Naltrexone

Today's med: Naltrexone (nal TREKS one)

(brand names: ReVia, Vivitrol; Index term: Naltrexone Hydrochloride)

Drug Class:  Opioid antagonist, Opioid receptor

Other Drugs in this class: Naloxone,Morphine/naltrexone, Pentazocine/Naloxone,

Buprenorphine/Naloxone, Naloxone Hydrochloride, Naltrexone Hydrochloride

Indications: Treatment of ethanol dependence; prevention of relapse in opioid dependent patients, following opioid detoxification

Action: Naltrexone (a pure opioid antagonist) is a cyclopropyl derivative of oxymorphone similar in structure to naloxone and nalorphine (a morphine derivative); it acts as a competitive antagonist at opioid receptor sites, showing the highest affinity for mu receptors.

Contraindications: Hypersensitivity to naltrexone or any component of the formulation; narcotic dependence or current use of opioid analgesics; acute opioid withdrawal; failure to pass naloxone challenge or positive urine screen for opioids; acute hepatitis; liver failure

Lab Interactions: May cause cross-reactivity with some opioid immunoassay methods.

Adverse Effects: Combined reporting of adverse events from oral and injectable formulations:

>10%:

Cardiovascular: Syncope (13%)

Central nervous system: Headache (3% to 25%), insomnia (3% to 14%), dizziness (4% to 13%), anxiety (2% to 12%), nervousness (4% to >10%)

Gastrointestinal: Nausea (10% to 33%), vomiting (3% to 14%), appetite decreased (14%), diarrhea (13%), abdominal pain (11%), abdominal cramping

Hepatic: ALT increased (13%)

Local: Injection site reaction (≤69%; includes bruising, induration, nodules, pain, pruritus, swelling, tenderness)

Neuromuscular & skeletal: Arthralgia (12%), CPK increased (11% to 39%)

Respiratory: Pharyngitis (7% to 11%)

1% to 10%:

Cardiovascular: Hypertension (5%)

Central nervous system: Suicidal thoughts (≤10%), depression (8%), somnolence (2% to 4%), fatigue (4%), chills, energy increased, feeling down, irritability

Dermatologic: Rash (6%)

Endocrine & metabolic: Polydipsia

Gastrointestinal: Dry mouth (5%), toothache (4%)

Genitourinary: Delayed ejaculation, impotency

Hepatic: AST increased (2% to 10%), GGT increased (7%)

Neuromuscular & skeletal: Muscle cramps (8%), back pain (6%)

Miscellaneous: Influenza (5%)

<1% (Limited to important or life-threatening): Angina, atrial fibrillation, blood pressure increased, cerebral aneurysm, chest pain, chest tightness, cholecystitis, cholelithiasis, colitis, COPD, dehydration, delirium, diaphoresis, DVT, dyspnea, ECG changes, eosinophilia (transient), eosinophilic pneumonia, GI hemorrhage, HF, hypercholesterolemia, hypersensitivity reaction (includes anaphylaxis, angioedema, and urticaria), ischemic stroke, leukocytosis, lymphadenopathy, MI, narcotic withdrawal, palpitation, pancreatitis, paralytic ileus, paranoia, PE, perirectal abscess, pneumonia, rigors, seizure, shortness of breath, suicide , tachycardia, thrombocytopenia

Warnings: Concerns related to adverse effects:

• Accidental opioid overdose: Patients who had been treated with naltrexone may respond to lower opioid doses than previously used. This could result in potentially life-threatening opioid intoxication. Patients should be aware that they may be more sensitive to lower doses of opioids after naltrexone treatment is discontinued, after a missed dose, or near the end of the dosing interval. Warn patients that any attempt to overcome opioid blockade during naltrexone therapy, could potentially lead to fatal opioid overdose; the opioid competitive receptor blockade produced by naltrexone is potentially surmountable in the presence of large amounts of opioids.

• Acute opioid withdrawal: May precipitate symptoms of acute withdrawal in opioid-dependent patients, including pain, hypertension, sweating, agitation, and irritability; in neonates: shrill cry, failure to feed.

• Eosinophilic pneumonia: Cases of eosinophilic pneumonia have been reported and should be considered in patients presenting with progressive hypoxia and dyspnea.

• Hepatocellular injury: [U.S. Boxed Warning]: Dose-related hepatocellular injury is possible; the margin of separation between the apparent safe and hepatotoxic doses appears to be ≤ fivefold. Discontinue therapy if signs/symptoms of acute hepatitis develop.

• Hypersensitivity reactions: Hypersensitivity, including anaphylaxis, has been reported.

