Naltrexone is an oral opiate receptor antagonist. It is derived from thebaine and is very similar in structure to oxymorphone. Like parenteral naloxone, naltrexone is a pure antagonist (i.e., agonist actions are not apparent), but naltrexone has better oral bioavailability and a much longer duration of action than naloxone. Clinically, naltrexone is used to help maintain an opiate-free state in patients who are known opiate abusers. Naltrexone is of greatest benefit in patients who take the drug as part of a comprehensive occupational rehabilitative program or other compliance-enhancing program. Unlike methadone or LAAM, naltrexone does not reinforce medication compliance and will not prevent withdrawal. Naltrexone has been used as part of rapid and ultrarapid detoxification techniques. These techniques are designed to precipitate withdrawal by administering opiate antagonists. These approaches are thought to minimize the risk of relapse and allow quick initiation of naltrexone maintenance and psychosocial supports. Ultrarapid detoxification is performed under general anesthesia or heavy sedation. While numerous studies have been performed examining the role of these detoxification techniques, a standardized procedure including appropriate medications and dose, safety, and effectiveness have not been determined in relation to standard detoxification techniques.1 Naltrexone supports abstinence, prevents relapse, and decreases alcohol consumption in patients treated for alcoholism. Naltrexone is not beneficial in all alcoholic patients and may only provide a small improvement in outcome when added to conventional therapy. The FDA approved naltrexone in 1984 for the adjuvant treatment of patients dependent on opiate agonists. FDA approval of naltrexone for the treatment of alcoholism was granted January 1995. The FDA approved Vivitrol, a once-monthly intramuscular naltrexone formulation used to help control cravings for alcohol in April 2006, and then in October 2010, the FDA approved Vivitrol for the prevention of relapse to opioid dependence after opioid detoxification.
Mechanism of Action: Like naloxone, naltrexone is a competitive antagonist at opiate receptors mu, kappa, and delta. Opiate receptors have been reclassified by an International Union of Pharmacology subcommittee as OP1 (delta), OP2 (kappa), and OP3 (mu). Naltrexone can either displace opiate agonists from binding at these receptors or prevent opiate binding. Naltrexone does not antagonize the effects of non-opiates such as cocaine, ethanol, amphetamines, barbiturates, or benzodiazepines. Blockade of opiate receptors by naltrexone is a competitive phenomenon and results in elimination of the euphoric effect of opiates. At usual opiate concentrations, naltrexone's greater affinity for the receptor prevents the binding of the opiate agonist to the receptor. However, when opiate concentrations are extremely high, the opiate can displace naltrexone, and respiratory depression and/or death is possible. Although naltrexone itself may possess some agonistic properties, these are minor compared to its potent antagonistic actions. Naltrexone is 17-times more potent than nalmorphine and twice as potent as naloxone. In patients who are physically dependent on opiates, naltrexone will precipitate an opiate withdrawal syndrome. Naltrexone use is not associated with tolerance or dependence, therefore, withdrawal from naltrexone does not occur. When co-administered with opiate agonists, naltrexone blocks the physical dependence to morphine, heroin, and other opiate agonists. Depending on the dose, the clinical effects of naltrexone can persist for up to 72 hours.
Endogenous opiods such as beta-endorphins and enkephalins may play an important role in alcoholism. An opioid reward system mediated by mu- and delta-receptors and an opposing aversions system mediated by kappa-receptors must be in balance to maintain a neutral state in regards to the development of addiction. Several therories regarding alcohol addiction and the function of endongeous opioids exist. All of these therories are based on an imbalance in favor of the endongenous reward pathways due to alcohol. Naltrexone inhibits the effects of endogenous opioids and decreases the positive or reward pathways associated with alcoholism. Naltrexone is not aversive therapy and will not produce a disulfiram-like reaction if opiates or ethanol are ingested while receiving naltrexone.
