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The contents of this blog contain topics relevant to end of life care written by our own hospice clinical pharmacists. Continue to check this site regularly for the newest post or subscribe to the RSS feed below.
Shane Donnelly, PharmD

Renal Dosing for Commonly Used Oral Antibiotics

The kidneys are one of the most important organs responsible for eliminating substances from the body. Structural damage to the excretion mechanisms of the kidneys slows the filtration and elimination process down, allowing drug metabolites to stay in the body for longer periods of time. For some medications with inactive and harmless metabolites, this is not a relevant issue. However, for medications with active metabolites or medications that are not completely metabolized by the liver, this poses a potentially significant problem. The inability to efficiently eliminate active drug molecules puts patients at risk for harmful adverse effects. Antibiotics are particularly interesting in this regard. When dosed appropriately and efficiently eliminated by the body, side effect profiles are often mild and harmless. However, when dosed inappropriately in a patient with renal impairment, active drug molecules or metabolites can build up and may induce or exacerbate neurological, cardiac, or pulmonary comorbid conditions.

The table below provides a foundation for dosing common antibiotics in patients with renal impairment. It is important to utilize this table in the manner in which it was intended; purely as a reference point. Individualize treatment based on the patient and the indication that is being treated.

Renal Dosing Guide for Commonly Used Oral Antibiotics  
 
Antibiotic Renal-Dosing Special Considerations  
Amoxicillin (Amoxil) Amoxicillin + Clavulanate Potassium (Augmentin)

Severe Impairment (CKD Stage 4) give 250-500 mg amoxicillin q12h

End-Stage Disease (CKD Stage 5) give  250-500 mg amoxicillin q24h

All products containing

875 mg of Amoxicillin or extended-release formulations should be avoided in patients with severe impairment.

 
Azithromycin (Z-Pack, Zithromax) None. Use with caution. No specific renal dosing required in manufacturer's labeling.  
Cefaclor (Ceclor) None. Use with caution. No specific renal dosing required in manufacturer’s labeling.  
Cefuroxime (Ceftin)

Severe Impairment (CKD Stage 4) give the indicated dose q24h

End-Stage Disease (CKD Stage 5) give the indicated dose q48h

Alternatively, may dose at 15 mg/kg/dose q24h in patients with End-Stage Disease.  
Cephalexin (Keflex)

Moderate-Severe Impairment (CKD Stage 3-4) give 500 mg q8-12h

End-Stage Disease (CKD Stage 5) give 500 mg q12-24h

Cost-effective option for treating skin and soft tissue infections and may be used as an alternative agent for uncomplicated UTIs.  
Ciprofloxacin (Cipro)

Moderate Impairment (CKD Stage 3) give 250-500 mg q12h

Severe Impairment (CKD Stage 4) give 250-500 mg q18h

End-Stage Disease (CKD Stage 5) give 250-500 mg q24h

If using extended-release formulation, dose at 500 mg q24h with Severe Impairment.  
Clarithromycin (Biaxin) Severe Impairment (CKD Stage 4) decrease the dose by 50% Many drug interactions. May need to decrease dose with certain HIV medication.  
Clindamycin (Cleocin) None Potential alternative to penicillin due to allergy.  
Doxycycline Monohydrate (Vibramycin) None Potential safe alternative for community-acquired pneumonia or MRSA in patients with renal dysfunction.  
Erythromycin (Ery-Tab) None Medication can be used to induce gastric motility.  
Levofloxacin (Levaquin)

Moderate Impairment (CKD Stage 3) give 250 mg q24h +/- 500 mg loading dose (or) 750 mg q48h

Severe Impairment (CKD Stage 4) give 250-500 mg q48h +/- 500-750 mg loading dose

Dosing largely depends on indication. Utilize dose of that fits the suspected organism/infection.  
Metronidazole (Flagyl) None. Use with caution. Metabolites may accumulate in patients with End-Stage Renal Disease.  
Nitrofurantoin (Macrobid, Macrodantin) Moderate Impairment (CKD Stage 3) note that use is contraindicated Some literature1 suggests nitrofurantoin can be used safely in patients with a CrCl >40 mL/min for short-term treatment of uncomplicated UTI's (<1 week).  
Penicillin V Potassium (Pen VK) Use with caution. Excretion of penicillin is prolonged in patients with renal impairment.  
Sulfamethoxazole/ Trimethoprim (Bactrim, Septra)

Severe Impairment (CKD Stage 4) decrease the dose by 50%

End-Stage Disease (CKD Stage 5) note that use is not recommended

Dosing is highly dependent on indication.

