In Summary

Commonly reported side effects of ritonavir include: asthenia, diarrhea, hypertriglyceridemia, increased gamma-glutamyl transferase, nausea, vomiting, and unpleasant taste. Other side effects include: abdominal pain, dyspepsia, fever, hyperlipidemia, increased serum alanine aminotransferase, peripheral paresthesia, dysgeusia, and oral paresthesia. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to ritonavir: oral capsule liquid filled, oral powder, oral solution, oral tablet

Along with its needed effects, ritonavir may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking ritonavir:

Less common

• Fainting
• feeling faint, dizzy, or lightheaded
• feeling of warmth or heat
• flushing or redness of the skin, especially on the face and neck
• headache
• sweating

Rare

• Confusion
• dehydration
• dry or itchy skin
• fruity mouth odor
• increased hunger
• increased thirst
• increased urination
• nausea
• vomiting
• weight loss

Incidence not known

• Bloating
• chills
• constipation
• convulsions
• cough
• darkened urine
• decreased urination
• difficulty with breathing
• dry mouth
• fast heartbeat
• fever
• hives or welts, itching, skin rash
• increase in heart rate
• indigestion
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of appetite
• loss of bladder control
• muscle spasm or jerking of all extremities
• noisy breathing
• pains in the stomach, side, or abdomen, possibly radiating to the back
• rapid breathing
• redness of the skin
• sudden loss of consciousness
• sunken eyes
• thirst
• tightness in the chest
• unusual tiredness or weakness
• wrinkled skin
• yellow eyes or skin

Some side effects of ritonavir may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Belching
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• change in sense of taste
• diarrhea
• dizziness
• general feeling of discomfort or illness
• heartburn
• lack or loss of strength
• sleepiness or unusual drowsiness
• trouble sleeping
• weakness

Less common

• Body aches or pain
• congestion
• delusions
• dementia
• difficulty with moving
• discouragement
• dryness or soreness of the throat
• excess air or gas in the stomach or intestines
• fear
• feeling sad or empty
• full feeling
• hoarseness
• increased urge to urinate during the night
• irritability
• lack of appetite
• loss of interest or pleasure
• mood or mental changes
• muscle pain or stiffness
• nervousness
• pain in the joints or in an unspecified location
• passing gas
• runny nose
• tender, swollen glands in the neck
• throat irritation
• tiredness
• trouble concentrating
• trouble swallowing
• voice changes
• waking to urinate at night

Incidence not known

• Gaining weight around your neck, upper back, breast, face, or waist

For Healthcare Professionals

Applies to ritonavir: oral capsule, oral powder for reconstitution, oral solution, oral tablet

General

The most frequently reported side effects associated with this drug alone and in combination with other antiretrovirals were gastrointestinal (including nausea, diarrhea, vomiting, upper and lower abdominal pain), neurological disturbances (including paresthesia, oral paresthesia), rash, and fatigue/asthenia.

When used as a pharmacokinetic enhancer, side effects were dependent on the coadministered protease inhibitor. The manufacturer product information for the coadministered protease inhibitor should be consulted.

Gastrointestinal

Pancreatitis (including some fatalities) has been reported in patients using this drug, including those who developed hypertriglyceridemia.

Limit for high chemistry included amylase greater than 2 times the upper limit of normal (2 x ULN).

Very common (10% or more): Diarrhea (including severe with electrolyte imbalance; up to 67.9%), nausea (up to 57.4%), vomiting (up to 31.9%), upper and lower abdominal pain (up to 26.4%), dyspepsia (up to 11.5%)

Common (1% to 10%): Flatulence, gastrointestinal (GI) hemorrhage, gastroesophageal reflux disease, mouth ulcer, pancreatitis, increased amylase, constipation, circumoral paresthesia, local throat irritation

Frequency not reported: Abnormal stools, bloody diarrhea, cheilitis, colitis, dry mouth, dysphagia, eructation, esophagitis, esophageal ulcer, fecal incontinence, gastritis, gastroenteritis, GI disorder, GI symptoms, gingivitis, ileitis, ileus, melena, oral moniliasis, periodontal abscess, pseudomembranous colitis, rectal disorder, rectal hemorrhage, sialadenitis, stomatitis, tenesmus, tongue edema, ulcerative colitis