Pharmacokinetics: Naltrexone is administered orally or intramuscularly. Naltrexone is widely distributed throughout the body, and antagonistic activity appears to be related to plasma and tissue concentrations.CSF concentrations are not known. Protein binding is roughly 21—28%. Naltrexone is metabolized to 6-beta-naltrexol, which also has antagonistic activity but is less potent than its parent. Significantly less 6-beta-naltrexol is generated following IM administration of naltrexone compared to administration of oral naltrexone due to a reduction in first-pass hepatic metabolism. Two other minor metabolites have been identified: 2-hydroxy-3-methoxy-6-beta-naltrexol and 2-hydroxy-3-methyl-naltrexone. The cytochrome P450 system is not involved in the metabolism of naltrexone. There appears to be little accumulation of naltrexone and 6-beta-naltrexol after chronic administration. Naltrexone is a highly extracted drug (> 98% metabolized), and extra-hepatic sites of metabolism may exist. Following hepatic metabolism, both naltrexone and its metabolites conjugate with glucuronic acid. The maximum serum concentration and systemic exposure for both naltrexone and 6-beta-naltrexol are dose proportional. Total naltrexone exposure is 3—4 fold higher after a single, 380 mg IM injection as compared with daily oral doses of 50 mg for 28 days.
Both naltrexone and its metabolite are excreted primarily by the kidney (53—79% of the dose). Only about 2% of naltrexone is excreted in the urine unchanged within 24 hours. 6-beta-naltrexol appears to undergo renal tubular secretion. Although naltrexone and its metabolites may undergo enterohepatic recycling, fecal elimination is a minor elimination pathway. The mean elimination half-life of naltrexone after oral administration is 4 hours, and the elimination half-life of 6-beta-naltrexol is roughly 14 hours. The mean elimination half-life of both naltrexone and 6-beta-naltrexol after intramuscular administration is 5—10 days; elimination of naltrexone is dependent on erosion of the polymer.
Oral absorption is rapid and almost complete (roughly 96%). Due to extensive first-pass metabolism in the liver, however, only 5—40% of the drug reaches the systemic circulation unchanged. Studies indicate that oral naltrexone 50 mg will block the pharmacologic effects of 25 mg IV heroin for as long as 24 hours. Additional data suggest that doubling the dose of naltrexone provides blockade for 48 hours and tripling the dose provides blockade for up to 72 hours.
Pharmacokinetic parameters of naltrexone given intramuscularly are essentially unchanged in patients with mild or moderate (Child-Pugh class A or B) hepatic impairment. The disposition of naltrexone in patients with either severe hepatic impairment has not been evaluated. In patients with compensated and decompensated liver cirrhosis, the AUC of oral naltrexone increased 5- and 10-fold, respectively, as compared to patients with normal liver function. Dosage adjustments may be necessary in patients with hepatic dysfunction.
Renal Impairment: Pharmacokinetic parameters of naltrexone given intramuscularly are essentially unchanged in patients with a creatinine clearance of 50—80 ml/minute. The disposition of naltrexone in patients with moderate to severe renal impairment has not been evaluated. Dosage adjustments may be necessary in patients with renal dysfunction.
For the maintenance treatment of alcohol dependence:
Adults: 50 mg PO once daily with food for 12 weeks has been shown to be effective. Other regimens or durations have not been evaluated in placebo-controlled trials, but include 50 mg PO once daily on weekdays and 100 mg PO on Saturdays; 100 mg PO every other day; or 150 mg PO every third day.2 A consensus panel recommends naltrexone treatment be individualized to meet the patient's needs. Some patients may require naltrexone doses of 100 mg/day PO. Initially, patients may require 3 to 6 months of naltrexone treatment. Certain patients may benefit from up to 1 year of treatment. To decrease gastrointestinal side effects, start with 12.5 mg to 25 mg PO once daily and gradually titrate the dose, split the daily dose, or adjust the administration times.3 Pharmacotherapy should be used as a part of a comprehensive management program that includes psychosocial support and treatment. Naltrexone does not eliminate or reduce alcohol withdrawal symptoms. If naltrexone is initiated early in the abstinence process, it will not prevent signs and symptoms that would be experienced if the drug had not been started.24
For relapse prevention following opioid detoxification in patients with opiate agonist dependence:
Adults: Initial dose of 25 mg PO with food. If no withdrawal signs occur, the patient may be started on 50 mg PO once daily therafter.2 NOTE: Naltrexone should be used as part of a comprehensive treatment plan that includes psychosocial support and medication compliance techniques. Patients must be opioid-free for a minimum of 7—10 days before starting naltrexone to avoid precipitation of opioid withdrawal.42
Neonates, Infants, Children, and Adolescents: Safety and efficacy have not been established.
