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Cibinqo

Cibinqo

Manufacturer:

Pfizer

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Abrocitinib.
Description
CIBINQO 50 mg film-coated tablets: Each film-coated tablet contains 50 mg abrocitinib.
CIBINQO 100 mg film-coated tablets: Each film-coated tablet contains 100 mg abrocitinib.
CIBINQO 200 mg film-coated tablets: Each film-coated tablet contains 200 mg abrocitinib.
Excipient with known effect: Each CIBINQO 50 mg film-coated tablet contains 1.365 mg of lactose monohydrate.
Each CIBINQO 100 mg film-coated tablet contains 2.73 mg of lactose monohydrate.
Each CIBINQO 200 mg film-coated tablet contains 5.46 mg of lactose monohydrate.
Excipients/Inactive Ingredients: Tablet core: Microcrystalline cellulose, Dibasic calcium phosphate anhydrous, Sodium starch glycolate, Magnesium stearate.
Film-coat: Hypromellose (E464), Titanium dioxide (E171), Lactose monohydrate, Macrogol/PEG, Triacetin (E1518), Iron red oxide (E172).
Action
Pharmacology: Pharmacodynamics: Mechanism of action: CIBINQO is a Janus kinase (JAK)1 inhibitor. JAKs are intracellular enzymes which transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of haematopoiesis and immune cell function. Within signalling pathways, JAKs phosphorylate and activate Signal Transducers and Activators of Transcription (STATs) which modulate intracellular activity including gene expression. CIBINQO modulates the signalling pathway at the point of JAK1, preventing the phosphorylation and activation of STATs.
CIBINQO reversibly and selectively inhibits JAK1 by blocking the adenosine triphosphate (ATP) binding site. In a cell-free isolated enzyme assay, CIBINQO has biochemical selectivity for JAK1 over the other 3 JAK isoforms JAK2 (28-fold), JAK3 (>340-fold) and tyrosine kinase (TYK) 2 (43-fold), and even higher selectivity over the broader kinome. In cellular settings, where JAK enzymes transmit signals in pairs (i.e., JAK1/JAK2, JAK1/JAK3, JAK1/TYK2, JAK2/JAK2, JAK2/TYK2), CIBINQO preferentially inhibits cytokine-induced STAT phosphorylation mediated by receptors utilising JAK1 relative to receptors utilising JAK2 only or JAK2/TYK2 pairs. The relevance of selective enzymatic inhibition of specific JAK enzymes to clinical effect is not currently known. Both the parent compound and the active metabolites inhibit cytokine signalling with similar levels of selectivity.
Pharmacodynamic effects: Clinical biomarkers: Treatment with CIBINQO was associated with dose-dependent reduction in serum markers of inflammation, including high sensitivity C-reactive protein (hsCRP), interleukin-31 (IL-31) and thymus and activation-regulated chemokine (TARC). These changes returned to near baseline within 4 weeks of drug discontinuation.
Cardiac electrophysiology: The effect of CIBINQO on the QTc interval was examined in subjects who received single doses of abrocitinib 600 mg in a placebo- and positive-controlled thorough QT study. In a concentration-QTc analysis, abrocitinib at therapeutic and supratherapeutic plasma concentrations did not lead to a prolongation of the QTc intervals.
Clinical efficacy and safety: The efficacy and safety of CIBINQO as monotherapy and in combination with background medicated topical therapies over 12 to 16 weeks were evaluated in 1,616 patients in 3 pivotal Phase 3 randomised, double-blind, placebo-controlled studies (MONO-1, MONO-2, and COMPARE). In addition, the efficacy and safety of CIBINQO in monotherapy over 52 weeks (with the option of rescue treatment in flaring subjects) was evaluated in 1,233 subjects in a Phase 3 induction, randomised withdrawal, double-blind, placebo-controlled study (REGIMEN). The patients in these 4 studies had moderate-to-severe atopic dermatitis as defined by Investigator's Global Assessment (IGA) score ≥3, Eczema Area and Severity Index (EASI) score ≥16, body surface area (BSA) involvement ≥10%, and Peak Pruritus Numerical Rating Scale (PP-NRS) ≥4 at baseline visit prior to randomisation. Patients who had a prior inadequate response or for whom topical treatments were medically unadvisable, or who had received systemic therapies were eligible for inclusion. All patients who completed the parent studies were eligible to enrol into the long-term extension study EXTEND.
Baseline characteristics: In the placebo-controlled studies (MONO-1, MONO-2, COMPARE) and the open label induction, randomised withdrawal study (REGIMEN) across all treatment groups 41.4% to 51.1% were female, 59.3% to 77.8% were Caucasian, 15.0% to 33.0% were Asian and 4.1% to 8.3% were Black, and the mean age was 32.1 to 37.7 years. In these studies, 32.2% to 40.8% had a baseline IGA of 4 (severe atopic dermatitis), and 41.4% to 59.5% of patients had received prior systemic treatment for atopic dermatitis. The baseline mean EASI score ranged from 28.5 to 30.9, the baseline PP-NRS ranged from 7.0 to 7.3 and the baseline Dermatology Life Quality Index (DLQI) ranged from 14.4 to 16.0.
