Taking leqvio

Here’s a clear, straightforward explanation from a medical perspective about *Leqvio* and how it should be administered.

Short answer:
Skipping the initial 3-month loading dose of Leqvio (inclisiran) is not ideal and not how the medication is designed to work, but it isn’t typically dangerous. The issue is that you may not get the full LDL-lowering effect without the loading dose.

How Leqvio Normally Works:

Leqvio’s recommended schedule is:

Dose #1.

Dose #2 at 3 months.

Then every 6 months.

That 3-month “loading dose” helps quickly bring your LDL down and stabilize the drug’s effect. After that, the twice-yearly schedule maintains it.

What happens if you skip the 3-month dose?

The medication will still work, but more slowly.

Your LDL level may not drop as much as intended.

It’s not harmful to your body to skip it—just less effective for cholesterol control.

The loading dose is recommended by all guidelines and the FDA, so skipping it is off-label.

Why your doctor may be suggesting this:

Sometimes clinics propose this if:

You’re moving and will not be able to return for the 3-month shot.

They want to avoid gaps in treatment once you’ve relocated.

It’s a practical workaround, but not the most effective medical approach.

What you can ask your doctor*

To make the best decision, you might ask:

“Is there a way to schedule the 3-month dose at my new location?”

“If I skip the loading dose, how much less LDL reduction should I expect?”

“Can you coordinate with another clinic so I follow the standard schedule?”

Bottom line:

Not dangerous, but not the recommended dosing.

Best: follow the standard 0-month → 3-month → every 6 months schedule.

Acceptable alternative only if logistics absolutely prevent the loading dose.

Welcome to Connect, @kyndaj2568. I assume you are concerned that getting Leqvio (Inclisiran) on a different schedule than recommended may be harmful, not asking about the drug itself.

Here is a link to the drug company’s locator page where you can type in a location and find a center to get your injection. To me, that makes more sense than taking it on your own schedule. https://leqvio-locator.com/

Is there a reason other than finding a place to get the shot that concerns your doctor?

There’s not enough information provided to give you a good answer. What is moving have to do with injections? The short answer is there’s no damage by postponing the injection over the long haul. However if you have the option to take it as it’s prescribed, that’s what I would fight for. I take it and there’s absolutely no side effects. In fact it clears my sinuses when I go in for the injection and I don’t have a clue why it hasn’t done anything over a couple years to lower my LPa number.

I took the first injection 3 months ago, not realizing it was a mRNA type injection. After 3 months, I still have a big read itchy patch where I got the injection. I also have had muscle and joint stiffness and pain, weakness, discomfort pain under tight ribs, leg/feet cramps, hoarse voice, oily hair, I started having osteoarthritis in my fingers, and I’m very weak tired.
The nurses said to not take 2nd shot until I see the doctor in January. I’m concerned that I’m having mRNA side effects of autoimmune disease, like with the mRNA Covid shots.
Is this possible?

1. Leqvio (inclisiran) is not an mRNA.

*This is extremely important.* Inclisiran does not use mRNA technology, and it does not work like the COVID-19 mRNA vaccines.

What it actually is:

Inclisiran is a *siRNA* (small interfering RNA) drug.

It does not enter the nucleus, does not alter DNA, and does not cause the immune response patterns seen with mRNA vaccines.

Its mechanism is gene silencing of PCSK9 in the liver only, which reduces LDL.

So the concerns about persistent mRNA side effects or “autoimmune reactions like COVID vaccines” do not apply to inclisiran.

2. Can inclisiran cause long-lasting side effects?

Most inclisiran side effects are mild and limited to the injection site.

Common ones:

Redness.

Itching.

Swelling.

These usually resolve within hours to a few days, rarely weeks.
Months of redness/itchiness at the injection site is unusual, and your nurse was right to pause the second dose until examined.

3. What about the other symptoms?

The symptoms you listed are not typical side effects of inclisiran:

Muscle/joint stiffness or pain.

Weakness.

Rib discomfort.

Leg/foot cramps.

Hoarse voice.

Oily hair.

New osteoarthritis.

Severe fatigue.

These are not known side effects from inclisiran in clinical trials or post-marketing safety monitoring.

In particular:

Autoimmune-type reactions have not been associated with inclisiran.

Systemic inflammation or multi-system symptoms have not been reported with inclisiran in the way some people reported after COVID vaccines.

So the pattern you’re describing does not match inclisiran’s known safety profile.

4. What is possible?

Several possibilities worth discussing with your doctor:

A. Delayed or exaggerated local hypersensitivity (likely for the red itchy patch).

Some people develop:

Prolonged redness.

Local inflammatory reactions.