Maximum Dosage Limits
150 mg/day PO; 380 mg/dose IM.
150 mg/day PO; 380 mg/dose IM.
Safety and efficacy have not been established.
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing: Naltrexone undergoes significant liver metabolism. In patients with severe hepatic dysfunction, up to a 10-fold increase in naltrexone AUC may be observed. Dosage adjustment may be necessary in patients with hepatic impairment. However, specific guidelines for dosage adjustments in patients with hepatic dysfunction are not available.
Patients with Renal Impairment Dosing: Both naltrexone and its active metabolite are excreted renally, and naltrexone doses may need adjustment for patients with renal impairment. However, specific guidelines for dosage adjustment in patients with renal impairment are not available.
General Administration Information: For storage information, see the specific product information within the How Supplied section.
In general, do not attempt treatment with naltrexone unless, in the medical judgment of the prescribing physician, there is no reasonable possibility of short-acting opiate agonist use within the past 7—10 days, and up to two weeks for long-acting opioids. If there is any question of occult opiate dependence, perform a challenge test. If the challenge test is positive, do NOT initiate naltrexone therapy. Repeat the test in 24 hours. If the test is negative and there are no other contraindications, naltrexone therapy may be started. If there is any doubt about the results of the test, hold naltrexone and repeat the challenge in 24 hours. Advise patient not to self-administer opiates while receiving naltrexone therapy.2
Route-Specific Administration: Oral Administration: Administer tablets by mouth with food to decrease nausea. Tablets are scored for splitting, if needed.23
Contraindications/Precautions: Naltrexone is contraindicated in patients with hypersensitivity to naltrexone or any components of the commercially available product. Naltrexone is incorporated in 75:25 polylactide-co-glycolide (PLG) at a concentration of 337 mg of naltrexone per gram of microspheres. The diluent is composed of carboxymethylcellulose sodium salt, polysorbate 20, sodium chloride, and water for injection. Naltrexone should also not be used in patients with a known hypersensitivity to naloxone or nalmefene because these three drugs are all structurally similar.
The use of naltrexone in patients with hepatic disease should be carefully considered due to the hepatotoxic effects of naltrexone and the potential for decreased clearance of naltrexone. Naltrexone does not appear to be hepatotoxic at recommended doses. However, the margin between a safe dose and a hepatotoxic dose appears to be five-fold or less. There may be a higher risk of hepatocellular injury with single doses above 50 mg, and use of higher doses and extended dosing intervals should balance the possible risks against the probable benefits. There are reports of hepatitis and significant hepatic dysfunction in association with exposure to naltrexone oral tablets and parenteral naltrexone. In patients treated with naltrexone tablets or injection who presented with elevated transaminases, other potential causes were often identified, including pre-existing alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other potentially hepatotoxic drugs. Opioid withdrawal does not typically manifest as clinically significant hepatic dysfunction, however, abruptly precipitated opioid withdrawal may lead to systemic sequelae including acute liver injury. Warn patients of the potential risk of hepatic injury and advise them to seek medical attention if they experience symptoms of acute hepatitis. Discontinue use of naltrexone if signs/symptoms of acute hepatitis occur.542
Depression, suicide, attempted suicide and suicidal ideation have been reported in patients receiving naltrexone for the treatment of opioid dependence. No causal relationship has been demonstrated. In the literature, endogenous opioids have been theorized to contribute to a variety of conditions. Monitor alcohol and opioid dependent patients, including those taking naltrexone, for the development of depression or suicidal thinking. Inform families and caregivers of patients being treated with naltrexone to monitor patients for the emergence of symptoms of depression or suicidality, and to report such symptoms to the patient’s healthcare provider.2
