Primaquine

259.35

259.35

201-987-2

27296

DTXSID8023509

Viscous liquid

P - Antiparasitic products, insecticides and repellents

2933499090

60.2

2.1

Solid

1.1±0.1 g/cm3

<25 °C

177 °C

226.6±28.7 °C

1.616

718.4g/L(25 ºC)

9.9X10-6 mm Hg at 25 deg C (est)

LD50 oral in mouse: 100mg/kg

Henry's Law constant = 1X10-14 atm-cu m/mole at 25 °C (est)

pKa1 = 2.9 (aromatic amine); pKa2 = 4.2 (secondary amine); pKa3 = 9.9 (primary amine) (est)

Upon decomposition emits NOx|Hydroxy radical reaction rate constant= 2.5X10-10 cu cm/molec-sec at 25 °C (est)|Yellow crystals from 90% ethanol. mp 197-198 °C. Moderately soluble in water /Phosphate/|Yellow crystals from 80% ethanol. mp 182-185 °C /Oxalate/

Primaquine phosphate tablets should be stored in well-closed, light-resistant containers at a temperature less than 40 deg C, preferably between 15-30 deg C.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl primaquine phosphate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Primaquine phosphate/

IDENTIFICATION: Primaquine phosphate is used to treat malaria caused by Plasmodium virax. Primaquine is an orange-red, odorless crystalline powder which has a bitter taste It is soluble in water and it is practically insoluble in alcohol, chloroform and ether. For elimination of primary and secondary exoerythrocytic stages of Plasmodium vivax, Plasmodium malariae and Plasmodium ovale and the primary exoerythrocytic forms only of Plasmodium falciparum. Primaquine must always be given in conjunction with full doses of a 4-aminoquinoline. HUMAN EXPOSURE: Main risks and target organs: Target organs are: cardiovascular, hematological system, and gastrointestinal. Acute, dose-dependent methemoglobinemia and hemolytic anemia occurs in persons with a deficiency of glucose-6-phosphate dehydrogenase (G6PD); leucopenia or agranulocytosis may also occur. Adverse effects with therapeutic doses are usually mild. Summary of clinical effects: Toxic manifestations include cardiovascular disturbances, especially ventricular dysrhythmias, abdominal cramps, vomiting, burning epigastric distress, headache, confusion, cyanosis, methemoglobinemia, leucocytosis or leucopenia, and anemia. Granulocytopenia, acute hemolytic anemia and acute hemolysis may occur in individuals who are hypersensitive to primaquine. Contraindications: The balance of risk and benefit should be considered when primaquine is administered under the following conditions: in acutely ill patients suffering from systemic disease characterized by a tendency to granulocytopenia (for example, patients with arthritis or lupus erythematosus). Agents capable of depressing the myeloid elements of the bone marrow (antineoplastic agents, colchicine, gold salts, penicillamine, phenylbutazone, quinacrine). Individuals who have shown previous idiosyncratic reaction to primaquine, individuals with a history of favism or acute haemolytic anaemia. Individuals with G6PD deficiency or NADH methemoglobin reductase deficiency; primaquine should be discontinued immediately if hemolysis occurs. Routes of entry: Oral: Oral absorption is the only common cause of intoxication. Absorption by route of exposure: Primaquine is readily absorbed from the gastrointestinal tract. The plasma concentration peaks within 1 to 3 hr after ingestion but is negligibly low after 24 hr Considerable inter-individual variation in peak plasma concentrations of primaquine has been reported with the same dose of the drug. Distribution by route of exposure: Primaquine is extensively distributed into body tissues. About 75% of primaquine in plasma is bound to proteins and high concentrations occur in erythrocytes. Primaquine crosses the placenta but it is uncertain whether significant amounts occur in breast milk. Biological half-life by route of exposure: Primaquine has a plasma elimination half-life of 3.7 to 9.6 hr in healthy adults. Metabolism: Primaquine is not subject to extensive first pass metabolism. However, it is readily