Amlodipine

Is amlodipine safe?

At the doses prescribed for blood pressure and angina, yes. Amlodipine has been sold in the US since 1992 as Norvasc, and in US placebo-controlled trials only 1.5% of people stopped it because of side effects, against about 1% on placebo. It has no boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary and no dependence. We score it 82.

Two things pull the score down. Swollen ankles are common at the top dose, and an overdose of amlodipine is far more dangerous than its everyday safety suggests.

Amlodipine is a calcium channel blocker of the dihydropyridine type. It relaxes the muscle in artery walls, so the heart pumps against less resistance. The US label starts adults on 5 mg once a day with a maximum of 10 mg; small, frail or older people and those with liver problems may start on 2.5 mg. It is also in many combination pills, including Caduet (with atorvastatin), Exforge (with valsartan) and Lotrel (with benazepril).

Ankle swelling: how common is it?

Oedema, puffy ankles, feet and lower legs, is the side effect most people notice. The US label shows a clear dose effect:

Daily dose	Oedema	Placebo
2.5 mg	1.8%	0.6%
5 mg	3.0%	0.6%
10 mg	10.8%	0.6%

Women are affected more often: 14.6% of women and 5.6% of men reported swelling in the trials. Flushing, palpitations and dizziness follow the same pattern and are also more common at 10 mg.

The swelling comes from widened arteries rather than the heart or kidneys failing, but swollen legs have other causes too, so it is worth a check. Doctors have several options, including a lower dose or a combination with another medicine. Do not stop or cut the dose on your own; talk to your doctor or pharmacist.

Why overdose is the real risk

At prescribed doses its effect builds slowly, and the label says a sudden drop in blood pressure is unlikely. Large overdoses are a different matter. The drug floods the body with a long-acting vasodilator: blood pressure can collapse, and the Maryland Poison Center notes that shock may appear several hours after the tablets were swallowed. With a half-life of 30 to 50 hours, illness can last days, and because amlodipine binds tightly to blood proteins, dialysis does not remove it.

The numbers have moved the wrong way. The American Academy of Clinical Toxicology, citing US poison centre data, reports 82 deaths from amlodipine overdose in 2020, up from 26 in 2011, probably because so many people now have it at home. That is why amlodipine gets an overdose score of 55, far below lisinopril. Keep it out of reach of children, and anyone who has swallowed several tablets needs hospital assessment even if they feel well. In the US call Poison Control on 1-800-222-1222; in the UK call 111, or 999 if the person is unwell.

Interactions and grapefruit

Amlodipine has fewer interactions than many heart medicines, but a few matter:

• Strong CYP3A4CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary inhibitors such as clarithromycin, itraconazole and some HIV drugs can raise amlodipine levels. Diltiazem raised them by 60% in a label study. Watch for dizziness and swelling.
• Simvastatin: amlodipine raises its levels, so the US label limits simvastatin to 20 mg a day. Atorvastatin is not affected.
• Cyclosporine and tacrolimus: amlodipine raises their levels, so transplant patients need blood level checks.
• Sildenafil and other blood pressure drugs: the effects add up.

Grapefruit is a point where sources differ. The US label lists grapefruit juice among things with no impact on amlodipine exposure. The NHS still tells people not to eat grapefruit or drink grapefruit juice because it can increase side effects. If grapefruit is part of your diet, ask your pharmacist.

Who should be careful

• People with severe narrowing of the aortic valve, who are more prone to low blood pressure.
• People with severe coronary artery disease: the label warns that angina can rarely worsen, or a heart attack occur, after starting or increasing the dose.
• People with severe liver disease, in whom amlodipine lasts longer (half-life of 56 hours), so doctors raise the dose slowly.
• Anyone pregnant or planning a pregnancy; the NHS says other medicines are usually preferred.
• Households with children or with someone at risk of self-harm, because of the overdose danger.

How we scored it

Dependence (98), track record (95), the absence of regulatory warnings (90) and serious side effects (86) are strong. Interactions (80) is solid. Overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (55) is the weakest factor because amlodipine poisoning is hard to treat and US deaths have risen.