Anadin

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Anadin uses

Anadin consists of Aspirin, Caffeine, Quinine Sulfate.

Aspirin:


Pharmacological action

Anadin is a NSAIDs. It has anti-inflammatory, analgesic and antipyretic effect, and inhibits platelet aggregation. The mechanism of action is associated with inhibition of COX activity - the main enzyme metabolism of arachidonic acid which is a precursor of prostaglandins which play a major role in the pathogenesis of inflammation, pain and fever. Reduction of prostaglandins (mainly E1) in the thermoregulation center leads to a decrease in body temperature due to expansion of blood vessels of the skin and increase perspiration. Analgesic effect of Anadin (Aspirin) is due to both central and peripheral effects. Reduces aggregation, platelet adhesion and thrombus formation through suppression of synthesis of thromboxane A2 in platelets.

Reduces mortality and risk of myocardial infarction in unstable stenocardia. It is effective in primary prevention of cardio-vascular system and secondary prevention of myocardial infarction. At a daily dose of 6 g or more inhibits the synthesis of prothrombin in the liver and increases the prothrombin time. Anadin (Aspirin) increases fibrinolytic activity of plasma and reduces the concentration of vitamin K-dependent coagulation factors (II, VII, IX, X). Increases the rate of hemorrhagic complications in carrying out surgical procedures, increases the risk of bleeding during therapy with anticoagulants. It stimulates the excretion of uric acid (violating its reabsorption in the renal tubules) but in high doses. The blockade of COX-1 in the mucosa of the stomach leads to inhibition of gastroprotective prostaglandins, which may lead to ulceration of the mucous membrane and subsequent bleeding.

Pharmacokinetics

When administered orally Anadin (Aspirin) is rapidly absorbed mainly from the proximal small intestine and to a lesser extent from the stomach. The presence of food in the stomach significantly affects the absorption of Anadin (Aspirin).

Metabolised in the liver by hydrolysis with the formation of salicylic acid with subsequent conjugation with glycine or two drugs. The concentration of salicylates in blood plasma is variable.

About 80% of salicylic acid binds to plasma proteins. Salicylates easily penetrate into many tissues and body fluids, including the cerebrospinal, peritoneal and synovial fluid. In small quantities salicylates are found in brain tissue, traces - in bile, sweat and feces. Quickly penetrates the placental barrier in small amounts excreted in breast milk.

For newborns salicylates may displace bilirubin from its association with albumin and promote bilirubin encephalopathy.

Penetration into the joint cavity is accelerated in the presence of hyperemia and edema, and slows down in the proliferative phase of inflammation.

If you have acidosis most of salicylate becomes unionized acid, good penetration into the tissue, including in the brain.

Anadin (Aspirin) withdraws mainly by active secretion in the tubules of the kidneys in unchanged form (60%) and in the form of metabolites. The withdraw of unchanged salicylate is dependent on the pH of urine (for alkalinization of urine increases ionized salicylates, worsening their reabsorption and increases excretion). T1/2 of Anadin (Aspirin) is approximately 15 minutes. T1/2 of salicylate at a reception in low doses is 2-3 h, with an increase in dose may increase to 15-30 hours. Newborns' elimination of salicylate is much slower than in adults.

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Why is Anadin prescribed?

Rheumatism, rheumatoid arthritis, infectious-allergic myocarditis, fever during infectious and inflammatory diseases, pain syndrome, weak and medium intensity of various origins (including neuralgia, myalgia, headache); based prevention of thrombosis and embolism, primary and secondary prevention of myocardial infarction, prevention of violations of cerebral circulation by ischemic type.

In the clinical immunology and allergy: a gradually increasing doses for a prolonged "aspirin" desensitization and the formation of stable tolerance to NSAIDs in patients with "aspirin asthma" and "aspirin triad."

Dosage and administration

Individual. For oral administration dosing of Anadin regimen depends on indication for use. Usual adult dose when used as antipyretic and analgesic is 500-1000 mg / day (up to 3 g) were divided into 3 admission.

In myocardial infarction, as well as for secondary prevention in patients after myocardial infarction - 40-325 mg 1 time a day (usually 160 mg). As an inhibitor of platelet aggregation - a dose of 300-325 mg / day, for a long time. At the dynamic circulatory disorders in men, cerebral thromboembolism, including to prevent a recurrence - 325 mg / day with gradual increase to a maximum of 1 g / day. For prevention of thrombosis or occlusion of the aortic shunt - by 325 mg every 7 h after intranasal gastric tube set, and then - through the mouth to 325 mg 3 times a day (usually in combination with dipyridamole, which abolished after 1 week, continuing the long-term treatment with Anadin (Aspirin)).

Anadin (Aspirin) side effects, adverse reactions

Digestive system: nausea, vomiting, anorexia, epigastric pain, diarrhea; rarely - occurrence of erosive and ulcerative lesions, bleeding from the gastrointestinal tract, abnormal liver function.

Central nervous system: long-term use may be dizziness, headache, reversible visual disturbances, tinnitus, aseptic meningitis.

Hemopoietic system: rarely - thrombocytopenia, anemia.

Blood coagulation system: rarely - haemorrhagic syndrome, prolongation of bleeding time.

Urinary system: rarely - renal dysfunction, with prolonged use - acute kidney failure, nephrotic syndrome.

Allergic reactions: rarely - skin rash, Quincke's edema, bronchospasm, "aspirin triad" (a combination of bronchial asthma, recurrent nasal polyposis, and paranasal sinuses and intolerance of Anadin (Aspirin) and medicines pirazolonic series).

Other: in some cases - Reye syndrome, long-term use - increased symptoms of chronic heart failure.

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Anadin contraindications

Exacerbation phase of erosive-ulcerative lesions in the gastrointestinal tract, gastro-intestinal bleeding, "aspirin triad", a history of indications urticaria, rhinitis, caused by taking Anadin (Aspirin) and other NSAIDs, hemophilia, hemorrhagic diathesis, gipoprotrombinemii, dissecting aneurysm of the aorta, portal hypertension, deficiency of vitamin K, liver and / or renal failure, deficiency of glucose-6-phosphate dehydrogenase, Reye syndrome, children's age (under 15 years - the risk of developing Reye syndrome in children with hyperthermia on a background of viral diseases), I and III trimester of pregnancy, lactation, hypersensitivity to Anadin (Aspirin) and other salicylates.

Using during pregnancy and breastfeeding

Anadin (acetylsalicylic acid) is contraindicated in I and III trimester of pregnancy. In pregnancy trimester II can a one-off reception on the strict condition.

This medication has a teratogenic effect: when used in the I trimester leads to top palatoschisis, in the III trimester - cause inhibition of labor (inhibition of prostaglandin synthesis), premature closure of the ductus arteriosus in the fetus, pulmonary vascular hyperplasia and hypertension in the pulmonary circulation.

Anadin (Aspirin) (acetylsalicylic acid) is excreted in breast milk, which increases the risk of bleeding in a child due to dysfunction of platelets, and therefore should not be applied Anadin (Aspirin) in the mother during lactation.

Special instructions

Anadin (Aspirin) with caution used in patients with liver diseases and kidney, bronchial asthma, erosive and ulcerative lesions, and bleeding from the digestive tract in history, with increased bleeding or while holding anticoagulant therapy, decompensated congestive heart failure.

Anadin (Aspirin) even in small doses reduces the excretion of uric acid from the organism that can cause an acute attack of gout in predisposed patients. When conducting long-term therapy and / or use of Anadin (Aspirin) in high doses required medical supervision and regular monitoring of hemoglobin levels.

The use of Anadin (Aspirin) as anti-inflammatory drugs in a daily dose of 5-8 g is limited due to the high probability of adverse effects from the gastrointestinal tract.

Before surgery to reduce bleeding during surgery and postoperative period should stop taking salicylates for 5-7 days.

During prolonged therapy is necessary to conduct a general analysis of blood and study of occult blood.

The use of Anadin (Aspirin) is contraindicated in pediatrics, as in the case of viral infection in children under the influence of Anadin (Aspirin) increases the risk of developing Reye syndrome. Symptoms of Reye syndrome are prolonged vomiting, acute encephalopathy, liver enlargement.

Duration of treatment (without consulting a doctor) with Anadin (Aspirin) should not exceed 7 days when administered as analgesic and more than 3 days as an antipyretic.

During treatment the patient should abstain from alcohol.

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Precautionary measures

Undesirable combined use with other NSAIDs and glucocorticoids. For 5-7 days before surgery should stop taking.

The probability of NSAID-gastropathy decreases in the appointment after a meal, use of tablets with buffer additives or coated with a special enteric-soluble shell. The risk of hemorrhagic complications is minimal when used in doses less than 100 mg / day.

Note that in predisposed patients Anadin (Aspirin) (even in small doses) reduces the excretion of uric acid from the body and can cause the development of acute attack of gout.

During prolonged therapy should regularly carry out the analysis of blood and to investigate faeces for occult blood. In connection with the observed cases hepatogenic encephalopathy is not recommended for relief of fever syndrome in children.

