Alexander C. Chester, MD

Statin-associated muscle symptoms are the most common side effects noted with statins, reported in 10% to 25% of patients receiving statin therapy. A very severe form of muscle problems is noted in less than 0.1% of patients receiving statin therapy and will not be discussed here.

Muscle symptoms associated with statin use include muscle weakness, muscle aches, stiffness, soreness, tenderness or cramps associated with exercise. Usually the muscle symptoms are symmetric and involve the thigh, shoulder or calf muscles. Symptoms generally occur within two to twelve weeks of starting the offending statin but may occur at any time in the course of treatment particularly if an additional factor is introduced.

Symptoms generally resolve over several weeks after discontinuing the medication although total resolution of symptoms may require several months. Risk factors include advanced age, female sex, lower muscle mass, vitamin D deficiency and physical disability. An increase in statin dose can also provoke muscle symptoms as can the introduction of another medication or substance that increases the concentration of the statin in the blood.

Because of a certain type of metabolism lovastatin (Mevacor), simvastatin (Zocor) and atorvastatin (Lipitor) are more prone to interactions with other medications. Additionally, tropical juices such as grapefruit, starfruit and pomegranate can greatly increase the blood levels of these statins thereby increasing the risk of adverse effects.

The flowing statins are associated with less risk of interaction: pravastatin (Pravacol), fluvastatin (Lescol), pitavastatin (Livalo) and rosuvastatin (Crestor).

Muscle problems are more common with simvastatin, particularly at higher dose, than with other statins. Pravastatin (Pravacol), fluvastatin (Lescol), pitavastatin (Livalo) and rosuvastatin (Crestor) are less commonly associated with muscle symptoms than other statins.

If you suspect muscle symptoms related to statin use it is important to call your doctor immediately to work on a plan. Often changing the medication or dose is effective in resolving the issue.

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Recently the U.S Food and Drug Administration issued a warning to doctors against the routine prescribing of fluoroquinolone antibiotics to those patients with bronchitis, sinusitis and uncomplicated urinary tract infections who have other treatment options.

The most common serious side effects associated with these medications are problems involving the tendons, however, the overall incidence is less than one percent. The most common tendon involved is the Achilles tendon (90% of fluoroquinolone-associated tendinopathy) which can be inflamed and painful or, in some cases, rupture. However, all weight bearing tendons can be involved.

The usual symptoms of Achilles tendon disorders are swelling and tenderness with sharp pain on walking. Rupture is usually preceded by these symptoms but may occur spontaneously. Symptoms usually occur 9-13 days after the initiation of fluoroquinolone therapy with most occurring in the first month. However, symptoms may occur many months after the start of therapy.

Most patients have a satisfactory recovery within two to four weeks although some patients can have prolonged symptoms, occasionally persisting for six months. Long-term problems with the tendon (swelling, pain, etc.) are estimated to occur in about 10% of cases.

Risk factors for fluoroquinolone-associated tendon problems include older age (older than 60 years in 70% of cases), receiving concomitant corticosteroid therapy (including inhaled nasal and pulmonary corticosteroids) and kidney dysfunction. Higher fluoroquinolone doses appear to be associated with greater risk.

Although all fluoroquinolones have been responsible for this side effect levofloxacin (Levaquin) and ofloxacin (Floxin) may possess a substantially greater propensity than other fluoroquinolones to cause tendon problems. The reason for this association is unknown.

When a fluoroquinolone must be used avoiding strenuous physical activity is important to prevent tendon trauma and rupture. Special caution must also be used in patients with pre-existing tendon disorders.

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In 95% of cases low thyroid hormone levels in a person are the result of the failure of the gland itself rather than a failure of the gland to receive the appropriate signal (thyroid stimulating hormone) from the pituitary gland. To correct a low thyroid state thyroid hormone is given as T4 in a tablet form calibrating the dose by measuring the thyroid stimulating hormone (TSH) which exists in a reciprocal relationship with T4. In other words, TSH is elevated when the thyroid dose is too low and TSH is suppressed when the thyroid dose is too high.

Thyroid hormone is given as T4 which is a prohormone converted to the active hormone (T3) by the body. Over the years some authorities have claimed that giving thyroid supplementation as a combination of T4 and T3 is superior to administering T4 alone. Multiple studies have not demonstrated any advantage of the combination preparation. Additionally, producing a standardized dose of this preparation is more difficult and subject to variation.

