Skip to Content

Qualaquin

Generic Name: Quinine Sulfate
Class: Antimalarials
VA Class: AP101
Chemical Name: (8S,9R)-6′-Methoxycinchonan-9-ol
Molecular Formula: C20H24N2O2
CAS Number: 60-93-5

Warning(s)

  • Serious and life-threatening hematologic reactions, including thrombocytopenia and hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP), may occur if quinine is used for treatment or prevention of nocturnal leg cramps.180

  • Chronic renal impairment associated with TTP reported.180

  • Known risks associated with use of quinine, in the absence of evidence of safety and efficacy of the drug for treatment or prevention of nocturnal leg cramps, outweigh any potential benefits for this unlabeled indication.180

    (See Use for Treatment or Prevention of Nocturnal Leg Cramps under Cautions.)

REMS:

FDA approved a REMS for quinine sulfate to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of quinine sulfate and consists of the following: medication guide and communication plan. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Antimalarial; alkaloid obtained from bark of the cinchona tree.185

Uses for Qualaquin

Treatment of Uncomplicated Malaria

Treatment of uncomplicated Plasmodium falciparum malaria.165 171 180 186 Also used for treatment of uncomplicated malaria caused by chloroquine-resistant P. vivax165 171 173 186 and for treatment of uncomplicated malaria when plasmodial species has not been identified.165 171 173 186

Designated an orphan drug by FDA for the treatment of malaria.179 Since malaria is a life-threatening infection, FDA states that the potential benefits of the drug outweigh the associated risks and justify its use for the treatment of malaria.182

For treatment of uncomplicated malaria caused by chloroquine-resistant P. falciparum in nonpregnant adults and children ≥8 years of age and for treatment of uncomplicated malaria in this age group when plasmodial species not identified and the disease was acquired in areas with chloroquine resistance, CDC recommends the fixed combination of atovaquone and proguanil (Malarone); the fixed combination of artemether and lumefantrine (Coartem); or a regimen that includes quinine in conjunction with doxycycline, tetracycline, or clindamycin.171 186 Because of serious adverse effects (e.g., severe neuropsychiatric reactions), use mefloquine only if the recommended treatment regimens cannot be used.171 186 If a quinine regimen is used, concomitant doxycycline or tetracycline generally preferred instead of concomitant clindamycin since more efficacy data exist regarding antimalarial regimens that include tetracyclines.171 186

For treatment of uncomplicated malaria caused by chloroquine-resistant P. vivax in nonpregnant adults and children ≥8 years of age, CDC recommends a regimen of quinine and doxycycline (or tetracycline) given in conjunction with primaquine; the fixed combination of atovaquone and proguanil (Malarone) given in conjunction with primaquine; or mefloquine given in conjunction with primaquine.171 186 Primaquine is necessary in these regimens to provide a radical cure and prevent relapse of P. vivax malaria.165 171 186

In children <8 years of age with chloroquine-resistant P. falciparum malaria or when the plasmodial species has not been identified and the disease was acquired in areas with chloroquine resistance, CDC recommends the fixed combination of atovaquone and proguanil (Malarone) or fixed combination of artemether and lumefantrine (Coartem); mefloquine can be considered if no other options are available.186 If a quinine regimen is used in children <8 years of age, CDC states that quinine monotherapy may be given for 7 days or a regimen of quinine and clindamycin can be given for the usually recommended duration.171 Alternatively, CDC states that a regimen of quinine and doxycycline or tetracycline can be considered in children <8 years of age in rare circumstances when other treatment options are not available or not tolerated and the benefits of including a tetracycline in the regimen are judged to outweigh risks.171 In children <8 years of age with chloroquine-resistant P. vivax malaria, CDC recommends mefloquine in conjunction with primaquine as the regimen of choice; if mefloquine is not available or not tolerated and if benefits outweigh risks, the fixed combination of atovaquone and proguanil or fixed combination of artemether and lumefantrine can be used as alternatives. 171 186

Slideshow: It’s Buggin’ Me! How to Safely Use an Insect Repellent

In pregnant women with uncomplicated malaria, CDC recommends a regimen of quinine and clindamycin for infections caused by chloroquine-resistant P. falciparum and a regimen of quinine for infections caused by chloroquine-resistant P. vivax.171 186 (See Pregnancy under Cautions.) Although tetracyclines generally are contraindicated in pregnant women, in rare circumstances (e.g., other treatment options not available or not tolerated), CDC states that quinine may be used in conjunction with doxycycline or tetracycline for treatment of uncomplicated malaria caused by chloroquine-resistant P. falciparum or P. vivax in pregnant women if benefits outweigh risks.171 186

Assistance with diagnosis or treatment of malaria is available from CDC Malaria Hotline at 770-488-7788 from 8:00 a.m. to 4:30 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after hours, on weekends, and holidays.171

Treatment of Severe Malaria

Follow-up treatment of severe malaria.171 186

Severe malaria usually is caused by P. falciparum and requires initial aggressive treatment with a parenteral antimalarial regimen initiated as soon as possible after diagnosis.171 186 200 Also can consider exchange transfusions if parasitemia is >10% or patient has cerebral malaria, altered mental status, nonvolume overload pulmonary edema, or renal complications and if potential benefits outweigh risks.186 200

For treatment of severe malaria in adults and children, CDC recommends an initial regimen of IV quinidine in conjunction with doxycycline, tetracycline, or clindamycin (administered orally or IV as tolerated).171 186 After parasitemia is reduced to <1% and oral therapy is tolerated, IV quinidine can be discontinued and oral quinine initiated to complete 7 or 3 days of total quinidine and quinine therapy as determined by the geographic origin of the infecting parasite (7 days if malaria was acquired in Southeast Asia or 3 days if acquired elsewhere).171 186

If IV quinidine is unavailable or cannot be used for initial treatment because of adverse effects or contraindications, parenteral artesunate is available from CDC under an investigational new drug (IND) protocol for emergency initial treatment of severe malaria.171 186

Assistance with diagnosis or treatment of malaria and assistance obtaining quinidine or artesunate for treatment of severe malaria is available by contacting the CDC Malaria Hotline at 770-488-7788 from 8:00 a.m. to 4:30 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after hours, on weekends, and holidays.171

Presumptive Self-treatment of Malaria

A regimen of quinine in conjunction with doxycycline has been recommended by some clinicians for presumptive self-treatment of malaria in travelers.165

Not approved by FDA for presumptive self-treatment of malaria in travelers180 and not recommended by CDC or other clinicians for such treatment.164 200

For presumptive self-treatment of malaria in travelers, CDC recommends the fixed combination of atovaquone and proguanil (Malarone) in those not already taking the drug for prevention of malaria.164 Contact CDC Malaria Hotline (770-488-7788) for information regarding other potential options for self-treatment if atovaquone and proguanil cannot be used.164

Prevention of Malaria

Not approved by FDA for prevention (prophylaxis) of malaria180 and not included in current CDC recommendations for prevention of malaria.164

CDC and other clinicians recommend use of other antimalarial agents (e.g., chloroquine [or hydroxychloroquine], mefloquine, doxycycline, fixed combination of atovaquone and proguanil hydrochloride) for prevention of malaria caused by susceptible plasmodia.164 165 166 168 169

Detailed recommendations regarding prevention of malaria are available from the CDC 24 hours a day from the voice information service (877-394-8747) or CDC website ().164

Babesiosis

Treatment of babesiosis caused by Babesia microti.102 103 165 169 178 181

IDSA states that all patients with active babesiosis (i.e., symptoms of viral-like infection and identification of babesial parasites in blood smears or by polymerase chain reaction [PCR] amplification of babesial DNA) should receive anti-infective treatment because of the risk of complications; however, symptomatic patients whose serum contains antibody to babesia but whose blood lacks identifiable babesial parasites on smear or babesial DNA by PCR should not receive treatment.178 Treatment is not recommended initially for asymptomatic individuals, regardless of results of serologic examination, blood smears, or PCR, but should be considered if parasitemia persists for >3 months.178

When anti-infective treatment of babesiosis is indicated, IDSA and other clinicians recommend a regimen of quinine and clindamycin or a regimen of atovaquone and azithromycin.165 169 178 181