Anadin (Aspirin) drug interactions

With simultaneous use of antacids containing magnesium and / or aluminum hydroxide, slow down and reduce the absorption of Anadin (Aspirin).

With simultaneous use of calcium channel blockers, means limiting intake of calcium or increasing the excretion of calcium from the body, increases the risk of bleeding.

With simultaneous use with Anadin (Aspirin) enhances the action of heparin and indirect anticoagulants, hypoglycemic funds derived sulfonylureas, insulin, methotrexate, phenytoin, valproic acid.

With simultaneous use of Anadin (Aspirin) with SCS increases the risk of ulcerogenic effect and occurrence of gastrointestinal bleeding.

With simultaneous use of decreasing the effectiveness of diuretics (spironolactone, furosemide).

With simultaneous use of other NSAIDs increases the risk of side effects. Anadin (Aspirin) may reduce plasma concentrations indomethacin, piroxicam.

With simultaneous use of gold drugs Anadin (Aspirin) can induce liver damage.

With simultaneous use decreases effectiveness of uricosuric medications (including probenecid, sulfinpirazon, benzbromarone).

With simultaneous use of Anadin (Aspirin) and alendronate sodium may develop severe esophagitis.

With simultaneous use of griseofulvin may be in breach Absorption of Anadin (Aspirin).

There is one case of spontaneous hemorrhage in the iris while taking Ginkgo Biloba extract on the background of prolonged use of Anadin (Aspirin) in a dose of 325 mg / day. It is believed that this may be due to additive inhibitory effect on platelet aggregation.

With simultaneous use of dipyridamole may increase Cmax of salicylate in plasma and AUC.

When applied simultaneously with Anadin (Aspirin) increased concentration of digoxin, barbiturates and lithium salts in the blood plasma.

With simultaneous use of salicylates in high doses with carbonic anhydrase inhibitors can intoxication salicylates.

Anadin (Aspirin) in doses of less than 300 mg have little effect on the effectiveness of captopril and enalapril. When Anadin (Aspirin) (acetylsalicylic acid) is admistered in high doses may decrease the effectiveness of captopril and enalapril.

With simultaneous application of caffeine increases the rate of absorption, plasma concentrations and bioavailability of Anadin (Aspirin).

With simultaneous use of Anadin (Aspirin) with metoprolol may increase Cmax of salicylate in blood plasma.

In the application of pentazocine on the background of long-term use of Anadin (Aspirin) in high doses there is a risk of severe adverse reactions in the kidneys.

With simultaneous application phenylbutazone reduces uricosuria caused by Anadin (Aspirin).

With simultaneous application of ethanol may exacerbate the effects of Anadin (Aspirin) on the gastrointestinal tract.

Anadin in case of emergency / overdose

May occur after receiving a single large dose or prolonged use. If a single dose of less than 150 mg / kg, acute poisoning feel light, 150-300 mg / kg - moderate, when using higher doses - heavy.

Symptoms: salicylism syndrome (nausea, vomiting, tinnitus, blurred vision, dizziness, severe headache, malaise, fever - a poor prognostic sign in adults). More severe poisoning - stupor, convulsions and coma, noncardiogenic pulmonary edema, abrupt dehydration, violations ABE (initially - respiratory alkalosis, then - metabolic acidosis), renal failure and shock.

In chronic overdose concentration determined in plasma are poorly correlated with the severity of intoxication. The greatest risk of chronic intoxication is found among elderly people at reception for a few days more than 100 mg / kg / day. In children and elderly patients the initial signs of salicylism are not always visible, and therefore desirable to periodically determine the concentration of salicylates in the blood. Level above 70 mg% indicates moderate or severe poisoning; above 100 mg% - on extremely heavy, a poor prognosis. If poisoning moderate require hospitalization for at least 24 hours.

Treatment: the provocation of vomiting, the appointment of activated charcoal and laxatives, monitoring ABE and electrolyte balance, depending on the state of metabolism - the introduction of sodium bicarbonate, solution of sodium citrate or sodium lactate. Raising reserve alkalinity increases the excretion of Anadin (Aspirin) by alkalinization of urine. Alkalinization of urine is shown at the level of salicylates above 40 mg%, is provided in / by infusion of sodium bicarbonate - 88 mEq in 1 liter of 5% glucose solution, the rate of 10-15 ml / kg / h. Restoring BCC and induction of diuresis (achieved by introducing a bicarbonate in the same dose and dilution, repeat 2-3 times); should be aware that intense infusion fluid elderly patients may lead to pulmonary edema. Not recommended the use of acetazolamide for alkalinization of urine (may cause acidemia and enhance the toxic effect of salicylates). Hemodialysis is shown at the level of salicylates over 100-130 mg%, and in patients with chronic poisoning - 40 mg% or lower in the presence of witnesses (refractory acidosis, progressive deterioration, severe damage of the CNS, pulmonary edema and renal failure). When pulmonary edema - a mixture of artificial ventilation, oxygen enriched, in the mode of positive end-expiratory pressure, to treat cerebral edema apply hyperventilation and osmotic diuresis.

Caffeine:



Active ingredient (in each tablet)

Anadin (Caffeine) 200mg

Purpose

Alertness aid

Use

  • helps restore mental alertness or wakefulness when experiencing fatigue or drowsiness

Warnings

For occasional use only

Do not use

  • in children under 12 years of age
  • as a substitute for sleep

When using this product limit the use of Anadin (Caffeine) containing medications, foods, or beverages because too much Anadin (Caffeine) may cause nervousness, irritability, sleeplessness, and occasionally, rapid heartbeat. The recommended dose of this product contains about as much Anadin (Caffeine) as a cup of coffee.

Stop use and ask a doctor if fatigue or drowsiness persists or continues to recur

If pregnant or breast-feeding, ask a health professional before use.

Keep out of reach of children.

In case of overdose, get medical help or contact a Poison Control Center right away.

Directions

  • adults and children 12 years of age and over: take 1 tablet not more often than every 3 to 4 hours.

Other information

  • store at room temperature
  • avoid excessive heat (greater than 100°F) or humidity

Inactive ingredients

carnauba wax, colloidal silicon dioxide, D&C yellow #10 aluminum lake, dextrose, FD&C yellow #6 aluminum lake, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, starch, titanium dioxide

Questions or comments?

Call toll-free 1-855-874-0970 weekdays


Display Panel Anadin (Caffeine): 16 ct. Package

Anadin (Caffeine)®

CAFFEINE ALERTNESS AID

16 TABLETS

200mg each

FUNCTIONAL Anadin (Caffeine)® for Mental Alertness

SAFE & EFFECTIVE

One tablet is equal to about a cup of coffee

Anadin (Caffeine)®

Making the Most of Every Day.®

Tamper Evident Feature: individually sealed in foil for your protection. Do not

use if foil or plastic bubble is torn or punctured.

Vivarin®, Vivarin® and design, stylization and trade dress, and FUNCTIONAL

CAFFEINE® are registered trademarks of Meda AB.

Distributed by:

Meda Consumer Healthcare Inc.

Marietta, GA 30062 ©2011 Meda AB

www.vivarin.com

16 ct. Package

Display Panel Anadin (Caffeine): 40 ct. Package

SAFE & EFFECTIVE

FUNCTIONAL Anadin (Caffeine)® for Mental Alertness

Anadin (Caffeine)®

Anadin (Caffeine) ALERTNESS AID

40 Tablets

200mg each

FUNCTIONAL Anadin (Caffeine)® for Mental Alertness

Tamper Evident Feature: Individually sealed in foil for your protection. Do not use if foil or plastic bubble is torn or punctured.

VIVARIN® helps restore mental alertness or wakefulness when experiencing fatigue or drowsiness (FDA approved uses), so you can accomplish all the things you want to do and all the things you need to do.

Vivarin®, Vivarin® and design, stylization and trade dress, and FUNCTIONAL

CAFFEINE® are registered trademarks of Meda AB.

Made in the U.S.A.

Anadin (Caffeine)®

Making the Most of Every Day.®

Distributed by:

Meda Consumer Healthcare Inc.

Marietta, GA 30062 ©2013 Meda AB

www.vivarin.com

40 ct. Package

Quinine Sulfate:


WARNING:

Anadin (Quinine Sulfate)® 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 Anadin (Quinine Sulfate) use in the absence of evidence of its effectiveness in the treatment or prevention of nocturnal leg cramps outweighs any potential benefit.

WARNING:

Anadin (Quinine Sulfate)® 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 Anadin (Quinine Sulfate) use in the absence of evidence of its effectiveness in the treatment or prevention of nocturnal leg cramps outweighs any potential benefit.

Dose and Administration
Hepatic Impairment (2.3) 4/2013
Warnings and Precautions
QT Prolongation and Ventricular Arrhythmias (5.3) 9/2012
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1 INDICATIONS AND USAGE

Anadin (Quinine Sulfate) (quinine sulfate) is an antimalarial drug indicated only for treatment of uncomplicated Plasmodium falciparum malaria. Anadin (Quinine Sulfate) has been shown to be effective in geographical regions where resistance to chloroquine has been documented [see Clinical Studies (14) ].