Naltrexone is contraindicated in patients who are receiving opioid analgesics, partial opiate agonists (e.g., buprenorphine), those with current physiologic opioid dependence, and those in acute opioid withdrawal. Administration of naltrexone to these patients may precipitate an abrupt withdrawal severe enough to require hospitalization, and in some cases management in the intensive care unit. To prevent precipitation of withdrawal, patients should be opioid-free (including tramadol) for a minimum of 7—10 days prior to initiation of naltrexone. When transitioning from buprenorphine or methadone, patients may be vulnerable to precipitation of withdrawal symptoms for up to two weeks. In every case, be prepared to manage withdrawal symptomatically with non-opioid medications because there is no completely reliable method for determining whether a patient has had an adequate opioid-free period. Since the absence of an opiate drug in the urine is often not sufficient proof that a patient is opiate-free, a naloxone challenge should be done if there is any question of occult opioid dependence. A naloxone challenge test may be helpful; however, a few case reports have indicated that patients may experience precipitated withdrawal despite having a negative urine toxicology screen or tolerating a naloxone challenge test (usually in the setting of transitioning from buprenorphine treatment). Make patients aware of the risks associated with precipitated withdrawal and the need to give an accurate account of last opioid use. A positive reaction to the naloxone challenge predicts a similar response to naltrexone. Use of naltrexone is contraindicated in an individual who fails the naloxone challenge test or who has a positive urine test for opioids.The naloxone challenge can be repeated in 24 hours. Assess patients treated for alcohol dependence for underlying opioid dependence and for any recent use of opioids prior to initiation of treatment with naltrexone. Precipitated opioid withdrawal has been observed in alcohol-dependent patients in circumstances where the prescriber had been unaware of the additional use of opioids or co-dependence on opioids.542
If a painful procedure such as surgery is planned, then naltrexone should be discontinued 72 hours prior to the procedure. Patients should be abstinent from opiate analgesia for at least 7 days before restarting naltrexone.
Naltrexone treated patients who require emergent opiate analgesia may require the administration of large opiate doses to provide adequate pain control, which may increase the risk of deep or prolonged respiratory depression. A rapidly acting opiate agonist is preferred for emergent analgesia to limit the duration of respiratory depression. Non-opiate receptor mediated actions (i.e., histamine-mediated) may occur with the use of opiates and should be expected (e.g., facial swelling, itching, generalized erythema or bronchoconstriction). Other alternatives for emergent analgesia in patients taking naltrexone include the use of regional analgesia, conscious sedation, non-opiate analgesics, or general anesthetics.
Attempts to overcome the antagonistic effects of naltrexone with large doses of an opiate agonist by patients maintained on naltrexone may result in potential for overdose or poisoning that may be fatal; cases of opioid overdose with fatal outcomes have been reported in patients after discontinuing treatment. Despite a prolonged pharmacologic effect, the blockade produced by naltrexone is surmountable. As the naltrexone blockade wanes and eventually dissipates, patients may respond to lower doses of opioids than previously used, potentially resulting in life-threatening opioid intoxication (respiratory compromise or arrest, circulatory collapse, etc.) if the patient uses previously tolerated doses of opioids. Patients are at particular risk at the end of the dosing interval, after missing a scheduled dose or after discontinuing naltrexone treatment. Patients should be informed of the serious consequences of attempting to overcome the opiate blockade and that they may be more sensitive to lower doses of opiate agonists once naltrexone therapy is stopped. Advise patients to inform family members and those closest to them of this increased sensitivity and risk of overdose.542
Naltrexone and its major active metabolite are excreted primarily by the kidney. Use caution in administering naltrexone to patients with renal impairment. Pharmacokinetic parameters of naltrexone given intramuscularly are essentially unchanged in patients with a creatinine clearance of 50—80 ml/minute. The disposition of naltrexone in patients with moderate to severe renal impairment has not been evaluated. Dosage adjustments may be necessary in patients with renal dysfunction.