metabolized in the liver to three metabolites: 8-(3-carboxyl-1-methyl-propylamino)-6-methoxy-quinoline, 5-hydroxy primaquine and 5-hydroxy-6-desmethyl-primaquine. The carboxyl derivative is the major metabolite found in plasma; it accumulates during repeated administration, when the plasma concentration greatly exceeds that of unchanged primaquine. These metabolites have appreciably less antimalarial activity than primaquine but their haemolytic activity, as assessed by formation of methemoglobin in vitro, is greater than that of the parent compound. Elimination by route of exposure: Only 3.6% of the dose of primaquine is excreted as unchanged drug. The principal metabolite is carboxyprimaquine. Mode of action: Toxicodynamics: Primaquine may cause hemolysis and methemoglobinemia. Certain ethnic groups, especially those arising in the Mediterranean basin, are more susceptible to these effects and primaquine sensitivity occurs in persons with G6PD deficiency. G6PD deficiency is genetically acquired; there are a large number of variants in which the extent of the deficiency differs. The sensitivity of individuals to primaquine therefore varies. G6PD is an enzyme which protects the erythrocyte from the direct oxidative effects of some drugs and chemicals by maintaining intracellular stores of reduced glutathione. In people who are G6PD deficient, oxidation of hemoglobin leads to precipitation within the cell, producing characteristic inclusions called Heinz bodies; increased oxidation of hemoglobin also produces methemoglobinemia. There is an increase in the generation of free radicals which also contribute to cellular damage. These effects ultimately cause hemolysis. Pharmacodynamics: The exact mechanism of anti-malarial activity of primaquine has not been determined, but the drug appears to bind to plasmodial DNA and interfere with its function. Human data: Adults: The toxicity of primaquine phosphate is dose-dependent; weekly administration (in combination with chloroquine) is less toxic than daily administration. Serious hematologic reactions may occur in some people with a G6PD deficiency even at the low weekly doses of primaquine used in combination with chloroquine for the prophylaxis of malaria. This occurs primarily in patients with a family or personal history of favism. Methemoglobinemia is more common in individuals with nicotinamide adenine dinucleotide methemoglobin reductase deficiency. About 10% of the black population with G6PD deficiency develop anaemia due to intravascular hemolysis at daily dose levels of 15 mg (base) and higher. Some darker-skinned Mediterranean populations are more sensitive than blacks. Teratogenicity: No reports are available to associate primaquine with congenital defects. Interactions: Primaquine should not be administered concurrently with any other drug that is likely to induce hemolysis or bone marrow depression (see section 4.3) as this may increase the risk of toxicity. Concurrent use of primaquine with bone marrow depressants may increase the risk of leukopenia. If concurrent use is essential, close observation for myelotoxicity should be considered. The toxicity of primaquine appears to be potentiated by antimalarial agents that are structurally similar (for example, quinacrine). Primaquine should not be administered to patients who have received quinacrine within the previous 3 months. Although primaquine inhibits the elimination of drugs which undergo oxidative metabolism (for example, antipyrine), therapeutic doses have no effect on paracetamol metabolism. The combination of chloroquine and primaquine with dapsone may prevent hemolysis in G6PD deficient subjects. The antimalarial effects of quinacrine and primaquine in various test organisms are synergistic with many antibiotics. After administration of primaquine, the metabolism of antipyrine (calculated from 0 to 24 h) to its 3 main metabolites, 3 hydroxymethyl-antipyrine, 4 hydroxy-antipyrine and norantipyrine, is significantly