The quinine and clindamycin regimen may be preferred for severe babesiosis.178 However, there is some evidence that, in patients with mild or moderate illness, the atovaquone and azithromycin regimen may be as effective and better tolerated than the quinine and clindamycin regimen.165 169 178 181 Consider use of exchange transfusions, especially in severely ill patients with high levels of parasitemia (≥10%), significant hemolysis, or compromised renal, hepatic, or pulmonary function.165 169 178

B. microti is transmitted by Ixodes scapularis ticks, which also may be simultaneously infected with and transmit Borrelia burgdorferi (causative agent of Lyme disease) and Anaplasma phagocytophilum (causative agent of human granulocytotropic anaplasmosis [HGA, formerly known as human granulocytic ehrlichiosis]).169 178 Consider possibility of coinfection with B. burgdorferi and/or A. phagocytophilum in patients who have severe or persistent symptoms despite appropriate anti-infective treatment for babesiosis.178

Nocturnal Recumbency Leg Muscle Cramps

Not approved by FDA for the treatment or prevention of nocturnal leg cramps.180 182 185 187 Should not be used in the management of this or related conditions (e.g. restless legs syndrome).180 182 185 187 201

Although quinine has been used in the past for the prevention and treatment of nocturnal recumbency leg muscle cramps (night cramps),175 176 177 182 184 185 198 there are no adequate and well-controlled studies evaluating efficacy and safety for this use.119 120 121 122 124 154 155 184 185

Quinine has a narrow margin of safety and may cause unpredictable serious and life-threatening hypersensitivity reactions, QT interval prolongation, serious cardiac arrhythmias (including torsades de pointes), serious hematologic reactions (including thrombocytopenia and HUS/TTP), and other serious adverse events (e.g., blindness, deafness) requiring medical intervention and hospitalization.180 184 185 187 188 191 193 201 Fatalities associated with use of the drug have been reported.180 185 187 201 (See Cautions.) The known risks associated with the use of quinine, in the absence of evidence of safety and efficacy of the drug for the treatment or prevention of nocturnal leg cramps, outweigh any potential benefits for this benign, self-limiting condition.180 184 185 187

FDA has determined that quinine preparations (including preparations containing any quinine salt alone or in fixed combination with vitamin E) are not generally recognized as safe and effective for treatment or prevention of nocturnal leg muscle cramps.185 Promotion of quinine for self-medication of nocturnal leg cramps has been prohibited in the US since February 1995 because of safety concerns.154 155 184 185 In addition, FDA ordered that marketing of all unapproved quinine preparations be discontinued as of December 11, 2006.182 (See Preparations.)

Qualaquin Dosage and Administration

Administration

Quinine is administered orally as quinine sulfate.180 186

Although quinine has been administered by slow IV infusion as quinine dihydrochloride, a parenteral preparation of the drug no longer is available for use in the US, either commercially or from CDC.148 149 When parenteral antimalarial therapy is indicated, use IV quinidine gluconate.148 149 171 186

Oral Administration

Administer orally.180

May be administered without regard to meals.180 Administration with food recommended to minimize possible GI irritation.165 180

Dosage

Available as quinine sulfate; dosage expressed in terms of the salt.180

The only FDA-approved preparation of quinine currently commercially available in the US is a capsule containing 324 mg of quinine sulfate (Qualaquin; distributed by AR Scientific, Inc); the drug was previously available in the US as capsules containing 325 mg.180 185 This difference in quinine preparations may result in minor disparities between some published dosage recommendations that were based on the previously available 325-mg capsules and dosage recommendations for the currently available 324-mg capsules.a

Pediatric Patients

Malaria
Treatment of Uncomplicated Malaria Caused by Chloroquine-resistant P. falciparum or Unidentified Plasmodial Species
Oral

Children ≥8 years of age: 10 mg/kg 3 times daily for 7 or 3 days as determined by the geographic origin of the infecting parasite (7 days if malaria was acquired in Southeast Asia or 3 days if acquired elsewhere).165 Use in conjunction with a 7-day regimen of oral doxycycline, tetracycline, or clindamycin.165 186

Children <8 years of age: If a quinine regimen is used, CDC states quinine monotherapy may be given for 7 days or quinine can be given in conjunction with clindamycin for the usually recommended duration.171 In rare circumstances, a regimen of quinine and doxycycline or tetracycline can be considered.171 (See Treatment of Uncomplicated Malaria under Uses.)

Do not exceed usual adult dosage.171 186

Treatment of Uncomplicated Malaria Caused by Chloroquine-resistant P. vivax
Oral

Children ≥8 years of age: 10 mg/kg 3 times daily for 7 or 3 days as determined by the geographic origin of the infecting parasite (7 days if malaria was acquired in Southeast Asia or 3 days if acquired elsewhere).165 Do not exceed usual adult dosage.171 186

Use in conjunction with a 7-day regimen of oral doxycycline or tetracycline and a 14-day regimen of oral primaquine.165 186 Primaquine is necessary to provide a radical cure and prevent relapse of P. vivax malaria.165 171 186

Treatment of Severe Malaria
Oral

10 mg/kg 3 times daily to complete 7 or 3 days of total IV quinidine and oral quinine therapy as determined by the geographic origin of the infecting parasite (7 days if malaria was acquired in Southeast Asia or 3 days if acquired elsewhere).199 Do not exceed usual adult dosage.171

IV quinidine gluconate must be used initially; after ≥24 hours and after parasitemia is reduced to <1% and oral therapy is tolerated, oral quinine may be substituted.186

Use quinidine/quinine regimen in conjunction with a 7-day regimen of doxycycline, tetracycline, or clindamycin (administered IV or orally as tolerated).186

Presumptive Self-treatment of Malaria
Oral

10 mg/kg 3 times daily for 7 or 3 days as determined by the geographic origin of the infecting parasite (7 days if malaria was acquired in Southeast Asia or 3 days if acquired elsewhere) given in conjunction with a 7-day regimen of oral doxycycline.165

Not included in current CDC recommendations for presumptive self-treatment of malaria in travelers.164

Babesiosis
Oral

IDSA recommends 8 mg/kg (up to 650 mg) every 8 hours in conjunction with clindamycin (7–10 mg/kg [up to 600 mg] IV or orally every 6–8 hours) given for 7–10 days.178

Other clinicians recommend 30 mg/kg daily in 3 divided doses given for 7–10 days in conjunction with oral clindamycin (20–40 mg/kg daily in 3 divided doses for 7–10 days).165

For mild to moderate babesiosis, clinical improvement should be evident within 48 hours after initiation of treatment and symptoms should resolve completely within 3 months.178 Low-grade parasitemia may persist in some patients for months after completion of treatment.178 Regardless of presence or absence of symptoms, IDSA suggests that retreatment be considered if babesial parasites or amplifiable babesial DNA is detected in blood ≥3 months after initial treatment.178

Adults

Malaria
Treatment of Uncomplicated Malaria Caused by Chloroquine-resistant P. falciparum or Unidentified Plasmodial Species
Oral

Manufacturer recommends 648 mg every 8 hours for 7 days for P. falciparum malaria.180 Manufacturer cautions that shorter regimens (3 days) have been used, but data regarding these regimens are limited and they may be less effective than a 7-day regimen.180

CDC and other clinicians recommend 650 mg (two 324-mg capsules) every 8 hours for 7 or 3 days as determined by the geographic origin of the infecting parasite (7 days if malaria was acquired in Southeast Asia or 3 days if acquired elsewhere).165 186 Use in conjunction with a 7-day regimen of oral doxycycline, tetracycline, or clindamycin.165 171 186

Pregnant women: CDC recommends 650 mg (two 324-mg capsules) every 8 hours for 7 or 3 days as determined by the geographic origin of the infecting parasite (7 days if malaria was acquired in Southeast Asia or 3 days if acquired elsewhere).186 Use in conjunction with a 7-day regimen of oral clindamycin.171 186 Alternatively, if benefits outweigh risks, used in conjunction with oral doxycycline or tetracycline.186

Treatment of Uncomplicated Malaria Caused by Chloroquine-resistant P. vivax
Oral

650 mg (two 324-mg capsules) every 8 hours for 7 or 3 days as determined by the geographic origin of the infecting parasite (7 days if malaria was acquired in Southeast Asia or 3 days if acquired elsewhere).165 186 Use in conjunction with a 7-day regimen of oral doxycycline or tetracycline and a 14-day regimen of oral primaquine.165 171 Primaquine is necessary to provide a radical cure and prevent relapse of P. vivax malaria.165 171 186

