Taking leqvio

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?

@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.

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.

@tommy901 Is the first dose of Leqvio/inclisiran that you referred to as a "loading dose" a different strength, quantity, or ingredients than the follow-on doses at 3 months and then 6 month intervals? If so, is it possible that the side effects would differ for the first dose as compared to future doses (i.e., less/more/different)?

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.

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.

@justlucky Here's what the experts say:

I can give you references if you need:

Here’s how Leqvio (inclisiran) dosing works and what it means for the “loading dose” vs later doses — including whether the first injection is different and if side effects can differ:

Dose Strength and Composition:

All doses of Leqvio (inclisiran) — the first one, the 3-month dose, and all subsequent 6-month doses — are the same strength, same formulation, and same ingredients:
284 mg of inclisiran in a single-dose 1.5 mL prefilled syringe. There is no higher-strength or different “loading” version used at the start.

What People Call a “Loading Dose”

The term “loading dose” people sometimes use for inclisiran isn’t because the first injection is a different strength — it’s simply referring to the dosing schedule:

First dose at start:

Second (same strength) at ~3 months

Then every 6 months thereafter
This early second injection helps establish the drug’s long-term effect on lowering LDL cholesterol more reliably and quickly.

Why the First Two Doses Are Timed That Way:

Inclisiran works by silencing production of PCSK9 in the liver, reducing LDL cholesterol over time. Because its effects are gradual and sustained (lasting months), the 3-month follow-up dose helps build up the cholesterol-lowering effect before spacing out to every 6 months.

If you miss the 3-month dose by a large margin, the schedule may be restarted — but the medication itself doesn’t change.

Can Side Effects Differ Between the First and Later Doses?

Yes — but not because the dose is different in strength or composition. All injections deliver the same amount of drug.

However, side effects can vary from person to person and from dose to dose for a few reasons:

Your early immune or tissue response:

Injection-site reactions (pain, redness, rash) or mild systemic effects can be more noticeable initially simply because it’s your body’s first exposure.

Some people report that initial doses feel different from later ones, although there’s no guarantee one is more or less likely to cause side effects.

Adaptation:

With many injectables, the body can adapt over time, meaning injection-site reactions or other transient effects might be less noticeable with later doses. But responses vary widely between individuals.

Expectations and reporting:

People often remember the first experience more, so subtle reactions later might feel less notable even at the same intensity.

In summary:

First, second, and maintenance doses are all the same strength and formulation.

The “loading” terminology refers to timing, not a different dose.

Side effects can differ between doses in some individuals, but this is due to how your body reacts — not because the medicine is different.

If you notice side effect patterns or have concerns, it’s always best to discuss them with your clinician. They can help interpret what’s expected versus what might warrant further evaluation.

**ALWAYS CONSULT A QUALIFIED MEDICAL PROFESSIONAL TO ADVISE YOU*.

@tommy901 Thank you for all that good info. You may be aware that the reason this member & others (like me) think that Leqvio (inclisiran) is an mRNA is because that factoid is available on many search sites .. so we are just repeating what we have read. May I ask why & how you this is not the case (& why you think that statement got is out there so widely. Thank you.

@tommy901 thanks very much for taking the time to answer so completely. This is very helpful.

@barb11brown As for why the “mRNA” label is so widespread:

Many search sites and summaries loosely group anything involving RNA as “mRNA,” even though that’s technically incorrect.

The public became familiar with the term “mRNA” during COVID, so it gets used as a catch-all.

Some articles oversimplify or misuse the terminology, and that error gets repeated.

So the short answer is: the statement is common because of terminology confusion, not because inclisiran actually functions as mRNA.

Hope that helps clear it up.