*Per LexiComp, Wolters Kluwer Health 2
**Degree of Impairment and estimated Glomerular Filtration Rate: Moderate Impairment (CKD Stage 3): CrCl < 60 mL/min; Severe Impairment (CKD Stage 4): CrCl < 30 mL/min; End-Stage Disease (CKD Stage 5): CrCl < 15 mL/min

Age over 65 years old, hypertension, cardiovascular disease, diabetes, tobacco use, and obesity are all risk factors for developing chronic kidney disease 4. Many patients admitted to hospice have at least one of these risk factors. Awareness of the common signs of chronic kidney disease (known risk factors, consistent itching, changes in urine output, etc.4 can help the team to safely utilize medication.

Ultimately, the decision to treat and effectively dose antibiotics relies on the constant vigilance of the palliative care/hospice team. Awareness of the common dosing of antibiotics, the indications, and dosing for renal impairment can lead to better outcomes for patients who experience the uncomfortable reality of their diseases.


References:
1. Oplinger M and Andrews CO. “Drug Information Rounds: Nitrofurantoin Contraindication in Patients With a Creatinine Clearance Below 60 mL/min: Looking for the Evidence,” Ann Pharmacother, 2013, 47(1):106-11. 
2. LexiComp. Hudson, Ohio: Wolters Kluwer Health; c1978-2015. https://online.lexi.com/lco/action/home. 
3. The National Kidney Foundation. GFR. 2014. Available at: https://www.kidney.org/kidneydisease/siemens_hcp_gfr. 
4. Mayoclinic.org. Chronic kidney disease Risk factors - Mayo Clinic. 2015. Available at: http://www.mayoclinic.org/diseases-conditions/kidney-disease/basics/risk-factors/con-20026778.

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Michelle Mikus, PharmD

Rectal Medication Seizure Management Options

In end of life care, often times the oral route of medication administration is not an option. However, it is important that seizure prophylaxis be maintained beyond the patient's ability to swallow and that treatment options are known. The good news about rectal administration of seizure medications is that many antiepileptics that patients take orally can be given rectally. In addition, the dosages of these medications do not need adjusted from oral to rectal.

Phenobarbital is one of the oldest medications used for seizure prophylaxis. This medication is weight based and also takes 4-5 hours to reach peak concentration. For that reason, phenobarbital should not be used for acute seizure episodes. Dosages are most often 1-3mg/kg orally or rectally in divided doses (1-2 times daily). Note phenobarbital is sedating.

Carbamazepine immediate release tablets can be used rectally. Ideally, the same daily oral dosage is given rectally in 6-8 small, divided doses and the crushed tablets are put in a gelatin capsule when possible. Most patients require daily doses between 800-1200mg. Note carbamazepine serum concentrations should be monitored. Carbamazepine suspensions can also be used and would need to be diluted with an equal volume of water.

Valproic acid and divalproex sodium are of the most commonly used medications for seizure prophylaxis. Fortunately, they too can be used rectally when oral administration is not possible. If using the liquid formulations, dilute with an equal volume of water. Optimal response is seen at doses below 60mg/kg/day, in divided doses.

Lastly, a lamotrigine rectal suspension can be prepared out of the immediate release or chewable tablets. This is done by crushing the tablets and mixing into 6-10mL of room temperature water. Most patients find success at a dose of 250mg twice daily.

Benzodiazepines such as diazepam and lorazepam are commonly used rectally for acute seizures and should not be excluded from this overview.

There are many reasons that a patient may need to be on an antiepileptic drug: epilepsy, brain metastases, and even disease progression, to name a few. Using the above information, management of these medications beyond the oral route is possible and dose conversions are not necessary.


References:
1. Connelly, J., & Weissman, D. Fast Fact #229: Seizure Management in the Dying Patient. Retrieved September 4, 2015, fromhttps://www.capc.org/fast-facts/229-seizure-management-dying-patient/
2. Krouwer H, Pallagi J, Graves N. Management of seizures in brain tumor patients at the end of life. J Palliat Med. 2000;3:465-475

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Lori Osso-Connor, PharmD, CGP

Serotonin Syndrome in the Elderly

Serotonin Syndrome or serotonin toxicity occurs when there is overstimulation of the peripheral and central serotonin receptors which causes serotonin to accumulate in the body. Increased serotonin levels can occur through the following mechanisms: increased serotonin production, inhibition of serotonin reuptake, inhibition of serotonin metabolism, increased serotonin release, and/or stimulation of the serotonin receptor. Any medication or combination of medications that can increase the concentration of serotonin can cause serotonin syndrome. The medications most likely to be involved in contributing to serotonin syndrome include selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitor (SNRIs), tricyclic antidepressants (TCAs) or serotonin modulator antidepressants (trazodone).

SSRIs are often used in the treatment of depression. The elderly population is at increased risk of experiencing depression due to disability, co-morbid conditions, and/or the death of loved ones. Therefore, the use of antidepressants in the elderly is common. SSRIs exert their effect by blocking the reuptake of CNS neuron serotonin in the brain. Some examples of SSRIs include: Prozac (fluoxetine), Paxil (paroxetine), Celexa (citalopram), Lexapro (escitalopram), and Zoloft (sertraline).