Pregnant women: CDC recommends 650 mg (two 324-mg capsules) every 8 hours for 7 days (regardless of where infection was acquired).186 Used alone171 186 or, if benefits outweigh risks, used in conjunction with oral doxycycline or tetracycline.186 Then, give chloroquine (300 mg [500 mg of chloroquine phosphate] once weekly) as prophylaxis for the duration of the pregnancy until primaquine can be given after delivery to provide a radical cure and prevent relapse.171 186

Treatment of Severe Malaria
Oral

650 mg (two 324-mg capsules) every 8 hours to complete 7 or 3 days of total IV quinidine and oral quinine therapy as determined by the geographic origin of the infecting parasite (7 days if malaria was acquired in Southeast Asia or 3 days if acquired elsewhere).186

IV quinidine gluconate must be used initially; after ≥24 hours and after parasitemia is reduced to <1% and oral therapy is tolerated, oral quinine may be substituted.186

Use quinidine/quinine regimen in conjunction with a 7-day regimen of doxycycline, tetracycline, or clindamycin (administered IV or orally as tolerated).186

Presumptive Self-treatment of Malaria
Oral

650 mg every 8 hours given for 7 or 3 days (7 days if malaria was acquired in Southeast Asia or 3 days if acquired elsewhere) in conjunction with a 7-day regimen of oral doxycycline.165

Not included in current CDC recommendations for presumptive self-treatment of malaria in travelers.164

Babesiosis
Oral

IDSA and other clinicians recommend 650 mg every 6–8 hours in conjunction with clindamycin (300–600 mg IV every 6 hours or 600 mg orally every 8 hours) given for 7–10 days.165 178

For mild to moderate babesiosis, clinical improvement should be evident within 48 hours after initiation of treatment and symptoms should resolve completely within 3 months.178 Low-grade parasitemia may persist in some patients for months after completion of treatment.178 Regardless of presence or absence of symptoms, IDSA suggests that retreatment be considered if babesial parasites or amplifiable babesial DNA is detected in blood ≥3 months after initial treatment.178

Prescribing Limits

Pediatric Patients

Treatment of Uncomplicated or Severe Malaria
Oral

Do not exceed usual adult dosage.171

Babesiosis
Oral

Maximum 650 mg per dose.178

Special Populations

Hepatic Impairment

Treatment of Uncomplicated Malaria

Reduced dosage not necessary in adults with mild to moderate hepatic impairment (Child-Pugh class A or B).180 Monitor such patients closely for adverse effects.180

Safety and pharmacokinetics in patients with severe hepatic impairment (Child-Pugh class C) not determined to date.180

Renal Impairment

Treatment of Uncomplicated Malaria

For adults with severe chronic renal failure, computer models indicate dosage should be modified to include a 648-mg loading dose followed 12 hours later by maintenance doses of 324 mg given every 12 hours.180

Safety and pharmacokinetics in patients with mild or moderate renal impairment not determined to date.180

Geriatric Adults

Treatment of Uncomplicated Malaria

Dosage adjustment not necessary.180

Cautions for Qualaquin

Contraindications

  • Hypersensitivity to quinine.180

  • History of potential hypersensitivity reactions associated with previous quinine use, including (but not limited to) thrombocytopenia, TTP, idiopathic thrombocytopenic purpura (ITP), HUS, or blackwater fever (acute intravascular hemolysis, hemoglobinuria, and hemoglobinemia).180 (See Hypersensitivity Reactions under Cautions.)

  • Hypersensitivity to mefloquine or quinidine.180 (See Hypersensitivity Reactions under Cautions.)

  • Prolonged QT interval.180 (See QT Prolongation and Other Cardiovascular Effects under Cautions.)

  • Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.180 (See G-6-PD Deficiency under Cautions.)

  • Myasthenia gravis.180 (See Myasthenia Gravis under Cautions.)

  • Optic neuritis.180

Warnings/Precautions

Warnings

Use for Treatment or Prevention of Nocturnal Leg Cramps

Quinine has a narrow margin of safety and may cause unpredictable serious and life-threatening hypersensitivity reactions, QT interval prolongation, serious cardiac arrhythmias (including torsades de pointes), serious hematologic reactions (including thrombocytopenia and HUS/TTP), and other serious adverse events (e.g., blindness, deafness) requiring medical intervention and hospitalization.180 184 185 187 193 201 Fatalities reported.180 185 201

Quinine is not approved by FDA for treatment or prevention of nocturnal leg cramps, and should not be used in the management of this or related conditions (e.g., restless legs syndrome).180 182 185 187 201 The known risks associated with use of quinine, in the absence of evidence of safety and efficacy of the drug for treatment or prevention of nocturnal leg cramps, outweigh any potential benefits for this benign, self-limiting condition.180 184 185 187

FDA has determined that quinine preparations (including preparations containing any quinine salt alone or in fixed combination with vitamin E) are not generally recognized as safe and effective for treatment or prevention of nocturnal leg muscle cramps.185 Promotion of quinine for self-medication of nocturnal leg cramps has been prohibited in the US since February 1995 because of safety concerns.154 155 184 185

Because of serious safety concerns, FDA initiated several regulatory actions in December 2006 to remove unapproved quinine preparations from the US market.182 185 187 Despite these efforts, quinine still is being prescribed for uses other than malaria, and FDA continues to receive reports of serious adverse effects associated with the drug.187

From April 2005 to October 2008, the FDA Adverse Event Reporting System (AERS) received 38 reports of serious adverse events associated with quinine (e.g., hematologic events, cardiovascular events, GI symptoms, hearing loss, rash, electrolyte imbalance, drug interactions).187 201 The majority of these reports (66%) involved patients who used quinine for unlabeled indications (prevention or treatment of leg cramps or restless leg syndrome),187 201 and most (63%) involved serious or potentially fatal hematologic events.201 (See Hematologic Effects under Cautions.)

Because of continued reports of serious adverse effects in patients using quinine for unlabeled indications, the FDA required and approved a REMS for quinine sulfate in 2010.201 202 The goals of the quinine REMS are to inform patients and health-care providers about the serious and life-threatening hematologic adverse events (thrombocytopenia and HUS/TTP) associated with use of quinine in the treatment or prevention of nocturnal leg cramps.202 The REMS requires that a quinine medication guide be provided to the patient each time the drug is dispensed and outlines a communication plan requiring initial and subsequent communications from the manufacturer to targeted groups of prescribers.202

Hematologic Effects

Serious, life-threatening, and sometimes fatal hematologic reactions, including thrombocytopenia144 180 188 201 and HUS/TTP,180 201 have been reported in patients receiving quinine, especially those using the drug for unlabeled indications (prevention or treatment of leg cramps or restless leg syndrome).187 201 Subsequent development of chronic renal impairment has occurred in patients with quinine-associated TTP.180 201

In 24 reported cases of serious hematologic reactions, median time to onset was approximately 2 weeks after initiation of quinine.201 Most recovered when the drug was discontinued and other therapeutic interventions initiated, but there were 2 fatalities (one related to TTP and the other related to hemolysis).201

If thrombocytopenia occurs, discontinue quinine since continued therapy puts patient at risk for fatal hemorrhage.180 Thrombocytopenia usually resolves within 1 week after quinine is discontinued.180 Quinine-induced thrombocytopenia is immune-mediated and re-exposure to quinine from any source may result in a more rapid and more severe course of thrombocytopenia compared to original episode.180

QT Prolongation and Other Cardiovascular Effects

QT interval prolongation has been reported in most studies evaluating oral or parenteral quinine and has occurred independent of the patient’s age, clinical status, or disease severity.180 Maximal increases in QT interval correlate with peak plasma quinine concentrations.180

Potentially fatal cardiac arrhythmias, including torsades de pointes and ventricular fibrillation, reported.180 At least 1 case of fatal ventricular arrhythmia reported in a geriatric patient with preexisting prolonged QT interval who received IV quinine sulfate for treatment of P. falciparum malaria.180

Do not use in patients with known prolonged QT interval.180 Avoid use in patients with clinical conditions known to prolong the QT interval (e.g., uncorrected hypokalemia, bradycardia, certain cardiac conditions) and in those receiving other drugs known to cause QT prolongation.180 (See Drugs that Prolong the QT Interval under Interactions.)