Clinical response: 12-week monotherapy (MONO-1, MONO-2) and 16-week TCS combination (COMPARE) studies: A significantly larger proportion of patients achieved both primary endpoints IGA 0 or 1 and/or EASI-75 with 100 mg or 200 mg once daily CIBINQO compared with placebo at Week 12 or Week 16 (see Table 1).
A significantly greater proportion of patients achieved at least a PP-NRS 4-point improvement with 100 mg or 200 mg once daily CIBINQO compared with placebo. This improvement was observed as early as Week 2 and persisting through Week 12 (Figure 1).
In the COMPARE study, superiority of CIBINQO 200 mg compared with dupilumab at Week 2 was demonstrated for the proportion of patients achieving PP-NRS 4-point improvement with significantly higher itch responses seen as early as Day 4 after the first dose.
Treatment effects in subgroups (e.g., weight, age, sex, race and prior systemic immunosuppressant treatment) in MONO-1, MONO-2 and COMPARE were consistent with the results in the overall study population. (See Table 1 and 2.)

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The proportion of patients who achieved PP-NRS4 over time in studies MONO-1, MONO-2 and COMPARE are shown in Figure 1. (See Figure 1.)

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Health-related outcomes: Both the 100 mg and 200 mg doses of CIBINQO, whether as monotherapy or combination therapy, led to a higher proportion of patients with reductions in DLQI than placebo at 12 weeks. Patients also had improved symptoms of atopic dermatitis, sleep disturbances, and anxiety and depression symptoms, from the patient's perspective, as measured by the POEM after 12 weeks, the sleep loss subscale of the SCORAD and the Hospital Anxiety and Depression Scale (HAD) scores.
Dose reduction: Open-label induction, randomised withdrawal study (REGIMEN): A total of 1,233 patients received open-label abrocitinib 200 mg once daily in the 12-week run-in phase. Among these patients, 798 patients (64.7%) met responder criteria (defined as achieving IGA [0 or 1] response and EASI-75) and were randomised to placebo (267 patients), abrocitinib 100 mg once daily (265 patients) or abrocitinib 200 mg once daily (266 patients).
Continuous treatment (200 mg continuous) and induction-maintenance treatment (200 mg for 12 weeks followed by 100 mg) prevented flare with 81.1% and 57.4% probability, respectively, versus 19.1% among patients who withdrew treatment (randomised to placebo) after 12 weeks of induction. Three hundred fifty-one (351) patients including 16.2% of 200 mg, 39.2% of 100 mg and 76.4% of placebo patients received rescue medication of 200 mg abrocitinib in combination with topical therapy. (See Figure 2.)

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Long-term efficacy: Eligible patients who completed the full treatment period of a qualifying parent study (e.g., MONO-1, MONO-2, COMPARE, REGIMEN) were considered for enrollment in the long-term extension study EXTEND. In EXTEND, patients received CIBINQO with or without background medicated topical therapy. Patients who were previously randomised to CIBINQO 100 mg or 200 mg once daily in parent studies continued the same dose in EXTEND as in the parent study, and the blind was maintained.
Among patients who achieved response after 12 weeks of treatment and entered EXTEND, the majority of patients maintained their response at Week 48 of cumulative treatment for both doses of CIBINQO [60% and 70% for IGA (0 or 1) response, 79% and 87% for EASI-75, and 62% and 83% for PP-NRS4 with 100 mg once daily and 200 mg once daily, respectively].
Among patients who did not achieve response after 12 weeks of treatment and entered EXTEND, a proportion of patients achieved late-onset response by Week 24 (from baseline) of continued treatment with CIBINQO [25% for IGA (0 or 1) response, and 50% and 59% for EASI-75 with 100 mg once daily and 200 mg once daily, respectively].
Patients who received dupilumab in the COMPARE study and subsequently entered EXTEND were randomised to either 100 mg or 200 mg of CIBINQO once daily upon entering EXTEND. Among non-responders to dupilumab, a substantial proportion of patients achieved response 12 weeks after switching to CIBINQO [34% and 47% for IGA (0 or 1) response, and 68% and 80% for EASI-75 with 100 mg once daily or 200 mg once daily, respectively].
Pharmacokinetics: Absorption: Abrocitinib is well-absorbed with over 91% extent of oral absorption and absolute oral bioavailability of approximately 60%. The oral absorption of abrocitinib is rapid and peak plasma concentrations are reached within 1 hour. Both Cmax and AUC of abrocitinib increased dose proportionally from 30 to 400 mg. Co-administration of CIBINQO with a high-fat meal had no clinically relevant effect on abrocitinib exposures (AUC and Cmax increased by approximately 26% and 29%, respectively, and Tmax was prolonged by 2 hours). In clinical studies, CIBINQO was administered without regard to food (see Dosage & Administration).
Distribution: After intravenous administration, the volume of distribution of CIBINQO is about 100 L. Approximately 64%, 37% and 29% of circulating abrocitinib and its active metabolites M1 and M2, respectively, are bound to plasma proteins. Abrocitinib and its active metabolites distribute equally between red blood cells and plasma.