Serotonin syndrome is often underdiagnosed and clinicians must be aware and identify early symptoms. Serotonin syndrome is diagnosed through clinical symptoms. The hallmark feature of serotonin syndrome is agitation. The common signs are usually a triad of features including: neuromuscular excitation (clonus, rigidity, hyperreflexia), autonomic stimulation (tachycardia, fever, sweating, diarrhea, hypertension), and changes in mental status (confusion, agitation, coma). The Hunter Serotonin Toxicity Criteria is recommended for diagnosing serotonin syndrome.

Serotonin syndrome may occur within minutes to hours of use of the offending medication(s). The severity could range from mild to severe, even resulting in death. Treatment consists of discontinuing the causative medication. Diazepam has been used to decrease hypertonicity. Serotonin antagonists such as cyproheptadine and chlorpromazine also have been used.
It is important for the pharmacist to be aware of medications that have the potential to cause serotonin syndrome and recognize to the signs and symptoms associated with it.

Medication Class Examples
Selective Serotonin Reuptake Inhibitors (SSRIs) citalopram (Celexa), fluoxetine (Prozac), fluvoxamine (Luvox), olanzapine/fluoxetine (Symbyax), paroxetine (Paxil)
Selective Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) duloxetine (Cymbalta), sibutramine (Meridia), venlafaxine (Effexor)
Triptans

almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex),

zolmitriptan (Zomig)

Miscellaneous

Medications- buspirone (Buspar), carbamazepine (Tegretol), cocaine, cyclobenzaprine (Flexeril), Fentanyl, 5-hydroxytryptophan, linezolid (Zyvox), lithium, L-tryptophan, meperidine (Demerol), methadone (Dolophine), methamphetamine (Desoxyn), methylene blue, metoclopramide (Reglan), mirtazapine (Remeron), ondansetron (Zofran), phenelzine (Nardil), selegiline (Eldepryl), St. John’s wart, tramadol (Ultram), tranylcypromine (Parnate), trazodone (Oleptro), valproic acid

Medication Classes- Ergot alkaloids, Tricyclic antidepressants

 


References:
1. Brown, Charles. "Drug-Induced Serotonin Syndrome." U.S. Pharmacist 17 Nov. 2010: Web. 27 Aug. 2015. 
2. Nguyen, Timothy, and Billy Sin. "A Case of an Older Adult Patients and Drugs Associated with Serotonin Syndrome." The Consultant Pharmacist 30.8 (2015): 455-57. 

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Irene Petrides, PharmD

Hyperkalemia in the Elderly

Hyperkalemia or a rise in serum potassium concentration is an electrolyte disorder that has the potential to be a life threating condition. With increased aged there is increased risk for hyperkalemia. In the elderly, the loss of renal mass and comorbid conductions results in decreased renal function.1,2 Therefore the common regulatory mechanism of managing potassium is disrupted.3 Many medications can be associated with contributing to hyperkalemia including potassium supplements, potassium sparing diuretics, nonsteroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, beta adrenergic blocking agents, heparin, digoxin, and trimethoprim-sulfamethoxazole.4 In order to avoid hyperkalemia certain precautions should be taken. This includes renal dosing and avoiding concomitant use of potassium altering medications. Signs and symptoms of hyperkalemia often are associated muscle paralysis, dyspnea, palpitations, nausea or vomiting and paresthesia. It is imperative to recognize these signs and symptoms as for hyperkalemia can be quickly fatal, resulting in respiratory paralysis or cardiac arrest.3

Management of hyperkalemia depends on severity and renal function. In patients with moderate potassium elevation and normal renal function, treatment simply results in identifying and removing the source of increased potassium levels and/or increasing the excretion of potassium.3 This includes a loop diuretic, aldosterone analogue, or initiating the controversial cation exchange resin (Kayexalate®).2 In patients with severe hyperkalemia and impaired renal function, aggressive treatment may comprise of intravenous insulin along with glucose, inhaled nebulized intravenous beta-2 agonist, intravenous calcium for cardiac toxicity, sodium bicarbonate to correct severe metabolic acidosis, and ultimately emergency dialysis.3

Kayexalate® (sodium polystyrene sulfonate) is a medication used in treatment of hyperkalemia. However it is important to keep in mind the safety label posted by the US Food and Drug administration in 2009.1 Kayexalate® is reported to cause colonic necrosis and other serious gastrointestinal adverse events including bleeding, ischemic colitis, and perforation.1,2 Therefore it is not recommended to use Kayexalate® with Sorbitol®.1,2,3 Due to this labeling, a more appropriate strategy in the treatment of mild to moderation hyperkalemia may be decreasing potassium intake increasing potassium depletion with the use of loop diuretics.1,2

In conclusion it is important to keep in mind prevention is key. A drug medication review is always necessary. All medications need to be evaluated especially over the counter medications. Many patients are on potassium supplements, non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors. Decreased renal function in addition to medications associated with drug induced hyperkalemia is a recipe for disaster in the aging population Ultimately, appropriate prevention is desired in addition to close monitoring as well as treatment when necessary.3,4


REFERENCES:

1 Kamel, K. S., and M. Schreiber. 'Asking The Question Again: Are Cation Exchange Resins Effective For The Treatment Of Hyperkalemia?'. Nephrology Dialysis Transplantation 27.12 (2012): 4294-4297. Web.

