Ritonavir

BRAND NAMES:

Empetus – Empetus has the main active ingredient ritonavir with the strength of 100mg in the market in oral tablets. Empetus 100 mg tablet is used in HIV treatment.

Kaletra -  It is a combination of lopinavir and ritonavir. It is available as pills and oral solutions. Lopinavir and ritonavir tablets are available in strengths of 100 mg/25 mg and 200 mg/50 mg, respectively. (400 mg/100 mg)/5mL combination oral solution is also available. 

Norvir -  Norvir contains ritonavir as the active ingredient sold as Norvir 100 mg tablets and oral powder.

Viekira Pak – It is used in the treatment of hepatitis C virus. It is a combinational drug of ombitasvir, paritaprevir and ritonavir(12.5 / 75 / 50mg).

MECHANISM OF ACTION:

Ritonavir's mechanism of action for HIV and Hepatitis C treatment is to inhibit the liver enzyme cytochrome P450 3A4. This cytochrome pathway also metabolizes other protease inhibitors. When ritonavir inhibits CYP450-3A4, the bioavailability of other antiretroviral medicines rises, resulting in a decrease in ARVs and an increase in serum drug levels. 

PHARMACOKINETICS:

Absorption: It takes around 2 to 4 hours to achieve its maximal plasma concentration. Food does not impact oral absorption.

Distribution: The volume of distribution is 0.41 ± 0.25 L/Kg.

Metabolism: Ritonavir is metabolized by cytochrome CYPP450(3A) isozymes and to a lesser extent by CYP2D6.

Excretion: Ritonavir is mainly excreted through feces. About 34% and 3.5% of the 600mg dose is excreted unchanged drug in the feces and urine.

PHARMACODYNAMICS:

Ritonavir is a protease inhibitor that works against HIV type 1. It inhibits HIV's protease, an enzyme necessary for the proteolytic breakdown of viral polyprotein precursors. Ritonavir binds to the active site of proteases, inhibiting their activity. This inhibitor hinders viral polyprotein cleavage, resulting in the generation of non-infectious viral particles. Protease inhibitors are always taken in conjunction with at least two additional anti-HIV medications.

DOSAGE AND ADMINISTRATION:

The route of administration is oral which is available in the form of tablets, oral suspensions, and soft gel capsules. Usually, ritonavir is used with the combinational drug lopinavir/ritonavir for the treatment of HIV. The small amount of ritonavir increases the bioavailability of the lopinavir.

The composition is available in tablets of lopinavir/ritonavir with strengths of 100 mg/25 mg and 200 mg/50 mg. whereas the oral solution 400 mg/100 mg per 5ml is used for the treatment.

• For HIV-1 patients, the suggested dosage is 400 mg/100 mg orally twice a day, or 800 mg/200mg by mouth once a day in patients with fewer than three lopinavir resistance-associated substitutions.
• For Patients with HIV Post-exposure prophylaxis, the recommended dosage is 400mg/100mg orally twice daily.

CONTRAINDICATIONS:

Ritonavir is contraindicated in patients with hypersensitivity, toxic epidermal necrolysis, and allergic reactions to ritonavir or its components.

DRUG INTERACTIONS:

Below are the drugs which should not be co-administered with ritonavir as it causes serious life-threatening issues.

• Sedative hypnotics – Midazolam, triazolam
• Ergot alkaloid – Dihydroergotamine, methylergonovine and ergotamine.
• Antiarrhythmics -  Amiodarone, dronedarone, quinidine, propafenone, flecainide
• HMG-COA Reductase inhibitors – Simvastatin, lovastatin
• Pulmonary arterial hypertension – Sildenafil, Lurasidone, Alfuzosin, Voriconazole, Lurasidone.

FOOD INTERACTIONS:

Avoid consuming alcohol.

ADVERSE EFFECTS:

• Hyperlipidemia
• Rhabdomyolysis
• Insomnia
• Dizziness
• Malaise
• Abdominal pain
• Hypertriglyceridemia
• Nausea
• Increase cardiovascular disease
• Hepatotoxicity
• Epidermal necrolysis
• Neutropenia
• Pancreatitis
• Leukopenia
• Diabetes mellitus

TOXICITY:

Taking an overdose of ritonavir than prescribed can lead to some toxic effects.

• Retinal toxicity
• Neurological effects
• Gastrointestinal effects
• Numbness