Ritonavir

Ritonavir is an FDA-registered drug product whose active ingredient is RITONAVIR. It is labelled by Amneal Pharmaceuticals LLC taken by oral and marketed as a human prescription drug product. Identifiers on file: NDC 65162-061, application ANDA208890, label effective 20260806. It is one of 3 FDA drug label records sharing the active ingredient RITONAVIR. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing RITONAVIR are most often described in connection with: ritonavir tablets, indicated combination, antiretroviral agents, treatment hiv-, hiv protease. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE Ritonavir tablets are indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. Ritonavir tablets are HIV protease inhibitors indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. (1)

2 DOSAGE AND ADMINISTRATION Adult patients: 600 mg twice-day with meals. (2.2) Pediatrics patients: Do not exceed 600 mg twice daily dose with meals for children greater than one month of age. The dose is based on body surface area. (2.3) Dose modification for ritonavir tablets is necessary when used with other protease inhibitors. (2.5) 2.1 General Administration Recommendations Ritonavir tablets must be used in combination with other antiretroviral agents. Administer ritonavir tablets orally. Swallow ritonavir tablets whole. Do not chew, break or crush ritonavir tablets. Take ritonavir tablets with meals. 2.2 Dosage Recommendations in Adults Recommended Dosage for Treatment of HIV-1: The recommended dosage of ritonavir tablets are 600 mg twice daily by mouth to be taken with meals. Use of a dose titration schedule may help to reduce treatment-emergent adverse events while maintaining appropriate ritonavir plasma levels. Start ritonavir tablets at no less than 300 mg twice daily and increase at 2 to 3 day intervals by 100 mg twice daily. Do not exceed the maximum dose of 600 mg twice daily upon completion of the titration [see Dosage and Administration (2.5) ] . 2.3 Dosage Recommendations in Pediatric Patients Ritonavir tablets must be used in combination with other antiretroviral agents [see Dosage and Administration (2.1) ] . The recommended dosage of ritonavir tablets in pediatric patients older than 1 month is 350 mg to 400 mg per m 2 twice daily by mouth to be taken with meals. Do not exceed 600 mg twice daily. Start ritonavir tablets at 250 mg per m 2 twice daily and increase at 2 to 3 day intervals by 50 mg per m 2 twice daily. If patients do not tolerate 400 mg per m 2 twice daily due to adverse events, use the highest tolerated dose for maintenance therapy in combination with other antiretroviral agents, or consider using alternative therapy [see Dosage and Administration (2.5) ] . 2.5 Dose Modification due to Drug Interaction Reduce dose of ritonavir tablets when used with other protease inhibitors: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir. Consult the full prescribing information and clinical study information of these protease inhibitors when they are co-administered with a reduced dose of ritonavir [see Warnings and Precautions (5.1) and Drug Interactions (7) ] .

4 CONTRAINDICATIONS Consult the prescribing information of the co-administered protease inhibitor for contraindication information for that product. Ritonavir tablets are contraindicated in patients with known hypersensitivity (e.g., toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome) to ritonavir or any of its ingredients. 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 Antiarrhythmics: amiodarone, dronedarone, flecainide, propafenone, quinidine Antifungal: voriconazole Anti-gout: colchicine Antipsychotics: lurasidone, pimozide Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine GI Motility Agent: cisapride HMG-CoA Reductase Inhibitors: lovastatin, simvastatin Microsomal triglyceride transfer protein (MTTP) Inhibitor: lomitapide o Non-opioid Analgesic (selective blocker of Na v 1.8 sodium channels): suzetrigine PDE5 Inhibitor: sildenafil (Revatio ® ) when used for the treatment of pulmonary arterial hypertension Sedative/Hypnotics: triazolam, orally administered midazolam Ritonavir is contraindicated with drugs that are potent CYP3A inducers where significantly reduced ritonavir 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 Herbal Products: St. John's Wort (hypericum perforatum) Ritonavir tablets are contraindicated in patients with known hypersensitivity to ritonavir (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome) or any of its ingredients. (4) Co-administration with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations may be associated with serious and/or life-threatening events. (4) Co-administration with drugs that significantly reduce ritonavir. (4)

