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Memantine: Drug information

Memantine: Drug information
(For additional information see "Memantine: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Namenda;
  • Namenda Titration Pak;
  • Namenda XR;
  • Namenda XR Titration Pack [DSC]
Brand Names: Canada
  • ACT Memantine;
  • APO-Memantine;
  • Ebixa;
  • MED-Memantine;
  • PMS-Memantine;
  • RAN-Memantine;
  • RIVA-Memantine;
  • SANDOZ Memantine FCT
Pharmacologic Category
  • N-Methyl-D-Aspartate (NMDA) Receptor Antagonist
Dosing: Adult
Alzheimer disease, moderate to severe

Alzheimer disease, moderate to severe (monotherapy or in combination with a cholinesterase inhibitor):

Oral:

Immediate release: Initial: 5 mg once daily; increase daily dose by 5 mg every week as tolerated to a target maximum dose of 20 mg/day. Note: Dose may be administered once daily or in 2 divided doses (Ref).

Extended release: Initial: 7 mg once daily; increase daily dose by 7 mg every week as tolerated to a target maximum dose of 28 mg once daily (Ref).

Dementia

Dementia (ie, Parkinson disease dementia, dementia with Lewy bodies, comorbid vascular dementia) (monotherapy or in combination with a cholinesterase inhibitor) (off-label use):

Oral: Immediate release: Initial: 5 mg once daily; increase dose by 5 mg every week as tolerated to a target maximum dose of 20 mg/day. Note: Dose may be administered once daily or in 2 divided doses (Ref).

Neurocognitive toxicity of whole brain irradiation, prevention

Neurocognitive toxicity of whole brain irradiation, prevention (off-label use):

Oral:

Immediate release: Initial: 5 mg once daily with the initiation of radiation; increase dose by 5 mg weekly as tolerated to a target maximum dose of 20 mg/day. Doses >5 mg/day may be given in 2 divided doses. Continue for up to 6 months after completion of whole brain radiation therapy (WBRT) (Ref).

Extended release: Initial: 7 mg once daily with the initiation of radiation; increase dose by 7 mg weekly as tolerated to a target maximum dose of 28 mg once daily. Continue for up to 6 months after completion of WBRT (Ref).

Discontinuation of therapy: Discontinuation of therapy may result in worsening of cognitive function. Avoid abrupt discontinuation except in the case of severe adverse drug reaction to minimize withdrawal symptoms (eg, altered mental status, hallucinations, delusions, insomnia, increased anxiety and agitation). In general, memantine should be tapered using a 50% dose reduction or stepwise reduction via available dose formulations every 4 weeks to the lowest dose prior to discontinuation. Consider re-initiation if clear worsening of the condition occurs after withdrawal (Ref).

Conversion from immediate release to extended release: Begin the ER product the day after the last dose of the IR product.

If current IR dose is 10 mg/day: Convert to ER capsule 14 mg once daily.

If current IR dose is 20 mg/day: Convert to ER capsule 28 mg once daily.

Missed doses : If several days of dosing are missed with either formulation, dosing may need to be resumed at lower doses and retitrated.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function: Note: Renal function may be estimated using the Cockcroft-Gault formula for dosage adjustment purposes.

Immediate release:

CrCl ≥50 mL/minute: No dosage adjustment necessary.

CrCl 30 to <50 mL/minute: Initial: 5 mg once daily; after at least 1 week of therapy and if tolerated, may increase in 5 mg increments no more frequently than weekly (Ref). However, predicted steady state exposures are 60% (Ref) to 100% (Ref) greater compared to those with normal kidney function; a reduced maximum dose may be necessary in some patients (Ref).

CrCl <30 mL/minute: Initial: 5 mg once daily; after at least 1 week of therapy and if tolerated, may increase to a target dose of 5 mg twice daily (Ref).

Extended release:

CrCl ≥50 mL/minute: No dosage adjustment necessary.

CrCl 30 to <50 mL/minute: Initial: 7 mg once daily; after at least 1 week of therapy and if tolerated, may increase in 7 mg increments no more frequently than weekly (Ref). However, predicted steady state exposures are 60% (Ref) to 100% (Ref) greater compared to those with normal kidney function; a reduced maximum dose may be necessary in some patients (Ref).