reduced. There is no selective effect on a particular metabolic pathway. Main adverse effects: Gastrointestinal tract: Dose-related gastrointestinal symptoms include anorexia, nausea, vomiting, epigastric distress, and abdominal cramps. Hematological system: Acute hemolytic anemia occurs most frequently in G6P Ddeficient individuals. It is usually self-limiting but in severe cases blood transfusion may be necessary. Methemoglobinemia, agranulocytosis, granulocytopenia and leucopenia are also reported. Methemoglobinemia can be severe in people who are nicotinamide dinucleotide (NADH) methemoglobin reductase deficient. Cardiovascular system: Hypertension and arrhythmias have been reported. Other: Headache, interference with visual accommodation and pruritus have been reported with primaquine. Adverse CNS effects, including depression and confusion, can also occur. Clinical effects: Acute poisoning: Ingestion: Toxic manifestations such as methemoglobinemia and cyanosis occur in most subjects; adverse gastrointestinal effects occur at higher doses. These doses also cause severe hematologic reactions such as leucopenia, anemia and intravascular hemolysis. Chronic poisoning: Ingestion: The adverse effects associated with chronic administration are similar to those which occur in acute poisoning. Course, prognosis, cause of death: Course: Commonly, symptoms of overdoses are nausea, abdominal pain, sometimes vomiting and jaundice. Hemolytic anemia may occur in G6PD deficiency but is usually self-limiting. Prognosis: If patient survives for 48 h recovery is likely. Death: Cardio-circulatory arrest may occur within 1 to 2 h of ingestion due to ventricular dysrhythmia or asystole. Hypotension is common and may progress rapidly to cardiogenic shock with increased central venous pressure. Hypertension and cardiac arrhythmias have been reported on rare occasions. Systematic description of clinical effects Cardiovascular: Based on its anti-arrhythmic activity in mice, primaquine is predicted to have quinidine like cardiotoxicity. Hypertension and cardiac arrhythmias have been reported on rare occasions. Respiratory: Respiratory arrest secondary to circulatory arrest or severe shock may occur within 1 to 2 hr following overdose. Neurological: CNS: In severe cases, headache, mental depression and confusion occur, especially in persons with prior exposure to chloroquine. Gastrointestinal: Abdominal cramps and epigastric distress have been reported. Hepatic: Hepatic function is unaffected. Dermatological: Pruritus and urticaria. Eye, ear, nose, throat: local effects: Diplopia; visual disturbances; blurred vision; irreversible changes to the cornea and retina; optic neuritis. Hematological: Toxic doses of primaquine induce marked bone marrow depression, methemoglobinemia, agranulocytosis and hemolytic anemia. Hemolytic anemia is commonest in persons with G6PD deficiency. The effects are more pronounced in the B-type G6PD deficiency (the Mediterranean type) than in the A-type (the type mainly present among black American and African populations) Immunological: Primaquine may also cause immunosuppression Metabolic: Fluid and electrolyte disturbances: Hypokalemia is common in severe intoxication. Others: Hypo- or hyperthermia and hypo- or hyperglycemia have been reported. Special risks: Pregnancy: Primaquine should be withheld from women with G6PD deficiency who are pregnant. If prophylaxis or treatment is essential, the possible benefits should outweigh the potential risks. Transplacental transfer of primaquine to a fetus with G6PD deficiency may result in life-threatening anemia and methemoglobinemia in utero. Breast-feeding: It is not known whether primaquine is excreted in breast milk. However, problems in man have not been documented. Enzyme deficiency: Primaquine should be used with caution in patients with G6PD deficiency who are receiving other drugs likely to induce hemolysis, (for example, nitrites, sulfonamides). /Primaquine phosphate/

