Simvastatin with Danazol Interaction Details

Brand Names Associated with Simvastatin

Brand Names Associated with Danazol

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 10, 2023

Interaction Effect

An increased risk of myopathy or rhabdomyolysis

Interaction Summary

Concomitant use of danazol and simvastatin is contraindicated due to increased risk of developing myopathy and rhabdomyolysis. In a case report, concomitant therapy with simvastatin 40 mg/day and danazol 600 mg/day resulted in fatal rhabdomyolysis in an 80-year-old man receiving danazol for idiopathic thrombocytopenic purpura . In another case report, a 68-year-old man on chronic simvastatin 40 mg/day developed rhabdomyolysis and acute renal failure 4 weeks after initiation of danazol 200 mg three times daily for autoimmune hemolytic anemia. Rhabdomyolysis and renal failure resolved after danazol discontinuation and temporary hemodialysis .

Severity

Contraindicated

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Concomitant use of danazol and simvastatin is contraindicated due to increased risk of developing myopathy and rhabdomyolysis.

Mechanism Of Interaction

Unknown

Literature Reports

A) Concomitant administration of simvastatin and danazol resulted in fatal rhabdomyolysis in an 80-year-old man with idiopathic thrombocytopenia purpura (ITP). This patient had been receiving simvastatin 20 mg/day for 2 years when danazol (400 mg then 200 mg per day) was started for treatment of ITP. After 3 months of combination simvastatin and danazol treatment, simvastatin was increased to 40 mg/day and danazol to 600 mg/day. Thirty-five days later, he was seen in the emergency room (ER) following an accidental fall caused by generalized weakness. In the ER, he complained of fatigue, mild pretibial edema, progressive bilateral leg pain, and cramping. Following examination, he was discharged from the ER with diagnoses of collapse and nasal contusion. Two days later, he was admitted to the hospital with oliguria, dark urine, muscle pain and tenderness. Laboratory tests revealed a creatine kinase (CK) of 22,700 units/L (100 times the ULN), a BUN of 42 mmol/L, a serum creatinine of 720 mcmol/L, and an AST and ALT of 442 and 314 unit/L, respectively. Despite medical management, including hemodialysis and drug discontinuation, his CK level rose to 35,000 unit/L. Six days after hospital admission for rhabdomyolysis, he died of acute renal failure. An assessment of causality on the Naranjo adverse drug reaction probability scale rated the association of rhabdomyolysis and concomitant use of danazol and simvastatin as probable. This patient had risk factors for statin-induced adverse events, including older age, renal dysfunction, and a history of type 2 diabetes mellitus .

B) A 68-year-old man developed rhabdomyolysis and acute renal failure following concomitant simvastatin and danazol therapy. He received chronic therapy for hyperlipidemia with simvastatin 40 mg/day. Other chronic concomitant medications included allopurinol, atenolol, furosemide, and acetylsalicylic acid, and he initiated danazol 200 mg three times daily for autoimmune hemolytic anemia previously treated with azathioprine and prednisone. Prior to admission, he had a 2-week history of decreased appetite, increased dyspnea, reduced urine output, and tea-colored urine. Four weeks after starting danazol therapy, he presented with a 5-day history of progressive muscle pain and weakness. He declined using any nonprescription medications and consumption of grapefruit juice. Upon admission, he was unable to lift his arms or stand up, and all medications were withheld. Relevant laboratory findings included a creatine kinase level of 50,060 unit/L, a BUN of 31.1 mmol/L, a serum creatinine of 1230 mcmol/L, a urine myoglobin level of greater than 10,000 mcg/L, and a potassium level of 7.9 mmol/L. He was treated for hyperkalemia and following 8 hemodialysis sessions, his oliguria resolved. Atenolol, acetylsalicylic acid, and prednisone were resumed and he was discharged 4 days later. An assessment of causality on the Naranjo adverse drug reaction probability scale rated the association of rhabdomyolysis and concomitant use of danazol and simvastatin as probable .

Simvastatin Overview

• Simvastatin is used together with diet, weight-loss, and exercise to reduce the risk of heart attack and stroke and to decrease the chance that heart surgery will be needed in people who have heart disease or who are at risk of developing heart disease. Simvastatin is also used to decrease the amount of fatty substances such as low-density lipoprotein (LDL) cholesterol (''bad cholesterol'') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol (''good cholesterol'') in the blood. Simvastatin may also be used to decrease the amount of cholesterol and other fatty substances in the blood in children and teenagers 10 to 17 years of age who have familial heterozygous hypercholesterolemia (an inherited condition in which cholesterol cannot be removed from the body normally). Simvastatin is in a class of medications called HMG-CoA reductase inhibitors (statins). It works by slowing the production of cholesterol in the body to decrease the amount of cholesterol that may build up on the walls of the arteries and block blood flow to the heart, brain, and other parts of the body.

• Accumulation of cholesterol and fats along the walls of your arteries (a process known as atherosclerosis) decreases blood flow and, therefore, the oxygen supply to your heart, brain, and other parts of your body. Lowering your blood level of cholesterol and fats with simvastatin has been shown to prevent heart disease, angina (chest pain), strokes, and heart attacks.

Danazol Overview

• Danazol is used to treat endometriosis (a condition in which the type of tissue that lines the uterus [womb] grows in other areas of the body and causes infertility, pain before and during menstrual periods, pain during and after sexual activity, and heavy or irregular bleeding)..Danazol is also used to treat fibrocystic breast disease (swollen, tender breasts with noncancerous lumps) when other treatments are not successful. Danazol is also used to prevent attacks in people with hereditary angioedema (inherited condition that causes episodes of swelling in the hands, feet, face, airway, or intestines). Danazol is in a class of medications called androgenic hormones. It works to treat endometriosis by shrinking the displaced tissue of the uterus. It works to treat fibrocystic breast disease by blocking the release of hormones that cause the breast pain and lumps. It works to treat hereditary angioedema by increasing the amount of a natural substance in the body.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.