CrCl <30 mL/minute: Initial: 7 mg once daily; after at least 1 week of therapy and if tolerated, may increase to a target dose of 14 mg once daily (Ref).

Hemodialysis, intermittent (thrice weekly): Not likely to be significantly dialyzable (large Vd) (Ref):

Immediate release: Dose as if the patient has a CrCl <30 mL/minute (Ref).

Extended release: Avoid use (Ref).

Peritoneal dialysis: Not likely to be significantly dialyzable (large Vd) (Ref):

Immediate release: Dose as if the patient has a CrCl <30 mL/minute (Ref).

Extended release: Avoid use (Ref).

CRRT or PIRRT (eg, sustained, low-efficiency diafiltration) : Not likely to be significantly dialyzed (large Vd) (Ref):

Immediate release: Dose as if the patient has a CrCl <30 mL/minute (Ref).

Extended release: Avoid use (Ref).

Dosing: Hepatic Impairment: Adult

Mild-to-moderate impairment: No dosage adjustment necessary.

Severe impairment:

US labeling: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.

Canadian labeling: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use is not recommended.

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule Extended Release 24 Hour, Oral, as hydrochloride:

Namenda XR: 7 mg, 14 mg, 21 mg, 28 mg

Namenda XR Titration Pack: 7 mg (7s) and 14 mg (7s) and 21 mg (7s) and 28 mg (7s) [DSC]

Generic: 7 mg, 14 mg, 21 mg, 28 mg

Solution, Oral, as hydrochloride:

Generic: 2 mg/mL (240 mL, 360 mL); 10 mg/5 mL (5 mL [DSC])

Tablet, Oral, as hydrochloride:

Namenda: 5 mg [contains fd&c blue #2 (indigotine), fd&c yellow #6 (sunset yellow)]

Namenda: 10 mg

Namenda Titration Pak: 5 mg (28s) and 10 mg (21s) [contains fd&c blue #2 (indigotine), fd&c yellow #6 (sunset yellow)]

Generic: 5 mg, 10 mg, 5 mg (28s) and 10 mg (21s)

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Ebixa: 10 mg [contains polysorbate 80]

Generic: 5 mg, 10 mg

Administration: Adult

Administer without regard to meals. Extended release capsules may be swallowed whole or entire contents of capsule may be sprinkled on applesauce and swallowed immediately; do not chew, crush, or divide. Withdraw and administer oral solution with provided dosing device; dose should be slowly squirted into the corner of the patient’s mouth. Do not mix oral solution with any other liquid. The Canadian labeling recommends tablets to be swallowed whole with water.

Use: Labeled Indications

Alzheimer disease, moderate to severe: Treatment of moderate to severe dementia of the Alzheimer type.

Use: Off-Label: Adult

Dementia (ie, Parkinson disease dementia, dementia with Lewy bodies, comorbid vascular dementia); Neurocognitive toxicity of whole brain irradiation, prevention

Medication Safety Issues
Sound-alike/look-alike issues:

Memantine may be confused with mesalamine, methadone

Adverse Reactions (Significant): Considerations
CNS effects

CNS effects, including confusion, dizziness, and headache, are the most commonly reported adverse reactions (Ref). Agitation, delusion, and hallucination have also been reported (Ref).

Mechanism: Not completely understood; binds with low affinity to the phencyclidine (PCP) site at the N-methyl-D-aspartate (NMDA) receptor. PCP has a high affinity to the NMDA receptor and can cause psychotomimetic effects, such as agitation, delusions, and hallucinations. Patients with a concomitant dopamine/glutamate imbalance may be more susceptible to these effects (Ref).

Risk factors:

• Dose titration may be a risk factor for transient confusion, especially in patients with severe dementia (Ref).

• Lewy body dementia, preexisting hallucinations, or concomitant use of a selective serotonin reuptake inhibitor may be risk factors for developing worsening or new-onset agitation, delusions, and hallucinations (Ref).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions similar in immediate and extended release formulations except as noted.

