Lopinavir And Ritonavir Cipla 40 mg and 10 mg ORAL PELLETS

LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS are indicated in combination with other antiretroviral medicines for the treatment of HIV infection.

LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS should be taken with food. Method of administration: Capsules containing the oral pellets should not be swallowed whole but should be administered with food as shown below (capsule contents should be emptied into ready-to-eat-porridge).

• 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 depicted above.
• Twist the ends of the capsule in opposite direction and pull apart so that the entire contents of the capsule are 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 medicine-porridge mixture should be eaten immediately. The oral pellets should not be chewed or crushed. They should not be stored for future use.
• Administration of the required dose should be followed by drinking water, to ensure that no pellets are left behind in the mouth.
• Repeat above steps for next dose.

Adults and children older than 12 years or children less than 12 years who weigh more than 40 kg: The recommended dose of lopinavir/ritonavir is 400 /100 mg (10 capsules) twice daily with food.

Children: 6 months to 12 years: The recommended dose of lopinavir/ritonavir in children weighing:

• 7 to 15 kg is 12/3 mg per kg twice daily with food.
• 15 to 40 kg is 10/2,5 mg per kg twice daily with food.

Concomitant therapy with efavirenz, nevirapine, amprenavir and nelfinavir: A dose increase is required and the recommended dose of lopinavir/ritonavir in children weighing:

• 7 to 15 kg is 13/3,25 mg per kg twice daily with food.
• 15 to 40 kg is 11/2,75 mg per kg twice daily with food.

LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS should not be administered once daily in patients under 18 years of age. LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS should not be administered to neonates before a post-menstrual age (first day of the motheru2019s 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.

LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS are contraindicated in patients with known hypersensitivity to lopinavir, ritonavir or any other ingredients of LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS. Severe hepatic insufficiency as LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS have not been studied in this condition. LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS should not be co-administered with medicines that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events. These medicines include medicines listed in Table 3. LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS are contraindicated with medicines 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.

Risk of serious adverse reactions due to interactions with other medicines. Initiation of LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS, a CYP3A inhibitor, in patients receiving medicines metabolised by CYP3A or initiation of medicines metabolised by CYP3A in patients already receiving LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS, may increase plasma concentrations of medicines metabolised by CYP3A. Initiation of medicines that inhibit or induce CYP3A may increase or decrease concentrations of LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS, respectively. These interactions may lead to:

• Clinically significant adverse reactions, potentially leading to severe, life-threatening or fatal events from greater exposures of concomitant medicines.
• Clinically significant adverse reactions from greater exposures of LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS.
• Loss of therapeutic effect of LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS and possible development of resistance.

See Table 4 for these possible and known significant medicine interactions (see u2018INTERACTIONSu2019). Consider the potential for medicine interactions prior to and during LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS therapy; review concomitant medicines during LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS therapy and monitor for the adverse reactions associated with the concomitant medicines (see u2018CONTRAINDICATIONSu2019 and u2018INTERACTIONSu2019).

LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS are inhibitors of CYP3A (cytochrome P450 3A) both in vitro and in vivo. Co-administration of LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS and medicines mainly metabolised by CYP3A (e.g. dihydropyridine calcium channel blockers, HMG-CoA reductase inhibitors, immunosuppressants and sildenafil) may result in increased plasma concentrations of the other medicines that could increase or prolong its therapeutic and adverse effects. Medicines that are predominantly metabolised by CYP3A and have high first pass metabolism appear to be the most susceptible to large increases in AUC (greater than 3-fold) when co-administered with LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS. Medicines that are contraindicated specifically due to the expected magnitude of interaction and potential for serious adverse events are listed in Table 3 under u2018CONTRAINDICATIONSu2019. LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS undergo hepatic metabolism CYP3A. Co-administration of LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS and medicines that induce CYP3A may decrease lopinavir plasma concentrations and reduce its therapeutic effect. Although not noted with concurrent ketoconazole, co-administration of LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS and other medicines that inhibit CYP3A may increase LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS plasma concentrations.

The safety of LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS in pregnant women has not been established, as there are no adequate and well-controlled studies in pregnant women. The use of LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS during pregnancy is not recommended. HIV-infected mothers should not breastfeed their infants to avoid risking postnatal transmission of HIV. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS. It is not known whether lopinavir is secreted in human milk.

LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS can cause visual disturbances and drowsiness and can therefore impair the ability to drive or operate machines. Caution is advised.