• Injection site reactions: Serious injection site reactions (eg, cellulitis, induration, hematoma, abscess, necrosis) have been reported with use, including severe cases requiring surgical debridement. Females appear to be at a higher risk. Patients should any injection site pain, swelling, bruising, pruritus, or redness that does not improve (or worsens). For I.M. use only in the gluteal muscle, do not administer I.V., SubQ, or into fatty tissue; incorrect administration may increase the risk of injection site reactions.

• Suicidal thoughts/depression: Suicidal thoughts and depression have been reported in both alcohol- and opioid-dependent patients; monitor closely.

Dosage form specific issues:

• Injection: Vehicle used in the injectable naltrexone formulation (polylactide-co-glycolide microspheres) has rarely been associated with retinal artery occlusion in patients with abnormal arteriovenous anastomosis following injection of other drug products that also use the polylactide-co-glycolide microspheres vehicle.

Other warnings/precautions:

• Detoxified opioid addiction: Patients should be opioid-free for a minimum of 7-10 days; use naloxone challenge test to confirm patient is opioid-free prior to therapy if there is any suspicion since urinary opioid screen may not be sufficient proof. Use of naltrexone does not eliminate or diminish withdrawal symptoms.

• Emergency pain management: In naltrexone-treated patients requiring emergency pain management, consider alternatives to opioid therapy (eg, regional analgesia, nonopioid analgesics, general anesthesia). If opioid therapy is required for pain therapy, patients should be under the direct care of a trained anesthesia provider.

Standard Dosing: 

Adults: Note: Do not initiate therapy until patient is opioid-free for at least 7-10 days as determined by urinalysis; consider naloxone challenge test to confirm patient is opioid-free if there is any suspicion since urinary opioid screen may not be sufficient proof.

Oral: Alcohol dependence, opioid dependence: Initial: 25 mg; if no withdrawal signs occur, administer 50 mg on day 2; maintenance regimen: 50 mg/day; alternative maintenance regimens may be used and include: 50 mg on weekdays with a 100 mg dose on Saturday; 100 mg every other day; or 150 mg every 3 days (degree of blockade may be reduced with extended dosing interval regimens and doses >50 mg may increase risk of hepatocellular injury)

I.M.: Alcohol dependence, opioid dependence: 380 mg once every 4 weeks

Administration

Oral: May be administered with or without food. Administration with food or after meals may minimize adverse gastrointestinal effects. Advise patient not to self-administer opiates while receiving naltrexone therapy.

I.M.: Vivitrol®: Administer I.M. into the upper outer quadrant of the gluteal area; must inject dose using one of the provided needles for administration. Use either the 1.5-inch 20-gauge needle or the 2-inch 20-gauge needle (for patients with a larger amount of subcutaneous tissue overlying the gluteal muscle). Avoid inadvertent injection into a blood vessel; do not administer I.V., SubQ, or into fatty tissue (the risk of serious injection site reaction is increased if given incorrectly as a SubQ injection or into fatty tissue instead of the gluteal muscle). Injection should alternate between the 2 buttocks. Do not substitute any components of the dose-pack.

Drug interactions: http://www.drugs.com/drug-interactions/naltrexone.html

A total of 450 drugs (2259 brand and generic names) are known to interact with naltrexone.

• 7 major drug interactions (14 brand and generic names)
• 443 moderate drug interactions (2245 brand and generic names)

Show all medications in the database that may interact with naltrexone.

No"tracks"zone...Naltrexone

Phentermine

Today's med: Phentermine (FEN ter meen) 

(brand names: Adipex-P, Suprenza, Lonamin; Index Term: Phentermine Hydrochloride)

Drug Class:  Sympathomimetic Amine Anorexiant, CNS Stimulant

Other Drugs in this class: Phendimetrazine, Amfepramone,Benzphetamine, Phentermine Hydrochloride,Diethylpropion hydrochloride,Phendimetrazine tartrate, Benzphetamine hydrochloride

Action:  Phentermine is a sympathomimetic amine with pharmacologic properties similar to the amphetamines. The mechanism of action in reducing appetite appears to be secondary to CNS effects, including stimulation of the hypothalamus to release norepinephrine.

Indications: Short-term (few weeks) adjunct therapy in obese patients with an initial body

mass index (BMI) ≥30 kg/m² or ≥27 kg/m² in the presence of other risk factors (eg, diabetes, hyperlipidemia, controlled hypertension); therapy should be used in conjunction with a comprehensive weight management program.