Naltrexone is classified as FDA pregnancy risk category C. There are no adequate and well-controlled studies in pregnant women. In some individuals, opiate antagonists have been associated with a change in baseline levels of some hypothalamic, pituitary, adrenal, or gonadal hormones, although the clinical significance is not known. In rat studies, there was an increase in early fetal loss and pseudopregnancy, and a decrease in pregnancy rate. There was no evidence of teratogenicity; however, rats do not form a significant amount of the major human metabolite, 6-B-naltrexol; therefore, the potential reproductive toxicity of 6-B-naltrexol in rats is not known. There were small increases in the numbers of testicular mesotheliomas in male rats and vascular tumors in female rats during a 2-year carcinogenicity study; however, no evidence of carcinogenicity was observed in mice.5 When considering the use of naltrexone during pregnancy for relapse prevention in alcohol or opiate dependence, the risks to the fetus of continued substance abuse by the mother should be weighed against the potential adverse effects from fetal exposure to naltrexone. Drug therapy should be considered only if supportive substance abuse prevention measures are ineffective. The effects of naltrexone during labor and delivery are unknown.
According to the manufacturer, naltrexone and its metabolite are excreted into human milk, and a decision should be made to discontinue breast-feeding or discontinue naltrexone, taking into consideration the importance of the drug to the mother. Animal studies have shown the potential for tumorigenicity.5 No reports describing the use of naltrexone during breast-feeding are available. According to the American Academy of Pediatrics (AAP), the maternal ingestion of large amounts of ethanol or opiates can cause adverse effects in the nursing infant.6 If supportive substance abuse prevention measures are ineffective, the risks to the nursing infant of continued ethanol or opiate abuse by the mother should be weighed against the potential for adverse drugs effects when determining whether to use naltrexone as a substance abuse deterrent during breast-feeding.
The safe use of naltrexone in neonates, infants, children, and adolescents < 18 years has not been established.
Naltrexone may cause dizziness (see Adverse Reactions). Tell patients about the importance of not driving or operating machinery until they know how this medicine will affect them.
Administer the extended-release injectable suspension of naltrexone cautiously to patients with thrombocytopenia, coagulopathy, or other bleeding disorders. Patients with thrombocytopenia, vitamin K deficiency, a coagulopathy (e.g., hemophilia), or receiving anticoagulant therapy should be monitored closely when given intramuscular naltrexone because bleeding can occur at the IM injection site. All steps to avoid hematoma formation are recommended.
Naltrexone extended-release injectable suspension (Vivitrol) is only for intramuscular administration; intravenous administration and subcutaneous administration should be avoided. The risk of serious injection site reactions may be increased when Vivitrol is deposited in subcutaneous or fatty tissue (see Adverse Reactions). Proper administration techniques and patient selection are imperative (see Administration). Consider alternate treatment for patients whose body habitus (obesity) precludes a gluteal intramuscular injection with the provided needle. Women may be physiologically at higher risk for injection site reactions because of typically higher gluteal fat thickness, and in fact, post-marketing reports of injection site reactions occur primarily in females. Also, a variable depth of subcutaneous tissue exists between patients; the depth is dependent on the gender and weight of the patient.
Pregnancy: Naltrexone is classified as FDA pregnancy risk category C. There are no adequate and well-controlled studies in pregnant women. In some individuals, opiate antagonists have been associated with a change in baseline levels of some hypothalamic, pituitary, adrenal, or gonadal hormones, although the clinical significance is not known. In rat studies, there was an increase in early fetal loss and pseudopregnancy, and a decrease in pregnancy rate. There was no evidence of teratogenicity; however, rats do not form a significant amount of the major human metabolite, 6-B-naltrexol; therefore, the potential reproductive toxicity of 6-B-naltrexol in rats is not known. There were small increases in the numbers of testicular mesotheliomas in male rats and vascular tumors in female rats during a 2-year carcinogenicity study; however, no evidence of carcinogenicity was observed in mice.5 When considering the use of naltrexone during pregnancy for relapse prevention in alcohol or opiate dependence, the risks to the fetus of continued substance abuse by the mother should be weighed against the potential adverse effects from fetal exposure to naltrexone. Drug therapy should be considered only if supportive substance abuse prevention measures are ineffective. The effects of naltrexone during labor and delivery are unknown.
