Overall, evidence is insufficient to conclude that simvastatin has an effect in delaying the onset and progression of AMD. Simvastatin is contraindicated with pregnancy, breastfeeding, and liver disease. Pregnancy must be avoided while on simvastatin due to potentially severe birth defects. Patients cannot breastfeed while on simvastatin due to potentially disrupting the infant's lipid metabolism. High doses of simvastatin are also contraindicated with the widely used antihypertensive amlodipine. A lower dose is also recommended in people taking the calcium channel blockers, verapamil and diltiazem, as well as those taking amiodarone. Common side effects (>1% incidence) may include indigestion and eczema. Rare side effects include joint pain, memory loss, and muscle cramps. Cholestatic hepatitis, hepatic cirrhosis, rhabdomyolysis (destruction of muscles and blockade of renal system), and myositis have been reported in patients receiving the drug chronically. Serious allergic reactions to simvastatin are rare. If the following signs of a serious allergic reaction occur, seek medical attention immediately: rash, hoarseness itching/swelling, dizziness, or difficulty swallowing/breathing. A type of DNA variant known as a single nucleotide polymorphism (SNP) may help predict individuals prone to developing myopathy when taking simvastatin; a study ultimately including 32,000 patients concluded the carriers of one or two risk alleles of a particular SNP, rs4149056, were at a five-fold or 16-fold increased risk, respectively. In 2012, the Clinical Pharmacogenetics Implementation Consortium has released guidelines regarding the use of rs4149056 genotype in guiding dosing of simvastatin and updated the guideline in 2014. In March 2012, the U.S. Food and Drug Administration (FDA) updated its guidance for statin users to address reports of memory loss, liver damage, increased blood sugar, development of type 2 diabetes, and muscle injury. The new guidance indicates:  On 19 March 2010, the FDA issued another statement regarding simvastatin, saying it increases the risk of muscle injury (myopathy) when taken at high doses or at lower doses in combination with other drugs. The highest dose rate causes muscle damage in 610 of every 10,000 people in contrast to a lower dose, which causes muscle damage in eight of 10,000 people.