Contraindications: Hypersensitivity or idiosyncrasy to phentermine or other sympathomimetic amines or any component of the formulation; history of cardiovascular disease (arrhythmias, congestive heart failure, coronary artery disease, stroke, uncontrolled hypertension); hyperthyroidism, glaucoma, agitated states, history of drug abuse; use during or within 14 days following MAO inhibitor therapy; pregnancy, breast-feeding

Adverse Effects: Frequency not defined. MOST COMMON: Tachycardia and Hypertension

Cardiovascular: Hypertension, ischemic events, palpitation, primary pulmonary hypertension and/or regurgitant cardiac valvular disease, tachycardia

Central nervous system: Dizziness, dysphoria, euphoria, headache, insomnia, overstimulation, psychosis, restlessness

Dermatologic: Urticaria

Endocrine & metabolic: Changes in libido

Gastrointestinal: Constipation, diarrhea, unpleasant taste, xerostomia

Genitourinary: Impotence

Neuromuscular & skeletal: Tremor

Standard Dosing: Note: Dosing is presented in terms of the salt, phentermine hydrochloride (not as phentermine base).

Oral: Children >16 years (OH YAY!) and Adults: Obesity:

Capsule, tablet: 15-37.5 mg/day given in 1-2 divided doses. Individualize to achieve adequate response with lowest effective dose.

Orally disintegrating tablet (ODT): One tablet (15 mg or 30 mg) every morning. Individualize to achieve adequate response with lowest effective dose.

Administration

Avoid late evening administration.

Capsules, tablets: Administer before breakfast or 1-2 hours after breakfast. Tablets may be divided in half and dose may be given in 2 divided doses.

Orally disintegrating tablets (Suprenza™): With dry hands, place tablet on the tongue and allow to dissolve, then swallow with or without water. May administer with or without food.

Dietary Considerations

Capsules, tablets: Should be taken before breakfast or 1-2 hours after breakfast; avoid taking in the late evening. Most effective when combined with a low-calorie diet and behavior modification counseling.

Lab Test Interference: May interfere with urine detection of amphetamines/methamphetamines (false-positive).

Drug interactions: http://www.drugs.com/drug-interactions/phentermine.html

A total of 440 drugs (3259 brand and generic names) are known to interact with phentermine.

• 83 major drug interactions (408 brand and generic names)
• 355 moderate drug interactions (2845 brand and generic names)
• 2 minor drug interactions (6 brand and generic names)

Show all medications in the database that may interact with phentermine.

Avoid: Cardiovascular disease, Glaucoma, Psychosis, Substance Abuse, TIc disorder, Diabetes and Liver disease. Moderate level interaction with food and alcohol. 

Phentermine....like an Amphetamine (increases release of NE)

Doxorubicin (Adriamycin)

Today's med: Doxorubicin (doks oh ROO bi sin)

(brand name: Adriamycin; Index terms: ADR, Adria, Doxorubicin Hydrochloride, Hydroxydaunomycin Hydrochloride)

Drug Class: Anthracycline Topoisomerase Inhibitor

Other Drugs in this class: Epirubicin,Daunorubicin, Idarubicin, Doxorubicin Hydrochloride, Epirubicin Hydrochloride,Daunorubicin Hydrochloride, Idarubicin Hydrochloride, Daunorubicin citrate

Indications:  Labeled Indications

Treatment of acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin’s disease, malignant lymphoma, soft tissue and bone sarcomas, thyroid cancer, small cell lung cancer, breast cancer, gastric cancer, ovarian cancer, bladder cancer, neuroblastoma, and Wilms' tumor

Use: Unlabeled

Treatment of multiple myeloma, endometrial carcinoma, uterine sarcoma, head and neck cancer, liver cancer, kidney cancer

Action:  Inhibition of DNA and RNA synthesis by intercalation between DNA base pairs by inhibition of topoisomerase II and by steric obstruction. Doxorubicin intercalates at points of local uncoiling of the double helix. Although the exact mechanism is unclear, it appears that direct binding to DNA (intercalation) and inhibition of DNA repair (topoisomerase II inhibition) result in blockade of DNA and RNA synthesis and fragmentation of DNA. Doxorubicin is also a powerful iron chelator; the iron-doxorubicin complex can bind DNA and cell membranes and produce free radicals that immediately cleave the DNA and cell membranes.

Absorption

Oral: Poor (<50%)

Distribution

V_d: 809-1214 L/m²; to many body tissues, particularly liver, spleen, kidney, lung, heart; does not distribute into the CNS; crosses placenta

Metabolism

Primarily hepatic to doxorubicinol (active), then to inactive aglycones, conjugated sulfates, and glucuronides

Contraindications: Hypersensitivity to doxorubicin, any component of the formulation, or to other anthracyclines or anthracenediones; recent MI, severe myocardial insufficiency, severe arrhythmia; previous therapy with high cumulative doses of doxorubicin, daunorubicin, idarubicin, or other anthracycline and anthracenediones; baseline neutrophil count <1500/mm³; severe hepatic impairment

Adverse Effects: Frequency not defined.