Biotransformation: The in vitro metabolism of abrocitinib is mediated by multiple CYP enzymes, CYP2C19 (~53%), CYP2C9 (~30%), CYP3A4 (~11%) and CYP2B6 (~6%). In a human radiolabeled study, abrocitinib was the most prevalent circulating species, with 3 polar mono-hydroxylated metabolites identified as M1 (3-hydroxypropyl), M2 (2-hydroxypropyl), and M4 (pyrrolidinone pyrimidine). At steady state, M2 (11%) and M4 (24%) are major metabolites and M1 (9.6%) is a minor metabolite. Of the 3 metabolites in circulation, M1 and M2 have similar JAK inhibitory profiles as abrocitinib, while M4 was pharmacologically inactive. The pharmacologic activity of CIBINQO is attributable to the unbound exposures of parent molecule (~60%) as well as M1 (~10%) and M2 (~30%) in systemic circulation. The sum of unbound exposures of abrocitinib, M1 and M2, each expressed in molar units and adjusted for relative potencies, is referred to as the abrocitinib active moiety.
Elimination: The total body clearance of abrocitinib is 22 L/hr. The elimination half-life of abrocitinib is about 6 hours. Steady-state plasma concentrations of abrocitinib are achieved within 48 hours after once daily administration. CIBINQO is eliminated primarily by metabolic clearance mechanisms, with less than 1% of the dose excreted in urine as unchanged drug. The urinary excretion of the metabolites of abrocitinib is 16%, 14% and 15% of the administered abrocitinib dose for M1, M2 and M4, respectively, and the metabolites are substrates of OAT3 transporter. As a percent of total clearance, the renal elimination for M1 is 74% and >90% for M2 and M4, while the faecal elimination of M1, M2, and M4 are 8%, 4%, and 2% respectively.
Special populations: Body weight, gender, genotype, race, and age: Body weight, gender, CYP2C19/2C9 genotype, race, and age did not have a clinically meaningful effect on CIBINQO exposure (see Dosage & Administration).
Adolescents (≥12 to <18 years): Based on population pharmacokinetic analysis, the mean CIBINQO steady-state exposures in adolescent patients compared to adults at their typical body weights was not significantly different.
Paediatric (<12 years): The pharmacokinetics of CIBINQO in paediatric patients under 12 years of age have not yet been established (see Dosage & Administration).
Renal impairment: In a renal impairment study, patients with severe (eGFR <30 mL/min) and moderate (eGFR 30 to <60 mL/min) renal impairment had approximately 191% and 110% increase in active moiety AUCinf, respectively, compared to patients with normal renal function (eGFR ≥90 mL/min; see Dosage & Administration). Pharmacokinetics of abrocitinib have not been determined in patients with mild renal impairment, however, based on the results observed in other groups, an increase of up to 70% in active moiety exposure is expected in patients with mild renal impairment (eGFR 60 to <90 mL/min). The increase of up to 70% is not clinically meaningful as the efficacy and safety of abrocitinib in atopic dermatitis patients with mild renal impairment (n=756) was comparable to the overall population in Phase 2 and 3 clinical studies. The eGFR in individual patients was estimated using Modification of Diet in Renal Disease (MDRD) formula.
CIBINQO has not been studied in patients with ESRD on renal replacement therapy (see Dosage & Administration). In Phase 3 clinical studies, CIBINQO was not evaluated in patients with atopic dermatitis with baseline creatinine clearance values less than 40 mL/min.
Hepatic impairment: Patients with mild (Child Pugh A) and moderate (Child Pugh B) hepatic impairment had approximately 4% decrease and 15% increase in active moiety AUCinf, respectively, compared to patients with normal hepatic function. These changes are not clinically significant, and no dose adjustment is required in patients with mild or moderate hepatic impairment (see Dosage & Administration). In clinical studies, CIBINQO was not evaluated in patients with severe (Child Pugh C) hepatic impairment (see Contraindications), or in patients screened positive for active hepatitis B or hepatitis C (see Precautions).
Toxicology: Preclinical safety data: General toxicity: In toxicity studies of up to 1 month of CIBINQO dosing in rats initiated at 6-8 weeks and 9-weeks of age, a bone dystrophy finding was noted, at exposure of greater than or equal to 22 times the human AUC at the maximum recommended human dose (MRHD) of 200 mg. No bone findings were observed in rats at any dose in the 6-month toxicity study (up to 25 times the human AUC at the MRHD of 200 mg) or in any of the toxicity studies in cynomolgus monkeys (up to 30 times the human AUC at the MRHD of 200 mg).
Genotoxicity: CIBINQO is not mutagenic in the bacterial mutagenicity assay (Ames assay). Although CIBINQO is aneugenic in the in vitro TK6 micronucleus assay, CIBINQO is not aneugenic or clastogenic based on the results of the in vivo rat bone marrow micronucleus assay.