Despite use for more than 50 years, primaquine has not been linked to significant serum aminotransferase elevations or to clinically apparent acute liver injury. Primaquine can cause hemolysis in patients with G6PD deficiency, which can result in mild jaundice.

Because quinacrine appears to potentiate the toxicity of antimalarial agents that are structurally related to primaquine, concomitant administration of quinacrine and primaquine is contraindicated and primaquine should not be administered to patients who have recently received quinacrine.|Aluminum and magnesium salts decrease the GI absoption of /primaquine/.|Concurrent use of primaquine with bone marrow depressants may increase the leukopenic effect; if concurrent use is require, close observation for myelotoxic effects should be considered.|Concurrent use of primaquine with other hemolytics may increase the potential for toxic side effects.

Methemoglobinemia can occur even with usual doses of primaquine ... and can be severe in individuals with congenital deficiency of nicotinamide adenine dinucleotide (NADH) methemoglobin reductase.|Therapeutic or higher doses of primaquine, via its oxidative metabolites, may cause acute hemolysis and hemolytic anemia in humans with glucose-6-phosphate dehydrogenase (G6PD) deficiency ... About 11% of African Americans have the A- variant ... which makes them vulnerable to hemolysis caused by prooxidant drugs such as primaquine. Sensitivity of erythrocytes to primaquine can be even more severe in some darker-hued Caucasian ethnic groups, including Sardinians, Sephardic Jews, Greeks, and Iranians. Because primaquine sensitivity is inherited by a gene on the X chromosome, hemolysis often is of intermediate severity in heterozygous females who have 2 populations of red cells, one normal and the other deficient in G6PD. Due to "variable penetrance," such females may be less frequently affected than predicted.

Primaquine's production and use as an antimalarial(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 5X10+4(SRC), determined from a structure estimation method(2), indicates that primaquine is expected to be immobile in soil(SRC). The pKa of primaquinex is 9.9(3), indicating that this compound will primarily exist in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Cations do not volatilize from moist soil surfaces(SRC). Primaquine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.9X10-6 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data were not available(2005, SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 5X10+4(SRC), determined from a structure estimation method(2), indicates that primaquine is expected to adsorb to suspended solids and sediment(SRC). The pKa of primaquine is 9.9(3), indicating that this compound will primarily exist in the cation form at pH values of 5 to 9 and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Cations do not volatilize from water surfaces. According to a classification scheme(5), an estimated BCF of 53(SRC), from an estimated log Kow of 3.15(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is moderate, assuming the compound is not metabolized by the organism(SRC). Biodegradation data were not available(SRC, 2005).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), primaquine, which has an estimated vapor pressure of 9.9X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase primaquine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 1.5 hours(SRC), calculated from its rate constant of 2.5X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase primaquine may be removed from the air by wet and dry deposition(SRC). Primaquine contains chromophores that may absorb at wavelengths >290 nm and therefore it may be susceptible to direct photolysis by sunlight; however, the exact rate of this reaction is not known(SRC).

The rate constant for the vapor-phase reaction of primaquine with photochemically-produced hydroxyl radicals has been estimated as 2.5X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1.5 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Primaquine is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(2). Primaquine contains chromophores that may absorb at wavelengths >290 nm and therefore it may be susceptible to direct photolysis by sunlight; however, the exact rate of this reaction is not known(SRC).

An estimated BCF of 53 was calculated for primaquine(SRC), using an estimated log Kow of 3.15(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC), provided the compound is not metabolized by the organism(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of primaquine can be estimated to be 5X10+4(SRC). According to a classification scheme(2), this estimated Koc value suggests that primaquine is expected to be immobile in soil. The estimated pKa of primaquine is 9.9(3), indicating that this compound will primarily exist in the cation form in the environment and cations generally adsorb more strongly to organic carbon and clay than their neutral counterparts(4).

An estimated pKa of 9.9(1) indicates primaquine will exist almost entirely in the cation form at pH values of 5 to 9 and therefore, volatilization from moist soil and water surfaces is not expected to be an important fate process. Primaquine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.9X10-6 mm Hg(SRC), determined from a fragment constant method(2).

While data specific to primaquine were not available(SRC, 2005), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through subsoils(1).

Occupational exposure to primaquine may occur through dermal contact with this compound at workplaces where primaquine is produced or used. Exposure to primaquine among the general population may be limited to those administered the drug as an antimalarial. (SRC)

For the treatment of malaria.|FDA Label

Primaquine is an aminoquinoline that has been used for the prevention and therapy of malaria for more than 50 years. Primaquine is not associated with serum enzyme elevations during therapy and has yet to be linked to instances of clinically apparent acute liver injury.