2 Sterns, R. H. et al. 'Ion-Exchange Resins For The Treatment Of Hyperkalemia: Are They Safe And Effective?'. Journal of the American Society of Nephrology 21.5 (2010): 733-735. Web.

3 Elliott, M. J. et al. 'Management Of Patients With Acute Hyperkalemia'. Canadian Medical Association Journal 182.15 (2010): 1631-1635.

4 Perazella, Mark A., and Rex L. Mahnensmith. 'Hyperkalemia In The Elderly'. J Gen Intern Med 12.10 (1997): 646-656. Web.

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Jessica Horsley, PharmD

Intranasal Medication Administration: Suitable Drugs and Devices

Compared to intravenous (IV) and other invasive routes of administration, intranasal (IN) administration of medications provides several benefits with regard to safety and efficacy. This route of administration is needleless, requires no sterile technique and is pain-free and well tolerated by patients. The transmucosal drug absorption offered by this route offers a rapid onset of action, with dosing and bioavailability similar to IV dosing.

Variability in intranasal drug absorption can be attributed to both drug and patient-related factors. Drug formulations should be concentrated and potent and of a volume of less than 1mL (preferably less than 0.2mL if possible). Physicochemical drug properties are of importance, as optimal absorption is dependent on the molecular weight and hydro- or lipophilicity of the drug. Lipophilic medications with a molecular weight of less than 300 Da are most suitable for IN administration. The patient’s transepithelial passage proves to be another variable affecting drug absorption. Abnormal nasal blood flow, rhinosinusitis, radiation to the head/neck, diseases affecting mucociliary clearance like cystic fibrosis, and cigarette smoking may all affect mucosal health, and therefore IN drug absorption. Drug interactions for IN administration are considered relative and include phenylephrine and oxymetazoline.

With regard to IN administration, most nursing professionals and even patients are familiar with nose drops or aerosol sprays like sodium chloride nasal spray or fluticasone. For those medications without a commercial nasal dosage form available, options for administration in the past have included compounding into drops/spray, or using a syringe and cotton ball. These methods may prove problematic due to immediate swallowing, rapid clearance, and posterior delivery of medication. A new option, drug atomization, now exists to address these failures in IN drug delivery. An atomized spray delivers small particles to the nasal mucosa rapidly and without regard to patient positioning. Three commercial devices exist for IN drug atomization: Mucosal Atomization Device, Accuspray Nasal Spray and Kurve Controlled Particle Dispersion. Although considered off-label use, the therapeutic uses of IN-administered drugs include seizures, hypoglycemia, opioid overdose, epistaxis and anesthesia. Suitable medications for IN administration applicable to the hospice population include fentanyl, benzodiazepines, ketamine, naloxone and lidocaine.1

2016 06 29 12 57 45

For information regarding nasal atomization products:

LMA MAD Nasal
http://www.lmana.com/pwpcontrol.php?pwpID=6359

BD Accuspray SCF
http://www.bd.com/pharmaceuticals/products/nasal-spray.asp

Kurve CPD
http://www.kurvetech.com/nasaltechnology.asp 

 


References:

1 Jen, C. No IV access, get MAD! Powerpoint presentation at: the American Society for Health-System Pharmacists Midyear Clinical Meeting; Dec 7-11 2014; Anaheim, CA.

2 Wolfe TR, Braude DA. Intranasal medication delivery for children: a brief review and update. Pediatrics. 2010;126(3):532-7.

3 Gallagher EJ. Nasogastric tubes: hard to swallow. Ann Emerg Med. 2004;44:138-41.

4 Pandey RK, Bahetwar SK, Saksena AK, Chandra G. A comparative evaluation of drops versus atomized administration of intranasal ketamine for the procedural sedation of young uncooperative pediatric dental patients: A prospective crossover trial. J Clin Pediatr Dent. 2011;36:79–84.

5 Tsze DS, Steele DW, Machan JT, Akhlaghi F, and Linakis JG. Intranasal ketamine for procedural sedation in pediatric laceration repair: a preliminary report. Pediatr Emerg Care. 2012 Aug;28(8):767-770.

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