Anadin (Quinine Sulfate) 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) ].

Anadin (Quinine Sulfate)® (quinine sulfate) is a cinchona alkaloid indicated for treatment of uncomplicated Plasmodium falciparum malaria (1).

2 DOSAGE AND ADMINISTRATION

  • Adults : 648 mg (two capsules) every 8 hours for 7 days (2.1).
  • Patients with severe chronic renal impairment: one loading dose of 648 mg (two capsules) followed 12 hours later by 324 mg (one capsule) every 12 hours for 7 days (2.2).

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) ].

Anadin (Quinine Sulfate) 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 Anadin 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 Anadin (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'

  • 324 mg hard gelatin, clear cap/clear body capsules, imprinted with 'AR 102' (3).

4 CONTRAINDICATIONS

Anadin (Quinine Sulfate) 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 Anadin (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) ].

Anadin (Quinine Sulfate) is contraindicated in patients with the following:

  • Prolongation of QT interval (4)
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency (4)
  • Myasthenia gravis (4)
  • Known hypersensitivity to quinine, mefloquine, or quinidine (4)
  • Optic neuritis (4)

5 WARNINGS AND PRECAUTIONS

  • Not indicated for the prevention or treatment of nocturnal leg cramps. Risk of serious and life-threatening adverse reactions.
  • Thrombocytopenia, including ITP and HUS/TTP, has been reported. Discontinue drug (5.2).
  • QT prolongation and ventricular arrhythmias. Avoid concomitant use with drugs known to prolong QT interval (5.3).
  • Avoid concomitant use with rifampin. Anadin (Quinine Sulfate) treatment failures have been reported (5.4).
  • Avoid concomitant use with neuromuscular blocking agents. Anadin (Quinine Sulfate) may potentiate neuromuscular blockade and cause respiratory depression (5.5).
  • Serious and life threatening hypersensitivity reactions. Discontinue drug (4, 5.6).
  • Atrial fibrillation and flutter. Paradoxical increase in ventricular rate may occur. Closely monitor digoxin levels if used concomitantly (5.7).
  • Hypoglycemia. Monitor for signs and symptoms (5.8).

5.1 Use of Anadin (Quinine Sulfate) for Treatment or Prevention of Nocturnal Leg Cramps

Anadin (Quinine Sulfate) 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 Anadin (Quinine Sulfate) 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 ]. Anadin (Quinine Sulfate) has been rarely associated with potentially fatal cardiac arrhythmias, including torsades de pointes, and ventricular fibrillation.

Anadin (Quinine Sulfate) 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) ].

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

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

Anadin (Quinine Sulfate) 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) ].

5.4 Concomitant Use of Rifampin

Treatment failures may result from the concurrent use of rifampin with Anadin (Quinine Sulfate), due to decreased plasma concentrations of quinine, and concomitant use of these medications should be avoided [see Drug Interactions (7.1) ].

5.5 Concomitant Use of Neuromuscular Blocking Agents

The use of neuromuscular blocking agents should be avoided in patients receiving Anadin. 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 [see Drug Interactions (7.2) ].

5.6 Hypersensitivity

Serious hypersensitivity reactions reported with Anadin (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.

Anadin (Quinine Sulfate) should be discontinued in case of any signs or symptoms of hypersensitivity [see Contraindications (4) ].

5.7 Atrial Fibrillation and Flutter

Anadin 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 [see Drug Interactions (7.2) ].

5.8 Hypoglycemia

Quinine stimulates release of insulin from the pancreas, and patients, especially pregnant women, may experience clinically significant hypoglycemia.

6 ADVERSE REACTIONS

Most common adverse reactions are a cluster of symptoms called "cinchonism", which occurs to some degree in almost all patients taking quinine: headache, vasodilation and sweating, nausea, tinnitus, hearing impairment, vertigo or dizziness, blurred vision, disturbance in color perception, vomiting, diarrhea, abdominal pain, deafness, blindness, and disturbances in cardiac rhythm or conduction.

To report SUSPECTED ADVERSE REACTIONS, contact Mutual Pharmaceutical Company, Inc. at 1-888-351-3786 or drugsafetyAnadin (Quinine Sulfate)urlpharma.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 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 Anadin (Quinine Sulfate). Most of these reactions are thought to be uncommon, but the actual incidence is unknown:

General: fever, chills, sweating, flushing, asthenia, lupus-like syndrome, and hypersensitivity reactions.

Hematologic: 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.

Neuropsychiatric: headache, diplopia, confusion, altered mental status, seizures, coma, disorientation, tremors, restlessness, ataxia, acute dystonic reaction, aphasia, and suicide.

Dermatologic: 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.

Respiratory: asthma, dyspnea, pulmonary edema.

Cardiovascular: 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.

Gastrointestinal: nausea, vomiting, diarrhea, abdominal pain, gastric irritation, and esophagitis.

Hepatobiliary: granulomatous hepatitis, hepatitis, jaundice, and abnormal liver function tests.

Metabolic: hypoglycemia and anorexia.

Musculoskeletal: myalgias and muscle weakness.

Renal: hemoglobinuria, renal failure, renal impairment, and acute interstitial nephritis.

Special Senses: 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.

7 DRUG INTERACTIONS

Interacting Drug Interaction
Drugs known to prolong QT interval. Anadin (Quinine Sulfate) prolongs QT interval, ECG abnormalities including QT prolongation and Torsades de Pointes. Avoid concomitant use (5.3).
Other antimalarials (e.g., halofantrine, mefloquine). ECG abnormalities including QT prolongation. Avoid concomitant use (5.3, 7.2).
CYP3A4 inducers or inhibitors Alteration in plasma quinine concentration. Monitor for lack of efficacy or increased adverse events of quinine (7.1).
CYP3A4 and CYP2D6 substrates Quinine is an inhibitor of CYP3A4 and CYP2D6. Monitor for lack of efficacy or increased adverse events of the co-administered drug (7.2).
Digoxin Increased digoxin plasma concentration (5.8, 7.1).

7.1 Effects of Drugs and Other Substances on Quinine Pharmacokinetics

Quinine is a P-gp substrate and is primarily metabolized by CYP3A4. Other enzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1 may contribute to the metabolism of quinine [see Clinical Pharmacology (12.3) ].

Antacids: Antacids containing aluminum and/or magnesium may delay or decrease absorption of quinine. Concomitant administration of these antacids with Anadin (Quinine Sulfate) should be avoided.

Antiepileptics (AEDs) (carbamazepine, phenobarbital, and phenytoin): Carbamazepine, phenobarbital, and phenytoin are CYP3A4 inducers and may decrease quinine plasma concentrations if used concurrently with Anadin (Quinine Sulfate).

Cholestyramine: In 8 healthy subjects who received Anadin (Quinine Sulfate) 600 mg with or without 8 grams of cholestyramine resin, no significant difference in quinine pharmacokinetic parameters was seen.

Cigarette Smoking (CYP1A2 inducer): In healthy male heavy smokers, the mean quinine AUC following a single 600 mg dose was 44% lower, the mean Cmax was 18% lower, and the elimination half-life was shorter (7.5 hours versus 12 hours) than in their non-smoking counterparts. However, in malaria patients who received the full 7-day course of quinine therapy, cigarette smoking produced only a 25% decrease in median quinine AUC and a 16.5% decrease in median Cmax, suggesting that the already reduced clearance of quinine in acute malaria could have diminished the metabolic induction effect of smoking. Because smoking did not appear to influence the therapeutic outcome in malaria patients, it is not necessary to increase the dose of quinine in the treatment of acute malaria in heavy cigarette smokers.

Grapefruit juice (P-gp/CYP3A4 inhibitor): In a pharmacokinetic study involving 10 healthy subjects, the administration of a single 600 mg dose of Anadin (Quinine Sulfate) with grapefruit juice (full-strength or half-strength) did not significantly alter the pharmacokinetic parameters of quinine. Anadin (Quinine Sulfate) may be taken with grapefruit juice.

Histamine H2-receptor blockers [cimetidine, ranitidine (nonspecific CYP450 inhibitors)]: In healthy subjects who were given a single oral 600 mg dose of Anadin (Quinine Sulfate) after pretreatment with cimetidine (200 mg three times daily and 400 mg at bedtime for 7 days) or ranitidine (150 mg twice daily for 7 days), the apparent oral clearance of quinine decreased and the mean elimination half-life increased significantly when given with cimetidine but not with ranitidine. Compared to untreated controls, the mean AUC of quinine increased by 20% with ranitidine and by 42% with cimetidine (p<0.05) without a significant change in mean quinine Cmax. When quinine is to be given concomitantly with a histamine H2-receptor blocker, the use of ranitidine is preferred over cimetidine. Although cimetidine and ranitidine may be used concomitantly with Anadin (Quinine Sulfate), patients should be monitored closely for adverse events associated with quinine.

Isoniazid: Isoniazid 300 mg/day pretreatment for 1 week did not significantly alter the pharmacokinetic parameter values of quinine. Adjustment of Anadin (Quinine Sulfate) dosage is not necessary when isoniazid is given concomitantly.

