Meningitis: What It Is and How to Avoid It Watch Video

Primaquine Phosphate

Class: Antimalarials
VA Class: AP101
CAS Number: 63-45-6

Introduction

Antimalarial; 8-aminoquinoline derivative.100

Uses for Primaquine Phosphate

Malaria

Treatment of malaria caused by Plasmodium vivax or P. ovale.100 134 143 Provides a radical cure to prevent relapse of malaria caused by these Plasmodium.100 143 Not usually active against asexual erythrocytic forms of Plasmodium; a regimen that includes a blood schizonticidal agent (e.g., chloroquine [or hydroxychloroquine]; quinine with doxycycline or tetracycline; mefloquine; fixed-combination of atovaquone and proguanil [atovaquone/proguanil]; fixed combination of artemether and lumefantrine [artemether/lumefantrine]) is always used in conjunction with primaquine for treatment of P. ovale or P. vivax malaria.143

Prevention of malaria (terminal prophylaxis) in travelers who received a suitable antimalarial for prevention of malaria but are returning from areas where P. vivax or P. ovale is endemic.115 121 134 143 If primaquine prophylaxis not used for terminal prophylaxis in individuals who may have been exposed to P. ovale or P. vivax malaria, delayed primary attacks or relapse caused by these Plasmodium can occur.115

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

Prevention of malaria (primary prophylaxis).115 121 134 Primaquine may be an option when other recommended antimalarials (choroquine [or hydroxychloroquine], atovaquone/proguanil, doxycycline, mefloquine) cannot be used for primary prophylaxis and is a good choice when travelers will be in areas with high incidence of P. vivax malaria.115 121 134 If primaquine used for primary prophylaxis, primaquine terminal prophylaxis not needed.115

Information on risk of malaria in specific countries and mosquito avoidance measures and recommendations regarding whether prevention of malaria indicated and choice of antimalarials for prevention are available from CDC at and .115

Assistance with diagnosis or treatment of malaria available from CDC Malaria Hotline at 770-488-7788 or 855-856-4713 from 9:00 a.m. to 5:00 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after hours and on weekends and holidays.143 144

Pneumocystis jiroveci Pneumonia

Treatment of Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (PCP); used in conjunction with clindamycin.109 110 112 113 114 116 117 119 122 123 124 130 131 134 155 Designated an orphan drug by FDA for treatment of PCP associated with AIDS.132

Co-trimoxazole is drug of choice for treatment of PCP, including PCP in HIV-infected adults, adolescents, and children.134 155 156 CDC, NIH, and IDSA recommend a regimen of primaquine and clindamycin as an alternative for treatment of mild, moderate, or severe PCP in HIV-infected adults and adolescents when co-trimoxazole cannot be used.155 Although data not available regarding use in children, CDC, NIH, IDSA, and AAP state that regimen of primaquine and clindamycin also can be considered an alternative to co-trimoxazole for treatment of PCP in HIV-infected children based on data in adults.156

Not recommended for prevention of initial episodes (primary prophylaxis) of PCP in HIV-infected individuals because data insufficient to determine efficacy;155 not included in recommendations for long-term suppressive or chronic maintenance therapy (secondary prophylaxis) of PCP in HIV-infected individuals.155 156

Primaquine Phosphate Dosage and Administration

General

  • Prior to use, perform appropriate laboratory tests to rule out glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.115 143 155 (See Cautions.)