Antimalarial Agents

Mesh Heading: Antimalarials|THERAP CAT: Antimalarial|Primaquine is an 8-aminoquinoline and is effective against intrahepatic forms of all types of malaria parasite. It is used to provide radical cure of P. vivax and P. ovale malaria, in combination with a blood schizontocide for the erythrocytic parasites. Primaquine is also gametocytocidal against P. falciparum and has significant blood stage activity against P. vivax (and some against asexual stages of P. falciparum). The mechanism of action is unknown.|Primaquine is indicated for the prevention of relapses (radical cure) of malaria caused Plasmodium vivax (and Plasmodium ovale). Primaquine is also effective against the gametocytes of P. falciparum. /Included in the US product labeling/|For more Therapeutic Uses (Complete) data for PRIMAQUINE (6 total), please visit the HSDB record page.

Acute hemolytic anemia may occur if primaquine is administered to patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. The severity of hemolytic anemia depends on the dose of the drug and the specific genetic defect in the individual with G-6-PD deficiency. In American and African Blacks with G-6-PD deficiency, hemolysis may be mild, self-limiting, and asymptomatic; however, in individuals of Mediterranean or certain Oriental extractions, hemolysis may be severe. ... Hemolytic anemia may also occur if primaquine is administered to individuals with other defects of the erythrocytic pentose phosphate pathway of glucose metabolism or in patients with certain hemoglobinopathies. Primaquine should be discontinued immediately if evidence of hemolytic anemia occurs (e.g., darkening of urine, marked fall in hemoglobin level or erythrocyte count).|Methemoglobinemia occurs occasionally, especially when the drug is administered to patients with NADH methemoglobin reductase deficiency.|Mild anemia, leukocytosis, and leukopenia have been reported occasionally with primaquine, and agranulocytosis has been reported rarely.|Nausea, vomiting, epigastric distress, and mild to moderate abdominal cramps occur occasionally with primaquine. Adverse GI effects may be lessened by administering primaquine with meals.|For more Drug Warnings (Complete) data for PRIMAQUINE (14 total), please visit the HSDB record page.

In vivo assessment suggests that tolerance of P. vivax to primaquine in East Asia and Oceania is greater than elsewhere.|P. vivax malaria resistant to primaquine has been induced by using subtherapeutic doses of the drug; however, resistance to the drug has been reported only occasionally.

Primaquine is an antimalarial agent and is the essential co-drug with chloroquine in treating all cases of malaria. In the blood, malaria parasites break down a part of the red blood cells known as haemoglobin. When this happens haemoglobin is divided into two parts; haem and globin. Haem is toxic to the malaria parasite. To prevent it from being damaged, the malaria parasite produces an chemical which converts the toxic haem into a non-toxic product. Primaquine acts by interfering with a part of the parasite (mitochondria) that is responsible for supplying it with energy. Without energy the parasite dies. This stops the infection from continuing and allows the person to recover. Primaquine kills the intrahepatic form of Plasmodium vivax and Plasmodium ovale, and thereby prevents the development of the erythrocytic forms that are responsible for relapses (it also kills gametocytes). Primaquine is not used in the prevention of malaria, only in the treatment. It has insignificant activity against the asexual blood forms of the parasite and therefore it is always used in conjunction with a blood schizonticide and never as a single agent. Primaquine has gametocytocidal activity against all plasmodia, including P. falciparum.

Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585) (See all compounds classified as Antimalarials.)

Rapidly absorbed; Bioavailability is approximately 96%.|Primaquine is well absorbed from the GI tract. Following oral administration, peak plasma concentrations of the drug generally are attained within 6 hours; plasma concentrations generally are negligible after 24 hours. Considerable interindividual variation in peak plasma concentrations of primaquine have been reported with the same dose of the drug.|Although specific information on the distribution of primaquine into body tissues and fluids is not available, the drug appears to be widely distributed in the body following oral administration. Primaquine has an apparent volume of distribution of about 150 to 250 L in healthy adults.|Extensively distributed; ... the whole-blood-to-plasma distribution ratio was 0.93 in one study of patients being treated with 15 mg (base) daily for 14 days.|For more Absorption, Distribution and Excretion (Complete) data for PRIMAQUINE (7 total), please visit the HSDB record page.