Use caution in patients with atrial fibrillation or atrial flutter.180 A paradoxical increase in ventricular response rate may occur with quinine, similar to that observed with quinidine.180 Monitor closely if digoxin is used to prevent a rapid ventricular response.180 (See Digoxin under Interactions.)

Avoid concomitant use with other drugs known to cause QT interval prolongation, including class IA antiarrhythmic agents (e.g., quinidine, procainamide, disopyramide) and class III antiarrhythmic agents (e.g., amiodarone, sotalol, dofetilide).180 (See Drugs That Prolong the QT Interval under Interactions.)

Avoid use with drugs that are CYP3A4 substrates and are known to cause QT prolongation (e.g., cisapride [available in the US only under a limited-use protocol], pimozide, halofantrine [not commercially available in the US], quinidine).180 (See Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes under Interactions.)

G-6-PD Deficiency

Potential for hemolysis and hemolytic anemia if used in patients with G-6-PD deficiency.180 Discontinue immediately if evidence of hemolysis occurs.180

Do not use in patients with G-6-PD deficiency.180

Myasthenia Gravis

Has neuromuscular blocking activity and may exacerbate muscle weakness if used in patients with myasthenia gravis.180

Do not use in patients with myasthenia gravis.180

Sensitivity Reactions

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylactic shock, anaphylactoid reactions, urticaria, serious rashes (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), angioedema, facial edema, bronchospasm, and pruritus, reported.180 185 191

Other serious adverse reactions also reported and may be due to hypersensitivity, including thrombocytopenia, HUS/TTP, ITP, blackwater fever, disseminated intravascular coagulation, leukopenia, neutropenia, granulomatous hepatitis, and acute interstitial nephritis.180 185 191 194 195 (See Hematologic Effects under Cautions.)

Cross-sensitivity to quinine has been documented in individuals hypersensitive to mefloquine or quinidine.180

Discontinue quinine if there are signs or symptoms of hypersensitivity (rash, hives, severe itching, severe flushing, trouble breathing).180

Photosensitivity Reactions

Photosensitivity reported.180 197

General Precautions

Cinchonism

A cluster of symptoms referred to as “cinchonism” occurs in practically all patients receiving quinine.180 Most manifestations of cinchonism are reversible and resolve following discontinuance of quinine.180

Manifestations of mild cinchonism include headache, vasodilation and sweating, nausea, tinnitus, hearing impairment, vertigo or dizziness, blurred vision, and disturbance in color perception.180 More severe cinchonism manifests as vomiting, diarrhea, abdominal pain, deafness, blindness, and disturbances in cardiac rhythm or conduction.180

Hypoglycemia

Quinine stimulates release of insulin from the pancreas,180 and quinine-induced hypoglycemia has been reported.180 196

Clinically important hypoglycemia may occur, especially in pregnant women.180

Specific Populations

Pregnancy

Category C.180

Crosses the placenta.180 Although quinine concentrations may be measurable in the fetus and cord blood of women who received the drug near the time of delivery (see Distribution under Pharmacokinetics), such concentrations may not be therapeutic for the fetus.180 If congenital malaria is suspected, evaluate the infant after delivery and treat with antimalarial agents if appropriate.180

Deafness and optic nerve hypoplasia have been reported rarely in children exposed in utero when the mother received high-dose quinine therapy during pregnancy.180

In animal studies evaluating sub-Q or IM quinine, teratogenic effects were demonstrated in some animal species, but not in others.180 In a study in women with P. falciparum malaria who received a 7-day regimen of oral quinine during various stages of pregnancy, there was no difference in the rate of stillbirths at >28 weeks of gestation or overall rate of congenital malformations compared with a control group without malaria or treatment with antimalarial agents during pregnancy.180 In addition, the rate of spontaneous abortion was higher in the women without malaria or treatment with antimalarial agents during pregnancy than in the women treated with quinine during pregnancy.180 In an epidemiologic survey, there was no increased risk of structural birth defects in 104 mother-child pairs exposed to quinine during the initial 4 months of gestation.180 Although published data of >1000 pregnancies exposed to quinine (majority of exposures occurred after first trimester) have not shown an increase in teratogenic effects over that of background rates in the general population, there are few well-controlled studies to date evaluating the drug in pregnant women.180

Hypoglycemia, due to increased pancreatic secretion of insulin, has been associated with quinine use, especially in pregnant women.180

There is no evidence to date that quinine causes uterine contractions at dosages recommended for the treatment of malaria.180 However, doses several fold higher than those used to treat malaria may stimulate the pregnant uterus.180

Malaria infection in pregnant women is associated with high risks of both maternal and perinatal morbidity and mortality.171 180 Pregnant women with P. falciparum malaria have an increased incidence of fetal loss (e.g., spontaneous abortion, stillbirth), preterm labor and delivery, intrauterine growth retardation, low birth weight, and maternal death.180 Therefore, prompt treatment of malaria during pregnancy is important.171 180

CDC recommends the use of quinine for the treatment of uncomplicated chloroquine-resistant P. falciparum or P. vivax malaria in pregnant women.171 186 (See Treatment of Uncomplicated Malaria under Uses.) CDC also states that pregnant women diagnosed with severe malaria should be treated aggressively.186 (See Treatment of Severe Malaria under Uses.)

The manufacturer states that quinine should be used during pregnancy only if potential benefits justify potential risks to the fetus and recommends that the risks and benefits of alternative treatments be considered.180

Lactation

Distributed into milk.180

Only limited information available regarding safety of quinine in breast-fed infants.180 Although quinine generally considered compatible with breast-feeding, assess the risks and benefits to the infant and mother and use with caution in nursing women.180

Plasma quinine concentrations may not be therapeutic in infants of nursing mothers receiving quinine.180 If malaria is suspected in the infant, provide appropriate evaluation and treatment.180

Pediatric Use

Manufacturer states safety and efficacy not established in children <16 years of age.180

Quinine is included in CDC recommendations for treatment of uncomplicated malaria in pediatric patients.171 186 (See Treatment of Uncomplicated Malaria under Uses.) The drug also is used for follow-up after an initial parenteral antimalarial regimen in children with severe malaria.199 200 (See Treatment of Severe Malaria under Uses.)

Geriatric Use

Clinical studies did not include sufficient numbers of individuals ≥65 years of age to determine whether they respond differently than younger adults.180 Other reported clinical experience has not identified differences in responses between geriatric adults and younger patients.180

Closely monitor geriatric patients for adverse effects.180

Hepatic Impairment

If used in adults with mild to moderate hepatic impairment (Child-Pugh class A or B), monitor closely for adverse effects associated with quinine.180 The effects of severe hepatic impairment (Child-Pugh class C) on safety and pharmacokinetics not determined to date.180

Renal Impairment

Reduced dosage recommended when used for treatment of acute uncomplicated malaria in adults with severe chronic renal failure.180 (See Renal Impairment under Dosage and Administration.) The effects of mild or moderate renal impairment on safety and pharmacokinetics not determined to date.180

Common Adverse Effects

Mild cinchonism, manifested as headache, vasodilation and sweating, nausea, tinnitus, hearing impairment, vertigo or dizziness, blurred vision, and disturbance in color perception, occurs in most patients.180 More severe cinchonism, manifested as vomiting, diarrhea, abdominal pain, deafness, blindness, and disturbances in cardiac rhythm or conduction, also reported.180

Interactions for Qualaquin

Metabolized principally by CYP3A4; may also be metabolized by other CYP enzymes, including 1A2, 2C8, 2C9, 2C19, 2D6, and 2E1.180

Drugs That Prolong the QT Interval

Because quinine prolongs the QT interval, an additive effect on the QT interval might occur if the drug is administered with other drugs that prolong the QT interval.180 Concomitant use of quinine in patients receiving other drugs known to cause QT prolongation, including class IA antiarrhythmic agents (e.g., quinidine, procainamide, disopyramide) and class III antiarrhythmic agents (e.g., amiodarone, sotalol, dofetilide) not recommended.180

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

In vivo and in vitro drug interaction studies suggest quinine may inhibit metabolism of drugs that are substrates of CYP3A4 and 2D6.180

Avoid use with drugs that are CYP3A4 substrates and are known to cause QT prolongation (e.g., cisapride [available in the US only under a limited-use protocol], pimozide, halofantrine [not commercially available in the US], quinidine).180

