Drug Information Questions

6/26/15

On Friday, I was able to answer quite a few drug information questions that had been asked of me. First the pharmacist received a call from the local provider office regarding a patient with mastitis who had both an amoxicillin allergy and cephalosporin allergy. She wanted to know what would be an appropriate next choice since she was currently breast feeding. According the the American Academy of Family Physicians there are 3 other acceptable options. The options include: ciprofloxacin, clindamycin, or sulfamethoxazole/trimethoprim. According to the manufacturer breast feeding is not recommended with ciprofloxacin although only 2.2% of the dose appears to be transmitted to the milk. In regards to clindamycin, the manufacturer says no breast feeding, but it does not appear to be in breast milk. With Bactrim they recommended only using it in mother's who babies are >2 months and are not immunocompromised. I called the provider and let them know the 3 other possibilities of medications so they could choose an appropriate therapy for the patient.

The other question I was asked by another pharmacist was can you split Abilify tablets? Although they are tablets, sources on the internet say you should swallow the tablet whole. It was difficult to find information as to why they state in the prescribing information they should be swallowed whole. In an article that was published in Current Psychiatry they created a handy list of medications that are acceptable to split and ones that are not. Abilify is on the list that is acceptable to split. In addition, many Medicaid formularies require tablet splitting as part of drug therapy to save on cost. I let the pharmacist know that it is acceptable to split Abilify tablets.

Blood Glucose Monitoring and Teaching

6/25/15

Tomorrow I have the great opportunity to teach a patient how to use a brand new blood glucose meter. The new meter is the Accu-Check Avia Plus. The first topic I looked into was blood sugar testing and when testing should be done with oral anti-glycemic medications. If the patient is within their A1C goal they only need to test once a day. If they are above goal, they need to test 2 to 3 times daily. Of course they should be testing if they start to experience any low blood sugars. 

My next thing I researched was the use of control solution. This solution is meter specific and needs to be used a few different situations. When using the control solution it is done just like testing blood, but a drop of liquid from the bottle is placed on the strip. A control test should be done in the following situations:

• Before using the meter for the first time
• When a new vial of test strips are opened
• If the vial of test strips are left open (allows to check for accuracy)
• If the meter is dropped (to check for accuracy)
• If your meter reading doesn't seem to be quite right (ex: you are feeling low, but it is reading high or you feel ok and it is reading very low)
• If you want to verify your technique in checking blood sugars 
• If you repeated the test that didn't seem right and it is still out the range you were expecting
• If you just want to know how your meter or strips are currently performing

Review of counseling

6/24/15

Today I had a lot of great counseling practice in. I counseled on various drugs and really became part of the pharmacy workflow. I counseled on drugs including but not limited to: antibiotics (doxycycline, clindamycine, azithromycin, etc), Depakote ER, alprazolam, and prednisone. It was a good opportunity to continue to work on my counseling skills as well as counsel on new drugs I haven't counseled on before such as Depakote. While here I did a review on Depakote so I felt confident counseling on the medication. 

Important counseling points with Depakote:

• If ER formulation do not chew or crush, swallow whole
• If stomach upset occurs, take with food
• Drowsiness is common initially so it is best to avoid driving before you know how the medication affects you
• Common side effects include: stomach upset, diarrhea, hair loss, and ringing of the ears 
• A more uncommon, but serious side effect is liver toxicity so it is important to inform the patient that the doctor should be monitoring the liver function

Another medication that came through the pharmacy that I have never counseled on was Tamoxifen:

• Tamoxifen is a SERM and can cause some estrogen related side effects 
• If upset stomach occurs take with food. 
• Side effects of this medication include: hot flashes, menstrual changes, vaginal dryness, and other hormonal changes. 
• In addition, there in an increased risk of blood clots with the medication so if the patient notices any shortness of breath or redness or swelling in the legs they should contact their physician immediately

FDA updates Pregnancy and Lactation Labeling

6/23/15

Today I did research related to the updated pregnancy and lactation labeling that will take effect beginning 6/30/15. It separates pregnancy and lactation into 3 new subheadings: 8.1 Pregnancy (includes Labor and Delivery), 8.2 Lactation, and 8.3 Females and Males of Reproductive Potential.  It will apply to all new drugs approved after June 30^th. Drugs that were approved after June 29, 2001 will have 3 years to comply with the new labeling. Those that were approved before June 29, 2001 do not need to adopt the new labeling requirements, but they will need to remove the current letter labeling. The new FDA labeling provides more detailed information about each risk rather than just stratifying the risk into a letter category. Finally, it will provide more guidance about clinical decision making to help clinicians make decisions about what medication to use. In addition, it will help quantify what exactly needs to be done when females or males use the medication related to pregnancy tests or appropriate contraception. 