The principal metabolite of primaquine is carboxyprimaquine, and plasma concentrations of the metabolite greatly exceed those of unchanged primaquine.|It is not known whether /carboxyprimaquine/ has antimalarial activity.|Primaquine is rapidly metabolized ... Three identified oxidative metabolites ... are 8-(3-carboxyl-1-methylpropylamino)-6-methoxyquinoline, 5-hydroxy primaquine, and 5-hydroxy-6-desmethylprimaquine. The carboxyl derivative is the major metabolite found in human plasma. After a single dose it reaches concentrations in plasma more than 10 times those of primaquine; this nontoxic metabolite also is eliminated more slowly and accumulates with multiple doses ... The 3 metabolites ... appear to have appreciably less antimalarial activity than does primaquine. However, except for the carboxyl derivative, their hemolytic activity, as assessed by formation of methemoglobin in vitro, is greater than that of the parent compound.

3.7-7.4 hours|Primaquine has a plasma half-life of 3.7-9.6 hours in healthy adults.|/The half-life of/ carboxyprimaquine is 22 to 30 hours.

Primaquine's mechanism of action is not well understood. It may be acting by generating reactive oxygen species or by interfering with the electron transport in the parasite. Also, although its mechanism of action is unclear, primaquine may bind to and alter the properties of protozoal DNA.|The precise mechanism of action has not been determined, but may be based on primaquine's ability to bind to and alter the properties of DNA. Primaquine is highly active against the exoeryhrocytic stages of plasmodium vivax and plasmodium ovale and against the primary exoerythrocytic stages of plasmodium falciparum. It is also highly active against the sexual forms of (gametocytes) plasmodia, especially P. falciparum, disrupting transmission of the disease by eliminating the reservoir from which the mosquito carrier is infected.|/Primaquine/ disrupts the parasitic mitochondria, thereby interrupting metabolic processes requiring energy.|... /Primaquine is one/ of /aromatic amine-containing/ xenobiotics ... capable to inducing oxidative injury in erythrocytes. These agents appear to potentiate the normal redox reactions and are capable of overwhelming the usual protective mechanisms. The interaction between these xenobiotics and hemoglobin leads to the formation of free radicals that denature critical proteins, including hemoglobin, thiol-dependent enzymes, and components of the erythrocyte membrane ... Oxidative denaturation of the globin chain decreases its affinity for the heme group, which may dissociate from the globin chain during oxidative injury ... The generation of free radicals may also lead to peroxidation of membrane lipids. This may affect the deformability of the erythrocyte and the permeability of the membrane to potassium. The alteration of the Na(+)/K(+) gradient is ... potentially lethal to the affected erythrocyte. Oxidative injury also impairs the metabolic machinery of the erythrocyte, resulting in a decrease in the concentration of ATP. Damage to the membrane can also permit leakage of denatured hemoglobin from the cell. Such free denatured hemoglobin can be toxic on its own. Free hemoglobin may irreversibly bind nitric oxide, resulting in vasoconstriction. Released hemoglobin may form nephrotoxic hemoglobin dimers, leading to kidney damage. /Oxidative hemolysis/

