Sex: M
Vaccine: COVID19, UNK, UNK, UNK
Symptoms: Limb discomfort, Mitral valve incompetence, Oedema peripheral, Platelet count, Pulmonary arterial hypertension
Clinical narrative: Influenza B exacerbating PAH (pulmonary arterial hypertension), AHRF; COVID 19 and pneumonia; COVID 19 and pneumonia; Pulmonary hypertension (pHTN) exacerbation, AHRF (acute hypoxemic respiratory failure) secondary to influenza B exacerbating PAH, pHTN treated with steroids as though to be flare due to lupus; AHRF secondary to Influenza B exacerbating PAH (pulmonary arterial hypertension), AHRF secondary to Flu B and PAH with baseline PAH; Influenza B; Volume overload; Worsening MR (mitral regurgitation); Steroid induced diabetes; Lupus flare; Lower extremity edema, 2+ pitting edema, to knees. 1+ dependent edema at thighs; Weight slowly coming down, weight up 4 lbs; Rash; Fever, temperature 101.1 F; Diarrhea; Leg healing; blisters on foot; limb discomfort;   A 57-year-old male patient received bnt162b2 (BNT162B2), via an unspecified route of administration on an unspecified date (Batch/Lot number was not reported) as unknown, single for covid-19 immunisation; methylprednisolone (MEDROL), oral from an unspecified date (Batch/Lot number was not reported) to an unspecified date, at 1.5 tablets by mouth, daily, qd for an unspecified indication; nifedipine (NIFEDIPINE), route of administration, start and stop date, batch/lot number and dose were not reported for an unspecified indication; treprostinil diolamin (ORENITRAM), oral from an unspecified date (Batch/Lot number was not reported) to an unspecified date, at 3.875 mg, 3x/day, oral from an unspecified date (Batch/Lot number was not reported) and ongoing, at 3 mg, 3x/day, oral from an unspecified date (Batch/Lot number was not reported) to an unspecified date, at 2.875 mg, 3x/day, oral from an unspecified date (Batch/Lot Number: 2101810; Expiration Date: 31Jan2023) and ongoing, at unspecified dose for an unspecified indication. Medical history included ongoing pulmonary arterial hypertension PAH/ High BP disorder/ increased pressure of pulmonary circulation , ongoing systemic lupus erythematosus , ongoing sleep apnoea syndrome on CPAP , ongoing hypercalcaemia , ongoing peripheral arterial occlusive disease , ongoing dyspnoea , covid-19 from an unknown date and unknown if ongoing  Brother positive , ongoing continuous positive airway pressure , ongoing hypertension , influenza immunisation from an unknown date and unknown if ongoing for Influenza B infection. Concomitant medications included ambrisentan (LETAIRIS) taken for an unspecified indication from an unspecified start date and ongoing; sildenafil citrate (REVATIO) taken for an unspecified indication from an unspecified start date and ongoing; calcium citrate, colecalciferol (CITRACAL + D [CALCIUM CITRATE;COLECALCIFEROL]) , digoxin (LANOXIN) ,epinephrine (EPIPEN) ,escitalopram oxalate (LEXAPRO) ,folic acid (FOLVITE [FOLIC ACID]) ,hydroxychloroquine sulfate (PLAQUENIL [HYDROXYCHLOROQUINE SULFATE]) ,famotidine (PEPCID [FAMOTIDINE]) ,furosemide (LASIX [FUROSEMIDE]) ,spironolactone (ALDACTONE [SPIRONOLACTONE]) ,apixaban (ELIQUIS) taken for an unspecified indication, start and stop date were not reported.  The patient experienced influenza b exacerbating pah (pulmonary arterial hypertension), ahrf (acute respiratory failure) on an unspecified date with outcome of recovered on 26Apr2021, covid 19 and pneumonia (covid-19 pneumonia) on an unspecified date with outcome of recovered on 26Apr2021, pulmonary hypertension (phtn) exacerbation, ahrf (acute hypoxemic respiratory failure) secondary to influenza b exacerbating pah, phtn treated with steroids as though to be flare due to lupus (pulmonary arterial hypertension) on an unspecified date with outcome of recovered on 26Apr2021, ahrf secondary to influenza b exacerbating pah (pulmonary arterial hypertension), ahrf secondary to flu b and pah with baseline pah; influenza b (influenza) on an unspecified date with outcome of recovered , volume overload (fluid overload) on an unspecified date with outcome of unknown , worsening mr (mitral regurgitation) (mitral valve incompetence) on an unspecified date with outcome of unknown , steroid induced diabetes (steroid diabetes) on an unspecified date with outcome of recovered , lupus flare (systemic lupus erythematosus) on an unspecified date with outcome of unknown , lower extremity edema, 2+ pitting edema, to knees. 