Carcinogenicity: No evidence of tumorigenicity was observed in Tg.rasH2 mice administered CIBINQO for 26 weeks at exposures equal to 0.6 and 0.2 times the human AUC at the MRHD of 200 mg in female and male mice, respectively. In the 104-week oral carcinogenicity study, CIBINQO resulted in statistically higher incidence of benign thymomas in female rats at exposures greater than or equal to 2.7 times the human AUC at the MRHD of 200 mg. No evidence of CIBINQO-related tumorigenicity was observed following oral CIBINQO administration in female rats at exposures equal to 0.6 times the human AUC at the MRHD of 200 mg or in male rats at exposures equal to 13 times the human AUC at the MRHD of 200 mg.
Reproductive and developmental toxicity: CIBINQO had no effects on male fertility or spermatogenesis at doses up to 70 mg/kg/day at exposures equal to 25 times the human AUC at the MRHD of 200 mg. CIBINQO resulted in effects on female fertility (lower fertility index, corpora lutea, and implantation sites) at exposures equal to 28 times the human AUC at the MRHD of 200 mg and higher postimplantation loss in rats at exposures greater than or equal to 10 times the human AUC at the MRHD of 200 mg. The effects on female fertility in rats reversed 1 month after cessation of CIBINQO administration. No effects on female fertility were noted at exposures equal to 1.9 times the human AUC at the MRHD of 200 mg.
No foetal malformations were observed in embryo-foetal development studies in rats or rabbits. In an embryo-foetal development study in pregnant rabbits, oral administration of CIBINQO during gestation days 7 to 19 had no effects on embryo-foetal survival or foetal morphological development at exposures equal to 7.6 times the human AUC at the MRHD of 200 mg. CIBINQO resulted in an increase incidences of unossified forelimb phalanges at exposures equal to 7.6 times the human AUC at the MRHD of 200 mg.
In an embryo-foetal development study in pregnant rats, oral administration of CIBINQO during gestation days 6 to 17 resulted in increased embryo-foetal lethality at exposures equal to 16 times the human AUC at the MRHD of 200 mg. No embryo-foetal lethality was observed in pregnant rats orally dosed with CIBINQO during organogenesis at exposures equal to 10 times the human AUC at the MRHD of 200 mg. CIBINQO resulted in increased incidences of skeletal variations of short 13th ribs at exposures greater than or equal to 10 times the human AUC at the MRHD of 200 mg and reduced ventral processes, thickened ribs, and unossified metatarsals were observed at exposures equal to 16 times the human AUC at the MRHD of 200 mg. No skeletal variations were noted in rats at exposures equal to 2.3 times the human AUC at the MRHD of 200 mg.
In a rat pre- and postnatal development study in pregnant rats, oral administration of CIBINQO during gestation day 6 through lactation day 21 resulted in dystocia with prolonged parturition and lower offspring body weights at exposures greater than or equal to 10 times the human AUC at the MRHD of 200 mg and lower postnatal survival at exposures equal to 16 times the human AUC at the MRHD of 200 mg. No maternal or developmental toxicity was observed in either dams or offspring at exposures equal to 2.3 times the human AUC at the MRHD of 200 mg.
Juvenile animal toxicity: In the juvenile rat study, oral administration of CIBINQO to rats initiated at postnatal Day 10 resulted in bone findings (malrotated and/or impaired use of the forelimbs, hindlimbs, or paws, fractures and/or abnormalities of the femoral head, and bony dystrophy), at exposures ≥0.8 times the human AUC at the MRHD of 200 mg. Irreversible low femur length and width were observed at exposures 26 times the human AUC at the MRHD of 200 mg.
Indications/Uses
CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis in adults (age 18 years and above) who are candidates for systemic therapy and whose disease is not adequately controlled with topical medications or for whom topical treatments are otherwise medically inadvisable.
Dosage/Direction for Use
Treatment should be initiated and supervised by a healthcare professional experienced in the diagnosis and treatment of conditions for which CIBINQO is indicated (see Indications/Uses).
Posology: The recommended dose of CIBINQO is 100 mg once daily. An initial dose of 200 mg once daily for 12 weeks followed by maintenance with 100 mg once daily may be appropriate for some patients who need rapid relief of symptoms. The lowest effective dose for maintenance should be used (see Pharmacology: Pharmacodynamics under Actions).
CIBINQO can be used with or without medicated topical therapies for atopic dermatitis.
Consider discontinuation of CIBINQO if adequate therapeutic benefit is not achieved after 24 weeks.
Treatment with CIBINQO should not be initiated in patients with a platelet count <150 × 103/mm3, an absolute lymphocyte count (ALC) <0.5 × 103/mm3, an absolute neutrophil count (ANC) <1 × 103/mm3 or who have a haemoglobin value <8 g/dL (see Precautions).
Missed doses: If a dose is missed, patients should be advised to take the dose as soon as possible unless it is less than 12 hours before the next dose, in which case the patient should not take the missed dose. Thereafter, resume dosing at the regular scheduled time.
Dose interruption: If a patient develops a serious infection, sepsis or opportunistic infection, consider interruption of CIBINQO until the infection is controlled (see Precautions).
Interruption of dosing may be needed for management of laboratory abnormalities as described in Table 3 (see Precautions).