Administration

Oral Administration

Administer orally;100 usually as a single daily dose at the same time each day.115

Take with food to decrease adverse GI effects (e.g., nausea, abdominal pain).121 134 161

Dosage

Available as primaquine phosphate;100 dosage usually expressed in terms of primaquine.100 121 134 144

Each 26.3-mg tablet of primaquine phosphate contains 15 mg of primaquine.100

Pediatric Patients

Malaria
Radical Cure of P. ovale or P. vivax Malaria
Oral

0.5 mg/kg (0.8 mg/kg of primaquine phosphate) once daily for 14 days.115 134 144

Terminal Prophylaxis of P. ovale or P. vivax Malaria
Oral

0.5 mg/kg (0.8 mg/kg of primaquine phosphate) once daily for 14 days.115 134

Individuals who received chloroquine, hydroxychloroquine, doxycycline, or mefloquine for primary prophylaxis: Administer primaquine terminal prophylaxis during final 2 weeks of primary prophylaxis or, if not feasible, administer for 14 days after primary prophylaxis discontinued.115

Individuals who received atovaquone/proguanil for primary prophylaxis: Administer primaquine terminal prophylaxis during final 7 days of primary prophylaxis and then for an additional 7 days or, if not feasible, administer for 14 days after primary prophylaxis discontinued.115

Primary Prophylaxis of Malaria
Oral

0.5 mg/kg (0.8 mg/kg of primaquine phosphate) once daily.115 121 134

Initiate prophylaxis 1–2 days prior to entering a malarious area and continue during stay and for 7 days after leaving the area.115 121

Pneumocystis jiroveci Pneumonia (PCP)
Treatment of Mild to Moderate PCP in HIV-infected Children
Oral

0.3 mg/kg (up to 30 mg) once daily for 21 days;134 156 used in conjunction with oral clindamycin (10 mg/kg [up to 300–450 mg] every 6 or 8 hours) given for 21 days.134 156

Treatment of Mild to Moderate PCP in HIV-infected Adolescents
Oral

30 mg once daily for 21 days;155 used in conjunction with oral clindamycin (300 mg every 6 hours or 450 mg every 8 hours) given for 21 days.155

Treatment of Moderate to Severe PCP in HIV-infected Children
Oral

0.3 mg/kg (up to 30 mg) once daily for 21 days;134 156 used in conjunction with IV clindamycin (10–25 mg/kg [up to 600 mg] every 6 or 8 hours) or oral clindamycin (10 mg/kg [up to 300–450 mg] every 6 or 8 hours) given for 21 days.134 156

Treatment of Moderate to Severe PCP in HIV-infected Adolescents
Oral

30 mg once daily for 21 days;134 155 used in conjunction with IV clindamycin (600 mg every 6 hours or 900 mg every 8 hours) or oral clindamycin (300 mg every 6 hours or 450 mg every 8 hours) given for 21 days.155

Adults

Malaria
Radical Cure of P. ovale or P. vivax Malaria
Oral

30 mg of primaquine (52.6 mg of primaquine phosphate) once daily for 14 days recommended by CDC and others.115 134 144 Manufacturer recommends 15 mg of primaquine (26.3 mg of primaquine phosphate) once daily for 14 days.100

As an alternative to the daily regimen or in patients with borderline G-6-PD deficiency, CDC recommends 45 mg of primaquine (79 mg of primaquine phosphate) once weekly for 8 weeks.143 144 Consultation with an expert in infectious disease and/or tropical medicine recommended if this alternative regimen considered for individuals with borderline G-6-PD deficiency.143 144 (See Hematologic Effects under Cautions.)

Terminal Prophylaxis of P. ovale or P. vivax Malaria
Oral

30 mg of primaquine (52.6 mg of primaquine phosphate) once daily for 14 days recommended by CDC and others.115 134 Manufacturer recommends 15 mg of primaquine (26.3 mg of primaquine phosphate) once daily for 14 days.100

Individuals who received chloroquine, hydroxychloroquine, doxycycline, or mefloquine for primary prophylaxis: Administer primaquine terminal prophylaxis during final 2 weeks of primary prophylaxis or, if not feasible, administer for 14 days after primary prophylaxis discontinued.115

Individuals who received atovaquone/proguanil for primary prophylaxis: Administer primaquine terminal prophylaxis during final 7 days of primary prophylaxis and then for an additional 7 days or, if not feasible, administer for 14 days after primary prophylaxis discontinued.115

