Medications Naltrexone
Acamprosate (Campral) Acamprosate (Campral) may be prescribed to help patients recovering from alcohol abuse or dependence to help decrease alcohol cravings and relieve emotional discomfort. Acamprosate’s action in alcohol use disorder is through modulating excitatory glutamate neurotransmission and enhancing GABA, which may help reduce alcohol cravings. It has been shown to significantly reduce the risk of returning to alcohol use after achieving abstinence and reducing the number of drinking days. It is an effective first-line alternative to naltrexone and is often chosen in patients taking opioids and those with severe liver disease. It is also a useful second- line treatment in patients who do not experience an adequate response to naltrexone. 204,213 Dosing for acamprosate is 666 mg tablets three times daily. Patients with moderate renal dysfunction, shown by a creatinine clearance of 30 to 50 ml/min, are recommended to begin at 333 mg three times daily. Lower dosing can also be considered for patients with a body weight less than 60 kg. Acamprosate is generally well tolerated; common side effects include nausea and diarrhea and, although rare, depression and suicidality. Renal function should be monitored; acamprosate is contraindicated in those with creatinine clearance less than 30 mL/min. There are no known drug interactions. Healthcare providers should counsel patients on the importance of adherence to acamprosate to ensure its effectiveness. 204,213 Choosing between Naltrexone and Acamprosate A number of factors can be considered when deciding between initiating naltrexone and acamprosate in a patient with alcohol use disorder. These include available formulations, ease of administration, side effects and presence of renal or hepatic disease. A large meta-analysis did not show a statistically significant difference between acamprosate and naltrexone in the percent of patients with a return to drinking, percent of patients with a return to heavy drinking, or the number of drinking days. Therefore, naltrexone or acamprosate can be seen as an appropriate initial treatment for alcohol use disorder, and patient- specific factors should be utilized to determine the best choice for a given patient. 204 Disulfiram (Antabuse) Disulfiram (Antabuse) is prescribed to help dissuade patients from drinking. Disulfiram works by inhibiting aldehyde dehydrogenase, the enzyme involved in metabolism of the primary metabolite of alcohol, acetaldehyde. If alcohol is consumed in the presence of disulfiram, acetaldehyde levels increase to toxic levels, creating very unpleasant side effects including nausea, vomiting, flushing, headache, dyspnea, palpitations, lowered blood pressure, and sympathetic overactivity. Symptoms typically begin within 10 minutes of consuming alcohol, and the severity of the reaction is typically related to the amount of alcohol ingested. Symptoms can last for several hours or up to a day. Some patients develop more severe reactions such as chest pain, seizures,
confusion, headache, or severe vomiting; these require further evaluation to rule out alternative conditions such as myocardial infarction. 204,213 Disulfiram is typically given in doses of 125 to 500mg per day. Disulfiram should not be administered to patients who are currently drinking or intoxicated with alcohol. Patients must be clearly informed about the effects of the drug and give permission for its use; this treatment’s effectiveness depends on the patient’s cooperation. Patients should be educated on hidden forms of alcohol, such as that found in mouthwash, and that the medication can continue to exert its effects for up to 14 days after discontinuation. Adherence can be a significant issue with disulfiram use; enlisting the help of a family member, roommate, or other support person can help keep the patient accountable. 204,213 Disulfiram is often reserved for second line therapy in patients with alcohol use disorder. Naltrexone and acamprosate appear to have more evidence of benefits with their use, and disulfiram has a number of physiological consequences if alcohol relapse occurs. However, some patients who have a clear goal of abstinence prefer the accountability that disulfiram requires. Studies have not shown high-strength evidence on the benefits of disulfiram, but it appears to have a clear role in motivated patients. 204 Disulfiram is contraindicated in patients with psychosis, clinically significant coronary artery disease, and known hypersensitivities to the medication. When alcohol is avoided, disulfiram is generally well-tolerated, but side effects may include drowsiness, metallic taste and headache. Serious side effects are rare but can include psychosis and hepatitis. Patients should have a hepatic panel drawn a few weeks after initiating treatment and repeat every 6 months with continued treatment. Patients with seizure disorders should avoid disulfiram due to the potential for seizures when alcohol is consumed while taking disulfiram. 204,213 Drug interactions with disulfiram include the following: 213,214 • Isoniazid: Can increase serum concentrations of isoniazid. Avoid concurrent use. • Metronidazole: May cause psychotic reaction because of the increased effects of both disulfiram and metronidazole. Avoid concurrent use. • Phenytoin: May increase toxic effect of phenytoin. Phenytoin levels must be carefully monitored, and dose adjusted as needed. • Warfarin: Disulfiram can increase the concentration of warfarin; therapy adjustments may be required. An important counseling point for disulfiram is for the patient to avoid any type of alcohol- containing product, even mouthwashes and cough syrups. These products may cause the unwanted reactions if taken while using disulfiram. Patients should also be counseled that if they do drink alcohol, fatal hypotension can occur. Reactions with alcohol ingestion may occur up to two weeks after disulfiram is stopped. 204,213
Naltrexone is an opioid receptor antagonist frequently used to treat opioid and alcohol abuse. It works by blocking mu opioid receptors and preventing binding, thus reducing the pleasurable effects of opioids. It reduces alcohol consumption by modulation of opioid systems, which reduces the reinforcing effects of alcohol. Naltrexone use has been associated with a reduction in the number of drinking days, reduced likelihood of returning to drinking, and is also thought to decrease cravings. It is the drug of choice in patients with concomitant opioid use disorder, since it is approved to treat both conditions. Patients should not be actively using opioids when naltrexone is started, since it can inhibit the effects of opioids and lead to noncompliance. 204,213 Naltrexone is available in oral tablets and an intramuscular formulation known as Vivitrol, which is administered every 4 weeks. The choice between dosage forms is based on patient preference; some patients show better adherence to daily dosages while others are more willing to attend monthly visits for injections. Typically, it is preferable to start intramuscular naltrexone to ensure adherence, though starting with oral tablets may be more appropriate in some cases, to see if liver enzymes are affected or side effects emerge, before committing to a longer course of treatment. 204,213 Intramuscular injections of naltrexone are given at a dose of 380 mg into the gluteal muscle every 4 weeks. Adverse reactions seen with intramuscular naltrexone include nausea, vomiting, diarrhea, fatigue, decreased appetite, and injection site reactions ranging from injection site pain to cellulitis and abscesses. Patients should be encouraged to report injection site reactions to their provider to prevent development into more serious skin conditions. 204,213 Oral naltrexone is typically started at 50 mg per day, though some studies have used up to 100 mg per day or started with 25 mg per day for a few days and increased to 50 mg once the lower dose is tolerated well. Side effects with oral naltrexone are similar to those with intramuscular naltrexone and include headache, dizziness, nausea, vomiting, diarrhea and abdominal pain; these tend to subside with regular use. Gastrointestinal side effects tend to be more common in women than in men. 204,213 Liver enzymes should be monitored within several weeks of starting either oral or injectable naltrexone, and monitored every 6 months during continued treatment because of the risk of increase with naltrexone. Patients with hepatic failure or acute hepatitis should also avoid using naltrexone. Naltrexone is not recommended for use in patients taking prescribed opioids, since naltrexone will decrease the effectiveness of opioids. Patients should be abstinent from opioids for 7 to 14 days prior to starting naltrexone, depending on the half- life of the opioid consumed. 204,213
38
Powered by FlippingBook