Quinine Sulfate (Qualaquin) Form

Quinine sulfate (Qualaquin®) is an antimalarial drug. FDA Approved Indication(s) Qualaquin is indicated for treatment of uncomplicated Plasmodium falciparum malaria.
Quinine sulfate has been shown to be effective in geographical regions where resistance to chloroquine has been documented. Limitation(s) of use: Qualaquin is not approved for:
• Treatment of severe or complicated P. falciparum malaria • Prevention of malaria • Treatment or prevention of nocturnal leg cramps Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Qualaquin is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Malaria (must meet all):

1. Diagnosis of one of the following (a or b):
   a. Uncomplicated Plasmodium falciparum malaria; b. Plasmodium vivax malaria (off-label);
2. Failure of a formulary antimalarial agent (e.g., atovaquone-proguanil, Coartem®, chloroquine, hydroxychloroquine, mefloquine), unless clinically significant adverse effects are experienced, all are contraindicated, or the causative species is resistant to all formulary antimalarial agents;
3. Member must use generic quinine, unless contraindicated or clinically significant adverse effects are experienced;

4. Dose does not exceed 1,944 mg (6 capsules) per day. Approval duration: 7 days Page 1 of 6

   CLINICAL POLICY
   Quinine Sulfate B. Babesiosis (off-label) (must meet all):

5. Diagnosis of babesiosis;
   2. Prescribed in combination with clindamycin;
   3. Dose does not exceed 1,944 mg (6 capsules) per day. Approval duration: Duration of request or 10 days (whichever is less) C. Other diagnoses/indications (must meet 1 or 2):
6. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
7. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Malaria or Babesiosis (off-label)
8. Re-authorization is not permitted. Member must meet the initial approval criteria.
   Approval duration: Not applicable
   B. Other diagnoses/indications (must meet 1 or 2):
9. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

10. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid. Page 2 of 6

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    Quinine Sulfate III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policy – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents; B. Prevention of malaria; C. Treatment or prevention of nocturnal leg cramps. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CDC: Centers for Disease Control and Prevention FDA: Food and Drug Administration G6PD: glucose-6-phosphate dehydrogenase
    HUS/TTP: hemolytic uremic syndrome/ thrombotic thrombocytopenic purpura
    Appendix B: Therapeutic Alternatives
    This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Drug Name Dosing Regimen Dose Limit/ Maximum Dose See dosing regimen 8 tablets/day (total of 6 doses over 3 days) 1 g (600 mg base) PO as initial dose(s) for malaria treatment; otherwise, 500 mg/dose (300 mg base/dose) PO. See dosing regimen See dosing regimen atovaquone-proguanil (Malarone®) Coartem® (artemether/lumefantrine) chloroquine (Aralen®) hydroxychloroquine (Plaquenil®) mefloquine
    Adults: 1 gram atovaquone/400 mg proguanil hydrochloride PO QD for 3 days Adults: 80 mg artemether/480 mg lumefantrine PO initially, then a second dose 8 hours later, then 1 dose PO twice daily (morning and evening) for the next 2 days for a total course of 24 tablets Adults: 1,000 mg (600 mg base) PO, then 500 mg (300 mg base) PO in 6 to 8 hours, then 500 mg (300 mg base) PO QD for 2 days. Adults: 800 mg (620 mg base) PO, then 400 mg (310 mg base) PO at 6, 24, and 48 hours after the initial dose for a total dose of 2 g (1.55 g base) Adults: 1,250 mg (administered as five 250 mg tablets) PO as a single dose. Alternatively, 750 mg PO as the initial dose, then 500 mg PO 6 to 12 hours later Page 3 of 6

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    Quinine Sulfate Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
    o Prolongation of QT interval o Glucose-6-phosphate dehydrogenase (G6PD) deficiency
    o Myasthenia gravis
    o Known hypersensitivity to quinine, mefloquine, or quinidine
    o Optic neuritis • Boxed warning(s): Qualaquin use for the treatment or prevention of nocturnal leg cramps may result in serious and life-threatening hematologic reactions, including thrombocytopenia and hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP). Chronic renal impairment associated with the development of TTP has been reported. The risk associated with Qualaquin use in the absence of evidence of its effectiveness in the treatment or prevention of nocturnal leg cramps outweighs any potential benefit. Appendix D: General Information • For more information on the treatment of malaria, refer to the CDC website:
    https://www.cdc.gov/malaria/resources/pdf/Malaria_Trx_Guide_for_US_Clinicians_202 208.pdf. • For more information on the treatment of babesiosis, refer to the CDC website: https://www.cdc.gov/parasites/babesiosis/health_professionals/index.html.
    V. Dosage and Administration
    Indication Malaria
    Dosing Regimen Adults (≥ 16 years of age): 648 mg (two capsules) PO Q8h for 7 days Maximum Dose 1,944 mg/day For chloroquine-resistant strains of P. vivax: use concurrently with primaquine phosphate for 14 days plus either tetracycline or doxycycline for 7 days For chloroquine-resistant strains of P. falciparum: use concurrently with tetracycline, clindamycin, or doxycycline for 7 days for chloroquine-resistant infections or infections of unknown resistance Adults: 648 mg PO TID-QID with concurrent administration of clindamycin IV for 7 - 10 days 1,944 mg/day Babesiosis (off- label) VI. Product Availability Capsule: 324 mg
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    Quinine Sulfate VII.