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Flolan (Epoprostenol Sodium) - Side Effects and Adverse Reactions

 
 



Adverse Reactions

During clinical trials, adverse events were classified as follows: (1) adverse events during dose initiation and escalation, (2) adverse events during chronic dosing, and (3) adverse events associated with the drug delivery system.

Adverse Events During Dose Initiation and Escalation

During early clinical trials, FLOLAN was increased in 2-ng/kg/min increments until the patients developed symptomatic intolerance. The most common adverse events and the adverse events that limited further increases in dose were generally related to vasodilation, the major pharmacologic effect of FLOLAN. The most common dose-limiting adverse events (occurring in ≥1% of patients) were nausea, vomiting, headache, hypotension, and flushing, but also include chest pain, anxiety, dizziness, bradycardia, dyspnea, abdominal pain, musculoskeletal pain, and tachycardia. Table 3 lists the adverse events reported during dose initiation and escalation in decreasing order of frequency.

Table 3. Adverse Events During Dose Initiation and Escalation

Adverse Events Occurring

in≥1% of Patients

FLOLAN

(n = 391)

Flushing

58%

Headache

49%

Nausea/vomiting

32%

Hypotension

16%

Anxiety, nervousness, agitation

11%

Chest pain

11%

Dizziness

8%

Bradycardia

5%

Abdominal pain

5%

Musculoskeletal pain

3%

Dyspnea

2%

Back pain

2%

Sweating

1%

Dyspepsia

1%

Hypesthesia/paresthesia

1%

Tachycardia

1%

Adverse Events During Chronic Administration

Interpretation of adverse events is complicated by the clinical features of PPH and PH/SSD, which are similar to some of the pharmacologic effects of FLOLAN (e.g., dizziness, syncope). Adverse events probably related to the underlying disease include dyspnea, fatigue, chest pain, edema, hypoxia, right ventricular failure, and pallor. Several adverse events, on the other hand, can clearly be attributed to FLOLAN. These include headache, jaw pain, flushing, diarrhea, nausea and vomiting, flu-like symptoms, and anxiety/nervousness.

Adverse Events During Chronic Administration for PPH

In an effort to separate the adverse effects of the drug from the adverse effects of the underlying disease, Table 4 lists adverse events that occurred at a rate at least 10% different in the 2 groups in controlled trials for PPH.

Table 4. Adverse Events Regardless of Attribution Occurring in Patients With PPH With ≥10% Difference Between FLOLAN and Conventional Therapy Alone

Adverse Event

FLOLAN

(n = 52)

Conventional Therapy

(n = 54)

Occurrence More Common With FLOLAN

General

Chills/fever/sepsis/flu-like symptoms

25%

11%

Cardiovascular

Tachycardia

35%

24%

Flushing

42%

2%

Gastrointestinal

Diarrhea

37%

6%

Nausea/vomiting

67%

48%

Musculoskeletal

Jaw pain

54%

0%

Myalgia

44%

31%

Nonspecific musculoskeletal pain

35%

15%

Neurological

Anxiety/nervousness/tremor

21%

9%

Dizziness

83%

70%

Headache

83%

33%

Hypesthesia, hyperesthesia, paresthesia

12%

2%

Occurrence More Common With Standard Therapy

Cardiovascular

Heart failure

31%

52%

Syncope

13%

24%

Shock

0%

13%

Respiratory

Hypoxia

25%

37%

Thrombocytopenia has been reported during uncontrolled clinical trials in patients receiving FLOLAN.

Table 5 lists additional adverse events reported in PPH patients receiving FLOLAN plus conventional therapy or conventional therapy alone during controlled clinical trials.

