bosentan

BOE-sen-tan

Therapeutic Classification: vasodilators

Pharmacologic Classification: endothelin receptor antagonists

REMS

Pulmonary arterial hypertension (PAH) (WHO Group 1).
Idiopathic or congenital PAH.

Antagonizes the effects of the neurohormone endothelin by binding to its receptor sites in endothelium and vascular smooth muscle.

Therapeutic effects:

Improved exercise capacity and decreased clinical deterioration.

Absorption: 50% absorbed following oral administration.

Distribution: Well distributed to tissues.

Protein Binding: >98%.

Metabolism/Excretion: Highly metabolized; one metabolite contributes to pharmacologic activity. Eliminated via biliary excretion; <3% excreted in urine.

Half-Life: 5 hr.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	3–5 hr	unknown

Contraindicated in:

Hypersensitivity;
Concurrent use of cyclosporine or glyburide;
Moderate to severe liver impairment or patients with ↑ liver enzymes;
OB: Pregnancy; Lactation.

Use Cautiously in:

Rep: Women of reproductive potential;
Pedi: Children 3 yr (safety and effectiveness not established).

CV: edema, hypotension, palpitations

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), flushing, pruritus, rash

EENT: nasopharyngitis

GI: dyspepsia, HEPATOTOXICITY

GU: ↓sperm counts

Hemat: anemia

Neuro: headache, fatigue

Misc: ANAPHYLAXIS, ANGIOEDEMA

Drug-drug:

Significantly ↓ cyclosporinelevels; cyclosporine significantly ↑ bosentan levels; concurrent use contraindicated.
↑risk of hepatotoxicity with glyburide; concurrent use contraindicated.
May ↓ effectiveness of hormonal contraceptives (additional method of contraception recommended).
Lopinavir/ritonavir or other ritonavir—containing regimens significantly ↑ levels (initiate bosentan at 62.5 mg once daily or every other day if receiving ritonavir-containing regimen for ≥10 days) (if initiating ritonavir in patient already receiving bosentan, discontinue bosentan for ≥36 hr before initiating ritonavir; can resume bosentan after ≥10 days at 62.5 mg once daily or every other day).
Ketoconazole↑ levels.
May ↓ levels of atorvastatin, lovastatin, sildenafil, simvastatin, sirolimus, tacrolimus, tadalafil, and warfarin.

PO (Adults and Children >12 yr and >40 kg): 62.5 mg twice daily for 4 wk initially, then ↑ to maintenance dose of 125 mg twice daily.
PO (Adults and Children >12 yr and <40 kg): 62.5 mg twice daily as initial and maintenance dose.
PO (Children 3–12 yr and 24.1–40 kg): 64 mg twice daily as initial and maintenance dose.
PO (Children 3–12 yr and 16.1–24 kg): 48 mg twice daily as initial and maintenance dose.
PO (Children 3–12 yr and 8.1–16 kg): 32 mg twice daily as initial and maintenance dose.
PO (Children 3–12 yr and 4–8 kg): 16 mg twice daily as initial and maintenance dose.

(Generic available)

Tablets: 62.5 mg; 125 mg
Tablets for oral suspension: 32 mg

Assess for signs and symptoms of primary pulmonary hypertension (dyspnea, exercise intolerance) prior to and periodically during therapy.
Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling, associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.

Lab Test Considerations:

Monitor serum AST, ALT, and bilirubin prior to and monthly during treatment. If AST and ALT are ↑ >3 and ≤5 times the upper limit of normal (ULN), confirm level with a second test. If confirmed, reduce dose or interrupt therapy and monitor AST and ALT every 2 wk. If AST and ALT return to pretreatment levels, continue therapy or resume therapy at starting dose and recheck AST and ALT within 3 days.If AST and ALT are >5 and ≤8 times the ULN, confirm level with a second test. If confirmed, stop therapy and monitor AST and ALT every 2 wk. Once AST and ALT return to normal levels, reintroduce therapy at starting dose and recheck AST and ALT levels within 3 days. If AST and ALT levels are >8 times the ULN, if clinical symptoms of liver injury (nausea, vomiting, fever, abdominal pain, jaundice, unusual lethargy or fatigue) occur, or if bilirubin levels are ≥2 times the ULN, discontinue therapy permanently.
- Verify negative urine or serum pregnancy test performed before starting and monthly before each new Rx.
- Monitor hemoglobin and hematocrit levels 1 and 3 mo after initiation of therapy and every 3 mo thereafter. May cause ↓ in hemoglobin.