Quinine has been shown to decrease metabolism of desipramine in some patients (see Desipramine under Interactions) and may decrease metabolism of some other drugs that are CYP2D6 substrates (e.g., debrisoquine [not commercially available in the US], dextromethorphan, flecainide, methoxyphenamine [not commercially available in the US], metoprolol, paroxetine).180 If used concomitantly with a CYP2D6 substrate, monitor closely for adverse effects associated with the CYP2D6 substrate.180

Drugs Affecting or Affected by P-glycoprotein Transport

Quinine is a substrate for and an inhibitor of P-glycoprotein,180 and has the potential to affect transport of drugs that are P-glycoprotein substrates.180

Specific Drugs and Laboratory Tests

Drug

Interaction

Comments

Antacids (aluminum-and/or magnesium-containing)

Delayed or decreased absorption of quinine180

Avoid concomitant use180

Antiarrhythmic agents (amiodarone, disopyramide, dofetilide, quinidine, procainamide, sotalol)

Possible additive effect on QT interval180

Concomitant use not recommended180

Anticoagulants (heparin)

Possible interference with the anticoagulant effects of heparin180

Clinical importance uncleara

Anticoagulants (oral) (e.g., warfarin)

Quinine may potentiate the anticoagulant effects of warfarin and other oral anticoagulants by depressing hepatic synthesis of vitamin K-dependent coagulation factors180

Closely monitor PT, PTT, or INR as indicated180

Anticonvulsants

Carbamazepine or phenobarbital: Increased peak plasma concentrations and AUC of the anticonvulsant;180 possible decreased plasma quinine concentrations180

Phenytoin: No effect on pharmacokinetics of the anticonvulsant;180 possible decreased plasma quinine concentrations180

Carbamazepine or phenobarbital: If concomitant use with quinine cannot be avoided, frequently monitor serum concentrations of the anticonvulsant and monitor closely for anticonvulsant adverse effects180

Cholestyramine

No effect on quinine pharmacokinetics180

Cigarette smoking

Decreased quinine AUC and peak plasma concentration when used in malaria patients who were heavy smokers;180 greater effect on quinine pharmacokinetics reported when the drug was given to healthy adults who were heavy smokers180

Smoking does not appear to influence the therapeutic outcome in malaria patients treated with quinine180

Manufacturer of quinine suggests that reduced clearance of quinine in patients with acute malaria (see Elimination under Pharmacokinetics) may diminish the metabolic induction effect of smoking on quinine pharmacokinetics180

Manufacturer states that increased quinine dosage not necessary when treating acute malaria in heavy cigarette smokers180

Desipramine

Decreased metabolism of desipramine in patients who are extensive CYP2D6 metabolizers; no effect in patients who are poor CYP2D6 metabolizers180

Monitor closely for adverse effects if quinine used concomitantly with desipramine180

Digoxin

Increased digoxin AUC and decreased biliary clearance of digoxin180

Closely monitor digoxin plasma concentrations; adjust digoxin dosage as necessary180

Grapefruit juice

No evidence of effect on quinine pharmacokinetics 180

Quinine may be taken with grapefruit juice180

Histamine H2-receptor antagonists (cimetidine, ranitidine)

Cimetidine: Decreased quinine clearance and prolonged quinine half-life125 126

Ranitidine: No effect on quinine pharmacokinetics180

Cimetidine: Monitor closely for adverse effects associated with quinine;125 126 180 if a pharmacokinetic interaction is suspected, assess patient’s clinical status and adjust quinine dosage as needed or substitute a different histamine H2-receptor antagonist (e.g., ranitidine)125 126

Ranitidine: May be preferred when a histamine H2-receptor antagonist is indicated in a patient receiving quinine180

HMG-CoA reductase inhibitors

Atorvastatin: Possible increased plasma atorvastatin concentrations and increased risk of myopathy or rhabdomyolysis; rhabdomyolysis with acute renal failure secondary to myoglobinuria reported rarely180

Carefully weigh benefits and risks if considering concomitant use of quinine and atorvastatin or other HMG-CoA reductase inhibitors that are CYP3A4 substrates (e.g., simvastatin, lovastatin)180

If used concomitantly, consider lower starting and maintenance dosages of the HMG-CoA reductase inhibitor and monitor closely for signs or symptoms of muscle pain, tenderness, or weakness, especially during initial therapy180

Discontinue the HMG-CoA reductase inhibitor if CPK concentrations are markedly elevated or if myopathy (defined as muscle aches or weakness in conjunction with CPK concentrations >10 times the ULN) is diagnosed or suspected180

Isoniazid

No clinically important effect on pharmacokinetics of quinine180

Quinine dosage adjustment not required180

Ketoconazole

Increased quinine AUC and decreased quinine clearance180

Quinine dosage adjustment not required; monitor closely for adverse effects associated with quinine180

Macrolides

Possible increased plasma quinine concentrations;180 although causal relationship not established, fatal torsades de pointes reported in a geriatric patient who was receiving concomitant therapy with quinine, erythromycin, and dopamine180

Avoid concomitant use180

Mefloquine

Potential additive cardiac effects;146 180 ECG abnormalities, including QT interval prolongation, may occur; increased risk for torsades de pointes or other serious ventricular arrhythmias180

Possible increased risk of seizures180

Do not use concomitantly146 169 180

Use sequentially with caution;146 147 because mefloquine has a long serum half-life (15–33 days),147 use caution if initiating quinine for treatment of malaria in patients who were receiving mefloquine for prophylaxis146 147

Midazolam

Does not affect metabolism of midazolam180

Neuromuscular blocking agents

Pancuronium: Potentiated neuromuscular blockade (e.g., respiratory depression, apnea) reported180

Succinylcholine or tubocurarine (not commercially available in the US): Possibility of potentiated neuromuscular blockade 180

Avoid use of neuromuscular blocking agents in patients receiving quinine180

Nevirapine

Concomitant use decreases AUC, peak plasma concentration, and elimination half-life of quinine and increases AUC and peak plasma concentration of 3-hydroxyquinine, the major metabolite of quinine190

Adjustment of quinine dosage may be necessary in patients receiving nevirapine190

Oral contraceptives

Quinine pharmacokinetics not affected by concomitant oral contraceptive therapy (progestin alone or estrogen in combination with progestin)180

Rifampin

Decreased quinine AUC and plasma concentrations;180 quinine treatment failure may occur180

Avoid concomitant use180

Ritonavir

Concomitant use increases quinine peak plasma concentration, AUC, and half-life;180 no clinically important effects on ritonavir pharmacokinetics180

Avoid concomitant use;180 if used concomitantly, quinine dosage may need to be reduced203

Tests, urinary corticosteroids or catecholamines

Quinine causes falsely elevated results when a modification of the Reddy-Jenkins-Thorn procedure is used for urinary 17-hydroxycorticosteroidsa or when the Zimmermann method is used for urinary 17-ketogenic steroids;180 no effect on modified Porter-Silber methoda

Quinine interferes with the Sobel and Henry modification of the trihydroxyindole method for determining urinary catecholamines, resulting in falsely increased concentrationsa

Tetracyclines

Increased quinine plasma concentrations180

Closely monitor for adverse effects associated with quinine180

Theophylline or aminophylline

Possible decreased plasma theophylline concentrations and reduced effects of theophylline or aminophylline180

Possible increased plasma quinine concentrations180

Monitor plasma theophylline concentrations frequently180

Quinine dosage adjustment not needed; closely monitor for quinine adverse effects180

Urinary alkalizers

Agents that increase urinary pH (e.g., acetazolamide, sodium bicarbonate) may increase plasma quinine concentrations 180

Qualaquin Pharmacokinetics

Absorption

Bioavailability

Oral bioavailability is 76–88% in healthy adults.180 Quinine exposure is higher in patients with malaria than in healthy adults,180 possibly because malaria may cause impaired hepatic function, which results in decreased quinine total body clearance and volume of distribution.106 107

In adults with uncomplicated P. falciparum malaria, mean AUC and peak plasma concentrations are higher and time to peak concentration is longer than that reported in healthy adults.180 Following a single oral dose, mean time to peak serum concentrations is 5.9 hours in adults with uncomplicated P. falciparum malaria compared with 2.8 hours in healthy adults.180

