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Mefloquine (Monograph)

Brand name: Lariam
Drug class: Antimalarials
VA class: AP101
Chemical name: (R*,S*)-(±)-α-2-Piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol
Molecular formula: C17H16F6N2O
CAS number: 53230-10-7

Medically reviewed by Drugs.com on Feb 26, 2024. Written by ASHP.

Introduction

Antimalarial; 4-quinolinemethanol derivative; quinine analog.

Uses for Mefloquine

Prevention of Malaria

Prevention (prophylaxis) of malaria caused by Plasmodium falciparum (including chloroquine-resistant P. falciparum) or P. vivax; designated an orphan drug by FDA for prevention of P. falciparum malaria resistant to chloroquine or other antimalarials.

Recommended by CDC and others as a drug of choice for prophylaxis in those traveling to areas where chloroquine-resistant P. falciparum has been reported; also can be used for prophylaxis in those traveling to areas where chloroquine-resistant P. falciparum malaria has not been reported.

Risk of acquiring malaria varies substantially from traveler to traveler and from region to region (even within a single country) because of differences in intensity of malaria transmission within the various regions and season, itinerary, duration, and type of travel. Malaria transmission occurs in large areas of Africa, Central and South America, parts of the Caribbean, Asia (including South Asia, Southeast Asia, and the Middle East), Eastern Europe, and the South Pacific. Mosquito avoidance measures must be used in conjunction with prophylaxis since no drug is 100% effective in preventing malaria.

Choice of antimalarial for prophylaxis depends on traveler’s risk of acquiring malaria in area(s) visited, risk of exposure to drug-resistant P. falciparum, other medical conditions (e.g., pregnancy), cost, and potential adverse effects.

Active only against asexual erythrocytic forms of Plasmodium (not exoerythrocytic stages) and cannot prevent delayed primary attacks or relapse of P. ovale or P. vivax malaria or provide a radical cure; terminal prophylaxis with 14-day regimen of primaquine may be indicated in addition to mefloquine prophylaxis if travelers were exposed in areas where P. ovale or P. vivax is endemic.

Information on risk of malaria in specific countries and mosquito avoidance measures and recommendations regarding whether prevention of malaria indicated and choice of antimalarials for prevention are available from CDC at [Web] and [Web].

Treatment of Uncomplicated Malaria

Treatment of uncomplicated malaria caused by mefloquine-susceptible P. falciparum (including chloroquine-resistant P. falciparum) or P. vivax; designated an orphan drug by FDA for this use.

For treatment of uncomplicated malaria caused by chloroquine-resistant P. falciparum or treatment of uncomplicated malaria when plasmodial species not identified, CDC recommends fixed combination of atovaquone and proguanil (atovaquone/proguanil), fixed combination of artemether and lumefantrine (artemether/lumefantrine), or regimen of quinine in conjunction with doxycycline, tetracycline, or clindamycin.

For treatment of uncomplicated malaria caused by chloroquine-susceptible P. falciparum, P. malariae, or P. knowlesi or treatment of uncomplicated malaria when plasmodial species not identified and infection was acquired in areas where chloroquine resistance has not been reported, CDC recommends chloroquine (or hydroxychloroquine). Alternatively, CDC states that any of the regimens recommended for treatment of uncomplicated chloroquine-resistant P. falciparum malaria may be used if preferred, more readily available, or more convenient.

Although mefloquine is an option for treatment of uncomplicated malaria caused by susceptible Plasmodium, CDC recommends the drug be used only when other recommended treatment regimens cannot be used.

For treatment of uncomplicated malaria caused by chloroquine-resistant P. vivax, CDC recommends regimen of quinine and doxycycline (or tetracycline) given in conjunction with primaquine, atovaquone/proguanil given in conjunction with primaquine, or mefloquine given in conjunction with primaquine. Because quinine, doxycycline (or tetracycline), atovaquone/proguanil, and mefloquine are active only against asexual erythrocytic forms of Plasmodium (not exoerythrocytic stages), 14-day regimen of primaquine indicated to prevent delayed primary attacks or relapse and provide a radical cure whenever any of these drugs used for treatment of P. vivax or P. ovale malaria.