Maintain an open airway and assist ventilation if necessary. Treat seizures, coma, hypotension, and methemoglobinemia if they occur. Treat massive hemolysis with blood transfusions if needed, and prevent hemoglobin deposition in the kidney tubules by alkaline diuresis... Continuously monitor ECG for at least 6 to 8 hours. Treat cardiotoxicity as for quinidine poisoning with sodium bicarbonate... Epinephrine infusion may be useful in treating hypotension via combined vasoconstrictor and inotropic actions... High dose diazepam has been reported to reduce mortality in animals and to ameliorate cardiotoxicity in human chloroquine poisonings. The mechanism of protection is unknown. /Chloroquine and Other Aminoquinolines/|Decontamination: Prehospital. Administer activated charcoal if available. Do not induce vomiting. Hospital. Administer activated charcoal. Perform gastric lavage for significant ingestions (eg, >30-50mg/kg). Gastric emptying is probably not necessary after small ingestions if activate charcoal can be given promptly. Because of extensive tissue distribution, enhanced removal procedures are ineffective. /Chloroquine and Other Aminoquinolines/|Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ The most important adverse effects are hemolytic anemia in patients with G6PD deficiency, other defects of the erythrocytic pentose phosphate pathway of glucose metabolism, or some other types of hemoglobinopathy. In patients with the African variant of G6PD deficiency, the standard course of primaquine generally produces a benign self-limiting anemia. In the Mediterranean and Asian variants, hemolysis may be much more severe. Therapeutic doses may also cause abdominal pain if administered on an empty stomach. Larger doses can cause nausea and vomiting. Methemoglobinaemia may occur. Other uncommon effects include mild anemia and leukocytosis. Overdosage may result in leukopenia, agranulocytosis, gastrointestinal symptoms, hemolytic anemia and methemoglobinaemia with cyanosis.|/SIGNS AND SYMPTOMS/ Symptoms of overdosage of primaquine include abdominal cramps, vomiting, burning epigastric distress, CNS and cardiovascular disturbances, cyanosis, methemoglobinemia, moderate leukocytosis or leukopenia, and anemia. The most striking symptoms are granulocytopenia and acute hemolytic anemia in sensitive individuals. Acute hemolysis occurs, but patients recover completely if the drug is discontinued.|/SIGNS AND SYMPTOMS/ ... The oxidized, denatured hemoglobin species /by primaquine/ comprise what has been designated sulfhemoglobin. The denatured hemoglobin can form aggregates that bind to the cell membrane to form inclusions called Heinz bodies, a hallmark of oxidative injury to erythrocytes. Heinz bodies can be visualized by use of phase-contrast microscopy or supravital stains such as crystal violet. These membrane-associated inclusions impair the deformability of the erythrocyte membrane and thus impede movement of erythrocytes through the microcirculation and the spleen. Heinz bodies are effectively removed from the erythrocyte by the spleen, so they are not often observed in peripheral blood samples from patients despite ongoing oxidative injury. However, the culling of Heinz bodies can alter the morphology of the affected cells, giving rise to what are called "bite" cells and "blister" cells ... /which/ look as though a portion of the cytoplasm had been cut away ... /Oxidative hemolysis/

Diphosphate, Primaquine

Primaquine phosphate tablets 15 mg (of primaquine)

Analyte: primaquine; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards /primaquine phosphate/|Analyte: primaquine; matrix: chemical purity; procedure: dissolution in water; addition of hydrochloric acid; potentiometric titration using suitable electrodes /primaquine phosphate/|Analyte: primaquine; matrix: pharmaceutical preparation (tablet); procedure: dissolution in water; addition of gold chloride solution; production of a violet-blue color (chemical identification) /primaquine phosphate/|Analyte: primaquine; matrix: pharmaceutical preparation (tablet); procedure: dissolution in water; addition of trinitrophenol; formation of a yellow precipitate (chemical identification) /primaquine phosphate/|For more Analytic Laboratory Methods (Complete) data for PRIMAQUINE (9 total), please visit the HSDB record page.

Analyte: primaquine; matrix: blood (plasma); procedure: high-performance liquid chromatography with electrochemical detection; limit of detection: 10 ng/mL|Analyte: primaquine; matrix: blood (serum); procedure: high-performance liquid chromatography with ultraviolet detection at 269 nm; limit of quantitation: 10 ng/mL|Analyte: primaquine; matrix: blood (plasma); procedure: high-performance liquid chromatography with electrochemical detection; limit of detection: 2 ng/mL|Analyte: primaquine; matrix: blood (plasma, blood cell); procedure: high-performance liquid chromatography with ultraviolet detection at 254 nm; limit of quantitation: 10 ng/mL|For more Clinical Laboratory Methods (Complete) data for PRIMAQUINE (7 total), please visit the HSDB record page.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients