Qualaquin

QUALAQUIN- quinine sulfate capsule
AR Scientific Inc.

WARNING:

QUALAQUIN® use for the treatment or prevention of nocturnal leg cramps may result in serious and life-threatening hematologic reactions, including thrombocytopenia and hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP). Chronic renal impairment associated with the development of TTP has been reported. The risk associated with QUALAQUIN use in the absence of evidence of its effectiveness in the treatment or prevention of nocturnal leg cramps outweighs any potential benefit (see WARNINGS).

1 INDICATIONS AND USAGE

QUALAQUIN (quinine sulfate) 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 [see Clinical Studies (14) ].

QUALAQUIN oral capsules are not approved for:

  • Treatment of severe or complicated P. falciparum malaria.
  • Prevention of malaria.
  • Treatment or prevention of nocturnal leg cramps [see Warnings and Precautions (5.1) ].

2 DOSAGE AND ADMINISTRATION

2.1 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 [see Clinical Studies (14) ].

QUALAQUIN should be taken with food to minimize gastric upset [see Clinical Pharmacology (12.3) ].

2.2 Renal Impairment

In patients with acute uncomplicated malaria and severe chronic renal impairment, the following dosage regimen is recommended: one loading dose of 648 mg QUALAQUIN 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 [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

2.3 Hepatic Impairment

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 [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

3 DOSAGE FORMS AND STRENGTHS

324 mg capsules — hard gelatin, clear cap/clear body, imprinted with ‘AR 102’

4 CONTRAINDICATIONS

QUALAQUIN is contraindicated in patients with the following:

  • Prolonged QT interval. 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 [see Warnings and Precautions (5.3) ].
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
  • Hemolysis can occur in patients with G6PD deficiency receiving quinine.
  • Known hypersensitivity reactions to quinine.
    • These include, but are not limited to, the following [see Warnings and Precautions (5.6) ]:
      • 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 [see Warnings and Precautions (5.6) ].
    • Myasthenia gravis. Quinine has neuromuscular blocking activity, and may exacerbate muscle weakness.
    • Optic neuritis. Quinine may exacerbate active optic neuritis [see Adverse Reactions (6) ].

5 WARNINGS AND PRECAUTIONS

5.1 Use of QUALAQUIN for Treatment or Prevention of Nocturnal Leg Cramps

QUALAQUIN 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 QUALAQUIN 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 [see Boxed Warning and Contraindications (4)].

5.2 Thrombocytopenia

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.

5.3 QT Prolongation and Ventricular Arrhythmias

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 [see Clinical Pharmacology (12.2) ]. Quinine sulfate has been rarely associated with potentially fatal cardiac arrhythmias, including torsades de pointes, and ventricular fibrillation.

QUALAQUIN 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) [see Clinical Pharmacology (12.2) ].

QUALAQUIN 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 QUALAQUIN. 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 [see Drug Interactions (7.1) ].

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 QUALAQUIN with these medications, or drugs with similar properties, should be avoided [see Drug Interactions (7.2) ].

Concomitant administration of QUALAQUIN 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 QUALAQUIN and mefloquine may also increase the risk of seizures [see Drug Interactions (7.2) ].

QUALAQUIN 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 [see Contraindications (4) ].

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2024. All Rights Reserved.