Pediatric patients with uncomplicated malaria generally can receive same treatment regimens recommended for adults using age- and weight-appropriate drugs and dosages. For treatment of uncomplicated chloroquine-resistant P. falciparum in children <8 years of age, atovaquone/proguanil or artemether/lumefantrine usually recommended; mefloquine can be considered if no other options available. For treatment of chloroquine-resistant P. vivax malaria in children <8 years of age, CDC recommends mefloquine given in conjunction with primaquine. Alternatively, if mefloquine not available or not tolerated and if potential benefits outweigh risks, atovaquone/proguanil or artemether/lumefantrine can be used for treatment of chloroquine-resistant P. vivax in this age group.

A drug of choice for treatment of uncomplicated malaria caused by chloroquine-resistant P. falciparum or chloroquine-resistant P. vivax in pregnant women. (See Pregnancy under Cautions.)

Because of resistance, not recommended for treatment of malaria acquired in Southeast Asia.

Assistance with diagnosis or treatment of malaria is available from CDC Malaria Hotline at 770-488-7788 or 855-856-4713 from 9:00 a.m. to 5:00 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after hours and on weekends and holidays.

Mefloquine Dosage and Administration

General

Administration

Oral Administration

Administer orally with ample water (at least 8 oz [240 mL] of water for an adult).

Do not administer on an empty stomach.

If patient receiving mefloquine for treatment of malaria vomits within 30 minutes after receiving a dose, give a full dose as replacement; if vomiting occurs within 30–60 minutes after the dose, give 50% of the dose as replacement. If vomiting recurs, monitor patient closely and consider alternative malaria treatment if improvement not observed within reasonable period of time.

For administration in children and others unable to swallow tablets, mefloquine tablets may be crushed and mixed with a small amount of liquid (e.g., water, milk, other beverage).

When a dose <125 mg (<½ of a 250-mg tablet) indicated for pediatric patients, gelatin capsules containing the calculated pediatric dosage should be prepared extemporaneously by a pharmacist using a crushed tablet.

Dosage

Available as mefloquine hydrochloride; dosage in the US usually expressed in terms of the salt. Each 250-mg tablet of mefloquine hydrochloride commercially available in the US is equivalent to 228 mg of mefloquine base. Other formulations (e.g., 275-mg mefloquine hydrochloride tablets containing 250 mg of the base) may be available in other countries.

Dosage in children is based on body weight.

Pediatric Patients

Prevention of P. falciparum or P. vivax Malaria
Oral

Infants and children weighing ≤45 kg: Approximately 5 mg/kg once weekly on same day each week, preferably after main meal. (See Table 1.) Only limited experience in those weighing <20 kg (especially those weighing <5 kg).

Children weighing >45 kg: 250 mg once weekly on same day each week, preferably after main meal.

Table 1. Mefloquine Dosage for Prevention of Malaria in Infants and Children Weighing ≤45 kg1115121

Weight (kg)

Dosage Once Weekly

≤9

5 mg/kg (prepared extemporaneously)

>9 up to 19

62.5 mg (¼ of a 250-mg tablet; prepared extemporaneously)

>19 up to 30

125 mg (½ of a 250-mg tablet)

>30 up to 45

187.5 mg (¾ of a 250-mg tablet)

Initiate mefloquine prophylaxis 1–2 weeks prior to entering malarious area and continue during and for 4 weeks after leaving the area. CDC recommends initiating mefloquine prophylaxis ≥2 weeks before travel. If there are concerns about tolerance or drug interactions, it may be advisable to initiate mefloquine prophylaxis 3–4 weeks prior to travel in individuals receiving other drugs to ensure that the combination of drugs is well tolerated and to allow ample time to switch to another antimalarial if necessary.

If exposure occurred in areas where P. ovale or P. vivax is endemic, terminal prophylaxis with a 14-day regimen of primaquine may be indicated; give during final 2 weeks of mefloquine prophylaxis or, if not feasible, give after mefloquine prophylaxis discontinued.

Treatment of Uncomplicated P. falciparum or P. vivax Malaria
Oral

Children ≥6 months of age: Manufacturer recommends 20–25 mg/kg and states that dividing dosage into 2 doses given 6–8 hours apart may reduce incidence and severity of adverse effects. CDC and other experts recommend that children receive 2-dose regimen consisting of an initial dose of 15 mg/kg followed by 10 mg/kg 6–12 hours later (total dose of 25 mg/kg).