1% to 10%:

Cardiovascular: Hypertension (4%), hypotension (ER: 2%)

Endocrine & metabolic: Weight gain (ER: 3%)

Gastrointestinal: Abdominal pain (ER: 2%), constipation (3% to 5%), diarrhea (ER: 5%), vomiting (2% to 3%)

Genitourinary: Urinary incontinence (ER: 2%)

Nervous system: Aggressive behavior (ER: 2%) (table 1), anxiety (ER: 4%) (table 2), confusion (IR: 6%) (table 3), depression (ER: 3%) (table 4), dizziness (5% to 7%) (table 5), drowsiness (3%) (table 6), fatigue (IR: 2%) (table 7), hallucination (IR: 3%) (table 8), headache (6%) (table 9), pain (IR: 3%) (table 10)

Memantine: Adverse Reaction: Aggressive Behavior

Drug (Memantine)

Placebo

Population

Dosage Form

Indication

Number of Patients (Memantine)

Number of Patients (Placebo)

2%

1%

Adults

ER tablets

Moderate to severe dementia of the Alzheimer’s type

341

335

Memantine: Adverse Reaction: Anxiety

Drug (Memantine)

Placebo

Population

Dosage Form

Indication

Number of Patients (Memantine)

Number of Patients (Placebo)

4%

3%

Adults

ER tablets

Moderate to severe dementia of the Alzheimer’s type

341

335

Memantine: Adverse Reaction: Confusion

Drug (Memantine)

Placebo

Population

Dosage Form

Indication

Number of Patients (Memantine)

Number of Patients (Placebo)

6%

5%

Adults

IR tablets

Dementia

940

922

Memantine: Adverse Reaction: Depression

Drug (Memantine)

Placebo

Population

Dosage Form

Indication

Number of Patients (Memantine)

Number of Patients (Placebo)

3%

1%

Adults

ER tablets

Moderate to severe dementia of the Alzheimer’s type

341

335

Memantine: Adverse Reaction: Dizziness

Drug (Memantine)

Placebo

Population

Dosage Form

Indication

Number of Patients (Memantine)

Number of Patients (Placebo)

7%

5%

Adults

IR tablets

Dementia

940

922

5%

1%

Adults

ER tablets

Moderate to severe dementia of the Alzheimer’s type

341

335

Memantine: Adverse Reaction: Drowsiness

Drug (Memantine)

Placebo

Population

Dosage Form

Indication

Number of Patients (Memantine)

Number of Patients (Placebo)

3%

1%

Adults

IR tablets

Dementia

940

922

3%

1%

Adults

ER tablets

Moderate to severe dementia of the Alzheimer’s type

341

335

Memantine: Adverse Reaction: Fatigue

Drug (Memantine)

Placebo

Population

Dosage Form

Indication

Number of Patients (Memantine)

Number of Patients (Placebo)

2%

1%

Adults

IR tablets

Dementia

940

922

Memantine: Adverse Reaction: Hallucination

Drug (Memantine)

Placebo

Population

Dosage Form

Indication

Number of Patients (Memantine)

Number of Patients (Placebo)

3%

2%

Adults

IR tablets

Dementia

940

922

Memantine: Adverse Reaction: Headache

Drug (Memantine)

Placebo

Population

Dosage Form

Indication

Number of Patients (Memantine)

Number of Patients (Placebo)

6%

3%

Adults

IR tablets

Dementia

940

922

6%

5%

Adults

ER tablets

Moderate to severe dementia of the Alzheimer’s type

341

335

Memantine: Adverse Reaction: Pain

Drug (Memantine)

Placebo

Population

Dosage Form

Indication

Number of Patients (Memantine)

Number of Patients (Placebo)

3%

1%

Adults

IR tablets

Dementia

940

922

Neuromuscular & skeletal: Back pain (3%)

Respiratory: Cough (IR: 4%), dyspnea (IR: 2%)

Postmarketing:

Cardiovascular: Bradycardia (rare: <1%) (Gallini 2008), cardiac failure (rare: <1%) (Gallini 2008), prolonged QT interval on ECG (rare: <1%) (Kajitani 2016; Takehara 2015)

