ribavirin

Absorption: Systemic absorption occurs following nasal and oral inhalation. Rapidly and extensively absorbed following oral administration, but undergoes first-pass hepatic metabolism (64% bioavailability).

Distribution: 70% of inhaled drug is deposited in the respiratory tract. Appears to concentrate in the respiratory tract and red blood cells.

Metabolism/Excretion: Eliminated from the respiratory tract by distribution across membranes, macrophages, and ciliary motion. Metabolized primarily by the liver; metabolites are renally excreted.

Half-Life: Inhaln: 9.5 hr (40 days in RBCs); oral: 43.6 hr (single dose); 12 days (multiple dose).

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
Inhaln	unknown	end of inhaln	unknown
PO	unknown	1.7–3 hr	12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Receiving mechanically assisted ventilation;
CCr <50 mL/min;
Significant/unstable cardiovascular disease;
Hemoglobinopathies;
Autoimmune hepatitis or hepatic decompensation before/during treatment;
Concurrent use of zidovudine;
OB: Pregnancy;
OB: Male partners of pregnant patients.

Use Cautiously in:

Sarcoidosis (may exacerbate condition);
Anemia (dose reduction/discontinuation may be required);
Any pre-existing cardiac disease;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: May result in ↓ growth in children.

Adv. Reactions/Side Effects ⬆ ⬇

Inhalation

CV: CARDIAC ARREST, hypotension

Derm: rash

EENT: blurred vision, conjunctivitis, erythema of the eyelids, ocular irritation, photosensitivity

Hemat: hemolytic anemia, reticulocytosis

Oral

Derm: pruritus (↓ in children)

EENT: optic neuritis, papilledema, retinal artery/vein thrombosis, retinal detachment, retinal hemorrhage, retinopathy (with macular edema), visual abnormalities

GI: anorexia (↑ in children), dry mouth, dyspepsia (↓ in children), vomiting (↑ in children)

GU: ↓fertility (males)

Hemat: hemolytic anemia

MS: arthralgia (↓ in children)

Neuro: depression, aggressive behavior, dizziness, emotional lability (↑ in children), faintness, fatigue (↓ in children), HOMICIDAL IDEATION, impaired concentration (↓ in children), insomnia (↓ in children), irritability (↓ in children), SUICIDAL IDEATION/ATTEMPTS

Resp: dyspnea (↓ in children)

Misc: fever (↑ in children)

Interactions ⬆ ⬇

Drug-drug:

Oral: May ↓ the antiretroviral action of zidovudine.
May ↑ hematologic toxicity of zidovudine.
May ↑ risk of pancytopenia when used with azathioprine.

Route/Dosage ⬆ ⬇

RSV Infection

Inhaln (Infants and Young Children): 300 mL of 20 mg/mL solution delivered via mist for 12–18 hr/day.

Chronic Hepatitis C

Viral Genotype 1 or 4
PO (Adults ≥75 kg): 600 mg twice daily for 48 wk.
PO (Adults <75 kg): 500 mg twice daily for 48 wk.
PO (Children ≥5 yr and ≥75 kg): 600 mg in the morning, then 600 mg in the evening for 48 wk.
PO (Children ≥5 yr and 60–74 kg): 400 mg in the morning, then 600 mg in the evening for 48 wk.
PO (Children ≥5 yr and 47–59 kg): 400 mg in the morning, then 400 mg in the evening for 48 wk.
PO (Children ≥5 yr and 34–46 kg): 200 mg in the morning, then 400 mg in the evening for 48 wk.
PO (Children ≥5 yr and 23–33 kg): 200 mg in the morning, then 200 mg in the evening for 48 wk.

Renal Impairment

PO (Adults ): CCr 30–50 mL/min: 200 mg/day alternating with 400 mg/day every other day for 48 wk; CCr <30 mL/min or Hemodialysis: 200 mg once daily for 48 wk.
Viral Genotype 2 or 3
PO (Adults ): 400 mg twice daily for 24 wk.
PO (Children ≥5 yr and ≥75 kg): 600 mg in the morning, then 600 mg in the evening for 24 wk.
PO (Children ≥5 yr and 60–74 kg): 400 mg in the morning, then 600 mg in the evening for 24 wk.
PO (Children ≥5 yr and 47–59 kg): 400 mg in the morning, then 400 mg in the evening for 24 wk.
PO (Children ≥5 yr and 34–46 kg): 200 mg in the morning, then 400 mg in the evening for 24 wk.
PO (Children ≥5 yr and 23–33 kg): 200 mg in the morning, then 200 mg in the evening for 24 wk.

Renal Impairment

PO (Adults ): CCr 30–50 mL/min: 200 mg/day alternating with 400 mg/day every other day for 24 wk; CCr <30 mL/min or Hemodialysis: 200 mg once daily for 24 wk.

