Ritopar

Approved Indication:

• Premature Labor (Preterm Labor): Ritodrine Hydrochloride is indicated for the management of premature labor in pregnant women (usually between 20 and 37 weeks of gestation) to delay delivery when there are no contraindications to prolonging pregnancy. It is primarily used to inhibit uterine contractions in early labor.

Off-label / Clinically Accepted Uses:

• Uterine Hyperactivity: Used in some clinical settings to manage excessive uterine contractions during labor induction or augmentation.
• Adjunct in Assisted Reproductive Techniques: Occasionally utilized to relax the uterus during embryo transfer in assisted reproduction procedures (limited data, not universally accepted).

Route: Intravenous (IV) infusion is the standard method of administration.

Adult (Pregnant Women):

• Initial Dose: Begin with 50 micrograms/minute via continuous IV infusion.
• Titration: Increase by 50 micrograms/minute every 10 minutes until contractions cease or maternal heart rate reaches 140–160 bpm.
• Maintenance Dose: Usually maintained between 150–350 micrograms/minute.
• Maximum Dose: Do not exceed 350 micrograms/minute in most cases.
• Duration: Continue infusion until uterine activity is adequately controlled (usually up to 12–48 hours); oral therapy may be started afterward if available (formulations limited).

Renal/Hepatic Impairment:

• Use with caution; specific dose adjustments not well-established due to limited data. Clinical monitoring is essential.

Elderly & Pediatrics:

• Not indicated.

Administration Notes:

• Monitor maternal heart rate, blood pressure, fluid balance, fetal heart rate, and uterine contractions closely.
• Infuse using a controlled infusion device.

Ritodrine Hydrochloride is a selective β2-adrenergic receptor agonist. It binds to β2-adrenergic receptors located on uterine smooth muscle, stimulating adenylate cyclase and increasing intracellular cyclic AMP (cAMP). Elevated cAMP levels lead to decreased intracellular calcium concentrations, causing relaxation of uterine smooth muscle. This tocolytic effect suppresses premature uterine contractions, delaying preterm labor. Ritodrine exhibits minimal activity on β1-adrenergic receptors but may still produce some cardiovascular effects at higher doses.

• Absorption: Administered IV; immediate onset of action.
• Distribution: Distributed widely in maternal tissues and crosses the placenta.
• Plasma Protein Binding: ~56%.
• Metabolism: Primarily metabolized in the liver via sulfation and conjugation.
• Half-life: ~1.7 to 2.6 hours.
• Excretion: Mainly excreted in urine as metabolites and small amounts of unchanged drug.
• Placental Transfer: Yes; measurable levels in fetal circulation.
• Breast Milk Excretion: Excreted in small amounts.

• Pregnancy: Former FDA Pregnancy Category B. Although used in pregnancy to treat preterm labor, it should be used only when the benefits outweigh potential risks. Monitor for maternal and fetal cardiovascular complications.
• Lactation: Excreted in small amounts in breast milk. Use with caution during breastfeeding due to potential effects on the neonate (e.g., tachycardia, hypoglycemia).
• Caution: Adequate maternal-fetal monitoring is essential during therapy. Avoid concurrent corticosteroid therapy if possible due to increased risk of pulmonary edema.

• Primary Class: Tocolytic Agent
• Subclass: β2-Adrenergic Agonist (Uterine Relaxant)

• Known hypersensitivity to Ritodrine or any component of the formulation
• Antepartum hemorrhage (e.g., placenta previa, placental abruption)
• Intrauterine fetal death
• Eclampsia or severe preeclampsia
• Severe hypertension or heart disease
• Hyperthyroidism
• Uncontrolled diabetes mellitus
• Pulmonary hypertension
• Angle-closure glaucoma

• Maternal cardiovascular risk: Monitor for tachycardia, arrhythmias, hypotension, or chest pain.
• Pulmonary edema: Especially with fluid overload or concurrent corticosteroid use.
• Electrolyte imbalance: Risk of hypokalemia.
• Hyperglycemia: Can occur due to β2 stimulation of hepatic glycogenolysis.
• Fetal risks: Tachycardia, hypoglycemia, and myocardial ischemia.
• Clinical Monitoring: Continuous maternal ECG, blood pressure, electrolytes, and fetal monitoring are necessary.
• Discontinue immediately if chest pain, arrhythmia, or pulmonary edema develops.

Common (≥10%):

• Cardiovascular: Palpitations, tachycardia, hypotension
• Nervous system: Tremor, anxiety, restlessness
• GI: Nausea, vomiting

Less Common (1–10%):

• Headache
• Flushing
• Sweating
• Insomnia

Serious/Rare:

• Pulmonary edema
• Myocardial ischemia or infarction
• Arrhythmias (e.g., atrial fibrillation, ventricular tachycardia)
• Severe hypotension
• Hypokalemia
• Hyperglycemia
• Fetal tachycardia or neonatal hypoglycemia

• MAO Inhibitors: May enhance sympathomimetic effects, increasing cardiovascular risk.
• Corticosteroids: Increased risk of pulmonary edema when used concomitantly.
• Other β-agonists (e.g., salbutamol): Additive cardiovascular effects.
• Antidiabetic agents: May antagonize effects of insulin or oral hypoglycemics due to hyperglycemia.
• Anesthetics (e.g., halothane): May increase risk of arrhythmias.
• Enzyme Interactions: Not significantly metabolized by CYP450 system; mainly conjugation.

• Recent Safety Reviews: EMA and FDA advisories highlight the need for cautious use due to cardiovascular and pulmonary risks. The FDA has discouraged prolonged use (>48–72 hours) due to maternal safety concerns.
• Label Changes: Black box warnings in some countries for risks of maternal pulmonary edema, arrhythmia, and myocardial ischemia.

• Storage Temperature: Store below 25°C.
• Light & Humidity: Protect from light and excessive humidity.
• Handling Precautions: For IV use only. Discard unused solution after opening.
• Stability: Do not freeze. Once diluted, use immediately or store as per manufacturer’s instruction (usually within 24 hours under refrigeration).