Infections and infestation: Frequent: otitis media, bronchitis, sinusitis, furunculosis, bacterial infections, pharyngitis, flu syndrome, gastroenteritis, sialadenitis, cellulitis, folliculitis, perineal abscess, upper respiratory tract infections. Neoplasm benign, malignant and unspecified: Less frequent: benign skin neoplasm, cyst, neoplasm. Blood and lymphatic system disorders: Frequent: anaemia, leukopenia, lymphadenopathy, neutropenia. Less frequent: splenomegaly. Immune system disorders: Frequent: hypersensitivity reactions including angioedema and urticaria. Less frequent: immune reconstitution syndrome. Endocrine disorders: Less frequent: male hypogonadism, Cushingu2019s syndrome and hypothyroidism. Metabolic and nutritional disorders: Frequent: blood glucose disorders including diabetes mellitus, hypertriglyceridaemia, hypercholesterolemia, decreased weight, decreased appetite. Less frequent: dehydration, oedema, avitaminosis, dehydration, lactic acidosis, obesity, anorexia, weight gain, hyperglycaemia, hyperamylaseaemia, hyperlipasaemia, lipomatosis. Psychiatric disorders: Frequent: anxiety. Less frequent: abnormal dreams, agitation, confusion, depression, emotional lability, libido decreased, nervousness, apathy, mood swings, abnormal thinking. Nervous system disorders: Frequent: headache (including migraine), insomnia, neuropathy (including peripheral neuropathy), dizziness. Less frequent: amnesia, somnolence, dyskinesia, ataxia, encephalopathy, facial paralysis, loss of taste, taste perversion, cerebral infarct, hypertonia, paraesthesia, peripheral neuritis, tremor, convulsions, extrapyramidal syndrome, balance disorder. Eye disorders: Less frequent: abnormal vision, eye disorder. Ear and labyrinth disorders: Less frequent: vertigo, tinnitus. Cardiac disorders: Less frequent: palpitations, pulmonary oedema, angina pectoris, atrioventricular block, arterial fibrillation, myocardial infarction, tricuspid valve incompetence. Vascular disorders: Frequent: hypertension. Less frequent: deep vein thrombosis, thrombophlebitis, varicose vein and vasculitis, vascular disorder, postural hypotension, vasodilation. Respiratory, thoracic and mediastinal disorders: Less frequent: bronchitis, otitis media, asthma, dyspnoea, lung oedema, rhinitis, sinusitis, increased cough. Gastrointestinal disorders: Frequent: diarrhoea, abdominal pain, abnormal stools, dyspepsia, nausea, vomiting, flatulence, pancreatitis, gastroenteritis, abdominal distension. Less frequent: enlarged abdomen, taste perversion, cholecystitis, constipation, dry mouth, dysphagia, enterocolitis, enteritis, eructation, oesophagitis, faecal incontinence, flatulence, gastritis, haemorrhagic colitis, duodenitis, gastric ulcer, gastroesophageal reflux disease, increased appetite, mouth ulceration, sialadenitis, stomatitis, ulcerative stomatitis, periodontitis, haemorrhoids, rectal haemorrhage. Hepato-biliary disorders: Frequent: hepatitis including AST, ALT and GGT increases. Less frequent: cholecystitis, cholangitis, jaundice, hepatomegaly, liver fatty deposit, liver tenderness, hyperbilirubinemia. Skin and subcutaneous tissue disorders: Frequent: rash (including maculopapular rash), lipodystrophy, acne, rash including eczema and seborrheic dermatitis, pruritus, night sweats. Less frequent: alopecia, dry skin, eczema, exfoliative dermatitis, face oedema, furunculosis, nail disorder, skin benign neoplasm, skin discolouration, skin ulcer, skin striae, allergic dermatitis, sweating, stretch marks, idiopathic capillaritis, vasculitis, alopecia. Frequency not known: Steven-Johnson Syndrome, erythema multiforme. Musculoskeletal, connective tissue and bone disorders: Frequent: myalgia, back pain, arthralgia, muscle disorders like weakness and spasms. Less frequent: arthrosis, pain in extremity, bone necrosis, joint disorder, myasthenia, rhabdomyolysis. Renal and urinary disorders: Less frequent: kidney calculus, urine abnormality, nephritis, albuminaria, hypercalcinuria, nephritis, hyperuricaemia, haematuria, abnormal urine odour. Reproductive system and breast disorders: Frequent: erectile dysfunction, amenorrhoea, menorraghia. Less frequent: abnormal ejaculation, gynaecomastia, impotence, breast enlargement. General disorders and administration site conditions: Frequent: asthenia, pain, fatigue. Less frequent: chest pain, substernal chest pain, chills, medicine interaction, medicine level increased, oedema, peripheral oedema, fever, malaise. Investigations: The following abnormalities have been reported in therapy-nau00efve adult patients: Less frequent: increased glucose, uric acid, AST, ALT, GGT, total cholesterol, triglycerides and amylase levels and decreased neutrophils. The following abnormalities have been reported in therapy-experienced (protease inhibitor) adult patients: Less frequent: increased glucose, total bilirubin, AST, ALT, GGT, total cholesterol, triglycerides and amylase and decreased inorganic phosphate. The following abnormalities have been reported in children: Less frequent: increased total bilirubin, AST, ALT, total cholesterol and amylase levels, and decreased sodium levels, platelet and neutrophil counts. Post-marketing data: The following have been reported: hepatitis, toxic epidermal necrolysis, Steven-Johnson syndrome, erythema multiforme, bradydysrhythmia.

Treatment of overdose with LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. There is no specific antidote for overdose with LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS. If indicated, elimination of unabsorbed medicine should be achieved by emesis. Administration of activated charcoal may also be used to aid in removal of unabsorbed medicine. Since LOPINAVIR AND RITONAVIR CIPLA 40/10 ORAL PELLETS are highly protein bound, dialysis is unlikely to be beneficial in significant removal of the medicine.