NAPLEX / Neurology

Answer A. Rivastigmine and galantamine are FDA approved for mild to moderate Alzheimer’s dementia. Memantine is FDA approved specifically for moderate to severe Alzheimer’s dementia but it is an NMDA antagonist and not an acetylcholinesterase Inhibitor. Donepezil is the only FDA approved acetylcholinesterase Inhibitor for use in severe dementia (mild-moderate).
Reference:
Rabins P, Rovner B, Rummans T, Schneider L, Tariot P. Guideline Watch (October 2014): Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias. FOCUS. 2017;15(1):110-128.doi:10.1176/appi.focus.15106.

Answer D. Acetylcholinesterase inhibitors prevent the degradation of acetylcholine enhancing its binding with receptors. Acetylcholine stimulates salivation. A patient would experience dry mouth from an anti-cholinergic medication but not an acetylcholinesterase inhibitor.
Reference:
Rivastigmine tartrate capsule [package insert]. Cranbury, NJ: Sun Pharmaceutical Industried Ltd; 2016

Answer B. Donepezil and galantamine have been used off label for Parkinson’s disease dementia but only rivastigmine is FDA approved for the indication.
Reference:
Exelon New FDA Drug Approval | CenterWatch. Centerwatchcom. 2017. Available at: http://www.centerwatch.com/drug-information/fda-approved-drugs/drug/957/exelon-rivastigmine-tartrate Accessed August 22, 2017.

Answer B, C. Long term use of acetylcholinesterase inhibitors has been associated with anorexia, weight loss, falls, hip fractures, syncope, bradycardia, and increased use of cardiac pacemakers.
Reference:
Rabins P, Rovner B, Rummans T, Schneider L, Tariot P. Guideline Watch (October 2014): Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias. FOCUS. 2017;15(1):110-128. doi:10.1176/appi.focus.15106.

Answer D. Mini Mental Status Examination (MMSE) has three categories for dementia: a score of 20-24 is mild dementia, 13-20 is moderate dementia, and less than 12 is severe dementia. Because the patient’s MMSE score is lower her dementia is worsening. Decreasing her dose to 3 mg BID with signs of worsening cognition and the absence of side effects would not be appropriate. Donepezil is in the same class of rivastigmine and would increase the risk of side effects. The maximum dose of rivastigmine is 12 mg/day orally making 8 mg BID inappropriate. Memantine can be used with acetylcholinesterase Inhibitors and would be an appropriate supplementation to rivastigmine as the patient’s cognitive function continues to decline.
Reference:
I. Rivastigmine tartrate capsule [package insert]. Cranbury, NJ: Sun Pharmaceutical Industried Ltd; 2016
II. Rabins P, Rovner B, Rummans T, Schneider L, Tariot P. Guideline Watch (October 2014): Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias. FOCUS. 2017;15(1):110-128. doi:10.1176/appi.focus.15106.

Answer B. Donepezil is available in tablet, solution, and disintegrating tablet forms. Galantamine is available in capsules, tablets, and solution. Memantine is available in capsules, tablets, and solution. Only rivastigmine is available in a transdermal patch formulation. Rivastigmine is also available in capsule and solution formulation.
Reference:
Colovic M, Krstic D, Lazarevic-Pasti T, Bondzic A, Vasic V. Acetylcholinesterase Inhibitors: Pharmacology and Toxicology. 2017.

Answer A. Both atypical and typical antipsychotics have been associated with increased risk of death in elderly patients treated for dementia-related psychosis. This caused the FDA to issue a black box warning for both classes to alert health care providers.
Reference:
Rabins P, Rovner B, Rummans T, Schneider L, Tariot P. Guideline Watch (October 2014): Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias. FOCUS. 2017;15(1):110-128. doi:10.1176/appi.focus.15106.