Food

When a single 324-mg dose of oral quinine sulfate capsules was administered with a high-fat meal in healthy adults, the time to peak concentrations was prolonged to approximately 4 hours; however, mean peak plasma concentration and AUC from 0–24 hours were similar to those achieved following oral administration of the drug under fasted conditions.180

Special Populations

Pharmacokinetics in children 1.5–12 years of age with uncomplicated P. falciparum malaria appear to be similar to that observed in adults with uncomplicated malaria.180 Following a single dose of 10 mg/kg of oral quinine sulfate in healthy children or children 1.5–12 years of age with uncomplicated P. falciparum malaria, mean time to peak quinine concentration was longer (4 versus 2 hours) and mean peak plasma concentration was higher (7.5 versus 3.4 mcg/mL) in children with uncomplicated P. falciparum malaria than in healthy children.180

Following a single 600-mg dose of oral quinine sulfate, the mean AUC in healthy geriatric adults 65–78 years of age is approximately 38% higher than in younger adults 20–35 years of age;180 mean time to peak quinine concentrations and mean peak plasma concentrations are similar in both age groups.180

Following a single 600-mg dose of oral quinine sulfate in adults with severe chronic renal failure not receiving any form of dialysis (mean serum creatinine 9.6 mg/dL), median AUC and mean peak plasma concentration increased by 195 and 79%, respectively, compared with adults with normal renal function.180 Effect of mild or moderate renal impairment on pharmacokinetics of quinine sulfate not determined to date.180

Following a single 600-mg oral dose of quinine sulfate in otherwise healthy adults with moderate hepatic impairment (Child-Pugh class B), mean AUC is increased 55% compared with healthy adults with normal hepatic function; mean peak plasma concentrations similar in both groups.180 Quinine absorption is prolonged in adults with hepatitis.180 Pharmacokinetic data not available to date for patients with severe hepatic impairment (Child-Pugh class C).180

Distribution

Extent

Volume of distribution is lower in patients with malaria than in healthy individuals or patients convalescing from malaria.106 Volume of distribution decreases with increasing severity of malarial infection.180

Intra-erythrocytic quinine concentrations are approximately 30–50% of plasma concentrations.180 Small amounts distributed into bile and saliva.a

Penetrates relatively poorly into CSF in patients with cerebral malaria;180 CSF quinine concentrations reported to be 2–7% of concurrent plasma concentrations.106 107 180

Readily crosses the placenta.180 In a small number of women who delivered live infants 1–6 days after starting quinine therapy, placental cord plasma quinine concentrations were 1–4.6 mg/L (mean: 2.4 mg/L) and mean ratio of cord plasma to maternal plasma quinine concentrations was 0.32.180 Such placental cord concentrations may not result in therapeutic fetal plasma quinine concentrations.180

Distributed into milk.180

Plasma Protein Binding

Approximately 69–92% in healthy adults.106 180

During active malarial infection, protein binding increased to 78–95%, which correlates with increases in α-1-acid glycoprotein that occur during malarial infection.180 In one study, quinine was approximately 93% bound to plasma proteins in patients with cerebral malaria and approximately 90% bound in patients with uncomplicated malaria or in patients convalescing from the disease.106

Elimination

Metabolism

Metabolized almost exclusively via hepatic oxidative (CYP) pathways into 4 primary metabolites (3-hydroxyquinine, 2’-quinone, O-desmethylquinine, and 10,11-dihydroxydihydroquinine) and 6 secondary metabolites resulting from further biotransformation of the primary metabolites.180

The major metabolite, 3-hydroxyquinine, is less active than the parent drug.180

In vitro studies indicate quinine is metabolized principally by CYP3A4 and may also be metabolized by other CYP enzymes, including 1A2, 2C8, 2C9, 2C19, 2D6, and 2E1.180

Elimination Route

Approximately 20% of a dose excreted unchanged in urine.180 Reabsorption of quinine is increased when urine is alkaline; rate of renal excretion of the drug is doubled when urine is acidic compared with when urine is alkaline.180

Negligible to minimal amounts removed by hemodialysis or hemofiltration.180

Half-life

Adults: 8–21 hours in those with malaria and 7–12 hours in those who are healthy or convalescing from the disease.106 107

Children 1–12 years of age: 11–12 hours in those with malaria and 6 hours in those convalescing from the disease.106

Geriatric adults: Mean elimination half-life is increased to 18.4 hours.180 Although renal clearance of quinine is similar in geriatric and younger adults, geriatric adults excrete a larger proportion of the dose in urine as unchanged drug compared with younger adults.180

Special Populations

Plasma concentrations are higher and plasma half-life may be prolonged in patients with malaria.106 107

Adults with hepatitis: Elimination half-life and apparent volume of distribution are increased, but weight-adjusted clearance not altered.180

Adults with severe chronic renal failure: Mean plasma half-life prolonged to 26 hours.180 Effects of mild and moderate renal impairment on pharmacokinetics and safety not determined to date.180

Stability

Storage

Oral

Capsules

20–25°C in tight container.180 Drug darkens on exposure to light.180

Actions and Spectrum

  • An alkaloid obtained from the bark of the cinchona tree; the levorotatory isomer of quinidine.185

  • Has several effects on skeletal muscle.a Increases the refractory period of muscle by a direct action on muscle fiber so that the response to tetanic stimulation is diminished;a has a curare-like effect and decreases the excitability of the motor endplate so that responses to repetitive nerve stimulation or acetylcholine are reduced;a and affects the distribution of calcium within muscle fiber.a

  • Has cardiovascular effects similar to those of quinidine.180

  • Exact mechanism of antimalarial activity not determined.180 Inhibits nucleic acid synthesis, protein synthesis, and glycolysis in P. falciparum and can bind with hemazoin in parasitized erythrocytes.180

  • A blood schizonticidal agent active against the asexual erythrocytic forms of P. falciparum,180 P. malariae,a P. ovale,a and P. vivax.189 Not gametocidal against P. falciparum.180 Inactive against sporozoites or pre-erythrocytic or exoerythrocytic forms of plasmodia.180

  • P. falciparum malaria clinically resistant to quinine has been reported in some areas of South America, Southeast Asia, and Bangladesh.180 Strains of P. falciparum with decreased susceptibility to quinine also can be selected in vivo.180

  • Although cross-resistance has been demonstrated rarely between quinine and 4-aminoquinoline derivatives, quinine may be active against some strains of P. falciparum resistant to chloroquine and/or sulfadoxine and pyrimethamine.a

Advice to Patients

  • Importance of taking the drug exactly as prescribed.180 Advise patients not to double the next dose if a dose is missed; if >4 hours has elapsed since the missed dose, patient should not take the missed dose and should take the next dose as previously scheduled.180

  • Importance of taking with food to minimize possible GI irritation.180

  • Importance of immediately contacting a clinician if malarial symptoms worsen or do not improve within 2 days of initiating quinine therapy or if fever recurs following completion of antimalarial therapy.180

  • Importance of immediately contacting a clinician if symptoms of hypersensitivity (e.g., rash, hives, severe itching, severe flushing, facial swelling, difficulty breathing), bleeding (e.g., easy bruising, severe nose bleed, bleeding gums, blood in urine or stool, unusual purple, brown, or red skin spots indicating bleeding under the skin), or heart problems (e.g., chest pain, rapid heartbeat, irregular heart rhythm, weakness, sweating, nervousness) occur.180

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.180

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.180

  • Importance of advising patients of other important precautionary information.180 (See Cautions.)

