Lopinavir and Ritonavir: Package Insert and Label Information

LOPINAVIR AND RITONAVIR — lopinavir and ritonavir tablet, film coated
Laurus Labs Limited

1 INDICATIONS AND USAGE

Lopinavir and ritonavir is indicated in combination with other antiretroviral agents for the treatment of HIV- 1 infection in adults and pediatric patients 14 days and older.

Limitations of Use:

  • Genotypic or phenotypic testing and/or treatment history should guide the use of lopinavir and ritonavir. The number of baseline lopinavir resistance-associated substitutions affects the virologic response to lopinavir and ritonavir [see Microbiology (12.4)].

2 DOSAGE AND ADMINISTRATION

2.1 General Administration Recommendations

Lopinavir and ritonavir tablets may be taken with or without food. The tablets should be swallowed whole and not chewed, broken, or crushed. Lopinavir and ritonavir oral solution must be taken with food.

2.3 Dosage Recommendations in Adults

Lopinavir and ritonavir can be given in once daily or twice daily dosing regimen at dosages noted in Tables 1 and 2. Lopinavir and ritonavir once daily dosing regimen is not recommended in:

Table 1. Recommended Dosage in Adults — Lopinavir and Ritonavir Once Daily Regimen
Lopinavir and Ritonavir Dosage Form Recommended Dosage
200 mg/50 mg Tablets 800 mg/200 mg (4 tablets) once daily
80 mg/20 mg per mL Oral Solution 800 mg/200 mg (10 mL) once daily
Table 2. Recommended Dosage in Adults — Lopinavir and Ritonavir Twice Daily Regimen
Lopinavir and Ritonavir Dosage Form Recommended Dosage
200 mg/50 mg Tablets 400 mg/100 mg (2 tablets) twice daily
80 mg/20 mg per mL Oral Solution 400 mg/100 mg (5 mL) twice daily

The dose of lopinavir and ritonavir must be increased when administered in combination with efavirenz, nevirapine or nelfinavir. Table 3 outlines the dosage recommendations for twice daily dosing when lopinavir and ritonavir is taken in combination with these agents.

Table 3. Recommended Dosage in Adults — Lopinavir and Ritonavir Twice Daily Regimen in Combination with Efavirenz, Nevirapine, or Nelfinavir
Lopinavir and Ritonavir Dosage Form Recommended Dosage
200 mg/50 mg Tablets and 100 mg/25 mg Tablets 500 mg/125 mg (2 tablets of 200 mg/50 mg+ 1 tablet of 100 mg/25 mg) twice daily
80 mg/20 mg per mL Oral Solution 520 mg/130 mg (6.5 mL) twice daily

2.4 Dosage Recommendations in Pediatric Patients

Lopinavir and ritonavir tablets and oral solution are not recommended for once daily dosing in pediatric patients younger than 18 years of age. The dose of the oral solution should be administered using the calibrated cup (supplied) or oral dosing syringe. Lopinavir and ritonavir 100/25 mg tablets should be considered only in children who have reliably demonstrated the ability to swallow the intact tablet.

Lopinavir and ritonavir oral solution is not recommended in neonates before a postmenstrual age (first day of the mother’s last menstrual period to birth plus the time elapsed after birth) of 42 weeks and a postnatal age of at least 14 days has been attained [see Warnings and Precautions (5.2)].

Lopinavir and ritonavir oral solution contains approximately 42% (v/v) ethanol and approximately 15% (w/v) propylene glycol. Total amounts of ethanol and propylene glycol from all medicines that are to be given to pediatric patients 14 days to 6 months of age should be taken into account in order to avoid toxicity from these excipients [see Warnings and Precautions (5.2) and Overdosage (10)].

Pediatric Dosage Calculations

Calculate the appropriate dose of lopinavir and ritonavir for each individual pediatric patient based on body weight (kg) or body surface area (BSA) to avoid underdosing or exceeding the recommended adult dose.

Body surface area (BSA) can be calculated as follows:Figure 1

The lopinavir and ritonavir dose can be calculated based on weight or BSA:

Based on Weight:

Patient Weight (kg) × Prescribed lopinavir dose (mg/kg) = Administered lopinavir dose (mg)

Based on BSA:

Patient BSA (m2) × Prescribed lopinavir dose (mg/m2) = Administered lopinavir dose (mg)

If lopinavir and ritonavir oral solution is used, the volume (mL) of lopinavir and ritonavir solution can be determined as follows:

Volume of lopinavir and ritonavir solution (mL) = Administered lopinavir dose (mg) ÷ 80 (mg/mL)

Oral Solution Dosage Recommendation in Pediatric Patients 14 Days to Less Than 18 Years:

Table 4 summarizes the recommended daily dosing regimen for pediatric patients 14 days to less than 18 years of age using the oral solution.

Lopinavir and ritonavir administered in combination with efavirenz, nevirapine, or nelfinavir in patients younger than 6 months of age is not recommended. Total dose of lopinavir and ritonavir oral solution in pediatric patients should not exceed the recommended adult daily dose of 400/100 mg (5mL) twice daily.