If a response not attained within 48–72 hours, use an alternative antimalarial; do not use mefloquine for retreatment.

For those with P. vivax malaria, a 14-day regimen of primaquine also indicated to provide a radical cure and prevent delayed attacks or relapse.

Adults

Prevention of P. falciparum or P. vivax Malaria
Oral

250 mg once weekly on same day each week, preferably after main meal.

Initiate mefloquine prophylaxis 1–2 weeks prior to entering malarious area and continue during and for 4 weeks after leaving the area. CDC recommends initiating mefloquine prophylaxis ≥2 weeks before travel. If there are concerns about tolerance or drug interactions, it may be advisable to initiate mefloquine prophylaxis 3–4 weeks prior to travel in individuals receiving other drugs to ensure that the combination of drugs is well tolerated and to allow ample time to switch to another antimalarial if required.

If exposure occurred in areas where P. ovale or P. vivax is endemic, terminal prophylaxis with a 14-day regimen of primaquine may be indicated; give during final 2 weeks of mefloquine prophylaxis or, if not feasible, give after mefloquine prophylaxis discontinued.

Treatment of Uncomplicated P. vivax or P. falciparum Malaria
Oral

A single dose of 1250 mg (five 250-mg tablets) recommended by manufacturer. CDC and others recommend a 2-dose regimen consisting of an initial 750-mg dose (three 250-mg tablets) followed by a 500-mg dose (two 250-mg tablets) given 6–12 hours later (total dose of 1250 mg).

If a response not attained within 48–72 hours, use an alternative antimalarial; do not use mefloquine for retreatment.

For those with P. vivax malaria, a 14-day regimen of primaquine also indicated to provide a radical cure and prevent delayed attacks or relapse.

Prescribing Limits

Pediatric Patients

Malaria
Prevention of P. falciparum or P. vivax Malaria
Oral

Maximum 250 mg once weekly.

Treatment of P. falciparum or P. vivax Malaria
Oral

Maximum 1250 mg.

Special Populations

Hepatic Impairment

No specific recommendations available regarding need for dosage adjustment in individuals with hepatic impairment. Increased mefloquine plasma concentrations may occur because of decreased elimination. (See Hepatic Impairment under Cautions.)

Renal Impairment

No specific recommendations available regarding need for dosage adjustment in individuals with renal impairment.

When used for prevention of malaria, limited data indicate dosage adjustment not necessary in those undergoing hemodialysis.

Cautions for Mefloquine

Contraindications

Warnings/Precautions

Warnings

Nervous System Effects

Dizziness, headache, and insomnia are the most frequently reported nervous system effects in patients receiving mefloquine. Abnormal dreams, altered consciousness, forgetfulness, motor and sensory neuropathy (including paresthesia, tremor, ataxia), seizures, vertigo, and tinnitus and hearing impairment also reported.

Patients with epilepsy or history of seizures may be at increased risk of seizure, although seizures have occurred in those without such a history. Do not use for prevention of malaria in epilepsy patients; use for treatment of malaria in such patients only if there are compelling medical reasons for such use.

Some adverse nervous system effects (e.g., dizziness or vertigo, tinnitus and hearing impairment, loss of balance) may occur shortly after mefloquine initiation, can continue for months or years after drug discontinuance, and may be permanent in some cases.

Discontinue mefloquine and substitute alternative antimalarial if neurologic effects (e.g., dizziness or vertigo, loss of balance) occur in a patient receiving mefloquine for malaria prevention.

Neuropsychiatric Effects

Severe neuropsychiatric disorders have been reported occasionally with mefloquine, including agitation or restlessness, anxiety, depression, mood changes, panic attacks, forgetfulness, confusion, hallucinations, aggression, psychotic or paranoid reactions, and encephalopathy. In some patients, these symptoms have been reported to continue for months or years after mefloquine was discontinued.

There have been rare cases of suicidal ideation and suicide in patients receiving mefloquine.