Metabolic

Very common (10% or more): Increased cholesterol (up to 65.2%), increased triglycerides (up to 33.6%)

Common (1% to 10%): Increased fasting triglycerides, hypertriglyceridemia, increased uric acid, hypercholesterolemia, increased glucose, gout, dehydration, anorexia, increased alkaline phosphatase, decreased potassium, decreased calcium

Uncommon (0.1% to 1%): Diabetes mellitus, increased magnesium, increased LDH, increased chloride, increased potassium, decreased sodium, decreased chloride, decreased magnesium

Rare (0.01% to 0.1%): Hyperglycemia

Frequency not reported: Alcohol intolerance, avitaminosis, enzymatic abnormality, xanthomatosis, redistribution/accumulation of body fat

Antiretroviral therapy:

-Frequency not reported: Redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance"), increased blood lipid levels, increased glucose levels

Protease inhibitor therapy:

-Postmarketing reports: New onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, hyperglycemia, diabetic ketoacidosis

Limits for high chemistry included cholesterol greater than 240 mg/dL, triglycerides greater than 800 mg/dL, triglycerides greater than 1500 mg/dL (greater than 16.9 mmol/L), fasting triglycerides greater than 1500 mg/dL (greater than 16.9 mmol/L), uric acid greater than 12 mg/dL (greater than 0.7 mmol/L), glucose greater than 13.8 mmol/L, alkaline phosphatase greater than 550 units/L, LDH greater than 1170 units/L, chloride greater than 122 mmol/L, and potassium greater than 6 mmol/L. Limits for low chemistry included potassium 3 mmol/L, calcium less than 3.45 mmol/L, chloride less than 84 mmol/L, magnesium less than 1 mmol/L, and sodium less than 123 mmol/L.

Increases of 30% to 40% from baseline have been reported for cholesterol levels and 200% to 300% for triglycerides.

Dehydration (usually associated with GI symptoms, and sometimes resulting in hypotension, syncope, or renal insufficiency) has been reported (including during postmarketing experience); orthostatic hypotension, syncope, and renal insufficiency have also been reported without known dehydration.

Hyperglycemia has also been reported during postmarketing experience in patients with and without known history of diabetes.

New onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, and hyperglycemia have been reported in HIV-infected patients receiving protease inhibitors; in some cases, diabetic ketoacidosis occurred. No causal relationship has been established.

Nervous system

Very common (10% or more): Paresthesia (including oral and peripheral paresthesia; up to 50.7%), dysgeusia (16.2%), dizziness (up to 15.6%), taste perversion (up to 15.5%), peripheral neuropathy (10.1%), headache

Common (1% to 10%): Syncope, seizure, somnolence

Frequency not reported: Abnormal gait, amnesia, aphasia, ataxia, coma, convulsion, dementia, grand mal convulsion, hearing impairment, hyperesthesia, hyperkinesia, hypoesthesia, incoordination, migraine, neuralgia, neuropathy, paralysis, peripheral neuropathic pain, peripheral sensory neuropathy, sleep disorder, speech disorder, stupor, subdural hematoma, tinnitus, tremor, vertigo, vestibular disorder, cerebral ischemia, cerebral venous thrombosis, taste loss

Postmarketing reports: Neurologic events

Syncope and seizure have also been reported during postmarketing experience.

Cardiac and neurologic events have been reported during postmarketing experience when this drug was used with disopyramide, mexiletine, nefazodone, fluoxetine, and beta blockers. Possible drug interaction could not be excluded.