Ketoconazole (CYP3A4 inhibitor): In a crossover study, healthy subjects (N=9) who received a single oral dose of quinine hydrochloride (500 mg) concomitantly with ketoconazole (100 mg twice daily for 3 days) had a mean quinine AUC that was higher by 45% and a mean oral clearance of quinine that was 31% lower than after receiving quinine alone. Although no change in the Anadin (Quinine Sulfate) dosage regimen is necessary with concomitant ketoconazole, patients should be monitored closely for adverse reactions associated with quinine.

Macrolide antibiotics (erythromycin, troleandomycin) (CYP3A4 inhibitors): In a crossover study (N=10), healthy subjects who received a single oral 600 mg dose of Anadin (Quinine Sulfate) with the macrolide antibiotic, troleandomycin (500 mg every 8 hours) exhibited a 87% higher mean quinine AUC, a 45% lower mean oral clearance of quinine, and a 81% lower formation clearance of the main metabolite, 3-hydroxyquinine, than when quinine was given alone.

Erythromycin was shown to inhibit the in vitro metabolism of quinine in human liver microsomes, an observation confirmed by an in vivo interaction study. In a crossover study (N=10), healthy subjects who received a single oral 500 mg dose of Anadin (Quinine Sulfate) with erythromycin (600 mg every 8 hours for four days) showed a decrease in quinine oral clearance (CL/F), an increase in half-life, and a decreased metabolite (3-hydroxyquinine) to quinine AUC ratio, as compared to when quinine was given with placebo.

Therefore, concomitant administration of macrolide antibiotics such as erythromycin or troleandomycin with Anadin (Quinine Sulfate) should be avoided [see Warnings and Precautions (5.3) ].

Oral contraceptives (estrogen, progestin): In 7 healthy females who were using single-ingredient progestin or combination estrogen-containing oral contraceptives, the pharmacokinetic parameters of a single 600 mg dose of Anadin (Quinine Sulfate) were not altered in comparison to those observed in 7 age-matched female control subjects not using oral contraceptives.

Rifampin (CYP3A4 inducer): In patients with uncomplicated P. falciparum malaria who received Anadin (Quinine Sulfate) 10 mg/kg concomitantly with rifampin 15 mg/kg/day for 7 days (N=29), the median AUC of quinine between days 3 and 7 of therapy was 75% lower as compared to those who received quinine monotherapy. In healthy subjects (N=9) who received a single oral 600 mg dose of Anadin (Quinine Sulfate) after 2 weeks of pretreatment with rifampin 600 mg/day, the mean quinine AUC and Cmax decreased by 85% and 55%, respectively. Therefore, the concomitant administration of rifampin with Anadin (Quinine Sulfate) should be avoided [see Warnings and Precautions (5.4) ].

Ritonavir: In healthy subjects who received a single oral 600 mg dose of Anadin (Quinine Sulfate) with the 15th dose of ritonavir (200 mg every 12 hours for 9 days), there were 4-fold increases in the mean quinine AUC and Cmax, and an increase in the mean elimination half-life (13.4 hours versus 11.2 hours), compared to when quinine was given alone. Therefore, the concomitant administration of ritonavir with Anadin (Quinine Sulfate) capsules should be avoided [see also Drug Interactions (7.2) ].

Tetracycline: In 8 patients with acute uncomplicated P. falciparum malaria who were treated with oral Anadin (Quinine Sulfate) (600 mg every 8 hours for 7 days) in combination with oral tetracycline (250 mg every 6 hours for 7 days), the mean plasma quinine concentrations were about two-fold higher than in 8 patients who received quinine monotherapy. Although tetracycline may be concomitantly administered with Anadin (Quinine Sulfate), patients should be monitored closely for adverse reactions associated with Anadin (Quinine Sulfate).

Theophylline or aminophylline: In 20 healthy subjects who received multiple doses of Anadin (Quinine Sulfate) (648 mg every 8 hours × 7 days) with a single 300 mg oral dose of theophylline, the quinine mean Cmax and AUC were increased by 13% and 14% respectively. Although no change in the Anadin (Quinine Sulfate) dosage regimen is necessary with concomitant theophylline or aminophylline, patients should be monitored closely for adverse reactions associated with quinine.

Urinary alkalizers (acetazolamide, sodium bicarbonate): Urinary alkalinizing agents may increase plasma quinine concentrations.

7.2 Effects of Quinine on the Pharmacokinetics of Other Drugs

Results of in vivo drug interaction studies suggest that quinine has the potential to inhibit the metabolism of drugs that are substrates of CYP3A4 and CYP2D6. Quinine inhibits P-gp and has the potential to affect the transport of drugs that are P-gp substrates.

Anticonvulsants : A single 600 mg oral dose of Anadin (Quinine Sulfate) increased the mean plasma Cmax, and AUC0–24 of single oral doses of carbamazepine (200 mg) and phenobarbital (120 mg) but not phenytoin (200 mg) in 8 healthy subjects. The mean AUC increases of carbamazepine, phenobarbital and phenytoin were 104%, 81% and 4%, respectively; the mean increases in Cmax were 56%, 53%, and 4%, respectively. Mean urinary recoveries of the three antiepileptics over 24 hours were also profoundly increased by quinine. If concomitant administration with carbamazepine or phenobarbital cannot be avoided, frequent monitoring of anticonvulsant drug concentrations is recommended. Additionally, patients should be monitored closely for adverse reactions associated with these anticonvulsants.

Astemizole (CYP3A4 substrate): Elevated plasma astemizole concentrations were reported in a subject who experienced torsades de pointes after receiving three doses of Anadin (Quinine Sulfate) for nocturnal leg cramps concomitantly with chronic astemizole 10 mg/day. The concurrent use of Anadin (Quinine Sulfate) with astemizole and other CYP3A4 substrates with QT prolongation potential (e.g., cisapride, terfenadine, halofantrine, pimozide and quinidine) should also be avoided [see Warnings and Precautions (5.3) ].

Atorvastatin (CYP3A4 substrate): Rhabdomyolysis with acute renal failure secondary to myoglobinuria was reported in a patient taking atorvastatin administered with a single dose of quinine. Quinine may increase plasma concentrations of atorvastatin, thereby increasing the risk of myopathy or rhabdomyolysis. Thus, clinicians considering combined therapy of Anadin (Quinine Sulfate) with atorvastatin or other HMG-CoA reductase inhibitors ("statins") that are CYP3A4 substrates (e.g., simvastatin, lovastatin) should carefully weigh the potential benefits and risks of each medication. If Anadin (Quinine Sulfate) is used concomitantly with any of these statins, lower starting and maintenance doses of the statin should be considered. Patients should also be monitored closely for any signs or symptoms of muscle pain, tenderness, or weakness, particularly during initial therapy. If marked creatine phosphokinase (CPK) elevation occurs or myopathy (defined as muscle aches or muscle weakness in conjunction with CPK values >10 times the upper limit of normal) is diagnosed or suspected, atorvastatin or other statin should be discontinued.

Desipramine (CYP2D6 substrate): Quinine (750 mg/day for 2 days) decreased the metabolism of desipramine in patients who were extensive CYP2D6 metabolizers, but had no effect in patients who were poor CYP2D6 metabolizers. Lower doses (80 mg to 400 mg) of quinine did not significantly affect the pharmacokinetics of other CYP2D6 substrates, namely, debrisoquine, dextromethorphan, and methoxyphenamine. Although clinical drug interaction studies have not been performed, antimalarial doses (greater than or equal to 600 mg) of quinine may inhibit the metabolism of other drugs that are CYP2D6 substrates (e.g., flecainide, debrisoquine, dextromethorphan, metoprolol, paroxetine). Patients taking medications that are CYP2D6 substrates with Anadin (Quinine Sulfate) should be monitored closely for adverse reactions associated with these medications.

Digoxin (P-gp substrate): In 4 healthy subjects who received digoxin (0.5 to 0.75 mg/day) during treatment with quinine (750 mg/day), a 33% increase in mean steady state AUC of digoxin and a 35% reduction in the steady state biliary clearance of digoxin were observed compared to digoxin alone. Thus, if Anadin (Quinine Sulfate) is administered to patients receiving digoxin, plasma digoxin concentrations should be closely monitored, and the digoxin dose adjusted, as necessary [see Warnings and Precautions (5.7) ].

Halofantrine: Although not studied clinically, quinine was shown to inhibit the metabolism of halofantrine in vitro using human liver microsomes. Therefore, concomitant administration of Anadin (Quinine Sulfate) is likely to increase plasma halofantrine concentrations [see Warnings and Precautions (5.3) ].

Mefloquine: In 7 healthy subjects who received mefloquine (750 mg) at 24 hours before an oral 600 mg dose of Anadin (Quinine Sulfate), the AUC of mefloquine was increased by 22% compared to mefloquine alone. In this study, the QTc interval was significantly prolonged in the subjects who received mefloquine and Anadin (Quinine Sulfate) 24 hours apart. The concomitant administration of mefloquine and Anadin (Quinine Sulfate) may produce electrocardiographic abnormalities (including QTc prolongation) and may increase the risk of seizures [see Warnings and Precautions (5.3) ].