Answer B. Memantine does not inhibit acetylcholinesterase, thus it has a lower prevalence of cholinomimetic tolerability issues such as nausea, vomiting, and diarrhea. Memantine is commonly associated with confusion, dizziness, and headache. Donepezil is associated with nausea, vomiting, and diarrhea but its effects are directly correlated with the dose. The higher the dose the greater frequency of side effects. Rivastigmine has the highest frequency of GI effects out of all the acetylcholinesterase Inhibitors. Taking rivastigmine with a meal can reduce the likelihood of GI side effects and the transdermal formulation of rivastigmine has superior tolerability compared to the oral formulation.
Reference:
Alva G, Cummings J. Relative Tolerability of Alzheimer's Disease Treatments. Psychiatry. 2008;5(11):27-36. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695725/. Accessed August 22, 2017.
Farlow M, Salloway S, Tariot P et al. Effectiveness and tolerability of high-dose (23 mg/d) versus standard-dose (10 mg/d) donepezil in moderate to severe Alzheimer's disease: A 24-week, randomized, double-blind study. Clinical Therapeutics. 2010;32(7):1234-1251. doi:10.1016/j.clinthera.2010.06.019.

Answer A. Patients treated in the olanzapine group experienced a worsening of functional skills compared to placebo. Patients assigned to receive antipsychotics for psychosis or agitated behavior did not demonstrate a significant improvement in cognitions, care needs, or quality of life compared to placebo.
Reference:
Sultzer D, Davis S, Tariot P et al. Clinical Symptom Responses to Atypical Antipsychotic Medications in Alzheimer’s Disease: Phase 1 Outcomes From the CATIE-AD Effectiveness Trial. American Journal of Psychiatry. 2008;165(7):844-854. doi:10.1176/appi.ajp.2008.07111779.

Answer: B. Primidone is an anticonvulsant drug that is structurally related to phenobarbital. Primidone is metabolized to phenobarbital and therefore shares its anticonvulsant and sedative properties. Primidone may be more effective than therapy with phenobarbital alone because primidone and both of its metabolites, phenobarbital and phenylethylmalonamide (PEMA), possess anticonvulsant activity.
Reference:
Mysoline (primidone) package insert. Bridgewater, NJ: Valeant Pharmaceuticals, LLC; 2016 Nov.

Answer: B. Primidone is an anticonvulsant drug that is structurally related to phenobarbital. Primidone is metabolized to phenobarbital and therefore shares its anticonvulsant and sedative properties. Primidone may be more effective than therapy with phenobarbital alone because primidone and both of its metabolites, phenobarbital and phenylethylmalonamide (PEMA), possess anticonvulsant activity.
Reference:
Mysoline (primidone) package insert. Bridgewater, NJ: Valeant Pharmaceuticals, LLC; 2016 Nov.

Answer: B. Corrected phenytoin (mg/L) = Observed phenytoin (mg/L) /(0.2 x albumin [g/dL]) + 0.1
= 17.8/(0.2 x 2.1)+ 0.1
= 17.8/0.42 + 0.1
= 42.48mg/L ← phenytoin level is high. Normal therapeutic range is: 10-20mg/dL
Reference:
Von Winckelmann SL, Spret I, Willems L. Therapeutic drug monitoring of phenytoin in critically ill patients. Pharmacotherapy 2008;28(11):1391–400.

Answer: D. The delayed-release action of divalproex allows for less frequent dosing than valproic acid in some patients. Divalproex sodium contains sodium valproate and valproic acid in a 1:1 molar stable co-ordination compound. Valproic acid, sodium valproate, and divalproex share the same pharmacology; however, there are pharmacokinetic differences among products.
Reference:
Depakote (divalproex sodium tablets) package insert. North Chicago, IL: AbbVie Inc.; 2016 Nov.

Answer A, B, C. Hepatotoxicity, including hepatic failure, has been fatal and may more commonly occur in the first 6 months of treatment. Valproic acid and its analogs are contraindicated in patients with known urea cycle disorders. Patients with urea cycle disorders have a genetic enzyme defect leading to an impaired ability to produce urea. Hyperammonemic encephalopathy has been reported following initiation of valproate therapy. Because of, inhibition of the secondary phase of platelet aggregation, and abnormal coagulation parameters complete blood counts and coagulation tests are recommended before initiating valproic acid therapy and at periodic intervals.
Reference:
Depacon (valproate sodium injection) package insert. North Chicago, IL: Abbvie Inc.; 2017 April.