Other

Very common (10% or more): Fatigue (including asthenia; 46.2%), asthenia (up to 14.2%), flushing/feeling hot (13.2%)

Common (1% to 10%): Edema, peripheral edema, peripheral coldness, fever, weight loss, malaise

Uncommon (0.1% to 1%): Decreased albumin

Frequency not reported: Breast pain, enlarged abdomen, accidental injury, cachexia, chest pain, chills, facial edema, facial pain, influenza syndrome, hypothermia, neck pain, neck rigidity, pain (unspecified), pelvic pain, substernal chest pain, ear pain, increased cerumen, parosmia, thirst

Postmarketing reports: Acute ergot toxicity (characterized by vasospasm, ischemia of extremities and other tissues [including the central nervous system])

Antiretroviral therapy:

-Frequency not reported: Increased weight

Limit for low chemistry included albumin less than 20 g/L.

Acute ergot toxicity has been reported when this drug was used with ergotamine or dihydroergotamine.

Hematologic

Limits for low hematology included WBCs less than 2.5 x 10(9)/L, RBCs less than 3 x 10(12)/L, hematocrit less than 30% (less than 0.3), neutrophils up to 0.5 x 10(9)/L, hemoglobin less than 8 g/dL, and platelet count less than 2 x 10(9)/L. Limits for high hematology included eosinophils greater than 1 x 10(9)/L, neutrophils greater than 20 x 10(9)/L, WBCs greater than 25 x 10(9)/L, and prothrombin time greater than 1.5 x ULN.

Increased bleeding (including spontaneous skin hematomas and hemarthrosis) in patients with hemophilia type A or B treated has been associated with protease inhibitors. In many of the reported cases, treatment with protease inhibitors was continued or restarted and some patients required additional factor VIII. A causal relationship between protease inhibitor therapy and these episodes has not been established.

Very common (10% or more): Decreased WBCs (up to 36.9%), decreased RBCs (up to 18.6%), decreased hematocrit (up to 17.3%)

Common (1% to 10%): Decreased neutrophils, decreased hemoglobin, thrombocytopenia, increased eosinophils, increased neutrophils, increased WBCs

Uncommon (0.1% to 1%): Increased prothrombin time, decreased platelet count

Frequency not reported: Acute myeloblastic leukemia, anemia, ecchymosis, leukopenia, lymphadenopathy, lymphocytosis, myeloproliferative disorder

Protease inhibitor therapy:

-Frequency not reported: Increased bleeding (including spontaneous skin hematomas, hemarthrosis) in hemophiliacs

Dermatologic

Toxic epidermal necrolysis has also been reported during postmarketing experience.

Alopecia has been reported in patients using indinavir or atazanavir plus this drug.

Very common (10% or more): Rash (including erythematous rash, maculopapular rash; up to 27.1%), pruritus (up to 12.2%)

Common (1% to 10%): Acne, acquired lipodystrophy, sweating

Rare (0.01% to 0.1%): Stevens-Johnson syndrome, toxic epidermal necrolysis

Frequency not reported: Contact dermatitis, dry skin, eczema, erythema multiforme, exfoliative dermatitis, folliculitis, fungal dermatitis, furunculosis, maculopapular rash, molluscum contagiosum, onychomycosis, photosensitivity reaction, psoriasis, pustular rash, seborrhea, skin discoloration, skin disorder, skin hypertrophy, skin melanoma, urticaria, vesiculobullous rash, alopecia

Respiratory

Very common (10% or more): Coughing (21.7%), oropharyngeal pain (15.9%), pharyngitis

Frequency not reported: Asthma, bronchitis, increased cough, dyspnea, epistaxis, hiccup, hypoventilation, interstitial pneumonia, larynx edema, lung disorder, rhinitis, sinusitis

Hepatic

Limits for high chemistry included GGT greater than 300 international units/L, AST greater than 180 international units/L, ALT greater than 215 international units/L, and total bilirubin greater than 61 mcmol/L.

Hepatic dysfunction (including some fatalities) has been reported, generally in patients taking multiple concurrent medications and/or with advanced AIDS.