Primary Prophylaxis of Malaria
Oral

30 mg of primaquine once daily.115 121 134

Initiate prophylaxis 1–2 days prior to entering a malarious area and continue during stay and for 7 days after leaving the area.115 121

Pneumocystis jiroveci Pneumonia (PCP)
Treatment of Mild to Moderate PCP
Oral

30 mg once daily for 21 days;134 155 used in conjunction with oral clindamycin (300 mg every 6 hours or 450 mg every 8 hours) given for 21 days.155

Treatment of Moderate to Severe PCP
Oral

30 mg once daily for 21 days;134 155 used in conjunction with IV clindamycin (600 mg every 6 hours or 900 mg every 8 hours) or oral clindamycin (300 mg every 6 hours or 450 mg every 8 hours) given for 21 days.155

Prescribing Limits

Pediatric Patients

Malaria
Treatment or Prevention of Malaria
Oral

Do not exceed adult dosage.115 144

Adults

Malaria
Treatment or Prevention of Malaria
Oral

Manufacturer states do not exceed 15 mg of primaquine (26.3 mg of primaquine phosphate) once daily for 14 days;100 CDC and others recommend 30 mg of primaquine (52.6 mg of primaquine phosphate).115 121 134 144

Special Populations

Hepatic Impairment

No specific recommendations available regarding need for dosage adjustment in individuals with hepatic impairment.100

Renal Impairment

No specific recommendations available regarding need for dosage adjustment in individuals with renal impairment.100

Geriatric Adults

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.100

Cautions for Primaquine Phosphate

Contraindications

  • Acutely ill patients who have systemic disease manifested by a tendency to develop granulocytopenia (e.g., rheumatoid arthritis, lupus erythematosus).100

  • Patients receiving other potentially hemolytic drugs or agents capable of depressing the myeloid elements of bone marrow.100

  • CDC states contraindicated for prevention or treatment of malaria in individuals with G-6-PD deficiency, in pregnant women, and during lactation (unless the woman and breast-fed infant have been determined not to have G-6-PD deficiency).115 143

Warnings/Precautions

Warnings

Hematologic Effects

Acute hemolytic anemia, possibly fatal, may occur if used in patients with G-6-PD deficiency.100 115 Perform appropriate laboratory testing to rule out G-6-PD deficiency before initiating primaquine.115 143 156

Hemolytic anemia may also occur if administered to individuals with other defects of the erythrocytic pentose phosphate pathway of glucose metabolism or in patients with certain hemoglobinopathies.100

Severity of hemolytic anemia depends on dosage and specific genetic defect in the individual with G-6-PD deficiency.100 In American and African blacks with G-6-PD deficiency, hemolysis may be mild, self-limiting, and asymptomatic; in individuals of Mediterranean or certain Asian extractions, hemolysis may be severe.a

Monitor closely if used in individuals who have had a previous idiosyncratic reaction to primaquine (as manifested by hemolytic anemia, methemoglobinemia, or leukopenia), individuals with a personal or family history of favism, or individuals with G-6-PD deficiency or NADH methemoglobin reductase deficiency.100

Monitor CBCs periodically during therapy.100 Do not exceed recommended dosage.100

Discontinue immediately if evidence of hemolytic anemia occurs (e.g., darkening of urine, marked fall in hemoglobin level or erythrocyte count).100

General Precautions

GI Effects

Nausea, vomiting, epigastric distress, and abdominal cramps reported;100 may be decreased by administration with food.121 134

Specific Populations

Pregnancy

Category C.b

Manufacturer states avoid during pregnancy; safe use during pregnancy not established.100

CDC and other experts state contraindicated for prevention or treatment of malaria in pregnant women.115 134 143

If a pregnant women requires treatment of P. vivax or P. ovale malaria, CDC recommends oral chloroquine (300 mg once weekly) for prophylaxis for the duration of the pregnancy and deferral of primaquine (to provide a radical cure) until after delivery and after the women has been tested and determined not to have G-6-PD deficiency.143 144