Answer C. Cases of life-threatening pancreatitis have been reported in both pediatric and adult patients receiving valproic acid or its analogs. Patients should be warned that abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis that require prompt medical evaluation. If pancreatitis is diagnosed, valproate should be discontinued.
Reference:
Clinical Pharmacology, Available at: http://www.clinicalpharmacology-ip.com/Forms/Monograph/monograph.aspx?cpnum=637&sec=moncontr&t=0 Accessed May 2017

Answer A, B, C. Common GI side effects of Valproic Acid and Divalproex Sodium are Weight gain, Nausea, Vomiting, Diarrhea, abdominal pain, dyspepsia. Divalproex sodium or valproic acid affects reproductive endocrine function in women. Menstrual irregularities defined as amenorrhea, oligomenorrhea, and prolonged cycles were common. Gynecomastia is not a side effect of Divalproex Sodium. For list of drugs that causes gynecomastia refer the reference. Gingival hyperplasia is a well-known side effect of phenytoin.
Reference:
Depakote (divalproex sodium tablets) package insert. North Chicago, IL: AbbVie Inc.; 2017 May.
Drug-induced gynecomastia. Giuseppe R, Mauro M. Available at: http://www.pharmaco-vigilance.eu/content/drug-induced-gynecomastia . Accessed May 2017

Answer D. Low albumin and poor kidney function affect phenytoin level. Phenytoin is one of numerous medications that can cause hypocalcemia, hypocalcemia does not affect the level of phenytoin.
Reference:
1.Jimenez, M, Duran, J, Abadin, J. Factors Affecting the Free Plasma Fraction of Phenytoin in Patients with Epilepsy. Clin. Drug Invest. 1998 Feb;( 2). Available at:https://www.ncbi.nlm.nih.gov/pubmed/18370478.
2. Ehrlich, S. Possible Interactions with Calcium. University of Maryland Medical Center. Last Updated 6/25/2007.Available at: http://umm.edu/health/medical/altmed/supplement-interaction/possible-interactions-with-calcium.

Answer B.
Corrected phenytoin (mg/L)= Observed phenytoin (mg/L) /(0.2 x albumin [g/dL]) + 0.1
= 17.8/(0.2 x 2.1)+ 0.1
= 17.8/0.42 + 0.1
= 42.48mg/L ← phenytoin level is high.
Normal therapeutic range is: 10-20mg/dL
Reference:
Faye Wu, M, Hing Lim W. Phenytoin: a guide to therapeutic drug monitoring. Proceedings of Singapore Healthcare. 2013. 22 (3). Accessed Mar 8 2017. Available at: http://journals.sagepub.com/doi/pdf/10.1177/201010581302200307.

Answer D. Common dose-related side effects of phenytoin include: Central nervous system effects: somnolence, fatigue, dizziness,confusion, visual disturbances, nystagmus and ataxia.
Reference:
Faye Wu, M, Hing Lim W. Phenytoin: a guide to therapeutic drug monitoring. Proceedings of Singapore Healthcare. 2013. 22 (3). Accessed Mar 8 2017. Available at: http://journals.sagepub.com/doi/pdf/10.1177/201010581302200307.

Answer A. Non dose-related side effects of phenytoin include: Gingival hyperplasia, hirsutism, thickening of facial features, vitamin D deficiency, folic acid deficiency, osteomalacia, peripheral neuropathy
Reference:
Faye Wu, M, Hing Lim W. Phenytoin: a guide to therapeutic drug monitoring. Proceedings of Singapore Healthcare. 2013. 22 (3). Accessed Mar 8 2017. Available at: http://journals.sagepub.com/doi/pdf/10.1177/201010581302200307.

Answer B. When Asians have the HLA-B*1502 allele, and they take phenytoin, they are at increased risk of Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The same concern is applicable to the prodrug of phenytoin, fosphenytoin.
Reference:
U.S. Department of Health and Human Services. Information for Healthcare Professionals: Phenytoin (marketed as Dilantin, Phenytek and generics) and Fosphenytoin Sodium (marketed as Cerebyx and generics). Food and Drug Administration. Updated Aug 2013. Available at: https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124788.htm .