Availability ⬆ ⬇

(Generic available)

Capsules: 200 mg
Powder for reconstitution for aerosol use (Virazole): 6 g/vial
Tablets: 200 mg; 400 mg; 600 mg

Assessment ⬆ ⬇

RSV: Assess patient for infection (vital signs, sputum, WBC) at beginning and during therapy.
- Obtain specimens for culture and sensitivity prior to initiating therapy. First dose may be given before receiving results.
- Assess respiratory status (lung sounds, quality and rate of respirations) and fluid status prior to and frequently throughout therapy. May require discontinuation depending on severity of impairment.
Chronic Hepatitis C: Monitor symptoms of hepatitis during therapy.
Assess for signs of neuropsychiatric disorders (irritability, anxiety, depression, suicidal ideation, aggressive behavior). May require discontinuation of ribavirin.
- Obtain ECG prior to therapy in patients with pre-existing cardiac disease. Assess patient for cardiovascular disorders (BP, HR, chest pain). ↓ dose or discontinue therapy if cardiac disorders occur. May cause MI.
- Assess for signs and symptoms of pancreatitis (nausea, vomiting, abdominal pain) during therapy. Discontinue therapy if these occur; may be fatal.

Lab Test Considerations:

Chronic Hepatitis C:Verify negative pregnancy test before starting therapy, periodically during therapy, and for 6 mo after final dose.
- Monitor CBC with differential prior to initiation, at wk 2, at wk 4, and regularly during therapy. If hemoglobin <10 g/dL in patients with no history of cardiac disease or ↓ >2 g/dL in any 4-wk treatment period in patients with history of stable cardiac disease,↓ ribavirin dose to 600 mg (200 mg in AM and 400 mg in PM). If hemoglobin <8.5 g/dL in patients with no history of cardiac disease or <12 g/dL despite dose reduction in patients with history of stable cardiac disease, discontinue combination therapy permanently. If dose withheld in children, may restart with 50% of original dose.
- Monitor basic metabolic panel prior to, after 4 wk, and periodically during therapy.
- Monitor liver function tests and thyroid-stimulating hormone prior to and periodically during therapy.
- May cause ↑ serum bilirubin and uric acid levels.

Implementation ⬆ ⬇

Do not confuse ribavirin with riboflavin.
Inhaln: Infants requiring assisted ventilation should be suctioned every 1–2 hr and pulmonary pressures monitored every 2–4 hr.
- Ribavirin treatment should begin within the first 3 days of RSV infection to be effective.
- Ribavirin aerosol should be administered using the Viratek SPAG model SPAG-2 only. Do not administer via other aerosol-generating devices. Usually administered using an infant oxygen hood attached to the SPAG-2 aerosol generator. Administration by face mask may be used if the oxygen hood cannot be used.
- Reconstitute ribavirin 6-g vial with preservative-free sterile water for injection or inhalation. Transfer to clean, sterilized Erlenmeyer flask of the SPAG-2 reservoir and dilute to a final volume of 300 mL. This recommended concentration (20 mg/mL) in the reservoir provides a concentration of aerosol ribavirin of 190 mcg/L of air over a 12-hr period. Solution should be discarded and replaced every 24 hr.
- Aerosol treatments should be administered continuously 12–18 hr/day for 3–7 days.
- Use gloves when handling intact tablets or capsules and face protection if there is concern for patient resistance or vomiting. Pregnant people should avoid providing direct patient care; when unavoidable, minimize exposure with use of gloves, face and eye protection, and respirator when appropriate.
PO: Administer with food.
- For children, determine if child is able to swallow 200-mg tablet. DNC: Capsules and tablets should not be opened, crushed, or broken.

Patient/Family Teaching ⬆ ⬇

RSV: Explain purpose and side effects of medication. Advise parents to read Patient Information before starting therapy.
Inform parents that ribavirin may cause blurred vision and photosensitivity.
Chronic Hepatitis C: Instruct patient to take ribavirin at the same time each day for the full course of therapy. Take missed doses as soon as remembered. If total day dose is missed, notify health care professional; do not double doses. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
- Advise patient to brush teeth twice daily, have regular dental examinations, and rinse mouth thoroughly after vomiting to prevent dental and periodontal disorders.
- May cause dizziness, confusion, fatigue, and drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
- Inform patient that ribavirin may not reduce the risk of transmission of the hepatitis C virus (HCV) to others or prevent cirrhosis, liver failure, or liver cancer.
- Discuss with patient the possibility of hair loss. Explore methods of coping.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Advise patient to stop taking ribavirin and notify health care professional immediately if rash with fever; blisters or sores in mouth, nose, or eyes; conjunctivitis; trouble breathing; hives or swelling; chest pain; severe stomach pain or low back pain; bloody diarrhea or bloody or black stools; bruising or unusual bleeding; change in vision; fever >100.5°F; worsening psoriasis; worsening depression; or suicidal thoughts occur.
- May cause fetal harm. Instruct women of reproductive potential and men with female partners of reproductive potential to use two forms of effective contraception during therapy and for at least 6 mo (females) and 9 mo (males) following conclusion of therapy. Men must use a condom. Avoid breastfeeding during therapy.
- Emphasize the importance of routine lab test to monitor for side effects.