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling. Drug Interactions [see Warnings and Precautions (5.1) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Pancreatitis [see Warnings and Precautions (5.3) ] Allergic Reactions/Hypersensitivity [see Warnings and Precautions (5.4) ] When co-administering ritonavir with other protease inhibitors, see the full prescribing information for that protease inhibitor including adverse reactions. The most frequently reported adverse drug reactions among patients receiving ritonavir alone or in combination with other antiretroviral drugs were gastrointestinal (including diarrhea, nausea, vomiting, abdominal pain (upper and lower), neurological disturbances (including paresthesia and oral paresthesia), rash, and fatigue/asthenia. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals LLC at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions in Adults The safety of ritonavir alone and in combination with other antiretroviral agents was studied in 1,755 adult patients. Table 1 lists treatment-emergent Adverse Reactions (with possible or probable relationship to study drug) occurring in greater than or equal to 1% of adult patients receiving ritonavir in combined Phase II/IV studies. The most frequently reported adverse drug reactions among patients receiving ritonavir alone or in combination with other antiretroviral drugs were gastrointestinal (including diarrhea, nausea, vomiting, abdominal pain (upper and lower)), neurological disturbances (including paresthesia and oral paresthesia), rash, and fatigue/asthenia. Table 1. Treatment-Emergent Adverse Reactions (With Possible or Probable Relationship to Study Drug) Occurring in greater than or equal to 1% of Adult Patients Receiving Ritonavir in Combined Phase II/IV Studies (N = 1,755) Adverse Reactions n % Eye disorders Blurred vision 113 6.4 Gastrointestinal disorders Abdominal Pain (upper and lower)* 464 26.4 Diarrhea including severe with electrolyte imbalance* 1,192 67.9 Dyspepsia 201 11.5 Flatulence 142 8.1 Gastrointestinal hemorrhage* 41 2.3 Gastroesophageal reflux disease (GERD) 19 1.1 Nausea 1,007 57.4 Vomiting* 559 31.9 General disorders and administration site conditions Fatigue including asthenia* 811 46.2 Hepatobiliary disorders Blood bilirubin increased (including jaundice)* 25 1.4 Hepatitis (including increased AST, ALT, GGT)* 153 8.7 Immune system disorders Hypersensitivity including urticaria and face edema* 114 8.2 Metabolism and nutrition disorders Edema and peripheral edema* 110 6.3 Gout* 24 1.4 Hypercholesterolemia* 52 3.0 Hypertriglyceridemia* 158 9.0 Lipodystrophy acquired* 51 2.9 Musculoskeletal and connective tissue disorders Arthralgia and back pain* 326 18.6 Myopathy/creatine phosphokinase increased* 66 3.8 Myalgia 156 8.9 Nervous system disorders Dizziness* 274 15.6 Dysgeusia* 285 16.2 Paresthesia (including oral paresthesia)* 889 50.7 Peripheral neuropathy 178 10.1 Syncope* 58 3.3 Psychiatric disorders Confusion* 52 3.0 Disturbance in attention 44 2.5 Renal and urinary disorders Increased urination* 74 4.2 Respiratory, thoracic and mediastinal disorders Coughing* 380 21.7 Oropharyngeal Pain* 279 15.9 Skin and subcutaneous tissue disorders Acne* 67 3.8 Pruritus* 214 12.2 Rash (includes erythematous and maculopapular)* 475 27.1 Vascular disorders Flushing, feeling hot* 232 13.2 Hypertension* 58 3.3 Hypotension including orthostatic hypotension* 30 1.7 Peripheral coldness* 21 1.2 * Represents a medical concept including several similar MedDRA PTs Laboratory Abnormalities in Adults Table 2 shows the percentage of adult patients who developed marked laboratory abnormalities. Table 2. Percentage of Adult Patients, by Study and Treatment Group, with Chemistry and Hematology Abnormalities Occurring in greater than 3% of Patients Receiving Ritonavir Study 245 Naive Patients Study 247 Advanced Patients Study 462 PI-Naive Patients Variable Limit Ritonavir plus ZDV Ritonavir ZDV Ritonavir Placebo Ritonavir plus Saquinavir Chemistry High Cholesterol > 240 mg/dL 30.7 44.8 9.3 36.5 8.0 65.2 CPK > 1000 IU/L 9.6 12.1 11.0 9.1 6.3 9.9 GGT > 300 IU/L 1.8 5.2 1.7 19.6 11.3 9.2 SGOT (AST) > 180 IU/L 5.3 9.5 2.5 6.4 7.0 7.8 SGPT (ALT) > 215 IU/L 5.3 7.8 3.4 8.5 4.4 9.2 Triglycerides > 800 mg/dL 9.6 17.2 3.4 33.6 9.4 23.4 Triglycerides > 1500 mg/dL 1.8 2.6 - 12.6 0.4 11.3 Triglycerides Fasting > 1500 mg/dL 1.5 1.3 - 9.9 0.3 - Uric Acid > 12 mg/dL - - - 3.8 0.2 1.4 Hematology Low Hematocrit < 30% 2.6 - 0.8 17.3 22.0 0.7 Hemoglobin < 8.0 g/dL 0.9 - - 3.8 3.9 - Neutrophils ≤ 0.5 x 10 9 /L - - - 6.0 8.3 - RBC < 3.0 x 10 12 /L 1.8 - 5.9 18.6 24.4 - WBC < 2.5 x 10 9 /L - 0.9 6.8 36.9 59.4 3.5 - Indicates no events reported. Adverse Reactions in Pediatric Patients Ritonavir has been studied in 265 pediatric patients greater than 1 month to 21 years of age. The adverse event profile observed during pediatric clinical trials was similar to that for adult patients. Vomiting, diarrhea, and skin rash/allergy were the only drug-related clinical adverse events of moderate to severe intensity observed in greater than or equal to 2% of pediatric patients enrolled in ritonavir clinical trials. Laboratory Abnormalities in Pediatric Patients The following Grade 3-4 laboratory abnormalities occurred in greater than 3% of pediatric patients who received treatment with ritonavir either alone or in combination with reverse transcriptase inhibitors: neutropenia (9%), hyperamylasemia (7%), thrombocytopenia (5%), anemia (4%), and elevated AST (3%). 6.2 Postmarketing Experience The following adverse events (not previously mentioned in the labeling) have been reported during post-marketing use of ritonavir. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to ritonavir exposure. Body as a Whole Dehydration, usually associated with gastrointestinal symptoms, and sometimes resulting in hypotension, syncope, or renal insufficiency has been reported. Syncope, orthostatic hypotension, and renal insufficiency have also been reported without known dehydration. Co-administration of ritonavir with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system. Cardiovascular System First-degree AV block, second-degree AV block, third-degree AV block, right bundle branch block have been reported [see Warnings and Precautions (5.5) ] . Cardiac and neurologic events have been reported when ritonavir has been co-administered with disopyramide, mexiletine, nefazodone, fluoxetine, and beta blockers. The possibility of drug interaction cannot be excluded. Endocrine System Cushing's syndrome and adrenal suppression have been reported when ritonavir has been co-administered with fluticasone propionate or budesonide. Nervous System There have been postmarketing reports of seizure. Also, see Cardiovascular System. Renal and Urinary Disorders Nephrolithiasis Skin and subcutaneous tissue disorders Toxic epidermal necrolysis (TEN) has been reported.