Do not use mefloquine for prevention of malaria in any individual with active depression, recent history of depression, generalized anxiety disorder, psychosis, schizophrenia, or other major psychiatric disorders. Use mefloquine with caution in individuals with a previous history of depression.

Some neuropsychiatric manifestations (e.g., acute anxiety, depression, restlessness, confusion) occurring in a patient receiving mefloquine prophylaxis suggest a risk for more serious psychiatric events or adverse neurologic effects.

Neuropsychiatric effects can occur in adults or children and may be particularly difficult to identify in children. If used for prolonged periods (e.g., for malaria prevention), evaluate patient periodically for neuropsychiatric effects. Vigilance required to monitor for such manifestations, especially in nonverbal children.

Discontinue mefloquine and substitute alternative antimalarial if neuropsychiatric manifestations (e.g., acute anxiety, depression, restlessness or confusion, suicidal ideation) occur in a patient receiving mefloquine for malaria prevention.

Interactions

Concomitant or sequential use with some other antimalarials (e.g., chloroquine, quinine, quinidine, halofantrine [not commercially available in US]) or certain other drugs (e.g., ketoconazole) may increase risk of potentially fatal prolongation of QTc interval and/or may increase risk for seizures. (See Interactions.)

Sensitivity Reactions

Hypersensitivity Reactions

Serious cutaneous reactions, including Stevens-Johnson syndrome, erythema multiforme, and cutaneous vasculitis, reported rarely.

General Precautions

Cardiac Effects

Mefloquine is a myocardial depressant, and mefloquine-induced changes in several cardiac parameters have been described. Bradycardia, extrasystoles, reversible sinus arrhythmia, first degree AV-block, and prolongation of QTc interval and abnormal T waves reported.

Hypertension, hypotension, flushing, syncope, chest pain, tachycardia, palpitations, and irregular pulse reported. Cardiopulmonary arrest, pericarditis, cardiovascular collapse, and MI reported rarely.

Weigh benefits of mefloquine against risks of adverse effects in patients with cardiac disease. Some experts state the drug should not be used in patients with cardiac conduction abnormalities.

Ocular Effects

Visual disturbances reported infrequently in patients receiving mefloquine. Dose-related ocular lesions (retinal degeneration, retinal edema, lenticular opacity) reported in long-term animal studies.

If used for prolonged periods (e.g., for malaria prevention), periodically perform ophthalmic examinations.

Selection and Use of Antimalarials

Do not use for initial treatment of severe malaria. Life-threatening, serious, or overwhelming malaria requires aggressive treatment with a parenteral antimalarial regimen.

Do not use for treatment of malaria in patients who received the drug for prevention of malaria.

Because of increased incidence of adverse effects and high failure rate, do not use mefloquine for retreatment in patients who did not respond to or were previously treated with the drug.

Concomitant or sequential use with some other antimalarials (e.g., chloroquine, quinine, quinidine, halofantrine [not commercially available in US]) may result in serious adverse effects. (See Interactions.)

Laboratory Monitoring

If used for prolonged periods (e.g., for malaria prevention), periodically evaluate liver function.

Specific Populations

Pregnancy

Category B.

Manufacturer states use mefloquine during pregnancy only when clearly needed and advise women of childbearing potential to use effective contraceptive measures while receiving the drug and for up to 3 months after last dose.

CDC and AAP recommend mefloquine as the drug of choice for prevention of malaria in women who are pregnant, or likely to become pregnant, if exposure to chloroquine-resistant P. falciparum unavoidable. CDC also states that mefloquine is a drug of choice for treatment of uncomplicated malaria caused by chloroquine-resistant P. falciparum or chloroquine-resistant P. vivax.

Although reproduction studies in mice, rats, and rabbits have shown teratogenic effects at doses similar to those used for malaria treatment, published data on use of mefloquine for prevention or treatment of malaria during pregnancy have not shown an increased risk of teratogenic effects or adverse pregnancy outcomes compared to the background rate in the general population.

Lactation

Distributed into milk. Use with caution in nursing women.

Because amount of mefloquine consumed by a nursing infant likely to be small, some clinicians suggest that risk to nursing infants of maternal use of prophylactic dosages of mefloquine is low.