Midazolam (CYP3A4 substrate): In 23 healthy subjects who received multiple doses of Anadin (Quinine Sulfate) 324 mg three times daily × 7 days with a single oral 2 mg dose of midazolam, the mean AUC and Cmax of midazolam and 1-hydroxymidazolam were not significantly affected. This finding indicates that 7-day dosing with Anadin (Quinine Sulfate) 324 mg every 8 hours did not induce the metabolism of midazolam.

Neuromuscular blocking agents (pancuronium, succinylcholine, tubocurarine): In one report, quinine potentiated neuromuscular blockade in a patient who received pancuronium during an operative procedure, and subsequently (3 hours after receiving pancuronium) received quinine 1800 mg daily. Quinine may also enhance the neuromuscular blocking effects of succinylcholine and tubocurarine [see Warnings and Precautions (5.5) ].

Ritonavir: In healthy subjects who received a single oral 600 mg dose of Anadin (Quinine Sulfate) with the 15th dose of ritonavir (200 mg every 12 hours for 9 days), the mean ritonavir AUC, Cmax, and elimination half-life were slightly but not significantly increased compared to when ritonavir was given alone. However, due to the significant effect of ritonavir on quinine pharmacokinetics, the concomitant administration of Anadin (Quinine Sulfate) capsules with ritonavir should be avoided [see also Drug Interactions (7.1) ].

Theophylline or aminophylline (CYP1A2 substrate): In 19 healthy subjects who received multiple doses of Anadin (Quinine Sulfate) 648 mg every 8 hours x 7 days with a single 300 mg oral dose of theophylline, the mean theophylline AUC was 10% lower than when theophylline was given alone. There was no significant effect on mean theophylline Cmax. Therefore, if Anadin (Quinine Sulfate) is co-administered to patients receiving theophylline or aminophylline, plasma theophylline concentrations should be monitored frequently to ensure therapeutic concentrations.

Warfarin and oral anticoagulants: Cinchona alkaloids, including quinine, may have the potential to depress hepatic enzyme synthesis of vitamin K-dependent coagulation pathway proteins and may enhance the action of warfarin and other oral anticoagulants. Quinine may also interfere with the anticoagulant effect of heparin. Thus, in patients receiving these anticoagulants, the prothrombin time (PT), partial thromboplastin time (PTT), or international normalization ratio (INR) should be closely monitored as appropriate, during concurrent therapy with Anadin (Quinine Sulfate).

7.3 Drug/Laboratory Interactions

Quinine may produce an elevated value for urinary 17-ketogenic steroids when the Zimmerman method is used.

Quinine may interfere with urine qualitative dipstick protein assays as well as quantitative methods (e.g., pyrogallol red-molybdate).

8 USE IN SPECIFIC POPULATIONS

  • Renal impairment: Reduce dose and dosing frequency for patients with severe chronic renal impairment.
  • Hepatic impairment: Closely monitor for adverse events. Quinine should not be administered in patients with severe (Child-Pugh C) hepatic impairment (2.3, 8.7, 12.3).
  • Pregnancy: Based on animal data may cause fetal harm. Use only if the potential benefit justifies the risk (8.1).
  • Nursing Mothers: Exercise caution when administering to a nursing woman (8.3).

8.1 Pregnancy

Pregnancy Category C

There are extensive published data but few well-controlled studies of Anadin (Quinine Sulfate) in pregnant women. Published data on over 1,000 pregnancy exposures to quinine did not show an increase in teratogenic effects over the background rate in the general population; however, the majority of these exposures were not in the first trimester. In developmental and reproductive toxicity studies, central nervous system (CNS) and ear abnormalities and increased fetal deaths occurred in some species when pregnant animals received quinine at doses about 1 to 4 times the human clinical dose. Quinine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

P. falciparum malaria carries a higher risk of morbidity and mortality in pregnant women than in the general population. Pregnant women with P. falciparum malaria have an increased incidence of fetal loss (including spontaneous abortion and stillbirth), preterm labor and delivery, intrauterine growth retardation, low birth weight, and maternal death. Therefore, treatment of malaria in pregnancy is important.

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

Quinine crosses the placenta with measurable blood concentrations in the fetus. In 8 women who delivered live infants 1 to 6 days after starting quinine therapy, umbilical cord plasma quinine concentrations were between 1.0 and 4.6 mg/L (mean 2.4 mg/L) and the mean (±SD) ratio of cord plasma to maternal plasma quinine concentrations was 0.32 ± 0.14. Quinine levels in the fetus may not be therapeutic. If congenital malaria is suspected after delivery, the infant should be evaluated and treated appropriately.

A study from Thailand (1999) of women with P. falciparum malaria who were treated with oral Anadin (Quinine Sulfate) 10 mg/kg 3 times daily for 7 days at anytime in pregnancy reported no significant difference in the rate of stillbirths at >28 weeks of gestation in women treated with quinine (10 of 633 women [1.6%]) as compared with a control group without malaria or exposure to antimalarial drugs during pregnancy (40 of 2201 women [1.8%]). The overall rate of congenital malformations (9 of 633 offspring [1.4%]) was not different for women who were treated with Anadin (Quinine Sulfate) compared with the control group (38 of 2201 offspring [1.7%]). The spontaneous abortion rate was higher in the control group (10.9%) than in women treated with Anadin (Quinine Sulfate) (3.5%) [OR = 3.1; 95% CI 2.1-4.7]. An epidemiologic survey that included 104 mother-child pairs exposed to quinine during the first 4 months of pregnancy, found no increased risk of structural birth defects was seen (2 fetal malformations [1.9%]). Rare and isolated case reports describe deafness and optic nerve hypoplasia in children exposed in utero due to maternal ingestion of high doses of quinine.

In animal developmental studies conducted in multiple animal species, pregnant animals received quinine by the subcutaneous or intramuscular route at dose levels similar to the maximum recommended human dose (MRHD; 32 mg/kg/day) based on body surface area (BSA) comparisons. There were increases in fetal death in utero in rabbits at maternal doses ≥ 100 mg/kg/day and in dogs at ≥ 15 mg/kg/day corresponding to dose levels approximately 0.5 and 0.25 times the MRHD respectively based on BSA comparisons. Rabbit offspring had increased rates of degenerated auditory nerve and spiral ganglion and increased rates of CNS anomalies such as anencephaly and microcephaly at a dose of 130 mg/kg/day corresponding to a maternal dose approximately 1.3 times the MRHD based on BSA comparison. Guinea pig offspring had increased rates of hemorrhage and mitochondrial change in the cochlea at maternal doses of 200 mg/kg corresponding to a dose level of approximately 1.4 times the MRHD based on BSA comparison. There were no teratogenic findings in rats at maternal doses up to 300 mg/kg/day and in monkeys at doses up to 200 mg/kg/day corresponding to doses approximately 1 and 2 times the MRHD respectively based on BSA comparisons.

In a pre- postnatal study in rats, an estimated oral dose of Anadin (Quinine Sulfate) of 20 mg/kg/day corresponding to approximately 0.1 times the MRHD based on BSA comparison resulted in offspring with impaired growth, lower body weights at birth and during the lactation period, and delayed physical development of teeth eruption and eye opening during the lactation period.

8.2 Labor and Delivery

There is no evidence that quinine causes uterine contractions at the doses recommended for the treatment of malaria. In doses several-times higher than those used to treat malaria, quinine may stimulate the pregnant uterus.

8.3 Nursing Mothers

There is limited information on the safety of quinine in breastfed infants. No toxicity was reported in infants in a single study where oral Anadin (10 mg/kg every 8 hours for 1 to 10 days) was administered to 25 lactating women. It is estimated from this study that breastfed infants would receive less than 2 to 3 mg per day of quinine base (< 0.4% of the maternal dose) via breast milk [see Clinical Pharmacology (12.3) ].

Although quinine is generally considered compatible with breastfeeding, the risks and benefits to infant and mother should be assessed. Caution should be exercised when administered to a nursing woman.

If malaria is suspected in the infant, appropriate evaluation and treatment should be provided. Plasma quinine levels may not be therapeutic in infants of nursing mothers receiving Anadin (Quinine Sulfate).

8.4 Pediatric Use

The safety and efficacy of Anadin (Quinine Sulfate) in pediatric patients under the age of 16 has not been established.

8.5 Geriatric Use

Clinical studies of Anadin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond to treatment differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

8.6 Renal Impairment

Clearance of quinine is decreased in patients with severe chronic renal failure. The dosage and dosing frequency should be reduced [see Dosage and Administration (2.2), Clinical Pharmacology (12.3) ].

8.7 Hepatic Impairment

In patients with severe hepatic impairment (Child-Pugh C), quinine oral clearance (CL/F) is decreased, volume of distribution (Vd/F) is increased, and half-life is prolonged, relative to subjects with normal liver function. Therefore, quinine is not indicated in patients with severe hepatic impairment and alternate therapy should be administered [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3) ].

