Lopinavir and Ritonavir Oral Pellets 40 mg/10 mg HIGHLIGHTS OF PRESCRIBING INFORMATION -------------------WARNINGS AND PRECAUTIONS------------------- These highlights do not include all the information needed to use The following have been observed in patients receiving Lopinavir and Lopinavir and Ritonavir Oral Pellets 40mg/10mg safely and Ritonavir: effectively. See full prescribing information for Lopinavir and • The concomitant use of Lopinavir and Ritonavir Oral Pellets and Ritonavir Oral Pellets. certain other drugs may result in known or potentially significant drug interactions. Consult the full prescribing information prior to Lopinavir and Ritonavir Oral Pellets for Oral Use and during treatment for potential drug interactions. (5.1, 7.3) • Toxicity in preterm neonates: Lopinavir and Ritonavir Oral Pellets ----------------------INDICATIONS AND USAGE------------------------- should not be used in preterm neonates in the immediate postnatal Lopinavir and Ritonavir Oral Pellets is an HIV-1 protease inhibitor period because of possible toxicities. A safe and effective dose of indicated in combination with other antiretroviral agents for the Lopinavir and Ritonavir in this patient population has not been treatment of HIV-1 infection in pediatric patients (14 days and older). established (2.2, 5.2) (1) • Pancreatitis: Fatalities have occurred; suspend therapy as clinically appropriate. (5.3) ------------------DOSAGE AND ADMINISTRATION------------------- • Hepatotoxicity: Fatalities have occurred. Monitor liver function Oral Pellets: The capsules should be opened and the contents should be before and during therapy, especially in patients with underlying sprinkled over sweetened porridge, which is at room temperature. The hepatic disease, including hepatitis B and hepatitis C, or marked entire mixture should be swallowed immediately. Do not chew or transaminase elevations. (5.4, 8.6) crush. (2) • QT interval prolongation and isolated cases of torsade de pointes Pediatric Patients (14 days and older): have been reported although causality could not be established. • Twice daily dose is based on body weight. (2.2) Avoid use in patients with congenital long QT syndrome, those • Do not use once daily administration in pediatric patients. with hypokalemia, and with other drugs that prolong the QT Concomitant Therapy in Pediatric Patients: interval. (5.1, 5.5, 12.3) • Dose adjustments of Lopinavir and Ritonavir may be needed when • PR interval prolongation may occur in some patients. Cases of co-administering with efavirenz, nevirapine, or nelfinavir. (2.2, 7.3) second and third degree heart block have been reported. Use with Lopinavir and Ritonavir Oral Pellets should not be administered to caution in patients with pre-existing conduction system disease, neonates before a postmenstrual age (first day of the mother’s last ischemic heart disease, cardiomyopathy, underlying structural heart menstrual period to birth plus the time elapsed after birth) of 42 weeks disease or when administering with other drugs that may prolong and a postnatal age of at least 14 days has been attained (2.2, 5.2) the PR interval (5.1, 5.6, 12.3) • Patients may develop new onset or exacerbations of diabetes ------------------DOSAGE FORMS AND STRENGTHS----------------- mellitus, hyperglycemia (5.7), immune reconstititution syndrome • Oral Pellets: 40 mg Lopinavir and 10 mg Ritonavir per capsule (3) (5.8), redistribution/accumulation of body fat. (5.10) • Total cholesterol and triglycerides elevations. Monitor prior to --------------------------CONTRAINDICATIONS-------------------------- therapy and periodically thereafter. (5.9) Hypersensitivity to Lopinavir and Ritonavir (e.g., toxic epidermal • Hemophilia: Spontaneous bleeding may occur, and additional necrolysis, Stevens-Johnson syndrome, erythema multiforme, urticaria, factor VIII may be required. (5.11) angioedema) or any of its ingredients, including ritonavir. (4) Coadministration with: -------------------------ADVERSE REACTIONS--------------------------- • drugs highly dependent on CYP3A for clearance and for which Commonly reported adverse reactions to Lopinavir and Ritonavir elevated plasma levels may result in serious and/or life-threatening included diarrhea, nausea, vomiting, hypertriglyceridemia and events. (4) hypercholesterolemia. (6.1, 6.2) • potent CYP3A inducers where significantly reduced lopinavir plasma concentrations may be associated with the potential for loss To report SUSPECTED ADVERSE REACTIONS, contact Cipla of virologic response and possible resistance and cross resistance. Ltd. at 1-866-604-3268 or FDA at 1-800-FDA-1088 or (4) www.fda.gov / medwatch --------------------------DRUG INTERACTIONS-------------------------- Coadministration of Lopinavir and Ritonavir can alter the plasma concentrations of other drugs and other drugs may alter the plasma concentrations of lopinavir. The potential for drug-drug interactions must be considered prior to and during therapy. (4, 5.1, 7, 12.3) See 17 for PATIENT COUNSELING INFORMATION and Medication Guide Revised: 5/2015 FULL PRESCRIBING INFORMATION: CONTENTS* 7.3 Established and Other Potentially Significant Drug Interactions 1 INDICATIONS AND USAGE 7.4 Drugs with No Observed or Predicted Interactions with 2 DOSAGE AND ADMINISTRATION Lopinavir and Ritonavir 2.2 Pediatric Patients 8 USE IN SPECIFIC POPULATIONS 3 DOSAGE FORMS AND STRENGTHS 8.1 Pregnancy 4 CONTRAINDICATIONS 8.3 Nursing Mothers 5 WARNINGS AND PRECAUTIONS 8.4 Pediatric Use 5.1 Risk of Serious Adverse Reactions Due to Drug Interactions 8.6 Hepatic Impairment 5.2 Toxicity in Preterm Neonates 10 OVERDOSAGE Reference ID: 3762262 5.3 Pancreatitis 11 DESCRIPTION 5.4 Hepatotoxicity 12 CLINICAL PHARMACOLOGY 5.5 QT Interval Prolongation 12.1 Mechanism of Action 5.6 PR Interval Prolongation 12.3 Pharmacokinetics 5.7 Diabetes Mellitus/Hyperglycemia 12.4 Microbiology 5.8 Immune Reconstitution Syndrome 13 NONCLINICAL TOXICOLOGY 5.9 Lipid Elevations 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 5.10 Fat Redistribution 14 CLINICAL STUDIES 5.11 Patients with Hemophilia 14.1 Adult Patients without Prior Antiretroviral Therapy 5.12 Resistance/Cross-resistance 14.2 Adult Patients with Prior Antiretroviral Therapy 6 ADVERSE REACTIONS 14.3 Other Studies Supporting Approval in Adult Patients 6.1 Adult Clinical Trial Experience 14.4 Pediatric Studies 6.2 Pediatric Clinical Trial Experience 16 HOW SUPPLIED/STORAGE AND HANDLING 6.3 Postmarketing Experience 16.1 Lopinavir and Ritonavir Oral Pellets 40mg /10 mg 7 DRUG INTERACTIONS 17 PATIENT COUNSELING INFORMATION 7.1 Potential for Lopinavir and Ritonavir to Affect Other Drugs *Sections or subsections omitted from the full prescribing information 7.2 Potential For Other Drugs To Affect Lopinavir are not listed FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE Lopinavir and Ritonavir Oral Pellets 40mg /10mg is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in pediatric patients (14 days and older). The following points should be considered when initiating therapy with lopinavir and ritonavir: • The use of other active agents with lopinavir and ritonavir is associated with a greater likelihood of treatment response [see Microbiology (12.4) and Clinical Studies (14)]. • Genotypic or phenotypic testing and/or treatment history should guide the use of lopinavir and ritonavir [see Microbiology (12.4)]. The number of baseline lopinavir resistance- associated substitutions affects the virologic response to lopinavir and ritonavir [see Microbiology (12.4)]. 2 DOSAGE AND ADMINISTRATION 2.2 Pediatric Patients Lopinavir and Ritonavir Oral Pellets should not be administered once daily in pediatric patients < 18 years of age. Lopinavir and Ritonavir Oral Pellets should not be administered to 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)]. Dosage The following table lists the number of capsules containing Lopinavir and Ritonavir Oral Pellets 40 mg/10 mg to be administered twice-daily, using a simplified weight band-based approach. Weight Band Number of capsules containing Lopinavir and Ritonavir Oral Pellets 40 mg/10 mg* needed to prepare each dose 5 kg to less than 6 kg 2 capsules (80 mg) 6 kg to less than 10 kg 3 capsules (120 mg) Reference ID: 3762262 10 kg to less than 14 kg 4 capsules (160 mg) 14 kg to less than 20 kg 5 capsules (200 mg) 20 kg to less than 25 kg 6 capsules (240 mg) 25 kg to less than 30 kg 7 capsules (280 mg) 30 kg to less than 35 kg 8 capsules (320 mg) Greater than or equal to 35 10 capsules (adult dose, 400mg) * without concomitant efavirenz, nevirapine, amprenavir or nelfinavir Administration Capsules containing Lopinavir and Ritonavir oral pellets should not be swallowed whole, and should be administered with food, as described below. Method of administration: • Place sweetened porridge, which is at room temperature, in a small bowl. • Obtain the prescribed number of capsules needed for a dose. • Hold both ends of the capsule between your fingertips as shown below. • Twist the ends of the capsule in opposite direction and pull apart so that the entire content of the capsule is sprinkled over the sweetened porridge. • Repeat this step for the prescribed number of capsules per dose. Ensure that the entire content of each capsule is sprinkled over the porridge. • This drug/food mixture