Breast-feeding: According to the manufacturer, naltrexone and its metabolite are excreted into human milk, and a decision should be made to discontinue breast-feeding or discontinue naltrexone, taking into consideration the importance of the drug to the mother. Animal studies have shown the potential for tumorigenicity.5 No reports describing the use of naltrexone during breast-feeding are available. According to the American Academy of Pediatrics (AAP), the maternal ingestion of large amounts of ethanol or opiates can cause adverse effects in the nursing infant.6 If supportive substance abuse prevention measures are ineffective, the risks to the nursing infant of continued ethanol or opiate abuse by the mother should be weighed against the potential for adverse drugs effects when determining whether to use naltrexone as a substance abuse deterrent during breast-feeding.
What should I tell my health care provider before I take this medicine? They need to know if you have any of these conditions:
• if you have used drugs or alcohol within 7 to 10 days
• kidney disease
• liver disease, including hepatitis
• an unusual or allergic reaction to naltrexone, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
How should I use this medicine? Take this medicine by mouth with a full glass of water. Follow the directions on the prescription label. Do not take this medicine within 7 to 10 days of taking any opioid drugs. Take your medicine at regular intervals. Do not take your medicine more often than directed. Do not stop taking except on your doctor's advice. Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.
Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.
What if I miss a dose? If you miss a dose and remember on the same day, take the missed dose. If you do not remember until the next day, ask your doctor or health care professional about rescheduling your doses. Do not take double or extra doses.
What may interact with this medicine? Do not take this medicine with any of the following medications:
• any prescription or street opioid drug like codiene, heroin, methadone
This medicine may also interact with the following medications:
This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.
What side effects may I notice from receiving this medicine? Side effects that you should report to your doctor or health care professional as soon as possible:
• allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
• breathing problems
• changes in vision, hearing
• dark urine
• depressed mood
• fast or irregular heart beat
• hallucination, loss of contact with reality
• light-colored stools
• right upper belly pain
• suicidal thoughts or other mood changes
• unusually weak or tired
• yellowing of the eyes or skin
Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
• aches, pains
• change in sex drive or performance
• feeling anxious
• loss of appetite, nausea
• runny nose, sinus problems, sneezing
• stomach pain
• trouble sleeping
This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What should I watch for while using this medicine? Your condition will be monitored carefully while you are receiving this medicine. Visit your doctor or health care professional regularly. For this medicine to be most effective you should attend any counseling or support groups that your doctor or health care professional recommends. Do not try to overcome the effects of the medicine by taking large amounts of narcotics or by drinking large amounts of alcohol. This can cause severe problems including death. Also, you may be more sensitive to lower doses of narcotics after you stop taking this medicine.
If you are going to have surgery, tell your doctor or health care professional that you are taking this medicine.
Do not treat yourself for coughs, colds, pain, or diarrhea. Ask your doctor or health care professional for advice. Some of the ingredients may interact with this medicine and cause side effects.
Wear a medical ID bracelet or chain, and carry a card that describes your disease and details of your medicine and dosage times.
You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how this medicine affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells. Alcohol may interfere with the effect of this medicine. Avoid alcoholic drinks.
Where should I keep my medicine? Keep out of the reach of children. Store at room temperature between 20 and 25 degrees C (68 and 77 degrees F). Throw away any unused medicine after the expiration date.
- 1. O'Connor PG, Kosten TR. Rapid and ultrarapid opioid detoxification techniques. JAMA 1998;279:229-234.
- 2. a. b. c. d. e. f. g. h. i. j. Revia (naltrexone hydrochloride) package insert. Pomona, NY: Duramed Pharmaceuticals, Inc. 2013 Oct.
- 3. a. b. Incorporating Alcohol Pharmacotherapies into Medical Practice: A review of the literature. Center for Substance Abuse Treatment. Rockville, MD: US Substance Abuse and Mental Health Services Administration; 2009.
- 4. a. b. c. d. e. Vivitrol (naltrexone extended release injectable suspension) package insert. Cambridge, MA: Alkermes, Inc.; 2013 Aug.
- 5. a. b. c. d. e. f. g. Naltrexone (naltrexone hydrochloride) package insert. Hazelwood, MO: Mallinckrodt, Inc. 2009 Feb.
- 6. a. b. American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89.