These include medications such as methadone, amiodarone, citalopram, and fluconazole. Other medications may increase the risk for a low level of potassium in the blood, thereby indirectly increasing the risk for QT prolongation. For example, dexamethasone, hydrochlorothiazide, and theophylline can lower the level of potassium in the blood. CNS depression
Lofexidine can depress the central nervous system (CNS), which, in combination with other CNS depressants, may reduce a persons ability to perform tasks that require skills and attention. For example, clobazam, gabapentin, and levetiracetam all can depress the CNS. Hypotension
The risk of hypotension (low blood pressure) is increased when lofexidine is combined with other drugs that lower blood pressure. These may include losartan, metoprolol, and pramipexole. Pharmacology
Lofexidine is an agonist at the α-2A, 2B, and 2C adrenergic receptor subtypes, with the highest activity at the alpha-2A receptor. Ki represents the dissociation constant for lofexidines binding to a specific subtype of alpha-2 receptor. The smaller the Ki value, the stronger the drug binds to the receptor to exert its activity. Lofexidine inhibits the release of norepinephrine in the central and peripheral nervous system, thereby reducing some of the symptoms of opioid withdrawal, but it has no documented effect on drug craving and endogenous opioid levels. Pharmacokinetics
Lofexidines oral bioavailability is about 90%, with extensive oral absorption. Peak plasma concentrations occur at 3 hours after a single administration, with a half-life of 11 hours. Lofexidine is extensively metabolized by the liver, and primarily cleared by the kidney. It is 80-90% plasma protein bound.
Anemia is common in fetuses exposed to warfarin as blood constantly seeps into the interstitial fluid or amniotic cavity. High doses of warfarin and heavy bleeding lead to abortion and stillbirth. Osteocalcin is another protein dependent on vitamin K for correct folding and function. Osteocalcin is normally secreted by osteoblast cells and plays a role in aiding correct bone mineralization and bone maturation. In the presence of warfarin and subsequent absence of vitamin K and active osteocalcin, bone mineralization and growth are stunted. Prevention
Fetal warfarin syndrome is prevented by withholding prescription to pregnant women or those trying to conceive. As warfarin can remain in the mothers body for up to five days, warfarin should not be administered in the days leading up to conception. Doctors must take care to ensure women of reproductive age are aware of the risks to the baby should they get pregnant, before prescribing warfarin. For some women, such as those with prosthetic heart valves, anticoagulation medication cannot be suspended during pregnancy as the risk of thrombus and emboli is too high. In such cases an alternate anticoagulant, which cannot pass through the placental barrier to the fetus, is proscribed in place of warfarin. Heparin is one such anticoagulant medication, although its efficacy in patients with prosthetic heart valves is not well established. New anticoagulant medications, which are efficacious and non-teratogenic such as ximelagatran continue to be developed.