Table 5. Adverse Events Regardless of Attribution Occurring in Patients With PPH With <10% Difference Between FLOLAN and Conventional Therapy Alone

Adverse Event

FLOLAN

(n = 52)

Conventional Therapy

(n = 54)

General

Asthenia

87%

81%

Cardiovascular

Angina pectoris

19%

20%

Arrhythmia

27%

20%

Bradycardia

15%

9%

Supraventricular tachycardia

8%

0%

Pallor

21%

30%

Cyanosis

31%

39%

Palpitation

63%

61%

Cerebrovascular accident

4%

0%

Hemorrhage

19%

11%

Hypotension

27%

31%

Myocardial ischemia

2%

6%

Gastrointestinal

Abdominal pain

27%

31%

Anorexia

25%

30%

Ascites

12%

17%

Constipation

6%

2%

Metabolic

Edema

60%

63%

Hypokalemia

6%

4%

Weight reduction

27%

24%

Weight gain

6%

4%

Musculoskeletal

Arthralgia

6%

0%

Bone pain

0%

4%

Chest pain

67%

65%

Neurological

Confusion

6%

11%

Convulsion

4%

0%

Depression

37%

44%

Insomnia

4%

4%

Respiratory

Cough increase

38%

46%

Dyspnea

90%

85%

Epistaxis

4%

2%

Pleural effusion

4%

2%

Skin and Appendages

Pruritus

4%

0%

Rash

10%

13%

Sweating

15%

20%

Special Senses

Amblyopia

8%

4%

Vision abnormality

4%

0%

Adverse Events During Chronic Administration for PH/SSD

In an effort to separate the adverse effects of the drug from the adverse effects of the underlying disease, Table 6 lists adverse events that occurred at a rate at least 10% different in the 2 groups in the controlled trial for patients with PH/SSD.

Table 6. Adverse Events Regardless of Attribution Occurring in Patients With PH/SSD With ≥10% Difference Between FLOLAN and Conventional Therapy Alone

Adverse Event

FLOLAN

(n = 56)

Conventional Therapy

(n = 55)

Occurrence More Common With FLOLAN

Cardiovascular

Flushing

23%

0%

Hypotension

13%

0%

Gastrointestinal

Anorexia

66%

47%

Nausea/vomiting

41%

16%

Diarrhea

50%

5%

Musculoskeletal

Jaw pain

75%

0%

Pain/neck pain/arthralgia

84%

65%

Neurological

Headache

46%

5%

Skin and Appendages

Skin ulcer

39%

24%

Eczema/rash/urticaria

25%

4%

Occurrence More Common With Conventional Therapy

Cardiovascular

Cyanosis

54%

80%

Pallor

32%

53%

Syncope

7%

20%

Gastrointestinal

Ascites

23%

33%

Esophageal reflux/gastritis

61%

73%

Metabolic

Weight decrease

45%

56%

Neurological

Dizziness

59%

76%

Respiratory

Hypoxia

55%

65%

Table 7 lists additional adverse events reported in PH/SSD patients receiving FLOLAN plus conventional therapy or conventional therapy alone during controlled clinical trials.

Table 7. Adverse Events Regardless of Attribution Occurring in Patients With PH/SSD With <10% Difference Between FLOLAN and Conventional Therapy Alone

Adverse Event*

FLOLAN

(n = 56)

Conventional Therapy

(n = 55)

General

Asthenia

100%

98%

Hemorrhage/hemorrhage injection site/hemorrhage rectal

11%

2%

Infection/rhinitis

21%

20%

Chills/fever/sepsis/flu-like symptoms

13%

11%

Blood and Lymphatic

Thrombocytopenia

4%

0%

Cardiovascular

Heart failure/heart failure right

11%

13%

Myocardial Infarction

4%

0%

Palpitation

63%

71%

Shock

5%

5%

Tachycardia

43%

42%

Vascular disorder peripheral

96%

100%

Vascular disorder

95%

89%

Gastrointestinal

Abdominal enlargement

4%

0%

Abdominal pain

14%

7%

Constipation

4%

2%

Flatulence

5%

4%

Metabolic

Edema/edema peripheral/edema genital

79%

87%

Hypercalcemia

48%

51%

Hyperkalemia

4%

0%

Thirst

0%

4%

Musculoskeletal

Arthritis

52%

45%

Back pain

13%

5%

Chest pain

52%

45%

Cramps leg

5%

7%

Respiratory

Cough increase

82%

82%

Dyspnea

100%

100%

Epistaxis

9%

7%

Pharyngitis

5%

2%

Pleural effusion

7%

0%

Pneumonia

5%

0%

Pneumothorax

4%

0%

Pulmonary edema

4%

2%

Respiratory disorder

7%

4%

Sinusitis

4%

4%

Neurological

Anxiety/hyperkinesia/nervousness/tremor

7%

5%

Depression/depression psychotic

13%

4%

Hyperesthesia/hypesthesia/paresthesia

5%

0%

Insomnia

9%

0%

Somnolence

4%

2%

Skin and Appendages

Collagen disease

82%

84%

Pruritus

4%

2%

Sweat

41%

36%

Urogenital

Hematuria

5%

0%

Urinary tract infection

7%

0%

*Adverse events that occurred in at least 2 patients in either treatment group.