Do not confuse Tracleer with Tricor.
PO: Administer in the morning and evening without regard to food. Dispersible tablets can be divided in half; avoid dividing into quarters. Disperse tablets for oral suspension in a minimal amount of water immediately before administration.
- Bosentan can only be prescribed through the Bosentan REMS Program. Prescribers and pharmacies must be enrolled in Bosentan REMS program. Patients must understand risks and benefits, and complete enrollment form. Information is available at www.BosentanREMSProgram.com or 1-866-359-2612.

Instruct patient to take bosentan as directed. Take missed doses as soon as remembered unless almost time for next dose; do not double doses. Do not stop taking bosentan without consulting health care professional; may cause an increase in symptoms. Explain the requirements of the Bosentan REMS Program.
Advise patient to notify health care professional immediately if nausea, vomiting, fever, abdominal pain, unusual tiredness, stomach pain, or jaundice occurs or if swelling of ankles or legs or difficulty breathing occurs.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any Rx, OTC, or herbal products.
Advise patient of the requirement of monthly lab tests to monitor for liver dysfunction.
Rep: May cause fetal harm. Hormonal contraceptives, including oral, injectable, transdermal, and implantable forms, may not be reliable when administered with bosentan. Instruct females of reproductive potential to use acceptable methods of contraception (1 highly effective form of contraception — intrauterine device [IUD] or tubal sterilization, or a combination of methods — hormonal method with a barrier method or two barrier methods) during and for 1 mo after therapy is completed. Hormonal contraceptives alone should not be used for contraception. If partner's vasectomy is the chosen method, a hormonal or barrier method must be used in addition to the vasectomy. Counsel patient on pregnancy prevention and emergency contraception. Patient should discontinue medication and inform health care professional immediately if pregnancy is suspected. Advise patient to avoid breastfeeding during therapy. Inform men that bosentan may cause decreased sperm count.

Improved exercise capacity and decreased rate of clinical progression in patients with PAH.

Tracleer

NDC Code

0054- West-Ward Pharmaceuticals Corp.
- 0054-0520- Bosentan
  - 0054-0520-21- 60 TABLET in 1 BOTTLE (0054-0520-21)

0054- West-Ward Pharmaceuticals Corp.
- 0054-0521- Bosentan
  - 0054-0521-21- 60 TABLET in 1 BOTTLE (0054-0521-21)

0591- Actavis Pharma, Inc.
- 0591-2511- bosentan
  - 0591-2511-60- 60 TABLET, FILM COATED in 1 BOTTLE (0591-2511-60)

0591- Actavis Pharma, Inc.
- 0591-2512- bosentan
  - 0591-2512-60- 60 TABLET, FILM COATED in 1 BOTTLE (0591-2512-60)

10148- CoTherix, Inc.
- 10148-125- bosentan
  - 10148-125-60- 1 BOTTLE, PLASTIC in 1 CARTON (10148-125-60) > 60 TABLET, FILM COATED in 1 BOTTLE, PLASTIC

10148- CoTherix, Inc.
- 10148-625- bosentan
  - 10148-625-60- 1 BOTTLE, PLASTIC in 1 CARTON (10148-625-60) > 60 TABLET, FILM COATED in 1 BOTTLE, PLASTIC

47335- Sun Pharmaceutical Industries, Inc.
- 47335-038- Bosentan
  - 47335-038-64- 10 BLISTER PACK in 1 CARTON (47335-038-64) > 3 TABLET, FILM COATED in 1 BLISTER PACK (47335-038-60)

47335- Sun Pharmaceutical Industries, Inc.
- 47335-038- Bosentan
  - 47335-038-86- 60 TABLET, FILM COATED in 1 BOTTLE (47335-038-86)

