DRUG INTERACTIONS

 The drug interaction potential of REVCOVI is not known.

U.S. FDA APPROVED  DRUGS DURING 2018

Sr.No-  44

ADVERSE REACTIONS-

 The most common adverse reactions reported were cough (50%) and vomiting (33%).

CONTRAINDICATIONS-                                                                                                       None  

WARNINGS AND PRECAUTIONS-    

 • Injection Site Bleeding in Patients with Thrombocytopenia: Increased risk of local bleeding in patients with thrombocytopenia; should not be used if thrombocytopenia is severe.

• Delay in Improvement of Immune Function: Protect immune deficient patients from infections until improvement in immune function.

 PATIENT COUNSELING INFORMATION-  

Importance of Compliance Counsel patients and caregivers that continuous therapy and adherence to the recommended drug schedule is important for the success of the treatment. 

Manufactured by: Leadiant Biosciences Inc., Gaithersburg, MD 20878, USA, U.S. License No. 2073 at Exelead Inc., 6925 Guion Rd, Indianapolis, IN 46268, USA

 CLINICAL PHARMACOLOGY-                               

1.Mechanism of Action-                                                                                                        SCID associated with a deficiency of ADA enzyme is a rare, inherited, and often fatal disease. ADA enzyme is involved in purine metabolism, catalyzing the irreversible hydrolytic deamination of adenosine or deoxyadenosine to inosine or deoxyinosine, respectively, as well as several naturally occurring methylated adenosine compounds.

2. Pharmacodynamics-                                                                                                      The effect of REVCOVI on the QT interval is not known. 

3. Pharmacokinetics-

The pharmacokinetics (PK) of REVCOVI were evaluated based on steady state plasma ADA activity in six patients with ADA-SCID (five adults and one pediatric) from two studies who received weekly IM injections at doses ranging from 4.99 to 19.6 mg.

Steady state ADA activity levels were reached following seven consecutive once weekly IM doses of REVCOVI.  In addition, dAXP activity levels in all patients at the majority of all sampling timepoints in Study 1 were less than 0.02 mmol/L.  

  USE IN SPECIFIC POPULATIONS-

1. Pregnancy -                                                                                                                     Risk Summary- Adequate and well-controlled studies with REVCOVI have not been conducted in pregnant women to inform a drug-associated risk. Animal reproduction studies have not been conducted with REVCOVI. It is not known whether REVCOVI can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.   

All pregnancies have a risk of birth defect, loss, or other adverse outcomes.

 In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.  

For patients treated with REVCOVI, more frequent monitoring of the health status for both the mother during pregnancy and the development of the offspring is recommended.  

2. Lactation-                                                                                                                        Risk Summary-  Human or animal lactation studies have not been conducted to assess the presence of  REVCOVI in breast milk, the effects on the breastfed infant, or the effects on milk production for the mother.   

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for REVCOVI and any potential adverse effects on the breastfed infant from REVCOVI or from the underlying maternal condition.

3. Pediatric Use-                                                                                                                  The safety and efficacy of REVCOVI have been established in pediatric patients.

4. Geriatric Use-                                                                                                                    REVCOVI was not studied in patients 65 years and older. 

  OVERDOSAGE-       

There are no reports of administration of REVCOVI in excess of the prescribed doses. The highest weekly prescribed dose administered in the clinical studies was 0.4 mg/kg. In nonclinical studies, there was no evidence of toxicity related to study drug at doses up to 1.8-fold the clinical dose (based on mean human AUC normalized to the dose of REVCOVI administered per patient), except for a slight increase in activated partial thromboplastin time (APTT).