Generic Name

Kaletra

Mechanism

• Dual component:
• Lopinavir – the active protease inhibitor that binds to the catalytic site of HIV‑1 protease, blocking cleavage of the Gag‑Pol polyprotein and preventing maturation of infectious virions.
• Ritonavir – mainly acts as a pharmacokinetic enhancer by competitively inhibiting CYP3A4, thereby increasing lopinavir plasma concentrations. It also possesses modest antiretroviral activity.
• The combination yields a synergistic antiviral effect and improves overall virologic suppression.

Pharmacokinetics

Key point: Ritonavir’s CYP3A4 inhibition extends lopinavir’s half‑life, requiring dose adjustment and contributing to drug‑drug interaction potential.

Indications

• HIV‑1 infection:
• First‑line or second‑line antiretroviral therapy in combination with nucleoside reverse transcriptase inhibitors (NRTIs).
• Salvage therapy for patients failing other regimens, when guided by resistance testing.
• Prevention of mother‑to‑child transmission (in selective settings where guidelines allow).

Contraindications

• Contraindications:
• Known hypersensitivity to lopinavir, ritonavir, or any excipient.
• Concomitant use of strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin).
• Warnings:
• Significant drug‑drug interactions due to CYP3A4 inhibition.
• Hepatic impairment: monitor liver function; severe hepatic disease (ALT > 5× ULN) contraindicated.
• Severe renal dysfunction: dose adjustment not required but monitor renal function.
• Lipid abnormalities: increases triglycerides and cholesterol; consider adjunct lipid‑lowering therapy.
• Pregnancy: Category C; use only if benefits outweigh risks.

Dosing

• Administration: Take with a meal or light snack to optimize absorption; avoid high‑fat meals if using PK‑dose.
• Reconstitution: If using compressed tablets, crush and mix with sterile water; give immediately.

Adverse Effects

• Management: Lipid‑lowering agents for hyperlipidemia; NRTI–adjusted diet for GI upset; monitor liver enzymes weekly during initiation; consider dose reduction or discontinuation if ALT/AST exceed 5× ULN.

Monitoring

• Baseline: CBC, CMP (ALT, AST, bilirubin), fasting lipid profile, renal function, CD4 count, HIV‑RNA.
• During therapy:
• ALT/AST every 2 weeks for first 2 months, then monthly.
• Lipid profile every 3 months.
• Viral load every 4–12 weeks until suppression; thereafter every 3–6 months.
• Adherence counseling; drug interaction review at each visit.
• Special: Check for drug interactions with CYP3A4 substrates; adjust dosages accordingly.

Clinical Pearls

• Pharmacokinetic boosting: Ritonavir’s primary role is not antiretroviral potency but CYP3A4 inhibition; this property can be leveraged to boost other protease inhibitors (e.g., darunavir) at lower ritonavir doses.
• Food‑dependent absorption: For the fixed‑dose 200/50 mg tablets, take with food to avoid erratic absorption; the PK‑dose (1000/200 mg) is more forgiving but still benefits from a light snack.
• Drug interactions: Avoid prescribing Kaletra with strong CYP3A4 inducers (e.g., rifampin, carbamazepine); if unavoidable, consider therapeutic drug monitoring of lopinavir concentration or use alternative regimens.
• Adverse effect mitigation: Co‑prescribe a statin only after confirming liver enzymes are stable; prefer rosuvastatin due to lower CYP3A4 metabolism.
• Pregnancy: Use only when no safer alternatives exist; provide thorough counseling on potential teratogenic risks and advise concurrent use of a reliable contraceptive.

Quick reference: To memorize the dosage, the mnemonic “1lopinavir 1​, 0ritonavir 0” (1000 mg/200 mg) reflects the PK‑dose, while the standard dose is 400/100 mg.