47335- Sun Pharmaceutical Industries, Inc.
- 47335-039- Bosentan
  - 47335-039-64- 10 BLISTER PACK in 1 CARTON (47335-039-64) > 3 TABLET, FILM COATED in 1 BLISTER PACK (47335-039-60)

47335- Sun Pharmaceutical Industries, Inc.
- 47335-039- Bosentan
  - 47335-039-86- 60 TABLET, FILM COATED in 1 BOTTLE (47335-039-86)

47781- Alvogen Inc.
- 47781-270- Bosentan
  - 47781-270-60- 60 TABLET, FILM COATED in 1 BOTTLE (47781-270-60)

47781- Alvogen Inc.
- 47781-271- Bosentan
  - 47781-271-60- 60 TABLET, FILM COATED in 1 BOTTLE (47781-271-60)

49884- Par Pharmaceutical, Inc.
- 49884-058- Bosentan
  - 49884-058-02- 60 TABLET, FILM COATED in 1 CONTAINER (49884-058-02)

49884- Par Pharmaceutical, Inc.
- 49884-059- Bosentan
  - 49884-059-02- 60 TABLET, FILM COATED in 1 CONTAINER (49884-059-02)

65162- Amneal Pharmaceuticals LLC
- 65162-873- Bosentan
  - 65162-873-06- 60 TABLET, FILM COATED in 1 BOTTLE (65162-873-06)

65162- Amneal Pharmaceuticals LLC
- 65162-874- Bosentan
  - 65162-874-06- 60 TABLET, FILM COATED in 1 BOTTLE (65162-874-06)

66215- Actelion Pharmaceuticals US, Inc.
- 66215-101- Tracleer
  - 66215-101-03- 10 BLISTER PACK in 1 CARTON (66215-101-03) > 3 TABLET, FILM COATED in 1 BLISTER PACK

66215- Actelion Pharmaceuticals US, Inc.
- 66215-101- Tracleer
  - 66215-101-06- 1 BOTTLE, PLASTIC in 1 CARTON (66215-101-06) > 60 TABLET, FILM COATED in 1 BOTTLE, PLASTIC

66215- Actelion Pharmaceuticals US, Inc.
- 66215-102- Tracleer
  - 66215-102-03- 10 BLISTER PACK in 1 CARTON (66215-102-03) > 3 TABLET, FILM COATED in 1 BLISTER PACK

66215- Actelion Pharmaceuticals US, Inc.
- 66215-102- Tracleer
  - 66215-102-06- 1 BOTTLE, PLASTIC in 1 CARTON (66215-102-06) > 60 TABLET, FILM COATED in 1 BOTTLE, PLASTIC

66215- Actelion Pharmaceuticals US, Inc.
- 66215-103- Tracleer
  - 66215-103-56- 4 BLISTER PACK in 1 CARTON (66215-103-56) > 14 TABLET, SOLUBLE in 1 BLISTER PACK (66215-103-14)

68180- Lupin Pharmaceuticals, Inc.
- 68180-386- Bosentan
  - 68180-386-07- 60 TABLET in 1 BOTTLE (68180-386-07)

68180- Lupin Pharmaceuticals, Inc.
- 68180-387- Bosentan
  - 68180-387-07- 60 TABLET in 1 BOTTLE (68180-387-07)

68382- Zydus Pharmaceuticals (USA) Inc.
- 68382-446- Bosentan
  - 68382-446-01- 100 TABLET, COATED in 1 BOTTLE (68382-446-01)

68382- Zydus Pharmaceuticals (USA) Inc.
- 68382-446- Bosentan
  - 68382-446-05- 500 TABLET, COATED in 1 BOTTLE (68382-446-05)

68382- Zydus Pharmaceuticals (USA) Inc.
- 68382-446- Bosentan
  - 68382-446-14- 60 TABLET, COATED in 1 BOTTLE (68382-446-14)

68382- Zydus Pharmaceuticals (USA) Inc.
- 68382-446- Bosentan
  - 68382-446-28- 180 TABLET, COATED in 1 BOTTLE (68382-446-28)

