium channel blockers such as amlodipine be avoided in patients susceptible to malignant hyperthermia and in the management of malignant hyperthermia.
Effects of amlodipine on other medicinal products
The blood pressure lowering effects of amlodipine adds to the blood pressure-lowering effects of other antihypertensive agents.
In clinical interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin or warfarin.
Simvastatin: Co-administration of multiple doses of 10 mg of amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily.
Tacrolimus: There is a risk of increased tacrolimus blood levels when co-administered with amlodipine but the pharmacokinetic mechanism of this interaction is not fully understood. In order to avoid toxicity of tacrolimus, administration of amlodipine in a patient treated with tacrolimus requires monitoring of tacrolimus blood levels and dose adjustment of tacrolimus when appropriate.
Cyclosporine: In a prospective study in renal transplant patients, an average 40% increase in trough cyclosporine levels was observed when used concomitantly with amlodipine. The co-administration of Sevikar with cyclosporine may increase exposure to cyclosporine. Monitor trough cyclosporine levels during concomitant use and cyclosporine dose reductions should be made as necessary.
4.6 Fertility, pregnancy and lactation
Pregnancy (see section 4.3)
There are no data about the use of Sevikar in pregnant patients. Animal reproductive toxicity studies with Sevikar have not been performed.
Olmesartan medoxomil (active ingredient of Sevikar)
The use of angiotensin II antagonists is not recommended during the first trimester of pregnancy (see section 4.4). The use of angiotensin II antagonists is contraindicated during the 2nd and 3rd trimesters of pregnancy (see sections 4.3 and 4.4).
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with angiotensin II antagonists, similar risks may exist for this class of drugs. Unless continued angiotensin II antagonists therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II antagonis |