Preparations

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

Because of serious safety concerns, including fatalities, associated with use of various quinine preparations, FDA ordered firms involved in the marketing of unapproved quinine preparations to discontinue marketing these preparations as of December 11, 2006.182 FDA also ordered that the manufacture of unapproved quinine preparations be discontinued as of February 13, 2007, and that interstate shipment of such preparations be discontinued on June 13, 2007.182 185 FDA recommends that individuals using such quinine preparations contact their healthcare provider with any questions or concerns.182

The only quinine sulfate preparation approved by FDA is Qualaquin (324-mg capsules) manufactured by Mutual Pharmaceutical Company, Inc. and distributed by AR Scientific, Inc. ().180 182 185 180 182 185

Quinine Sulfate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

324 mg (of quinine sulfate)

Qualaquin

AR Scientific

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Qualaquin 324MG Capsules (AR SCIENTIFIC): 30/$194.93 or 90/$543.96

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

21. Katz B, Weetch M, Chopra S. Quinine-induced granulomatous hepatitis. Br Med J. 1983; 286:264-5. [PubMed 6402064]

100. Morgan MD, Rainford DJ, Pusey CD et al. The treatment of quinine poisoning with charcoal hemoperfusion. Postgrad Med J. 1983; 59:365-7. [PubMed 6634542]

101. White NJ, Warrell DA, Chanthavanich P et al. Severe hypoglycemia and hyperinsulinemia in falciparum malaria. N Engl J Med. 1983; 309:61-6. [IDIS 172605] [PubMed 6343877]

102. Wittner M, Rowin KS, Tanowitz HB et al. Successful chemotherapy of transfusion babesiosis. Ann Intern Med. 1982; 96:601-4. [IDIS 150109] [PubMed 7200341]

103. Anon. Clindamycin and quinine treatment for Babesia microti infection. MMWR Morb Mortal Wkly Rep. 1983; 32:65-6,72. [PubMed 6405180]

106. White NJ. Clinical pharmacokinetics of antimalarial drugs. Clin Pharmacokinet. 1985; 10:187-215. [IDIS 202191] [PubMed 3893840]

107. Report of a WHO Scientific Group. Advances in malaria chemotherapy. Technical Report Series No 711. Geneva: World Health Organization; 1984:21-33,60-85,97-8.

112. Phillips RE, Warrell DA, White NJ et al. Intravenous quinidine for the treatment of severe falciparum malaria. N Engl J Med. 1985; 312:1273-8. [IDIS 199397] [PubMed 3887162]

113. Boland ME, Roper SMB. Complications of quinine poisoning. Lancet. 1985 date>; 1:384-5.

114. Henry J. Quinine for night cramps. BMJ. 1985; 291:3. [IDIS 202405] [PubMed 3926053]

115. Gibbs JL, Trafford A. Quinine amblyopia treated by combined haemodialysis and activated resin haemoperfusion. Lancet. 1985; 1:752-3. [IDIS 198472] [PubMed 2858017]

116. Looareesuwan S, White NJ, Karbwang J et al. Quinine and severe falciparum malaria in late pregnancy. Lancet. 1985; 2:4-8. [IDIS 202039] [PubMed 2861481]

117. Chow AW. Pharmacokinetics and safety of antimicrobial agents during pregnancy. Rev Infect Dis. 1985; 7:287-313. [IDIS 200121] [PubMed 3895351]

119. Food and Drug Administration. Establishment of a monograph for OTC internal analgesic, antipyretic and antirheumatic products. Docket No. 77N–0094 Fed Regist. 1977; 42:35345-621.

120. Food and Drug Administration. Quinine for the treatment of nocturnal leg muscle cramps for over-the-counter human use; establishment of a monograph; and reopening of administrative record. Docket No. 77N–0094 Fed Regist. 1982; 47:43562-4.

121. Food and Drug Administration. Internal analgesic, antipyretic, and antirheumatic drug products for over-the-counter human use; tentative final monograph for drug products for the treatment and/or prevention of nocturnal leg muscle cramps. Docket No. 77N–0094 Fed Regist. 1985; 50:46588-94. (IDIS 206847)

122. Anon. Quinine for “night cramps” Med Lett Drugs Ther. 1986; 28:110.

123. Dyson EH, Proudfoot AT, Prescott LF et al. Death and blindness to overdose of quinine. BMJ. 1985; 291:31-3. [IDIS 202415] [PubMed 3926054]

124. Warburton A, Royston JP, O’Neil CJ et al. A quinine a day keeps the leg cramps away? Br J Clin Pharmacol. 1987; 23:459-65.

125. Wanwimolruk S, Sunbhanich M, Pongmarutai M et al. Effects of cimetidine and ranitidine on the pharmacokinetics of quinine. Br J Clin Pharmacol. 1986; 22:346-50. [IDIS 221465] [PubMed 3768247]

126. Mangini RJ, ed. Drug interaction facts. St. Louis: JB Lipincott Co; 1987(Apr):479a.

128. Kriegman AG (Ciba-Geigy, Summit, NJ): Personal communication; 1987 Oct 20.

129. Centers for Disease Control. Intravenous quinidine gluconate in the treatment of severe Plasmodium falciparum infections. MMWR Morb Mortal Wkly Rep. 1985; 34:371-2. [IDIS 201687] [PubMed 3923321]

130. Agosti JM, Miller KD, Pappaioanou M et al. Plasmodium falciparum malaria and intravenous quinidine gluconate. Ann Intern Med. 1985; 103:307. [IDIS 202762] [PubMed 3893261]

131. Centers for Disease Control. Notice of claimed investigational exemption for a new drug (Quinidine Gluconate Injection USP). FD Form 1571. Atlanta, GA; 1985.

132. Rudnitsky G, Miller KD, Padua T et al. Continuous-infusion quinidine gluconate for treating children with severe Plasmodium falciparum malaria. J Infect Dis. 1987; 155:1040-3. [IDIS 228420] [PubMed 3549916]

133. Jaeger A, Saunder P, Kopferschmitt J et al. Clinical features and management of poisoning due to antimalarial drugs. Med Toxicol Adverse Drug Exp. 1987; 2:242-73. [IDIS 233506] [PubMed 3306266]

134. Ellenhorn MJ, Barceloux DG. Medical toxicology: diagnosis and treatment of human poisoning. New York: Elsevier; 1988:390-5.

135. Okitolonda W, Delacollette C, Malengreau M et al. High incidence of hypoglycaemia in African patients treated with intravenous quinine for severe malaria. BMJ. 1987; 295:716-8. [IDIS 234642] [PubMed 3117315]

139. Krogstad DJ, Herwaldt BL. Antimalarial agents: specific treatment regimens. Antimicrob Agents Chemother. 1988; 32:957-61. [IDIS 244086] [PubMed 3056248]

140. Herwaldt BL, Krogstad DJ. Antimalarial agents: specific chemoprophylaxis regimens. Antimicrob Agents Chemother. 1988; 32:953-6. [IDIS 244085] [PubMed 3056247]

141. Krogstad DJ. Chemoprophylaxis and treatment of malaria. N Engl J Med. 1988; 319:1538-40. [IDIS 248326] [PubMed 3185677]

143. Punukollu RC, Kumar S, Mullen KD. Quinine hepatotoxicity: an underrecognized or rare phenomenon? Arch Intern Med. 1990; 150:1112-3.

144. Freiman JP. Fatal quinine-induced thrombocytopenia. Ann Intern Med. 1990; 112:308-9. [IDIS 263377] [PubMed 2297210]

146. Anon. Mefloquine for malaria. Med Lett Drugs Ther. 1990; 32:13-4.

147. Karbwang J. Clinical pharmacokinetics of mefloquine. Clin Pharmacokinet. 1990; 19:264-79. [PubMed 2208897]

148. Anon. Treatment of severe Plasmodium falciparum malaria with quinidine gluconate: discontinuation of parenteral quinine from CDC drug service. MMWR Morb Mortal Wkly Rep. 1991; 40:240. [PubMed 1848916]

149. . Treatment with quinidine gluconate of persons with severe Plasmodium falciparum infection: discontinuation of parenteral quinine from CDC Drug Service. MMWR Recomm Rep. 1991; 40:21-3. [PubMed 1850497]

150. Miller KD, Greenberg AE. Treatment of severe malaria in the United States with a continuous infusion of quinidine gluconate and exchange transfusion. N Engl J Med. 1989; 321:65-70. [IDIS 256804] [PubMed 2659994]

152. Wyler DJ. Malaria: overview and update. Clin Infect Dis. 1993; 16:449-58. [IDIS 312108] [PubMed 8513046]

154. Food and Drug Administration. Drug products for the treatment and/or prevention of nocturnal leg muscle cramps for over-the-counter human use—final rule (Docket No. 77N-0094). Fed Regist. 1994; 59(161):43234-52.

155. Wolfe SM. Letter to the US Food and Drug Administration regarding the over-the-counter use of quinine sulfate. Washington, DC: Public Citizen’s Health Research Group; 1994 Sept 8.

156. Macguire RB, Stroncek DF. Recurrent pancytopenia, coagulopathy, and renal failure associated with multiple quinine-dependent antibodies. Ann Intern Med. 1993; 119:215-7. [IDIS 318973] [PubMed 8323089]

157. Schmitt SK. Quinine-induced pancytopenia and coagulopathy. Ann Intern Med. 1994; 120:90-1. [PubMed 8250466]

158. Spearing RL, Hickton CM, Sizeland P et al. Quinine-induced disseminated intravascular coagulation. Lancet. 1990; 336:1535-7. [IDIS 275606] [PubMed 1979368]

159. Janssen Pharmaceutica. Hismanal (astemizole) tablets prescribing information. Titusville, NJ; 1998 Feb.

160. Janssen Pharmaceutica, Titusville, NJ: Personal communication.

161. Hoechst Marion Roussel, Kansas City, MO: Personal communication.

162. Klausner MA. Dear healthcare provider letter regarding new information concerning drug interaction of astemizole with quinine. Titusville, NJ; 1996 Mar 25.

163. Marion Merrell Dow. Seldane (terfenadine) 60-mg tablets prescribing information. In: Physicians’ desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:1536-8.

164. Centers for Disease Control and Prevention. Health information for international travel, 2010. Atlanta, GA: US Department of Health and Human Services; 2010. Updates available from CDC website ().

165. Anon. Drugs for parasitic infections. Treatment Guidelines from The Medical Letter. 2010;8:e1-20. From the Medical Letter website (). Aug 2008.

166. Lobel HO. Update on prevention of malaria for travelers. JAMA. 1997; 278:1767-71. [IDIS 395515] [PubMed 9388154]

168. Wolfe MS. Protection of travelers. Clin Infect Dis. 1997; 25:177-86. [IDIS 392200] [PubMed 9332506]

169. American Academy of Pediatrics. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.

170. White NJ. The treatment of malaria. N Engl J Med. 1996; 335:800-6. [IDIS 372602] [PubMed 8703186]

171. Centers for Disease Control and Prevention. CDC treatment guidelines: Treatment of malaria (guidelines for clinicians). 2009 Jun. From the CDC website: (). Accessed 2010 Nov 3.

173. Krogstad DJ. Plasmodium species (malaria). In: Mandell GL, Bennett JE, Dolin R eds. Mandell, Douglas and Bennett’s principles and practice of infectious diseases. 5th ed. New York: Churchill Livingstone; 2000:2817-31.

174. Glynne P, Salama A, Chaudhry A et al. Quinine-induced immune thrombocytopenic purpura followed by hemolytic uremic syndrome. Am J Kidney Dis. 1999; 33:133-7. [IDIS 421491] [PubMed 9915279]

175. Man-Son-Hing M, Wells G, Lau A. Quinine for nocturnal leg cramps: a meta-analysis including unpublished data. J Gen Intern Med. 1998; 13:600-6. [PubMed 9754515]

176. Diener HC, Dethlefsen U, Dethlefsen-Gruber S et al. Effectiveness of quinine in treating muscle cramps: a double-blind, placebo-controlled, parallel-group, multicentre trial. Int J Clin Pract. 2002; 56:243-6. [IDIS 482132] [PubMed 12074203]

177. Kanaan N, Sawaya R. Nocturnal leg cramps. Clinically mysterious and painful—but manageable. Geriatrics. 2001; 56:34,39-42. [PubMed 11417373]

178. Wormser GP, Dattwyler RJ, Shapiro ED et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006; 43:1089-134. [PubMed 17029130]

179. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD; 2002 Oct 15. From FDA web site (). Accessed 2007 Feb 7.

180. AR Scientific, Inc. Qualaquin (quinine sulfate) capsules prescribing information. Philadelphia, PA; 2011 Apr.

181. Krause PJ, Lepore T, Sikand VK et al. Atovaquone and azithromycin for the treatment of babesiosis. N Engl J Med. 2000; 343:1454-8. [IDIS 455399] [PubMed 11078770]

182. US Food and Drug Administration. FDA advances effort against marketed unapproved drugs: FDA orders unapproved quinine drugs from the market and cautions consumers about “off-label” use of quinine to treat leg cramps. FDA News. Document P06-195. 2006 Dec 11. From FDA website ().

184. El-Tawil S, Musa TA, El-Tawil T, et al. Quinine for muscle cramps (Protocol). The Cochrane Library. From their web site (). Accessed 2/20/2007.

185. US Food and Drug Administration. Drug products containing quinine; enforcement action dates. [Docket No.2006N-0476] Fed Regist. 2006; 71:75557-60.

186. Centers for Disease Control and Prevention. Guidelines for treatment of malaria in the United States (based on drugs currently available for use in the United States–updated May 18, 2009). From the CDC website. Accessed 2011 Mar 1.

187. US Food and Drug Administration. Quinine sulfate (marketed as qualoquin) off-label (not approved by FDA) use of quinine. FDA Drug Safety Newsletter. 2009; 2:11-13. From FDA website ().

188. Brinker AD, Beitz J. Spontaneous reports of thrombocytopenia in association with quinine: clinical attributes and timing related to regulatory action. Am J Hematol. 2002; 70:313-7. [PubMed 12210813]

189. Chotivanich K, Sattabongkot J, Choi YK et al. Antimalarial drug susceptibility of Plasmodium vivax in the Republic of Korea. Am J Trop Med Hyg. 2009; 80:902-4. [PubMed 19478246]

190. Soyinka JO, Onyeji CO, Omoruyi SI et al. Effects of concurrent administration of nevirapine on the disposition of quinine in healthy volunteers. J Pharm Pharmacol. 2009; 61:439-43. [PubMed 19298689]

191. Howard MA, Hibbard AB, Terrell DR et al. Quinine allergy causing acute severe systemic illness: report of 4 patients manifesting multiple hematologic, renal, and hepatic abnormalities. Proc (Bayl Univ Med Cent). 2003; 16:21-6. [PubMed 16278718]

192. Everts RJ, Hayhurst MD, Nona BP. Acute pulmonary edema caused by quinine. Pharmacotherapy. 2004; 24:1221-4. [PubMed 15460183]

193. Prasad RS, Kodali VR, Khuraijam GS et al. Acute confusion and blindness from quinine toxicity. Eur J Emerg Med. 2003; 10:353-6. [PubMed 14676522]

194. Baliga RS, Wingo CS. Quinine induced HUS-TTP: an unusual presentation. Am J Med Sci. 2003; 326:378-80. [PubMed 14671503]

195. Knower MT, Bowton DL, Owen J et al. Quinine-induced disseminated intravascular coagulation: case report and review of the literature. Intensive Care Med. 2003; 29:1007-11. [PubMed 12682720]

196. Limburg PJ, Katz H, Grant CS et al. Quinine-induced hypoglycemia. Ann Intern Med. 1993; 119:218-9. [PubMed 8323090]

197. Ljunggren B, Hindsén M, Isaksson M. Systemic quinine photosensitivity with photoepicutaneous cross-reactivity to quinidine. Contact Dermatitis. 1992; 26:1-4. [PubMed 1600732]

198. Fung MC, Holbrook JH. Placebo-controlled trial of quinine therapy for nocturnal leg cramps. West J Med. 1989; 151:42-4. [PubMed 2669346]

199. Praygod G, de Frey A, Eisenhut M. Artemisinin derivatives versus quinine in treating severe malaria in children: a systematic review. Malar J. 2008; 7:210. [PubMed 18928535]

200. Griffith KS, Lewis LS, Mali S et al. Treatment of malaria in the United States: a systematic review. JAMA. 2007; 297:2264-77. [PubMed 17519416]

201. US Food and Drug Administration. Drug Safety Communication: New risk management plan and patient medication guide for Qualaquin (quinine sulfate). 2010 Jul 8. From FDA website. Accessed 2010 Nov 3.

202. AR Holding Company, Inc. NDA 21-799: Qualaquin (quinine sulfate) capsules Risk Evaluation and Mitigation Strategy (REMS). From FDA website. Accessed 2010 Nov 3.

203. Abbott Laboratories. Norvir (ritonavir) soft gelatin capsules and oral solution prescribing information. North Chicago, IL; 2010 Apr.

a. AHFS Drug Information 2009. McEvoy, GK, ed. Quinine sulfate. Bethesda, MD: American Society of Health-System Pharmacists; 2009:882-8.

(web2)