Pediatric Use

Safety and efficacy not established for treatment of malaria in children <6 months of age.

Only limited data available regarding use for prevention or treatment of malaria in children weighing <20 kg (especially those weighing <5 kg).

CDC states use of mefloquine for prevention or chemoprophylaxis of malaria may be considered in infants and children of any age, depending on risk of exposure to drug-resistant Plasmodium.

Use in children for treatment of acute uncomplicated malaria caused by P. falciparum is supported by evidence from adequate and well-controlled studies in adults and from published open-label and comparative studies in children <16 years of age.

Children of any age can contract malaria, and indications for prophylaxis and treatment of malaria in children are the same as those for adults.

Because of risks associated with malaria infection in children <6 weeks of age or weighing <5 kg, some experts recommend advising parents of such infants not to travel to countries with endemic malaria.

Children ≤6 years of age being treated for malaria experience early vomiting (within 1 hour of drug administration) more frequently than individuals 7–50 years of age; early vomiting may be a possible cause of treatment failure in some children. If a replacement dose not tolerated (see Administration under Dosage and Administration), closely monitor child and consider alternative antimalarial treatment if child does not improve within a reasonable period of time.

Geriatric Use

Response in patients ≥65 years of age does not appear to differ from that in younger adults.

Because mefloquine associated with ECG abnormalities, consider the greater frequency of cardiac disease observed in the elderly and weigh benefits of mefloquine therapy in geriatric individuals against possibility of adverse cardiac effects.

Hepatic Impairment

Mefloquine elimination may be prolonged and plasma concentrations increased in patients with hepatic impairment, resulting in increased risk of adverse effects.

Common Adverse Effects

GI effects (nausea, vomiting, loose stools or diarrhea, abdominal pain); CNS effects (dizziness, vertigo); neuropsychiatric events (headache, somnolence, sleep disorders); rash; pruritus.

Drug Interactions

Metabolized by CYP3A4; does not inhibit or induce CYP isoenzymes.

Substrate for and inhibitor of P-glycoprotein.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction with drugs that are CYP3A4 inhibitors (possible increased mefloquine concentrations and increased potential for adverse effects associated with the drug). Use concomitantly with caution.

Potential pharmacokinetic interaction with drugs that are CYP3A4 inducers (possible decreased mefloquine concentrations and possible decreased efficacy of the antimalarial). Use concomitantly with caution.

Pharmacokinetic interactions not expected if mefloquine used concomitantly with drugs that are substrates for CYP isoenzymes.

Drugs Affecting P-glycoprotein Transport System

Potential pharmacokinetic interactions if used concomitantly with drugs that are substrates for or are known to modify expression of P-glycoprotein; clinical importance unknown.

Drugs Affecting QT Interval

Possibility of prolongation of QT interval if used concomitantly with other drugs that alter cardiac conduction, including antiarrhythmic agents, β-adrenergic blocking agents, calcium-channel blocking agents, antihistamines, tricyclic antidepressants, and phenothiazines. Some experts state that mefloquine may be used concomitantly with β-adrenergic blocking agents in patients without an underlying arrhythmia.

Specific Drugs

Drug

Interaction

Comments

Anticonvulsants (carbamazepine, phenobarbital, phenytoin, valproic acid)

Possible decreased anticonvulsant concentrations and reduced seizure control

Mefloquine generally contraindicated in patients with history of seizures; if used in an individual receiving an anticonvulsant, monitor anticonvulsant concentrations and adjust dosage as necessary

Antimalarial agents

Artemether/lumefantrine: Decreased concentrations and AUC of lumefantrine possibly because of mefloquine-induced decrease in bile production; no effect on pharmacokinetics of artemether or mefloquine

Chloroquine, quinine, or quinidine: Possibility of serious ECG abnormalities, including QTc interval prolongation, and increased risk of seizures

Halofantrine (not commercially available in US): Use after mefloquine has resulted in potentially fatal prolongation of QTc interval

Artemether/lumefantrine: If used shortly after mefloquine, administer artemether/lumefantrine dose with food and monitor for decreased efficacy

Chloroquine, quinine, or quinidine: Do not use concomitantly with mefloquine; use sequentially with caution; do not administer mefloquine until ≥12 hours after last dose of any of these drugs; if initiating quinidine in a patient who received mefloquine within preceding 12 hours, do not use loading dose of quinidine