1+ dependent edema at thighs (oedema peripheral) on an unspecified date with outcome of not recovered , weight slowly coming down, weight up 4 lbs (weight fluctuation) on an unspecified date with outcome of not recovered , rash (rash) on an unspecified date with outcome of recovered , fever, temperature 101.1 f (pyrexia) on an unspecified date with outcome of recovered in 2021, diarrhea (diarrhoea) on an unspecified date with outcome of recovered in 2021, leg healing; blisters on foot (blister) on an unspecified date with outcome of recovered , limb discomfort (limb discomfort) on an unspecified date with outcome of recovering. The events were serious as medically significant and hospitalization from 16Apr2021 to 26Apr2021. The patient underwent lab tests and procedures which included blood creatinine: 1.68 on 24Apr2021, 1.59  on 25Apr2021, 1.54  on 26Apr2021, blood glucose: 90 on 24Apr2021, 117 on 25Apr2021, 90 on 26Apr2021, blood potassium: 4.1 on 24Apr2021, 4.4 on 25Apr2021, 4.4 on 26Apr2021, blood sodium: 141 on 24Apr2021, 141 on 25Apr2021 , 141 on 26Apr2021, blood urea: 39 on 24Apr2021, 39 on 25Apr2021, 37 on 26Apr2021.  Body temperature 101.1 Fahrenheit in 2021, Catheterisation cardiac Revealed moderate pulmonary hypertension with right atrium (RA) 7, right ventricle (RV) 12, pressure wave (PW) 15, PA 62/ 25/40, PA saturation 63 %, CO 7, CI 3.52, on 21Apr2021, Haemoglobin 8.4 on 24Apr2021, 8.2 on 25Apr2021, 8.3 on 26Apr2021, Platelet count 146 on 24Apr2021, 159 on 25Apr2021, 159 on 26Apr2021. Red blood cell count 3.31 on 24Apr2021, 3.24 on 25Apr2021, 3.30 on 26Apr2021. Weight stable at 155 lbs, up by 4 lbs since discharge from hospital, slowly coming down on unknown dates, White blood cell count 4.79 on 24Apr2021, 5.51 on 25Apr2021, 5.41 on 26Apr2021. The action taken in response to the events for bnt162b2 was not applicable, for methylprednisolone was temporarily withdrawn on an unspecified date, for nifedipine was permanently withdrawn on an unspecified date, for treprostinil diolamin was dose not changed.   Clinical course: This case is a solicited report received on 31Mar2021 from a consumer via pharmacy. This 57-year-old, 210-lb male patient began therapy with Orenitram (treprostinil diethanolamine), on 01Aug2019 for primary pulmonary arterial hypertension. The patient was supplied with Orenitram 0.25mg, 1mg, 2.5mg and 0.125mg and the current dose was reported as 3.875mg, via oral (PO) route, every eight hours (q8h). On 23Mar2021, the patient experienced event COVID-19 and pneumonia (COVID-19 pneumonia, hospitalization, medically significant). Concomitant medications included: Letairis (ambrisentan) and Revatio (sildenafil citrate). Relevant medical history included: primary pulmonary arterial hypertension. On 23Mar2021, 1 year 7 months 23 days after initiating PO Orenitram, the patient was hospitalized due to COVID-19 and pneumonia and discharged on 29Mar2021. The patient was on oxygen at the time of reporting. Follow-up information was received as solicited report on 15Apr2021 from a consumer via Accredo specialty pharmacy. On 06Apr2021, the patient had pneumonia (pneumonia, medically significant and hospitalized). Additional lot number and expiration date were added to 2.5 mg concentration of PO Orenitram. On 06Apr2021, 1 year 8 months 6 days after initiating PO Orenitram, the patient was hospitalized due to pneumonia and remained hospitalized at the time of reporting. The patient was also hospitalized in Mar2021 for COVID (previously reported COVID-19 pneumonia). The reporter did not provide causality for the event of pneumonia. Additional spontaneous information was received on 19Apr2021 from a consumer (social worker) via Accredo specialty pharmacy. Event of pneumonia was omitted and subsumed under COVID-19 pneumonia. Since 06Apr2021, the patient remained hospitalized due to COVID (previously reported COVID-19 pneumonia). Follow-up information was received on 27Apr2021, from a nurse on behalf of the reporting physician via a query response. On 16Apr2021, the patient had acute hypoxemic respiratory failure (AHRF) from COVID, AHRF secondary to Influenza B exacerbating PAH (pulmonary arterial hypertension), AHRF secondary to Flu B and PAH with baseline PAH (acute respiratory failure, hospitalized, medically significant), pulmonary hypertension (pHTN) exacerbation, AHRF (acute hypoxemic respiratory failure) secondary to influenza B exacerbating PAH, pHTN treated with steroids as though to be flare due to lupus (pulmonary arterial hypertension, hospitalized and medically significant), AHRF secondary to Flu B and PAH with baseline PAH (influenza, hospitalized), volume overload (fluid overload, hospitalized). On an unreported date in 2021, the patient had fever, temperature 101.1 F (pyrexia). On an unreported date, the patient had worsening MR (mitral regurgitation) (mitral valve incompetence, medically significant), steroid