Addyi (filbanserin) Drug Information

·         Background

o   HSDD 7.7 to 14% of premenopausal women in the US or 5.5 to 8.6 million individuals

o   developed by Sprout pharmaceuticals

o   approved by FDA on June 4, 2015

·         Indication

o   hypoactive sexual desire disorder (HSDD)

·         Adverse effects

o   fainting, nausea, dizziness, sleepiness, low blood pressure

·         Mechanism

o   mechanism is unknown

o   mixed agonist/antagonist effect on postsynaptic serotonergic receptors

o   5HT1A agonist and 5HT2A antagonist

·         Concerns

o   avoid with alcohol due to concerns about central nervous system depression, hypotension, syncope

o   avoid in pregnant women

o   avoid with strong or moderate CYP3A4 inhibitors

o   prior to HSDD, it was considered for antidepressant indication and though all antidepressants have a black box warning for suicides, there is no sign of increase risk with filbanserin

·         Pharmacokinetics

o   peak levels reached in 45 to 60 minutes of administration

o   peak levels are delayed by 1 to 3 hours with meal

o   terminal elimination half-life is 12 hours

o   taking with high fat high calorie meal increases exposure 50%

o   administration with CYP3A4 inhibitors (ketoconazole, fluconazole) increases filbanserin 4.5 and 7 times, respectively

o   hormonal contraceptives are weak inhibitors of CYP3A4, but increase filbanserin 40%

Source:

Pharmacy Times. What to Know About “Female Viagra” Backed by FDA Panel.  http://www.pharmacytimes.com/news/what-to-know-about-female-viagra-backed-by-fda-panel#sthash.UW4UXYXR.dpuf

Drug Information Question

Question – Patient receives a prescription for Lamisil (terbinafine) 250mg for 10days and is inquiring when he may be allowed to drink alcohol again as he plans to attend a wedding on day 11.

Answer – Lamasil has a half-life of 22 to 26 hours with the half-life of 200 to 400 hours from skin and adipose tissue. Half-life is the amount of time needed to decrease the amount of drug in the body 50%. It usually takes 5 half-lives for the drug to be eliminated from the body close to 100%. With a half-life of 24 hours it would take approximately 5 days for terbinafine to be eliminated from the body. It would be best to wait 5 days before consuming alcohol after finishing the course of terbinafine. I called Novartis and they recommended not drinking alcohol with this product and they said they could not make a recommendation for after the patient stopped taking the medication.

Source:

Terbinafine hydrochloride.  DrugPoints Summary.  Micromedex 2.0.  Truven Health Analytics, Inc. Greenwood Village, CO.  Available at: http://www.micromedexsolutions.com.  Accessed June 16, 2015.

Key Drug Interactions

Key Drug Interactions

·         Serotonin syndrome

o   Mental status changes, agitation, diaphoresis, tachycardia, death

o   monoamine oxidase inhibitor (MAOI) - phenelzine or tranylcypromine sulfate

o   dextromethorphan, meperidine, and SSRI such as fluoxetine

o   stop fluoxetine 5 weeks before MAOI due to long half-life of metabolite norfluoxetine

o   wait 2 after MAOI ends and SSRI begins 

·         Digoxin and Quinidine

o   Increase in digoxin levels

o   Quinidine displaces digoxin from binding sites and leading to a decreased Vd of digoxin

o   Quinidine decreases renal and nonrenal excretion of digoxin

·         Sildenafil and Isosorbide mononitrate

o   Hypotension due to sildenafil being a PDE5 inhibitor and nitrates increase cGMP

·         Potassium (chloride, bicarbonate, citrate, acetate, gluconite, and iodide) and potassium sparing diuretics (spironolactone, amiloride, triamterene)

o   Leads to hyperkalemia, cardiac failure, and death especially in patients in renal impairment