Close monitoring is recommended for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment, as exposure to quinine may be increased relative to subjects with normal liver function [see Clinical Pharmacology (12.3) ].

10 OVERDOSAGE

Quinine overdose can be associated with serious complications, including visual impairment, hypoglycemia, cardiac arrhythmias, and death. Visual impairment can range from blurred vision and defective color perception, to visual field constriction and permanent blindness. Cinchonism occurs in virtually all patients with quinine overdose. Symptoms range from headache, nausea, vomiting, abdominal pain, diarrhea, tinnitus, vertigo, hearing impairment, sweating, flushing, and blurred vision, to deafness, blindness, serious cardiac arrhythmias, hypotension, and circulatory collapse. Central nervous system toxicity (drowsiness, disturbances of consciousness, ataxia, convulsions, respiratory depression and coma) has also been reported with quinine overdose, as well as pulmonary edema and adult respiratory distress syndrome.

Most toxic reactions are dose-related; however, some reactions may be idiosyncratic because of the variable sensitivity of patients to the toxic effects of quinine. A lethal dose of quinine has not been clearly defined, but fatalities have been reported after the ingestion of 2 to 8 grams in adults.

Quinine, like quinidine, has Class I antiarrhythmic properties. The cardiotoxicity of quinine is due to its negative inotropic action, and to its effect on cardiac conduction, resulting in decreased rates of depolarization and conduction, and increased action potential and effective refractory period. ECG changes observed with quinine overdose include sinus tachycardia, PR prolongation, T wave inversion, bundle branch block, an increased QT interval, and a widening of the QRS complex. Quinine's alpha-blocking properties may result in hypotension and further exacerbate myocardial depression by decreasing coronary perfusion. Quinine overdose has been also associated with hypotension, cardiogenic shock, and circulatory collapse, ventricular arrhythmias, including ventricular tachycardia, ventricular fibrillation, idioventricular rhythm, and torsades de pointes, as well as bradycardia, and atrioventricular block [see Warnings and Precautions (5), Clinical Pharmacology (12.3) ].

Quinine is rapidly absorbed, and attempts to remove residual Anadin (Quinine Sulfate) from the stomach by gastric lavage may not be effective. Multiple-dose activated charcoal has been shown to decrease plasma quinine concentrations [see Clinical Pharmacology (12.3) ].

Forced acid diuresis, hemodialysis, charcoal column hemoperfusion, and plasma exchange were not found to be effective in significantly increasing quinine elimination in a series of 16 patients.

11 DESCRIPTION

Anadin (Quinine Sulfate) (quinine sulfate) is a cinchona alkaloid chemically described as cinchonan-9-ol, 6'-methoxy-, (8α, 9R)-, sulfate (2:1) (salt), dihydrate with a molecular formula of (C20H24N2O2)2-H2SO4-2H2O and a molecular weight of 782.96.

The structural formula of Anadin (Quinine Sulfate) is:

Anadin (Quinine Sulfate) occurs as a white, crystalline powder that darkens on exposure to light. It is odorless and has a persistent very bitter taste. It is only slightly soluble in water, alcohol, chloroform, and ether.

Anadin (Quinine Sulfate) is supplied for oral administration as capsules containing 324 mg of the active ingredient Anadin (Quinine Sulfate) USP, equivalent to 269 mg free base. Inactive ingredients: corn starch, magnesium stearate, and talc.

Chemical Structure

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Quinine is an antimalarial agent [see Clinical Pharmacology ].

12.2 Pharmacodynamics

QTc interval prolongation was studied in a double-blind, multiple dose, placebo- and positive-controlled crossover study in young (N=13, 20 to 39 years) and elderly (N=13, 65 to 78 years) subjects. After 7 days of dosing with Anadin (Quinine Sulfate) 648 mg three times daily, the maximum mean (95% upper confidence bound) differences in QTcI from placebo after baseline correction was 27.7 (32.2) ms.

Prolongation of the PR and QRS interval was also noted in subjects receiving Anadin (Quinine Sulfate). The maximum mean (95% upper confidence bound) difference in PR from placebo after baseline-correction was 14.5 (18.0) ms. The maximum mean (95% upper confidence bound) difference in QRS from placebo after baseline-correction was 11.5 (13.3) ms. [see Warnings and Precautions (5.3) ].

12.3 Pharmacokinetics

Absorption

The oral bioavailability of quinine is 76 to 88% in healthy adults. Quinine exposure is higher in patients with malaria than in healthy subjects. After a single oral dose of Anadin, the mean quinine Tmax was longer, and mean AUC and Cmax were higher in patients with uncomplicated P. falciparum malaria than in healthy subjects, as shown in Table 1 below.

Healthy Subjects

(N = 23)

Mean ± SD

Uncomplicated P. falciparum Malaria Patients

(N = 15)

Mean ± SD

Dose (mg/kg)Anadin (Quinine Sulfate) dose was 648 mg (approximately 8.7 mg/kg) in healthy subjects; and 10 mg/kg in patients with malaria 8.7 10
Tmax (h) 2.8 ± 0.8 5.9 ± 4.7
Cmax (mcg/mL) 3.2 ± 0.7 8.4
AUC0–12 (mcg*h/mL) 28.0 73.0

Anadin (Quinine Sulfate) capsules may be administered without regard to meals. When a single oral 324 mg capsule of Anadin (Quinine Sulfate) was administered to healthy subjects (N=26) with a standardized high-fat breakfast, the mean Tmax of quinine was prolonged to about 4.0 hours, but the mean Cmax and AUC0-24h were similar to those achieved when Anadin (Quinine Sulfate) capsule was given under fasted conditions [see Dosage and Administration (2.1) ].

Distribution

In patients with malaria, the volume of distribution (Vd/F) decreases in proportion to the severity of the infection. In published studies with healthy subjects who received a single oral 600 mg dose of Anadin (Quinine Sulfate), the mean Vd/F ranged from 2.5 to 7.1 L/kg.

Quinine is moderately protein-bound in blood in healthy subjects, ranging from 69 to 92%. During active malarial infection, protein binding of quinine is increased to 78 to 95%, corresponding to the increase in α1-acid glycoprotein that occurs with malaria infection.

Intra-erythrocytic levels of quinine are approximately 30 to 50% of the plasma concentration.

Quinine penetrates relatively poorly into the cerebrospinal fluid (CSF) in patients with cerebral malaria, with CSF concentration approximately 2 to 7% of plasma concentration.

In one study, quinine concentrations in placental cord blood and breast milk were approximately 32% and 31%, respectively, of quinine concentrations in maternal plasma. The estimated total dose of quinine secreted into breast milk was less than 2 to 3 mg per day [see Use in Specific Populations (8.1, 8.3) ].

Metabolism

Quinine is metabolized almost exclusively via hepatic oxidative cytochrome P450 (CYP) pathways, resulting in four primary metabolites, 3-hydroxyquinine, 2´-quinone, O-desmethylquinine, and 10,11-dihydroxydihydroquinine. Six secondary metabolites result from further biotransformation of the primary metabolites. The major metabolite, 3-hydroxyquinine, is less active than the parent drug.

In vitro studies using human liver microsomes and recombinant P450 enzymes have shown that quinine is metabolized mainly by CYP3A4. Depending on the in vitro experimental conditions, other enzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1 were shown to have some role in the metabolism of quinine.

Elimination/Excretion

Quinine is eliminated primarily via hepatic biotransformation. Approximately 20% of quinine is excreted unchanged in urine. Because quinine is reabsorbed when the urine is alkaline, renal excretion of the drug is twice as rapid when the urine is acidic than when it is alkaline.

In various published studies, healthy subjects who received a single oral 600 mg dose of Anadin (Quinine Sulfate) exhibited a mean plasma clearance ranging from 0.08 to 0.47 L/h/kg (median value: 0.17 L/h/kg) with a mean plasma elimination half-life of 9.7 to 12.5 hours.

In 15 patients with uncomplicated malaria who received a 10 mg/kg oral dose of Anadin (Quinine Sulfate), the mean total clearance of quinine was slower (approximately 0.09 L/h/kg) during the acute phase of the infection, and faster (approximately 0.16 L/h/kg) during the recovery or convalescent phase.

Extracorporeal Elimination: Administration of multiple-dose activated charcoal (50 grams administered 4 hours after quinine dosing followed by 3 further doses over the next 12 hours) decreased the mean quinine elimination half-life from 8.2 to 4.6 hours, and increased the mean quinine clearance by 56% (from 11.8 L/h to 18.4 L/h) in 7 healthy adult subjects who received a single oral 600 mg dose of Anadin (Quinine Sulfate). Likewise, in 5 symptomatic patients with acute quinine poisoning who received multiple-dose activated charcoal (50 grams every 4 hours), the mean quinine elimination half-life was shortened to 8.1 hours in comparison to a half-life of approximately 26 hours in patients who did not receive activated charcoal [see Overdosage (10) ].