Table 4. Lopinavir and Ritonavir Oral Solution Daily Dosage Recommendations in Pediatric Patients 14 days to Less Than 18 Years Without Concomitant Efavirenz, Nevirapine, or Nelfinavir
Patient Age Based on Weight (mg/kg) Based on BSA (mg/m2)Frequency
14 days to 6 months 16/4 300/75 Given twicedaily
Older than 6 months to less than 18 years Less than 15 kg 12/3 230/57.5 Given twicedaily
15 kg to 40 kg 10/2.5

Tablet Dosage Recommendation in Pediatric Patients Older than 6 Months to Less than 18 Years:

Table 5 provides the dosing recommendations for pediatric patients older than 6 months to less than 18 years of age based on body weight or body surface area for lopinavir and ritonavir tablets.

Table 5. Lopinavir and Ritonavir Tablet Daily Dosage Recommendations in Pediatric Patients > 6 Months to < 18 Years of Age Without Concomitant Efavirenz, Nevirapine, or Nelfinavir
Body Weight (kg) Body Surface Area (m2)*Recommended number of 100/25 mg Tablets Twice Daily
≥15 to 25≥0.6 to < 0.92
>25 to 35≥0.9 to < 1.43
>35≥1.44
* Lopinavir and ritonavir oral solution is available for children with a BSA less than 0.6 m2 or those who are unable to reliably swallow a tablet.

Concomitant Therapy: Efavirenz, Nevirapine, or Nelfinavir

Dosing recommendations using oral solution

Table 6 provides the dosing recommendations for pediatric patients older than 6 months to less than 18 years of age based on body weight or body surface area for Lopinavir and Ritonavir Oral Solution when given in combination with efavirenz, nevirapine, or nelfinavir:

Table 6. Lopinavir and Ritonavir Oral Solution Daily Dosage Recommendations for Pediatric Patients >6 Months to < 18 Years of Age With Concomitant Efavirenz, Nevirapine, or Nelfinavir
Patient Age Based on Weight (mg/kg) Based on BSA (mg/m2)Frequency
> 6 months to< 18 years <15 kg13/3.25300/75Given twice daily
≥15 kg to 45 kg 11/2.75

Dosing recommendations using tablets

Table 7 provides the dosing recommendations for pediatric patients older than 6 months to less than 18 years of age based on body weight or body surface area for lopinavir and ritonavir tablets when given in combination with efavirenz, nevirapine, or nelfinavir.

Table 7. Lopinavir and Ritonavir Tablet Daily Dosage Recommendations for Pediatric Patients > 6 Months to < 18 Years of Age With Concomitant Efavirenz , Nevirapine, or Nelfinavir
Body Weight (kg) Body Surface Area (m2)*Recommended number of 100/25 mg Tablets Twice Daily
≥15 to 20≥0.6 to < 0.82
>20 to 30≥0.8 to < 1.23
>30 to 45≥1.2 to <1.74
>45≥1.75 [see Dosage and Administration (2.4)]
* Lopinavir and ritonavir oral solution is available for children with a BSA less than 0.6 m2 or those who are unable to reliably swallow a tablet. Please refer to the individual product labels for appropriate dosing in children.

Figure 1

2.5 Dosage Recommendations in Pregnancy

Administer 400/100 mg of lopinavir and ritonavir twice daily in pregnant patients with no documented lopinavir-associated resistance substitutions.

  • Once daily lopinavir and ritonavir dosing is not recommended in pregnancy [see Use in Specific Populations (8.1) and Clinical Pharmacology (12.3)].
  • There are insufficient data to recommend dosing in pregnant women with any documented lopinavir-associated resistance substitutions.
  • No dosage adjustment of lopinavir and ritonavir is required for patients during the postpartum period.
  • Avoid use of lopinavir and ritonavir oral solution in pregnant women [see Use in Specific Populations (8.1)].

3 DOSAGE FORMS AND STRENGTHS

Tablets:

Lopinavir and Ritonavir Tablets USP, 200 mg/50 mg: Yellow colored, film coated oval shaped biconvex tablets debossed with “LA58” on one side and plain on other side.

Lopinavir and Ritonavir Tablets USP, 100 mg/25 mg: Yellow colored, film coated oval shaped biconvex tablets debossed with “LA59” on one side and plain on other side.

4 CONTRAINDICATIONS

  • Lopinavir and ritonavir is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, urticaria, angioedema) to any of its ingredients, including ritonavir.
  • Lopinavir and ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening reactions [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

○ Alpha 1- Adrenoreceptor Antagonist : alfuzosin

○ Antianginal: ranolazine

○ Antiarrhythmic: dronedarone

○ Anti-gout: colchicine

○ Antipsychotics: lurasidone, pimozide

○ Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine

○ GI Motility Agent: cisapride

○ Hepatitis C direct acting antiviral: elbasvir/grazoprevir

○ HMG-CoA Reductase Inhibitors: lovastatin, simvastatin

○ Microsomal triglyceride transfer protein (MTTP) Inhibitor: lomitapide

○ PDE5 Inhibitor: sildenafil (Revatio®) when used for the treatment of pulmonary arterial hypertension

○ Sedative/Hypnotics: triazolam, orally administered midazolam

  • Lopinavir and ritonavir is contraindicated with drugs that are potent CYP3A inducers where significantly reduced lopinavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance and cross-resistance [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)].

○ Anticancer Agents: apalutamide
○ Antimycobacterial: rifampin ○ Herbal Products: St. John’s Wort (hypericum perforatum)

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