AnswerD. If CRCL < 20 mL/min then Corrected Phenytoin
Corrected phenytoin = Total phenytoin Level / ((0.1 x albumin) + 0.1)
= 10.8/(0.1x2.1) + 0.1
= 34.8mcg/mL
Reference:
Wu, M, Lim, W. Phenytoin: A Guide to Therapeutic Drug Monitoring. Proceedings of Singapore Healthcare. 22 (3):198-202. 2013. Available at: http://journals.sagepub.com/doi/pdf/10.1177/201010581302200307. Accessed March 8, 2017.

Answer C. 1.5 mg of fosphenytoin is equivalent to 1 mg of phenytoin equivalents (150 mg of fosphenytoin for 100 mg of phenytoin equivalent).
Reference:
Millares-Sipin, C, Alafris, A, et al.Phenytoin and Fosphenytoin. In: Cohen H. Cohen H Ed. Henry Cohen.eds. Casebook in Clinical Pharmacokinetics and Drug Dosing New York, NY: McGraw-Hill

Answer C
Reference:
Rogers S, Cavazos J, Susan J. Chapter 40. Epilepsy. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. DiPiro J.T., Talbert R.L., Yee G.C., Matzke G.R., Wells B.G., Posey L Eds. Joseph T. DiPiro, et al.eds. Pharmacotherapy: A Pathophysiologic Approach, 9e New York, NY: McGraw-Hill; 2014.

Answer E. If a patient has poor renal function, it is important adjust the dose of levetiracetam.
Reference:
Levetiracetam. [package insert]. Rockford, IL: Mylan Institutional, LLC. Nov 2016.

Answer B. Medications that are FDA approved for tonic-clonic seizures include: lamotrigine, levetiracetam and topiramate. Gabapentin is used for newly diagnosed and refractory adjunct partial seizures.
Reference:
Rogers S, Cavazos J, Susan J. Chapter 40. Epilepsy. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. DiPiro J.T., Talbert R.L., Yee G.C., Matzke G.R., Wells B.G., Posey L Eds. Joseph T. DiPiro, et al.eds. Pharmacotherapy: A Pathophysiologic Approach, 9e New York, NY: McGraw-Hill; 2014.

Answer C. For newly diagnosed generalized absence seizures, it is acceptable to use either lamotrigine, valproic acid or ethosuximide.
Reference:
Rogers S, Cavazos J, Susan J. Chapter 40. Epilepsy. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. DiPiro J.T., Talbert R.L., Yee G.C., Matzke G.R., Wells B.G., Posey L Eds. Joseph T. DiPiro, et al.eds. Pharmacotherapy: A Pathophysiologic Approach, 9e New York, NY: McGraw-Hill; 2014.

Answer D. According to medwatch, the FDA Safety Information and Adverse Event Reporting System, there have been reports in clinical trials with patients having increased P-R interval while taking lacosamide.
Reference:
Department of Health and Human Services. U.S. Food and Drug Administration. Available at:https://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm342620.htm. Published February 2013. Accessed March 8, 2017.

Answer A. There is a strong relationship between HLA-B*1502 and carbamazepine-induced SJS and TEN in Han-Chinese, Thai, and Malaysian populations.1 This same relationship and between HLA*1502 and SJS/TEN has been also found with phenytoin and lamotrigine.
Reference:
1. Tangamornsuksan, W, Chaiyakunapruk, N, et al. Relationship between the HLA-B*1502 allele and carbamazepine-induced stevens-johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. JAMA Dermatol. 2013;149(9):1025-1032.

Answer B. According to the manufacturer, the following additional adverse reactions have been reported: Hemopoietic System: Aplastic anemia, agranulocytosis, pancytopenia, bone marrow depression, thrombocytopenia, leukopenia, leukocytosis, eosinophilia, acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda.
Reference:
Tegretol. [package insert]. East Hanover, NJ. Novartis Pharmaceuticals Corporation. Sept 2015.

Answer C. There is a black box warning for a serious hypersensitivity reaction that manifests as a rash in patients who take lamotrigine, therefore it’s important to start at the lowest dose possible and slowly increase the dose to decrease the likelihood of the reactions occurring.
Reference:
Kanner, A. Lamotrigine-induced Rash: Can We Stop Worrying? Epilepsy Curr. 2005 Sep; 5(5): 190–191. doi:10.1111/j.1535-7511.2005.00060.x. http://onlinelibrary.wiley.com/doi/10.1111/j.1535-7511.2005.00060.x/abstract.