In 6 patients with quinine poisoning, forced acid diuresis did not change the half-life of quinine elimination (25.1 ± 4.6 hours vs. 26.5 ± 5.8 hours), or the amount of unchanged quinine recovered in the urine, in comparison to 8 patients not treated in this manner [see Overdosage (10) ].

Specific Populations

Pediatric Patients: The pharmacokinetics of quinine in children (1.5 to 12 years old) with uncomplicated P. falciparum malaria appear to be similar to that seen in adults with uncomplicated malaria. Furthermore, as seen in adults, the mean total clearance and the volume of distribution of quinine were reduced in pediatric patients with malaria as compared to the healthy pediatric controls. Table 2 below provides a comparison of the mean ± SD pharmacokinetic parameters of quinine in pediatric patients vs. healthy pediatric controls.

Healthy Pediatric Controlsage 1.5 to 12 years

(N = 5)

Mean ± SD

P. falciparum Malaria Pediatric Patients

(N = 15)

Mean ± SD

Tmax (h) 2.0 4.0
Cmax (mcg/mL) 3.4 ± 1.18 7.5 ± 1.1
Half-life (h) 3.2 ± 0.3 12.1 ± 1.4
Total CL (L/h/kg) 0.30 ± 0.04 0.06 ± 0.01
Vd (L/kg) 1.43 ± 0.18 0.87 ± 0.12

Geriatric Patients: Following a single oral dose of 600 mg Anadin (Quinine Sulfate), the mean AUC was about 38% higher in 8 healthy elderly subjects (65 to 78 years old) than in 12 younger subjects (20 to 35 years old). The mean Tmax and Cmax were similar in elderly and younger subjects after a single oral dose of Anadin (Quinine Sulfate) 600 mg. The mean oral clearance of quinine was significantly decreased, and the mean elimination half-life was significantly increased in elderly subjects compared with younger subjects (0.06 vs. 0.08 L/h/kg, and 18.4 hours vs. 10.5 hours, respectively). Although there was no significant difference in the renal clearance of quinine between the two age groups, elderly subjects excreted a larger proportion of the dose in urine as unchanged drug than younger subjects (16.6% vs. 11.2%).

After a single 648 mg dose or at steady state, following Anadin (Quinine Sulfate) 648 mg given three times daily for 7 days, no difference in the rate and extent of absorption or clearance of quinine was seen between 13 elderly subjects (65 to 78 years old) and 14 young subjects (20 to 39 years old). The mean elimination half-life was 20% longer in the elderly subjects (24.0 hours) than in younger subjects (20.0 hours). The steady state Cmax (±SD) and AUC0-8 (±SD) for healthy volunteers are 6.8 ± 1.24 mcg/mL and 48.8 ± 9.15 mcg*h/mL, respectively, following 7 days of oral Anadin (Quinine Sulfate) 648 mg three times daily. The steady state pharmacokinetic parameters in healthy elderly subjects were similar to the pharmacokinetic parameters in healthy young subjects.

Renal Impairment: Following a single oral 600 mg dose of Anadin (Quinine Sulfate) in otherwise healthy subjects with severe chronic renal failure not receiving any form of dialysis (mean serum creatinine = 9.6 mg/dL), the median AUC was higher by 195% and the median Cmax was higher by 79% than in subjects with normal renal function (mean serum creatinine = 1 mg/dL). The mean plasma half-life in subjects with severe chronic renal impairment was prolonged to 26 hours compared to 9.7 hours in the healthy controls. Computer assisted modeling and simulation indicates that in patients with malaria and severe chronic renal failure, a dosage regimen consisting of one loading dose of 648 mg Anadin (Quinine Sulfate) followed 12 hours later by a maintenance dosing regimen of 324 mg every 12 hours will provide adequate systemic exposure to quinine [see Dosage and Administration (2.2) ]. The effects of mild and moderate renal impairment on the pharmacokinetics and safety of Anadin (Quinine Sulfate) are not known.

Negligible to minimal amounts of circulating quinine in the blood are removed by hemodialysis or hemofiltration. In subjects with chronic renal failure (CRF) on hemodialysis, only about 6.5% of quinine is removed in 1 hour. Plasma quinine concentrations do not change during or shortly after hemofiltration in subjects with CRF [see Overdosage (10) ].

Hepatic Impairment: In otherwise healthy subjects with mild hepatic impairment (Child-Pugh A; N=10), who received a single 500 mg dose of Anadin (Quinine Sulfate), there was no significant difference in quinine pharmacokinetic parameters or exposure to the primary metabolite, 3-hydroxyquinine as compared to healthy controls (N=10). In otherwise healthy subjects with moderate hepatic impairment (Child-Pugh B; N=9) who received a single oral 600 mg dose of Anadin (Quinine Sulfate), the mean AUC increased by 55% without a significant change in mean Cmax, as compared to healthy volunteer controls (N=6). In subjects with hepatitis, the absorption of quinine was prolonged, the elimination half-life was increased, the apparent volume of distribution was higher, but there was no significant difference in weight-adjusted clearance. Therefore, in patients with mild to moderate hepatic impairment, dosage adjustment is not needed, but patients should be monitored closely for adverse effects of quinine [see Use in Specific Populations (8.7) ].

In subjects with severe hepatic impairment (Child-Pugh C; N=10), quinine oral clearance (CL/F) was reduced as was formation of the primary 3-hydroxyquinine metabolite. Volume of distribution (Vd/F) was higher and the plasma elimination half-life was increased. Therefore, quinine is not indicated in this population and alternate therapy should be administered [see Dosage and Administration (2.3) ].

12.4 Microbiology

Mechanism of Action

Quinine inhibits nucleic acid synthesis, protein synthesis, and glycolysis in Plasmodium falciparum and can bind with hemazoin in parasitized erythrocytes. However, the precise mechanism of the antimalarial activity of Anadin (Quinine Sulfate) is not completely understood.

Activity In Vitro and In Vivo

Anadin (Quinine Sulfate) acts primarily on the blood schizont form of P. falciparum. It is not gametocidal and has little effect on the sporozoite or pre-erythrocytic forms.

Drug Resistance

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

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Carcinogenicity studies of quinine have not been conducted.

Mutagenesis

Genotoxicity studies of quinine were positive in the Ames bacterial mutation assay with metabolic activation and in the sister chromatid exchange assay in mice. The sex-linked recessive lethal test performed in Drosophila, the in vivo mouse micronucleus assay, and the chromosomal aberration assay in mice and Chinese hamsters were negative.

Impairment of Fertility

Published studies indicate that quinine produces testicular toxicity in mice at a single intraperitoneal dose of 300 mg/kg corresponding to a dose of approximately 0.75 times the maximum recommended human dose (MRHD; 32 mg/kg/day) and in rats at an intramuscular dose of 10 mg/kg/day, 5 days/week, for 8 weeks corresponding to a daily dose of approximately 0.05 times the MRHD based on body surface area (BSA) comparisons. The findings include atrophy or degeneration of the seminiferous tubules, decreased sperm count and motility, and decreased testosterone levels in the serum and testes. There was no effect on testes weight in studies of oral doses of up to 500 mg/kg/day in mice and 700 mg/kg/day in rats (approximately 1.2 and 3.5 times the MRHD respectively based on BSA comparisons). In a published study in 5 men receiving 600 mg of quinine TID for one week, sperm motility was decreased and percent sperm with abnormal morphology was increased; sperm count and serum testosterone were unaffected.

14 CLINICAL STUDIES

Quinine has been used worldwide for hundreds of years in the treatment of malaria. Thorough searches of the published literature identified over 1300 references to the treatment of malaria with quinine, and from these, 21 randomized, active-controlled studies were identified which evaluated oral quinine monotherapy or combination therapy for treatment of uncomplicated P. falciparum malaria. Over 2900 patients from malaria-endemic areas were enrolled in these studies, and more than 1400 patients received oral quinine. The following conclusions were drawn from review of these studies:

In areas where multi-drug resistance of P. falciparum is increasing, such as Southeast Asia, cure rates with 7 days of oral quinine monotherapy were at least 80%; while cure rates for 7 days of oral quinine combined with an antimicrobial agent (tetracycline or clindamycin) were greater than 90%. In areas where multi-drug resistance of the parasite was not as widespread, cure rates with 7 days of quinine monotherapy ranged from 86 to 100%. Cure was defined as initial clearing of parasitemia within 7 days without recrudescence by day 28 after treatment initiation. P. falciparum malaria that is clinically resistant to quinine has been reported in some areas of South America, Southeast Asia, and Bangladesh, and quinine may not be as effective in those areas.

Completion of a 7-day oral quinine treatment regimen may be limited by drug intolerance, and shorter courses (3 days) of quinine combination therapy have been used. However, the published data from randomized, controlled clinical trials for shorter regimens of oral quinine in conjunction with tetracycline, doxycycline, or clindamycin for treatment of uncomplicated P. falciparum malaria is limited, and these shorter course combination regimens may not be as effective as the longer regimens.