Dermatologic: Stevens-Johnson syndrome (rare: <1%)

Gastrointestinal: Pancreatitis (rare: <1%)

Hematologic & oncologic: Agranulocytosis (rare: <1%), leukopenia (including neutropenia) (rare: <1%), pancytopenia (rare: <1%), thrombocytopenia (rare: <1%), thrombotic thrombocytopenic purpura (rare: <1%)

Hepatic: Cholestatic hepatitis (rare: <1%) (Ferrara 2008)

Hypersensitivity: Fixed drug eruption (rare: <1%) (Saito 2017)

Nervous system: Agitation (rare: <1%) (Monastero 2007; Ridha 2005), delusion (rare: <1%) (Monastero 2007; Ridha 2005), loss of consciousness (rare: <1%) (Savic 2013), mania (rare: <1%) (Duan 2018), seizure (rare: <1%) (Peltz 2005), suicidal ideation (rare: <1%)

Ophthalmic: Epithelial keratopathy (Feng 2015)

Renal: Acute renal failure (rare: <1%) (Horikawa 2013; Tsukamoto 2013)

Contraindications

Hypersensitivity to memantine or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity: Rare skin hypersensitivity reactions (eg, Stevens-Johnson syndrome) have been reported; advise patients to report skin reactions immediately.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease; although adverse cardiac events were infrequent in clinical trials, an increased incidence of cardiac failure, bradycardia, and hypertension/hypotension was observed.

• Hepatic impairment: Use with caution in patients with severe hepatic impairment. The Canadian labeling recommends avoiding use in severe impairment due to a lack of data in this population.

• Ophthalmic disease: Worsening of corneal condition has been observed in a clinical trial. Reversible corneal endothelial dysfunction may occur; case report where noted around keratoplasty (Feng 2015).

• Renal impairment: Use with caution in patients with renal impairment; dose adjustments may be required.

• Seizure disorder: Use with caution in patients with a history of seizure disorder; may increase risk of seizures.

Other warnings/precautions:

• Urine pH: Clearance is significantly reduced by alkaline urine; use caution with alkalinizing medications, dietary changes, or patient conditions that may increase urine pH.

Metabolism/Transport Effects

Substrate of OCT2

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alkalinizing Agents: May increase the serum concentration of Memantine. Risk C: Monitor therapy

Benperidol: Memantine may diminish the therapeutic effect of Benperidol. Risk C: Monitor therapy

Carbonic Anhydrase Inhibitors: May increase the serum concentration of Memantine. Risk C: Monitor therapy

NMDA Receptor Antagonists: May enhance the adverse/toxic effect of Memantine. Risk C: Monitor therapy

Trimethoprim: May enhance the adverse/toxic effect of Memantine. Specifically, the risk of myoclonus and/or delirium may be increased. Trimethoprim may increase the serum concentration of Memantine. Risk C: Monitor therapy

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies.

Breastfeeding Considerations

It is not known if memantine is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring Parameters

Cognitive function; functional outcomes (eg, Activities of Daily Living [ADLs], Instrumental Activities of Daily Living [IADLs]); periodic ophthalmic exam (Canadian labeling)

Mechanism of Action

Glutamate, the primary excitatory amino acid in the CNS, may contribute to the pathogenesis of Alzheimer's disease (AD) by overstimulating various glutamate receptors leading to excitotoxicity and neuronal cell death. Memantine is an uncompetitive antagonist of the N-methyl-D-aspartate (NMDA) type of glutamate receptors, located ubiquitously throughout the brain. Under normal physiologic conditions, the (unstimulated) NMDA receptor ion channel is blocked by magnesium ions, which are displaced after agonist-induced depolarization. Pathologic or excessive receptor activation, as postulated to occur during AD, prevents magnesium from reentering and blocking the channel pore resulting in a chronically open state and excessive calcium influx. Memantine binds to the intra-pore magnesium site, but with longer dwell time, and thus functions as an effective receptor blocker only under conditions of excessive stimulation; memantine does not affect normal neurotransmission.