Injection-site dermatitis.

This can last weeks, occasionally longer.

B. Coincidental illness*

Things like:

Viral infections.

Thyroid issues

Vitamin deficiencies (B12, D, magnesium).

Autoimmune conditions unrelated to the drug.

Perimenopause/menopause.

Stress-related disorders.

These can all cause exactly the systemic symptoms you listed.

C. Statin intolerance (if you’re also on a statin)*

Statins can cause muscle pains, weakness, fatigue, and cramps. If inclisiran was started at the same visit as a statin adjustment, people often misattribute the symptoms.

D. A separate rheumatologic issue:

New osteoarthritis or joint problems and fatigue have nothing to do with inclisiran.

5. Is inclisiran known to trigger autoimmune disease?

No.
There is no evidence in trials or pharmacovigilance data that inclisiran causes:

Autoimmune disease.

Systemic inflammatory responses.

Autoimmune flares.

Chronic fatigue-type syndromes.

*This is very different from the rare autoimmune reactions reported after COVID mRNA vaccination.*

6. Is it good that they told you to delay the second dose?

Yes. That’s the correct and cautious approach.

Before your next injection, your doctor should:

Examine the injection site.

Review blood work (CBC, inflammation markers, liver function, thyroid, B12, vitamin D, CK, etc.).

Consider whether the symptoms align with another diagnosis.

Decide if continuing inclisiran is safe.

Most doctors would delay the next dose in this situation.

7. Should you be worried about permanent damage?

Inclisiran does not:*

Alter DNA.

Persist long-term, the way mRNA may in lymph nodes.

Trigger autoimmunity.

Your symptoms are concerning and deserve evaluation, but they do not fit inclisiran’s known risks or mechanism of action.

I hope this gives you a better perspective on this subject.

@tommy901 Thank-you for the info. One question please: do we current.y have long term data on side effects? How long term? 2. (looks like I lied when I said « one » question)? How trustworthy is the data on people with autoimmune diseases like MS, since they were excluded from trials, I assume?

@tatiana987 Trial protocols and inclusion/exclusion lists for the ORION program generally excluded people with “severe concomitant non-cardiovascular disease” and had other exclusions that tend to screen out unstable or severe systemic illnesses. The formal protocols include neurological exams and other screening steps. That means people with active, unstable, or severe autoimmune diseases (including many people with MS) were often excluded or under-represented. The phase-3 publications and protocol appendices list these exclusions.

I could not find any completed, large clinical trial that specifically enrolled people with MS to evaluate inclisiran safety in that population. That leaves limited direct evidence for MS patients.

Remaining unknowns:

Mechanism: inclisiran is an siRNA that acts in the liver to reduce PCSK9 production (it’s not a broadly immunosuppressive drug). That mechanism reduces the biological plausibility of causing systemic autoimmune flares, but it doesn’t eliminate possibility of immune reactions (e.g., injection hypersensitivity, rare immune events) or very rare long-term effects that only show up in larger or longer datasets.

Because MS and other autoimmune conditions were under-represented, the issue cannot be highly confident about the absence of very rare autoimmune flares or interactions with disease-modifying therapies for MS — the trials were not designed to answer that question.

Practical implications / reasonable next steps

If someone has MS (or another autoimmune disease), it’s reasonable to:

1. Discuss with both the prescribing cardiologist and the patient’s neurologist before starting Leqvio, especially if the MS is active or they’re on immunomodulatory/immunosuppressive therapy.

2. Be alert for new/worsening neurological symptoms or other autoimmune symptoms after dosing and report them promptly.

3. Know that dermatologic/injection-site reactions and arthralgia are the most common side effects; serious allergic reactions are rare but listed in the label.

There is reassuring multi-year safety data for inclisiran from pooled analyses and open-label extensions (follow-up into the multi-year range, with some groups reported beyond 3–6 years and >12,000 patient-years reported in pooled analyses). The safety profile has been consistent (injection-site reactions, arthralgia, some respiratory infections; rare hypersensitivity). However, people with autoimmune diseases such as MS were largely not included in the pivotal trials, so direct trial evidence in that population is limited; therefore extra caution, close monitoring, and consultation with the neurologist are sensible if considering Leqvio for someone with MS.

@tommy901 Many thanks for yr thorough and careful answer. It helps, but I have to remind you that you ask what is not possible again, namely that we « Discuss with both the prescribing cardiologist and the patient’s neurologist before starting Leqvio ». That would be excellent, but the large corporation that provides medical care here does not allow it. Waits are months long for an appointment and the doctors treat the screen provided information rather than the human being in front of them. Add language differences and multiple conditions and medications and you have people who look for help on blogs like this and from our evil monster AI systems and try to figure things out for themselves.