16 HOW SUPPLIED / STORAGE AND HANDLING

16.1 How Supplied

Anadin capsules USP, 324 mg are available as clear/clear capsules imprinted AR 102:

Bottles of 30 NDC 13310-153-07
Bottles of 100 NDC 13310-153-01
Bottles of 500 NDC 13310-153-05
Bottles of 1000 NDC 13310-153-10

16.2 Storage

Store at 20° to 25°C (68° to 77°F).

Dispense in a tight container as defined in the USP.

17 PATIENT COUNSELING INFORMATION

See FDA-approved Medication Guide

17.1 Dosing Instructions

Patients should be instructed to:

  • Take all of the medication as directed.
  • Take no more of the medication than the amount prescribed.
  • Take with food to minimize possible gastrointestinal irritation.

If a dose is missed, patients should also be instructed not to double the next dose. If more than 4 hours has elapsed since the missed dose, the patient should wait and take the next dose as previously scheduled.

17.2 FDA-Approved Medication Guide

MEDICATION GUIDE

Anadin (Quinine Sulfate)®

(kwol-a-kwin)

(Quinine sulfate) Capsules

Read the Medication Guide that comes with Anadin (Quinine Sulfate) ® before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. You and your healthcare provider should talk about Anadin (Quinine Sulfate) ® when you start taking it and at regular checkups. Anadin (Quinine Sulfate) ® is not approved for the treatment of night-time leg cramps.

What is the most important information I should know about Anadin (Quinine Sulfate)®?

Anadin (Quinine Sulfate)® used to treat or prevent leg cramps may cause serious side effects or even death.

  • Anadin (Quinine Sulfate) ® may cause your blood cell (platelet) count to drop causing serious bleeding problems. In some people, serious kidney problems can happen.
  • Anadin (Quinine Sulfate)® may cause problems with your heart rhythm that can lead to death.
  • Anadin (Quinine Sulfate)® may cause serious allergic reactions.

Call your healthcare provider right away if you have:

  • easy bruising
  • severe nose bleed
  • blood in urine or stool
  • bleeding gums
  • appearance of unusual purple, brown or red spots on your skin (bleeding under your skin)
  • rash
  • hives
  • severe itching
  • severe flushing
  • swelling of your face
  • trouble breathing
  • chest pain
  • rapid heartbeat
  • irregular heart rhythm
  • weakness
  • sweating
  • nervousness

Taking Anadin (Quinine Sulfate)® with some other medicines can increase the chance of serious side effects. Tell your healthcare provider if you take any other medicines.

Certain medicines can cause the blood levels of Anadin (Quinine Sulfate) ® to be too high or too low in your body. It is important for you to tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements.

Anadin (Quinine Sulfate)® and other medicines may affect each other causing serious side effects or death. Even medicines that you may take for a short period of time, such as antibiotics, can mix in your blood with Anadin (Quinine Sulfate)® and cause serious side effects or death. Do not start taking a new medicine without telling your healthcare provider or pharmacist.

What is Anadin (Quinine Sulfate)®?

Anadin (Quinine Sulfate) ® is a prescription medication used to treat malaria (uncomplicated) caused by the parasite Plasmodium falciparum.

Anadin (Quinine Sulfate)® is Not approved to:

  • Prevent malaria
  • Treat severe or complicated malaria
  • Prevent or treat night-time leg cramps

It is not known if Anadin (Quinine Sulfate)® is safe and works in children younger than 16 years old.

Who should not take Anadin (Quinine Sulfate)®?

Do not take Anadin (Quinine Sulfate)® if you have:

  • certain heart rhythm problems (atrial fibrillation) or abnormal electrocardiogram (ECG) (QT prolongation).
  • low levels of an enzyme called Glucose-6-phosphate dehydrogenase (G6PD).
  • an autoimmune disease (myasthenia gravis) that leads to muscle weakness.
  • had allergic reactions to quinine, quinidine, or mefloquine (Lariam®).
  • had serious side effects to quinine (QUALAQUIN®), such as low platelets, which are necessary for your blood to clot.
  • an inflammation of the nerve important for vision (optic neuritis).

What should I tell my healthcare provider before starting Anadin (Quinine Sulfate)®?

Before you take Anadin (Quinine Sulfate)®, tell your healthcare provider if you:

  • Have heart problems.
  • Have kidney problems.
  • Have liver problems.
  • Have any other medical condition.
  • Are pregnant or could be pregnant. Treatment of malaria is important because it can be a serious disease for a pregnant woman and her unborn baby. Your healthcare provider can tell you more about the benefits and risks of taking this medication during pregnancy. Low blood sugar (hypoglycemia) can be seen in pregnant women while taking Anadin (Quinine Sulfate)®. This can include sweating, weakness, nausea, vomiting, or confusion. You and your healthcare provider can decide if Anadin (Quinine Sulfate) ® is right for you.
  • Are breast-feeding. Small amounts of Anadin (Quinine Sulfate) ® can pass into your breast milk. You and your healthcare provider can decide if you should breastfeed while taking Anadin (Quinine Sulfate) ® .

Tell your healthcare provider about all the medicines you take, including prescription medicines, vitamins and herbal supplements.

How should I take Anadin (Quinine Sulfate)®?

  • Take Anadin (Quinine Sulfate) ® exactly as your healthcare provider tells you to take it.
  • Your healthcare provider will tell you how many Anadin (Quinine Sulfate)® capsules to take and when to take them.
  • To lower the chance of stomach upset, take Anadin (Quinine Sulfate)® with food.
  • Finish all the Anadin (Quinine Sulfate) ® that is prescribed even if you feel better. Do not stop taking the medication without talking to your healthcare provider.
  • Do not take more than the amount prescribed. Do not take more than 2 capsules at one time or more than 3 doses in one day. If you take more than the prescribed dose, call your healthcare provider right away.
  • If you forget to take Anadin (Quinine Sulfate)®, do not double the next dose. If it has been more than 4 hours since the missed dose, just wait and take the regular dose at the next scheduled time. Call your healthcare provider if you are not sure what to do.
  • If you take too much Anadin (Quinine Sulfate)®, call your healthcare provider or go to the nearest emergency room right away.

Call your healthcare provider right away if:

  • If you feel worse, or if you do not start feeling better within 1 or 2 days of starting to take Anadin (Quinine Sulfate)®.
  • If your fever comes back after finishing treatment with Anadin (Quinine Sulfate)®.

What are the possible side effects of Anadin (Quinine Sulfate)®?

Anadin (Quinine Sulfate)® may cause serious side effects.

  • See "What is the most important information I should know about Anadin (Quinine Sulfate) ®" section.
  • Low blood sugar (hypoglycemia). This can include sweating, weakness, nausea, vomiting, or confusion.

Common side effects with Anadin (Quinine Sulfate) ® include:

  • headache
  • sweating
  • flushing
  • nausea
  • ringing in your ears
  • diarrhea
  • deafness
  • hearing loss
  • dizziness (vertigo)
  • blurred vision
  • changes in how you see color
  • vomiting
  • stomach pain
  • blindness

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all of the possible side effects of Anadin (Quinine Sulfate) ® . For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Anadin (Quinine Sulfate)®?

  • Keep the capsules in a tightly closed container.
  • Do not refrigerate or freeze.
  • Store at 20°C to 25°C (68ºF to 77°F).

Keep Anadin (Quinine Sulfate)® and all medicines out of the reach of children.

General Information about Anadin (Quinine Sulfate)®

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Anadin (Quinine Sulfate) ® for a condition for which it was not prescribed. Do not give Anadin (Quinine Sulfate) ® to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about Anadin (Quinine Sulfate) ® . If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about Anadin (Quinine Sulfate) ® that is written for healthcare professionals.

For more information, go to www. QUALAQUIN.com or call 1-888-351-3786.

What are the ingredients in Anadin (Quinine Sulfate)®?

Active Ingredients: Anadin (Quinine Sulfate), USP

Inactive Ingredients: Corn starch, magnesium stearate, talc

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured for:

AR SCIENTIFIC, INC.

Philadelphia, PA 19124 USA

by:

MUTUAL PHARMACEUTICAL COMPANY, INC.

Philadelphia, PA 19124 USA

Rev 23, April 2013

PRINCIPAL DISPLAY PANEL - 324 mg Capsule Bottle Label

100 CAPSULES

NDC 13310-153-01

Anadin (Quinine Sulfate) ®

Anadin (Quinine Sulfate)

capsules USP

324 mg

DISPENSE THE ACCOMPANYING

MEDICATION GUIDE TO EACH PATIENT

AR

SCIENTIFIC

Rx only

Anadin pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Anadin available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Anadin destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Anadin Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Anadin pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."VIVARIN (CAFFEINE) TABLET [MEDA CONSUMER HEALTHCARE INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."BUFFERIN LOW DOSE BUFFERED ASPIRIN (ASPIRIN) TABLET [NOVARTIS CONSUMER HEALTH, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."QUALAQUIN (QUININE SULFATE) CAPSULE [AR SCIENTIFIC INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Anadin?

Depending on the reaction of the Anadin after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Anadin not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Anadin addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sdrugs.com conducted a study on Anadin, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Anadin consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Rachana Salvi, MD Pharmacology

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