The lady presented with a 4-week history of increasing muscle weakness, resulting in a fall down the stairs on the day of admission. There was very little muscle pain.
Her background history included hyperetension & hypercholestrolaemia, and she was taking amlodipine 10 mg OD, bendroflumethiazide 2.5 mg OD and simvastatin 80 mg OD. She had been on these medications for ~2 years.
On admission, she had grade 4/5 muscle weakness proximally in both upper and lower limbs, without fasciculations or UMN signs. Cranial nerves were not involved.
Tests showed normal renal function, electrolytes & FBC. CK was elevated at 14000 U/l. Urine dipstick showed 4+ blood, but RBC within normal limits on microscopy.
ANA, ENA, dsDNA, Ig were all negative or within normal limits. ESR & CRP were not raised. MR scan of thigh muscles showed diffuse oedema and enhancement on T2 weighted images.
Thoughts?
The lady had statin induced rhabdomyolysis.
ReplyDeleteThis is a pretty common scenario in clinical practice, where a patient comes in with very high CK, with or without associated weakness or pain. Statins are implicated in muscle pain but overt rhabdomyolysis, as in this case, is rare. However, two factors increased the risk of such an event in this lady- firstly, the choice and dosage of statin and secondly, the co-administration of amlodipine.
Among the statins, simvastation and lovastatin are metabolised by CYP3A4 and carry the highest risk of myotoxicity. Pravastatin and fluvastatin are not metabolised by CYP3A4 are considered relatively safe, as is rosuvastatin, which is only partially metabolised by CYP3A4.
Further, the dosage matters. Doses of simvastatin above 40 mg carry an exponentially higher risk of muscle toxicity and is therefore not recommended. In Chinese subjects, doses above 20 mg should not be used. This lady was receiving 80 mg daily.
Finally, co-prescribing drugs which are also metabolised by CYP3A4 or inhibit the enzymes of CYP3A4, increases the risk of statin toxicity manifold. There is an extensive list of such drugs (see http://en.wikipedia.org/wiki/CYP3A4), but medications in common usage are calcium channel blockers and fibrates, paricularly gemfibrozil, which are often used in the same subjects as statins for the management of hypertension and hypertriglyceridemia. If such drugs need to be co-prescribed, it's best to use pravastatin or fluvastatin and avoid gemfibrozil in favour of bezafibrate if the subject has mixed hyperlipidemia.
You may have noticed that the lady had 4+ blood in her urine but no RBC on urinalysis. This is characteristic of myoglobinuria, which gives the same test on commonly used dipsticks as urine haemoglobin.
In this case. simvastatin was stopped, and the lady made an uneventful recovery. There was no renal damage.
...yes as I was working on it.. ur response is in hand....I was a bit shocked at the dosage of Simvas here we r never exceeding 20mg...also no RBC in Microscopy but 4+ blood in Status indicate Myoglobinuria.....gud Renal damage was averted or else in Rhabdomyolysis chances r there.....1yr ago a pt.aged 32/m with high levels of Chol & TG wouldnt be controlled with Simvas & Lopid(Gemfib).I put him on Fibral 200mg to which he didn't respond enough ....aft increasing the dose of Fibral to 400mg in divided dosage he developed high color Urine with muscle fatigue nd pain....quickly I put off the mediacations & he recovered in a weeks time...Ur case reminded me of tht episode nd I am shaky with the Lipid medicines whn it comes to increase in dosage...in Maldives Islands Atorvastatin , Fenofibrate & Gemfibrozil, Simvastatin is only available...pl formulate a safe combination choosing frm these....Ur word will be the last....Tnx...!!!
ReplyDeleteFor a combination of hypercholestrolemia and mild hypertriglyceridemia, I would only use a statin without a fibrate. At such low TG levels (<200 mg/dl, even up to 500 mg/dl), there is no risk of acute pancreatitis and any CV risk will be lowered by the statin.
ReplyDeleteFor higher TG levels in association with a raised cholesterol, given the limitations you describe, I'd use a combination of atorvastatin upto 20 mg daily with fenofibrate. Atorvastatin is now generic. I would not use gemfibrozil at all with a fibrate. I'd check all other medications to make sure they are not metabolised by or do not inhibit CYP3A4.
Additionally, for all levels of raised TG, I'd consider adding w-3 fatty acids such as Omacor at doses of at least 3g daily. This has a TG lowering effect, although one study indicated that these can raise cholesterol. Omacor may be available in Maldives.
Finally, there is no role for fat restriction in moderate TGemia (<500 mg/dl). Dietary fat disappears quickly from blood and does not contribute to high TG serum levels until TG levels cross 1000 mg/dl. At levels below 500 mg/dl, the need is a hypocaloric diet to lose weight, particularly cutting down on carbs such as refined sugar, fruit juice and other sources of sucrose or fructose, which lead to endogenous TG synthesis in VLDL. At TG levels above 1000 mg/dl, however, chylomicrons are cleared very slowly from blood and drastic reductions in dietary fat (20-40 mg daily) is indicated.
....well enunciated....these fine tunings will help me for sure...yes Omega3 is available here... the situation here is every 5th pt. is a DLP/DM/HTN pt & average age is lower.Currently,surprisingly, it seems Thyroiditis is on the rise since last mth...on the lines of DeQuervain's....I always remember Ur course correction about our old Hyperthyroidism pt.whose Neomercazole bottle of 100 tbs were refunded....Ur v popular here amongst my people here, believe me...!!!...Tnx...
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