Lactation

CDC states contraindicated during lactation, unless the woman and breast-fed infant have been determined not to have G-6-PD deficiency.115

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.100

Select dosage with caution (starting at the low end of dosage range) because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.100

Common Adverse Effects

Hematologic effects (hemolytic anemia, leukocytosis, leukopenia); GI effects (nausea, vomiting, epigastric distress, abdominal cramps).100

Primaquine Phosphate Pharmacokinetics

Absorption

Bioavailability

Well absorbed from GI tract.a Peak plasma concentrations generally are attained within 6 hours; plasma concentrations may be negligible after 24 hours.a

Considerable interindividual variation in peak plasma concentrations reported.a

Distribution

Extent

Widely distributed following oral administration.101

Information on distribution into milk not available.115

Elimination

Metabolism

Extensively and rapidly metabolized in the liver.101 The principal metabolite is carboxyprimaquine; plasma concentrations of the metabolite greatly exceed those of unchanged primaquine.101

Elimination Route

Only small amounts excreted unchanged in urine.101

Half-life

3.7–9.6 hours in healthy adults.101

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C) in tight, light-resistant container.100

Actions and Spectrum

  • Tissue schizonticidal agent active against the preerythrocytic and exoerythrocytic forms of Plasmodium falciparum, P. malariae, P. ovale, and P. vivax.a Also gametocytocidal against Plasmodium, especially the gametocytes of P. falciparum.a

  • Has some activity against the asexual erythrocytic forms of P. vivax, but generally inactive against the erythrocytic forms of Plasmodium.a

  • Mechanism of antimalarial activity unknown;161 may involve interference with Plasmodium DNA.a

Advice to Patients

  • Necessity of taking protective measures to reduce contact with mosquitoes (protective clothing, insect repellents, mosquito nets, remaining in air-conditioned or well-screened areas).115 121 134

  • Possibility of contracting malaria during travel, regardless of prophylactic regimen used.115 121 134

  • Importance of seeking medical attention as soon as possible if febrile illness develops during or after return from a malaria-endemic area and of informing clinician of possible malaria exposure.115 121 134

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.100

  • Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.100 115 143

  • Importance of advising patients of other important precautionary information.100 (See Cautions.)

Preparations

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

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Primaquine Phosphate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

15 mg (of primaquine)*

Primaquine Phosphate Tablets

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Primaquine Phosphate 26.3MG Tablets (SANOFI-AVENTIS U.S.): 30/$58.31 or 90/$146.93

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions March 5, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

100. Sanofi-Aventis. Primaquine phosphate tablets, film-coated prescribing information. Bridgewater, NJ; 2013 Jan.

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

109. Ruf B, Pohle HD. Clindamycin/primaquine for Pneumocystis carinii pneumonia. Lancet. 1989; 2:626-7. [IDIS 259200] [PubMed 2570324]

110. Toma E, Fournier D, Poisson M et al. Clindamycin with primaquine for Pneumocystis carinii pneumonia. Lancet. 1989; 1:1046-8. [IDIS 254599] [PubMed 2566001]

112. Black JR, Feinberg J, Murphy RL et al. Clindamycin and primaquine as primary treatment for mild and moderately severe Pneumocystis carinii pneumonia in patients with AIDS. Eur J Clin Microbiol Infect Dis. 1991; 10:204-7. [PubMed 2060532]

113. Joseph P, Marzouk J, Phelps R. Oral clindamycin plus primaquine for Pneumocystis carinii pneumonia. Sixth International Conference on AIDS. 1990:373. Abstract No. 2078.

114. Kay R, DuBois RE. Clindamycin/primaquine therapy and secondary prophylaxis against Pneumocystis carinii pneumonia in patients with AIDS. South Med J. 1990; 83:403-4. [IDIS 266040] [PubMed 2321069]

115. Centers for Disease Control and Prevention. CDC health information for international travel, 2014. Atlanta, GA: US Department of Health and Human Services. Updates may be available at CDC website.

