Carboprost Tromethamine

Approved Indications:

• Postpartum Hemorrhage (PPH): For the treatment of severe postpartum hemorrhage due to uterine atony that is unresponsive to conventional methods (e.g., oxytocin, ergometrine).
• Therapeutic Abortion: Used to induce abortion in the second trimester (13 to 20 weeks of gestation) for medical reasons, including:
• Intrauterine fetal death
• Missed abortion
• Molar pregnancy
• Failure of other abortion methods

Off-label or Clinically Accepted Uses:

• Uterine Atony Prevention: Occasionally used intraoperatively in high-risk cesarean deliveries to prevent uterine atony and hemorrhage.
• Management of Inevitable Abortion: As adjunct therapy in women experiencing heavy bleeding due to incomplete miscarriage.

Route of Administration: Intramuscular (IM) injection

Adults:

• Postpartum Hemorrhage:
• Initial dose: 250 mcg IM
• Repeat every 15–90 minutes if necessary
• Maximum total dose: 2 mg (8 doses)
• Second Trimester Abortion:
• Dose: 250 mcg IM every 1.5 to 3.5 hours
• Adjust dosing based on uterine response
• Maximum total dose: 12 mg

Special Populations:

• Elderly: Not indicated
• Pediatrics: Not indicated
• Renal Impairment: Use with caution; no dosage adjustment defined, but monitor closely
• Hepatic Impairment: Use cautiously; monitor for increased adverse effects

Administration Notes:

• Shake ampoule well before use
• Administer deep IM in the upper outer quadrant of the gluteal muscle
• Do not administer intravenously or intrathecally

Carboprost Tromethamine is a synthetic analogue of prostaglandin F2α. It binds to prostanoid FP receptors on uterine smooth muscle, promoting strong uterine contractions (myometrial activity), which leads to expulsion of uterine contents and reduction of postpartum bleeding. Additionally, it causes vasoconstriction of uterine vessels and decreases uterine blood flow, further supporting hemostasis. These combined effects are responsible for its effectiveness in inducing abortion and controlling postpartum hemorrhage due to uterine atony.

• Absorption: Rapidly absorbed after intramuscular injection.
• Distribution: Extensively distributed to the uterus; crosses the placenta minimally.
• Metabolism: Primarily metabolized in the lungs and liver through enzymatic oxidation and reduction.
• Half-life: Approximately 8 minutes (short plasma half-life).
• Elimination: Metabolites are excreted primarily via the kidneys (urine), with some fecal excretion.

• Pregnancy: Not assigned under current FDA labeling. Contraindicated except for therapeutic abortion or life-saving postpartum indications. It is intended for use during pregnancy under specific, medically supervised conditions (e.g., abortion or hemorrhage).
• Lactation:
• Carboprost is excreted in minimal amounts into breast milk.
• Due to its short half-life and limited systemic exposure, it is considered generally safe during breastfeeding.
• However, caution is advised, especially in neonates with immature hepatic or renal function.

• Primary Class: Oxytocic Agent (Uterotonic)
• Subclass: Prostaglandin F2α Analogue

• Known hypersensitivity to carboprost tromethamine or other prostaglandins
• Active pelvic inflammatory disease
• Acute cardiac, renal, pulmonary, or hepatic disease
• Asthma (especially poorly controlled)
• Hypotension or hypertension
• Epilepsy or history of seizures
• Known or suspected ectopic pregnancy (in abortion indication)

• Asthma: High risk of bronchospasm; contraindicated in patients with reactive airway disease
• Cardiovascular Disorders: Can cause increased blood pressure or hypotension, tachycardia, or arrhythmias
• Pulmonary Conditions: Risk of pulmonary edema or bronchoconstriction
• Gastrointestinal Effects: May cause severe vomiting or diarrhea; use cautiously in patients with GI disease
• Renal/Hepatic Impairment: Use with caution; increased risk of toxicity
• Sepsis and Fever: May mask signs of systemic infection; monitor closely
• Monitoring Required:
• Uterine tone and bleeding
• Vital signs
• Signs of hypersensitivity or anaphylaxis
• Respiratory status (in patients with a history of lung disease)

Common Side Effects:

• Gastrointestinal: Nausea, vomiting, diarrhea, abdominal cramps
• Cardiovascular: Hypertension, hypotension, flushing, bradycardia
• Respiratory: Cough, dyspnea
• General: Chills, fever, shivering
• Injection Site: Pain or swelling

Serious/Rare Side Effects:

• Bronchospasm or severe asthma exacerbation
• Pulmonary edema
• Anaphylaxis or severe hypersensitivity reactions
• Uterine rupture (especially with overuse)
• Seizures (rare but possible in susceptible patients)

• Oxytocic Agents (e.g., Oxytocin): Synergistic effect may cause excessive uterine contractions or rupture; use with caution.
• Ergot Alkaloids (e.g., Methylergometrine): May increase risk of vasospasm and hypertension.
• Beta-blockers: May reduce bronchodilatory effect and exacerbate bronchoconstriction.
• NSAIDs: Theoretical risk of antagonizing prostaglandin effects; clinical significance is limited.
• Anesthetics: Concomitant use may increase cardiovascular or respiratory adverse effects.

Enzyme Interactions: Not metabolized via CYP450 enzymes; low potential for hepatic drug-drug interactions.

• WHO & FIGO Guidelines: Carboprost remains a second-line agent for postpartum hemorrhage when oxytocin and ergometrine fail or are contraindicated.
• New Cautions Emphasized: Updated warnings emphasize extra care in patients with pulmonary conditions due to severe respiratory complications reported in post-marketing surveillance.
• EMA Notes: Reinforced safety surveillance for use in asthmatic patients due to increasing reports of bronchospasm.

• Temperature: Store between 2°C to 8°C (Refrigerated conditions)
• Light Sensitivity: Protect from light; store in original packaging
• Handling: Do not freeze; discard if frozen
• Stability: Use immediately after opening the ampoule
• Special Note: Do not use if solution appears cloudy or discolored