Special dosage instructions: In patients receiving strong inhibitors of cytochrome P450 (CYP) 2C19 (e.g., fluvoxamine, fluconazole, fluoxetine and ticlopidine), the recommended dose of CIBINQO should be reduced by half to 100 mg or 50 mg once daily. The use of CIBINQO is not recommended concomitantly with moderate or strong inducers of CYP2C19/CYP2C9 enzymes (e.g., rifampin, apalutamide, efavirenz, enzalutamide, phenytoin) (see Interactions).
Renal impairment: No dose adjustment is required in patients with mild renal impairment, i.e., estimated glomerular filtration rate (eGFR) of 60 to <90 mL/min.
In patients with moderate renal impairment (eGFR 30 to <60 mL/min), the recommended dose of CIBINQO should be reduced by half to 100 mg or 50 mg once daily (see Pharmacology: Pharmacokinetics under Actions).
In patients with severe renal impairment (eGFR <30 mL/min), the recommended dose of CIBINQO should be 50 mg once daily. The dosing of CIBINQO in severe renal impairment patients is based on modelling and simulation which demonstrated comparability of active moiety exposures to patients with normal renal function administered doses of 100 mg and 200 mg once daily.
CIBINQO has not been studied in patients with end-stage renal disease (ESRD) on renal replacement therapy.
Hepatic impairment: No dose adjustment is required in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment (see Pharmacology: Pharmacokinetics under Actions). CIBINQO must not be used in patients with severe (Child Pugh C) hepatic impairment (see Contraindications).
Elderly population: The risks and benefits of the recommended dose for patients ≥65 years of age should be considered (see Precautions). There are no conclusive data in patients 75 years of age and older.
Paediatric population: Use in paediatric patients under 12 years of age is not recommended.
Method of administration: CIBINQO is to be taken orally once daily with or without food at approximately the same time each day.
In patients who experience nausea while taking CIBINQO, taking with food may improve nausea.
CIBINQO tablets should be swallowed whole with water and should not be split, crushed, or chewed.
Overdosage
CIBINQO was administered in clinical studies up to a single oral dose of 800 mg. There is no experience with overdose of CIBINQO. There is no specific antidote for overdose with CIBINQO. In case of an overdose, it is recommended that the patient be monitored for signs and symptoms of adverse reactions. Treatment should be symptomatic and supportive.
Pharmacokinetics data up to and including a single oral dose of 800 mg in healthy adult volunteers indicate that more than 90% of the administered dose is expected to be eliminated within 48 hours.
Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in Description.
Active serious systemic infections, including tuberculosis (TB) (see Precautions).
Severe hepatic impairment (see Dosage & Administration).
Pregnancy and breast-feeding (see Use in Pregnancy & Lactation).
Special Precautions
Serious infections: Serious infections have been reported in patients receiving CIBINQO. The most frequent serious infections in clinical studies were herpes simplex, herpes zoster, and pneumonia (see Adverse Reactions).
Treatment must not be initiated in patients with an active, serious systemic infection (see Contraindications).
The risks and benefits of treatment with CIBINQO should be carefully considered prior to initiating in patients: with chronic or recurrent infection; who have been exposed to TB; with a history of a serious or an opportunistic infection; who have resided or travelled in areas of endemic TB or endemic mycoses; or with underlying conditions that may predispose them to infection.
Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with CIBINQO. A patient who develops a new infection during treatment with CIBINQO should undergo prompt and complete diagnostic testing and appropriate antimicrobial therapy should be initiated. Discontinuation of CIBINQO should also be considered until the infection has resolved.
Tuberculosis: Patients should be screened for tuberculosis (TB) before starting CIBINQO therapy and consider yearly screening for patients in highly endemic areas for TB. CIBINQO must not be given to patients with active TB (see Contraindications). For patients with a new diagnosis of latent TB or prior untreated latent TB, preventive therapy for latent TB should be started prior to initiation of CIBINQO.
Viral reactivation: Viral reactivation, including herpes virus reactivation (e.g., herpes zoster, herpes simplex), was reported in clinical studies (see Adverse Reactions). The rate of herpes zoster infections was higher in patients 65 years of age and older and patients with severe atopic dermatitis at baseline (see Adverse Reactions). If a patient develops herpes zoster, temporary interruption of treatment should be considered until the episode resolves.
Eczema herpeticum (disseminated viral infection mostly due to herpes simplex virus) was also reported in clinical studies with CIBINQO. The condition is characterised by rapid spread of vesicular and erosive lesions, fever and malaise inpatients with atopic dermatitis and requires prompt treatment with antiviral agents. Discontinuation or interruption of CIBINQO therapy until the resolution of an eczema herpeticum infection should be considered, depending on the seriousness of the event.
Screening for viral hepatitis should be performed in accordance with clinical guidelines before starting therapy and during therapy with CIBINQO. Patients with evidence of active hepatitis B or hepatitis C (positive hepatitis C PCR) infection were excluded from clinical studies (see Pharmacology: Pharmacokinetics under Actions). Patients who were hepatitis B surface antigen negative, hepatitis B core antibody positive, and hepatitis B surface antibody positive had testing for hepatitis B virus (HBV) DNA. Patients who had HBV DNA above the lower limit of quantification (LLQ) were excluded. Patients who had HBV DNA negative or below LLQ could initiate treatment with CIBINQO; such patients had HBV DNA monitored. If HBV DNA is detected, a liver specialist should be consulted.