Pharmacokinetics

Absorption: Well absorbed

Distribution: 9 to 11 L/kg

Protein binding: 45%

Metabolism: Partially hepatic, primarily independent of the CYP enzyme system; forms 3 metabolites (minimal activity)

Half-life elimination: Terminal: ~60 to 80 hours

Time to peak, serum: Immediate release: 3 to 7 hours; Extended release: 9 to 12 hours

Excretion: Urine (74%; ~48% of the total dose as unchanged drug; undergoes active tubular secretion moderated by pH-dependent tubular reabsorption; excretion reduced by alkaline urine pH)

Pharmacokinetics: Additional Considerations

Altered kidney function: Mean AUC0-∞ increased by 4%, 60%, and 115% in patients with mild, moderate, and severe renal impairment, respectively. The terminal elimination half-life increased by 18%, 41%, and 95% in patients with mild, moderate, and severe renal impairment, respectively.

Hepatic function impairment: Terminal elimination half-life increased by ~16% in patients with moderate hepatic impairment.

Sex: Women had ~45% greater exposure than men; however, there was no difference in exposure when body weight was taken into account.

Pricing: US

Capsule ER 24 Hour Therapy Pack (Memantine HCl ER Oral)

7 mg (per each): $15.26 - $15.28

14 mg (per each): $15.26 - $15.28

21 mg (per each): $15.26 - $15.28

28 mg (per each): $15.26 - $15.28

Capsule ER 24 Hour Therapy Pack (Namenda XR Oral)

7 mg (per each): $18.59

14 mg (per each): $18.59

21 mg (per each): $18.59

28 mg (per each): $18.59

Solution (Memantine HCl Oral)

2 mg/mL (per mL): $2.05 - $2.67

Tablets (Memantine HCl Oral)

5 mg (per each): $6.04 - $6.10

10 mg (per each): $6.04 - $6.10

28 x 5 MG &21 x 10 MG (per each): $6.10

Tablets (Namenda Oral)

5 mg (per each): $8.90

10 mg (per each): $8.90

Tablets (Namenda Titration Pak Oral)

28 x 5 MG &21 x 10 MG (per each): $8.89

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Abixa (BD, PH, UA);
  • Admed (KR);
  • Admenta (IN);
  • Akatinol (AR, CO, CR, CU, DO, GT, HN, NI, PA, PY, SV, UY);
  • Albix (HK, KR);
  • Alois (BR);
  • Alzema (LB);
  • Amint-10 (PH);
  • Axura (AT, BE, BG, CH, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, IT, MT, NL, PL, PT, RO, RU, SE, SK, TR);
  • Carrier (PY);
  • Cerentia (EG);
  • Cognitine (PH);
  • Cordure (CO);
  • Delmenda (EG);
  • Dementa (BD);
  • Denigma (PH, UA);
  • Ebix (BR);
  • Ebixa (AE, AR, AT, AU, BE, BG, BH, CH, CL, CN, CY, CZ, DE, DK, EE, EG, ES, FI, FR, GB, GR, HK, HR, HU, IE, IL, IS, IT, JO, KR, KW, LB, LT, LU, MT, MX, MY, NL, NO, NZ, PK, PL, PT, QA, RO, RU, SA, SE, SG, SI, SK, TH, TR, TW);
  • Esmirtal (PE);
  • Eutebrol (CL, CR, DO, EC, GT, HN, NI, PA, PE, SV);
  • Evy (TW);
  • Exenta (LB);
  • Foliant (LK);
  • Limember (PE);
  • Lindex (CL, EC);
  • Lucidex (AR);
  • Manotin (TW);
  • Mantomed (NL);
  • Marbodin (DK);
  • Marixino (BE, CZ, HR, IE, LV, MT, NL, SG);
  • Mema (UA);
  • Memadem-10 (PH);
  • Memanto (KR);
  • Memanxa (AU);
  • Memary (JP);
  • Mementor (ZW);
  • Memogen (BD);
  • Memolan (AT);
  • Memora (LB);
  • Memoria (BH);
  • Memox (IL, UA);
  • Memry (PH);
  • Memxa (HK, TH);
  • Mentin (ZW);
  • Mentixa (DK);
  • Mentra (IN, PH);
  • Mirvedol (HU);
  • Nematine (HU);
  • Nemdatine (BE, CZ, IE, LV, NL, NO, SG);
  • Neumantine (TH);
  • Neuroplus (EC);
  • Pentabixa (EG);
  • Remtin (BD);
  • Tabixa (BH);
  • Vilimen (TR);
  • Vivimex (CL);
  • Witgen (TW);
  • Zider (BR);
  • Zimerz (PH)