FDA lists 3 drug label records with RITONAVIR as the active ingredient. The most common dosage forms and the manufacturers with the most records are summarised below; strengths, pack sizes and inactive ingredients can still differ between apparently similar products.

4 FDA recall record(s) match this product name or manufacturer. A match means the firm or product name appears in the enforcement report; confirm lot numbers and dates against the official FDA notice before acting.

What is Ritonavir used for?
1 INDICATIONS AND USAGE Ritonavir tablets are indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. Ritonavir tablets are HIV protease inhibitors indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. (1)

Who makes Ritonavir?
Amneal Pharmaceuticals LLC is the labeler of record for Ritonavir. 3 FDA label records share the active ingredient RITONAVIR, so generic and branded versions may come from different companies; the manufacturer named on your pack is the one that matters for any enquiry.

What form does Ritonavir come in?
administered by oral. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is Ritonavir prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Are there other products containing RITONAVIR?
Yes. 3 FDA drug label records list RITONAVIR as the active ingredient. Products with the same active ingredient can usually be substituted only when a prescriber or pharmacist confirms it is appropriate.

Has Ritonavir been recalled?
4 FDA recall record(s) match this product name or manufacturer. Review the recall and safety notices section on this page and confirm lot numbers against the official FDA enforcement report.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.