·         Clonidine and Propanolol

o   Rebound hypertension when suddenly stopping clonidine

o   Clonidine is a central alpha-2 adrenergic agonist that causes a decrease in NE

o   Alpha-1 receptors then become sensitized because of less norepinephrine

o   With suddenly withdrawn a large increase in norepinephrine occurs leading to vasoconstriction by the sensitized alpha1 receptors

o   Body cannot compensate because the beta-2 receptors are blocked

·         Warfarin and NSAID (diflunisal, ketoprofen, piroxicam, sulindac, diclo-fenac, and ketorolac)

o   increase the risk of GI bleeding

o   acetaminophen or nonacetylated salicylates (magnesium salicylate or salsalate) is an alternative

·         Theophylline and Ciprofloxacin

o   Increase in theophylline levels

o   Theophylline is metabolized by CYP1A2

o   Ciprofloxacin, clarithromycin, erythromycin, fluvoxamine, and cimetidine inhibit CYP1A2

o   levofloxacin or ofloxacin is an alternative

·         Pimozide and Ketoconazole

o   Prolong QT interval and ventricular arrhythmias (torsades de pointes)

o   Pimozide is metabolized by CYP3A4

o   Ketoconazole, fluconazole inhibit CYP3A4

o   Terbinafine is safer

·         Methotrexate and Probenecid or Penicillins or Salicylates

o   Increase methotrexate levels

o   Probenecid inhibits renal secretion

o   methotrexate toxicity include diarrhea, vomiting, diaphoresis, renal failure, and death

o   alternatives include acetaminophen not salicylates or NSAIDS (celecoxib okay, rofexcoxib NOT okay)

·         Bromocriptine and Pseudoephedrine

o   peripheral vasoconstriction, ventricular tachycardia, seizures, and possibly death

o   Bromocriptine dopamine agonist for Parkinson’s (first line therapy is bromocriptine or other dopamine agonist such as ropinirole, pramipexole, or pergolide

o   Avoid all sympathomimetics with bromocriptine

Source: http://www.pharmacytimes.com/publications/issue/2002/2002-11/2002-11-7010

Theophylline

·         xanthine derivative

·         treats asthma and stable COPD to relax the bronchial smooth muscle

·         serum theophylline concentration of 10–20mg/L 

·         Symptoms of theophylline toxicity

o   Nausea

o   Vomiting

o   Gastric irritation

o   Diarrhea

o   Palpitations

o   Tachycardia

o   Arrhythmias

o   Headache

o   Central nervous system stimulation

o   Insomnia

o   Convulsions

·         Metabolized in the liver by CYP1A2

o   Cirrhosis and congestive heart failure reduce theophylline clearance

·         Common drug interactions

o   Benzodiazepines

§  theophylline antagonizes the sedative and anxiolytic effects of benzodiazepines

o   H2-receptor antagonists

§  theophylline concentrations are increased by cimetidine

§  famotidine, nizatidine, and ranitidine do not interact

o   Ciprofloxacin

§  theophylline concentrations are increased

o   Erythromycin

§  theophylline concentrations are increased because theophylline clearance is reduced

o   Levothyroxine

§  theophylline concentrations are increased with hypothyroidism treatment

o   Methotrexate

§  theophylline concentrations are increased because theophylline clearance is reduced

§  might reduce methotrexate-induced neurotoxicity and methotrexate efficacy

o   Phenytoin

§  theophylline concentrations are decreased because increases the clearance of theophylline

·         Age

o   neonates and elderly have reduced theophylline clearance

·         Smokers

o   smokers need higher theophylline doses than non-smokers

o   tobacco smoke induces CYP1A2

o   smoking cessation results in increase in serum theophylline concentrations

o   reduce theophylline dose with smoking cessation

·         Adverse effects

o   risk of QT-interval prolongation with theophylline AND citalopram or fluoxetine together

o   low potassium, magnesium or calcium can cause QT prolongation

Source: http://www.pharmaceutical-journal.com/learning/learning-article/theophylline-interactions/20065570.article