For country code abbreviations (show table)
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  2. Alva G, Cummings JL. Relative tolerability of Alzheimer's disease treatments. Psychiatry (Edgmont). 2008;5(11):27-36. [PubMed 19724715]
  3. Ballard C, Thomas A, Gerry S, et al. MAIN-AD investigators. A double-blind randomized placebo-controlled withdrawal trial comparing memantine and antipsychotics for the long-term treatment of function and neuropsychiatric symptoms in people with Alzheimer's disease (MAIN-AD). J Am Med Dir Assoc. 2015;16(4):316-322. [PubMed 25523285]
  4. Based on expert opinion.
  5. Brown PD, Gondi V, Pugh S, et al. Hippocampal avoidance during whole-brain radiotherapy plus memantine for patients with brain metastases: phase III trial NRG oncology CC001. J Clin Oncol. 2020;38(10):1019-1029. doi:10.1200/JCO.19.02767 [PubMed 32058845]
  6. Brown PD, Pugh S, Laack NN, et al; Radiation Therapy Oncology Group (RTOG). Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol. 2013;15(10):1429-1437. doi:10.1093/neuonc/not114 [PubMed 23956241]
  7. Di Santo SG, Prinelli F, Adorni F, Caltagirone C, Musicco M. A meta-analysis of the efficacy of donepezil, rivastigmine, galantamine, and memantine in relation to severity of Alzheimer's disease. J Alzheimers Dis. 2013;35(2):349-361. [PubMed 23411693]
  8. Duan J, Lao C, Chen J, et al. Memantine induces manic episode in a 73-year-old patient with vascular neurocognitive disorder: a case report. Neuropsychiatr Dis Treat. 2018;14:1395-1398. doi:10.2147/NDT.S160832 [PubMed 29881276]
  9. Ebixa (memantine) [product monograph]. Montreal, Quebec, Canada: Lundbeck Canada Inc; May 2015.
  10. Emre M, Tsolaki M, Bonuccelli U, et al; 11018 Study Investigators. Memantine for patients with Parkinson's disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010;9(10):969-977. doi:10.1016/S1474-4422(10)70194-0 [PubMed 20729148]
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  14. Gallini A, Sommet A, Montastruc JL; French PharmacoVigilance Network. Does memantine induce bradycardia? A study in the French PharmacoVigilance Database. Pharmacoepidemiol Drug Saf. 2008;17(9):877-881. doi:10.1002/pds.1620 [PubMed 18500725]
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  16. Horikawa N, Yamada H, Uchimura N. Memantine-associated renal impairment in a patient with Alzheimer's disease. Psychiatry Clin Neurosci. 2013;67(2):126. doi:10.1111/pcn.12020 [PubMed 23438167]
  17. Howard R, McShane R, Lindesay J, et al. Donepezil and memantine for moderate-to-severe Alzheimer's disease. N Engl J Med. 2012;366(10):893-903. doi:10.1056/NEJMoa1106668 [PubMed 22397651]
  18. Jones RW, Bayer A, Inglis F, Barker A, Phul R. Safety and tolerability of once-daily versus twice-daily memantine: a randomised, double-blind study in moderate to severe Alzheimer's disease. Int J Geriatr Psychiatry. 2007;22(3):258-262. doi:10.1002/gps.1752 [PubMed 17243195]
  19. Kajitani K, Yanagimoto K, Monji A, Maruyama T. Memantine exacerbates corrected QT interval prolongation in Alzheimer's disease: a case report from an unintentional rechallenge. J Am Geriatr Soc. 2016;64(1):232-233. doi:10.1111/jgs.13897 [PubMed 26782892]
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