Cardiovascular:

Acute cardiotoxicity: Atrioventricular block, bradycardia, bundle branch block, ECG abnormalities, extrasystoles (atrial or ventricular), sinus tachycardia, ST-T wave changes, supraventricular tachycardia, tachyarrhythmia, ventricular tachycardia

Delayed cardiotoxicity: LVEF decreased, CHF (manifestations include ascites, cardiomegaly, dyspnea, edema, gallop rhythm, hepatomegaly, oliguria, pleural effusion, pulmonary edema, tachycardia); myocarditis, pericarditis

Central nervous system: Malaise

Dermatologic: Alopecia, itching, photosensitivity, radiation recall, rash; discoloration of saliva, sweat, or tears

Endocrine & metabolic: Amenorrhea, dehydration, infertility (may be temporary), hyperuricemia

Gastrointestinal: Abdominal pain, anorexia, colon necrosis, diarrhea, GI ulceration, mucositis, nausea, vomiting

Genitourinary: Discoloration of urine

Hematologic: Leukopenia/neutropenia (75%; nadir: 10-14 days; recovery: by day 21); thrombocytopenia and anemia

Local: Skin “flare” at injection site, urticaria

Neuromuscular & skeletal: Weakness

Postmarketing and/or case reports: Anaphylaxis, azoospermia, bilirubin increased, coma (when in combination with cisplatin or vincristine), conjunctivitis, fever, gonadal impairment (children), growth failure (prepubertal), hepatitis, hyperpigmentation (nail, skin & oral mucosa), infection, keratitis, lacrimation, myelodysplastic syndrome, neutropenic fever, neutropenic typhlitis, oligospermia, peripheral neurotoxicity (with intra-arterial doxorubicin), phlebosclerosis, radiation recall pneumonitis (children), secondary acute myelogenous leukemia, seizure (when in combination with cisplatin or vincristine), sepsis, shock, Stevens-Johnson syndrome, systemic hypersensitivity (including urticaria, pruritus, angioedema, dysphagia, and dyspnea), toxic epidermal necrolysis, transaminases increased, urticaria

Standard Dosing: (see 5 minute clinical consult for dosing adjustments d/t toxicity and disease conditions)

I.V.: Refer to individual protocols. Note: Lower dosage should be considered for patients with inadequate marrow reserve (due to old age, prior treatment or neoplastic marrow infiltration)

Children:

35-75 mg/m²/dose every 21 days or

20-30 mg/m²/dose once weekly or

60-90 mg/m²/dose given as a continuous infusion over 96 hours every 3-4 weeks

Adults: Usual or typical dose: 60-75 mg/m²/dose every 21 days or

60 mg/m²/dose every 2 weeks (dose dense) or

40-60 mg/m²/dose every 3-4 weeks or

20-30 mg/m²/day for 2-3 days every 4 weeks or

20 mg/m²/dose once weekly

Administration

Vesicant. Administer I.V. push over at least 3-5 minutes or by continuous infusion (infusion via central venous line recommended). Avoid extravasation associated with severe ulceration and soft tissue necrosis. Flush with 5-10 mL of I.V. solution before and after drug administration. Incompatible with heparin. Monitor for local erythematous streaking along vein and/or facial flushing (may indicate rapid infusion rate).

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH, 2012).

Drug interactions: http://www.drugs.com/drug-interactions/doxorubicin.html

A total of 410 drugs (1349 brand and generic names) are known to interact with doxorubicin.

• 73 major drug interactions (184 brand and generic names)
• 273 moderate drug interactions (851 brand and generic names)
• 64 minor drug interactions (314 brand and generic names)

Show all medications in the database that may interact with doxorubicin.

CYP3A4, CYP2D6 Inhibitors

DoxoRubicin...DNA and RNA synthesis inhibition.

37 year old male with recurrent upper abdominal pain

A 37-year-old executive returns to your office for follow-up of recurrent upper abdominal pain. He initially presented 6 weeks ago, complaining of an increase in frequency and severity of burning epigastric pain, which he has experienced occasionally for more than 2 years. Now the pain occurs three or four times per week, usually when he has an empty stomach, and it often awakens him at night. The pain usually is relieved within minutes by food or over-the-counter antacids but then recurs within 2 to 3 hours. He admitted that stress at work had recently increased and that because of long working hours, he was drinking more caffeine and eating a lot of take-out foods. His medical history and review of systems were otherwise unremarkable, and, other than the antacids, he takes no medications. His physical examination was normal, including stool guaiac that was negative for occult blood.

➤ What is your diagnosis?

➤ What dietary recommendations should you give the patient?

➤ What medication is indicated?

➤ What botanicals are indicated?

➤ What botanicals are contraindicated?  

His symptoms resolved completely with the diet changes and daily use of the medication.

Results of laboratory tests performed at his first visit show no anemia, but his serum Helicobacter pylori antibody test was positive.

➤ What is your next step?