Clinical trials are sets of tests which are carried out by medical researchers as well as developers in order to establish a drug’s efficacy or its safety profile. Simvastatin, like any other successfully marketed drugs have undergone numerous tests in order to affirm its place as one of the most trusted and effective statins out there in the market.

Pre-marketing Clinical Trials

The pre-marketing clinical trials of Simvastatin (Zocor) were done under the supervision of Merck & Co. and they were designed to find out the adverse effects that will emerge which in turn will be the cause of discontinued use. In addition, the studies also aimed to find out the most common adverse effects that needed to be addressed and managed.

In an 18-month pre-marketing clinical study, 2,423 patients were involved and a minimal 1.4% of it discontinued their use of Simvastatin because of adverse effects or reactions. The most common adverse reactions noted as the cause of discontinuance are:
•Gastrointestinal disorders with 0.5%
•Myalgia and arthralgia at 0.1% each

On the other hand, the most common side effect occurrences were:
•Upper respiratory tract reactions or infections at 9%
•Headaches at 7.4%
•Abdominal pains at 7.3%
•Constipation at 6.6%
•And nausea at 5.4%

The said incidences have a greater than 5% rate in the controlled clinical trials.

Another study done during the drug’s pre-marketing clinical trial is the one called “the Heart Protection Study” or HPS. The comprehensive study includes a whopping number of 20,536 subjects in a span of 5 years mean. This study only records the discontinuance of use due to the incidences of adverse reaction or effects. As a result, the Simvastatin study recorded the discontinuation rate at only 4.8%. On the other hand, the incidence of myopathy or rhabdomyolysis was lesser than 0.1%. All of these results were compared to placebo and all the patients were given a 40 mg dose per day.

In one of the clinical trials, a study about the results of the administration of 80 mg dosage per day was compared to those that were given with only 20 mg every day. The results show a significant increase in the incidence of myopathy and rhabdomyolysis.

Post-Marketing Experience

Post marketing clinical trials are designed to further establish the safety profile of the now marketed drug. It aims to show if there are still side effects that got passed from the pre- marketing phase of Simvastatin.

From the studies, additional side effects were recorded. These adverse reactions were:
•Pruritus or itchiness
•Alopecia or baldness
•Skin reactions like rash, discoloration, dryness and others.
•Pancreatitis
•Paresthesia or the sensation of “pins and needles”
•Peripheral neuropathy
•Anemia
•Erectile dysfunction
•Non-fatal hepatic failure
•Interstitial lung disease
•Depression
Other than these, there are also rare occasions of cognitive impairment like memory loss and forgetfulness. However, this side effect is also reported among all available statins which concludes that the cognitive impairment is a collective adverse reaction from all statins and not Simvastatin alone.

What is Simvastatin?
Simvastatin is a hypolipidemic drug or simply a drug designed to lower the patient’s blood cholesterol level; more specifically the bad cholesterol known as low density lipoprotein or LDL. This drug component belongs to the pharmaceutical category or family of statins which are specifically effective in lowering the cholesterol level by inhibiting HMG-CoA reductase – an enzyme that plays a big role in the cholesterol liver production.
Previous to its patent expiry, Simvastatin was marketed by Merck & Co under the commonly known brand Zocor. After its patent expiration on June 2006, the drug was further sold under different brands and companies bearing the same generic compound. Later on, it also has been combined with other chemical compounds to create a synergistic product that aims to lower the bad cholesterol level. Not commonly known though is the compound’s origin from the product of fermentation of the mold Aspergillus terreus.

What are its Indications?
In line with Simvastatin’s marketing path, the drug was primarily indicated to patients who have an abnormally high level of bad cholesterol in their system. However, it is also medically prescribed to patients who are suffering from coronary heart disease, diabetes mellitus, and other risky systemic diseases that are closely associated with strokes and heart attacks. Studies have shown that the class effect of cholesterol reduction can benefit these patients significantly. However, like any other hypolipidemic drugs, Simvastatin is prescribed or recommended only by medical doctors after all the safer, non-chemical options have been exhausted. These options include rest, exercise and diet.

What are its Contraindications?
Naturally, not unlike any other substance, Simvastatin is contraindicated to patients who have experienced allergic reactions from the said component. It is also not to be taken by patients who are pregnant because of possible birth defects are probable. Lactating mothers should not take drug, too, since it can upset the baby’s own fat metabolism. Lastly, those patients who have existing liver problems are also greatly discouraged in using it since it can very well worsen the existing condition.
What are Simvastatin’s Drug Interactions?
Startlingly, the Simvastatin along with other drugs have an unusual interaction with grapefruits. The said fruit has its own component that slows the metabolism of Simvastatin in the body which in turn rises up the component’s plasma level. This is why it is advised not to eat grapefruits or other products containing it to avoid the hazard of toxicity.
The FDA has also warned the use of Simvastatin combined with amiodarone. The combination was studied to have caused the breakdown of skeletal tissues or the condition known as rhabdomyolysis. This condition is very harmful to one’s kidneys and may lead to its function failure.

The interaction incidence is said to dose-related.
Another dose-related interaction is the drug’s risk of myopathy or muscle injury. The warning was issued against its 80mg formulation.
In 2010, the FDA also released the list of drugs not to be taken with Simvastatin because of the same way grapefruit is cautioned. The drugs to be named below are found to increase the plasma level of the drug thus increasing also the risks of myopathy or rhabdomyolysis.
As cited, the drugs are:

• Itraconazole
• Ketoconazole
• Erythromycin
• Clarithromycin
• Telithromycin
• HIV proteas inhibitors
• Nefazodone
• Gemfibrozil
• Cyclosporine
• Danazole
• Amiodarone
• Verapamil

They say that cholesterol is a carriage that brings the horrors of coronary heart disease and the complications of diabetes mellitus. For some time, those who have high levels of low-density lipids in their blood have to rely on diet, exercise and a lot more weight reduction just to [...] Continue Reading…