induced diabetes (steroid diabetes, medically significant), lower extremity edema, 2+ pitting edema, to knees 1+ dependent edema at thighs (oedema peripheral), weight slowly coming down, weight up 4 lbs (weight fluctuation), rash (rash), diarrhea (diarrhoea), and leg healing (limb discomfort). Co-suspect medications included: nifedipine, COVID-19 Vaccine, and Medrol (methylprednisolone). Additional concomitant medications included: Citracal + d (calcium citrate, ergocalciferol), Lanoxin (digoxin), Epipen (epinephrine), Lexapro (escitalopram oxalate), Folvite (folic acid), Plaquenil (hydroxychloroquine sulfate), Pepcid (famotidine), Lasix (furosemide), Aldactone (spironolactone) and Eliquis (apixaban). Additional relevant medical history included: calcium deficiency, systemic lupus erythematosus (SLE), obstructive sleep apnea (OSA) on Continuous positive airway pressure (CPAP), hypercalcemia, chronically high peripheral artery disease (PAD), hypertension and multifactorial stable SOB (shortness of breath). Patient's family history included: COVID-19 (brother positive). Additional dosage regimen of 3 mg (q8h) and 2.875 mg, (q8h) were added to PO Orenitram. On 16Apr2021, 1 year 8 months 16 days after initiating PO Orenitram, the patient was hospitalised due to acute hypoxemic respiratory failure (AHRF) from COVID (previously reported COVID-19 pneumonia) and for AHRF secondary to influenza B exacerbating PAH, then transferred to the other hospital with volume overload and diuresis. The patient was presented with volume overload and needed oxygen requirement (none needed at home prior to both hospitalizations). The patient's breathing and oxygen were improved with diuresis. Patient's pulmonary hypertension was treated with steroids as though to be flare due to lupus. Patient was given intravenous (IV) solumedrol (25 mg in AM and 16 mg in PM) as per the discussion with rheumatology and pulmonary hypertension cardiology with improvement in oxygen status. On 24Apr2021, the patient relevant diagnostic and laboratory test included: complete blood count (CBC) WBC (white blood count) 4.79, RBC (Red blood cell count) 3.31, Hgb (hemoglobin) 8.4, Plt (Platelet count) 146. Comprehensive metabolic panel (CMP) Na (sodium) 141, K (potassium) 4.1, Blood urea nitrogen (BUN) 39, Creatinine 1.68, glucose 90. On 25 Apr 2021, the patient had relevant diagnostic and laboratory test included WBC 5.51, RBC 3.24, Hgb 8.2, Plt 159. Na 141, K 4.4, BUN 39, Creatinine 1.59, glucose 117. On 26 Apr 2021, the patient had relevant diagnostic and laboratory test included White blood cells (WBC) 5.41, Red blood cells (RBC) 3.30, hemoglobin (hgb) 8.3, platelet (Plt) 159. Na 141, K 4.4, BUN 37, creatinine 1.54, and glucose 90. The patient was discharged on 26 Apr 2021. Patient's physical exam at the time of discharge showed pulse 65 bpm, respiratory rate 18 per minute, blood pressure (BP) 138/78 mmHg, temperature 36.5 C and weight was 90.9 kg. The patient was breathing comfortably in no distress on 2 Litre nasal cannula (NC). Minimal crackles appreciated in the morning posteriorly. The patient had 2+ pitting edema, to knees 1+ dependent edema at thighs and edema unchanged but overall leg size decreased. Continues to be pitting but improved on the day of discharge. Patient's discharge diagnosis pulmonary hypertension exacerbation. Patient's diuretics were increased from 40 mg daily to 60 mg daily and may needed more diuretics. Discharge medications included: Protonix (pantoprazole), Demadex (torsemide), Medrol (methylprednisolone), Citracal + d (calcium citrate, ergocalciferol), Lanoxin (digoxin), EpiPen (epinephrine), Lexapro (escitalopram oxalate), Folvite (folic acid), Plaquenil (hydroxychloroquine sulfate). Patient's medications of Pepcid, Lasix, and Aldactone were stopped after discharge from the hospital. The patient was instructed to take pantoprazole 40 mg daily while on steroids and when steroids tapered, he had to discontinue it in future and would stop pantoprazole and resume taking home dose of famotidine. Patient was on nifedipine at home and physician thought to be the contributing factor to lower extremity edema so stopped taking the nifedipine in house. It was reported that steroid induced the diabetes. It was reported that the patient needs transesophageal echocardiogram (TEE) due to had worsening MR (mitral regurgitation) but not agreeable at that time. The patient tried ethacrynic acid 50 mg daily but felt it was not making a difference with his weight. The patient went back on the Bumex (bumetanide) on Friday. Patient's weight slowly coming down to see doing good later on Bumex, his rash subsiding and leg was healing. Patient's weight was stable at 155 lbs and had multifactorial stable shortness of breath (SOB). Patient's weight was above baseline and needed more diuretics. Patient had been in touch with his COVID positive brother who was symptomatic and refused to be covid testing quarantining at that time. On 24 Feb 2021, the patient got his first dose of COVID-19 vaccine and his temperature was 101.1 F. The patient would take Tylenol (paracetamol) and monitor if fever persists to 48 hours he would go to the urgent care. Patient was started on Eliquis and felt much better and no longer to had temperatures and diarrhea. On an 21 Apr 2021, the patient had right heart catheterization which revealed moderate pulmonary hypertension with right atrium (RA) 7, right ventricle (RV) 12, pressure wave (PW) 15, PA 62/ 25/40, PA saturation 63 %, CO 7, CI 3.52. Patient had chronically high PAD's and could not take metolazone secondary to hypercalcemia and pending admission for colonoscopy with the physician. Patient reminded multiple times by physician for getting a COVID swab. The patient also had increased 4 lb weight since discharge from the hospital. Additional concomitant medications included: methotrexate, lactobacillus, and zolpidem. Patient had COVID 19 pneumonia (1st episode) on 23 Mar 2021 and 2nd episode on 06 Apr 2021. It was reported that the patient had blister on foot from ill-fitting shoe and leg was healed (at the time of reporting). Patient's pulmonary hypertension (PHTN) was thought to be worsening due to lupus flair and was treated with intravenous (IV) solumedrol. Lupus flair was treated with steroids and Plaquenil (hydroxychloroquine) was continued. Volume overload was treated with diuretics and oxygen. The patient had steroid induced diabetes and had to monitor HbA1c. Influenza B was treated with Tamiflu (oseltamivir), fluid resuscitation CPAP, doxycycline and Zoysa. The patient had received flu vaccination prior to Influenza B infection. it was also confirmed that patient did not have colonoscopy and had not received SQ Remodulin.Outcome of the events of oedema peripheral and weight fluctuation was updated to not recovered. The reporter assessed the causal relationship between the PO Orenitram and the events COVID-19 pneumonia, acute respiratory failure, pulmonary arterial hypertension, influenza, fluid overload, mitral valve incompetence, steroid diabetes, oedema peripheral, weight fluctuation, rash, pyrexia, diarrhoea, and blister as not related. The reporter did not provide causality for the events of systemic lupus erythematosus. Case Comment/Senders Comment: The company has assessed the serious adverse events of COVID-19 pneumonia, acute respiratory failure, pulmonary arterial hypertension, influenza, fluid overload, mitral valve incompetence, steroid diabetes, and systemic lupus erythematosus as not related to Orenitram. The event of COVID-19 pneumonia was related to the ongoing SARS-CoV-2 pandemic, and the event influenza was related to seasonal Influenza B. The event acute respiratory failure was likely related to acute influenza, but was also possibly impacted by pulmonary insult from COVID-19 pneumonia , and underlying lupus associated with PAH. The event pulmonary arterial hypertension was likely an exacerbation of the underlying PAH due to the concurrent infections. The event mitral valve incompetence and fluid overload were likely related to cardiac dysfunction associated with the underlying chronic and progressive PAH. The event steroid diabetes was likely related to co-suspect medication Medrol, which was used as treatment for the lupus, although co-suspect medication nifedipine was possibly contributory to the event in view of its safety profile and as such cannot be excluded. The event systemic lupus erythematosus was likely an exacerbation of underlying lupus associated with PAH. Information about lot/batch number has been requested.  The reporter's assessment of the causal relationship of the events with the suspect products was not provided at the time of this report. Since no determination has been received, the case is managed based on the company causality assessment.; Sender's Comments: Based on the available information the events drug ineffective, rash, fever and diarrhea were possibly related to BNT162B2 vaccine. The other reported events are assessed unrelated to BNT162B2. The event steroid induced diabetes was possibly related to Methylprednisolone; the other events were unlikely related to Methylprednisolone. None of the events is considered related to Nifedipine. The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to Regulatory Authorities, Ethics Committees and Investigators, as appropriate.