There is about a six week lag between an adjustment in T4 and the final change in the TSH level. Therefore, one cannot assume that more thyroid medication is required after a dose increase because of a failure of TSH to normalize until six weeks have passed. Additionally, T4 has a seven day half-life which insures a constant blood level throughout the day even though the tablet is taken only once a day and makes changes in blood level slow to appear.

Although TSH is used as the marker for thyroid dose adjustment checking the actual level of free thyroid hormone in the blood is important when initiating therapy and occasionally over the years to monitor therapy.

As mentioned in a previous blog, there is some debate about what is the proper TSH target. Traditionally normal TSH is defined as about 0.5 to 5 mU/L. These normal values are based on wide population studies that, by necessity, include individuals with low thyroid hormone levels and, therefore, elevated TSH levels. Using a proper sample population that excludes all individuals with thyroid abnormalities produces a value of 2.5 mU/L as an upper limit for TSH. It may be possible for a person to feel not quite right with a TSH of 4.9, for example, and to feel better with a TSH of 1.9.

Even when an appropriate dose of thyroid is started other factors can interfere with delivering the correct dose to the blood stream. The amount of hormone delivered to the blood steam from a particular thyroid hormone preparation (bioavailability) is standardized by the pharmaceutical firm and supervised by the government. While it used to be thought that a particular name brand was more reliable this has not proven to be the case. However, different generic preparations can have different bioavailability. If there is some concern after a different generic has been started checking the TSH will determine if altered bioavailability is an issue.

Thyroid hormone may not be properly absorbed thereby confusing attempts to find the proper dose. Ideally, it should be taken on an empty stomach one hour before breakfast or in the evening two hours after the last meal. Taking it with food or even coffee can diminish absorption. Taking it with certain other medications or supplements such as calcium, iron or Prilosec can interfere with absorption.

Many medications interfere with T4 becoming active in the blood steam even if they are not taken simultaneously with the thyroid dose. Practically speaking, if a person is on certain medications that interact with thyroid medication the dose can be altered to correct the issue. Problems usually only arise when a new interfering medication is initiated and the TSH is not checked to make the necessary adjustments in dose.

Your thyroid dose may need adjustment upwards if you put on weight. Additionally, your thyroid may be producing some hormone that might decrease over years requiring an increase in the thyroid dose. In any case, it is important to check the TSH yearly and, of course, if symptoms develop to insure that the thyroid dose is proper.

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High blood pressure (hypertension) is defined as a systolic (top number) blood pressure of greater than 140 and/or a diastolic (bottom number) greater than 90. When one of these numbers is abnormal doctors generally consider treatment. However, a single reading indicating a mild abnormality by itself is not enough to merit medication.

About 20 to 25 percent of people with a mildly abnormal blood pressure reading in a doctor’s office have “white coat hypertension,” or blood pressure abnormality only when measured by the physician. Readings done at home or at work are normal.

White coat hypertension does not carry the cardiovascular risks (heart disease and stroke) that regular hypertension does. Documenting home blood pressure requires about 12 measurements over one week that include both morning and evening readings. Of note, normal readings for home determinations (<135/<85) are defined slightly lower than those in a physician’s office.

Additionally, the white coat hypertension effect often wears off with repeated measurement even in the physician’s office. If the doctor notes multiple normal values after an initial elevated reading the initial elevation is not considered evidence of hypertension.

Sometimes the measurement results are quite erratic and the presence or absence of hypertension is unclear. A device that measures blood pressure frequently throughout an entire day can settle the issue. Ambulatory blood pressure monitoring (ABPM) is the best method of defining whether a person has a blood pressure problem.

ABPM measures blood pressure every 15 minutes during the day and every half hour during the night. The nighttime readings are very important since an elevated blood pressure during sleep is a concern.

The ABPM criteria for hypertension are somewhat lower than those for blood pressures taken in a physician’s office: a 24-hour average of 130/80 or above; a daytime average of 135/85 or above; or, a nighttime (sleeping) average of 120/70 or above.

Since blood pressure medication is usually a lifetime commitment it is important to insure that the diagnosis of hypertension is correct.

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