Very common (10% or more): Increased GGT (up to 19.6%)

Common (1% to 10%): Increased AST, increased ALT, hepatitis (including increased AST, ALT, GGT), increased blood bilirubin (including jaundice), increased total bilirubin

Frequency not reported: Exacerbation of chronic liver disease, cholangitis, cholestatic jaundice, hepatic coma, hepatomegaly, hepatosplenomegaly, liver damage, liver function tests abnormal, hepatic transaminase elevations exceeding 5 x ULN, clinical hepatitis, jaundice

Postmarketing reports: Hepatic dysfunction (including some fatalities)

Musculoskeletal

Very common (10% or more): Arthralgia and back pain (18.6%), increased creatine phosphokinase (CPK; up to 12.1%)

Common (1% to 10%): Myalgia, myopathy/increased CPK, myositis, rhabdomyolysis

Frequency not reported: Arthritis, arthrosis, bone disorder, bone pain, extraocular palsy, joint disorder, leg cramps, muscle cramps, muscle weakness, twitching, osteonecrosis

Limit for high chemistry included CPK greater than 1000 international units/L.

Osteonecrosis has been reported, particularly in patients with advanced HIV disease, long-term combination antiretroviral therapy, or other risk factors (including corticosteroid use, alcohol use, severe immunosuppression, higher body mass index).

Hypersensitivity

Common (1% to 10%): Hypersensitivity (including urticaria, face edema)

Rare (0.01% to 0.1%): Anaphylaxis

Frequency not reported: Allergic reactions (including urticaria, mild skin eruptions, bronchospasm, angioedema)

Ocular

Common (1% to 10%): Blurred vision

Frequency not reported: Abnormal electrooculogram, abnormal electroretinogram, abnormal vision, amblyopia/blurred vision, blepharitis, conjunctivitis, diplopia, eye disorder, eye pain, iritis, photophobia, uveitis, visual field defect, vitreous disorder

Genitourinary

Common (1% to 10%): Increased urination, menorrhagia

Frequency not reported: Albuminuria, cystitis, dysuria, glycosuria, hematuria, impotence, nocturia, penis disorder, polyuria, urethritis, urinary frequency, urinary retention, urinary tract infection, vaginitis

Menorrhagia has also been reported during postmarketing experience.

Cardiovascular

Common (1% to 10%): Hypertension, hypotension (including orthostatic hypotension), vasodilation

Uncommon (0.1% to 1%): Myocardial infarction

Frequency not reported: PR interval prolonged, cardiovascular disorder, palpitation, peripheral vascular disorder, phlebitis, postural hypotension, tachycardia, vasospasm, hemorrhage

Postmarketing reports: Orthostatic hypotension, first-degree atrioventricular (AV) block, second-degree AV block, third-degree AV block, right bundle branch block, cardiac events

Myocardial infarction has also been reported during postmarketing experience.

Cardiac and neurologic events have been reported during postmarketing experience when this drug was used with disopyramide, mexiletine, nefazodone, fluoxetine, and beta blockers. Possible drug interaction could not be excluded.

Psychiatric

Common (1% to 10%): Confusion, disturbance in attention, insomnia, anxiety, abnormal thinking

Frequency not reported: Abnormal dreams, depression, depersonalization, emotional lability, euphoria, agitation, hallucinations, decreased libido, manic reaction, nervousness, personality disorder

Renal

Common (1% to 10%): Renal impairment (e.g., oliguria, elevated creatinine)

Uncommon (0.1% to 1%): Acute renal failure, increased creatinine

Frequency not reported: Renal calculus, renal failure, abnormal kidney function, kidney pain, pyelonephritis, increased BUN

Postmarketing reports: Renal insufficiency

Limit for high chemistry included creatinine greater than 0.3 mmol/L.

Renal insufficiency was reported in 3 AIDS patients receiving this drug. All cases occurred within 10 to 15 days after starting this drug and all were reversible upon discontinuation.

Immunologic

Frequency not reported: Immune reconstitution syndrome, autoimmune disorders in the setting of immune reconstitution (e.g., Graves' disease, polymyositis, Guillain-Barre syndrome)

Endocrine

Cushing's syndrome and adrenal suppression have been reported when this drug was used with fluticasone or budesonide.

Common (1% to 10%): Decreased free and total thyroxin

Frequency not reported: Adrenal cortex insufficiency, hormone level altered

Postmarketing reports: Cushing's syndrome, adrenal suppression