Answer A. Dose related Syndrome of Inappropriate Antidiuretic Hormone (SIADH) occurs with carbamazepine.
Reference:
Carbamazepine [prescribing information]. North Wales, PA: Teva; September 2014.

Answer D.

Answer: C Dose-dependent hyperammonemia usually occurs when topiramate is taken in combination with valproic acid, but it can also occur with topiramate monotherapy
Reference:
Topamax (topiramate) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals Inc; April 2014.

Answer: C Topiramate is a weak carbonic anhydrase inhibitor that increases urinary pH and reduces urinary citrate excretion ultimately promoting kidney stone formation.
Reference:
Topamax (topiramate) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals Inc; April 2014.

Answer: C Topiramate is a weak carbonic anhydrase inhibitor that increases urinary pH and reduces urinary citrate excretion ultimately promoting kidney stone formation.
Reference:
Topamax (topiramate) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals Inc; April 2014.

Answer: C Valproic acid has the following black box warning: life-threatening pancreatitis reported in both children and adults receiving valproate. Sometimes described as hemorrhagic with rapid progression from initial symptoms to death. Cases have been reported after initial use as well as after several years of use.
Reference:
Jones, M, et al. Drug-induced acute pancreatitis: a review. Ochsner J. 2015 Spring;15(1):45-51. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365846/.

Answer: A – Parkinson’s disease is a progressive, multifactorial, neurodegenerative disease which results from aggregation of α-synuclein, mitochondrial dysfunction, lysosomal and vesicle transportation issues, and neuroinflammation that collectively results in the accelerated neuronal death of dopaminergic neurons.
Reference:
Bloem BR, Okun MS, Klein C. Parkinson's disease. Lancet. 2021 Jun 12;397(10291):2284-2303. doi: 10.1016/S0140-6736(21)00218-X. Epub 2021 Apr 10. PMID: 33848468.

Answer: D It is important to monitor liver functions tests plasma ammonia levels in patients on divalproex sodium. It is also imperative that complete blood counts coagulation tests are assessed as well.

Answer: C If patient is seizure-free for 3-5 years, it is OK to gradually taper down over a minimum of month time period. It should never be abruptly discontinued due to increased risk of relapse. It is optimal to decrease dose to 200mg daily for a month, then to 100 mg daily for a month before discontinuing it.
Reference:
Ranganathan, L, Ramaratnam, S.Rapid versus slow withdrawal of antiepileptic drugs.Cochrane Database Syst Rev. 2006 Apr 19;(2): CD005003. https://www.ncbi.nlm.nih.gov/pubmed/16625621.

Answer: E – At present, no therapy can slow down or arrest the progression of Parkinson's disease, however, emerging therapies exist and are currently being examined in clinical studies. Such research includes vaccines, neuroinflammatory therapies, diets and microbiome, cannabinoids, gene therapy, and next generation adaptive deep brain tissue stimulation.
Reference:
Bloem BR, Okun MS, Klein C. Parkinson's disease. Lancet. 2021 Jun 12;397(10291):2284-2303. doi: 10.1016/S0140-6736(21)00218-X. Epub 2021 Apr 10. PMID: 33848468.

Answer: C – Carbidopa/levodopa is the most effective agent in treatment of Parkinson’s disease, however, it is usually initiated later on in the disease course and to the patients who are over 60 years of age due to its side effect - dyskinesia. Patients who are <60 years old, and complain of a mild tremor that is not impairing their quality of life can be started on an anticholinergic drug (benztropine), or propranolol. For patients who are <60 years old and are complaining of bradykinesia along with mild tremors dopamine agonist is an appropriate initial therapy because it is less likely to cause dyskinesia compared to levodopa/carbidopa. Three DA agonists include pramipexole, ropinirole, and rotigotine. Initial dose of Pramipexole is 0.125 mg TID, with a maximum dose of 4.5mg daily. Ropinirole starting dose is 0.25mg TID - the only correct answer choice on the list.
Reference:
Pharmacological Treatment of Parkinson’s Disease, A Review. Journal of American Medical Association. 2014. April 23;311(16): 1670-1683.