BTW I have two neurologists, one an MS specialist and one an opthomologist-neurologist. The second is young, beautiful, not yet destroyed by the system and willing to skip her lunch to see me. She even dared to instruct me that I might want to hold up on taking Nurtec, which was prescribed by the other neurologist. I take that as a warning.

@tatiana987 You hit the nail perfectly on the head with the issues that you addressed.

You’re describing a situation many patients face — multiple specialists who don’t communicate, conflicting treatment plans, and a healthcare system that makes coordination nearly impossible. Those concerns are real, and they matter when deciding whether Leqvio is safe for someone with MS or neurologic conditions. As for reminding, I've been reminding myself for 20+ years as to the fact that our health care system is in critical condition.

Here are few suggestions (maybe):

1. The statement “Talk to all your specialists”, is hardly ever realistic — and you’re right to push back.

You’re absolutely correct: in many healthcare systems, true interdisciplinary coordination simply doesn’t happen. That means patients are left carrying the entire burden of connecting the dots between cardiology, neurology, and primary care.

Your experience — long waits, clinicians relying on computer prompts, language barriers — is exactly why people end up asking questions in forums and online tools. It’s not neglect on your part; it’s a systemic failure.

2. Your MS and neurological history do justify caution with any new medication.

Since the pivotal Leqvio trials excluded many autoimmune or neuroimmune patients, the long-term safety data in people with MS is limited. That doesn’t mean Leqvio is unsafe — but it does mean uncertainty exists.

So your hesitation and desire for more clarity are completely reasonable.

3. The fact that one neurologist told you to “hold off on Nurtec” is a red flag worth exploring.

This tells me:

At least one of your neurologists is thinking holistically, not just following guidelines.

They suspect a medication interaction, side-effect overlap, or diagnostic confusion.

They are worried enough to override another specialist — which is uncommon unless there’s a credible concern.

That reinforces that you need a unified plan, even if the system won’t give you one automatically.( It's like "duh", how do you do that).

4. What you can do when your doctors won’t coordinate? (Duh again).

There "might be" some practical steps that actually work:

a. Bring a one-page medication and condition summary
List all meds, doses, conditions, recent side effects, and what each specialist has said.
Doctors engage better with a single page than a long explanation.

b. Ask one neurologist one key question:

> “Do you see any reason Leqvio could worsen autoimmune activity or neurologic stability in my case?”

Specialists are much better at answering a single concrete question than at giving broad judgments.

c. Ask the cardiologist one matching question:

> “I have MS. Are you aware of any immunologic concerns with Leqvio for someone like me?”

You don’t need them to talk to each other — you just need their answers in your hands.

d. Keep the helpful neurologist as your point person.
The young ophthalmologist-neurologist who took the time to think critically and protect you? That’s the doctor who will give the most honest risk-benefit thinking. MS specialists can sometimes be overly narrow; she seems willing to look at your whole picture.

5. The emotional and systemic burden you describe is valid and important.

Your frustration is legitimate:

You’re trying to navigate multiple conditions.

You’re being asked to make decisions without "clear" guidance.

You’re "forced" to rely on online information because the system doesn’t allow timely collaboration.

This isn’t “patients doing it wrong.”
This is patients trying to survive a dysfunctional system.

6. The core takeaway about Leqvio in your situation:

There is long-term data for the general population — 5–6 years so far — but there is not long-term data in people with autoimmune diseases like MS. That doesn't automatically make it dangerous, but it means:

Your decision should be cautious.

It should be individualized.

One neurologist’s hesitation (like the Nurtec warning) should be considered a meaningful signal.

This whole situation is really hard to put into perspective. It's just like we have been put on a remote island with great hopes that someone will come along and save us. But the odds are not in our favor.

@tommy901 Again thank you for taking the time to listen and respond so carefully. I have already copied and pasted the suggested question to the two neurologists.

I really appreciated your speaking of doctors as if they were children for whom we have to make things simpler. Not to insult doctors, as kids absorb information lots better than most adults do. A simple question is best for most people, including docs. My son, who writes medical AI and software, advised me (when I had trouble getting help with heart rate increase caused by monitor on the chest) anyway, the notion that heart rate might go up based on blue-tooth-like signal from the device nearly directly over the heart and on the skin, that notion was too much for most doctors, said my brilliant son. He told me to point out the skin rash and the obvious heat of the device, but not suggest that my changed heart rhythm was related to the device. I was not to mention that idea if I wanted a helpful response. Plain, uncomplicated, black and white, concrete questions are best, says the brilliant kid. And asking only one question, a simple one, is best, no doubt in my mind.