Drug-induced lupus erythematosus is an autoimmune disorder caused by chronic use of certain drugs. These drugs cause an autoimmune response (the body attacks its own cells) producing symptoms similar to those of systemic lupus erythematosus (SLE). There are 38 known medications to cause DIL but there are three that report the highest number of cases:  hydralazine, procainamide, and quinidine. While the criteria for diagnosing DIL has not been thoroughly established, symptoms of DIL typically present as muscle pain and joint pain. Generally, the symptoms recede after discontinuing use of the drugs. Signs and symptoms
Signs and symptoms of drug-induced lupus erythematosus include the following:
Joint pain (arthralgia) and muscle pain (myalgia)
Fatigue
Serositis—inflammation of the tissues lining the heart and lungs. Anti-histone antibodies in 95% of cases among those taking procainamide, hydralazine, chlorpromazine, and quinidine; however, these antibodies have been found in a smaller proportion of patients associated with other medications, including minocycline, propylthiouracil, and statins.These signs and symptoms are not side effects of the drugs taken which occur during short term use. DIL occurs over long-term and chronic use of the medications listed below. While these symptoms are similar to those of systemic lupus erythematosus, they are generally not as severe unless they are ignored which leads to more harsh symptoms, and in some reported cases, death. Causes
The processes that lead to drug-induced lupus erythematosus are not entirely understood.
Ramelteon and fluvoxamine should not be coadministered.Ramelteon has significant drug–drug interaction with the following drugs: amiodarone, ciprofloxacin, fluvoxamine, ticlopidine. Ramelteon should be administered with caution in patients taking other CYP1A2 inhibitors, strong CYP3A4 inhibitors such as ketoconazole, and strong CYP2C9 inhibitors such as fluconazole.Efficacy may be reduced when ramelteon is used in combination with potent CYP enzyme inducers such as rifampin, since ramelteon concentrations may be decreased. Pharmacology
Pharmacodynamics
Ramelteon is a melatonin receptor agonist with both high affinity for melatonin MT1 and MT2 receptors and selectivity over the non-human MT3 receptor. Ramelteon demonstrates full agonist activity in vitro in cells expressing human MT1 or MT2 receptors, and high selectivity for human MT1 and MT2 receptors compared to the non-human MT3 receptor. The affinity of ramelteon for the MT1 and MT2 receptors is 3 to 16 times higher than that of melatonin. Ramelteon has 8-fold higher affinity for the MT1 receptor over the MT2 receptor. The binding profile of ramelteon distinguishes it from melatonin, tasimelteon, and agomelatine.The major metabolite of ramelteon, M-II, is active and has approximately one-tenth and one-fifth the binding affinity of the parent molecule for the human MT1 and MT2 receptors, respectively, and is 17- to 25-fold less potent than ramelteon in in vitro functional assays. Although the potency of M-II at MT1 and MT2 receptors is lower than the parent drug, M-II circulates at higher concentrations than the parent producing 20- to 100-fold greater mean systemic exposure when compared to ramelteon.