Deltyba^® (Tablets) Instructions for Use

Marketing Authorization Holder

R-Pharm JSC (Russia)

Manufactured By

Otsuka Pharmaceutical, Co. Ltd. (Japan)

Labeled By

R-PHARM GERMANY, GmbH (Germany)

ATC Code

J04AK06 (Delamanid)

Active Substance

Delamanid (Rec.INN registered by WHO)

Dosage Form

Deltyba®

Film-coated tablets 50 mg: 48 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets yellow, round, slightly convex, with a bevel, with the inscription “DLM” and “50” on one side.

Excipients: hypromellose phthalate, povidone, alpha-tocopherol, microcrystalline cellulose, sodium starch glycolate, carmellose calcium, colloidal silicon dioxide, magnesium stearate, lactose monohydrate, hypromellose, macrogol 8000, titanium dioxide, talc, yellow iron oxide dye (E172).

8 pcs. – aluminum blisters (6) – cardboard packs.

Clinical-Pharmacological Group

Antituberculosis drug

Pharmacotherapeutic Group

Antitubercular agent

Pharmacological Action

An antituberculosis agent, a nitro-dihydro-imidazooxazole derivative. It inhibits the biosynthesis of mycolic acid in the mycobacterial cell wall.

It is highly active against Mycobacterium tuberculosis, including multidrug-resistant strains, and is also active against Mycobacterium kansasii and Mycobacterium bovis.

It has high therapeutic efficacy when used in low doses. The minimum inhibitory concentration (MIC) is 0.006-0.024 µg/ml.

Delamanid does not exhibit cross-resistance with other antituberculosis drugs.

Pharmacokinetics

After a single oral dose of 100 mg of delamanid, the C_max in plasma is 135 ng/ml. The absolute bioavailability is 25-47%.

Taking delamanid with food increases the bioavailability of the drug by approximately 2.7 times compared to taking it on an empty stomach.

Steady-state concentration is reached after 10-14 days. The apparent V_d is 2100 L. Plasma protein binding is 99.5%, primarily with albumin.

Delamanid is metabolized by the isoenzymes CYP3A4, CYP1A1, CYP2D6 and to a lesser extent CYP2E1 to form four main metabolites (M1-M4); M1 and M3 account for 13-18% of the total metabolites in plasma.

Delamanid is excreted primarily in feces, less than 5% in urine. T_1/2 ranges from 30 to 38 hours.

Indications

As part of combination therapy for pulmonary tuberculosis with multidrug resistance in adult patients.

ICD codes

Dosage Regimen

Take orally with food to enhance bioavailability.

Administer 100 mg twice daily (morning and evening) for a total daily dose of 200 mg.

Swallow the tablet whole; do not crush or chew.

The standard treatment duration is 24 weeks as part of a combination regimen.

Initiate therapy only after confirmation of multidrug-resistant tuberculosis.

Continue treatment for the full prescribed duration, even if symptoms improve.

Monitor ECG before initiation, and regularly during treatment due to risk of QT interval prolongation.

Assess serum potassium, calcium, and magnesium levels before and during therapy.

Do not administer with strong CYP3A4 inducers (e.g., rifampicin, carbamazepine).

Use with caution when co-administering other drugs known to prolong the QT interval.

Discontinue if significant QT prolongation or arrhythmias occur.

The maximum recommended daily dose is 200 mg; do not exceed this limit.

Adverse Reactions

Nervous system disorders insomnia, somnolence, sleep disorder, dizziness, headache, paresthesia, hypesthesia, peripheral neuropathy, herpes zoster, radiculitis, tremor, neurosis.

Psychiatric disorders psychotic disorder, delusional disorder, agitation, anxiety disorder, depression, dysphoria, restlessness, aggression, panic disorder, adjustment disorder with depressed mood, increased libido, apathy.

Eye disorders allergic conjunctivitis, dry eye syndrome, photophobia.

Ear and labyrinth disorders ear pain, tinnitus, balance disorder.

Blood and lymphatic system disorders thrombocytopenia, reticulocytosis, anemia, eosinophilia, leukopenia.

Metabolism and nutrition disorders hypokalemia, hyperuricemia, hypertriglyceridemia, hypocalcemia, hypercholesterolemia.

Cardiac disorders QT interval prolongation on ECG, ST segment depression on ECG, ventricular extrasystole, first-degree AV block, arterial hypertension, arterial hypotension, palpitations.

Respiratory, thoracic and mediastinal disorders dyspnea, cough, hemoptysis, rhinorrhea.

Gastrointestinal disorders decreased appetite, oral paresthesia, oral and pharyngeal candidiasis, oropharyngeal pain, dysphagia, nausea, vomiting, diarrhea, constipation, dyspepsia, gastritis, impaired liver function, increased transaminase levels, increased GGT levels.

Renal and urinary disorders hematuria, urinary retention, dysuria, nocturia.

Skin and subcutaneous tissue disorders dermatitis, skin itching, rash, maculopapular rash, erythematous rash, acne, hyperhidrosis, alopecia, eosinophilic pustular folliculitis, tinea versicolor, hematoma.

Allergic reactions urticaria.

Musculoskeletal and connective tissue disorders arthralgia, myalgia, osteochondrosis, muscle weakness, pain in muscles and bones,

Other asthenia, pyrexia, dry throat, hot flush, dehydration, chest pain, chest discomfort, abdominal pain, abdominal discomfort, low back pain, limb pain, peripheral edema, increased or decreased blood cortisol levels, prolonged aPTT.

Contraindications

Hypersensitivity to delamanid; plasma albumin concentration less than 28 g/L; QT interval prolongation, ventricular arrhythmia, severe coronary artery disease; concomitant use with strong CYP3A4 inducers (rifampicin, carbamazepine); pregnancy, breastfeeding period; age under 18 years.

Use in Pregnancy and Lactation

The use of delamanid is not recommended during pregnancy and breastfeeding.

Pediatric Use

Contraindicated for use under the age of 18 years.

Special Precautions

The use of delamanid may cause QT_c interval prolongation due to potassium channel blockade.

Before starting delamanid and during treatment, an ECG should be performed, as well as a blood test to monitor the concentration of potassium, calcium, magnesium, and proteins.

Animal studies show that Delamanid may weaken vitamin K-dependent blood clotting, increasing prothrombin time and aPTT.

Drug Interactions

Caution should be exercised with the concomitant use of other drugs that prolong the QT interval (moxifloxacin, clofazimine, lopinavir/ritonavir, ondansetron), as well as strong inducers or inhibitors of CYP3A4.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.