Vaccination: Use of live, attenuated vaccines during or immediately prior to CIBINQO therapy is not recommended. Prior to initiating CIBINQO, it is recommended that patients be brought up to date with all immunisations, including prophylactic herpes zoster vaccinations, in agreement with current immunisation guidelines.
Venous thrombotic events including pulmonary embolism: Events of deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving Janus kinase (JAK) inhibitors including CIBINQO (see Adverse Reactions). CIBINQO should be used with caution in patients at high risk for DVT/PE. Risk factors that should be considered in determining the patient's risk for DVT/PE include older age, obesity, a medical history of DVT/PE, prothrombotic disorder, use of combined hormonal contraceptives or hormone replacement therapy, patients undergoing major surgery, or prolonged immobilisation. If clinical features of DVT/PE occur, CIBINQO treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment.
Malignancy (including non-melanoma skin cancers): Immunomodulatory drugs may increase the risk of malignancies including lymphoma. More cases of malignancies were observed with a JAK inhibitor other than CIBINQO compared with TNF inhibitors in the treatment of rheumatoid arthritis. Malignancies, including non-melanoma skin cancer (NMSC), were observed in clinical studies with CIBINQO. Clinical data are insufficient to assess the potential relationship of exposure to CIBINQO and the development of malignancies. Long-term safety evaluations are ongoing.
The risks and benefits of CIBINQO treatment should be considered prior to initiating in patients with a known malignancy other than a successfully treated NMSC or cervical cancer in situ or when considering continuing CIBINQO therapy in patients who develop a malignancy. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.
Haematologic abnormalities: Confirmed ALC <0.5 × 103/mm3 and platelet count <50 × 103/mm3 were observed in less than 0.5% of patients in clinical studies. Treatment with CIBINQO should not be initiated in patients with a platelet count <150 × 103/mm3, an ALC <0.5 × 103/mm3, an ANC <1 × 103/mm3 or who have a haemoglobin value <8 g/dL (see Dosage & Administration). Platelet count and ALC should be monitored 4 weeks after initiation of therapy with CIBINQO and thereafter according to routine patient management (see Table 3).
Lipids: Dose-dependent increase in blood lipid parameters were reported in patients treated with CIBINQO (see Adverse Reactions). Lipid parameters should be assessed approximately 4 weeks following initiation of CIBINQO therapy and thereafter according to their risk for cardiovascular disease. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined. More serious cardiac adverse events have been observed with a JAK inhibitor other than CIBINQO compared with TNF inhibitors in the treatment of rheumatoid arthritis. Patients should be monitored and managed according to clinical guidelines, due to the known cardiovascular risks associated with hyperlipidaemia.
Laboratory monitoring: (See Table 3.)

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Excipients: Lactose: Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Sodium content: This medicinal product contains less than 1 mmol sodium (23 mg) per tablet. Patients on low sodium diets can be informed that this medicinal product is essentially 'sodium-free'.
Effects on ability to drive and use machines: No studies have been conducted on the effect of CIBINQO on driving ability or ability to operate machinery. Patients should be informed that dizziness has been reported during treatment with CIBINQO (see Adverse Reactions).
Use in the Elderly: A total of 145 patients 65 years of age and older were enrolled in CIBINQO studies. The safety profile observed in elderly patients was similar to that of the adult population with the following exceptions: a higher proportion of patients 65 years of age and older discontinued from clinical studies and were more likely to have serious adverse events compared to younger patients; patients 65 years and older were more likely to develop low platelet and ALC values; the incidence rate of herpes zoster in patients 65 years of age and older was higher than that of younger patients (see Adverse Reactions). There are no conclusive data in patients above 75 years of age and older.
Use In Pregnancy & Lactation
Pregnancy: There are no or limited amount of data on the use of CIBINQO in pregnant women. Studies in animals have shown reproductive toxicity (see Pharmacology: Toxicology: Preclinical safety data under Actions). CIBINQO is contraindicated during pregnancy (see Contraindications).
Women of childbearing potential: Women of reproductive potential should be advised to use effective contraception during treatment and for 1 month following the final dose of CIBINQO. Pregnancy planning and prevention for females of reproductive potential is encouraged.
Breast-feeding: There are no data on the presence of CIBINQO in human milk, the effects on the breast-fed infant, or the effects on milk production. CIBINQO was secreted in milk of lactating rats. A risk to newborns/infants cannot be excluded and CIBINQO is contraindicated during breast-feeding.
Fertility: Based on the findings in rats, oral administration of CIBINQO may result in temporary reduced fertility in females of reproductive potential. These effects on female rat fertility were reversible 1 month after cessation of CIBINQO oral administration (see Pharmacology: Toxicology: Preclinical safety data under Actions).
Adverse Reactions
Summary of safety profile: The most commonly reported adverse reactions occurring in ≥2% of patients treated with CIBINQO 200 mg in placebo-controlled studies are nausea (15.1%), headache (7.9%), acne (4.8%), herpes simplex (4.2%), blood creatine phosphokinase increased (3.8%), dizziness (3.4%), and abdominal pain upper (2.2%). The most frequent serious adverse reactions are infections (0.3%) (see Precautions).
Tabulated list of adverse reactions: A total of 3,128 patients were treated with CIBINQO in clinical studies in atopic dermatitis representing 2,089 patient-years of exposure. There were 994 patients with at least 48 weeks of exposure. Five placebo-controlled studies were integrated (703 patients on 100 mg once daily, 684 patients on 200 mg once daily and 438 patients on placebo) to evaluate the safety of CIBINQO in comparison to placebo for up to 16 weeks.
Listed in Table 4 are adverse reactions observed in atopic dermatitis clinical studies presented by system organ class and frequency, using the following categories: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. (See Table 4.)

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Description of selected adverse reactions: Infections: In placebo-controlled studies, for up to 16 weeks, infections have been reported in 27.4% of patients treated with placebo and in 34.9% and 34.8% of patients treated with CIBINQO 100 mg and 200 mg, respectively. Most infections were mild or moderate. The percentage of patients reporting infection-related adverse drug reactions in the 200 mg and 100 mg groups compared to placebo were: herpes simplex (4.2% and 2.8% vs 1.4%), herpes zoster (1.2% and 0.6% vs 0%), pneumonia (0.1% and 0.1% vs 0%). Herpes simplex was more frequent in patients with a history of herpes simplex or eczema herpeticum. Most of the herpes zoster events involved a single dermatome and were non-serious. All the opportunistic infections were cases of multidermatomal cutaneous herpes zoster (0.6%), most of which were non-serious. The incidence rate of herpes zoster in patients 65 years of age and older (7.40 per 100 patient-years) was higher than that of patients 18 to less than 65 years of age (3.44 per 100 patient-years) and less than 18 years of age (2.12 per 100 patient-years). The incidence rate of herpes zoster in patients with severe atopic dermatitis at baseline (4.93 per 100 patient-years) was higher than that of patients with moderate atopic dermatitis at baseline (2.49 per 100 patient-years) (see Precautions).
In placebo-controlled studies, for up to 16 weeks, the rate of serious infections was 1.81 per 100 patient-years in patients treated with placebo, 3.32 per 100 patient-years in patients treated with CIBINQO 100 mg, and 1.12 per 100 patient-years in patients treated with CIBINQO 200 mg. Among all patients treated with CIBINQO, including the long-term extension study, the rate of serious infections was 2.65 per 100 patient-years in patients treated with CIBINQO 100 mg and 2.33 per 100 patient-years in patients treated with CIBINQO 200 mg. The most commonly reported serious infections were herpes simplex, herpes zoster, and pneumonia (see Precautions).
Venous thrombotic events including pulmonary embolism: Among all patients treated with CIBINQO, including the long-term extension study, the rate of PE was 0.23 per 100 patient-years for 200 mg and 0 for per 100 patient-years for 100 mg. The rate of DVT was 0.23 per 100 patient-years in the 200 mg group and 0 per 100 patient-years in the 100 mg group (see Precautions).
Thrombocytopenia: In placebo-controlled studies, for up to 16 weeks, treatment was associated with a dose-related decrease in platelet count. Maximum effects on platelets were observed within 4 weeks, after which the platelet count returned towards baseline despite continued therapy. Confirmed platelet counts of <50 × 103/mm3 were reported in 0.1% of patients exposed to 200 mg, and in 0 patients treated with 100 mg or placebo. Among all patients exposed to CIBINQO, including the long-term extension study, confirmed platelet counts of <50 × 103/mm3 were reported in 0.1% of patients treated with 200 mg, occurring at Week 4. A higher proportion of patients 65 years of age and older developed a platelet count nadir <75 × 103/mm3 (see Precautions).
Lymphopenia: In placebo-controlled studies, for up to 16 weeks, confirmed ALC <0.5 × 103/mm3 occurred in 0.3% of patients treated with 200 mg and 0% of patients treated with 100 mg or placebo. Both cases occurred in the first 4 weeks of exposure. Among all patients exposed to CIBINQO, including the long-term extension, confirmed ALC <0.5 × 103/mm3 were reported in 0.3% of patients treated with 200 mg and 0.1% of patients treated with 100 mg, most of whom were 65 years of age and older (see Precautions).
Lipid elevations: In placebo-controlled studies, for up to 16 weeks, there was a dose-related increase in low-density lipoprotein cholesterol (LDL-c), total cholesterol, and high-density lipoprotein cholesterol (HDL-c) relative to placebo at Week 4 which remained elevated through the final visit in the treatment period. There was no meaningful change in the LDL/HDL ratio in patients treated with abrocitinib relative to patients treated with placebo. Events related to hyperlipidaemia occurred in 0.4% of patients exposed to 100 mg, 0.6% of patients exposed to 200 mg and 0% patients exposed to placebo (see Precautions).
Creatine phosphokinase elevations (CPK): In placebo-controlled studies, for up to 16 weeks, significant increases in CPK values (>5 × ULN) occurred in 1.8% of patients treated with placebo, 1.8% of patients treated with 100 mg and 3.8% of patients treated with 200 mg of CIBINQO, respectively. Most elevations were transient, and none led to discontinuation. In the clinical studies, there were no reported events of rhabdomyolysis.
Nausea: In placebo-controlled studies, for up to 16 weeks, nausea was reported in 1.8% of patients treated with placebo and in 6.3% and 15.1% of patients treated with 100 mg and 200 mg, respectively. Discontinuation due to nausea occurred in 0.4% of patients treated with CIBINQO. Among patients with nausea, 63.5% of patients had onset of nausea in the first week of therapy. The median duration of nausea was 15 days. Most of the cases were mild to moderate in severity.
Psychiatric disorders: Patients who showed suicidal ideation(s)/behaviour(s) in relevant preliminary investigations were excluded from the clinical trials.
Adolescent population: A total of 635 adolescents (12 to less than 18 years of age) were enrolled in CIBINQO atopic dermatitis studies. The safety profile observed in adolescents in atopic dermatitis clinical studies was similar to that of the adult population (see Dosage & Administration).
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.
Drug Interactions
Potential for other medicines to affect pharmacokinetics of abrocitinib: Abrocitinib is metabolised predominantly by CYP2C19 and CYP2C9 enzymes, and to a lesser extent by CYP3A4 and CYP2B6 enzymes, and its active metabolites are renally excreted and are substrates of the organic anion transporter 3 (OAT3). Therefore, exposures of abrocitinib and/or its active metabolites may be affected by medicinal products that strongly inhibit or induce CYP2C19 or CYP2C9 or inhibit the OAT3 transporter. Dose adjustments, as appropriate, based on these results are outlined in Dosage & Administration.
Co-administration with CYP2C19/CYP2C9 inhibitors: When CIBINQO 100 mg was administered concomitantly with fluvoxamine (a strong CYP2C19 and moderate CYP3A inhibitor) or fluconazole (a strong CYP2C19, moderate CYP2C9 and CYP3A inhibitor), the extent of exposure of abrocitinib active moiety (see Pharmacology: Pharmacokinetics under Actions) increased by 91% and 155%, respectively, compared with administration alone (see Dosage & Administration).
Co-administration with CYP2C19/CYP2C9 inducers: Administration of CIBINQO 200 mg after multiple doses with rifampin, a strong inducer of CYP enzymes, resulted in reduction of abrocitinib active moiety exposures by approximately 56% (see Dosage & Administration).
Co-administration with OAT3 inhibitors: When CIBINQO 200 mg was administered concomitantly with probenecid, an OAT3 inhibitor, abrocitinib active moiety exposures increased by approximately 66%. This is not clinically significant, and a dose adjustment is not needed.
Co-administration with products which increase gastric pH: The effect of elevating gastric pH with antacids, H2-receptor antagonists (famotidine), or proton pump inhibitors (omeprazole) on the pharmacokinetics of abrocitinib has not been studied and may reduce the absorption of abrocitinib due to the low solubility of abrocitinib at pH above 4.
Other in vitro interactions: In vitro, abrocitinib or its metabolites were not significant inhibitors or inducers of CYP enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) or of uridine diphosphate-glucuronyltransferases (UGTs) (UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7). Abrocitinib or its metabolites at clinically meaningful concentrations are not inhibitors of organic anion transporter (OAT)3, organic cation transporter (OCT)1, multidrug and toxin compound extrusion protein (MATE)1/2K and breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1/1B3, bile salt export pump (BSEP), OAT1 or OCT2.
Potential for CIBINQO to affect pharmacokinetics of other medicines: No clinically significant effects of CIBINQO were observed in drug interaction studies with oral contraceptives (e.g., ethinyl oestradiol/levonorgestrel). In vitro, abrocitinib is an inhibitor of P glycoprotein (P-gp). Co-administration of dabigatran etexilate (a P-gp substrate), with a single dose of CIBINQO 200 mg increased dabigatran AUCinf and Cmax by approximately 53% and 40%, respectively, compared with administration alone. The effect of abrocitinib on pharmacokinetics of digoxin, a P-gp substrate with a narrow therapeutic index, has not been evaluated. Caution should be exercised as the levels of digoxin may increase.
Caution For Usage
Incompatibilities: Not applicable.
Special precautions for disposal and other handling: Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Storage
Keep in original package.
MIMS Class
Other Dermatologicals
ATC Classification
D11AH08 - abrocitinib ; Belongs to the class of agents for atopic dermatitis, excluding corticosteroids. Used in the treatment of atopic dermatitis.
Presentation/Packing
FC tab 50 mg (pink, oval, 10.50 mm long and 4.75 mm wide, debossed with "PFE" on one side and "ABR 50" on the other) x 4 x 7's. 100 mg (pink, round, 9.00 mm in diameter, debossed with "PFE" on one side and "ABR 100" on the other) x 4 x 7's. 200 mg (pink, oval, 18.42 mm long and 8.00 mm wide, debossed with "PFE" on one side and "ABR 200" on the other) x 4 x 7's.
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