Evaluation/Desired Outcomes ⬆ ⬇

Resolution of the signs and symptoms of RSV.
Decreased progression and sequelae of chronic hepatitis C. Therapy with peginterferon alfa-2a and ribavirin should be discontinued if at least a 2-log 10 reduction from baseline in HCV RNA by 12 wk of therapy or undetectable HCV RNA levels after 24 wk of therapy.

US Brand Names ⬆ ⬇

~~Copegus,~~ ~~Rebetol,~~ Virazole

Canadian Brand Names ⬆ ⬇

Code ⬆

NDC Code

0187- Bausch Health US, LLC
- 0187-0007- Virazole
  - 0187-0007-01- 1 VIAL, GLASS in 1 CARTON (0187-0007-01) / 1 POWDER, FOR SOLUTION in 1 VIAL, GLASS

42494- Cameron Pharmaceuticals
- 42494-423- Ribavirin
  - 42494-423-01- 1 VIAL, GLASS in 1 CARTON (42494-423-01) / 1 POWDER, FOR SOLUTION in 1 VIAL, GLASS

44657- Curia Italy S.r.l.
- 44657-0076-
  - 44657-0076-1- 25 kg in 1 DRUM (44657-0076-1)

63629- Bryant Ranch Prepack
- 63629-2149- Ribavirin
  - 63629-2149-1- 1 VIAL, GLASS in 1 CARTON (63629-2149-1) / 1 POWDER, FOR SOLUTION in 1 VIAL, GLASS

65862- Aurobindo Pharma Limited
- 65862-207- Ribavirin
  - 65862-207-05- 500 TABLET, FILM COATED in 1 BOTTLE (65862-207-05)

65862- Aurobindo Pharma Limited
- 65862-207-
  - 65862-207-39- 3000 TABLET, FILM COATED in 1 BAG (65862-207-39)

65862- Aurobindo Pharma Limited
- 65862-207- Ribavirin
  - 65862-207-68- 168 TABLET, FILM COATED in 1 BOTTLE (65862-207-68)

65862- Aurobindo Pharma Limited
- 65862-290- Ribavirin
  - 65862-290-05- 500 CAPSULE in 1 BOTTLE (65862-290-05)

65862- Aurobindo Pharma Limited
- 65862-290- Ribavirin
  - 65862-290-18- 180 CAPSULE in 1 BOTTLE (65862-290-18)

65862- Aurobindo Pharma Limited
- 65862-290-
  - 65862-290-39- 3000 CAPSULE in 1 BAG (65862-290-39)

65862- Aurobindo Pharma Limited
- 65862-290- Ribavirin
  65862-290-42- 42 CAPSULE in 1 BOTTLE (65862-290-42)

65862- Aurobindo Pharma Limited
- 65862-290- Ribavirin
  - 65862-290-56- 56 CAPSULE in 1 BOTTLE (65862-290-56)

65862- Aurobindo Pharma Limited
- 65862-290- Ribavirin
  - 65862-290-70- 70 CAPSULE in 1 BOTTLE (65862-290-70)

65862- Aurobindo Pharma Limited
- 65862-290- Ribavirin
  - 65862-290-84- 84 CAPSULE in 1 BOTTLE (65862-290-84)

65862- Aurobindo Pharma Limited
- 65862-409-
  - 65862-409-37- 50 kg in 1 DRUM (65862-409-37)

66122- Zhejiang Cheng Yi Pharmaceutical Co., Ltd.
- 66122-0002-
  66122-0002-1- 51 kg in 1 DRUM (66122-0002-1)

68382- Zydus Pharmaceuticals USA Inc.
- 68382-395- RIBAVIRIN
  68382-395-04- 4 VIAL in 1 CARTON (68382-395-04) / 1 POWDER, FOR SOLUTION in 1 VIAL

68475- Navinta LLC
- 68475-003- RIBAVIRIN
  - 68475-003-04- 4 VIAL in 1 CARTON (68475-003-04) / 1 POWDER, FOR SOLUTION in 1 VIAL

68682- Oceanside Pharmaceuticals
- 68682-019- Ribavirin
  - 68682-019-01- 1 VIAL, GLASS in 1 CARTON (68682-019-01) / 1 POWDER, FOR SOLUTION in 1 VIAL, GLASS

68682- Oceanside Pharmaceuticals
- 68682-019- Ribavirin
  - 68682-019-06- 4 VIAL, GLASS in 1 CARTON (68682-019-06) / 1 POWDER, FOR SOLUTION in 1 VIAL, GLASS

72162- Bryant Ranch Prepack
- 72162-1331- Ribavirin
  - 72162-1331-2- 1 VIAL, GLASS in 1 CARTON (72162-1331-2) / 1 POWDER, FOR SOLUTION in 1 VIAL, GLASS

73301- LSNE, Inc
- 73301-006-
  - 73301-006-01- 100 mL in 1 VIAL (73301-006-01)

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