SOHONOS (palovarotene)

There are 1 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction

Drug Names

Selected Retinoids (Systemic)/Tetracyclines SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Both systemic tetracyclines(1-4,14) and systemic retinoids(5-14) have been independently associated with medication-induced intracranial hypertension. CLINICAL EFFECTS: The concurrent use of oral retinoids(5-12) with tetracyclines has been associated with pseudotumor cerebri (benign intracranial hypertension). Early signs of pseudotumor cerebri include papilledema (inflammation of the optic nerve), headache, nausea, vomiting, and visual disturbances such as blurred vision, double vision, and loss of vision.(15) PREDISPOSING FACTORS: Women of childbearing age who are overweight or have a previous history of intracranial hypertension are at a greater risk of developing intracranial hypertension.(15) PATIENT MANAGEMENT: The UK(5) and US(6) manufacturers of acitretin state state that concurrent use with tetracyclines is contraindicated. The UK manufacturer of isotretinoin states that concurrent use with tetracyclines is contraindicated.(7) The US manufacturer of isotretinoin states that the concurrent use of tetracyclines should be avoided.(8) The US manufacturer of minocycline states that the administration of isotretinoin should be avoided shortly before, during and shortly after minocycline therapy.(2) The UK manufacturers of oral tretinoin and alitretinoin states that concurrent use with tetracyclines is contraindicated.(9,11) The Canadian manufacturer of palovarotene states that coadministration of tetracycline derivatives should be avoided.(12) Patients who present with symptoms of pseudotumor cerebri should be screened for papilledema. If papilledema is present, they should discontinue the drug and be referred to a neurologist for further treatment.(5-13) DISCUSSION: The concurrent use of isotretinoin and tetracyclines has been associated with pseudotumor cerebri.(5-13) A review of ocular side effects from the National Registry of Drug-Induced Ocular Side Effects, the World Health Organization, the Food and Drug Administration, and medical journals from 1979 to 2003 found 6 patients who developed intracranial hypertension while taking concurrent minocycline or tetracycline with tretinoin, acitretin, or etretinate.(13)

AVIDOXY, AVIDOXY DK, BENZODOX 30, BENZODOX 60, BISMUTH-METRONIDAZOLE-TETRACYC, DEMECLOCYCLINE HCL, DORYX, DORYX MPC, DOXY 100, DOXYCYCLINE HYCLATE, DOXYCYCLINE IR-DR, DOXYCYCLINE MONOHYDRATE, EMROSI, MINOCIN, MINOCYCLINE ER, MINOCYCLINE HCL, MINOCYCLINE HCL ER, MONDOXYNE NL, MORGIDOX, NUZYRA, ORACEA, OXYTETRACYCLINE HCL, PYLERA, SEYSARA, TARGADOX, TETRACYCLINE HCL, TIGECYCLINE, TYGACIL, XERAVA, XIMINO

Drug contraindication overview.

*Pregnancy. *History of allergy or hypersensitivity to retinoids or toany component of thepalovarotene formulation. Anaphylaxisand other allergicreactions have occurred with other retinoids.

Adverse reaction overview.

The most common adverse reactions of palovarotene (>=10% of patients) reported in clinical studies include dry skin, dry lips, arthralgia, pruritus, extremity pain, rash, alopecia, erythema, headache, back pain, skin exfoliation, nausea, musculoskeletal pain, myalgia, dry eyes, hypersensitivity, peripheral edema, and fatigue.

The safety and effectiveness of palovarotene for the treatment of fibrodysplasia ossificans progressiva (FOP) have been established in pediatric female patients 8 years of age and older and male patients 10 years of age and older. The safety and effectiveness of palovarotene for the treatment of FOP have not been established in pediatric female patients less than 8 years of age and male patients less than 10 years of age; palovarotene is not recommended in these patients because of the potential for premature epiphyseal closure. Clinical studies have shown that growing patients with open epiphyses are at serious risk of developing irreversible premature epiphyseal closure when treated with palovarotene.

In clinical studies with palovarotene, assessments of growth and bone safety in growing children included linear and knee height, femur and tibia length measured by Whole-Body Computed Tomography, and hand/wrist and knee radiographs. Premature epiphyseal closure has been identified as an irreversible serious risk associated with palovarotene therapy. Premature epiphyseal closure was observed as early as 6 months after initiating therapy, with the majority of casesoccurring at or after 12 months.

In palovarotene-treated patients, there was a trend of declining height Z-scores in adolescents, potentially due to a loss of linear height and/or increasing spinal deformity. The long-term effects on final height in patients with FOP treated with palovarotene have not been established. Prior to starting treatment with palovarotene, all growing children should undergo baseline clinical and radiological assessments including, but not limited to, an assessment of skeletal maturity via hand/wrist and knee x-rays, standard growth curves, and pubertal staging.

Continued monitoring is recommended every 6-12 months until patients reach skeletal maturity (e.g., epiphyseal closure) or final adult height.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None