Important drug ranges

Drug	Normal Range	Abnormal Range
Acetaminophen	varies	> 250 mcg/mL
Amikacin	15 to 25 mcg/mL	> 25 mcg/mL
Aminophylline	10 to 20 mcg/mL	> 20 mcg/mL
Amitriptyline	120 to 150 ng/mL	> 500 ng/mL
Carbamazepine	5 to 12 mcg/mL	> 12 mcg/mL
Cyclosporine	100 to 400 ng/mL (12 hours after dose)	> 400 ng/mL
Desipramine	150 to 300 ng/mL	> 500 ng/mL
Digoxin	0.8 to 2.0 ng/mL	> 2.4 ng/mL
Disopyramide	2 to 5 mcg/mL	> 5 mcg/mL
Ethosuximide	40 to 100 mcg/mL	> 100 mcg/mL
Flecainide	0.2 to 1.0 mcg/mL	> 1.0 mcg/mL
Gentamicin	5 to 10 mcg/mL	> 12 mcg/mL
Imipramine	150 to 300 ng/mL	> 500 ng/mL
Kanamycin	20 to 25 mcg/mL	> 35 mcg/mL
Lidocaine	1.5 to 5.0 mcg/mL	> 5 mcg/mL
Lithium	0.8 to 1.2 mEq/L	> 2.0 mEq/L
Methotrexate	varies	> 10 mcmol/L over 24-hours
Nortriptyline	50 to 150 ng/mL	> 500 ng/mL
Phenobarbital	10 to 30 mcg/mL	> 40 mcg/mL
Phenytoin	10 to 20 mcg/Ml	> 30 mcg/mL
Primidone	5 to 12 mcg/mL	> 15 mcg/mL
Procainamide	4 to 10 mcg/mL	> 16 mcg/mL
Quinidine	2 to 5 mcg/mL	> 10 mcg/mL
Salicylate	varies	> 300 mcg/mL
Sirolimus	4 to 20 ng/mL (12 hours after dose; varies)
Tacrolimus	5 to 15 ng/mL (12 hours after dose)
Theophylline	10 to 20 mcg/mL	> 20 mcg/mL
Tobramycin	5 to 10 mcg/mL	> 12 mcg/mL
Valproic acid	50 to 100 mcg/mL	> 100 mcg/mL

Source:

http://www.nlm.nih.gov/medlineplus/ency/article/003430.htm

Addiction Treatment

Key Recommendations from the American Pain Society on the use of methadone for pain

·         Assess likelihood of patient adherence

·         Patient education regarding risk of cardiac arrhythmias, onset of action, and communicating to health care team about new prescription or nonprescription drugs

·         Baseline ECG in patients with risk for QTc prolongation (family history, drug-induced, or electrolyte abnormalities)

·         Follow up ECG

o   Within 2 to 4 weeks in those at risk or those with history of QTc prolongation

o   If total daily methadone dose > 30mg

o   If total daily methadone dose > 100mg

o   Signs of ventricular arrhythmia (palpitations, syncope, pre-syncope)

·         Methadone is contraindicated in patients with QTc >500ms

·         Address reversible causes of QTc prolongation before starting methadone when QTc is between 450 to 500

·         Methadone is initiated < 2.5mg every 8 hours in opioid naïve patients

·         Methadone is initiated < 40mg daily in opioid tolerant patients

·         Dose cannot be titrated up more than every 5 to 7 days

·         Assess adverse effects 3 to 5 days after initiation of methadone

·         Methadone should be avoided with benzodiazepine

Additional Definitions

·         Misuse – using medication other than as directed

·         Abuse – using a medication for nonmedical purpose (ex: getting high)

·         Aberrant behavior – departing from strict adherence to the prescribed plan of care

·         Addiction – impaired control over drug use, compulsive use, craving

·         Pseudoaddiction – untreated pain exhibit aberrant behavior, but resolves with adequate pain control

·         Dependence – withdrawal symptoms due to stopping or decreasing the drug

·         Tolerance – decreased effectiveness of drug over time. Higher doses needed to get same effect.

·         Diversion – using a drug for recreational purposes

·         Hyperalgesia – escalating doses of opioids results in increase in pain severity or change in pain quality

Additional Drugs

·         Treatment of opioid abuse - Naltrexone, methadone, and buprenorphine

·         Treatment of alcohol abuse - Naltrexone, acamprosate, and disulfiram

·         Treatment of tobacco addiction - Bupropion, varenicline

Source:

Pharmacy Times. Managing Opioid Medications for Pain Relief While Preventing Overdose, Diversion, and Misuse: The Role of the Pharmacist.

http://www.drugabuse.gov/publications/drugfacts/treatment-approaches-drug-addiction