Although the relationship to FLOLAN administration has not been established, pulmonary embolism has been reported in several patients taking FLOLAN and there have been reports of hepatic failure.

Adverse Events Attributable to the Drug Delivery System

Chronic infusions of FLOLAN are delivered using a small, portable infusion pump through an indwelling central venous catheter. During controlled PPH trials of up to 12 weeks’ duration, up to 21% of patients reported a local infection and up to 13% of patients reported pain at the injection site. During a controlled PH/SSD trial of 12 weeks’ duration, 14% of patients reported a local infection and 9% of patients reported pain at the injection site. During long-term follow-up in the clinical trial of PPH, sepsis was reported at least once in 14% of patients and occurred at a rate of 0.32 infections/patient per year in patients treated with FLOLAN. This rate was higher than reported in patients using chronic indwelling central venous catheters to administer parenteral nutrition, but lower than reported in oncology patients using these catheters. Malfunctions in the delivery system resulting in an inadvertent bolus of or a reduction in FLOLAN were associated with symptoms related to excess or insufficient FLOLAN, respectively (see ADVERSE REACTIONS: Adverse Events During Chronic Administration).

Observed During Clinical Practice

In addition to adverse reactions reported from clinical trials, the following events have been identified during post-approval use of FLOLAN. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to FLOLAN.

Blood and Lymphatic

Anemia, hypersplenism, pancytopenia, splenomegaly.

Endocrine and Metabolic

Hyperthyroidism.



REPORTS OF SUSPECTED FLOLAN SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Flolan. The information is not vetted and should not be considered as verified clinical evidence.

Possible Flolan side effects / adverse reactions in 54 year old female

Reported by a consumer/non-health professional from United States on 2011-10-05

Patient: 54 year old female weighing 58.0 kg (127.6 pounds)

Reactions: Gastrointestinal Haemorrhage, Urinary Tract Infection, Oesophageal Haemorrhage

Adverse event resulted in: hospitalization

Suspect drug(s):
Flolan

Other drugs received by patient: Depo-Provera; Oxycontin; Loperamide HCL; Pyridostigmine Bromide; Fludrocortisone Acetate; Triamcinolone; Zinc Sulfate; Lactulose; Acetaminophen; Cream; Potassium; Zofran; Neomycin; Furosemide; TPN; Macrobid; Oxycodone HCL; Albuterol; Lubriderm; Doxycycline; Midodrine Hydrochloride; Xifaxan; Sandostatin; Multi-Vitamin; Sildenafil Citrate; Keflex



Possible Flolan side effects / adverse reactions in 44 year old female

Reported by a consumer/non-health professional from United States on 2011-10-06

Patient: 44 year old female weighing 115.0 kg (253.0 pounds)

Reactions: Cardiac Failure, Pain in JAW

Adverse event resulted in: hospitalization

Suspect drug(s):
Flolan

Other drugs received by patient: Imodium; Risperidone; Bentyl; Mobic; Celexa; Naproxen (Aleve); Tramadol HCL; Revatio; Potassium; Gabapentin; Prilosec; Furosemide; Paxil CR



Possible Flolan side effects / adverse reactions in 60 year old female

Reported by a consumer/non-health professional from United States on 2011-10-07

Patient: 60 year old female

Reactions: Eye Operation, Adverse Event, Infection

Adverse event resulted in: hospitalization

Suspect drug(s):
Flolan

Other drugs received by patient: Revatio; Coumadin



See index of all Flolan side effect reports >>

Drug label data at the top of this Page last updated: 2006-01-04

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