68382- Zydus Pharmaceuticals (USA) Inc.
- 68382-446- Bosentan
  - 68382-446-77- 10 BLISTER PACK in 1 CARTON (68382-446-77) > 10 TABLET, COATED in 1 BLISTER PACK (68382-446-30)

68382- Zydus Pharmaceuticals (USA) Inc.
- 68382-447- Bosentan
  - 68382-447-01- 100 TABLET, COATED in 1 BOTTLE (68382-447-01)

68382- Zydus Pharmaceuticals (USA) Inc.
- 68382-447- Bosentan
  - 68382-447-05- 500 TABLET, COATED in 1 BOTTLE (68382-447-05)

68382- Zydus Pharmaceuticals (USA) Inc.
- 68382-447- Bosentan
  - 68382-447-14- 60 TABLET, COATED in 1 BOTTLE (68382-447-14)

68382- Zydus Pharmaceuticals (USA) Inc.
- 68382-447- Bosentan
  - 68382-447-28- 180 TABLET, COATED in 1 BOTTLE (68382-447-28)

68382- Zydus Pharmaceuticals (USA) Inc.
- 68382-447- Bosentan
  - 68382-447-77- 10 BLISTER PACK in 1 CARTON (68382-447-77) > 10 TABLET, COATED in 1 BLISTER PACK (68382-447-30)

69097- Cipla USA Inc.
- 69097-377- BOSENTAN
  - 69097-377-03- 60 TABLET, FILM COATED in 1 BOTTLE (69097-377-03)

69097- Cipla USA Inc.
- 69097-377- BOSENTAN
  - 69097-377-76- 1 BLISTER PACK in 1 CARTON (69097-377-76) > 14 TABLET, FILM COATED in 1 BLISTER PACK

69097- Cipla USA Inc.
- 69097-378- BOSENTAN
  - 69097-378-03- 60 TABLET, FILM COATED in 1 BOTTLE (69097-378-03)

69097- Cipla USA Inc.
- 69097-378- BOSENTAN
  - 69097-378-76- 1 BLISTER PACK in 1 CARTON (69097-378-76) > 14 TABLET, FILM COATED in 1 BLISTER PACK

70771- Cadila Healthcare Limited
- 70771-1017- Bosentan
  - 70771-1017-1- 100 TABLET in 1 BOTTLE (70771-1017-1)

70771- Cadila Healthcare Limited
- 70771-1017- Bosentan
  - 70771-1017-4- 10 BLISTER PACK in 1 CARTON (70771-1017-4) > 10 TABLET in 1 BLISTER PACK (70771-1017-2)

70771- Cadila Healthcare Limited
- 70771-1017- Bosentan
  - 70771-1017-5- 500 TABLET in 1 BOTTLE (70771-1017-5)

70771- Cadila Healthcare Limited
- 70771-1017- Bosentan
  - 70771-1017-6- 60 TABLET in 1 BOTTLE (70771-1017-6)

70771- Cadila Healthcare Limited
- 70771-1017- Bosentan
  - 70771-1017-8- 180 TABLET in 1 BOTTLE (70771-1017-8)

70771- Cadila Healthcare Limited
- 70771-1018- Bosentan
  - 70771-1018-1- 100 TABLET in 1 BOTTLE (70771-1018-1)

70771- Cadila Healthcare Limited
- 70771-1018- Bosentan
  - 70771-1018-4- 10 BLISTER PACK in 1 CARTON (70771-1018-4) > 10 TABLET in 1 BLISTER PACK (70771-1018-2)

70771- Cadila Healthcare Limited
- 70771-1018- Bosentan
  - 70771-1018-5- 500 TABLET in 1 BOTTLE (70771-1018-5)

70771- Cadila Healthcare Limited
- 70771-1018- Bosentan
  - 70771-1018-6- 60 TABLET in 1 BOTTLE (70771-1018-6)

70771- Cadila Healthcare Limited
- 70771-1018- Bosentan
  - 70771-1018-8- 180 TABLET in 1 BOTTLE (70771-1018-8)

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Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

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Contraind./Precautions ⬆ ⬇

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Assessment ⬆ ⬇

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