Answer: B – Dopamine agonists cause side effects such as sudden sleep attacks and impulsive control disorders; gambling, hyper-sexual behaviors, and excessive shopping can occur while taking these agents. Ropinirole is the only dopamine agonist on the list.
Reference:
Diagnosis and prognosis of new onset of Parkinson disease; an evidence based review. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006. April 11;66(7):968-975.

Answer: B - Dopamine agonists cause side effects such as sudden sleep attacks and impulsive control disorders; gambling, hyper-sexual behaviors, and excessive shopping can occur while taking these agents. Pramipexole is the only dopamine agonist on the list.
Reference:
Diagnosis and prognosis of new onset of Parkinson disease; an evidence based review. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006. April 11;66(7):968-975.
Bloem BR, Okun MS, Klein C. Parkinson's disease. Lancet. 2021 Jun 12;397(10291):2284-2303. doi: 10.1016/S0140-6736(21)00218-X. Epub 2021 Apr 10. PMID: 33848468.

Answer: E - Hallucinations can be a feature of later stages of PD, or they could occur due to use of medications that treat the disease; since the patient realizes the hallucinations are not real, and he denies associated distress due to hallucinations the pharmacological therapy is not indicated. If the hallucinations become increased in intensity or become troublesome for the patient, decrease or discontinuation of antiparkinsonian drugs, or initiation of clozapine or quetiapine can help combat the hallucinations.
Reference:
Pharmacological Treatment of Parkinson’s Disease, A Review. Journal of American Medical Association. 2014. April 23;311(16): 1670-1683

Answer: A. Metoclopramide, prochlorperazine, and promethazine worsen parkinsonian symptoms and should be avoided. Serotonin antagonist, ondansetron can lead to severe hypotension and loss of consciousness when given with apomorphine, and should therefore be avoided to treat nausea associated with use of apomorphine. Nausea caused by all other dopaminergic agents should be treated with ondansetron or domperidone.
Reference:
Pharmacological Treatment of Parkinson’s Disease, A Review. Journal of American Medical Association. 2014. April 23;311(16): 1670-1683.
Kwan C, Frouni I, Bédard D, Hamadjida A, Huot P. Ondansetron, a highly selective 5-HT3 receptor antagonist, reduces L-DOPA-induced dyskinesia in the 6-OHDA-lesioned rat model of Parkinson's disease. Eur J Pharmacol. 2020 Mar 15;871:172914. doi: 10.1016/j.ejphar.2020.172914. Epub 2020 Jan 8. PMID: 31926127

Answer: C – Anticholinergics and beta blockers are initial agents of choice in patients younger than 60 years old who present with tremor as their only symptom of PD. The only beta blocker used is propranolol, while anticholinergics include benztropine and trihexyphenidyl. Benztropine 1-2mg TID is used in management of tremor and can lead to side effects such as dry mouth, urinary retention, nausea and others.
Reference:
Diagnosis and prognosis of new onset of Parkinson disease; an evidence based review. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006. April 11;66(7):968-975

Answer: D – Amantadine is one of the most common drugs that can lead to livedo reticularis, a reversible side effect that presents as an erythematous-cyanotic well defined spots. After the condition appears on the skin, it has a variable clinical course ranging between 1 and 48 months. Discontinuation of medication is necessary to resolve this condition.
Reference:
Amantadine-Induced Livedo Reticularis – A Case Report. Anais Brasileiros De Dermatologia. 2015. September; 90(5): 745-747. Amantadine hydrochloride capsules [prescribing information]. Bridgewater, NJ: Alembic Pharmaceuticals, Inc; April 2017.
Quaresma MV, Gomes AC, Serruya A, Vendramini DL, Braga L, Buçard AM. Amantadine-induced livedo reticularis--Case report. An Bras Dermatol. 2015 Sep-Oct;90(5):745-7. doi: 10.1590/abd1806-4841.20153394. PMID: 26560223; PMCID: PMC4631243.