Side Effects of Cytotec (misoprostol)

Cytotec (misoprostol) is a synthetic (man-made) prostaglandin used to reduce the risk of stomach ulcers in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs, for example, aspirin, ibuprofen, etc.) for pain and various inflammatory conditions, for example, arthritis. 

Cytotec is used primarily in patients at high risk for stomach ulcers when treated with NSAIDs, such as the elderly, patients with concomitant debilitating diseases, and patients with a history of ulcers. 

Prostaglandins are chemicals that are made within many organs of the body including the stomach. In the stomach, prostaglandins are believed to protect the inner lining of the stomach from the ulcer-producing effects of NSAIDs. 

Scientists now believe that NSAIDs produce ulceration by preventing the production of prostaglandins in the stomach. Synthetic prostaglandins such as Cytotec given orally "replace" the prostaglandins whose production is inhibited by NSAIDs and have been shown to protect the lining of the stomach from NSAID-induced ulcers. 

Common side effects of Cytotec include

• diarrhea and
• abdominal pain.

Less common side effects of Cytotec include

• headache,
• menstrual cramps,
• nausea, and
• gas (flatulence).

Allergic reactions have also been reported.

Serious side effects of Cytotec include

• profound and persistent diarrhea (rare).

Cytotec has no clinically important drug interactions. 

Cytotec should never be used during pregnancy since it can cause abortion, premature birth, or birth defects. Uterine rupture has been reported when Cytotec was administered to pregnant women to induce labor or to induce abortion beyond the eighth week of pregnancy. 

It is unknown if Cytotec is excreted in human breast milk; however, it should not be administered to breastfeeding mothers because it could cause significant diarrhea in nursing infants.

Common side effects include

• diarrhea and
• abdominal pain.

Diarrhea is more common with higher doses and usually resolves with continued administration. Rarely, profound and persistent diarrhea necessitates stopping the drug.

Less common side effects include

• headache,
• menstrual cramps,
• nausea, and
• flatulence.

Allergic reactions have also been reported.

The following have been reported as adverse events in subjects receiving Cytotec:

Gastrointestinal

• In subjects receiving Cytotec 400 or 800 mcg daily in clinical trials, the most frequent gastrointestinal adverse events were diarrhea and abdominal pain.
• The incidence of diarrhea at 800 mcg in controlled trials in patients on NSAIDs ranged from 14-40% and in all studies (over 5,000 patients) averaged 13%.
• Abdominal pain occurred in 13-20% of patients in NSAID trials and about 7% in all studies, but there was no consistent difference from placebo.
• Diarrhea was dose related and usually developed early in the course of therapy (after 13 days), usually was self-limiting (often resolving after 8 days), but sometimes required discontinuation of Cytotec (2% of the patients).
• Rare instances of profound diarrhea leading to severe dehydration have been reported.
• Patients with an underlying condition such as inflammatory bowel disease, or those in whom dehydration, were it to occur, would be dangerous, should be monitored carefully if Cytotec is prescribed.
• The incidence of diarrhea can be minimized by administering after meals and at bedtime, and by avoiding coadministration of Cytotec with magnesium-containing antacids.

Gynecological

• Women who received Cytotec during clinical trials reported the following gynecological disorders:
  • spotting (0.7%),
  • cramps (0.6%),
  • hypermenorrhea (0.5%),
  • menstrual disorder (0.3%) and
  • dysmenorrhea (0.1%).
• Postmenopausal vaginal bleeding may be related to Cytotec administration. If it occurs, diagnostic workup should be undertaken to rule out gynecological pathology.

Elderly

• There were no significant differences in the safety profile of Cytotec in approximately 500 ulcer patients who were 65 years of age or older compared with younger patients.
• Additional adverse events which were reported are categorized as follows.

Incidence Greater Than 1%

• In clinical trials, the following adverse reactions were reported by more than 1% of the subjects receiving Cytotec and may be causally related to the drug:
  • nausea (3.2%),
  • flatulence (2.9%),
  • headache (2.4%),
  • dyspepsia (2.0%),
  • vomiting (1.3%), and
  • constipation (1.1%).
• However, there were no significant differences between the incidences of these events for Cytotec and placebo.

Causal Relationship Unknown

The following adverse events were infrequently reported. Causal relationships between Cytotec and these events have not been established but cannot be excluded:

Body as a whole: aches/pains, asthenia, fatigue, fever, chills, rigors, weight changes.

Skin: rash, dermatitis, alopecia, pallor, breast pain.

Special senses: abnormal taste, abnormal vision, conjunctivitis, deafness, tinnitus, earache.

Respiratory: upper respiratory tract infection, bronchitis, bronchospasm, dyspnea, pneumonia, epistaxis.

Cardiovascular: chest pain, edema, diaphoresis, hypotension, hypertension, arrhythmia, phlebitis, increased cardiac enzymes, syncope, myocardial infarction (some fatal), thromboembolic events (e.g., pulmonary embolism, arterial thrombosis, and CVA).

Gastrointestinal: GI bleeding, GI inflammation/infection, rectal disorder, abnormal hepatobiliary function, gingivitis, reflux, dysphagia, amylase increase.

Hypersensitivity: anaphylactic reaction

Metabolic: glycosuria, gout, increased nitrogen, increased alkaline phosphatase.

Genitourinary: polyuria, dysuria, hematuria, urinary tract infection.

Nervous system/Psychiatric: anxiety, change in appetite, depression, drowsiness, dizziness, thirst, impotence, loss of libido, sweating increase, neuropathy, neurosis, confusion.

Musculoskeletal: arthralgia, myalgia, muscle cramps, stiffness, back pain.

Blood/Coagulation: anemia, abnormal differential, thrombocytopenia, purpura, ESR increased.

Cytotec has not been shown to interfere with the beneficial effects of aspirin on signs and symptoms of rheumatoid arthritis. Cytotec does not exert clinically significant effects on the absorption, blood levels, and antiplatelet effects of therapeutic doses of aspirin. Cytotec has no clinically significant effect on the kinetics of diclofenac or ibuprofen.

Prostaglandins such as Cytotec may augment the activity of oxytocic agents, especially when given less than 4 hours prior to initiating oxytocin treatment. Concomitant use is not recommended.