116. Ruf B, Rohde I, Pohle HD. Efficacy of clindamycin/primaquine versus trimethoprim/sulfamethoxazole in primary treatment of Pneumocystis carinii pneumonia. Eur J Clin Microbiol Infect Dis. 1991; 10:207-10. [PubMed 2060533]

117. Toma E. Clindamycin/primaquine for treatment of Pneumocystis carinii pneumonia in AIDS. Eur J Clin Microbiol Infect Dis. 1991; 10:210-3. [PubMed 2060534]

119. Reviewers’ comments (personal observations).

121. . Advice for travelers. Treat Guidel Med Lett. 2012; 10:45-56. [PubMed 22777212]

122. Vildé JL, Remington JS. Role of clindamycin with or without another agent for the treatment of pneumocystosis in patients with AIDS. J Infect Dis. 1992; 166:694-5. [IDIS 301385] [PubMed 1500762]

123. Smith D, Gazzard B. Treatment and prophylaxis of Pneumocystis carinii pneumonia. Drugs. 1991; 42:628-39. [PubMed 1723365]

124. Noskin GA, Murphy RL, Black JR et al. Salvage therapy with clindamycin/primaquine for Pneumocystis carinii pneumonia. Clin Infect Dis. 1992; 14:183-8. [IDIS 295061] [PubMed 1571426]

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

130. Lane HC, Laughon BE, Falloon J et al. Recent advances in the management of AIDS-related opportunistic infections. Ann Intern Med. 1994; 120:945-55. [IDIS 330618] [PubMed 7909657]

131. Smith GH. Treatment of infections in the patient with acquired immunodeficiency syndrome. Arch Intern Med. 1994; 154:949-73. [IDIS 329350] [PubMed 8179453]

132. Food and Drug Administration. List of orphan designations and approvals. From FDA web site.

133. Fryauff DJ, Baird JK, Basri H et al. Randomised placebo-controlled trial of primaquine for prophylaxis of falciparum and vivax malaria. Lancet. 1995; 346:1190-3. [IDIS 355612] [PubMed 7475658]

134. Anon. Drugs for parasitic infections. Treat Guidel Med Lett. 2010; 8:e1-16.

135. Weiss WR, Oloo AJ, Johnson A et al. Daily primaquine is effective for prophylaxis against falciparum malaria in Kenya: comparison with mefloquine, doxycycline, and chloroquine plus proguanil. J Infect Dis. 1995; 171:1569-75. [IDIS 348465] [PubMed 7769294]

143. Centers for Disease Control and Prevention. CDC treatment guidelines: Treatment of malaria (guidelines for clinicians). 2013 Jul. From the CDC website. Accessed 2013 Sep 27.

144. Centers for Disease Control and Prevention. Guidelines for treatment of malaria in the United States (based on drugs currently available for use in the United States–updated July 1, 2013). From the CDC website. Accessed 2013 Sep 27.

155. Panel on Opportunistic Infections in HIV-infected Adults and Adolescents. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America (May 7, 2013). Updates may be available at HHS AIDS Information (AIDSinfo) website.

156. Panel on Opportunistic Infection in HIV-exposed and HIV-infected children, US Department of Health and Human Services (HHS). Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children: recommendations from the National Institutes of Health, Centers for Disease Control and Prevention, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics (Nov 6, 2013). Updates may be available at HHS AIDS Information (AIDSinfo) website.

161. World Health Organization (WHO). Guidelines for the treatment of malaria. 2nd edition. Geneva, Switzerland: World Health Organization; 2010. Updates may be available at WHO website.

a. AHFS Drug Information 2004. McEvoy GK, ed. Primaquine Phosphate. Bethesda, MD: American Society of Health-System Pharmacists; 2004:835-6.

b. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 6th ed. Philadelphia; PA: Lippincott Wiliams & Wilkins; 2002:1154.

Hide
(web5)