Quinine

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# Black Box Warning

# Overview
Quinine is a cinchona alkaloid, antimalarial and  anti-Infective Agent, that is FDA approved for the treatment of of uncomplicated Plasmodium falciparum malaria. There is a Black Box Warning for this drug as shown here.  Common adverse reactions include cinchonism include headache, vasodilation and sweating, nausea, tinnitus, hearing impairment, vertigo or dizziness, blurred vision, and disturbance in color perception..

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)
- Quinine sulphate is an antimalarial drug indicated only for treatment of uncomplicated Plasmodium falciparum malaria. Quinine sulfate has been shown to be effective in geographical regions where resistance to chloroquine has been documented.
- Quinine sulphate oral capsules are not approved for:
- Treatment of severe or complicated P. falciparum malaria.
- Prevention of malaria.
- Treatment or prevention of nocturnal leg cramps

### Dosing Information
- Treatment of Uncomplicated P. falciparum malaria
- For treatment of uncomplicated P. falciparum malaria in adults: Orally, 648 mg (two capsules) every 8 hours for 7 days.
- Quinine sulphate should be taken with food to minimize gastric upset.
- In patients with acute uncomplicated malaria and severe chronic renal impairment, the following dosage regimen is recommended: one loading dose of 648 mg Quinine sulphate followed 12 hours later by maintenance doses of 324 mg every 12 hours.
- The effects of mild and moderate renal impairment on the safety and pharmacokinetics of quinine sulfate are not known.
- Adjustment of the recommended dose is not required in mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment, but patients should be monitored closely for adverse effects of quinine. Quinine should not be administered in patients with severe (Child-Pugh C) hepatic impairment.

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
There is limited information regarding off-label use and dosage for adults.

### NonGuideline-Supported Use
- Babesiosis
- Malaria, Uncomplicated, Plasmodium vivax

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Quinine sulphate in pediatric patients.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Quinine sulphate in pediatric patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Quinine sulphate in pediatric patients.

# Contraindications
Quinine sulphate is contraindicated in patients with the following:
- One case of a fatal ventricular arrhythmia was reported in an elderly patient with a prolonged QT interval at baseline, who received quinine sulfate intravenously for P. falciparum malaria.
- Hemolysis can occur in patients with G6PD deficiency receiving quinine.
- These include, but are not limited to, the following:
- Thrombocytopenia
- Idiopathic thrombocytopenia purpura (ITP) and Thrombotic thrombocytopenic purpura (TTP)
Hemolytic uremic syndrome (HUS)
- Blackwater fever (acute intravascular hemolysis, hemoglobinuria, and hemoglobinemia)
- Known hypersensitivity to mefloquine or quinidine: cross-sensitivity to quinine has been documented.
- Myasthenia gravis. Quinine has neuromuscular blocking activity, and may exacerbate muscle weakness.
- Optic neuritis. Quinine may exacerbate active optic neuritis

# Warnings

### Use of Quinine for Treatment or Prevention of Nocturnal Leg Cramps:
- Quinine sulphate may cause unpredictable serious and life-threatening hematologic reactions including thrombocytopenia and hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) in addition to hypersensitivity reactions, QT prolongation, serious cardiac arrhythmias including torsades de pointes, and other serious adverse events requiring medical intervention and hospitalization. Chronic renal impairment associated with the development of TTP, and fatalities have also been reported. The risk associated with the use of Quinine sulphate in the absence of evidence of its effectiveness for treatment or prevention of nocturnal leg cramps, outweighs any potential benefit in treating and/or preventing this benign, self-limiting condition.
- Quinine-induced thrombocytopenia is an immune-mediated disorder. Severe cases of thrombocytopenia that are fatal or life threatening have been reported, including cases of HUS/TTP. Chronic renal impairment associated with the development of TTP has also been reported. Thrombocytopenia usually resolves within a week upon discontinuation of quinine. If quinine is not stopped, a patient is at risk for fatal hemorrhage. Upon re-exposure to quinine from any source, a patient with quinine-dependent antibodies could develop thrombocytopenia that is more rapid in onset and more severe than the original episode.
- QT interval prolongation has been a consistent finding in studies which evaluated electrocardiographic changes with oral or parenteral quinine administration, regardless of age, clinical status, or severity of disease. The maximum increase in QT interval has been shown to correspond with peak quinine plasma concentration. Quinine sulfate has been rarely associated with potentially fatal cardiac arrhythmias, including torsades de pointes, and ventricular fibrillation.
- Quinine sulphate has been shown to cause concentration-dependent prolongation of the PR and QRS interval. At particular risk are patients with underlying structural heart disease and preexisting conduction system abnormalities, elderly patients with sick sinus syndrome, patients with atrial fibrillation with slow ventricular response, patients with myocardial ischemia or patients receiving drugs known to prolong the PR interval (e.g. verapamil) or QRS interval (e.g. flecainide or quinidine).
- Quinine sulphate is not recommended for use with 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).
- The use of macrolide antibiotics such as erythromycin should be avoided in patients receiving Quinine sulphate. Fatal torsades de pointes was reported in an elderly patient who received concomitant quinine, erythromycin, and dopamine. Although a causal relationship between a specific drug and the arrhythmia was not established in this case, erythromycin is a CYP3A4 inhibitor and has been shown to increase quinine plasma levels when used concomitantly. A related macrolide antibiotic, troleandomycin, has also been shown to increase quinine exposure in a pharmacokinetic study.
- Quinine may inhibit the metabolism of certain drugs that are CYP3A4 substrates and are known to cause QT prolongation, e.g., astemizole, cisapride, terfenadine, pimozide, halofantrine and quinidine. Torsades de pointes has been reported in patients who received concomitant quinine and astemizole. Therefore, concurrent use of Quinine sulphate with these medications, or drugs with similar properties, should be avoided.
- Concomitant administration of Quinine sulphate with the antimalarial drugs, mefloquine or halofantrine, may result in electrocardiographic abnormalities, including QT prolongation, and increase the risk for torsades de pointes or other serious ventricular arrhythmias. Concurrent use of Quinine sulphate and mefloquine may also increase the risk of seizures.
- Quinine sulphate should also be avoided in patients with known prolongation of QT interval and in patients with clinical conditions known to prolong the QT interval, such as uncorrected hypokalemia, bradycardia, and certain cardiac conditions.
- Treatment failures may result from the concurrent use of rifampin with Quinine sulphate, due to decreased plasma concentrations of quinine, and concomitant use of these medications should be avoided.
- The use of neuromuscular blocking agents should be avoided in patients receiving Quinine sulphate. In one patient who received pancuronium during an operative procedure, subsequent administration of quinine resulted in respiratory depression and apnea. Although there are no clinical reports with succinylcholine or tubocurarine, quinine may also potentiate neuromuscular blockade when used with these drugs.
- Serious hypersensitivity reactions reported with quinine sulfate include anaphylactic shock, anaphylactoid reactions, urticaria, serious skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, angioedema, facial edema, bronchospasm, and pruritus.
- A number of other serious adverse reactions reported with quinine, including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), thrombocytopenia, immune thrombocytopenic purpura (ITP), blackwater fever, disseminated intravascular coagulation, leukopenia, neutropenia, granulomatous hepatitis, and acute interstitial nephritis may also be due to hypersensitivity reactions.
- Quinine sulphate should be discontinued in case of any signs or symptoms of hypersensitivity.
- Quinine sulphate should be used with caution in patients with atrial fibrillation or atrial flutter. A paradoxical increase in ventricular response rate may occur with quinine, similar to that observed with quinidine. If digoxin is used to prevent a rapid ventricular response, serum digoxin levels should be closely monitored, because digoxin levels may be increased with use of quinine.
- Quinine stimulates release of insulin from the pancreas, and patients, especially pregnant women, may experience clinically significant hypoglycemia.

# Adverse Reactions

## Clinical Trials Experience

### Overall
- Quinine can adversely affect almost every body system. The most common adverse events associated with quinine use are a cluster of symptoms called "cinchonism", which occurs to some degree in almost all patients taking quinine. Symptoms of mild cinchonism include headache, vasodilation and sweating, nausea, tinnitus, hearing impairment, vertigo or dizziness, blurred vision, and disturbance in color perception. More severe symptoms of cinchonism are vomiting, diarrhea, abdominal pain, deafness, blindness, and disturbances in cardiac rhythm or conduction. Most symptoms of cinchonism are reversible and resolve with discontinuation of quinine.
- The following ADVERSE REACTIONS have been reported with quinine sulfate. Most of these reactions are thought to be uncommon, but the actual incidence is unknown:
- Fever, chills, sweating, flushing, asthenia, lupus-like syndrome, and hypersensitivity reactions.
- Agranulocytosis, hypoprothrombinemia, thrombocytopenia, disseminated intravascular coagulation, hemolytic anemia; hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, petechiae, ecchymosis, hemorrhage, coagulopathy, blackwater fever, leukopenia, neutropenia, pancytopenia, aplastic anemia, and lupus anticoagulant.
- Headache, diplopia, confusion, altered mental status, seizures, coma, disorientation, tremors, restlessness, ataxia, acute dystonic reaction, aphasia, and suicide.
- Cutaneous rashes, including urticarial, papular, or scarlatinal rashes, pruritus, bullous dermatitis, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, fixed drug eruption, photosensitivity reactions, allergic contact dermatitis, acral necrosis, and cutaneous vasculitis.
- Asthma, dyspnea, pulmonary edema.
- Chest pain, vasodilatation, hypotension, postural hypotension, tachycardia, bradycardia, palpitations, syncope, atrioventricular block, atrial fibrillation, irregular rhythm, unifocal premature ventricular contractions, nodal escape beats, U waves, QT prolongation, ventricular fibrillation, ventricular tachycardia, torsades de pointes, and cardiac arrest.
- Nausea, vomiting, diarrhea, abdominal pain, gastric irritation, and esophagitis.
- Granulomatous hepatitis, hepatitis, jaundice, and abnormal liver function tests.
- Hypoglycemia and anorexia.
- Myalgias and muscle weakness.
- Hemoglobinuria, renal failure, renal impairment, and acute interstitial nephritis.
- Visual disturbances, including blurred vision with scotomata, sudden loss of vision, photophobia, diplopia, night blindness, diminished visual fields, fixed pupillary dilatation, disturbed color vision, optic neuritis, blindness, vertigo, tinnitus, hearing impairment, and deafness.

## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Quinine sulphate in the drug label.

# Drug Interactions
There is limited information regarding Quinine Drug Interactions in the drug label.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA): 
There is no FDA guidance on usage of Quinine in women who are pregnant.
Pregnancy Category (AUS): 
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Quinine in women who are pregnant.

### Labor and Delivery
There is no FDA guidance on use of Quinine during labor and delivery.

### Nursing Mothers
There is no FDA guidance on the use of Quinine in women who are nursing.

### Pediatric Use
There is no FDA guidance on the use of Quinine in pediatric settings.

### Geriatic Use
There is no FDA guidance on the use of Quinine in geriatric settings.

### Gender
There is no FDA guidance on the use of Quinine with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Quinine with respect to specific racial populations.

### Renal Impairment
There is no FDA guidance on the use of Quinine in patients with renal impairment.

### Hepatic Impairment
There is no FDA guidance on the use of Quinine in patients with hepatic impairment.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Quinine in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Quinine in patients who are immunocompromised.

# Administration and Monitoring

### Administration
There is limited information regarding Quinine Administration in the drug label.

### Monitoring
There is limited information regarding Quinine Monitoring in the drug label.

# IV Compatibility
There is limited information regarding the compatibility of Quinine and IV administrations.

# Overdosage
There is limited information regarding Quinine overdosage.  If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

# Pharmacology
There is limited information regarding Quinine Pharmacology in the drug label.

## Mechanism of Action
There is limited information regarding Quinine Mechanism of Action in the drug label.

## Structure
There is limited information regarding Quinine Structure in the drug label.

## Pharmacodynamics
There is limited information regarding Quinine Pharmacodynamics in the drug label.

## Pharmacokinetics
There is limited information regarding Quinine Pharmacokinetics in the drug label.

## Nonclinical Toxicology
There is limited information regarding Quinine Nonclinical Toxicology in the drug label.

# Clinical Studies
There is limited information regarding Quinine Clinical Studies in the drug label.

# How Supplied
There is limited information regarding Quinine How Supplied in the drug label.

## Storage
There is limited information regarding Quinine Storage in the drug label.

# Images

## Drug Images

## Package and Label Display Panel

# Patient Counseling Information
There is limited information regarding Quinine Patient Counseling Information in the drug label.

# Precautions with Alcohol
Alcohol-Quinine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

# Brand Names
There is limited information regarding Quinine Brand Names in the drug label.

# Look-Alike Drug Names
There is limited information regarding Quinine Look-Alike Drug Names in the drug label.

# Drug Shortage Status

# Price