Halofantrine: Do not use concomitantly with mefloquine or within 15 weeks after last mefloquine dose

HIV protease inhibitors (PIs)

Ritonavir: Decreased AUC of ritonavir; no effect on mefloquine pharmacokinetics

Ritonavir-boosted PIs: Pharmacokinetic interaction unknown

HIV PIs: Some experts recommend caution if mefloquine used in patients receiving PIs

Ketoconazole

Substantially increased mefloquine concentrations, AUC, and elimination half-life; increased risk of potentially fatal prolongation of QTc interval

Do not use ketoconazole concomitantly with mefloquine or within 15 weeks after last mefloquine dose

Rifampin

Decreased concentrations, AUC, and elimination half-life of mefloquine

Manufacturer of mefloquine states use concomitantly with caution; some experts recommend avoiding concomitant use if possible and considering use of rifabutin (instead of rifampin) or using an alternative antimalarial

Typhoid Vaccine

Possibility of interference with immune response to typhoid vaccine live oral since mefloquine has in vitro activity against Salmonella typhi

Delay vaccination with typhoid vaccine live oral for 24 hours after mefloquine dose; complete typhoid vaccination ≥3 days before initiating mefloquine prophylaxis

Mefloquine Pharmacokinetics

Absorption

Bioavailability

Mefloquine is a racemic mixture of 2 erythro enantiomers whose rates of release, absorption, transport, action, degradation, and elimination may differ.

Slowly absorbed from GI tract; peak concentrations in blood or plasma attained within 6–24 hours and appear to be proportional to dose.

Food

Limited evidence indicates that bioavailability greater when administered with food than when administered in fasting state.

Special Populations

Some evidence that peak blood or plasma concentrations of mefloquine are substantially higher in Asians than in other ethnic groups. Reason for this ethnic variation not determined; may involve differences in volume of distribution secondary to the relatively lower body fat in Asians or differences in enterohepatic circulation of mefloquine in Asians.

Distribution

Extent

Widely distributed into body tissues and fluids.

Concentrates in erythrocytes to a greater extent than in plasma.

Distributed into CNS. However, because GI absorption may be incomplete and erratic in patients with severe malaria, do not rely on oral mefloquine therapy for malaria involving the CNS.

Distributed into milk in low concentrations.

Plasma Protein Binding

98% bound to plasma proteins.

Elimination

Metabolism

Metabolized in the liver, but metabolic fate not fully determined.

Extensively metabolized by CYP isoenzyme system, probably by CYP3A4.

Plasma concentrations of the principal metabolite, the 4-carboxylic acid derivative, exceed those of mefloquine.

Elimination Route

Mefloquine and its metabolites are excreted in feces, with only small amounts (<13% combined) eliminated in urine.

Undergoes biliary excretion and extensive enterohepatic circulation; some evidence suggests that enterohepatic circulation and fecal elimination may be increased in patients with malaria compared with those in healthy adults.

Mefloquine and its 4-carboxylic acid metabolite not appreciably removed by hemodialysis.

Half-life

Terminal elimination half-life shows considerable interindividual variation, ranging from 13–33 days (mean: 21 days) in healthy adults and about 10–15 days in patients with uncomplicated malaria.

Faster elimination in patients with uncomplicated malaria relative to healthy individuals may result from decreased enterohepatic recirculation and increased fecal elimination.

In Thai children with uncomplicated malaria, a terminal elimination half-life of 9.8–10.7 days was reported in those 6–24 months of age and 5–12 years of age.

Special Populations

Mefloquine elimination may be prolonged in patients with hepatic impairment, resulting in higher plasma concentrations.

Alterations in mefloquine pharmacokinetics have been documented in pregnant women (e.g., increased mefloquine clearance in late pregnancy); such changes not considered clinically relevant.

Stability

Storage

Oral

Tablets

20–25°C. Protect from light.

Actions and Spectrum

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Mefloquine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

250 mg*

Mefloquine Hydrochloride Tablets (scored)

AHFS DI Essentials™. © Copyright 2024, Selected Revisions March 5, 2014. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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