belumosudil

Contraindicated in:

Moderate or severe hepatic impairment without liver GVHD;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Severe renal impairment;
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Children <12 yr (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema, hypertension

Derm: pruritus, rash

EENT: nasal congestion

F and E: hyperkalemia, hypocalcemia, hypophosphatemia

GI: abdominal pain, diarrhea, dysphagia, ↑liver enzymes, nausea

GU: ↑serum creatinine, ↓fertility

Hemat: anemia, bleeding, lymphopenia, neutropenia, thrombocytopenia

Metab: ↓appetite

MS: arthralgia, muscle spasm, pain

Neuro: headache, weakness

Resp: cough, dyspnea

Misc: fever, infection

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A inducers, including rifampin, may ↓ levels and effectiveness; ↑ belumosudil dose during concurrent use.
Proton pump inhibitors may ↓ levels and effectiveness; ↑ belumosudil dose during concurrent use.
May ↑ levels and risk of toxicity of UGT1A1 substrates, including raltegravir; avoid concurrent use.
May ↑ levels and risk of toxicity of P-glycoprotein (P-gp) substrates, including dabigatran; avoid concurrent use. If concurrent use unavoidable, ↓ dose of P-gp substrate.
May ↑ levels and risk of toxicity of OATP1B1 substrates or breast cancer resistance protein (BCRP) substrates, including rosuvastatin; avoid concurrent use. If concurrent use unavoidable, ↓ dose of OATP1B1 substrate or BCRP substrate.

Availability ⬆ ⬇

Route/Dosage ⬆ ⬇

PO (Adults and Children ≥12 yr): 200 mg once daily until progression of chronic GVHD occurs requiring new systemic therapy. Concurrent use of strong CYP3A inducer or proton pump inhibitor: 200 mg twice daily until progression of chronic GVHD occurs requiring new systemic therapy.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Acts as an inhibitor of rho-associated, coiled-coil containing protein kinase (ROCK), which results in a reduction in proinflammatory responses.

Therapeutic effects:

Reduced severity of chronic GVHD,

Classifications ⬆ ⬇

Therapeutic Classification: none assigned

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: 64% absorbed following oral administration. Absorption ↑ with high-fat, high-calorie meals.

Distribution: Widely distributed to tissues.

Protein Binding: 99.9%.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP3A4 isoenzyme, with some metabolism by the CYP2C8 and CYP2D6 isoenzymes and UGT1A9. Primarily excreted in the feces (85%; 30% as unchanged drug), with <5% excreted in urine.

Half-Life: 19 hr,

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1.3–2.5 hr	24 hr

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken (especially proton pump inhibitors) and to consult a health care professional before taking other medications.
Instruct patient to take medication as directed at the same time each day with food and a whole glass of water. Take missed doses as soon as remembered unless almost time for next dose. Do not double doses. Do not share medication with others, even if they have similar symptoms; may be harmful. Keep out of children's reach.
- Explain need for continued medical follow-up to assess effectiveness and possible side effects of medication. Periodic lab tests will be needed.
- Emphasize importance of hydration during therapy. Frequent side effects are nausea, vomiting, and diarrhea. Take prescribed antiemetic or antidiarrheal as needed.
- Inform the patient that cough and nasal congestion can occur; difficulty breathing should be reported immediately. If sleep apnea already present, continue regular use of BIPAP or CPAP at bedtime.
- Advise the patient to report signs and symptoms of bleeding (fatigue, easy bruising, nosebleeds, bloody urine or stools, conjunctival hemorrhage, skin rash).
- Advise patient to immediately report signs and symptoms of infection (fever, chills, malaise, conjunctivitis, sore throat, toothache, earache, cough, trouble breathing, persistent diarrhea, UTI, rashes, wounds that will not heal).
- Advise patient to consult health care professional before treating headache, joint pain, and muscle aches with OTC pain medications; regular use of acetaminophen should be avoided.
- May cause fetal harm. Instruct patient to notify health care professional if pregnancy if planned or suspected or if breastfeeding. Advise females of reproductive potential to use effective contraception and avoid breastfeeding during therapy and for 1 wk after last dose. Advise men with female partners of reproductive potential to use effective contraception during therapy and for 1 wk after last dose.

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Indications ⬇

Contraind./Precautions ⬆ ⬇