Pretomanid

Pretomanid is a prescription medication used for the treatment of multidrug-resistant (MDR) tuberculosis. 

• Pretomanid is available under the following different brand names: Dovprela

Common side effects of Pretomanid include:

• Nerve problems,
• Heartburn,
• Stomach pain,
• Loss of appetite,
• Nausea,
• Vomiting,
• Diarrhoea,
• Cough,
• Chest pain,
• Headache,
• Muscle and bone pain,
• Acne,
• Rash,
• Itching,
• Abnormal blood tests for the liver or pancreas,
• Unusual weight loss,
• Hunger,
• Sweating,
• Irritability,
• Dizziness,
• Fast heart rate,
• Anxiety, and
• Shakiness  

Serious side effects of Pretomanid include:

• Hives,
• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat,
• Fast or pounding heartbeats,
• Fluttering in the chest,
• Shortness of breath,
• Sudden dizziness,
• Tremors,
• Weakness,
• Problems with balance,
• Vision changes,
• Severe ongoing nausea and vomiting,
• Cough with mucus or blood,
• Chest pain that gets worse with breathing or coughing,
• Numbness, tingling, burning, or prickly feeling in the arms, hands, legs, or feet,
• Nausea,
• Loss of appetite,
• Stomach pain (upper right side),
• Tiredness,
• Itching,
• Dark urine,
• Yellowing of the skin or eyes (jaundice),
• Fever,
• Easy bruising,
• Unusual bleeding,
• Pale skin,
• Cold hands and feet, and
• Lightheadedness

Rare side effects of Pretomanid include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out. 

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 200 mg

Tuberculosis

Adult dosage

• Dosage regimen
  • Pteromalid 200 mg orally every day for 26 weeks
  • Bed aquiline 400 mg orally every day for 2 weeks, then, 200 mg 3 per week with at least 48 hours between doses for 24 weeks (total of 26 weeks)
  • Linezolid 1200 mg orally once a day for 26 weeks; adjust the dose as necessary (600 mg/day, further reduction to 300 mg/day, or interrupt dosing) for myelosuppression, peripheral neuropathy, or optic neuropathy

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Pretomanid has severe interactions with no other drugs.
• Pretomanid has serious interactions with at least 102 other drugs.
• Pretomanid has moderate interactions with no other drugs.
• Pretomanid has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Pretomanid is contraindicated in patients for whom bedaquiline and/or linezolid are contraindicated

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Pretomanid?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Pretomanid?”

Cautions

• Hepatic adverse reactions were reported with the combination; interruption of the treatment may be necessary; obtain ALT, AST, alkaline phosphatase, and bilirubin at a minimum at baseline, at 2 weeks, and then monthly
• Myelosuppression reported with the combination (known adverse effect of linezolid); consider decreasing or interrupting linezolid dosing if the patient has worsening myelosuppression
• Peripheral and optic neuropathy reported (known adverse effect of linezolid); interrupt linezolid if necessary
• QT prolongation was reported with combination, although cardiac electrophysiology testing of pretomanid did not demonstrate prolonged QTc; discontinue if clinically significant ventricular arrhythmia or a QTcF interval of greater than 500 ms develops; if syncope occurs, obtain an ECG to detect QT prolongation
• Pretomanid caused testicular atrophy and impaired fertility in male rats; effects on human male fertility have not been fully evaluated
• Lactic acidosis reported with the combination (known adverse effect of linezolid); immediately evaluate patient (including bicarbonate and lactic acid levels) if recurrent nausea or vomiting occurs; consider interrupting linezolid dosing or entire combination
• Drug interaction overview
  • Regimen associated with hepatotoxicity; avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid
  • Pretomanid may be in part metabolized by CYP3A4; avoid coadministration of strong or moderate CYP3A4 inducers
  • In vitro studies demonstrated that pretomanid significantly inhibits OAT3; monitor for increased adverse effects and consider dosage reduction for OAT3 substrates

Pregnancy and Lactation

• No data are available on use in pregnant women
• Clinical considerations
  • Active TB in pregnancy is associated with adverse maternal and neonatal outcomes, including maternal anemia, cesarean delivery, preterm birth, low birth weight, birth asphyxia, and perinatal infant death
• Infertility
  • Males: Reduced fertility and testicular toxicity cannot be definitively ruled out as of August 2019
• Lactation
  • No data are available regarding the presence of pretomanid in human milk, or its effects on milk production or the breastfed infant
  • Detected in rat milk; when a drug is present in animal milk, the drug will likely be present in human milk
  • Because of the potential for adverse reactions in nursing infants, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant